Neuro Midterm 2

decreased/slow movement due to loss of dopamine/direct pathway in basal ganglia ex. Parkinsonism

what classifies a hypokinetic disorder?

excessive movement caused by loss of direct basal ganglia pathway/inhibition of thalamus ex. chorea, dystonia

what classifies a hyperkinetic disorder?

caudate nucleus, putamen, globus pallidus, subthalamic nucleus, substantia nigra

what are the parts of the basal ganglia?

It functions as the gas pedal, facilitating movements

what is the purpose of direct pathway in the basal ganglia?

It functions as the break pedal, inhibiting movement

what is the purpose of the indirect pathway in the basal ganglia?

what brain structures are connected to the basal ganglia through the caudate?

the limbic system, visual pathway, oculomotor structures, motor cortex, and frontal cortex

bradykinesia, rigidity, and rest tremor

what are the features of parkinsonism?

degeneration, infection, drugs, toxins, vascular problems, tumors

what are the causes of parkinsonism?

The direct pathway is not working, so the indirect pathway is always on resulting in an inhibited thalamus and therefore unstimulated motor cortex

how does Parkinson’s disease affect the basal ganglia pathways?

through a clinical diagnosis

how is Parkinson’s diagnosed?

Yes, especially with aging population-mean onset of 62 years

Is PD very common?

multifactorial: genetic factors, environmental toxins (manganese, MPTP, CO), AGING

what is the etiology of PD?

Deposition of alpha-synuclein in Lewy bodies, dopaminergic neuronal degeneration in pars compacta of substantia nigra, degeneration of pigmented nuclei in brainstem-spinal cord-cortex-gut

what happens in PD pathologically?

They are misfolded so they cannot be degraded and accumulate

why do alpha-synuclein deposit on Lewy bodies?

oligodendroglia/astroglia release autophagy inducers to eat the dying cells, and microglia/astroglia release inflammatory modulators to that cause inflammation

what happens to glia cells from deposited alpha-synuclein?

It becomes colorless because melanin is not produced from the metabolism of dopamine

what visible change happens in PD to the substantia nigra?

anxiety ,depression, constipation, REM sleep disorders

what symptoms may manifest 10 years before the onset of Parkinsonism?

hypothesized to be the gut or the nose

where does PD start?

as levodopa in order to cross BBB

how must dopamine be administered to have effect on PD?

fatigue, apathy, anxiety depression, sleep disturbances, ANS regulation, cognitive dysfunction

what are non-motor problems associated with PD?

counseling, exercise, administration of Ca or vitamin D

what are other treatments for PD?

multiple medications and physio

how is moderate PD managed?

DBS in globus pallidus or subthalamic nucleus

how is advanced PD treated?

medications, infections, metabolic disorders, toxins, hormones, vascular problems

what are the acute causes of chorea?

genetic, dopaminergic blockers, infections, nutrition, endocrine

what are the chronic causes of chorea?

autosomal dominant inheritance

what kind of inheritance pattern does Huntington’s have?

autosomal dominant CAG repeat (>40x) at the end of chromosome 4, age of onset/progression is dependent on the size of the triplet repeat

what are the characteristics of Huntington’s disease?

restlessness, motor impersistence, slowing of eye movements

what are the HD motor features in the early stage?

chorea gradually becomes more apparent and disabling

what are the HD motor features in the moderate stage?

chorea lessens, significant rigidity/bradykinesia, gait/balance problems

what are the HD motor features in the late stage?

motor-cognitive-psychiatric dysfunction, weight loss, apathy

what are the clinical features of HD?

degeneration of caudate/putamen results in enlarged ventricles

what is the effect of HD on the basal ganglia?

1/10000 people-more prevalent in white population

what is the prevalence of HD?

ongoing psychosocial support, genetic counselling, research

what treatments are available for HD?

abnormal sustained contraction and postures, may be associated with tremor, may be alleviated by sensory tricks

what is dystonia?

brain injury, toxins, genetic components, cerebral palsy, decreased dopamine

what is the etiology for dystonia?

dystonia caused by a DYT 1 mutation that has early onset and is progressive

what is primary generalized dystonia?

dystonia that has adult onset and is non-progressive, can be in: eyes, mouth and jaw, neck, fingers/hands

what is focal dystonia?

botox

what is the primary treatment for focal dystonia?

brief, non-rhythmic semi-suppressible movements

what are tics?

a syndrome characterized by multiple motor/vocal tics that last longer than one year

what is Tourette’s syndrome?

stroke

acute neurological impairment due to brain ischemia or hemorrhage

ischemic stroke

clot blocks blood from flowing to an area of the brain causing neurological deficits

hemorrhagic stroke

bleeding occurs inside or around the brain

very common

how common are strokes?

