1. The management of advanced Parkinson’s disease Dr J Paul Milnes Consultant Physician Airedale NHS Trust

4. Managing the patient and family with advanced Parkinson’s disease Almost every discipline has a role to play Almost every discipline has a role to play Specialist clinical teams must remain involved throughout the illness. Specialist clinical teams must remain involved throughout the illness. The Parkinson’s disease nurse specialist has a pivotal role The Parkinson’s disease nurse specialist has a pivotal role Other agencies including, the Parkinson’s Disease Society, provide support and information Other agencies including, the Parkinson’s Disease Society, provide support and information

5. Outline of the lecture A few facts about Parkinson’s disease A few facts about Parkinson’s disease The problems encountered as the disease progresses The problems encountered as the disease progresses Highlight important management points Highlight important management points

6. Epidemiology of Parkinson’s disease Approximately 1% of the population over 60 years has Parkinson’s disease Approximately 1% of the population over 60 years has Parkinson’s disease The number of cases increase with age The number of cases increase with age The ageing population is expected to dramatically increase the number of cases The ageing population is expected to dramatically increase the number of cases Parkinson’s disease may affect between 5 and 10% of the nursing home population Parkinson’s disease may affect between 5 and 10% of the nursing home population

7. Changes in the brain in Parkinson’s disease Loss of dopaminergic neurones from the substantia nigra is an essential feature of Parkinson’s disease Loss of dopaminergic neurones from the substantia nigra is an essential feature of Parkinson’s disease The presence of Lewy bodies The presence of Lewy bodies

9. Changes in the brain in Parkinson’s disease There’s more to Parkinson’s disease than the substantia nigra involvement There’s more to Parkinson’s disease than the substantia nigra involvement Braak has demonstrated the progression of abnormalities in the brain as Parkinson’s disease progresses Mov Disord 2006; 21: 2042 Braak has demonstrated the progression of abnormalities in the brain as Parkinson’s disease progresses Mov Disord 2006; 21: 2042

12. The diagnosis of Parkinson’s disease Don’t be afraid to question the diagnosis even at a relatively late stage Don’t be afraid to question the diagnosis even at a relatively late stage

13. Do all people with Parkinson’s disease have tremor? Up to 20% of cases never develop tremor at any stage of the illness Up to 20% of cases never develop tremor at any stage of the illness

14. Do all people with Parkinson’s disease have reduction and slowness of movement?

15. Hypokinesia and bradykinesia Poverty and slowness of movement Poverty and slowness of movement Must be present to make the diagnosis Must be present to make the diagnosis Reduced facial expression Reduced facial expression Slow shuffling gait Slow shuffling gait Reduced arm swing Reduced arm swing Reduced swallowing Reduced swallowing Difficulty turning Difficulty turning Small handwriting Small handwriting Difficulty with fine movements affecting the whole range of activities of daily living Difficulty with fine movements affecting the whole range of activities of daily living Usually asymmetrical Usually asymmetrical

16. UKPDS Brain Bank Criteria Step1 Diagnosis of a parkinsonian syndrome Step1 Diagnosis of a parkinsonian syndrome Bradykinesia (slowness of movement) and at least one of the following Bradykinesia (slowness of movement) and at least one of the following Muscular rigidity Muscular rigidity Rest tremor Rest tremor Postural instability unrelated to primary visual, vestibular or proprioceptive dysfunction Postural instability unrelated to primary visual, vestibular or proprioceptive dysfunction Step2 Exclusion criteria for Parkinson’s Disease Step2 Exclusion criteria for Parkinson’s Disease Step3 Supportive criteria for Parkinson’s Disease Step3 Supportive criteria for Parkinson’s Disease

17. Differential diagnosis of Parkinson’s Disease Essential tremor Essential tremor Diffuse Lewy Body Disease Diffuse Lewy Body Disease Cerebrovascular disease Cerebrovascular disease Progressive supranuclear palsy Progressive supranuclear palsy Multiple system atrophy Multiple system atrophy Trauma or toxin related Trauma or toxin related Drug induced Drug induced Others Others

18. The diagnosis of Parkinson’s disease Don’t be afraid to question the diagnosis because it can be difficult Don’t be afraid to question the diagnosis because it can be difficult Has a specialist been involved? Has a specialist been involved? Up to 25% error rate for non specialist hospital doctors Up to 25% error rate for non specialist hospital doctors “The diagnosis of Parkinson’s disease should be reviewed regularly and reconsidered if atypical features develop” NICE 2006 “The diagnosis of Parkinson’s disease should be reviewed regularly and reconsidered if atypical features develop” NICE 2006

