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parkinsonism-180214104126.pdf
- 1. DR RAMDHAN KRKAMAT PG (3rd year) JLNMCH, Bhagalpur
- 2. History & epidemiology -Introduction and Conclusion Anatomy & physiology Pathology of Parkinsonism Clinical features & diagnosis of Parkinsonism Management of Parkinsonism Pathology of Alzheimer’s disease Clinical Feature & Diagnosis of Alzheimer’s Management Of Alzheimer’s Disease
- 3. Parkinsonism is ageneric term that is used to define a syndrome manifest as bradykinesia with rigidity and/or tremor. It has a differential diagnosis (Table 449-2) that reflects damage to different components of the basal ganglia. Among the different forms of parkinsonism, PD is the most common (approximately 75% of cases).
- 4. Parkinsonism is aclinical syndrome characterized by motor symptoms like bradykinesia,tremor and rigidity. Classification of theParkinsonism Primary parkinsonism (Parkinson’s disease) • Sporadic/Idiopathic • Genetic Parkinsonism-plus syndromes (Atypical parkinsonism) • Progressive supranuclear palsy (PSP) • Multiple system atrophy(MSA) • Cerebellar type (MSA-c) • Parkinsons type(MSA-p) • Cortical-basal ganglionic degeneration(CBGD) • Frontotemporal dementia(FTD)
- 5. Secondary parkinsonism(environmental etiology) • Drugs induced(Antipsychotic medications, Reserpine, Tetrabenazine) • Postencephalitic(infection) • Toxins: MPTP, cyanide,CO, Mn, hexane • Heavy metal (iron, manganese) • Vascular • Brain tumors • Head trauma • Normal-pressure hydrocephalus • Liver failure
- 6. OTHER NEURODEGENERATIVE DISORDER •Wilsonsdisease •Huntingtons disease •Neurodegenaration with brain iron accumulation •SCA 3 (spinocerebellar ataxia) •Fragile x-associated ataxia-tremor parkinsonism. •Prion disease •Dystonia-parkinsonism (DYT3) •Alzheimers disease with parkinsonism
- 9. Neurodegenerative diseases Parkinson’s Disease Alzheimer’sDisease Huntington’s Disease Amyotrophic lateral sclerosis (ALS) SpinocerebellarAtaxia
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- 12. Began to experiencetremors and stiffness of his left arm while he walked Changes in his posture and unusual movements of his left arm. Sleep disturbances Gait problems- stooped posture Symptoms gradually worsened with time Case 1 Mr Anil chaudhry, 65 years old man, a retired university professor……
- 13. Case 2 Mrs Meenadevi, 76 years old woman Lived alone for several years Brought to the neurological department, by her daughter, memory impairment General and neurological examinations- normal Speech – highly anomic , paraphasic Unable to provide birth month, year, current year Cognitive domain – below average
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- 15. History of Parkinson’s Disease Firstclear medical description: James Parkinson in An Essay on the Shaking Palsy (1817) Jean-Martin Charcot- Influential in refining and expanding this early description & in disseminating information internationally Named the disorder as Parkinson’s disease
- 16. William Gowers- Slightmale predominance of the disorder, joint deformities typical of the disease. Richer and Meige Babinski - Babinski sign Brissaud Greenfield and Bosanquet- Clear delineation of the brain stem lesions
- 17. Epidemiology of Parkinson’s disease Prevalence Crude prevalence –India - 328 per 100,00 Incidence Crude annual incidence rates- 1.5 per 100,000 population (China) in 1986 to 14.8 (Finland) through 1968 to 1970.
- 18. Gender differences Slightlymore common in men than in women Male to female ratio- 1.2:1 to 1.5:1 Geographic distribution Crude prevalence • China - 15 per 100,000 • India - 328 per 100,000 • Mississippi, USA - 131 per 100,000 • Argentina - 657 per 100,000
- 19. Ethnic distribution Whitepeople in Europe and North America have a higher prevalence, around 100 to 350 per 100,000 population. Asians in Japan & China and Africans have lower rates, around one-fifth to one-tenth of those in whites.
