Degenerative Neurological Diseases Flashcards
1
Q
Degenerative Diseases
Overview
A
Diseases of gray matter characterized principally by the progressive loss of neurons with associated secondary changes in white matter tracts.
- Common pathologic process seen in many of these ⇒ accumulation of protein aggregates
- Two other general characteristics:
- Pattern of neuronal loss is selective, affecting one or more groups of neurons while leaving others intact
- Diseases arise without any clear inciting event in patients without previous neurologic deficits
2
Q
Degenerative Disease
Locations
A
-
Cerebral Cortex
- Alzheimer
-
Fronto Temporal Lobar Degenerations (FTLD)
- Includes Pick Disease
- Vascular Dementia
-
Basal Ganglia
- Parkinson
- Huntington
-
Motor Neurons
- ALS and similar diseases (adults)
- Werdnig Hoffman Disease (children)
3
Q
Dementia
Definition
A
“Degenerative Cortical Disease”
Syndrome comprising “global” impairment of higher cortical functions in the absence of gross clouding of consciousness.
Affects memory, capacity to solve problems of everyday living, performance of learned perceptual (motor skills, correct social skills), and control of emotional reactions.
4
Q
Dementia
Etiologies
A
- Degenerative diseases
- Chronic Infections
- Vitamin Deficiencies
- Toxins
- Diffuse Brain Injury
- Metabolic Disorders
- Mass Lesions
- Genetic Diseases
5
Q
Alzheimer Disease
Overview
A
“Senile Dementia of Alzheimer’s Type –SDAT”
-
Most common cause of dementia in the elderly
- Rarely symptomatic before age 50
-
Incidence rises with age:
- 1% of 60-65 y/o
- 40% of 85-89 y/o
- 5-10% of cases are familial
- Examination of brain tissue is necessary for definitive diagnosis
- Clinical and radiographic assessment is 80-90% accurate
6
Q
Alzheimer
Gross Findings
A
- Variable degree of cortical atrophy
- Widening of the cerebral sulci most pronounced in frontal, temporal, and parietal lobes
- Significant atrophy ⇒ compensatory ventricular enlargement (hydrocephalus ex vacuo) secondary to loss of parenchyma
7
Q
Alzheimer
Molecular Genetics and Pathogenesis
A
-
Accumulation of Amyloid β (Aβ) and tau proteins in specific brain regions
- Likely d/t excessive production and defective removal
- Plaques ⇒ Deposits of aggregated Aβ peptides in neuropil
-
Tangles ⇒ Aggregates of the microtubule binding protein tau
- Develop intracellularly and then persist extracellularly after neuronal death
8
Q
Alzheimer Disease
Histological Changes
A
- Changes can be found in brains of elderly nondemented individuals
- Alzheimer disease dx is based on clinical and pathologic features
- Changes are most severe in certain regions particularly the hippocampal pyramidal cell layer
- Cannot see these changes using H and E, need special silver stains to see the senile plaques and neurofibrillary tangles
- Findings associated with severe loss of neurons in the brain and loss of brain tissue ⇒ seen as cerebral atrophy
9
Q
Alzheimer Disease
Histological Features
A
-
Neuritic (senile) plaques
- Extracellular accumulations of organelles and amyloid protein
-
Neurofibrillary tangles
- Intracellular accumulation of organelles, neurofilaments, and microtubular proteins
- Become extracellular after death of neuron
-
Cerebral amyloid angiopathy (CAA)
- Vascular amyloid is predominantly Aβ40
- Also true when CAA occurs without AD
-
Granulovacuolar degeneration
- Formation of small clear intraneuronal cytoplasmic vacuoles
- Each contains an argyrophilic granule
- Seen in great abundance in hippocampus and olfactory bulb in Alzheimer disease
-
Hirano bodies
- Elongated, glassy, eosinophilic bodies
- Contains paracrystalline arrays of beaded filaments w/ actin as their major component
- Found most commonly within hippocampal pyramidal cells
10
Q
Alzheimer Disease
Clinical Features
A
- Entorhinal cortex ⇒ direction loss [spatial] (Major hippocampal input)
- Hippocampus ⇒ memory loss
- Neocortex ⇒ loss of higher cortical functions
Degree of dementia correlates better with neurofibrillary tangles and loss of synapses than with neuritic plaques
