Module 14.docx

Neurodegenerative Disorders Lecture Guide Parkinson’s Disease Neurotransmitter problem: __Dopamine____ Necessary for: for efficiency and grace of __movement___ Produced by: basal ganglia : Dopamine thalamus vs Cerebellum acetylcholine thalamus. Deficiency leads to uncoordinated movements such asrec...

Neurodegenerative Disorders Lecture Guide Parkinson’s Disease Neurotransmitter problem: __Dopamine____ Necessary for: for efficiency and grace of __movement___ Produced by: basal ganglia : Dopamine thalamus vs Cerebellum acetylcholine thalamus. Deficiency leads to uncoordinated movements such asreceiving smooth coordination receiving messages. Incidence: Age: 50 2nd most common degenerative nervous system disorder AD #1 Sometimes occurs in younger adults Affects both men and women Etiology: unknown - Multifactorial Genetics Environment Lead to cell death of cells in _parkinson disease. Maybe autoimmunity related to: Viral exposure and molecular mimicry Presentation - S/S: Tremors and rigidity Stooped posture Short, shuffling steps CLASS ACT: Character of tremors: Tremors, tremors 3, Pill rolling Tremors Location: Hand and feet … neck and face Unilateral to bilateral Aggravating factors: Resting and postural tremor Activity relieves the tremor. Diagnosis: Physical Exam _80_% loss of dopamine before symptoms occur __Rhythmic__ movement or tremors bradykinesia: Slow movement …can begin with tremors that occur _at rest_ and stop with _activity_ and proceed to rigidity. Character: Jerky cogwheel movements Once movement is begun Location: Unilateral 🡪 bilateral Aggravating Factors: Most evident during __passive__ range of motion (PROM). Bradykinesia: difficulty in attempt to walk, turn or change stride May freeze Lean forward Small, shuffling steps Impaired physical mobility Stiff facial features Rigid throat muscles → drooling, dysphagia Risk for _aspiration_ - leading cause of death definitive tests: There is no definitive test for Parkinson disease as MRI or CAT Scan would not be helpful. A trained neurologist is looking at history and physical examination would make the diagnosis and certainly response to dopamine replacement would be significant while replacing the dopamine by mouth and resolution of the symptoms would suggest this person has parkinson disease. Autonomic Nervous System issues → impacts autonomic ganglia Orthostatic hypotension Risk for injury: Falling related to orthostatic hypotension. Loss of postural reflexes → Parasympathetic effects Constipation Urine retention Other issues Slow, monotonous, poorly articulated speech Impaired _verbal_ _communication_ Muscle rigidity 🡪 lessened ability to deep breathe…problems with respiratory muscle movement: Ineffective Airway Clearance ...Risk for aspiration and pneumonia. Cognitive dysfunction…late in disease Lewy body dementia: misfolded protein alpha-synuclein Treatment Goal: restore normal balance of neurotransmitters Goal: Reduce the rigidity and improve mobility….improve quality of life Medication: To replace lost Dopamine Levodopa-Carbidopa gel infusion (LCIG) - inhibits the peripheral metabolism of levodopa. Restore balance between dopamine and acetylcholine. Deep brain stimulation - interrupt atypical signaling pathways. Young-Onset Parkinson’s Disease Family history A longer survival Multiple Sclerosis Degeneration of the myelin sheath autoimmune disease: genetic susceptibility + environmental triggers Disease of Central Nervous System Targets oligodendrocytes and myelin sheath Myelin breakdown (demyelination) → nerve transmission becomes Strong and erratic. Affects saltatory conduction Damaged Myelin → signals from nerves do not travel as well S/S: signal does not reach its target Diagnosis: History paresthesias: Numbness and tinglings visual impairments:Blurry of vision, double vision, and temporary blindness. Often have periods of exacerbation: (disease ) and remissions (prolonged) Often returning to normal or near normal level of neural function in the beginning Later there may be no improvement between episodes Physical Motor symptoms: weakness, dragging a foot Foot drop Risk for injury: Falls Optic neuritis - Diplopia, eye pain, burning, and temporary blindness. involuntary contractions, stiffness Imbalance in electrical activity → hyperactive stretch reflexes. sacral nerves → spinal cord; bladder → urinary retention or incontinence; Rectum →constipation; Male →impotence impaired cognition: more than 50% Diagnostic tests MRI Visual evoked potential [VEP] – checking for speed of nerve conduction Spinal tap – check for Myelin basic protein & inflammation Treatment Goal: preserve ability of nerves to conduct an impulse, reduce # of flare ups, maintain quality of life Flare-ups: immunosuppression therapy Amyotrophic Lateral Sclerosis (Lou Gehrig’s Disease) Environmental “trigger” bumps electron from outer shell…damaged cells steals electron from cell membrane [motor neuron cell bodies in this case] → damage motor neurons → loss of motor function lose upper neuron motor cell body in cerebral cortex lose motor cell body of lower motor neuron No message gets to skeletal muscles → muscle atrophy related to reduced innervation → muscle weakness to paralysis “Wasted” respiratory muscles 🡪 respiratory failure Electrodiagnostics Stimulate muscles directly = contraction… ALS is not a problem with the muscles. Nerve conduction is delayed Review Questions: ALS is a disease of the upper and lower motor neurons. A person with ALS will have slower nerve conduction velocity. Persons with ALS often succumb to respiratory failure. Persons with ALS will have skeletal muscles that are less than normal size. The change in size is the result of reduced innervation. …remember the concept of disuse atrophy….in this case disuse brought on by reduced innervation, reduced depolarization → reduced ability of the skeletal muscles to contract Summary ALS alters the anatomy of the motor neurons → alters the physiology Loss of motor neuron cell body → motor impulse not initiated → neuron has no impulse to conduct, skeletal muscles cannot contract → disuse atrophy → weakness, loss of muscle function – including respiratory muscle function Example of Drug Therapy Radicava [Rah-da-cava] helps to control excessive oxidative* stress in the body. …ALS: damaging oxidative processes occur at a higher than normal rate. *removing electrons Huntington’s Disease Autosomal dominant – defect on chromosome 4 Degeneration of neurons of basal ganglia 🡪 random jerky movements, dementia Too many repeating nucleotides forming misfolded protein Cause of death Pneumonia or other infections Injuries related to falls Complications related to the inability to swallow Review Name this pathophysiology Multiple Sclerosis - is an Autoimmune destruction of myelin sheath in CNS → disturbance in nerve transmission (slower and more erratic). Etiology? Autoimmune with an environment component. Genetic susceptibility + trigger. Name this Patho: read as plaques in the brain MS … white plaque = scars (MS = many scars). More scars = more symptoms. This reminds me of multiple sclerosis because: Diplopia (optic neuritis … diplopia and possible blindness = presenting symptoms in many persons with MS. This image reminds me of Parkinson’s Disease because reduction in dopamine = muscle rigidity, bradykinesia, and resting tremors. This image reminds me of… Parkinson’s Disease: Dopamine deficiency = acetylcholine predominates = “excitation” and muscle rigidity. How does this image relate to Parkinson’s Disease? Resting tremors … disappear with intentional movement. How does this image relate to Parkinson’s Disease? Bradykinesia … loss of postural reflexes = risk for injury (falls). Bradykinesia in swallowing = risk for aspiration. This image reminds me of … ALS: Upper and lower motor neuron cell bodies are lost → reduction in stimulation or skeletal muscles = atrophy, This image reminds me of ALS because: Motor nerve damage → reduced skeletal muscle innervation, including the respiratory muscles → respiratory muscle atrophy → respiratory arrest as the cause of death. …..might also think about dysphagia and risk for aspiration.