Nucleus accumbens stimulation in partial epilepsy—A randomized controlled case series

Neuromodulative treatment options are warranted in patients with difficult‐to‐treat epilepsy. However, acquisition of controlled data on deep brain stimulation has so far been achieved only for the centromedian and anterior thalamic nucleus. In a case series of four patients with intractable partial epilepsy, a randomized controlled cross‐over protocol was used to get insight into efficacy and safety of 3‐month nucleus accumbens stimulation. Seizure frequency, neurocognitive testing, “Liverpool Seizure Severity Score,” “Quality of Life in Epilepsy Inventory,” “Beck Depression Inventory,” and “Mini International Neuropsychiatric Interview” were obtained at every visit. In a subsequent open‐label phase, nucleus accumbens stimulation responders underwent concomitant anterior thalamic nucleus stimulation, whereas nonresponders received solely thalamic stimulation. Under nucleus accumbens stimulation, three of four patients had ≥50% reduction in frequency of disabling seizures without further improvement with additional anterior thalamic nucleus stimulation. Patient‐reported outcome and neurocognitive testing remained unchanged. Accumbens stimulation is safe and seems to be a suitable option in intractable partial epilepsy. The current findings require substantiation by an adequately powered multicenter study.     

Psychological outcome profiles in childhood‐onset temporal lobe epilepsy

Purpose: To examine the effect of childhood‐onset temporal lobe epilepsy (TLE) on long‐term psychological function and to identify outcome profiles related to the natural course and treatment of TLE. Methods: Psychological function was studied in a prospective, community‐based cohort of childhood‐onset TLE, approximately 13 years following seizure onset. Fifty‐three patients were assessed using a semi‐structured psychosocial interview, supplemented by self‐report questionnaires measuring quality‐of‐life, depression, self‐esteem, and anxiety. Results: Common patterns were observed, giving rise to four distinct patient groups and psychological outcomes: (1) patients who experienced spontaneous remission of their seizures fared best; their psychological profile was characterized by heightened worry about the possibility of seizure recurrence; (2) patients who progressed to surgery and were seizure free reported adjustment difficulties associated with learning to become “well”; (3) patients who progressed to surgery and were not seizure free had the poorest psychological outcomes, with depression featuring prominently; and (4) patients with ongoing intractable epilepsy reported psychological and social features consistent with the effects of their chronic illness. Discussion: Patients with childhood‐onset TLE face distinctive long‐term psychological challenges. The specific nature of these challenges can be understood in terms of the natural evolution and treatment of their epilepsy.     

Design considerations for a multicenter randomized controlled trial of early surgery for mesial temporal lobe epilepsy

Purpose: To describe the trial design for the multicenter Early Randomized Surgical Epilepsy Trial (ERSET). Patients with pharmacoresistant epilepsy are generally referred for surgical treatment an average of two decades after onset of seizures, often too late to avoid irreversible disability. ERSET was designed to assess the safety and efficacy of early surgical intervention compared to continued pharmacotherapy. Methods: ERSET is a randomized controlled, parallel group clinical trial with blinded outcome adjudication. Participants are patients with mesial temporal lobe epilepsy (MTLE) older than the age of 12 who have had pharmacoresistant seizures for not >2 years and are determined by detailed evaluation to be surgical candidates prior to randomization. The primary outcome measure is seizure freedom in the second year of a 2‐year follow‐up period. Health‐related quality of life (HRQOL), neurocognitive function, ancillary outcomes, and adverse events were also measured. Results: Significant methodologic problems addressed by the study design included the following: recruitment of participants early in the course of epilepsy; establishment of operational definitions for “pharmacoresistant” and “early”; and standardization of diagnostic testing, medical treatment, and surgical interventions across multiple centers. Discussion: Rigorous trial designs to assess surgical interventions in epilepsy are necessary to provide evidence to guide treatment. This article is the first of a series; trial results will be reported in subsequent publications.     

