Analysis of Heart Rate Variability in Individuals Affected by Amyotrophic Lateral Sclerosis.

INTRODUCTION: Amyotrophic lateral sclerosis (ALS) produces alterations in the autonomic nervous system (ANS), which explains the cardiac manifestations observed in patients. The assessment of heart rate variability (HRV) is what best reflects the activity of the ANS on heart rate. The Polar H7 Bluetooth® device proves to be a non-invasive and much faster technology than existing alternatives for this purpose. OBJECTIVE: The goal of this study is to determine HRV using Polar H7 Bluetooth technology in ALS patients, comparing the obtained measurements with values from healthy individuals. METHOD: The sample consisted of 124 participants: 68 diagnosed with ALS and 56 healthy individuals. Using Polar H7 Bluetooth technology and the ELITE HRV application, various HRV measurements were determined for all participants, specifically the HRV index, RMSSD, RMSSD LN, SDNN index, PNN50, LF, HF, LF/HF ratio, HR average, and HF peak frequency. RESULTS: Statistically significant differences were observed between ALS patients and healthy individuals in the HRV index, RMSSD, RMSSD LN, SDNN index, PNN50, HF, and LF, where healthy individuals exhibited higher scores. For the HR average, the ALS group showed a higher value. Values were similar when comparing men and women with ALS, with only a higher HF peak frequency observed in women. CONCLUSION: The Polar H7 Bluetooth® device is effective in determining heart rate variability alterations in ALS, being a promising prognostic tool for the disease.

Perspectives of Implementation of Closed-Loop Deep Brain Stimulation: From Neurological to Psychiatric Disorders.

BACKGROUND: Deep brain stimulation (DBS) is a highly efficient, evidence-based therapy to alleviate symptoms and improve quality of life in movement disorders such as Parkinson's disease, essential tremor, and dystonia, which is also being applied in several psychiatric disorders, such as obsessive-compulsive disorder and depression, when they are otherwise resistant to therapy. SUMMARY: At present, DBS is clinically applied in the so-called open-loop approach, with fixed stimulation parameters, irrespective of the patients' clinical state(s). This approach ignores the brain states or feedback from the central nervous system or peripheral recordings, thus potentially limiting its efficacy and inducing side effects by stimulation of the targeted networks below or above the therapeutic level. KEY MESSAGES: The currently emerging closed-loop (CL) approaches are designed to adapt stimulation parameters to the electrophysiological surrogates of disease symptoms and states. CL-DBS paves the way for adaptive personalized DBS protocols. This review elaborates on the perspectives of the CL technology and discusses its opportunities as well as its potential pitfalls for both clinical and research use in neuropsychiatric disorders.

Deep-brain stimulation of the human nucleus accumbens-medial septum enhances memory formation.

Deep-brain stimulation (DBS) is a potential novel treatment for memory dysfunction. Current attempts to enhance memory focus on stimulating human hippocampus or entorhinal cortex. However, an alternative strategy is to stimulate brain areas providing modulatory inputs to medial temporal memory-related structures, such as the nucleus accumbens (NAc), which is implicated in enhancing episodic memory encoding. Here, we show that NAc-DBS improves episodic and spatial memory in psychiatric patients. During stimulation, NAc-DBS increased the probability that infrequent (oddball) pictures would be subsequently recollected, relative to periods off stimulation. In a second experiment, NAc-DBS improved performance in a virtual path-integration task. An optimal electrode localization analysis revealed a locus spanning postero-medio-dorsal NAc and medial septum predictive of memory improvement across both tasks. Patient structural connectivity analyses, as well as NAc-DBS-evoked hemodynamic responses in a rat model, converge on a central role for NAc in a hippocampal-mesolimbic circuit regulating encoding into long-term memory. Thus, short-lived, phasic NAc electrical stimulation dynamically improved memory, establishing a critical on-line role for human NAc in episodic memory and providing an empirical basis for considering NAc-DBS in patients with loss of memory function.

Importance of Soft Skills in Health Sciences Students and Their Repercussion after the COVID-19 Epidemic: Scoping Review.

