Abstract Background During modified gap-balancing technique, there is no consensus on the best method for obtaining appropriate soft-tissue balance and determining the femoral component rotation. ...Methods Sixty-five varus osteoarthritic patients underwent primary posterior-stabilized total knee arthroplasty using modified gap-balancing technique. The influence of joint distraction force on the soft-tissue balance measurement during the modified gap-balancing technique was evaluated with Offset Repo-Tensor between the osteotomized surfaces at extension, and between femoral posterior condyles and tibial osteotomized surface at flexion of the knee before the resection of femoral posterior condyles. The joint center gap (millimeters) and varus ligament balance (°) were measured under 20, 40, and 60 pounds of joint distraction forces, and the differences in these values at extension and flexion (the value at flexion minus the value at extension) were also calculated. Results The differences in joint center gap (−6.7, −6.8, and −6.9 mm for 20, 40, and 60 pounds, respectively) and varus ligament balance (3.5°, 3.8°, and 3.8°) at extension and flexion were not significantly different among different joint distraction forces, although the joint center gap and varus ligament balance significantly increased stepwise at extension and flexion as the joint distraction force increased. Conclusion The difference in joint center gap and varus ligament balance at extension and flexion were consistent even among the different joint distraction forces. This novel index would be useful for the determination of femoral component rotation during the modified gap-balancing technique.
Abstract Background We describe the brain magnetic resonance imaging (MRI) abnormalities and neuropathologic findings in patients with Sturge-Weber syndrome and medically refractory epilepsy. Methods ...We retrospectively reviewed the clinical features, preoperative MRI studies, and pathologic findings of all patients with Sturge-Weber syndrome who underwent excisional surgery for intractable epilepsy at Boston Children's Hospital between 1993 and 2011. Results Eleven patients (male/female = 4/7) with Sturge-Weber syndrome were identified who underwent surgery for intractable epilepsy (mean age 13 ± 6.2 months), including hemispherectomy (n = 10) and focal cortical resection (n = 1). Mean age at seizure onset was 15 ± 11 weeks. Fifty-five percent (n = 6) of patients exhibited two different types of seizures, and 18% (n = 2) had three types of seizures. Focal clonic seizures were the most common type, occurring in nine patients; apnea was the second most common, occurring in four patients. Brain MRIs were reviewed in five patients. Histopathologic examination revealed signs of varied degrees of cortical morphologic anomaly in seven of 11 patients. Overall, there were no abnormalities in the MRIs that corresponded directly with the pathologic findings except in one patient with polymicrogyria. Conclusions In spite of pathologic findings of cortical anomalies in varied degrees, these findings could not be readily detected on brain MRIs. The failure to detect focal cortical dysplasia on MRIs may be attributable to the subtle microscopic nature of the abnormalities; in some of the older individuals, the imaging studies available for review were done during an advanced stage of the disease.
Abstract Background Hemispherectomy is a surgical procedure used to treat medically intractable epilepsy in children with severe unilateral cortical disease secondary to acquired brain or congenital ...lesions. The major surgical approaches for hemispherectomy are anatomic hemispherectomy, traditional functional hemispherectomy, and peri-insular hemispherotomy. We describe the epilepsy outcome, including the need for reoperation, after hemispherectomy in patients with brain malformations or acquired brain lesions who underwent hemispherectomy for refractory epilepsy. Methods We conducted a retrospective observational study at Children's Hospital Boston. Cases were ascertained from a research database of patients who underwent epilepsy surgery from 1997 to 2011. Data were obtained from electronic medical records and office charts. Outcome after surgery was defined as improvement in seizures (quantity and severity) represented by the Engel classification score measured at last follow-up, with a minimum of 12 months of follow-up. The need for reoperation for completion of hemispheric disconnection. We also examined whether placement of ventriculoperitoneal shunt was required after hemispherectomy was a secondary outcome. Results We identified 36 patients who underwent hemispherectomy for severe, medically intractable epilepsy. Group 1 (n = 14) had static acquired lesions, and group 2 (n = 22) had malformations of cortical development. Mean age at surgery for group 1 was 9 years (S.D. 5.5) and 2.77 years for group 2 (S.D. 4.01; P < 0.001). The seizure outcome was good in both groups (Engel score I for 25, II for three, III for six, and IV for two patients) and did not differ between the two groups. In group 1, five patients underwent anatomic hemispherectomy (one had prior focal resection), four underwent functional hemispherectomy, and five underwent peri-insular hemispherotomy; none required a second procedure. In group 2, a total of 14 patients had anatomic hemispherectomy (of these, three had had limited prior focal resection), five had functional hemispherectomy, and three had peri-insular hemispherotomy. Among the patients in group 2 who had had functional hemispherectomy, one required reoperation to complete the disconnection and one required peri-insular hemispherotomy because of persistent seizures. In group 1, three patients underwent a ventriculoperitoneal shunt, and from these patients two underwent anatomic hemispherectomy and one had functional hemispherectomy. In group 2, 12 patients had ventriculoperitoneal shunt, and all of them had anatomic hemispherectomy as a first or second procedure. Conclusion Seizure outcome after hemispherectomy is good in patients with acquired lesions and with developmental malformations. Although the seizure outcome was similar in the three procedures, the complication rate was higher with anatomic hemispherectomy than with the more recent functional hemispherectomy and peri-insular hemispherotomy. The group with cortical malformations generally had surgery at a younger age; two patients with malformations of cortical development who underwent functional hemispherectomy required second surgeries. The need for reoperation in these cases may reflect the anatomic complexity of developmental hemispheric malformations, which may lead to incomplete disconnection.
