Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0013421 (dystonia)
 8,418 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Niemann-Pick disease type C (NPC) is a rare, neurovisceral lipid storage disorder caused by genetic defects in lipid transporting proteins. It is distinct from Niemann-Pick types A and B (sphingomyelin lipidoses) and displays genetic (mutations in the NPC1 or NPC2[=HE1] gene), biochemical, and clinical heterogeneity. Late infantile to juvenile forms of NPC predominate and are characterised by atypical behaviour, ataxia, dysarthria, dysphagia, dystonia, cataplexy, vertical gaze palsy, splenomegaly, and dementia. In adult variants, psychosis and dementia are common, and dysarthria, ataxia, splenomegaly, and vertical gaze palsy are further facultative signs. Routine laboratory results including serum cholesterol are normal. In bone marrow smears, sea-blue histiocytes are often demonstrated and foam cells sometimes seen. The diagnosis is confirmed by detecting free cholesterol accumulation in perinuclear granules (lysosomes) and reduced cholesterol esterification after challenge with exogenous low-density lipoprotein in fibroblasts. Alternatively or additionally, mutational analysis can be performed. Treatment is restricted to symptomatic measures, since there is no specific therapy.
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PMID:[Niemann-Pick disease type C--a neurometabolic disease through disturbed intracellular lipid transport]. 1455 97

Nocturnal disturbances are common in Parkinson's disease (PD) patients, with almost 70% of these patients reporting nocturnal disturbances. The etiology of sleep disturbances in patients with PD is still controversial. They might be dependent on dopaminergic drugs, on disease progression, or on a combination of these two factors. Nocturnal disturbances can be categorized in four groups: 1) PD-related motor symptoms, including nocturnal akinesia, early-morning dystonia, painful cramps, tremor, and difficulty turning in bed; 2) treatment-related nocturnal disturbances; 3) psychiatric symptoms, including hallucinations, vivid dreams, depression, dementia, insomnia, psychosis, and panic attacks; 4) other sleep disorders, including insomnia, REM behavioral disorder (RBD), restless legs syndrome (RLS), periodic leg movements (PLMS), and excessive daytime sleepiness (EDS). Specific treatment options are supplied for every group. A global evaluation of nocturnal disturbances would provide clinicians with a valuable tool to establish an optimal regimen that could positively influence all nocturnal disturbance categories and thus improve PD management on. However, it is important to consider that management of some nocturnal disturbances in a group may worsen nocturnal symptoms of another group or may increase EDS. PD-related symptoms can be treated with long-acting DA agonists to obtain continuous DA receptor stimulation during the night. Both treatment-related nocturnal disturbances and psychiatric symptoms may be related to drug treatment, and therefore, in both cases, drug reduction or discontinuance should be considered. Some sleep disorders, such as RLS and PLMS, may be controlled by DA agents, and others, such as insomnia and EDS, may be improved by reducing dopaminergic stimulation.
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PMID:Treatment of nocturnal disturbances and excessive daytime sleepiness in Parkinson's disease. 1550 42

Many psychiatric illnesses, including chronic schizophrenia, bipolar disorder, and dementia, are characterized by episodes of acute agitation, making administration of oral agents difficult or impossible. Ziprasidone, the first atypical antipsychotic available in both intramuscular (IM) and oral formulations, has demonstrated significant control of acute agitation within 15 minutes, as seen in two 24-hour studies in patients with schizophrenia. Improvement was maintained for > or = 4 hours, and a low incidence of extrapyramidal symptoms, akathisia, and dystonia as well as no excessive sedation were observed Also, two 7-day studies (n = 132 and n = 306) and one 6-week study (n = 567) of sequential IM/oral ziprasidone versus IM/oral haloperidol in patients with psychotic disorders found IM ziprasidone more effective than IM haloperidol within 3 days of IM treatment; both drugs produced further comparable improvements in efficacy parameters after transition to oral therapy. IM ziprasidone was associated with a lower incidence of movement disorders than was haloperidol in all of these studies. Overall, discontinuations were similar for IM ziprasidone and haloperidol in the comparative trials, including the sequential IM/oral studies. However, in the 6-week sequential IM/oral trial, the rate of discontinuation due to adverse events was twice as high among haloperidol vs ziprasidone patients. This report focuses on the pharmacology, clinical efficacy, and tolerability of IM ziprasidone, and provides an overview of the utility of other commonly used antipsychotics in the management of acute psychotic agitation.
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PMID:The utility of intramuscular ziprasidone in the management of acute psychotic agitation. 1551 47

