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Myasthenia gravis future or investigational therapies

Mohammad Ahmed — Mon, 24 Aug 2026 23:59:42 GMT

Updated according to the International Consensus Guidance for Management of Myasthenia Gravis 2020 Update

← Older revision		Revision as of 23:59, 24 August 2026
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	__NOTOC__		__NOTOC__
	{{Myasthenia gravis}}		{{Myasthenia gravis}}
	{{CMG}}		{{CMG}} {{AE}} {{HMA}}

	==Overview==		==Overview==
			Several therapies for [[myasthenia gravis]] (MG) remain under active investigation, and important questions persist regarding the optimal use of recently introduced agents. Areas of ongoing study include [[Complement system\|complement]] inhibition, targeted [[B-cell]] therapies, and the role of newer immunotherapies in disease subgroups and stages not yet well characterized.

	==Future Or Investigational Therapies==		==Future Or Investigational Therapies==

			* '''Complement inhibition:''' [[Eculizumab]], a monoclonal antibody against complement [[Complement component 5\|C5]], is established for severe, refractory [[Acetylcholine receptor\|AChR]] antibody–positive generalized [[Myasthenia gravis\|MG]], but its longer-term role continues to evolve. Unresolved questions include the duration of therapy needed to reach and maintain treatment goals, efficacy in populations not studied in the pivotal trials (such as thymomatous and seronegative MG), and its potential value in additional disease stages, including [[myasthenic crisis]], acute exacerbations, and earlier (non-refractory) [[Acetylcholine receptor\|AChR]] antibody–positive disease.
			* '''B-cell–targeted therapy:''' [[Rituximab]], an anti-[[CD20]] monoclonal antibody, shows the most consistent benefit in [[MuSK]] antibody–positive disease, whereas its efficacy in refractory [[Acetylcholine receptor\|AChR]] antibody–positive [[Myasthenia gravis\|MG]] remains uncertain. Optimal dosing regimens, timing, and patient selection are still being defined, and randomized data are limited.
			* '''Steroid-sparing immunosuppressants:''' The comparative effectiveness of agents such as [[methotrexate]] relative to better-established steroid-sparing drugs remains incompletely defined, and high-quality randomized evidence is lacking.
			* '''Other directions:''' Additional research priorities include the management of [[Myasthenia gravis\|MG]] that arises as an immune-related adverse event of immune checkpoint inhibitors, and refinement of treatment strategies across the spectrum of disease severity, antibody status, and thymic pathology.<ref>Narayanaswami, P., Sanders, D. B., Wolfe, G., Benatar, M., Cea, G., Evoli, A., Gilhus, N. E., Illa, I., Kuntz, N. L., Massey, J., Melms, A., Murai, H., Nicolle, M., Palace, J., Richman, D., & Verschuuren, J. (2021). International consensus guidance for management of myasthenia gravis: 2020 update: 2020 Update. ''Neurology'', ''96''(3), 114–122. https://doi.org/10.1212/WNL.0000000000011124</ref>

	==References==		==References==

Myasthenia gravis cost-effectiveness of therapy

Mohammad Ahmed — Mon, 24 Aug 2026 23:52:26 GMT

Updated according to the International Consensus Guidance for Management of Myasthenia Gravis 2020 Update

← Older revision		Revision as of 23:52, 24 August 2026
Line 1:		Line 1:
	__NOTOC__		__NOTOC__
	{{Myasthenia gravis}}		{{Myasthenia gravis}}
	{{CMG}}		{{CMG}} {{AE}} {{HMA}}

	==Overview==		==Overview==
			Formal cost-effectiveness data for [[myasthenia gravis]] (MG) therapy are limited. Treatment selection nonetheless incorporates cost considerations, particularly in positioning newer, high-cost biologic agents relative to established, lower-cost immunotherapies.

			== Cost-Effectiveness of Therapy ==

			Established [[Immunosuppressive drug\|immunosuppressants]] and [[thymectomy]] remain the foundation of chronic [[Myasthenia gravis\|MG]] management. Older steroid-sparing agents such as [[azathioprine]], [[Mycophenolate sodium\|mycophenolate mofetil]], and [[methotrexate]] are relatively inexpensive, and their corticosteroid-sparing effect can lower the long-term costs linked to chronic steroid toxicity. [[Thymectomy]] likewise reduces immunotherapy requirements and hospitalizations for exacerbations over time.

			Newer biologic agents are substantially more expensive and are generally reserved for refractory disease:

			* '''Eculizumab''', a complement [[Complement component 5\|C5]] inhibitor, is effective in severe, refractory [[acetylcholine receptor]] (AChR) antibody–positive generalized [[Myasthenia gravis\|MG]] but is a high-cost therapy best reserved for patients in whom other immunotherapies have failed to achieve treatment goals. Its use adds further expense for mandatory [[Meningococcal Vaccine\|meningococcal vaccination]] and, when treatment cannot be delayed, antibiotic prophylaxis.
			* '''Rituximab''' is a reasonable early option in [[MuSK]] antibody–positive disease that responds poorly to first-line therapy, but its benefit in refractory [[Acetylcholine receptor\|AChR]] antibody–positive MG is uncertain, a consideration relevant when weighing its cost against expected clinical benefit.

			A stepwise approach is generally favored, in which lower-cost, better-established therapies are used first and higher-cost biologics are reserved for refractory disease until stronger comparative cost-effectiveness evidence is available.<ref>Narayanaswami, P., Sanders, D. B., Wolfe, G., Benatar, M., Cea, G., Evoli, A., Gilhus, N. E., Illa, I., Kuntz, N. L., Massey, J., Melms, A., Murai, H., Nicolle, M., Palace, J., Richman, D., & Verschuuren, J. (2021). International consensus guidance for management of myasthenia gravis: 2020 update: 2020 Update. ''Neurology'', ''96''(3), 114–122. https://doi.org/10.1212/WNL.0000000000011124</ref>

	==References==		==References==

Myasthenia gravis primary prevention

Mohammad Ahmed — Mon, 24 Aug 2026 23:43:12 GMT

Immune Checkpoint Inhibitors and De Novo MG

← Older revision		Revision as of 23:43, 24 August 2026
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	There are no established measures that prevent the onset of [[Myasthenia gravis\|MG]]. Prevention efforts are therefore limited to avoiding or cautiously using drugs capable of provoking de novo disease. The 2020 MGFA guidance identifies several agents that can precipitate MG in previously unaffected individuals, including [[D-penicillamine]] (strongly linked to drug-induced MG), [[chloroquine]] and [[hydroxychloroquine]], and immune checkpoint inhibitors used in cancer therapy. Where clinically feasible, these agents should be used only when necessary, with monitoring for emerging [[neuromuscular]] symptoms.<ref name=":0">Narayanaswami, P., Sanders, D. B., Wolfe, G., Benatar, M., Cea, G., Evoli, A., Gilhus, N. E., Illa, I., Kuntz, N. L., Massey, J., Melms, A., Murai, H., Nicolle, M., Palace, J., Richman, D., & Verschuuren, J. (2021). International consensus guidance for management of myasthenia gravis: 2020 update: 2020 Update. ''Neurology'', ''96''(3), 114–122. https://doi.org/10.1212/WNL.0000000000011124</ref>		There are no established measures that prevent the onset of [[Myasthenia gravis\|MG]]. Prevention efforts are therefore limited to avoiding or cautiously using drugs capable of provoking de novo disease. The 2020 MGFA guidance identifies several agents that can precipitate MG in previously unaffected individuals, including [[D-penicillamine]] (strongly linked to drug-induced MG), [[chloroquine]] and [[hydroxychloroquine]], and immune checkpoint inhibitors used in cancer therapy. Where clinically feasible, these agents should be used only when necessary, with monitoring for emerging [[neuromuscular]] symptoms.<ref name=":0">Narayanaswami, P., Sanders, D. B., Wolfe, G., Benatar, M., Cea, G., Evoli, A., Gilhus, N. E., Illa, I., Kuntz, N. L., Massey, J., Melms, A., Murai, H., Nicolle, M., Palace, J., Richman, D., & Verschuuren, J. (2021). International consensus guidance for management of myasthenia gravis: 2020 update: 2020 Update. ''Neurology'', ''96''(3), 114–122. https://doi.org/10.1212/WNL.0000000000011124</ref>

	== Immune Checkpoint Inhibitors and De Novo MG ==		=== Immune Checkpoint Inhibitors and De Novo MG ===
	ICIs targeting [[CTLA-4]] ([[ipilimumab]]), PD-1 ([[nivolumab]], [[pembrolizumab]], [[Cemiplimab-rwlc\|cemiplimab]]), and [[PD-L1]] ([[atezolizumab]], [[durvalumab]], [[avelumab]]) can trigger new-onset [[Myasthenia gravis\|MG]], with reported frequencies of roughly 0.1–0.2% among patients on PD-1 inhibitors. ICI-associated MG tends to appear early in treatment, is frequently severe with a high rate of respiratory crises, and may overlap with [[myositis]] and [[myocarditis]]. To reduce risk and enable early detection, the guidance advises:		ICIs targeting [[CTLA-4]] ([[ipilimumab]]), PD-1 ([[nivolumab]], [[pembrolizumab]], [[Cemiplimab-rwlc\|cemiplimab]]), and [[PD-L1]] ([[atezolizumab]], [[durvalumab]], [[avelumab]]) can trigger new-onset [[Myasthenia gravis\|MG]], with reported frequencies of roughly 0.1–0.2% among patients on PD-1 inhibitors. ICI-associated MG tends to appear early in treatment, is frequently severe with a high rate of respiratory crises, and may overlap with [[myositis]] and [[myocarditis]]. To reduce risk and enable early detection, the guidance advises:

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	* There is currently insufficient evidence to recommend routine [[Acetylcholine receptor\|AChR]] antibody testing before starting ICIs in patients without known [[Myasthenia gravis\|MG]].<ref name=":0" />		* There is currently insufficient evidence to recommend routine [[Acetylcholine receptor\|AChR]] antibody testing before starting ICIs in patients without known [[Myasthenia gravis\|MG]].<ref name=":0" />

	== Immunization Considerations ==		=== Immunization Considerations ===
	Because [[immunosuppressive therapy]] is central to [[Myasthenia gravis\|MG]] management, live-attenuated [[vaccines]] are contraindicated once [[immunosuppression]] is under way. Ensuring appropriate immunization before immunosuppression, and following ACIP or local vaccination guidance, is relevant to preventing infectious complications rather than MG itself.<ref name=":0" />		Because [[immunosuppressive therapy]] is central to [[Myasthenia gravis\|MG]] management, live-attenuated [[vaccines]] are contraindicated once [[immunosuppression]] is under way. Ensuring appropriate immunization before immunosuppression, and following ACIP or local vaccination guidance, is relevant to preventing infectious complications rather than MG itself.<ref name=":0" />

Myasthenia gravis secondary prevention

Mohammad Ahmed — Mon, 24 Aug 2026 23:42:25 GMT

← Older revision		Revision as of 23:42, 24 August 2026
(One intermediate revision by the same user not shown)
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	__NOTOC__		__NOTOC__
	{{Myasthenia gravis}}		{{Myasthenia gravis}}
	{{CMG}}		{{CMG}} {{AE}} {{HMA}}

	==Overview==		==Overview==
	~~There are no established measures for the~~ secondary prevention of Myasthenia gravis.		No formal secondary-prevention program exists for [[myasthenia gravis]] (MG). In practical terms, however, once [[Myasthenia gravis\|MG]] is established, efforts to prevent worsening, exacerbations, and [[myasthenic crisis]] are important, and the 2020 Myasthenia Gravis Foundation of America (MGFA) International Consensus Guidance provides guidance most relevant to this goal, principally avoidance of drugs that aggravate MG, precautions with immune checkpoint inhibitors (ICIs), and required [[vaccination]] before [[Complement system\|complement]]-inhibitor therapy.

	==Secondary Prevention==		==Secondary Prevention==
	There are no established measures for the secondary prevention of Myasthenia gravis.		There are no formally established measures for the secondary prevention of [[Myasthenia gravis\|MG]]. Preventive care therefore focuses on reducing the risk of clinical deterioration in patients with known disease.<ref name=":0">Narayanaswami, P., Sanders, D. B., Wolfe, G., Benatar, M., Cea, G., Evoli, A., Gilhus, N. E., Illa, I., Kuntz, N. L., Massey, J., Melms, A., Murai, H., Nicolle, M., Palace, J., Richman, D., & Verschuuren, J. (2021). International consensus guidance for management of myasthenia gravis: 2020 update: 2020 Update. ''Neurology'', ''96''(3), 114–122. https://doi.org/10.1212/WNL.0000000000011124</ref>

			=== Avoiding Drugs That Worsen MG ===
			Numerous medications can aggravate [[Myasthenia gravis\|MG]] or precipitate crisis, and awareness of them is central to preventing exacerbations. Agents with the strongest evidence for worsening MG include:

			* Certain antibiotics, [[aminoglycosides]], [[fluoroquinolones]] (which carry an FDA boxed warning), [[macrolides]], and [[telithromycin]] (which should not be used in [[Myasthenia gravis\|MG]] at all).

			* Cardiovascular drugs such as [[beta-blockers]] and [[procainamide]].
			* [[Magnesium]], particularly when given intravenously.
			* [[Antimalarial drug\|Antimalarials]] ([[chloroquine]], [[hydroxychloroquine]]) and [[D-penicillamine]].
			* [[Botulinum toxin]], [[quinine]], iodinated contrast media, [[statins]], and [[deferoxamine]].

			These drugs need not be absolutely prohibited; reported associations are sometimes rare or coincidental. Decisions should weigh the individual risk–benefit balance, use alternatives where possible, and include monitoring for worsening when an implicated drug is necessary.<ref name=":0" />

			=== Precautions With Immune Checkpoint Inhibitors ===
			In patients with preexisting [[Myasthenia gravis\|MG]] who require cancer [[immunotherapy]], well-controlled disease is not an absolute barrier to ICI use, but steps to limit deterioration are advised: avoiding combined [[CTLA-4]] plus PD-1/[[PD-L1]] regimens because of the greater risk of severe immune-related events, monitoring respiratory and bulbar function closely, and continuing [[Myasthenia gravis\|MG]]-directed treatment throughout. Should overt [[Myasthenia gravis\|MG]] emerge or flare during therapy, prompt high-dose [[corticosteroids]] together with [[Plasmapheresis\|plasma exchange]] or [[Intravenous immunoglobulin\|IVIG]] may be required, and the decision to stop the ICI depends on the oncologic situation.<ref name=":0" />

			=== Vaccination Before Complement Inhibitor Therapy ===
			Because [[eculizumab]] increases susceptibility to [[Neisseria meningitidis\|meningococcal]] infection, meningococcal immunization (both conjugate ACWY and serogroup B vaccines) is required at least two weeks before initiating therapy. If treatment must begin sooner, antibiotic prophylaxis should be provided and continued for at least two weeks after vaccination. ACIP or local immunization recommendations should be followed.<ref name=":0" />

			=== Corticosteroid Initiation ===
			Starting [[corticosteroids]] can transiently worsen [[Myasthenia gravis\|MG]] within the first two weeks, occasionally precipitating crisis. Careful monitoring during initiation, and consideration of gradual dose escalation or inpatient observation in patients with bulbar or respiratory involvement, helps prevent steroid-induced deterioration.<ref name=":0" />

	==References==		==References==

Myasthenia gravis primary prevention

Mohammad Ahmed — Mon, 24 Aug 2026 23:34:00 GMT

← Older revision		Revision as of 23:34, 24 August 2026
(3 intermediate revisions by the same user not shown)
Line 1:		Line 1:
	__NOTOC__		__NOTOC__
	{{Myasthenia gravis}}		{{Myasthenia gravis}}
	{{CMG}}		{{CMG}} {{AE}} {{HMA}}

	==Overview==		==Overview==
	~~There are no established measures for~~ the ~~primary prevention~~ of Myasthenia gravis.		No proven strategy exists to prevent the initial development of [[myasthenia gravis]] (MG), an [[autoimmune disorder]] of unclear inciting cause. However, certain medications are recognized to trigger new-onset (de novo) [[Myasthenia gravis\|MG]] or unmask subclinical disease, and awareness of these agents, particularly immune checkpoint inhibitors (ICIs), is the main practical form of risk reduction of MG.

