Seizures in children with primary brain tumors: incidence and long-term outcome

PURPOSE: To estimate the incidence and long-term outcome of brain tumor related seizures in children and to identify risk factors for adverse seizure outcome. METHODS: Analysis of medical records of children treated for brain tumor and seizures in a single institution. Children were identified from hospital database and neurology clinic records. Seizure status was characterized for the 6 months prior to most recent follow-up. RESULTS: Median follow-up after first seizure of the 157 analyzed children was 3.3 years. Tumor location was supratentorial in 81% and posterior fossa in 19%. Initial anti-epileptic drugs were phenytoin (n=52), carbamazepine (n=38), phenobarbital (n=14), gabapentin (n=31), or others (n=22). Seizures were controlled in 65% of the children and uncontrolled in 35% (17% intractable). Gabapentin showed a trend toward better seizure control (p=0.06). Neurologic deficit, T2 peri-cavity hyperintensity, and EEG slow waves were independently predictive of uncontrolled seizures by multivariate analysis. CONCLUSIONS: T2 peri-cavity hyperintensity, focal neurologic deficits, and EEG slow waves predict poor seizure control in children with brain tumors. Seizures can be controlled in most patients with brain tumors. Gabapentin use as first anti-epileptic drug needs to be studied prospectively.     

Safety and efficacy of clobazam versus phenytoin-sodium in the antiepileptic drug treatment of solitary cysticercus granulomas

BACKGROUND: It is now agreed that the prognosis of seizure disorder due to solitary cysticercus granuloma (SCG) is generally good. However, the choice antiepileptic drugs (AEDs) remain empirical, with no comparative trials of different AEDs being available. AIMS: To determine the safety and efficacy (measured by the incidence of 'treatment failure') of clobazam in comparison to standard treatment with phenytoin-sodium for prevention of seizures in persons with solitary cysticercus granulomas (SCGs). SETTINGS AND DESIGN: This pilot study was conducted in a neurology department of a medical college hospital in the form of a prospective, randomized, open-labeled trial. MATERIALS AND METHODS: Forty-eight patients with seizures due to SCG were randomized in an open-labeled trial to either, clobazam (1 mg/kg oral loading followed by 0.5 mg/kg/d) (n=21) or phenytoin (15 mg/kg, oral loading in 3 divided doses over 24 h, followed by 5 mg/kg/d) (n=27). They were followed over 6 months with the primary outcome measure being treatment failure (either discontinuation or modification of AEDs) due to either adverse effects or breakthrough seizures. RESULTS: Treatment failures were noted to be significantly less common (P =0.03) in the clobazam-treated group (n=1; 4.7%) than in phenytoin-treated group (n=9; 33.3%). These included one patient (4.7%) in the clobazam-group who had breakthrough seizures and 3 (11.1%) who had breakthrough seizures and 6 (22.2%) in the phenytoin-treated group who had adverse effects requiring treatment discontinuation. CONCLUSIONS: Clobazam was well tolerated, safe and more effective than phenytoin in the AED treatment of patients with SCG.     

Cutaneous adverse drug reaction in patients with epilepsy after acute encephalitis

Patients with epilepsy after encephalitis/encephalopathy (EAE) often have refractory seizures, resulting in polytherapy with the risk of adverse reactions due to anti-epileptic drugs (AEDs). We focused on the characteristics of cutaneous adverse reaction (CAR). In this retrospective study, the medical records of 67 patients who were diagnosed as having EAE in our hospital were reviewed and the clinical characteristics were analyzed. Immunological biomarkers including cytokines, chemokines, granzyme B, soluble tumor necrosis factor receptor 1 (s-TNFR 1), matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1) were measured in 22 patients. CARs attributed to AEDs were observed in 16 of 67 EAE patients (23.9%) (CAR group). High CAR rates were observed with phenytoin, lamotrigine, phenobarbital, and carbamazepine. Severe CARs were found in three of 67 patients (4.5%). The frequencies of CARs were significantly higher in patients with encephalitis onset older than five years of age. CAR occurred only in patients who had onset of EAE within 6 months after encephalitis. The durations from acute encephalitis to CARs were within one year for almost all AEDs, except lamotrigine. The proportion of patients with serumregulated on activation normal T cell expressed and secreted (RANTES) levels higher than the upper limit of normal range was significantly higher in CAR group than in non-CAR group. Patients in the early stage of EAE and patients with encephalitis onset older than five years of age may be at higher risk of CARs to AEDs, especially to phenytoin, lamotrigine, phenobarbital, and carbamazepine. RANTES may be a biomarker for susceptibility to CARs in EAE patients.     

