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

Four patients affected by severe Parkinson's disease developed leucopenia (900-1200 WBC) during treatment of psychosis (3) or untreatable insomnia (1) with clozapine (37.5-75 mg/day). Clozapine withdrawal was followed by recovery of leucopenia (4000-6000 WBC) in two weeks with no need for the administration of leucokines. After 1-6 months olanzapine was administered (increasing the dose from 2.5 to 10 mg/day) to treat persisting disturbances, but the drug induced severe worsening of parkinsonism and also this drug had to be withdrawn.
 ...
PMID:Leucopenia induced by low dose clozapine in Parkinson's disease recedes shortly after drug withdrawal. Clinical case descriptions with commentary on switch-over to olanzapine. 1121 59

Objective: To assess the long-term safety and efficacy of pramipexole in advanced Parkinson's disease over a four year time period.Methods: This study is an open-label extension trial of pramipexole for Parkinson's disease open to patients completing a double-blind placebo controlled safety and efficacy trial of this drug. Three hundred and six patients entered the trial. These patients had moderate to severe PD (stage II-IV Hoehn and Yahr during off time) and were experiencing motor fluctuations. Patients were titrated over a six week period and then entered a maintenance phase which lasted up to 50 months. Patients were evaluated every 3 months using the Unified Parkinson's Disease Rating Scale (UPDRS II, III and IV) and modified Schwab and England scale (S/E).Results: Sixty-four percent (197) of the 306 patients who entered this study completed it. Patients showed steady improvement over the 6 week ascending dose interval when pramipexole was reintroduced into the trial as the open-label study medication. Over the duration of the trial patients slowly returned to their baseline levels. This was true for all measures evaluated except for the UPDRS part IV. On UPDRS part IV patients remained below their baseline score which indicated an improvement for the duration of the study. Patterns similar to the overall scores were seen when the individual components of the UPDRS scale part II for "on" and "off" periods and part III were evaluated. However tremor during "on" periods showed improvement over baseline for the duration of the trial. The most common adverse events secondary to pramipexole occurring in greater than 10% of patients included dyskinesias, asymptomatic orthostatic hypotension, dizziness, insomnia, and hallucinations.Conclusion: Pramipexole was well tolerated for up to 4 years. Pramipexole treatment appeared to show continued efficacy in the treatment of Parkinson's disease for 3 years in this open-label descriptive study. After 3 years there was a gradual return to baseline motor states perhaps suggesting progression of Parkinson's disease.
 ...
PMID:The long-term safety and efficacy of pramipexole in advanced Parkinson's disease. 1124 92

The objectives of this study were to describe the prevalence of insomnia and depressive symptoms in patients with Parkinson's disease (PD) and to relate those symptoms to health-related quality of life. A total of 102 patients living at home, most of them moderately to severely disabled, were interviewed. Of them 43 patients were women with a mean age of 70 (range 58-79). The mean age for the men was 71 (range 56-80). Time since diagnosis was <2 years for 57%, 2-10 years for 31% and >10 years for 12%. The geriatric depression scale (GDS) and Livingston's insomnia scale were used. The results were related to quality of life as measured with the SF-36 health survey. The prevalence of insomnia was 80%. Moderate depressive symptoms were found in 47% and severe depressive symptoms in 5%. Patients with insomnia or with depressive symptoms had a significantly impaired quality of life on all eight scales of the SF-36. In a stepwise regression analysis the presence of pain and ache and depressive symptoms were significantly related to insomnia. The variables most related to depressive symptoms were Hoehn and Yahr group and insomnia. Hoehn and Yahr groups (more disability) were significantly related to insomnia and depressive symptoms. Thus, insomnia and depressive symptoms are prevalent in PD and influence quality of life and should, therefore, be considered when evaluating patients with PD.
 ...
PMID:Insomnia and depressive symptoms in patients with Parkinson's disease. Relationship to health-related quality of life. An interview study of patients living at home. 1125 Dec 36

