Neuropathological Diseases Lesson 15 PDF

- Acetylcholine - Activates **muscarinic receptors** - Muscarinic receptors found in SA node, bronchial smooth muscle, salivary glands - **Blocked by anticholinergics** - Activates **nicotinic receptors** - Nicotinic receptors found in aut...

- Acetylcholine - Activates **muscarinic receptors** - Muscarinic receptors found in SA node, bronchial smooth muscle, salivary glands - **Blocked by anticholinergics** - Activates **nicotinic receptors** - Nicotinic receptors found in autonomic ganglia, skeletal muscle - **Blocked by neuromuscular blockers** - Acetylcholinesterase inhibitors indirectly increase the amount of acetylcholine at nicotinic receptors found in the NMJ by inhibiting the action of acetylcholinesterase - Acetylcholinesterase inhibitor drugs = neostigmine, pyridostigmine, edrophonium, physostigmine - Anticholinergics = antimuscarinics - These drugs work by competitively blocking the binding of acetylcholine and preventing receptor activation in muscarinic receptors - Bulbar symptoms = related to the corticobulbar tract; oropharyngeal weakness, difficulty swallowing and managing oral secretions - **Myasthenia** gravis = MG - **Grave muscle weakness that improves with rest** - **Autoimmune destruction of the postsynaptic nicotinic acetylcholine receptors at the NMJ by antibodies produced by the thymus** (for 85% of MG cases) - Leads to a reduced number of functional acetylcholine receptors at the NMJ - Symptoms = skeletal muscle weakness that worsens after activity and improves with rest, diplopia, dysarthria, dysphagia, difficulty chewing, limited facial expressions - Symptoms start at eyes and move down - Associated with other autoimmune disease e.g. rheumatoid arthritis, lupus, polymyositis, autoimmune thyroiditis/hyperthyroidism - Life expectancy is normal - Disease characterized by remissions and exacerbations - Exacerbation triggers = stress, infection, surgery, pregnancy - Pregnancy and myasthenia gravis - Acute postpartum respiratory failure can occur - Babies born to moms with MG may experience transient sx because antibodies can cross through the placenta and also attack the fetal postsynaptic nAChR - Preferentially use amide-based LA because pyridostigmine can decrease levels of ester-based LA - Diagnosis - Tensilon/edrophonium test to increase acetylcholine levels which resulted in symptom improvement - Blood tests to detect serum acetylcholine receptor antibodies - Electromyography - Thymus imaging - Hyperplasia - Thymoma - Treatment - Mild disease treatment = Anticholinesterase drugs e.g. PO pyridostigmine is most common - Moderate disease treatment = anticholinesterase, corticosteroids, IVIG, immunosuppressants, monoclonal antibodies - Severe disease treatment = plasmapheresis, thymectomy - Pyridostigmine - Excess dosing causes cholinergic crisis - 20% as potent as neostigmine - Cholinesterase inhibitors given IV should be 1/30 of oral dose - Thymectomy - Thymus is a lymphoid organ of the immune system located behind the sternum - Thymoma = cancer of the thymus - Hyperplasia = inflammation of the thymus - Thymectomy can put MG in remission - Performed via full or partial sternotomy or via VATs or transcervical incision - Preop considerations = optimize medical management - Aspiration risk so consider RSI, pretreat with reglan/H2 blockers - Avoid routine sedatives. If you have to use sedation, reduce the dose by a lot e.g. 0.5 mg of versed - Want pt to take normal dose of anticholinesterase - Want to schedule patient for first case in the morning because they are typically strongest in the morning - Consider regional techniques but be aware high regional techniques e.g. supraclavicular block can cause worsening of respiratory sx - Postop mechanical ventilation predictors - BMI\>28 - Disease duration \>6 years - Bulbar sx - Concomitant pulmonary disease - Peak inspirator pressure \ women - Autonomic dysfunction causes dry mouth, constipation, erectile dysfunction, reduced sweating - Treatment = treat tumor; 3,4 diaminopyrimidine to increase presynaptic calcium to increase release of acetylcholine - Do not respond well to anticholinesterases - Anesthetic considerations for LEMS - Same general precautions as MG - Increased sensitivity to