CH38: Degenerative Diseases Flashcards
Process of neuronal, myelin or tissue breakdown, degradative productive of which evoke a reaction of phagocytosis and cellular astrogliosis but usually with minimal or no inflammation (p. 1082)
Degeneration
Degenerative diseases have 2 outstanding categories (p. 1083)
- Affect specific parts or functional systems of the nervous system
- Begin insidiously after a long period of normal nervous system function and pursue a gradually progressive course
Convulsions disease in Alzheimers disease are rare until late in the illness, when up to how many percent of patients are reportedly have infrequent seizures? (p. 1087)
5%
5 deficits that may represent the opening features of Alzheimer disease (p. 1087)
Amnesia Dysnomia Visuospatial disorientation Paranoia and personality changes Executive dysfunction
In checking for naming, Alzheimer patients will fail (p. 1088)
below 8 items in any 1 category
or 25 items total if given to name in all 3
Criteria for Alzheimers: (p. 1088)
- dementia defined by clinical examination
- patient older than 40 years old
- deficits in 2 or more areas of cognition
- absence of disturbed consciousness
- exclusion of other brain diseases
Alzheimers brain is reduced by how many percent (p. 1089)
20%
Widespread loss of nerve cells in which layer of entorhinal cortex (p. 1089)
layer II
Marked neuronal loss in AD, which structures (p. 1089)
hippocampus
medial temporal cortex spec parahippocampal gyri and subiculum
nucleus basalis of Meynert and locus ceruleus
Pathological findings in AD:
- neurofibrillary tangles
thick fiber-like strands of silver staining material in the forms of loops, coils or tangled masses - Neuritic plaques
spherical deposits of amorphous material scattered throughout the cerebral cortex and easily seen by PAS - Granulovacuoular degeneration
most evident in the pyramidal layer of hippocampus
In AD, Which correlates best with the severity of dementia (p. 1089)
Neurofibrillary tangles
If any part of the brain is disproportionately affected by the changes of AD it is the which structure (p. 1089)
Hippocampus particularly CA1 and CA2 zones
Entorhinal cortex
Subiculum
Amygdala
Discrete cytoskeletal protein that promotes the assembly of microtubules, stabilizes their structure and participates in synaptic plasticity (p. 1090)
Tau composed chemically of b transferrin
Protein toxic to several models of AD (p. 1090)
AB42
These are catalytic components of gamma secretase , the enzyme the oriduces the Abeta42 fragment (p. 1091)
Presenillin 1 and 2
Product of inadequate functioning of the progranulin gene that is also deposited in the neurons of that may impact the severity of AD; also implicated in the pathogenesis of FTD and motor neuron disease (p. 1091)
TDP-43
PET studies indicate that tau deposition in the inferior temporal and parietal cortices, more clearly than amyloid, differentiate normal older individuals from those with MCI or AD and (p. 1091)
Tau is more closely aligned with temporal lobe cortical atrophy
Proteins assocaited with early and late AD (p. 1093)
EARLY: APP, Presenillin 1, Presenillin 2;
LATE: Apolipoprotein E, Ubiquitin, TREM2
Which ApoE is associated with a tripling of thee risk of developing sporadic Alzheiers disease? (p. 1093)
ApoE4
This polymorphism is implicated in the AD causes inadequate phagocytic clearance of amyloid (p. 1093)
TREM2
Codes a protein that interacts with PS1 and PS2 and participates in proteasomal degradation (p. 1093)
UBQNL1
CT scan finding in AD (p. 1093)
