Suppression of Complex Visual Hallucinatory Experiences by Occipital Transcranial Magnetic Stimulation: A Case Report

We report a patient with visual hallucinations and illusions along with an associated visual field defect after bilateral ischemic damage to his occipital visual cortex. These hallucinations were long-standing and of both simple and complex (well-formed) type. Application of low frequency (1 Hz) repetitive Transcranial Magnetic Stimulation (rTMS) to the occipital cortex led to a complete cessation of visual hallucinatory symptoms. The use of TMS to probe the neurophysiology, and possibly alleviate, visual hallucinatory experiences is discussed.     

Position Statement and Practice Guidelines on the Use of Multi-Dose Activated Charcoal in the Treatment of Acute Poisoning

In preparing this Position Statement, all relevant scientific literature was identified and reviewed critically by acknowledged experts using agreed criteria. Well-conducted clinical and experimental studies were given precedence over anecdotal case reports and abstracts were not usually considered. A draft Position Statement was then produced and subjected to detailed peer review by an international group of clinical toxicologists chosen by the American Academy of Clinical Toxicology and the European Association of Poisons Centres and Clinical Toxicologists. The Position Statement went through multiple drafts before being approved by the Boards of the two societies.

The Position Statement includes a summary statement for ease of use and is supported by detailed documentation which describes the scientific evidence on which the Statement is based.

Although many studies in animals and volunteers have demonstrated that multiple-dose activated charcoal increases drug elimination significantly, this therapy has not yet been shown in a controlled study in poisoned patients to reduce morbidity and mortality. Further studies are required to establish its role and the optimal dosage regimen of charcoal to be administered.

Based on experimental and clinical studies, multiple-dose activated charcoal should be considered only if a patient has ingested a life-threatening amount of carbamazepine, dapsone, phenobarbital, quinine, or theophylline. With all of these drugs there are data to confirm enhanced elimination, though no controlled studies have demonstrated clinical benefit.

Although volunteer studies have demonstrated that multiple-dose activated charcoal increases the elimination of amitriptyline, dextropropoxyphene, digitoxin, digoxin, disopyramide, nadolol, phenylbutazone, phenytoin, piroxicam, and sotalol, there are insufficient clinical data to support or exclude the use of this therapy.

The use of multiple-dose charcoal in salicylate poisoning is controversial. One animal study and 2 of 4 volunteer studies did not demonstrate increased salicylate clearance with multiple-dose charcoal therapy. Data in poisoned patients are insufficient presently to recommend the use of multiple-dose charcoal therapy for salicylate poisoning.

Multiple-dose activated charcoal did not increase the elimination of astemizole, chlorpropamide, doxepin, imipramine, meprobamate, methotrexate, phenyítoin, sodium valproate, tobramycin, and vancomycin in experimental and/or clinical studies.

Unless a patient has an intact or protected airway, the administration of multiple-dose activated charcoal is contraindicated. It should not be used in the presence of an intestinal obstruction. The need for concurrent administration of cathartics remains unproven and is not recommended. In particular, cathartics should not be administered to young children because of the propensity of laxatives to cause fluid and electrolyte imbalance.

In conclusion, based on experimental and clinical studies, multiple-dose activated charcoal should be considered only if a patient has ingested a life-threatening amount of carbamazepine, dapsone, phenobarbital, quinine, or theophylline.

This Position Statement was drafted by JA Vale, EP Krenzelok, and GD Barceloux.     

Midazolam andDiazepam for Pediatric Seizures in the Prehospital Setting

Objective. The objective of this study was to compare the efficacy andadverse events associated with the use of diazepam andmidazolam for the treatment of pediatric seizures in the prehospital setting. Methods. This was a retrospective cohort study of all patients younger than 18 years treated for a seizure with a benzodiazepine by emergency medical services in Multnomah County, Oregon, from 1998 to 2001. The emergency medical services system consists of a single private advanced life support transporting ambulance service with fire department first responders that are all advanced life support capable. The benzodiazepine used changed from diazepam to midazolam at the midpoint of this period. The primary outcomes were termination of the seizure by arrival to the emergency department (ED), recurrence of seizure while in the ED, or the requirement for active airway interventions including intubation. The two cohorts were also compared for demographics, past history of seizures, long-term use of seizure medications, response times, route of administration, use of second doses of benzodiazepines, andfinal disposition. Results. Forty-five patients were treated with diazepam, and48 were treated with midazolam. The two cohorts were comparable except the diazepam cohort had a significantly increased proportion of patients with previous afebrile seizures (53% vs. 25%; p = 0.005). The midazolam cohort had an increased use of nonintravenous route for initial dosing (65% vs. 42%; p = 0.02). The two cohorts were equivalent in rates of termination of seizures before to ED arrival, recurrence of seizures in the ED, requiring airway support or a second dose of benzodiazepine, andadmission to the hospital. Conclusions. Diazepam andmidazolam appear to be equivalent in treating seizures andcausing adverse events. Paramedics appear to be administering midazolam intramuscularly more often than they use diazepam rectally.     