succinylcholine and NDNMBDs - Stiff person syndrome - Progressive disorder characterized by stiffness and rigidity - Can be associated with cancer - Treat = treat cancer, IVIG, benzos - Polymyositis - Inflammatory myopathy of skeletal muscles that affects primarily proximal limb muscles, thoracic muscles, and oropharyngeal muscles - Pts prone to dysphagia, aspiration, and pneumonia - May experience cardiac conduction defects - Treated with corticosteroids, immunoglobulin, immunomodulators - Limbic encephalitis - Degenerative autoimmune CNS disorder - Characterized by personality changes, hallucinations, seizures, ANS dysfunction, dementia, asymmetric loss of sensation in extremities - 60% of cases are associated with cancer - Acute flaccid paralysis - Infectious motor neuropathy caused by viral infection of brainstem and spinal cord lower motor neurons - Severe weakness and meningitis following acute viral infection e.g. West Nile disease, poliomyelitis - Tetanus - Caused by bacterial infection characterized by episodic masseter and neck muscle spasms - Sustained spasm of airway musculature can cause airway obstruction and respiratory failure - Botulism - Caused by bacteria where it infects the presynaptic release of acetylcholine similar to LEMS - Infants can get botulism from honey - Symptoms = acute onset of symmetric facial weakness, ptosis, bulbar weakness, and ophthalmoplegia followed by progressive descending flaccid paralysis - Guillain-Barre syndrome - Neuromuscular emergency - Autoimmune disease affecting peripheral nerves and nerve roots that is usually triggered by an acute infection - Also known as AIDP = acute inflammatory demyelinating polyneuropathy - Acute infection causes = flu, COVID, campylobacter from undercooked poultry, vaccinations - Sx = weakness, ataxia, and bilateral paresthesia that starts in lower extremities and ascends bilaterally - Anesthetic implications - Aspiration risk due to cranial nerve paralysis - Autonomic dysfunction - Exaggerated hypotension on induction and related to hypovolemia - Exaggerated response to DL and surgical stimulation - Avoid succs due to hyperkalemia from dennervation, decrease doses if NDNMBDs are needed - ALS - Degenerative motor neuron disease that affects both upper and lower motor neurons leading to destruction of the NMJ - Fatal disease with no known cure - Riluzole can prolong life by 2-3 months - Neurx diaphragm pacing system - Sx = muscle weakness, atrophy - Appear first in arms, hands, legs, and swallowing muscles - Spasticity in upper extremities and flaccidity in the lower extremities until there is no function - Cause of death is respiratory failure or CV collapse - Anesthetic implications - Avoid succs, increased sensitivity to NDNMBDs - Postop ventilatory depression - Respiratory complications are common - Regional techniques - FDA black box warning regarding the usage of succinylcholine in pediatric pts due to muscular dystrophy - Duchenne muscular dystrophy - Most common and most severe of muscular dystrophies caused by a genetic defect resulting in a deficit of dystrophin - Affects mostly males i.e. x-linked recessive disorder - Signs and symptoms = progressive weakness, clumsy gait, Gower's sign, neck flexor weakness, pseudohypertrophy of muscles (especially calves) - Gower's sign = using hands to help get up due to pelvic girdle weakness - Disease course = progressive disease where pt's are confined to a wheelchair by 12, chronic respiratory insufficiency, GI and cardiac involvement - Anesthetic considerations - These pts have macroglossia -- difficult airway management - Delayed gastric emptying/intestinal hypomotility -- increased aspiration risk - Pulmonary and cardiac complications are common - Avoid succs and volatile anesthetics due to hyperkalemia and rhabdomyolysis - The reaction with volatile anesthetics is thought to be due to the abnormal sarcolemma in muscular dystrophy, which is prone to calcium dysregulation and muscle damage resulting in MH-like sx - NDNMBs may have delayed onset and prolonged duration - Serum CK levels are initially elevated 50-100x normal early in disease with progressively decreasing levels when there is no muscle left to break down - Becker muscular dystrophy - Similar presentation to Duchenne