Effects of common anti-epileptic drug monotherapy on serum levels of homocysteine, vitamin B12, folic acid and vitamin B6.

There is emerging evidence to support the unfavorable effects of some anti-epileptic drugs on the plasma homocysteine concentrations. Elevated homocysteine levels induced by anti-epileptic drug administration can theoretically increase not only the risk of vascular occlusive diseases, but also the risk of resistance to anti-epileptics and development of refractory epilepsy. To investigate the effect of common anti-epileptic drugs on the homocysteine metabolism, a total of 75 epileptic patients receiving phenytoin (n=16), carbamazepine (n=19), or valproic acid (n=22) and no anti-epileptic drug (n=18) were enrolled. Eleven age- and sex-matched healthy subjects served as the control group. Blood concentrations of homocysteine, folic acid, Vitamin B12 and pyridoxal 5'-phosphate (active circulating form of Vitamin B6) were measured. Compared to the control group, epileptic patients on anti-epileptic drug had higher blood levels of homocysteine. No difference in homocysteine concentrations was observed among epileptic patients in terms of the anti-epileptic drug used. Patients receiving phenytoin had significantly lower folic acid levels and those receiving carbamazepine had marginally lower pyridoxal 5'-phosphate levels in comparison with those using other anti-epileptic drugs. A negative correlation between homocysteine and folic acid concentrations was detected in epileptic patients on anti-epileptic drug. The duration of anti-epileptic drug use was correlated to the decrease of folic acid levels, but not with changes observed in homocysteine, Vitamin B12 and pyridoxal 5'-phosphate levels. No relationship between seizure frequency and homocysteine levels was observed in epileptic patients. Our results confirm that common anti-epileptic drugs has disadvantageous effects on homocysteine status. Because there was no significant change in homocysteine concentrations in epileptic patients who were not receiving an anti-epileptic drug, and no positive correlation between seizure frequency and homocysteine levels, we suggest that increase of homocysteine levels may be due to anti-epileptic drug use, rather than being epileptic in origin. Additionally, the underlying mechanism for homocysteine increase seems to be a decrease of cofactor molecules in patients using carbamazepine and phenytoin (pyridoxal 5'-phosphate and folic acid, respectively). However, changes observed are not related to the alteration in the levels of cofactors and remain unclear in the patients using valproic acid.     

Phenytoin Induced Erythema Multiforme after Cranial Radiation Therapy

The prophylactic use of phenytoin during and after brain surgery and cranial irradiation is a common measure in brain tumor therapy. Phenytoin has been associated with variety of adverse skin reactions including urticaria, erythroderma, erythema multiforme (EM), Stevens-Johnson syndrome, and toxic epidermal necrolysis. EM associated with phenytoin and cranial radiation therapy (EMPACT) is a rare specific entity among patients with brain tumors receiving radiation therapy while on prophylactic anti-convulsive therapy. Herein we report a 41-year-old female patient with left temporal glial tumor who underwent surgery and then received whole brain radiation therapy and chemotherapy. After 24 days of continous prophylactic phenytoin therapy the patient developed minor skin reactions and 2 days later the patient returned with generalized erythamatous and itchy maculopapuler rash involving neck, chest, face, trunk, extremities. There was significant periorbital and perioral edema. Painful mucosal lesions consisting of oral and platal erosions also occurred and prevented oral intake significantly. Phenytoin was discontinued gradually. Systemic admistration of corticosteroids combined with topical usage of steroids for oral lesions resulted in complete resolution of eruptions in 3 weeks. All cutaneous lesions in patients with phenytoin usage with the radiotherapy must be evoluated with suspicion for EM.     