Phenytoin-associated severe hypocalcemia with seizures in a patient with a TSC2-PKD1 contiguous gene syndrome

Abstract

We report the case of an inaugural episode of generalized seizures in a 40-year-old male with a history of chronic kidney disease associated with TSC2-PKD1 contiguous gene syndrome. This patient was under prophylactic treatment of phenytoin since 2 years because of a subarachnoid hemorrhage due to a ruptured cerebral aneurysm. Laboratory results revealed therapeutic range of phenytoin levels, but severe hypocalcemia associated with profound vitamin D deficiency that could not be explained by secondary hyperparathyroidism alone. The interaction of phenytoin on the P-450 cytochromes activity has been demonstrated to accelerate the rate of 25-hydroxivitamin D₃ and 1α,25-dihydroxivitamin D₃ catabolism into inactive metabolites, leading to hypocalcemia. Physicians should be aware of significant phenytoin interactions on vitamin D metabolism which may lead to symptomatic hypocalcemia in patients with chronic kidney disease.     

Oxcarbazepine

Oxcarbazepine (OXC) (Trileptal^®, Novartis) is one of the recently introduced anti-epileptic drugs (AEDs) in the US. This drug has demonstrated efficacy as adjunctive therapy in adults and children, and as monotherapy in adults for the treatment of seizures of partial onset. There is also convincing evidence of its efficacy in patients with newly diagnosed and refractory trigeminal neuralgia. In addition, the initial efficacy results of oxcarbazepine in other neuropathic pain conditions and in bipolar disorders are encouraging. In this review, recommendations on the optimal clinical use of OXC are given based on its pharmacokinetic profile, efficacy and tolerability in those various conditions.     

Risk of seizures associated with psychotropic medications: emphasis on new drugs and new findings

Psychotropic medications in the classes of antidepressants, antipsychotics and mood stabilisers have been recognised in the literature and clinical settings as having high epileptogenic potential. Among these three classes, clozapine, tricyclic antidepressants (TCAs) and lithium are agents that clinicians have historically recognised as precipitants of drug-induced seizures. There are few reports that review the epileptogenic risk of newer psychotropic agents; in this qualitative review, the authors provide an update on the most recently published reports on seizures associated with antidepressants, antipsychotics, mood stabilisers, anxiolytics and sedative-hypnotics. In general, the epileptogenic risks of the newer psychotropic agents appear to be quite low as long as dosing strategies are consistent with recommended guidelines. Whilst newer psychotropic medications appear to be safe in patients with epilepsy, few studies have specifically addressed this population. In addition, the potential for drug interactions between antiepileptic drugs and psychotropics may be substantial with certain agents. For example, many psychotropes are both substrates and inhibitors of cytochrome P450 (CYP450) isoenzymes, whilst many antiepileptic drugs are both substrates and inducers of CYP450 activity. Every attempt should be made to minimise potential interactions when these agents are concomitantly administered.     

The withdrawal of antiepileptic drugs in patients with non-epileptic seizures: safety considerations

The majority of patients with psychogenic non-epileptic seizures (PNES) do not have epilepsy. There are a number of compelling reasons to take these patients off antiepileptic drugs (AEDs), including drug toxicity and teratogenicity, as well as possibly poorer outcome of PNES and increased risk of iatrogenic harm when patients present to emergency rooms on AEDs as emergencies. However, many patients with PNES who do not have epilepsy remain on AEDs postdiagnosis. Some studies do report patients taken off medication as an outcome measure, but with no assessment of the safety of withdrawal, or specification of the criteria for ‘excluding’ epilepsy. One study has assessed the safety of taking patients satisfying some simple criteria for the absence of an underlying epilepsy off AEDs, and has found the procedure to be safe, given appropriate postwithdrawal follow-up. Patients with PNES who do not have evidence of epilepsy should be referred to a centre with appropriate expertise in epilepsy diagnosis so that AEDs can be withdrawn in safe conditions.     

Pharmacology and clinical experience with tiagabine

Tiagabine (TGB), a recently approved anti-epileptic drug (AED), has a specific and unique mechanism of action involving the inhibition of γ-aminobutyric acid (GABA) re-uptake into neurones and glia. TGB is potent and has linear and predictable pharmacokinetics. It does not induce or inhibit hepatic metabolism and has no clinically significant effects on the serum concentrations of other AEDs or commonly used non-AEDs. Double-blind, placebo-controlled studies in primarily hepatic enzyme-induced patients showed that TGB 30 - 56 mg/day is an effective add-on treatment for all subtypes of partial seizures. The most common adverse effects in the trials were dizziness, asthenia (weakness), somnolence, accidental injury, infection, headache, nausea and nervousness. These side effects were usually mild to moderate in severity and generally did not require medical intervention. Long-term safety studies show continued efficacy of TGB over time and no evidence of tolerance for efficacy. Open studies confirm that patients with medically refractory partial epilepsy can be successfully converted to TGB monotherapy and that TGB may be effective for other seizure types, such as infantile spasms.