	==Primary Prevention==		==Primary Prevention==
	There are no established measures for the ~~primary prevention~~ of Myasthenia gravis.		There are no established measures that prevent the onset of [[Myasthenia gravis\|MG]]. Prevention efforts are therefore limited to avoiding or cautiously using drugs capable of provoking de novo disease. The 2020 MGFA guidance identifies several agents that can precipitate MG in previously unaffected individuals, including [[D-penicillamine]] (strongly linked to drug-induced MG), [[chloroquine]] and [[hydroxychloroquine]], and immune checkpoint inhibitors used in cancer therapy. Where clinically feasible, these agents should be used only when necessary, with monitoring for emerging [[neuromuscular]] symptoms.<ref name=":0">Narayanaswami, P., Sanders, D. B., Wolfe, G., Benatar, M., Cea, G., Evoli, A., Gilhus, N. E., Illa, I., Kuntz, N. L., Massey, J., Melms, A., Murai, H., Nicolle, M., Palace, J., Richman, D., & Verschuuren, J. (2021). International consensus guidance for management of myasthenia gravis: 2020 update: 2020 Update. ''Neurology'', ''96''(3), 114–122. https://doi.org/10.1212/WNL.0000000000011124</ref>

			== Immune Checkpoint Inhibitors and De Novo MG ==
			ICIs targeting [[CTLA-4]] ([[ipilimumab]]), PD-1 ([[nivolumab]], [[pembrolizumab]], [[Cemiplimab-rwlc\|cemiplimab]]), and [[PD-L1]] ([[atezolizumab]], [[durvalumab]], [[avelumab]]) can trigger new-onset [[Myasthenia gravis\|MG]], with reported frequencies of roughly 0.1–0.2% among patients on PD-1 inhibitors. ICI-associated MG tends to appear early in treatment, is frequently severe with a high rate of respiratory crises, and may overlap with [[myositis]] and [[myocarditis]]. To reduce risk and enable early detection, the guidance advises:

			* Counseling candidates for ICI therapy about the possibility of [[Myasthenia gravis\|MG]] and other immune-related neurologic complications before treatment begins.
			* Close clinical surveillance, especially of respiratory and bulbar function, during therapy so that emerging weakness is recognized promptly.
			* There is currently insufficient evidence to recommend routine [[Acetylcholine receptor\|AChR]] antibody testing before starting ICIs in patients without known [[Myasthenia gravis\|MG]].<ref name=":0" />

			== Immunization Considerations ==
			Because [[immunosuppressive therapy]] is central to [[Myasthenia gravis\|MG]] management, live-attenuated [[vaccines]] are contraindicated once [[immunosuppression]] is under way. Ensuring appropriate immunization before immunosuppression, and following ACIP or local vaccination guidance, is relevant to preventing infectious complications rather than MG itself.<ref name=":0" />

	==References==		==References==
	~~{{Reflist\|2}}~~
	[[Category:Needs content]]		[[Category:Needs content]]
	[[Category:Rheumatology]]		[[Category:Rheumatology]]
	[[Category:Neurology]]		[[Category:Neurology]]
	[[Category:Disease]]		[[Category:Disease]]
			<br />

	{{WH}}		{{WH}}
	{{WS}}		{{WS}}

FORZINITY- elamipretide hydrochloride injection

Anum Ijaz — Mon, 24 Aug 2026 18:38:06 GMT

← Older revision		Revision as of 18:38, 24 August 2026
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	====Dosage Modifications For Renal Impairment====		====Dosage Modifications For Renal Impairment====
	* Refer to Table 1 for dosage modifications in adults with renal impairment.		* Refer to the Table for dosage modifications in adults with renal impairment.

	<table class="wikitable">		<table class="wikitable">

FORZINITY- elamipretide hydrochloride injection

Anum Ijaz — Mon, 24 Aug 2026 18:35:57 GMT

Created page with "{{DrugProjectFormSinglePage |authorTag={{AIJ}} |aOrAn=a |drugClass=mitochondrial cardiolipin binder. |indicationType=treatment |indication=Barth syndrome in adult and pediatric patients weighing at least 30 kg, to improve muscle strength. |adverseReactions=injection site reactions. |blackBoxWarningTitle='''<span style="color:#FF0000;">TITLE</span>''' |blackBoxWarningBody=''<span style="color:#FF0000;">Condition Name:</span>'' (Content) |fdaLIADAdult====Barth Syndrome..."

New page

{{DrugProjectFormSinglePage
|authorTag={{AIJ}}
|aOrAn=a
|drugClass=mitochondrial cardiolipin binder.
|indicationType=treatment
|indication=[[Barth syndrome]] in adult and pediatric patients weighing at least 30 kg, to improve muscle strength.
|adverseReactions=injection site reactions.
|blackBoxWarningTitle='''<span style="color:#FF0000;">TITLE</span>'''
|blackBoxWarningBody=''<span style="color:#FF0000;">Condition Name:</span>'' (Content)
|fdaLIADAdult====Barth Syndrome===
* FORZINITY is indicated to improve muscle strength in adult and pediatric patients with Barth syndrome weighing at least 30 kg.
* This indication is approved under accelerated approval based on an improvement in knee extensor muscle strength, an intermediate clinical endpoint.
* Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.

====Dosing Information====
* The recommended dosage of FORZINITY in patients weighing at least 30 kg is 40 mg subcutaneously once daily.
* Patients should receive the dose at the same time each day.

====Missed Dose====
* If a dose is missed, skip the dose and take the next dose of FORZINITY at the scheduled time. Do not take a double dose of FORZINITY.

====Dosage Modifications For Renal Impairment====
* Refer to Table 1 for dosage modifications in adults with renal impairment.

<table class="wikitable">
<tr><th>Estimated Glomerular Filtration Rate (eGFR) (mL/minute)</th><th>Recommended Dosage</th></tr>
<tr><td>Greater than or equal to 30 mL/minute</td><td>40 mg subcutaneously once daily</td></tr>
<tr><td>Less than 30 mL/minute and NOT on dialysis</td><td>20 mg subcutaneously once daily</td></tr>
</table>

* There is insufficient information to recommend a dosage regimen in adults with eGFR less than 30 mL/minute and on dialysis.
* There is insufficient information to recommend a dosage regimen in pediatric patients weighing 30 kg or greater with renal impairment.

====Important Administration Instructions====
* FORZINITY is a clear, colorless to yellow aqueous solution that contains the preservative, benzyl alcohol.
* Visually inspect each vial of FORZINITY for particulate matter and cloudiness prior to administration, whenever solution and container permit.
* Do not use if the solution is cloudy or particulate matter is present.
* Adult patients or caregivers may administer FORZINITY after proper training in preparing FORZINITY vials for administration, if a healthcare provider determines that it is appropriate, and with medical follow-up as necessary.
* Use aseptic technique to prepare and administer FORZINITY.
* Administer FORZINITY by subcutaneous injection in the abdomen (at least 2 inches from the navel) or outer thigh and rotate the injection site daily.
* Do not inject where the skin is tender, bruised, red, or hard.
* Avoid injecting into scars or stretch marks.
* Refer to the Instructions for Use for preparation and administration.
* FORZINITY is for single-patient-use only.
* Do not mix other products in the same syringe.
* Discard vials 8 days after first opening.
|offLabelAdultGuideSupport=There is limited information regarding ''Off-Label Guideline-Supported Use'' of FORZINITY- elamipretide hydrochloride injection in adult patients.
|offLabelAdultNoGuideSupport=There is limited information regarding ''Off-Label Non–Guideline-Supported Use'' of FORZINITY- elamipretide hydrochloride injection in adult patients.
|offLabelPedGuideSupport=There is limited information regarding ''Off-Label Guideline-Supported Use'' of FORZINITY- elamipretide hydrochloride injection in pediatric patients.
|offLabelPedNoGuideSupport=There is limited information regarding ''Off-Label Non–Guideline-Supported Use'' of FORZINITY- elamipretide hydrochloride injection in pediatric patients.
|contraindications=* Serious hypersensitivity to elamipretide or any of the excipients in FORZINITY.
|warnings====Risk of Benzyl Alcohol Toxicity in Neonates===
* FORZINITY is not approved for use in neonates.
* Serious adverse reactions, including fatal reactions, of new onset or worsening metabolic acidosis that progressed to neurotoxicity, and in some cases gasping syndrome, have been reported in low-birth weight neonates (less than 2,500 grams) and preterm neonates (gestational age less than 34 weeks) who received benzyl alcohol (BA)-containing drugs intravenously.
* FORZINITY is not approved for intravenous use.
* Gasping syndrome is a life-threatening condition in neonates caused by BA toxicity and is primarily characterized by multiorgan dysfunction secondary to metabolic acidosis, which leads to gasping respirations and death.
* The minimum amount of BA at which these serious adverse reactions, including fatal reactions, may occur is not known (FORZINITY contains 20 mg of BA per mL).

===Hypersensitivity===
* Hypersensitivity reactions, including serious allergic reactions requiring emergency medical intervention, have been reported in patients receiving FORZINITY.
* These reactions have included skin manifestations such as rash, papular lesions, and eczematous dermatitis, as well as respiratory symptoms including cough.
* Reactions may occur within minutes to months after treatment initiation.
* Monitor patients for signs and symptoms of hypersensitivity reactions during treatment.
* If a serious hypersensitivity reaction occurs, do not administer further doses of FORZINITY and institute appropriate emergency treatment, including epinephrine, antihistamines, and corticosteroids as clinically indicated.
* Patients who have experienced a serious hypersensitivity reaction should not be rechallenged with FORZINITY.
* For mild to moderate skin reactions, consider treatment with topical corticosteroids and oral antihistamines.
* Consider discontinuation of FORZINITY if persistent or severe skin reactions develop.
|clinicalTrials=* Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
* In the FORZINITY clinical development program, 12 male patients aged 12 to 35 years with genetically-confirmed Barth syndrome received treatment with daily subcutaneous injections of 40 mg FORZINITY.
* Eleven of these 12 patients were Caucasian.
* Patients first participated in a double-blind, placebo-controlled crossover trial where they were randomized to one of two sequences: 12 weeks of FORZINITY in Period 1 then a 4-week washout followed by 12 weeks of placebo in Period 2 or 12 weeks of placebo in Period 1 then a 4-week washout followed by 12 weeks of FORZINITY in Period 2.
* Ten patients completed the randomized trial and entered the open-label extension period where they received FORZINITY once daily.
* Eight of these patients received FORZINITY for 168 weeks, three of whom received FORZINITY for a total of 192 weeks.
* Adverse reactions occurring more commonly on FORZINITY than on placebo include injection site reactions such as injection site erythema, pain, induration, pruritus, bruising, and urticaria.

'''Eosinophilia:''' Increases in absolute eosinophil counts were noted frequently in studies where duration of administration of FORZINITY was 30 days or greater. Eosinophil counts generally peaked around 90 days after initial exposure (mean increase from baseline ~0.5 to 0.6 × 10<sup>3</sup>/uL) and returned to baseline levels after 6 to 12 months of continuous exposure or after discontinuation of FORZINITY. The elevation in eosinophils was not associated with clinical manifestations or changes in other laboratory parameters.

'''Summary of Adverse Drug Reactions in the Placebo-Controlled Crossover Study, Barth Safety Population'''

<table class="wikitable">
<tr><th>Adverse Reaction</th><th>Combined (Periods 1 and 2)<br>Elamipretide<br>N=12<br>n (%)</th><th>Combined (Periods 1 and 2)<br>Placebo<br>N=12<br>n (%)</th></tr>
<tr><td>Any local administration reaction</td><td>12 (100)</td><td>8 (67)</td></tr>
<tr><td>Injection site erythema</td><td>12 (100)</td><td>3 (25)</td></tr>
<tr><td>Injection site induration</td><td>8 (67)</td><td>2 (17)</td></tr>
<tr><td>Injection site pruritus</td><td>8 (67)</td><td>2 (17)</td></tr>
<tr><td>Injection site pain</td><td>9 (75)</td><td>5 (42)</td></tr>
<tr><td>Injection site bruising</td><td>3 (25)</td><td>0</td></tr>
<tr><td>Injection site urticaria</td><td>3 (25)</td><td>0</td></tr>
<tr><td>Injection site hemorrhage</td><td>0</td><td>1 (8)</td></tr>
</table>
|useInPregnancyFDA='''Risk Summary'''
* Barth Syndrome is a rare, X-linked, recessive, genetic disorder and is not likely to affect females.
* Therefore, there are no data with FORZINITY use in pregnant women to evaluate for a drug-related risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes.
* In animal reproduction studies, no adverse developmental outcomes occurred at any dose tested (see Data).
* FORZINITY contains benzyl alcohol as a preservative.
* Because benzyl alcohol is rapidly metabolized by a pregnant woman, benzyl alcohol exposure in the fetus is unlikely.
* The background risk of major birth defects and miscarriage for the indicated population is unknown.
* All pregnancies have a background risk of birth defect, loss, or other adverse outcomes.
* In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.
|useInNursing='''Risk Summary'''
* Barth Syndrome is a rare, X-linked, recessive, genetic disorder and is not likely to affect females.
* Therefore, there is no data to evaluate the presence of FORZINITY in human milk, the effect on the breastfed infant, or the effects on milk production.
* FORZINITY contains benzyl alcohol.
* Because benzyl alcohol is rapidly metabolized by a lactating female, benzyl alcohol exposure in the breastfed infant is unlikely.
* The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for FORZINITY and any potential adverse effects on the breastfed infant from FORZINITY or from the underlying maternal condition.
|useInPed=* The safety and effectiveness of FORZINITY to improve muscle strength have been established in pediatric patients with Barth syndrome weighing at least 30 kg.
* Use of FORZINITY for this indication is supported by improvement in knee extensor muscle strength, an intermediate clinical endpoint, observed in an open-label extension study of FORZINITY that included seven pediatric patients aged 12 years and older.
* The safety and effectiveness of FORZINITY have not been established in pediatric patients weighing less than 30 kg.
* FORZINITY is not approved for use in neonates.
* Serious adverse reactions, including fatal reactions, of new onset or worsening metabolic acidosis that progressed to neurotoxicity, and in some cases gasping syndrome, have been reported in low-birth weight neonates and preterm neonates who received BA containing drugs intravenously (FORZINITY is not approved for intravenous use).
* Gasping syndrome is a life-threatening condition in neonates caused by BA toxicity that is characterized by new onset or worsening metabolic acidosis with gradual neurological deterioration, seizures, intracranial hemorrhage, hematologic abnormalities, skin breakdown, hepatic and renal failure, hypotension, bradycardia, and gasping respirations followed by death.
* In reported cases, BA in amounts of 99 to 234 mg/kg/day produced blood BA levels of 6.6 to 14.9 mg/dL, but the minimum amount of BA at which gasping syndrome may occur in neonates is not known (FORZINITY contains 20 mg of BA per mL).
|useInRenalImpair====Renal Impairment===
* No dosage adjustment is required for patients with mild (eGFR 60 to 89 mL/min) or moderate (eGFR 30 to 59 mL/min) renal impairment.
* The FORZINITY dose should be reduced by one half administered subcutaneously once daily in adults with severe renal impairment (eGFR less than 30 mL/min) who are not on dialysis.
* FORZINITY has not been studied in patients with renal failure on dialysis.

