Management of Neurological Conditions at End of Life

Transcription

1 Management of Neurological Conditions at End of Life Erwin B. Montgomery Jr. MD Professor of Neurology McMaster University, Hamilton ON Medical Director Greenville Neuromodulation Center, Greenville PA USA

2 Faculty/Presenter Disclosure Faculty: Dr. Erwin Montgomery Relationships with commercial interests: Grants/Research Support: FHC In. Speakers Bureau/Honoraria: Book Royalties Consulting Fees: None Other: None

3 Greenville Neuromodulation Center Non-profit corporation in the Commonwealth of Pennsylvania dedicated to the advancement of neuromodulation therapies, such as Deep Brain Stimulation, through research, technology development, education and training

4 Conflict of Interest Disclosure Dr. Montgomery is an inventor on a number of patents and author of a number of textbooks related to neuromodulation and Parkinson s disease Consultant to FHC, Inc. a for profit company supplying equipment, materials and systems for intraoperative neurophysiological monitoring during Deep Brain Stimulation lead implantation surgery

5 Caveats If Off-label, experimental or investigational drugs, biologics, devices, or diagnostics are mentioned, they will be identified as such Dr. Montgomery is new to Canada and is learning Canadian policies, rules, and regulations. Much of what is discussed is in the context of experiences in the United States. Knowledge of good medical care knows no boundaries but implementation is a different matter. Dr. Montgomery makes no claims as to the correct spelling of any word in the presentations.

6 Learning Objectives Recognition that the holistic care at end of life is extraordinarily complex and challenging; far beyond the expertise of most neurologists. Only by working together with other disciplines can the extraordinary range of concerns be met.

7 Learning Objectives Focus on Parkinson s disease Common particularly in the elderly Prevalence of parkinsonism (per 100 population) for the age groups 65 to 69 = to 74 = to 79 = to 84 = to 89 = 5.1 Likely an underestimate, false negative rate ~29% de Rijk MC, et al. Prevalence of parkinsonism and Parkinson's disease in Europe: the EUROPARKINSON Collaborative Study. European Community Concerted Action on the Epidemiology of Parkinson's disease. J Neurol Neurosurg Psychiatry Jan;62(1):10-5.

8 Learning Objectives Focus on Parkinson s disease Common particularly in the elderly Highlight specific issues centered on Motoric Mobility Non-motoric Dysphagia Cognitive problems Emotional problems

9 Parkinson Syndrome Idiopathic Parkinson s disease vs. Atypical Parkinsonism Idiopathic Parkinson s disease (74% of patients) 97% respond to levodopa therapy Response becomes complicated over time» Difficult pharmacokinetics and pharmacodynamics Shorter duration of effects Increased adverse effects, such as dyskinesia

10 Parkinson Syndrome Atypical Parkinsonism (26% of patients) Neurodegenerative MultiSystems Atrophy (MSA) Progressive supranuclear Palsy (PSA) 24% will respond to levodopa but not robust or sustained Non-degenerative (lower body Parkinsonism) Vascular (infarct) Parkinsonism Normal Pressure Hydrocephalus

11 Drug Induced Parkinsonism Amisulpride Amoxapine (Asendin ) Chloractil/Largactil Chlorpromazine hydrocloride Clopixol Denzapine Depixol Domatil/Sulpitil/Sulpor (Sulparex is discontinued) Dozic/Haldol/Serenace Flupenthixol Fluphenazine hydrochloride Haloperidol Melleril Methotrimeprazine/Levomepromazine Metoclopramide Reglan Modecate/Moditen/Motival (includes nortriptyline) Nozinan Olanzapine Zyprexa Oxypertine Oxypertine Pericyazine Neulactil Perphenazine Fentazin, Pimozide Orap Piportil Pipotiazine Prochlorperazine Prochlorperazine (Compazine, Stemzine, Buccastem, Stemetil, Phenotil) Promazine Promazine hydrochloride Risperidone Risperdal Solian Stelazine Stemetil Sulpiride Thioridazine Trifluoperazine Triptafen (Perphenazine+amitriptyline) Zoleptil Zotepine Zuclopenthixol acetate

