DRAQ7 as an Alternative to MTT Assay for Measuring Viability of Glioma Cells Treated With Polyphenols.

BACKGROUND/AIM: The tetrazolium-based MTT cytotoxicity assay is well established for screening putative anti-cancer agents. However, it has limitations including lack of reproducibility with glioma cells treated with polyphenols. The aim of this study was to evaluate whether a flow cytometric assay with the anthraquinone, DRAQ7, was a better alternative than the colorimetric MTT assay for measuring cell viability. MATERIALS AND METHODS: Two glioma cell lines (IPSB-18, U373) and 1 pancreatic cancer cell line (AsPC-1) were treated with 4 polyphenols, namely red grape seed extract, red clover extract, anthocyanin-rich extract and curcumin. Cell viability was assessed using MTT assay and DRAQ7 staining. RESULTS: Limitations of MTT assay included lack of sensitivity and interference with the structure and absorbance spectra of polyphenols. Also, DMSO was toxic to glioma cells. Microscopic observations of cells treated with polyphenols confirmed the range of IC50 values evaluated by DRAQ7, but not by the MTT assay. CONCLUSION: DRAQ7 is a better alternative than MTT for measuring viability of glioma cells treated with brightly coloured polyphenols.

Subacute neocortical stimulation (SNCS) and its effects on epileptic activity in adults and children diagnosed with focal cortical dysplasia (FCD).

BACKGROUND: Chronic intracranial electrical stimulation is now widely used as treatment for drug resistant epilepsy. Subacute neocortical stimulation (SNCS) can also be performed during EEG recordings with intracranial electrodes (iEEG), but its diagnostic value remains largely unknown. METHODS: We assessed the effects of SNCS on the frequency of seizures and epileptiform discharges (EDs) during 290 h of iEEG- from 12 patients (6 adults, 6 children) with epilepsy secondary to focal cortical dysplasia (FCD). RESULTS: In 9/12 patients, SNCS periods showed decreased seizure-frequency (Median -73 %, p = 0.0093). At baseline, incidence of EDs were correlated with seizure-frequency (Spearman r = 0.59). However, this correlation disappeared during SNCS and a significant change in the incidence of EDs was observed. In addition, there was a trend towards greater reduction in seizure-frequency during SNCS in patients who underwent surgery. CONCLUSION: In summary, SNCS can reduce seizure-frequency and changes ED-frequency. The variability in ED changes may be explained by different effects of SNCS depending on electrode location. The magnitude of seizure reduction during SNCS suggests that this technique could contribute to preoperative assessment in epilepsy surgery.

Short-lasting retroorbital pain attacks as a form of ictal epileptic headache: Case report.

BACKGROUND AND OBJECTIVES: Ictal epileptic headache is a rare form of painful seizure, habitually consisting of migrainous or tension-type headache. We describe a case of a patient with short-lasting, severe retroorbital pain attacks caused by frontal lobe epilepsy. CASE REPORT: A 25-year-old male patient presented with recurrent attacks of paroxysmal, short-lasting, excruciating left periorbital and facial pain mainly occurring from sleep. After intracranial EEG exploration and resection of a right prefrontal focal cortical dysplasia, long-term seizure and headache remission was obtained. DISCUSSION: Our case extends the clinical and neuroanatomical spectrum of ictal epileptic headache and suggests that long-term remission can be obtained by resective epilepsy surgery. It also reinforces the role of the prefrontal cortex in the pain matrix and pain generation. CONCLUSION: Despite its rarity, ictal epileptic headache should be suspected in selected patients, particularly those with other ictal symptoms and signs, history of epileptic seizures, or neuroimaging abnormalities.

The Single Word Auditory Comprehension (SWAC) test: A simple method to identify receptive language areas with electrical stimulation.

