Transcript 22-Manejo de enfermedad de parkinson y otras distonías

Parkinson’s Disease
THERAPY IN NEUROLOGY COURSE,
2015
MOVEMENT DISORDERS
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 )
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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.
Características atípicas de PK:
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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.
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?
Tratamiento temprano del PD :
considerar
• Qué tanto le afecta los síntomas personal
/profesional ?
• Edad
• Comorbilidad ( sueño )
• Sensibilidad efectos secundarios.
• Costo
Se debe postponer levodopa 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 .
Levodopa
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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.
• 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 )
Agonistas
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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 .
Otras opciones
• Amantadine
• Inhibidor MAO-b ( no probado efecto
neuroprotector )
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.
• 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 ) .
Opciones
• Disminuir intervalo entre tomas ( es mejor al
inicio no aumentar dosis )
• Agregar agonista , inhibidor MAO ( selegelina ,
rasagalina ) o inhibidor COMT ( entacapone ).
• Considerar apomorfina.
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.
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.
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.
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 .
Manejo disquinesias problema.
• Reducir dosis de levodopa . Y de ser posible
intervalo .
• Aumentar agonista.
• Suspender inhibidores de la MAO-B o de la
COMT.
Manejo DK
• Asociar amantadina. ( a menudo con efecto
dramático y largo tiempo ).
• Antagonista receptores de NMDA.
• Considerar Estimulación cerebral profunda (
Gpi )
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.
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 .
Marcapaso no con la eficacia esperada
– considerar -:
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Dx
Colocación
Parámetros de estimulación .
Medicamentos para PK
Comorbilidad como depresión .
Falls in Parkinson’s disease
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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
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Economize medications (TCAs,
benzodiazepines)
Physical therapy/Tai Chi
Home safety: bars in bathroom, remove throw
rugs, banisters on stairs, lighting at night, etc.
Educate patient: avoid carrying things while
walking, hand on banister, etc.
Walker (my preference is UStep but others with
4 wheels are fine); hiking poles; laser cane
Knee pads
U step walker
Laser cane
Manejo síntomas no motores
Orthostatic hypotension
• Be alert to presentations of OH other than traditional
near-syncope
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fatigue
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cognitive impairment
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falls
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coat hanger sign
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Look for OH
First try to eliminate any causal or contributing
medications especially DA agonists, TCAs,
antihypertensives
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
Medications which can be considered
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o fludrocortisone
o midodrine
o droxidopa
o Be sure to use last dose early to avoid
supine hypertension overnight
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
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
Treatment options
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o Keep one eye closed while reading
o Prism
o Eye patch
o Reading glasses with masking tape over one
of the lenses
Sleep Disorders
Excessive daytime sleepiness
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Inquire about sleep hygiene
Critical evaluation of medications (esp DA
agonists)
Consider primary sleep disorder (OSA)
Common in advanced PD especially with
dementia
Often difficult to treat
May use Modafanil or Armodafanil (I have not
been impressed)
Methylphenidate
Insomnia
• Remember, insomnia is a symptoms, not a disease
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Try to determine cause for insomnia
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Important considerations:
• PD symptoms interfering with initiating or maintaining
sleep (tremor, difficult turning, cramps, etc.) which can
be improved with adjustment of PD meds (e.g.,
controlled release levodopa HS)
• o Depression/insomnia
• o Nocturia
REM behavioral disturbance
• Dream enactment
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Very common in PD
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May precede PD by years or decades
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Need history from bed partner
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Can cause “falling” out of bed
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If infrequent and mild, not in need of treatment
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Move potentially injurious objects from around bed
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Options: low dose clonazepam (I start with 0.125mg)
or melatonin
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
• 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
Impulse control disorders and
dopamine agonist withdrawal
syndrome
• o Approximately 15% of patients with PD will
develop an impulse control disorder (ICD)
• o The most common include gambling,
shopping, sexual behavior, eating and
hobbyism
• o They are often challenging to diagnose and
are often done surreptiously
• o They are most closely associated with
dopamine agonists and are dose related
• Other potential risk factors include male sex,
younger age and younger age of onset of PD;
• prior history of ICD including substance abuse
and gambling and impulsive personality traits
• o Prior to initiating dopaminergic therapy,
especially with a DA agonist, patient and their
family should be warned about this potential
side effect
• o It is important to screen for ICD at each visit
• 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
Dementia in PD
• Dementia is common in PD, affecting at least
40% of patients over the course of the disease,
with some studies reporting up to 80%.
• Important to consider remediable causes and not
just assume it is PD dementia
• Education of the patient, caregiver and family
• When PD is complicated by dementia, it adds a
much greater burden to the caregiver.
• Significant factor in predicting nursing home
placement
• First step in management is to eliminate as many
drugs as possible
• o Cholinesterase inhibitors can be used. Recent
evidence-based reviews demonstrate greatest
evidence for rivastigmine with less convincing
evidence for donepezil galantamine and
Memantine
Impart realistic expectations if a cholinesterase
inhibitor is used. No proven neuroprotective
• effect of cholinesterase inhibitors for PDD so if no
meaningful benefit, discontinue.
Psychosis in PD
• Common problem but uncommonly addressed
• o Patients/caregivers reluctant to bring up
• o Important to ask about, especially when PD is
complicated by cognitive impairment
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Delusions (infidelity [delusional jealousy],
paranoia)
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Hallucinations: visual (formed) , tactile or
auditory hallucinations
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Illusions
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If infrequent with retained insight and not-bothersome, not
necessary to treat
o If problematic
Eliminate as many meds as possible (I try to use just levodopa in
advance PD, especially when there is dementia)
Options
Seroquel (despite limited evidence, generally seen as first choice)
Clozaril (risk of leukopenia but most effective and underutilized)
Cholinesterase inhibitors
Pimavanserin (5HT2A inverse agonist): pending approval