Clobazam is equally safe and efficacious for seizures associated with Lennox-Gastaut syndrome across different age groups: Post hoc analyses of short- and long-term clinical trial results.

The peak age at onset of Lennox-Gastaut syndrome (LGS) is between 3 and 5years. Patients with LGS frequently experience multiple types of treatment-refractory seizures and require lifelong therapy with several antiepileptic drugs. Here, post hoc analyses of clinical trials (phase III trial OV-1012 and open-label extension trial OV-1004) provide short- and long-term efficacy and safety data of adjunctive clobazam in patients with LGS stratified by age at baseline (≥2 to <12years, ≥12 to <17years, and ≥17years). In OV-1012, 301 patients were screened, 238 were randomized, 217 comprised the modified intention-to-treat population, and 177 completed the study. A total of 267/306 patients (61 of 68 from phase II trial OV-1002 and 206 of 238 from phase III trial OV-1012) entered the open-label extension trial. Demographics and clinical characteristics were similar between different age groups in OV-1012 and OV-1004. No differences in efficacy or adverse events were observed across age groups in OV-1012 and OV-1004. The results of these post hoc analyses show that adjunctive clobazam over the short and longterm was similarly effective and well-tolerated in both pediatric and adult patients with LGS.

Stable dosages of clobazam for Lennox-Gastaut syndrome are associated with sustained drop-seizure and total-seizure improvements over 3 years.

OBJECTIVE: To determine long-term safety and efficacy of adjunctive clobazam for patients with Lennox-Gastaut syndrome (LGS). METHODS: Eligible patients from two randomized controlled trials (Phase II OV-1002 and Phase III OV-1012) were able to enroll in open-label extension (OLE) study OV-1004 beginning in December 2005 and received clobazam until they discontinued (mandatory at 2 years for patients outside the United States) or until study completion in March 2012. Patients in the United States could have received clobazam for 6 years before it became commercially available. Efficacy assessments included changes in rates of drop seizures and total seizures, responder rates (≥50%, ≥75%, or 100% decreases in seizure frequency vs. baseline), sustained efficacy over time, concomitant antiepileptic drug (AED) use, and global evaluations. Safety assessments included exposure to clobazam, laboratory assessments, physical and neurologic examinations, vital sign monitoring, electrocardiography monitoring, and adverse event reporting. RESULTS: Of 267 patients who enrolled in the OLE, 188 (70%) completed the trial. Two hundred seven patients were from the United States, which was the only country in which patients could be treated with clobazam for >2 years. Forty-four patients were treated with clobazam for 5 years, and 11 for 6 years. Because of the low number of Year 6 patients, this group is not reported separately. Improvements in baseline seizure rates were very stable over the course of the study, with a median 85% decrease in drop seizures at Year 1, 87% at Year 2, 92% at Year 3, 97% at Year 4, and a 91% decrease for patients who had reached Year 5. Similar results were observed for total seizures (79% decrease at both Years 1 and 2, 82% decrease at Year 3, 75% decrease at Year 4, and 85% decrease at Year 5). Responder rates were also stable for the duration of the trial. Of patients who had achieved a ≥50% decrease in median drop-seizure frequency from baseline to Month 3, 86% still had that degree of drop-seizure reduction at Year 3 (and 14% lost their initial responses), and 47% were drop-seizure-free. Most patients who had achieved drop-seizure freedom in the original controlled trials remained drop-seizure-free in the OLE. Based on parents' and physicians' ratings of global evaluations, 80% of patients were "very much improved" or "much improved" after 3 years. Of the 43 patients with concomitant AED data who were treated for 5 years, 30% increased, 19% decreased, and 51% had no change in numbers of AEDs versus their Week 4 regimens. The mean modal clobazam dosage was 0.90 mg/kg/day at Year 1 and 0.97 mg/kg/day at Year 5, suggesting that study patients did not need significant increases in dosage over time. The safety profile was what would be expected for clobazam for LGS patients over a 5-year span, and no new safety concerns developed over time. SIGNIFICANCE: In this largest and longest-running trial in LGS, adjunctive clobazam sustained seizure freedom and substantial seizure improvements at stable dosages through 3 years of therapy in this difficult- to-treat patient population. A PowerPoint slide summarizing this article is available for download in the Supporting Information section here.

