Neurological disorders (Neurodegenerative) + Endocrine Disorders

Huntington’s Disorder

-neurodegenerative disorder with motor sxs, but also emotional and cognitive

-onset age: 30-50 yo (peak yrs of life)

-life expectancy following sx onset: 10-30 yrs

Cause of Huntington’s

-autosomal dominant gene (offspring have 50% of inheriting)

-mutated version of huntingtin gene on chromosome 4

Neurotransmitters involved in Huntington’s

0.) glutamate excitoxicity kills off GABA-producing neurons in BG

1.) low GABA from loss of GABA-producing neurons in BG (no inhibition of movement)

2.) dopamine is relatively high, and runs wild (jerky chorea)

Affective sxs of Huntington’s

-depression, mood swings, irritability

-mood sxs come first (first sign of brain tissue loss)

Cognitive sxs of HD

-striatum dies off, so it can’t filter out input → impaired concentration, ST memory loss

-no striatum to receive input from PFC → impaired judgment

Primary motor sx of HD

chorea – jerky dance-like movements in upper body

(relatively high dopamine)

Motor sxs in later-stage HD

(over time, not only is motor inhibition impacted but also initiation, bc BG is hollowed out)

-rigidity, bradykinesia (slowed voluntary movement)

-difficulty walking, speaking, swallowing

Differences btwn HD + PD

HD: hyperkinetic (chorea, lurching), bradykinesia only comes later

-loss of GABA (movement inhibition)

PD: resting tremor (pill-rolling), bradykinesia (slowed movement), rigidity

-loss of dopamine (movement initiation; dopamine = oil needed for smooth movement)

Variants of ApoE gene is linked to

Increased risk for NCD (d/t Parkinson's, Alzheimer's, with Lewy bodies, and vascular NCD)

Motor sxs of Parkinson’s

(park, TRAPped)

-Hard to get moving, shuffling, freezing

-resting Tremor (pill-rolling)

-Rigidity in upper body

-Akinesia – inability to move muscles voluntarily, sudden freezing/immobility; bradykinesia

-Postural instability, high risk for falls

What is bradykinesia + rigidity in Parkinson’s disease?

Brady = slowed (bradycardia = slow HR)

-Bradykinesia – slowed voluntary movement

-slow shuffling gait

-decreased eye blinking

Rigidity – led-pipe rigidity, and cogwheel rigidity (catch-and-release, combo of tremor + rigidity)

-rigidity is caused by low dopamine (dopamine is oil needed for smooth movement, initiating + inhibition movement)

-Rigidity and bradykinesia → mask-like facial expression (not necessarily depression)

Non-motor sxs of Parkinson’s

Travels up brainstem (GI to nose); GASPS (gasping for dopamine)

-GI

-Anosmia – loss of smell

-Sleep disturbance

-Pain

-Sad – anxiety and depression

Mood sx of Parkinson’s

-anxiety and depression

-up to 50% experience depression

*depressive sxs precede motor sxs in ~20% of cases

Neurotransmitters involved in PD

DANG

-Dopamine: low, from loss of dopamine-producing cells in SN

-Glutamate: high, excitoxicity → disease progression

-Ach: low ←→ posture/gait + balance impairments, and cognitive decline

-Norepinephrine: low, causing non-motor sxs (depression)

Treatments for Parkinson’s

1.) Levodopa – most effective with bradykinesia and reducing rigidity

2.) Dopamine agonists

3.) Deep brain stimulation – surgical implantation of electrodes + pulse generator under chest skin (sends electrical impulses to motor brain areas)

Levadopa/L-Dopa (what it’s effective for, side effects)

-first-line med for PD, converts to dopamine in the brain

-most effective with reducing bradykinesia + rigidity

-more SEs than dopamine agonists:

• dystonia (involuntary muscle contractions twisting into painful postures, myoclonus (one-off jerks)

