Lecture 6: CNS & PNS Pathology

Comprehensive question-and-answer flashcards covering degenerative, demyelinating, congenital, infectious, and peripheral nervous system pathologies from the CNS & PNS Pathology lecture.

What are the major degenerative and demyelinating diseases of the CNS?

Alzheimer disease, Parkinson disease and Parkinsonism, Huntington disease (chorea), Amyotrophic lateral sclerosis (ALS), and Multiple sclerosis.

What congenital malformations and perinatal brain injuries are discussed in CNS pathology?

Hydrocephalus, neural tube defects (spina bifida), cerebral palsy, and epilepsy.

What CNS infections are discussed in this lecture?

Meningitis and poliomyelitis.

What peripheral nervous system pathologies are discussed in this lecture?

Neurofibroma and neurofibromatosis, schwannoma, and neuroma.

What is Alzheimer disease?

A progressive neurodegenerative disease and the number one cause of dementia, accounting for more than 60% of cases.

Who described Alzheimer disease and when?

Dr. Alois Alzheimer in 1906.

What causes Alzheimer disease?

The cause is not completely understood; most cases are sporadic and less than 2% are inherited.

What genetic risk factor is found in 40% to 80% of Alzheimer disease patients?

Epsilon 4 mutation of the apolipoprotein E (APOE) gene.

What genes are associated with Alzheimer disease risk?

APOE, amyloid precursor protein (chromosome 21), and presenilin 1 and 2.

What is the typical age of onset for Alzheimer disease?

Most patients are older than 65 years.

What is early-onset Alzheimer disease?

Alzheimer disease occurring from the 30s to 50s and accounting for about 10% of cases.

What possible protective factor is associated with Alzheimer disease?

Higher education may have a protective effect.

How are Alzheimer disease symptoms commonly classified?

Early-stage (mild), middle-stage (moderate), and late-stage (severe).

What occurs in early-stage Alzheimer disease?

Short-term memory loss, difficulty finding words and names, difficulty performing familiar tasks, and problems planning and organizing.

What occurs in middle-stage Alzheimer disease?

Increasing impairment of learning and memory, agnosia, apraxia, loss of vocabulary and language fluency, fading long-term memories, sundowning, delusions, and wandering.

What is agnosia?

A defect in perception.

What is apraxia?

A defect in movement or inability to perform purposeful movements despite intact motor function.

What is sundowning?

Restlessness, confusion, and agitation that worsen at dusk.

What occurs in late-stage Alzheimer disease?

Worsening memory and cognition, loss of bladder and bowel control, muscle loss, difficulty swallowing, loss of awareness, inability to communicate, dependence on caregivers, and susceptibility to infections such as pneumonia.

What gross brain changes occur in Alzheimer disease?

Atrophy of the cerebral cortex, especially the hippocampus

Enlargement of the ventricles

Why does hippocampal atrophy cause symptoms in Alzheimer disease?

It impairs learning new information and forming new memories.

What are neurofibrillary tangles?

Abnormal accumulations involving cytoskeletal tau protein within neurons.

What are senile plaques?

Extracellular deposits of amyloid between neurons.

What do neurofibrillary tangles do?

Collections of tau protein block synaptic communication between neurons.

What do amyloid plaques do?

Deposits between neurons that hinder neuronal communication.

What percentage of Alzheimer disease cases are autosomal dominant familial forms?

About 0.1%.

Which genes are commonly mutated in familial Alzheimer disease?

Amyloid precursor protein, presenilin 1, and presenilin 2.

How is Alzheimer disease diagnosed clinically?

Mini Mental Status Examination (MMSE).

What lumbar puncture findings support Alzheimer disease diagnosis?

Elevated amyloid beta 42, elevated p-tau, and plasma p-tau-217.

What imaging studies are used in Alzheimer disease diagnosis?

CT scan, MRI, and FDG-PET.

What medications are used to treat Alzheimer disease?

Cholinesterase inhibitors (donepezil, rivastigmine, galantamine), memantine, amyloid-directed antibodies (donanemab and lecanemab), and psychotropic medications.

Do Alzheimer disease treatments reverse memory loss?

No, they may only slow progression.

Which former U.S. president died from Alzheimer disease in 2004?

Ronald Reagan.

What is Parkinson disease?

A long-term neurodegenerative disease that primarily affects motor function.

Who described Parkinson disease and when?

Dr. James Parkinson in 1817.

What causes Parkinson disease?

Likely a combination of genetic and environmental factors.

What environmental risk factors are associated with Parkinson disease?

Head trauma and pesticide exposure.

What is the usual age of onset for Parkinson disease?

Most patients are older than 60 years.

What is early-onset Parkinson disease?

Parkinson disease occurring before age 50.

Which sex is more commonly affected by Parkinson disease?

Males.

What are the motor signs and symptoms of Parkinson disease?

Resting tremor, rigidity, bradykinesia or akinesia, shuffling gait, and postural instability.

Where does Parkinsonian tremor usually begin?

In one hand or one leg.

Can Parkinsonian tremor affect the face?

Yes, it can affect the jaw and tongue.

What is rigidity in Parkinson disease?

Muscle stiffness with limited movement.

What is bradykinesia?

Slow movement.

What is akinesia?

Absence of movement.

Why is postural instability dangerous in Parkinson disease?

Falls and bone fractures are common.

What does the mnemonic TRAPS stand for?

Tremor, Rigidity, Akinesia, and Posture.