Soft skills (SKs) are skills related to the interaction among people and their way of dealing with tasks. Increasingly valued in the workplace, they are especially relevant in health professionals due to the importance of the relationship among them and their patients and families. Given their importance, the university training of healthcare professionals must promote the development of SKs. The COVID-19 pandemic has been a turning point in many areas, changing the learning process and, even more, the use of these soft skills as a fundamental ingredient in human relationships. The aim of this study was to analyse the available evidence regarding SKs in health science students, specifically nursing students, and to describe whether there is a worsening in the development of such skills after the COVID-19 pandemic. According to the PRISMA-ScR methodology for systematic reviews, this study included articles on social skills and possible changes in these skills as a consequence of the pandemic in health sciences students The results highlight the importance of these emotional competences for future nurses, being particularly relevant for communication and emotional self-awareness and showing their influence on academic aspects, such as academic performance or mental health and coping skills. A major limitation of the present study was not considering aspects such as compassion or empathy. However, the novelty provided by this work is the analysis of the changes in SKs produced as a consequence of the pandemic. It is definitely clear that there is a need to enhance emotional intelligence, and thus soft skills, in future health professionals.

DNA Methylation Description of Hippocampus, Cortex, Amygdala, and Blood of Drug-Resistant Temporal Lobe Epilepsy.

Epigenetic changes such as DNA methylation were observed in drug-resistant temporal lobe epilepsy (DR-TLE), a disease that affects 25-30% of epilepsy patients. The main objective is to simultaneously describe DNA methylation patterns associated with DR-TLE in hippocampus, amygdala, surrounding cortex to the epileptogenic zone (SCEZ), and peripheral blood. An Illumina Infinium MethylationEPIC BeadChip array was performed in 19 DR-TLE patients and 10 postmortem non-epileptic controls. Overall, 32, 59, and 3210 differentially methylated probes (DMPs) were associated with DR-TLE in the hippocampus, amygdala, and SCEZ, respectively. These DMP-affected genes were involved in neurotrophic and calcium signaling in the hippocampus and voltage-gated channels in SCEZ, among others. One of the hippocampus DMPs (cg26834418 (CHORDC1)) showed a strong blood-brain correlation with BECon and IMAGE-CpG, suggesting that it could be a potential surrogate peripheral biomarker of DR-TLE. Moreover, in three of the top SCEZ's DMPs (SHANK3, SBF1, and MCF2L), methylation status was verified with methylation-specific qPCR. The differentially methylated CpGs were classified in DMRs: 2 in the hippocampus, 12 in the amygdala, and 531 in the SCEZ. We identified genes that had not been associated to DR-TLE so far such as TBX5, EXOC7, and WRHN. The area with more DMPs associated with DR-TLE was the SCEZ, some of them related to voltage-gated channels. The DMPs found in the amygdala were involved in inflammatory processes. We also found a potential surrogate peripheral biomarker of DR-TLE. Thus, these results provide new insights into epigenetic modifications involved in DR-TLE.

Neuronal and astrocytic tetraploidy is increased in drug-resistant epilepsy.

AIMS: Epilepsy is one of the most prevalent neurological diseases. A third of patients with epilepsy remain drug-resistant. The exact aetiology of drug-resistant epilepsy (DRE) is still unknown. Neuronal tetraploidy has been associated with neuropathology. The aim of this study was to assess the presence of tetraploid neurons and astrocytes in DRE. METHODS: For that purpose, cortex, hippocampus and amygdala samples were obtained from patients subjected to surgical resection of the epileptogenic zone. Post-mortem brain tissue of subjects without previous records of neurological, neurodegenerative or psychiatric diseases was used as control. RESULTS: The percentage of tetraploid cells was measured by immunostaining of neurons (NeuN) or astrocytes (S100ß) followed by flow cytometry analysis. The results were confirmed by image cytometry (ImageStream X Amnis System Cytometer) and with an alternative astrocyte biomarker (NDRG2). Statistical comparison was performed using univariate tests. A total of 22 patients and 10 controls were included. Tetraploid neurons and astrocytes were found both in healthy individuals and DRE patients in the three brain areas analysed: cortex, hippocampus and amygdala. DRE patients presented a higher number of tetraploid neurons (p = 0.020) and astrocytes (p = 0.002) in the hippocampus than controls. These results were validated by image cytometry. CONCLUSIONS: We demonstrated the presence of both tetraploid neurons and astrocytes in healthy subjects as well as increased levels of both cell populations in DRE patients. Herein, we describe for the first time the presence of tetraploid astrocytes in healthy subjects. Furthermore, these results provide new insights into epilepsy, opening new avenues for future treatment.

Caring for the Elderly Enhances Positive Attitudes Better Than Knowledge in Nursing Students.

