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  1. 1. parkinsonism shwethaBy Dr.SHWETHA.A.P
  2. 2. Also called : • Parkinson's Syndrome • Atypical Parkinson's • Secondary Parkinson's
  3. 3. INTRODUCTION Parkinsonism is a clinical definition of variety of underlying pathologies that can cause parkinson’s like symptom . There are a number of disorders that can produce the symptoms referred to as Parkinsonisms. Parkinson’s is one of the parkinsonian disorders.
  4. 4. Studied & discovered by James Parkinson (1817) in his essay on the shaking palsy. Pathology was not well understood until the early 20th century. In 1919, Tretiakoff observed that the most critical abnormality in pd was the loss of neurons in the substantia nigra pars compacta of the midbrain. In the 1950s,the importance of dopamine and its depletion from the basal ganglia as the key to understanding the pathophysiology and pathologic biochemistry of pd was discovered.
  5. 5. Essay on the shaking palsy – James Parkinson 1817 “involuntary tremulous motion , with lessened muscular power, in part not in action and even when supported ;with a propensity to bend the trunk forward, and to pass from a walking to a running pace , the senses and intellect being uninjured
  6. 6. causes •Parkinson's disease (PD) is the most common cause of parkinsonism, •A wide-range of other aetiologies may lead to a similar set of symptoms, including 1. Some toxins 2. A few metabolic diseases 3. Its most common cause is as a side effect of medications,mainly neuroleptic antipsychotics 4. Antidepressants
  7. 7. • Impaired release of dopamine - Idiopathic parkinsonism. • Drug depleting dopamine store - reserpine, tetrabenzine • Toxin damaging dopaminergic neuron • Viral infection- Encephalitis ,Japanese encephalitis • Trauma-repeated head injury[punch drunk syndrome] • Miscellaneus-wilson disease,huntingtion’s disease Causes
  8. 8. CLASSIFICATION Primary = Idiopathic = Parkinson’s Disease Secondary = Acquired = Parkinsonism
  9. 9. CLINICAL DEFINITIONS (Lewy bodies = aggregation of protein alpha-synuclein in brain neurons) Parkinsonism Parkinson Disease 1. Resting tremor 2. Bradykinesia 3. Cogwheel rigidity 4. Impaired postural reflexes 5. PD can be one among the parkinsonian disorder & many other. 6. Won’t respond to dopamine replacement therapy. Parkinsonian symp. plus 1. Asymmetric onset 2. DOPA responsive 3. Absence of Saccadic problems & Early, severe orthostasis 4. Lewy bodies in SN 5. Respond to dopamine replacement therapy
  10. 10. Demonstration of Parkinsonian Gait
  11. 11. 1. Parkinson’s disease Also called Parkinson Disease, Parkinson's, Idiopathic Parkinsonism, Primary Parkinsonism, PD , Hypokinetic Rigid Syndrome/HRS, or Paralysis Agitans •2nd most commonest neurodegenerative disease. •Affects men and women of all races, all occupations, and all countries •Mean age of onset is about 60 years, but cases can be seen in patients in their 20s, and even younger
  12. 12. Parkinson’s disease is a chronic progressive degenerative disorder of the CNS caused by an imbalance b/w dopaminergic & cholinergic activity in the brain due to degeneration of dopaminergic neurons resulting in depleted levels of dopamine in the brain leading to motor function disorder & various other extra pyramidal symptoms. DEFINITION
  13. 13. Parkinson's Defined •Parkinson disease is a brain disorder. •It occurs when certain nerve cells (neurons) in a part of the brain called the substantia nigra die or become impaired. •Normally, these cells produce a vital chemical known as dopamine. Dopamine allows smooth, coordinated function of the body's muscles and movement. •When approximately 80% of the dopamine-producing cells are damaged, the symptoms of Parkinson disease appear. In short
  14. 14. Causes of Parkinson’s  Genetics –  15 – 25% of people with Parkinson's report having a relative with the disease .  The vast majority of Parkinson's cases are not directly inherited, but researchers have discovered several genes that can cause the disease in a small number of families.  Environmental Factors – Epidemiological research has identified several factors that may be linked to PD, including • Rural living, • Well water, • Herbicide use • Exposure to pesticides. There is though no evidence to prove there is environmental factors that cause Parkinsons.
