Newer anti-epileptic drugs, vitamin status and neuropathy: A cross-sectional analysis.

OBJECTIVE: Whether new antiepileptic drugs (AEDs) may result in neuropathy is unknown but possible given their effects on vitamin metabolism. This analysis aimed to determine frequency and correlates of neuropathy in subjects treated with new AEDs in relation to drug used, length of exposure and serum vitamin B12 and folate levels. METHODS: We performed a cross-sectional study of 52 consecutive epileptic subjects. Presence of neuropathy was determined using the Utah Early Neuropathy Score (UENS). Exposure to anti-epileptic drugs was quantified. Serum vitamin B12 and folate levels were measured. RESULTS: Commonly used AEDs were levetiracetam (28/52), carbamazepine (20/52), lamotrigine (20/52), sodium valproate (10/52) and zonisamide (10/52). Eight of 52 (15.4%) patients had neuropathy. There was no association with any particular AED. Neuropathy correlated with age (P=0.038) and total exposure to AEDs (P=0.032). UENS correlated with age (P=0.001), total AED exposure (P=0.001) and serum vitamin B12<240ng/L (P=0.018). Independent association of neuropathy was found with total AED exposure (P=0.032), but not age. UENS was independently associated with total exposure to AEDs (P<0.001), vitamin B12<240ng/L (P=0.002), but not age. Serum vitamin B12 and folate levels were highly inter-correlated (P<0.001). CONCLUSIONS: Neuropathy appears to be associated with the length of exposure to new AEDs. This may relate to the effects of new AEDs on vitamin B12 and folate metabolism. Although further research from controlled studies is needed and despite the presence of other possible confounding factors, monitoring for neuropathy and vitamin B12 and folate levels merits consideration in patients on long-term treatment with new AEDs.

Specialist management of routine dental procedures in adults with refractory epilepsy.

Little published information exists about the management of dental treatment procedures for people with epilepsy who, despite their medication, continue to have seizures. This paper draws on relevant literature in neurology and anaesthetics to provide a multi-speciality consensus on methods of assessment and adjunctive treatment options in order to manage the risk of a clinically significant seizure occurring during a procedure. It aims to enhance current guidelines and practice in the provision of specialist care for this diverse group.

Remacemide hydrochloride as an add-on therapy in epilepsy: a randomized, placebo-controlled trial of three dose levels (300, 600 and 1200 mg/day) in a Q.I.D. regimen.

Remacemide hydrochloride is a low-affinity, non-competitive N-methyl-D-aspartic acid (NMDA) receptor channel blocker, under investigation in epilepsy. This double-blind, placebo-controlled, multicentre study assessed the safety and efficacy of remacemide hydrochloride or placebo, as adjunctive therapy, in 252 adult patients with refractory epilepsy who were already taking up to three antiepileptic drugs (including an enzyme-inducer). Patients were randomized to one of three doses of remacemide hydrochloride (300, 600 or 1200 mg /day) or placebo Q.I.D., for up to 15 weeks. An increasing percentage of responders (defined as a reduction in seizure frequency from baseline of > or =50%) was seen with increasing remacemide hydrochloride dose. At 1200 mg /day, 23% of patients were responders compared with 7% on placebo. This difference was significant (P = 0.016), as was the overall difference between treatments (P = 0.038). Adverse events: dizziness, abnormal gait, gastrointestinal disturbance, somnolence, diplopia and fatigue were mild or moderate in severity. Carbamazepine and phenytoin plasma concentrations were well controlled and maintained within target ranges, with no evidence of improved seizure control due to increases in the concentrations of these drugs. A dose-dependent, significant, increase in responders following adjunctive remacemide hydrochloride compared with placebo was observed. Remacemide hydrochloride was well tolerated.

Wernicke-Korsakoff syndrome in head injury: a missed insult.

