Parkinson's Disease

Parkinson's Disease Movement disorder (>50 age) [rest of word obscured] -> Degeneration of Dopamine Producing neuron in Substantia nigra -> Progressive; Adult-onset * More common with age * Most common neurological disorder Cause -> No known cause [rest of word obscured] Genetic -> mutation in PINK 1, PARK IN, ALPHA Synuclein gene * Toxic impurity (MATP) rarely Found in recreational drug MPPP/desmethyl Prodine Synthetic opioid Risk factor -> Pesticide Gene variants LRRK2 [rest of word obscured] Pathology -> [word obscured] gradually disappears Death of Dopaminergic neurons in Substantia nigra also [word obscured] found in [word obscured] disease -> Lewy body -> Eosinophilic Alpha-synuclein (unknown) -> Part of Basal ganglia -> Controls movements by connect to motor cortex [Diagram of brain structures including Caudate, Striatum, Putamen, Thalamus, Substantia Nigra, Pars Reticulata, Pars Compacta, and arrows indicating connections and functions] Striatum (Caudate) (Putamen) -> Pars Reticulata -> Receive from striatum -> send to Thalamus via? GABA. Pars Compacta -> Send to striatum via dopamine neurons In nigrostriatal pathway Thalamus -> Help stimulate Cerebral cortex -> movement Partly Pars reticulata -> In this PD, [word obscured] neuron die -> HYPOKINESIS Substantia Pars compacta Nigra affected area Slow movement. [rest of word obscured] Asymmetric Symp tremor -> Involuntary Shakiness DD [rest of word obscured] * "Pill-rolling" * "Resting tremor" -> Present at rest diminishes with movement. Rigidity -> Stiffness "Cogwheel Rigidity" [rest of word obscured] DD Essential tremor + Stooped Posture [rest of word obscured] Action tremor. + Almost expressionless. Bradykinesia - Slow -> from difficulty initiating movement. Hypokinesia - Lessened [rest of word obscured] -> Legs freeze up Akinesia - Absence. * Shuffling gait Postural Instability. * Problem with balance. * Can lead to falls. Difficult in [rest of word obscured] & swallow Depression, dementia, sleep disturb, difficulty swelling. -> Dysfun in other part (eg) Dretan tall cortex -> Dysfun in other neurotransmitter [rest of word obscured] Acetylcholine. Treatment -> goal help with symp but can't stop neurodegeneration Strategy -> Increase Dopamine Signaling. * Dopamine can't cross BBB. * Levodopa (precursor of dopamine) convert by Dopamine. But also occur peripherally (with nigra striatal neurons) Least stimulate epinephrine (arrhythmias) So, stop this use Carbidopa. (Inhibit Peripheral DOPA [rest of word obscured] Levodopa + Carbidopa. Can't cross BBB (2) Amantadine -> antiviral, ↑ dopamine production (3) Dopamine agonist -> stimulate D. production (M risk) (adj) Monotherapy Delay use of * Bromacriptine (Ergot) fungal derivative (Shoping Levodopa-carbidopa & Pramipexole is not Ergot gambling Levodopa-induced Ropinirole. Dyskinesia (4) Inhibitor of COMT - Catecholamine-O-methyltransferase Keep Tolcapone inhibit COMT -> dopamine, levodopa on blood Entacapone degrade. (5) * Selegiline Inhibits (MAO-B -> dopamine) Rasagiline degrade [rest of word obscured] (6) Anticholinergics (for cognitive impairment) also MEMANTINE keep To balance betw Dopamine & Acetylcholine (eg) Benztropine (help with tremors) Surgical Deep brain Stimulation (in basal ganglia) Counteract aberrant signaling Criteria to diagnose PD: (1) Adequate response to dopaminergic T. (2) Levodopa-induced dyskinesias. } ≥2 criteria (3) Rest Tremor of limb (4) Olfactory loss (smell) or Cardiac sympathetic denervation PD confirmed.