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Background Individuals with intellectual disabilities (ID) may have difficulties in performing daily living tasks. Among other daily living tasks, independent oral hygiene is an essential life skill for people with ID. Materials and methods Four children with intellectual disabilities (two males and two females, ages 7-11) participated in the experiment. We employed the KinectTM V2 sensor to gamify oral hygiene skill training. Specifically, a non-concurrent multiple baseline design was adopted to demonstrate the relation between game-based intervention and independent oral hygiene skills. Results All students learned how to brush their teeth independently and maintained the skill 4 weeks later with the introduction of the game-based training. Social validity results showed the teachers and parents considered the video game was useful. Conclusions The proposed Kinect-based video game might be used for effective training of elementary students with ID to improve oral hygiene independently.

Purpose On 24/04/2018, the United Kingdom (UK) Medicines and Healthcare Products Regulatory Agency (MHRA) clarified previous policies by issuing a statement, that the use of sodium valproate is contraindicated in women of childbearing potential unless the conditions of a pregnancy prevention programme are met, and only if other treatments are ineffective or not tolerated. We evaluated the impact of this over the first year of implementation in a tertiary epilepsy centre. Methods Cross-sectional study of all women under active follow up, or newly referred, of childbearing age (16–55 years), taking valproate for the treatment of epilepsy, over 12 months from 01/05/2018. Results We identified 125 cases, with 31 newly referred in response to MHRA regulations. 9.6% of patients did not attend their appointment, 35.2% had a learning disability (LD), which in 19.2% was sufficiently severe that they could not consent to a sexual relationship. Patients with LD prescribed valproate were significantly younger, and more likely to have a focal or uncharacterised epilepsy than patients without LD. In 46.4% of patients, MHRA regulations were followed: women were already using highly active contraception (HAC), HAC was started, or valproate withdrawn. In 24.8% of cases, women elected to continue valproate, and were not willing to use HAC. Conclusions In 53.6% of cases, MHRA regulations contraindicating the use valproate in women of childbearing potential could not be followed fully, due to lack of patient attendance, lack of applicability in severe LD, or ethical concerns relating to patient choice.

Clinical Features Which Predict Neuronal Surface Autoantibodies in New-Onset Focal Epilepsy: Implications for Immunotherapies McGinty RN, Handel A, Moloney T, et al. J Neurol Neurosurg Psychiatry. 2020;92(3):291-294. doi:10.1136/jnnp-2020-325011Objective:To generate a score which clinically identifies surface-directed autoantibodies in adults with new-onset focal epilepsy and evaluate the value of immunotherapy in this clinical setting.Methods:Prospective clinical and autoantibody evaluations in a cohort of 219 consecutive patients with new-onset focal epilepsy.Results:A total of 10.5% (23/219) of people with new-onset focal epilepsy had detectable serum autoantibodies to known or novel cell surface antigenic targets. Nine of 23 with autoantibodies were diagnosed with encephalitis, by contrast to 0/196 without autoantibodies (P < .0001). Multivariate analysis identified 6 features which predicted autoantibody positivity (area under the curve = 0.83): age ≥54 years, ictal piloerection, lowered self-reported mood, reduced attention, magnetic resonance imaging limbic system changes, and the absence of conventional epilepsy risk factors. Eleven (79%) of 14 patients with detectable autoantibodies, but without encephalitis, showed excellent long-term outcomes (modified Rankin Score = 0) despite no immunotherapy. These outcomes were superior to those of immunotherapy-treated patients with confirmed autoantibody-mediated encephalitis (P < .05).Conclusions:Seizure semiology, cognitive and mood phenotypes, alongside inflammatory investigation findings, aid the identification of surface autoantibodies among unselected people with new-onset focal epilepsy. The excellent immunotherapy-independent outcomes of autoantibody-positive patients without encephalitis suggest immunotherapy administration should be guided by clinical features of encephalitis, rather than autoantibody positivity. Our findings suggest that, in this cohort, immunotherapy-responsive seizure syndromes with autoantibodies largely fall under the umbrella of autoimmune encephalitis. Antibodies Contributing to Focal Epilepsy Signs and Symptoms Score. de Bruijn M, Bastiaansen AEM, Mojzisova H, et al. Ann Neurol. 2021;89(4):698-710. doi:https://doi.org/10.1002/ana.26013.Objective:Diagnosing autoimmune encephalitis (AIE) is difficult in patients with less fulminant diseases such as epilepsy. However, recognition is important, as patients require immunotherapy. This study aims to identify antibodies in patients with focal epilepsy of unknown etiology and to create a score to preselect patients requiring testing.Methods:In this prospective, multicenter cohort study, adults with focal epilepsy of unknown etiology, without recognized AIE, were included, between December 2014 and December 2017, and followed for 1 year. Serum, and if available cerebrospinal fluid, were analyzed using different laboratory techniques. The ACES score was created using factors favoring an autoimmune etiology of seizures (AES), as determined by multivariate logistic regression. The model was externally validated and evaluated using the Concordance (C) statistic.Results:We included 582 patients, with median epilepsy duration of 8 years (interquartile range = 2-18). Twenty (3.4%) patients had AES, of whom 3 had anti-leucine-rich glioma inactivated 1, 3 had anti-contactin-associated protein-like 2, 1 had anti-N-methyl-d-aspartate receptor, and 13 had antiglutamic acid decarboxylase 65 (enzyme-linked immunosorbent assay concentrations >10 000 IU/mL). Risk factors for AES were temporal magnetic resonance imaging hyperintensities (odds ratio [OR] = 255.3, 95% CI = 19.6-3332.2, P < .0001), autoimmune diseases (OR = 13.31, 95% CI = 3.1-56.6, P = .0005), behavioral changes (OR = 12.3, 95% CI = 3.2-49.9, P = .0003), autonomic symptoms (OR = 13.3, 95% CI = 3.1-56.6, P = .0005), cognitive symptoms (OR = 30.6, 95% CI = 2.4-382.7, P = .009), and speech problems (OR = 9.6, 95% CI = 2.0-46.7, P = .005). The internally validated C-statistic was 0.95 and 0.92 in the validation cohort (n = 128). Assigning each factor 1 point, an antibodies contributing to focal epilepsy signs and symptoms (ACES) score ≥2 had a sensitivity of 100% to detect AES, and a specificity of 84.9%.Interpretation:Specific signs point toward AES in focal epilepsy of unknown etiology. The ACES score (cutoff ≥ 2) is useful to select patients requiring antibody testing.

