Neuro Week 7.pdf

Summary: GB is an autoimmune disorder targeting peripheral ns, resulting in lower motor neuron impairment of hypotonia, hypo-hyperreflexia, & sensory & motor loss initial acute phase survival high potential to recover • 5.1 Guillain- Barre Syndrome Guillain-Barré Syndrome: autoimmune disorder that...

Summary: GB is an autoimmune disorder targeting peripheral ns, resulting in lower motor neuron impairment of hypotonia, hypo-hyperreflexia, & sensory & motor loss initial acute phase survival high potential to recover • 5.1 Guillain- Barre Syndrome Guillain-Barré Syndrome: autoimmune disorder that targets peripheral nervous system (more often myelin sheath around axon fibers) • acute inflammation/demyelination of motor/sensory peripheral nerves • impaired nerve signal propagation for motor/sensory signals Impacts • muscle activation • strength • sensory feedback incidence rate: 1 to 2 per 100,000 people • high mortality rate 3-10% (normally in acute phase) • complications: respiratory failure, pneumonia, cardiac arrest, autonomic dysfunction if survive the acute phase: 20% present w/ chronic residual deficits • inability to walk, muscle weakness, sensory impairment bc all peripheral n are demyelinated • present with chronic fatigue • 75% near to complete recovery (even walking) -> W fatigue patient history • prior infectious disease 2-3 weeks before any sensory/motor impairment GB can plateau 4 wks of onset • linked to C-jejuni, cytomegalovirus, or epstein-barr virus, vaccines (flu/covid) d gastrointestinal illness that causes immune system to fight by generating - antibodies • fight off c-jejuni virus but cross react w/ gangliosides on peripheral n. molecular mimicry & complement activation • antibodies attach to both C-jejuni & peripheral n of body • attacks both antibodies that find complements on peripheral n ↓ become cross reactive @ nodes of ranvier or on schwann cells ↓ initiate attack on n. / disrupt n conduction by damaging voltage gated sodium channels or damaging/detaching from myelin sheath ↓ where they attack will determine the syndrome AMAN or AIDP AIDP subtype • most common • acute inflammatory demylenating polyneuropathy • myelin membranes attacked by cross reactive antibodies (both sensory & motor) cranial, autonomic, pain signals AMAN subtype • motor axonal neuropathy variant • more prevalent in asia, central & south america • cross reactive antibodies injure axonal membranes and only motor nerves AMSAN • acute motor and sensory axonal neuropathy • attack on motor and sensory peripheral n axons Plateau of GB • occurs 4 weeks of onset (most severe point of disease) • leads to the 3-10% mortality rate Nerve conduction tests • nerve propagation initially impaired but not the muscle • DISEASE OF N. LESION NOT MOTOR TRACT • lower motor neuron impairments not upper motor neuron impairments day 4: no impairment to n. normal conduction velocity/response to stim @ rest no muscle activity normal motor unit activity w/ voluntary contraction as disease progresses & attacks n. longer response times and decreased motor units w/ voluntary contraction three weeks after onset slowed or incalculable n conduction velocity, muscle fibrillation @ rest & poor motor unit recruitment AIDP variant • sensory motor pattern or impairment of peripheral n CN, ANS Fxn AMAN variant • pure motor impairments throughout body lower motor n. bc only peripheral n. attacked Miller Fisher varient • primarily cranial n & brainstem attacked • abnormal muscle coordination/ataxia • paralysis of eye muscles/facial weakness • doesn’t effect motor n. of limbs/trunk Differential diagnosis • MS • Chronic inflammatory demyelinating disease (CIPD) • spinal cord injury • botulism • myasthenia gravis/polymytosis MAKE FC FOR COMPARING EMG READINGS FOR EACH DISEASE 5.2 Amyotrophic Lateral Sclerosis Amyotrophic Lateral Sclerosis (ALS) more commonly known as Lou Gehrig’s disease -it is a progressive, selective disease that attacks motor neurons only, but both upper and lower motor neurons, both in the central and peripheral nervous system -people afflicted with ALS will have a combination of upper and lower motor neuron symptoms varying from hypo and hyperreflexia, generalized weakness, muscle atrophy and paralysis -presentation of upper versus lower motor neuron symptoms will vary throughout the body, depending on which motor neurons have been