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410 Sulthiame vs placebo in treatment of benign epilepsy with centrotemporal spikes (Rolandic epilepsy)
A44
Abstracts
Case 3: A Z-year-old girl was treated for epileptic encephalopathy with clobazam and VPA at increasing doses up to 55g/kg/day. Neutropenia, hypofibrinogenaemia, prolonged prothrombin time and thrombocytopenia with anti-GPIaIIa and GPIbIX AAb were detected before a surgical procedure. The change from VPA to vigabatrin led to the resolution of biological abnormalities but was associated with epilepsy relapse. VPA was thus reintroduced inducing both a clinical improvement and the recurrence of the biological anomalies. Case 4: A 33-year-old woman was treated with VPA (30mg/kg/day) after surgery and local irradiation for a frontal astrocytoma. An unexpected bleeding occurred 4 years later during surgery, requiring packed red blood cells transfusions. Despite a normal bleeding time, ex uivo platelet aggregation evidenced a platelet dysfunction due to an anti-platelet autoantibody (AAb) against platelet glycoprotein (GP) IaIIa. These biological as well as clinical anomalies were related to VPA treatment, as they all resolved after drug discontinuation, allowing surgery without complication. These four cases confirm that VPA-linked haematological abnormalities are generally clinically silent, specific, dose-dependent and reversible. These characteristics suggest that it is possible to maintain the treatment with close biological and clinical surveillance in case of severe epilepsia controlled by VPA. However, VPA-induced platelet dysfunction carries the risk of severe bleeding during surgery, suggesting that a platelet aggregation test should be systematically performed in the preoperative period, even in case of normal bleeding time. We have demonstrated for the first time the presence of specific AAb against GPIaIIa, GPIBIX and GPIIbIIa. This allows us to propose an autoimmune mechanism accounting during VPA therapy: this gives a strong support to the previously proposed autoimmune mechanism of VPAinduced thrombocytopenia and platelet dysfunction.
blind observer. Target criterion was the number of terminal events per group while terminal events were defined as a first seizure after a 7-day run-in period, adverse events requiring cessation of trial medication, development of another form of epilepsy, or termination of trial by parents or patient. In all 40 boys and 26 girls aged 3-10 years participated; 31 patients were randomized to STM and 35 to placebo. Results: 25/31 STM patients (80.6%) and lo/35 placebo patients (31%) completed the trials without terminal events (p < 0.0001; Fisher’s exact x2 test). The majority of terminal events were seizures (n = 25); parents requested termination of the trial in two placebo patients during the run-in period. Four patients (two in each group) were excluded from the study because of administrative reasons. While all sleep EEGs at baseline showed at least one specific focus, about 29% patients in the STM zts 2.9% in the placebo group achieved a permanent normalization of sleep EEGs, while in 19.4% (STM) ZIS 45.7% (placebo) EEGs depicted pathology at follow-ups. Conclusions: It is the first time that in a controlled study it could be demonstrated that STM is effective to control epileptic seizure as well as effective on specific EEG features. In this trial patients suffering from BECTS and > two seizures during past 6 months had a high risk of early seizure recurrence when staying untreated. STM was remarkably effective and tolerability was excellent. The use as drug of first choice in children with BECTS is justified when considering alternatives.
217
Are there benefits, in addition to improved seizure control, for children receiving vagus nerve stimulation? P RAWLINS
Via Christi Regional Medical Center, Wichita, Kansas, USA 410
Sulthiame vs placebo in treatment of benign epilepsy with centrotemporal spikes (Rolandic epilepsy) D RATING,
T BAST,’ C WOLF
for the Sulthiame
study
group
Ruprecht-Karls-UniversitZt, Kinderklinik, Department of Paediatric Neurology, Heidelberg, Germany; ‘Desitin Arzneimittei GmbH, Hamburg, Germany
Introduction: In most textbooks carbamazepine (CBZ) is recommended as first-line drug in the treatment of children suffering from benign epilepsy with centrotemporal spikes (BECTS; Rolandic epilepsy). Furthermore in the English literature it is questioned whether sulthiame (STM; Ospolot@) is effective at all while German epileptologists see STM as the drug of choice in Rolandic epilepsy. Methods: To evaluate the efficacy and tolerability of STM in children suffering from BECTS (2 two seizures during past 6 months; age 3-11 years; no prior anti-epileptic treatment after 6th month of life) a double-blind parallelgroup trial was set up. Patients were randomized to either 5mg STM/kg body weight or placebo for 6 months. Plasma levels and EEGs were overseen by a
Rationale: Chronic intermittent vagus nerve stimulation (VNS) is an effective adjunct treatment for medically intractable seizures. Family functioning is suboptimal when a child has uncontrolled epilepsy compounded by disruptive behaviour. The aim of this paper is to document improved temperament in four of four children receiving VNS and the resulting influence on caregiver perceptions. Method: At our centre, 14 patients with intractable epilepsy were implanted with the Cyberonics, Inc. Vagus Nerve Stimulator. Of these, four were under 21 years of age, mentally retarded and incapable of independent living. They experienced a long history of disruptive behaviour and received full-time special education services. These factors contributed to altered family functioning per parent report. A change in disposition, leading to enhanced socialization and pleasant parent-child interaction was documented from teacher reports, investigator observation, parent global evaluation scale and parent interviews. Medications, school programmes and primary caretaker remained constant.
