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Parkinson's

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Parkinson's disease (PD) belongs to a group …

Parkinson's disease (PD) belongs to a group
of conditions called motor system disorders, which are the result of the loss
of dopamine-producing brain cells. The four primary symptoms of PD are tremor,
or trembling in hands, arms, legs, jaw, and face; rigidity, or stiffness of the
limbs and trunk; bradykinesia, or slowness of movement; and postural
instability, or impaired balance and coordination. As these symptoms become
more pronounced, patients may have difficulty walking, talking, or completing
other simple tasks. PD usually affects people over the age of 50.  Early
symptoms of PD are subtle and occur gradually.  In some people the disease
progresses more quickly than in others.  
As the disease progresses, the
shaking, or tremor, which affects the majority of PD patients may begin to
interfere with daily activities.  Other symptoms may include depression
and other emotional changes; difficulty in swallowing, chewing, and speaking;
urinary problems or constipation; skin problems; and sleep disruptions. 
There are currently no blood or laboratory tests that have been proven to help
in diagnosing sporadic PD.  Therefore the diagnosis is based on medical
history and a neurological examination.  The disease can be difficult to
diagnose accurately.   Doctors may sometimes request brain scans or
laboratory tests in order to rule out other diseases.
Parkinson's disease (PD) belongs to a group
of conditions called motor system disorders, which are the result of the loss
of dopamine-producing brain cells. The four primary symptoms of PD are tremor,
or trembling in hands, arms, legs, jaw, and face; rigidity, or stiffness of the
limbs and trunk; bradykinesia, or slowness of movement; and postural
instability, or impaired balance and coordination. As these symptoms become
more pronounced, patients may have difficulty walking, talking, or completing
other simple tasks. PD usually affects people over the age of 50.  Early
symptoms of PD are subtle and occur gradually.  In some people the disease
progresses more quickly than in others.  
As the disease progresses, the
shaking, or tremor, which affects the majority of PD patients may begin to
interfere with daily activities.  Other symptoms may include depression
and other emotional changes; difficulty in swallowing, chewing, and speaking;
urinary problems or constipation; skin problems; and sleep disruptions. 
There are currently no blood or laboratory tests that have been proven to help
in diagnosing sporadic PD.  Therefore the diagnosis is based on medical
history and a neurological examination.  The disease can be difficult to
diagnose accurately.   Doctors may sometimes request brain scans or
laboratory tests in order to rule out other diseases.

Parkinson's disease (PD) belongs to a group
of conditions called motor system disorders, which are the result of the loss
of do

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  • 1. Fitango Education Health Topics Parkinsonshttp://www.fitango.com/categories.php?id=272
  • 2. OverviewParkinsons disease (PD) belongs to a groupof conditions called motor system disorders, whichare the result of the lossof dopamine-producing brain cells. The fourprimary symptoms of PD are tremor, 1
  • 3. Overviewor trembling in hands, arms, legs, jaw, and face;rigidity, or stiffness of thelimbs and trunk; bradykinesia, or slowness ofmovement; and posturalinstability, or impaired balance and coordination.As these symptoms become 2
  • 4. Overviewmore pronounced, patients may have difficultywalking, talking, or completingother simple tasks. PD usually affects people overthe age of 50.  Earlysymptoms of PD are subtle and occurgradually.  In some people the disease 3
  • 5. Overviewprogresses more quickly than inothers.  As the disease progresses, theshaking, or tremor, which affects the majority ofPD patients may begin tointerfere with daily activities.  Othersymptoms may include depression 4
  • 6. Overviewand other emotional changes; difficulty inswallowing, chewing, and speaking;urinary problems or constipation; skin problems;and sleep disruptions. There are currently no blood or laboratory teststhat have been proven to help 5
  • 7. Overviewin diagnosing sporadic PD.  Therefore thediagnosis is based on medicalhistory and a neurological examination.  Thedisease can be difficult todiagnose accurately.   Doctors maysometimes request brain scans or 6
  • 8. Overviewlaboratory tests in order to rule out other diseases.Parkinsons disease (PD) belongs to a groupof conditions called motor system disorders, whichare the result of the lossof dopamine-producing brain cells. The fourprimary symptoms of PD are tremor, 7
  • 9. Overviewor trembling in hands, arms, legs, jaw, and face;rigidity, or stiffness of thelimbs and trunk; bradykinesia, or slowness ofmovement; and posturalinstability, or impaired balance and coordination.As these symptoms become 8
  • 10. Overviewmore pronounced, patients may have difficultywalking, talking, or completingother simple tasks. PD usually affects people overthe age of 50.  Earlysymptoms of PD are subtle and occurgradually.  In some people the disease 9
  • 11. Overviewprogresses more quickly than in others.  As the disease progresses, theshaking, or tremor, which affects the majority ofPD patients may begin tointerfere with daily activities.  Othersymptoms may include depression 10
  • 12. Overviewand other emotional changes; difficulty inswallowing, chewing, and speaking;urinary problems or constipation; skin problems;and sleep disruptions. There are currently no blood or laboratory teststhat have been proven to help 11
  • 13. Overviewin diagnosing sporadic PD.  Therefore thediagnosis is based on medicalhistory and a neurological examination.  Thedisease can be difficult todiagnose accurately.   Doctors maysometimes request brain scans or 12
  • 14. Overviewlaboratory tests in order to rule out other diseases.Parkinsons disease (PD) belongs to a groupof conditions called motor system disorders, whichare the result of the loss 13
  • 15. Overviewof dopamine-producing brain cells. The fourprimary symptoms of PD are tremor,or trembling in hands, arms, legs, jaw, and face;rigidity, or stiffness of thelimbs and trunk; bradykinesia, or slowness ofmovement; and postural 14
  • 16. Overviewinstability, or impaired balance and coordination.As these symptoms becomemore pronounced, patients may have difficultywalking, talking, or completingother simple tasks. PD usually affects people overthe age of 50.  Early 15
  • 17. Overviewsymptoms of PD are subtle and occurgradually.  In some people the diseaseprogresses more quickly than inothers.  As the disease progresses, theshaking, or tremor, which affects the majority ofPD patients may begin to 16
  • 18. Overviewinterfere with daily activities.  Othersymptoms may include depressionand other emotional changes; difficulty inswallowing, chewing, and speaking;urinary problems or constipation; skin problems;and sleep disruptions.  17
  • 19. OverviewThere are currently no blood or laboratory teststhat have been proven to helpin diagnosing sporadic PD.  Therefore thediagnosis is based on medicalhistory and a neurological examination.  Thedisease can be difficult to 18
  • 20. Overviewdiagnose accurately.   Doctors maysometimes request brain scans orlaboratory tests in order to rule out other diseases.Parkinsons disease (PD) belongs to a groupof conditions called motor system disorders, whichare the result of the loss 19
  • 21. Overviewof dopamine-producing brain cells. The fourprimary symptoms of PD are tremor,or trembling in hands, arms, legs, jaw, and face;rigidity, or stiffness of thelimbs and trunk; bradykinesia, or slowness ofmovement; and postural 20
  • 22. Overviewinstability, or impaired balance and coordination.As these symptoms becomemore pronounced, patients may have difficultywalking, talking, or completingother simple tasks. PD usually affects people overthe age of 50.  Early 21