Levetiracetam Versus Phenytoin: A Comparison of Efficacy of Seizure Prophylaxis and Adverse Event Risk Following Acute or Subacute Subdural Hematoma Diagnosis

Background

Although both levetiracetam and phenytoin are used for seizure prophylaxis in subdural hematomas (SDHs), there is little data on their comparative efficacies. We compared the efficacy and risk of using levetiracetam versus phenytoin for seizure prophylaxis following acute or subacute SDH diagnosis.

Methods

In this retrospective cohort study, the clinical data registry at a tertiary care hospital was searched for all cases of acute or subacute SDHs that were admitted to hospital in 2002, 2003, or 2011. Risk of clinical and/or electrographic seizures, and risk of adverse drug events were compared between the two exposure arms.

Results

124 subjects in the phenytoin arm and 164 subjects in the levetiracetam arm were included. There was no significant difference in clinical and/or electrographic seizure risk, though there was a decreased risk of adverse events in the levetiracetam arm (p < 0.001). In subjects with midline shift >0 mm, levetiracetam was associated with an increased risk of electrographic seizures during hospitalization (p = 0.028) and a decreased risk of adverse drug effects (p = 0.001), compared with phenytoin use.

Conclusions

Levetiracetam generally appears to have a similar efficacy to phenytoin in preventing clinical and/or electrographic seizures following acute/subacute SDH diagnosis, though patients with midline shift >0 mm may have associated with a higher risk of electrographic seizures on levetiracetam compared with patients on phenytoin. Levetiracetam is associated with a lower risk of adverse drug effects. A prospective, randomized study would more definitively determine any difference in efficacy and risk between phenytoin and levetiracetam.     

The influence of seizure type on the efficacy of plasma concentrations of phenytoin, phenobarbital, and carbamazepine

Plasma concentrations of phenytoin, phenobarbital, or carbamazepine were monitored prospectively during successful single-drug therapy in 78 patients who had various types of epileptic seizures. Mean plasma concentrations necessary for complete control of tonic-clonic seizures alone were as follows: phenytoin, 14 micrograms/mL (n = 28); phenobarbital, 18 micrograms/mL (n = 10); and carbamazepine, 5.5 micrograms/mL (n = 2). Epilepsy with simple or complex partial seizures alone or together with tonic-clonic seizures was completely controlled at the following plasma concentrations: phenytoin, 23 micrograms/mL (n = 25); phenobarbital, 37 micrograms/mL (n = 5); and carbamazepine, 7 micrograms/mL (n = 7). Higher plasma concentrations of phenytoin, phenobarbital, and carbamazepine are necessary for control in epilepsy with simple or complex partial seizures compared with epilepsy with tonic-clonic seizures alone. The efficacy of plasma concentrations of phenytoin, phenobarbital, and carbamazepine varies with the type of seizure.     

拉莫三嗪对特殊类型癫癎的疗效观察

目的观察拉莫三嗪(LTG)对特殊类型人群(育龄期女性)部分发作性癫癎患者的疗效和安全性。方法临床确诊的育龄期女性部分性发作癫癎患者90例,LTG单药治疗,定期随访,进行疗效和不良反应的观察。结果 LTG单药治疗育龄期女性部分性发作癫癎患者的有效率在76.7%以上,患者在用药后无一例重度不良反应。结论 LTG对育龄期女性部分性发作癫癎患者的疗效确切,安全性好,对怀孕和生育过程影响较小。     

