Neuropathology

What is Dementia?

Is not a specific disease, but is progressive and is worse with time. It is not a normal aging progress and occurs in older people. Loss of cognitive functioning occurs.

What causes Dementia?

• Neuron degeneration ➡️ neurons die, oxidative stress causes damage from ROS waste on neuroglia

• Atherosclerosis ➡️ decrease in blood flow ➡️ ischemia ➡️ hypoxia ➡️ infarction

• Brain tissue compression ➡️ CHRONIC, epidural or subdural hematoma or a tumor

• Brain trauma ➡️ repeated blows to the head (boxers, football players)

• Genetic predisposition ➡️ linked to genetic abnormality, NOT FAMILIAL

What is Alzheimers Disease?

A progressive neurological disorder effecting memory, thinking skills, the inability to carry out simplest tasks.

Alzheimers is the most common what?

Most common type of dementia
➡️ (Alzheimers Dementia)

Late Onset Alzheimers

• 95% common

• Not genetic or linked to any gene

• Sporadic = most common

• Alteration of apolipoprotien E ➡️ high cholesterol increases risk for Alz.

Early Onset Alzheimers

• FAMILIAL

• 5% rare

• Diagnosed in early 30-40s

• Caused by Trisomy 21/Down Syndrome

Cause of Alzheimers

• Extracellular deposition of β-amyloid (Senile neuritic plaques)

• Intracellular accumulation of tau protein (Neurofibrillary tangles)

Alzheimers S&S

• Extends 10-20 years

• Behavioral changes

• Forgetfulness ➡️ progressive memory loss ⭐️Telltale sign: Patients forgetting to pay their bills, or forgetting their everyday routine tasks

Alzheimers Diagnostics

No definite clinical diagnostic tests, only based on a series of questions and if the patient meets the criteria

Alzheimers Treatment

• No specific treatment

• Anticholinesterase drugs

• Aducanumab

• Team approach

What is Parkinson's Disease?

Progressive, neurodegenerative disease of the melanin-containing dopaminergic neurons in the substantia nigra, pars compacta

⭐️Severe degeneration of the basal ganglia
- Caused in older patients 50-60s

Primary Parkinsons

⭐️ Idiopathic: no idea what causes it
- Majority of the population diagnosed with this type

Secondary Parkinsons

Caused by something else
Ex: Environmental factors, anti-psychotics, pseudo-parkinsonism

Parkinsons S&S

⭐️ RESTING TREMOR

• Stooped posture & rigidity

• Pill rolling tremor

• Cockwheel rigidity (slow wind up and rapid action)

• Masked facies (the face is frozen)

• Short shuffling steps ⭐️ In early stages of parkinsons, patients will often hide their resting tremor in their hands

Parkinsons Diagnosis

No diagnostic tests, based on S&S

Parkinsons Treatment

💊 Dopamine agonist (Levodopa)
💊 MAOB inhibitor
💊 Anticholinerdic drugs
💊 Amantadine
⭐️ Team approach

What is Huntingtons Disease?

Progressively debilitating neurodegenerative inherited disease
⭐️Autosomal dominant disorder, caused by 1 bad gene, chromosome 4
- Does not manifest until the 30-40s (younger)
⚠️ Progressive atrophy of the brain

Pathophysiology of Huntingtons

• Hyperkinetic disorder

• Involves the basal ganglia & frontal cortex

• Depletion of GABA in the basal nuclei

• Levels of ACH in brain appear reduced

Huntingtons S&S

• Mood swings

• Restlessness

• Choreiform movements

Huntington diagnostics?

- DNA analysis
⭐️ A familial genetic abnormality, and can be tested for

Huntington treatment?

⚠️ NO SPECIFIC TREATMENT
- Symptomatic therapies only

Huntington's mortality rate caused by?

Most patients don't die from the neurologic disease:

• Infections

• Heart disease ⚠️ Suicide: the more common cause, only a 5 year life expectancy given when diagnosed

What is Amyotrophic Lateral Sclerosis (ALS)?

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

⭐️Aka "Lou Gehrigs disease"

Pathophysiology of ALS?

⚠️ NOT CLEAR

• SOD1 gene mutation

• Damage to glutamate uptake channels in astrocytes

• Military vets (specifically Gulf War veterans) at risk (not sure why!!)

• Athletes, repeated trauma increases risk

⭐️Cognition & sensory is UNIMPAIRED ⚠️Death due to respiratory failure

ALS treatment?