We report our pediatric experience with lacosamide, a new antiepileptic drug, approved by the US Food and Drug Administration as adjunctive therapy in focal epilepsy in patients more than 17 years ...old. We retrospectively reviewed charts for lacosamide use and seizure frequency outcome in patients with focal epilepsy (Wilcoxon signed rank test). Sixteen patients (7 boys) were identified (median dose 275 mg daily, 4.7 mg/kg daily; mean age 14.9 years, range 8-21 years). Patients were receiving a median of 2 antiepileptic drugs (interquartile range IQR 1.7-3) in addition to having undergone previous epilepsy surgery ( n = 3), vagus nerve stimulation ( n = 9), and ketogenic diet ( n = 3). Causes included structural (encephalomalacia and diffuse encephalitis, 1 each; stroke in 2) and genetic abnormalities (Aarskog and Rett syndromes, 1 each) or cause not known ( n = 10). Median seizure frequency at baseline was 57 per month (IQR 7-75), and after a median follow-up of 4 months (range 1-13 months) of receiving lacosamide, it was 12.5 per month (IQR 3-75), ( P < 0.01). Six patients (37.5%; 3 seizure free) were classified as having disease that responded to therapy (≥50% reduction seizure frequency) and 10 as having disease that did not respond to therapy (<50% in 3; increase in 1; unchanged in 6). Adverse events (tics, behavioral disturbance, seizure worsening, and depression with suicidal ideation in 1 patient each) prompted lacosamide discontinuation in 4/16 (25%). This retrospective study of 16 children with drug-resistant focal epilepsy demonstrated good response to adjunctive lacosamide therapy (median seizure reduction of 39.6%; 37.5% with ≥50% seizure reduction) without severe adverse events.
Abstract Background Clobazam has been used in clinical practice as an adjunctive treatment for diverse seizure types and epilepsy syndromes. We evaluated the efficacy and safety of clobazam in a ...large sample of patients with refractory epilepsy at a tertiary pediatric center. Methods We retrospectively reviewed patients treated with clobazam between January 2001 and July 2013 who had a follow-up visit at least one month after starting clobazam. Response was defined as ≥50% reduction in seizure frequency compared with baseline seizure frequency during the 3 months before the introduction of clobazam. We examined the relationship between dose range and response rate. Results Four-hundred twenty-five patients were prescribed clobazam, of whom 300 (median age 9.1 years, interquartile range 4.7-13.3 years) had follow-up data greater than 1 month. Median follow-up was 5 months (interquartile range 3-11 months). Response to treatment with clobazam was observed in 203 of 300 (67.7%) patients, of whom 84 (28%) became seizure-free. The median starting dose was 0.2 (interquartile range 0.13-0.33) mg/kg/day with a target dose of 0.48 (0.26-0.80) mg/kg/day. Twenty-seven (9%) patients discontinued clobazam, 16 (59.3%) because adverse effects, 10 (37%) because of a lack of efficacy, and one (3.7%) because of a combination of adverse effects and lack of efficacy. The most common adverse effects were tiredness in 44 of 300 (14.6%) and mood or behavioral changes in 23 (7.7%). Conclusions Clobazam is a well-tolerated antiepileptic drug with good response rates in pediatric patients with refractory epilepsy.
