Parkinson's Disease PDF

Parkinson Disease Presented by: 1. Hala Eyad 2. Fatima Tariq  Introduction -Definition: Parkinson disease (PD) is a neurodegenerative condition that involves the progressive depletion of dopaminergic neurons in the basal ganglia, particularly the substantia nigra. Parkin...

Parkinson Disease Presented by: 1. Hala Eyad 2. Fatima Tariq  Introduction -Definition: Parkinson disease (PD) is a neurodegenerative condition that involves the progressive depletion of dopaminergic neurons in the basal ganglia, particularly the substantia nigra. Parkinson disease is the most common hypokinetic movement disorder  Epidemiology -Prevalence: 2nd most common neurodegenerative disorder following Alzheimer disease -Age of onset: ∼ 60 years in sporadic cases -Parkinson’s disease is common, probably affecting about 1–2% of the population aged 60+years, with no significant gender bias  Risk factors ❑ Genetic factors: 10–15% of all cases are familial. ❑ Environmental factors (e.g., exposure to manganese and other substances) ❑ Diet/metabolism (e.g., low levels of vitamin D, high iron intake, obesity) ❑ History of traumatic brain injury  Pathophysiology ▪ Parkinson’s disease is primarily associated with the gradual loss of cells in the substantia nigra of the brain. This area is responsible for the production of dopamine. Dopamine is a chemical messenger that transmits signals between two regions of the brain to coordinate activity. For example, it connects the substantia nigra and the corpus striatum to regulate muscle activity. ▪ If there is deficiency of dopamine in the striatum the nerve cells in this region “fire” out of control. This leaves the individual unable to direct or control movements. This leads to the initial symptoms of Parkinson’s disease. As the disease progresses, other areas of the brain and nervous system degenerate as well causing a more profound movement disorder.  Pathology -Macroscopically: atrophy of the substantia nigra in advanced Parkinson’s disease is recognizable by loss of the characteristic melanin pigmentation of this region -Microscopically: severe neuronal loss is demonstrable in the substantia nigra , remaining neurones often containing a distinctive intracellular inclusion, the Lewy body -Lewy bodies (hyaline inclusion bodies) are a key neuronal finding in the brains of patients with Parkinson disease -Lewy bodies composed of α-synuclein (intracellular eosinophilic inclusion A)  Eitology -Parkinson disease: ▪ Idiopathic ▪ Contributing genetic factors  Parkinsonism -Parkinsonism, also known as “atypical Parkinson’s,” “secondary Parkinson’s,” -Refers to symptoms and signs of Parkinson disease and can result from many conditions -Is syndrome comprising bradykinesia and either resting tremor or rigidity or both o Medications that cause parkinsonian side effects: 1. Neuroleptic drugs: chlorpromazine – haloperidol – perphenazine 2. Metoclopramide 3. Reserpine o MPTP: an illegal drug that metabolizes to MPP+ , damaging the substantia nigra o Metabolic disorders: Wilson disease → Hepatolenticular degeneration: presentation involves hepatitis (liver cirrhosis) – dementia – parkinsonism  Parkinsonism o Toxins: e.g., manganese, carbon monoxide, carbon disulfide o Cerebrovascular disease (vascular parkinsonism): subcortical arteriosclerotic encephalopathy o CNS infections: bacterial – viral – protozoa o Other neurodegenerative diseases like(e.g., genetic abnormalities in Huntington disease) o Traumatic: ‘punch-drunk syndrome’ chronic head injury in boxers – patients have parkinsonian features often in combination with cerebellar damage and cognitive deficits (dementia pugilistica)  Clinical features -Overview: Signs of PD gradually progress over time: The course is usually > 10 years. Motor signs are unilateral at onset Motor signs are asymmetrical Preclinical (prodromal) stage with nonmotor signs may precede the onset of motor signs (clinical phase).  Preclinical stage I. Constipation II. Anosmia III. Sleep disturbance IV.Mood disorders: Depression – apathy – anxiety  Clinical stage -Motor signs: Parkinsonism is required for the diagnosis of Parkinson disease. 1. Parkinsonism: Unilateral onset is characteristic of Parkinson disease. o Core feature of PD o Is a syndrome comprising of: 1) Bradykinesias: slowness of voluntary movements 2) Pill-rolling tremor at rest that subsides with voluntary movements (routine tasks) but increases with emotional stress most seen in hands 3) Rigidity ‘Cogwheel rigidity’ (like small start and stop movements like a gear) 2. Postural instability: imbalance and tendency to fall due to an impairment of the righting reflexes, which normally entail small balancing movements 3. Gait abnormality: Parkinsonian gait: shuffling gait with quickened and shortened steps (Festinating gait)  Clinical stage -Other motor findings: 1. Stooped posture 2. Masked face (expressionless face) 3. Micrographia 4. Dementia in advanced stages → Mnemonic: Parkinson disease causes people to feel TRAPped o Tremor (“pill rolling”) o Rigidity (cogwheeling) o Akinesia/bradykinesia o Postural instability  Clinical stage -Nonmotor findings: 1. Autonomic symptoms: o Orthostatic hypotension o Oily skin o Urinary urgency o Impaired sexual function 2. Neuropsychiatric symptoms: o Depression 3. Disordered sleep (sleep fragmentation) 4. Hyposmia, anosmia  Diagnosis -Parkinson disease is a clinical diagnosis -Evaluate for typical clinical features of PD based on detailed patient history and physical examination -A diagnosis of PD requires the presence of parkinsonism (i.e., bradykinesia and either resting tremor, rigidity, or both) -Supportive findings: Olfactory loss - Clear benefit from dopaminergic medication -Imaging is not routinely required for diagnosis but can be considered under specialist guidance if the diagnosis is unclear -Levodopa challenge test: performed to support the diagnosis of PD or as part of the evaluation prior to implantation of a deep brain stimulator. The result is positive if administration of levodopa relieves symptoms.  Management -No cure — goals are to delay disease progression and relieve symptoms -Best initial treatment: 1. Carbidopa-levodopa (Sinemet)—drug of choice for treating parkinsonian symptoms It ameliorates all the symptoms of Parkinson disease. It is the most effective of all the antiparkinsonian drugs Levodopa is a dopamine precursor that can cross the blood-brain barrier. Carbidopa blocks the peripheral conversion of levodopa to prevent the side effects of levodopa (nausea and vomiting). Early side effects: Hallucinations, dizziness, headache Late side effects: Dyskinesis (Involuntary movements) can occur after 5 to 7 years of therapy. This is a major concern and may warrant delay in initiating carbidopa-levodopa for as long as possible. 2. Dopamine-receptor agonists (bromocriptine, pramipexole). Used in early stages of the disease. May control symptoms and delay need for levodopa for several years.  Management -Next best treatment: 1.Selegiline: it inhibits monoamine oxidase B activity ‘MAO-B’ (increases dopamine activity) o It may be neuroprotective and may ↓ the need for levodopa o Side effects: Confusion and insomnia 2. Catechol-O-methyltransferase (COMT) inhibitors (entacapone or tolcapone) o are not given alone but ↑ the availability of levodopa to the brain and may ↓ motor fluctuations. 3. Anticholinergics (trihexyphenidyl or benztropine): o used in younger patients whose primary symptom is tremor (Patients with tremor as a major symptom of Parkinson disease have a better prognosis than those who have bradykinesia as a predominant finding) o Do not use in older patients or demented patients. -If medical therapy is insufficient, surgical pallidotomy or deep brain stimulators may produce clinical benefit