Parkinson's disease (PD)second most common age-related neurodegenerative disorder

clinical symptoms, motor symptoms

Nonmotor symptoms

The Dark Side of the MoonNonmotor Symptoms in Parkinson's disease

Nonmotor Symptoms P.DDepressionAnxietyPsychosisDementiaFATIGUE Sleep DysfunctionAutonomic DysfunctionSensory Dysfunction

Depression

Common ( 7 to 76%) may represent the first manifestation of PD comparison with patients without PD: anxiety pessimism irrationality suicidal ideation

higher frequency of MDD in patients with akinetic-rigid subtype when compared with a tremor-dominant

It is still controversial whether Depression has been associated with a worse motor progression

TreatmentThere is no clear consensus regarding the use of antidepressants for the treatment of depression in patients with PDthe antidepressant effect of PD therapy has to be evaluated before adding specific antidepressive therapy

Dopamine agonists reduce depression in PD Pramipexole demonstrated to have the same efficacy of SSRI in MDd beneficial effect on mood and motivational symptoms in PD patients without depression Ropinirole reduce depression

MAO)-B inhibitors weak antidepressant properties

TCAs effective in treating depression not well tolerated due to anticholinergic side effects

SSRI effective in treating depression potentially serotonin syndrome aggravating motor symptoms recent studies evidenced that SSRIs only rarely aggravate motor symptoms in PD, and that sertralinemay be the least mirtazapine (presynaptic 2-antagonist) effective in treating depression demonstrated in reducing Parkinsonian tremor

drug selection should be based on potential advantages versus potential side effects.

Anxiety

affects nearly 40% of patients with PDThe most common anxiety disorders in PD are panic attacks (especially during off-periods)

Benzodiazepines should be used cautiously because they may increase adverse effects

Buspirone, with dopaminergic effects, is well tolerate 10 40 mg

Psychosis

The most common type of psychotic symptoms in PD are hallucinations (visual )and delusions (paranoid)

Hallucinations in treated PD patients is 1540%

Delusions occur in up to 10% of patients.

when the hallucinations occur early in the course of the disease, especially without any dopaminergic treatment, a diagnosis of levy body disease should be considered.

treatmentExcluding general causes of hallucination/confusion(fever & metabolic dysfunction & drug)Reducing the dose or the number of antiparkinsonian drug anticholinergic drugs amantadine (COMT) inhibitors dopamine agonists Levodopa Atypical antipsychoticsCholinesterase inhibitors

Atypical antipsychotics Clozapineand quetiapinedo not appear to worsen parkinsonism as do other atypical , and the typical neuroleptics clozapine is the only atypical antipsychotic fully recommended for the treatment of psychosis in PD. because of the side effect of agranulocytosis, which requires frequent blood testing Quetiapine represents the most commonly used antipsychotic treatment in PD patients.

Cholinesterase inhibitors rivastigmine, the only cholinesterase inhibitor that is US FDA-approved for the treatment of dementia in PD, demonstrated an improvement in neuropsychiatric symptoms in PD patients with dementia

Dementia

higher risk of developing dementia 30 -40%

mean duration of PD before diagnosis of dementia is 10 years

subtle cognitive deficits can be identified in the early stages

Risk factors for PDD include: age visual hallucinations severe motor symptoms : rigidity postural instability gait disturbances

Management of dementia in PDsystematic assessment

Anticholinergics, amantadine and benzodiazepines should be avoided because of their relationship with a reduction in cognitive performances.

Dopamine agonists should be used cautiously Cholinesterase inhibitors

Cholinesterase inhibitors donepezil and rivastigmine have been demonstrated to significantly improve cognitive impairment

memantine, can improvement of cognitive symptoms, even if its triggering effect on psychosis may limit the use in clinical practice.

FATIGUEFatigue is a common problem in patients with Parkinson disease

Treatment of fatigue in PD begins with an attempt to identify the cause. Excessive daytime sleepiness and depression are both the most common and the most treatable identifiable causes.

