Neurodegenerative disorders

Question 1

Disease of Grey mattered characterized by progressive loss of neurons with associated secondary changes in the white matter tract. Presence of protein aggregates that are resistant to degradation through the ubiquitin proteasome system. Histologically seen as INCLUSION

Answer 1

Neurodegenerative Disorders

Question 2

————- and ———— are neurodegenerative disorders of the Cerebral Cortex Neurons

Answer 2

Alzhemier and PICK (frontotemporal Lobar Degenerations)

Question 3

———- and ———- are degenerative disorders of the Basal Ganglia

Answer 3

Parkinson and Huntington

Question 4

——— is a degenerative disorder of the Spinocerebellar

Answer 4

Friedreich Ataxia

Question 5

————— is a neurodegenerative disorder Motor neurons

Answer 5

Amyotrophic Lateral Sclerosis (ALS)

Question 6

What are the Early mutations in Alzheimer disease and which is the most common?

Answer 6

APP gene on Chromosome 21 (Down syndrome)
PSEN-1 gene on chromosome 14 (Most common)
PSEN-2 gene on Chromosome 1

Down Syndrome associated from excess doses of APP gene on Chr 21 which results in excess cerebral amyloid production

APP- Amyloid Precursor Protein

Question 7

Late onset of Alzhemier Disease is caused by?

Answer 7

Apo Ę gene on chromosome 19 (Apo E 4) allele

Question 8

What are the risk factors of Alzheimer disease

Answer 8

Age > 70 years
Positive family history (suggests genetic contribution- Autosomal dominance

Question 9

What is the earliest gross pathological changes in Alzheimer disease and what causes cognitive decline in the disease?

Answer 9

Question 10

3 Microscopic Changes in Alzheimer disease

Answer 10

1. Extracellular neuritic (senile) plaques- Beta Amyloid Protein
2. intracellular neurofibrillary tangles - Hyperphosphorylated microtubules associated protein - PTAU
3. cerebral amyloid angiopathy

Question 11

What enzyme cleaves APP( Amyloid precursor protein) that leads to the production of AB peptides - Extracellular neuritic (senile) plaques

Answer 11

Beta Secretase and Y secretaries

Question 12

Clinical Consequences of —————- disease begins with MEMORY impairment (Hippocampus), progresses to language and Visio spatial deficits, executive dysfunction, organization problems, navigational difficulties, word-finding END stage: rigidity, mute, incontinent, bedridden and needs assistance with eating, dressing and toileting

Answer 12

Alzheimer disease

Question 13

What are the generalized MRI finding in Alzheimer disease

Answer 13

Generalized or focal cerebral atrophy- ENLARGED ventricle and prominent cerebral Sulci (Ex Vacoule)

Question 14

Age onset is 5th to 7th decade, Alteration in personality, Behavior and altered speech pattern precede Memory Loss; Apathy, Disinhibition; socially inappropriate and compulsive behavior

Answer 14

frontier-Temporal Dementia -PICK disease

Question 15

A frontotemporal lobar degeneration (Knife -edge) Cholinergic system is relatively spared compared to Alzheimer disease

Answer 15

PICK disease (fronto-temporal lobe) a frontal anterior loss of temporal lobes

Question 16

Tau or TDP -43 is seen in 90% of patient s of Frontotemporal dementia (PICK) True or False?

Answer 16

True

Question 17

What is the main pathophysiology of PICK disease? Which Protein is mutated?

Answer 17

Microtubules associated protein Tau (MAPT) (Chromosome 17) Tau +

Question 18

Genetic Basis of Frontotemporal dimentia (PICK disease)

Answer 18

Question 19

Differences between PICK Disease and HIV associated Dementia based on pathological features

Answer 19

PICK - A round intracellular aggregates of hyperphosphorylated Tau (3R tau)

HIV associated Dementia- Presence of MICROGLIAL nodules- which are clusters of activated immune cells in the brain

Question 20

———— dementia is seen in Advance HIV pt who have CD4 counts < 200/mm.
Subcritical dementia which includes attention or working memory deficit, executive dysfunction and slow information processing

Histology: cluster of Microglial cells/ macrophages around small foci of necrotic brain tissue

Answer 20

HIV associated Dementia

Question 21

Basal Ganglia structure

Answer 21

Caudate nucleus : curved structure surrounding the lateral ventricles in a C shape
Putamen: lateral to caudate nucleus
Globus Pallidus (External and Internal)
Subthalamic Nucleus (STN): situated below the thalmus
Substantial Nigra :

Question 22

Striatum is made up of ———- and ———- which secretes ____________ and inhibitory transmitter

Answer 22

Caudate Nucleus and Putamen; GABA

Question 23

Images of Basal Ganglia

Answer 23

Question 24

Substantial Nigra secrete ————-

Answer 24

Dopamine

Question 25

Degeneration of dopamine fibres occurs at?

Answer 25

Subtantial Nigra Completa

Question 26

GPRC receptors: ———- acts on Gs and ———- acts in Gi

Answer 26

G1 receptor; G2 receptor

Question 27

Cardinal feature of Parkinson Disease: TRAP

Answer 27

Question 28

Second most common age-related neurodegenerative disease; Mean age about 60yrs; Early Onset <40yrs are associated with gene mutation: Alpha-synuclein Glycocerebrosidase (GBA) LRRK2 PINK1/ Parkin

Answer 28

Parkinson Disease

Question 29

The pathological Hallmark features of Parkinson Disease

Answer 29

Question 30

Answer 30

Subthalamic Nucleus - take this away and there will be no excitation on GPi cos Glutamate won’t be able to stimulate GPi to release GABA

Question 31

Parkinson disease - Gross and Microscopic Features (Normal, Reductionnof pigment in SNc in PD, Lewy bodies

Answer 31

Question 32

Which protein is deposited in Lewy bodies?