  • 23. Overviewsymptoms of PD are subtle and occurgradually.  In some people the diseaseprogresses more quickly than in others.  As the disease progresses, theshaking, or tremor, which affects the majority ofPD patients may begin to 22
  • 24. Overviewinterfere with daily activities.  Othersymptoms may include depressionand other emotional changes; difficulty inswallowing, chewing, and speaking;urinary problems or constipation; skin problems;and sleep disruptions.  23
  • 25. OverviewThere are currently no blood or laboratory teststhat have been proven to helpin diagnosing sporadic PD.  Therefore thediagnosis is based on medicalhistory and a neurological examination.  Thedisease can be difficult to 24
  • 26. Overviewdiagnose accurately.   Doctors maysometimes request brain scans orlaboratory tests in order to rule out other diseases.Parkinsons disease (PD) belongs to a group 25
  • 27. Overviewof conditions called motor system disorders, whichare the result of the lossof dopamine-producing brain cells. The fourprimary symptoms of PD are tremor,or trembling in hands, arms, legs, jaw, and face;rigidity, or stiffness of the 26
  • 28. Overviewlimbs and trunk; bradykinesia, or slowness ofmovement; and posturalinstability, or impaired balance and coordination.As these symptoms becomemore pronounced, patients may have difficultywalking, talking, or completing 27
  • 29. Overviewother simple tasks. PD usually affects people overthe age of 50.  Earlysymptoms of PD are subtle and occurgradually.  In some people the diseaseprogresses more quickly than inothers.  As the disease progresses, the 28
  • 30. Overviewshaking, or tremor, which affects the majority ofPD patients may begin tointerfere with daily activities.  Othersymptoms may include depressionand other emotional changes; difficulty inswallowing, chewing, and speaking; 29
  • 31. Overviewurinary problems or constipation; skin problems;and sleep disruptions. There are currently no blood or laboratory teststhat have been proven to helpin diagnosing sporadic PD.  Therefore thediagnosis is based on medical 30
  • 32. Overviewhistory and a neurological examination.  Thedisease can be difficult todiagnose accurately.   Doctors maysometimes request brain scans orlaboratory tests in order to rule out other diseases.Parkinsons disease (PD) belongs to a group 31
  • 33. Overviewof conditions called motor system disorders, whichare the result of the lossof dopamine-producing brain cells. The fourprimary symptoms of PD are tremor,or trembling in hands, arms, legs, jaw, and face;rigidity, or stiffness of the 32
  • 34. Overviewlimbs and trunk; bradykinesia, or slowness ofmovement; and posturalinstability, or impaired balance and coordination.As these symptoms becomemore pronounced, patients may have difficultywalking, talking, or completing 33
  • 35. Overviewother simple tasks. PD usually affects people overthe age of 50.  Earlysymptoms of PD are subtle and occurgradually.  In some people the diseaseprogresses more quickly than in others.  As the disease progresses, the 34
  • 36. Overviewshaking, or tremor, which affects the majority ofPD patients may begin tointerfere with daily activities.  Othersymptoms may include depressionand other emotional changes; difficulty inswallowing, chewing, and speaking; 35
  • 37. Overviewurinary problems or constipation; skin problems;and sleep disruptions. There are currently no blood or laboratory teststhat have been proven to helpin diagnosing sporadic PD.  Therefore thediagnosis is based on medical 36
  • 38. Overviewhistory and a neurological examination.  Thedisease can be difficult todiagnose accurately.   Doctors maysometimes request brain scans orlaboratory tests in order to rule out other diseases. 37
  • 39. OverviewParkinsons disease (PD) belongs to a groupof conditions called motor system disorders, whichare the result of the lossof dopamine-producing brain cells. The fourprimary symptoms of PD are tremor, 38
  • 40. Overviewor trembling in hands, arms, legs, jaw, and face;rigidity, or stiffness of thelimbs and trunk; bradykinesia, or slowness ofmovement; and posturalinstability, or impaired balance and coordination.As these symptoms become 39
  • 41. Overviewmore pronounced, patients may have difficultywalking, talking, or completingother simple tasks. PD usually affects people overthe age of 50.  Earlysymptoms of PD are subtle and occurgradually.  In some people the disease 40
  • 42. Overviewprogresses more quickly than inothers.  As the disease progresses, theshaking, or tremor, which affects the majority ofPD patients may begin tointerfere with daily activities.  Othersymptoms may include depression 41
  • 43. Overviewand other emotional changes; difficulty inswallowing, chewing, and speaking;urinary problems or constipation; skin problems;and sleep disruptions. There are currently no blood or laboratory teststhat have been proven to help 42
  • 44. Overviewin diagnosing sporadic PD.  Therefore thediagnosis is based on medicalhistory and a neurological examination.  Thedisease can be difficult todiagnose accurately.   Doctors maysometimes request brain scans or 43
  • 45. Overviewlaboratory tests in order to rule out other diseases.Parkinsons disease (PD) belongs to a groupof conditions called motor system disorders, whichare the result of the lossof dopamine-producing brain cells. The fourprimary symptoms of PD are tremor, 44
  • 46. Overviewor trembling in hands, arms, legs, jaw, and face;rigidity, or stiffness of thelimbs and trunk; bradykinesia, or slowness ofmovement; and posturalinstability, or impaired balance and coordination.As these symptoms become 45
  • 47. Overviewmore pronounced, patients may have difficultywalking, talking, or completingother simple tasks. PD usually affects people overthe age of 50.  Earlysymptoms of PD are subtle and occurgradually.  In some people the disease 46
  • 48. Overviewprogresses more quickly than in others.  As the disease progresses, theshaking, or tremor, which affects the majority ofPD patients may begin tointerfere with daily activities.  Othersymptoms may include depression 47
  • 49. Overviewand other emotional changes; difficulty inswallowing, chewing, and speaking;urinary problems or constipation; skin problems;and sleep disruptions. There are currently no blood or laboratory teststhat have been proven to help 48
  • 50. Overviewin diagnosing sporadic PD.  Therefore thediagnosis is based on medicalhistory and a neurological examination.  Thedisease can be difficult todiagnose accurately.   Doctors maysometimes request brain scans or 49
  • 51. Overviewlaboratory tests in order to rule out other diseases. 50
  • 52. SymptomsEarly symptoms of PD are subtle and occurgradually. Affected people may feel mild tremorsor have difficulty getting outof a chair.  They may notice that they speaktoo softly or that their 51
  • 53. Symptomshandwriting is slow and looks cramped or small.They may lose track of a wordor thought, or they may feel tired, irritable, ordepressed for no apparentreason. This very early period may last a long timebefore the more classic andobvious symptoms appear. 52
  • 54. SymptomsFriends or family members may be the firstto notice changes in someone with early PD. Theymay see that the persons face 53
  • 55. Symptomsperson does not move an arm or leg normally.They also may notice that theperson seems stiff, unsteady, or unusually slow.As the disease progresses, the shaking or 54
  • 56. Symptomstremor that affects the majority of Parkinsonspatients may begin to interferewith daily activities. Patients may not be able tohold utensils steady or theymay find that the shaking makes reading anewspaper difficult. Tremor is 55
  • 57. Symptomsusually the symptom that causes people to seekmedical help.People with PD often develop a so-called parkinsonian 56
