CNS-II

Question 1

Def. of early onset dementia

Answer 1

o Cases of dementia in adults ranging from 18 to 65 years of age
 Learning and memory
 Can’t be independent anymore

Question 2

what is the most common cause of dementia in adults

Answer 2

alzheimers disease

Question 3

what are the neuropathologic changes that occur in the brain in Alzheimers disease

Answer 3

• Essential neuropathologic changes”
o Neuritic plaques
o Extracellular deposits of amyloid beta peptides
o Neurofibrillary tangles (tau proteins)

Question 4

Pathogenesis of AD

Answer 4

• Amyloid precursor protein (APP) cleaved by beta-secretase and gamma-secretase
• Mutations in presenilin 1 (PSEN1) or presenilin 2 (PSEN2)  production of amyloid beta plaques

Question 5

what do the tau proteins cause in the brain

Answer 5

• Tau:

o hyperphosphorylated and aggregates → Causes an inflammatory response

Question 6

Genetic risk factors for early-onset AD

Answer 6

o Early-onset Alzheimer’s
 Younger than age 65 (40s and 50s)
 Mutations in APP, PSEN1, and PSEN2
 ANY OF THESE THREE MUTATE AND THERE WILL BE A 100% CHANCE OF AD

Question 7

Genetic risk factors for late-onset AD

Answer 7

 People age 65 and older

 Carries of APOE e4

Question 8

Pre-symptomatic period occurs due to ?

Answer 8

genetic mutations in APP1, PSEN1 or PSEN2

Question 9

Cardinal Clinical symptoms of AD

Answer 9

o Memory impairment

o Executive function and judgement/problem solving behavioral and psychological symptoms

Question 10

Pathogenesis of Parkinson’s

Answer 10

– Interplay of genes and the environment
o Basal ganglia circuits
 Dopamine depletion in the substania nigra ultimately results in:
 Increased inhibition (GABA) of the thalamus
 Reduced excitatory input (glutamate) into the motor cortex

Question 11

hallmark pathology of Parkinsons disease

Answer 11

lewy body

Question 12

The brain compensates for the dopamine depletion by?

Answer 12

o Increasing the synthesis of dopamine in surviving neurons
o Proliferation of dopamine receptors
o Gap junctions allowing rapid communications between neurons increase dramatically

Question 13

Clinical Features of PD

Answer 13

o Tremor
 “rest tremor” and intermittent
o Bradykinesia
 Generalized slowness of movement
o Rigidity
 Increased resistance to passive movement about a joint
 Pts feel like it’s taking them forever to do something
o Postural Instability
 An impairment of postural reflexes that cause a feeling of imbalance and a tendency to fall

Question 14

Amyotrophic Lateral Sclerosis (ALS) is defined by?

Answer 14

• Definition: persistently progressive neurodegenerative disorder that causes:
o Muscle weakness (motor neuron degeneration)
o Disability
o Eventually death

Question 15

Amyotrophic Lateral Sclerosis (ALS) established risk factors and environmental factors ?

Answer 15

•	Sporadic: 90 to 95%→ Sporadic and familial ALS. Approximately 90% cases of ALS are called “sporadic,” meaning the cause or causes of the disease are unknown. 
•	Established risk factors 
o	Age 
o	Family history 
•	Environmental factors 
o	Smoking 
o	Environmental toxin exposure 
o	Military Service

Question 16

Etiology of ALS

Answer 16

•	Etiology (unknown, but they’re hypothesis)
o	Abnormalities in RNA metabolism 
o	Excitotoxicity 
o	Viral Infections 
o	Inflammatory Responses

Question 17

Pathology of ALS

Answer 17

o Intracellular inclusions in degenerating neurons and glia
→ Characterized by motor neuron degeneration and death with gliosis
→ Spinal cord becomes atrophic
→ The affected muscles show denervation atrophy

Question 18

Clinical Features of ALS

Answer 18

o Upper motor neuron:
 findings of weakness with slowness, hyperreflexia, and spasticity
 Due to degeneration of Frontal Motor Neurons
o Lower motor neurons:
 Findings of weakness, atrophy, and fasciculations (muscle twitch)
 Due to degermation of lower motor neurons in the brainstem and spinal cord

Question 19

pathogenesis of multiple sclerosis and alternate theories

Answer 19

o Immunopathology:
 Begins as an inflammatory immune-mediated disorder
 Microglia forms a complex with the activated T-cells leads to destruction of myelin and oligodendrocytes
 Areas of CNS affected are referred to as “lesions” or “plaques”
o Alternate Theories:
 A possible immune (but not autoimmune) etiology
 Genetically determined

Question 20

Main Disease Patterns of multiple sclerosis?

