Parkinsonism, Parkinson’s Disease

Parkinson's Disease, SYMPTOMS OF PARKINSONISM, STAGES OF PARKINSONISM, ETIOLOGY OF PARKINSONISM, PATHOPHYSIOLOGY OF PARKINSONISM, TREATMENT OF PARKINSONISM.

1. DR. SIDDHARTH DUTTA PARKINSON’S DISEASE

2. INTRODUCTION The disease was first described as “ shaking palsy” by James Parkinson 1817. Jean-Martin Charcot propped its current name honouring James Parkinson . Synonyms: Parkinson’s Disease Idiopathic or primary parkinsonism Hypokinetic rigid syndrome Paralysis agitans

3. Parkinson’s disease is a progressive disorder that is caused by degeneration of nerve cells in the part of the brain called the substantia nigra , which controls movement. These nerve cells die or become impaired , losing the ability to produce an important chemical called dopamine . Incidence of Parkinson disease increase with age, but an estimated 4% of the people with PD are diagnosed before the age of 50. Men are one and half time more likely to have PD than women.

4. SYMPTOMS OF PARKINSONISM

5. PRIMARY MOTOR SYMPTOMS SECONDARY MOTOR SYMPTOMS NONMOTOR SYMPTOMS

6. Resting Tremors: shaking of the hands, arms or legs, especially when the limb is is rest position. Primary Motor S ymptoms

7. Bradykinesia: The word bradykinesia is logically derived from two Greek roots: brady & kinesis. Brady = slow, Kinesis = Motion Slowed ability to start and continue movements , and impaired ability to adjust the body's position .

8. Rigidity: Abnormal stiffness in the limb or other part of the body.

9. Postural Instability: impaired balance or difficulty in standing or walking.

10. Walking/Gait Problems: b radykinesia and postural instability both contribute to the walking and gait difficulties in Parkinson’s disease

11. Dystonia: is a movement disorder in which a person's muscles contract uncontrollably . The contraction causes the affected body part to twist involuntarily, resulting in repetitive movements or abnormal postures . Secondary Motors Symptoms

12. Micrographia : is an acquired disorder that features abnormally small , cramped handwriting or the progression to progressively smaller handwriting .

13. Mask Like Expression: people with PD have a  mask - like expression , their face has less facial movements and appears less animated. The scientific term for this is hypomimia , which means a reduction in the expressiveness of the face that is marked by diminished animation and movement of the facial muscles.

14. Sexual Dysfucntion : erectile dysfunction (ED) is the most common  sexual problem for men with Parkinson's. Medication side effects, progressing  disease and   non-motor symptoms , such as anxiety or apathy , can decrease sex drive, erections  and orgasm.

15. Akasthisia : is a movement disorder characterized by a feeling of inner restlessness and inability to stay still.

16. Cramping

17. Reduced swallowing movements/drooling of saliva

18. Shuffling gait: appears as if the person is dragging their feet as they walk . Steps may also be shorter in stride (length of the step) in a  shuffling gait . The   shuffling gait  is also seen with the reduced arm movement during walking .

19. Speech problems: Sometimes  speech  sounds breathy or hoarse. People with  Parkinson‘s people talk slowly, but some speak rapidly, even stuttering stammering .

20. Stooped posture: Parkinson's affects control of automatic activities , so posture changes may occur without the brain's automatic reminders to stand up straight. These changes may include stooped or rounded shoulders, decreased low back curve or forward lean of the head or whole body, making you look hunched over .

21. Nonmotor Symptoms Parkinson's experience nonmotor symptoms, those that do not involve movement, coordination, physical tasks or mobility . Symptoms: Loss of smell Constipation REM behaviour disorder Mood disorders Orthostatic hypotension

22. STAGES OF PARKINSONISM

23. Parkinson's Disease appears to have five different stages:

24. ETIOLOGY OF PARKINSONISM

25. Parkinson disease is caused by the death of the nerve cells in the substania niagra , which produce the neurotransmitter dopamine Without dopamine, the brain is unable to transmit messages between nerve cells, resulting in a decrease in muscle function . When 80% of dopamine producing cells are damaged, the symptoms of Parkinson disease start to appear.

26. Oxidative Stress: Neurons depends on oxidative metabolism for survival in which shows production of reactive compound such as H 2 O 2 and oxiradicals is may lead to cell death. Apoptosis: It is a process of programmed cell death. It often associated with excitotoxicity .

27. Genetic Factor: In the past 10 years, researchers have identified a number of rare instances where Parkinson's disease appears to be caused by a single genetic mutation. In these cases, the mutated gene is passed from generation to generation, resulting in a great number of Parkinson's disease cases within an extended family . Mutations in the LRRK2 gene are the greatest genetic contributor to Parkinson's disease disovered to date.

