Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004134 (ataxia)
 15,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Aging is a physiological process that shares many behavioral, biochemical and neuroendocrine phenomena with the pathophysiological situation of unresolved stress, as well as with a pharmacologically induced syndrome resulting from chronic benzodiazepine (BZ) consumption. Behavioral findings include symptoms such as drowsiness, ataxia, fatigue, confusion, weakness, dizziness, vertigo, syncope, reversible dementia, depression, impairment of intellectual, psychomotor and sexual function, agitation, auditory and visual hallucinations, paranoid ideation, panic, delirium, depersonalization, sleepwalking, aggressivity, orthostatic hypotension, and insomnia. Neuroendocrine findings include: central depletion of noradrenaline (NA), dopamine, adrenaline (AD), and serotonin (5-HT); reduction in the ratio of circulating NA/AD as well as platelet 5-HT and increase of AD, plasma free 5-HT and cortisol. These disturbances together with the increased platelet aggregability observed in the three groups are typical of unresolved-stress situations. Immunological findings include significant reduction of peripheral T lymphocytes (CD3, CD4, CD8) and the CD4/CD8 ratio, CD16 and gamma-delta cells. On the other hand, the three groups (elderly subjects, subjects faced with unresolved stress, and BZ consumers) show increase of the CD57 lymphocyte subset as well as natural killer cytotoxicity. Alterations of several biological markers have also been found, specifically in the oral glucose tolerance test, the intramuscular clonidine test, and the supine/orthostasis/exercise test. From a clinical point of view, the three groups appear to be more susceptible to the appearance and progression of many acute and chronic diseases (infectious and malignant diseases). As a result, chronic consumption of BZs should be avoided in both the elderly and subjects in unresolved-stress situations.
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PMID:Benzodiazepines: tolerability in elderly patients. 884 97

Serotonin syndrome, a condition with numerous clinical neurological manifestations, is the result of central serotonergic hyperstimulation. Features of the syndrome include mental status and behavioral changes (agitation, excitement, hypomania, obtundation), motor system involvement (myoclonus, hemiballismus, tremor, hyperreflexia, motor weakness, dysarthria, ataxia) and autonomic symptoms (fever, chills, diarrhea). Serotonin syndrome has been reported exclusively in patients on medications for psychiatric illness and Parkinsonism, despite the fact that the putative action of many antimigraine agents also involves the serotonin system. We herein report six patients with migraine who developed symptoms suggestive of the serotonin syndrome. Five were taking one or more serotomimetic agents for migraine prophylaxis (sertraline, paroxetine, lithium, imipramine, amitriptyline). In each case the symptoms and signs developed in close temporal proximity with use of a migraine abortive agent known to interact with serotonin receptors. In three instances the agent was subcutaneous sumatriptan and, in three, intravenous dihydroergotamine. In each instance the symptoms were transient and there was full recovery. With the ever increasing use of migraine medications active at serotonin receptor sites, cases of serotonin syndrome will likely occur more frequently. It is important that physicians treating migraine are aware of the serotonin syndrome and are able to recognize its varying presentations.
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PMID:Serotonin syndrome complicating migraine pharmacotherapy. 886 67

In 1914, Von Monakow described diaschisis, the recovery of lost cortical function in regions positionally distant from, but linked by neuronal tracts to, the primary site of cortical damage. Cerebellar diaschisis after cortical insult is detailed in the literature; however, cortical diaschisis after cerebellar insult remains a rarely reported occurrence. We describe a 36-year-old woman with rupture of a right-sided cerebellar arteriovenous malformation who developed such expected cerebellar signs as ataxia, dysmetria, and nystagmus. Days later, the patient developed profound impulsivity, disinhibition, and psychomotor agitation. Single photon emission computed tomography (SPECT) showed decreased perfusion of the bilateral frontal and temporal lobes, consistent with regional loss of neural activity. Eventual clinical improvement corresponded with reperfusion of those regions, identified on follow-up SPECT. This case documents cortical diaschisis following cerebellar insult and shows that diaschisis must be considered in patients with cerebral injury manifesting cortical deficits remote from the site of primary pathology.
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PMID:Cerebral diaschisis following cerebellar hemorrhage. 916 80

