Seizure differential diagnosis

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]


Differential diagnosis of epileptic seizures may include: concussion, drug intoxication or withdrawal, migraine, psychogenic nonepileptic events, panic attacks, sleep disorders, syncope, transient global amnesia, and transient ischemic attack (TIA).

Differentiating Seizure from other Conditions

Differential diagnosis of epileptic seizures may include:[1]

A quick algorithm to differentiate seizure from other causes of altered mental status is demonstrated below:

Clinical presentation
Loss of conscoiusness
• Transient?
• Rapid onset?
• Short duration?
• Spontaneous recovery?
Altered consciousnes
Aborted SCD
Epileptic seizure
Rare causes
• Reflex syncope
Orthostatic hypotension
Cardiac syncope
• Tonic
• Clonic
• Tonic-clonic
• Atonic
• Pseudo-epileptic
• Pseudo-syncopal

Abbreviations: SCD: Sudden cardiac death;T-LOC: Transient-Loss of consciousness.

The above algorithm adopted from ESC guideline [2]

It can be difficult to distinguish a seizure from other conditions causing a collapse, abnormal movements or other seizure manifestations. A 2007 evidence-based review from the American Academy of Neurology and the American Epilepsy Society recommends an electroencephalogram (EEG, brain wave activity) and brain imaging with CT scan or MRI scan in the work-up of adults presenting with a first apparently unprovoked seizure. Blood tests, lumbar puncture or toxicology screening can be helpful in specific circumstances suggestive of an underlying cause like meningitis or drug overdose, but there is insufficient evidence to support their routine use in the work-up of an adult with an apparently unprovoked first seizure.[3]

Differentiating a seizure from other conditions such as syncope can be difficult. In addition, 5% of patients with a positive tilt table test may have seizure-like activity that seems to be due to cerebral hypoxia.[4]

As seizures have a differential diagnosis, it is common for patients to be simultaneously investigated for cardiac and endocrine causes. Checking glucose levels, for example, is a mandatory action in the management of seizures as hypoglycemia may cause seizures, and failure to administer glucose would be harmful to the patient. Other causes typically considered are syncope and cardiac arrhythmias, and occasionally, panic attacks and cataplexy. For more information, see non-epileptic seizures.

Neurosyphilis can present with seizures and must be differentiated from other causes of seizures.[5]

Diseases Symptoms Physical Examination Past medical history Diagnostic tests Other Findings
Headache LOC Motor weakness Abnormal sensory Motor Deficit Sensory deficit Speech difficulty Gait abnormality Cranial nerves CT /MRI CSF Findings Gold standard test
Meningitis + - - - - + + - - History of fever and malaise - Leukocytes,


↓ Glucose

CSF analysis[6] Fever, neck


Encephalitis + + +/- +/- - - + +/- + History of fever and malaise + Leukocytes, ↓ Glucose CSF PCR Fever, seizures, focal neurologic abnormalities
Brain tumor[7] + - - - + + + - + Weight loss, fatigue + Cancer cells[8] MRI Cachexia, gradual progression of symptoms
Hemorrhagic stroke + + + + + + + + - Hypertension + - CT scan without contrast[9][10] Neck stiffness
Subdural hemorrhage + + + + + - - - + Trauma, fall + Xanthochromia[11] CT scan without contrast[9][10] Confusion, dizziness, nausea, vomiting
Neurosyphilis[12][5] + - + + + + - + - STIs + Leukocytes and protein CSF VDRL-specifc

CSF FTA-Ab -sensitive[13]

Blindness, confusion, depression,

Abnormal gait

Complex or atypical migraine + - + + - - + - - Family history of migraine - - Clinical assesment Presence of aura, nausea, vomiting
Hypertensive encephalopathy + + - - - - + + - Hypertension + - Clinical assesment Delirium, cortical blindness, cerebral edema, seizure
Wernicke’s encephalopathy - + - - - + + + + History of alcohal abuse - - Clinical assesment and lab findings Ophthalmoplegia, confusion
CNS abscess + + - - + + + - - History of drug abuse, endocarditis, immunosupression + leukocytes, glucose and protien MRI is more sensitive and specific High grade fever, fatigue,nausea, vomiting
Drug toxicity - + - + + + - + - - - - Drug screen test Lithium, Sedatives, phenytoin, carbamazepine
Conversion disorder + + + + + + + + History of emotional stress - - Diagnosis of exclusion Tremors, blindness, difficulty swallowing
Metabolic disturbances (electrolyte imbalance, hypoglycemia) - + + + + + - - + - - Hypoglycemia, hypo and hypernatremia, hypo and hyperkalemia Depends on the cause Confusion, seizure, palpitations, sweating, dizziness, hypoglycemia
Multiple sclerosis exacerbation - - + + - + + + + History of relapses and remissions + CSF IgG levels

