Transcript Non motor symptoms of PD File

Non motor symptoms of PD
JM Trejo, MD
Non motor symptoms of PD
INTRODUCTION
• Disabling but little regarded
• Autonomic dysfunction , sleep and
pain/sensorial symptoms
• Appear early but get worse
SUMMARY
• A-We will address treatment of Autonomic
dysfunction , sleep and pain/sensorial
symptoms
• B-Treatment of psychiatric complications of
PD, and cognitive impairment and dementia
associated to PD
Treatment OF AUTONOMIC
DYSFUNCTION
• Both central and peripheral
• Heterogeneous
• Influenced by anti-Parkinson drugs
Orthostatic hypotension-1
• Drop of at least 20 mmHg in systolic blood
pressure or 10 mmHg of diastolic
• Sympathetic denervation of arteries
• Orthostatic intolerance,presyncope-syncope
or asymptomatic
• Worse in advanced stages
Orthostatic hypotension:
General treatment-1
• Rule out other aggravating conditions (as
anemia)
• Consider possible adverse effects drugs (stop
or reduce hypotensive drugs , consider
reducing dopaminergic drugs)
• Frequent and light meals, increase water
intake (2-2.5 liters / day) and salt (more than 8
g / day
Orthostatic hypotension:
General treatment-2
• No alcohol and avoid caffeine at night
• Physical treatment : sleep with elevated (2030 cm) bed headboard.
• Moderate exercise
Orthostatic hypotension:
Pharmacologic treatment 1
• Domperidone: Dose: 10 mg every 8 hours
• Fludrocortisone: Dose: 0.05-0.2 mg/day.
Monitor edema or supine hypertension and
to control sodium levels ( hypernatremia) and
potassium ( hypokalemia).
• Midodrine: Dose: 2.5-10 mg every 8 hours.
Monitor the possibility of supine
hypertension. Contraindicated in heart disease
Orthostatic hypotension:
Pharmacologic treatment 2
• L -threo- dihydroxyphenylserine (L- DOPS ) or
droxidopa: Dosage: 100-300 mg every 8 hours.
• Less evidence : piridostigmine , indomethacin,
octreotide , ephedrine, yohimbine,
dihydroergotamine, desmopressin and
erythropoietin.
Table 1. Pharmacological treatment of autonomic dysfunction in Parkinson's
disease : recommendations based Evidence of the Movement Disorder of
Society ( MDS ), 2011
ORTHOSTATIC HYPOTENSION
Evidence is lacking
SIALORREA
Glycopyrrolate
Possibly useful
Botulinum Toxin
Clinically useful
DRUG PROVOKED NAUSEA/VOMITING
Domperidone
Possibly useful
CONSTIPATION
Macrogol in osmotic solution
Possibly useful
URINARY DYSFUNCTION
Evidence is lacking
ERECTILE DYSFUNCTION
Sildenafilo
Evidence is lacking
HYPERHIDROSIS
Botulinum toxin (axillar/palmar)
Evidence A/B (AAN)
Sialorrea (drooling)
• In advanced stages.
• Reduced swallowing
• Specific exercises.
• Chewing gum.
Sialorrea
Pharmacologic treatment.
• Sublingual1% atropine ophthalmic solution
twice daily.
• Sublingual ipratropium bromide ( up to 4
times/week)
• Glycopyrrolate: Dose:1 mg every 12 hours.
• Botulinum toxin in parotid and submandibular
glands.
Gastrointestinal dysfunction:
Delayed gastric emptying
• Postprandial discomfort.
• Delayed ON periods.
• Improves with domperidone (10 mg every 8
hours ), as nausea and vomiting provoked by
dopaminergic medication does.
Gastrointestinal dysfunction:
Constipation
• Constipation is very common.
• Rule out other diseases.
• Rule out pharmacologic adverse effects
(anticholinergics , tricyclic antidrepresants , etc).
• Diet : adecuate hydratation and diet high in fiber
content.
• Psyllium or methylcellulose
• Moderate exercise.
Constipation:
Pharmacologic treatment-1
• Lactulose or polyethylene glycol (macrogol,
Movicol®).