attacked *key difference* in ALS is that the motor neurons responsible for bowel and bladder management down in the in sacral region, and eye movement, so in the ocular motions, up in the cranial nerves, are spared Epidemiology Etiology ALS incididence rate: 1-3 per 100,000 people -mean diagnosis age is in the late 50’s -condition affects males greater than females -when assessing patients, keep in mind the prevalence of a condition as well as epidemiology to rule in or out, diagnoses Cause: is fairly unknown and is determined to be multifactorial 2 factors of ALS development 1. Genetic mutation 2. Chemical toxicity Family inheritance is responsible for ~5-10% of ALS cases most cases are linked to sporadic genetic mutations -having the gene does not guarantee the disease but may predispose an individual to getting the disease Chemical toxicity has been linked to the development of ALS, likely creating an environment that supports neuronal death Progression of ALS is rapid ~1-5 year disease duration before death -some individuals have survived greater than 10 years after the diagnosis ALS a selective targeting of the motor neurons in the CNS and PNS -both motor tract and motor neuron dysfunction result In the brain betz cells w/in the motor cortex degenerate, causing demyelination and gliosis of the cortical spinal and corticobulbar tracts, accounting for the lateral sclerosis part of the disease name -motor cranial nerve nuclei are attacked, but spare the ocular motion from CN 3,4,6 -anterior horn cells in the SN are also targeted, resulting in a massive loss of lower motor neuron control Pathophysiology ALS is a multifactorial event of molecular interactions that result in neurodegeneration condition has been linked to impaired glutamate intake, resulting in glutamate excitotoxicity. Mutation of SOD genes (superoxide dismutase) may be linked to misfolded proteins that then lead to poor anti-oxidation and mitochondrial dysfunction -alterations can lead to: increased inflammation, poor nerve signaling, and neuronal death at the motor unit level in the anterior horn of the SC -attack of the motor nerve cell bodies called result in demyelination, wallerian degeneration, and in the end stage of the condition, retrograde atrophy of the myelinated nerve fibers due to disue Dying forward hypothesis initially degeneration of the pyramidal motor Betz cells w/in the motor and premotor cortex Leads to anterograde degeneration of bulbar and spinal motor neurons due to glutamate excitotoxicity Conversely Dying back hypothesis researchers propose that : the lower motor neurons that are initially attacked, then spread to upper motor neurons *neither theory is perfect as they do not fully account for the possibility that upper and lower motor neuron degeneration can occur independently and concurrently with each other* EMG exists muscle fibrillations and fasciculatons whole at rest some degree of abnormal muscle activity when there is no intent to contract a muscle Voluntary contraction activated motor units are less in number polyphasic- ineffective contraction w high amplitude and long duration patterns -in contrast to the motor units that are activated in a voluntary contraction in a normal individual motor units are closely spaced together, lack polyphasic pattern and indicate a high # of motor units recruited ALS: Impairments varied lower and upper motor neuron impairments like: -hypotonia to hypertonia -hyporeflexia to hyerreflexia -muscle flaccidity to muscle spasms -will have muscle weakness of the affected muscles and potentially general disuse atrophy and sparing of the sensory system. -mid stage or end stage of the disease, patients will often have complaints of musculoskeletal pain due to lack of motion and/or pressure in bed bc they can’t move -still have the same sensations -complaints of muscle cramps and muscle fasciculations -will also present with non-motor symptoms, including cognitive impairment and emotional lability, also known as a pseudobulbar effect -50% of patients with ALS have emotional lability—pathological crying or laughing in form of emotional incontinence ALS can also present primarily with a bulbar system onset, so cranial nerve dysfunction, or limb onset, weakness in the limbs, primarily Neuromuscular conditions that you may consider for differential diagnosis, or share similarities with -frontal temporal