Childhood-onset nonprogressive chronic encephalitis

PurposeThe purpose of this study was to describe a series of patients with pathologically proven chronic encephalitis who had a nonprogressive course during a long follow-up, suggestive of a “benign” variant of Rasmussen's encephalitis (RE).MethodsFour patients who were referred to our Comprehensive Epilepsy Program at London Health Science Centre in London, Ontario, were diagnosed with chronic encephalitis on a pathological basis after epilepsy surgery to treat their partial-onset seizures.ResultsNone of our four cases followed the typical course of RE despite their childhood-onset seizures between ages 2 and 12 years. One was preceded by a mild head trauma and fever at onset. None had epilepsia partialis continua (EPC). Their long-term follow-up revealed a nonprogressive form of the syndrome with respect to the neurological examination, EEG, MRI, and neuropsychological findings.ConclusionThese cases extend the spectrum of childhood-onset intractable epilepsy with chronic encephalitis to include nonprogressive variants of RE. The absence of EPC may be a prognostic indicator of a nonprogressive course.     

Neuropathological spectrum of Rasmussen encephalitis

BACKGROUND: Rasmussen encephalitis (RE) is a chronic epileptic disorder of unknown etiology, and is clinically characterized by progressive neurological deterioration, focal seizures often progressing to intractable epilepsy, cognitive decline and hemispheric atrophy. AIMS: We report the spectrum of neuropathological changes seen in RE, and discuss the evolutionary mechanisms of this disease. MATERIALS AND METHODS: Surgically obtained specimens from RE patients diagnosed during 2002-2004 at this institute were evaluated for the presence and extent of different histopathological features of RE. The H&E and immunohistochemistry stained slides were also evaluated for the type and distribution pattern of inflammatory infiltrates, along with a semiquantitative evaluation for the severity of inflammation. RESULTS: Four cases of RE were admitted during the study period, all of which presented with partial seizures with successive deterioration to intractable epilepsy. The age at onset varied between 5 and 10 years (mean 7.8 years), with three male and one female patients. Subsequently, all four patients underwent hemispherotomy. Histopathological features of perivascular lymphocytic infiltrate, neuronal loss, microglial nodules, and reactive astrocytosis, with or without evidence of neuronophagia confirmed a diagnosis of RE. These cases also had varying degrees of T-cell-rich (CD3-positive) inflammatory infiltrates and CD68-immunopositive microglial proliferation. It was observed that the severity of inflammation had a trend to inversely correlate with the duration of symptoms. CONCLUSION: It is proposed that an accurate evaluation and histopathological grading of these lesions may possibly have a role in patient prognostication.     

Medical treatment of Rasmussen's Encephalitis: A systematic review

Rasmussen's encephalitis (RE) is a severe, rare, chronic inflammatory brain disease resulting in drug-resistant epilepsy and progressive destruction of one hemisphere with loss of neurological function. RE is associated with a deterioration of background electroencephalography (EEG) activity, a progressive atrophy on magnetic resonance imaging (MRI) imaging and an extensive positron emission tomography hypometabolism over the affected hemisphere. RE is an immune-mediated disease, with a predominant role of CD8+ T cytotoxic cells, microglial cells, and activation of inflammasome pathway. The diagnosis of RE is based on clinical (intractable epilepsy and neurological deterioration), electrophysiological (unilateral EEG slowing) and MRI (hemiatrophy) criteria. Antiseizure medications are generally unable to stop seizures. The most effective procedure is hemispherotomy (surgical disconnection of one cerebral hemisphere), but this is associated with permanent motor and neurological deficits. Treatments targeting the immune system are recommended especially in the early stages of the disease or in patients with slow disease progression and mild deficits and/or not eligible for surgery. Based on the pathophysiology, several immunotherapies have been tried in RE (none exhaustively: corticosteroid, intravenous immunoglobulins, tacrolimus, azathioprine, adalimumab, mycophenolate mofetil, natalizumab). However, only small cohorts have been reported without comparative study. In this review, we will summarise some pathophysiological mechanisms of RE, before reporting the literature data concerning immunotherapies. We then discuss the limitations of these studies and the prospects for further research.     

