CNS Diseases and Demyelination Quiz

Diseases of the CNS

• Acquired conditions preferentially damage myelin, preserving axons, affecting impulse transmission.
• Demyelination results from immune-mediated destruction, infections, and inherited disorders.
• Cerebral Edema, Hydrocephalus, Raised Intracranial Pressure & Herniation, Congenital Anomalies, Trauma & Infection, Cerebrovascular Disease, Tumors, and Toxic and Acquired Metabolic Disease are all CNS diseases.

Demyelinating Diseases of the CNS

• Demyelinating diseases are caused by various pathologic processes.
• Multiple sclerosis (MS) is the most common demyelinating disorder.
• Neuromyelitis Optica (NMO) targets aquaporin-4 (AQP4), the major water channel of astrocytes.
• Central Pontine Myelinolysis is associated with rapid correction of hyponatremia.

Multiple Sclerosis (MS)

• MS is an immune-mediated disease with distinct episodes of neurological deficits.
• Onset is rare in childhood or after 50 years of age.
• Women are affected twice as often as men.
• Lesions occur anywhere in the CNS, leading to diverse clinical manifestations.
• Optic neuritis, brainstem involvement, and spinal cord lesions are common symptoms.
• CSF examination shows elevated protein levels and moderate pleocytosis.
• Grossly, lesions appear firm, well-circumscribed, and depressed.
• Microscopically, active plaques are cellular with lipid-laden macrophages.

Multiple Sclerosis (MS): Immunopathogenesis

• Pre-existing autoreactive T-cells are activated in the periphery.
• Activated T-cells migrate into the CNS and proliferate.
• T-cells are reactivated by encountering CNS antigens presented by antigen-presenting cells.

Neuromyelitis Optica (NMO)

• NMO primarily affects women.
• It involves synchronous optic neuritis and spinal cord demyelination.
• The presence of aquaporin-4 antibodies (AQP4 IgG) is a defining characteristic.
• Acute attacks are treated with glucocorticoids or plasma exchange.
• Long-term therapies aim to decrease antibody titers or inhibit complement.

Central Pontine Myelinolysis

• Also known as Osmotic Demyelination Syndrome.
• Characterized by myelin loss in the pons.
• Occurs due to rapid osmolality increase, damaging oligodendrocytes.
• Onset occurs 2 to 6 days after rapid correction of hyponatremia.
• Central Pontine Myelinolysis is also known as Osmotic Demyelination Syndrome.

Neurodegenerative Diseases

• Neurodegenerative diseases are characterized by the progressive loss of neurons, often associated with protein aggregates.
• They can be classified by anatomic localization and pathologic features.
• Each disease is characterized by unique clinical patterns, inclusions, and genetic causes.

Prion Diseases

• Prion diseases are rapidly progressive neurodegenerative disorders caused by prion protein (PrP) misfolding.
• They can be sporadic, familial, or transmitted.
• PrP misfolding leads to protein aggregation and intercellular spread.
• Spongiform change and rapid dementia are characteristic.

Prion Diseases: Examples

• Creutzfeldt-Jakob disease is the most common type.
• Sporadic forms account for 90% of cases.
• Familial forms are caused by mutations in the PRNP gene.
• Gerstmann-Sträussler-Scheinker syndrome, Fatal Familial Insomnia, Kuru (Human), Scrapie, and Bovine Spongiform Encephalitis are other examples.

Alzheimer Disease (AD)

• The most prevalent cause of dementia in older adults.
• Prevalence doubles every 5 years, affecting older populations significantly.
• Early signs include cognitive impairment and memory deficits.
• Gradually, it progresses to profound disability, muteness, and immobility.
• Hallmark features are amyloid plaques and neurofibrillary tangles.

Alzheimer Disease (AD): Pathology

• Amyloid plaques are deposits of aggregated Aẞ peptides in the neuropil.
• Neurofibrillary tangles are aggregates of microtubule-binding protein tau, found intracellularly and extracellularly.
• Damaged mitochondria, oxidative stress, Aß dimerization, neuronal loss, and genetic factors like APP gene mutations contribute to AD pathology.