  • 58. Symptomshurrying forward (called festination), and reducedswinging of the arms. Theyalso may have trouble initiating movement (starthesitation), and they may stopsuddenly as they walk (freezing). 57
  • 59. SymptomsPD does not affect everyone the same way,and the rate of progression differs amongpatients.  Tremor is the majorsymptom for some patients, while forothers, tremor is nonexistent or veryminor. 58
  • 60. SymptomsPD symptoms often begin on one side of thebody.  However, as it progresses, the diseaseeventually affects 59
  • 61. Symptomssymptoms are often less severe on one side thanon the other.  The fourprimary symptoms of PD are:-- **Tremor** 60
  • 62. Symptoms. The tremor associated with PD has acharacteristic appearance. Typically, the tremortakes the form of a rhythmicback-and-forth motion at a rate of 4-6 beats persecond. It may involve thethumb and forefinger and appear as a "pill rolling"tremor.  61
  • 63. SymptomsTremor often begins in a hand, althoughsometimes a foot or the jaw is affectedfirst. It is most obvious when the hand is at rest orwhen a person is understress.  For example, the shaking maybecome more pronounced a few seconds 62
  • 64. Symptomsafter the hands are rested on a table. Tremor usually disappears duringsleep or improves with intentional movement.-- **Rigidity**. Rigidity, or a resistance to 63
  • 65. Symptomsmovement, affects most people with PD. A majorprinciple of body movement isthat all muscles have an opposing muscle.Movement is possible not just becauseone muscle becomes more active, but because theopposing muscle relaxes. In PD, 64
  • 66. Symptomsrigidity comes about when, in response to signalsfrom the brain, the delicatebalance of opposing muscles is disturbed. Themuscles remain constantly tensedand contracted so that the person aches or feelsstiff or weak. The rigidity 65
  • 67. Symptomsbecomes obvious when another person tries tomove the patients arm, which willmove only in ratchet-like or short, jerkymovements known as"cogwheel" rigidity.-- **Bradykinesia** 66
  • 68. Symptoms. Bradykinesia, or the slowingdown and loss of spontaneous and automaticmovement, is particularlyfrustrating because it may make simple taskssomewhat difficult.  Theperson cannot rapidly perform routinemovements. Activities once performed 67
  • 69. Symptomsquickly and easily — such as washing or dressing— may take several hours.-- **Postural instability**. Postural instability,or impaired balance, causes patients to falleasily.  Affected people also 68
  • 70. Symptomsmay develop a stooped posture in which the headis bowed and the shoulders aredrooped.  69
  • 71. SymptomsEarly symptoms of PD are subtle and occurgradually. Affected people may feel mild tremorsor have difficulty getting outof a chair.  They may notice that they speaktoo softly or that theirhandwriting is slow and looks cramped or small.They may lose track of a word 70
  • 72. Symptomsor thought, or they may feel tired, irritable, ordepressed for no apparentreason. This very early period may last a long timebefore the more classic andobvious symptoms appear. 71
  • 73. SymptomsFriends or family members may be the firstto notice changes in someone with early PD. Theymay see that the persons facelacks expression and animation (known as "maskedface") or that theperson does not move an arm or leg normally.They also may notice that the 72
  • 74. Symptomsperson seems stiff, unsteady, or unusually slow.As the disease progresses, the shaking ortremor that affects the majority of Parkinsonspatients may begin to interfere 73
  • 75. Symptomswith daily activities. Patients may not be able tohold utensils steady or theymay find that the shaking makes reading anewspaper difficult. Tremor isusually the symptom that causes people to seekmedical help. 74
  • 76. SymptomsPeople with PD often develop a so-called parkinsoniangait that includes a tendency to leanforward, small quick steps as ifhurrying forward (called festination), and reducedswinging of the arms. They 75
  • 77. Symptomsalso may have trouble initiating movement (starthesitation), and they may stopsuddenly as they walk (freezing).PD does not affect everyone the same way, 76
  • 78. Symptomsand the rate of progression differs amongpatients.  Tremor is the majorsymptom for some patients, while forothers, tremor is nonexistent or veryminor. 77
  • 79. SymptomsPD symptoms often begin on one side of thebody.  However, as it progresses, the diseaseeventually affectsboth sides.  Even after the disease involvesboth sides of the body, thesymptoms are often less severe on one side thanon the other.  The four 78
  • 80. Symptomsprimary symptoms of PD are:-- **Tremor**. The tremor associated with PD has a 79
  • 81. Symptomscharacteristic appearance. Typically, the tremortakes the form of a rhythmicback-and-forth motion at a rate of 4-6 beats persecond. It may involve thethumb and forefinger and appear as a "pill rolling"tremor.  80
  • 82. SymptomsTremor often begins in a hand, althoughsometimes a foot or the jaw is affectedfirst. It is most obvious when the hand is at rest orwhen a person is understress.  For example, the shaking maybecome more pronounced a few seconds 81
  • 83. Symptomsafter the hands are rested on a table. Tremor usually disappears duringsleep or improves with intentional movement.-- **Rigidity**. Rigidity, or a resistance to 82
  • 84. Symptomsmovement, affects most people with PD. A majorprinciple of body movement isthat all muscles have an opposing muscle.Movement is possible not just becauseone muscle becomes more active, but because theopposing muscle relaxes. In PD, 83
  • 85. Symptomsrigidity comes about when, in response to signalsfrom the brain, the delicatebalance of opposing muscles is disturbed. Themuscles remain constantly tensedand contracted so that the person aches or feelsstiff or weak. The rigidity 84
  • 86. Symptomsbecomes obvious when another person tries tomove the patients arm, which willmove only in ratchet-like or short, jerkymovements known as"cogwheel" rigidity.-- **Bradykinesia** 85
  • 87. Symptoms. Bradykinesia, or the slowingdown and loss of spontaneous and automaticmovement, is particularlyfrustrating because it may make simple taskssomewhat difficult.  Theperson cannot rapidly perform routinemovements. Activities once performed 86
  • 88. Symptomsquickly and easily — such as washing or dressing— may take several hours.-- **Postural instability**. Postural instability,or impaired balance, causes patients to falleasily.  Affected people also 87
  • 89. Symptomsmay develop a stooped posture in which the headis bowed and the shoulders aredrooped.  88
  • 90. TreatmentAt present, there is no cure for PD, but a variety ofmedications provide dramatic relief from thesymptoms. Usually, patients are given levodopacombined with carbidopa. Carbidopa delays theconversion of levodopa into dopamine until itreaches the brain. 89
  • 91. TreatmentNerve cells can use levodopa to make dopamineand replenish the brains dwindling supply.Although levodopa helps at least three-quarters ofparkinsonian cases, not all symptoms respondequally to the drug. Bradykinesia and rigidityrespond best, while tremor may be only marginallyreduced. Problems with balance and othersymptoms may not be alleviated at all.Anticholinergics may help control tremor andrigidity.  90
  • 92. TreatmentOther drugs, such asbromocriptine, pramipexole, and ropinirole, mimicthe role of dopamine in the brain, causing theneurons to react as they would to dopamine. Anantiviral drug, amantadine, also appears to reducesymptoms. In May 2006, the FDA approvedrasagiline to be used along with levodopa forpatients with advanced PD or as a single-drugtreatment for early PD.  91
  • 93. TreatmentIn some cases, surgery may be appropriate if thedisease doesnt respond to drugs. A therapy calleddeep brain stimulation (DBS) has now beenapproved by the U.S. Food and DrugAdministration. In DBS, electrodes are implantedinto the brain and connected to a small electricaldevice called a pulse generator that can beexternally programmed.  92
