John C. DeToledo

Changes in body weight with chronic, high-dose gabapentin therapy

The authors reviewed changes in body weight in 44 patients treated with Gabapentin (GPN) for a period of 12 or more months. All patients had a seizure disorder and the dose of GPN was increased aiming at complete seizure control or until side effects limited further increase. Twenty-eight patients were receiving GPN dosages of > 3000 mg/day. Observed changes in body weight were as follows 10 patients gained more than 10% of their baseline weight, 15 patients gained 5% to 10% of baseline, 16 patients had no change, and 3 patients lost 5% to 10% of their initial weight. Weight increase started between the second and the third months of GPN treatment in most patients and tended to stabilize after 6 to 9 months of treatment, although the doses of GPN remained unchanged. Weight gain occurred in patients taking GPN in combination with each of the major antiepileptic drugs including Felbatol and also occurred with GPN monotherapy.

Lidocaine and seizures.

Lidocaine has a concentration-dependent effect on seizures. At lower concentrations it has anticonvulsant properties, whereas concentrations above 15 microg/mL frequently result in seizures in laboratory animals and man. Seizures induced by lidocaine in experimental conditions invariably start in the amygdala. Despite the clear focal onset in these experimental models, the seizures emerging in patients given intravenous (i.v.) lidocaine are almost invariably generalized and without any clear signs of focality. Given the prevalence of partial seizures and the frequent use of lidocaine, a higher incidence of partial seizures would be expected with its use. Yet this is clearly not the case. These facts suggest that a history of partial seizures is not a major risk factor for the precipitation of partial seizures in patients treated with intravenous lidocaine.

Fosphenytoin and phenytoin in patients with status epilepticus: improved tolerability versus increased costs.

Tonic-clonic status epilepticus (TCSE) is the most common neurological emergency and affects approximately 60 000 patients each year in the US. The risk of complications increases substantially as TCSE lasts longer than 60 minutes. Ideally, drugs used to treat this condition should be well tolerated when administered as rapid intravenous infusions and should not interfere with patients’ state of consciousness or cardiovascular and respiratory functions. Because of its efficacy, absence of sedation or respiratory suppression, intravenous phenytoin has largely replaced phenobarbital (phenobarbitone) as the second agent of choice (following the administration of a benzodiazepine) in the treatment of TCSE. While the efficacy of phenytoin in the treatment of acute seizures and TCSE is well established, the parenteral formulation of phenytoin has several inherent shortcomings which compromise its tolerability and limit the rate of administration. Intravenous phenytoin has been associated with fatal haemodynamic complications and serious reactions at the injection site including skin necrosis and amputation of extremities.Fosphenytoin, a phenytoin prodrug, has the same pharmacological properties as phenytoin but none of the injection site and cardiac rhythm complications of intravenous infusions of phenytoin. While fosphenytoin costs more than intravenous phenytoin, treating the acute and chronic complications of TCSE itself, and the complications of intravenous phenytoin can also be costly. All other factors being equal, there is no doubt that fosphenytoin is better tolerated and can be delivered faster than intravenous phenytoin; 2 measures that clearly improve outcome in patients with TCSE. The tolerability of intramuscular fosphenytoin also extends its use to clinical situations where prompt administration of a nondepressing anticonvulsant is indicated but secure intravenous access and cardiac monitoring are not available, such as treatment of seizures by rescue squads in the field and serial seizures in the institutionalised, elderly and other patients with intractable epilepsy.

Epilepsy and Religious Experiences: Voodoo Possession

Summary: Epileptic seizures have a historical association with religion, primarily through the concept of spirit possession. Five cases where epileptic seizures were initially attributed to Voodoo spirit possession are presented. The attribution is discussed within the context of the Voodoo belief system.

Seizures, lateral decubitus, aspiration, and shoulder dislocation: Time to change the guidelines?

The recommendation to position a patient having a seizure on a lateral decubitus is aimed at minimizing the risk of aspiration. The authors reviewed the database of the Epilepsy Foundation Clinic of South Florida for patients with epilepsy treated for pneumonia between May 1999 and May 2000 and patients admitted to two university telemetry units who had dislocation of the shoulder during an epileptic seizure. Over 2 months, 2 of 733 adults with intractable seizures had aspiration pneumonia after a generalized tonic clonic seizure (GTCS). Although no study has specifically addressed the problem of aspiration pneumonia in adults with GTCS, our findings suggest this problem is not common. From the two epilepsy centers, 5 of 806 patients dislocated a shoulder during a seizure. Video recordings showed that these patients were positioned in a lateral decubitus by staff while still having the convulsion. The dislocated shoulder in all cases was on the lower side. The risk of shoulder dislocation in a convulsing patient positioned in a lateral decubitus is less than 1%. Nevertheless, dislocations can result in disabling recurrences and are easily preventable. Because aspiration is more likely in the postictal rather than ictal phase of a GTCS, when oral secretions are not usually increased and there is cessation of respiratory movements, lateral decubitus should only be implemented after cessation of the convulsion. In inpatients (such as those on telemetry), secretions may be better managed by bedside aspiration of the oral cavity.