Do no harm--but first we need to know more: the case of adverse drug reactions with antiepileptic drugs

An adverse drug reaction (ADR) is defined by the World Health Organization as a noxious, unintended, and undesired drug effect, when used for therapeutic purposes in humans. ADRs to anti-epileptic drugs (AEDs) significantly impact the quality of life of people with epilepsy and account for a little less than half of all recorded treatment failures with AEDs. Hence prevention and early recognition of ADRs constitute an important aspect of management of epilepsy. Recent developments have improved our ability to predict and hence potentially prevent the occurrence of some of the serious ADRs to AEDs. One example is the potential prediction of the risk of severe cutaneous hypersensitivity reactions including Stevens Johnson syndrome and toxic epidermal necrolysis by testing for expression of HLA BFNx011502 allele in people of Asian origin who are prescribed carbamazepine. The association between HLA BFNx011502 expression and carbamazepine skin reactions has been documented in India but the role of HLA testing in Indian populations needs to be clarified in larger studies across different ethnic groups within the country.     

Choice and administration sequence of antiepileptic agents for status epilepticus and frequent seizures in children

We investigated the sequence of the administration, the efficacy and the safety of antiepileptic drugs (AED) given intravenously for the treatment of status epilepticus and frequent seizures in children. Our institute has a recommended sequence of AED administration for treatment of status epilepticus: the first-line agent is diazepam (0.3 - 0.5 mg/kg administered intravenously, once or twice). The second-line drugs include midazolam (0.15 - 0.4 mg/kg intravenously, once or twice, and if necessary, followed by continuous infusion at 0.06 - 0.18 mg/kg/hour), lidocaine (1 - 2 mg/kg intravenously, once or twice, and if necessary, followed by continuous infusion at 2 - 4 mg/kg/hour) and phenytoin (10 - 20 mg/kg, infused slowly). For those patients who previously experienced a seizure which was refractory to diazepam but responsive to the second-line agent, it was recommended to use the second-line agent as a first-line agent. When seizures were refractory to the first and second-line agents, thiopental was administered (3 - 10 mg/kg intravenously, and if necessary, followed by continuous infusion at 2 -5 mg/kg/hour). The etiologies of 177 occasions of status epilepticus and frequent seizures were categorized into two groups:epilepsy (n = 95) and situation-related seizures (n = 82). Situation-related seizures included febrile seizures (n = 44), acute encephalopathy/encephalitis (n = 31) and benign infantile convulsions (n = 7). The ages of the patients ranged from 0.1 to 18.4 years (average +/- SD:3.69 +/- 3.15 years). Diazepam was administered as the first-line drug on 157 of 177 occasions (88.7%). On 116 occasions the second-line agents were administered. Midazolam and lidocaine were injected as the second-line agent on 54 (46.6%), and on 33 (28.4%) occasions, respectively, although both midazolam and lidocaine injections were off-label use for seizure control in Japan. Thiopental was used as the third to fifth-line agent. Effective ratios (effective occasions/total occasions) of each drug were the following: thiopental 19/21 (90.4%), midazolam 57/99 (57.6%), lidocaine 25/60 (41.7%), phenytoin 16/41 (39.0%), diazepam 59/164 (36.0%). Thiopental was statistically more effective than midazolam, lidocaine, diazepam or phenytoin (p < 0.01), and midazolam was statistically more effective than diazepam (p < 0.01) or phenytoin (p < 0.05). Administration of thiopental caused complications more frequently than the other agents (p < 0.01): The complications by thiopental were severe in some cases requiring intratracheal intubations and artificial ventilation. From the viewpoint of both efficacy and safety, midazolam should be recommended as one of the first-line agents for status epilepticus.     