  15. 15. CLINICAL FEATURES Cardinal Features Other Motor Features Nonmotor Features • Bradykinesia • Rest tremor • Rigidity •Gait disturbance/postural instability •Micrographia •Masked facies (hypomimia)equalize •Reduced eye blink •Soft voice (hypophonia) •Dysphagia •Freezing • Anosmia • Sensory disturbances (e.g., pain) • Mood disorders (e.g., depression) • Sleep disturbances • Autonomic disturbances • Orthostatic hypotension • Gastrointestinal disturbances • Genitourinal disturbances • Sexual dysfunction • Cognitive impairment/Dementia
  16. 16. C/F TREMORS(4-6hz) RIGIDITY Tremors[pill rolling] at rest,  Decreases on action.  Usually first in finger/thumb. Coarse flexion/extension of finger[pill rolling & drum beating] -Cog wheel type especially in upper limb {stiffness in all direction of movement}. - Plastic type {lead type} mostly appreciated in legs.(hypertonicity felt in a parkinsonian limb throughout the range of movements of a joint.) - In trunk rigidity manifest by flexed& stooped posture
  17. 17. C/F HYPOKINESIA Characterized by poverty & slowness of movement. Slowness in initiating movement. Hand writing : Micrographia Gait - Patient walk with short step , with a tendency to run{as they are catching their own centre of gravity}-festinating gait General – • Expressionless face with staring look with infrequent blinking. • Monotonus speech. • Dementia & depression in advance stage
  18. 18. EPIDEMIOLOGY OF PD Increased risk Decreased risk 1. Pesticide exposure 2. Pre-menopausal oopherectomy 3. Familial aggregation 1. Smoking 2. Coffee 3. High plasma urate
  19. 19. Pathologic definitions (20th Century) • Lewy bodies within damaged substantia nigra (and other brainstem pigmented nuclei) • “Incidental” Lewy bodies represent pre-clinical Parkinson’s disease
  20. 20. ANATOMICAL •The basal ganglia,( a group of "brain structures" )innervated by the dopaminergic system, are the most seriously affected brain areas in PD •main pathological characteristic of PD is cell death in the substantia nigra and, more specifically, the ventral (front) part of the pars compacta, affecting up to 70% of the cells by the time death occurs •Macroscopic alterations can be noticed on cut surfaces of the brainstem, where neuronal loss can be inferred from a reduction of melanin pigmentation in the substantia nigra and locus coeruleus PATHOLOGY
  21. 21. • Histopathology (microscopic anatomy) of the substantia nigra and several other brain regions shows neuronal loss and lewy bodies in many of the remaining nerve cells. •Neuronal loss is accompanied by death of astrocytes(star- shaped glial cells) and activation of the microglia(another type of glial cell) •Lewy bodies are a key pathological feature of pd (A lewy body (stained brown) in a brain cell of the substantia nigra in parkinson's disease. The brown colour is positive immuno - histochemistry staining for alpha-synuclein)
  22. 22. PATHOLOGY • Pathology begins in the peripheral autonomic nervous system, olfactory system, and dorsal motor nucleus of the vagus nerve in the lower brainstem, and then spreads in a sequential manner to affect the upper brainstem and cerebral hemispheres. • Dopamine neurons are affected in midstage disease. • Several studies suggest that symptoms reflecting nondopaminergic degeneration such as constipation, anosmia, rapid eye movement (rem) behavior sleep disorder, and cardiac denervation precede the onset of the classic motor features of the illness.
  23. 23. PATHOLOGY • Degeneration of dopaminergic neurons in the substantia nigra pars compacta (snc), reduced striatal dopamine, and intracytoplasmic proteinaceous inclusions known as lewy bodies . • Neuronal degeneration with lewy body formation can also affect cholinergic neurons of the nucleus basalis of meynert (NBM), norepinephrine neurons of the locus coeruleus (LC), serotonin neurons in the raphe nuclei of the brainstem, and neurons of the olfactory system, cerebral hemispheres, spinal cord, and peripheral autonomic nervous system. • This "nondopaminergic" pathology is likely responsible for the nondopaminergic clinical features
  24. 24. SIGNS AND TESTS  The healthcare provider may be able to diagnose secondary parkinsonism based on the patient's history, symptoms, and physical examination.  However, the symptoms may be difficult to assess, particularly in the elderly.  For example, the tremor may not appear when the person is sitting quietly with the arms in the lap. The posture changes may be similar to those caused by osteoporosis or other changes associated with aging. The lack of facial expression may be a sign of depression.