Have antiepileptic drug prescription claims changed following the FDA suicidality warning? An evaluation in a state Medicaid program.

OBJECTIVE: In January 2008, the Food and Drug Administration (FDA) communicated concerns and, in May 2009, issued a warning about an increased risk of suicidality for all antiepileptic drugs (AEDs). This research evaluated the association between the FDA suicidality communications and the AED prescription claims among members with epilepsy and/or psychiatric disorder. METHODS: A longitudinal interrupted time-series design was utilized to evaluate Oklahoma Medicaid claims data from January 2006 through December 2009. The study included 9289 continuously eligible members with prevalent diagnoses of epilepsy and/or psychiatric disorder and at least one AED prescription claim. Trends, expressed as monthly changes in the log odds of AED prescription claims, were compared across three time periods: before (January 2006 to January 2008), during (February 2008 to May 2009), and after (June 2009 to December 2009) the FDA warning. RESULTS: Before the FDA warning period, a significant upward trend of AED prescription claims of 0.01% per month (99% CI: 0.008% to 0.013%, p<0.0001) was estimated. In comparison to the prewarning period, no significant change in trend was detected during (-20.0%, 99% CI: -70.0% to 30.0%, p=0.34) or after (80.0%, 99% CI: -20.0% to 200.0%, p=0.03) the FDA warning period. After stratification, no diagnostic group (i.e., epilepsy alone, epilepsy and comorbid psychiatric disorder, and psychiatric disorder alone) experienced a significant change in trend during the entire study period (p>0.01). CONCLUSIONS: During the time period considered, the FDA AED-related suicidality warning does not appear to have significantly affected prescription claims of AED medications for the study population.

Efficacy and tolerability of adjunctive lacosamide in patients aged <4 years with focal seizures.

OBJECTIVE: Primary objective was to evaluate efficacy of lacosamide administered concomitantly with 1-3 antiseizure medications in young children with uncontrolled focal (partial-onset) seizures. METHODS: Double-blind, parallel-group trial (SP0967: NCT02477839/2013-000717-20) conducted between June 2015 and May 2020 at hospitals and clinics in 25 countries. Patients (aged ≥1 month to <4 years) with uncontrolled focal seizures were randomized 1:1 to adjunctive lacosamide or placebo using an interactive voice/web response system and stratified by age. After a 20-day titration period, patients who reached target-dose range (8-12 mg/kg/day) entered a 7-day maintenance period. Region-specific primary efficacy variables were based on ≤72-h video-electroencephalograms: change in average daily frequency (ADF) of electrographic focal seizures as measured on end-of-maintenance video-electroencephalogram versus end-of-baseline video-electroencephalogram (United States); 50% responder rate (≥50% reduction in ADF of focal seizures) during maintenance (European Union). RESULTS: In total, 255 patients were randomized (lacosamide/placebo: 128/127) and received ≥1 trial medication dose. Percentage reduction in ADF of focal seizures for lacosamide (116 patients) versus placebo (120 patients) was 3.2% (95% confidence interval = -13.6 to 17.5, p = 0.69). 50% responder rate was 41.4% for lacosamide (116 patients), 37.5% for placebo (120 patients) (p = 0.58). Treatment-emergent adverse events were reported by 44.5% of lacosamide-treated patients (placebo 51.2%). INTERPRETATION: Adjunctive lacosamide did not show superior efficacy versus placebo in young children with focal seizures. However, efficacy variables were potentially affected by high variability and low reliability between readers in video-electroencephalogram interpretation. Lacosamide was generally well tolerated; safety profile was acceptable and consistent with that in adults and children aged ≥4 years.

"Simple febrile seizures plus (SFS+)": more than one febrile seizure within 24 hours is usually okay.

This study aimed to investigate whether children with recurrent febrile seizures within a 24-hour period need to be worked up differently from children with simple febrile seizures. Inclusion criteria included the following: (i) children with first seizure cluster between 4 months and 3 years of age, (ii) children who had more than one febrile seizure within 24 hours, and (iii) children who returned to baseline between and after each event. Thirty-two patients met the inclusion criteria over a 3-year period. All patients underwent brain CT and/or MRI and EEG. All head CTs were normal. Two children had abnormal MRI findings - both benign: one is thought to represent postictal changes, and the other one is an incidental arachnoid cyst. Of the 4 abnormal EEGs, one showed epileptiform discharges, while the others showed generalized ictal or postictal features. We propose the term "simple febrile seizures plus (SFS+)" to describe children who have more than one seizure within 24 hours but who are otherwise not different in presentation from children with SFS.