OBJECTIVES: Resective surgery for medically refractory epilepsy in proximity to speech receptive areas requires balancing adequate resection of the epileptogenic zone for optimal seizure control with preservation of function. We develop a simple test (Single Word Auditory Comprehension or SWAC) to localize speech receptive areas by evaluating patients' ability to comprehend a single word. METHODS: Patients were studied during presurgical or intraoperative assessment for epilepsy with intracranial electrodes. They were asked to listen to a common word (target word) and to describe what it meant without saying the target word. Electrical stimulation (trains of biphasic 2-ms pulses, 50 Hz for 3 s) was delivered while the patient listened to the target word, not while the patient explained the meaning of the word. In six patients, SWAC test was carried out during extraoperative chronic recordings, and in one patient in the operating theater under local anesthesia. RESULTS: Among the 7 patients where the test identified deficits, 6 underwent resection (4 temporal, 1 supramarginal, and 1 occipital). Two patients showed temporary minor speech deficits after resection. No patient showed permanent speech deficits after resection. CONCLUSION/SIGNIFICANCE: The SWAC test is reliable, simple and fast to implement, and suitable for intraoperating mapping. It could be used as a simple initial test to identify receptive language areas where more complex additional tests can be performed.

The Role of Thalamus Versus Cortex in Epilepsy: Evidence from Human Ictal Centromedian Recordings in Patients Assessed for Deep Brain Stimulation.

BACKGROUND: The onset of generalized seizures is a long debated subject in epilepsy. The relative roles of cortex and thalamus in initiating and maintaining the different seizure types are unclear. OBJECTIVE: The purpose of the study is to estimate whether the cortex or the centromedian thalamic nucleus is leading in initiating and maintaining seizures in humans. METHODS: We report human ictal recordings with simultaneous thalamic and cortical electrodes from three patients without anesthesia being assessed for deep brain stimulation (DBS). Patients 1 and 2 had idiopathic generalized epilepsy whereas patient 3 had frontal lobe epilepsy. Visual inspection was combined with nonlinear correlation analysis. RESULTS: In patient 1, seizure onset was bilateral cortical and the belated onset of leading thalamic discharges was associated with an increase in rhythmicity of discharges, both in thalamus and cortex. In patient 2, we observed bilateral independent interictal discharges restricted to the thalamus. However, ictal onset was diffuse, with discharges larger in the cortex even though they were led by the thalamus. In patient 3, seizure onset was largely restricted to frontal structures, with belated lagging thalamic involvement. CONCLUSION: In human generalized seizures, the thalamus may become involved early or late in the seizure but, once it becomes involved, it leads the cortex. In contrast, in human frontal seizures the thalamus gets involved late in the seizure and, once it becomes involved, it lags behind the cortex. In addition, the centromedian nucleus of the thalamus is capable of autonomous epileptogenesis as suggested by the presence of independent focal unilateral epileptiform discharges restricted to thalamic structures. The thalamus may also be responsible for maintaining the rhythmicity of ictal discharges.

Intracranial stimulation for children with epilepsy.

OBJECTIVES: To evaluate the efficacy of intracranial stimulation to treat refractory epilepsy in children. METHODS: This is a retrospective analysis of a pilot study on all 8 children who had intracranial electrical stimulation for the investigation and treatment of refractory epilepsy at King's College Hospital between 2014 and 2015. Five children (one with temporal lobe epilepsy and four with frontal lobe epilepsy) had subacute cortical stimulation (SCS) for a period of 20-161 h during intracranial video-telemetry. Efficacy of stimulation was evaluated by counting interictal discharges and seizures. Two children had thalamic deep brain stimulation (DBS) of the centromedian nucleus (one with idiopathic generalized epilepsy, one with presumed symptomatic generalized epilepsy), and one child on the anterior nucleus (right fronto-temporal epilepsy). The incidence of interictal discharges was evaluated visually and quantified automatically. RESULTS: Among the three children with DBS, two had >60% improvement in seizure frequency and severity and one had no improvement. Among the five children with SCS, four showed improvement in seizure frequency (>50%) and one chid did not show improvement. Procedures were well tolerated by children. CONCLUSION: Cortical and thalamic stimulation appear to be effective and well tolerated in children with refractory epilepsy. SCS can be used to identify the focus and predict the effects of resective surgery or chronic cortical stimulation. Further larger studies are necessary.