  • 94. TreatmentDBS can reduce the need for levodopa and relateddrugs, which in turn decreases the involuntarymovements called dyskinesias that are a commonside effect of levodopa. It also helps to alleviatefluctuations of symptoms and to reducetremors, slowness of movements, and gaitproblems. DBS requires careful programming ofthe stimulator device in order to work correctly. 93
  • 95. TreatmentAt present, there is no cure for PD, but a variety ofmedications provide dramatic relief from thesymptoms. Usually, patients are given levodopacombined with carbidopa. Carbidopa delays theconversion of levodopa into dopamine until itreaches the brain. 94
  • 96. TreatmentNerve cells can use levodopa to make dopamineand replenish the brains dwindling supply.Although levodopa helps at least three-quarters ofparkinsonian cases, not all symptoms respondequally to the drug. Bradykinesia and rigidityrespond best, while tremor may be only marginallyreduced. Problems with balance and othersymptoms may not be alleviated at all.Anticholinergics may help control tremor andrigidity.  95
  • 97. TreatmentOther drugs, such as bromocriptine, pramipexole,and ropinirole, mimic the role of dopamine in thebrain, causing the neurons to react as they wouldto dopamine. An antiviral drug, amantadine, alsoappears to reduce symptoms. In May 2006, theFDA approved rasagiline to be used along withlevodopa for patients with advanced PD or as asingle-drug treatment for early PD.  96
  • 98. TreatmentIn some cases, surgery may be appropriate if thedisease doesnt respond to drugs. A therapy calleddeep brain stimulation (DBS) has now beenapproved by the U.S. Food and DrugAdministration. In DBS, electrodes are implantedinto the brain and connected to a small electricaldevice called a pulse generator that can beexternally programmed.  97
  • 99. TreatmentDBS can reduce the need for levodopa and relateddrugs, which in turn decreases the involuntarymovements called dyskinesias that are a commonside effect of levodopa. It also helps to alleviatefluctuations of symptoms and to reduce tremors,slowness of movements, and gait problems. DBSrequires careful programming of the stimulatordevice in order to work correctly. 98
  • 100. PrognosisPD is not by itself a fatal disease, but itdoes get worse with time.   The average lifeexpectancy of a PD patient isgenerally the same as for people who do not havethe disease.  However, in 99
  • 101. Prognosisthe late stages of the disease, PD may causecomplications such as choking,pneumonia, and falls that can lead todeath.  Fortunately, there are manytreatment options available for people with PD. 100
  • 102. PrognosisThe progression of symptoms in PD may take20 years or more.  In somepeople, however, the disease progresses morequickly.  There is no way to predict whatcourse the disease will take for 101
  • 103. Prognosisan individual person.  One commonly usedsystem for describing how thesymptoms of PD progress is called the Hoehn andYahr scale. 102
  • 104. Prognosis **Hoehn and Yahr Staging of ParkinsonsDisease** 103
  • 105. Prognosis **Hoehn and Yahr Staging of Parkinsons**Stage one**Symptoms on one side of the body only. 104
  • 106. Prognosis **Hoehn and Yahr Staging of ParkinsonsSymptoms on both sides of the body. No impairment of balance.**Stage three** 105
  • 107. Prognosis **Hoehn and Yahr Staging of ParkinsonsBalance impairment.  Mild tomoderate disease.  Physically independent.**Stage four** 106
  • 108. Prognosis **Hoehn and Yahr Staging of ParkinsonsSevere disability, but still able to walkor stand unassisted.**Stage five** 107
  • 109. Prognosis **Hoehn and Yahr Staging of Parkinsonsassisted. 108
  • 110. Prognosis **Hoehn and Yahr Staging of ParkinsonsAnother commonly used scale is the UnifiedParkinsons Disease Rating Scale (UPDRS). Thismuch more complicated scale hasmultiple ratings that measure mentalfunctioning, behavior, and mood;activities of daily living; and motor function. Boththe Hoehn and Yahr scale 109
  • 111. Prognosis **Hoehn and Yahr Staging of Parkinsonsand the UPDRS are used to measure howindividuals are faring and how muchtreatments are helping them.With appropriate treatment, most people 110
  • 112. Prognosis **Hoehn and Yahr Staging of Parkinsonswith PD can live productive lives for many yearsafter diagnosis. PD is not by itself a fatal disease, but itdoes get worse with time.   The average lifeexpectancy of a PD patient isgenerally the same as for people who do not havethe disease.  However, in 111
  • 113. Prognosis **Hoehn and Yahr Staging of Parkinsonsthe late stages of the disease, PD may causecomplications such as choking,pneumonia, and falls that can lead todeath.  Fortunately, there are manytreatment options available for people with PD. 112
  • 114. Prognosis **Hoehn and Yahr Staging of ParkinsonsThe progression of symptoms in PD may take20 years or more.  In somepeople, however, the disease progresses morequickly.  There is no way to predict whatcourse the disease will take for 113
  • 115. Prognosis **Hoehn and Yahr Staging of Parkinsonsan individual person.  One commonly usedsystem for describing how thesymptoms of PD progress is called the Hoehn andYahr scale. 114
  • 116. Prognosis **Hoehn and Yahr Staging of ParkinsonsDisease** 115
  • 117. Prognosis **Hoehn and Yahr Staging of Parkinsons**Stage one**Symptoms on one side of the body only. 116
  • 118. Prognosis **Hoehn and Yahr Staging of ParkinsonsSymptoms on both sides of the body. No impairment of balance.**Stage three** 117
  • 119. Prognosis **Hoehn and Yahr Staging of ParkinsonsBalance impairment.  Mild tomoderate disease.  Physically independent.**Stage four** 118
  • 120. Prognosis **Hoehn and Yahr Staging of ParkinsonsSevere disability, but still able to walkor stand unassisted.**Stage five** 119
  • 121. Prognosis **Hoehn and Yahr Staging of Parkinsonsassisted. 120
  • 122. Prognosis **Hoehn and Yahr Staging of ParkinsonsAnother commonly used scale is the UnifiedParkinsons Disease Rating Scale (UPDRS). Thismuch more complicated scale hasmultiple ratings that measure mentalfunctioning, behavior, and mood;activities of daily living; and motor function. Boththe Hoehn and Yahr scale 121
  • 123. Prognosis **Hoehn and Yahr Staging of Parkinsonsand the UPDRS are used to measure howindividuals are faring and how muchtreatments are helping them.With appropriate treatment, most people 122
  • 124. Prognosis **Hoehn and Yahr Staging of Parkinsonswith PD can live productive lives for many yearsafter diagnosis.  123
  • 125. ResearchIn recent years, Parkinsons research hasadvanced to the point that halting the progressionof PD, restoring lostfunction, and even preventing the disease are allconsidered realistic 124
  • 126. Researchgoals.  While the ultimate goal of preventingPD may take years to achieve,researchers are making great progress inunderstanding and treating PD. 125
  • 127. Researchresearch is genetics.  Studying the genesresponsible for inherited casescan help researchers understand both inheritedand sporadic cases of the disease.Identifying gene defects can also help researchersunderstand how PD occurs, 126
  • 128. Researchdevelop animal models that accurately mimic theneuronal death in human PD,identify new drug targets, and improve diagnosis.As discussed in the “What Genes are Linked 127
  • 129. Researchto Parkinsons Disease?" section, several geneshave been definitivelylinked to PD in some people.  Researchersalso have identified a number ofother genes that may play a role and are workingto confirm these 128
  • 130. Researchfindings.  In addition, several chromosomalregions have been linked to PDin some families.  Researchers hope toidentify the genes located in thesechromosomal regions and to determine which ofthem may play roles in PD. 129
  • 131. ResearchResearchers funded by NINDS are gatheringinformation and DNA samples from hundreds offamilies with PD and areconducting large-scale gene expression studies toidentify genes that are 130