True fatigue unassociated with sleepiness or depression is more difficult to treat

Suboptimally treated bradykinesia sometimes presents as subjective fatigue

Medications used for empiric treatment of fatigue, such as amantadineand stimulants, such as methylphenidate

Sleep Dysfunction

Sleep dysfunction 75 to 98% in the PD population

Disorders of sleep initiation and maintenance Excessive daytime sleepiness (EDS) Sleep attack (SA) Rapid eye movements behavior disorder (RBD )

Disorders of sleep initiation and maintenanceSleep fragmentation, the most common manifestation

characterized by reduction in the stages III/IV or REM sleep

could be due to : motor manifestations of PD, such as o dystonia and cramp bladder dysfunction, such as nocturia. Restless-legs syndrome (RLS) Sleep apnea

Treatment should include good sleep hygiene Improved control of motor symptoms of PD Treatment of RLS (dopaminergic agents)

Hypnotic agents is not first line for potential side effects, specifically confusion and daytime sleepiness. There are no controlled data on any specific hypnotic agent in PD Ramelteon, a new hypnotic agent approved for sleep initiation insomnia, which is a ligand of melatonin receptors, may be useful in PD ( 8 mg orally once a day, 30 minutes prior to bedtime)

Excessive daytime sleepiness (EDS)very common among patients with PD, up to 50%

Factors that contribute to EDS is motor disability, nocturnal sleep impairment depression and dementia,

higher prevalence of somnolence in patients treated with dopamine agonists

modafinilhas notbeen effective for treating drowsiness in patients with PD.

Sleep attack (SA)sleepiness that occurs without warning

Patients may be unaware of prodromal sleepiness

dopaminergic drugs provoke excessive daytime sedation

Rapid eye movements behavior disorder (RBD )prevalence in PD patients ranges between 33 and 60%

male > female this male predominance are not yet known

treated with clonazepam in small doses (0.251 mg) dopaminergic agents (DA , levodopa) donepezil Melatonin was reported to be effective at doses of 312 mg.

Autonomic Dysfunction

Cardiovascular DysfunctionGastrointestinal SymptomsUrinary & Sexual DysfunctionHyperhydrosis

Cardiovascular Dysfunction

PD patients have higher BP at the off-stage than at on-stage

patients with the onoff type of motor fluctuation have higher resting heart rate, greater orthostatic BP

Early diagnosis and symptomatic treatment of orthostatic hypotension can greatly improve quality of life and, improve cardiovascular mortality

Treatment

reduction of dopamine agonists is often necessary

Domperidone, a peripheral dopamine-blocking agentreduction of antihypertensive drugincrease BP -adrenergic agents such as midodrine salt-retaining mineralcorticoids (e.g., fludrocortisone). Pyridostigmine was reported to be effective in neurogenic orthostatic hypotension but has not been specifically tested in PD.[ Nonpharmacological elevation of the head of the bed by 1030, increase in salt and fluid intake and the use of waist-high compression stockings.

Gastrointestinal Symptoms

Constipation exercise, dietary modifications, increases in fluid intake and ultimately use of laxatives (Psyllium, bisacodyl) coexistent abdominopelvic dyssynergia could be worsened by the use of laxatives

recalcitrant constipation neostigmine, symbiotic yogurt containing components, botulinum toxin injections and sacral nerve stimulation.

Dysphagia the risk of food inhalation no evidence of increased survival in patients receiving enteral tube feeding.

Nausea often due to dopamine replacement therapy adjustment of the timing of levodopa therapy in relation to food and the use of domperidone.

Hypersalivation reduced ability to swallow rather than overproduction of saliva Anticholinergics and injection of botulinum toxin into the salivary glands are therapeutic option

Urinary & Sexual Dysfunction

Patients usually develop detrusor muscle hyperactivity Oxybutynin and tolterodine memory loss and constipation, must be taken into consideration

Sexual dysfunction: male erectile dysfunction .60% of PDSildenafil citrate has been found to be safe and effective

Hyperhydrosisrelated to hypothalamic dysfunctionTreatment options for hyperhydrosis are limited.Propranolol has been helpful in some cases.

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