Comparative gene expression profiling of ADAMs, MMPs, TIMPs, EMMPRIN, EGF-R and VEGFA in low grade meningioma.

MMPs (matrix metalloproteinases), ADAMs (a disintegrin and metalloproteinase) and TIMPs (tissue inhibitors of metalloproteinases) are implicated in invasion and angiogenesis: both are tissue remodeling processes involving regulated proteolysis of the extracellular matrix, growth factors and their receptors. The expression of these three groups and their correlations with clinical behaviour has been reported in gliomas but a similar comprehensive study in meningiomas is lacking. In this study, we aimed to evaluate the patterns of expression of 23 MMPs, 4 TIMPs, 8 ADAMs, selective growth factors and their receptors in 17 benign meningiomas using a quantitative real-time polymerase chain reaction (qPCR). Results indicated very high gene expression of 13 proteases, inhibitors and growth factors studied: MMP2 and MMP14, TIMP-1, -2 and -3, ADAM9, 10, 12, 15 and 17, EGF-R, EMMPRIN and VEGF-A, in almost every meningioma. Expression pattern analysis showed several positive correlations between MMPs, ADAMs, TIMPs and growth factors. Furthermore, our findings suggest that expression of MMP14, ADAM9, 10, 12, 15 and 17, TIMP-2, EGF-R and EMMPRIN reflects histological subtype of meningioma such that fibroblastic subtype had the highest mRNA expression, transitional subtype was intermediate and meningothelial type had the lowest expression. In conclusion, this is the first comprehensive study characterizing gene expression of 8 ADAMs in meningiomas. These neoplasms, although by histological definition benign, have invasive potential. Taken together, the selected elevated gene expression pattern may serve to identify targets for therapeutic intervention or indicators of biological progression and recurrence.

Prognostic value of the second ictal intracranial pattern for the outcome of epilepsy surgery.

OBJECTIVE: To investigate the prognostic value of the second ictal pattern (SIP) that follows the first ictal pattern (FIP) seen at seizure onset in order to predict seizure control after epilepsy surgery. METHODS: SIPs were analysed in 344 electro-clinical and subclinical seizures recorded with intracranial electrodes in 63 patients. SIPs were classified as (a) electrodecremental event (EDE); (b) fast activity (FA); (c) runs of spikes; (d) spike-wave activity; (e) sharp waves; (f) alpha activity; (g) delta activity and (h) theta activity. Engel surgical outcome scale was used. RESULTS: The mean follow-up period was 42.1 months (SD=30.1). EDE was the most common SIP seen (41%), followed by FA (19%), spike-wave activity (18%), alpha activity (8%), sharp-wave activity (8%), delta activity (3%), runs of spikes (2%) and theta activity (2%). EDE as SIP was associated with favourable outcome when compared with FA (p=0.0044) whereas FA was associated with poor outcome when compared with any other pattern (p=0.0389). FA as SIP tends to occur after EDE (75%) whereas EDE tends to evolve from a FIP containing FA (77%). SIP extent was focal in 46% of patients, lobar in 24%, multilobar in 14% and bilateral in 16%. There is a gradual decrease in the proportion of Engel grade I with the extent of SIP. Focal and delayed (in temporal lobe epilepsy) SIPs appear to be associated with better outcome. CONCLUSIONS: As SIP, EDE was associated with favourable surgical outcome whereas FA was associated with poor outcome, probably because outcome is dominated by FIP. SIGNIFICANCE: EDE as SIP should not discourage surgery. However, FA as SIP should be contemplated with caution. SIP focality and latency can have prognostic value in epilepsy surgery.

Electrical Stimulation of the Anterior Cingulate Gyrus Induces Responses Similar to K-complexes in Awake Humans.