  • 132. Researchabnormally active or inactive in PD.  Theyalso are comparing geneactivity in PD with gene activity in similar diseasessuch as progressive supranuclearpalsy.  131
  • 133. ResearchSome scientists have found evidence thatspecific variations in the DNA of mitochondria –structures in cells thatprovide the energy for cellular activity — canincrease the risk of getting PD, 132
  • 134. Researchwhile other variations are associated with alowered risk of the disorder. Theyalso have found that PD patients have moremitochondrial DNA (mtDNA) variationsthan patients with other movement disorders orAlzheimers disease. Researchers 133
  • 135. Researchare working to define how these mtDNA variationsmay lead to PD.In addition to identifying new genes forPD, researchers are trying to learn how known PD 134
  • 136. Researchgene mutations cause disease.  Forexample, a 2005 study found that thenormal alpha-synuclein protein may help otherproteins that are important fornerve transmission to fold correctly.  Otherstudies have suggested that 135
  • 137. Researchthe normal parkin protein protects neurons from avariety of threats, includingalpha-synuclein toxicity and excitotoxicity.Scientists continue to study environmental 136
  • 138. Researchtoxins such as pesticides and herbicides that cancause PD symptoms inanimals.  They have found that exposingrodents to the pesticide rotenoneand several other agricultural chemicals can causecellular and behavioral 137
  • 139. Researchchanges that mimic those seen in PD.  Otherstudies have suggested thatprenatal exposure to certain toxins can increasesusceptibility to PD inadulthood. An NIH-sponsored programcalled the Collaborative Centers 138
  • 140. Researchfor Parkinsons Disease Environmental Research(CCPDER) focuses on howoccupational exposure to toxins and use of caffeineand other substances mayaffect the risk of PD. 139
  • 141. ResearchAnother major area of PD research involvesthe cells protein disposal system, called theubiquitin-proteasome system. Ifthis disposal system fails to work correctly, toxinsand other substances maybuild up to harmful levels, leading to celldeath.  The 140
  • 142. Researchubiquitin-proteasome system requires interactionsbetween several proteins,including parkin and UCH-L1. Therefore, disruptionof the ubiquitin-proteasomesystem may partially explain how mutations inthese genes cause PD. 141
  • 143. ResearchOther studies focus on how Lewy bodies formand what role they play in PD.  Some studiessuggest that Lewy bodies area byproduct of degenerative processes withinneurons, while others indicate 142
  • 144. Researchthat Lewy bodies are a protective mechanism bywhich neurons lock away abnormalmolecules that might otherwise be harmful. Additional studies have foundthat alpha-synuclein clumps alter gene expressionand bind to vesicles within 143
  • 145. Researchthe cell in ways that could be harmful. Another common topic of PD research isexcitotoxicity – overstimulation of nerve cells thatleads to cell damage or 144
  • 146. Researchdeath. In excitotoxicity, the brain becomesoversensitized to theneurotransmitter glutamate, which increasesactivity in the brain. The dopaminedeficiency in PD causes overactivity of neurons inthe subthalamic nucleus, 145
  • 147. Researchwhich may lead to excitotoxic damage there and inother parts of the brain.Researchers also have found that dysfunction ofthe cells mitochondria canmake dopamine-producing neurons vulnerable toglutamate.  146
  • 148. ResearchOther researchers are focusing on howinflammation may affect PD. Inflammation iscommon to a variety ofneurodegenerative diseases, includingPD, Alzheimers disease, HIV-1-associated 147
  • 149. Researchdementia, and amyotrophic lateral sclerosis.Several studies have shown thatinflammation-promoting molecules increase celldeath after treatment with thetoxin MPTP. Inhibiting the inflammation with drugsor by genetic engineering 148
  • 150. Researchprevented some of the neuronal degeneration inthese studies.  Otherresearch has shown that dopamine neurons inbrains from patients with PD havehigher levels of an inflammatory enzyme calledCOX-2 than those of people 149
  • 151. Researchwithout PD.  Inhibiting COX-2 doubled thenumber of neurons that survivedin a mouse model for PD.Since the discovery that MPTP causes 150
  • 152. Researchparkinsonian symptoms in humans, scientists havefound that by injecting MPTPand certain other toxins into laboratoryanimals, they can reproduce the brainlesions that cause these symptoms. This allowsthem to study the mechanisms of 151
  • 153. Researchthe disease and helps in the development of newtreatments.  They alsohave developed animal models with alterations ofthe alpha-synuclein and parkingenes.  Other researchers have used geneticengineering to develop mice 152
  • 154. Researchwith disrupted mitochondrial function in dopamineneurons.  These animalshave many of the characteristics associated withPD. 153
  • 155. Researchcharacteristics that can reveal whether the diseaseis developing orprogressing – are another focus of research. Such biomarkers could helpdoctors detect the disease before symptomsappear and improve diagnosis of the 154
  • 156. Researchdisease.  They also would show ifmedications and other types of therapyhave a positive or negative effect on the course ofthe disease.  Some ofthe most promising biomarkers for PD are brainimaging techniques.  For 155
  • 157. Researchexample, some researchers are using positronemission tomography (PET) brainscans to try to identify metabolic changes in thebrains of people with PD andto determine how these changes relate to diseasesymptoms.  Other 156
  • 158. Researchpotential biomarkers for PD include alterations ingene expression.Researchers also are conducting manystudies of new or improved therapies for 157
  • 159. Research(DBS) is now FDA-approved and has been used inthousands of people with PD,researchers continue to try to improve thetechnology and surgical techniquesin this therapy.  For example, some studiesare comparing DBS to the best 158
  • 160. Researchmedical therapy and trying to determine whichpart of the brain is the bestlocation for stimulation.  Another clinicaltrial is studying how DBSaffects depression and quality of life.  159
  • 161. ResearchOther clinical studies are testing whethertranscranial electrical polarization (TEP) ortranscranial magnetic stimulation(TMS) can reduce the symptoms of PD. InTEP, electrodes placed on the scalp are 160
  • 162. Researchused to generate an electrical current thatmodifies signals in the brainscortex.  In TMS, an insulated coil of wire onthe scalp is used togenerate a brief electrical current. 161
  • 163. ResearchOne of the enduring questions in PDresearch has been how treatment with levodopaand other dopaminergic drugsaffects progression of the disease. Researchers are continuing to try toclarify these effects.  One study hassuggested that PD patients with a 162
  • 164. Researchlow-activity variant of the gene for COMT (whichbreaks down dopamine) performworse than others on tests of cognition, and thatdopaminergic drugs may worsencognition in these people, perhaps because thereduced COMT activity causes 163
  • 165. Researchdopamine to build up to harmful levels in someparts of the brain.  In thefuture, it may become possible to test for suchindividual gene differences inorder to improve treatment of PD. 164
  • 166. ResearchA variety of new drug treatments are inclinical trials for PD.  These include a drugcalled GM1 ganglioside thatincreases dopamine levels in the brain. Researchers are testing whether 165
  • 167. Researchthis drug can reduce symptoms, delay diseaseprogression, or partially restoredamaged brain cells in PD patients.  Otherstudies are testing whether adrug called istradefylline can improve motorfunction in PD, and whether a drug 166
  • 168. Researchcalled ACP-103 that blocks receptors for theneurotransmitter serotonin willlessen the severity of parkinsonian symptoms andlevodopa-associatedcomplications in PD patients. Other topics ofresearch include 167