muscular dystrophy but with an adolescent onset - Avoid succs - Myotonic muscular dystrophy - Multi-system disorder causing myotonia that becomes apparent in 20-30s - Myotonia = spasticity = delayed relaxation after contraction - Affects distal muscles more than proximal muscles - Signs and symptoms are similar to premature aging e.g. cataracts, endocrine dysfunction, cardiac issues - Avoid succs - Facioscapulohumeral muscular dystrophy - Characterized by weakness of face and shoulder girdle - Respiratory muscles are usually spared - Limb girdle dystrophy - Characterized by progressive weakness and elevated CK levels - Possible cardiac and respiratory involvement - Myotonia congenita - Genetic disease causing myotonia - No cure, no cardiac involvement, and normal lifespan - Abnormal response to succinylcholine and NDNMBs - Prolonged contraction/muscle spasms - Trismus and difficult airway management - Avoid hyperthermia - Avoid shivering in any patient with myotonia - Periodic paralysis - Diseases causing spontaneous episodes of weakness or paralysis - Can be genetic or acquired - Periodic paralysis can be caused by potassium imbalance and thyroid hormones - Hypokalemic periodic paralysis - Secondary hypokalemic paralysis - Hyperkalemic periodic paralysis - Thyrotoxic periodic paralysis - Secondary hyperkalemic paralysis - Multiple sclerosis - Autoimmune CNS disease with inflammation, demyelination, axonal damage - Risk factors = hereditary, Epstein-Barr infection, female, other autoimmune disease, cigarette smoking - Sx = muscle stiffness, paresthesia, visual problems, LE paralysis, epilepsy - No known cure - Treatment = corticosteroids, anti-inflammatory agents, immunosuppressants - Anesthetic considerations - Monitor temperature because increased body temp causes exacerbations - Avoid succs - Altered sensitivity to NDNMBDs - Limited physiological reserve - Reduced MAC requirements and delayed emergence - Regional anesthesia = spinal anesthesia associated with worsening of symptoms, peripheral nerve blocks can be a good choice - While MS destroys the myelin of the central nervous system (the brain, spinal cord, and optic nerves), Guillain-Barré Syndrome (GBS) destroys the myelin of the peripheral nerves - Stress dose of steroids should be considered to administer to pts who take chronic steroids - Chronic steroid use can cause suppression of the HPA axis causing adrenal suppression/insufficiency - Give dose preinduction or on induction - Consider giving intraoperatively if you are struggling to maintain BP - Huntington's disease - Rare progressive neurodegenerative disease that leads to degenerative changes in the brain - Autosomal dominant inherited disease - Sx = dystonia/choreiform movements, depression and psychosis, dementia, hypothalamic atrophy and endocrine changes - Dystonia = involuntary twitching; difficulty walking, speaking, and swallowing - Treatment is palliative - Tetrabenazine to treat chorea - Antiepileptics - Antidepressants - Anesthetic considerations - Avoid central anticholinergics, reglan - Increased sensitivity to succinylcholine and NDNMBDs - Aspiration risk - Dementia = umbrella term for loss of memory and other thinking abilities severe enough to interfere with daily life - Anesthetic considerations - Benzos may worsen confusion and delirium - Inhalation agents may increase delirium - Combination of IV and regional to avoid or reduce opioid exposure - Alzheimer's disease caused by abnormal deposits of proteins from amyloid plaques and tau tangles throughout the brain - Major cause of dementia in the US - Progressive degenerative disease caused by neuronal apoptosis - Exact cause unknown - Plaques - Tangles - Late signs = extrapyramidal signs, apraxias, aphasia, cortical atrophy, ventricular enlargement - Risk factors = HLD, CV disease, depression, TBI, smoking, anticholinergics - Pts with Alzheimer\'s have lower levels of acetylcholine so treatment involves cholinesterase inhibitors - Frontotemporal dementia caused by abnormal amounts or forms of tau and TDP-43 proteins accumulating inside neurons in the frontal and temporal lobes - Lewy body dementia caused by abnormal deposits of Lewy bodies affecting the brain's chemical messengers - Vascular dementia caused by conditions