  25. 25.  Examination may show increased muscle tone, tremors of the Parkinson's type, and difficulty initiating or completing voluntary movements. Reflexes are usually normal.  Tests are not usually specific for secondary parkinsonism but may be used to confirm or rule out other disorders that may cause similar symptoms.
  26. 26. DIFFERENTIAL DIAGNOSIS •Diagnosis is mainly clinical and is based on the clinical findings. •Among the most common are • Side effects of drugs (mainly the major tranquilizers such as haloperidol), • Strokes involving the basal ganglia, • Degenerative disorders such as Progressive Supranuclear Palsy (PSP), Corticobasal Ganglionic Degeneration, Olivopontocerebellar Degeneration, Multiple System Atrophy, and Huntington's Disease.
  27. 27. TREATMENT presently no cure or prevention of Parkinson's disease. Treatment strategies 1. Conservative Approach 2. Neuroprotective Approach 3. Symptomatic Approach
  28. 28. Conservative approach 1. Avoid all drugs until symptoms are troublesome 2. When symptoms become troublesome start amantadine and an anticholinergic 3. When symptoms become disabling introduce L- Dopa or agonists at minimal doses
  29. 29. Neuroprotective approach 1. All newly diagnosed cases should be started on Selegeline 2. When symptoms become disabling add dopaminergic drugs
  30. 30. Symptomatic approach • At diagnosis ,treatment immediately started with dopaminergic drugs • Treatment continually modified in order to maintain maximum function for the maximum amount of time
  31. 31. DRUG THERAPY Drugs acting on dopaminergic system: 1. Dopamine precursors: L-dopa 2. Dopa decarboxylase inhibitors: carbidopa & benserazide 3. Dopamine agonists: bromocryptine, pergolide, peribidil, ropinirole, pramipexole 4. Dopamine facilitators: amantadine 5. MAO-B inhibitor: selegiline 6. COMT-inhibitors: entacapone, tolcapone Drugs acting on central cholinergic system: 1. Central anticholinergics: trihexiphenidyl, procyclidine, biperidin. 2. Central antihistaminics; orphenadrine, promethazine
  32. 32. PREVENTIVE TREATMENT Amantadine or anticholinergic medications Levodopa/carbidopa Dopamine agonists Vitamin E- has been suggested to lower the risk of PD risk. Health Food- papaya and blueberries have been suggested to slow nerve cell death. **Neither one of these medications have provided any real evidence that they slow down the progression of Parkinson’s or manages symptoms.
  33. 33. PHYSICAL THERAPY  Physical therapy is helpful in Parkinsonism. It maintains muscle tone, flexibility, improves posture and gait.  Speech therapy and occupational therapy may help promote function and independence, and may help maintain skills and positive attitude and minimize depression.
  34. 34. SURGERY •Newest Version of surgery- DBS, (deep brain stimulation) this was developed in 1990 and is the standard treatment. Procedure •Electrodes are inserted into the targeted brain region using MRI and neurophysiological mapping to ensure that they are in the right place. •Next an impulse generator or IPG (similar to a pacemaker) is implanted under the collarbone to provide an electrical impulse to a part of the brain involved in motor function. •Patients have a controller, which allows them to check the battery and to turn the device on or off. An IPG battery lasts for three to five years and is easy to replace under local anesthesia.