Patients with Parkinson's disease can experience a number of sleep disorders, including insomnia, parasomnias and daytime somnolence [specifically, excessive daytime sleepiness (EDS) and sleep attacks]. Insomnia is a frequent and important complaint of patients with the disease. Both the pathology of Parkinson's disease and dopaminergic drugs may contribute to the much higher than expected frequency of sleep fragmentation and disrupted sleep among these patients. In addition, coexisting depression seems to be a major and frequent risk factor for insomnia in Parkinson's disease. After recognising a sleep problem, the first step in management is to examine and diagnose the type of insomnia and possible medical or psychological factors that may disturb nocturnal sleep. The next step is to give the patient appropriate advice on sleep hygiene. Increasing the dosage of dopaminergic drug treatment will often increase sleep disruption and should be avoided unless the patient's sleep is primarily disturbed by the motor manifestations of parkinsonism during the night. Depression should be looked for and if appropriate be treated in any patients with insomnia. If it becomes necessary to treat the patient with an hypnosedative agent, it is important to use a drug with a short half-life and that manifests as few adverse effects as possible the next morning. Up-to-date guidelines for the use of hypnosedatives should be followed. Patients with Parkinson's disease experience a wide range of parasomnias. The majority of behaviours may be related to rapid eye movement (REM) sleep behaviour disorder (RBD) or to a spectrum of symptoms ranging from vivid dreaming to psychosis. RBD is effectively treated with clonazepam. In addition, the atypical antipsychotics have given physicians new and better treatment options for psychotic symptoms in individuals with Parkinson's disease. EDS is common in Parkinson's disease, while sleep attacks seem to be rare manifestations of the disease or its treatment. Significant EDS is found in 15% of patients with Parkinson's disease compared with in 1% of healthy elderly people. Sleep attacks are observed in patients treated with all dopaminergic medications but have recently been brought to prominence because of their association with the newer dopamine agonists ropinirole and pramipexole. Patients with Parkinson's disease should be informed about the possibility of developing sleep problems during the day when prescribed new drugs. Appropriate actions with regard to driving must be taken if significant and persistent daytime somnolence or sleep attacks appear.
 ...
PMID:Sleep disorders in patients with Parkinson's disease: epidemiology and management. 1146 32

The aim of our study was to assess the prevalence of the specific disorders of the circadian rhythm of cortisol and melatonin in the patients with sleep disorders. The group of our patients consisted of 93 persons (25 men, 68 women), from 4-72 years (mean age 38.3 years) with a sleep disorders. These patients were studied on Department of Neurology of 1st Medical Faculty of Charles University in Prague during years 1997-1999. Patients were divided by the clinical diagnosis into many subgroups: idiopathic hypersomnia (IH) 24 patients and other hypersomnias 8, narcolepsy 22, degenerative disorders 9, delay sleep phase syndrome (DSPS) 7, periodic leg movements syndrome (PLMS) 6, insomnia 7 and Parkinson's disease 10 patients. Twelve salivary samples were taken from each patient during a period of 24 hours in order to investigate the circadian secretion pattern of melatonin and cortisol. Salivary melatonin and cortisol levels were estimated by radioimmunoassay in the Department of Physiology of the Academy of Science, Czech Republic. Significant differences were found between our patients and the control group in idiopathic hypersomnia--acrophase of melatonin was delayed and secretion was prolonged. Patients suffered from narcolepsy often displayed multiple peak of melatonin secretion. The peak of the melatonin concentration occurred later in DSPS (non significantly). Low level of melatonin and prolonged signal of melatonin was in Parkinson's disease patients.
 ...
PMID:[Sleep disorders and the 24-hour profile of melatonin and cortisol]. 1170 73

