Carlos Trenado

Transcranial Direct Current Stimulation in Mesial Temporal Lobe Epilepsy and Hippocampal Sclerosis

BACKGROUND Transcranial direct current stimulation (tDCS) has been evaluated in medication refractory epilepsy patients. The results have been inconclusive and protocols have varied between studies. OBJECTIVE To evaluate the safety and efficacy of two protocols of tDCS in adult patients with mesial temporal lobe epilepsy and hippocampal sclerosis (MTLE-HS). METHODS This is a randomized placebo-controlled, double-blinded clinical trial, with 3 arms, 3 sessions, 5 sessions and placebo stimulation. Frequency of seizures (SZs), interictal epileptiform discharges (IEDs) and adverse effects (AEs) were registered before and after treatment, and at 30 and 60 days follow-up. Descriptive statistics, k-related samples, Friedmans test, and relative risk (RR) estimation were used for analysis. RESULTS We included twenty-eight subjects (3d n = 12, 5d n = 8, placebo n = 8), 16/28 (57%) men, age 37.8(±10.9) years old. There was a significant reduction of the frequency of SZs at one (p = 0.001) and two (p = 0.0001) months following cathodal tDCS compared to baseline in the 3 arms (p = 0.0001). The mean reduction of SZ frequency at two months in both active groups was significantly higher than placebo (-48% vs. -6.25%, p < 0.008). At 3 days (-43.4% vs. -6.25%, p < 0.007) and 5 days (-54.6% vs. -6.25%, p < 0.010) individual groups showed a greater reduction of SZs. A significant IED reduction effect was found between baseline and immediately after interventions (p = 0.041) in all groups. Side effects were minor. CONCLUSIONS Cathodal tDCS technique of 3 and 5 sessions decreased the frequency of SZs and IEDs (between baseline and immediately post-tDCS) in adult patients with MTLE-HS compared to placebo tDCS.

Effect of mechanical tactile noise on amplitude of visual evoked potentials: multisensory stochastic resonance

The present investigation documents the electrophysiological occurrence of multisensory stochastic resonance in the human visual pathway elicited by tactile noise. We define multisensory stochastic resonance of brain evoked potentials as the phenomenon in which an intermediate level of input noise of one sensory modality enhances the brain evoked response of another sensory modality. Here we examined this phenomenon in visual evoked potentials (VEPs) modulated by the addition of tactile noise. Specifically, we examined whether a particular level of mechanical Gaussian noise applied to the index finger can improve the amplitude of the VEP. We compared the amplitude of the positive P100 VEP component between zero noise (ZN), optimal noise (ON), and high mechanical noise (HN). The data disclosed an inverted U-like graph for all the subjects, thus demonstrating the occurrence of a multisensory stochastic resonance in the P100 VEP.

Oscillatory coupling of the subthalamic nucleus in obsessive compulsive disorder

Sir, We read, with utmost interest, the recently published paper in Brain (Accolla et al., 2016) that used the combination of neurophysiological recordings of local field potentials (LFPs) with MRI to investigate functional organization of the subthalamic nucleus (STN) in patients with Parkinson’s disease. Deep brain stimulation (DBS) electrode contacts that picked up beta oscillations, a well known signature of STNs in Parkinson’s disease, were used for whole brain probabilistic tractography seeding. Based on their data, the authors stated “that (i) beta oscillations are not restricted to a ‘motor’ STN area; and (ii) that the ‘motor’ STN is not connected exclusively with motor cortical areas”. The authors concluded ‘that beta oscillations have a main but not exclusive motor significance, and that STN might be organized following a topographical specialization’. We would like to provide additional data that underscore some of these assumptions by recordings from the ‘nonmotor’ STN and its oscillatory network in a different disease entity: obsessive compulsive disorder (OCD). DBS of the STN is a powerful treatment for Parkinson’s disease and recently also for severe OCD (Mallet et al., 2008). STN-cognitive-limbic oscillatory loops (e.g. with the cingulate gyrus) may play a key role in the modulatory effect of STN-DBS in OCD and emotional-cognitive side effects in Parkinson’s disease. Local STN oscillations (Bastin et al., 2014) but not patterns of STN connections in OCD have been investigated so far. For details of the scientific background, please see the online Supplementary material. To address this issue, especially concerning its differences to Parkinson’s disease, we now report on a case of OCD with combined LFP-MEG (magnetoencephalography) recordings. A 42-year-old female patient with severe OCD (washing compulsions) underwent bilateral DBS of the anteromedial (‘non-motor’) STN. Intraoperatively, resting multi-unit activity and LFPs were recorded simultaneously. DBS electrodes where externalized and postoperatively, resting simultaneous recordings of MEG and STN-LFP were performed (details in Supplementary material). Over a follow-up of 3 years the patient showed a stable and even ameliorating effect of DBS on the YaleBrown Obsessive-Compulsive Scale (Y-BOCS) compared to baseline (3 versus 39 points) (Wojtecki et al., 2016). Intraoperative LFP showed that local theta-, alphaand beta-oscillations were observed with dominance on the posterior trajectory in both hemispheres. In postoperative LFPMEG recordings, high beta coherence was apparent between the STN and the sensorimotor cortex, whereas theta-coupling was evident between the STN and the anterior cingulate cortex (ACC) (Fig. 1). Our example gives first insight into coherent STN-cortical oscillations in OCD. doi:10.1093/brain/awx164 BRAIN 2017: Page 1 of 3 | e1