⚠️ No specific treatment

- Stem cell therapy under investigation
💊 Riluzole (Rilutek) slows further damage to neurons
💊 Edavarone lowers the toxic environment and scavenges for free radicals
⭐️ Team approach
⚠️Like Parkinsons, patients decline very rapidly

Hemorrhage

Increased intracranial pressure (ICP) will cause local ischemia and generalized symptoms; blood compresses the brain

Arteriovenous malformation

When artery and a vein connects, high O2 blood in arteries are mixed with low O2 veins

Transient Ischemic Attacks (TIAs)

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

⭐️ Decrease in blood flow, NO neuronal cell death

• REVERSIBLE

• Most commonly caused by atherosclerosis

♀ Women are protected by estrogen until menopause

TIA S&S

⚠️ IS A WARNING SIGN, can lead to a stroke if not treated

• Are difficult to diagnose after the attack, directly related to the location of ischemia

• Visual disturbances

• Numbness & paresthesia

• Transient aphasia or confusion

TIA Diagnostics

• MRI (preferred) or a CT

• Carotid doppler

• Angiography

TIA Management

• DECREASE RISKS

• Initiate in stroke prevention therapy

Cerebrovascular Accidents (CVAs)

A CVA (stroke) is an infarction of brain tissue that results from a lack of blood

• There are 2 types:

• Ischemic: occlusion of a cerebral blood vessel

• Hemorrhagic: rupture of cerebral vessel

⚠️ 5 minutes of ischemia → irreversible neuronal damage

CVA Risk Factors?

• African Americans at higher risk

• 5th COD in the US

• Leading cause of disability

Thrombus CVA

→ Atherosclerosis in cerebral artery
→ Onset is gradual may be preceded by TIAs; occurs at rest
→ Localized, less permanent damage
→ Minimal ICP

Embolus CVA

→ Atherosclerosis of carotid artery of systemic source (heart)
→ Onset is sudden ⚠️
→ Minimal ICP
→ Localized unless multiple emboli present

Hemorrhage CVA

→ Hypertension, arteriosclerosis (poorly controlled hypertension)
→ Onset is sudden, occurs with activity ⚠️
→ High ICP
→ Widespread and severe, and often fatal (subarachnoid is most fatal)

CVA S&S

• Depends on location of obstruction and also the size of the artery involved

• Abrupt onset of hemiparesis, hemisensory deficits

• 👀 Loss of vision in one or both eyes, double vision

• Nystagmus

• Dysarthia

• Facial droop

• Ataxia

• Vertigo (rarely in isolation)

• Aphasia

• Headaches (HEMORRHAGIC ONLY)

• Sudden decrease in level of consciousness (Hemorrhagic can cause as well)

NIHSS

NIH Stroke Scale

• Assists with rapid diagnosis

• Predicts size and severity

• Predict short and long term outcomes

Treatment of CVAs

💊 Fibrinolytic tPA 💊 Antiplatelet: aspirin 💊 Glucocorticoids 💊 Blood pressure control

• Mechanical thrombectomy

• Supportive treatment ❗️TREAT UNDERLYING PROBLEMS TO PREVENT RECURRENCES

Prevention of CVAs

💊 Aspirin

• Healthier diet, reduced hyperlipidemia 💊 Antihypertensive

• Control diabetes type 2

• 🚭 STOP SMOKING!!

• Exercise

• Lifestyle changes

Meningitis

Bacterial, viral or fungal infection of the meninges of the brain

Bacterial: more fatal
Viral (aseptic): more common
Fungal: happens in immunocompromised patients

Meningitis S&S

• High fever with chills

• Stiff neck

• Headache

• Confusion & sleepiness

• Vomiting (from pain)

• Dislike/pain from bright lights ⚠️ Sometimes red or purple spots or bruises on the skin: OMINOUS SIGN OF DIC

Kernig Sign

Extension of the knee is painful or limited in extension

Brudzinski Sign

Passive flexion of neck, causes a hip & knee flexes

Pathophysiology of Meningitis

• Hematogenous: by blood

• Direct contiguous spread (ex: sinusitis)

🦠 Organisms:

• Neisseria meningiditis (gram -)

• Streptococcus pneumonia (gram +)

Meningitis diagnostics

- Lumbar puncture/spinal tap
⭐️ Culture before you treat, high morbidity rate

Bacterial spinal tap

• increased PMNs & neutrophils

• decreased glucose (bacteria eats)

Viral spinal tap

• increased lymphocytes

• normal glucose

Fungal/TB spinal tap

• increased lymphocytes

• decreased glucose

Meningitis treatment?

• Rapid diagnosis and Tx essential to prevent morbidity and mortality

• Aggressive antimicrobial therapy 💊 Glucocorticoids 💉 Vaccines are available

What is Multiple Sclerosis?

Progressive, inflammatory, demyelinating disease of the central nervous system ⚠️ AUTOIMMUNE ⚠️ Impacts

• Impacts women more than men

• Appears 20-40 years of age; 40 years is the limit, but has been seen developing in older people

• Over time, neural degeneration becomes irreversible; function is lost

Multiple Sclerosis Pathophysiology

Inflammation ➡️ Destruction of myelin sheath ➡️ Demyelination ➡️ Scar formation ➡️ Plaque formation

- Targets oligodendrocytes in the CNS

Multiple Sclerosis S&S

• Paresthesia

• Weakness

• Blurred vision

• Double vision

• Urinary incontinence

• Loss of coordination

• Dysarthia

Multiple Sclerosis Diagnostics

MRI for diagnosis & monitoring; can see the plaque on the brain and determine the severity

Multiple Sclerosis Treatment

• No definitive treatment; not a one size fits all treatment

• Tx is tailored to the patient, what works for one might not work for another