Utility and safety of prolonged video-EEG monitoring in a tertiary pediatric epilepsy monitoring unit.

Prolonged video-EEG (vEEG) monitoring helps characterize paroxysmal events and epilepsy. There is limited literature in pediatrics describing the safety and utility of vEEG. We retrospectively reviewed 454 pediatric epilepsy monitoring unit admissions over two years. Final event diagnoses, duration of seizures, and medical complications were analyzed. Two hundred twenty admissions (48.4%) captured epileptic seizures, 150 (33.0%) captured nonepileptic events, and 84 (18.5%) failed to capture any events. Medical complications were seen in 4 patients (1.8%) with no long-term complications. Seventeen episodes of status epilepticus occurred in 13 patients. This constituted 2.9% of all admissions and 5.9% of admissions with epileptic seizures. The median duration of status was 26 min, and three patients required transfer to the pediatric intensive care unit. Video-EEG monitoring had a high yield in capturing events and differentiating epileptic from nonepileptic events. Our pediatric patients experienced greater risk of status epilepticus but lesser risk of injury.

Status epilepticus in childhood.

Status epilepticus (SE) remains a life-threatening condition that afflicts both adults and children, and may occur at onset of epilepsy, especially in children. Febrile SE is the most common cause in children, while other symptomatic causes are less frequent compared to adults. The aetiological workup that must be undertaken in all cases includes neuroimaging and electroencephalography. The various electroencephalographic patterns seen in patients with SE along with the out-of-hospital treatment for SE in children and treatment strategies in cases that are refractory to first-line medical treatments are discussed. Medically induced coma may be necessary in refractory cases, although the optimal agents to use and degree of electroencephalographic suppression in children remain unclear. Neurosurgery is not a well-known treatment option that could be considered for refractory cases. Although the prognosis has probably improved over the years, it remains a potential life-threatening emergency.

Refractory Jeavons Syndrome from Birth Symptomatic to PLCB1 Mutation.

Jeavons syndrome is a common, often misdiagnosed or overlooked epileptic syndrome presenting with a triad of eyelid myoclonia with or without absence seizures, eye closure-induced EEG paroxysms, and photosensitivity. We present a seven-year-old female who presented with eyelid myoclonia evident since birth with absence seizures and migraines with associated photosensitivity. An EEG with photic stimulation confirmed the diagnosis of Jeavons syndrome. Genetic testing showed a heterozygous mutation in the PLCB1 gene which has been linked to early onset epilepsies and encephalopathic epilepsies. This mutation and her clinical presentation identifies another etiology of Jeavons syndrome and confirms it can begin from birth. Its presence highlights the importance of genetic testing in epileptic patients to better understand the links between genetics and epilepsy syndromes so appropriate treatment can be initiated.

Human subtelomeric copy number gains suggest a DNA replication mechanism for formation: beyond breakage-fusion-bridge for telomere stabilization.

Constitutional deletions of distal 9q34 encompassing the EHMT1 (euchromatic histone methyltransferase 1) gene, or loss-of-function point mutations in EHMT1, are associated with the 9q34.3 microdeletion syndrome, also known as Kleefstra syndrome [MIM#610253]. We now report further evidence for genomic instability of the subtelomeric 9q34.3 region as evidenced by copy number gains of this genomic interval that include duplications, triplications, derivative chromosomes and complex rearrangements. Comparisons between the observed shared clinical features and molecular analyses in 20 subjects suggest that increased dosage of EHMT1 may be responsible for the neurodevelopmental impairment, speech delay, and autism spectrum disorders revealing the dosage sensitivity of yet another chromatin remodeling protein in human disease. Five patients had 9q34 genomic abnormalities resulting in complex deletion-duplication or duplication-triplication rearrangements; such complex triplications were also observed in six other subtelomeric intervals. Based on the specific structure of these complex genomic rearrangements (CGR) a DNA replication mechanism is proposed confirming recent findings in Caenorhabditis elegans telomere healing. The end-replication challenges of subtelomeric genomic intervals may make them particularly prone to rearrangements generated by errors in DNA replication.