Alteration of cortical excitability and its modulation by Miglustat in Niemann-Pick disease type C

Niemann-Pick type C (NP-C) is a rare, neurodegenerative, lysosomal storage disease. Cortical excitability using different transcranial magnetic stimulation (TMS) protocols together with clinical and neuropsychological testing was longitudinally assessed in a patient with NP-C. Cerebellar inhibition, a measure for the integrity of the cerebello-thalamo-cortical network, was impaired. Short-latency afferent inhibition, a measure for cholinergic transmission, and cognitive functions were also impaired and improved under Miglustat treatment. Short interval intracortical facilitation, a marker for glutamatergic neurotransmission, was absent initially but increased after treatment with Miglustat. Our results provide new insights into pathophysiological mechanisms of NP-C and the response to Miglustat treatment.

Dynamic changes of the intraocular pressure and the pressure of cerebrospinal fluid in nonglaucomatous neurological patients

To describe the dynamic changes of the intraocular pressure (IOP) and intracranial pressure (ICP) with normal or pathological values (intracranial hypertension) in nonglaucomatous neurological patients during lumbar punction (LP).

Combined Invasive Subcortical and Non-invasive Surface Neurophysiological Recordings for the Assessment of Cognitive and Emotional Functions in Humans.

In spite of the success in applying non-invasive electroencephalography (EEG), magneto-encephalography (MEG) and functional magnetic resonance imaging (fMRI) for extracting crucial information about the mechanism of the human brain, such methods remain insufficient to provide information about physiological processes reflecting cognitive and emotional functions at the subcortical level. In this respect, modern invasive clinical approaches in humans, such as deep brain stimulation (DBS), offer a tremendous possibility to record subcortical brain activity, namely local field potentials (LFPs) representing coherent activity of neural assemblies from localized basal ganglia or thalamic regions. Notwithstanding the fact that invasive approaches in humans are applied only after medical indication and thus recorded data correspond to altered brain circuits, valuable insight can be gained regarding the presence of intact brain functions in relation to brain oscillatory activity and the pathophysiology of disorders in response to experimental cognitive paradigms. In this direction, a growing number of DBS studies in patients with Parkinsons disease (PD) target not only motor functions but also higher level processes such as emotions, decision-making, attention, memory and sensory perception. Recent clinical trials also emphasize the role of DBS as an alternative treatment in neuropsychiatric disorders ranging from obsessive compulsive disorder (OCD) to chronic disorders of consciousness (DOC). Consequently, we focus on the use of combined invasive (LFP) and non-invasive (EEG) human brain recordings in assessing the role of cortical-subcortical structures in cognitive and emotional processing trough experimental paradigms (e.g. speech stimuli with emotional connotation or paradigms of cognitive control such as the Flanker task), for patients undergoing DBS treatment.