Arterial spin labeling hyperperfusion in Rasmussen's encephalitis: Is it due to focal brain inflammation or a postictal phenomenon?

Background and purpose

The study evaluated the utility of arterial spin labeling (ASL) perfusion imaging in Rasmussen's encephalitis (RE).

Rasmussen encephalitis: long-term outcome after surgery

Background and purpose

Rasmussen encephalitis (RE) is characterized by intractable epilepsy, progressive hemiparesis, and unilateral hemispheric atrophy. The progression of the symptoms to significant neurological impairment usually occurs within months to a few years. RE causes are unknown, although evidence of an autoimmune process has been extensively described in the literature. Antiepileptic drugs are usually not effective to control seizures or cerebral atrophy; despite data supporting a beneficial effect of early immunosuppressive and immunomodulatory interventions, for intractable seizures in RE patients with advanced disease, epilepsy surgery in the form of hemispheric disconnection has been considered the treatment of choice. This work describes the clinical and electrographic analyses, as well as the post-operative evolution of patients with RE.

Materials and methods

This work includes all the patients with RE evaluated from January 1995 to January 2008 by the Ribeirão Preto Epilepsy Surgery Program (CIREP), taking variables such as gender; age at epilepsy onset; seizure semiology; seizure frequency; interictal and ictal electroencephalographic (EEG) findings; age at surgery, when done; duration of epilepsy; surgery complications; follow-up duration; anatomo-pathological findings; post-surgery seizure; language and cognitive outcome; and anti-epileptic drug treatment after surgery into account.

Results

Twenty-five patients were evaluated; thirteen were female. Mean age of epilepsy onset was 4.4?±?2.0 years. There were no differences between patients with slow and fast evolution with respect to age of epilepsy onset (p?=?0.79), age at surgery (p?=?0.24), duration of epilepsy (0.06), and follow-up (p?=?0.40). There were no correlations between the presence of bilateral EEG abnormalities or the absence of spikes and post-operative seizure outcome (p?=?0.06). Immunomodulatory therapy was tried in 12 patients (48%). Twenty-three patients underwent surgery. The mean follow-up was 63.3 months. Eleven patients had total seizure control. Twelve individuals persisted with seizures consisting of mild facial jerks (six patients), occasional hemigeneralized tonic–clonic seizures (three patients), and frequent tonic–clonic seizures (three patients). Mental and language impairment was observed in 15 and 12 patients, after surgery, respectively. Eight patients presented post-operative cognitive decline, while only two patients had cognitive improvement. Comparing pre- and post-operative language deficits, 66.7% of the 12 patients with language disturbance did not improve after surgery.

Conclusions

This retrospective study reported the clinical and electrographic analysis, as well as the evolution of 23 patients with RE. Patients were divided into two groups: fast evolution and slow evolution to hemiparesis and epilepsia partialis continua. These groups may represent different RE substrates. Fourteen patients achieved satisfactory seizure control, three patients had partial response to surgery, and five patients had maintenance of the pre-operative condition. All patients with left-side involvement presented with some language disturbance, which did not improve after surgery in 66.6% of patients. Cognitive evaluation showed that the majority of the patients did not have any significant improvement, and 38.1% had cognitive deterioration after surgery.     

Extrarolandic electroclinical findings in the evolution of adult-onset Rasmussen's encephalitis