Cutaneous drug eruptions by current antiepileptics: case reports and alternative treatment options

Serious cutaneous drug eruptions due to antiepileptics have been defined for many drugs like carbamazepine, diphenylhydantoin, phenytoin and valproate. In recent years, adverse cutaneous reactions due to the current antiepileptic drugs have also been reported. In this paper, two cases are presented: a 48-year-old female receiving gabapentin for postherpetic neuralgia who developed leukocytoclastic vasculitis after 8 weeks and a 23-year-old male receiving lamotrigine for epileptic seizures who developed toxic epidermal necrolysis (TEN) in 15 days. Alternative therapy approaches with practical suggestions are also discussed.     

Risk of angioedema associated with levetiracetam compared with phenytoin: Findings of the observational health data sciences and informatics research network

Recent adverse event reports have raised the question of increased angioedema risk associated with exposure to levetiracetam. To help address this question, the Observational Health Data Sciences and Informatics research network conducted a retrospective observational new‐user cohort study of seizure patients exposed to levetiracetam (n = 276,665) across 10 databases. With phenytoin users (n = 74,682) as a comparator group, propensity score‐matching was conducted and hazard ratios computed for angioedema events by per‐protocol and intent‐to‐treat analyses. Angioedema events were rare in both the levetiracetam and phenytoin groups (54 vs. 71 in per‐protocol and 248 vs. 435 in intent‐to‐treat). No significant increase in angioedema risk with levetiracetam was seen in any individual database (hazard ratios ranging from 0.43 to 1.31). Meta‐analysis showed a summary hazard ratio of 0.72 (95% confidence interval [CI] 0.39–1.31) and 0.64 (95% CI 0.52–0.79) for the per‐protocol and intent‐to‐treat analyses, respectively. The results suggest that levetiracetam has the same or lower risk for angioedema than phenytoin, which does not currently carry a labeled warning for angioedema. Further studies are warranted to evaluate angioedema risk across all antiepileptic drugs.     

Determinants of tiagabine (TGB) efficacy and safety. A Polish multicenter study of 1307 patients with focal epilepsy

Tiagabine (TGB) is a novel anti-epileptic drug providing new therapeutic possibilities to patients with focal seizures resistant to treatment. Since there is no clear algorithm for the best add-on therapy, the aim of our work was to establish factors that statistically significantly affect tiagabine efficacy and toxicity in patients with focal seizures. Data in the study were obtained from over 200 neurologists all over Poland. A group of 1307 patients aged from 3.5 to 80 years with drug-resistant focal epilepsy participated in the study. They were under observation for 16 weeks when receiving TGB as an add-on therapy. Prior to TGB treatment they had at least 1 seizure per month (mean 7.42 +/- 9.86) during the past 3 months. On the study completion 40.47% of the patients were seizure-free for at least a month. Two factors turned out to be significant for TGB efficacy: the number of drugs used since the onset of epilepsy (p = 0.005) and seizure type (p = 0.047). The best outcome was attained in patients with simple partial seizures. Co-medication with phenytoin was better than TGB + carbamazepine or TGB + valproic acid. The factor determining the presence of side effects was the rate of TGB dose increment during the first six weeks of treatment. Toxicity of TGB was not related to its target dose. Tiagabine is a safe and efficient anti-epileptic drug for children and adults with focal epilepsy. Efficacy of tiagabine treatment depends on the number of drugs administered since the epilepsy onset and on the type of seizures. A slow dose increment is crucial for safety of TGB treatment.     

Specific cognitive dysfunction in children with epileptic mothers

Specific cognitive abilities and motor function were investigated at 5.5 years in 104 children with epileptic mothers and in 105 control children, all with normal general intelligence. The majority (89 per cent) of the children of epileptic mothers had been exposed to anti-epileptic drugs during pregnancy, most commonly phenytoin (69 per cent). Maternal seizures had occurred during pregnancy in 52 per cent. A significant difference, with poorer performance in the study group, was found in block design (WPPSI) and auditory closure (ITPA). Significantly more study than control children had some type of specific cognitive dysfunction. Within the study group, increased risk was associated with maternal partial seizures, with seizures occurring during pregnancy, and with low paternal education, but not with exposure to anti-epileptic drugs. Three possible mechanisms of this effect are suggested: subtle brain-damage associated with fetal asphyxia during the mothers' generalized convulsions; genetically transmitted brain abnormalities; and psychosocial disadvantage limiting partner choice.     

