What are the major demyelinating disorders, such as Multiple Sclerosis (MS), Guillain-Barré Syndrome (GBS), Chronic Inflammatory Demyelinating Polyneuropathy (CIDP), and Acute Disseminated Encephalomyelitis (ADEM)?

Major Demyelinating Disorders

The major demyelinating disorders include Multiple Sclerosis (MS), Neuromyelitis Optica Spectrum Disorder (NMOSD), MOG-antibody associated encephalomyelitis (MOG-EM), Acute Disseminated Encephalomyelitis (ADEM), Guillain-Barré Syndrome (GBS), and Chronic Inflammatory Demyelinating Polyneuropathy (CIDP). These can be systematically categorized by their anatomic location—central nervous system (CNS) versus peripheral nervous system (PNS)—and their temporal course—acute versus chronic 1.

Central Nervous System Demyelinating Disorders

Multiple Sclerosis (MS)

• MS is the most frequent demyelinating disorder of the CNS, characterized by focal demyelinated lesions with partial axonal preservation affecting both white and gray matter 1.
• The pathologic hallmark includes demyelinated plaques in cerebral cortex, cerebellar cortex, brainstem nuclei, and spinal cord, with lesions disseminated in space and time 2, 1.
• Spinal cord involvement occurs in 80-90% of MS patients, most commonly affecting the cervical cord 2.
• MS can present as relapsing-remitting, secondary progressive, or primary progressive forms, with qualitatively similar pathology but quantitatively different lesion prevalence 1.

Neuromyelitis Optica Spectrum Disorder (NMOSD)

• NMOSD is an inflammatory disease with primary astrocyte injury mediated by aquaporin-4 (AQP4) antibodies, distinct from MS 1.
• Characterized by optic neuritis and longitudinally extensive transverse myelitis (LETM), defined as spinal cord lesions ≥3 vertebral segments 2.
• Brain lesions, when present, tend to predominate around the third and fourth ventricles, unlike the periventricular distribution in MS 2.

MOG-Antibody Associated Encephalomyelitis (MOG-EM)

• MOG-EM presents with monophasic or relapsing acute optic neuritis, myelitis, brainstem encephalitis, or encephalitis 2.
• Distinguished by MOG-IgG antibodies and features including longitudinally extensive optic nerve lesions, prominent papilledema, bilateral simultaneous optic neuritis, and absence of CSF-restricted oligoclonal bands 2.
• More frequent in young children with acquired demyelinating disease (up to 70%) compared to adults (≤1% in Western countries) 2.

Acute Disseminated Encephalomyelitis (ADEM)

• ADEM is a monophasic demyelinating condition typically manifesting as encephalopathy, often post-infectious 2.
• Spinal cord involvement occurs in approximately 25% of ADEM cases 2.
• MRI shows large, confluent T2 brain lesions, distinguishing it from MS which shows periventricular ovoid lesions and Dawson's fingers 2.
• Disease onset often occurs within 4 days to 4 weeks after vaccination 2.

Peripheral Nervous System Demyelinating Disorders

Guillain-Barré Syndrome (GBS)

• GBS is an acute inflammatory demyelinating polyradiculoneuropathy and the most common cause of acute flaccid paralysis, with global incidence of 1-2 per 100,000 person-years 2.
• Presents with ascending weakness and sensory signs, typically starting in legs and progressing to arms and cranial muscles 2.
• Characterized by flaccid paralysis with areflexia or hyporeflexia due to peripheral nerve involvement 3.
• Electrophysiological subtypes include acute inflammatory demyelinating polyradiculoneuropathy (AIDP), acute motor axonal neuropathy (AMAN), and acute motor sensory axonal neuropathy (AMSAN) 2.
• Most patients reach maximum disability within 2 weeks; 20% develop respiratory failure requiring mechanical ventilation 2.
• Mortality is 3-10% even with optimal care, partly due to autonomic nervous system involvement causing cardiac arrhythmias and blood pressure instability 2.

Chronic Inflammatory Demyelinating Polyneuropathy (CIDP)

• CIDP is characterized by progressive or relapsing symmetric weakness with areflexia or hyporeflexia and flaccid paralysis 3, 4.
• Represents a significant proportion of initially undiagnosed acquired neuropathies 4.
• Distinguished from transverse myelitis by absence of hyperreflexia—CIDP shows peripheral nerve demyelination while transverse myelitis shows upper motor neuron involvement with spastic paralysis 3.

Critical Diagnostic Distinctions

Acute-Onset CIDP versus GBS

• Acute-onset CIDP (A-CIDP) can initially mimic severe GBS but shows arrest in improvement or deterioration during rehabilitation phases 5.
• Close follow-up during the recovery phase with serial electrodiagnostic studies showing prominent demyelinating changes months after presentation distinguishes A-CIDP from GBS 5.

ADEM versus Malignant MS

• Good clinical outcome from a postinfectious, monophasic episode correlating with regressive demyelinating lesions on MRI after more than 2 years best differentiates ADEM from malignant MS 6.
• Initial MRI lesions and therapeutic efficacy have limited value in early differentiation 6.

Common Diagnostic Pitfalls

• Confusing hyperreflexia with areflexia is a critical error—this single finding distinguishes upper motor neuron pathology (transverse myelitis, MS) from peripheral nerve pathology (GBS, CIDP) 3.
• Longitudinally extensive transverse myelitis in young adults is rarely MS; MOGAD or NMOSD should be considered first 3.
• Progressive disease course makes MOG-EM highly unlikely due to very low pre-test probability 2.