  35. 35. THANK YOU
  36. 36. Parkinson's Defined •Parkinson disease is a brain disorder. •It occurs when certain nerve cells (neurons) in a part of the brain called the substantia nigra die or become impaired. •Normally, these cells produce a vital chemical known as dopamine. Dopamine allows smooth, coordinated function of the body's muscles and movement. •When approximately 80% of the dopamine-producing cells are damaged, the symptoms of Parkinson disease appear. In short
  37. 37. CLINICAL PRESENTATION Altered body image (depression) Poor balance Bradykinesia (slow movement) Bradyphrenia (slowness of thought) Constipation Dribbling/drooling Dyskinesias (involuntary movements) Dysphagia (difficulty swallowing Dystonia (pain spasms) Excessive sweating (impaired thermoregulation) Hullucinations (visual) Postural hypotension Restless leg syndrome (leg aches, tingle, or burn) Rigidity Sleep disturbance Slurring/slowing of speech Tremor
  38. 38. The key signs of Parkinson disease are: • Tremor (shaking) • Slowness of movement • Rigidity (stiffness) • Difficulty with balance Other signs of Parkinson disease may include: • Small, cramped handwriting • Stiff facial expression • Shuffling walk • Muffled speech • Depression
  39. 39. Demonstration of Parkinsonian Gait
  40. 40. PATHOLOGY • The primary symptoms of Parkinson's disease result from greatly reduced activity of dopamine-secreting cells caused by cell death in the pars compacta region of the substantia nigra. • There are five major pathways in the brain connecting other brain areas with the basal ganglia. These are known as the motor, oculo- motor,associative, limbic and orbitofrontal circuits, with names indicating the main projection area of each circuit. • All of them are affected in PD, and their disruption explains many of the symptoms of the disease since these circuits are involved in a wide variety of functions including movement, attention and learning. Scientifically, the motor circuit has been examined the most intensively.
  41. 41. Additional Info : DOPAMINE: • It is a principle inhibitory NT in the brain whose distribution is restricted to the dopaminergic neurons of substantia nigra (extra pyramidal motor center), limbic system & hypothalamus. • All catecholamine's most of dopamine secreted in the synapse is recaptured by reuptake mechanism involving dopamine transporters. They are also degraded by MAO & COMT. ACETYLCHOLINE: • It is an excitatory NT which is well distributed in various regions in the brain & also secreted by the cholinergic neurons of the caudate nucleus in the basal ganglia. Along with dopamine they together regulate the motor function. • Ach is quickly degraded in the synapse by choline esterase enzyme.
  42. 42. Clinical definitions Parkinsonism 1. Resting tremor 2. Bradykinesia 3. Cogwheel rigidity 4. Impaired postural reflexes 5. Parkinson Disease Parkinson Disease Parkinsonian symp. Plus 1. Asymmetric onset 2. DOPA responsive 3. Absence of 1. Saccadic problems 2. Early, severe orthostasis 4. Lewy bodies in SN
  43. 43. LEVODOPA • Levodopa has been the most widely used treatment for over 30 years. • L-DOPA is converted into dopamine in the dopaminergic neurons by dopa decarboxylase • .Since motor symptoms are produced by a lack of dopamine in the substantia nigra, the administration of L-DOPA temporarily diminishes the motor symptoms
  44. 44. TOLCAPONE • Inhibits the COMT enzyme, which degrades dopamine, thereby prolonging the effects of levodopa. • Used to complement levodopa • Possible side effects such as liver damage DOPAMINE AGONISTS •Bind to dopaminergic post-synaptic receptors in the brain have similar effects to levodopa. • were initially used for individuals experiencing on-off fluctuations and dyskinesias as a complementary therapy to levodopa; • They are now mainly used on their own as an initial therapy for motor symptoms with the aim of delaying motor complications. • When used in late pd they are useful at reducing the off periods.
  45. 45. MAO-B inhibitors (selegiline and rasagiline) • Increase the level of dopamine in the basal ganglia by blocking its metabolism. • They inhibit monoamine oxidase-b (mao-b) which breaks down dopamine secreted by the dopaminergic neurons. • The reduction in mao-b activity results in increased l-dopa in the striatum. • Used as monotherapy • Improve motor symptoms and delay the need for levodopa in early disease, • Produce more adverse effects • Less effective than levodopa.
  46. 46. Other surgical methods 1. Unilateral thalamotomy -- can be used to reduce tremor. 2. Unilateral Pallidotomy is an effective technique for reducing contralateral levodopa induced dyskinesias. 3. Unilateral deep brain stimulation of the thalamus for tremor may also be of benefit for tremor. 4. Neural transplantation is no longer felt to be effective treatment. 5. Gamma knife -- thallamotomy or pallidotomy can be performed with focussed radiation