The selective pharmacology of the selective serotonin reuptake inhibitors (SSRIs) results in a lower potential for pharmacodynamic drug interactions relative to other antidepressants such as the tricyclic antidepressants (TCAs) and monoamine oxidase inhibitors (MAOIs). However, the SSRIs have been implicated in the development of the serotonin syndrome--a potentially life-threatening complication of treatment with psychotropic drugs. The syndrome is produced most often by the concurrent use of two or more drugs that enhance central nervous system serotonin activity and often goes unrecognized because of the varied and nonspecific nature of its clinical features. The serotonin syndrome is characterized by alterations in cognition (disorientation, confusion), behavior (agitation, restlessness), autonomic nervous system function (fever, shivering, diaphoresis, diarrhea), and neuromuscular (ataxia, hyperreflexia, myoclonus) activity. The difference between this syndrome and the occurrence of adverse effects caused by serotonin reuptake inhibitors alone is the clustering of the signs and symptoms, their severity, and their duration. There are important pharmacokinetic interactions between SSRIs and other serotonergic drugs due principally to their effects on the cytochrome P450(CYP) isoenzymes, the potential for which varies widely amongst the SSRI group, which may increase the likelihood of a pharmacodynamic interaction. The exceptionally long washout period required after fluoxetine discontinuation may cause additional problems and/or inconvenience. Patients with serotonin syndrome usually respond to discontinuation of drug therapy and supportive care alone, but they may also require treatment with antiserotonergic agent such as cyproheptadine, methysergide, and/or propranolol. To reduce the occurrence, morbidity, and mortality of the serotonin syndrome, it must be both prevented by prudent pharmacotherapy and given prompt recognition when it is present.
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PMID:Selective serotonin reuptake inhibitor-induced serotonin syndrome: review. 916 67

A 53-year-old man presented with progressive ataxia two and a half years prior to admission. Initially he was treated in a local hospital for 4 months with a diagnosis of spinocerebellar degeneration. Subsequently he developed psychomotor excitement with hallucination and was admitted to a mental hospital for 7 months with a diagnosis of Wernicke's encephalopathy. After a year of partial remission, he presented with increasing difficulty in thinking and walking. On admission he developed mental agitation and excitement, ocular flutter and opsoclonus, and prominent cerebellar ataxia. A lymphocytic pleocytosis in the CSF and a high-intensity lesion in the superior cerebellar peduncle of the upper brainstem revealed on a T2-weighted MRI led to a diagnosis of brainstem encephalitis. Treatment with steroid (two series of 3 days of 1,000mg methylprednisolone DIV, followed by 60mg oral prednisolone) brought about a dramatic improvement in mental and ocular symptoms corresponding with the CSF findings. He was left with mild cerebellar ataxia and returned to work on a small dose of steroids. Differential diagnoses including Bickerstaff's encephalitis and pathomechanism were discussed.
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PMID:[Steroid responsive chronic brainstem encephalitis featuring mental symptoms, abnormal eye movement and cerebellar ataxia]. 923 54

Selfotel (CGS 19755), a competitive N-methyl-D-aspartate antagonist, is neuroprotective in experimental models of ischemic cerebral injury. We studied the safety and tolerability of a single intravenous dose (0.5 to 2.0 mg/kg) of selfotel in neurosurgery patients. Thirty-two neurosurgical patients undergoing intracranial surgery were given ascending doses of selfotel 2 to 14 h before surgery. Serum selfotel levels were measured over a period of 24 h. Cerebrospinal fluid (CSF) levels were measured 1.5 to 18 h after dosing. Frequent side effects included psychomimetic symptoms such as hallucinations, abnormal dreaming, agitation, and paranoia among 20 (66%) patients. Ataxia was seen among five (16%) and dizziness among eight (25%). Symptoms occurred 38 min to 40 h from administration and persisted 5 min to 4 days. Symptom severity worsened with increasing area under the curve measurements and doses above 1.0 mg/kg. All symptoms were reversible and easily treated with intravenous haloperidol. Modest elevations of hepatic enzymes were observed among four patients. No patient had severe adverse reactions. Maximum selfotel levels attained were 143 mumol (serum) and 4.76 mumol (CSF). Peak serum levels among six patients were within potentially neuroprotective ranges. CSF levels remained detectable up to 18 h after dosing. No obvious relationship was seen between CSF drug levels and symptoms. Selfotel in doses of 0.5 to 2.0 mg/kg can be administered safely to neurosurgical patients. Maximum serum levels attained were within the range shown to be neuroprotective in experimental studies. Side effects even at the highest levels are tolerable and reversible. Selfotel use in patients at risk for cerebral injury should be further explored.
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PMID:Dose escalation safety and tolerance study of the competitive NMDA antagonist selfotel (CGS 19755) in neurosurgery patients. 957 82