Rasmussen's encephalitis (RE) is a rare immunomediated disorder characterized by unilateral hemispheric atrophy, drug-resistant focal epilepsy, and progressive neurological deficits. Its onset typically occurs in childhood, though it has also been reported in adult age (A-RE) with atypical clinical features. The aim of this study was to describe the electroclinical features in a group of seven patients with A-RE.We retrospectively studied seven women aged 23–43 years (mean: 32.1 years) with a diagnosis of RE according to commonly accepted diagnostic criteria. All the patients were clinically evaluated and underwent prolonged video-EEG monitoring, laboratory investigations, and high-resolution MRI follow-up.All the patients displayed an ictal electroclinical pattern whose evolution varied. We identified an early phase characterized by polymorphic ictal electroclinical manifestations (temporal semiology in five cases, frontal in one, and parietal in the remaining case) and a late phase clinically characterized by viscerosensitive phenomena followed by somatosensitive signs, experiential symptoms, and motor signs in all the cases. In the late phase, the ictal EEG pattern was characterized by monomorphic, pseudorhythmic, repetitive slow-wave theta activity over the frontal and central regions, with ipsilateral propagation and/or secondary spreading to contralateral perisylvian structures. Patients were treated with a combination of AEDs and immunotherapy (steroids and IVIg); epilepsy surgery was performed in 3 cases.Our results show that A-RE is characterized by early and late clinical- and EEG-different features which may reflect a progressive involvement of a specific “extrarolandic” network in the advanced phase of the disease and may suggest that the electroclinical expression of RE varies according to the different stages of the pathological process.     

Spatiotemporal neuronal correlates of seizure generation in focal epilepsy

Purpose: Focal seizures are thought to reflect simultaneous activation of a large population of neurons within a discrete region of pathologic brain. Resective surgery targeting this focus is an effective treatment in carefully selected patients, but not all. Although in vivo recordings of single‐neuron (i.e., “unit”) activity in patients with epilepsy have a long history, no studies have examined long‐term firing rates leading into seizures and the spatial relationship of unit activity with respect to the seizure‐onset zone. Methods: Microelectrode arrays recorded action potentials from neurons in mesial temporal structures (often including contralateral mesial temporal structures) in seven patients with mesial temporal lobe epilepsy. Key Findings: Only 7.6% of microelectrode recordings showed increased firing rates before seizure onset and only 32.4% of microelectrodes showed any seizure‐related activity changes. Surprisingly, firing rates on the majority of microelectrodes (67.6%) did not change throughout the seizure, including some microelectrodes located within the seizure‐onset zone. Furthermore, changes in firing rate before and at seizure onset were observed on microelectrodes located outside the seizure‐onset zone and even in contralateral mesial temporal lobe. These early changes varied from seizure to seizure, demonstrating the heterogeneity of ensemble activity underlying the generation of focal seizures. Increased neuronal synchrony was primarily observed only following seizure onset. Significance: These results suggest that cellular correlates of seizure initiation and sustained ictal discharge in mesial temporal lobe epilepsy involve a small subset of the neurons within and outside the seizure‐onset zone. These results further suggest that the “epileptic ensemble or network” responsible for seizure generation are more complex and heterogeneous than previously thought and that future studies may find mechanistic insights and therapeutic treatments outside the clinical seizure‐onset zone.     

Developmental and epileptic encephalopathies: recognition and approaches to care

The term “developmental and epileptic encephalopathy” (DEE) refers to when cognitive functions are influenced by both seizure and interictal epileptiform activity and the neurobiological process behind the epilepsy. Many DEEs are related to gene variants and the onset is typically during early childhood. In this setting, neurocognition, whilst not improved by seizure control, may benefit from some precision therapies. In patients with non‐progressive diseases with cognitive impairment and co‐existing epilepsy, in whom the epileptiform activity does not affect or has minimal effect on function, the term “developmental encephalopathy” (DE) can be used. In contrast, for those patients with direct impact on cognition due to epileptic or epileptiform activity, the term “epileptic encephalopathy” (EE) is preferred, as most can revert to their normal or near normal baseline cognitive state with appropriate intervention. These children need aggressive treatment. Clinicians must tailor care towards individual needs and realistic expectations for each affected person; those with DE are unlikely to gain from aggressive antiseizure medication whilst those with EE will gain. Patients with DEE might benefit from a precision medicine approach in order to reduce the overall burden of epilepsy.     

