Demyelinating Diseases Overview

Demyelinating Diseases

• Demyelinating diseases are a group of neurological disorders.
• These are acquired conditions causing preferential damage to myelin, while preserving axons.
• Classifications include infectious, immune-mediated, inherited, and metabolic types.

Learning Objectives

• Define demyelinating diseases.
• Categorize different types of demyelinating diseases.
• Detail the aetiology, morphology and clinical features of multiple sclerosis.

Classification of Demyelinating Disorders

• Infective: Progressive Multifocal Leukoencephalopathy (PMLE), Subacute Sclerosing Panencephalitis (SSPE).
• Immune-mediated: Multiple Sclerosis (MS).
• Inherited: Adrenoleukodystrophy, Metachromatic leukodystrophy, other leukodystrophies.
• Metabolic: Vitamin B12 deficiency, Central pontine myelinolysis.

Demyelinating Disease Definition

• A demyelinating disease targets the nervous system, damaging the myelin sheath of neurons.
• Damage impairs signal transmission in nerves.
• Results in deficiencies in sensation, movement, cognition, or other functions.
• Causes can span genetics, infectious agents, autoimmune responses or unknown factors.

Types of Demyelinating Diseases

• Demyelinating myelinoclastic diseases: The healthy myelin is destroyed by toxic, chemical or autoimmune substances.
• Demyelinating leukodystrophic diseases: Myelin is abnormal and degenerates. This type of demyelination has also been termed "dysmyelinating" by Poser.

Multiple Sclerosis (MS)

• In MS, the body's immune system plays a role in the damage.
• T-cells are present in lesions.
• Macrophages (and possibly mast cells) contribute to the damage.
• This is an inflammatory demyelinating disease of the central nervous system.

Proposed causes for demyelination

• Genetics is a factor.
• Environmental factors, such as viral infections or chemical exposure.
• Organophosphate poisoning.
• Chronic exposure to neuroleptics (drugs).
• Vitamin B12 deficiency.

Pathology of MS

• MS is a chronic inflammatory disease targeting the CNS, characterized by acute and chronic lesions in the white matter.
• Repeated inflammation attacks lead to demyelination of axons.
• Neuron transmission is compromised, as electrical signals can't be restored.
• Axonal loss might even occur early, before symptoms are visible.

Other Demyelinating Disorders

• Neuromyelitis optica (bilateral optic neuritis).
• Acute disseminated encephalomyelitis (ADEM).
• Acute necrotizing hemorrhagic leukoencephalitis (a post-viral or post-vaccine condition).
• Central pontine myelinolysis

Demyelination and Axonal Degeneration in MS

• Charts illustrating the stages from normal myelination to complete demyelination and axonal degeneration in Multiple Sclerosis.

Immunological Mechanism in MS

• Elevated IgG levels present in the cerebrospinal fluid (CSF) of MS patients are noted.
• Oligoclonal bands are seen in CSF immunoelectrophoresis, but not in serum.
• Myelin basic protein-reactive T lymphocytes are present in both CSF and serum of MS patients.

Clinical Course of MS

• MS can exhibit different courses.
• Unpredictable/ rapidly progressive.
• Benign: Mild exacerbations; complete remissions; minimal disability.
• Exacerbation-remitting: Periods of worsening followed by recovery.
• Chronic relapsing: Progressive condition with relapses and partial recoveries.
• Chronic progressive: Continuous worsening.

Clinical Manifestations of Demyelinating Diseases

• General symptoms: Headache, delirium, coma, seizures, meningeal irritation, fever.
• Focal neurological signs: Depending on the affected nerves.
• Rare: Spinal cord involvement; cerebellum and cranial nerve palsies.
• Cerebrospinal fluid (CSF): Increased protein, increased lymphocytes; rarely, it is normal.

Symptoms and Signs of Demyelinating Diseases

• Visual symptoms: Diplopia, facial pain, vertigo, dizziness, hearing disorders, and signs suggesting cranial neuritis.
• Internuclear ophthalmoplegia (INO): Reduced adduction of the eye.
• Suggestive of long tracts systems involvement: Weakness, pyramidal signs, patchy sensory distribution, chronic pain, dysaesthesia, painful leg spasms.
• Sphincter disorders: Frequency, urgency, incontinence, hesitation, difficulty starting urination, constipation, fecal incontinence.
• Cognitive and psychiatric abnormalities: Memory loss, concentration problems, executive dysfunction, depression, anxiety, euphoria.

Diagnosis of MS

• No single test confirms MS.
• Diagnosis relies on multiple symptoms, including multiple signs, exacerbations, and remissions.
• Clinical criteria used for diagnosis.

Differential Diagnoses of Demyelinating Diseases

• Encephalomyelopathy
• Systemic lupus erythematosus (SLE), and central nervous system vasculitis.
• Vascular malformation
• Gliomas of the brainstem
• Syringomyelia
• Progressive multifocal leukoencephalopathy
• Infections (e.g., Brucella, tuberculosis, AIDS).

Laboratory Tests for Demyelinating Diseases

• There are no definite laboratory tests for many demyelinating diseases.
• Neuroimaging (MRI)
• Cerebrospinal fluid (CSF) analysis.
• Evoked response studies (e.g., visual-evoked potentials).

MRI for Demyelination

• MRI is used to identify lesions.
• FLAIR (Fluid Attenuated Inversion Recovery) and T1 with gadolinium enhancement scans.
• The technique identifies "black holes" in the T1 scans that show demyelination.

Oligoclonal Bands in CSF

• Bands in the CSF are used to detect immune response in MS.
• Detects patterns that differentiate between normal and abnormal CSF sample.

Visual evoked potentials

• Evoked potential studies provide a neurophysiological means of assessing optic nerve involvement and demyelinating diseases.

Acute Disseminated Encephalopathy

• Acute inflammatory condition in the brain, potentially affecting the spinal cord.
• Monophasic encephalitis or myelitis are noted.
• White matter of the brain or spinal cord is often affected.
• Process severity ranges from mild to severe and fatal.
• Follow-up after vaccinations and acute infections. May not have an obvious antecedent when it presents.

This quiz covers demyelinating diseases, their definitions, classifications, and specific conditions such as Multiple Sclerosis. Participants will explore the various types, including infectious and immune-mediated disorders, along with their clinical features. Gain a comprehensive understanding of these neurological conditions and their impact on the myelin sheath.