- 20. Age Distribution Lesscommon before 50 years of age & increases steadily with age thereafter up to the ninth decade. ~1 in every 200 persons aged 60–69 had PD in the United States (US) and Western Europe. For people in their 70’s, this increased to ~1 person with PD in every 100 people, For people in their 80’s, ~1 in every 35 had PD
- 22. Incidence “Every fourseconds, a new case of dementia occurs somewhere in the world.” Cohort longitudinal studies provide rates between 10 and 15 per thousand. Advancing age -primary risk factor Women- higher risk of developing AD particularly in the population older than 85
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- 25. GRAY MATTER(COLLECTION) •CORPOUS STRATUM •AMYGDALOID •CLAUSTRUM •SUBTHALAMICNUCLEI •SUBSTANTIANIGRA
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- 38. Cognition(caudate circuit) eg:A personseeing a lion approach ???? FUNCTIONS Executes Learned Patterns of Motor Activity eg:writing of letters of the alphabet. hammering nails, shooting a basketball through a hoop,
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- 46. Etiology Idiopathic Genetic Parkinson’s disease Resultsdue to reduction in the striatal dopamine content due to damage of nigrostriatal pathway.
- 48. PARKINSON’S DISEASE Neurodegenerative disorderwhich affects the extrapyramidal system.
- 50. Idiopathic Ageing Usual occurrencein late middle age, and increases in its prevalence at older ages Loss of striatal dopamine and dopamine of cells in the SN with age
- 51. Genetic factors PD maybe multifactorial in etiology with genetic contributions The younger the age of symptom onset, the more likely genetic factors play a dominant role At least ten single gene mutations identified
- 52. Mutations in genecoding Alpha synuclein and LRRK2 (leucine rich repeat kinase 2) - Autosomal dominant PD Mutations in gene coding Parkin,DJ-1and PINK1- Autosomal recessive PD
- 53. Pathogenesis Three major mechanismsin dopaminergic neuron loss Mitochondrial dysfunction Oxidative and nitrosative stress Ubiquitin proteosome system dysfunction
- 56. Morphology Macroscopic: Pallor or depigmentationof neurons in substantia nigra and locus ceruleus
- 57. Microscopic Loss of pigmented,catecholaminergic neurons Intraneuronal Lewy bodies within t h e pigmented neurons of the substantia nigra. Lewy bodies are cytoplasmic eosinophilic round to elongated inclusions that often have a dense core sourrounded by halo. Lewy bodies are composed of Alpha –synuclein
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- 60. Clinical Features & Diagnosisof Parkinsonism
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- 62. Motor symptoms Characterized byFour cardinal features : Bradykinesia (or Hypokinesia) Tremor atrest Rigidity Posturalinstability
- 63. Bradykinesia Slowness of movementswith a progressive loss of amplitude or speed. Difficulty with planning, initiation and execution of movements.
- 64. Clinical Manifestations ofBradykinesia Difficulties with tasks requiring fine motor control: Loss of spontaneous movements andgesturing Hypomimia (decreased facial expression) MASK LIKE FACE Decreased spontaneousblinking Hypophonia Micrographia Sialorrhoea
- 67. Why Bradykinesia inParkinsonism?? “Driving while stepping on the brakes”
- 69. Rest Tremor Tremor :Rhythmical & involuntary shaking, trembling or quivering movements of the muscles. Rest tremor ( 4 - 6 Hertz) : Maximal when the limb is at rest Disappears with voluntary movement and sleep Alternating contraction of agonist and antagonist muscles at a rapid pace Usually Unilateral at onset
- 70. Involves the hands,lips, chin, jaw and legs . “Pil l-rolling” Tremor:
- 71. Rigidity Increased muscle tonefelt during examination by passive movement Both the agonist and antagonist muscles are involved Rigidity : Cogwheelrigidity Lead-piperigidity
- 73. Postural instability Stooped Posture UNIVERSALFLEXION : Extreme neck flexion, Extreme anterior truncal flexion (camptocormia) & Flexion of elbows and knees.
- 74. Festinating / ShufflingGait: i) Difficulty to initiate walking ii) Shortened stride iii) Reduced arm swing iv) Rapid small steps (shuffling) RUNNING AFTER THE CENTRE OF GRAVITY Freezing phenomenon
- 75. Non-motor symptoms Neuropsychiatric Depression &Anxiety disorders Apathy Autonomic disturbance (dysautonomia) Urinary dysfunction Constipation Sensory symptoms pain Restless legs syndrome Olfactory dysfunction
- 76. Sleep disturbances REM behaviordisorder excessive day timedrowsiness Cognitive impairment Dementia : In >80% of patients after 20 years of disease
- 81. Diagnosis of Parkinsonism Diagnosisis primarily clinical, based on history and examination Confirmatory diagnosis : Histological demonstration of the intraneuronal Lewy bodies on autopsy. CT scan & MRI exclude other causes.
- 82. Examination of signs Bradykinesia: Ask patient to do repetitive movements as quickly and as possible • opening and closing the hand • tapping thumb and index fingers • or tapping the foot on the ground Rest tremor: Differentiate from the intentional tremor seen in cerebellar disease Best observed while the patient is focused on a particular mental task.