12 Motoric Motor manifestations Affects any movement Slowness or absence of movement Kinesia paradoxica Can create misunderstanding of the patient Tremor Not consistent between and within patient Rigidity Gait and postural abnormalities

13 Levodopa Short plasma half-life (90 minutes) Early third spacing in the brain can prolong effects but buffering diminishes with disease duration and severity Dosing interval begins to approach plasma half-life in advanced disease

14 Levodopa First address peak-dose effect Questions I ask to help assess the peak-dose effect are: 1. Is there much change in the symptoms during the day? If there are no fluctuations and the patient s symptoms are bothersome, then it is likely the patient s peak-dose effect is sub-therapeutic and the individual doses are insufficient. If there are times where the symptoms are sufficiently controlled, then the dose just prior to those times may be sufficient. If there are no fluctuations and the patient s symptoms are not bothersome or limiting, then the size of each dose may be sufficient and the dosing interval is not too long as to cause a wearing-off effect. 2. How is the patient when the patient is at his or her best compared to when the patient is at his or her worst? If there is no difference and the patient s symptoms are not satisfactorily controlled, then the peak-dose likely is insufficient. 3. Does the patient have involuntary movements, can t sit still or is moving around too much? This suggests that the patient is experiencing dyskinesia which would suggest that the dose just prior to when these involuntary movements are noted may be too large.

15 Levodopa Second, dosing interval 1. Is there much change in the symptoms during the day? If there are no fluctuations and the patient s symptoms are not bothersome or limiting, then the size of each dose may be sufficient and the dosing interval is not too long as to cause a wearing-off effect. 2. How is the patient when the patient is at his or her best compared to when the patient is at his or her worst? If there is not difference and the patient s symptoms are not satisfactorily controlled, then the peak-dose likely is insufficient. 3. How does the patient or caregiver know when it is time to take the subsequent dose of medication? If the patient knows because the symptoms are returning, then the dosing interval may be too long. If the patient knows by looking at the clock or a timer, then fluctuations are less likely. 4. Can the patient or caregiver tell when it is time for the patient to take the next dose of medication? Assuming that the peak-dose effect for each dose is optimal, then the ability for the patient or caregiver to tell that the next dose is due indicates a dosing interval that is too long, hence wearing off effect. If the patient or caregiver cannot tell and the peak-dose effects are optimal, then the dosing interval is likely optimal.

16 Maximum dose of levodopa That will produces intolerable adverse effects that cannot be circumvented In clinical trials for Deep Brain Stimulation, the average dose of levodopa (as levodopa equivalents) for candidates was 2500 mg per day A great many patients are undertreated

17 Levodopa Absorbed only in distal jejunum If taken with meals delays absorption by 28% and delays peak by 30 minutes Should be taken ½ hour before or 1 hour after meals

18 Levodopa Absorbed by enzymatic facilitated transport Across the gut epithelium and across the blood brain barrier Competes with large neutral amino acids from protein ingestion Issue of nutritional supplementation High carb and fats, low protein

19 Adjuncts to Levodopa Drugs to improve bioavailability of levodopa Carbidopa (blocks aromatic amino acid decarboxylase) Optimal dose at least 100 mg per day COMT-inhibitors Entacapone Short half-life must be taken with each dose of levodopa MAO-B inhibitors Selegiline and rasagiline

20 Adjuncts to Levodopa Dopamine agonists Higher risk of short term adverse effects Used as levodopa sparing agents Minimize long term risks of levodopa such as dyskinesia.