We present a comprehensive review of sleep studies performed in patients with brain lesions complemented by 16 additional personal selected cases and by discussion of the corresponding animal data. The reader is cautioned about the risk of establishing an erroneous correlation between abnormal sleep and a given disorder due to the important inter and intra variability of sleep parameters among individuals. Salient points are stressed: the high frequency of post-stroke sleep breathing disorders is becoming increasingly recognised and may, in the near future, change the way this condition is managed. Meso-diencephalic bilateral infarcts induce a variable degree of damage to both waking and non-REM sleep networks producing and abnormal waking and sometimes a stage 1 hypersomnia reduced by modafinil or bromocriptine, which can be considered as a syndrome of cathecholaminergic deficiency. Central pontine lesions induce REM and non-REM sleep insomnia with bilateral lateral gaze paralysis. Bulbar stroke leads to frequent sleep breathing disorders. Polysomnography can help define the extent of involvement of various degenerative diseases. Fragmented sleep in Parkinson's disease may be preceded by REM sleep behavioural disorders. Multiple system atrophies are characterised by important sleep disorganization. Sleep waking disorganization and a specific ocular REM pattern are often seen in supra-nuclear ophtalmoplegia. In Alzheimer patients, sleep perturbations parallel the mental deterioration and are possibly related to cholinergic deficiency. Fronto-temporal dementia may be associated with an important decrease in REM sleep. Few narcoleptic syndromes are reported to be associated with a tumour of the third ventricle or a multiple sclerosis or to follow a brain trauma; all these cases raise the question whether this is a simple coincidence, a revelation of a latent narcolepsy or, as in non-DR16/DQ5 patients, a genuine symptomatic narcolepsy. Trypanosomiasis and the abnormal prion protein precociously after sleep patterns. Polysomnography is a precious tool for evaluating brain function provided it is realised under optimal conditions in stable patients and interpreted with caution. Several unpublished cases are presented: one case of pseudohypersomnia due to a bilateral thalamic infarct and corrected by modafinil, four probable late-onset autosomal recessive cerebellar ataxias without sleep pattern anomalies, six cases of fronto-temporal dementia with strong reduction in total sleep time and REMS percentage on the first polysomnographic night, one case of periodic hypersomnia associated with a Rathke's cleft cyst and four cases of suspected symptomatic narcolepsy with a DR16-DQ5 haplotype, three of which were post-traumatic without MRI anomalies, and one associated with multiple sclerosis exhibiting pontine hyper signals on MRI.
 ...
PMID:Sleep and brain lesions: a critical review of the literature and additional new cases. 1181 Sep 86

Sleep-disordered breathing may be present in patients with degenerative diseases affecting the brainstem. Indeed, this last structure contains the executive system of rapid eye movement (REM) sleep (tegmentum of the pons), of respiratory drive (medulla oblongata and pons) and motor neurons of upper airways dilators (fifth, seventh, ninth, tenth and twelfth cranial roots). Patients with Parkinson's disease suffer frequently from insomnia, partly caused by nocturnal motor disability, and from REM sleep behavior disorder. In 20 percent of the patients, excessive daytime sleepiness is caused by a sleep apnea syndrome, with a partly levodopa-dependent upper airway dysfunction. In 40 percent of the patients, sleepiness mimics a secondary narcolepsy and may be associated with hypnagogic hallucinations. During supranuclear palsy, REM sleep is progressively curtailed with rare sleep-disordered breathing. Patients with multiple systemic atrophy may present a nocturnal stridor caused by laryngeal palsy and benefit from tracheotomy or continuous nasal positive airway pressure. Seldom sleep and respiratory studies in genetic ataxic diseases suggest a normal respiratory drive, occasional diaphragmatic dysfunction and night hypopneas. During amyotrophic lateral sclerosis, the progressive loss of phrenic nerve leads to a diaphragmatic dysfunction, dyspnea and a lesser survival. Adequate ventilation is jeopardized during REM sleep with a consequent loss of this state.
 ...
PMID:[Respiratory disorders during sleep in degenerative diseases of the brain stem]. 1192 29

We sought to estimate the frequency and nature of sleep disturbances in Indian Parkinson's disease (PD) patients. One hundred forty nine consecutive PD patients attending the Movement Disorders Clinic of the All India Institute of Medical Sciences, New Delhi, India and 115 age-matched healthy controls participated. After clinical evaluation, sleep assessment was done using a 23-question, validated sleep questionnaire. Mean age of PD patients and the duration of illness were 58.37 (S.D. 10.45) years and 5.7 (S.D. 3.85) years, respectively. The mean age of the controls was 56.50 (S.D. 11.45) years (P > 0.05). Sleep problems were seen in 63 (42%) PD patients compared to 12% of controls. These were: insomnia in 32%, nightmares in 32%, and excessive day time sleepiness in 15% of PD patients as compared with 5%, 5% and 6%, respectively, in controls (P < 0.025). Presence of nightmares was significantly associated with higher Hoehn and Yahr score (P < 0.002), high unified Parkinson's disease rating scale (UPDRS) Part I score (P < 0.000) and levodopa dose (P < 0.025). Excessive daytime sleepiness correlated with higher Hoehn and Yahr stage (P < 0.004), and levodopa dose (P < 0.040). The sleep latency was longer in PD patients as compared to controls (P < 0.000). Multiple logistic regression analysis showed association of sleep disturbances with UPDRS Part III, Schwab and England score, levodopa dose, rigidity score, and bradykinesia score. Sleep problems are much more common in PD patients compared to controls (P < 0.001), and correlate with increased severity of disease.
 ...
PMID:Sleep disorders in Parkinson's disease. 1221 Aug 75