Clan CA cysteine proteases, also known as papain-like proteases, play important roles throughout the malaria parasite life cycle and are therefore potential drug targets to treat this disease and prevent its transmission. In order to study the biological function of these proteases and to chemically validate some of them as viable drug targets, highly specific inhibitors need to be developed. This is especially challenging given the large number of clan CA proteases present in Plasmodium species (ten in Plasmodium falciparum), and the difficulty of designing selective inhibitors that do not cross-react with other members of the same family. Additionally, any efforts to develop antimalarial drugs targeting these proteases will also have to take into account potential off-target effects against the 11 human cysteine cathepsins. Activity-based protein profiling has been a very useful tool to determine the specificity of inhibitors against all members of an enzyme family. However, current clan CA proteases broad-spectrum activity-based probes either target endopeptidases or dipeptidyl aminopeptidases, but not both subfamilies efficiently. In this study, we present a new series of dipeptydic vinyl sulfone probes containing a free N-terminal tryptophan and a fluorophore at the P1 position that are able to label both subfamilies efficiently, both in Plasmodium falciparum and in mammalian cells, thus making them better broad-spectrum activity-based probes. We also show that some of these probes are cell permeable and can therefore be used to determine the specificity of inhibitors in living cells. Interestingly, we show that the choice of fluorophore greatly influences the specificity of the probes as well as their cell permeability.

Aim: The Scratch programming language allows learner developers to write games. The Kinect2Scratch extension makes Scratch games with bodily motion control possible by connecting to Microsoft's Kinect sensor. This study examined the feasibility and possible efficacy of a suite of motion-controlled games designed for upper extremity (UE) training in children with cerebral palsy (CP) using Kinect2Scratch. Materials and Methods: This is a proof-of-concept study. We developed three games, requiring three UE movement patterns (shoulder holding, reaching, and handclap), for use in children with CP. The primary outcome was feasibility, addressed by adherence, engagement, satisfaction, and safety. The secondary outcome was efficacy, which was evaluated by Quality of Upper Extremities Skills Test (QUEST), Box and Block Test (BBT), Melbourne Assessment 2 (MA2) test, and ABILHAND-kids score. Results: Thirteen children with CP (mean age 6.9 years) received 24 sessions of training (30 minutes per session). The adherence rate was 100%. During the first 2 weeks of training, children had a significantly higher level of participation in Kinect2Scratch training than in conventional rehabilitation [Pittsburgh Participation Scale, median (interquartile range [IQR]), 6 (3–6) vs. 4 (3–6) P = 0.04]. However, during the last 2 weeks of training, there was no significant difference in participation between the Kinect2Scratch and conventional training [Pittsburgh Rehabilitation Participation Scale, median (IQR), 4 (3–5) vs. 4 (3–6) P = 0.55]. Most children enjoyed playing the games. The mean score of enjoyment was 4.54 ± 0.66. There were no adverse events during the training periods. The children had significant improvement in total score of QUEST and MA2. There were no significant improvements in BBT and ABILHAND-kids score. Conclusion: Using Kinect2Scratch games for UE training is a feasible adjunctive program for children with CP.

