Neurodegenerative Flashcards
Most common degenerative disorder
1st Alzheimer’s
2nd IPD
Most common familial type of IPD
PARK-8 gene: AD, chromosome 12, enzyme LRRK-2 (leucine rich repeat kinase)
Onset of postural instability in Parkinson’s disease vs P+
IPD 8-10 years
MSA: 5 years
PSP: 2 years
Most initial non-motor symptoms in IPD
Anosmia/hyposmia
Wilson disease genetics
Autosomal recessive ch13, mutation in ATP7B
IPD PET scan findings: decreased uptake in what areas
Dopaminergic dorsal striatum (🟢putamen🟢 < caudate) , then nigrostriatal pathway
Most likely to cause hallucination from IPD medications
Amanatadine and dopamine agonists > carbidopa/levodopa
Most likely to cause dyskinesia from IPD medications
Levodopa/carbidopa > dopamine agonists and COMT-I
Best option of DBS for dyskinesia in IPD
DBS-GPi
Contraindications of DBS-STN in IPD
1- Severe depression and psychosis
2-Cognitive decline
3-Age > 70
4-Brain atrophy
5-On-phase Freezing of gait
What is the goal of DBS-STN
Decrease Dopaminergic medications by 50%
Preferred surgical management of tremor in IPD
Thalamotomy or DBS on ventral intermediate nucleus (VIM)
Treatment of restless leg syndrome
Dopamine agonist or gabapentin
Treatment of ٍREM sleep disorders
Clonazepam or melatonin in elderly
Treatment of orthostatic hypotension in IPD
Fludrocortisone
Increase fluid intake
Midodrine
List of tauopathies (5)
1-Alzheimers’ disease
2-FTD
3-CBD
4-PSP
5-pick disease
List of syncleinopathies (5)
PALMR
1-Parkinson’s disease
2- Autonomic failure
3-Lewy body dementia
4-MSA
5-Spontaneous REM sleep behavioral disorder
FDG PET in different types of P+
MSA: putamen and/or cerebellar
LBD: occipital
PSP: prefrontal cortex (anterior cingulate)
CBD: frontopraietal
——-
Alzheimer’s: parietal-temporal > frontal
FTD: frontotemporal
Pathology in different Parkinson’s plus syndromes
MSA: oligodendro-glial cytoplasmic inclusion (GCI)
DLB: Lewy bodies
PSP: tufted Astro yes
CBD: globose neurofibrillary tangles and ballooned neurons (achromasia)
Wilson disease imaging findings and pathology
-CT brain: symmetrical hypodensity of putamen
-MRI T2 and FLAIR: bil symmetrical hyper-intense basal ganglia (putamen), thalami, and dentate nuclei. midbrain face of panda sign.
-Pathology: Alzheimer’s type 2 cells and opalski cells
MCC of toxin induced Parkinsonism (environmental) and typical location
Manganese
Globus pallidus and STN
Huntington’s disease genetics
AD on Chromosome 4, CAG repeat sequence
⚫️CAG >= 40 : high penetrance + have the disease
⚫️CAG 36-39 : reduced penetrance + have the disease
⚪️CAG 27-35 : intermediate penetrance + don’t have the disease
⚪️CAG <27 : normal
Huntington’s disease imaging findings
MRI: unilateral or bilateral caudate atrophy and dilated lateral ventricles
PET: unilateral or bilateral caudate hypo-metabolism
First line Tx for Sydenham’s chorea
Valproic acid
Huntingtons disease FDA approved therapy
Tetrabenazine
Causes of drug induced chorea
Levodopa (MCC) + dopamine agonists
Lamotrigine
Lithium
OCP
Estrogen
Cocaine
Amphetamine
Methadone
First line for adult onset focal dystonia
Botulinum toxin type A
Best medical treatments for dystonia (if non-responsive to Botox or generalized)
1- Anticholinergics (benzotropine, trihexyphenidyl), effective in 40%
2- Baclofen, effective in 20%
3- Benzodiazepine, effective in 15%
Preferred type of DBS in dyskinesia and/or dystonia (refractory and generalized)
Globus pallidus
What is the gene for inherited myoclonus-dystonia, and what is the best treatment
-Gene: 3-sacroglycan gene (SGCE)
-First option: gamma hydroxybutyric acid. Second option: clonazepam or Valproic acid.
