Neurological Study Guide

General concept of degenerative disease

• True neuronal death

• Not just aging changes

• Primarily affect grey matter

• Selective or generalized loss

• Atrophy may be local or global

What is dementia?

Chronic, progress failure of cerebral functions such as orientation, memory, language, judgement, decision making, and behavior

Dementia is not a specific disease, rather a group of symptoms caused by brain damage

True

Dementia typically occurs in ____ people but is NOT a normal aging process

older

Pathophysiology of dementia

• Neuron degeneration

• Brain trauma

• Atherosclerosis of cerebral vessels

• Compression of brain tissue

• Genetic predisposition

• CNS infections and neuroinflammation

Alzheimer’s disease

A progressive neurological deterioration affecting memory, thinking, and the ability to carry out simple tasks

The most common cause of dementia in older persons is

Alzheimer’s disease

The key risk factor for developing Alzheimer’s is

increasing age

Forms of Alzheimers disease

• Late onset (90-95% of cases): Sporadic or Apolipoprotein E alteration

• Early onset (5-10%): Familial (pre-senile), Nonfamilial (down syndrome)

The most common form of Alzheimer’s

Sporadic

Intracellular pathophysiology of Alzheimer’s disease

Intracellular accumulation of hyperphosphorylated tau protein leads to neurofibrillary tangles (NFTs), which distort microtubule spacing, impairing axonal transport

Alzheimer’s (Tau Proteins): Cognitive decline correlates better with neurofibril tangles load than plaque count

True

Extracellular pathophysiology of Alzheimer’s

Beta-amyloid protein is cleaved from amyloid precursor protein leading to senile (neuritic plaque)

Alzheimer’s is progressive usually spanning throughout

10-20 years

Signs and Symptoms: The 5 A’s of Alzheimers

• Amnesia - memory loss

• Agnosia - Difficulty recognizing objects or people

• Aphasia - Speech difficulty

• Anosognosia - Loss of self awareness

• Apraxia - Loss of learned movements

Early signs and symptoms of Alzheimer’s

• Forgetfulness

• Emotionally upset

Late signs and symptoms of Alzheimer’s

• Memory loss

• Disorientation

• Confusion

• Lack of concentration

• Decline in problem solving

• Brain atrophy

Brain atrophy (Alzheimer’s)

• Shrinkage of cerebral cortex and hippocampus

• Enlargement of ventricles

Definitive confirmation for Alzheimer’s disease is

post-mortem brain examination

Diagnostic tests for Alzheimer’s

• Physical exam

• Neurological and mental status exam with psychiatric assessment

• Post mortem brain biopsy

You are working in John P’s nursing home. You are caring for a patient named Davis, aged 79. Lately, Davis family has been complaining the Davis has had memory loss, speech difficulty, and loss of learned movements. Davis is likely to have which of the following conditions?

Alzheimer’s disease

Parkinson’s disease

Progressive neurodegenerative disease of the basal ganglia with the loss of dopamine-producing neurons

There is no cure for Alzheimer’s

True

Goals of treating Alzheimers

• Maintain function

• Treat underlying process

• Manage behavior

• Supporting patients/caregivers as a team

Pathogenesis of Parkinson’s disease

Intraneuronal Lewy body inclusions composed of alpha-synuclein

Lack of dopamine best describes which neurodegenerative disease?

Parkinson’s disease

Types of Parkinson’s disease

• Primary (no known cause): Idiopathic, increases with age (>60 years), and genetic

• Secondary (known cause): Environmental, antipsychotic medication, vascular, repeated head trauma

Primary Parkinson’s disease description/characteristics

No known cause, genetic, and increases with age (>60 years)

Secondary Parkinson’s disease description/characteristics

There is a known cause

• Environmental (pesticides/herbicides)

• Antipsychotic medications

• Repeated head trauma (Pseudoparkinsonism)

Parkinson’s with no known cause is ________, while Parkinson’s with a cause is ________-

primary, secondary

Ali Mohamad, a former professional boxer, retired due to repeated head trauma. Recently, they have been exposed to pesticides and are actively taking antipsychotic medications. This puts Ali at SEVERE risk for

Secondary parkinsons disease

Signs of Parkinson’s disease

• Tremor

• Masked face

• Muscle rigidity

• Stopped posture

• Flexed arms, elbows, wrist, hips, and knee

• Slow movement

• Short shuffling steps

Rethinking Parkinsonism Terminology: True neurodegeneration is termed

Idiopathic Parkinson’s disease

Rethinking Parkinsonism Terminology: Parkinson’s from a drug reaction, such as antipsychotics, is termed

Drug-induced/Secondary Parkinsonism

Rethinking Parkinsonism Terminology: The proposed term for distinct neurodegenerative diseases is