Results: Four of the four children had improved behaviour within 6 weeks of initiation of VNS compared with baseline. Educators documented improved social-
Abstracts
Case 3: A Z-year-old girl was treated for epileptic encephalopathy with clobazam and VPA at increasing doses up to 55g/kg/day. Neutropenia, hypofibrinogenaemia, prolonged prothrombin time and thrombocytopenia with anti-GPIaIIa and GPIbIX AAb were detected before a surgical procedure. The change from VPA to vigabatrin led to the resolution of biological abnormalities but was associated with epilepsy relapse. VPA was thus reintroduced inducing both a clinical improvement and the recurrence of the biological anomalies. Case 4: A 33-year-old woman was treated with VPA (30mg/kg/day) after surgery and local irradiation for a frontal astrocytoma. An unexpected bleeding occurred 4 years later during surgery, requiring packed red blood cells transfusions. Despite a normal bleeding time, ex uivo platelet aggregation evidenced a platelet dysfunction due to an anti-platelet autoantibody (AAb) against platelet glycoprotein (GP) IaIIa. These biological as well as clinical anomalies were related to VPA treatment, as they all resolved after drug discontinuation, allowing surgery without complication. These four cases confirm that VPA-linked haematological abnormalities are generally clinically silent, specific, dose-dependent and reversible. These characteristics suggest that it is possible to maintain the treatment with close biological and clinical surveillance in case of severe epilepsia controlled by VPA. However, VPA-induced platelet dysfunction carries the risk of severe bleeding during surgery, suggesting that a platelet aggregation test should be systematically performed in the preoperative period, even in case of normal bleeding time. We have demonstrated for the first time the presence of specific AAb against GPIaIIa, GPIBIX and GPIIbIIa. This allows us to propose an autoimmune mechanism accounting during VPA therapy: this gives a strong support to the previously proposed autoimmune mechanism of VPAinduced thrombocytopenia and platelet dysfunction.
blind observer. Target criterion was the number of terminal events per group while terminal events were defined as a first seizure after a 7-day run-in period, adverse events requiring cessation of trial medication, development of another form of epilepsy, or termination of trial by parents or patient. In all 40 boys and 26 girls aged 3-10 years participated; 31 patients were randomized to STM and 35 to placebo. Results: 25/31 STM patients (80.6%) and lo/35 placebo patients (31%) completed the trials without terminal events (p < 0.0001; Fisher’s exact x2 test). The majority of terminal events were seizures (n = 25); parents requested termination of the trial in two placebo patients during the run-in period. Four patients (two in each group) were excluded from the study because of administrative reasons. While all sleep EEGs at baseline showed at least one specific focus, about 29% patients in the STM zts 2.9% in the placebo group achieved a permanent normalization of sleep EEGs, while in 19.4% (STM) ZIS 45.7% (placebo) EEGs depicted pathology at follow-ups. Conclusions: It is the first time that in a controlled study it could be demonstrated that STM is effective to control epileptic seizure as well as effective on specific EEG features. In this trial patients suffering from BECTS and > two seizures during past 6 months had a high risk of early seizure recurrence when staying untreated. STM was remarkably effective and tolerability was excellent. The use as drug of first choice in children with BECTS is justified when considering alternatives.
217
Are there benefits, in addition to improved seizure control, for children receiving vagus nerve stimulation? P RAWLINS
Via Christi Regional Medical Center, Wichita, Kansas, USA 410
Sulthiame vs placebo in treatment of benign epilepsy with centrotemporal spikes (Rolandic epilepsy) D RATING,
T BAST,’ C WOLF
for the Sulthiame
study
group
Ruprecht-Karls-UniversitZt, Kinderklinik, Department of Paediatric Neurology, Heidelberg, Germany; ‘Desitin Arzneimittei GmbH, Hamburg, Germany
Introduction: In most textbooks carbamazepine (CBZ) is recommended as first-line drug in the treatment of children suffering from benign epilepsy with centrotemporal spikes (BECTS; Rolandic epilepsy). Furthermore in the English literature it is questioned whether sulthiame (STM; Ospolot@) is effective at all while German epileptologists see STM as the drug of choice in Rolandic epilepsy. Methods: To evaluate the efficacy and tolerability of STM in children suffering from BECTS (2 two seizures during past 6 months; age 3-11 years; no prior anti-epileptic treatment after 6th month of life) a double-blind parallelgroup trial was set up. Patients were randomized to either 5mg STM/kg body weight or placebo for 6 months. Plasma levels and EEGs were overseen by a
Rationale: Chronic intermittent vagus nerve stimulation (VNS) is an effective adjunct treatment for medically intractable seizures. Family functioning is suboptimal when a child has uncontrolled epilepsy compounded by disruptive behaviour. The aim of this paper is to document improved temperament in four of four children receiving VNS and the resulting influence on caregiver perceptions. Method: At our centre, 14 patients with intractable epilepsy were implanted with the Cyberonics, Inc. Vagus Nerve Stimulator. Of these, four were under 21 years of age, mentally retarded and incapable of independent living. They experienced a long history of disruptive behaviour and received full-time special education services. These factors contributed to altered family functioning per parent report. A change in disposition, leading to enhanced socialization and pleasant parent-child interaction was documented from teacher reports, investigator observation, parent global evaluation scale and parent interviews. Medications, school programmes and primary caretaker remained constant.
Results: Four of the four children had improved behaviour within 6 weeks of initiation of VNS compared with baseline. Educators documented improved social-