19. The management of Parkinson’s disease

20. The management of the disease can be planned in four stages Nursing Older People 2004; 16:1 Diagnosis Diagnosis Maintenance Maintenance Complex Complex Palliative Palliative

21. Audit of 73 cases in Cornwall Parkinsonism and related disorders 1999; 5(S53) Mean duration of the disease 14.6 years Mean duration of the disease 14.6 years Average duration of the four stages Average duration of the four stages Diagnosis 1.5 years Diagnosis 1.5 years Maintenance 6 years Maintenance 6 years Complex 5 years Complex 5 years Palliative 2.2 years Palliative 2.2 years

22. The palliative phase of Parkinson’s disease Patients become increasingly disabled and dependant Patients become increasingly disabled and dependant The palliative phase of Parkinson’s disease has been defined by The palliative phase of Parkinson’s disease has been defined by Inability to tolerate adequate dopaminergic therapy Inability to tolerate adequate dopaminergic therapy Unsuitability for surgery Unsuitability for surgery The presence of advanced co-morbidity which is life threatening or disabling The presence of advanced co-morbidity which is life threatening or disabling

23. The palliative phase of Parkinson’s disease NICE Guidance 2006 Palliative care does not correlate with imminent death in Parkinson’s disease Palliative care does not correlate with imminent death in Parkinson’s disease Shift from a therapeutic pharmacological approach to one which places a greater emphasis on quality of life issues Shift from a therapeutic pharmacological approach to one which places a greater emphasis on quality of life issues

24. The palliative phase of Parkinson’s disease NICE Guidance 2006 It should be possible to seek advice from specialist palliative care teams, not just at the end of life, but at any stage after diagnosis It should be possible to seek advice from specialist palliative care teams, not just at the end of life, but at any stage after diagnosis Recognising the needs of carers at an early stage will enable people to stay at home for as long as possible Recognising the needs of carers at an early stage will enable people to stay at home for as long as possible Many carers will have become “experts in Parkinson’s disease” themselves Many carers will have become “experts in Parkinson’s disease” themselves

25. Palliative care and specialist care for PD patients in nursing homes Between 5 and 10% of nursing home residents have Parkinson’s disease Between 5 and 10% of nursing home residents have Parkinson’s disease Many may remain undiagnosed Many may remain undiagnosed The support from specialist services is inadequate and inconsistent The support from specialist services is inadequate and inconsistent This population poses huge challenges to us all This population poses huge challenges to us all

26. NICE Guidance 2006 The care of people with Parkinson’s disease is best undertaken in a multidisciplinary way throughout each stage of the disease The care of people with Parkinson’s disease is best undertaken in a multidisciplinary way throughout each stage of the disease

27. Advanced Parkinson’s disease Motor problems Motor problems Non-motor problems Non-motor problems

28. Motor problems in advanced disease include Failing mobility and falls Failing mobility and falls Deterioration in the whole range of activities of daily living Deterioration in the whole range of activities of daily living More frequent “off” periods More frequent “off” periods Speech impairment Speech impairment Swallowing difficulty Swallowing difficulty Dyskinesias – abnormal movements related to drugs Dyskinesias – abnormal movements related to drugs Less predictable response to medication Less predictable response to medication

29. Motor problems in advanced disease The delicate balance between the benefits and side effects of drug treatment The delicate balance between the benefits and side effects of drug treatment The crucial role of other professionals and carers The crucial role of other professionals and carers The importance of ensuring the correct timing of medication - especially in hospital and care homes The importance of ensuring the correct timing of medication - especially in hospital and care homes

30. The crucial role of other professionals and carers

31. Levodopa (madopar & sinemet) Levodopa is the most important treatment of the later stages of Parkinson’s disease Levodopa is the most important treatment of the later stages of Parkinson’s disease It is the most effective drug for treating motor problems It is the most effective drug for treating motor problems The side effects are not as extreme as some of the other medications The side effects are not as extreme as some of the other medications Diet can influence its effect in advanced Parkinson’s disease Diet can influence its effect in advanced Parkinson’s disease

