Neurodegenerative Pathologies

Drastric and acute changes in cognition (Diff dx to alzheimers disease)

Delirium

What protiens cause damage to neuronal tissue in alzheimer’s disease?

Amyloid plaques and neurofibrillary tangles

Risk factors for AD

over 65 years old, female, black population, genetics, poor CV health, hearing and vision loss, low social activities

Gene for AD

APOE

Types of APOE genes (one from each parent)

2: protective

3: neutral

4: increase risk

Prevention for AD

Exercise, diet, mind acitvity, GLP-1, sleep, avoid social isolation

Pathogenesis of AD

Accumulation of B-amylooid, typically cleared during sleep, protiens create plaques, inflammation response triggered, increased free radicals

Where does accumulation of tangles start

Hipppocampus (short term memory)

What describes symptoms of alzheimers that worsen at night

Sundowning

What do PET scans detect for AD?

Clusters of amyloid proetiens and tau

Treatment for AD

Lifestyle, medications (Leqembi, kisunla), cholinersterase inhibitors, sleep improvement

What are the side effects of target B-amyloid plaques for AD?

Expensive and brain bleeds/swelling

What are the main clinical signs of ALS

UMN and LMN present, weakness in a single limb (Motor)

What is Amyotrophic lateral sclerosis

Neurodegenerative disease of motor neurons and brain and anterior horn cells of SC

ALS risk factors

Mens, after 50, white population, majorirty have no genetic link

What is the genetic component of ALS called

FALS (familial ALS), autosomal dominant

What protein aggregate is associated with ALS?

SOD1 and TPD-43

Pathogenesis of ALS

UMN: motor cortex and corticospinal tracts

LMN: anterior horn cells (gliosis and loss of myelinated fibers)

What is gliosis?

Hardening and sclerotic process, calcium ions flooding the motor neurons

Common S/Sx of ALS

Fatigue, weakness, muscle cramps, fasaiculations (eventual frontotemproal dementia)

Are psuedobulbar signs UMN or LMN?

UMN

Are bulbar signs UMN or LMN?

LMN

Psuedobulbar signs of ALS

dysarthria, dysphagia, emotional liability, hyperreflexive gag reflex

Bulbar signs of ALS

Dysarthira and dysphagia (CN 9-12)

What sympotms are preserved with ALS

Senesation, eye movement, bowel and ballder function

What is the most common cause of dealth in ALS

respiratory failure (effects on diaphragm and chest musculature)

Medication for ALS

Riluzole (neuroprotective to remove glutamate), radicava (improve immune system by targeting oxidative stress)

What is multiple sclerosis

Demyelination of axons in CNS and destruction of oligoendrocytes that cause axonal damage

Pathogenesis of MS

Formation of sclerotic plaques and atrophy of white matter

Risk factors for MS

Women, 20-50 years old, infection, genetics, vitamin d deficiency(living further from the equator), smoking, epstein barr

What gene is associated with MS

HLA-DRB

What is the first sign of MS

Viion chagnes

S/Sx of MS

vision changes(optic neuritis, gaze palsies, nystagmus, vertigo), paresthesias (MS hug), pain, lhermitte sign, weakness, poor coordination, increase tone/spasticity, fatigue, depression, bowel and bladder dysfucntion

Optic neuritis

Unilateral, painful loss of vision

Lhermitte’s sign

Sudden electric shock pain through the spine and limbs when the neck is flexed

What is the McDonald criteria and what pathology is it used for?

Dissemination in time and space (more that 1 episode, more than 1 lesion in SC/brain), MS

4 subtypes of MS

Clinically isolated sydnrome, relapsing remitting MS, Secondary progressinve MS, Primary progressive

MS subtype: clinically isolated syndrome

First episode of symtpoms, may stil be treatmed with therpay

MS subtype: Relapsing remitting MS

Most common, bursts of active attacking, then recovery/remyleination can occur during inactive period // disability slowly increases over time

MS subtype: secondary progressive MS

starts with RRMS, but eventual remyleination can recover causing axon damage, progressively worsens over time (faster)

MS subtype: Primary progressive MS

Progressive worsening without returning to baseline, no recovery ocuring but with some periods of stabiltiy

Treatments for MS

DMARDs (disease modifying treatments), corticosteroids for relapses, diet, lifestyle, temperature contrl (worse in heat)

What is the protein aggregate for MS

NONE! just imporper healing process and sclerosis

Genetic association with AD, ALS and MS

AD: AOPE, PSEN

ALS: SOD1, C90RF72

MS: HLA-DRB

Protein aggregates of AD, ALS and MS

AD: beta-amyloid

ALS: TDP-43

MS: none