disproportionate atrophy of the hippocampi and a corresponding enlargement of the temporal orns of the lateral ventricles
Beyond PET and related imaging studies there are no established biologic markers of Alzheimers disease with a possible exception of the (p. 1094)
ratio of tau to Ab42 (tau amyloid ratio)
The ratio is low in AD
Acetylcholinesterase inhibitor (p. 1095)
Donepezil
Acetyllcholine receptor antgonist succinulcholine is used prior to general anesthesia. Why need to be careful (p. 1095)
The effects may be prolonged in patients taking Donepezil
Which drug is slightly preferable in the treatment of psychosis, aggression or agitation? (p. 1095)
Olanzapine
Dementia and parkinsnism are related to NF changes in the cerebral cortex and substantia nigri (p. 1095)
Guamanian Parkinson- dementia complex
Dementia from motor neuron disease (p. 1095)
Neurofibrillary change is the most prominent feature wheres amyloid plaques are negligible in number or absent
Punch-drunk syndrome
chronic traumatic encephalopathy
What are the depoitions in Lobar Atrophies? (p. 1096)
Tau, progranulin, amyloid, synuclein
Depositon of agyrophilic intractoplasmic inclusions in FTD (p. 1096)
Pick bodies
Diffusely staining ballooned neurons (p. 1096)
Pick cells
Two main variants in lobar atrophies (p. 1097)
Behavoiral variant Language variant (progressive nonfluent, semantic, logopenic)
This disease is defined by diffuse involvement of cortical neurons with Lewy body inclusions and by an absence or inconspicous number of neurofibrillary tangles and amyloid plaque (p. 1097)
Lew Body Dementia
Main components of Lew Body (p. 1097)
Ubiquitin and alpha- synuclein
Diagnostic criteria for LBD (p. 1097)
2/3:
Parkinsonian syndrome
Fluctuations in behvior and cognition
Recurrent hallucinations
Characteristic of Parkinsons in LBD patients (p. 1097)
favorably repond to L Dopa INITIALLY or not at all
Most characteristic feature besides the movement disorder in LBD (p. 1098)
vacuous, anxious state with intermittent psuchotic or delirious behavior
Parkinsons Disease and LBD VS other dementias via PET (p. 1098)
reductions in lenticular nuclei and caudate activity in radiolabled dopamine transporter or dopamine receptor
For blood presssure changes in LBD, this drug is prescribed (p. 1098)
Midodrine
Anticholinesterse inhibitor used in reducing delusions, hallucinations and anxiet in LBD (p. 1098)
Rivastigmine
A selective serotonin 5-HT2A inverse agonist usd to treat psychosis in Parkinson disease which hs shown some modest benefit for psychosis nd hallucinations in a tria in LBD without worsening motor symptoms (p. 1089)
Primavanserin
Dominannt inherited adult- onset dementia with fulminant evolution (p. 1098)
Neuroserpinopathy
Findings in neuroserpinopathy (p. 1089)
Large eosinophilic, PAS- positive intaraneuronal inclusions that ocntain aggregates f neuroserpin
Triad is dominant inheritance, choreoathetosis, dementia (p. 1089)
Huntington disease
The CAG triplet codes for? (p. 1090)
glutamine
HDL2 Huntington disease like 2 is associated with?(p. 090)
CATCG, expansion of juntophilin 3 gene
HDL2 more associated with Westphal variant
First to appear in Huntingon disese (p. 1099)
Alterations of personality; Memory is spared
Opposite of HD and PD in terms of blinking (p. 1100)
In PD, blinking is diminshed; in HD blinking is increased
Gross pathology in HD (p. 1100)
Gross atrophy bilaterally of the hed of the caudate nucleus and putamen
Check bicaudate-to-cranial ratio
Spares the nucleus accumbens
Comment on size of sequence in HD (p. 1101)
