Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0030567 (Parkinson's disease)
63,064 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Treatment of parkinsonism becomes more difficult as the disease progresses, and results from increasing neuronal degeneration, side effects from antiparkinsonian medications, or most often, a combination of each. Neurodegenerative parkinson symptoms may result from substantia nigra destruction, or from other areas in the nervous system. These include the cortex (cognitive and psychiatric disorders), brainstem (bulbar abnormalities), intermediolateral cell column (autonomic disturbances), among others. Medication side effects produce motor fluctuations, dyskinesias, delirium, hallucinations, psychosis, orthostatic hypotension, sleep disorders, and a host of other well-recognized complications. This article is divided into sections concerning motor fluctuations, gait difficulty bulbar disturbances, autonomic disturbances, sleep disorders, cognitive disorders, and psychiatric disorders, and is an attempt to provide the reader with strategies for treating common complications in the advanced Parkinson's disease patient.
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PMID:Managing late complications of Parkinson's disease. 1009 88

Psychotic symptoms have become increasingly common in patients with idiopathic Parkinson's disease and other parkinsonian syndromes. This increased prevalence of psychoses is in part a reflection of the greater longevity of people with Parkinson's disease and, to a certain extent, is a consequence of our success in treating the motor symptoms of these syndromes. The psychotic symptoms associated with Parkinson's disease can be as varied as the motor symptoms. They stem from interactions between the underlying neuropathologies of the syndromes and the adverse effects associated with chronic antiparkinsonian drug administration. In patients with advanced Parkinson's disease, there is also a high prevalence of affective comorbidity. This increase in affective symptoms and the relatively high incidence of cognitive and affective side effects of the antiparkinsonian medications contribute to the increase in psychoses observed in these older patients. The most significant risk factors for developing psychosis in Parkinson's disease are (1) coexistence of dementia, (2) protracted sleep disturbances, and (3) nighttime use of long-acting dopaminomimetics. This article reviews the phenomenology, pathophysiology, and treatment of psychosis associated with parkinsonism and discusses how atypical antipsychotic medications have revolutionized the management of the symptoms and improved the quality of life of those affected.
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PMID:Management of psychotic aspects of Parkinson's disease. 1033 70

The frequency of sleep complaints in patients with Parkinson's disease (PD) is estimated to be between 60-90% and a variety of either disease-related or secondary mechanisms and the dopaminergic treatment itself contributes to the development of different sleep disturbances. These comprise slight, fragmented sleep with increased number of arousals and awakenings, and PD-specific motor phenomena such as nocturnal immobility, rest tremor, eye-blinking, dyskinesias, and other phenomena such as periodic and nonperiodic limb movements in sleep, restless legs syndrome, fragmentary myoclonus, and respiratory dysfunction in sleep. Depression and hallucinations/psychosis further complicate the picture. The incidence of REM sleep behavior disorder (RBD) with nightmares and violent behavior is increased in PD and may occur as a preclinical disease-related symptom. A careful sleep history of patients and their partners, polysomnograms when necessary, motor and psychiatric assessments should precede individual treatment strategies, which include adjusting dopaminergic daytime treatment, benzodiazepines for RBD, reduction of anticholinergic drugs, and, if necessary, clozapine for nocturnal psychosis.
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PMID:Sleep dysfunction in Parkinson's disease. 1078 36

The pedunculopontine nucleus (PPN) is located in the dorso-lateral part of the ponto-mesencephalic tegmentum. The PPN is composed of two groups of neurons: one containing acetylcholine, and the other containing non-cholinergic neurotransmitters (GABA, glutamate). The PPN is connected reciprocally with the limbic system, the basal ganglia nuclei (globus pallidus, substantia nigra, subthalamic nucleus), and the brainstem reticular formation. The caudally directed corticolimbic-ventral striatal-ventral pallidal-PPN-pontomedullary reticular nuclei-spinal cord pathway seems to be involved in the initiation, acceleration, deceleration, and termination of locomotion. This pathway is under the control of the deep cerebellar and basal ganglia nuclei at the level of the PPN, particularly via potent inputs from the medial globus pallidus, substantia nigra pars reticulata and subthalamic nucleus. The PPN sends profuse ascending cholinergic efferent fibers to almost all the thalamic nuclei, to mediate phasic events in rapid-eye-movement sleep. Experimental evidence suggests that the PPN, along with other brain stem nuclei, is also involved in anti-nociception and startle reactions. In idiopathic Parkinson's disease (IPD) and parkinson plus syndrome, overactive pallidal and nigral inhibitory inputs to the PPN may cause sequential occurrences of PPN hypofunction, decreased excitatory PPN input to the substantia nigra, and aggravation of striatal dopamine deficiency. In addition, neuronal loss in the PPN itself may cause dopamine-resistant parkinsonian deficits, including gait disorders, postural instability and sleep disturbances. In patients with IPD, such deficits may improve after posteroventral pallidotomy, but not after thalamotomy. One of the possible explanations for such differences is that dopamine-resistant parkinsonian deficits are mediated to the PPN by the descending pallido-PPN inhibitory fibers, which leave the pallido-thalamic pathways before they reach the thalamic targets.
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PMID:The pedunculopontine nucleus: its role in the genesis of movement disorders. 1081 16