Treatment of corticosteroid refractory optic neuritis in multiple sclerosis patients with intravenous immunoglobulin

Background: Patients with severe visual loss because of optic neuritis refractory to high dose corticosteroids have limited therapeutic options. The use of intravenous immunoglobulin (IVIG) has been advocated in the past, but data are scarce. In this study, we use a protocol different from those used in other studies, with different timing and dosage. Methods: Consecutive patients with corticosteroid‐refractive optic neuropathy were treated with IVIG and compared with control patients who received only corticosteroids in an open‐label, non‐randomized, controlled prospective study. Results: Twenty‐three patients received treatment with IVIG and 24 matched patients who did not receive treatment with IVIG were followed as controls. All patients had visual acuity 20/400 or worse in the affected eye. There was significant improvement in the IVIG group with 18/23 (78%) subjects reaching near normal vision (20/30 or better), compared with the control group with only 3/24 (12.5%) responding similarly. Conclusions: The use of IVIG, following corticosteroids, may be useful using the protocol described herein, with sustained pulsed dosing. A larger controlled trial is indicated to confirm these results.     

Intravenous high-dose gammaglobulins for intractable childhood epilepsy

Immunological mechanisms have been implicated in the pathogenesis of epileptic seizures in some patients and in experimental animal models of epilepsy. A beneficial effect of high dose intravenous gammaglobulin (IVIG) has been demonstrated for some children with intractable epilepsy. In this study we treated 9 children ages 1.1–9.2 years (mean 5.0 years) with intractable epilepsy not responsive to conventional antiepileptic drugs (AEDs) and steroid therapy. Eight children and Lennox-Gastaut syndrome and 1 had complex partial seizures with secondary generalization. Each child received 3 doses of IVIG (200 mg/kg of polyvalent immunoglobulin) on Days 1, 15 and 36. Concomitant AEDs were not changed. Four children had complete remission, 3 had partial response with a more than 50% reduction in seizure frequency and 2 had no response. Onset of response varied from immediate to 7 months after the last injection. No toxicity was noted. Duration of remission was 9 months in 1 case. The other 3 cases have remained in remission to date with a follow up period of 22–26 months. We conclude that IVIG is a safe therapy which appears to be effective in some children with intractable seizures. Children with shorter duration of their seizure disorder (<1 year) and relatively preserved cognitive function (IQ> 70) appear to have a more favorable response. Larger scale controlled trials are needed to determine the optimal timing and dosage, as well as to identify specific subgroups which may benefit most from IVIG treatment.     

The effects of duration of intractable epilepsy on memory function

We assessed whether duration (time since diagnosis) of intractable epilepsy is associated with progressive memory loss in 250 individuals with left or right temporal lobe epilepsy and those diagnosed with psychogenic nonepileptic seizures. Verbal and nonverbal memory function was assessed using several memory assessment measures administered to all individuals as part of a larger neuropsychological assessment. Multivariate multiple regression analyses demonstrated that duration of temporal lobe epilepsy and age of seizure onset are significantly related to verbal memory deficits in patients with epilepsy. The interaction between duration of epilepsy and diagnostic group was nonsignificant, as was the interaction between age at spell onset and diagnostic group. As measured by several neuropsychological memory tests, duration of disease adversely affects verbal memory performance in patients diagnosed with temporal lobe epilepsy. Our study also supports the notion that age at seizure onset significantly affects verbal memory performance in this population. These results have implications for the strategy of treatment and counseling of patients with intractable temporal lobe epilepsy.     

Onset of intractability and its course over time: the Dutch study of epilepsy in childhood