The serotonin syndrome is a rare, but potentially fatal complication to treatment with serotonin reuptake inhibitors. Due to increasing prescription of these drugs the condition must be expected to occur more often. Symptoms include changes in mental status (confusion, agitation and restlessness), neuromuscular symptoms (shivering, ataxia, myoclonus and hyperreflexia) and autonomic dysfunction (fever, diaphoresis, hypertension and tachycardia). The syndrome is most often produced by concurrent use of two or more drugs that enhance serotonin neurotransmission. Monotherapy may also elicit the syndrome. We report the development of serotonin syndrome with a fatal outcome in a patient treated with paroxetin++. Interactions with alimemazin++, melperon++ and karbamazepin may have contributed to the outcome. The serotonin syndrome usually resolves within 24 hours when the suspected drugs are discontinued. However, there may be a dramatic progression of symptoms requiring intensive supportive care to prevent death.
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PMID:[Serotonin syndrome with fatal outcome caused by selective serotonin reuptake inhibitors]. 1038 11

Gabapentin (GBP) is a antiepileptic drug (AED) indicated as adjunct therapy for treatment of partial seizures, with and without secondary generalization, in patients 12 and older with epilepsy. GBP (1-(aminomethyl) cyclohexaneacetic acid) is structurally related to gamma-aminobutyric acid (GABA), which readily crosses the blood-brain barrier. Radiolabeled GBP binds throughout the central nervous system in anatomic areas important in treatment of seizures. Its precise mechanism of action is unknown. An open-label, dose-ranging study of doses up to 1,800 mg produced > or =50% seizure reductions [responder rate (RR)] in 29% of patients with partial seizures. Three double-blind, placebo-controlled, parallel add-on trials at doses of 300-1,800 mg have produced RR of up to 28%, with a placebo RR of 8-10%. An active controlled, parallel group comparison of 600 mg to 2,400 mg in monotherapy conversion design showed no significant difference among the 600 mg, 1,200 mg, and 2,400 mg groups compared to a placebo group. An inpatient, active-controlled comparison of 300 mg and 3,600 mg in a parallel-design monotherapy trial showed that time to exit from the study was significantly longer for the 3,600-mg group and the completion rate significantly higher (53% vs. 17%) for patients receiving 3,600 mg/day vs. 300 mg/day of GBP. Successful double-blind, placebo-controlled trials in refractory childhood partial seizures and benign childhood epilepsy with centrotemporal spikes have been recently concluded. Absence was not successfully treated in one small double-blind trial. Open-label reports emphasize adjustments of patients to higher doses than those indicated in the package labeling. An open-label trial of GBP therapy in patients with partial seizures (n = 2,216) produced progressively greater seizure freedom rates as patients were titrated from > or =900 mg daily to > or = 1,800 mg daily (15.1% vs. 33.4%), with a similar effect on RR (18.1% vs. 44.9%). An add-on, open-label study treating partial seizures (n = 141) reported an RR of 71%, with 46% seizure-free in the last 8 weeks of treatment and doses up to 2,400 mg daily. A comparison trial of three doses of GBP to 600 mg of carbamazepine showed similar retention rates for 1,800 mg of GBP and 600 mg of CBZ. Another study reported 48% of patients experiencing 50% reduction, nine of whom had doses greater than 2,400 mg. Treatment in children has reported a 34.4% RR in 32 children with refractory partial seizures. A French open-label adjunctive trial documented a 33.9% RR; 13.4% were seizure-free during the evaluation period. Adverse experiences most commonly noted included somnolence, dizziness, and ataxia. Weight gain was sometimes reported with higher doses of GBP, and pediatric reports cite prominent behavioral changes, including hyperactivity, irritability, and agitation. GBP appears best used at doses at and potentially above those suggested in its package labeling. Although efficacy occurs at lower levels, increased GBP doses are associated with additional efficacy. Reports suggest that initiation at 2,400 mg or 3,600 mg may not be associated with increased adverse experiences. Titration to 900 or 1,200 mg on the first day of GBP therapy appear to be well tolerated.
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PMID:Gabapentin. 1053 Jun 96