such as blood clots that disrupt blood flow in the brain - Parkinson's disease - Chronic and progressive degenerative disease due to loss of dopamine - Leads to Increased activity of basal ganglia nuclei - Leads to Thalamic inhibition - Presence of Lewy bodies in substantia nigra and alpha-synuclein - Symptoms = resting tremor, pill-rolling, rigidity, shuffling gait, stooped posture, autonomic dysfunction, sialorrhea i.e. increased secretions - Treatment - Dopaminergic agents e.g. Levidopa - Dopamine receptor agonists - COMT-inhibitors which prevent the carboxylation of dopamine - Surgical interventions = thalatomy, pallidotomy, placement of DBS electrodes - Anesthetic considerations - Aspiration risk - Continue medication regimen except for DBS (i.e. deep brain stimulation) surgery - Alfentanil and fentanyl can cause dystonia when given quickly - Fentanyl and morphine can cause increased muscle rigidity - Avoid antidopaminergc drugs e.g. phenothiazines, butyrophenones, dopamine antagonists, Haldol, droperidol, reglan - Acetylcholinesterase inhibitors when used for PD dementia are associated with a prolonged effect of succinylcholine and increased resistance to NMBDs. Stop 1-2 weeks prior to surgery if possible - Avoid centrally-acting anticholinergics - Avoid meperidine in pts taking MAOIs - Lewy body = clumps of abnormal protein in dopamine producing cells in the brain - Motor sx typically present prior to cognitive impairment - Most pts with Parkinson's disease have Lewy bodies - Deep brain stimulation - used to treat advanced Parkinson's disease - Electrodes are implanted in the brain to stimulate subthalmic nucleus or globus pallidus pars interus - Use awake techniques with sedation so device can be tested intraoperatively - Device can cause HTN, seizures, and electrical interference - Device can be damaged or reprogrammed by electrocautery or MRI - Charcot-Marie tooth disease (CMTD) - Genetic mutation that causes defects in myelin formation causing reduced nerve conduction - Sx usually start in the foot with weakness in legs and hands - Anesthetic implications - Sensitivity to succinylcholine and NDNMBDs - Epilepsy - Seizure = paroxysmal alteration in neurological function caused by synchronous, rhythmic depolarization of cortical neurons - Seizure activity can elevate brain metabolism by 400% - Can be caused by neurological or medical conditions e.g. TBI, drug withdrawal, brain tumor, metabolic disorders, CNS degenerative diseases, uremia, hypoglycemia - Prodroma = early clinical manifestations - Aura = peculiar sensation preceding the onset of a seizure - Ictus = episode of the seizure - Postictal state = period immediately following the cessation of seizure activity - Classified by site of origin, degree of awareness, and level of body movement - Motor seizures - Tonic = stiffening of body muscles with falling and loss of consciousness - Atonic = sudden loss of muscle tone with no loss of consciousness - Myoclonic= no loss of consciousness - Tonic-clonic = grand mal - Hyperkinetic = motor activity with or without preserved awareness - Non-motor seizures - Sensory - Cognitive - Emotional/affective - Autonomic - Anesthesia considerations for seizure - Most perioperative seizures in non-epileptic patients are due to metabolic derangements from hyponatremia, hypocalcemia, hypoglycemia - Acute seizure management - Manage airway - ID and treat underlying metabolic disturbances - Propofol 10-20 mg IV bolus. Propofol is GABA agonist = anticonvulsant - Benzos = GABA agonists = versed, or diazepam - Many seizure medications alter hepatic metabolism of other medications - Increased dosage requirements of IV anesthetics and NDNMBs - Anesthesia for epilepsy seizure - Surgery indicated for discrete epileptic focus, usually in the temporal lobe - Avoid benzos for planned electrocorticography - Increased doses for muscle relaxants, opioids, and dexmedetomidine may be required for pts on anticonvulsants - Status epilepticus = continuous motor seizure lasting \> 20 mins or series of seizures without awakening - Seizures lasting \>5 mins are unlikely to resolve spontaneously - Treat with benzos and add anticonvulsant if unsuccessful - Avoid NMBDs - Increased O2 consumption can cause severe hypoxemia and death