32. Protein intake interferes with levodopa therapy Protein intake interferes with levodopa therapy Levodopa and some amino acids, in protein rich foods, compete for the same carriers in the intestinal mucosa and blood brain barrier Levodopa and some amino acids, in protein rich foods, compete for the same carriers in the intestinal mucosa and blood brain barrier The data suggest that patients with advanced Parkinson’s disease should adjust daily protein intake and shift protein intake to the evening The data suggest that patients with advanced Parkinson’s disease should adjust daily protein intake and shift protein intake to the evening The use of low protein foods to reduce off periods after meal The use of low protein foods to reduce off periods after meal Mov Disord 2006; 21(10): 1682

33. Beware of an unexpected change in the speed of a patient’s deterioration

34. Consider other contributory factors Consider other contributory factors Reassess for intercurrent physical or mental health problems Reassess for intercurrent physical or mental health problems Common precipitants include Common precipitants include Infection Infection Depression Depression Drug side effects Drug side effects

35. Case study 80 year old man with advanced Parkinson’s disease 80 year old man with advanced Parkinson’s disease Marked deterioration in his mobility over a 6 week period Marked deterioration in his mobility over a 6 week period Recurrent falls and more drowsy Recurrent falls and more drowsy No recent changes in drug treatment or signs of infection No recent changes in drug treatment or signs of infection Specialist review and further investigation Specialist review and further investigation

36. Urgent CT Brain Scan

41. Neurosurgical treatment

42. Non-motor features in advanced Parkinson’s disease Are they important? Are they important? Yes Yes

43. Sydney Multicentre Study of Parkinson’s Disease Hely et al. Mov Dis 2005; 20(2): 190 Report on people with PD who survive 15 years from diagnosis Report on people with PD who survive 15 years from diagnosis One third of the 149 people recruited had survived One third of the 149 people recruited had survived

44. Sydney Multicentre Study PD survivors at 15 years 81% Falls 81% Falls 84% cognitive decline 84% cognitive decline 50% hallucinations and depression 50% hallucinations and depression 50% choking 50% choking 41% urinary incontinence 41% urinary incontinence 35% symptomatic postural hypotension 35% symptomatic postural hypotension

45. Sydney Multicentre Study PD survivors at 15 years 40% were living in an aged care facility 40% were living in an aged care facility 95% experienced L-dopa induced dyskinesia and end of dose failure of medication 95% experienced L-dopa induced dyskinesia and end of dose failure of medication “The most disabling long-term problems of Parkinson’s Disease relate to symptoms not improved by L-dopa” “The most disabling long-term problems of Parkinson’s Disease relate to symptoms not improved by L-dopa” The non-motor problems The non-motor problems

46. Non-motor features in advanced Parkinson’s disease Neuropsychiatric Neuropsychiatric Sleep disorders Sleep disorders Autonomic symptoms Autonomic symptoms Gastrointestinal symptoms Gastrointestinal symptoms Sensory symptoms Sensory symptoms Others Others

47. Non-motor features in advanced Parkinson’s disease Neuropsychiatric Neuropsychiatric Depression Depression Anxiety Anxiety Hallucinations Hallucinations Delusions Delusions Dementia Dementia

48. Non-motor features in advanced Parkinson’s disease Sleep disorders include Sleep disorders include Restless legs Restless legs REM sleep behaviour disorder REM sleep behaviour disorder Excessive daytime sleepiness Excessive daytime sleepiness Vivid dreams Vivid dreams Insomnia Insomnia

49. Non-motor features in advanced Parkinson’s disease Autonomic symptoms Autonomic symptoms Bladder disturbances Bladder disturbances Sweating Sweating Orthostatic hypotension Orthostatic hypotension Sexual dysfunction Sexual dysfunction

50. Non-motor features in advanced Parkinson’s disease Gastrointestinal symptoms Gastrointestinal symptoms Dribbling of saliva Dribbling of saliva Difficulty with swallowing Difficulty with swallowing Acid reflux Acid reflux Nausea and vomiting Nausea and vomiting Constipation Constipation

51. Non-motor features in advanced Parkinson’s disease Other symptoms Other symptoms Pain Pain Loss of smell Loss of smell Fatigue Fatigue Double vision Double vision

52. Screening for non-motor symptoms A questionnaire has been developed A questionnaire has been developed This can be downloaded from the Parkinson’s Disease Society website This can be downloaded from the Parkinson’s Disease Society website