Long-term safety and efficacy of clobazam for Lennox-Gastaut syndrome: interim results of an open-label extension study.

In an ongoing open-label extension (OV-1004), patients with Lennox-Gastaut syndrome who had completed 1 of 2 randomized controlled trials (OV-1002 [Phase II] or OV-1012 [Phase III]) are receiving clobazam at dosages ≤2.0 mg/kg/day (≤80 mg/day). Of 306 eligible patients from OV-1002 or OV-1012, 267 entered the open-label extension. As of the interim date, July 1, 2010, 213 patients (79.8%) had remained in the trial, and 189 had received clobazam for ≥12 months, 128 for ≥18 months, and 94 for ≥24 months. Median percentage decreases in average weekly rates of drop seizures were 71.1% and 91.6% at Months 3 and 24. Mean modal and mean maximum daily dosages were 0.94 mg/kg and 1.22 mg/kg for those who had received clobazam for ≥1 year. The 4 most common adverse events were upper respiratory tract infection (18.4%), fall (14.2%), pneumonia (13.9%), and somnolence (12.7%). Clobazam's adverse event profile was consistent with its profile in controlled trials.

Efficacy of the ketogenic diet in Lennox-Gastaut syndrome: a retrospective review of one institution's experience and summary of the literature.

AIM: To determine the efficacy of the ketogenic diet for children with Lennox-Gastaut syndrome (LGS) at our institution and in the literature. METHOD: The records of children with LGS initiated on the ketogenic diet at our institution from 1994 to 2010 were reviewed. Inclusion criteria included the presence of ≤2.5Hz spike-and-wave complexes on electroencephalogram, multiple seizure types including tonic, atonic, or atypical absence, developmental delay, and age under 1 year. We additionally reviewed the literature for cases of LGS treated with the ketogenic diet and their outcomes. RESULTS: Seventy-one children (41 males, 30 females, median age 3y 6mo, range 18mo-18y), with LGS were initiated on the ketogenic diet. Using an intent-to-treat analysis, after 6 months, 36 (51%) achieved more than 50% seizure reduction, 16 (23%) experienced more than 90% seizure reduction, and 1 (1%) achieved seizure freedom. Results were similar after 12 months. Age, sex, side effects, valproate use, and history of infantile spasms were not predictive of more than 90% seizure reduction. In the literature, 88 of 189 (47%) children with LGS had more than 50% seizure reduction after 3 to 36 months of ketogenic diet treatment. INTERPRETATION: The ketogenic diet is efficacious in the treatment of LGS, with approximately one-half of children responding at 12 months.

Maximizing Quality of Life in Children with Epilepsy.

Arguably significant progress and improvement in the medical and surgical treatments of seizures and epilepsy in children have occurred; however, there have been relatively fewer efforts in optimizing the care of lifestyle complications related to the disease state. Many patients have significant behavioral and mental health comorbidities, including ADHD (attention deficit hyperactivity disorder), which should be treated. After epilepsy surgery, only seizure freedom results in improved quality of life (QOL). Improved compliance leads to better seizure control and ensuring that caregivers have a rescue treatment helps empower patients. Education and improving seizure illness perception is beneficial. Cannabidiol may have benefits other than seizure control. The majority of children are mainly concerned about the stigma attached to having epilepsy. Driving affecting older children is discussed. Restrictions on these children should be minimized and enabling regular activities maximized.

Successful third surgery for a case of status gelasticus: lessons learned after nearly 200 cases of hypothalamic hamartoma surgical resection.

We report the case of a 3-year-old boy with status gelasticus symptomatic to a giant hypothalamic hamartoma despite two previous hypothalamic hamartoma surgeries using pterional approaches from each side. Following his third resection employing an endoscopic, transventricular approach, he has been seizure free for 6 months with significant cognitive, behavioral, and electroencephalographic improvement. This case reinforces the importance of surgery for a form of status epilepticus and in addition that repeat (three) surgeries can be successful, indeed life changing. The optimal surgical approaches and management plan for hypothalamic hamartoma surgery-including subtemporal, subfrontal, transcallosal, and endoscopic approaches-are discussed, including how these treatment decisions have evolved as a result of our large series experience.