Background\ud Dissociative seizures are paroxysmal events resembling epilepsy or syncope with characteristic features that allow them to be distinguished from other medical conditions. We aimed to compare the effectiveness of cognitive behavioural therapy (CBT) plus standardised medical care with standardised medical care alone for the reduction of dissociative seizure frequency.\ud \ud Methods\ud In this pragmatic, parallel-arm, multicentre randomised controlled trial, we initially recruited participants at 27 neurology or epilepsy services in England, Scotland, and Wales. Adults (≥18 years) who had dissociative seizures in the previous 8 weeks and no epileptic seizures in the previous 12 months were subsequently randomly assigned (1:1) from 17 liaison or neuropsychiatry services following psychiatric assessment, to receive standardised medical care or CBT plus standardised medical care, using a web-based system. Randomisation was stratified by neuropsychiatry or liaison psychiatry recruitment site. The trial manager, chief investigator, all treating clinicians, and patients were aware of treatment allocation, but outcome data collectors and trial statisticians were unaware of treatment allocation. Patients were followed up 6 months and 12 months after randomisation. The primary outcome was monthly dissociative seizure frequency (ie, frequency in the previous 4 weeks) assessed at 12 months. Secondary outcomes assessed at 12 months were: seizure severity (intensity) and bothersomeness; longest period of seizure freedom in the previous 6 months; complete seizure freedom in the previous 3 months; a greater than 50% reduction in seizure frequency relative to baseline; changes in dissociative seizures (rated by others); health-related quality of life; psychosocial functioning; psychiatric symptoms, psychological distress, and somatic symptom burden; and clinical impression of improvement and satisfaction. p values and statistical significance for outcomes were reported without correction for multiple comparisons as per our protocol. Primary and secondary outcomes were assessed in the intention-to-treat population with multiple imputation for missing observations. This trial is registered with the International Standard Randomised Controlled Trial registry, ISRCTN05681227, and ClinicalTrials.gov, NCT02325544.\ud \ud Findings\ud Between Jan 16, 2015, and May 31, 2017, we randomly assigned 368 patients to receive CBT plus standardised medical care (n=186) or standardised medical care alone (n=182); of whom 313 had primary outcome data at 12 months (156 [84%] of 186 patients in the CBT plus standardised medical care group and 157 [86%] of 182 patients in the standardised medical care group). At 12 months, no significant difference in monthly dissociative seizure frequency was identified between the groups (median 4 seizures [IQR 0–20] in the CBT plus standardised medical care group vs 7 seizures [1–35] in the standardised medical care group; estimated incidence rate ratio [IRR] 0·78 [95% CI 0·56–1·09]; p=0·144). Dissociative seizures were rated as less bothersome in the CBT plus standardised medical care group than the standardised medical care group (estimated mean difference −0·53 [95% CI −0·97 to −0·08]; p=0·020). The CBT plus standardised medical care group had a longer period of dissociative seizure freedom in the previous 6 months (estimated IRR 1·64 [95% CI 1·22 to 2·20]; p=0·001), reported better health-related quality of life on the EuroQoL-5 Dimensions-5 Level Health Today visual analogue scale (estimated mean difference 6·16 [95% CI 1·48 to 10·84]; p=0·010), less impairment in psychosocial functioning on the Work and Social Adjustment Scale (estimated mean difference −4·12 [95% CI −6·35 to −1·89]; p

Objective: To examine a rural-serving HBPC program's 12-year experience and historical trends to inform future program direction and expansion. Background: There is limited information about longitudinal trends in mature hospital-based palliative care (HBPC) programs serving racially diverse rural populations. Methods: This is a retrospective cross-sectional study of operational and patient-reported outcomes from the University of Alabama at Birmingham (UAB) Center for Palliative and Supportive Care (CPSC) inpatient (n=11,786) and outpatient (n=315) databases from October 2004 to March 2016. Results: Inpatients were a mean age of 63.7 years, male (50.1%), white (62.3%), general medicine referred (19.5%), primarily for goals of care (84.4%); 47.1% had "do not resuscitate/do not intubate" status and 46.9% were transferred to the Palliative Care and Comfort Unit (PCCU) after consultation. Median time from admission to consultation was three days, median PCCU length of stay (LOS) was four days, and median hospital LOS was nine days. Increased emergency department and cardiology referrals were notable in later years. Outpatients' mean age was 53.02 years, 63.5% were female, 76.8% were white, and 75.6% had a cancer diagnosis. Fatigue, pain, and disturbed sleep were the most common symptoms at the time of the visit; 34.6% reported mild-to-moderate depressive symptoms. Of patients reporting pain (64.8%), one-third had 50% or less relief from pain treatment. Discussion: The CPSC, which serves a racially diverse rural population, has demonstrated robust growth. We are poised to scale and spread our lessons learned to underserved communities.