Neuroleptic malignant syndrome (NMS) is an uncommon potentially fatal side effect of neuroleptic drugs, characterized by movement disorder, altered mental status and autonomic instability. A single dose of clotiapine was administered to an 11-year old male with acute psychosis. The previously healthy child had signs consistent with NMS including hyperthermia, hypertension, motor and mental changes. Repeat examination performed two weeks later, demonstrated that while his hyperthermia subsided, his mental status deteriorated. Olanzapine was administered, after which the child had hyperthermia, dystonia and more pronounced restlessness, once again consistent with NMS. He developed respiratory failure and was intubated and mechanically ventilated. Lorazepam, dantrolene and bromocriptine were administered as treatment of possible NMS. His mental condition, movement disorder and autonomic dysfunction improved significantly. Two weeks later, the patient was discharged in good general condition without the need for any ongoing medical treatment. There are only few case reports of NMS in children treated with olanzapine, an atypical antipsychotic. In children, caution must be exercised when prescribing antipsychotics, particularly atypical antipsychotics as these drugs may cause NMS. Because of the low incidence of NMS, a high index of suspicion is needed to identify cases so prompt treatment can be undertaken.
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PMID:Neuroleptic malignant syndrome in a child treated with an atypical antipsychotic. 1553 33

Parkinson's disease is associated with classical Parkinsonian features that respond to dopaminergic therapy. Neuropsychiatric sequelae include dementia, major depression, dysthymia, anxiety disorders, sleep disorders, and sexual disorders. Panic attacks are particularly common. With treatment, visual hallucinations, paranoid delusions, mania, or delirium may evolve. Psychosis is a key factor in nursing home placement, and depression is the most significant predictor of quality of life. Clozapine may be the safest treatment for psychotic features, but more research is needed to establish the efficacy of antidepressant treatments. Dementia with Lewy bodies, the second most common dementia in the elderly, may present in association with systematized delusions, depression, or RBD. Early evidence suggests the utility of rivastigmine, donepezil, low-dose olanzapine, and quetiapine in treating DLB. Parkinson-plus syndromes generally lack a good response to dopaminergic treatment and evidence additional features, including dysautonomia, cerebellar and pontine features, eye signs, and other movement disorders. MSA is associated with dysautonomia and RBD. SND (MSA-P) is associated with frontal cognitive impairments, but dementia, psychosis, and mood disorders have not been strikingly apparent unless additional pathological findings are present. In SDS (MSA-A), impotence is almost ubiquitous; urinary incontinence is frequent; depression is occasional, and sleep apnea should be treated to avoid sudden death during sleep. OPCA neuropsychiatric correlates await further definition. Progressive supranuclear palsy neuropsychiatric features include apathy, subcortical dementia, pathological emotionality, mild depression and anxiety, and lack of appreciable response to donepezil. CBD usually is recognized by early frontal dementia with ideomotor apraxia, often in the right upper extremity, attended later by poorly responsive unilateral Parkinsonism, with additional signs including cortical reflex myoclonus, limb dystonia, alien limb, oculomotor apraxia when asked to look horizontally, depression, personality changes, and, occasionally, Kluver-Bucy syndrome. The neuropsychiatry of FTDP-17 involves apraxia, executive impairment, personality changes, hyperorality, and occasional psychosis. Future research in these Parkinsonian disorders should target the characterization of neuropsychiatric sequelae and their treatment.
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PMID:The neuropsychiatry of Parkinson's disease and related disorders. 1555 Feb 93