Answer 20

o Clinically isolated syndrome
 First attack of a disease with inflammatory demyelination, but has yet to fulfill MS diagnostic criteria
 With no previous evidence of MS: newly diagnosed
o Relapsing-Remitting (RR)
 Clearly defined relapses with fully recovery
o Secondary Progressive (SP)
 Initial RR disease course followed by gradual worsening (transitional)
o Primary progressive (PP)
 Progressive accumulation of disability (w/ or w/o remission)

Question 21

Symptoms of multiple sclerosis

Answer 21

• Symptoms: (polysymptomatic onset)
o Sensory in limbs
o Visual loss
o Motor (subacute)

Question 22

What are gliomas

Answer 22

o Gliomas are primary brain tumors that show histologic features of glial cells
 Glial cells are the cells that support the nerve cells (astrocytes, oligodendrocytes, ependymal cells)

Question 23

what type of brain tumors are diffuse gliomas?

Answer 23

o	Astrocytomas 
	Diffuse Gliomas
o	Oligodendrogliomas 
	Diffuse Gliomas 
o	Ependymomas 
o	Mixed Gliomas

Question 24

Gliomas can be classified into three categories they are?

Answer 24

• Classifications of diffuse gliomas
o Mutation of the IDH -OR- IDH Wildtype (stays normal) astrocytomas
 Enzyme in kreb’s cycle
o Mutation of IDH -AND- Co-Chromosomal deletion of chromosome 1 and 19( causes loss of tumor suppressor gene)oligodendrogliomas
o IDH-mutant -OR- IDH- wild type glioblastoma
• Systemic symptoms

Question 25

Systemic symptoms of diffuse gliomas

Answer 25

• Systemic symptoms o Headache ICP o Seizures  ICP o N/V  ICP o Depressed level of consciousness   perfusion to brain o Neurocognitive dysfunction   perfusion to brain

Question 26

Focal symptoms of diffuse gliomas

Answer 26

• Focal Symptoms o Weakness o Sensory loss

Question 27

Astrocytoma | • Formation of astrocytoma: grade II astrocytoma is associated with:

Answer 27

o Mutations in IDH1 o Inactivation of the TP53 o Mutations in the chromatin regulator gene

Question 28

• IDH and its link to gliomas:

Answer 28

o Acquiring a somatic mutation in either IDH-1 or IDH-1  accumulation of the oncometabolite 2-hydroxyglutarate (2-HG) o Elevated levels in 2-HG can cause  Changes in DNA and histone methylation (epigenetic)  Abnormalities in cellular differentiation  Tumorigenesis (oncogenic)

Question 29

The transition from low-grade to high grade (malignant) glioma is associated with?

Answer 29

o Cell cycle checkpoint inactivation o Tumor suppressor gene inactivation o Angiogenesis

Question 30

what brain tumors are considered High-grade gliomas?

Answer 30

o Anaplastic gliomas | o Glioblastoma

Question 31

what is a meningioma

Answer 31

• Definition: | o Predominantly benign tumors of adults arising from the meninges

Question 32

What are risk factors for a Meningioma

Answer 32

o Prior radiation therapy (ionizing radiation) to the head and neck, typically decades earlier  Therapeutic -cancer  Atomic bomb survivors

Question 33

What is the etiology of a meningioma and what are the clinical features?

Answer 33

• Etiology: o Abnormal chromosome 22 • Clinical Features o Usually slow-growing tumors o Headache and weakness in an arm or leg are the most common symptoms o Often express progesterone receptors  Tumor will grow faster in pregnant women ( due to high progesterone levels)

Question 34

The most common brain tumor in adults is? What are the common most primary sites of this tumor

Answer 34

``` o Lung ** o Skin (melanoma) o Kidney o Breast o GI tract ```

Question 35

How do metastatic tumors come to be?

Answer 35

o Circulating tumor cells use the bloodstream or lymph system initially migrate and enter the lungs, then move on to the brain

Question 36

What are the clinical features of metastatic brain tumors

Answer 36

o Headache o Focal neurologic dysfunction: Hemiparesis o Cognitive dysfunction