Demyelinating Diseases Flashcards
Demyelinating Disorders
Disorders characterized by loss of myelin around the axons
Types of Myelin Disorders
- Loss of myelination (demyelination) - damage to normal myelin
- Multiple sclerosis, Myelinolysis & Post-infectious/immune (ADEM, AHEM) - Improper formation of myelin (Dysmyelination) - defective myelin synthesis or turnover
Multiple Sclerosis
Autoimmune demyelinating disorder w/ episodes of disease activity that produce white matter lesions
MC demyelinating disease
“Relapsing & Remitting” course
Epidemiology, Etiology & RFs of MS
F:M = 2:1 (Young adults- 20-30 years) Unknown etiology - Smoking - Low Vit D (Farther away from equator) - Race (white) - EBV infection - Genes- HLA-DR Exacerbated by Inc body temp (hot baths, exercise)
Pathogenesis of MS
Autoimmune response directed against components of the myelin sheath
• Th1 and Th17 T cells react against myelin antigens and secrete cytokines –>
recruitment and activation of leucocytes –> demyelination
Both genetic and environmental factors are implicated
Gross morphology changes in MS
- Multifocal white matter lesion
Plaques
- Firmer than surrounding areas
- Well-circumscribes, slightly depressed, glassy appearing, gray-tan lesions
- Commonly adjacent to ventricles, in optic nerves, chiasm, brainstem, ascending & descending fiber tracts, etc.
Microscopic changes in MS
Active plaques
- Abundant macrophages & ongoing myelin breakdown
- Perivascular lymphocytic inflammation
Inactive plaques
- Little/no myelin left
- Prominent astrocytic proliferation & gliosis
CFs of MS
- Acute optic neuritis - painful unilateral vision loss w/ Marcus Gunn pupil
- Diplopia, ataxia, scanning speech, intention tremor, nystagmus/INO (b/l > u/l) (Brainstem / Cerebellar)
- Weakness & spasticity (Pyramidal tract)
- Electric-shock sensation, neurogenic bladder, paraparesis, sensory effects on truck & extremity - Spinal cord
Lab finding in MS
CSF
- Inc proteins (MBP- Myelin Basic Protein)
- Inc Immunoglobulins (IgG) (oligoclonal bands are diagnostic)
- Moderate pleocytosis
MS Treatment
B-interferon, Glatiramer & Natalizumab
- Slow relapses & progression
IV steroids
- Acute flares
Post-Infectious Demyelination
Immune-mediated demyelination ff infections
Etiology & Pathogenesis of Post Infectious Demyelination
- Viral infections or Vaccination
- Cross-reacting Ab –> Myelin damage
Patterns of Post- Infectious Demyelination
- Acute Disseminated Encephalomyelitis (ADEM)
2. Acute Hemorrhagic Encephalomyelitis (AHEM)
Acute Disseminated Encephalomyelitis (ADEM)
- Rapid progression (1-2wks after infection)
- Non-localizing symptoms (different from MS)
- Most recover completely
Acute Hemorrhagic Encephalomyelitis (AHEM)
- Mostly children & young adults
- Usually fatal (more devastating than ADEM)
Central Pontine Myelinolosis
Non-immune damage to oligodendrocytes in the pons
Etiology of Central Pontine Myelinolysis
After rapid Hyponatremia correction
- Renal or hepatic disease
- Severe vomiting & diarrhea
- CHF
- SIADH
CFS & Pathogenesis of Central Pontine Myelinolysis
Acute b/l paralysis
Unknown pathogenesis
Thiamine Deficiency Encephalopathy
“Wernicke Encephalopathy”
- Abrupt onset
RFs of Thiamine Deficiency
- Chronic alcoholism
- Gastric disorders
CFs of Thiamine deficiency
TRIAD of
- Encephalopathy & confusion
- Ocular palsies
- Ataxia
Treatment of Thiamine deficiency
Thiamine administration (early) - Delayed treatment can cause irreversible memory disturbances "Korsakoff's syndrome", no new memories & confabulations