11
Q
Alzheimer Disease
Genetic Predisposition
A
- Small number of families transmit early-onset AD as a dominant genetic trait
- Also see form of AD in adults with Down Syndrome
- Both show over-representation of genes on Chromosome 21 ⇒ coding for cerebral amyloid
- Unclear relevance in sporadic AD
12
Q
Frontotemporal Lobar Degenerations
(FTLD)
A
- Heterogeneous set of disorders
- See focal degeneration of frontal and/or temporal lobes
- Alterations in personality, behavior, and language (aphasias) precede memory loss
- Divided into two groups by what is in the cellular inclusions:
- FTLD-tau
- FTLD-TDP
13
Q
FTLD-tau
A
- Affected regions show neuronal loss and reactive gliosis
- Tau-containing inclusions in neuron cytoplasm
- Inclusions can take form of tangles or smooth contoured inclusions (Pick bodies)
14
Q
Pick Disease
A
- Type of FTLD-tau
-
Gyral atrophy
- Relatively confined to anterior portion of frontal lobes and lower portions of temporal lobes
- Superior gyrus, parietal and occipital lobes spared
- More severe than in Alzheimer’s ⇒ ‘knife edge cortex’
-
Pick Bodies
- Spherical neuronal inclusions ⇒ push nucleus to one side
- Made of neurofilaments (tau)
- Stains positively for silver
- Do not persist after neuronal death
-
Early-onset behavioral changes (rare):
- Alterations in personality [Frontal Lobe]
- Language disturbances [Temporal Lobe]
- Most cases are sporadic
- Few familial forms linked to mutations in tau
15
Q
Vascular Dementia
A
- Vascular injury can cause dementia
- Treatment of vasculitis will cause cognitive improvement
- Etiologies:
- Hypoperfusion ⇒ multiple small infarcts, cortical laminar necrosis
- Chronic HTN ⇒ diffuse white matter injury (Binswanger disease)
- Embolism ⇒ strategic infarcts to hippocampus, DM thalamus or frontal cortex
16
Q
Lacunar Infarcts
A
- Seen only in the nervous system
- Occurs in deep penetrating arteries and arterioles supplying:
- Basal ganglia
- Hemispheric white matter
- Brainstem
- Chronic untreated HTN ⇒ arteriolar sclerosis and occlusion
- Results in single or multiple, small, cavitary infarcts ⇒ lacunes (lacunar infarcts)
- Tiny cystic (lake-like spaces) occur in: lenticular nucleus > thalamus > internal capsule > deep white matter > caudate nucleus > pons
- Microscopic appearance: cavities due to lost tissue with scattered fat-laden MΦ and surrounding gliosis
- Depending on location ⇒ clinically silent or cause severe neurologic impairment (can see a Parkinson’s-like syndrome)
19
Q
Parkinson Disease
Histology
A
- Loss of the pigmented, catecholaminergic neurons in basal ganglia associated with gliosis
- ± Lewy bodies in remaining neurons
- Single or multiple, cytoplasmic, eosinophilic, round to elongated inclusions that often have a dense core surrounded by a pale halo
- Composed of fine filaments, densely packed in the core but loose at the rim
26
Q
Huntington Disease
Pathogenesis
A
- Striatal neurons are lost and fibrillary gliosis is extensive
- Loss of striatal output ⇒ ⊗ subthalamic nucleus ⇒ dysregulation of motor activity and choreoathetosis (early)
- Neuronal loss from the cerebral cortex correlates with cognitive changes and dementia (later)
30
Q
Amyotrophic Lateral Sclerosis
Clinical Features
A
- Early: Asymmetric hand weakness, cramping and spasticity of arms and legs
- Then: Decreased muscle strength and mass; and fasciculations (motor unit contractions)
- Eventually: Respiratory muscles affected; recurrent bouts of pneumonia
- Death usually occurs in 5-10 years
- Spinal Cord: demyelination in corticospinal tracts and atrophy of anterior nerve roots
31
Q
Werdnig-Hoffman Disease
A
- Motor neuron disease of infants, usually symptomatic at birth
- Poor suck, weak cry, little movement of arms or legs
- Differential diagnosis is some type of primary muscle disease
- Some cases seem sporadic, others genetically determined as either recessive or autosomal traits
- Pathology: changes similar to those found in adult motor neuron disease
- Children usually die during first few years of life