Association between HLA-B*1502 allele and antiepileptic drug-induced cutaneous reactions in Han Chinese

A previous study conducted in Taiwan found a 100% association between HLA-B*1502 allele and carbamazepine-induced Stevens-Johnson syndrome (SJS) in Han Chinese subjects, with an extremely high odds ratio compared with carbamazepine-tolerant subjects (odds ratio = 2,504). We examined this association in 24 Hong Kong Han Chinese subjects who had cutaneous adverse reactions induced by different antiepileptic drugs (AEDs). They were matched with 48 AED-tolerant controls. HLA-B*1502 was associated with severe cutaneous reactions (SCR) induced by AEDs, which included carbamazepine, phenytoin, and lamotrigine (p = 0.001, odds ratio = 17.6), but was not associated with maculopapular exanthema (MPE) (p = 0.32). Further studies in larger samples of ethnically matched subjects should be conducted to confirm the findings. Identification of genetic polymorphisms predisposing to development of AED-induced SCR offers the possibility of avoiding these high-risk drugs in genetically susceptible individuals.     

Phenytoin: effective but insidious therapy for epilepsy in people with intellectual disability

Phenytoin (5,5-diphenylhydantoin), which has been in use for 60 years, is still an important antiepileptic drug. Its primary mechanism of action is modulation of the sustained repetitive firing of neurones by direct inhibition and blockage of voltage-gated sodium channels in the neuronal cell membrane, and by delay of cellular reactivation. The plasma protein binding of phenytoin is normally between 90% and 95%. The drug is rapidly distributed from the blood to the tissues and is almost completely metabolized in the liver. The plasma phenytoin concentration normally reaches the steady-state level within 1-2 weeks. The half-life of phenytoin is less than 20 h in low doses, but is prolonged in high doses, newborn infants and elderly people. The half-life is shortened when phenytoin is given concomitantly with an enzyme-inducing drug, such as phenobarbital or carbamazepine. Phenytoin is effective for treating generalized tonic-clonic seizures, partial seizures with or without generalization, and convulsive status epilepticus. Over the years, many new, and even serious, adverse effects of phenytoin have been recognized. Phenytoin encephalopathy, manifesting as cognitive impairment and a cerebellar syndrome, is an important adverse neurological effect, the development of which depends on the saturation kinetics of phenytoin, individual differences in phenytoin metabolism, an inhibitory effect of certain drugs on phenytoin metabolism, or the ability of certain drugs to displace phenytoin from plasma proteins, leading to an increase in the plasma level of unbound phenytoin. Because of its potentially adverse effects, phenytoin is not recommended as the first choice for treating epileptic seizures, except as a co-drug for managing convulsive status epilepticus. In patients with epilepsy who also have intellectual disability, and are susceptible to balance disturbances and cognitive dysfunction, it is wise to replace phenytoin with another drug, such as carbamazepine or oxcarbazepine. The long-term use of phenytoin is not recommended for patients with loss of locomotion, marked cognitive impairment, or symptoms and signs of cerebellar disease. The prevention of phenytoin intoxication, with the subsequent development of phenytoin-induced encephalopathy, depends on careful observation of the patients and frequent monitoring of plasma levels of phenytoin and other concomitantly administered antiepileptic drugs.     