Risk of aspiration pneumonia after an epileptic seizure: a retrospective analysis of 1634 adult patients.

We reviewed the incidence of aspiration pneumonia secondary to seizures in three populations of patients with chronic epilepsy: 733 outpatients seen in an Epilepsy Foundation clinic; 806 adult patients admitted to two university video telemetry units; and 95 institutionalized, profoundly retarded adult patients with chronic epilepsy. Two of the 733 adults who had seizures in the outpatient setting and 2 of the 806 patients who had one or more epileptic seizures in the telemetry units developed aspiration pneumonia. In the 95 institutionalized patients, there were 17 instances of aspiration pneumonia after a generalized seizure and 32 instances of aspiration unrelated to seizures over a 12-month period. Our findings suggest that aspiration pneumonia is not a common complication of seizures in otherwise healthy adults. The increased incidence of aspiration in developmentally delayed individuals seems to derive from a combination of factors. Increased oral secretions, impaired swallowing mechanisms, and difficulty in attaining adequate patient positioning significantly increased the risk of aspiration.

Status Epilepticus Associated with the Combination of Valproic Acid and Clomipramine

An epileptic patient well controlled on valproic acid (VPA) developed a prolonged episode of status epilepticus 12 days after initiation of 75 mg of clomipramine (CMI) to treat depression. Serum level of VPA in the emergency room was unchanged from her previous levels; serum level of CMI was very elevated despite the relatively small dose of CMI. A pharmacokinetic interaction between VPA, an enzyme inhibitor, and CMI has not been described but seemed to have occurred in this patient. Decreased metabolism of CMI and its metabolites, increased free CMI fraction, and precipitation of a nonlinear saturation kinetic state has been described when CMI was used concomitantly with other highly protein-bound, enzyme-inhibiting compounds. This case provides reasonable evidence that the combination of VPA and CMI may result in elevation of levels of CMI and possibly of its metabolites and may precipitate seizures in patients with an underlying predisposition. The elevated serum level of CMI at the time of the seizures, despite the relatively small oral dose of the drug, suggests that VPA may have inhibited its metabolism and/or elimination.

Fosphenytoin: Pharmacokinetics and Tolerance of Intramuscular Loading Doses

Summary:  Purpose: Fosphenytoin (FPHT; Cerebyx) is well absorbed when given intramuscularly (IM). All prior pharmacokinetic studies had the first plasma sample obtained 30 min after IM administration. The objectives of this study were to determine the rate and extent of FPHT absorption and to evaluate the tolerability of IM FPHT compared with IM saline.

Skin eruption with gabapentin in a patient with repeated AED-induced Stevens-Johnson's syndrome.

Skin eruptions have been reported with the use of all antiepileptic drugs and there is a significant risk of cross-reactivity between these agents in causing serious eruptions such as Stevens-Johnsons syndrome. Gabepentin is usually considered a safe agent for patients with a previous history of drug allergies and there have been no cases of skin eruption reported to the gabapentin post marketing surveillance. We report a patient who had severe Stevens-Johnsons syndrome induced by phenytoin and later by carbamazepine. Subsequent use of gabapentin also resulted in a skin eruption which was limited to the lower extremities but without systemic or mucosal involvement. This case suggests that patients with a strong history of drug-induced idiosyncratic reactions may experience such reactions to gabapentin as well.

Restraining patients and shoulder dislocations during seizures

We describe 3 patients whose shoulders dislocated as the movements of the arm were restricted during a generalized tonic clonic seizure over an 18-month period. The first patient had both shoulders dislocated when observers sat on his arms during the convulsion. The second patient had a convulsion while in a forced lateral decubitus position and dislocated the shoulder on that side. The third patient dislocated the shoulder and fractured the acromion as she was held by her arms in a chair during a convulsion. Despite the large number of patients with refractory epilepsy under our care, no cases of spontaneous shoulder dislocation occurred during that period of time.