Sleep disturbances in the elderly may not be a result of the aging process per se, but rather are likely caused by many factors that are amenable to treatment. These factors include medical and psychiatric problems, medications, and circadian rhythm changes, all of which can cause difficulties during sleep at night, and can lead to complaints of insomnia. Other factors that cause disturbances include a high prevalence of specific sleep disorders such as sleep disordered breathing (SDB), periodic limb movements during sleep (PLMS) and rapid eye movement (REM) sleep behavior disorder (RBD). Although these disorders are more prevalent in the older than younger population, they are not exclusive to this age group, and treatment options that are applicable to young adults are also applicable to older adults. On the other hand, dementia and Parkinson's disease are two neurologic disorders that are almost exclusive to the elderly and most often involve sleep disturbances. Because there are many causes of sleep complaints, when considering treatment options one must identify the underlying problem. If caused by illness, effective treatment of a specific medical or psychiatric problem should help alleviate the sleep problem as well. Changes in the timing of drug administration may improve sleep. For the treatment of chronic insomnia, behavior techniques should always be used in combination with pharmacologic therapy, and sedative-hypnotic medications should be considered when appropriate. The treatment of choice for obstructive sleep apnea is continuous positive airway pressure (CPAP). For PLMS, dopaminergic agents are most effective. For RBD, clonazepam effectively controls the aversive sleep behaviors. Sleep disturbances secondary to dementia and Parkinson's disease are usually problematic for the patient as well as the caregiver, whether in the home or in the nursing home. Proper management of these disturbances is beneficial in terms of delaying institutionalization and reducing nursing care costs, as well as improving the quality of life for both patient and caregiver.
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PMID:Sleep Disorders in the Elderly. 1112 56

Somatic and psychiatric illnesses are commonly associated. Cardiovascular disorders, Parkinson's disease and stroke are especially often associated with depression as also anxiety and sleep disturbances. Psychophytopharmaceuticals, which are usually well tolerated, are highly suitable for this purpose. To treat mild to moderate episodes of depression, extracts of St. John's Wort are employed, but recently reported interactions with coumarin, theophylline and also estrogen preparations, need to be considered. Unspecific anxiety states can be treated with extracts of kava. At present, no herbal preparation can be recommended for the treatment of sleep disorders, as no unequivocal proof of efficacy in patients with such problems has yet been established.
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PMID:[Psychiatric comorbidity in somatic disorders. Psychophytopharmaceuticals are worth a try]. 1143 62

A patient in stage 3-4 of the Unified Parkinson's Disease Rating Scale (UPDRS), or in stage 4-5 of Hoehn and Yahr staging scale, or a patient with 0-50% activities of daily living scale of Schwab and England is considered a Late Parkinson's Disease (LPD) patient. The prevalence of disturbed sleep in Parkinson's Disease (PD) was found to vary according to an objective rating, from 60 to 98%. The factors predicting the quality of life in PD patients are: depression, sleep disturbances and dependence. The present article proposes the insertion of the following items as a chapter in a revised UPDRS based on updated knowledge in sleep arousal disturbances in PD. V. SLEEP-AROUSAL DISTURBANCES: Sleep disturbances 43. Light fragment sleep (LFS) 44. Sleep-related breathing disorders (SRBD) 45. Restless legs-periodic leg movements during sleep (RLS-PLM) 46. REM behavioral disorders (RBD) 47. Sleep-related hallucinations (SRH) 48. Sleep-related psychotic behavior (SRPB) Arousal disturbances 49. Sleep attacks (SA) 50. Excessive daytime sleepiness (EDS). Approaching the treatment of disturbed sleep in LPD means postponement of the institutionalization of the LPD patient, allowing the spouse or the caregiver a quiet nights sleep. This approach consists of three steps, each one of major importance. (1) Correct diagnosis based on detailed anamnesis of the patient, of the spouse or of the caregiver; a one week recording on a symptom diary (log) by the patient or the caregiver; excluding co morbidities. Then choosing the most appropriate sleep test, if necessary: polysomnography (PSG), multiple sleep latency test (MSLT), multiple wake latency test (MWLT), actigraphy or video-PSG. This first step allows the diagnosis of one of the above mentioned sleep-arousal disturbances. (2) The non-specific therapeutic approach consists of: (a) checking the sleep effect on motor performance: beneficial, worse or neutral. (b) Dopaminergic adjustment is necessary due to the progression of the nigrostriatal degeneration and the increased sensitivity of the terminals which alter the normal modulator mechanisms of motor centers in LPD patients. Among the many neurotransmitters of the nigro-striatal pathway one can distinguish two with a major influence on REM and non-REM sleep. REM sleep corresponds to an increased cholinergic receptor activity and a decreased dopaminergic activity. This is the reason why REM sleep deprivation by suppressing cholinergic receptor activity ameliorates LPD motor symptoms. L-Dopa and its agonists by suppressing cholinergic receptors suppress REM sleep. L-Dopa has also an arousal effect on Non-REM sleep, repeatedly awakening the patient and enhancing the fragmentation due to the involuntary movements. (c) Socio-physical assistance. (3) The specific therapy consists of: LFS-Sinemet CR, Tolcapone, Intranasal Desmopressin, Domperidon, Cisapride and neurosurgery; SRBD-CPAP, UPPP, nasal interventions, losing weight; RLS-PLM-Benzodiazepine (Clonazepam), Opioid, Apomorphine infusion; RBD-Clonazepam and dopaminergic agonists; SRH-Clozapine, Risperidone; SRPD-Nortriptyline, Clozapine, Olanzepine; SA-adjustment; EDS-arousing drugs. Each therapeutic approach must be tailored to the individual LPD patient.
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PMID:Approaching disturbed sleep in late Parkinson's Disease: first step toward a proposal for a revised UPDRS. 1148 77