EEG and video-EEG seizure monitoring has limited utility in patients with hypothalamic hamartoma and epilepsy.

PURPOSE: Hypothalamic hamartomas (HHs) are a malformation of the ventral hypothalamus and tuber cinereum, associated with gelastic seizures and epilepsy. We sought to determine the spectrum of electroencephalography (EEG) abnormalities in a large cohort of HH patients. METHODS: Data was collected for HH patients undergoing evaluation between 2003 and 2007. Data included seizure history, prior treatment, and results of diagnostic studies. After informed consent, data were entered into a database. KEY FINDINGS: We reviewed 133 HH patients. Mean age at time of data analysis was 15.7 years (59.4% male). Most patients had gelastic (77%) and/or complex partial seizures (58%). Records for 102 EEG studies on 73 patients were reviewed. Interictal epileptiform abnormalities were seen in 77%, localizing predominately to the temporal and frontal regions. Records for 104 video-EEG (VEEG) studies on 65 patients were reviewed. Of 584 gelastic seizures (GS) captured, no ictal EEG change was noted in 438 (75%). Of GS with localizing features, 89% suggested onset from the temporal and/or frontal regions. There were 160 complex partial seizures (CPS). For those with localizing features, 100% localized to the temporal and/or frontal head regions. EEG and VEEG findings correlated with the side of HH attachment. VEEG did not influence outcome. SIGNIFICANCE: EEG features in HH patients are diverse. The majority of gelastic seizures fail to demonstrate change in the EEG. The lack of EEG changes with many clinical seizures, and the false localization seen in those events with an ictal change suggest the utility of EEG is limited in the evaluation of these patients.

Surgical resection of hypothalamic hamartomas for severe behavioral symptoms.

Hypothalamic hamartomas (HHs) are associated with treatment-resistant epilepsy. Many patients also experience severe and sometimes disabling psychiatric problems. The most common behavioral symptoms consist of paroxysms of uncontrolled anger related to poor frustration tolerance. These can include violence, resulting in disrupted family or school relationships, and legal consequences including incarceration. In a large cohort of patients undergoing surgical resection of HHs for refractory epilepsy, 88% of families described an improvement in overall behavioral functioning [1]. Here, we describe four patients (three males, mean age=11.9 years) who underwent surgical resection of HHs largely for behavioral indications. Three patients had relatively well controlled seizures, and one had no history of epilepsy. All patients had striking improvement in their psychiatric comorbidity. HH resection can result in significant improvement in behavioral functioning, even in patients with relatively infrequent seizures. Further investigation under approved human research protocols is warranted.

Orbitozygomatic resection for hypothalamic hamartoma and epilepsy: patient selection and outcome.

PURPOSE: This study aims to examine the outcomes of ten patients after orbitozygomatic (OZ) pterional surgery in cases of refractory epilepsy caused by hypothalamic hamartomas (HH). METHODS: Ten patients with HH and treatment-resistant epilepsy (mean age 18.3 years, range 0.7 to 42.7) underwent HH resection with an OZ approach (n = 8) or an OZ approach combined with a transventricular endoscopic approach (n = 2). Follow-up for the patients ranged from 0.5 to 6.2 years (mean 3.1). Outcomes were prospectively monitored with the use of a proprietary database. RESULTS: Four patients (40%) are seizure-free, and four (40%) have had greater than 50% reduction in seizures. One patient had no significant change in seizure frequency, and one patient died unexpectedly 2.8 years after surgery. Six patients had total or near-total HH resection (98-100% of HH lesion volume). Of these, four of six (66%) were seizure-free, and two had at least greater than 50% reduction in seizures. Residual complications include diabetes insipidus (n = 1), poikilothermia (n = 1), visual field deficit (n = 1), and hemiparesis (n = 1). Eight families (80%) reported improved quality of life. CONCLUSIONS: Patients with treatment-resistant epilepsy and tumors with an inferior or horizontal plane of attachment to the hypothalamus should continue to be approached from below. Those with both intrahypothalamic and parahypothalamic components may require approaches from above and below, either simultaneously or staged. For appropriately selected patients, the success of controlling seizures with an OZ is comparable to results utilizing transcallosal or transventricular approaches. The likelihood of controlling seizures appears to correlate with extent of resection.