• Movicol 13.8g sachet, powder for oral
solution. Dose: 1-3 sachets each day.
• Lubiprostone: Dose: 24 mcg/12- 24 hours
Constipation:
Pharmacologic treatment-2
• Docusate sodium: Dose: 50-150 mg / day.
• Glycerin suppositories and cleansing enemas.
• Paradoxical anal sphincter contraction:
apomorphine or botulinum toxin infiltrations
of puborectalis muscle
Urinary dysfunction
• Nocturia and urinary urgency or frequency.
• Hyperactivity of the detrusor muscle.
• Obstructive symptoms and incontinence are
less frequent.
Urinary dysfunction
General treatment
• Rule out other diseases ( urinary tract
infections , diabetes, prostatic , etc).
• Consider drug adverse effects.
• Reduce the intake of liquids before bedtime.
Urinary dysfunction
Pharmacological treatment-1
• Detrusor hyperactivity:oxybutynin (10-20 mg/
day) or tolderodine (1-2 mg every 12 hours).
Contraindicated in glaucoma and adverse
effects (dry mouth, slow gastrointestinal motility ,
worsening of obstructive uropathy and mental confusion).
• Nocturnal polyuria: intranasal desmopressin.
Adverse effects: hyponatremia and fluid
retention.
Urinary dysfunction
Pharmacological treatment-2
• Trospium Chloride and detrusor infiltration
with botulinum toxin improve its overactivity.
• Subcutaneous apomorphine and Prazosine
improve obstructive symptoms.
Urinary dysfunction
Other treatment
• Bilateral subthalamic stimulation can also
improve detrusor hyperactivity.
• Some patients may need intermittent
catheterization, suprapubic catheter or
permanent transuretral.
Sexual dysfunction-1
• Erectile dysfunction , present in 60-70 % of
men with PD.
• Rule out other medical problems ( urologic ,
endocrine , depression, etc. ).
• Consider possible adverse effects of drugs
Sexual dysfunction
Pharmacological treatment
• Sildenafil (Viagra®):Dose: 25-100 mg .
• Alprostadil: cavernous injections or
transurethral suppositories.
• Subcutaneous apomorphine.
Hyperhidrosis
• Other causes: post-menopausia,
thyrotoxicosis, chronic infections, other
systemic diseases.
• Proper hydratation and avoid hot
environments.
• Adjust dopaminergic therapy.
Hyperhidrosis
Pharmacologic treatment
-Beta-blockers in
ON period
hyperhidrosis.
-Axillary or palmar
hyperhidrosis can
be treated with
botulinum toxin
TREATMENT OF SLEEP DISORDERS
• Primary sleep dysfunction.
• Also contribute: motor, autonomic (nicturia)
and neuropsychiatric problems ( anxiety,
depression, dementia) drug adverse effects.
• Main sleep problems are insomnia,
hypersomnia, REM sleep behaviour disorder
and periodic limb movements.
Insomnia
• The most common sleep disturbance in PD.
• Both difficulty to start sleeping (sleep onset
insomnia) and to maintain it (maintenance
insomnia).
• Avoid diurnal naps and stimulants at night and
have adequate environmental conditions to go
to sleep
Insomnia: General Treatment
• Treat other causes: sleep apneas , REM sleep
behavior disorder, restless leg syndrome ,
periodic limb movements.
• Discard adverse drug effects: selegiline,
amantadine.
• Establish regular sleep patterns , make some
exercise during the day , restrict diurnal naps
Insomnia:Pharmacologic Treatment-1
• Prolonged release dopamine agonists either
oral (ropinirole, pramipexole ) or transdermal
(rotigotine).
• Slow absorption levodopa ( 200 mg / night).
• Sedating antidepressants ( amitriptyline,
trazodone, mirtazapine , mianserin, etc. . )
Insomnia:Pharmacologic Treatment-2
• For a limited period: Lormetacepam,
zolpidem, zopiclone, eszopiclone.