Pathological features of Thiamine Deficiency
Foci of hemorrhage & necrosis in mamillary bodies, thalamus & peri-aqueductal gray matter
Neurological manifestation of Alcohol
- Peripheral neuropathy
- Cerebellar degeneration
- Seizures (withdrawal syndrome)
- Wernicke-Korsakoff syndrome - Thiamine deficiency
Types of Glioma/ Glial cell tumors
- Astrocytes
- Pilocytic astrocytoma
- Glioblastoma - Oligodendrocytes
- Ependymal cells
Types of Astrocytoma
- Pilocytic astrocytoma (Grade 1)
2. Glioblastoma (Grade4 - Infiltrating)
Pilocytic Astrocytoma
- Childhood
- Cerebellum
- BRAF translocation
- Cystic lesion w/ mural nodule
- Bipolar cells w/ hairlike/pilo processes w. eosinophilic rod-like structures (Rosenthal fibers)
- Glial Fibrillary Acidic Protein (GFAP) +ve on IHC
Glioblastoma
- Grade 4 metastatic tumor
- Cerebrum
- IDH wild or mutant (better prognosis)
- Infiltrating tumor w/ hemorrhage & necrosis
- Crossed the midline (Corpus callosum) “Butterfly glioma”
- Microvascular proliferation w/ area of “Pseudo-palisading” necrosis
- GFAP +ve on IHC
Oligodendroglioma
- Adults (40-50 years)
- Cerebrum (frontal & temporal)
- IDH mutation & 1p and 19q codeletion
- Gray, cystic mass w/ focal hemorrhage & calcifications
- Cells w/ round nuclei, clear cytoplasm forming halos & thin-walled capillaries “Fried egg appearance”
- Insidious - years of antecedent neurological symptoms especially seizures
Ependymoma
- 0-20 years = 4th ventricle BUT Adults = Spinal cord
- Ependymal cells lining ventricular cavity
- NF2 gene on Chr22 (spine)
Hydrocephalus & Spinal cord deficits - Round-oval nuclei & abundant granule chromatin; Variable fibrillary background
- Rosettes w/ long processes extending into the lumen
- “Perivascular Pseudo-rosettes” - surrounding vessels
Embryonal tumors
Medulloblastoma
- Neuroectodermal origin
- Small round cells (remnants of normal progenitor cells during embryology)
Medulloblastoma
- MC CNS malignancy in children
- Cerebellum (posterior fossa)
- Wnt-B catenin pathway & MYC overexpression
- Grade 4; Highly malignant –> Through CSF “Drop metastasis” to Cauda equina”
- Tx = Radiosensitive but poor prognosis (better w/ B-catenin involvement)
- Well-circumscribes, gray, friable (May involve Leptomeninges)
- Sheets of small round blue anaplastic cells w/ hyperchromatic nuclei, abundant mitosis & scant cytoplasm
“Homer Wright Rosettes” in Classic type
Meningioma
- Arachnoid meningothelial cell (attached to dura)
- Adults
- External surface of brain or Ventricular system
- Chr 22q
- Prognosis depends on size, location, surgical accessibility & histological grade
- Whorled, tight clusters of cells w/o visible cell membrane + “Psammoma bodies”
Associated w/ NFA - Multiple meningioma + 8th nerve Schwannoma or glial tumors
Schwannoma
- Benign encapsulated tumor that may occur in soft tissues, internal organs or spinal nerve roots
- Vestibular branch of CN8 “Acoustic neuroma/ Vestibular schwannoma”
- Chr 22q & NF2 association
- Well-circumscribed mass loosely attached to nerve
- Antoni A area (dense & pink), Antoni B area (loose & pale) & Hyalinized blood vessels
“Verocay bodies” –> Nuclei of tumor cells in Antoni A area aligned in palisading rows
Secondary CNS tumors
MC metastatic carcinomas from Lungs, breast, skin (melanoma), kidney & GIT
- Sharply-demarcated masses @ grey-white matter junction
- 25-50% of intracranial tumors