Ethical considerations in paediatric neurology: neuromuscular disease and epilepsy.

The pace of developing technology with respect to many diagnostic tests, as well as available treatments including artificial ventilation, may have progressed at a faster rate than our ethical, humane ability to decide on the optimal choices for our patients. In fact, who should make these choices; physicians or patients and families? Certain ethical aspects of neuromuscular disorders and epilepsy are reviewed. For neuromuscular disease, the example of Duchenne muscular dystrophy (DMD) with regards to genetic testing, relatively early wheelchair placement and individualised invasive ventilation is discussed. In epilepsy, performing neurosurgery in severely impaired children is probably appropriate in some cases if desired by the family. Financial and human costs restrict therapies and testing for epilepsy as well as other neurological and medical diseases. Whether it is ethical to consider costs in medical treatment or not, it is certainly a reality.

Repeat surgery for hypothalamic hamartoma in refractory epilepsy.

OBJECT: Hypothalamic hamartomas (HHs) often cause pharmacoresistant epilepsy, incapacitating behavioral abnormalities, and cognitive decline. Surgical intervention offers the patient the best opportunity of seizure resolution, which occurs in approximately 50%­60% of patients, and improvement in both cognitive and behavioral difficulties. For those in whom the initial operation has failed, further medical treatment options remain quite limited, whereas, in some cases, a second surgery may improve seizure outcome. The authors retrospectively reviewed their surgical cases to document the success rate and complications of reoperations in patients with HHs. METHODS: Data were obtained from the HH epilepsy surgery database at the Barrow Neurological Institute between 2003 and 2010. Surgical treatment consisted of open and endoscopic procedures, as well as radiosurgery. Demographic details, seizure history, presurgical evaluation, and postoperative follow-up data were evaluated. RESULTS: In the last 7 years, 21 (13%) of 157 patients underwent reoperation after an initial epilepsy operation. The initial surgical approach in the 21 patients included: endoscopic (8 patients [38%]), transcallosal (8 patients [38%]), orbitozygomatic (3 patients [14%]), and radiosurgery (2 patients [10%]). Of the 8 patients who initially underwent endoscopic resection, repeat procedures included: radiosurgery in 4 (50%), an orbitozygomatic approach in 2 (25%), repeat endoscopy in 1 (12.5%), and a transcallosal approach in 1 (12.5%). Repeat procedures after an initial transcallosal resection included: endoscopic resection in 2 (25%); radiosurgery in 1 (12%); an orbitozygomatic approach in 2 (25%), and repeat transcallosal surgery in 3 (38%). Predominant seizure types that recurred after the first surgery were gelastic seizures, complex partial seizures, and tonic-clonic seizures. Magnetic resonance imaging in all patients prior to reoperation demonstrated either residual HH and/or connection with the mammillary bodies. Review of patients with more than 6 months of follow-up since the last surgery showed greater than 90% reduction in seizures in 4 patients (19%) and by 50%­90% in 10 patients (48%). Two patients were seizure free, and in 5 patients (24%) there was no change in seizure frequency. Following reoperation, none of the patients had any worsened behavioral issues such as increased rage attacks or disruptive violent behavior. New postoperative complications after reoperation included hemiparesis, thalamic stroke (asymptomatic and symptomatic), hyperphagia, and panhypopituitarism. CONCLUSIONS: Reoperation should be considered in selected patients with HH in whom initial epilepsy surgery fails because more than half the patients have significant reductions in seizure.

Long-term outcome after emergency resection of hypothalamic hamartomas for status gelasticus.