53. The NMS Quest Study Mov Disord 2006; 21(7): 916 International multidisciplinary group of experts International multidisciplinary group of experts Development of a non-motor symptom screening tool comprising of 30 items Development of a non-motor symptom screening tool comprising of 30 items The number of symptoms correlated closely with advancing age and duration of disease The number of symptoms correlated closely with advancing age and duration of disease Problems previously unknown to health professionals were frequently highlighted Problems previously unknown to health professionals were frequently highlighted

55. Management points for some common non-motor symptoms Depression Depression Dementia Dementia Hallucinations Hallucinations Sleep problems Sleep problems

56. Depression in Parkinson’s disease is common and easily overlooked

57. Depression Affects up to 50% of patients with Parkinson’s Disease Affects up to 50% of patients with Parkinson’s Disease Low threshold for diagnosing depression in Parkinson’s disease Low threshold for diagnosing depression in Parkinson’s disease The strongest predictor of PD quality of life in several surveys The strongest predictor of PD quality of life in several surveys J Neurol Neurosurg Psychiatry 1999; 66: 431 J Neurol Neurosurg Psychiatry 1999; 66: 431 J Neurol Neurosurg Psychiatry 2000; 69: 308 J Neurol Neurosurg Psychiatry 2000; 69: 308

58. Depression Features of depression and Parkinson’s disease overlap Features of depression and Parkinson’s disease overlap The diagnosis can be overlooked The diagnosis can be overlooked If untreated can affect motor function If untreated can affect motor function

59. Management Holistic - multi-disciplinary team input Holistic - multi-disciplinary team input Liaison with mental health services Liaison with mental health services Medication Medication

60. Medication for depression Factors to consider Factors to consider Ensure optimal treatment of the motor problems Ensure optimal treatment of the motor problems Side effects limit the value of the older antidepressant drugs Side effects limit the value of the older antidepressant drugs The presence of anxiety The presence of anxiety

61. Treatment of depression - NICE Guidance 2006 There is insufficient evidence from clinical trials of the efficacy or safety of any antidepressant therapy in Parkinson’s disease There is insufficient evidence from clinical trials of the efficacy or safety of any antidepressant therapy in Parkinson’s disease There is an urgent need for further research to establish safe and effective treatments for depression in Parkinson’s disease There is an urgent need for further research to establish safe and effective treatments for depression in Parkinson’s disease

62. Hallucinations in Parkinson’s disease May begin as visual hallucinations which are non-frightening May begin as visual hallucinations which are non-frightening As the disease progresses the hallucinations may become more distressing and paranoid delusions may develop As the disease progresses the hallucinations may become more distressing and paranoid delusions may develop

63. Hallucinations in Parkinson’s disease May be a direct effect of the disease May be a direct effect of the disease Could be related to drug treatment Could be related to drug treatment Consider intercurrent illness Consider intercurrent illness Impaired vision and environment Impaired vision and environment Consider depression Consider depression Significant risk of dementia Significant risk of dementia

64. Dementia in Parkinson’s disease Dementia is the progressive loss of global cognitive function Dementia is the progressive loss of global cognitive function At least half the patients with Parkinson’s disease will ultimately develop dementia At least half the patients with Parkinson’s disease will ultimately develop dementia Typically PD dementia affects visuospatial abilities, learning, verbal fluency, working memory and mental flexibility Typically PD dementia affects visuospatial abilities, learning, verbal fluency, working memory and mental flexibility Memory loss is less prominent than in other common dementias Memory loss is less prominent than in other common dementias

65. Management of PD dementia Non-drug strategies – education and practical support for patient and carers Non-drug strategies – education and practical support for patient and carers Withdrawal of medication – ultimately leaving levodopa Withdrawal of medication – ultimately leaving levodopa Treat depression Treat depression Use of atypical antipsychotic drugs Use of atypical antipsychotic drugs Use of cholinesterase inhibitors Use of cholinesterase inhibitors

66. Stepwise reduction in drug treatment Focus treatment on the most effective PD drugs with the least side effects Focus treatment on the most effective PD drugs with the least side effects Reduce from the top Reduce from the top Anticholinergics Anticholinergics Selegiline Selegiline Amantadine Amantadine Dopamine agonists (eg ropinirole/ pramipexole) Dopamine agonists (eg ropinirole/ pramipexole) COMT (eg entacapone) COMT (eg entacapone) Apomorphine Apomorphine L-dopa L-dopa