Treatment for hereditary essential myoclonus
1- clonazepam
2- 5-hydroxytryptophan
Treatment options for lance Adams syndrome
1- clonazepam
2- ipracetam
3-Keppra
4-Valproic acid
Difference between essential palatal myoclonus and symptomatic palatal myoclonus
🔲Essential palatal myoclonus: +ve ear clicks, disappears during sleep, affected muscle tensor veli palatini, -ve MRI findings.
🔲Symptomatic palatal myoclonus: -ve ear clicks, persistent during sleep, affected muscle Levator veli palatini, MRI : olivary hypertrophy. M>F
First line therapy for restless leg syndrome
1- DA : pramipexole , or ropinirole or pergolide
2- Levodopa
First line therapy for stiff-man syndrome
1-Diazepam
2- alt: clonazepam
First line therapy for hemifacial spasms
1- botox injections (90% improvement)
2- surgical if refractory
Stiff man syndrome pathophysiology
Antibodies against GAD (glutamic acid decarboxylase) in 70%
Others: paraneoplastic or endocrinopathy
6 domain for cognition:
1- Memory and learning
2- Perceptual motor
3- Executive function
4- Social cognition
5- Language
6- Complex attention
Annual progression rate of MCI (mild cognitive impairment) to AD
In clinic 10-15% (LATEST study in sa 6-7%)
In community 5-10%
Alzheimer’s disease genetics
🟢Sporadic 95%
🟡Familial 5%: earliest and most common presenilin-1 > Amyloid precursor protein (APP) > presenilin-2
Susceptibility gene (only higher risk, not causative): aploliporotein 4
What type of memory is affected in Alzheimer’s disease, and what type is spared
Episodic memory and delayed recall is affected
Spared: procedural, old remote memory, and working memory
Pathology of Alzheimer’s disease
-Neurofibrillary tangles (tau deposition)
-Helical filaments
-Amyloid plaques (senile plaques)
-Lewy bodies (only in hippocampus)
Most common phenotype of FTD
FTD behavioral variant: accumulation of TDP 43 due to mutation in Ch 9/C9ORF72
Most common primary neurodegenerative cause of dementia in all ages
1- Alzheimer’s
2- Lewy body dementia
3- FTD
Most common primary neurodegenerative cause of dementia in <65yo
1- Young onset Alzheimer’s
2- FTD
3- Lewy body dementia
Most common primary and secondary cause of dementia
1-Alzheimer’s disease
2- Vascular dementia
3-Lewy body dementia
4-FTD
Treatment of FTD behavioral type
For behavioral and psychiatric symptoms: SSRI first line
For aggression and disinhibition: clonazepam, quetiapine, respiredone
AVOID ChEI and memantine as it worsens behavioral symptoms.
Treatment of Lewy body dementia
Based on symptoms
Hallucinations: quetiapine is best
REM sleep disorder: clonazepam or melatonin
Parkinsonism: Same as Parkinson’s
Depression: SSRI
Anxiety: sertraline
Cognitive: donepezil, galantamine, rivastigmine
RLS: DA, gabapentin, CD/LD
Orthostatic hypotension: fludrocortisone, midodrine
Most common behavioral symptoms in vascular dementia
Depression
What is the cognitive deficits seen in vascular dementia
Executive dysfunction
What is the cognitive deficit seen in Lewy body dementia
Working memory and attention
Characteristic EEG finding in anti-NMDA encephalitis
Delta brush pattern
Genetics of CJD
-Sporadic CJD: Met or Val at codon 129
-Variant CJD: Met at codon 129
-Iatrogenic CJD: Met at codon 129
-Familial CJD: glutamine-lysine at codon 200 (Most common)> codon 178
-Fatal familial insomnia (FFI): codon 178 + codon 129