  • 169. Researchcontrolled-release formulas of PD drugs andimplantable pumps that give acontinuous supply of levodopa.Some researchers are testing potential 168
  • 170. Researchneuroprotective drugs to see if they can slow theprogression of PD.  Onestudy, called NET-PD (Neuroexploratory Trials inParkinsons Disease), isevaluating minocycline, creatine, coenzyme Q10,and GPI-1485 to determine if 169
  • 171. Researchany of these agents should be considered forfurther testing.  The NET-PDstudy may evaluate other possible neuroprotectiveagents in the future. Drugs found to be successful in the pilot phasesmay move to large phase III 170
  • 172. Researchtrials involving hundreds of patients.  Aseparate group of researchers isinvestigating the effects of either 1200 or 2400milligrams of coenzyme Q10 in600 patients.   Several MAO-B inhibitors,including selegiline, 171
  • 173. Researchlazabemide, and rasagiline, also are in clinical trialsto determine if theyhave neuroprotective effects in people with PD.Nerve growth factors, or neurotrophic 172
  • 174. Researchfactors, which support survival, growth, anddevelopment of brain cells, areanother type of potential therapy for PD. One such drug, glial cellline-derived neurotrophic factor (GDNF), has beenshown to protect dopamine 173
  • 175. Researchneurons and to promote their survival in animalmodels of PD.  This drughas been tested in several clinical trials for peoplewith PD, and the drugappeared to cause regrowth of dopamine nervefibers in one person who received 174
  • 176. Researchthe drug.  However, a phase II clinical studyof GDNF was halted in 2004because the treatment did not show any clinicalbenefit after 6 months, andsome data suggested that it might even beharmful.  Other neurotrophins 175
  • 177. Researchthat may be useful for treating PD includeneurotrophin-4 (NT-4), brain-derivedneurotrophic factor (BDNF), and fibroblast growthfactor 2 (FGF-2). 176
  • 178. Researchdietary supplements can slow PD, several clinicalstudies are testing whethersupplementation with vitamin B12 and othersubstances may be helpful. A 2005study found that dietary restriction — reducing thenumber of calories normally 177
  • 179. Researchconsumed – helped to increase abnormally lowlevels of the neurotransmitterglutamate in a mouse model for early PD. The study also suggested thatdietary restriction affected dopamine activity inthe brain.  Another 178
  • 180. Researchstudy showed that dietary restriction before theonset of PD in a mouse modelhelped to protect dopamine-producingneurons.  179
  • 181. Researchthat might improve some of the secondarysymptoms of PD, such as depression andswallowing disorders.  One clinical trial isinvestigating whether a drugcalled quetiapine can reduce psychosis or agitationin PD patients with 180
  • 182. Researchdementia and in dementia patients withparkinsonian symptoms. Some studies alsoare examining whether transcranial magneticstimulation or a food supplementcalled s-adenosyl-methionine (SAM-e) can alleviatedepression in people with 181
  • 183. ResearchPD, and whether levetiracetam, a drug approved totreat epilepsy, can reducedyskinesias in Parkinsons patients withoutinterfering with other PD drugs. 182
  • 184. Researchimplant cells to replace those lost in thedisease.  Researchers areconducting clinical trials of a cell therapy in whichhuman retinal epithelialcells attached to microscopic gelatin beads areimplanted into the brains of 183
  • 185. Researchpeople with advanced PD.  The retinalepithelial cells producelevodopa.  The investigators hope that thistherapy will enhance brainlevels of dopamine. 184
  • 186. ResearchStarting in the 1990s, researchersconducted a controlled clinical trial of fetal tissueimplants inpeople with PD. They attempted to replacelost dopamine-producing neuronswith healthy ones from fetal tissue in order toimprove movement and the 185
  • 187. Researchresponse to medications.  While many ofthe implanted cells survived inthe brain and produced dopamine, this therapywas associated with only modestfunctional improvements, mostly in patients underthe age of 60.  186
  • 188. ResearchUnfortunately, some of the people who receivedthe transplants developeddisabling dyskinesias that could not be relieved byreducing antiparkinsonianmedications. 187
  • 189. ResearchAnother type of cell therapy involves stemcells.  Stem cells derived from embryos candevelop into any kind of cellin the body, while others, called progenitorcells, are more restricted.  188
  • 190. ResearchOne study transplanted neural progenitor cellsderived from human embryonicstem cells into a rat model of PD.  The cellsappeared to triggerimprovement on several behavioral tests, althoughrelatively few of the 189
  • 191. Researchtransplanted cells became dopamine-producingneurons.  Other researchersare developing methods to improve the number ofdopamine-producing cells thatcan be grown from embryonic stem cells in culture. 190
  • 192. ResearchResearchers also are exploring whether stemcells from adult brains might be useful in treatingPD.  They have shownthat the brains white matter contains multipotentprogenitor cells that can 191
  • 193. Researchmultiply and form all the major cell types of thebrain, includingneurons. Gene therapy is yet another approach to 192
  • 194. Researchtreating PD.  A study of gene therapy in non-human primate models of PD istesting different genes and gene-deliverytechniques in an effort to refinethis kind of treatment.  An early-phaseclinical study is also testing 193
  • 195. Researchwhether using the adeno-associated virus type 2(AAV2) to deliver the gene fora nerve growth factor called neurturin is safe foruse in people with PD. Another study is testing the safety of gene therapyusing AAV to deliver a gene 194
  • 196. Researchfor human aromatic L-amino aciddecarboxylase, an enzyme that helps convertlevodopa to dopamine in the brain.  Otherinvestigators are testingwhether gene therapy to increase the amount ofglutamic acid decarboxylase, 195
  • 197. Researchwhich helps produce an inhibitoryneurotransmitter called GABA, might reducethe overactivity of neurons in the brain that resultsfrom lack of dopamine. 196
  • 198. Researchis to use a vaccine to modify the immune system ina way that can protectdopamine-producing neurons.  One vaccinestudy in mice used a drug calledcopolymer-1 that increases the number of immuneT cells that secrete 197
  • 199. Researchanti-inflammatory cytokines and growth factors.The researchers injectedcopolymer-1-treated immune cells into a mousemodel for PD. The vaccinemodified the behavior of supporting (glial) cells inthe brain so that their 198
  • 200. Researchresponses were beneficial rather than harmful. Italso reduced the amount ofneurodegeneration in the mice, reducedinflammation, and increased productionof nerve growth factors. Another study delivered avaccine containing 199
  • 201. Researchalpha-synuclein in a mouse model of PD andshowed that the mice developedantibodies that reduced the accumulation ofabnormal alpha-synuclein. While these studies are preliminary, investigatorshope that similar approachesmight one day be tested in humans. 200
  • 202. ResearchIn recent years, Parkinsons research hasadvanced to the point that halting the progressionof PD, restoring lostfunction, and even preventing the disease are allconsidered realisticgoals.  While the ultimate goal of preventingPD may take years to achieve, 201
  • 203. Researchresearchers are making great progress inunderstanding and treating PD.One of the most exciting areas of PDresearch is genetics.  Studying the genes 202
  • 204. Researchcan help researchers understand both inheritedand sporadic cases of the disease.Identifying gene defects can also help researchersunderstand how PD occurs,develop animal models that accurately mimic theneuronal death in human PD, 203