BACKGROUND: The brain region responsible for the initiation of K-complexes has not been identified to date. OBJECTIVE: To determine the brain region responsible for originating K-complexes. METHODS: We reviewed all 269 patients assessed for epilepsy surgery with intracranial electrodes and single pulse electrical stimulation (SPES) at King's College Hospital between 1999 and 2013. Intracranial EEG responses to electrical stimulation at orbitofrontal, frontal, cingulate, temporal and parietal loci were compared visually with each patient's K-complexes and the degree of resemblance was quantified. RESULTS: Among the 269 patients, K-complex-like responses were exclusively observed in all 6 patients who had depth electrodes in the cingulate cortex. In each patient, the stimulation site eliciting the response of greatest similarity to the patient's K-complex was located within the dorso-caudal anterior cingulate. The K-complex like responses were evoked when the patients were awake. CONCLUSION: Our findings provide the first causal evidence that the cingulate gyrus initiates the widespread synchronous activity that constitutes the K-complex. The induction of K-complex-like responses during wakefulness suggests that the mechanisms required for the initiation of K-complexes are separate from those involved in sleep.

Incidence of functional bi-temporal connections in the human brain in vivo and their relevance to epilepsy surgery.

The incidence of functional connections between human temporal lobes and their latencies were investigated using intracranial EEG responses to electrical stimulation with 1 msec single pulses in 91 patients assessed for surgery for treatment of epilepsy. The areas studied were amygdala, hippocampus, parahippocampal gyrus, fusiform gyrus, inferior and mid temporal gyrus. Furthermore, we assessed whether the presence of such connections are related to seizure onset extent and postsurgical seizure control. Responses were seen in any region of the contralateral temporal lobe when stimulating temporal regions in 30 patients out of the 91 (32.96%). Bi-hippocampal or bi-amygdalar projections were seen in only 5% of temporal lobes (N = 60) and between both fusiform gyri in 7.1% (N = 126). All other bilateral connections occurred in less than 5% of hemispheres. Depending on the structures, latencies ranged between 20 and 90 msec, with an average value of 60.2 msec. There were no statistical difference in the proportion of patients showing Engel Class I between patients with and without contralateral temporal connections. No difference was found in the proportion of patients showing bilateral or unilateral seizure onset among patients with and without contralateral temporal projections. The present findings corroborate that the functionality of bilateral temporal connections in humans is limited and does not affect the surgical outcome.

Prognostic value of intracranial seizure onset patterns for surgical outcome of the treatment of epilepsy.

OBJECTIVE: To investigate if intracranial EEG patterns at seizure onset can predict surgical outcome. METHODS: Ictal onset patterns from intracranial EEG were analysed in 373 electro-clinical seizures and subclinical seizures from 69 patients. Seizure onset patterns were classified as: (a) Diffuse electrodecremental (DEE); (b) Focal fast activity (FA); (c) Simultaneous onset of fast activity and diffuse electrodecremental event (FA-DEE); (d) Spikes; (e) Spike-wave activity; (f) Sharp waves; (g) Alpha activity; (h) Delta activity. Presence of preceding epileptiform discharge (PED) was also studied. Engel and ILAE surgical outcome scales were used. RESULTS: The mean follow-up period was 42.1 months (SD=30.1). Fast activity was the most common seizure onset pattern seen (33%), followed by (FA-DEE) (20%), DEE (19%), spike-wave activity (12%), sharp-waves (6%), alpha activity (6%), delta activity (3%) and spikes (1%). Preceding epileptiform discharges were present in 75% of patients. FA was associated with favourable outcome (p=0.0083) whereas DEE was associated with poor outcome (p=0.0025). A widespread PED was not associated with poor outcome (p=0.9559). There was no clear association between seizure onset pattern and specific pathology, except possibly between sharp/spike waves and mesial temporal sclerosis. CONCLUSIONS: FA activity is associated with favourable outcome. DEE at onset was associated with poor surgical outcome. Widespread/bilateral PEDs were not associated with poor or good outcome. SIGNIFICANCE: FA appears to be the best marker for the epileptogenic zone. Surgery should be contemplated with caution if DEE is the first ictal change. However, a widespread/bilateral PED at onset is common and should not discourage surgery.

Can single pulse electrical stimulation provoke responses similar to spontaneous interictal epileptiform discharges?