• dyskinesias – dysfunctional involuntary movements, SE of dopamine meds

Dystonia

(twisting, painful postures)

-involuntary muscle contractions leading to twisting into painful postures

(walking with feet and toes contracted inward)

Myoclonus

-sudden, one-off muscle jerks/contractions

Neuroleptic malignant syndrome

-Neuroleptic malignant = abrupt cut-off from dopamine, too little dopamine

-Comes from:

1.) adverse reaction to antipsychotics (aka neuroleptics)

2.) withdrawal from PD medications (dopamine supply is suddenly cut off)

-dopamine = oil for smooth movement

-when smooth movement is impossible (no oil) → extreme rigidity, fever, high HR

Dopamine agonists also treat… (conditions with too little dopamine)

-Neuroleptic malignant syndrome

-Restless leg syndrome – dip in dopamine at night

Hyperthyroidism sxs

-hypersecretion of thyroid hormones

-increased metabolism, appetite (→ weight loss)

-increased HR, body temperature (→ heat intolerance)

-emotional lability, insomnia

-reduced attention span

Hypothyroidism sxs

-hypersecretion of thyroid hormones

-decreased metabolism, decreased appetite (→ weight gain)

-reduced HR, body temperature (→ cold intolerance)

-depression, lethargy, decreased libido

-confusion, impaired memory and concentration

Vasopressin (what does it do?, released by what?)

-aka antidiuretic hormone

Central diabetes insipidus

-caused by low vasopressin

-d/t damage in pituitary gland, where ADH is released

-urinating/passing lots of diluted water, extreme thirst, dehydration, constipation, weight loss, low BP

Pancreas

-releases insulin, maintains BG balance

-if pancreas releases too much insulin (e.g., tumor) → hypoglycemia

Diabetes mellitus

-d/t too little insulin released, or body can’t use the insulin released

Type 1 diabetes

-autoimmune disease that kills off insulin-producing cells in the pancreas

-genetic predisposition + viral infections that trigger the autoimmune repsonse

Type 2 diabetes

-pancreas produces too little insulin, or the body can’t use the insulin

What does EEG measure?

-brain activity (electrical impulses are recorded as brain waves)

-dx of seizure disorders and sleep disorders

-TBI and tumors (to check for abnormal brain activity, seizures)

-confirm brain death

Structural and functional neuroimaging techniques

Structural neuroimaging: CT (x-ray) and MRI, DTI

Functional neuroimaging: fMRI, PET, SPECT

Pros/Cons of MRI vs. CT

-CT is usually available in ER, less costly, quicker

-but exposes to x-rays, not accurate/detailed for brain tissue

-MRI is more accurate, detects microhemorrhages, contusions (small areas of bruising), gliosis (scarring)

-but time intensive, loud, costly

Diffusion tensor imaging (DTI)

Diffusion = white-water rafting (tracks water movement in white matter)

-maps brain’s white matter (myelinated axons), detects any structural microdamage in neural pathways

-does this via tracking water movement in axons

-Uses: TBI (check for structural damage to neural pathways), to check for white matter/neural pathway structural integrity in disorders (NCD, Scz, ASD, epilepsy, multiple sclerosis)

Functional neuroimaging techniques work by…

-assessing glucose or O2 consumption, through measuring regional cerebral blood flow (rCBF) or blood volume

fMRI

-functional neuroimaging technique: measures brain activity

-tracks blood flow and O2 levels using magnetic and radio waves (oxygenated vs. deoxygenated blood has different magnetic properties)

PET and SPECT

-uses radioactive tracers to measure glucose metabolism, as a proxy for brain activity

Are neuroimaging (e.g., fMRI, PET) techniques sufficient to diagnose NCD due to Alzheimers?

No! But neuroimaging can rule out other possible cognitive disorders

e.g., PET (tracking glucose metabolism) is useful for ruling out frontotemporal NCD (occurs in different regions than Alzheimer’s)