  • 205. Researchidentify new drug targets, and improve diagnosis.As discussed in the “What Genes are Linkedto Parkinsons Disease?" section, several geneshave been definitively 204
  • 206. Researchlinked to PD in some people.  Researchersalso have identified a number ofother genes that may play a role and are workingto confirm thesefindings.  In addition, several chromosomalregions have been linked to PD 205
  • 207. Researchin some families.  Researchers hope toidentify the genes located in thesechromosomal regions and to determine which ofthem may play roles in PD. 206
  • 208. Researchinformation and DNA samples from hundreds offamilies with PD and areconducting large-scale gene expression studies toidentify genes that areabnormally active or inactive in PD.  Theyalso are comparing gene 207
  • 209. Researchactivity in PD with gene activity in similar diseasessuch as progressive supranuclearpalsy. Some scientists have found evidence that 208
  • 210. Researchspecific variations in the DNA of mitochondria –structures in cells thatprovide the energy for cellular activity — canincrease the risk of getting PD,while other variations are associated with alowered risk of the disorder. They 209
  • 211. Researchalso have found that PD patients have moremitochondrial DNA (mtDNA) variationsthan patients with other movement disorders orAlzheimers disease. Researchersare working to define how these mtDNA variationsmay lead to PD. 210
  • 212. ResearchIn addition to identifying new genes forPD, researchers are trying to learn how known PDgenes function and how thegene mutations cause disease.  Forexample, a 2005 study found that the 211
  • 213. Researchnormal alpha-synuclein protein may help otherproteins that are important fornerve transmission to fold correctly.  Otherstudies have suggested thatthe normal parkin protein protects neurons from avariety of threats, including 212
  • 214. Researchalpha-synuclein toxicity and excitotoxicity.Scientists continue to study environmentaltoxins such as pesticides and herbicides that cancause PD symptoms in 213
  • 215. Researchanimals.  They have found that exposingrodents to the pesticide rotenoneand several other agricultural chemicals can causecellular and behavioralchanges that mimic those seen in PD.  Otherstudies have suggested that 214
  • 216. Researchprenatal exposure to certain toxins can increasesusceptibility to PD inadulthood. An NIH-sponsored programcalled the Collaborative Centersfor Parkinsons Disease Environmental Research(CCPDER) focuses on how 215
  • 217. Researchoccupational exposure to toxins and use of caffeineand other substances mayaffect the risk of PD.Another major area of PD research involves 216
  • 218. Researchthe cells protein disposal system, called theubiquitin-proteasome system. Ifthis disposal system fails to work correctly, toxinsand other substances maybuild up to harmful levels, leading to celldeath.  The 217
  • 219. Researchubiquitin-proteasome system requires interactionsbetween several proteins,including parkin and UCH-L1. Therefore, disruptionof the ubiquitin-proteasomesystem may partially explain how mutations inthese genes cause PD. 218
  • 220. ResearchOther studies focus on how Lewy bodies formand what role they play in PD.  Some studiessuggest that Lewy bodies area byproduct of degenerative processes withinneurons, while others indicate 219
  • 221. Researchthat Lewy bodies are a protective mechanism bywhich neurons lock away abnormalmolecules that might otherwise be harmful. Additional studies have foundthat alpha-synuclein clumps alter gene expressionand bind to vesicles within 220
  • 222. Researchthe cell in ways that could be harmful. Another common topic of PD research isexcitotoxicity – overstimulation of nerve cells thatleads to cell damage or 221
  • 223. Researchdeath. In excitotoxicity, the brain becomesoversensitized to theneurotransmitter glutamate, which increasesactivity in the brain. The dopaminedeficiency in PD causes overactivity of neurons inthe subthalamic nucleus, 222
  • 224. Researchwhich may lead to excitotoxic damage there and inother parts of the brain.Researchers also have found that dysfunction ofthe cells mitochondria canmake dopamine-producing neurons vulnerable toglutamate.  223
  • 225. ResearchOther researchers are focusing on howinflammation may affect PD. Inflammation iscommon to a variety ofneurodegenerative diseases, includingPD, Alzheimers disease, HIV-1-associated 224
  • 226. Researchdementia, and amyotrophic lateral sclerosis.Several studies have shown thatinflammation-promoting molecules increase celldeath after treatment with thetoxin MPTP. Inhibiting the inflammation with drugsor by genetic engineering 225
  • 227. Researchprevented some of the neuronal degeneration inthese studies.  Otherresearch has shown that dopamine neurons inbrains from patients with PD havehigher levels of an inflammatory enzyme calledCOX-2 than those of people 226
  • 228. Researchwithout PD.  Inhibiting COX-2 doubled thenumber of neurons that survivedin a mouse model for PD.Since the discovery that MPTP causes 227
  • 229. Researchparkinsonian symptoms in humans, scientists havefound that by injecting MPTPand certain other toxins into laboratoryanimals, they can reproduce the brainlesions that cause these symptoms. This allowsthem to study the mechanisms of 228
  • 230. Researchthe disease and helps in the development of newtreatments.  They alsohave developed animal models with alterations ofthe alpha-synuclein and parkingenes.  Other researchers have used geneticengineering to develop mice 229
  • 231. Researchwith disrupted mitochondrial function in dopamineneurons.  These animalshave many of the characteristics associated withPD. 230
  • 232. Researchcharacteristics that can reveal whether the diseaseis developing orprogressing – are another focus of research. Such biomarkers could helpdoctors detect the disease before symptomsappear and improve diagnosis of the 231
  • 233. Researchdisease.  They also would show ifmedications and other types of therapyhave a positive or negative effect on the course ofthe disease.  Some ofthe most promising biomarkers for PD are brainimaging techniques.  For 232
  • 234. Researchexample, some researchers are using positronemission tomography (PET) brainscans to try to identify metabolic changes in thebrains of people with PD andto determine how these changes relate to diseasesymptoms.  Other 233
  • 235. Researchpotential biomarkers for PD include alterations ingene expression.Researchers also are conducting manystudies of new or improved therapies for 234
  • 236. Research(DBS) is now FDA-approved and has been used inthousands of people with PD,researchers continue to try to improve thetechnology and surgical techniquesin this therapy.  For example, some studiesare comparing DBS to the best 235
  • 237. Researchmedical therapy and trying to determine whichpart of the brain is the bestlocation for stimulation.  Another clinicaltrial is studying how DBSaffects depression and quality of life.  236
  • 238. ResearchOther clinical studies are testing whethertranscranial electrical polarization (TEP) ortranscranial magnetic stimulation(TMS) can reduce the symptoms of PD. In TEP,electrodes placed on the scalp are 237
  • 239. Researchused to generate an electrical current thatmodifies signals in the brainscortex.  In TMS, an insulated coil of wire onthe scalp is used togenerate a brief electrical current. 238
  • 240. ResearchOne of the enduring questions in PDresearch has been how treatment with levodopaand other dopaminergic drugsaffects progression of the disease. Researchers are continuing to try toclarify these effects.  One study hassuggested that PD patients with a 239
  • 241. Researchlow-activity variant of the gene for COMT (whichbreaks down dopamine) performworse than others on tests of cognition, and thatdopaminergic drugs may worsencognition in these people, perhaps because thereduced COMT activity causes 240
  • 242. Researchdopamine to build up to harmful levels in someparts of the brain.  In thefuture, it may become possible to test for suchindividual gene differences inorder to improve treatment of PD. 241