===Dosage Modifications For Renal Impairment===
* Refer to Table 1 for dosage modifications in adults with renal impairment.

<table class="wikitable">
<tr><th>Estimated Glomerular Filtration Rate (eGFR) (mL/minute)</th><th>Recommended Dosage</th></tr>
<tr><td>Greater than or equal to 30 mL/minute</td><td>40 mg subcutaneously once daily</td></tr>
<tr><td>Less than 30 mL/minute and NOT on dialysis</td><td>20 mg subcutaneously once daily</td></tr>
</table>

* There is insufficient information to recommend a dosage regimen in adults with eGFR less than 30 mL/minute and on dialysis.
* There is insufficient information to recommend a dosage regimen in pediatric patients weighing 30 kg or greater with renal impairment.
|useInHepaticImpair====Specific Populations (Clinical Pharmacology)===
* No hepatic metabolism was observed for elamipretide in vitro.
* Hepatic impairment is not expected to alter the pharmacokinetics (PK) of elamipretide.
|administration=* FORZINITY is a clear, colorless to yellow aqueous solution that contains the preservative, benzyl alcohol.
* Visually inspect each vial of FORZINITY for particulate matter and cloudiness prior to administration, whenever solution and container permit.
* Do not use if the solution is cloudy or particulate matter is present.
* Adult patients or caregivers may administer FORZINITY after proper training in preparing FORZINITY vials for administration, if a healthcare provider determines that it is appropriate, and with medical follow-up as necessary.
* Use aseptic technique to prepare and administer FORZINITY.
* Administer FORZINITY by subcutaneous injection in the abdomen (at least 2 inches from the navel) or outer thigh and rotate the injection site daily.
* Do not inject where the skin is tender, bruised, red, or hard.
* Avoid injecting into scars or stretch marks.
* Refer to the Instructions for Use for preparation and administration.
* FORZINITY is for single-patient-use only.
* Do not mix other products in the same syringe.
* Discard vials 8 days after first opening.
|monitoring=====Hypersensitivity====
* Monitor patients for signs and symptoms of hypersensitivity reactions during treatment.
* If a serious hypersensitivity reaction occurs, do not administer further doses of FORZINITY and institute appropriate emergency treatment, including epinephrine, antihistamines, and corticosteroids as clinically indicated.
* Patients who have experienced a serious hypersensitivity reaction should not be rechallenged with FORZINITY.
* For mild to moderate skin reactions, consider treatment with topical corticosteroids and oral antihistamines.
* Consider discontinuation of FORZINITY if persistent or severe skin reactions develop.
|mechAction=FORZINITY is a mitochondrial cardiolipin binder that localizes to the inner mitochondrial membrane and improves mitochondrial morphology and function.
|structure=* FORZINITY contains elamipretide, a mitochondrial cardiolipin binder.
* Elamipretide is isolated as a hydrochloride salt that is freely soluble in water.
* The chemical name for elamipretide hydrochloride is L-Phenylalaninamide, D-arginyl-2,6-dimethyl-L-tyrosyl-L-lysyl-, hydrochloride (1:3).
* Its molecular formula is C32H49N9O5∙3HCl and its molecular weight is 749.2.
* All amino acid residues in FORZINITY have the L configuration except for arginine which has the D configuration.
* The peptide sequence is denoted as D-Arg-2,6-dimethyl-Tyr-Lys-Phe-NH2.
* FORZINITY is a ready-to-use sterile, clear, colorless to yellow aqueous solution supplied as single-patient-use vials containing 3.5 mL solution for subcutaneous injection.
* Each 0.5 mL dose of FORZINITY contains 40 mg of elamipretide (equivalent to 46.8 mg elamipretide hydrochloride), 10 mg benzyl alcohol as a preservative, and 2.07 mg monobasic sodium phosphate (as monohydrate).
* The product may contain hydrochloric acid or sodium hydroxide to adjust pH.
* The pH of FORZINITY solution is 4.7 to 6.1.
|PD='''Effects on QTc Interval'''

'''Cardiac electrophysiology'''
* Clinically significant QTc interval prolongation was not observed at 3 times the peak concentration of the maximum recommended FORZINITY dose.
|PK=====Absorption====
* Elamipretide exposure increases proportionally over a dose range of 2 to 80 mg following daily subcutaneous injections with minimal accumulation.
* Maximum elamipretide concentrations were reached between 0.5 to 1 hour after subcutaneous administration.
* The absolute bioavailability following subcutaneous administration is approximately 92%.
* FORZINITY exposure is comparable after subcutaneous injection to the thigh or to the abdomen.

====Distribution====
* Elamipretide is distributed throughout total body water with an approximate volume of distribution of 0.5 L/kg.
* There is low binding to plasma proteins (approximately 39%).

====Elimination====

'''Metabolism'''
* Elamipretide is metabolized via sequential C-terminal degradation to the M1 tripeptide and M2 dipeptide metabolites, which do not have pharmacological activity.

'''Excretion'''
* Elamipretide and its metabolites M1 and M2 are excreted in the urine.
* At 48 hours post-dose, approximately 100% of the FORZINITY dose was recovered in the urine as either elamipretide, M1, or M2 in patients with normal renal function.

====Specific Populations====
* Elamipretide exposure (AUC) increased by 39% in subjects with creatinine clearance 60 to 89 mL/min, 75% in subjects with creatinine clearance 30 to 59 mL/min, and 125% in subjects with creatinine clearance less than 30 mL/min not on dialysis.
* Renal impairment was categorized based on 24-hour measured urinary creatinine clearance.
* There was minimal accumulation of elamipretide with daily dosing, regardless of the severity of renal impairment.
* There was a significant increase in exposure of the M1 and M2 metabolites, up to 280% and 640%, respectively, in subjects with severe renal impairment not on dialysis (creatinine clearance less than 30 mL/min).
* While the effect of renal impairment on elamipretide pharmacokinetics was characterized using 24-hour measured urinary creatinine clearance, analyses conducted with estimated glomerular filtration (CKD-EPI equation) support the recommendations for use in this specific population.
* No hepatic metabolism was observed for elamipretide in vitro.
* Hepatic impairment is not expected to alter the pharmacokinetics (PK) of elamipretide.

====Drug Interaction Studies====

'''In Vitro Studies'''
* Elamipretide does not inhibit CYP1A, CYP2D6, CYP2E1, CYP2B6, CYP2C8, CYP2C9, CYP2C19, or CYP3A.
* Elamipretide does not induce metabolism by CYP1A2, CYP2B6, or CYP3A4.
* Elamipretide does not inhibit the activity of OCT2, BCRP, OAT1, OAT3, OATP1B1, OATP1B3, P-gp, or MATE2-K.
* Elamipretide is an inhibitor of MATE1 (IC50 3.53 μM).

'''In Vivo Clinical Studies'''
* Administration of elamipretide (0.1 mg/kg/hour for 4 hours via intravenous infusion) starting 4 hours after a single dose of 650 mg aspirin did not affect the PK of aspirin and its metabolite, salicylic acid.
* There was no impact on the antiplatelet activity of aspirin when co-administered with elamipretide.
* Administration of elamipretide (0.1 mg/kg/hour for 4 hours via intravenous infusion) starting 4 hours after a single dose of 300 mg clopidogrel did not significantly affect the PK of clopidogrel.
* There was no impact on the anti-thrombotic activity of clopidogrel when co-administered with elamipretide.
* Administration of elamipretide (0.25 mg/kg/hour for 4 hours via intravenous infusion) had no significant impact on activated partial thromboplastin time (aPTT) and anti-factor Xa activity of unfractionated heparin, when co-administered 7 hours after starting the unfractionated heparin infusion.
|nonClinToxic=====Carcinogenesis, Mutagenesis, Impairment of Fertility====
* Carcinogenicity studies have not been conducted with elamipretide.
* Elamipretide was negative in an in vitro bacterial reverse mutation assay, a chromosomal aberration assay in Chinese hamster ovary cells, and an in vivo rat bone marrow micronucleus assay.
* Subcutaneous doses of elamipretide in rats of up to 20 mg/kg/day, approximately 5-times the clinical exposure at the MRHD of 40 mg, did not adversely affect fertility or reproductive performance.
|clinicalStudies=* FORZINITY was evaluated in a randomized, double-blind, placebo-controlled, crossover trial and its 192-week, open-label, single-arm extension period.
* The randomized trial evaluated the efficacy and safety of once daily FORZINITY 40 mg injected subcutaneously for 12 weeks in 12 subjects ≥12-years-old and >30 kg with genetically confirmed Barth syndrome.
* The primary endpoints for the randomized trial were distance walked during 6-minute walk test and Total Fatigue Score on the Barth syndrome Symptom Assessment.
* FORZINITY was not superior to placebo on these primary endpoints.
* Ten subjects completed the randomized trial and entered the extension period designed to evaluate long-term safety and tolerability of FORZINITY.
* Eight of these 10 subjects participated through Week 168 of the extension period.
* Knee extensor muscle strength measured by handheld dynamometry was evaluated as one of the secondary endpoints in the randomized trial and in the extension period.
* Increases in knee extensor muscle strength were not observed during the randomized trial but were observed during the extension period.
* At the pre-dose baseline visit at the start of the randomized trial, median (min, max) muscle strength was 124 (92, 176) newtons.
* Table 3 shows descriptive changes from pre-dose baseline for knee extensor muscle strength during the randomized controlled trial and extension period.

'''Descriptive Statistics, Changes from Baseline in Muscle Strength (newtons)'''

<table class="wikitable">
<tr><th>Visit</th><th>N</th><th>Median Change</th><th>Min, Max Change</th></tr>
<tr><td colspan="4"><strong>Randomized Controlled Trial</strong></td></tr>
<tr><td>Week 12 Placebo</td><td>12</td><td>-5</td><td>-31, 48</td></tr>
<tr><td>Week 12 Elamipretide</td><td>12</td><td>4</td><td>-41, 86</td></tr>
<tr><td colspan="4"><strong>Open-Label Extension Period</strong></td></tr>
<tr><td>Week 12</td><td>10</td><td>34</td><td>7, 95</td></tr>
<tr><td>Week 24</td><td>9</td><td>68</td><td>3, 90</td></tr>
<tr><td>Week 36</td><td>8</td><td>57</td><td>9, 92</td></tr>
<tr><td>Week 48</td><td>8</td><td>41</td><td>-2, 144</td></tr>
<tr><td>Week 72</td><td>8</td><td>35</td><td>-4, 100</td></tr>
<tr><td>Week 168</td><td>8</td><td>63</td><td>38, 78</td></tr>
</table>
|howSupplied=* FORZINITY (elamipretide) injection is a sterile, clear, colorless to yellow aqueous solution supplied as:
* Carton containing four 280 mg/3.5 mL (80 mg/mL) single-patient-use vials (NDC 72507-800-04)
|storage=* Store refrigerated at 2°C to 8°C (36°F to 46°F). Do not freeze.
* Following the first dose, the opened vial can be stored either refrigerated 2°C to 8°C (36°F to 46°F) or at room temperature between 20°C to 25°C (68°F to 77°F).
* Discard vials 8 days after first opening.
|packLabel=Add Display panel
|fdaPatientInfo====Patient Counseling Information===
* Advise the patient and caregiver to read the FDA-approved patient labeling (Instructions for Use).
* Instruct patients and caregivers to discard vials 8 days after first opening.
* Instruct patients and caregivers on how to prepare and administer the correct dose of FORZINITY using aseptic technique.
* Instruct patients and caregivers to administer FORZINITY by subcutaneous injection in the abdomen (at least 2 inches from the navel) or outer thigh and to rotate the injection site daily according to the Instructions for Use.
* Instruct patients and caregivers not to inject where the skin is tender, bruised, red, or hard and to avoid injecting into scars or stretch marks.
* Inform patients and caregivers that injection site reactions such as erythema, pain, induration, pruritus, bruising, or urticaria can be treated with antihistamines or topical corticosteroids.
* Advise the patient and caregiver to discontinue FORZINITY and seek immediate medical attention if any signs or symptoms of an immediate hypersensitivity reaction occur.

===Instructions for Use===
* This Instructions for Use contains information on how to inject FORZINITY.
* Read this Instructions for Use before you inject a dose of FORZINITY for the first time.
* This information does not take the place of talking to your healthcare provider about your medical condition or treatment. Ask your healthcare provider about any instructions you do not understand.
* Your or your child's healthcare provider will show you how to prepare and inject FORZINITY before you use the vial for the first time. It is recommended that FORZINITY injections be prepared and given by adults or adult caregivers.
* FORZINITY is for injection under the skin (subcutaneous injection).
* FORZINITY is injected 1 time each day, at the same time each day.
* If a dose of FORZINITY is missed, skip that dose, and take the next dose of FORZINITY at the next scheduled time. Do not double a dose of FORZINITY.
* FORZINITY vial contains enough medicine for more than 1 dose.
* Do not mix FORZINITY with other medicines in the same syringe.
|alcohol=Alcohol-FORZINITY- elamipretide hydrochloride injection interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.
|brandNames=[[Forzinity]]
}}

WAYRILZ- rilzabrutinib tablet, film coated

Anum Ijaz — Mon, 24 Aug 2026 18:20:30 GMT

Created page with "{{DrugProjectFormSinglePage |authorTag={{AIJ}} |aOrAn=a |drugClass=Bruton's tyrosine kinase (BTK) inhibitor |indicationType=treatment |indication=adult patients with persistent or chronic immune thrombocytopenia (ITP) who have had an insufficient response to a previous treatment. |adverseReactions=diarrhea, nausea, headache, abdominal pain, and COVID-19. |blackBoxWarningTitle='''<span style="color:#FF0000;">TITLE</span>''' |blackBoxWarningBody=''<..."

