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Parkinson's disease (PD)

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Parkinson's disease (PD). second most common age-related neurodegenerative disorder clinical symptoms, motor symptoms Nonmotor symptoms. Nonmotor Symptoms in Parkinson's disease. The Dark Side of the Moon. - PowerPoint PPT Presentation

Text of Parkinson's disease (PD)

  • 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.