Treatment of seizure emergencies: convulsive and non-convulsive status epilepticus

Status epilepticus (SE), defined as recurrent epileptic seizures without complete recovery between seizures, is one of the most serious manifestations of epilepsy. Generalized convulsive status epilepticus (GCSE) is the most common and most life-threatening form of SE, and aging increases the mortality risk. In a recent study of treatment of GCSE, 226 of 518 evaluable patients (43.6%) were of age 65 or older. In the 157 elderly patients with overt GCSE, phenobarbital was successful as first-line treatment in 71.4%, lorazepam in 63%, diazepam and phenytoin in 53.3%, and phenytoin alone in 41.5%. Phenobarbital and lorazepam were more successful than phenytoin alone. In the 69 elderly patients with subtle GCSE, success as the first treatment was 30.8% for phenobarbital, 14.3% for lorazepam, 11.8% for phenytoin, and 7.7% for diazepam and phenytoin. Overall, the results were similar to those reported for the entire study. Lorazepam, because of ease of use, is probably the best drug for the initial treatment of overt GCSE in the elderly; phenobarbital may be the best drug for subtle GCSE in this group, but more data are needed. The term "nonconvulsive SE" has been used to include complex partial SE and absence SE - both of which present as an "epileptic twilight state" - and SE in comatose patients. The diagnosis can be challenging, particularly in the elderly, as overlapping clinical features and electroencephalogram patterns can be seen in SE and in a variety of encephalopathic conditions. There is a suggestion that aggressive treatment of elderly patients with nonconvulsive SE may worsen prognosis. Clearly, there is a need for more data to better understand management of elderly patients with both convulsive and nonconvulsive SE.     

Intravenous phenytoin in acute treatment of seizures

Large doses of phenytoin were administered on 159 occasions to 139 adult patients. Most patients had had more than three seizures or were in status epilepticus. Based on response to treatment, patients could be divided into two groups. Those with excellent response (recurrent seizures, 10%; mortality, 1%) included known epileptics with exacerbation of seizures (n = 75), atypical alcohol withdrawal (6), or miscellaneous conditions (17). Those with poor results (recurrent seizures, 57% mortality, 38%) included patients with anoxic or metabolic encephalopathy (14), stroke or other vascular disease (14), brain tumor (5), or trauma (5).     

Rash from antiepileptic drugs: influence by gender, age, and learning disability

PURPOSE: Cutaneous adverse reactions from antiepileptic drugs (AEDs) are common, but have received little scientific attention from a clinical point of view. We wanted to study the incidence of skin reactions of current AEDs and to explore their relation to clinical parameters such as gender, age, and learning disability. METHODS: Consecutive patients with epilepsy were studied retrospectively. A detailed survey of medical records concerning all treatment with AEDs was performed. RESULTS: A total of 663 patients were included with altogether 2,567 exposures to 15 different AEDs. Skin reactions were found in 14% of the patients and in 5% of the exposures. Ninety-seven percent of the reactions occurred to either carbamazepine (CBZ, 11%), phenytoin (PHT, 8%), lamotrigine (LTG, 8%), oxcarbazepine (8%), or phenobarbital (2%). Skin reactions developed significantly more often in females than in males (19% vs. 8%), and significantly less often in patients with learning disability than in other patients (7% vs. 16%). These differences were significant for CBZ, PHT, and LTG when analyzed separately. Females displayed higher rash frequency during the reproductive years, while men experienced less frequent rash in the same phase of life. CONCLUSIONS: Fertile females have a higher risk for skin reactions compared to males, probably due to hormonal factors. Patients with learning disability appeared to have a lower risk than other patients in this study. Hygiene factors may possibly be underlying.     

An Evaluation of Anti-Epileptic Treatment in People with Mental Handicap

The anti-epileptic drugs, carbamazepine and sodium valproate, were used to control generalised seizures (tonic clonic) and absence seizures in people with mental handicap in Brock-hall Hospital, who were not well-controlled with other drugs like phenobarbitone, phenytoin and primidone. The results indicated that the number of seizures decreased dramatically with these newer anti-convulsants and without the need for polypharmacy, as was the norm previously. In addition, nurses' ratings of the patients suggested a reduction in the number of problem behaviour towards other patients and staff, and more amenable and pleasant behaviour.