Parkinson-Like Disorders

Pathogenesis (process) of Parkinson’s disease

• Progressive loss of dopaminergic neurons in substantia nigra pars compacta

• Misfolded alpha-synuclein aggregates into intracellular Lewy bodies

• Mitochondrial dysfunction and oxidative stress accelerate neuronal death

Pathophysiology of Parkinson’s disease

• Dopamine depletion disrupts the nigrostriatal pathway, impairing modulation of thalamocorticol motor circuits

• Net effect: excess inhibition of movement leads to bradykinesia and rigidity

• Degeneration eventually extends to non-dopaminergic systems (autonomic, olfactory, cognitive)

Mr. Park has been admitted to the emergency room with suspicions of having a neurodegenerative disease. Mr. Park presents with tremor and muscle rigidity. Park’s movements are quite slow. Upon further evaluation, you find out that Mr. Park has chronically taken antipsychotic medicine. Mr. Park likely has

Parkinson’s disease

Huntington disease (aka huntington chorea)

An autosomal dominant disease described as progressive, debilitating inherited disease

Parkinsons disease is a _______ disease

hypokinetic

Huntington disease is a _____ disease

hyperkinetic

Huntingtons usually does not manifest symptoms until age __

40

Huntington’s disease is caused from mutation of

HTT gene on chromosome 4 (4p16.3)

Functions of huntingtin protein

• Cell signaling

• Transport

• Anti-apoptosis

• DNA repair

Signs and symptoms of Huntington’s disease

• Mood swing

• Restlessness

• Emotional damage

• Dementia

• Choreiform movements without conscious effort

CAG Trinucleotide Repeat and Genetic Anticipation: Normal

CAG is repeated 10-35 times

CAG Trinucleotide Repeat and Genetic Anticipation: HD

36-120+ times, (≥40 repeats → almost always develops disease)

CAG Trinucleotide Repeat and Genetic Anticipation: Larger expansions lead to…

earlier onset, more severe disease — the molecular basis of genetic anticipation across generations

Pathogenesis of Huntington’s

• Expanded CAG repeat produced a mutant huntingtin protein with abnormal polyglutamine tract

• Protein misfolding and aggregation impair normal protein clearance pathways

• Results in downstream transcriptional dysregulation and mitochondrial dysfunction

Pathophysiology of Huntington’s

• Loss of GABAergic neurons in the caudate and putamen lead to hyperkinetic disorder

• Progresses to generalized cerebral corticol atrophy

• Disrupted pathway underlies chorea and cognitive decline

• Acetylcholine levels also appear reduced

The loss of GABAergic neurons in the caudate and putamen lead to ________ disorder (Huntington’s)

hyperkinetic

In Huntington’s, there is progressive atrophy of the brain.

True

Diagnosis for Huntington’s disease

DNA Analysis (CAG repeat count)

Many Huntington patients die to

All of the above

Amyotrophic lateral sclerosis (ALS) (also known as Lou Gehrig’s disease)

Rapidly progressive and fatal neurodegenerative disease of upper and lower motor neurons

Cognition regarding Lou Gehrig’s / ALS

• Cognition is preserved in most patients

• 50% of patients show some cognitive/behavioral involvement

• A smaller subset (about 10%) develop frontotemporal dementia

Pathogenesis of ALS

• Idiopathic

• SOD gene mutation damages glutamine uptake channels in astrocytes

• Genetic cause of ALS and frontotemporal dementia - C9orf72 repeat expansion

People at risk for ALS

• Those who experience repeated trauma (athletes)

• Military veterans (Gulf War 1991)

Pathophysiology of Amytrophic Lateral Sclerosis

• Loss of upper neurons leads to spastic paralysis and hyperreflexia

• Lower motor neuron damage leads to flaccid paralysis and decreased muscle tone/reflexes

• Progressive weakness, loss of fine motor control; stumbling and falls are common

• Death from respiratory failure

Death in ALS patients is usually

Respiratory failure

Spastic paralysis and hyperrflexia indicates

Upper motor neuron loss

Flaccid paralysis and decreased muscle tone/reflexes indicates

Lower motor neuron damage

Manifestations of ALS

• Limb weakness/cramping

• Dysphagia

• Hypotonia

• Single muscle group paresis that spreads (partial muscle weakness)

• Incoordination

• Slurred speech

The average survival of an ALS patient is

3-5 years

Name all neurodegenerative diseases learned

• Amytrophic Lateral Sclerosis / Lou Gehrig’s

• Huntington’s disease

• Parkison’s disease

• Alzheimer’s disease

Loco is a 75-year old war veteran. He presents to the clinic with limb cramping and hypotonia. Loco has not eaten in 3 days due his ongoing dysphagia. Loco is likely to have which disease?