Rufinamide is a new antiepileptic drug recently approved as adjunctive treatment for generalized seizures in Lennox-Gastaut syndrome. We undertook a retrospective analysis of 77 patients with ...refractory epilepsy and receiving rufinamide to evaluate the drug's efficacy, tolerability, safety, and dosing schedules. It appeared efficacious in diverse epilepsy syndromes, with the highest responder rate in focal cryptogenic epilepsies (81.1% of patients with >50% response rate), and in diverse seizure types, with the highest responder rate in tonic/atonic and partial seizures (48.6% and 46.7% of patients with >50% response rate, respectively). Rufinamide was well tolerated: only 13% of patients developed side effects necessitating drug withdrawal. These findings suggest that rufinamide may possess good efficacy and tolerability, and that its efficacy may extend to epilepsy syndromes beyond Lennox-Gastaut, including both partial and generalized epilepsy syndromes.
Abstract Background This study evaluated whether the reduction in epileptiform activity after treatment with high-dose diazepam in continuous spikes and waves during sleep persists over time. ...Patients Patients aged 1 to 21 years with continuous spikes and waves during sleep who received high-dose nocturnal diazepam and who had electroencephalogram follow-up were included. Twenty-nine patients met the inclusion criteria and underwent a total of 48 high-dose diazepam treatment cycles. Results An overnight reduction of the spike wave percentage of at least 25% (i.e., 75-50%) occurred in 29 cycles (20 patients), and persisted within 6 months in 16 of 29 cycles (12 patients), but returned to baseline in three of 29 cycles (three patients). An overnight reduction of at least 50% (i.e., 75-25%) occurred in 15 cycles (13 patients), and persisted within 6 months in eight of 15 cycles (eight patients), but returned to baseline in three cycles (three patients). Twenty of 29 cycles that responded in the short term had persistent response on follow-up. Thirteen cycles of treatment were associated with mild side effects that did not recur with repeated treatment cycles. Conclusions Treatment with high-dose diazepam reduced epileptiform activity in continuous spikes and waves during sleep in the short term, and improvement persisted for several months in most cycles. Short-term response predicted persistence of this effect on subsequent follow-up.
Abstract We describe the short-term effects of high-dose oral diazepam on sleep-potentiated epileptiform activity in patients with electric status epilepticus during sleep. We enrolled patients ...treated with high-dose oral bedtime diazepam from 2001-2009. We defined spike percentage as the percentage of 1-second bins containing at least one spike, and calculated it during three randomly selected 5-minute samples of wakefulness throughout the day and during the first 5 minutes of every hour of non-rapid eye movement sleep at night. In this study, patients were considered to demonstrate sleep-potentiated epileptiform activity when their spike percentage during sleep was increased by ≥50% compared with wakefulness. Twenty-nine children (18 boys) were included (median age, 7.4 years). Twenty-four hours after receiving high-dose diazepam, epileptiform activity was significantly reduced (76.7% at baseline vs 40.8% 24 hours after high-dose diazepam; Wilcoxon signed ranks test, Z = −4.287, P < 0.0001). Seven patients (24.1%) manifested mild, reversible side effects during the first 48 hours after diazepam administration. High-dose oral diazepam effectively and safely reduced epileptiform activity in patients with electric status epilepticus during sleep.
Abstract Objective Pyridoxine is converted to its biologically active form, pyridoxal-5-phosphate (P5P) by the enzyme pyridox(am)ine oxidase (PNPO), and serves as a cofactor in nearly 200 reactions ...in the central nervous system (CNS). PNPO deficiency leads to P5P dependent epilepsy, typically a neonatal or infantile onset epileptic encephalopathy treatable with P5P or in some cases pyridoxine. Following identification of retinopathy in a patient with PNPO deficiency that was reversible with P5P therapy, we report the systemic manifestations of PNPO deficiency.. Methods A series of six patients with confirmed homozygous PNPO mutations were identified who presented to our center over the course of two years for phenotyping of neurologic and systemic manifestations. Results Five out of six were born prematurely, three had anemia and failure to thrive, and two had elevated alkaline phosphatase. A movement disorder was observed in two children and a reversible retinopathy was observed in the most severely affected infant. All subjects had neonatal onset epilepsy and were on a continuum of developmental delay to profound encephalopathy. EEG features included background slowing and disorganization, absent sleep features, and multifocal and generalized epileptiform discharges. All the affected probands carried homozygous PNPO mutations (c.674 G>T, c.686 G>A and c.352G>A). Conclusion In addition to the well described epileptic encephalopathy, PNPO deficiency causes a range of neurologic and systemic manifestations. A movement disorder, developmental delay and encephalopathy, as well as retinopathy, anemia, and failure to thrive add to the broadening clinical spectrum of P5P dependent epilepsy.
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