Acute Flaccid Myelitis: A Clinical Review

Olwen C. Murphy, MBBCh, MRCPI; Carlos A. Pardo, MD

Semin Neurol. 2020;40(2):211-218.

Abstract and Introduction

Abstract

Acute flaccid myelitis (AFM) is an emerging disorder primarily affecting children that is characterized by acute flaccid paralysis accompanied by abnormalities of the spinal cord gray matter on magnetic resonance imaging. In most cases, prodromal fever or respiratory symptoms occur, followed by acute-onset flaccid limb weakness. Respiratory, axial, bulbar, facial, and extraocular muscles may also be affected. The clinical manifestations have been described as "polio-like," due to striking similarities to cases of poliomyelitis. The primary site of injury in AFM is the anterior horn cells of the spinal cord, resulting in a motor neuronopathy. Seasonal peaks of cases have occurred in the United States every 2 years since 2012. However, AFM remains a rare disease, which can make it challenging for physicians to recognize and differentiate from other causes of acute flaccid paralysis such as Guillain–Barre syndrome, spinal cord stroke, and transverse myelitis. Epidemiological evidence suggests that AFM is linked to a viral etiology, with nonpolio enteroviruses (in particular enterovirus D68) demonstrating a plausible association. The epidemiology, possible etiological factors, clinical features, differential diagnosis, treatment, and outcomes of AFM are discussed in this review.

Introduction

Acute flaccid myelitis (AFM) is a recently recognized disorder of the spinal cord characterized by acute-onset flaccid paralysis with associated gray matter-predominant abnormalities on magnetic resonance imaging (MRI) of the spinal cord. AFM predominantly affects children, and is usually preceded by a prodromal febrile or infectious illness. The disorder bears a striking resemblance to poliomyelitis in terms of the natural history, radiological, laboratory, and neurophysiological features, and therefore has been widely termed "polio-like." While there are some clinical features that may overlap with other causes of acute flaccid paralysis, a diagnosis of AFM can be made with confidence based on the clinical and paraclinical features discussed herein. The etiology and pathophysiology of AFM is not fully understood, but epidemiological evidence suggests the disorder is linked to a viral trigger (particularly enterovirus D68). Many questions about AFM remain unanswered, including expected long-term outcomes for patients, and potential strategies to treat or prevent the disorder.

1 2 3 4 5 6 7 8 9 10 11

Next Section

Table 1. Summary of evidence for an association between enterovirus D68 infection and acute flaccid myelitis
Clinical evidence
1. Prodromal febrile, respiratory, and/or gastrointestinal illness
2. Similar clinical, radiological, and neurophysiological features to poliomyelitis
3. Enterovirus D68 detected in respiratory specimens of many patients with AFM
4. Enterovirus D68 detected in CSF of a handful of AFM cases
Epidemiological evidence
1. Temporal association between AFM cases and outbreaks of enterovirus D68 infection
2. Association has been identified in multiple regions worldwide
3. Increased odds of enterovirus D68 detection in patients presenting with AFM as compared with patients presenting with uncomplicated respiratory infections
Virological evidence
1. Genome mutations and diversification of enterovirus D68 in recent years coincided with recognition of AFM
2. Mice develop a clinical syndrome similar to AFM when infected with modern strains of enterovirus D68
3. Neuronal cell culture studies suggest that enterovirus D68 is neurotropic

Abbreviations: AFM, acute flaccid myelitis; CSF, cerebrospinal fluid.

Table 2. Clinical features of acute flaccid myelitis
Prodromal illness • Occurs in most patients • Common symptoms: fever, wheeze, cough, rhinorrhea • Less common symptoms: vomiting and diarrhea • Sick contacts often reported
Weakness • Limbs (1 to 4): upper > lower extremities, proximal > distal muscles, usually asymmetric • Neck, axial, respiratory, bulbar, facial, and extraocular muscles can also be affected • Flaccid areflexic/hyporeflexic weakness • Respiratory failure common • Evolves over hours to days
Other possible neurological manifestations • Headache or neck stiffness at onset of weakness • Neuropathic pain in affected limbs, neck, or back • Autonomic features: bladder dysfunction, bowel dysfunction, labile blood pressure, cardiac arrhythmia

Table 3. Differential diagnosis of acute flaccid paralysis
	Acute flaccid myelitis	Transverse myelitis	Spinal cord stroke	Guillain–Barré syndrome	Acute disseminated encephalomyelitis
Prodromal illness	Yes	Frequent	No	Possible	Frequent
Neurological evolution	Hours to days	Days to weeks	Hours	Hours to days	Days to weeks
Motor deficits	Always	Frequent	Always	Frequent	Frequent
Sensory deficits	Minimal	Almost always	Possible	Frequent	Frequent
Bladder/bowel dysfunction	Possible	Frequent	Frequent	Possible	Frequent
Encephalopathy	Uncommon	No	No	No	Yes
CSF white cell count	Moderate pleocytosis	Mild to moderate pleocytosis	Normal to mild pleocytosis	Normal to mild pleocytosis	Mild to moderate pleocytosis
CSF protein	Normal to mild elevation	Normal to mild elevation	Normal to mild elevation	Moderate to marked elevation as syndrome evolves	Normal to mild elevation
MRI spine lesion(s)	Extensive gray matter hyperintensity and edema	Discrete lesion(s), white ± gray matter	Typically anterior cord lesion, gray matter predominant	No	Discrete lesion(s), white ± gray matter
MRI spine enhancement	Possible (nerve roots)	Yes	None to minimal	Possible (nerve roots)	Yes
Brainstem MRI lesion(s)	Common: dorsal pons	Uncommon	No	No	Possible
Supratentorial MRI lesions	Uncommon	Depends on etiology	No	No	Yes
EMG/NCS: motor neuropathy/neuronopathy	Yes	Rarely	Often	Possible with some variants	Rarely