Show changes

Sandbox:JAF MS laboratory findings

Matt Pijoan — Mon, 24 Aug 2026 15:18:58 GMT

Matt Pijoan deleted page Sandbox:JAF MS laboratory findings Author request

Sandbox

Anum Ijaz — Sun, 23 Aug 2026 19:20:49 GMT

Show changes

Tension headache prevention

Hasnain Ali — Sun, 23 Aug 2026 13:18:29 GMT

← Older revision		Revision as of 13:18, 23 August 2026
Line 2:		Line 2:
	{{Tension headache}}		{{Tension headache}}
	{{CMG}} {{AE}} {{SAI}}		{{CMG}} {{AE}} {{SAI}}


	== Overview ==		== Overview ==

User:Sophia Saad

Nehal Eid — Sat, 22 Aug 2026 20:53:37 GMT

@@ Line 1: / Line 1: @@
 __NOTOC__
-[[User:Sophia Saad|Sophia Saad]][mailto:scsaad23@yahoo.com]
+[[User:Sophia Saad|Sophia Saad]][mailto:sophia.csaad@gmail.com]
 ==Current Position==
 *'''Crisis Text Line Volunteer for https://www.crisistextline.org
@@ Line 12: / Line 12: @@
 *'''Public Health'''
 == Wikidoc contributions ==

User:Nehal Eid

Nehal Eid — Sat, 22 Aug 2026 20:22:37 GMT

← Older revision		Revision as of 20:22, 22 August 2026
Line 1:		Line 1:
	[[File:WhatsApp Image 2025-01-21 at 3.49.56 PM (2).jpg\|thumb\|Nehal Eid, M.D.]]		[[File:WhatsApp Image 2025-01-21 at 3.49.56 PM (2).jpg\|thumb\|Nehal Eid, M.D.]]
	[[User:Nehal Eid\|Nehal Eid, MD]][mailto:~~nehalelsaeed98~~@gmail.com]		[[User:Nehal Eid\|Nehal Eid, MD]][mailto:nehal.r.eid@gmail.com]

	== Education ==		== Education ==

User:Sophia Saad

Nehal Eid — Sat, 22 Aug 2026 20:21:50 GMT

← Older revision		Revision as of 20:21, 22 August 2026
(One intermediate revision by the same user not shown)
Line 1:		Line 1:
			__NOTOC__
	~~'''~~Sophia Saad ~~<br>~~		[[User:Sophia Saad\|Sophia Saad]][mailto:scsaad23@yahoo.com]
	~~'''Contact:'''~~ [mailto:scsaad23@yahoo.com]

	==Current Position==		==Current Position==
	*'''Crisis Text Line Volunteer for https://www.crisistextline.org		*'''Crisis Text Line Volunteer for https://www.crisistextline.org
	*'''Associate Editor-In Chief''' for WikiDoc.org		*'''Associate Editor-In Chief''' for WikiDoc.org

	==Interests==		==Interests==
	*'''Neurology'''		*'''Neurology'''
Line 14:		Line 11:
	*'''Interventional Cardiology'''		*'''Interventional Cardiology'''
	*'''Public Health'''		*'''Public Health'''
			== Wikidoc contributions ==

User talk:C Michael Gibson

Julinka Auta Fernandes — Sat, 22 Aug 2026 17:00:45 GMT

Request deletion of my sandbox page: new section

← Older revision		Revision as of 17:00, 22 August 2026
Line 96:		Line 96:

	I recently added [[Agronomy]] but the captcha security system would not allow the urls even when I correctly solved it. Are some urls not allowed? --[[User:Marshallsumter\|Marshallsumter]] ([[User talk:Marshallsumter\|talk]]) 03:15, 2 July 2018 (UTC)		I recently added [[Agronomy]] but the captcha security system would not allow the urls even when I correctly solved it. Are some urls not allowed? --[[User:Marshallsumter\|Marshallsumter]] ([[User talk:Marshallsumter\|talk]]) 03:15, 2 July 2018 (UTC)

			== Request deletion of my sandbox page ==



			Hello Dr. Gibson,

			I am the original author of the following two WikiDoc sandbox pages:

			* [[Sandbox:JAF_MS_laboratory_findings]]
			* [[SAndbox:_JAF_MS_ECG]]

			These were temporary work-in-progress sandbox pages. I have moved the content I need to my personal sandbox and have blanked the old pages.

			I would like to request permanent deletion of both pages under G7 (author requests deletion / author blanked).

			Thank you for your help.

			[[User:Julinka Auta Fernandes\|Julinka Auta Fernandes]] ([[User talk:Julinka Auta Fernandes\|talk]]) 17:00, 22 August 2026 (UTC)

SAndbox: JAF MS ECG

Julinka Auta Fernandes — Sat, 22 Aug 2026 15:55:11 GMT

Blanking my personal sandbox page; content moved to my personal sandbox

Show changes

User:Julinka Auta Fernandes/sandbox MS ECG

Julinka Auta Fernandes — Sat, 22 Aug 2026 15:54:24 GMT

Created page with "__NOTOC__ {{Multiple sclerosis}} {{CMG}}; {{AE}} {{Fs}} {{JAF}} ==Overview== An electrocardiogram (ECG) is '''not used to diagnose multiple sclerosis (MS)''', and there are no ECG findings that are specific or diagnostic for MS. The diagnosis of MS is established using clinical findings together with appropriate paraclinical evidence, including MRI and, when appropriate, cerebrospinal fluid (CSF) biomarkers, according to the 2024..."

New page

__NOTOC__
{{Multiple sclerosis}}
{{CMG}}; {{AE}} {{Fs}} {{JAF}}

==Overview==

An [[electrocardiogram]] ([[ECG]]) is '''not used to diagnose multiple sclerosis (MS)''', and there are no ECG findings that are specific or diagnostic for MS. The diagnosis of MS is established using clinical findings together with appropriate paraclinical evidence, including [[magnetic resonance imaging|MRI]] and, when appropriate, cerebrospinal fluid (CSF) biomarkers, according to the 2024 revisions of the McDonald criteria.<ref name="Montalban2025">{{cite journal|last1=Montalban|first1=Xavier|last2=Lebrun-Frénay|first2=Christine|last3=Oh|first3=Jiwon|last4=Arrambide|first4=Georgina|last5=Moccia|first5=Marcello|last6=Amato|first6=Maria Pia|last7=Amezcua|first7=Lilyana|last8=Banwell|first8=Brenda|last9=Bar-Or|first9=Amit|last10=Barkhof|first10=Frederik|last11=Butzkueven|first11=Helmut|last12=Ciccarelli|first12=Olga|last13=Chataway|first13=Jeremy|last14=Cohen|first14=Jeffrey A.|last15=Comi|first15=Giancarlo|last16=Correale|first16=Jorge|last17=Deisenhammer|first17=Florian|last18=Filippi|first18=Massimo|last19=Fiol|first19=Julie|last20=Freedman|first20=Mark S.|last21=Fujihara|first21=Kazuo|last22=Granziera|first22=Cristina|last23=Green|first23=Ari J.|last24=Hartung|first24=Hans-Peter|last25=Hellwig|first25=Kerstin|last26=Kappos|first26=Ludwig|last27=Kimbrough|first27=Dorlan|last28=Killestein|first28=Joep|last29=Lublin|first29=Fred|last30=Marignier|first30=Romain|last31=Marrie|first31=Ruth Ann|last32=Miller|first32=Aaron|last33=Otero-Romero|first33=Susana|last34=Ontaneda|first34=Daniel|last35=Ramanathan|first35=Sudarshini|last36=Reich|first36=Daniel|last37=Rocca|first37=Maria A.|last38=Rovira|first38=Àlex|last39=Saidha|first39=Shiv|last40=Salter|first40=Amber|last41=Sastre-Garriga|first41=Jaume|last42=Saylor|first42=Deanna|last43=Solomon|first43=Andrew J.|last44=Sormani|first44=Maria Pia|last45=Stankoff|first45=Bruno|last46=Tintoré|first46=Mar|last47=Tremlett|first47=Helen|last48=Van der Walt|first48=Anneke|last49=Viswanathan|first49=Shanthi|last50=Wiendl|first50=Heinz|last51=Wildemann|first51=Brigitte|last52=Yamout|first52=Bassem|last53=Zaratin|first53=Paola|last54=Calabresi|first54=Peter A.|last55=Coetzee|first55=Timothy|last56=Thompson|first56=Alan J.|title=Diagnosis of multiple sclerosis: 2024 revisions of the McDonald criteria|journal=The Lancet Neurology|volume=24|issue=10|year=2025|pages=850–865|doi=10.1016/S1474-4422(25)00270-4|pmid=40975101}}</ref>

The principal roles of ECG in a person with MS are evaluation of suspected cardiovascular disease or arrhythmia, assessment of selected cardiovascular autonomic abnormalities, and cardiac safety monitoring when initiating certain disease-modifying therapies, particularly [[sphingosine-1-phosphate receptor modulator]]s.

==Electrocardiogram==

===ECG and the diagnosis of multiple sclerosis===

An ECG does '''not''' establish or exclude a diagnosis of MS. The 2024 McDonald criteria do not include ECG findings as a diagnostic criterion.<ref name="Montalban2025"/>

MRI has a central role in the diagnosis of MS. The 2024 MAGNIMS-CMSC-NAIMS consensus recommendations address MRI assessment of the brain and spinal cord and incorporate the [[optic nerve]] as a fifth anatomical location, in addition to the periventricular, juxtacortical or cortical, infratentorial, and spinal cord regions. The consensus also addresses susceptibility-sensitive MRI markers, including the central vein sign and paramagnetic rim lesions, when appropriate.<ref name="Barkhof2025">{{cite journal|last1=Barkhof|first1=Frederik|last2=Reich|first2=Daniel S.|last3=Oh|first3=Jiwon|last4=Rocca|first4=Maria A.|last5=Li|first5=Dong-Kyu B.|last6=Sati|first6=Partha|last7=Azevedo|first7=Christina J.|last8=Bagnato|first8=Francesco|last9=Calabresi|first9=Peter A.|last10=Ciccarelli|first10=Olga|last11=Dwyer|first11=Michael G.|last12=DeLuca|first12=Gian|last13=Filippi|first13=Massimo|last14=Gauthier|first14=Susan|last15=Kappos|first15=Ludwig|last16=Newsome|first16=Stephen D.|last17=Ontaneda|first17=Daniel|last18=Rovira|first18=Àlex|title=2024 MAGNIMS-CMSC-NAIMS consensus recommendations on the use of MRI for the diagnosis of multiple sclerosis|journal=The Lancet Neurology|volume=24|issue=10|year=2025|pages=866–879|doi=10.1016/S1474-4422(25)00304-7|pmid=40975102}}</ref>

Therefore, ECG abnormalities such as [[atrial fibrillation]], ventricular arrhythmias, [[Long PR interval|PR-interval]] abnormalities, [[U wave]]s, [[Q wave]]s, bundle branch block, or other nonspecific ECG abnormalities should '''not''' be described as findings suggestive or diagnostic of MS. Such findings require evaluation according to standard cardiovascular practice and the clinical context.

===Cardiovascular autonomic dysfunction===

MS may be associated with abnormalities of cardiovascular autonomic regulation. A systematic review and meta-analysis of 43 studies involving 1,518 people with MS and 1,062 healthy controls found differences in several measures of heart rate variability (HRV), including reduced RMSSD, pNN50, high-frequency power, and low-frequency power in people with MS compared with healthy controls.<ref name="Mirmosayyeb2026">{{cite journal|last1=Mirmosayyeb|first1=Omid|last2=Yazdan Panah|first2=Mohammad|last3=Alinejadfard|first3=Mohammadreza|last4=Oraee|first4=Soroush|last5=Vaheb|first5=Saeed|last6=Shaygannejad|first6=Vahid|title=Heart rate variability in people with multiple sclerosis: A systematic review and meta-analysis|journal=Acta Neurologica Belgica|volume=126|issue=1|year=2026|pages=67–83|doi=10.1007/s13760-025-02829-5|pmid=40587005}}</ref>

Other systematic reviews have similarly reported abnormalities of cardiac autonomic regulation in MS, particularly involving measures of heart-rate variability, although studies have used heterogeneous methods.<ref name="Findling2020">{{cite journal|last1=Findling|first1=Oliver|last2=Hauer|first2=Lisa|last3=Pezawas|first3=Thomas|last4=Rommer|first4=Patrick S.|last5=Struhal|first5=Wolfgang|last6=Sellner|first6=Johannes|title=Cardiac Autonomic Dysfunction in Multiple Sclerosis: A Systematic Review of Current Knowledge and Impact of Immunotherapies|journal=Journal of Clinical Medicine|volume=9|issue=2|year=2020|pages=335|doi=10.3390/jcm9020335|pmid=31991711}}</ref>

ECG-derived HRV assessment may provide information about autonomic cardiovascular regulation in selected patients or research settings. However, HRV abnormalities are '''not specific for MS and are not diagnostic criteria for MS'''.<ref name="Mirmosayyeb2026"/><ref name="Findling2020"/>

When cardiovascular autonomic dysfunction is clinically suspected, assessment may include orthostatic heart rate and blood-pressure measurements and, when appropriate, additional autonomic testing. ECG-based HRV assessment should be selected according to the clinical question and is not routinely required in every patient with MS.

===ECG and sphingosine-1-phosphate receptor modulators===

ECG has an important role in the cardiac safety assessment of selected [[sphingosine-1-phosphate receptor modulator]]s used for MS. These medications can cause reductions in heart rate and slowing of atrioventricular conduction, particularly during treatment initiation. Cardiac assessment and monitoring requirements differ among individual agents because of differences in dose-titration regimens and cardiac safety profiles.<ref name="GilenyaFDA2025">{{cite web|title=GILENYA (fingolimod) prescribing information|publisher=U.S. Food and Drug Administration|year=2025|url=https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/022527s044lbl.pdf}}</ref><ref name="MayzentEMA">{{cite web|title=MAYZENT (siponimod) product information|publisher=European Medicines Agency|url=https://www.ema.europa.eu/en/medicines/human/EPAR/mayzent}}</ref><ref name="ZeposiaFDA">{{cite web|title=ZEPOSIA (ozanimod) prescribing information|publisher=Bristol Myers Squibb|url=https://packageinserts.bms.com/pi/pi_zeposia.pdf}}</ref><ref name="PonvoryEMA">{{cite web|title=PONVORY (ponesimod) product information|publisher=European Medicines Agency|url=https://www.ema.europa.eu/en/documents/product-information/ponvory-epar-product-information_en.pdf}}</ref>

Before initiating an S1P receptor modulator, cardiovascular history, baseline heart rate, relevant medications, and potential conduction or rhythm abnormalities should be assessed according to the prescribing information for the individual drug. Cardiology consultation should be considered when clinically significant pre-existing cardiovascular disease or conduction abnormalities are present.