67. Antipsychotic drugs Older drugs – “Typical antipsychotic” drugs should be avoided Older drugs – “Typical antipsychotic” drugs should be avoided Atypical antipsychotic drugs may help Atypical antipsychotic drugs may help Quetiapine is often used but little hard data Quetiapine is often used but little hard data Clozapine is of benefit but rarely used in the UK Clozapine is of benefit but rarely used in the UK Caution with Olanzapine and Risperidone in people at risk of stroke Caution with Olanzapine and Risperidone in people at risk of stroke

68. Cholinesterase inhibitors The group of drugs originally introduced to treat Alzheimer’s disease The group of drugs originally introduced to treat Alzheimer’s disease NICE Guidance 2006 NICE Guidance 2006 Used successfully in patients with PD dementia Used successfully in patients with PD dementia Further research is recommended to identify those patients who will benefit Further research is recommended to identify those patients who will benefit Rivastigmine is currently licensed for the treatment of PD dementia Rivastigmine is currently licensed for the treatment of PD dementia

70. Sleep related problems of Parkinson’s disease Take an accurate history Take an accurate history

71. Sleep related problems of Parkinson’s disease Age Ageing 2006; 35: 220 Insomnia directly due to the effects of Parkinson’s disease on central sleep regulation centres in the brain Insomnia directly due to the effects of Parkinson’s disease on central sleep regulation centres in the brain Motor function related Motor function related Urinary difficulties Urinary difficulties Neuropsychiatric problems Neuropsychiatric problems

72. Management of sleep disorders General measures General measures Treatment of specific problems Treatment of specific problems

73. General measures to cope with insomnia A warm bath 2 hours before bedtime A warm bath 2 hours before bedtime Hot milk or a light snack at bedtime Hot milk or a light snack at bedtime Handrails or satin sheets to help turning Handrails or satin sheets to help turning Avoid stimulants such as tea and coffee at bedtime Avoid stimulants such as tea and coffee at bedtime Review other tablets Review other tablets Care with hypnotic drugs but sometimes helpful Care with hypnotic drugs but sometimes helpful

74. Motor function related Restless legs Restless legs Abnormal leg movements Abnormal leg movements Difficulty turning in bed Difficulty turning in bed Medication changes may help Medication changes may help

75. Urinary problems at night include - Nocturia – frequent micturition at night - is common Nocturia – frequent micturition at night - is common Is it related to Parkinson’s disease or another problem? Is it related to Parkinson’s disease or another problem? Exclude active infection and incomplete bladder emptying Exclude active infection and incomplete bladder emptying Incontinence related to poor mobility Incontinence related to poor mobility

76. Neuropsychiatric causes of sleep disturbance Depression is common and treatable Depression is common and treatable Panic attacks Panic attacks Treatment determined by time of occurrence Treatment determined by time of occurrence Cognitive problems Cognitive problems Distressing dreams and hallucinations Distressing dreams and hallucinations Review drug treatment Review drug treatment Consider quetiapine Consider quetiapine REM Sleep behaviour disorder REM Sleep behaviour disorder

77. REM Sleep Behaviour Disorder People enact their dreams People enact their dreams Talking Talking Shouting Shouting Falling out of bed Falling out of bed Even attacking their partner Even attacking their partner Drugs can help Drugs can help Clonazepam Clonazepam Others Others

78. Useful sources of information Parkinson’s Disease Society www.parkinsons.org.uk 2006 NICE Guidance www.nice.org.uk

79. Summary Parkinson’s disease affects 1% of the population over 60 years old Parkinson’s disease affects 1% of the population over 60 years old Specialist support at diagnosis and throughout the disease is essential Specialist support at diagnosis and throughout the disease is essential There is inadequate support for PD patients in nursing homes There is inadequate support for PD patients in nursing homes The management becomes increasingly complex and needs input from the whole range of carers and clinical staff The management becomes increasingly complex and needs input from the whole range of carers and clinical staff Think of other contributory causes if there is an unexpected deterioration in symptom control Think of other contributory causes if there is an unexpected deterioration in symptom control The importance of the non-motor symptoms in advanced Parkinson’s disease has only recently received significant attention The importance of the non-motor symptoms in advanced Parkinson’s disease has only recently received significant attention