The longer sequence on either 2 alleles determines the age of onset
The size of expansion of the normal allele exerting no influence
How many CAG repeats confers risk of developing clinical manifestation at some time re:HD? (p. 1101)
36
Pertubations of iron metabolism that may be toxic to neurons is found in (p. 1102)
Hallervorden-Spatz disease, now called PANK disease
Adult-onset chorea, myoclonus and rigidity (p. 1102)
DRPLA
Drugs that can cause chorea (p. 1102)
amphetamines, cocaine, TCA, lithim, isonizid, linezolid
Dopamine antagonis used to partially supre movement disorder of HD (p. 1102)
Haloperidol
Drug contraindicated in HDwho are suicidal (p. 1102)
Tetrbenazine and Deutetrabenazine
Finding in Famiial Dementia with Spastic Paraparesis patchy but gross swelling of the arterioles which gave teh staining reactions for amyloid (P. 1103)
Scholz perivascular plaques
Mild dementia wbut wth impairment of retentive memory, dysnomia, dyscalculia, sometimes nonfluent aphasia and deficits in visual integratin; overshadowed by rigidity and spasticity of the limbs and peripheral nerve disorder (p. 1103)
Adult Polyglcosan Body Disease
CBDG vs PD? (p.1106)
in CBGD, rigidity, hyperactive DTR nd Babnski signs are combined with aparaxia
Most dependable feature of PD (p. 1106)
Early sign of resting alternating tremor that is more prominent in one arm
How many percent of PD fail to display the characteristic tremor and approximately how many does not respond to L Dopa?(p. 1106)
25%
10% dont respond to LDopa
Spastic bulbar palsy vs PD? (p. 1107)
Unilateral and bilateral CST
Hyperactive facial reflexes
Spasmodic crying, laughing
Most constant and pertinent pathologic finding in both idiopathic and postencepalitic PD?(p. 1108)
loss of pigmented cells in the SN and other pigmented nuclei in LC, dorsam motor nucleus of vagus
Pigmented nuclei contain eosinophilic cytoplasmic inclusions (p. 1108)
Lew bodies
Rate limitiing enzme for the synthesis of Dopamine (p. 1108)
Tyrosine hydroxylase
Earliest changes of the brain in PD (p. 1108)
cnges in dorsal glosopharngeal-vagal and anterior olfactory nuclei
Neurotoxin that produces irreversible signs of parkinsonism and selective destruction of cells in the SN (p. 1108)
MPTP
Ubiquiting protein ligase that participates in the removal of unecesary proteins from cells trough the proteasomal sytem (p. 1110)
Parkin
Dopamine responsive dystonia (p. 1111)
Segawa disease
COMTinhibitor that extends the plasma half-life and the duration of L-dopa effect by preventing its breakdown (p. 1112)
Entecapone
Dopamine agonists (p. 1113)
Ropinorole
Pramipexole
These drugs are not used in PD anymore because of the risk of cardiac valvular damage, particularly in higher dosage (p. 1113)
Pergolide
Cabergoline
Anticholinergic drugs in PD (p. 1114)
Trihexypenidyl
Benztropine
Ethopropazine
Mechanism of action is unknown but antagonism of NMDA or release of stored dopamine has been proposed (p. 1114)
Amantadine
Attempts to slow the disease by vitamin antocoaxidants have met generally negative results except (p. 1114)
Coenzyme Q10
This drug has been said to provide addtional benefit of suppressing dyskinesias in PD but its hematologic risks have led to its limited use (p. 115)
Clozapine
DBS targets (p. 1116)
posterior and ventral medial parts of the subthalamic nucleus
globus pallidus interna
Who will benefit DBS the most? (p. 1116)
Patient who maintain mobility but requires a dose of L-dopa that produces unacceptable dyskinesias and who is constantly cycling between on and off periods
Mechanism of DBS (p. 1116)