Answer 32

Hyperphosphorylated Tau proteins - alpha Synuclein

Question 33

Decriminate Parkinson Disease Dementia (PDD) and Dementia with Lewy Bodies (DLB)

Answer 33

In Dementia with Lewy Bodies, Dementia occurs first along with Hullucination In Parkinson Disease Dementia, Dementia occurs last following loss of movement disorders (first)

Question 34

Lewy bodies are present throughout the brain in 3 stages _______, ————-, and ———— poor response to Levodopa

Answer 34

Brain stem predominant Transitional limbic Diffuse neocortical

Question 35

Classification of forms of Parkinsonism based on clinocopathological features

Question 36

True or false: Wilson disease and Fragile X can cause Parkinson disease?

Answer 36

True

Question 37

What is the the toxic metabolite of MPTP (1-methyl-4-phenyl-1,2, 3, 6- Tetrahydropyridine ? How can you treat?

Answer 37

MPP+ (1-methyl-4-phenylpyridinium ion . treatment by MAOB inhibitor

Question 38

Transmitters for Locus Coeruleus (Parkinson Disease) and Substantial Innominata

Answer 38

-Norepinephrine -Chlornerginic

Question 39

Two important histological features for Huntington are ————— and ————-

Answer 39

1. Lost of spiny neurons 2. Reactive Gliosis (proliferation of astrocytes)

Question 40

An autosomal dominant disease with onset 25-45years due to the prominent loss of medium size spiny neurons and Gliosis in the caudate nucleus and putamen (Straitum disorder)

Answer 40

Huntington Disease

Question 41

Rapid, nonpatterned, Involuntary Choreiform movements, OCULOMOTOR deficit, behavior abnormalities, progressive dementia, Early stage: Focal or segmental Chorea Advance stage: Reduction in Chorea and the emergence of Dystonia, rigidity, bradykinesia, and myoclonus

Answer 41

Characteristics of Huntington disease

Question 42

—————Disease caused by DECREASE —————-and unbalanced ——————— in the striatum (Caudate nucleus and Putamen) leading to Chorea

Answer 42

Huntington disease, GABA, Dopamine

Question 43

What repeat (3X) is found in Huntington gene on Chromosome 4p?

Answer 43

Question 44

Gross and microscopic presentation of Huntington Disease

Answer 44

FLAIR -MRI shows enlargement of the lateral ventricles reflecting atrophy of the caudate lobe (arrows)

Question 45

An auto recessive disease, a spinocerebellar degenerative disease that manifest in 1st decade of life and wheel chair by 5years, Death from Pulmonary infections or cardiac disease

Answer 45

Friedrich Ataxia

Question 46

Pathophysiology of —————— is a trinucleotide repeats (GAA) on the Frataxin gene on Chromosome ————causing mitochondrial iron overload which leads to oxidative damage and degeneration of both CNS and PNS

Answer 46

Friedrich Ataxia; Chromosome 9

Question 47

An Autosomal recessive disease that presents with Spastic weakness, staggering gait, frequent fall

Answer 47

Friedrich ataxia

Question 48

Associated with HYPERTROPHIC CARDIOMYOPATHY, kyphoscolosis, FOOT ABNORMALITIES, and DIabetes

Answer 48

FRIEDRICH ATAXIA

Question 49

Histologic findings: Degeneration if neurons in the spinal cord, brain stem, cerebellum and the Betz cells if the motor cortex is associated with?

Answer 49

Friedrich Ataxia

Question 50

Summary of Friedrich Ataxia

Answer 50

Question 51

Identify the Disease

Answer 51

Friedrich Ataxia

Question 52

An Autosomal Recessive disorder due to Mutated ATM GENE —-> unable to repair double strand DNA breaks—-increase cancer development?

Answer 52

Ataxia Telangiectasia

Question 53

Increased risk for Carcinomas gloom as and lymphomas, death by second decade with clinical presentations: -Ataxia (Cerebellar degeneration) -Spider angiomas (Telangiectasia) -Skin, conjunctiva and brain -Decreased immunocompetence (Recurrent Sinopulmonary infections)

Answer 53

Ataxia Telangiectasia

Question 54

What disorder is this?

Answer 54

Ataxia Telangiectasia

Question 55

Autopsy was done and there was a problem with the Diaphragm… what disease?

Answer 55

ALS- Amyotrophic lateral Sclerosis

Question 56

Mean age is 57 years, Autosomal dominant disease and the most common MOTOR Neuron Disease

Answer 56

ALS -Amyotrophic lateral Sclerosis

Question 57

Identify this disease

Answer 57

ALS

Question 58

What is the classical Triad of ALS? Hint: ASH

Answer 58

Question 59

The most concerning site of LMN degeneration in ALS is ————-

Answer 59

Diaphragm

Question 60

What are the pathological features of ALS?

Answer 60

Question 61

In a Microscope, THIN VENTRAL ROOTS is associated with —————-disease?

Answer 61

ALS

Question 62

Identify this Disease based on the image

Answer 62

ALS

Question 63

Alzheimer disease is the leading cause of Dementia (True or False)

Answer 63

True

Question 64

————— disease results from Trinucleotide repeats (CAG) in ————-gene

Answer 64

Huntington Disease; Huntington gene

Question 65

Disease associated with progressive depletion of dopaminergic neurons—- Lewy bodies (Intracellular eosinophilia inclusion) in Substantial Nigra

Answer 65

Parkinson Disease

Question 66

Disease associated with trinuclotide repeats (GAA) on in the frataxin gene

Answer 66

Friedreich Ataxia

Question 67

Mutation of gene that encodes protein C9orf72, Cu-Zn Superoxide Dismutase (SOD1)

Answer 67

ALS