Parkinson ’ s Disease

1. Parkinson’s Disease THERAPY IN NEUROLOGY COURSE, 2015 MOVEMENT DISORDERS

2. Antes de iniciar tratamiento • Esté seguro del diagnóstico • En autopsias hasta 20 % otras causas. • En cada consulta replantearse el dx , a veces sólo el tiempo hace aparentes otros Dx ( PSP, MSA )

3. Características clínicas a favor de PK: • Inicio unilateral o asimétrico. • Tremor clásico de reposo. • Beneficio sostenido con levodopa y desarrollo eventual de fluctuaciones y disquinesias. • No historia de exposición a medicamentos bloqueen DA un año antes del inicio de sx.

4. Características atípicas de PK: • No respuesta a levodopa. • Caidas tempranas . • Rápida progresión ( Signo silla de ruedas ) • Signos bulbares tempranos. • Demencia temprana , delirios , alucinaciones . • Disautonomía temprana y prominente. • Signos no esperados en PK : apraxia , ataxia , piramidal , etc. • Sacadas verticales lentas /parálisis mirada superior.

5. Tratamiento temprano PD A 65 year executive secretary is seen for a 9mo history of tremor of the dominant right hand. All movements with the right hand are slower and she tends to drag the right foot. The following activities take more time and effort:writing, typing, dialing the phone, applying makeup, getting dressed, and preparing food. Others have asked why she limps and she finds this embarrassing. The exam confirms features of PD. How should she be treated?

6. Tratamiento temprano del PD : considerar • Qué tanto le afecta los síntomas personal /profesional ? • Edad • Comorbilidad ( sueño ) • Sensibilidad efectos secundarios. • Costo

7. Se debe postponerlevodopa para evitar fluctuaciones futuras ? • Levodopa vs agonista como tx inicial ( levo es más probable que produzca DK y fluctuaciones ). • Sin embargo a 5 a son leves y no discapacitantes. • Considerar el beneficio clínico de levodopa /efectos sec de los agonistas .

8. Levodopa • No postponer si síntomas son problemáticos. • No justificación para LEVODOPAPHOBIA • Iniciar levodopa 100/25 mg ( tid ) • Discutir expectativas de tx ( puede que tremor no resuelva o necesite altas dosis ) • No ventaja con levodopa de liberación extendida.

9. No beneficio y aumento de DK si se inicia con carbidopa/levodopa/entacapone • Puede ser horario de cada 4 horas , sin comidas ( no necesario al inicio ) • Muchos pacientes no necesitan levodopa HS. • Mayores de 70 A levodopa como primera opción ( pocas fluctuaciones motoras )

10. Agonistas • Ej bromocriptina , pramipexole • Ideal paciente joven con sx leves. • Menos eficaz que levodopa . • Ventaja : dosificación ej 1 o bid. • Vigilar por ICD ( impulse control disorders ) • En pacientes con somnolencia o insomnio observar .

11. Otras opciones • Amantadine • Inhibidor MAO-b ( no probado efecto neuroprotector )

13. Manejo fluctuaciones motoras . • A 66 year old man with a 5 year history of PD can now feel when it is time to take levodopa as he starts to shuffle, is slower, and has return of tremor. • He takes carbidopa/levodopa 25/100, 2 tablets at 7am, noon and 6pm.

14. La primera fluctuación motora es fin de dosis ( end-of-dose wearing off ). • Antes de un ajuste si al paciente esa pérdida de efecto no le preocupa no se hacen cambios ( ej un retorno del tremor antes de la sgte dosis ) .

15. Opciones • Disminuir intervalo entre tomas ( es mejor al inicio no aumentar dosis ) • Agregar agonista , inhibidor MAO ( selegelina , rasagalina ) o inhibidor COMT ( entacapone ). • Considerar apomorfina.

17. Síntomas al despertar: distonía y aquinesia • A 61 year old woman with a 12 year history of PD notices that when she first gets out of bed in the morning that her foot turns in and is painful. This makes it very difficult to ambulate. About 30 min after taking levodopa it resolves.