The objective of this work was to determine the predictors of depressive symptoms among spouse caregivers of Parkinson's disease (PD) patients. Little is known about the strain in giving care to PD patients and how the motor, cognitive, and behavioral complications of PD contribute to depression among spouse caregivers. Forty-five consecutive PD patients and their spouse caregivers agreed to be evaluated after a routine clinic visit. Patient demographic data and the presence of hallucinations, delusions, incontinence, and sleep disturbances were obtained. The patients were assessed using the Unified Parkinson's Disease Rating Scale (UPDRS-motor section), Hoehn and Yahr (H&Y) staging, and the Mini-Mental State Examination (MMSE). Depressive symptoms were assessed using the 17-item Hamilton Depression Scale (HAMD-17) and the Beck Depression Inventory-II (BDI-II) on patients and spouses. Thirty men and 15 women had a mean age of 71.5 years (range 53-85), average PD duration of 10 years (range 1-26), a mean "on" H&Y stage of 2.8 and an MMSE mean score of 26 (range 13-30). There was good correlation between the HAMD-17 and the BDI-II scores in both patients (r = 0.69, P = 0.001) and spouses (r = 0.66, P < 0.001). A moderate correlation was noted between the spouse HAMD-17 score and the patient UPDRS-motor score (r = 0.34; P = 0.02), the age of PD onset (r = 0.33; P = 0.02) and patient HAMD-17 scores (r= 0.29; P = 0.05). A stronger correlation was noted between spouse HAMD-17 scores and the years of PD duration (r= 0.43; P = 0.003). There was a significant difference in the mean spouse HAMD-17 scores among PD patients with sleep disturbances versus those who did not (10.2 vs. 6.4; P = 0.04). However, on stepwise regression analysis, only the duration of PD remained significant (adjusted r = 0.17; P = 0.003). No difference was noted with hallucinations, delusions or incontinence. We concluded that the duration of PD appears to be the strongest predictor of depressive symptoms among spouse-caregivers in this small cohort.
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PMID:Predictors of depressive symptoms among spouse caregivers in Parkinson's disease. 1174 46

Many patients suffering from Parkinson's disease complain about chronic fatigue and daytime somnolence. During the last few years attention has been drawn to "sleep attacks", which are supposed to be due mainly to dopamine agonists. Sleep disturbances during the night are quite frequent. It is important to search for the probable causes in each individual case in order to be able to install an efficacious treatment.
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PMID:[Fatigue, daytime somnolence and sleep disorders in Parkinson patients]. 1193 47

The existence of circadian rhythms and their implication in many pathologic processes have been underlined in several diseases but have not been evaluated in Parkinson's disease. The aim of this paper is to review diurnal variations of clinical, biologic, or experimental factors described with Parkinson's disease. Clinical data often report daily fluctuations of motor activity pattern, but the effect of the stage of the disease and the respective roles of drugs are difficult to evaluate. Sleep disturbances in Parkinson's disease patients also reveal alterations of circadian rhythms. Autonomic dysfunction, described in Parkinson's disease, reveals numerous alterations in circadian regulations including loss of circadian rhythm of blood pressure, increased diurnal blood pressure variability, and postprandial hypotension. Many biologic indices such as cortisol, catecholamines, and melatonin are also altered. Circadian rhythms in dopaminergic systems as well as possible daily fluctuations in kinetics of drug treatments are likely involved in such variations. Few clinical studies have been devoted to circadian patterns of drug response. As for other diseases where biologic rhythms are concerned Parkinson's disease therapy may be influenced by further understanding of circadian influence.
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PMID:Biologic rhythms and Parkinson's disease: a chronopharmacologic approach to considering fluctuations in function. 1215 6


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