====Fingolimod====

Before initiating [[fingolimod]], an ECG should be obtained as part of first-dose cardiac assessment. Initiation of fingolimod can cause bradycardia and atrioventricular conduction abnormalities.<ref name="GilenyaFDA2025"/>

Patients initiating fingolimod should be observed for at least 6 hours after the first dose for signs and symptoms of bradycardia, with hourly pulse and blood-pressure measurements. ECG should be obtained before dosing and at the end of the observation period.<ref name="GilenyaFDA2025"/>

Additional monitoring should be provided if clinically important bradycardia or conduction abnormalities occur. Overnight continuous ECG monitoring is required in specified higher-risk circumstances, including certain pre-existing cardiovascular or cerebrovascular conditions, prolonged QTc or increased risk of QT prolongation, and concomitant treatment with drugs that slow heart rate or atrioventricular conduction.<ref name="GilenyaFDA2025"/>

First-dose monitoring is also required when fingolimod is restarted after specified treatment interruptions because effects on heart rate and atrioventricular conduction may recur after reinitiation.<ref name="GilenyaFDA2025"/>

====Siponimod====

Before initiating [[siponimod]], cardiovascular assessment should include consideration of baseline ECG findings and pre-existing conduction abnormalities. Siponimod can cause bradycardia and atrioventricular conduction delays, particularly during treatment initiation.<ref name="MayzentEMA"/>

Patients with certain pre-existing cardiac conditions, including sinus bradycardia with a heart rate below 55 beats per minute, a history of first- or second-degree Mobitz type I atrioventricular block, myocardial infarction, or heart failure, should be observed for 6 hours after the first dose for signs and symptoms of bradycardia. In these patients, ECG should be obtained before dosing and at the end of the observation period.<ref name="MayzentEMA"/>

If clinically significant bradyarrhythmia or conduction abnormalities occur, further evaluation and monitoring should be performed according to the product information and clinical circumstances.<ref name="MayzentEMA"/>

====Ozanimod====

[[Ozanimod]] is initiated using a dose-titration regimen that attenuates the magnitude of the initial heart-rate reduction.<ref name="ZeposiaFDA"/>

Before starting ozanimod, patients should be assessed for relevant cardiovascular disease and conduction abnormalities. Ozanimod can cause a transient decrease in heart rate and atrioventricular conduction delays, particularly during treatment initiation.<ref name="ZeposiaFDA"/>

Routine prolonged first-dose cardiac monitoring is '''not universally required''' with the recommended ozanimod titration regimen. Cardiology consultation should be considered in patients with relevant conduction abnormalities or concomitant use of drugs that decrease heart rate or atrioventricular conduction.<ref name="ZeposiaFDA"/>

====Ponesimod====

Before initiating [[ponesimod]], an ECG should be obtained to identify pre-existing conduction abnormalities. Ponesimod is initiated using a dose-titration regimen to reduce cardiac effects during treatment initiation.<ref name="PonvoryEMA"/>

First-dose 4-hour monitoring is recommended for patients with sinus bradycardia with a heart rate below 55 beats per minute, first- or second-degree Mobitz type I atrioventricular block, or a history of myocardial infarction or heart failure occurring more than 6 months before treatment initiation and in stable condition.<ref name="PonvoryEMA"/>

For patients requiring first-dose monitoring, the patient should be monitored for 4 hours with at least hourly pulse and blood-pressure measurements. ECG should be obtained at the end of the observation period.<ref name="PonvoryEMA"/>

Additional monitoring is required if clinically significant bradycardia or conduction abnormalities occur, according to the product information.<ref name="PonvoryEMA"/>

===ECG abnormalities in patients with multiple sclerosis===

ECG abnormalities in a patient with MS should not be considered characteristic ECG manifestations of MS.

Potential abnormalities may include:

*[[Sinus bradycardia]] or other heart-rate abnormalities, particularly during initiation of S1P receptor modulator therapy.
*[[Atrioventricular block]] or PR-interval prolongation, particularly during initiation of S1P receptor modulator therapy.
*[[QT interval|QTc prolongation]], particularly in the presence of pre-existing QT prolongation, electrolyte abnormalities, concomitant QT-prolonging medications, or specific drug-related risks.
*[[Atrial fibrillation]] or other atrial arrhythmias.
*Ventricular arrhythmias.
*Bundle branch block or other conduction abnormalities.

These findings are '''nonspecific''' and should be evaluated according to standard cardiovascular practice. Their presence does not establish a diagnosis of MS.<ref name="GilenyaFDA2025"/><ref name="MayzentEMA"/><ref name="ZeposiaFDA"/><ref name="PonvoryEMA"/>

The previously reported association of individual ECG findings such as atrial fibrillation, ventricular arrhythmia, Q waves, U waves, or isolated PR-interval changes with MS should not be interpreted as evidence that these findings are diagnostic of MS.

===Ambulatory ECG monitoring===

Ambulatory ECG monitoring, including Holter monitoring or longer-duration rhythm monitoring, is '''not routinely indicated solely because a patient has MS'''.

Ambulatory ECG monitoring may be appropriate when symptoms or clinical findings suggest intermittent arrhythmia, including unexplained [[palpitations]], [[syncope]], [[presyncope]], episodic bradycardia, unexplained tachycardia, or other suspected intermittent rhythm disturbances.

The choice and duration of ambulatory monitoring should be based on symptom frequency and standard cardiovascular practice.

===ECG in patients with cardiovascular symptoms===

Patients with MS should undergo cardiovascular evaluation according to their symptoms and individual cardiovascular risk factors. A 12-lead ECG is appropriate when clinically indicated, including evaluation of chest pain, suspected ischemia, palpitations, syncope or presyncope, unexplained dyspnea, suspected arrhythmia, or suspected medication-related cardiac effects.

These cardiovascular indications should be distinguished from MS diagnosis: ECG is not a routine diagnostic investigation for MS.

===Interpretation of an abnormal ECG===

An abnormal ECG in a patient with MS should not automatically be attributed to MS. The differential diagnosis should include primary cardiac disease, myocardial ischemia, electrolyte abnormalities, medication effects, autonomic dysfunction, structural heart disease, conduction-system disease, and primary cardiac arrhythmias.

ECG findings should be interpreted together with the patient's symptoms, cardiovascular history, medication list, physical examination, and relevant laboratory and imaging findings. Additional evaluation, such as echocardiography or ambulatory rhythm monitoring, should be performed when clinically indicated.

===Key clinical points===

*'''ECG is not a diagnostic test for multiple sclerosis.'''
*'''There are no ECG findings that are specific or diagnostic for MS.'''
*The 2024 McDonald criteria do not include ECG as a diagnostic criterion.<ref name="Montalban2025"/>
*MRI and appropriate CSF/biomarker assessment, together with clinical findings, are central to modern MS diagnosis.<ref name="Montalban2025"/><ref name="Barkhof2025"/>
*MS may be associated with cardiovascular autonomic dysfunction and altered HRV, but these findings are not specific for MS and are not diagnostic criteria.<ref name="Mirmosayyeb2026"/><ref name="Findling2020"/>
*ECG may be useful when cardiovascular symptoms, suspected arrhythmia, or selected autonomic dysfunction are present.
*ECG has an important medication-safety role with S1P receptor modulators, but monitoring requirements differ among fingolimod, siponimod, ozanimod, and ponesimod.
*Fingolimod requires pre-dose and post-observation ECG assessment with at least 6 hours of first-dose observation.<ref name="GilenyaFDA2025"/>
*Siponimod requires cardiovascular assessment and 6-hour first-dose monitoring with ECG in patients with specified pre-existing cardiac conditions.<ref name="MayzentEMA"/>
*Ozanimod uses dose titration, and routine prolonged first-dose cardiac monitoring is not universally required with the recommended titration regimen.<ref name="ZeposiaFDA"/>
*Ponesimod requires baseline cardiovascular assessment, with 4-hour first-dose monitoring for patients with specified pre-existing cardiac conditions.<ref name="PonvoryEMA"/>
*Ambulatory ECG monitoring is reserved for clinically indicated evaluation of suspected intermittent arrhythmia and is not routinely required solely because of MS.

==References==

{{Reflist|2}}

{{WH}}
{{WS}}

User:Julinka Auta Fernandes/sandbox MS laboratory findings

Julinka Auta Fernandes — Sat, 22 Aug 2026 15:27:31 GMT

Created page with "__NOTOC__ {{Template:Multiple sclerosis}} {{CMG}}; {{AE}} {{Fs}} {{JAF}} ==Overview== Cerebrospinal fluid (CSF) analysis provides laboratory evidence that can support the diagnosis of multiple sclerosis (MS), contribute to the 2024 McDonald diagnostic criteria, and assist in excluding alternative diagnoses. Evidence of intrathecal immunoglobulin synthesis is demonstrated by either CSF-restricted oligoclonal bands (OCBs) or the kappa free light..."

New page

__NOTOC__
{{Template:Multiple sclerosis}}
{{CMG}}; {{AE}} {{Fs}} {{JAF}}

==Overview==
Cerebrospinal fluid ([[Cerebrospinal fluid|CSF]]) analysis provides laboratory evidence that can support the diagnosis of multiple sclerosis (MS), contribute to the 2024 McDonald diagnostic criteria, and assist in excluding alternative diagnoses. Evidence of intrathecal immunoglobulin synthesis is demonstrated by either CSF-restricted oligoclonal bands (OCBs) or the [[kappa free light chain]] (κ-FLC) index. These findings are not specific for MS and must be interpreted together with the clinical and MRI findings.<ref name="pmid40975101">{{cite journal |vauthors=Montalban X, Lebrun-Frenay C, Oh J, et al. |title=Diagnosis of multiple sclerosis: 2024 revisions of the McDonald criteria |journal=Lancet Neurol. |volume=24 |issue=10 |pages=850–865 |date=October 2025 |pmid=40975101 |doi=10.1016/S1474-4422(25)00270-4 |url=https://pubmed.ncbi.nlm.nih.gov/40975101/}}</ref><ref name="pmid40967951">{{cite journal |vauthors=Deisenhammer F, Hegen H, Arrambide G, Banwell BL, Coetzee T, Gnanapavan S, Montalban X, Tumani H, Willrich MA, Freedman MS |title=Positive cerebrospinal fluid in the 2024 McDonald criteria for multiple sclerosis |journal=eBioMedicine |volume=120 |pages=105905 |date=October 2025 |pmid=40967951 |doi=10.1016/j.ebiom.2025.105905 |url=https://pubmed.ncbi.nlm.nih.gov/40967951/}}</ref>

==Laboratory Findings==

==== CSF analysis: ====
* [[CSF]] analysis is useful in patients with suspected [[multiple sclerosis]] when the clinical or MRI findings do not by themselves establish the diagnosis, when CSF evidence is required by the 2024 McDonald criteria, or when an alternative diagnosis must be excluded. CSF analysis may not be necessary when the clinical presentation and MRI findings are characteristic and already fulfill the diagnostic criteria, provided there are no features suggesting a mimic.<ref name="pmid40975101"/><ref name="pmid36527368">{{cite journal |vauthors=Hegen H, Arrambide G, Gnanapavan S, Kaplan B, Khalil M, Saadeh R, Teunissen C, Tumani H, Villar LM, Willrich MAV, Zetterberg H, Deisenhammer F |title=Cerebrospinal fluid kappa free light chains for the diagnosis of multiple sclerosis: a consensus statement |journal=Mult. Scler. |volume=29 |issue=2 |pages=182–195 |date=February 2023 |pmid=36527368 |doi=10.1177/13524585221134217 |url=https://pubmed.ncbi.nlm.nih.gov/36527368/}}</ref>

* Routine CSF evaluation in suspected MS should consider [[white blood cell]] count, differential cell profile, [[albumin quotient]], and assessment of intrathecal immunoglobulin synthesis. Additional CSF studies, including glucose, lactate, microbiological testing, cytology, or other targeted investigations, should be guided by the clinical presentation and suspected alternative diagnoses.<ref name="pmid36527368"/>

* CSF-restricted oligoclonal bands (OCBs) are evidence of intrathecal [[IgG]] synthesis and remain an established laboratory biomarker in MS. OCBs are '''not specific for MS''' and may also occur in other inflammatory, infectious, autoimmune, and neoplastic disorders.<ref name="pmid40975101"/><ref name="pmid36527368"/>

* OCB patterns 2 and 3 demonstrate intrathecal IgG synthesis. A positive OCB result generally requires '''at least 2 bands in CSF that are absent from the paired serum sample'''. OCB testing is conventionally performed by [[isoelectric focusing]] followed by IgG-specific immunodetection using paired CSF and serum samples.<ref name="pmid36527368"/><ref name="pmid40967951"/>

* OCBs are detected in more than 90% of patients with clinically definite MS, but they may also occur in important mimics. OCBs are detected in approximately 25% or fewer of patients with [[neuromyelitis optica spectrum disorder]] and in approximately 10% of patients with [[MOG antibody-associated disease]]. Therefore, a positive OCB result should not be regarded as diagnostic of MS in isolation.<ref name="pmid40967951"/>

* The [[kappa free light chain]] (κ-FLC) index is accepted as an alternative to OCBs for demonstrating intrathecal immunoglobulin synthesis under the 2024 McDonald criteria. A κ-FLC index of '''≥6.1''' is the recommended consensus decision threshold. The index should be calculated from paired CSF and serum κ-FLC and albumin measurements, and each laboratory should verify the cutoff for its validated assay.<ref name="pmid40967951"/>

* κ-FLC has diagnostic performance comparable with OCB. The 2025 consensus reported equivalent diagnostic accuracy at the 95% confidence level, with approximately 90% concordance between the two methods. In uncommon discordant cases, measurement of both κ-FLC and OCB may be considered.<ref name="pmid40967951"/>

* Validated [[turbidimetric]] or [[nephelometric]] assays should be used for κ-FLC testing. External proficiency-testing programs are available, and laboratories should use assays validated for CSF and serum and perform appropriate local verification before clinical implementation.<ref name="pmid40967951"/><ref name="pmid36527368"/>

* Higher κ-FLC index values may have prognostic associations with increased disease activity; however, this prognostic application should be distinguished from its established diagnostic role in demonstrating intrathecal immunoglobulin synthesis.<ref name="pmid40967951"/>

* The [[IgG index]] is a quantitative measure of intrathecal IgG synthesis but has substantially lower diagnostic sensitivity than OCBs and is '''no longer recommended as the quantitative alternative to OCB''' for demonstrating intrathecal immunoglobulin synthesis. κ-FLC is the preferred quantitative alternative.<ref name="pmid36527368"/><ref name="pmid40967951"/>

* A negative OCB or κ-FLC result does '''not''' by itself exclude MS. Conversely, a positive OCB or κ-FLC result does not by itself establish MS. Laboratory findings must be interpreted together with the clinical presentation and MRI findings, and alternative diagnoses should be appropriately excluded.<ref name="pmid40975101"/><ref name="pmid40967951"/>

* CSF findings may assist in excluding alternative diagnoses that can mimic MS, including [[central nervous system infection]], [[neuromyelitis optica spectrum disorder]], [[MOG antibody-associated disease]], [[vasculitis]], other autoimmune or inflammatory disorders, and [[neoplastic disease]]. Additional CSF and serum investigations should be selected according to the clinical context and relevant diagnostic red flags.<ref name="pmid36527368"/><ref name="pmid40975101"/>

