Acute flaccid myelitis

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Syed Hassan A. Kazmi BSc, MD [2]

Synonyms and keywords:; Acute flaccid paralysis, acute flaccid paralysis with anterior myelitis, paralysis with anterior myelitis, AFM, Enterovirus D68-Associated Anterior Myelitis

Historical Perspective

• In 2014, physicians in California and Colorado (USA) noted an increase in the number of patients presenting with the acute onset of flaccid paralysis and MRI findings consistent with lesions in the gray matter of the spinal cord.
• In 2014, a total of 120 cases were identified in the US and 22 were identified in 2015
• In 2016, 145 cases of AFM were diagnosed across the USA.

Causes

Acute flaccid myelitis (AFM) may be caused by viral infections or environmental toxins. The following viruses are known to be associated with AFM:

• West Nile Virus
• Coxsackievirus
• Adenovirus
• Poliovirus
• Enterovirus 71 (EV 71) and Entervirus D68 (EV 68)

Differentiating Acute Flaccid Myelitis From Other Diseases

The following table differentiates acute flaccid myelitis from other diseases that cause muscle weakness, hypotonia, and flaccid paralysis:

Diseases	History and Physical								Diagnostic tests		Other Findings
	Motor Deficit	Sensory deficit	Cranial nerve Involvement	Autonomic dysfunction	Proximal/Distal/Generalized	Ascending/Descending/Systemic	Unilateral (UL) or Bilateral (BL) or No Lateralization (NL)	Onset	Lab or Imaging Findings	Specific test
Adult Botulism	+	-	+	+	Generalized	Descending	BL	Sudden	Toxin test	Blood, Wound, or Stool culture	Diplopia, Hyporeflexia, Hypotonia, possible respiratory paralysis
Infant Botulism	+	-	+	+	Generalized	Descending	BL	Sudden	Toxin test	Blood, Wound, or Stool culture	Flaccid paralysis (Floppy baby syndrome), possible respiratory paralysis
Guillian-Barre syndrome	+	-	-	-	Generalized	Ascending	BL	Insidious	CSF: ↑Protein ↓Cells	Clinical & Lumbar Puncture	Progressive ascending paralysis following infection, possible respiratory paralysis
Eaton Lambert syndrome	+	-	+	+	Generalized	Systemic	BL	Intermittent	EMG, repetitive nerve stimulation test (RNS)	Voltage gated calcium channel (VGCC) antibody	Diplopia, ptosis, improves with movement (as the day progresses)
Myasthenia gravis	+	-	+	+	Generalized	Systemic	BL	Intermittent	EMG, Edrophonium test	Ach receptor antibody	Diplopia, ptosis, worsening with movement (as the day progresses)
Electrolyte disturbance	+	+	-	-	Generalized	Systemic	BL	Insidious	Electrolyte panel	↓Ca++, ↓Mg++, ↓K+	Possible arrhythmia
Organophosphate toxicity	+	+	-	+	Generalized	Ascending	BL	Sudden	Clinical diagnosis: physical exam & history	Clinical suspicion confirmed with RBC AchE activity	History of exposure to insecticide or living in farming environment. with : Diarrhea, Urination, Miosis, Bradycardia, Lacrimation, Emesis, Salivation, Sweating
Tick paralysis (Dermacentor tick)	+	-	-	-	Generalized	Ascending	BL	Insidious	Clinical diagnosis: physical exam & history	-	History of outdoor activity in Northeastern United States. The tick is often still latched to the patient at presentation (often in head and neck area)
Tetrodotoxin poisoning	+	-	+	+	Generalized	Systemic	BL	Sudden	Clinical diagnosis: physical exam & dietary history	-	History of consumption of puffer fish species.
Stroke	+/-	+/-	+/-	+/-	Generalized	Systemic	UL	Sudden	MRI +ve for ischemia or hemorrhage	MRI	Sudden unilateral motor and sensory deficit in a patient with a history of atherosclerotic risk factors (diabetes, hypertension, smoking) or atrial fibrillation.
Poliomyelitis	+	+	+	+/-	Proximal > Distal	Systemic	BL or UL	Sudden		PCR of CSF	Asymmetric paralysis following a flu-like syndrome.
Transverse myelitis	+	+	+	+	Proximal > Distal	Systemic	BL or UL	Sudden	MRI & Lumbar puncture	MRI	History of chronic viral or autoimmune disease (e.g. HIV)
Neurosyphilis	+	+	-	+/-	Generalized	Systemic	BL	Insidious	MRI & Lumbar puncture	CSF VDRL-specifc CSF FTA-Ab -sensitive	History of unprotected sex or multiple sexual partners. History of genital ulcer (chancre), diffuse maculopapular rash.
Muscular dystrophy	+	-	-	-	Proximal > Distal	Systemic	BL	Insidious	Genetic testing	Muscle biopsy	Progressive proximal lower limb weakness with calf pseudohypertrophy in early childhood. Gower sign positive.
Multiple sclerosis exacerbation	+	+	+	+	Generalized	Systemic	NL	Sudden	↑CSF IgG levels (monoclonal)	Clinical assessment and MRI	Blurry vision, urinary incontinence, fatigue
Amyotrophic lateral sclerosis	+	-	-	-	Generalized	Systemic	BL	Insidious	Normal LP (to rule out DDx)	MRI & LP	Patient initially presents with upper motor neuron deficit (spasticity) followed by lower motor neuron deficit (flaccidity).
Inflammatory myopathy	+	-	-	-	Proximal > Distal	Systemic	UL or BL	Insidious	Elevated CK & Aldolase	Muscle biopsy	Progressive proximal muscle weakness in 3rd to 5th decade of life. With or without skin manifestations.