Background and Objectives: There is a growing interest in the measurement of attitudes towards older people in healthcare professionals, as there is a need to implement interventions to improve ageist attitudes. A one group pretest-posttest study was carried out to explore the change in nursing student attitudes towards the elderly during their university careers. Materials and Method: A total of 97 nursing students were enrolled. Attitudes were analyzed using Kogan's Attitudes Toward Old People Scale. Results: The attitude was positive from the beginning of the study, with a score of 110.06 (12.92). No differences were observed after completing the subject "Care of the elderly" (106.21 (10.77)), though a significant increase was recorded after the completion of clinical placement (142.88 (12.64)), with a large effect size (η2p = 0.754). The score of the positive items was significantly increased, but not that of the negative items, as ageist attitude was not reduced. Conclusion: The current curricular design, that includes taking the theoretical course before clinical placement in the geriatric area, increases positive attitudes in nursing students but does not reduce ageist attitudes.

Interventions to improve attitudes toward older people in undergraduate health and social sciences students. A systematic review and meta-analysis.

OBJECTIVE: To determine which interventions are the most effective in improving attitudes toward older persons in undergraduate health and social sciences students. DESIGN: Systematic review and meta-analysis. DATA SOURCES: A literature search was made in PubMed, EBSCO and SCOPUS and additional records were identified by manual searching. The selection criteria were studies that evaluated an intervention designed to improve positive attitudes; studies in undergraduate health and social sciences students; and studies using direct instruments to measure attitudes. REVIEW METHODS: Two independent reviewers extracted study-level data from records using a common data collection spreadsheet. Two reviewers also assessed study quality by using the Cochrane Risk of Bias Tool. The primary outcome was the effect of an intervention upon attitudes toward older people, while the secondary outcome was the effect upon knowledge about aging and older people in those studies that had previously assessed subject attitude. The meta-analysis was carried out based on mixed statistical models. RESULTS: The search identified 53 eligible studies published during 1982-2020, comprising 35 pre-post studies and 18 randomized clinical trials, of which 14 were included in the meta-analysis. A strongly significant effect upon attitudes was observed for empathy-based interventions (differences of standardized mean differences (dSMD) = 1.26; 95%CI: 0.04-2.48; p = 0.04), knowledge + empathy-based interventions (dSMD = 0.22; 95%CI: 0.05-0.39; p = 0.01), and knowledge + clinical skills-based interventions (dSMD = 0.22; 95%CI: 0.01-0.43; p = 0.04). The overall effect was dSMD = 0.50; 95%CI: 0.01-0.43; p = 0.004. In addition, a positive effect in terms of increased knowledge about the older was observed after knowledge + empathy-based and knowledge + clinical skills-based interventions (dSMD = 0.24; 95%CI: 0.07-0.40; p = 0.005). CONCLUSIONS: Interventions to improve attitudes in health and social sciences students are effective, with those based on empathy having the greatest impact. Improving attitudes among future professionals could improve the management and quality of care of older people. More rigorous and better designed studies are recommended to determine the effect of the interventions. Registered on PROSPERO ID: CRD42021220677. TWITTABLE ABSTRACT: Ageism is present in healthcare settings. Empathy-based interventions are the most effective strategies in health and social sciences students.

Factors Affecting Attitudes towards Older People in Undergraduate Nursing Students.

BACKGROUND: The population of older people is increasing worldwide. The social and healthcare systems need many nurses to care for the elderly. Positive attitudes increase the preference to work with older people and improve the quality of care. This study describes attitudes towards the elderly in a sample of nursing students, and analyzes the potential factors influencing these attitudes. METHODS: A cross-sectional study was carried out in nursing students during the academic course 2017-2018. Kogan's Attitude Toward Old People Scale was used to assess student attitudes towards older people. RESULTS: The study included 377 undergraduate nursing students, of which 75.9% were women. The mean age was 22.23 (5.69) years. Attitude proved positive, with a mean Kogan's score of 131.04 (12.66). Women had higher scores than men, with a mean difference of 7.76 (95% CI: 4.87-10.66; p < 0.001). The male sex, age ≥ 25 years, and previous experience with institutionalized older adults worsened attitudes, while studying the subject of geriatrics, each higher course within the degree, work placements in hospitals and nursing homes, and previous experience with community older adults or with older relatives favored a more positive attitude. Participants with no interest in working with older adults yielded lower scores. CONCLUSIONS: Attitudes towards the elderly among nursing students are positive. Women have a more positive attitude. Analyzing the factors that improve attitudes in nursing students is suggested, as it may contribute to improve nursing care.