OBJECT: Gelastic seizures are epileptic events characterized by bouts of laughter. They are rare and mostly associated with hypothalamic hamartomas (HHs). Status gelasticus, a rare form of status epilepticus, is defined as a prolonged cluster of gelastic seizures (> 20-30 minutes) without necessarily involving loss of awareness between seizures. Emergency resection of the hamartoma is highly effective in these situations and should be considered as early as possible. The authors retrospectively reviewed their surgical cases to document the success, complications, and long-term follow-up after emergency resection of HHs for status gelasticus. METHODS: The authors report on a retrospective case series from a single tertiary care center. Three patients who presented with status gelasticus underwent emergency resection of HHs. Demographic details, seizure history, medical treatment, and postoperative follow-up data were evaluated. Long-term follow-up (minimum 2 years) data were obtained either from the last clinic visit notes or via telephone and e-mail contacts. The institutional review board at St. Joseph's Hospital approved this study. RESULTS: In the last 7 years, of 157 patients who underwent HH resection, the resection was performed on an emergency basis for status gelasticus in 3 cases. At emergency surgery, these 3 patients ranged in age from 9 months to 3.5 years. All of the patients were boys. Delalande and Fohlen Type II, III, and IV lesions were present in the 3 patients. Surgical approaches for resection of HH included an orbitozygomatic, transcallosal anterior interforniceal approach and endoscopic resection. Status gelasticus was terminated following emergency surgery in all cases, and 1 patient was seizure free. Postsurgical complications included, in 1 case, a small right thalamic infarct with mild transient left hemiparesis, which completely resolved within 2 days. Within 2 years of their original surgery, 2 patients underwent further elective surgeries (endoscopic resection and radiosurgery for persistent symptomatic seizures). Follow-up since their most recent surgery ranged from 8 months to 2 years. Two patients were seizure free and 1 patient had greater than 50% reduction in seizures. CONCLUSIONS: Status gelasticus associated with HHs can be successfully terminated by emergency resection of the HH. Long-term follow-up in the present series suggests good seizure freedom results or at least greater than 50% reduction in seizures, although repeat operations were necessary.

Syndrome of alternating hypernatremia and hyponatremia after hypothalamic hamartoma surgery.

OBJECT: In this paper, the authors' goal was to describe the occurrence of alternating hypernatremia and hyponatremia in pediatric patients who underwent resection of hypothalamic hamartomas (HHs) for epilepsy. Hypernatremia in patients after pituitary or hypothalamic surgery can be caused by diabetes insipidus (DI), whereas hyponatremia can occur due to a syndrome of inappropriate antidiuretic hormone, cerebral salt wasting, or excessive administration of desmopressin (DDAVP). The triphasic response after surgery in the pituitary region can also explain variations in sodium parameters in such cases. METHODS: One hundred fifty-three patients with HH who underwent surgery were enrolled in a prospective study to monitor outcomes. Of these, 4 patients (2.6%) were noted to experience dramatic alterations in serum sodium values. The medical records of these patients were identified and evaluated. RESULTS: Patients' ages at surgery ranged from 1.2 to 6.0 years. All patients were girls. Two patients had Delalande Type IV lesions (of 16 total Type IV lesions surgically treated) and 2 had Type III lesions (of 39 total Type III lesions). All patients had a history of gelastic seizures refractory to medication. Seizure frequency ranged from 3 to 300 per day. After surgery, all patients experienced hypernatremia and hyponatremia. The largest fluctuation in serum sodium concentration during hospitalization in a single patient was 53 mEq/L (range 123-176 mEq/L). The mean absolute difference in maximum and minimum sodium values was 38.2 mEq/L. All patients exhibited an initial period of immediate DI (independent of treatment) after surgery followed by a period of hyponatremia (independent of treatment), with a minimum value occurring between postoperative Days 5 and 8. All patients then returned to a hypernatremic state of DI, and 3 patients still require DDAVP for DI management. A second occurrence of hyponatremia lasting several days without DDAVP administration occurred in 2 patients during their hospitalization between periods of hypernatremia. One patient stabilized in the normal range of sodium values prior to discharge from rehabilitation without the need for further intervention. At last follow-up, 3 patients are seizure-free. CONCLUSIONS: Severe instability of sodium homeostasis with hypernatremia and hyponatremia is seen in up to 2.6% of children undergoing open resection of HH. This risk appears to be related to HH type, with a higher risk for Types III (2 [5.1%] of 39) and IV (2 [12.5%] of 16) lesions. Here, the authors describe alternating episodes of hypernatremia and hyponatremia in the postoperative period following HH surgery. Management of this entity requires careful serial assessment of volume status and urine concentration and will often require alternating salt replacement therapy with DDAVP administration.