(monoclonal bands)

Clinical assesment and MRI [14] Blurry vision, urinary incontinence, fatigue
Seizure + + - - + + - - + Previous history of seizures - Mass lesion Clinical assesment and EEG [15] Confusion, apathy, irritability,


  1. Johnson EL (2019). "Seizures and Epilepsy". Med Clin North Am. 103 (2): 309–324. doi:10.1016/j.mcna.2018.10.002. PMID 30704683.
  2. Moya, A.; Sutton, R.; Ammirati, F.; Blanc, J.-J.; Brignole, M.; Dahm, J. B.; Deharo, J.-C.; Gajek, J.; Gjesdal, K.; Krahn, A.; Massin, M.; Pepi, M.; Pezawas, T.; Granell, R. R.; Sarasin, F.; Ungar, A.; van Dijk, J. G.; Walma, E. P.; Wieling, W.; Abe, H.; Benditt, D. G.; Decker, W. W.; Grubb, B. P.; Kaufmann, H.; Morillo, C.; Olshansky, B.; Parry, S. W.; Sheldon, R.; Shen, W. K.; Vahanian, A.; Auricchio, A.; Bax, J.; Ceconi, C.; Dean, V.; Filippatos, G.; Funck-Brentano, C.; Hobbs, R.; Kearney, P.; McDonagh, T.; McGregor, K.; Popescu, B. A.; Reiner, Z.; Sechtem, U.; Sirnes, P. A.; Tendera, M.; Vardas, P.; Widimsky, P.; Auricchio, A.; Acarturk, E.; Andreotti, F.; Asteggiano, R.; Bauersfeld, U.; Bellou, A.; Benetos, A.; Brandt, J.; Chung, M. K.; Cortelli, P.; Da Costa, A.; Extramiana, F.; Ferro, J.; Gorenek, B.; Hedman, A.; Hirsch, R.; Kaliska, G.; Kenny, R. A.; Kjeldsen, K. P.; Lampert, R.; Molgard, H.; Paju, R.; Puodziukynas, A.; Raviele, A.; Roman, P.; Scherer, M.; Schondorf, R.; Sicari, R.; Vanbrabant, P.; Wolpert, C.; Zamorano, J. L. (2009). "Guidelines for the diagnosis and management of syncope (version 2009): The Task Force for the Diagnosis and Management of Syncope of the European Society of Cardiology (ESC)". European Heart Journal. 30 (21): 2631–2671. doi:10.1093/eurheartj/ehp298. ISSN 0195-668X.
  3. Krumholz A, Wiebe S, Gronseth G, Shinnar S, Levisohn P, Ting T, Hopp J, Shafer P, Morris H, Seiden L, Barkley G, French J; Quality Standards Subcommittee of the American Academy of Neurology; American Epilepsy Society. Practice Parameter: evaluating an apparent unprovoked first seizure in adults (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology and the American Epilepsy Society. Neurology 2007; 69(21): 1996-2007. PMID 18025394
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  9. 9.0 9.1 Birenbaum D, Bancroft LW, Felsberg GJ (2011). "Imaging in acute stroke". West J Emerg Med. 12 (1): 67–76. PMC 3088377. PMID 21694755.
  10. 10.0 10.1 DeLaPaz RL, Wippold FJ, Cornelius RS, Amin-Hanjani S, Angtuaco EJ, Broderick DF; et al. (2011). "ACR Appropriateness Criteria® on cerebrovascular disease". J Am Coll Radiol. 8 (8): 532–8. doi:10.1016/j.jacr.2011.05.010. PMID 21807345.
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  12. Liu LL, Zheng WH, Tong ML, Liu GL, Zhang HL, Fu ZG; et al. (2012). "Ischemic stroke as a primary symptom of neurosyphilis among HIV-negative emergency patients". J Neurol Sci. 317 (1–2): 35–9. doi:10.1016/j.jns.2012.03.003. PMID 22482824.
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