high frequency impulses disrupt local neuronal activity; functional equivalent of an ablative lesion
Hypotension in PD responds to (p. 1117)
Fludricortisone
Droxidopa
Pyridostigmine
Midodrine
Post mortem findings in MSA (p. 1117)
extensive los of neurons in teh ona compacta of the SN; but no Lew bodies or NF tangles in the remaining cells
Secondary pallidal atrophy
Why is there orthostatic hypotension in MSA?(p, 117)
los of intermediolateral horn cells and pigmented nuclei in the brain stem
Other autonimic features of Shy Drager syndrome (p. 1117)
erectile dysfunction loss of sweating dry mouth miosis urinary retention or incontinence
Features not supportive of MSA (p. 1118)
pill rolling tremor hallucinations dementia family history of ataxia eye movement are not prominent in MSA
MRI findings in MSA (p. 1118)
hot cross bun
Most common complaint for PSP (p. 1119)
unsteadiness of gait
Characteristic symptoms of PSP (p. 1119)
supranuclear ophthalmoplegi
pseudobulbar palsy
axial dystonia
Other eye signs in PSP (p. 1119)
ability to converge is los eventually
pupils become small but remain round and reactive to both light nd accomodtive stimuli
Face of PSP (p. 1119)
worried appearance
PSP vs PD (p. 1119)
facial expression of PSP is more tonic grimace than lck of movement
lack of tremor
erect rather than stopped posture
promience of occulomotor abnormalities
Applause sign (p. 1119)
In PSP, fils to stop clapping after neig asked to do so only 3 times
MRI finding in PSP (p. 1119)
Hummingbird sign
Mouse ears sign
Gabanergic agonist of BZD receptor reported to ameliorate the akinesia and rigidity of PSP (p. 11121)
Zolpidem
Most common presentation for CBGD (p. 11121)
asymmetrical clmsine of the limbs
Ballooned and chromatolytic neurons with eccentric nucleu in CBGD (p. 1121)
neuronal chromasia
Corticostriatospinal degeneration (p. 122)
Jakob disease
2 categories of acanthocytosis with chorea (p. 1122)
HARP: hypobetalipoproteiniemia, acanthocytosis, retinitis pigmentosa, pallidal degeneration
Bassen Korenzweig disease: mainly lacks lipid abnormality
Disorder with acanthocytosis with gradual development of chorea in middle to late life, characterized by degeneration of the caudata and putamen and a myopathy (p. 1123)
McLeod disease
remember: KX protein, Kell antigen
Most common mutation in dystonia musculorum deformans (p. 1123)
DYT1 which encodes torsin A; deletion of a single glutamate from the torsin A peptide
Protein affected in Segawa syndrome (p. 1124)
GTP cyclohydrolase
Feature of Segawa syndrome (p. 1125)
disappearance of marked subsidence of the symptoms after a period of sleep and worsenig as the day progresses
Expresion of this trinucelotide is most common in Friedreich Ataxia (p. 1127)
GAA tricucleotide repeat within FXN
Other notes in Freidreich Ataxia (p. 1127)
emotional lability had been prominent
tendon reflexes are abolished
half of patients have cardiomyopathy
gene: frataxin
Pathologic finding in Freidreich Ataxia (p. 1128)
spinal cord is thin
posterior columns, CST and SC tracts are all depleted of myelinated fibers
Vitamen E deficiency vs Freidrich ataxia (p. 1128)
absence of dysarthria and of skeletal or cardiac abrnormalities in vitamin-deficiency illness
Treatment improves cerebellar symptoms of FA (p. 1128)
oral 5- hydroxytryptophan
Treatment reducing progression of ventricular hypertrophy in Freideich ataxia (p. 128)
idebenone
What is the main distinction of Cerebellar Cortical Ataxia and MSA with cerebellar degeneration? (p. 1129)
In CC,pontine nuclei is spared.