A survey of the use of thiamine in patients at risk from Wernicke-Korsakoff syndrome (WKS) in Scottish specialist neurosurgical units, and a 2-year retrospective study of 218 at-risk patients admitted to a regional neurosurgical unit with a head injury were undertaken. Although responses to the survey indicated otherwise, the study revealed that there was no consistent practice regarding thiamine administration. Overall, 20.6% of patients received thiamine, with an alcohol history being the only factor correlating with thiamine administration. Of known alcoholics and heavy drinkers, 56.1% and 26.2% respectively received thiamine as in-patients; 44.5% of patients received additional carbohydrate loads in the form of i.v. dextrose or parenteral nutrition, but only 28.9% of these received thiamine as well. Although the actual thiamine status of these patients was not known, given the difficulties of diagnosing WKS in the presence of a head injury, the conclusion is that written protocols are needed in units to ensure that head injury patients at risk of WKS receive appropriate thiamine treatment or prophylaxis.

Thiamine deficiency in head injury: a missed insult?

Practice regarding the use of thiamine in head-injured patients at risk of Wernicke-Korsakoff syndrome in Scottish neurosurgical units was surveyed by questionnaire and revealed no clear policy. A 2 year retrospective study of 218 admissions to one of these units of patients who had taken alcohol shortly before sustaining head injury is also described. The minority (20.6%) of the total had been given thiamine, with just over half (56.1%) of those categorized as alcoholic receiving this treatment. Additional carbohydrate loads, in the form of i.v. dextrose or parenteral nutrition, had been given to 44.5% of patients and only 28.9% of this group had also been given thiamine. The dose and duration of thiamine given was inadequate in most cases. It is suggested that failure to ensure that head injury patients at risk of Wernicke-Korsakoff syndrome receive appropriate thiamine prophylaxis represents a missed and treatable additional insult to the damaged brain.

Impaired joint mobility in Guillain-Barré syndrome: a primary or a secondary phenomenon?

Three patients with Guillain-Barré syndrome had significant residual impairment of joint mobility. Pain in the limbs and axial skeleton was a prominent early feature, as were autonomic disturbances and bulbar involvement resulting in prolonged mechanical ventilation. All three patients developed marked joint stiffness and contractures despite having physiotherapy from the outset. The skeletal problems and complications became major components of disability despite improving neurological status.

Bioavailability and dissolution of proprietary and generic formulations of phenytoin.

A comparative study of the bioavailability of seven formulations of phenytoin was carried out on 17 patients with epilepsy who were taking phenytoin regularly as part of their drug therapy. Three patients withdrew for personal reasons. No significant differences were found between Epanutin capsules and other generic formulations. However significant differences were noted between the generic products. Phenytoin BP tablets manufactured by Regent Laboratories (now withdrawn) had a relative bioavailability of only 76% compared with tablets manufactured by A H Cox and Company. In vitro dissolution tests requirements were met by all formulations of generic 100 mg tablets, and it was concluded that in vitro dissolution tests are not reliable indicators of biological equivalence. Significantly higher plasma levels were found with Epanutin Infatabs, but this was accounted for by their higher content of phenytoin, which is present in the acid form rather than the sodium salt.

Inhaled lodoxamide tromethamine in the treatment of perennial asthma: a double-blind placebo-controlled study.

The efficacy of lodoxamide tromethamine in the treatment of asthma was studied in a 16-week double-blind, placebo-controlled study of 68 perennial allergic subjects with asthma. Patients received either lodoxamide tromethamine, 0.25 mg four times daily, or placebo, administered by metered-dose inhaler. Response to treatment was assessed by analyzing changes in asthma symptoms, inhaled bronchodilator requirements, and pulmonary function when compared to a 2-week baseline period. Patients treated with lodoxamide tromethamine demonstrated an improvement in daytime breathing difficulty, cough, sputum production, and sleep (p less than 0.01 to 0.05), but improvement was not significantly different from that demonstrated by placebo-treated patients. Patients from both treatment groups were able to reduce their inhaled bronchodilators (p less than 0.01), but again no significant difference was apparent between lodoxamide tromethamine and placebo treatment, nor were there any differences in peak expiratory flow rate or FEV1 between the two groups. Seven patients who received lodoxamide tromethamine withdrew because of a sensation of heat and gastrointestinal symptoms. Thus, although lodoxamide tromethamine possesses potent mast cell-stabilizing activity in vitro, we have failed to demonstrate any useful long-term effect in the treatment of mild allergic asthma.