Background Virtual reality and interactive video games could decrease the demands on the time of the therapists. However, the cost of a virtual reality system and the requirement for technical support limits the availability of these systems. Commercial exergames are not specifically designed for therapeutic use, most patients with hemiplegic stroke are either too weak to play the games or develop undesirable compensatory movements. Aim To develop Kinect2Scratch games and compare the effects of training with therapist-based training on upper extremity (UE) function of patients with chronic stroke. Design A randomized controlled single-blinded trial. Setting An outpatient rehabilitation clinic of a tertiary hospital. Population Thirty-three patients with chronic hemiplegic stroke. Methods We developed 8 Kinect2Scratch games. The participants were randomly assigned to either a Kinect2Scratch game group or a therapist-based training group. The training comprised 24 sessions of 30 minutes over 12 weeks. The primary outcome measure was the Fugl-Meyer UE scale and the secondary outcome measures were the Wolf Motor Function Test and Motor Activity Log. Patients were assessed at baseline, after intervention, and at the 3-month follow-up. We used the Pittsburgh participation scale (PPS) to assess the participation level of patients at each training session and an accelerometer to assess the activity counts of the affected UE of patients was used at the 12th and 24th training sessions. Results Seventeen patients were assigned to the Kinect2Scratch group and 16 were assigned to the therapist-based training group. There were no differences between the two groups for any of the outcome measures postintervention and at the 3-month follow-up (all P>0.05). The level of participation was higher in the Kinect2Scratch group than in the therapist-based training group (PPS 5.25 vs. 5.00, P=0.112). The total activity counts of the affected UE was significantly higher in the Kinect2Scratch group than in the therapist-based training group (P Conclusions Kinect2Scratch game training was feasible, with effects similar to those of therapist-based training on UE function of patients with chronic stroke. Clinical rehabilitation impact Kinect2Scratch games are low-cost and easily set-up games, which may serve as a complementary strategy to conventional therapy to decrease therapists' work load.

Purpose\ud \ud \ud Phenytoin is an effective anticonvulsant for focal epilepsy. Its use can be associated with long-term adverse effects including cerebellar ataxia. Whilst phenytoin is toxic to Purkinje cells in vitro; the clinical and radiological phenotype and mechanism of cerebellar degeneration in vivo remain unclear. We describe the prevalence, clinical and radiological characteristics of phenytoin-related ataxia.\ud \ud \ud \ud Methods\ud \ud \ud Patients with epilepsy receiving treatment with phenytoin were recruited from the Epilepsy clinics at Royal Hallamshire Hospital, Sheffield, UK. Neurological examination was performed on all patients after recruitment. Patients were categorised into those with and without ataxia. We determined the severity of ataxia clinically (SARA score) and the pattern of cerebellar involvement by neuroimaging (MRI volumetry and MR spectroscopy).\ud \ud \ud \ud Results\ud \ud \ud Forty-seven patients were recruited. Median duration of epilepsy was 24 years, median duration of phenytoin treatment was 15 years and current median phenytoin daily dose was 325 mg. Fifty-five percent of patients complained of poor balance. Clinical evidence of ataxia was seen in 40% patients. Gait, stance and heel-shin slide were the predominant features of cerebellar dysfunction. MRI demonstrated structural, volumetric and functional deficits of the cerebellum. Only one patient with ataxia had phenytoin levels above the normal range.\ud \ud \ud \ud Conclusions\ud \ud \ud Cerebellar ataxia is present in 40% of patients with epilepsy and chronic exposure to phenytoin. Patients on long-term phenytoin have reduced cerebellar volume even if they have no clinical evidence of ataxia. Evidence of structural deficits on imaging suggests a predilection for vermian involvement.