• Melatonin: Dose: 3-5 mg / night (maximum 50
mg )
Hypersomnia
• Diurnal sleepiness is common, especially in
advanced stages.
• Sometimes sudden sleep attacks.
• Can be due to nocturnal sleep disorders.
• Can be worsened by dopaminergic drugs.
Hypersomnia: General treatment
• Treat nocturnal insomnia causes.
• Reduce dose of drugs involved (dopamine
agonists…).
• Do not drive if sleep attacks.
Hypersomnia: Pharmacologic
Treatment
• Modafinil: Dosage: 200-400 mg / day. Because
adverse effects, in general do not use.
• Sodium oxybate. Dose 3-9 g / night (in two
divided doses)
REM Sleep behaviour Disorder
• In REM sleep behaviour disorder, muscular
tone is maintained.
• Frequent parasomnia
• Years before motor symptoms.
• Motor activity can damage patient o spouse.
REM Sleep behaviour Disorder
General Treatment
• Discard mimics: nightmares, periodic limb
movements, sleep apnea.
• Antidepressants or bisoprolol can worsen it.
• safe sleep environement
REM Sleep behaviour Disorder
Pharmacologic Treatment
• Clonazepam: Dose: 0.5-2 mg / night.
• Melatonin: dose: 3-12 mg / night.
• If associated dementia: rivastigmine,
donepezil or memantine.
Restless legs syndrome and periodic
limb movements.
• Urge to move the legs at the end of the
evening or during the night.
• In 20% of patients.
• Some patients may associate periodic limb
movements during sleep.
Restless legs syndrome and periodic
limb movements: General Treatment
• Discard iron deficiency, renal failure or
polyneuropathy.
• Reduce dopaminergic blockers,
antidepressants, antihystaminics or calcium
antagonists.
• Avoid stimulants such as caffeine
• Limb mobilization, baths , massage and
relaxing exercises
Restless legs syndrome and periodic
limb movements: Pharmacologic
Treatment
• Prolonged release dopamine agonists either
oral (ropinirole, pramipexole ) or transdermal
(rotigotine).
• Slow absorption levodopa ( 200 mg / night).
• Clonazepam ( 0.5-2 mg/night).
• Other: neuromodulators ( gabapentin ,
pregabalin , carbamazepine, etc. . ) and
opioids in refractory cases (codeine ,
dextropropoxifen , oxycodone , etc. . ) .
TREATMENT OF PAIN AND
SENSORIAL SYMPTOMS-1
• Pain in 80%. Different
types:
– Muscoloskeletal: due to
akinesia or overcontraction
– Radicular and neuropathic
pain due to other diseases is
worsened
– Dystonic pain : Striatal toe in
OFF phase.
TREATMENT OF PAIN AND SENSORIAL
SYMPTOMS-2
• Primary parkinsonian pain: improve partially
with l-dopa.
• Discomfort associated with akathisia (a
sensation of internal unrest): improve partially
with l-dopa.
• Restless legs syndrome
• More than one type may be present
TREATMENT OF PAIN AND SENSORIAL
SYMPTOMS: General Treatment
• Treat orthopedic, rheumatologic or neurologic
concomitant diseases
• Physiotherapy program suited to the
predominant diseases
TREATMENT OF PAIN AND SENSORIAL
SYMPTOMS:Pharmacologic Treatment-1
• Primary type pain and akathisia: adjust
dopaminergic treatment to reduce
fluctuations and increase dopaminergic tone
• Painful distonia: anticholinergics, baclofen,
clonazepam, botulinum toxin
• Treat anxiety and depression
• Neuropathic or primary type: amitryptiline,
gabapentine, pregabaline
TREATMENT OF PAIN AND SENSORIAL
SYMPTOMS:Pharmacologic Treatment-2
WHO guidelines:
• -Fist level: Non Steroidal Antiinflamatory
Drugs, paracetamol (acetaminophen)
• -Second level: mild opiates (codeine,
tramadol, dextropropoxiphen…)
• -Third level: potent opioids (morphine,
meperidine, fentanilo,…) with domperidone or
laxatives if needed
TREATMENT OF PAIN AND SENSORIAL
SYMPTOMS: Other Treatments
• Subthalamic nucleus or internal globus pallidus
stimulation or surgery improves pain related with
akinesia, rigidity, dystonia
• It also improves primary parkinsonian pain and
akathisia
• OTHER SENSORIAL SYMPTOMS:
• Disturbances of smell : hyposmia , cacosmia
• Visual disturbances : disturbance in color
perception , blurred vision
Psychiatric problems in PD (except
dementia):
• 1-Affective disorders : depression, apathy ,
anxiety
• 2-Psychotic disorders : hallucinations and
delusions
• 3-Disorders of impulse control : compulsive
gambling, Pathological hypersexuality,
punding , etc
• Due to PD pathology or to treatment
TREATMENT OF DEPRESSION. Placebocontrolled antidepressants useful in PD:
• 7. 50% of PD suffer melancholic or major
depression and 50 % minor depression.