* The 2024 McDonald criteria and CSF consensus recommendations apply to pediatric and adult patients with both relapsing and progressive-onset MS. CSF findings should therefore be interpreted within the same overall diagnostic framework in these populations.<ref name="pmid40975101"/><ref name="pmid40967951"/>

* [[Neurofilament light chain]] (NfL) is '''not recommended as a diagnostic biomarker''' for MS. CSF and blood/serum NfL may have prognostic and disease-monitoring applications, including assessment of inflammatory activity, new MRI lesions, treatment response, and risk of progression, but NfL should not be used as a substitute for OCB or κ-FLC when diagnostic intrathecal immunoglobulin evidence is required.<ref name="pmid40967951"/><ref name="pmid41015047">{{cite journal |vauthors=Chitnis T, Magliozzi R, Abdelhak A, Kuhle J, Leppert D, Bielekova B |title=Blood and CSF biomarkers for multiple sclerosis: emerging clinical applications |journal=Lancet Neurol. |volume=24 |issue=12 |pages=1066–1078 |date=December 2025 |pmid=41015047 |doi=10.1016/S1474-4422(25)00249-2 |url=https://pubmed.ncbi.nlm.nih.gov/41015047/}}</ref>

* [[Glial fibrillary acidic protein]] (GFAP) is an emerging biomarker of astrocytic injury and is associated particularly with progressive forms of MS and progression independent of relapse activity. GFAP may have prognostic and disease-monitoring applications but is '''not an established diagnostic biomarker''' under the 2024 McDonald criteria.<ref name="pmid41015047"/>

* [[Chitinase-3-like protein 1]] (CHI3L1) is an emerging biomarker associated with progression independent of relapse activity and selected MRI lesion characteristics. CHI3L1 is '''not an established diagnostic biomarker''' for MS.<ref name="pmid41015047"/>

* [[CXCL13]] and other proposed fluid biomarkers remain emerging or investigational biomarkers. Their potential prognostic or disease-monitoring roles are being studied, but they are '''not established diagnostic criteria''' for MS and should not replace OCB or κ-FLC.<ref name="pmid41015047"/>

* The 2024 McDonald criteria should be applied when the clinical likelihood of MS is sufficiently high; CSF biomarkers should not be used in isolation to make an MS diagnosis. Careful clinical assessment, MRI interpretation, and exclusion of a better alternative diagnosis remain essential.<ref name="pmid40967951"/>

==References==
{{reflist|2}}
{{WH}}
{{WS}}

[[Category:Neurology]]
[[Category:Orthopedics]]
[[Category:Rheumatology]]

Influenza resident survival guide

Mohammed Braizat — Sat, 22 Aug 2026 15:08:32 GMT

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Influenza cost-effectiveness of therapy

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User:Julinka Auta Fernandes/sandbox MS CT

Julinka Auta Fernandes — Sat, 22 Aug 2026 14:33:38 GMT

← Older revision		Revision as of 14:33, 22 August 2026
(2 intermediate revisions by the same user not shown)
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	~~NOTOC~~
	{{Multiple sclerosis}}		{{Multiple sclerosis}}
	{{CMG}}; {{AE}} {{Fs}}		{{CMG}}; {{AE}} {{Fs}} {{JAF}}

	==Overview==		==Overview==
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	CT may demonstrate nonspecific abnormalities such as [[brain atrophy]], white-matter hypoattenuation, or, less commonly, areas of [[contrast]] enhancement. These findings are not specific for MS and cannot establish the diagnosis.<ref name="ACR"/>		CT may demonstrate nonspecific abnormalities such as [[brain atrophy]], white-matter hypoattenuation, or, less commonly, areas of [[contrast]] enhancement. These findings are not specific for MS and cannot establish the diagnosis.<ref name="ACR"/>

	The 2024 [[McDonald criteria]] and the 2024 MAGNIMS-CMSC-NAIMS consensus recommendations emphasize MRI as the principal imaging modality for the diagnosis and evaluation of MS.<ref name="McDonald2024">{{cite journal \|vauthors=Montalban X, Oh J, Stangel M, et al. \|title=Diagnosis of multiple sclerosis: 2024 revisions of the McDonald criteria \|journal=Lancet Neurology \|volume=24 \|issue=10 \|pages=850–865 \|date=October 2025 \|pmid=40975101 \|doi=10.1016/S1474-4422(25)00270-4 \|url=}}</ref><ref name="MAGNIMS2024">{{cite journal \|vauthors=Barkhof F, Reich DS, Oh J, et al. \|title=2024 MAGNIMS-CMSC-NAIMS consensus recommendations on the use of MRI for the diagnosis of multiple sclerosis \|journal=Lancet Neurology \|volume=24 \|issue=10 \|pages=866–879 \|date=October 2025 \|pmid=40975102 \|doi=10.1016/S1474-4422(25)00304-7 \|url=}}</ref>		The 2024 McDonald criteria and the 2024 MAGNIMS-CMSC-NAIMS consensus recommendations emphasize MRI as the principal imaging modality for the diagnosis and evaluation of MS.<ref name="McDonald2024">{{cite journal \|vauthors=Montalban X, Oh J, Stangel M, et al. \|title=Diagnosis of multiple sclerosis: 2024 revisions of the McDonald criteria \|journal=Lancet Neurology \|volume=24 \|issue=10 \|pages=850–865 \|date=October 2025 \|pmid=40975101 \|doi=10.1016/S1474-4422(25)00270-4 \|url=}}</ref><ref name="MAGNIMS2024">{{cite journal \|vauthors=Barkhof F, Reich DS, Oh J, et al. \|title=2024 MAGNIMS-CMSC-NAIMS consensus recommendations on the use of MRI for the diagnosis of multiple sclerosis \|journal=Lancet Neurology \|volume=24 \|issue=10 \|pages=866–879 \|date=October 2025 \|pmid=40975102 \|doi=10.1016/S1474-4422(25)00304-7 \|url=}}</ref>

	==CT scan==		==CT scan==

User:Julinka Auta Fernandes/sandbox MS CT

Julinka Auta Fernandes — Sat, 22 Aug 2026 14:27:38 GMT

Created page with "**NOTOC** {{Multiple sclerosis}} {{CMG}}; {{AE}} {{Fs}} ==Overview== CT scan has a limited and nonspecific role in the evaluation of suspected multiple sclerosis (MS). Conventional CT is not the preferred imaging modality for the diagnosis or routine monitoring of MS. Current American College of Radiology (ACR) Appropriateness Criteria support magnetic resonance imaging (MRI) rather than CT for initial imaging when central nervous system demyelinating disea..."

New page

**NOTOC**
{{Multiple sclerosis}}
{{CMG}}; {{AE}} {{Fs}}

==Overview==

[[CT scan]] has a limited and nonspecific role in the evaluation of suspected [[multiple sclerosis]] (MS). Conventional CT is not the preferred imaging modality for the diagnosis or routine monitoring of MS. Current American College of Radiology (ACR) Appropriateness Criteria support [[magnetic resonance imaging]] (MRI) rather than CT for initial imaging when central nervous system demyelinating disease is suspected.<ref name="ACR">{{cite web |title=ACR Appropriateness Criteria®: Demyelinating Diseases |publisher=American College of Radiology |url=https://acsearch.acr.org/docs/3197165/Narrative}}</ref>

CT may demonstrate nonspecific abnormalities such as [[brain atrophy]], white-matter hypoattenuation, or, less commonly, areas of [[contrast]] enhancement. These findings are not specific for MS and cannot establish the diagnosis.<ref name="ACR"/>

The 2024 [[McDonald criteria]] and the 2024 MAGNIMS-CMSC-NAIMS consensus recommendations emphasize MRI as the principal imaging modality for the diagnosis and evaluation of MS.<ref name="McDonald2024">{{cite journal |vauthors=Montalban X, Oh J, Stangel M, et al. |title=Diagnosis of multiple sclerosis: 2024 revisions of the McDonald criteria |journal=Lancet Neurology |volume=24 |issue=10 |pages=850–865 |date=October 2025 |pmid=40975101 |doi=10.1016/S1474-4422(25)00270-4 |url=}}</ref><ref name="MAGNIMS2024">{{cite journal |vauthors=Barkhof F, Reich DS, Oh J, et al. |title=2024 MAGNIMS-CMSC-NAIMS consensus recommendations on the use of MRI for the diagnosis of multiple sclerosis |journal=Lancet Neurology |volume=24 |issue=10 |pages=866–879 |date=October 2025 |pmid=40975102 |doi=10.1016/S1474-4422(25)00304-7 |url=}}</ref>

==CT scan==

[[CT scan]] is not recommended as the primary imaging test for the diagnosis of MS when MRI is available. In the current ACR Appropriateness Criteria for suspected central nervous system demyelinating disease, CT examinations are generally rated ''Usually Not Appropriate'' for initial evaluation, whereas MRI is the preferred imaging modality.<ref name="ACR"/>

Findings that may be seen on CT in patients with MS include:

* [[Brain atrophy]], which is nonspecific and may occur in established MS
* Areas of white-matter hypoattenuation or other nonspecific abnormalities
* Occasional [[Contrast medium|contrast]] enhancement associated with disruption of the [[blood brain barrier]]

These CT findings are neither sufficiently sensitive nor specific to diagnose MS. Contrast enhancement on CT is nonspecific and should not be regarded as a substitute for MRI assessment of inflammatory disease activity or for application of the current MS diagnostic criteria.<ref name="ACR"/><ref name="McDonald2024"/>

The 2024 McDonald criteria incorporate clinical and paraclinical evidence and recognize five anatomical regions relevant to dissemination in space: periventricular, cortical or juxtacortical, infratentorial, spinal cord, and optic nerve. These diagnostic concepts are principally evaluated using MRI and cannot be adequately assessed with conventional CT.<ref name="McDonald2024"/>

The 2024 MAGNIMS-CMSC-NAIMS consensus recommendations describe the expanded role of MRI in the diagnosis of MS, including standardized MRI acquisition and interpretation and the use of additional MRI markers such as the [[central vein sign]] and [[paramagnetic rim lesions]] when appropriate.<ref name="MAGNIMS2024"/>

CT may still be appropriate in selected clinical circumstances when the purpose of imaging is to evaluate an alternative diagnosis or an acute complication rather than to establish or monitor MS. This may include selected emergency presentations or situations in which MRI is unavailable, contraindicated, or cannot be performed promptly. The indication for CT should be based on the specific clinical question.<ref name="ACR"/>

Routine CT is not recommended for monitoring MS disease activity. MRI is the preferred modality for follow-up assessment of MS and for detection of new or enlarging lesions and other imaging evidence of disease activity.<ref name="ACR"/><ref name="MAGNIMS2024"/>

The previously described ''double delayed high dose CT'' (DDHD CT) technique is not included in current MS diagnostic criteria or contemporary American or European recommendations for MS imaging. The historical use of DDHD CT to demonstrate enhancing lesions or assess changes following [[steroid]] therapy should therefore not be used to guide current diagnosis or management of MS.

==References==
{{Reflist|2}}

{{WH}}
{{WS}}
[[Category: (Name of the system)]]

Influenza future or investigational therapies

Mohammed Braizat — Sat, 22 Aug 2026 14:02:32 GMT

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SAndbox: JAF MS ECG

Julinka Auta Fernandes — Sat, 22 Aug 2026 09:46:55 GMT

← Older revision		Revision as of 09:46, 22 August 2026
(One intermediate revision by the same user not shown)
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	__NOTOC__		__NOTOC__
	{{Multiple sclerosis}}		{{Multiple sclerosis}}
	{{CMG}}; {{AE}} {{Fs}}		{{CMG}}; {{AE}} {{Fs}} {{JAF}}

	==Overview==		==Overview==

	An [[electrocardiogram]] ([[ECG]]) is '''not used to diagnose multiple sclerosis (MS)''', and there are no ECG findings that are specific or diagnostic for MS. The diagnosis of MS is established using clinical findings together with appropriate paraclinical evidence, including [[magnetic resonance imaging\|MRI]] and, when appropriate, cerebrospinal fluid (CSF) biomarkers, according to the 2024 revisions of the McDonald criteria.<ref name="Montalban2025">{{cite journal\|last1=Montalban\|first1=X.\|last2=Lebrun-Frénay\|first2=C.\|last3=Oh\|first3=J.\|last4=Arrambide\|first4=G.\|last5=Moccia\|first5=M.\|last6=Amato\|first6=~~M. P.~~\|last7=Amezcua\|first7=L.\|last8=Banwell\|first8=B.\|last9=Bar-Or\|first9=A.\|last10=Barkhof\|first10=F.\|last11=Butzkueven\|first11=H.\|last12=Ciccarelli\|first12=O.\|last13=Chataway\|first13=J.\|last14=Cohen\|first14=J. A.\|last15=Comi\|first15=G.\|last16=~~Deisenhammer~~\|first16=F.\|last17=~~Filippi~~\|first17=M.\|last18=~~Green~~\|first18=~~A. J.~~\|last19=~~Kappos~~\|first19=L.\|last20=~~Miller~~\|first20=A.\|last21=~~Rocca~~\|first21=~~M. A.~~\|last22=~~Ramanathan~~\|first22=S.\|last23=~~Reich~~\|first23=~~D. S~~.\|last24=~~Rovira~~\|first24=À.\|last25=~~Thompson~~\|first25=A. J.\|title=Diagnosis of multiple sclerosis: 2024 revisions of the McDonald criteria\|journal=The Lancet Neurology\|volume=24\|issue=10\|year=2025\|pages=850–865\|doi=10.1016/S1474-4422(25)00270-4\|pmid=40975101}}</ref>		An [[electrocardiogram]] ([[ECG]]) is '''not used to diagnose multiple sclerosis (MS)''', and there are no ECG findings that are specific or diagnostic for MS. The diagnosis of MS is established using clinical findings together with appropriate paraclinical evidence, including [[magnetic resonance imaging\|MRI]] and, when appropriate, cerebrospinal fluid (CSF) biomarkers, according to the 2024 revisions of the McDonald criteria.<ref name="Montalban2025">{{cite journal\|last1=Montalban\|first1=Xavier\|last2=Lebrun-Frénay\|first2=Christine\|last3=Oh\|first3=Jiwon\|last4=Arrambide\|first4=Georgina\|last5=Moccia\|first5=Marcello\|last6=Amato\|first6=Maria Pia\|last7=Amezcua\|first7=Lilyana\|last8=Banwell\|first8=Brenda\|last9=Bar-Or\|first9=Amit\|last10=Barkhof\|first10=Frederik\|last11=Butzkueven\|first11=Helmut\|last12=Ciccarelli\|first12=Olga\|last13=Chataway\|first13=Jeremy\|last14=Cohen\|first14=Jeffrey A.\|last15=Comi\|first15=Giancarlo\|last16=Correale\|first16=Jorge\|last17=Deisenhammer\|first17=Florian\|last18=Filippi\|first18=Massimo\|last19=Fiol\|first19=Julie\|last20=Freedman\|first20=Mark S.\|last21=Fujihara\|first21=Kazuo\|last22=Granziera\|first22=Cristina\|last23=Green\|first23=Ari J.\|last24=Hartung\|first24=Hans-Peter\|last25=Hellwig\|first25=Kerstin\|last26=Kappos\|first26=Ludwig\|last27=Kimbrough\|first27=Dorlan\|last28=Killestein\|first28=Joep\|last29=Lublin\|first29=Fred\|last30=Marignier\|first30=Romain\|last31=Marrie\|first31=Ruth Ann\|last32=Miller\|first32=Aaron\|last33=Otero-Romero\|first33=Susana\|last34=Ontaneda\|first34=Daniel\|last35=Ramanathan\|first35=Sudarshini\|last36=Reich\|first36=Daniel\|last37=Rocca\|first37=Maria A.\|last38=Rovira\|first38=Àlex\|last39=Saidha\|first39=Shiv\|last40=Salter\|first40=Amber\|last41=Sastre-Garriga\|first41=Jaume\|last42=Saylor\|first42=Deanna\|last43=Solomon\|first43=Andrew J.\|last44=Sormani\|first44=Maria Pia\|last45=Stankoff\|first45=Bruno\|last46=Tintoré\|first46=Mar\|last47=Tremlett\|first47=Helen\|last48=Van der Walt\|first48=Anneke\|last49=Viswanathan\|first49=Shanthi\|last50=Wiendl\|first50=Heinz\|last51=Wildemann\|first51=Brigitte\|last52=Yamout\|first52=Bassem\|last53=Zaratin\|first53=Paola\|last54=Calabresi\|first54=Peter A.\|last55=Coetzee\|first55=Timothy\|last56=Thompson\|first56=Alan J.\|title=Diagnosis of multiple sclerosis: 2024 revisions of the McDonald criteria\|journal=The Lancet Neurology\|volume=24\|issue=10\|year=2025\|pages=850–865\|doi=10.1016/S1474-4422(25)00270-4\|pmid=40975101}}</ref>

