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parkinson disease clinical biochemistry
- 2. Description of Disease Parkinson’s disease (PD) is typically considered a chronic, progressive neurodegenerative movement disorder. However, it is now known to have variety of non motor symptoms as well. Tremor Rigidity Akinesia/Bradykinesia Postural Instability Major Symptoms-TRAP Other motor symptoms include: Gait Dystonia Hypophonia Drooling Dysphagia Fatigue Akathesia
- 3. Defining PD Named after James Parkinson who published 'An Essay on the Shaking Palsy' in 1817, which established Parkinson’s as a recognised medical condition. He studied at the London Hospital Medical College, qualifying as a surgeon in 1784 when he was 29.
- 4. Defining PD -Degenerative, progressive disease affecting the basal ganglia. Movement disorders: 1) Akinetic-rigid syndromes - Slowed movement. - Increased tone. 2) Dyskinesias -Added, uncontrollable movements. - Essential tremor, chorea, myoclonus, tics.
- 6. Statistics Annual incidence- 0.2/1000. Prevalence- 1/500 (127 000 people in the UK). Tends to affect ≥50 years. 1/20 is under the age of 20 years. Incidence and prevalence increase with age. Equal sex incidence.
- 7. Aetiology Unknown aetiology. Several theories: Nicotine- IPD is less prevalent in smokers than lifelong abstainers. MPTP- caused severe parkinsonism in young drug abusers. Genetic factors- clustering of early-onset PD in some families.
- 8. Pathology Basal ganglia: Group of nuclei in the brain situated at the base of the forebrain (striatum, globus pallidus, substantia nigra [SN], nucleus accumbens, subthalamic nucleus). Associated with voluntary motor control, procedural learning, eye movements, cognitive and emotional functions.
- 9. Pathology Reduced dopaminergic output from SN Inclusion bodies (Lewy bodies) develop in nigral cells Degeneration in other basal ganglia nuclei Neurons in subthalamic nucleus become more active than usual in inhibiting activation of the cortex Bradykinesia Depletion of pigmented dopaminergic neurons in SN
- 10. Pathology
- 14. Clinical features Resting Tremor Pill-rolling at rest Arms/legs/ feet /jaw/tongue Present: -At rest -When distracted Diminished: -On action
- 15. Clinical features Rigidity Cogwheel rigidity (upper limbs) Increased tone when opposite arm moves actively Lead pipe rigidity (legs) Flexed posture
- 19. INITIAL SYMPTOMS OF PARKINSON DISEASE 60% OF SUBSTANTIA NIGRA DOPAMINERGIC NEURONS ALREADY LOST AT ONSET DOPAMINE CONTENT OF STRIATUM IS ONLY 20% OF NORMAL MOTOR SYMPTOMS ARE PROMINENT , i.e. TREMOR, STIFFNESS & SLOWNESS, LOSS OF DEXTERITY, GAIT DISTURBANCE, AND MUSCLE ACHES, PAINS AND CRAMPS. S.N. PATHOLOGY: BLACK BROWN TAN
- 20. NON-MOTOR SYMPTOMS OF PARKINSON DISEASE BEHAVIORAL – DEPRESSION, ANXIETY, DECREASED MOTIVATION, PERSONALITY CHANGES, LESS INCLINATION TO SPEAK, BRADYPHRENIA SENSORY – NON-SPECIFIC PAINS, AKATHISIA, RESTLESS LEGS AND OTHER SLEEP PROBLEMS AUTONOMIC – CONSTIPATION, BLADDER DYSFUNCTION, IMPOTENCE, LOW BLOOD PRESSURE
- 21. DIFFERENTIAL DIAGNOSIS OF PARKINSON DISEASE ESSENTIAL TREMOR – OCCASIONALLY CONFUSED WITH PARKINSON DISEASE. HOWEVER, 20% OF ET PATIENTS DEVELOP PD SECONDARY PARKINSONISM, i.e. DRUGS, NPH, INFECTIONS, etc. “PARKINSON – PLUS” SYNDROMES, i.e. CBD, LBD, AD, MSA, PSP HEREDODEGENERATIVE – HD, WILSON, HALLERVORDEN-SPATZ
- 22. TREATMENT OF PARKINSON DISEASE MEDICAL DOPAMINERGIC AGENTS ANTI- CHOLINERGICS; etc. SURGICAL ABLATIVE RESTORATIVE D.B.S. PHYSICAL THERAPIES P.T. O.T. SPEECH OMT, BIOFEEDBACK EXERCISE Rx, TAI-CHI PSYCHOTHERAPIES COUNSELLING SOCIAL WORK MEDS., etc.
- 23. WHEN TO START TREATMENT FOR PARKINSON DISEASE WHEN DISEASE MANIFESTATIONS INTERFERE WITH SOCIAL AND VOCATIONAL ACTIVITIES, WORSENING OR GAIT OR BALANCE OR OTHER ACTIVITIES OF DAILY LIVING. PARTNERSHIP WITH PATIENT!
