Neurodegenerative disease Flashcards
Pathology of Alzheimer’s disease
Extracellular plaques (beta amyloid) Intracellular tangles (tau proteins) Generalized cerebral atrophy: narrowed gyri and widened sulci, dilated ventricles
Pathology of Pick’s disease
Intracellular Pick bodies made up of tau proteins
Selective atrophy of frontal and temporal lobes
Pathology of dementia with Lewy bodies
Intracellular Lewy bodies made up of alpha synuclein
Pathology of Parkinson’s disease
Intracellular Lewy bodies made up of alpha synuclein
Atrophy of the substantia nigra
Pathology of ALS
Intracellular speroids made up of neurofilament subunits/superoxide dismutase (SOD1)
Pathology of multisystem atrophy
Glial inclusions made of alpha synuclein and tau proteins
Atrophy of putamen (grey-green color), SN, cerebellum, pons and olivary nuclei
Differential diagnosis of patient presenting with dementia
Stroke Infectious (CJD, syphilis, HIV) Neoplasms Drugs/toxins Metabolic Vitamin deficiencies (Vit B)
What are the 3 main neurodegenerative diseases affecting the cerebral cortex?
Alzheimer’s disease
Lewy body disease
Frontotemporal dementias (Picks)
What are the 2 main neurodegenerative diseases of the basal ganglia?
Parkinson’s disease
Huntingtons disease
What are the major neurodegenerative diseases of the cerebellum and spinal cord?
Multiple system atrophy
ALS
Spinal muscular atrophy
Friedreich’s ataxia
2 types of Alzheimers disease?
Familial (early onset): autosomal dominant
Sporadic (late onset)
What disorder is often associated with AD?
Down syndrome. The APP gene is located on chromosome 21, which is duplicated in Down’s patients.
What genes are associated with late onset AD?
ApoE4 on chromosome 19 increases risk
ApoE2 is protective
Presentation of a patient with dementia with Lewy bodies
Initially dementia and visual hallucinations, followed by parkinsonian symptoms
Presentation of patient with Pick’s disease
Aphasia progressing to dementia
Very rare
Etiology/Pathogenesis of Huntington’s disease
Autosomal dominant chromosome 4 mutation leads to abnormal expansion of CAG triplet repeat
Decreased levels of GABA and Ach in the caudate causes choreiform movements
Symptoms of multiple system atrophy
In 4th-6th decade, variable combination of parkinsonism, cerebellar ataxia and autonomic dysfunction
What is Werdnig-Hoffman Disease?
Spinal muscular atrophy type 1: floppy baby
Autosomal recessive disorder (c5: SMN gene) causing degeneration of lower motor neurons, atrophy of distal muscles
What is Kugelberg-Walander disease?
Spinal muscular atrophy type 2
Similar to type 1, but later presentation
What is the most common form of hereditary ataxia?
Friedreich’s ataxia
What is Friedreich’s ataxia?
Autosomal recessive disorder causes trinucleotide repeat on chromosome 9
Leads to degeneration of the cerebellum (ataxia) and degeneration of spinal cord tracts (loss of sensation, strength and reflexes)
Pathologic findings of vascular dementia
Multiple strokes
Single stroke in strategic site
Small vessel disease
Histology/Pathology of Wernicke’s encephalopathy
Acute: Normal mamillary body dimensions with recent petechial hemorrhages
Chronic: shrunken mamillary bodies, brown discoloration, central gliosis
Effects of methanol toxicity
Permanent loss of vision, delirium, convulsions, coma, death due to global hypoxic injury, white matter necrosis and hemorrhages/infarction