Parkinson Disease (PD)

• A neurodegenerative disease caused by loss of dopaminergic neurons in the substantia nigra.
• It presents as Parkinsonism, characterized by masked facies, stooped posture, slowed movement, festinating gait, rigidity, and tremor.
• Diagnosis is based on Parkinsonism triad without toxic or other underlying etiologies.

Parkinson Disease (PD): Pathology

• Lewy bodies, accumulations of α-synuclein, are a diagnostic hallmark.
• Mitochondrial dysfunction and mutations in genes like DJ-1, PINK1, parkin, and LRRK2 are implicated in PD pathogenesis.

Huntington Disease (HD)

• An autosomal dominant disease resulting in striatal neuron degradation.
• It causes progressive movement disorder and dementia.
• Jerky, hyperkinetic movements, bradykinesia, and rigidity are early signs.
• It's relentless and fatal, with an average course of 15 years.
• Caudate nucleus and putamen atrophy are prominent features.
• Microscopic examination reveals striatal neuronal loss and huntingtin-containing protein aggregates.

Huntington Disease (HD): Genetics

• Caused by a trinucleotide repeat expansion in the HTT gene.
• The expanded CAG repeats encode a polyglutamine region in the huntingtin protein.

Amyotrophic Lateral Sclerosis (ALS)

• A progressive disorder with loss of upper and lower motor neurons.
• Leading to muscle denervation and weakness, ultimately resulting in paralysis.
• Most common form is sporadic, but familial forms account for 20% of cases.

Amyotrophic Lateral Sclerosis (ALS): Pathology

• Degeneration of upper and lower motor neurons with toxic protein accumulation.
• Mutations in SODD1, C9orf72, TDP-43, and FUS genes are associated with ALS.

Vitamin Deficiencies

• Thiamine (Vitamin B1) deficiency causes Wernicke-Korsakoff syndrome.
• Wernicke encephalopathy is characterized by acute psychosis and ophthalmoplegia.
• Korsakoff syndrome involves short-term memory disturbance and confabulation.
• Vitamin B12 deficiency leads to Subacute combined degeneration of the spinal cord.
• Lesions affect myelin formation, causing numbness, tingling, and ataxia in the lower extremities.

Neurologic Sequelae of Metabolic Disturbances

• Hypoglycemia impairs brain energy production, causing selective damage to cortical neurons.
• Hyperglycemia, associated with uncontrolled diabetes, leads to ketoacidosis or hyperosmolar coma.
• Hepatic Encephalopathy, occurring with liver dysfunction, involves elevated ammonia levels and proinflammatory cytokines.
• Carbon monoxide exposure inhibits tissue oxygen utilization, causing selective neuronal injury.
• Chronic alcohol abuse is linked to various neurologic sequelae, including Wernicke-Korsakoff syndrome and cerebellar dysfunction.

74 year old female with blunt head trauma

• Patient presents with a right temporal bone fracture and mild cerebral edema following a motor vehicle accident.
• Two days later, her serum sodium levels are low (109 mmol/L).
• After correcting her hyponatremia, she rapidly becomes confused and exhibits limb weakness.
• This is most likely due to central pontine myelinolysis (CPM), a serious neurological complication caused by rapid correction of hyponatremia, especially in individuals with existing brain injury.

Central Pontine Myelinolysis

• CPM is a demyelinating disorder that affects the pons, a part of the brainstem responsible for motor control, sensation, and consciousness.
• Symptoms include confusion, weakness, paralysis, and difficulty swallowing.
• Fundoscopic examination is usually normal, as CPM does not typically cause papilledema.
• Although rare, CPM can occur in patients with severe hyponatremia, rapid correction of hyponatremia, or underlying brain injury.

Key Points

• Rapid correction of hyponatremia can be dangerous, especially in patients with brain injury.
• Central pontine myelinolysis (CPM) is a serious complication of rapid hyponatremia correction.
• Patients with CPM should be monitored closely for neurological deterioration.

Test your knowledge on various diseases of the central nervous system (CNS), with a focus on demyelinating conditions such as Multiple Sclerosis and Neuromyelitis Optica. This quiz covers the mechanisms, symptoms, and pathologies associated with CNS diseases. Dive into understanding the complexities of how these conditions affect the nervous system.