What non-motor symptoms occur in Parkinson disease?

Cognitive deficits, eye and vision problems, hallucinations, psychosis, depression, anxiety, and altered sense of smell.

What visual finding is associated with Parkinson disease?

Slow or infrequent blinking, called a serpentine stare.

What early sensory symptom may occur in Parkinson disease?

Loss or alteration of smell.

What is the pathology of Parkinson disease?

Loss of neurons in the substantia nigra with reduced dopamine production.

How does dopamine loss affect movement in Parkinson disease?

It reduces movement control by inhibiting the direct pathway and stimulating the indirect pathway.

Is Parkinson disease a hypokinetic or hyperkinetic disorder?

Hypokinetic basal ganglia disease.

What are Lewy bodies?

Abnormal protein accumulations found in increased numbers in Parkinson disease.

How do Lewy bodies affect the brain?

They disrupt dopamine production and impair mental capacity and behavior.

What is the gold-standard symptomatic treatment for Parkinson disease?

Levodopa/carbidopa.

How long does symptomatic drug therapy often provide control in Parkinson disease?

Approximately 4 to 6 years.

What MAO-B inhibitors may be used in Parkinson disease?

Drugs in the MAO-B inhibitor class for early disease management.

What dopamine agonists can be used in Parkinson disease?

Ropinirole and pramipexole.

What anticholinergic drugs may be used for Parkinsonian tremor?

Trihexyphenidyl and benztropine.

What is deep brain stimulation?

A reversible surgical treatment for Parkinson disease that does not destroy brain tissue and can be adjusted over time.

What advantages does deep brain stimulation offer?

It is reversible, adjustable, and can be performed bilaterally without significantly increasing adverse effects.

Which famous individuals had Parkinson disease?

Muhammad Ali, Pope John Paul II, and Michael J. Fox.

What is Parkinsonism?

A group of neurologic disorders that resemble Parkinson disease but are not caused by degeneration of Parkinson disease neurons.

What symptoms characterize Parkinsonism?

Tremor, rigidity, bradykinesia, and postural instability.

What causes Parkinsonism?

Brain disease, medications, toxins, infections, and chronic head trauma.

What is dementia with Lewy bodies?

The second most common dementia after Alzheimer disease and a disorder involving impaired dopamine production.

What is drug-induced Parkinsonism?

Parkinsonian symptoms resulting from medications that block dopamine.

What other causes of Parkinsonism are listed?

HIV infection, paraquat exposure, and chronic traumatic encephalopathy.

What is Huntington disease?

A neurodegenerative disease of the basal ganglia that commonly causes chorea.

What causes Huntington disease?

An autosomal dominant mutation in the huntingtin gene.

How does the huntingtin mutation affect the brain?

Production of abnormal huntingtin protein damages the brain.

Who described Huntington disease and when?

Dr. George Huntington in 1872.

At what age does Huntington disease usually begin?

Middle age.

What motor symptoms occur in Huntington disease?

Jerky uncontrolled movements (chorea), difficulty chewing, and difficulty swallowing.

What cognitive symptoms occur in Huntington disease?

Difficulty planning and abstract thinking, progressing to memory loss and dementia.

What psychiatric symptoms occur in Huntington disease?

Anxiety, depression, and obsessive-compulsive behavior.

What pathology is seen in Huntington disease?

Atrophy of the caudate nucleus and neuronal loss.

Which neurotransmitter is reduced in Huntington disease?

Gamma-aminobutyric acid (GABA).

Is Huntington disease hyperkinetic or hypokinetic?

Hyperkinetic basal ganglia disease.

How does Huntington disease compare with Parkinson disease?

Huntington disease is hyperkinetic, whereas Parkinson disease is hypokinetic.

How is Huntington disease managed?

Experimental gene therapy and medications that reduce chorea.

Which famous musician died from Huntington disease?

Woody Guthrie.

What is amyotrophic lateral sclerosis (ALS)?

A degenerative disease affecting corticospinal tracts and both upper and lower motor neurons.

Why is ALS called amyotrophic?

Loss of nerve stimulation causes muscles to become small and weak.

Why is ALS called sclerosis?

Degeneration is followed by scarring of nervous tissue.

What causes ALS?

Unknown, but hereditary and environmental factors are implicated, including SOD1 mutations.

What is the typical age range for ALS?

Most commonly in people aged 40 to 60 years, especially males.

What are the major symptoms of ALS?

Asymmetric limb weakness, fasciculations, clonus, hyperreflexia, weakness of mastication and speech muscles, and swallowing difficulty.

What body functions are usually spared in ALS?

Bowel function, bladder function, and sensation.

What percentage of ALS patients have cognitive or behavioral problems?

Approximately 30% to 50%.

What is the usual survival after ALS diagnosis?

Approximately 2 to 6 years.

Why is ALS called Lou Gehrig disease in the United States?

Because baseball player Lou Gehrig developed and died from ALS.

Who is a well-known example of slowly progressive early-onset ALS?

Stephen Hawking.

What is multiple sclerosis (MS)?

A demyelinating disease characterized by destruction of myelin sheaths in the CNS.

What replaces myelin in MS?

Glial plaques or sclerotic scars.

Why do neurologic deficits occur in MS?

Demyelinated axons cannot properly conduct nerve impulses.

What types of deficits occur in MS?

Cognitive, sensory, and motor deficits.

What causes MS?

An immune-mediated process in which T cells attack myelin.