What is the differential diagnosis for acute transverse myelitis?

Differential Diagnosis for Acute Transverse Myelitis

The differential diagnosis for acute transverse myelitis is extensive and must systematically exclude infectious, inflammatory, vascular, compressive, metabolic, and toxic etiologies, with particular attention to distinguishing it from multiple sclerosis, neuromyelitis optica spectrum disorder, and Guillain-Barré syndrome based on clinical presentation and MRI characteristics.

Demyelinating and Inflammatory Disorders

Primary Demyelinating Conditions

• Multiple sclerosis (MS): Distinguished by dissemination in time and space on MRI, with lesions typically shorter than 3 vertebral segments 1
• Neuromyelitis optica spectrum disorder (NMOSD): Characterized by longitudinally extensive transverse myelitis (LETM) affecting ≥3 contiguous vertebral segments, positive aquaporin-4 IgG antibody, and specific MRI patterns including dorsal medulla/area postrema lesions 1, 2, 3
• Acute disseminated encephalomyelitis (ADEM): Monophasic demyelinating disease that should not be diagnosed as MS unless new symptoms or imaging abnormalities appear more than 3 months after clinical onset 1, 3
• MOG antibody-associated disorder: Presents with demyelinating features distinct from classic MS 1

Other Inflammatory Conditions

• Sarcoidosis: Systemic granulomatous disease with CNS involvement 1
• Sjögren syndrome: Autoimmune disorder with potential spinal cord involvement 1
• Systemic lupus erythematosus: Can cause acute disseminated lupus erythematosus with spinal cord manifestations 1

Infectious Etiologies

Viral Infections

• HIV-associated myelitis: Direct viral infection or metabolic disturbance in AIDS patients 1, 4
• HTLV-1 myelopathy: Chronic progressive myelitis from direct spinal cord infection 1, 4
• Herpes viruses: Including cytomegalovirus, Epstein-Barr virus, varicella zoster virus, and herpes simplex virus 1
• Arthropod-borne viruses: Zika virus, chikungunya virus, West Nile virus causing acute flaccid myelitis 1
• Enteroviruses: Enterovirus D68 and A71 causing acute flaccid paralysis 1, 2, 4
• Poliovirus: Causes acute flaccid paralysis through cytolytic infection of anterior horn cells 1, 4
• Rabies: Endemic in certain regions, particularly low-income countries 1

Bacterial and Spirochetal Infections

• Lyme borreliosis: Polyradiculoneuritis from Borrelia burgdorferi, more common in Europe and North America 1
• Syphilis: Meningovascular syphilis can mimic demyelinating disease 1
• Tuberculosis: Can cause transverse myelitis, particularly in endemic regions 1
• Diphtheria: Bacterial infection causing polyradiculoneuritis 1

Vascular Disorders

• Spinal cord infarction: Acute ischemic injury to the spinal cord 1
• Vasculitis: Inflammatory vessel disease affecting spinal cord perfusion 1
• Phospholipid antibody syndrome: Multifocal cerebral ischemia or infarction in young adults 1
• CADASIL: Cerebral autosomal dominant arteriopathy with subcortical infarcts 1
• Takayasu's disease: Large vessel vasculitis 1
• Carotid dissection: Can present with neurologic deficits 1

Compressive and Structural Lesions

• Spinal cord compression: From tumor, abscess, or herniated disc requiring urgent exclusion 1, 5
• Brainstem or spinal cord tumors: Primary or metastatic malignancies 1
• Leptomeningeal metastases or neurolymphomatosis: Malignant infiltration of meninges 1
• Cauda equina syndrome: Compression of nerve roots below the spinal cord 1

Peripheral Nerve and Neuromuscular Disorders

Critical Distinction from Guillain-Barré Syndrome

• Guillain-Barré syndrome (GBS): Presents with flaccid paralysis and reduced/absent reflexes due to peripheral nerve involvement, contrasting with the spastic paralysis and hyperreflexia seen in transverse myelitis from upper motor neuron damage 2, 5
• Chronic inflammatory demyelinating polyneuropathy (CIDP): Acute onset variant can mimic transverse myelitis 1
• Myasthenia gravis: Neuromuscular junction disorder 1
• Lambert-Eaton myasthenic syndrome: Presynaptic neuromuscular disorder 1

Metabolic and Nutritional Disorders

• Vitamin B12 deficiency: Causes subacute combined degeneration of the spinal cord 1
• Vitamin B1 deficiency: Associated with beriberi or Wernicke's encephalopathy 1
• Vitamin E deficiency: Can cause myelopathy 1
• Copper deficiency: Causes myeloneuropathy 1
• Electrolyte disorders: Hypokalaemia, hypokalaemic thyrotoxic periodic paralysis, hypophosphataemia, hypermagnesaemia 1
• Thyroid disorders: Hyperthyroidism and hypothyroidism 1
• Porphyria: Metabolic disorder affecting nervous system 1

Toxic Exposures

• Organophosphate poisoning: Common toxic cause, particularly in agricultural regions 1
• Heavy metal poisoning: Lead, thallium, arsenic 1
• Toxic alcohols: Diethylene glycol, ethylene glycol, methanol, ethanol 1
• Industrial toxins: N-hexane, paraquat 1
• Drug-induced: Colchicine, chloroquine, emetine, statins 1
• Snakebite envenomation: Regional consideration in endemic areas 1

Other Conditions

• Paraneoplastic syndromes: Cerebellar ataxia or myelopathy associated with malignancy, often with elevated CSF IgG 1
• Critical illness polyneuropathy: In intensive care settings 1
• Acute rhabdomyolysis or myopathy: Muscle breakdown causing weakness 1
• Mitochondrial disease: Genetic disorders affecting energy metabolism 1
• Leukodystrophies: Genetic disorders of myelin, particularly in children and teenagers 1
• Functional/conversion disorder: Psychogenic cause requiring exclusion of organic pathology 1
• Botulism and tetanus: Clostridial infections causing paralysis 1
• Meningitis/meningoencephalitis: Infectious or inflammatory involvement of meninges and brain 1

Key Clinical Pitfalls

A critical diagnostic error is failing to recognize that transverse myelitis causes spastic paralysis with hyperreflexia (upper motor neuron signs), while conditions like Guillain-Barré syndrome cause flaccid paralysis with hyporeflexia (lower motor neuron signs) 2, 5. This fundamental distinction guides the entire diagnostic workup and prevents misdiagnosis.

Geographic variation significantly impacts the differential diagnosis, with infections like HIV, HTLV-1, and arboviral diseases more common in low- and middle-income countries, while Lyme disease and certain autoimmune conditions predominate in high-income countries 1.

The presence of longitudinally extensive transverse myelitis (≥3 vertebral segments) should immediately raise suspicion for NMOSD and prompt aquaporin-4 IgG testing 1, 2. Conversely, shorter lesions with periventricular brain involvement suggest MS 1.

Pediatric cases require special consideration, as vascular causes, vitamin deficiencies, and chronic inflammatory demyelinating polyneuropathy occur less frequently in children, while infectious causes and atypical presentations with meningism are more common 1.