2 carotid arteries and 2 vertebral arteries

how does blood get into the brain?

vessel problems, heart problems, blood problems, and mitochondrial disease

what causes impaired blood flow to the brain?

atherosclerosis and atrial fribrillation

what are the two most common problems that impair blood flow to the brain?

50-60 ml/100g/min

what is the normal amount of cerebral blood flow to the brain?

20 ml/100g/min

what is the CBF threshold for synaptic transmission?

12 ml/100g/min

what is the CBF for irreversible damage?

infarct core

the region of irreversible damage caused by stroke

penumbra

the region of reversible damage to the brain by stroke

cellular injury and death

what happens to the brain in ischemic stroke?

neurons, astrocytes, oligodendrocytes, endothelial cells

what cells in the brain are injured/killed during ischemic stroke?

blood brain barrier disruption

in ischemic stroke what is a consequence of cellular death?

**A**potosis-autophagy-necrosis

**E**xcitotoxicity

**I**nflammation

**O**xidative stress/reactive oxygen species

**M**itochondrial

what are the mechanisms for cell injury/death in ischemic stroke?

BBB, autoregulation, no external elastic lamina

how are brain vessels different from regular blood vessels?

collection of endothelium, astrocytes, pericytes, and neurons that limit entry of blood products into brain

what is the blood brain barrier and what is its function?

neuronal regulation, pCO2, neuropeptides, and cytokines

what are the mechanisms of autoregulation?

the vessels become very fragile and will rupture easily

what is the consequence of brain blood vessels having no external elastic lamina?

thrombosis

what biological process is central to ischemic stroke?

activates plasminogen to form plasmin which degrades fibrin blood clots

what does the drug tissue plasminogen activator do?

a minor version of a stroke that has complete recovery in 24 hours

what is a transient ischemic attack?

presence of infarct

what is the difference between ischemic stroke and TIA on CT/MRI?

middle cerebral arteries, posterior cerebral arteries, and anterior cerebral arteries

what are the main arteries that branch off the carotid/ventral arteries?

ABCs, reperfusion/recanalization, neuroprotection, prevent complications, rehabilitation

what is involved with acute stroke management?

treating vascular factors, antiplatelet/anticoagulant, treat underlying cause

what are the ways to prevent stroke?

airway breathing circulation

what are the ABCs for acute stroke treatment?

restoring blood flow to the brain by opening up arteries

what is recanalization?

IV tissue plasminogen activator and endovascular therapy

what are two recanalization techniques?

prevent hyperglycemia, hypoxia, hypoperfusion, hyperthermia

what is the point of neuroprotection?

little absolute benefit, slightly better chance of mild neurological deficit, tiny hemorrhage risk

what is the effect of tPA on ischemic stroke?

technique for removing blood clot by going through groin with cathether

what is endovascular therapy?

contains a CT scan for fast action

what is the benefit of the stroke ambulance?

stabilize blood pressure, stabilize glucose levels, prevent pneumonia, keep brain cool

how is further brain injury prevented after stroke?

hypertension

what is the major cause of stroke?

low salt/fat diet, plenty of exercise, smoking cessation, stop heavy drinking

what are the everyday ways to prevent stroke?

diabetes and hyperlipidemia

what other factors may cause stroke?

am artery-artery embolism that creates a fibrous plaque that ruptures which requires thrombosis which blocks artery

what is carotid atherosclerosis?

carotid endarterectomy or stent

what is the treatment for carotid atherosclerosis?

medical management with statin and antiplatelet drugs

what is the treatment for intracranial atherosclerosis?

reduce platelet stickiness

what do antiplatelet drugs do?

angioplasty/stenting

what is the treatment for intracranial atherosclerosis for patients refractory to medical management

a tear in the artery wall

what is carotid/vertebral dissection?

subintimal hematoma

what is the risk factor for artery dissections?

the formation of a blood clot in the artery wall

what is subintimal hematoma

angiogram, antiplatelet or anticoagulation

what are the treatments for artery dissection?

younger people

who are dissection the most problem for?

lipohyalinosis or microatheroma of fine lenticulostriate arteries

what are the microvascular diseases associated with small vessel lacunar stroke?

longstanding hypertension and diabetes

what are the causes of lacunar strokes?

antiplatelet

what is the treatment for lacunar stroke?

a clot forms in the heart can embolizes to brain

what is a cardioembolic stroke?

atrial fibrillation

what is the biggest risk factor for cardioembolic strokes?

artia oscillates with weird contractions which can cause blood pooling

what is atrial fibrillation?

anticoagulation agents: warfarin, dabigatran, apixaban, rivroxaban

what is the treatment for atrial fibrillation?

in dura mater, arachnoid layer, subarachnoid space, and intracerebrally

where can hemorrhagic strokes happen?

hemorrhage into brain parenchyma

what is an intracerebral hemorrhage?

neurological deficits, headache, and altered level of consciousness

how do intracerebral hemorrhages present?

hypertension

what is the main cause of intracerebral hemorrhage?