We present the analysis of a prospective multicentre study to investigate genetic effects on the prognosis of newly treated epilepsy. Patients with a new clinical diagnosis of epilepsy requiring medication were recruited and followed up prospectively. The clinical outcome was defined as freedom from seizures for a minimum of 12 months in accordance with the consensus statement from the International League Against Epilepsy (ILAE). Genetic effects on remission of seizures after starting treatment were analysed with and without adjustment for significant clinical prognostic factors, and the results from each cohort were combined using a fixed-effects meta-analysis. After quality control (QC), we analysed 889 newly treated epilepsy patients using 472 450 genotyped and 6.9 × 10(6) imputed single-nucleotide polymorphisms. Suggestive evidence for association (defined as Pmeta5.0 × 10(-7)) with remission of seizures after starting treatment was observed at three loci: 6p12.2 (rs492146, Pmeta = 2.1 × 10(-7), OR[G] = 0.57), 9p23 (rs72700966, Pmeta = 3.1 × 10(-7), OR[C] = 2.70) and 15q13.2 (rs143536437, Pmeta = 3.2 × 10(-7), OR[C] = 1.92). Genes of biological interest at these loci include PTPRD and ARHGAP11B (encoding functions implicated in neuronal development) and GSTA4 (a phase II biotransformation enzyme). Pathway analysis using two independent methods implicated a number of pathways in the prognosis of epilepsy, including KEGG categories 'calcium signaling pathway' and 'phosphatidylinositol signaling pathway'. Through a series of power curves, we conclude that it is unlikely any single common variant explains4.4% of the variation in the outcome of newly treated epilepsy.

Summary Purpose Autoantibodies to specific neurologic proteins are associated with subacute onset encephalopathies, which often present with seizures that are poorly controlled by conventional antiepileptic drugs (AEDs). Previous cross-sectional studies have found specific neurologic antibodies in a small proportion of people with established epilepsy, but these investigations have seldom included patients with recent diagnosis. Methods We screened two large epilepsy cohorts to investigate the prevalence of multiple autoantibodies in adult patients with either established or newly diagnosed, untreated epilepsy. Key Findings Eleven percent of patients had antibodies to one or more antigen: voltage-gated potassium channel (VGKC) complex proteins (5%), glycine receptors (3%), and glutamic acid decarboxylase (GAD) and N-methyl-d-aspartate (NMDA) receptors (1.7% each). There was no difference in the prevalence of antibodies, individually or collectively, between patients with established and newly diagnosed epilepsy or with generalized or focal epilepsy. There was, however, a significantly higher prevalence of positive antibody titers in patients with focal epilepsy of unknown cause than in those with structural/metabolic focal epilepsy (14.8% vs. 6.3%; p

Previous studies suggest that ictal panic symptoms are common in patients with psychogenic nonepileptic seizures (PNES). This study investigates the frequency of panic symptoms in PNES and if panic symptoms, just before or during episodes, can help distinguish PNES from the other common causes of transient loss of consciousness (TLOC), syncope and epilepsy.Patients with secure diagnoses of PNES (n=98), epilepsy (n=95) and syncope (n=100) were identified using clinical databases from three United Kingdom hospitals. Patients self-reported the frequency with which they experienced seven symptoms of panic disorder in association with their episodes. A composite panic symptom score was calculated on the basis of the frequency of symptoms.8.2% of patients with PNES reported "never" experiencing any of the seven panic symptoms in their episodes of TLOC. Patients with PNES reported more frequent panic symptoms in their attacks than those with epilepsy (p0.001) or syncope (p0.001), however, patients with PNES were more likely "rarely" or "never" to report five of the seven-ictal panic symptoms than "frequently" or "always" (45-69% versus 13-29%). A receiver operating characteristic analysis demonstrated that the composite panic symptom score distinguished patients with PNES from the other groups (sensitivity 71.1%, specificity 71.2%), but not epilepsy from syncope.Patients with PNES report TLOC associated panic symptoms more commonly than those with epilepsy or syncope. Although panic symptoms are reported infrequently by most patients with PNES, a composite symptom score may contribute to the differentiation between PNES and the other two common causes of TLOC.

Prolonged paralysis due to a quantitative or qualitative deficiency of pseudocholinesterase activity is an uncommon but known side effect of succinylcholine. We describe a patient who experienced prolonged paralysis following administration of succinylcholine for general anesthesia and endotracheal intubation for an emergent cesarean section despite laboratory evidence of normal enzyme function. The patient required mechanical ventilation in the intensive care unit for several hours following surgery. The patient was extubated following return of full muscle strength and had a good outcome. The enzyme responsible for the metabolism of succinylcholine, pseudocholinesterase, was determined to be low in quantity in this patient but was functionally normal. This low level, by itself, was unlikely to be solely responsible for the prolonged paralysis. The patient likely had an abnormal pseudocholinesterase enzyme variant that is undetectable by standard laboratory tests.