Long-term surgical results of supplementary motor area epilepsy surgery

OBJECTIVE Supplementary motor area (SMA) epilepsy is a well-known clinical condition; however, long-term surgical outcome reports are scarce and correspond to small series or isolated case reports. The aim of this study is to present the surgical results of SMA epilepsy patients treated at 2 reference centers in Mexico City. METHODS For this retrospective descriptive study (1999-2014), 52 patients underwent lesionectomy and/or corticectomy of the SMA that was guided by electrocorticography (ECoG). The clinical, neurophysiological, neuroimaging, and pathological findings are described. The Engel scale was used to classify surgical outcome. Descriptive statistics, Student t-test, and Friedman, Kruskal-Wallis, and chi-square tests were used. RESULTS Of these 52 patients, the mean age at epilepsy onset was 26.3 years, and the mean preoperative seizure frequency was 14 seizures per month. Etiologies included low-grade tumors in 28 (53.8%) patients, cortical dysplasia in 17 (32.7%) patients, and cavernomas in 7 (13.5%) patients. At a mean follow-up of 5.7 years (range 1-10 years), 32 patients (61%) were classified as Engel Class I, 16 patients (31%) were classified as Engel Class II, and 4 (8%) patients were classified as Engel Class III. Overall seizure reduction was significant (p = 0.001). The absence of early postsurgical seizures and lesional etiology were associated with the outcome of Engel Class I (p = 0.05). Twenty-six (50%) patients had complications in the immediate postoperative period, all of which resolved completely with no residual neurological deficits. CONCLUSIONS Surgery for SMA epilepsy guided by ECoG using a multidisciplinary and multimodality approach is a safe, feasible procedure that shows good seizure control, moderate morbidity, and no mortality.

Correlation Between Bispectral Index and Electrocorticographic Features During Epilepsy Surgery

Surgical resection guided by intraoperative electrocorticography (iECoG) has been in clinical use for many decades. The use of the bispectral index (BIS) for monitoring depth of anesthesia during different types of surgery, including epilepsy surgery, is increasing nowadays. The BIS is an EEG-derived variable indicating cortical electrical activity. However, the correlation between the BIS score and the iECoG score, with the purpose of optimizing the quality and time of the iECoG recordings in epilepsy surgery is unknown. The goal of this study was to evaluate the correlation between BIS values and iECoG parameters during the epilepsy surgery under anesthesia with propofol and fentanyl. This is a prospective study that included patients with epilepsy who underwent epilepsy surgery guided by BIS and iECoG (September 2008 to October 2013). Clinical, physiological, and sociodemographic characteristics are shown. We correlated the iECoG parameters (presence of burst suppressions [BS], suppression time [seconds], background frequency [Hz], and type of iECoG score by Mathern et al) with BIS values. We included 28 patients, 15/28 (53.5%) female, general mean age of 30.5 years (range 13-56 years). Patients underwent epilepsy surgery: 22/28 (79%) temporal and 6/28 (21%) extratemporal. We found a nonlinear polynomial cubic relationship between the mentioned variables noting that a BIS range of 40 to 60 gave the following results: iECoG BS periods <5 seconds, background frequency 10 to 17 Hz, and iECoG score 2 characterized by lack of >20-Hz background frequencies. No BS were observed with a BIS > 60. In conclusion BIS values and iECoG parameters during the epilepsy surgery under anesthesia with propofol and fentanyl have a nonlinear correlation. BS patterns were not found with a BIS > 60. These findings show that BIS is a nonlinear multidimensional measure, which possesses high variability with the iECoG parameters. BS patterns are not found with BIS > 60.

Focal seizure induced by preoperative navigated transcranial magnetic stimulation in a patient with anaplastic oligoastrocytoma

We report the following TMS-related seizure. The subject was a 41 year old woman with the diagnosis of an anaplastic oligoastrocytoma (WHO grade III) located at the right sensorimotor region. The patient underwent subtotal tumor resection 4 years ago with adjuvant chemotherapy and radiation. Due to a progression of the tumor with slight arm paresis, another surgical resection was planned. The patient had the following risk factors for TMSinduced seizure: brain tumor, prior brain surgery, occasional (every 6e8 weeks) symptomatic focal seizures with transient Todd Paresis for a couple of hours. Anticonvulsive treatment with levetirazetam 500 mg b. i. d. was discontinued by the patient earlier due to agitation and mood change. Thus, her medication only consisted of sertraline 100 mg q. d. On the day of the event, the subject had no additional risk factors.

Local field potential oscillations of the globus pallidus in cervical and tardive dystonia

BACKGROUND Reports about neural oscillatory activity in the globus pallidus internus (GPi) have targeted general (GD) and cervical dystonia (CD), however to our knowledge they are nonexistent for tardive dystonia (TD). METHODS Local field potentials (LFPs) from seven CD and five TD patients were recorded intraoperatively. We compared LFP power in thetadelta, alpha and beta band during rest and sensory palmar stimulation (SPS) in patients with general anesthesia and local/analgo sedation. RESULTS We found prominent LFP power activity in thetadelta for both CD and TD. Unlike TD, a significant difference between rest and SPS was revealed for CD. CONCLUSIONS Our data support the presence of LFP oscillatory activity in CD and TD. Thetadelta power modulation in the GPi is suggested as a signature for sensory processing in CD.