28. Environmental factors: On the opposite end of the continuum, in the early 1980s, a group of heroin users in California took drugs from a batch contaminated with a substance called MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) . After ingesting this chemical, the drug users were stricken with a form of Parkinson's disease that was primarily, if not exclusively , "environmental" in origin.

29. Family history : Having a parent or sibling with Parkinson's disease is thought to nearly double your risk of developing the disease. 5 to 10 percent of people who have Parkinson's disease also have a family member with it. Head injury : There is evidence that people who have experienced head injuries that knocked them unconscious may be at an increased risk of developing Parkinson's disease .

30. Factors That Protect Against Parkinson’s Disease: Caffeine: People who consume more caffeine appear to have a reduced risk of developing Parkinson's disease as opposed to those who only consume a little caffeine or none at all. Cigarette smoking: A number of studies have found that people who smoke cigarettes are less likely to develop Parkinson's disease than those who don't.

31. PATHOPHYSIOLOGY OF PARKINSONISM

32. Loss of dopaminergic neurons in Substania Nigra (symptoms will appear after 60% to 80%) Presence of Lewy body : Lewy body stained strongly with antibodies of Alpha- synuclein and other ubiquitinated damaged proteins. Cholinergic and Serotoninergic deficits may account for some non-motor symptoms (cognitive impairment / dementia and depression)

33. TREATMENT OF PARKINSONISM

34. The main aim of treatment in Parkinson's Disease is to minimize symptoms. In early stage p harmacological option for the treatment of PD is multiple. Current Treatment For PD Levodopa Drugs Dopamine Agonist MAO-B inhibitors Anticholinergics Amantidine

35. Levodopa It used to control the symptoms of Parkinson’s disease in all stages .It is also called Dopamine replacement therapy . Mechanism When taken by mouth levodopa is absorbed into the blood from the small intestine. It is then 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 symptom.

36. Side Effects: nausea v o m iti n g low blood pressure d ry mouth. In some individuals it may cause confusion and hallucinations. In the long-term, use of dopamine replacement can also lead to dyskinesias and m otor fluctuations.

37. Dopamine antagonist ( Apomorphine ) : Used in early stage of PD to reduce symptoms . These were also used initially for individuals experiencing on-off fluctuations and dyskinesias as a complementary therapy to levodopa . When used in late PD they are useful at reducing the off periods. Effective in people those are younger than 60 . They control disorders (such as compulsive sexual activity and eating, and pathological gambling and shopping) even more strongly than levodopa . Side Effects: Drowsiness , Hallucinations, Insomnia, and Constipation.

38. MAO-B INHIBITORS: MAO–B ( monoamine oxidase B ) inhibitors (safinamide, selegiline and rasagiline ) can help nerve cells make better use of the dopamine. There has been some doubt as to its safety, but this is also controversial and the subject of ongoing research. Selegiline has an amphetamine-like metabolite (by-product). This means it can cause insomnia and hallucinations in some people . The usual dose is 5-10 mg in the morning . They are useful to reduce fluctuations between on and off periods . Side Effect: Headaches, Aching joints, Indigestion, Flu-like symptoms and Depression .

39. Anticholinergic Therapy: Redressing the balance between dopaminergic and cholinergic neurons appears to be some compensation for the overall deficit in dopamine function. These have a useful effect on tremor & rigidity, but do not help bradykinesia. They can be prescribed early in the disease before bradykinesia is a problem, but should be avoided in elderly patients in whom they cause confusion/dementia/hallucinations . Other side-effects include dry mouth, blurred vision, difficulty with micturition / constipation. Many anticholinergics are available: orphenadrine (50-100 mg 8-hourly).

40. Amatadine : While the mechanism of action of amantadine in the treatment of PD is not known, it is believed to release brain dopamine from nerve endings making it more available to activate dopaminergic receptors. This has a mild, usually short-lived effect on bradykinesia, but may be used early in the disease before more potent treatment is needed. The dose is 100 mg 8- or 12-hourly. Side-effects: nausea , dizziness ( light headedness ) and insomnia, livedo reticularis , peripheral oedema, confusion, seizures .

41. Alternative treatment approaches Surgery : Stereotactic thalamotomy can be used to treat tremor, though this is needed relatively infrequently because of the medical treatments available . Other stereotactic lesions are currently undergoing evaluation in particular pallidotomy to help in the management of drug-induced dyskinesia . Implantation of dopamine rich fragments of brain into the striatum Implantation of stem cells Midbrain neurones transplanted into the striatum Immortalised neuronal precursor cells

42. Physiotherapy & rehab : Patients at all stages of Parkinson's disease benefit from physiotherapy, which helps reduce rigidity & corrects abnormal posture . Speech therapy may help in cases where dysarthria & dysphonia interfere with communication.