Temporal lobe epilepsy (TLE) has been associated with the phenomenon of accelerated long-term forgetting (ALF), in which memories are retained normally over short delays but are then lost at an accelerated rate over days or weeks. The causes of ALF, and whether it represents a consolidation deficit distinct from the one associated with forgetting over short delays, remain unclear. In addition, methodological issues have made results of some previous studies difficult to interpret. This study used improved methodology to investigate the role of seizure activity in ALF. Forgetting was assessed in participants with TLE (who have involvement of temporal lobe structures) and idiopathic generalised epilepsy (IGE; in which seizures occur in the absence of identified structural pathology in the temporal lobes). Learning of novel stimuli was matched between patients with TLE, patients with IGE and healthy controls matched for age and IQ. Results indicated that the TLE group showed accelerated forgetting between 30-min and three-weeks, but not between 40-s and 30-min. In contrast, rates of forgetting did not differ between patients with IGE and controls. We conclude that (1) ALF can be demonstrated in TLE in the absence of methodological confounds; (2) ALF is unlikely to be related to the experience of epilepsy that does not involve the temporal lobes; (3) neither seizures during the three-week delay nor polytherapy was associated with ALF.

"Taking the history" remains the most important diagnostic tool in the assessment of people who have lost consciousness. The distinction of epileptic and non-epileptic seizures (NES) is particularly difficult and relevant. Whereas epileptic seizures can usually be controlled with antiepileptic drugs, NES are considered an expression of psychosocial distress and may improve with psychotherapy. The recording of typical seizures with simultaneous video and electroencephalography (EEG) can produce almost complete certainty about the diagnosis but access to video-EEG is limited, the test is very expensive and often video-EEG fails to capture typical seizures. A German research group used conversation analysis (CA) to examine patients' descriptions of seizures to their doctors. They found that certain linguistic and interactional features clustered together and that these clusters were usually concordant with particular medical diagnoses. This study was undertaken to establish whether the observations made in German-speaking patients could be replicated in English speakers presenting to a less specialised epilepsy service. The findings presented here are based on transcripts of interviews with 11 patients admitted to a neurology ward in England because their consultant felt unable to make a clear diagnosis clinically. Transcripts were only analysed if the diagnosis of epilepsy or NES had been proven with video-EEG. The medical diagnosis was only disclosed to the linguist once a linguistic hypothesis of the diagnosis had been formulated to ensure that the linguist's decision would not be influenced by factors not contained in the 30-min-interview between doctor and patient. The linguist predicted the correct diagnosis in all cases.

Background: The memory deficits in patients with temporal lobe epilepsy (TLE) are associated with epileptogenic lesions of the temporal lobes, especially hippocampal sclerosis. Memory deficits have been extensively studied in TLE, but the presence of pre-existing temporal lobe abnormality has confounded studies on the relationship between memory dysfunction and seizure activity. Idiopathic generalised epilepsy (IGE) is characterised by primary generalised seizures and is found to occur in the absence of any macroscopic brain abnormalities. IGE is therefore ideal for investigations on the effects of seizure activity on memory and cognition. Aim and methods: Magnetic resonance spectroscopy (MRS) and neuropsychological testing were used to investigate the relationship between epileptic seizures, memory performance and neuronal dysfunction in the temporal lobes of a group of patients with IGE. 30 patients and 15 healthy controls participated in the study. Results: Patients with IGE were found to perform worse than controls on tests of speed of information processing, general cognitive performance and a range of memory tests, including face recognition, word recognition, verbal recall and complex figure recall. The performance of the patient group on the visual recognition and verbal recall sections of the Doors and People Test was found to correlate with MRS ratios of N-acetyl aspartate:choline and N-acetyl aspartate:creatine in the temporal lobes. Conclusion: This result supports the hypothesis that memory deficits in epilepsy may be due to neuronal dysfunction secondary to epileptic activity itself in the absence of any macroscopic lesions in the temporal lobes.

Chronic headaches can be debilitating for many patients. They often have a nebulous etiology, unpredictable course, and can be difficult to manage. We describe a post-traumatic headache that began after a motor vehicle collision. The patient sustained multiple injuries including a scalp laceration and bilateral occipital condyle fractures. Oral agents were unable to quell this patient's headaches. The diagnosis of occipital neuralgia was suspected based on history and presentation. Our patient received dramatic relief after ultrasound guided bilateral greater occipital nerve blocks.