Deep Brain Stimulation of the Nucleus Accumbens, Ventral Striatum, or Internal Capsule Targets for Medication-Resistant Obsessive-Compulsive Disorder: A Multicenter Study.

BACKGROUND: Deep brain stimulation of the nucleus accumbens, ventral striatum, or internal capsule region has shown a 45%-60% response rate in adults with severe treatment-refractory obsessive-compulsive disorder, regardless of which target is used. We sought to improve the effectiveness of deep brain stimulation by placing the electrode along a trajectory including these 3 targets, enabling a change of stimulation site depending on the patient's response. METHODS: This study used the medical records of 14 patients from 4 different Spanish institutions: 7 from the Hospital Universitario La Princesa, 3 from the Hospital Universitario Central de Asturias, 2 from Hospital Universitario Fundación Jiménez Díaz, and 2 from Hospital Universitari Son Espases. All patients were operated on under the same protocol. Qualitative and quantitative data were collected. RESULTS: Of 14 patients, 11 showed significant improvement in obsessive-compulsive disorder symptoms, as evident in a reduction ≥35% in Yale-Brown Obsessive Compulsive Scale scores following stimulation relative to preoperative scores. Seven patients responded to stimulation at the nucleus accumbens (the first area we set for stimulation), whereas 4 patients needed to have the active contact switched to the internal capsule to benefit from stimulation. CONCLUSIONS: Deep brain stimulation of the nucleus accumbens, internal capsule, and ventral striatum significantly benefited our cohort of patients with medication-resistant obsessive-compulsive disorder. Electrode insertion through the 3 main targets might confer additional therapeutic efficacy.

Prediction of Memory Impairment in Epilepsy Surgery by White Matter Diffusion.

OBJECTIVE: To analyze the relationship between cognitive performance and white matter integrity in patients with temporal lobe epilepsy (TLE) to establish radiologic criteria to help with patient selection for surgery. METHODS: The study included 19 adults with temporal lobe epilepsy. A tractography analysis of fractional anisotropy and mean diffusivity (MD) of the following fascicles was performed: arcuate fascicle, cingulum, fornix, inferior fronto-occipital fascicle, inferior longitudinal fascicle, parahippocampal fibers of the cingulum, and uncinate fascicle. The Wechsler Memory Scale-Third Edition neuropsychological test was performed to evaluate short- and long-term verbal (Logical Memory I and II subtests) and nonverbal (Visual Reproduction I and II subtests) memory. Relationships between memory scores and diffusion were calculated. RESULTS: Lower Logical Memory I subtest scores were correlated with lower MD of the right inferior fronto-occipital fascicle, while lower Logical Memory II subtest scores were related to higher values of fractional anisotropy in bilateral cingulum, right uncinate, and right parahippocampal fibers of the cingulum and lower MD in left cingulum fascicle. Finally, lower values in Visual Reproduction I subtest scores were associated with lower values in MD in right cingulum and inferior fronto-occipital fascicles. CONCLUSIONS: Structural changes of some white matter tracts were associated with deterioration of both short- and long-term memory. These alterations were more associated with verbal memory than with nonverbal memory. These changes mainly consist of an increase in fractional anisotropy and a decrease in MD, which could be interpreted as reorganization phenomena. Diffusion tensor imaging could be a useful tool for cognitive assessment in surgical candidates with temporal lobe epilepsy who are not suitable for neuropsychological testing or in whom their results do not lead to definitive conclusions.

Neurophysiological Characterization of Thalamic Nuclei in Epileptic Anaesthetized Patients.

Deep brain stimulation (DBS) requires precise localization, which is especially difficult at the thalamus, and even more difficult in anesthetized patients. We aimed to characterize the neurophysiological properties of the ventral intermediate (V.im), ventral caudal (V.c), and centromedian parvo (Ce.pc) and the magnocellular (Ce.mc) thalamic nuclei. We obtained microelectrode recordings from five patients with refractory epilepsy under general anesthesia. Somatosensory evoked potentials recorded by microelectrodes were used to identify the V.c nucleus. Trajectories were reconstructed off-line to identify the nucleus recorded, and the amplitude of the action potential (AP) and the tonic (i.e., mean frequency, density, probability of interspike interval) and phasic (i.e., burst index, pause index, and pause ratio) properties of the pattern discharges were analyzed. The Mahalanobis metric was used to evaluate the similarity of the patterns. The mean AP amplitude was higher for the V.im nucleus (172.7 ± 7.6 µV) than for the other nuclei, and the mean frequency was lower for the Ce.pc nucleus (7.2 ± 0.8 Hz) and higher for the V.c nucleus (11.9 ± 0.8 Hz) than for the other nuclei. The phasic properties showed a bursting pattern for the V.c nucleus and a tonic pattern for the centromedian and V.im nuclei. The Mahalanobis distance was the shortest for the V.im/V.c and Ce.mp/Ce.pc pairs. Therefore, the different properties of the thalamic nuclei, even for patients under general anesthesia, can be used to positively define the recorded structure, improving the exactness of electrode placement in DBS.

