Huntingtons Disease Alzheimers Disease
Description Progressive,fatal, highly
penetrant, autosomal
dominant disorder
characterized by motor,
behavioral and cognitive
dysfunction
Defect Short Arm of Chromosome 4
Long repeat of CAG
Symptoms Dominant Inheritance - Onset of mental changes is
Choreoathetosis
Dementia - Gradual development of
(Personality Disorder,
Dementia, Movement Disorder)
- Simplest geometric forms and
Dysarthria, gait disturbance
and oculomotor abnormalities
Pathogenesis Increase in polyglutamate
repeatsin the coding sequence
Lobar Atrophies Lewy Body Dementia
Most common cause of dementia Atrophy is circumscribed
in older adults (frontal, temporal)
Progresive deficits of memory, FTD: behavioral symptoms
visuospatial orientation, predominate early in FTD
judgement, personality and compared to AD
language
Reduction of choline Picks disease
acetyltransferase and -
acetylcholine in the hippocampus
nd neocortex
Picks Disease 2/3 symptoms
insidious
First
forgetfulness (remote 1. Talkative
memories are preserved and 2. Lighthearted
recent ones are lost) 3. Cheerful o axious
4. Constantly on th
patterns cant be copied (pt move
forgets how to use common 5. Occupied w/ trifles
objects and tools while 6. Attentive to every
retaining the necessary motor passing ncident
power and coordination of
these activities Second
1. Taciturn
Early Stage: benign forgetfulness 2. Inert
Middle Stage: unable to work, 3. Emotionally dull
easily lost and confused, Apraxia 4. Lacking in initiative
and impulse
Late stage: Loss of judgement and
reasoning, delusions, Capgras FTD
syndrome - Behavioral symptoms
predominate early
Loss of cells in the basal forebrain PICK DISEASE
nuclei (Meynert)
Parkinson Disease ALS
2nd most frequent Progressive Progressive disorder
pathologic diagnosis neurodegenerative in which there is loss
established disease of UMN in the
cerebral cortex and
LBD LMN in the spinal
- Diffuse involvement cord and brain stem
of cortical neurons
wth LB inclusions
and by an absence
of tangles an
plaques
Hypo-bradykinesia Atrophic weakness of
Parkinsonian features Resting tremor han, forearms
Dementia (fluctuation Postural instability Spasticity of arms,
in behavior and Rigidity legs
cognition) Hyperreflexia (Neck,
Frequency tendency to Clin features: pharnx, larynx, trunk,
episodic delirium Expersionless face legs)
(recurrent Poverty and slowness of
hallucination) voluntary movement
REM sleep disorder Resting tremor (pill
rolling)
Stooped posture
Axial instability
Rigidity
Festinating gait
Presence of Lewy PD is marked by Loss of neurons
Bodies and Neuritis prominent hypokinetic results in denervation
 oof huntingtin gene
Degeneration of striatal
neurons
Leading to loss of GABA
(uncontrolled movement)
Diagnosis Genetic Testing
CT: Cerebral Atrophyof Caudate
Normal Dopamine
Accumulation of AB and tau
proteins (excessiveproduction
and defective removal)
AB peptides: plaques in
neutrophils
Tangles: aggregates of
microtubule tau
Progressive degenerative
disorder characterized by
selectie involvement of
anterior frontal and
temporal neocortex and
intraneural cycoplastmc
inclusion (Pick bodies) with
conspicuous sparing of
posteror 2/3 of superior
temporal gyrus and rare
involvement of parietal
oroccipital lobe
FTD
- Tau containing
inclusions
- TDP43-containing
inclusions
Pick Bodies: agyrophilic,
staining positivey with
Bielschowsky silve method
(Tau)
FTD: FTLD-tau, FTLD-TDP
throughout the movement disorder that of mules, producing
specific brainstem is caused by loss of weakness that
nuclei, substancia dopaminergicneurons becomes profoundas
nigra, amygdala, from substantia nigra disease proesses
cingulate nucleus, and
neocortex
Lewy bodies
- Intraneuronal
cytoplasmic
inclusions that
stain with PAS and
ubiquitin as well as
alpha-synuclein
- Straight
neurofilamens 7-
20 nm long with
surrounding
amorphous
material
Idiopathic PD
- Substantia nigra
Diffuse Lewy Body
- Basal forebrain
and
pedunculopontine
nucleus
Treatment Ballismus and Choreoathetosis:
Benzodiazepines
Parkinsonian symptoms:
Carbidopa, Levodopa
Pramipexole, Ropinorole
Bromocriptine
Major Depressive Disorder:
SSRI
Genetics Autosomal Dominant
No evidence of salutary ffect
- Cerebral vasodilators,
stimulants, L-dopa, Vit B,
C, E
- Oral physostigmne
- Choline, lecithin
- Cholinergic precursor
Modest effect
- Acetylcholinesterase
inhibitors
Approved effect in late-stage
- NMDA glutaminergic
antagonist (Memantine)
L-Dopa and L-dopa
Modifying Drugs
- With
decarboxylase
inhibitor
- COMT inhibitors
Dopamine Agonists
Anticholinergic Agents
Surgical measures