Neuro11 Pathology Flashcards
Dementia
A decrease in cognitive ability, memory, or function with intact consciousness.
Alzheimer’s disease
Most common cause in elderly. Down syndrome patients have an increased risk of developing Alzheimer’s. Familial form (10%) associated with the following genes:
- Early onset: APP (21), presenilin-1 ( 14), presenilin-2 ( 1 )
- Late onset: ApoE4 ( 19)
ApoE2 ( 19) is protective
Histological/Gross findings in Alzheimer’s disease
Widespread cortical atrophy
- decreased ACh
- Senile plaques: extracellular Beta-amyloid core; may cause amyloid angiopathy leads to intracranial hemorrhage; ABeta-amyloid synthesized by cleaving amyloid precursor protein
- Neurofibrillary tangles: intracellular, abnormally phosphorylated tau protein = insoluble cytoskeletal elements; tangles correlate with degree of dementia
Pick’s disease (frontotemporal dementia)
Dementia, aphasia, parkinsonian aspects; change in personality.
Spares parietal lobe and posterior 2/3 of superior temporal gyrus.
Histological/Gross findings Pick’s disease
- Pick bodies (intracellular, aggregated tau protein)
- Frontotemporal atrophy
Lewy body dementia
Parkinsonism with dementia and hallucinations.
Histological/Gross findings Lewy body dementia
- a-synuclein defect
Creutzfeldt-Jakob disease (CJD)
Rapidly progressive (weeks to months) dementia with myoclonus.
Histological/Gross findings Creutzfeldt-Jakob disease (CJD)
- Spongiform cortex
- Prions (PrPc leads to Prpsc sheet [resistant to proteases])
Other causes of Dementia
Multi-infarct (2nd most common in elderly), syphilis, HIV, vitamin B12 deficiency, Wilson’s disease, Normal Pressure Hydrocephalus
Multiple sclerosis
Autoimmune inflammation and demyelination of CNS (brain and spinal cord). Patients can present with optic neuritis (sudden loss
of vision), MLF syndrome (internuclear ophthalmoplegia), hemiparesis, hemisensory symptoms, or bladder/bowel incontinence.
Relapsing and remitting course. Most often affects women in their 20s and 30s; more common in whites.
Charcot’s classic triad of MS is a SIN :
Scanning speech
Intention tremor, Incontinence, Internuclear ophthalmoplegia
Nystagmus
Findings in Multiple sclerosis
Increased protein (IgG) in CSF. Oligoclonal bands are diagnostic. MRI is gold standard. Periventricular plaques (areas of oligodendrocyte loss and reactive gliosis) with destruction of axons.
Treatment of Multiple sclerosis
Beta-interferon, immunosuppression, natalizumab. Symptomatic treatment for neurogenic bladder (catheterization, muscarinic antagonists), spasticity (baclofen, GABA receptor agonist), pain (opioids) .
Guillain-Barre syndrome (acute inflammatory demyelinating polyradiculopathy)
Inflammation and demyelination of peripheral nerves and motor fibers of ventral roots (sensory effect less severe than motor), causing symmetric ascending muscle weakness beginning in distal lower extremities. Facial paralysis in 50% of cases. Autonomic function may be severely affected (e.g., cardiac irregularities, hypertension, or hypotension). Almost all patients survive; the majority recover completely after weeks to months.
Associated with infections: autoimmune attack of peripheral myelin due to molecular mimicry (e.g., Campylobacter jejuni or herpesvirus infection), inoculations, and stress, but no definitive link to pathogens. Respiratory support is critical until recovery. Additional treatment: plasmapheresis, IV immune globulins.
Findings in Guillain-Barre syndrome
Increased CSF protein with normal cell count (albuminocytologic dissociation) . Increased protein leads to papilledema.
Progressive multifocal leukoencephalopathy (PML)
Demyelination of CNS due to destruction of oligodendrocytes. Associated with JC virus and seen in 2-4% of AIDS patients (reactivation of latent viral infection) . Rapidly progressive, usually fatal.
Acute disseminated (postinfectious) encephalomyelitis
Multifocal perivenular inflammation and demyelination after infection (e.g., chickenpox, measles) or certain vaccinations (e.g., rabies, smallpox).
Metachromatic leukodystrophy
Autosomal-recessive lysosomal storage disease, most commonly due to arylsulfatase A deficiency. Buildup of sulfatides leads to impaired production of myelin sheath.
Charcot-Marie-Tooth disease
-also known as hereditary motor and sensory neuropathy (HMSN).
Group of progressive hereditary nerve disorders related to the defective production of proteins involved in the structure and function of peripheral nerves or the myelin sheath
Krabbe’s Disease
Autosomal recessive lysosomal storage disease due to deficiency of galactocerebrosidase. Buildup of galactocerebroside destroys myelin sheath