The frequency, phenomenology, and risk factors of hallucinations and delusions were investigated in 64 consecutive inpatients with Parkinson's disease. Fifty patients were admitted to our hospital with symptoms related to Parkinson's disease: psychiatric problems 27 (psychosis 22; anxiety 2; depression 2; mania 1): motor symptoms, 20 (wearing-off 5; akinesia 4; freezing 4; postural instability 4; dyskinesia 2; tremor 2; dystonia 1), and sensory symptoms, 3. Fourteen patients were admitted with other medical problems (pneumonia 4; cerebral infarction 3; bone fracture 3; lumbago 2; seizure 1; cat bite 1). Totally 49 patients had psychiatric problems. Psychosis was present in 43 patients, dementia in 10, depression in 8, mania in 1, anxiety in 10, agitation in 6, stereotypy in 2, and hypersexuality in 2. Of the 43 patients with psychoses, 40 presented with visual hallucinations, 18 with auditory hallucinations, and 23 with delusions. To determine what the clinical correlates with the severity of psychosis were, we divided the patients into 3 groups: the severe group, 22 patients admitted because of psychotic symptoms; the mild group, 21 patients admitted because of problems other than psychosis but presenting psychotic symptoms; and the control group, 21 patients who had no psychotic symptoms. Incidences of auditory hallucinations and delusions were higher in the severe group as compared to the mild group. Patients in the severe group had higher Hoehn-Yahr stages, lower Mini-Mental State Examination scores, decreased H/M ratios of cardiac 123I-MIBG uptake, and lower frequencies of background activity on electroencephalograms. There were no differences in age at admission, age at onset of Parkinson's disease, duration of illness, amounts of levodopa and dopamine agonists received, Hamilton's depression rating scores, and brain MR findings, including atrophy and ischemic changes. Emergence of psychotic symptoms in parkinsonian patients appears to be clearly associated with impaired cognitive function. Therefore, it may be associated with the disease process itself. Terms such as dopaminomimetic or levodopa-induced psychosis may not be appropriate when describing psychosis in Parkinson's disease.
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PMID:[Psychoses in patients with Parkinson's disease; their frequency, phenomenology, and clinical correlates]. 1571 92

Low affinity dopamine (DA) D2 antagonists such as the substituted (S)-3-phenylpiperidine (-)-OSU6162 have been proposed to be putative antipsychotic agents not endowed with extrapyramidal side effects (EPS). In the present study we investigated the effects of (-)-OSU6162 on (-)-apomorphine and d-amphetamine-induced behaviours in EPS sensitised Cebus apella monkeys. (-)-OSU6162 was administered subcutaneously in doses of 1, 3, 6 and 9 mg/kg alone and in combination with (-)-apomorphine (0.25 mg/kg) or d-amphetamine (0.5 mg/kg). (-)-OSU6162 inhibited (-)-apomorphine-(1-9 mg/kg) as well as d-amphetamine (3-9 mg/kg)-induced arousal and stereotypy. EPS did not occur when (-)-OSU6162 was administered in combination with (-)-apomorphine or d-amphetamine. However, when (-)-OSU6162 was administered alone, dystonia was observed at high doses (6 and 9 mg/kg) in two out of six monkeys. The present study shows that (-)-OSU6162 can inhibit (-)-apomorphine-induced behaviours in non-human primates at doses that do not cause EPS. When (-)-OSU6162 was tested against d-amphetamine-induced behaviours a separation between dose levels that inhibit d-amphetamine effects and cause EPS was not observed. The data further substantiate a role for low affinity DA D2 antagonists in the pharmacological treatment of psychosis.
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PMID:The substituted (S)-3-phenylpiperidine (-)-OSU6162 reduces apomorphine- and amphetamine-induced behaviour in Cebus apella monkeys. 1579 89

The authors report 2 patients with schizophrenia who developed focal tardive dystonia secondary to treatment with atypical antipsychotics (risperidone, olanzapine). When quetiapine was gradually introduced and other antipsychotics were discontinued, these patients experienced remarkable and sustained improvement of their dystonic symptoms, without loss of psychotic symptom control. The mechanism by which quetiapine may improve tardive dystonia caused by other atypical antipsychotics is unclear. Due to its receptor and pharmacologic profile, quetiapine is the atypical antipsychotic that is most similar to clozapine (without its hematologic side effects), which leads the authors to consider it for the treatment of tardive movement disorders.
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PMID:Quetiapine in the treatment of focal tardive dystonia induced by other atypical antipsychotics: a report of 2 cases. 1606 2