OBJECTIVE: To estimate the proportion of patients where EEG responses to single pulse electrical stimulation (SPES) are similar to spontaneous interictal epileptiform discharges (IEDs) in the same patient, and whether such resemblance is related to seizure onset. METHODS: We have visually compared the morphology, topography and distribution of IEDs and of SPES responses in 36 patients with intracranial EEG recordings during presurgical evaluation. RESULTS: Each patient showed between 3 and 17 different IED patterns, located at seizure onset zone and elsewhere. Only 13 patients showed the highest incidence and amplitude of IEDs at the site of focal seizure onset. Twenty-eight patients showed early responses which were similar to at least one IED pattern. Thirty patients showed delayed responses which were always similar to at least one IED pattern and were always located at seizure onset or in its vicinity. CONCLUSIONS: Early SPES responses often, and delayed responses always, were similar to at least one IED pattern in the same patient. The IEDs resembling delayed responses were those associated with seizure onset. SIGNIFICANCE: The similarities between IEDs and SPES responses suggest that SPES can trigger the mechanisms responsible for generating IEDs, which may become a tool to study the pathophysiology of IEDs.

Interictal estimation of intracranial seizure onset in temporal lobe epilepsy.

OBJECTIVES: To evaluate the lateralizing and localizing values of interictal focal slow activity (IFSA), single pulse electrical stimulation (SPES) and (18)FDG PET, in order to estimate their potential to complement ictal intracranial recordings and reduce prolonged monitoring in patients with temporal lobe epilepsy. METHODS: The study includes 30 consecutive patients with bilateral temporal subdural electrodes and focal seizure onset. IFSA, SPES and (18)FDG PET when available, were visually assessed and their combined lateralization was based on the majority of the individual lateralizing tests. RESULTS: In the 18 patients who had all three tests, lateralization was congruent with seizure onset areas in 15 (83%). When lateralized (15 patients), (18)FDG PET was always congruent with intracranial seizure onset. In all 12 patients without (18)FDG PET, lateralization combining IFSA and SPES was congruent with seizure onset, including two with bilateral independent seizure onset on subdural monitoring. 22 out of the 23 patients who had surgery enjoyed favorable outcome (Engel I or II). CONCLUSION: Intracranial IFSA and SPES can reliably predict the side and site (mesial versus lateral temporal) of seizure onset when they lateralize to the same side. SIGNIFICANCE: (18)FDG PET can be useful in planning electrode implantation. During intracranial recordings, IFSA and SPES have the potential to reduce telemetry time, risks and costs.

The value of Magnetoencephalography to guide electrode implantation in epilepsy.

To investigate if Magnetoencephalography (MEG) can add non-redundant information to guide implantation sites for intracranial recordings (IR). The contribution of MEG to intracranial recording planning was evaluated in 12 consecutive patients assessed pre-surgically with MEG followed by IR. Primary outcome measures were the identification of focal seizure onset in IR and favorable surgical outcome. Outcome measures were compared to those of 12 patients matched for implantation type in whom non-invasive pre-surgical assessment suggested clear hypotheses for implantation (non-MEG group). In the MEG group, non-invasive assessment without MEG was inconclusive, and MEG was then used to further help identify implantation sites. In all MEG patients, at least one virtual MEG electrode generated suitable hypotheses for the location of implantations. No differences in outcome measures were found between non-MEG and MEG groups. Although the MEG group included more complex patients, it showed similar percentage of successful implantations as the non-MEG group. This suggests that MEG can contribute to identify implantation sites where standard methods failed.

Preoperative estimation of seizure control after resective surgery for the treatment of epilepsy.