• Nortryptiline 50 mg/day
• Venlafaxine 75-225 mg/day
• Citalopram 20 mg/day
• Paroxetine 30-40 mg/day (not 20 mg)
• Sertraline 50-150 mg/day
• Dopaminergic agonist Pramipexol
TREATMENT OF ANXIETY
• Fluctuating: appears 30 minutes before motor
fluctuations so improve motor fluctuations
• Continous:
– short half-life benzodiacepines: alprazolam,
loracepam, oxacepam
– Antidepressants: sertraline, citalopram
TREATMENT OF APATHY
• Is a decrease of conduct aimed at a
goal , of motivation and affective expression.
• In 50% of patients.
• It is associated with dementia
• Not to confuse with depression
• Only evidence of improvement of
Rivastigmine (9-12 mg/day) in PD with
dementia
TREATMENT OF PSYCHOSIS-1
• In 25% of nondemented and up to 65%
demented patients
• Initially visual hallucinations with preserved
insight
• Later visual, auditory, loss of insight,
associated with institutionalization.
• 1-Withdraw in this order until improvement:
anticholinergics, dopamine agonists, rasagiline
or selegiline, tolcapone or entacapone
TREATMENT OF PSYCHOSIS-2
• 2-If depression, antidepressants may improve
hallucinations
• 3-If dementia, try Rivastigmine
• 4-Neuroleptics (risk of worsening motor
symptoms): Quetiapine (25-200 mg/day),
Ziprasidone (20-40 mg/day), Aripiprazol (5-10
mg/day), Olanzapine(2,5-10 mg/day),
Clozapine (25-50 mg) with periodic blood tests
(agranulocytosis risk)
TREATMENT OF DISORDERS
IMPULSE CONTROL
• In 17% of PD with any dopaminergic agonist.
• Pathological gambling, hypersexuality,
compulsive shopping, binge eating, punding
• Underestimated due to lack of comunication
• Withdraw dopaminergic agonist.
• Escitalopram, carbamazepine, topiramate,
quetiapine, may also improve
TREATMENT OF DEMENTIA IN PD
• No specific treatment for Mild Cognitive
Impairment but can improve when treating
concomitant depression or sleep disorder
• Dementia: Rivastigmine (6-12 mg/day)
improves global cognition, executive and
visuospatial, functions and memory. It also
improves apathy and hallucinations.
Non Motor Symptoms Scale 2007
(Severity 0-3; Frequency: 1-4; Score: Severity x Frequency)
NON-MOTOR SYMPTOMS QUESTIONAIRE IN PARKINSON´S DISEASE
BIBLIOGRAPHY
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terapéutica en Trastornos del movimiento. Catalán MJ (ed.).
Editorial Nature Publishing Group Iberoamérica. Madrid,
2013. Pp. 58-74
• 2-Chaudhuri KR , Odin P , Antonini A, Martinez -Martin P.
Parkinson 's disease : the non - engine issues . Parkinsonim
Relat Disord 2011 , 17 : 717-23
• 3-Olanow CW, Stocchi F, Lang AE. Non-motor and nondopaminergic features in Parkinson´s disease. WileyBlackwell. Oxford, 2011.