dementia, -cranial nerve damage, -spinal cord injury, -primary lateral sclerosis, -spinal muscular atrophy, -peripheral neuropathies. Summary: ALS is a fast, progressing neurological diseases that affects fxn, primarily due to motor neruon and tract damage within the CNS inherited autosomal disease 5.3 Spinal Muscular Atrophy (SMA) SMA • rare hereditary neuromuscular disorder • loss of motor neurons -> muscle wasting/ weakness most common genetic cause of death in infants • distubance b/w muscles & motor neurons motor neurons in brainstem / SC • control essential skeletal muscle activity • gradually weaken • control movement of arms, legs, face, chest • waste away • develop twitching (fasciculations) throat, tongue ex: walking, breathing, swallowing LMN - nerves trying to elicit a contraction to a single muscle • decreased force production epidemiology / etiology • 1 in 6,000 - 10,000 babies • 25,000 + in US have rn • impacts every race & gender equally • 6 mill in US who are carriers of SMA gene (1 in 50 ppl) one copy of normal SMN1 gene one mutated version can pass onto biological children but be healthy themselves need both copies in order to have SMA pathophysiology defects in both copies of SMN1 on chromosome 5q Survival motor neuron 1 gene (on chromosome 5q) • produces survival motor neuron protein: maintains health & normal fxn of motor neurons SMA: insufficient lvls of SMN protein -> loss of motor neurons in SC -> weakness/wasting of skeletal muscle (mainly trunk/upper leg/arm muscles & muscles of hand/feet) severity depends on how well SMN2 genes can make enough protein w/o SMN1 SMA • inherited autosomal disease (recessive) • need 2 mutated genes to have it ex: carriers only have one mutated gene w/o symptoms if have 4 kids, could have one unaffected & one affected • can affected more than one person in generation • & cousins different types of SMA type 1 - ACUTE SMA (werdnig-hoffmann syndrome) • infantile onset SMA • most severe & common • symptoms: 6 months (cannot sit) • quick progression, death by 2 (respiratory infections) type 2 - intermediate SMA (juvenile SMA, chronic SMA) • symptoms 6-18months old (can sit,, may stan w/ support @ early age, cannot walk) • life expectancy: early childhood to adulthood type 3 - mild SMA “kugelberg-welander syndrome” • symptoms18 months to early adulthood • can stand/walk but have muscle weakness Impairments: • normal life expectancy • progressive weakness of voluntary muscles: arms, legs, & respiratory first type 4 - Later onset SMA mild form • symptoms in adulthood (30s) • muscle weakness • normal life expectancy • associated probs: poor head control, difficulties swallowing, scoliosis, jt contractures summary: • progressive hereditary genetic disorder • degeneration of ant horn cells & muscle weakness • leading genetic cause of death in infants & toddlers trunk & leg & arm muscles more than hands and feet 5.4 Multiple Sclerosis MS a chronic, inflammatory, autoimmune disease of the CNS -similar to GB syndrome in that it involves demyelination Ms- results in lifelong chronic disability, progressing with each attack, flare up of the condition, but does not however necessarily significantly impact lifespan Lifespan have similar life expectancy as their non-diseased counterparts Etiology Interaction bw environmental factors like: pathogens, chemicals and diet, genetic mutations/variations- can increase suspectibility to developing MS or modify the severity of the condition if it persists Geogrpaphy -in respect to where the distance one lives from the equator -countries located further from the equator (like Canada or Northern European countries) have increased incidences of MS -unclear why this is the case Ms- is 3x more common in women researches believe it is bc of hormones Pathophysiology occurs in different stages 1. There’s an inflammatory attack in the CNS by T cells that attack oligodendrocytes 2. Progressive, acute, inflammatory attacks that result in overall loss of oligodendrocytes and impair remyelination of axons within the CNS -results in: impaired nerve signaling, impacting multiple and varied fxns and abilities coordinated by the CNS -Overtime the lack of remyelination and repeated attacks end in neuronal damage and death Autoreactive CD4+ cell outside of brain T cells set off a cascade of proinflammatory cells, such as monocytes, and other T cells and plasma B cells, along