PURPOSE: Predicting seizure control after epilepsy surgery is difficult. The objectives of this work are: (a) to estimate the value of surgical procedure, presence of neuroimaging abnormalities, need for intracranial recordings, resection lobe, pathology, durations of epilepsy and follow-up period to predict postsurgical seizure control after epilepsy surgery and (b) to provide empirical estimates of successful outcome after different combinations of the above factors in order to aid clinicians in advising patients presurgically about the likelihood of success under their patients' individual circumstances. METHODS: We report postsurgical seizure control from all 243 patients who underwent resective surgery for epilepsy at King's College Hospital between 1999 and 2011. Among the 243 patients, 233 had lobar or sub-lobar resections, 8 had multilobar resections and 2 had excision of a hypothalamic hamartoma. We examined the relation between postsurgical seizure control and type of surgical procedure, presence of neuroimaging abnormalities, pathology, resection lobe and the need of intra-cranial electrodes to identify seizure onset. RESULTS: Among the 243 patients, 126 (52%) enjoyed outcome grade I, 40 (16%) had grade II, 51 (21%) had grade III and 26 (11%) had grade IV (mean follow-up 41.1 months). Normal neuroimaging or need for intracranial recordings was not associated with poorer outcome. Patients undergoing temporal resections showed better outcome than those with frontal resections, due to the poor outcome seen in frontal patients with normal neuroimaging. Among temporal resections, there was no difference in outcome between patients with and without neuroimaging abnormalities. Among patients with lesions on imaging, temporal and frontal resections showed similar outcomes. Likelihood of favourable outcome under the patient's individual circumstances was estimated by the tables provided. There was an 8-9% decrease in the percentage of grade I between follow-up at 12 and >36 months. CONCLUSION: Overall, nearly 70% of patients undergoing resective surgery enjoy favourable post-surgical seizure control. Normal neuroimaging should not discourage surgery in temporal patients but is a negative prognostic sign in normal MRI frontal patients. There were no statistical differences in outcome between patients with neuroimaging lesions in frontal or temporal lobes.

Role of single pulse electrical stimulation (SPES) to guide electrode implantation under general anaesthesia in presurgical assessment of epilepsy.

PURPOSE: Single-pulse electrical stimulation (SPES) during intracranial recordings is part of the epilepsy presurgical evaluation protocol at King's College Hospital (London). Epileptiform responses correlated to the stimulus (delayed responses - DRs) tend to occur in areas of seizure onset, thereby allowing interictal identification of epileptogenic cortex in patients suffering refractory epilepsy. This preliminary study investigated the validity of SPES in the operating theatre under general anaesthesia (GA) during the implantation procedure, aiming to improve the positioning of intracranial electrodes. METHODS: Twelve drug-resistant epilepsy patients implanted with depth and/or subdural electrodes were studied. SPES (1 ms pulses, 4-8 mA, 0.2 Hz) was performed during both intra-operative electrode implantation under GA and chronic intracranial ECoG recordings, and the two recordings were compared in terms of cortical responses produced by stimulation and their electrode location. RESULTS: In 8/12 patients, SPES during chronic recordings produced DRs positively correlated to seizure onset and/or early seizure propagation areas. Of those eight patients, four showed DRs during electrode implantation under GA over the same electrode contacts. Among the four patients without DR during GA, three had continuous localized spontaneous epileptiform discharges, which made interpretation of SPES responses unreliable. CONCLUSION: This study showed that, under GA, DRs can be reliably replicated, without false positive epileptiform responses to SPES, although the method's sensitivity is greatly reduced by spontaneous discharges. Results support SPES as a complementary technique that can be used to improve electrode placement during epilepsy surgery when no profound interictal activity is present.

Patient and staff satisfaction with 'day of admission' elective surgery.

OBJECTIVES: To evaluate patient and staff satisfaction with day of admission surgery in a neurosurgical unit and its effect on theatre start times. METHODS AND DESIGN: Patients were admitted to a Neurosciences admission lounge (NAL) for neurosurgery on the morning of their operation if deemed appropriate by their neurosurgical consultant. All patients in the NAL were asked to complete patient satisfaction questionnaires. Staff members involved in the care of these patients also completed a satisfaction questionnaire. Theatre start times were compared with those whose patients had been admitted prior to the day of surgery. 378 patients admitted on the day of surgery, 16 doctors (5 anaesthetists, 7 neurosurgeons and 4 neuro high dependency unit, HDU doctors) and 5 nurses. Patients completed an anonymised emotional mapping patient satisfaction questionnaire, and short interviews were carried out with staff members. Theatre start times were obtained retrospectively from the theatre database for lists starting with patients admitted on the day of surgery, and lists starting with patients admitted prior to the day of surgery. RESULTS: 83% of patients felt positive on arrival in the NAL and 88% felt positive on being seen by the doctors and nurses prior to surgery. Overall 79% of patients gave positive responses throughout their patient pathway. 90% of staff were positive about day of admission surgery and all staff members were satisfied that there were no negative effects on surgical outcome. Theatre start time was on average 27 minutes earlier in patients admitted on the day of surgery. CONCLUSIONS: Neurosurgical patients, appropriately selected, can be admitted on the day of surgery with high staff and patient satisfaction and without delaying theatre start times.