	The principal roles of ECG in a person with MS are evaluation of suspected cardiovascular disease or arrhythmia, assessment of selected cardiovascular autonomic abnormalities, and cardiac safety monitoring when initiating certain disease-modifying therapies, particularly [[sphingosine-1-phosphate receptor modulator]]s.		The principal roles of ECG in a person with MS are evaluation of suspected cardiovascular disease or arrhythmia, assessment of selected cardiovascular autonomic abnormalities, and cardiac safety monitoring when initiating certain disease-modifying therapies, particularly [[sphingosine-1-phosphate receptor modulator]]s.
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	An ECG does '''not''' establish or exclude a diagnosis of MS. The 2024 McDonald criteria do not include ECG findings as a diagnostic criterion.<ref name="Montalban2025"/>		An ECG does '''not''' establish or exclude a diagnosis of MS. The 2024 McDonald criteria do not include ECG findings as a diagnostic criterion.<ref name="Montalban2025"/>

	MRI has a central role in the diagnosis of MS. The 2024 MAGNIMS-CMSC-NAIMS consensus recommendations address MRI assessment of the brain and spinal cord and incorporate the [[optic nerve]] as a fifth anatomical location, in addition to the periventricular, juxtacortical or cortical, infratentorial, and spinal cord regions. The consensus also addresses susceptibility-sensitive MRI markers, including the central vein sign and paramagnetic rim lesions, when appropriate.<ref name="Barkhof2025">{{cite journal\|last1=Barkhof\|first1=F.\|last2=Reich\|first2=D. S.\|last3=Oh\|first3=J.\|last4=Rocca\|first4=M. A.\|last5=Li\|first5=~~D. K.~~ B.\|last6=Sati\|first6=P.\|last7=Azevedo\|first7=C. J.\|last8=Bagnato\|first8=F.\|last9=Calabresi\|first9=P. A.\|last10=Ciccarelli\|first10=O.\|last11=Dwyer\|first11=M. G.\|last12=DeLuca\|first12=~~G. C.~~\|last13=Filippi\|first13=M.\|last14=Gauthier\|first14=S.\|last15=Kappos\|first15=L.\|last16=Newsome\|first16=S. D.\|last17=Ontaneda\|first17=D.\|last18=Rovira\|first18=À.\|title=2024 MAGNIMS-CMSC-NAIMS consensus recommendations on the use of MRI for the diagnosis of multiple sclerosis\|journal=The Lancet Neurology\|volume=24\|issue=10\|year=2025\|pages=866–879\|doi=10.1016/S1474-4422(25)00304-7\|pmid=40975102}}</ref>		MRI has a central role in the diagnosis of MS. The 2024 MAGNIMS-CMSC-NAIMS consensus recommendations address MRI assessment of the brain and spinal cord and incorporate the [[optic nerve]] as a fifth anatomical location, in addition to the periventricular, juxtacortical or cortical, infratentorial, and spinal cord regions. The consensus also addresses susceptibility-sensitive MRI markers, including the central vein sign and paramagnetic rim lesions, when appropriate.<ref name="Barkhof2025">{{cite journal\|last1=Barkhof\|first1=Frederik\|last2=Reich\|first2=Daniel S.\|last3=Oh\|first3=Jiwon\|last4=Rocca\|first4=Maria A.\|last5=Li\|first5=Dong-Kyu B.\|last6=Sati\|first6=Partha\|last7=Azevedo\|first7=Christina J.\|last8=Bagnato\|first8=Francesco\|last9=Calabresi\|first9=Peter A.\|last10=Ciccarelli\|first10=Olga\|last11=Dwyer\|first11=Michael G.\|last12=DeLuca\|first12=Gian\|last13=Filippi\|first13=Massimo\|last14=Gauthier\|first14=Susan\|last15=Kappos\|first15=Ludwig\|last16=Newsome\|first16=Stephen D.\|last17=Ontaneda\|first17=Daniel\|last18=Rovira\|first18=Àlex\|title=2024 MAGNIMS-CMSC-NAIMS consensus recommendations on the use of MRI for the diagnosis of multiple sclerosis\|journal=The Lancet Neurology\|volume=24\|issue=10\|year=2025\|pages=866–879\|doi=10.1016/S1474-4422(25)00304-7\|pmid=40975102}}</ref>

	Therefore, ECG abnormalities such as [[atrial fibrillation]], ventricular arrhythmias, [[Long PR interval\|PR-interval]] abnormalities, [[U wave]]s, [[Q wave]]s, bundle branch block, or other nonspecific ECG abnormalities should '''not''' be described as findings suggestive or diagnostic of MS. Such findings require evaluation according to standard cardiovascular practice and the clinical context.		Therefore, ECG abnormalities such as [[atrial fibrillation]], ventricular arrhythmias, [[Long PR interval\|PR-interval]] abnormalities, [[U wave]]s, [[Q wave]]s, bundle branch block, or other nonspecific ECG abnormalities should '''not''' be described as findings suggestive or diagnostic of MS. Such findings require evaluation according to standard cardiovascular practice and the clinical context.
Line 21:		Line 21:
	===Cardiovascular autonomic dysfunction===		===Cardiovascular autonomic dysfunction===

	MS may be associated with abnormalities of cardiovascular autonomic regulation. A systematic review and meta-analysis found differences in heart rate variability (HRV) ~~measures~~ in people with MS compared with healthy controls~~, supporting an association between MS and altered cardiac autonomic function~~.<ref name="Mirmosayyeb2026">{{cite journal\|last1=Mirmosayyeb\|first1=O.\|title=Heart rate variability in people with multiple sclerosis: A systematic review and meta-analysis\|journal=Acta Neurologica Belgica\|year=~~2025~~\|pmid=40587005}}</ref>		MS may be associated with abnormalities of cardiovascular autonomic regulation. A systematic review and meta-analysis of 43 studies involving 1,518 people with MS and 1,062 healthy controls found differences in several measures of heart rate variability (HRV), including reduced RMSSD, pNN50, high-frequency power, and low-frequency power in people with MS compared with healthy controls.<ref name="Mirmosayyeb2026">{{cite journal\|last1=Mirmosayyeb\|first1=Omid\|last2=Yazdan Panah\|first2=Mohammad\|last3=Alinejadfard\|first3=Mohammadreza\|last4=Oraee\|first4=Soroush\|last5=Vaheb\|first5=Saeed\|last6=Shaygannejad\|first6=Vahid\|title=Heart rate variability in people with multiple sclerosis: A systematic review and meta-analysis\|journal=Acta Neurologica Belgica\|volume=126\|issue=1\|year=2026\|pages=67–83\|doi=10.1007/s13760-025-02829-5\|pmid=40587005}}</ref>

	Other systematic reviews have similarly reported abnormalities of cardiac autonomic regulation in MS, particularly involving measures of heart-rate variability, although studies have used heterogeneous methods.<ref name="Findling2020">{{cite journal\|last1=Findling\|first1=O.\|last2=Hauer\|first2=L.\|last3=Pezawas\|first3=T.\|last4=Rommer\|first4=P. S.\|last5=Struhal\|first5=W.\|last6=Sellner\|first6=J.\|title=Cardiac Autonomic Dysfunction in Multiple Sclerosis: A Systematic Review of Current Knowledge and Impact of Immunotherapies\|journal=Journal of Clinical Medicine\|volume=9\|issue=2\|year=2020\|pages=335\|doi=10.3390/jcm9020335\|pmid=31991711}}</ref>		Other systematic reviews have similarly reported abnormalities of cardiac autonomic regulation in MS, particularly involving measures of heart-rate variability, although studies have used heterogeneous methods.<ref name="Findling2020">{{cite journal\|last1=Findling\|first1=Oliver\|last2=Hauer\|first2=Lisa\|last3=Pezawas\|first3=Thomas\|last4=Rommer\|first4=Patrick S.\|last5=Struhal\|first5=Wolfgang\|last6=Sellner\|first6=Johannes\|title=Cardiac Autonomic Dysfunction in Multiple Sclerosis: A Systematic Review of Current Knowledge and Impact of Immunotherapies\|journal=Journal of Clinical Medicine\|volume=9\|issue=2\|year=2020\|pages=335\|doi=10.3390/jcm9020335\|pmid=31991711}}</ref>

	ECG-derived HRV assessment may provide information about autonomic cardiovascular regulation in selected patients or research settings. However, HRV abnormalities are '''not specific for MS and are not diagnostic criteria for MS'''.<ref name="Mirmosayyeb2026"/><ref name="Findling2020"/>		ECG-derived HRV assessment may provide information about autonomic cardiovascular regulation in selected patients or research settings. However, HRV abnormalities are '''not specific for MS and are not diagnostic criteria for MS'''.<ref name="Mirmosayyeb2026"/><ref name="Findling2020"/>

SAndbox: JAF MS ECG

Julinka Auta Fernandes — Sat, 22 Aug 2026 08:36:39 GMT

Created page with "__NOTOC__ {{Multiple sclerosis}} {{CMG}}; {{AE}} {{Fs}} ==Overview== An electrocardiogram (ECG) is '''not used to diagnose multiple sclerosis (MS)''', and there are no ECG findings that are specific or diagnostic for MS. The diagnosis of MS is established using clinical findings together with appropriate paraclinical evidence, including MRI and, when appropriate, cerebrospinal fluid (CSF) biomarkers, according to the 2024 revision..."

New page

__NOTOC__
{{Multiple sclerosis}}
{{CMG}}; {{AE}} {{Fs}}

==Overview==

An [[electrocardiogram]] ([[ECG]]) is '''not used to diagnose multiple sclerosis (MS)''', and there are no ECG findings that are specific or diagnostic for MS. The diagnosis of MS is established using clinical findings together with appropriate paraclinical evidence, including [[magnetic resonance imaging|MRI]] and, when appropriate, cerebrospinal fluid (CSF) biomarkers, according to the 2024 revisions of the McDonald criteria.<ref name="Montalban2025">{{cite journal|last1=Montalban|first1=X.|last2=Lebrun-Frénay|first2=C.|last3=Oh|first3=J.|last4=Arrambide|first4=G.|last5=Moccia|first5=M.|last6=Amato|first6=M. P.|last7=Amezcua|first7=L.|last8=Banwell|first8=B.|last9=Bar-Or|first9=A.|last10=Barkhof|first10=F.|last11=Butzkueven|first11=H.|last12=Ciccarelli|first12=O.|last13=Chataway|first13=J.|last14=Cohen|first14=J. A.|last15=Comi|first15=G.|last16=Deisenhammer|first16=F.|last17=Filippi|first17=M.|last18=Green|first18=A. J.|last19=Kappos|first19=L.|last20=Miller|first20=A.|last21=Rocca|first21=M. A.|last22=Ramanathan|first22=S.|last23=Reich|first23=D. S.|last24=Rovira|first24=À.|last25=Thompson|first25=A. J.|title=Diagnosis of multiple sclerosis: 2024 revisions of the McDonald criteria|journal=The Lancet Neurology|volume=24|issue=10|year=2025|pages=850–865|doi=10.1016/S1474-4422(25)00270-4|pmid=40975101}}</ref>

The principal roles of ECG in a person with MS are evaluation of suspected cardiovascular disease or arrhythmia, assessment of selected cardiovascular autonomic abnormalities, and cardiac safety monitoring when initiating certain disease-modifying therapies, particularly [[sphingosine-1-phosphate receptor modulator]]s.

==Electrocardiogram==

===ECG and the diagnosis of multiple sclerosis===

An ECG does '''not''' establish or exclude a diagnosis of MS. The 2024 McDonald criteria do not include ECG findings as a diagnostic criterion.<ref name="Montalban2025"/>

MRI has a central role in the diagnosis of MS. The 2024 MAGNIMS-CMSC-NAIMS consensus recommendations address MRI assessment of the brain and spinal cord and incorporate the [[optic nerve]] as a fifth anatomical location, in addition to the periventricular, juxtacortical or cortical, infratentorial, and spinal cord regions. The consensus also addresses susceptibility-sensitive MRI markers, including the central vein sign and paramagnetic rim lesions, when appropriate.<ref name="Barkhof2025">{{cite journal|last1=Barkhof|first1=F.|last2=Reich|first2=D. S.|last3=Oh|first3=J.|last4=Rocca|first4=M. A.|last5=Li|first5=D. K. B.|last6=Sati|first6=P.|last7=Azevedo|first7=C. J.|last8=Bagnato|first8=F.|last9=Calabresi|first9=P. A.|last10=Ciccarelli|first10=O.|last11=Dwyer|first11=M. G.|last12=DeLuca|first12=G. C.|last13=Filippi|first13=M.|last14=Gauthier|first14=S.|last15=Kappos|first15=L.|last16=Newsome|first16=S. D.|last17=Ontaneda|first17=D.|last18=Rovira|first18=À.|title=2024 MAGNIMS-CMSC-NAIMS consensus recommendations on the use of MRI for the diagnosis of multiple sclerosis|journal=The Lancet Neurology|volume=24|issue=10|year=2025|pages=866–879|doi=10.1016/S1474-4422(25)00304-7|pmid=40975102}}</ref>

Therefore, ECG abnormalities such as [[atrial fibrillation]], ventricular arrhythmias, [[Long PR interval|PR-interval]] abnormalities, [[U wave]]s, [[Q wave]]s, bundle branch block, or other nonspecific ECG abnormalities should '''not''' be described as findings suggestive or diagnostic of MS. Such findings require evaluation according to standard cardiovascular practice and the clinical context.