Prediction of Laterality in Temporal Lobe Epilepsy Using White Matter Diffusion Metrics.

BACKGROUND: Diagnostic methods of the epileptogenic area continue to be a challenge in epilepsy surgery research. We hypothesized that temporal lobe epilepsy (TLE) will result in white matter changes that can be detected using diffusion tensor imaging. Measurement of white matter diffusivity will therefore be useful for presurgical assessment. METHODS: Twelve patients with TLE who had undergone temporal lobectomy and amygdalohippocampectomy were included. In 6 patients, magnetic resonance imaging (MRI) showed evidence of mesial temporal sclerosis (m-TLE), whereas the 6 remaining MRI studies were informed without any abnormality (nl-TLE). All had excellent outcomes from surgery. Patients were compared with 12 age- and sex-matched controls. Five pairs of white matter fiber tracts were traced, and fiber tract fractional anisotropy and mean diffusivity were calculated. RESULTS: There were several alterations in diffusion parameters in white matter tracts, both ipsilateral and on the contralateral side, these alterations were more pronounced in the hemisphere ipsilateral to the epileptogenic focus. m-TLE patients had more alterations on ipsilateral side than nl-TLE patients, but similar alterations on contralateral side and bilateral fornix. The discriminant function analysis successfully lateralized all the patients with left TLE, 83.3% of the patients with right TLE, and all nl-TLE. CONCLUSIONS: Our results suggest that there are alterations in diffusion parameters in white matter tracts both in m-TLE and nl-TLE patients. Diffusion tensor imaging could be a useful presurgical tool to help establish the laterality of TLE, including patients with "normal" MRI. Further studies with a larger number of patients would be necessary to confirm these results.

Effectiveness of vagal nerve stimulation in medication-resistant epilepsy. Comparison between patients with and without medication changes.

BACKGROUND: Vagal nerve stimulation (VNS) response is not immediate. A progressive decline in seizure frequency is usually found during a period of 12-18 months after implantation. During this time, the patient's medication is usually modified, which can create doubts about whether their clinical improvement is due to medication changes or to VNS itself. Our goal is to compare two groups of patients treated with VNS, with and without changes in their medication. METHODS: We prospectively analyze 85 patients who were treated with VNS in our hospital between 2005 and 2014. In 43 patients, changes in the antiepileptic drugs (EAD) were not allowed during the postoperative follow-up and they were compared with 42 patients who were left at the option of neurologist make changes in medication. We analyzed the clinical situation at 18 months and compared the two groups. RESULTS: Overall, 54.1% of patients had a reduction in seizures of 50% or higher (responders). In the group with no changes in medication, responders reached 63%, while in the group in which changes in medication were allowed, 45.2% were responders. Between responders and non-responders, there were no statistical differences in type of epilepsy, frequency, previous surgery, or intensity of stimulation. CONCLUSIONS: We did not find a statistical difference in seizure frequency reduction between patients with or without changes in medication during their follow-up, so changes in medication did not improve the outcome. Furthermore, the absence of changes in AED can help to optimize the parameters of the stimulator in order to improve its effectiveness.

Intrasellar chordoma associated with a primitive persistent trigeminal artery.