- 24. WHY DELAY THERAPY? MINIMAL EFFECT ON ADL PATIENT PREFERENCE DRUG SIDE EFFECTS “LEVODOPA SPARING STRATEGY” TO FORESTALL LONG TERM COMPLICATIONS OF THE DRUG
- 25. WHAT ABOUT NEUROPROTECTIVE AGENTS? ATTEMPT TO SLOW OR IMPEDE DISEASE PROGRESSION AND CELL DEATH. HARD TO EVALUATE AS SOME AGENTS ALSO CONFER A SYMPTOMATIC BENEFIT. IDENTIFICATION OF PRE-CLINICAL DISEASE STATE AND BIOMARKER IS A PRIORITY OF CURRENT RESEARCH. PET AND SPECT?
- 26. SOME NEUROPROTECTIVE AGENTS – MANY ONGOING STUDIES SERMS – PROTECT AGAINST DOPA-ERGIC NEURONAL DEGENERATION VITAMIN E (TS) – ENRICHES SUBST NIGRA MITOCHONDRIA, DECREASED OXIDATIVE STRESS COENZYME Q10 – ATTENUATES MPTP EFFECTS ON DOPAMINE NEURONS SELEGILINE – PRESERVES MITOCHONDRIAL CO-Q10 LEVELS MINOCYCLINE – INTERFERES WITH ACTIVATION OF APOPTOTIC PATHWAYS
- 27. MORE NEUROPROTECTIVE AGENTS AMANTADINE – NMDA RECEPTOR ANTAGONIST DOPAMINE AGONISTS – ANTI-OXIDANT, PROTECT DOPAMINE NEURONS, etc. CALM-PD STUDY – PRAMIPEXOLE VS. L- DOPA – SPECT REAL-PET STUDY – ROPINIROLE VS. L-DOPA – FD-PET EARLY PD - CO-Q-10, MAOBI’S. DOPAMINE AGONISTS AS SYMPTOMATIC TREATMENT
- 28. TREATMENT OF EARLY PARKINSON DISEASE CONSIDER: CO-Q-10, VITAMIN E (TS) – MAY HELP LEG CRAMPS? SELEGILINE OR RASAGILINE (2ND GENERATION MAOBI) – AMPHETAMINE EFFECT? AMANTADINE – RAPID ONSET OF ACTION, AVOID IN COGNITIVE PROBLEMS ANTI-CHOLINERGICS – ESPECIALLY GOOD FOR TREMOR – NOT SO FOR ELDERLY DOPAMINE AGONISTS – PRAMIPEXOLE AND ROPINIROLE. LONG ACTING
- 29. Differential diagnosis Features Others Multiple systems atrophy Parkinsonism -Autonomic failure -Cerebellar involvement -Pyramidal tract degeneration -Postural hypotension -Sphincter disturbance (impotence/urinary sxx) -Cerebellar signs Progressive supranuclear palsy -Supranuclear paralysis of eye movements -pyramidal signs -cognitive impairment -Axial rigidity -Failure of vertical gaze Lewy body dementia -Early progressive dementia -Nocturnal wanderings +/- confusion Drug-induced parkinsonism -Symmetrical disease -Younger patient -Taking dopamine antagonists/lithium Vascular parkinsonism Sudden onset -Stuttering progression -Minimal tremor -Lower limbs affected >upper limbs -MRI diagnosis
- 30. DRUGS FOR PD Medical: Levodopa + peripheral decarboxylase inhibitor (E.g. Carbidopa, Benserazide). -Levodopa: Precursor of dopamine stimulates remaining neurons to produce more dopamine. -Decarboxylase inhibitor: Prevents peripheral decarboxylation to dopamine and .:. peripheral SE’s.
- 31. Management Side effects of levodopa: -N&V -Confusion -Visual hallucinations -Delusions -Chorea LT effects: -Levodopa-induced involuntary movements. -Gradually ineffective after several years. -Episodes of immobility (freezing). THEREFORE drugs are avoided until clinically necessary (significant disability) because of delayed unwanted effects.
- 32. Management Other medical treatment options: -Dopamine receptor agonists (Bromocriptine/Cabergoline). -Amantadine. -Rivastigmine (cognitive changes). -Antioxidant compounds (Vitamins C & E- possible neuroprotective agents).
- 33. Management Surgical -Stereotactic thalamotomy- temporary improvement of symptoms. Physiotherapy - Reduces rigidity & corrects abnormal posture. Speech therapy -Dysarthria/dysphonia. Neuropsychiatric - SSRI’s for depression.
- 34. REFERENCES Britton, Thomas C. "NONMOTOR ASPECTS OF PARKINSON'S DISEASE." Current Medical Literature: Neurology 20 (2004): 45- 50. "Parkinson's Disease." Current Medical Literature: Neurology 23 (2007): 44-48. Marceglia, Sara, and Alberto Priori. "Sex, genes, hormones and nigral neurodegeneration: two different Parkinson's diseases in males and in females." Future Neurology 2 (2007): 499-503. "Literature Review: Pathophysiology." Current Medical Literature: Parkinson's Disease 5 (2003): 59-61. "Literature Review: Medical Treatment." Current Medical Literature: Parkinson's Disease 5 (2003): 66-70. "Literature Review: Surgical Treatment." Current Medical Literature: Parkinson's Disease 5 (2003): 71-72.