OBJECTIVE: Epileptic seizures, syncope, and psychogenic nonepileptic seizures (PNES) account for over 90% of presentations with transient loss of consciousness (TLOC). The patient's history is crucial for the diagnosis, but the diagnostic value of individual semiologic features is limited. This study explores the diagnostic potential of a comprehensive questionnaire focusing on TLOC-associated symptoms. METHODS: A total of 386 patients with proven epilepsy, 308 patients with proven PNES, and 371 patients with proven syncope were approached by post to recruit 100 patients in each diagnostic group. Symptoms were self-reported on an 86-item questionnaire (the Paroxysmal Event Profile [PEP]) using a 5-point Likert scale (always to never). Data were subjected to exploratory factor analysis (EFA) followed by confirmatory factor analysis (CFA). Factors were used to differentiate between diagnoses by pairwise and multinomial regression. RESULTS: Patients with PNES reported more and more frequent TLOC-associated symptoms than those with epilepsy or syncope (p < 0.001). EFA/CFA identified a 5-factor structure based on 74/86 questionnaire items with loadings ≥0.4. Pairwise logistic regression analysis correctly classified 91% of patients with epilepsy vs those with syncope, 94% of those with PNES vs those with syncope, and 77% of those with epilepsy vs those with PNES. Multinomial logistic regression analysis yielded a similar pattern. CONCLUSIONS: Clusters of self-reported TLOC symptoms can be used to direct patients to appropriate investigation and treatment pathways for syncope on the one hand and seizures on the other, although additional information is required for a reliable distinction, especially between epilepsy and PNES.

The purpose of this study was to investigate whether patients with multiple sclerosis (MS) and their partners show adversarial growth and to examine which psychological and disability variables contribute to this in patients and their partners. The study also investigated the relationship between growth and distress. Seventy-two patients with MS and their partners provided demographic information and completed measures of posttraumatic growth, illness perceptions, depression, cognitive function and disability. Both patients and partners showed adversarial growth, with patients reporting significantly higher growth than partners. The only significant predictor for patient growth was partner growth, and vice versa. Dissimilarity in illness representations between patients and their partners on the consequences of MS dimension, patient mood and patient growth accounted for significant variance in partner growth. The findings support the idea of a 'communal search for meaning' where patients and their partners experience the trauma of having a chronic illness and subsequently find positive aspects together.

OVB3-PE is an immunotoxin composed of a murine monoclonal antibody reactive with human ovarian cancer and conjugated to Pseudomonas exotoxin (PE). Twenty-three patients with refractory ovarian cancer were treated intraperitoneally (IP) with escalating doses of OVB3-PE to study toxicity, pharmacokinetics, antiimmunotoxin antibody formation, and antitumor response. Dose-limiting CNS toxicity occurred after repeated doses at 5 and 10 micrograms/kg. Other non-dose-limiting toxicities included transient elevation of liver enzymes, fever, and gastrointestinal toxicity. Pharmacokinetics of IP and serum OVB3-PE were determined in 16 patients. Peak peritoneal fluid levels exceeded the in vitro median effective dose at all doses tested. At doses of 1 to 2 micrograms/kg, the immunotoxin concentration in the peritoneal fluid remained constant for up to 8 hours and dropped to negligible levels after 12 hours. At the 5 and 10 micrograms/kg doses, levels remained high for up to 24 hours (greater than 100 ng/mL) and then gradually decreased and became undetectable (less than 4 ng/mL) after 72 hours. Serum levels of OVB3-PE were also analyzed in 16 patients. At doses of 1 micrograms/kg and 2 micrograms/kg, serum levels were not detectable (less than 5 ng/mL). However, after doses of 5 or 10 micrograms/kg, peak serum level occurred at 24 hours after each dose and dropped to negligible levels by 72 hours. Sera from 12 patients were analyzed for anti-PE antibodies and antibodies to mouse immunoglobulin (HAMA). All patients developed antibodies against PE within 14 days of therapy. Domain II of PE appeared to be the most immunogenic portion of the PE molecule. HAMA was detected on day 14 of therapy in nine patients, on day 21 in two, and on day 28 in one patient. No clinical antitumor responses were observed. We conclude that IP OVB3-PE at dose levels of 5 micrograms/kg (x 3) and 10 micrograms/kg (x 2) is accompanied by dose-limiting toxic encephalopathy. Neurologic toxicity is likely to be due to crossreactivity of OVB3 to normal human brain tissue, which was not appreciated during preclinical screening.

Autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE) is a relatively benign epilepsy syndrome with few comorbidities. Here we describe two families with unusually severe ADNFLE, with associated psychiatric, behavioral, and cognitive features. Detailed clinical data on 17 affected individuals were obtained, and genotyping of microsatellite markers, linkage analysis, and sequencing of candidate genes was performed. The severe ADNFLE phenotype in these families was often refractory to treatment, with status epilepticus occurring in 24% of subjects. Psychiatric or behavioral disorders occurred in 53%, with intellectual disability in 24%, and developmental regression in two individuals. No mutations were identified in alpha4, alpha2, or beta2 nAChR subunits. In one family there was evidence of linkage to a region of 15q24 without nAChR subunit genes. In conclusion, severe ADNFLE has significant medical, psychiatric, and intellectual morbidity. The molecular basis of severe ADNFLE is unknown but may involve non-nAChR-related mechanisms.