Purpose: Intractability in epilepsy is difficult to define, and little is known about its onset, course, and duration. We investigated these aspects (as well as the occurrence of intractability) during long‐term follow‐up in patients with epilepsy, focusing on possible explanations for the variation in time of onset and duration of intractability. Methods: After diagnosis, 453 patients with childhood‐onset epilepsy had a 5‐year follow‐up with regular visits and data collection. Ten years later they received a questionnaire with items concerning epilepsy, which was completed by 413 patients resulting in a mean follow‐up of 15 years. Intractability during the first 5 years was compared with that in the last year of follow‐up. Intractability was defined as having no 3‐month remission during a 1‐year period despite adequate medical treatment. Key Findings: At least 12.1% of the cohort had a period of intractability during the 15‐year follow‐up, and 8.5% were intractable in the final year. Of the patients with idiopathic etiology 4.3% had a period of intractability versus 17.0% for those with cryptogenic, and 22.6% for those with remote symptomatic etiology (p < 0.001). Other risk factors at baseline were younger age at first seizure, generalized cryptogenic/symptomatic or localization‐related symptomatic epilepsy, mental retardation, and febrile convulsions before enrollment. The cumulative risk of a period of intractability was 6.1% (95% confidence interval [CI] 3.7–8.5) at 2 years follow‐up and 8.2% (95% CI 5.4–11.0) at 5 years. The mean time to onset of intractability during the first 5 years of follow‐up was 1.6 (95% CI 1.3–2.0; median 1.0) years and the mean duration of intractability during these 5 years was 3.3 (95% CI 2.8–3.8; median 3.6) years. Fifteen patients were intractable only during the first 5 years of follow‐up (group A), and 19 subjects were intractable both during the first 5 years and the last year of follow‐up (group B). Compared with group A, group B had shorter remission and a longer time to intractability during the first 5 years and more were intractable in the fifth year of follow‐up. Sixteen other patients had a late onset of intractability after 5 years of follow‐up, sometimes after long periods of remission (group C). No significant differences in baseline characteristics were found among groups A, B, and C, but slightly more children in groups B and C became mentally retarded during the follow‐up. In all groups, antiepileptic drugs were of little use in preventing and ending intractability. Significance: There is a large unpredictable variation in time of onset, course, and duration of intractability, with a higher chance of final intractability after a poor course during the first 5 years of follow‐up. The natural course of epilepsy probably best explains the variable course of intractability. The effect of medication seems to be minor.     

Vagus nerve stimulation for epilepsy: is output current correlated with acute response?

OBJECTIVES: Vagus nerve stimulation (VNS) is an effective treatment for intractable epilepsy. It is unknown whether acute response is correlated with the amplitude of output current. The purpose of this study was to determine if the output current of VNS is correlated with percent reductions in seizure frequency and response. MATERIALS AND METHODS: Retrospective analysis of a multicenter randomized trial of three unique paradigms of VNS was carried out in patients with intractable partial onset epilepsy. Output current at 1 and 3 months was correlated with percent reduction in seizure frequency and response rates. RESULTS: Sixty-one subjects were enrolled and completed the study. Output current, ranging from 0.25 to 1.5 mA, was not correlated with reductions in seizure frequency, or with > or = 50% reduction in seizures. Six of seven initial non-responders did experience > or = 50% reductions in seizures after current was increased. CONCLUSIONS: The output current is not a major determinant of acute response to VNS for epilepsy. Many patients respond to low current (<1 mA). Some (20%) initial non-responders may respond to an increase in output current.     

Randomized,controlled trial of miglustat in Gaucher's disease type 3

Objective

To evaluate the efficacy and safety of miglustat, concomitant with enzyme replacement therapy (ERT), in patients with Gaucher's disease type 3 (GD3).

Methods

This 24‐month, phase II, open‐label clinical trial of miglustat in GD3 was conducted in two phases. During the initial 12 months, patients were randomized 2:1 to receive miglustat or “no miglustat treatment.” The randomized phase was followed by an optional 12‐month extension phase in which all patients received miglustat. All patients received ERT during the 24‐month period. The primary efficacy end points were change from baseline to months 12 and 24 in vertical saccadic eye movement velocity as determined by the peak amplitude versus amplitude regression line slope. Secondary end points included changes in neurological and neuropsychological assessments, pulmonary function tests, liver and spleen organ volumes, hematological and clinical laboratory assessments, and safety evaluations.

