CNS PT-2 Test II

Question 1

Early onset Dementia (EOD)

Answer 1

Evidence of a significant cognitive decline in adults between 18 and 65.

Question 2

Main causes of EOD looked at in class.

Answer 2

Alzheimer disease

Parkinson disease dementia

MS

Question 3

Alzheimer Disease

Answer 3

Most common cause of dementia in older adults

Essential Neuropathologic changes

Neuritic plaques

Deposits of amyloid beta (AB) peptides

Mutation causes abnormal cleavage of amyloid precursor protein causing aggregations of AB proteins.

Neurofibrillary tangles

Inflammatory kinases destabilize microtubules freeing Tau monomers that aggregate into neurofibrillary tangles.

Question 4

Genetic Risk Factors of AD

Answer 4

Early-Onset Alzheimers (<65 y/o in 40s and 50s)

Primarily caused by mutations in APP, PSEN1/2.

Late-Onset Alzheimers

Over 65 carrier of APOE e4

Question 5

Pathophysiology of Parkinson Disease Basal Ganglia Circuits

Answer 5

Dopamine Depletion in the substantia nigra ultimately results in:

Increased inhibition of the thalamus

Reduced excitatory input to the motor cortex

Lewey Bodies - Eosinophilic aggregates of proteins.

Question 6

Compensatory mechanisms in PD

Answer 6

Compensate for dopamine depletion by:

Increased production of dopamine in surviving neurons

Upregulation of Dopamine receptors

Increase in gap junctions

Question 7

Clinical features of PD

Answer 7

Tremor

Rest tremor and intermittent

Bradykinesia

Generalized slow movement

Rigidity

increased resistance to movement around a joint

Postural instability

an impairment of postural reflexes causing feeling of imbalance and tendency to fall

Question 8

Amyotrophic Lateral Sclerosis (ALS)

Answer 8

A persistantly progressive neurodegenerative disorder that causes:

Muscle weakness (motor neuron degeneration)

disability

eventual death

Sporadic 90-95%

Risk Factors

Age

Family History

Environmental factors

Smoking

Toxin exposure

Military service

Question 9

Etiology of ALS

Answer 9

Abnormalities in RNA Metabolism

Excitotoxicity

Viral infections

Inflammatory response

Question 10

Pathology of ALS

Answer 10

Intracellular inclusions in the degenerating neurons and glia

Motor Neuron degeneration and death with gliosis

Spinal cord becomes atrophic

Affected muscles dhow denervation atrophy

Question 11

Clinical features of ALS

Answer 11

Upper motor neuron

findings of weakness with slowness, hyperreflexia, and spasticity

due to degeneration of frontal motor neurons

Lower Motor neuron

findings of weakness, atrophy, and fasciculations

due to degeneration of lower motor neurons in the brainstem and spinal cord

Question 12

Multiple Sclerosis (MS)

Answer 12

A heterogeneous disease with variable clinical and pathologic features

Question 13

Immunopathology of MS

Answer 13

Begins as an inflammatory immune-mediated disorder

Microglia form a complex with the activated T cells causing destruction of the myelin and oligodendrocytes

Areas of CNS affected are referred to as lesions or plaques

Question 14

Alternate theories of MS

Answer 14

A possible immune, but not autoimmune etiology

Genetic determination

Question 15

Disease patterns of MS

Answer 15

CIS (first attack no follow-up)

Relapsing-Remitting (Clear relapses with full recovery)

Secondary-Progressive (Initial RR disease with gradual worsening)

Primary-Progressive (progressive accumulation of disability)

Question 16

Primary Brain Tumors (Gliomas)

Answer 16

Ependymomas

Mixed gliomas

Diffuse Gliomas

Astrocytomas

Oligodendrogliomas

Question 17

Classifications of diffuse gliomas (Brain Tumors)

Answer 17

Isocitrate dehydrogenase (IDH)-mutant or IDH-wildtype astrocytomas

IDH-mutant and 1p19q-codeleted oligodendrogliomas

IDH-mutant or IDH wildtype glioblastoma

Question 18

Astrocytoma

Answer 18

Formation of astrocytoma: grade II is associated with:

mutations in IDH1

Inactivation of the TP53

Mutations in the chromatin regulator gene

Question 19

Astrocytoma IDH and its link to gliomas

Answer 19

Acquiring a somatic mutation in either IDH1 or IDH2 leads to accumulation of oncometabolite 2-hydroxyglutarate (2-HG)

Elevated 2-HG can cause:

Changes in DNA and histone methylation

Abnormalities in cellular differentiation

Tumorigenesis

Question 20

Low-Grade, Malignant, and High-Grade Gliomas

Answer 20

Transition from low-grade to malignant grade glioma is associated with:

Cell Cycle checkpoint inactivation

Tumor suppressor gene inactivation

Angiogenesis

High-Grade gliomas

anaplastic glioma

glioblastoma

Question 21

Meningoma

Answer 21

Predominantly benign tumors of adults arising from the meninges

Risk from prior radiation therapy to head and neck (Typically decades old)

Arises from abnormal Chromosome 22

Slow Growing

Common symptoms - headache and arm/leg weakness

Progesterone receptors lead to faster growth in pregnancy

Question 22

Metastatic Brain Tumors

Answer 22

Most common brain tumor in adult.

Common primary sites

Lung

Skin

Kidney

Breast

GI Tract

Question 23

Etiology and clinical features of Metastatic Brain Tumors

Answer 23

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

Commonly present with;

Headache

Focal neurologic dysfunction

Cognitive dysfunction