Summary Background Carbamazepine is widely accepted as a drug of first choice for patients with partial onset seizures. Several newer drugs possess efficacy against these seizure types but previous randomised controlled trials have failed to inform a choice between these drugs. We aimed to assess efficacy with regards to longer-term outcomes, quality of life, and health economic outcomes. Methods SANAD was an unblinded randomised controlled trial in hospital-based outpatient clinics in the UK. Arm A recruited 1721 patients for whom carbamazepine was deemed to be standard treatment, and they were randomly assigned to receive carbamazepine, gabapentin, lamotrigine, oxcarbazepine, or topiramate. Primary outcomes were time to treatment failure, and time to 12-months remission, and assessment was by both intention to treat and per protocol. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN38354748. Findings For time to treatment failure, lamotrigine was significantly better than carbamazepine (hazard ratio [HR] 0·78 [95% CI 0·63–0·97]), gabapentin (0·65 [0·52–0·80]), and topiramate (0·64 [0·52–0·79]), and had a non-significant advantage compared with oxcarbazepine (1·15 [0·86–1·54]). For time to 12-month remission carbamazepine was significantly better than gabapentin (0·75 [0·63–0·90]), and estimates suggest a non-significant advantage for carbamazepine against lamotrigine (0·91 [0·77–1·09]), topiramate (0·86 [0·72–1·03]), and oxcarbazepine (0·92 [0·73–1·18]). In a per-protocol analysis, at 2 and 4 years the difference (95% CI) in the proportion achieving a 12-month remission (lamotrigine-carbamazepine) is 0 (−8 to 7) and 5 (−3 to 12), suggesting non-inferiority of lamotrigine compared with carbamazepine. Interpretation Lamotrigine is clinically better than carbamazepine, the standard drug treatment, for time to treatment failure outcomes and is therefore a cost-effective alternative for patients diagnosed with partial onset seizures.

AIM/METHODS: Endoscopic ultrasound (EUS) guided biopsy is not widely available in the U.K., and sub-carinal nodes can be difficult to biopsy percutaneously. Tissue obtained from these nodes can influence patient management. We describe our initial experience with EUS guided transoesophageal biopsy of sub-carinal nodes using a Pentax FG-34 EUS probe and a 22G Hancke–Villman or Echotip needle in 20 patients. RESULTS: Malignant cells were obtained from the nodes in 13 patients, and in another patient in whom the node biopsy was negative, small cell carcinoma cells were obtained from a lesion in the liver. There were no complications. CONCLUSIONS: Mediastinoscopy to obtain tissue, or the blind treatment of presumed malignancy was avoided in all the patients in whom a positive biopsy was obtained. In many of these patients, more conventional methods to obtain a tissue diagnosis had already failed. The problem solving capability of this safe, well-tolerated technique is discussed.Roberts, S. A. . Clinical Radiology 55 , 832–836.

Summary Autosomal dominant nocturnal frontal-lobe epilepsy (ADNFLE) is a recently identified partial epilepsy in which two different mutations have been described in the α4 subunit of the neuronal nicotinic acetylcholine receptor ( CHRNA4 ). An additional seven families are presented in which ADNFLE is unlinked to the CHRNA4 region on chromosome 20q13.2. Seven additional sporadic cases showed no evidence of defective CHRNA4. One of the families showed evidence of linkage to 15q24, close to the CHRNA3 / CHRNA5 / CHRNB4 cluster (maximum LOD score of 3.01 with D15S152 ). Recombination between ADNFLE and CHRNA4 , linkage to 15q24 in one family, and exclusion from 15q24 and 20q13.2 in others demonstrate genetic heterogeneity with at least three different genes for ADNFLE. The CHRNA4 gene and the two known CHRNA4 mutations are responsible for only a minority of ADNFLE. Although the ADNFLE phenotype is clinically homogeneous, there appear to be a variety of molecular defects responsible for this disorder, which will provide a challenge to the understanding of the basic mechanism of epileptogenesis.

In order to improve epilepsy services, Doncaster Hospital doctors and general practitioners agreed upon a collaborative approach. A district epilepsy service was inaugurated around specialist services based in a hospital clinic. Guidelines were produced to clarify respective roles and to assist non-specialist hospital doctors and general practitioners in epilepsy management. A novel feature of the new service was the appointment of a community-based specialist liaison nurse. The new service is perceived to be effective, and the contribution of the specialist nurse to represent an important advance in epilepsy care. It has been possible to supervise complicated changes in medication successfully at home with a reduction in the need to attend clinic or GP. Counselling and support for patients and families, previously lacking, has been a major contribution. Evaluation to determine the extent to which the service meets the needs of those in the local population with epilepsy is planned. This document describes the first 5 years of the service and the scope and content of the specialist liaison nurse's role.