- 83. Rigidity: Increased resistanceto passive movements Postural stability The “Pull test” is performed in order to assess postural stability
- 84. UK Parkinson’s DiseaseSociety Brain Bank’s clinical criteria for the diagnosis of probable Parkinson’s disease Step 1 Bradykinesia At least one of the following criteria: • Rigidity • Rest tremor (4–6 Hz ) • Postural instability (not caused by primary visual, vestibular, cerebellar or proprioceptive dysfunction) Step 2 Exclude other causes of parkinsonism
- 85. Step 3 Atleast three of the following supportive (prospective) criteria: • Unilateral onset • Rest tremor • Progressive disorder • Persistent asymmetry • Severe levodopa induced chorea (dyskinesia) • Clinical course of 10 years or more
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- 89. No definitecure Relief ofcardinal signs- rigidity, tremor , & akinesia Correction of mood changes Treatment of other symptoms such a s depression,sleep disturbance . Treatment of cause when possible
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- 91. 1.General Measures Physiotherapy Speech therapy Dietaryc o n t r o l s
- 92. Physiotherapy Helps to reducerigidity Correctsabnormalposture Improves walking , turning & balance
- 93. Speech therapy Helpful inpatients where dysarthria and dysphonia interferes communication
- 94. Dietary controls Include high-fiberdiet Choose foods low in saturated fat and cholesterol. Avoid high protein diet
- 95. Drug Therapy Does notprevent disease progression but improves quality of life Drug therapy Dopaminergic activity Cholinergic activity
- 96. Classification of drugs Drugsaffecting Dopaminergic system Dopamine precursors: Levodopa Peripheral decarboxylase inhibitors: Carbidopa MAO-B Inhibitors: Selegiline, rasagiline. COMT Inhibitors: Tolcapone, entacapone. Dopamine releasing drugs:Amantadine Dopamine receptor agonists:Bromocriptine, pergolide, cabergoline, ropinirole, rotigotine,pramipexole. Drugs affecting Cholinergic system Central anticholinergic: Trihexyphenidyl,Benztropine, Biperidine, procyclidine. Antihistaminics: Promethazine
- 100. Levodopa ‘Gold-standard' treatment forParkinson's.. Therapautic benefit is nearly complete in early stages but declines as disease advances(“Wearing-off effect”) 1-2% cross BBB Improves cardinal signs- tremor, rigidity and akinesia.
- 101. Side Effects At theinitiation of therapy Nausea, vomiting, hypotension, cardiac arrhythmias, angina, taste alteration. Avoided by gradual titration Long-term complications Dyskinesias Behavioural effects: hallucination, psychosis On–off effect Wearing-off effect (“on” episodes when the drug is working and “off” episodes when parkinsonian features return)
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- 103. Ergot derivatives: (e.g., bromocriptine,pergolide, cabergoline) and were associated with ergot-related side effects, including cardiac valvular damage. Second generation of nonergot dopamine agonists : (e.g., pramipexole, ropinirole, rotigotine) Dopamine agonist Side effect: oNausea,vomiting, and orthostatic hypotension. o Hallucinations and cognitive impairment are more than levodopa so use cautiosly in age more than 70 oSedation with sudden unintended episodes of falling asleep while driving a motor vehicle have been reported.
- 104. MAO-B INHIBITORS Monotherapyin early disease. Reduced “off” time when used as an adjunct to levodopa in patients with motor fluctuations.
- 105. COMT INHIBITORS: Levodopawith a COMT inhibitor reduces “off” time and prolongs “on” time. Two COMT inhibitors have been approved, tolcapone and entacapone.
- 106. Anticholinergic drugs: Their majorclinical effect is on tremor, although it is not certain that this benefit is superior to what can be obtained with agents such as levodopa and dopamine agonists. Still, they can be helpful in individual patients with severe tremor. Their use is limited particularly in the elderly, due to their propensity to induce a variety of side effects including urinary dysfunction, glaucoma, and particularly cognitive impairment.
- 107. Treatment approaches tonewly diagnosed PD
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- 110. PARKINSONISM CASE 1 Mr Poudel,65 years old man Difficulty in walking and speaking , tremor in left hand and leg Sleep disturbances
- 111. Rx: Levodopa 250 mg+carbidopa25mg Medication reduced his symptoms but did not stop the disease from getting worst. His loss of mobility and speech impairment limited his social interactions. He and his wife also have had to give up many of their retirement travel plans.
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