18. Opciones de manejo (Síntomas al despertar: distonía y aquinesia ) • Levodopa CR al acostarse ? ( no efecto tan prolongado ) • Si se despierta a miccionar levodopa CR o regular lo más cercano a la hora de despertarse. • Tomarse una levodopa regular apenas se despierte ( en agua carbonatada se absorbe más rápido ) • Apomorfina • Toxina botulínica.

20. Manejo de las disquinesias inducidas por levodopa • A 71 year old man with a 15 year history of PD has dyskinesias which usually start as soon as levodopa kicks in and include head bobbing, tongue protrusion, facial grimacing and truncal twisting. He is taking carbidopa/levodopa 25/250 every 3-4 hours, rasagiline and pramipexole 0.5mg tid.

21. Puntos a aclarar de las disquinesias • A menudo incomodan más a los demás que al mismo pcte. • Si no es problemático no tratar . • Siempre solicitar que el paciente haga un diario con las horas de aparición . • Si se confunde con tremor acentuado esperar a ver una crisis en la oficina .

22. Manejo disquinesias problema. • Reducir dosis de levodopa . Y de ser posible intervalo . • Aumentar agonista. • Suspender inhibidores de la MAO-B o de la COMT.

23. Manejo DK • Asociar amantadina. ( a menudo con efecto dramático y largo tiempo ). • Antagonista receptores de NMDA. • Considerar Estimulación cerebral profunda ( Gpi )

24. Estimulación profunda ( cuando considerar ) • Tremor discapacitante y refractario a t xy /o fluctuaciones motoras a pesar de tx óptimo • Debe mantenerse ON con la levodopa. • Cognitivo/psiquiátrica estable. • Levodopa intestinal gel : una alternativa potencial.

25. Puntos a considerar con DBS • El dx debe ser PK no Pk plus. • Realizarse en centros multidisciplinarios y con experiencia. • Definir expectativas ( ej balance no mejor , excepto que fuera parte de los periódos OFF ), efecto puede observarse 10 años después pero al progresar la enfermedad el beneficio tiende a no ser evidente .

26. Marcapaso no con la eficacia esperada – considerar -: • Dx • Colocación • Parámetros de estimulación . • Medicamentos para PK • Comorbilidad como depresión .

28. Falls in Parkinson’s disease •  Try to determine when/why falls happen •  Often seen in setting of executive dysfunction with impulsivity, decreased insight and impaired judgment •  Optimize motor fluctuations (minimize off time) •  Check for orthostatic hypotension

29.  Economizemedications (TCAs, benzodiazepines) •  Physicaltherapy/Tai Chi •  Home safety: bars in bathroom, removethrowrugs, banistersonstairs, lighting at night, etc. •  Educatepatient: avoidcarryingthingswhilewalking, handonbanister, etc. •  Walker (mypreferenceisUStepbutotherswith 4 wheels are fine); hikingpoles; laser cane •  Kneepads

30. U step walker

31. Laser cane

32. Manejo síntomas no motores

33. Orthostatic hypotension • Be alerttopresentations of OH otherthantraditionalnear-syncope •  fatigue •  cognitiveimpairment •  falls •  coathangersign •  Look for OH •  First try toeliminateany causal orcontributingmedicationsespecially DA agonists, TCAs, antihypertensives

34. Non-pharmacologic measures: • increase water/salt intake; avoid standing quickly; avoid large meals and alcohol; avoid hot baths or showers; support hose (impossible for most patients with PD to use); keep the head of the bed propped up; recognize the earliest symptoms and sit or use an isometric exercise

35. Medicationswhich can be considered • o fludrocortisone • o midodrine • o droxidopa • o Be sure to use last dose early to avoid supine hypertension overnight

36. Sialorrhea • o Drooling is a common problem in PD. For most patients it is an annoyance but for some,particularly with advanced PD, it can be problematic. Pooling of saliva in the mouth can interfere with talking and poses a risk for aspiration. There are relatively few proven therapies for treatment of drooling. • o Options: anticholinergics (intraorally vs systemic) • o I typically try oral atropine drops (1% ophthalmic solution) with fair success • o Local injection of botulinum toxin into salivary glands is what I have found most beneficial