===Cardiovascular autonomic dysfunction===

MS may be associated with abnormalities of cardiovascular autonomic regulation. A systematic review and meta-analysis found differences in heart rate variability (HRV) measures in people with MS compared with healthy controls, supporting an association between MS and altered cardiac autonomic function.<ref name="Mirmosayyeb2026">{{cite journal|last1=Mirmosayyeb|first1=O.|title=Heart rate variability in people with multiple sclerosis: A systematic review and meta-analysis|journal=Acta Neurologica Belgica|year=2025|pmid=40587005}}</ref>

Other systematic reviews have similarly reported abnormalities of cardiac autonomic regulation in MS, particularly involving measures of heart-rate variability, although studies have used heterogeneous methods.<ref name="Findling2020">{{cite journal|last1=Findling|first1=O.|last2=Hauer|first2=L.|last3=Pezawas|first3=T.|last4=Rommer|first4=P. S.|last5=Struhal|first5=W.|last6=Sellner|first6=J.|title=Cardiac Autonomic Dysfunction in Multiple Sclerosis: A Systematic Review of Current Knowledge and Impact of Immunotherapies|journal=Journal of Clinical Medicine|volume=9|issue=2|year=2020|pages=335|doi=10.3390/jcm9020335|pmid=31991711}}</ref>

ECG-derived HRV assessment may provide information about autonomic cardiovascular regulation in selected patients or research settings. However, HRV abnormalities are '''not specific for MS and are not diagnostic criteria for MS'''.<ref name="Mirmosayyeb2026"/><ref name="Findling2020"/>

When cardiovascular autonomic dysfunction is clinically suspected, assessment may include orthostatic heart rate and blood-pressure measurements and, when appropriate, additional autonomic testing. ECG-based HRV assessment should be selected according to the clinical question and is not routinely required in every patient with MS.

===ECG and sphingosine-1-phosphate receptor modulators===

ECG has an important role in the cardiac safety assessment of selected [[sphingosine-1-phosphate receptor modulator]]s used for MS. These medications can cause reductions in heart rate and slowing of atrioventricular conduction, particularly during treatment initiation. Cardiac assessment and monitoring requirements differ among individual agents because of differences in dose-titration regimens and cardiac safety profiles.<ref name="GilenyaFDA2025">{{cite web|title=GILENYA (fingolimod) prescribing information|publisher=U.S. Food and Drug Administration|year=2025|url=https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/022527s044lbl.pdf}}</ref><ref name="MayzentEMA">{{cite web|title=MAYZENT (siponimod) product information|publisher=European Medicines Agency|url=https://www.ema.europa.eu/en/medicines/human/EPAR/mayzent}}</ref><ref name="ZeposiaFDA">{{cite web|title=ZEPOSIA (ozanimod) prescribing information|publisher=Bristol Myers Squibb|url=https://packageinserts.bms.com/pi/pi_zeposia.pdf}}</ref><ref name="PonvoryEMA">{{cite web|title=PONVORY (ponesimod) product information|publisher=European Medicines Agency|url=https://www.ema.europa.eu/en/documents/product-information/ponvory-epar-product-information_en.pdf}}</ref>

Before initiating an S1P receptor modulator, cardiovascular history, baseline heart rate, relevant medications, and potential conduction or rhythm abnormalities should be assessed according to the prescribing information for the individual drug. Cardiology consultation should be considered when clinically significant pre-existing cardiovascular disease or conduction abnormalities are present.

====Fingolimod====

Before initiating [[fingolimod]], an ECG should be obtained as part of first-dose cardiac assessment. Initiation of fingolimod can cause bradycardia and atrioventricular conduction abnormalities.<ref name="GilenyaFDA2025"/>

Patients initiating fingolimod should be observed for at least 6 hours after the first dose for signs and symptoms of bradycardia, with hourly pulse and blood-pressure measurements. ECG should be obtained before dosing and at the end of the observation period.<ref name="GilenyaFDA2025"/>

Additional monitoring should be provided if clinically important bradycardia or conduction abnormalities occur. Overnight continuous ECG monitoring is required in specified higher-risk circumstances, including certain pre-existing cardiovascular or cerebrovascular conditions, prolonged QTc or increased risk of QT prolongation, and concomitant treatment with drugs that slow heart rate or atrioventricular conduction.<ref name="GilenyaFDA2025"/>

First-dose monitoring is also required when fingolimod is restarted after specified treatment interruptions because effects on heart rate and atrioventricular conduction may recur after reinitiation.<ref name="GilenyaFDA2025"/>

====Siponimod====

Before initiating [[siponimod]], cardiovascular assessment should include consideration of baseline ECG findings and pre-existing conduction abnormalities. Siponimod can cause bradycardia and atrioventricular conduction delays, particularly during treatment initiation.<ref name="MayzentEMA"/>

Patients with certain pre-existing cardiac conditions, including sinus bradycardia with a heart rate below 55 beats per minute, a history of first- or second-degree Mobitz type I atrioventricular block, myocardial infarction, or heart failure, should be observed for 6 hours after the first dose for signs and symptoms of bradycardia. In these patients, ECG should be obtained before dosing and at the end of the observation period.<ref name="MayzentEMA"/>

If clinically significant bradyarrhythmia or conduction abnormalities occur, further evaluation and monitoring should be performed according to the product information and clinical circumstances.<ref name="MayzentEMA"/>

====Ozanimod====

[[Ozanimod]] is initiated using a dose-titration regimen that attenuates the magnitude of the initial heart-rate reduction.<ref name="ZeposiaFDA"/>

Before starting ozanimod, patients should be assessed for relevant cardiovascular disease and conduction abnormalities. Ozanimod can cause a transient decrease in heart rate and atrioventricular conduction delays, particularly during treatment initiation.<ref name="ZeposiaFDA"/>

Routine prolonged first-dose cardiac monitoring is '''not universally required''' with the recommended ozanimod titration regimen. Cardiology consultation should be considered in patients with relevant conduction abnormalities or concomitant use of drugs that decrease heart rate or atrioventricular conduction.<ref name="ZeposiaFDA"/>

====Ponesimod====

Before initiating [[ponesimod]], an ECG should be obtained to identify pre-existing conduction abnormalities. Ponesimod is initiated using a dose-titration regimen to reduce cardiac effects during treatment initiation.<ref name="PonvoryEMA"/>

First-dose 4-hour monitoring is recommended for patients with sinus bradycardia with a heart rate below 55 beats per minute, first- or second-degree Mobitz type I atrioventricular block, or a history of myocardial infarction or heart failure occurring more than 6 months before treatment initiation and in stable condition.<ref name="PonvoryEMA"/>

For patients requiring first-dose monitoring, the patient should be monitored for 4 hours with at least hourly pulse and blood-pressure measurements. ECG should be obtained at the end of the observation period.<ref name="PonvoryEMA"/>

Additional monitoring is required if clinically significant bradycardia or conduction abnormalities occur, according to the product information.<ref name="PonvoryEMA"/>

===ECG abnormalities in patients with multiple sclerosis===

ECG abnormalities in a patient with MS should not be considered characteristic ECG manifestations of MS.

Potential abnormalities may include:

*[[Sinus bradycardia]] or other heart-rate abnormalities, particularly during initiation of S1P receptor modulator therapy.
*[[Atrioventricular block]] or PR-interval prolongation, particularly during initiation of S1P receptor modulator therapy.
*[[QT interval|QTc prolongation]], particularly in the presence of pre-existing QT prolongation, electrolyte abnormalities, concomitant QT-prolonging medications, or specific drug-related risks.
*[[Atrial fibrillation]] or other atrial arrhythmias.
*Ventricular arrhythmias.
*Bundle branch block or other conduction abnormalities.

These findings are '''nonspecific''' and should be evaluated according to standard cardiovascular practice. Their presence does not establish a diagnosis of MS.<ref name="GilenyaFDA2025"/><ref name="MayzentEMA"/><ref name="ZeposiaFDA"/><ref name="PonvoryEMA"/>

The previously reported association of individual ECG findings such as atrial fibrillation, ventricular arrhythmia, Q waves, U waves, or isolated PR-interval changes with MS should not be interpreted as evidence that these findings are diagnostic of MS.

===Ambulatory ECG monitoring===

Ambulatory ECG monitoring, including Holter monitoring or longer-duration rhythm monitoring, is '''not routinely indicated solely because a patient has MS'''.

Ambulatory ECG monitoring may be appropriate when symptoms or clinical findings suggest intermittent arrhythmia, including unexplained [[palpitations]], [[syncope]], [[presyncope]], episodic bradycardia, unexplained tachycardia, or other suspected intermittent rhythm disturbances.

The choice and duration of ambulatory monitoring should be based on symptom frequency and standard cardiovascular practice.

===ECG in patients with cardiovascular symptoms===

Patients with MS should undergo cardiovascular evaluation according to their symptoms and individual cardiovascular risk factors. A 12-lead ECG is appropriate when clinically indicated, including evaluation of chest pain, suspected ischemia, palpitations, syncope or presyncope, unexplained dyspnea, suspected arrhythmia, or suspected medication-related cardiac effects.

These cardiovascular indications should be distinguished from MS diagnosis: ECG is not a routine diagnostic investigation for MS.

===Interpretation of an abnormal ECG===

An abnormal ECG in a patient with MS should not automatically be attributed to MS. The differential diagnosis should include primary cardiac disease, myocardial ischemia, electrolyte abnormalities, medication effects, autonomic dysfunction, structural heart disease, conduction-system disease, and primary cardiac arrhythmias.

ECG findings should be interpreted together with the patient's symptoms, cardiovascular history, medication list, physical examination, and relevant laboratory and imaging findings. Additional evaluation, such as echocardiography or ambulatory rhythm monitoring, should be performed when clinically indicated.

===Key clinical points===

*'''ECG is not a diagnostic test for multiple sclerosis.'''
*'''There are no ECG findings that are specific or diagnostic for MS.'''
*The 2024 McDonald criteria do not include ECG as a diagnostic criterion.<ref name="Montalban2025"/>
*MRI and appropriate CSF/biomarker assessment, together with clinical findings, are central to modern MS diagnosis.<ref name="Montalban2025"/><ref name="Barkhof2025"/>
*MS may be associated with cardiovascular autonomic dysfunction and altered HRV, but these findings are not specific for MS and are not diagnostic criteria.<ref name="Mirmosayyeb2026"/><ref name="Findling2020"/>
*ECG may be useful when cardiovascular symptoms, suspected arrhythmia, or selected autonomic dysfunction are present.
*ECG has an important medication-safety role with S1P receptor modulators, but monitoring requirements differ among fingolimod, siponimod, ozanimod, and ponesimod.
*Fingolimod requires pre-dose and post-observation ECG assessment with at least 6 hours of first-dose observation.<ref name="GilenyaFDA2025"/>
*Siponimod requires cardiovascular assessment and 6-hour first-dose monitoring with ECG in patients with specified pre-existing cardiac conditions.<ref name="MayzentEMA"/>
*Ozanimod uses dose titration, and routine prolonged first-dose cardiac monitoring is not universally required with the recommended titration regimen.<ref name="ZeposiaFDA"/>
*Ponesimod requires baseline cardiovascular assessment, with 4-hour first-dose monitoring for patients with specified pre-existing cardiac conditions.<ref name="PonvoryEMA"/>
*Ambulatory ECG monitoring is reserved for clinically indicated evaluation of suspected intermittent arrhythmia and is not routinely required solely because of MS.

==References==

{{Reflist|2}}

{{WH}}
{{WS}}

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Aiden Nguyen — Sat, 22 Aug 2026 03:38:30 GMT

Created page with "Aiden Nguyen[mailto:aidennguyen7@gmail.com]"

New page

[[User: Aiden Nguyen|Aiden Nguyen]][mailto:aidennguyen7@gmail.com]

USMLE Step 3

Gromeromd — Fri, 21 Aug 2026 18:30:49 GMT

← Older revision		Revision as of 18:30, 21 August 2026
(4 intermediate revisions by the same user not shown)
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	Step 3 is the final exam of the [[United States Medical Licensing Examination]]™ ([[USMLE]]™) series of examinations. It is part of the licensing requirements for M.D.s, D.O.s, and FMGs to practice medicine in the United States.		Step 3 is the final exam of the [[United States Medical Licensing Examination]]™ ([[USMLE]]™) series of examinations. It is part of the licensing requirements for M.D.s, D.O.s, and FMGs to practice medicine in the United States.
	It is considered the final step in the series of medical licensure examinations. It generally is a pre-requisite of the majority of the state licensing boards, and it is usually taken during intern year in residency training. It is a two-day examination that includes multiple choice questions and clinical case scenarios (CCS) that assess medical knowledge in the clinical setting. Step 3 provides a final assessment of physicians assuming independent responsibility for delivering general medical care. {{Template:Physician education and training in the United States}}		It is considered the final step in the series of medical licensure examinations. It generally is a pre-requisite of the majority of the state licensing boards, and it is usually taken during intern year in residency training. It is a two-day examination that includes multiple choice questions and clinical case scenarios (CCS) that assess medical knowledge in the clinical setting. Step 3 provides a final assessment of physicians assuming independent responsibility for delivering general medical care. {{Template:Physician education and training in the United States}}

	== Exam Content ==		== Exam Content ==

	Step 3 assesses whether you can apply medical knowledge and understanding of biomedical and clinical science essential for the unsupervised practice of medicine, with emphasis on patient management in ambulatory settings.		Step 3 assesses whether you can apply medical knowledge and understanding of biomedical and clinical science essential for the unsupervised practice of medicine, with emphasis on patient management in ambulatory settings.

	Topics include:		Topics include:
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	\|All subjects (population)		\|All subjects (population)
	\|}		\|}
	'''''TP''': true positive; '''FP:''' false negative; '''TN:''' true negative; '''FN:''' false negative''		'''''TP''': true positive; '''FP:''' false negative; '''TN:''' true negative; '''FN:''' false negative''


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	Find a general summary on how to approach CCS cases on Step 3 on a step-wise approach:		Find a general summary on how to approach CCS cases on Step 3 on a step-wise approach:

			'''1. GENERAL INFO: ''' write age, gender, chief complaint on your erasable board
	'''1. GENERAL INFO: ''' write age, gender, chief complaint on your erasable board

	* Symptoms (pain, fever, vomit) to address them later on 🡪 (morphine, acetaminophen, phenergan)		* Symptoms (pain, fever, vomit) to address them later on 🡪 (morphine, acetaminophen, phenergan)
	* Write social history (smoking, sex) to address towards the end of the case		* Write social history (smoking, sex) to address towards the end of the case

User:Julinka Auta Fernandes/sandbox

Julinka Auta Fernandes — Fri, 21 Aug 2026 17:56:31 GMT

← Older revision		Revision as of 17:56, 21 August 2026
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	__NOTOC__		__NOTOC__
	{{Template:Multiple sclerosis}}		{{Template:Multiple sclerosis}}
	{{CMG}}; {{AE}} {{Fs}}		{{CMG}}; {{AE}} {{Fs}} {{JAF}}

	==Overview==		==Overview==