IMMUNE-MEDIATED CNS DISEASES (MS)

What is the fundamental mechanism underlying immune-mediated CNS diseases?

Loss of immune tolerance → immune system attacks self-antigens in the nervous system.

What normally prevents autoimmune attack in the CNS?

Immune tolerance mechanisms that distinguish self from non-self.

What goes wrong in autoimmune CNS diseases?

Self-antigens are misidentified as foreign → immune-mediated attack.

What immune components drive CNS autoimmune disease?

Autoreactive T cells, autoantibodies, and abnormal antigen presentation.

What is epitope spreading?

Expansion of immune response to new self-antigens, worsening disease over time.

What are the four main immune-mediated CNS diseases?

MS, ADEM, NMO, autoimmune encephalitis.

Which disease is chronic and demyelinating?

Multiple sclerosis.

Which disease is acute and post-infectious?

ADEM.

Which disease targets astrocytes via antibodies?

Neuromyelitis optica.

What is the definition of multiple sclerosis?

An immune-mediated CNS disease with inflammation disseminated in space and time causing demyelination and neurodegeneration.

What is the first step in MS pathogenesis?

Loss of immune tolerance → autoreactive T cells escape.

What triggers MS immune activation?

EBV, genetics, and environmental factors.

How do immune cells enter the CNS in MS?

By crossing the blood–brain barrier.

What occurs during CNS inflammation in MS?

Activation of T cells, B cells, macrophages, and cytokine release.

What structure is primarily damaged in MS?

Myelin (via oligodendrocyte injury).

What causes permanent disability in MS?

Axonal damage and neurodegeneration.

What dominates early vs late MS pathology?

Early = inflammation; late = neurodegeneration.

What is the sequence of MS pathophysiology?

Immune activation → BBB crossing → inflammation → demyelination → axonal loss.

What is the function of myelin?

Enables rapid saltatory conduction.

What happens to conduction when myelin is lost?

Slowing or complete conduction block.

Why do MS symptoms occur?

Conduction failure in demyelinated pathways.

What types of symptoms result from demyelination?

Weakness, sensory loss, and visual disturbances.

What is the strongest genetic risk factor for MS?

HLA-DRB1*1501.

What virus is strongly linked to MS?

Epstein-Barr virus.

What environmental factors increase MS risk?

Low vitamin D and smoking.

What populations have higher MS prevalence?

Females and people at higher latitudes.

What is the key concept linking MS risk factors?

Gene–environment interaction.

What are the three clinical types of MS?

RRMS, SPMS, PPMS.

What defines relapsing-remitting MS?

Attacks with recovery between episodes.

What defines secondary progressive MS?

Gradual worsening after relapsing phase.

What defines primary progressive MS?

Progressive decline from onset.

How does MRI activity compare to clinical relapses in MS?

~10:1 (most disease is subclinical).

What defines an MS relapse?

New neurological symptoms lasting >24 hours due to inflammation.

What must be excluded before diagnosing a relapse?

Fever, infection, or heat (pseudo-relapse).

What is a classic example of MS relapse?

Optic neuritis (vision loss + eye pain).

What is the core diagnostic principle of MS?

Dissemination in space and time.

What does MRI show in MS?

Lesions in multiple CNS regions.

What CSF finding supports MS diagnosis?

Oligoclonal IgG bands.

Are oligoclonal bands diagnostic of MS?

No, they are supportive only.

What do visual evoked potentials detect in MS?

Slowed conduction due to demyelination.

Why does MS disability progress even without relapses?

Ongoing neurodegeneration (axonal loss, mitochondrial failure, microglial activation).

How are MS relapses treated?

High-dose corticosteroids.

What is the goal of disease-modifying therapies (DMTs)?

Reduce relapses and slow disability progression.

What is the modern treatment target in MS?

NEDA (No Evidence of Disease Activity).

What is ADEM and how does it differ from MS?

Acute, post-infectious CNS inflammation with encephalopathy and simultaneous lesions.

What CSF finding is often absent in ADEM?

Oligoclonal bands.

What antibody causes neuromyelitis optica?

Aquaporin-4 antibody.

What is primarily damaged in NMO?

Astrocytes.

What are key clinical features of autoimmune encephalitis?

Memory loss, behavioural change, and seizures.