Amytrophic lateral sclerosis / Lou Gehrig’s

Cerebrovascular Disease: Overview

Neurological disorders caused by pathologic processes in blood vessels

Pathogenesis of Cerebrovascular Diseases

• Ischemia (with/without infarction; local/global)

• Hemorrhagic

• Vascular malformation (AV malformation)

Cerebrovascular disease (general): Increased intracranial pressure can lead to

All of the above

Transient Ischemia Attack (TIA)

Transient episode of reversible, neurologic dysfunction caused by focal brain, spinal cord, or retinal ischemia without acute infarction

Symptoms of TIA typically resolve in _ hour(s)

1

Symptoms of TIA always resolve with __ hours

24

TIA is a critical warning sign for stroke. Describe these warning signs.

• 1 in 3 patients progress to stroke within 90 days

• Highest risk is within 48 hours of TIA

The most common cause of TIA is

Atherosclerosis

Transient ischemic attack is the leading cause of disability in the US and 5th leading cause of death in the US

True

TIA is

reversible.

Causes of TIA

• Atherosclerosis

• Vascular spasm

• Arteritis

• Mass lesions

Signs and Symptoms of TIA

Difficult to diagnose after attack has passed; directly related to location of ischemia

• Muscle weakness in arm/leg

• Visual disturbances

• Numbness/parathesia

• Transient aphasia/confusion

Diagnosis of TIA

• Important to rule out other causes first

• MRI (preferred) or CT scan

• Carotid doppler

• Angiography

Management of TIA

• Initiate stroke prevention therapy

• Risk stratification

Cerebrovascular accident (aka Stroke)

An infarction of the brain tissue due to hypoperfusion (lack of blood supply)

• Leading cause of disability

__% of strokes are recurrent

25

Which group of people are at higher risk for stroke?

African-American

Ischemic stroke

• Blood vessel occlusion by a thrombus or an embolus

• Risk factor is atherosclerosis

Hemorrhagic stroke

• Rupture of a cerebral vessel

• High morbidity and mortality

• Risk factor: Hypertension

• Types: intracerebral hemorrhage, subarachnoid hemorrhage

Nonmodifable risk factors for stroke

Age, sex, family history, ethincity

Modifiable risk factors for stroke

• Hypertension

• Diabetes Mellitus

• Smoking

• Sedentary lifestyle

Signs and Symptoms of CVA

• Loss of voluntary movement and sensation on OPPOSITE side of body (contralateral)

• Initial flaccid paralysis later becoming spastic paralysis

BE-FAST for Strokes/CVA

• Balance - sudden loss of balance

• Eyes - Sudden vision changes

• Face drooping

• Arm weakness

• Speech difficulty

• Time - Call 911

Stroke scale: NIH stroke scale

• Designed to rapidly diagnose

• Predict short/long term outcomes

Acute complications of stroke/CVA

• Increased ICP/cerebral edema, herniation

• Hemorrhagic transformation of an ischemic stroke

• Seizures

• Aspiration pneumonia

• Deep vein thrombosis

• Pulmonary embolism

Chronic complications of stroke/CVA

• Post stroke disability: hemiparesis, spasticity

• Aphasia, dysphagia

• Post-stroke depression

• Vascular dementia; increased recurrence risk

Stroke prevention methods

• Healthier diet

• Stop smoking

• Weight/exercise management

• Control hypertension

• Control type II diabetes

• Lifestyle modification

• Aspirin

Name the cerebrovascular diseases we learned

• Transient ischemic attack

• Cerebrovascular attack/stroke

You are hanging out with your friend, Season 8 Lion. Suddenly, he has a sudden loss of balance and falls to the floor. Upon further inspection, you notice he has vision changes and face drooping. You recognize that this is

Cerebrovascular attack

Meningitis

Inflammation of the menigis

Types of meningitis

• Bacterial: Most severe (G- neisseria meningitidis and G+ streptococcus pneumoniae)

• Viral: Most common

• Fungal: Associated with the immunocompromised

Which bacteria are associated with meningitis?

• G+ streptococcus pneumoniae

• G- neisseria meningitidis

Pathogenesis of Meningitis: Hematogenous Seeding

Bacteria colonize nasopharynx → Enter bloodstream after mucosal invasion → Cross blood-brain barrier into subarachnoid space → Leads to direct inflammatory/immune-mediated reaction

Pathogenesis of Meningitis: Direct contiguous spread

• Organisms enter CSF via neighboring structures (otitis media, sinusitis), foreign objects (medical devices), or operative procedures

• Viruses may also spread via retrograde neuronal transmission