Pathological finding in Holmes type (p. 1129)
symmetrical atrophy of the cerebellum mainlythe anterior lobe and vermis
Alcoholic cerebellar degeneration vs Holmes type cerebellar cortical ataxia (p. 1129)
In alcohol-nutritional disase, there is accompnying polyneuropathy and reduced ankle reflexes
Fragile X Tremor- Ataxic Premutation Syndrome (p. 1130)
50 to 200 CGG repeat sequence
OPCA with neuropathy and sloed eye movements (p. 1131)
Wadia type
Findings in Machado-Joseph-Azorean Disease (p. 1131)
degeneration of the dentate nuclei and spinocerebellar tract and loss of anterior horn cells, neurons of pons, SN and occulomotor nuclei
unstable number of CAG repeating sequences in ataxin-3
MRI findings in Machado-Joseph-Azorean diseae (p. 1131)
reduced width of the superior and middle cerebellar peduncles, atroph of the frontal and temporal lobe, smallness of the pons and globus pallidus
DRPLA vs Huntington (p. 1131)
main consideration when chorea is a prominent feature
Notes on DRPLA (p. 1131)
unstable CAG trinucleotide repeat in ATN1 which codes for protein atrophin 1
On paroxysmal ataxias, this drug is proven effective to lessen the attacks in patients with calcium channel gene mutation (p. 112)
Oral acetazolamide
Triad of ALS (p. 1134)
atrophic weaknes of the hands and forearms
fasciculations and slifht spasticity of the arms and legs
generalized hyperreflexia
Principal pathologic finding in ALS (p. 1135)
loss of nerve cells in teh anterior horns of the spinal cord and motor nuclei of the lower brainstem
Comment on SOD1 gene ALS (p. 1136)
the nonmotor systems seem to be more affected
slower pace than usual ALS, some partients surviving for 15 years or longer
illness presentation is symmetrical
(p. 1136)
Progresive Musculular Atrophy
Difference between PMA and ALS (p. 1136)
tendon reflexes are diminished in PMA
Reflex found in progressive bulbar palsy (p. 1136)
Bulldogreflex
jaw snaps hut involuntarily
20% of ALS suspects have a slowly progressive corticospinal tract disorder that begins with pure spastic paraparesis (p. 1137)
Primary Lateral Sclerosis
Partial cervical and spinal amyotrophy (p. 138)
Hirayama disease
40%of forms of ALS with known family history is assocaited with the hexanucelotide expansion of __ (p. 1138)
C9orf72 gene
Treatment for ALS (p. 1139)
Antigultamate agent Riluzole
Edaravone
Masitinib
The ability to count to 25 ith a full efort in a single breath correponds to the vital capcity of approximately ___(p. 1140)
2.5L
This determines teh severity and time of onset of SMA (p. 1141)
SMN2
Types of SMA (p. 1141)
SMA1 Werdnig Hoffmann
SMA2 Dubowitz
SMA3 Kugelberg-Welnder
After cystic fibrosis, it is the most frequent cause of death from a recessively inherited disease (p. 1141)
Werdng-Hoffman disease
Characteristic posture of SMA1: (p. 1141)
arms abducted and flexed at the elbow, legsin the frog position with external rotation and abduction at hips and flexion at hips and knees
SMA vs fatty acid metaolism disorders (p. 1142)
preservaton of tendon reflexes
relative lack of preogression of muscle weaknes
This antisense oligonucleotide modifies the spilicing of SMN2 to result in increased production of SMN protein in motor neurons and comepnsate for the mutated SMN1. (p. 1143)
Nusinersen
Distal muscular atrophy with prominet bulbar signs and less often, ocular palsies (p. 1143)
Kennedy Disease
Mutation in Kennedy Disease (p. 1143)
SLC52A3, a riboflvin transporter
hence some beneficial effect is derived from administration of riboflavin
In Leber Herediatary Optic Atrophy, which color is first affected (p. 1146)
blue-yellow; red-green is relatively preserved
Primary structural change in Leber Hereditary Optic Atrophy (p. 1146)
Peripapillary vasculopathy
In RP, affected are which laters (p. 1146)
BOTH neuroepithelium and pigment epithelium
First symptom in RP (p. 1146)
nyctalopia
Ophthalmoscopic examination in RP (p. 1146)
pigmentary deposits that assume the configuration of bone corpuscle, attenuated vessels and pallor of optic discs
Patognomonic “dark choroid” pattern (p. 1147)
Stargardt Disease
Hereditary Hearing Los wth Retinal Disease (p. 1147)
RP:
Usher syndrome: with congentital hearing loss
Refsum syndrome: with polyneuropathy
Alstrom sndrome: with hypogonadism
Cockayne syndrome: with dwarfism, mental retardation, premature senility and photosensitive dermatitis