Shielded battery syndrome: a new hardware complication of deep brain stimulation.

BACKGROUND: Deep brain stimulation hardware is constantly advancing. The last few years have seen the introduction of rechargeable cell technology into the implanted pulse generator design, allowing for longer battery life and fewer replacement operations. The Medtronic® system requires an additional pocket adaptor when revising a non-rechargeable battery such as their Kinetra® to their rechargeable Activa® RC. This additional hardware item can, if it migrates superficially, become an impediment to the recharging of the battery and negate the intended technological advance. AIM: To report the emergence of the 'shielded battery syndrome', which has not been previously described. METHODS: We reviewed our deep brain stimulation database to identify cases of recharging difficulties reported by patients with Activa RC implanted pulse generators. RESULTS: Two cases of shielded battery syndrome were identified. The first required surgery to reposition the adaptor to the deep aspect of the subcutaneous pocket. In the second case, it was possible to perform external manual manipulation to restore the adaptor to its original position deep to the battery. CONCLUSIONS: We describe strategies to minimise the occurrence of the shielded battery syndrome and advise vigilance in all patients who experience difficulty with recharging after replacement surgery of this type for the implanted pulse generator.

In vivo neuronal firing patterns during human epileptiform discharges replicated by electrical stimulation.

OBJECTIVE: To describe neuronal firing patterns observed during human spontaneous interictal epileptiform discharges (IEDs) and responses to single pulse electrical stimulation (SPES). METHODS: Activity of single neurons was recorded during IEDs and after SPES in 11 consecutive patients assessed with depth EEG electrodes and attached microelectrodes. RESULTS: A total of 66 neurons were recorded during IEDs and 151 during SPES. We have found essentially similar patterns of neuronal firing during IEDs and after SPES, namely: (a) a burst of high frequency firing lasting less than 100 ms (in 39% and 25% of local neurons, respectively for IED and SPES); (b) a period of suppression in firing lasting around 100-1300 ms (in 19% and 14%, respectively); (c) a burst followed by suppression (in 10% and 12%, respectively); (d) no-change (in 32% and 50%, respectively). CONCLUSIONS: The similarities in neuronal firing patterns associated with IEDs and SPES suggest that, although both phenomena are initiated differently, they result in the activation of a common cortical mechanism, probably initiated by brief synchronised burst firing in some cells followed by long inhibition. SIGNIFICANCE: The findings provide direct in vivo human evidence to further comprehend the pathophysiology of human focal epilepsy.

Prefrontal cortex dysfunction and 'Jumping to Conclusions': bias or deficit?

The 'beads task' is used to measure the cognitive basis of delusions, namely the 'Jumping to Conclusions' (JTC) reasoning bias. However, it is not clear whether the task merely taps executive dysfunction - known to be impaired in patients with schizophrenia - such as planning and resistance to impulse. To study this, 19 individuals with neurosurgical excisions to the prefrontal cortex, 21 unmedicated adults with Attention Deficit Hyperactivity Disorder (ADHD), and 25 healthy controls completed two conditions of the beads task, in addition to tests of memory and executive function as well as control tests of probabilistic reasoning ability. The results indicated that the prefrontal lobe group (in particular, those with left-sided lesions) demonstrated a JTC bias relative to the ADHD and control groups. Further exploratory analyses indicated that JTC on the beads task was associated with poorer performance in certain executive domains. The results are discussed in terms of the executive demands of the beads task and possible implications for the model of psychotic delusions based on the JTC bias.