Demyelinating Diseases
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Direct answer
Dissemination in time and space defines multiple sclerosis: immune-mediated demyelination of the central nervous system producing periventricular, juxtacortical, infratentorial and spinal cord plaques, a relapsing-remitting course in most patients, and oligoclonal immunoglobulin G bands in the cerebrospinal fluid. Neuromyelitis optica spectrum disorder, proportionately commoner in Indian and other Asian populations than in the West, is an aquaporin-4 antibody disease that strikes optic nerves and longitudinally extensive spinal cord lesions, needs different therapy, and behaves differently enough that mislabelling it as multiple sclerosis harms patients. Central pontine myelinolysis — osmotic demyelination — follows over-rapid correction of hyponatraemia and is iatrogenic in origin.
What you must remember
- Plaque pathology: sharply demarcated perivenular demyelination with relative axonal preservation, macrophages laden with myelin debris, CD4 lymphocyte and macrophage infiltrate; gliosis gives the hardened plaque its name; shadow plaques mark partial remyelination.
- Classic sites: periventricular white matter (Dawson fingers pointing toward ventricles), optic nerve, brainstem, cerebellar peduncles, cervical cord — symptoms follow sites: optic neuritis, internuclear ophthalmoplegia, sensory and motor relapses.
- Charcot triad: nystagmus, intention tremor and scanning (explosive) speech — the classical bedrock viva answer for established multiple sclerosis.
- Diagnosis: McDonald criteria — dissemination in time (new lesions on serial imaging or gadolinium-enhancing plus non-enhancing lesions at once) and in space (lesions in at least two of the characteristic sites), supported by oligoclonal bands.
- Neuromyelitis optica: aquaporin-4 immunoglobulin G; severe often-bilateral optic neuritis plus longitudinally extensive transverse myelitis spanning three or more vertebral segments; relapse prevention uses immunosuppression such as rituximab or azathioprine, and attacks are treated with methylprednisolone and plasma exchange.
- ADEM: acute disseminated encephalomyelitis of children after infection or vaccination — monophasic, multifocal, perivenular demyelination with fever and encephalopathy.
- Osmotic demyelination: central pontine myelinolysis when hyponatraemia (classically below about 120 millimoles per litre) is corrected faster than roughly 8 to 10 millimoles per day — quadriparesis, dysarthria and the locked-in state; alcoholics and malnourished patients are most susceptible.
- Progressive multifocal leukoencephalopathy closes the differential: JC virus demyelination without inflammation in the immunosuppressed.
Two cord lesions, two antibodies
A 28-year-old woman develops numbness of both legs over a week, with a spinal cord lesion on magnetic resonance imaging. The single most consequential question is how long the lesion is. A short, eccentric, peripherally located lesion with a normal aquaporin-4 antibody fits multiple sclerosis: the management is immunomodulation, and the long-term enemy is stepwise accumulation of disability. A lesion spanning six vertebral segments with cavitation and a positive aquaporin-4 immunoglobulin G fits neuromyelitis optica spectrum disorder — proportionately commoner in Indian patients — where the disease is relapse-driven, each attack potentially devastating, and the treatment is sustained immunosuppression with agents such as rituximab or azathioprine, with plasma exchange reserved for severe attacks.
The consequences of confusing them are concrete: interferons, the traditional multiple sclerosis platform, are ineffective or arguably harmful in neuromyelitis optica, so the antibody test is not academic. Add the CSF contrast — oligoclonal bands typical of multiple sclerosis, usually absent in neuromyelitis optica — and the separation is robust at the bedside. The third member of the triad, MOG antibody disease, announces itself in younger patients with ADEM-like multifocal demyelination after infection, often recovering well; its recognition spares patients lifelong therapy they may not need. This reasoned comparison is the section of the topic that distinguishes a prepared candidate.
Where students slip
The iatrogenic trap is the memorable one: a postoperative sodium of 112 corrected enthusiastically to 140 within a day produces a quadriparetic patient with a trident-shaped pontine lesion — prevention is gradual correction, which is why fluid balance questions in orals end at demyelination. Second, "dissemination in time and space" is recited without content; the exam wants the imaging translation — new lesions on serial scans, or simultaneous enhancing and non-enhancing lesions. Third, every white matter lesion in a young adult is called multiple sclerosis, overlooking neuromyelitis optica's Indian relevance and ADEM's monophasic post-infectious pattern.
Frequently asked questions
Which criteria diagnose multiple sclerosis and what do they require?
The McDonald criteria — dissemination of lesions in time and space, demonstrated clinically or by magnetic resonance imaging, supported by cerebrospinal oligoclonal bands.
What are oligoclonal bands?
Bands of immunoglobulin G on electrophoresis of cerebrospinal fluid, indicating intrathecal antibody synthesis, present in the great majority of multiple sclerosis patients.
What defines a longitudinally extensive transverse myelitis?
A spinal cord lesion spanning three or more vertebral segments, characteristic of aquaporin-4 positive neuromyelitis optica spectrum disorder, commoner in Indian patients.
Which antibody distinguishes neuromyelitis optica from multiple sclerosis?
Aquaporin-4 immunoglobulin G, targeting the water channel on astrocyte end-feet; its positivity redirects therapy from immunomodulation to immunosuppression.
Why does rapid correction of hyponatraemia cause demyelination?
Adapted brain cells lose osmolytes during chronic hyponatraemia; rapid sodium rise outpaces osmotic recovery, killing oligodendrocytes in the pons — osmotic demyelination.
What is acute disseminated encephalomyelitis?
A monophasic post-infectious or post-vaccinial demyelination of children with encephalopathy and multifocal deficits, treated with corticosteroids and generally recovering.