with T helper cells. These proinflammatory cells cross the blood-brain barrier into the central nervous system. Here, they're able to attack the myelin sheaths of the axons, along with the oligodendrocytes themselves. The breakdown of myelin that occurs further triggers an inflammatory response that leads to astrogliosis and microgliosis, or death of astrocytes and microglia. Types of MS 1. Radiologically isolated condition that results in MRI findings similar to those with MS, but are incidentally foundmeaning no report of neurological symptoms instead found thru MRI 2. Clinically isolated single attack that individual may or may not fully recover from 3. Relapsing-remitting clearly defined attacks or new neurological symptoms -followed by times of complete, or partial recovery or remission periods 4. Secondary progressive initially may show as relapsing-remitting but later presents as progressive worsening in neurological fxn or disability over time 5. Primary progressive a phenotype that results in worsening neurological fxn or disability from the onset of symptoms w/o early relapses or remissions Impairments -demyelination occurs anywhere in the CNS during autoimmune acute inflammatory periods -hard to predict next flair up -no particular pattern— other than it being w/in white matter of brain *important to note that the multiple sclerosis will result in an upper motor neuron lesion presentation, so spasticity, hypertonia or hyperreflexia* MS manifests in many different ways Neuromuscular conditions to consider for differential diagnosis, or share similarities with MS are: Guillain- Barre syndrome, neuromyelitis optica, stroke, encephalitis, vasculitis, Lyme disease, and lupus. summary multiple sclerosis is an auto immune disease due to demyelination of the CNS. I t's progressive, results in chronic disability, and has varied clinical presentation due to the widespread locations of myelin within the brain 5.5 Parkinson’s Disease 1817 by James Parkinson’s “shaking palsy” - involuntary tremulous motion w/ lessened muscular power in parts, not an action, even w/ trunk bend, walking, running & senses & intellect parkinson’s overview • fenestration • 2 most common neurodegenerative after alzheimer’s • symptoms: rigidity, bradykinesia, micrographia, masked face, postural abnormalities, resting tremor cause: loss of neurons -> decrease in dopamine in substantia nigra -> impaired n. transmission • in brainstem & scar/lewy body formation etiology/epidemiology • 85% diagnosed over age of 65 (1% increase per decade after 55) • 930,00 in US • men more likely • multifactorial causes: environmental, chemical toxicity (pesticides, herbicides, magnetic fields) genetic predisposition • 1 gene not responsible but 11 PARK associated pathophysiology loss of neurons in substantia nigra & pedunculopontine nucleus loss of dopamine stores formation. of lewy bodies, gliosis, cell death swallow tail sign: lack of black in structure deficiency of neurotransmitter: dopamine substantia nigra degeneration: altered fxn of direct/indirect loops no dopamine -> striatum can’t inhibit direct/go pathway through globus pallidus & external segment -> increase tonic inhibition of thalamus -> decreased motor activation parkinson’s on the pedunculopontine nucleus affects reticulospinal tract -> lateral corticosponal tract lateral corticospinal tract: mild excitation off flexors/mild inhibition of extensors • because of increased globus pallidus inhibition of motor thalamus reticulospinal tract: responsible for postural control/postural rxns • over activity of both flex/extensors ex: trunk/proximal girdle rigidity cluster 3: postural instability & gait difficulty • worse motor impairments • akinesia, hypokinesia, bradykinesia, rigidity, postural imbalance, freezing of gait, hypomimia • non motor signs affecting wellbeing & sleep: depression, psychosis, dementia, autonomic dysfunction cluster 4: tremor dominant • unilateral symptoms, w/ resting, inaction tremors • slower progress of disease • poor response to dopamine treatment differential diagnosis • normal pressure hydrocephalus • parkinson’s plus syndromes of progressive supranuclear palsy • multi-system atrophy • cortical basal ganglion is degeneration • lewy body dementia, dystonia, huntingtons disease summary: parkinsons is.a neurodegenerative movement disorder bc of degeneration of substantia nigra & pedunculopontine nucleus of basal ganglia. Multifactorial etiology, results in motor and non motor impairment (postural gait/tremor) 5.6 Huntington’s Disease Huntington’s disease is a genetic neurodegenerative condition that involves degeneration of striatum, primarily the caudate nucleus -progressive, fatal Caused by: mutation in a single gene Epitology ~2.71 to 7 per 100.000 worldwide Typically ages 30-50 mean onset at about 40 yrs old Disease progression is fast but slower than ALS Death: 15-20 yrs from disease onset -individuals have observable behavioral disturbances way before motor impairments manifest Etiology Window of 36-39 Huntington (HTT) gene repeats of CAG -located in chromosome 4 • Cytosine-adenine-guanine (CAG) sequence sequence less than 36 is normal -repeats of 40 or more will lead to disease indicated potential for disease but severity is unclear - 3% sporadic mutation, rest is familial inheritance -higher # of repeats is predictive of earlier disease onset Autosomal dominant inheritance pattern indicated that having a single copy of the gene or mutation will lead to the disease & a child of an affected person has 50% chance of inheriting gene (disease itself) Pathopysiology - abnormal length of the cytosine-adenine-guanine repeat sequences causes decreased transport & decreased release of brain derived neurotrophic factor.(BDNF) ↓ leads to degeneration of the medium spiny neurons within the striatum. -degeneration occurs due overstimulation, excitotoxicity, neurotoxicity, increased inflammation with active microglia, and decreased growth and neuron survival. Degeneration of caudate and putamen= decreased signaling in indirect pathway causes striatum to be less able to inhibit globus pallidus externus ↓ Globus pallidus then is able to further inhibit subthalamic nucleus- decreasing activity of globus pallidus internal segment ↓ Facilitated decrease disinhibition of thalamus and increase excitablility of frontal cortex = Increased excitablility leads to hyperkinesia and changes to no motor fxns of BG Refer to image V Decrease volume of cerebellum and cerebrum Increase size of lateral ventricles Degeneration of caudate can be seen in MRI or postmortem Image above: huntingtons -there is a decrease in caudate size, cerebellum and cerebrum Image below has no disease Impairments Neuromuscular conditions that you may consider for differential diagnosis, or share similarities with Huntington's disease include: spinocerebellar ataxia, chorea, Friedereich's ataxia , dystonia conversely Parkinson's disease. Summary: Huntington’s disease is a neurodegenerative movement disorder (like Parkinson’s) is due to degeneration of caudate of the striatu Results in choreiform mvmnt and hyperkinesia -early impact on cognitive, emotional and behavioral systems compared to motor systems -condition is mainly inherited through autosomal dominant inheritance patter w 100% penetrance -fatal~15-20 years of diagnosis POP QUIZ 1. ELICITATION OF WHICH SPINAL REFLEX RESULTS IN ANTAGONIST MUSCLE A- phasic reflex B- stepping pattern C- crossed extensor D- reciprocal inhibition 2. riding on bus standing facing forward trying to stabilize, bus stops abruptly which two tracts would help with core and balance righting rxm to prevent from falling A D F G S 3. where does mossy fiber input to cerebellum originate from? a pontine nucleus b. thalamus c. red nuclei d. inferior olive 4. a. activity in neuron C will increase b. decrease c. unchanged 5, if it were possible to sustain damage to neurons that project striatum to globus pallidus externus which would you expect to happen • DECREASED • INCREASED • NO CHANGE IN AMT OF MOVEMENT answers 1. D stepping - in spinal cord more for walking cross- noxious stim so contra and ipsi activated inhibition - interneurons inhibit antagonist group phasic stretch - deep tendon stretch 2. FG A - ant corticospinal (movement of Upper limb movement & trunk) are the same as med D - rubrospinal, distal extensors F- vestíbulo spinal - balance, posture G- reticulosponal - posture S- lateral corticospinal - king of voluntary movement 3. pontine nucleus • climbing olive • mossy pontine in pons 4. decreases IM CONFUSED HOW a inhibiting b - tonic b inhibiting c at rest a- decreases then less able to inhibit b, so b can do it’s job more bc not inhibited (og job to inhibit c), so C activity will decrease HOWWWWWW 5. increased