21 Adjuncts to Levodopa Deep Brain Stimulation No upper age limit Issue of biological rather and chronological age

22 Management of Levodopa-dose Nausea and vomiting limiting adverse effect Supplemental use of carbidopa (Lodosyn) 25 mg three times a day Caution in exceeding 200 mg per day May enter the CNS to reduce conversion of levodopa to dopamine

23 Dysphagia Pneumonia Leading cause of death (30%) in patients with PD Dysphagia leading cause of pneumonia Diagnosis 25% silent aspirators High index of suspicion Coughing or choking when eating or drinking

24 Dysphagia Evaluation Best positive and NEGATIVE predictive value Video Fluoroscopic Evaluation of Speech (VFES) Modified Barium Swallow) Bedside (clinical) evaluation and Fiberoptic Endoscopy Evaluation of Swallowing (FEES) Cannot demonstrate mechanism(s) Important for treatment Poor negative value If positive then VFES If negative then VFES Why do anything else but VFES?

25 Abrupt Discontinuation of Dopaminergic Agents Neuroleptic-malignant-like syndrome High fever, altered levels of consciousness, a marked increase in muscle tone, autonomic disturbance, and elevation of serum creatine kinase (CK) Rhabdomyolysis, disseminated intravascular coagulation (DIC), and acute renal failure May present as an FUO (fever of undetermined origin)

26 Abrupt Discontinuation of Dopaminergic Agents I.V. levodopa (generally unavailable) Apomorphine (problem of precipitous hypotension in patient already at risk) Transdermal rotigotine (Neupro) patch 2 to 6 mg per 24 hrs

27 Psychosis Prevention Low level illumination Parkinson s disease reduces visual acuity Reassurance Don t discount their fears or concerns Find ways that the patient will be reassured Avoid agitation If in chronic care facility, personal belongings to reduce strangeness of environment

28 Psychosis Prevention Avoid psychoactive agents Acute psychosis Psychosis from withdrawal

29 Psychosis Use of anti-parkinson medications From most likely to least likely to produce psychosis Anticholinergics Amantadine Dopamine agonists Pramipexole Ropinirole Rotigotine Controlled release carbidopa/levodopa Immediate release carbidopa/levodopa

30 Treatment Psychosis Differentiate psychosis from delirium Marked autonomic dysfunction and depressed levels of consciousness suggest delirium Very different differential diagnosis» Toxic, metabolic and infectious causes

31 Treatment Anti-psychotics Psychosis All typical antipsychotics can markedly worsen parkinsonism Most atypical antipsychotics with the exception of quetiapine (Seroquel) and clozapine (Clozaril) will worsen parkinsonism Associated with increase risk of sudden death (small) Clozapine associated with a 1.8% risk of agranulocytosis Increased risk of unexplained death in elderly with dementia

32 State of confusion Capgrass syndrome Cholinesterase inhibitors Psychosis Galantamine -allosteric potentiation of nicotinic acetylcholine receptors

33 Depression Part of the syndrome independent of disability Confusion between parkinsonism and depression High index of suspicion Depression in elderly presents differently compared to young More cognitive problems (pseudodementia) Bradykinesia particularly mask-like faces versus psychomotor retardation Thoughts of death or dying may or may not suggest depression Anhedonia perhaps a good marker Parkinsonism may improve with aggressive treatment of depression ECT

34 Dopamine dysregulation syndrome Impulse control problems Gambling Hypersexual behavior Hypomania Dysphoria compulsive shopping Compulsive repetitive stereotypic motor behaviors (punding) Eating disorders Aggressive behavior

35 modified Edmonton Symptom Assessment System Scale for PD (ESAS-PD) Miyasaki JM, Long J, Mancini D, Moro E, Fox SH, Lang AE, Marras C, Chen R, Strafella A, Arshinoff R, Ghoche R, Hui J. Palliative care for advanced Parkinson disease: an interdisciplinary clinic and new scale, the ESAS-PD. Parkinsonism Relat Disord Dec;18 Suppl 3:S6-9. doi: /j.parkreldis Epub 2012 Aug 3. PubMed PMID:

36 TAKE-HOME MESSAGES Parkinson s disease is common particularly in the elderly and likely to be encountered in the patients in palliative care. Patients may experience motoric and non-motoric symptoms and disabilities. Further the compromised patient is at risk for complications from and due to the treatment of Parkinson s disease. But many are eminently treatable.