Patients with acute psychosis often exhibit agitation, which can be distressing and hazardous to others as well as to the patient. In such psychiatric emergencies, intramuscular antipsychotic agents can be easier to administer than oral formulations, and they have the added advantage of more rapid absorption and a faster onset of action. However, intramuscular formulations of conventional antipsychotics, which have been the standard treatment, are associated with acute dystonia and other movement disorder-related adverse events. Ziprasidone is the first atypical antipsychotic to be clinically available in both intramuscular and oral formulations in the US. The intramuscular formulation of ziprasidone, ziprasidone mesylate, uses sulfobutylether beta-cyclodextrin to solubilise the drug by complexation. The pharmacokinetics of intramuscular ziprasidone include rapid attainment of therapeutic drug level (time to reach peak serum concentration [tmax]<or=60 minutes postdose), a mean terminal elimination half-life ranging from 2 to 5 hours, bioavailability of approximately 100%, exposure to drug that increases in a dose-related manner and little drug accumulation even after 3 days of repeated intramuscular administration. The metabolism and elimination of intramuscular ziprasidone have not been extensively evaluated. The principal difference between any oral versus intramuscular formulations of a drug is in first-pass metabolism. Oral ziprasidone is eliminated mainly via the hepatic route and <1% is eliminated in urine and <4% in faeces as unchanged drug. That would not be expected to change with the intramuscular route of administration. Low concentrations of ziprasidone are seen 12-18 hours after the last intramuscular injection. The rapid clearance of ziprasidone from plasma after an intramuscular administration results in little to no persistence of plasma drug level when switching from intramuscular to oral drug administration. No clinically significant age-, sex- or race-related effects on the pharmacokinetics of intramuscular or oral ziprasidone have been noted, and the tolerability and cardiovascular safety profiles of intramuscular ziprasidone have been well characterised in clinical trials.
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PMID:Pharmacokinetics and therapeutics of acute intramuscular ziprasidone. 1623 65

Acute agitation is a common psychiatric emergency often treated with intramuscular (i.m.) medication when rapid control is necessary or the patient refuses to take an oral agent. Conventional i.m. antipsychotics are associated with side effects, particularly movement disorders, that may alarm patients and render them unreceptive to taking these medications again. Ziprasidone (Geodon) is the first second-generation, or atypical, antipsychotic to become available in an i.m. formulation. Ziprasidone IM was approved by the Food and Drug Administration in 2002 for the treatment of agitation in patients with schizophrenia. In October 2004, a roundtable panel of physicians with extensive experience in the management of acutely agitated patients met to review the first 2 years of experience with this agent. This monograph, a product of that meeting, discusses clinical experience to date with ziprasidone IM and offers recommendations on its use in various settings. In clinical trials, patients treated with ziprasidone IM demonstrated significant and rapid (within 15-30 minutes) reduction in agitation and improvement in psychotic symptoms, agitation, and hostility to an extent greater than or equal to that attained with haloperidol i.m. Tolerability of ziprasidone IM was superior to that of haloperidol IM, with a lower burden of movement disorders. Clinical trials have also shown that ziprasidone IM can be administered with benzodiazepines without adverse consequences. Transition from i.m. to oral ziprasidone has been well tolerated, with maintenance of symptom control. The most common adverse events associated with ziprasidone IM were insomnia, headache, and dizziness in fixed-dose trials and insomnia and hypertension in flexible-dose trials. No consistent pattern of escalating incidence of adverse events with escalating ziprasidone doses has been observed. Changes in QTc interval associated with ziprasidone at peak serum concentrations are modest and comparable to those seen with haloperidol IM. Results of randomized clinical trials of ziprasidone IM have been corroborated in studies in real-world treatment settings involving patients with extreme agitation or a recent history of alcohol or substance abuse. In these circumstances, clinically significant improvement was seen within 30 minutes of ziprasidone IM administration, without regard to the suspected underlying etiology of agitation. Agents with a good safety/tolerability profile, such as ziprasidone IM, may be more cost effective long term than older agents, due to reduced incidence of acute adverse effects (eg, acute dystonia) that often require extended periods of observation. Additional trials of ziprasidone IM in agitated patients in a variety of clinical setting are warranted to generate comparative risk/benefit data with conventional agents and other second-generation antipsychotics.
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PMID:Best clinical practice with ziprasidone IM: update after 2 years of experience. 1624 23


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