Alteration in the isoprenoid metabolites--digoxin, ubiquinone, and dolichol--have been reported in neuronal degeneration (Parkinson's disease), oncogenesis (central nervous system glioma), functional neuropsychiatric disorders (schizophrenia and epilepsy), and immune-mediated disorders (multiple sclerosis). The coexistence of these disorders has been documented in literature and a central dysfunction related to digoxin and the isoprenoid pathway may underlie all these disorders. A family with a high prevalence of Parkinson's disease, schizophrenia, neoplasms, syndrome X, rheumatoid arthritis, and epilepsy has been described. The psychological behavioral patterns of the family were: creativity and high IQ, hypersexual behavior, reduced appetite and eating behavior, insomnia and reduced sleep patterns, increased tendency for spirituality, increased tendency for addiction, less bonding and affectionate behavior, and left handedness/right hemispheric dominance. Digoxin, an endogenous Na(+)-K+ ATPase inhibitor secreted by the hypothalamus, was found to be elevated and red blood cell (RBC) membrane Na(+)-K+ ATPase activity was found to be reduced in all the disorders and in the indexed family studied. Hypothalamic digoxin can modulate conscious perception and its dysfunction may lead to schizophrenia. Digoxin can also preferentially upregulate tryptophan transport over tyrosine, resulting in increased levels of depolarizng tryptophan catabolites, serotonin, quinolinic acid, strychnine, and nicotine, and decreased levels of hyperpolarizing tyrosine catabolites, dopamine, noradrenaline, and morphine, contributing to membrane Na(+)-K+ ATPase inhibition in all the above disorders and the indexed family. Digoxin-induced membrane Na(+)-K+ ATPase inhibition can result in increased intracellular Ca2+ and reduced Mg2+ levels, leading on to glutamate excitotoxicity, oncogene activation, and immune activation. Digoxin-induced altered Ca2+/Mg2+ ratios, reduced ubiquinone, and increased dolichol can affect glycoconjugate metabolism, membrane formation and structure, and mitochondrial function, leading to the diverse disorders described above, including those in the indexed family. The isoprenoid pathway and neurotransmitter patterns were compared in right-handed/LH dominant and left-handed/RH dominant individuals. The left-handed/RH dominant individuals compared to right-handed/LH dominant individuals had elevated hydroxymethylglutarylcoenzyme A reductase activity, with increased serum digoxin and dolichol levels. The serum ubiquinone, serum Mg2+ and RBC Na(+)-K+ ATPase activity were reduced in left-handed/RH dominant individuals. The left-handed/RH dominant individuals compared to right-handed/LH dominant individuals had elevated levels of serum tryptophan, quinolinic acid, serotonin, nicotine, and strychnine. The levels of tyrosine, dopamine, noradrenaline, and morphine were low in left-handed/RH dominant compared to right-handed/LH dominant individuals. The hyperdigoxinemic state indicates right hemispheric dominance. Hypothalamic digoxin can thus function as the master conductor of the neuroimmunoendocrine orchestra and coordinate the functions of various cellular organelles.
 ...
PMID:Central role of hypothalamic digoxin in conscious perception, neuroimmunoendocrine integration, and coordination of cellular function: relation to hemispheric dominance. 1232 12

This study assessed the sensitivity of individual depressive symptoms and their relative contribution to the diagnosis of depressive disorder in patients with Parkinson's disease. The Structured Clinical Interview for DSM-IV Depression and the Hamilton and Montgomery-Asberg depression rating scales (Ham-D, MADRS) were administered to 149 consecutive nondemented patients. The contribution of the individual items of these scales to the diagnosis of "depressive disorder" was calculated by discriminant analysis. The discriminant models based on the Ham-D and MADRS scores were both highly significant. Nonsomatic core symptoms of depression had the highest correlation coefficient. Somatic items had mostly low correlation coefficients, with the exception of reduced appetite and early morning wakening (late insomnia). Nonsomatic symptoms of depression appear to be the most important for distinguishing between depressed and nondepressed patients with Parkinson's disease, along with reduced appetite and early morning awakening.
 ...
PMID:The contribution of somatic symptoms to the diagnosis of depressive disorder in Parkinson's disease: a discriminant analytic approach. 1255 75


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>