Results

Thirty patients were enrolled, of whom 21 were randomized to miglustat and 9 to “no miglustat treatment.” Twenty‐eight patients entered the 12‐month extension phase. No significant between‐group differences in vertical saccadic eye movement velocity or in the other neurological or neuropsychological evaluations were observed. Organ volumes and hematological parameters remained stable in both treatment groups, but improvement in pulmonary function and decrease of chitotriosidase levels were observed with miglustat compared with patients receiving ERT alone.

Interpretation

Miglustat does not appear to have significant benefits on the neurological manifestations of GD3. However, miglustat may have positive effects on systemic disease (pulmonary function and chitotriosidase activity) in addition to ERT in patients with GD3. Ann Neurol 2008;64:514–522     

An open study of tacrolimus therapy in Rasmussen encephalitis

Seven patients with Rasmussen encephalitis (RE) were treated with the immunosuppressant tacrolimus and followed for a median of 22.4 months. They were compared with 12 historical untreated RE patients (median follow-up 13.9 months). The tacrolimus-treated patients had a superior outcome regarding neurologic function and progression rate of cerebral hemiatrophy but no better seizure outcome. No treated patient, but 7 of 12 control patients, became eligible for hemispherectomy. Tacrolimus did not have any major side effects.     

Vagus Nerve Stimulation for Intractable Epilepsy: Outcomes in Children and Adults

Objectives. Vagus nerve stimulation (VNS) is an accepted treatment for medically intractable epilepsy. However, predictive factors associated with responsiveness to VNS remained unclear. We therefore sought to identify predictive factors that influence responsiveness to VNS in both children and adults. Materials and Methods. We evaluated a retrospective series of 31 patients who underwent VNS for intractable epilepsy at Asan Medical Center from 1998 to 2006. Eighteen patients were younger than 18 years, while 13 patients were aged 18 years or older. We assessed mean seizure frequency, the number of antiepileptic drugs each patient was taking, seizure type, etiology, age at seizure onset, age at implantation, and duration of epilepsy. Results. Forty‐three percent of all patients had a seizure reduction of more than 50%. Ten (59%) children had a 50% reduction in their seizures, while three adults (23%) had such a response. Two factors were significantly different between responders and non‐responders: age at implantation and age of seizure onset. In a logistic regression analysis, however, no factors were independently associated with the response to VNS. Transient hoarseness and cough were observed in eight of all patients and wound infection and generator failure in one patient each. Conclusions. These results suggest that VNS may be a more effective treatment in children with intractable epilepsy than in adults. It remains difficult to predict which patients will respond to VNS therapy.     

Is major depressive disorder specifically associated with mesial temporal sclerosis?

Purpose: Whether a specific lesion such as mesial temporal sclerosis (MTS) increases the risk for a mood disorder in epilepsy remains subject to debate. Despite evidence of limbic system involvement in the genesis of emotional symptoms, recent studies fail to support an association between depression and MTS. We aimed to clarify this controversial issue by overcoming prior methodologic limitations, hypothesizing that rates of major depressive disorder (MDD) would be higher in patients with MTS. Methods: Three hundred eight patients with focal epilepsy (International League Against Epilepsy [ILAE] criteria), were classified into three groups on the basis of neuroimaging findings: MTS, a lesion different from MTS, or absence of lesion. Patients were assessed using the Structured Interview for DSM‐IV axis I psychiatric disorders (SCID‐I), by a psychiatrist blinded to epilepsy subtype. The Spanish version of the Hospital Anxiety and Depression Scale (HADS) was also administered. A complete logistic regression analysis was performed to investigate the association between MTS and MDD. Key Findings: MTS increased the likelihood of a lifetime MDD by nearly 2.5. No other current or “postseizure onset” lifetime Axis I DSM‐IV psychiatric disorder was associated with MTS. Female gender, primary education, comorbid anxiety disorders, and antidepressant treatment were also associated with an increased risk of MDD. Marriage was found to be a protective factor for MDD. Significance: Our results support a specific association between MTS and lifetime “postseizure onset,” MDD. The lack of association with current depression is in line with the hypothesis that the link between MTS and depression is more of a chronic than a state‐dependent condition.