  • 243. ResearchA variety of new drug treatments are inclinical trials for PD.  These include a drugcalled GM1 ganglioside thatincreases dopamine levels in the brain. Researchers are testing whether 242
  • 244. Researchthis drug can reduce symptoms, delay diseaseprogression, or partially restoredamaged brain cells in PD patients.  Otherstudies are testing whether adrug called istradefylline can improve motorfunction in PD, and whether a drug 243
  • 245. Researchcalled ACP-103 that blocks receptors for theneurotransmitter serotonin willlessen the severity of parkinsonian symptoms andlevodopa-associatedcomplications in PD patients. Other topics ofresearch include 244
  • 246. Researchcontrolled-release formulas of PD drugs andimplantable pumps that give acontinuous supply of levodopa.Some researchers are testing potential 245
  • 247. Researchneuroprotective drugs to see if they can slow theprogression of PD.  Onestudy, called NET-PD (Neuroexploratory Trials inParkinsons Disease), isevaluating minocycline, creatine, coenzymeQ10, and GPI-1485 to determine if 246
  • 248. Researchany of these agents should be considered forfurther testing.  The NET-PDstudy may evaluate other possible neuroprotectiveagents in the future. Drugs found to be successful in the pilot phasesmay move to large phase III 247
  • 249. Researchtrials involving hundreds of patients.  Aseparate group of researchers isinvestigating the effects of either 1200 or 2400milligrams of coenzyme Q10 in600 patients.   Several MAO-B inhibitors,including selegiline, 248
  • 250. Researchlazabemide, and rasagiline, also are in clinical trialsto determine if theyhave neuroprotective effects in people with PD.Nerve growth factors, or neurotrophic 249
  • 251. Researchfactors, which support survival, growth, anddevelopment of brain cells, areanother type of potential therapy for PD. One such drug, glial cellline-derived neurotrophic factor (GDNF), has beenshown to protect dopamine 250
  • 252. Researchneurons and to promote their survival in animalmodels of PD.  This drughas been tested in several clinical trials for peoplewith PD, and the drugappeared to cause regrowth of dopamine nervefibers in one person who received 251
  • 253. Researchthe drug.  However, a phase II clinical studyof GDNF was halted in 2004because the treatment did not show any clinicalbenefit after 6 months, andsome data suggested that it might even beharmful.  Other neurotrophins 252
  • 254. Researchthat may be useful for treating PD includeneurotrophin-4 (NT-4), brain-derivedneurotrophic factor (BDNF), and fibroblast growthfactor 2 (FGF-2). 253
  • 255. Researchdietary supplements can slow PD, several clinicalstudies are testing whethersupplementation with vitamin B12 and othersubstances may be helpful. A 2005study found that dietary restriction — reducing thenumber of calories normally 254
  • 256. Researchconsumed – helped to increase abnormally lowlevels of the neurotransmitterglutamate in a mouse model for early PD. The study also suggested thatdietary restriction affected dopamine activity inthe brain.  Another 255
  • 257. Researchstudy showed that dietary restriction before theonset of PD in a mouse modelhelped to protect dopamine-producingneurons.  256
  • 258. Researchthat might improve some of the secondarysymptoms of PD, such as depression andswallowing disorders.  One clinical trial isinvestigating whether a drugcalled quetiapine can reduce psychosis or agitationin PD patients with 257
  • 259. Researchdementia and in dementia patients withparkinsonian symptoms. Some studies alsoare examining whether transcranial magneticstimulation or a food supplementcalled s-adenosyl-methionine (SAM-e) can alleviatedepression in people with 258
  • 260. ResearchPD, and whether levetiracetam, a drug approved totreat epilepsy, can reducedyskinesias in Parkinsons patients withoutinterfering with other PD drugs. 259
  • 261. Researchimplant cells to replace those lost in thedisease.  Researchers areconducting clinical trials of a cell therapy in whichhuman retinal epithelialcells attached to microscopic gelatin beads areimplanted into the brains of 260
  • 262. Researchpeople with advanced PD.  The retinalepithelial cells producelevodopa.  The investigators hope that thistherapy will enhance brainlevels of dopamine. 261
  • 263. ResearchStarting in the 1990s, researchersconducted a controlled clinical trial of fetal tissueimplants inpeople with PD. They attempted to replacelost dopamine-producing neuronswith healthy ones from fetal tissue in order toimprove movement and the 262
  • 264. Researchresponse to medications.  While many ofthe implanted cells survived inthe brain and produced dopamine, this therapywas associated with only modestfunctional improvements, mostly in patients underthe age of 60.  263
  • 265. ResearchUnfortunately, some of the people who receivedthe transplants developeddisabling dyskinesias that could not be relieved byreducing antiparkinsonianmedications. 264
  • 266. ResearchAnother type of cell therapy involves stemcells.  Stem cells derived from embryos candevelop into any kind of cellin the body, while others, called progenitor cells,are more restricted.  265
  • 267. ResearchOne study transplanted neural progenitor cellsderived from human embryonicstem cells into a rat model of PD.  The cellsappeared to triggerimprovement on several behavioral tests, althoughrelatively few of the 266
  • 268. Researchtransplanted cells became dopamine-producingneurons.  Other researchersare developing methods to improve the number ofdopamine-producing cells thatcan be grown from embryonic stem cells in culture. 267
  • 269. ResearchResearchers also are exploring whether stemcells from adult brains might be useful in treatingPD.  They have shownthat the brains white matter contains multipotentprogenitor cells that can 268
  • 270. Researchmultiply and form all the major cell types of thebrain, includingneurons. Gene therapy is yet another approach to 269
  • 271. Researchtreating PD.  A study of gene therapy in non-human primate models of PD istesting different genes and gene-deliverytechniques in an effort to refinethis kind of treatment.  An early-phaseclinical study is also testing 270
  • 272. Researchwhether using the adeno-associated virus type 2(AAV2) to deliver the gene fora nerve growth factor called neurturin is safe foruse in people with PD. Another study is testing the safety of gene therapyusing AAV to deliver a gene 271
  • 273. Researchfor human aromatic L-amino aciddecarboxylase, an enzyme that helps convertlevodopa to dopamine in the brain.  Otherinvestigators are testingwhether gene therapy to increase the amount ofglutamic acid decarboxylase, 272
  • 274. Researchwhich helps produce an inhibitoryneurotransmitter called GABA, might reducethe overactivity of neurons in the brain that resultsfrom lack of dopamine. 273
  • 275. Researchis to use a vaccine to modify the immune system ina way that can protectdopamine-producing neurons.  One vaccinestudy in mice used a drug calledcopolymer-1 that increases the number of immuneT cells that secrete 274
  • 276. Researchanti-inflammatory cytokines and growth factors.The researchers injectedcopolymer-1-treated immune cells into a mousemodel for PD. The vaccinemodified the behavior of supporting (glial) cells inthe brain so that their 275
  • 277. Researchresponses were beneficial rather than harmful. Italso reduced the amount ofneurodegeneration in the mice, reducedinflammation, and increased productionof nerve growth factors. Another study delivered avaccine containing 276
  • 278. Researchalpha-synuclein in a mouse model of PD andshowed that the mice developedantibodies that reduced the accumulation ofabnormal alpha-synuclein. While these studies are preliminary, investigatorshope that similar approachesmight one day be tested in humans. 277

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