Epidemiology and Demographics

Incidence and Prevalence

USA

• From June 1, 2012 to July 31, 2015, 59 reported cases met the California Department of Public Health (CDPH) case definition of acute flaccid myelitis (AFM), which defines AFM as acute onset of flaccid limb paralysis along with a lesion in the gray matter of the spinal cord.
• Between August and December of 2014, 120 children from 34 US states met the criteria of AFM as outlined by the CDC.
• From August 2014 through October 2018, CDC has received information on a total of 404 confirmed cases of acute flaccid myelitis (AFM) across the US; most of the cases have occurred in children
• In 2015, 22 people were confirmed to have AFM. (Note: The cases occurred in 17 states across the U.S.)
• In 2016, 149 people were confirmed to have AFM. (Note: The cases occurred in 39 states across the U.S. and DC)
• In 2017, CDC received information for 33 confirmed cases of AFM. (Note: The cases occurred in 16 states across the U.S.)
• In October 2018, the New York State Department of Health (NYSDOH) confirmed 39 cases of the enterovirus EV-D68 in children across the state which was associated with an increase in number of cases of AFM.

Acute Flaccid Myelitis number of confirmed cases from August 2014 to October 2018 based on AFM case definition: Onset of acute limb weakness and an MRI showing a spinal cord lesion largely restricted to gray matter

Risk Factors

The following risk factors increase the risk of development of AFM:

• Pulmonary comorbities (Asthma, COPD)
• Immunocompromised states (Immunosuppressants, organ transplantation, diabetes, systemic autoimmune diseases, hematologic malignancies)

Natural History, Complications and Prognosis

Natural History

• The clinical course of AFM typically consists of three phases:
  • Prodormal phase
  • Progressive neurological injury phase
  • Convalescent phase

Prodormal phase

• A prodromal, often febrile, illness often precedes the onset of neurological deficits in most patients by a median of 5 days.
• The prodormal period consists of respiratory symptoms such as rhinorrhea, cough, or pharyngitis and/or gastrotestinal symptoms such as nausea, vomiting or diarrhea.
• Some patients report clinical improvement in their preceding illness before return of fever accompanied by headaches, stiff neck, or pain in the neck, back, or affected limb around the time of neurological deficit onset

Progressive neurological injury

• The pattern of limb weakness in AFM corresponds to a lower motor neuron lesion and upper extremities are more commonly affected.
• Involvement of cranial nerves points towards lesions in the cranial nerve motor nuclei of the brainstem
• On CSF examination, mild pleocytosis with mildly elevated protein may be seen
• On MRI, confluent, longitudinally extensive gray matter lesions may be seen in spinal cord. This may progress to nerve root enhancement on MRI in 2-3 weeks.
• On electromyography (EMG), reduced recruitment of motor unit potentials (MUPs) and low amplitude of compound muscle action potentials may be seen.

Convalescent phase

• Months after the initial acute neurological illness, patients suffering from AFM may smild improvements with rehabilitation therapies.
• On CSF examination, pleocytosis may resolve and protein remains elevated
• On EMG, fibrillations may be seen

Complications

AFM may lead to the development of following complications:

• Respiratory failure
• Urinary tract infections
• Skin ulcers and traumatic injury (specially in the affected extremity)
• Progressive muscular atrophy

Diagnosis

Diagnostic Criteria

Diagnosis	Criteria
Confirmed	Acute onset of flaccid limb weakness AND An MRI showing a spinal cord lesion largely restricted to gray matter and spanning one or more spinal segments
Probable	Acute onset of flaccid limb weakness AND Cerebrospinal fluid (CSF) with pleocytosis (white blood cell count 9 5 cells/mm3

Symptoms

The following are the symptoms of acute flaccid myelitis:

• Acute onset of flaccid limb paralysis (asymmetric)
• Fever
• Pain in the paralytic limb
• Eyelid drooping

• Difficulty with swallowing or slurred speech

• Cranial nerve abnormalities
• Headache
• Neck pain
• Bowel/bladder changes