37. Diplopia • Assuming there is no other cause unrelated to PD (myasthenia, ischemic VI palsy, etc.), then diplopia in PD is usually due to a combination of an exphoria combined with convergence insufficiency It is typically horizontal and worse at near

38. Treatment options • o Keep one eye closed while reading • o Prism • o Eye patch • o Reading glasses with masking tape over one of the lenses

39. Sleep Disorders

40. Excessive daytime sleepiness •  Inquireaboutsleephygiene •  Criticalevaluation of medications (esp DA agonists) •  Considerprimarysleepdisorder (OSA) •  Common in advanced PD especiallywithdementia •  Oftendifficulttotreat •  May use ModafanilorArmodafanil (I havenotbeenimpressed) •  Methylphenidate

41. Insomnia • Remember, insomniais a symptoms, not a disease •  Try to determine cause forinsomnia •  Importantconsiderations: • PD symptomsinterferingwithinitiatingormaintainingsleep (tremor, difficultturning, cramps, etc.) which can be improvedwithadjustment of PD meds (e.g., controlledreleaselevodopa HS) • o Depression/insomnia • o Nocturia

42. REM behavioral disturbance • Dream enactment •  Very common in PD •  May precede PD by years or decades •  Need history from bed partner •  Can cause “falling” out of bed •  If infrequent and mild, not in need of treatment •  Move potentially injurious objects from around bed •  Options: low dose clonazepam (I start with 0.125mg) or melatonin

43. Depression and anxiety in PD • Both are very common in PD and often inadequately recognized and treated • o Mood disorders may fluctuate with motor fluctuations •  Panic when off •  Despondency when off •  Hypomania when on

44. Treatment •  Recognition/education •  TCAs, SSRIs, SNRIs (relatively limited evidence base and no clear benefit of one vs • another) •  ECT if refractory or intolerant of meds

45. Impulse control disorders and dopamineagonistwithdrawalsyndrome • o Approximately 15% of patientswith PD willdevelopan impulse control disorder (ICD) • o Themostcommonincludegambling, shopping, sexual behavior, eating and hobbyism • o They are oftenchallengingtodiagnose and are often done surreptiously • o They are mostcloselyassociatedwithdopamineagonists and are doserelated

46. Otherpotentialriskfactorsincludemale sex, youngerage and youngerage of onset of PD; • prior history of ICD includingsubstance abuse and gambling and impulsivepersonalitytraits • o Prior toinitiatingdopaminergictherapy, especiallywith a DA agonist, patient and theirfamilyshould be warnedaboutthispotentialsideeffect • o Itisimportanttoscreenfor ICD at eachvisit

47. The treatment of choice for a ICD is gradual reduction/withdrawal of a DA agonist or the • presumed offending drug (which can include levodopa and amantadine) • o Recognize that withdrawal of a DA agonist can be problematic and this is known as the • “dopamine agonist withdrawal syndrome” which includes anxiety and insomnia

48. Dementia in PD • Dementiaiscommon in PD, affecting at least 40% of patientsoverthecourse of thedisease, withsomestudiesreporting up to 80%. • Importanttoconsider remediable causes and notjustassumeitis PD dementia • Education of thepatient, caregiver and family • When PD iscomplicatedbydementia, itadds a muchgreaterburdentothecaregiver. • Significant factor in predictingnursing home placement

49. Firststep in managementistoeliminate as manydrugs as possible • o Cholinesteraseinhibitors can be used. Recentevidence-basedreviewsdemonstrategreatestevidenceforrivastigminewithlessconvincingevidencefordonepezilgalantamine and Memantine Impartrealisticexpectationsif a cholinesteraseinhibitorisused. No provenneuroprotective • effect of cholinesteraseinhibitorsfor PDD so if no meaningfulbenefit, discontinue.

50. Psychosis in PD • Commonproblembutuncommonlyaddressed • o Patients/caregiversreluctanttobring up • o Importanttoaskabout, especiallywhen PD iscomplicatedbycognitiveimpairment • o Includes •  Delusions (infidelity [delusionaljealousy], paranoia) •  Hallucinations: visual (formed) , tactileorauditoryhallucinations •  Illusions