In humans, hydromorphone (HMOR) is metabolised principally by conjugation with glucuronic acid to form hydromorphone-3-glucuronide (H3G), a close structural analogue of morphine-3-glucuronide (M3G), the major metabolite of morphine. In a previous study we described the biochemical synthesis of H3G together with a preliminary evaluation of its pharmacology which revealed that it is a neuroexcitant in rats in a manner analogous to M3G. Thus the aims of the current study were to quantify the neuro-excitatory behaviours evoked by intracerebroventricular (icv) H3G in the rat and to define its potency relative to M3G. Groups of adult male Sprague-Dawley rats received icv injections (1 microL) of H3G (1 - 3 microg), M3G (2 - 7 microg) or vehicle via a stainless steel guide cannula that had been implanted stereotaxically seven days prior to drug administration. Behavioural excitation was monitored by scoring fifteen different behaviours (myoclonic jerks, chewing, wet-dog-shakes, rearing, tonic-clonic-convulsions, explosive motor behaviour, grooming, exploring, general activity, eating, staring, ataxia, righting reflex, body posture, touch evoked agitation) immediately prior to icv injection and at the following post-dosing times: 5, 15, 25, 35, 50, 65 and 80 min. H3G produced dose-dependent behavioural excitation in a manner analogous to that reported previously for M3G by our laboratory and reproduced herein. H3G was found to be approximately 2.5-fold more potent than M3G, such that the mean (+/- S.D.) ED50 values were 2.3 (+/- 0.1) microg and 6.1 (+/- 0.6) microg respectively. Thus, our data clearly imply that if H3G crosses the BBB with equivalent efficiency to M3G, then the myoclonus, allodynia and seizures observed in some patients dosed chronically with large systemic doses of HMOR, are almost certainly due to the accumulation of sufficient H3G in the central nervous system, to evoke behavioural excitation.
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PMID:Hydromorphone-3-glucuronide: a more potent neuro-excitant than its structural analogue, morphine-3-glucuronide. 1145 32

Cases involving ingestion of a dextromethorphan-containing product recorded at a poison control center were studied. A retrospective review of all consultations involving the ingestion of Coricidin HBP Cough & Cold tablets recorded by the California Poison Control System was conducted for the period from January 1 to October 1, 2000. Computerized charts on the consultations were reviewed to obtain data on patient age and sex, number of tablets taken, reason for tablet ingestion, symptoms, treatment, disposition, and outcome. A total of 92 charts (for 92 patients) documenting Coricidin HBP Cough & Cold tablet ingestion were reviewed. The reason for tablet ingestion was classified as abuse in 65 patients (71%), a suicide attempt in 8 (9%), misuse in 1 (1%), malicious administration in 1 (1%), and normal use (but with an adverse drug reaction) in 1 (1%); 16 patients (17%) consumed the tablets for an unknown reason. The 92 patients comprised 42 males and 50 females. Among all patients, 78 (85%) were 13-17 years old, and among those classified as having abusive intent, 58 (89%) were in the same age range. The most commonly reported signs and symptoms associated with ingestion were tachycardia (50 patients), hypertension (29), lethargy (40), mydriasis (20), agitation (15), ataxia or dizziness (20), and vomiting (9). Sixty-one patients (66%) had some alteration in mental status. Fifty-six (61%) were treated in the emergency department; 11 (12%) were admitted. All patients recovered completely. Information on the ingestion of Coricidin HBP Cough & Cold tablets recorded at a poison control center indicated a high rate of abuse of the product among teenagers.
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PMID:Abuse of Coricidin HBP cough & cold tablets: episodes recorded by a poison center. 1159 95


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