Chordomas located primarily in the sellar region are uncommon, and may be misdiagnosed non-functioning pituitary adenoma. Furthermore, the association of a persistent primitive trigeminal artery (PPTA) with an intrasellar chordoma is extremely rare, and no similar cases have been reported in the literature to date. The coexistence of intrasellar chordoma (ISC) and PPTA makes safe and complete tumor resection challenging, and preoperative endovascular occlusion of this artery may be helpful. We report a case of a 32-year-old man who developed right hemifacial paresthesias and a cranial nerve six palsy. MRI study demonstrated the presence of a primary ISC associated with a PPTA. Angiographic balloon test occlusion of the PPTA revealed no neurological changes, so this vessel was endovascularly occluded by coiling. The lesion was subtotally removed through a sublabial transsphenoidal approach, without intraoperative bleeding complications. Histological examination of the lesion was consistent with the diagnosis of chordoma. Detailed preoperative neurovascular evaluation may be useful to detect vascular anomalies associated with intracranial chordomas, such as PPTA. In this report we emphasize the importance of appropriate treatment of vascular anomalies prior intrasellar lesions resection that may facilitate surgery and avoid potential hazardous intraoperative bleeding complications.

Primary central neurocytoma of the mesencephalic tectum in a pediatric patient.

PURPOSE: Neurocytomas are tumors or neuronal differentiation, typically located within the supratentorial ventricular system. The extraventricular location is uncommon. A limited number of cases involving the brainstem have been reported and may be misdiagnosed as brainstem gliomas. Furthermore, midbrain neurocytomas are extremely rare, and no similar cases in pediatric patients have been reported in the literature to date. Brainstem location of neurocytomas often precludes gross total removal of the lesion, and in these cases, adjuvant therapies may be helpful. METHODS: We report a case of a 16-year-old child who presented with signs and symptoms of increased intracranial pressure. The magnetic resonance imaging study demonstrated the presence of a primary mesencephalic tectum lesion causing obstructive hydrocephalus. The patient underwent emergent ventriculoperitoneal shunt implantation, resolving the hydrocephalus and the clinical symptoms. The lesion was partially removed through a suboccipital craniotomy and supracerebellar infratentorial approach to the mesencephalic tectum, without intraoperative complications. RESULTS: Histological examination of the lesion was consistent with the diagnosis of extraventricular neurocytoma. The patient was referred to the oncology department for additional treatment with Gamma Knife radiosurgery. CONCLUSIONS: Although brainstem neurocytoma is rare, this case demonstrates that it should be included in the differential diagnosis of brainstem gliomas. Because of brainstem tumor location, complete surgical removal may be challenging or not possible, with a high risk of postoperative neurological deficits. Adjuvant therapies may prevent local tumor growth in cases of tumor remnants or recurrences following microsurgery in selected cases.

Deep brain stimulation of the centromedian thalamic nucleus for the treatment of generalized and frontal epilepsies.

PURPOSE: Deep brain stimulation (DBS) of the thalamus is an emerging surgical option for people with medically refractory epilepsy that is not suitable for resective surgery, or in whom surgery has failed. Our main aim was to evaluate the efficacy of bilateral centromedian thalamic nucleus (CMN) DBS for seizure control in generalized epilepsy and frontal lobe epilepsy with a two-center, single-blind, controlled trial. METHODS: Participants were adults with refractory generalized or frontal lobe epilepsy. Seizure diaries were kept by patients/carers prospectively from enrollment. The baseline preimplantation period was followed by a control period consisting of a blind stimulation-OFF phase of at least 3 months, a 3-month blind stimulation-ON phase, and a 6-month unblinded stimulation-ON phase. The control period was followed by an unblinded long-term extension phase with stimulation-ON in those patients in whom stimulation was thought to be effective. KEY FINDINGS: Eleven patients were recruited at King's College Hospital (London, United Kingdom United Kingdom) and at University Hospital La Princesa (Madrid, Spain). Among the five patients with frontal lobe epilepsy, only one patient had >50% improvement in seizure frequency during the blind period. In the long-term extension phase, two patients with frontal lobe epilepsy had >50% improvement in seizure frequency. All six patients with generalized epilepsy had >50% improvement in seizure frequency during the blind period. In the long-term extension phase, five of the six patients showed >50% improvement in the frequency of major seizures (one became seizure free, one had >99% improvement, and three had 60-95% reduction in seizure frequency). Among patients with generalized epilepsy, the DBS implantation itself appears to be effective, as two patients remained seizure free during 12 and 50 months with DBS OFF, and the remaining four had 50-91% improvement in the initial 3 months with DBS OFF. SIGNIFICANCE: DBS implantation and stimulation of the CMN appears to be a safe and efficacious treatment, particularly in patients with refractory generalized epilepsy. CMN stimulation was not as effective in frontal lobe epilepsy, which requires further studies. DBS of the CMN should be considered as a treatment option, particularly in patients with refractory generalized epilepsy syndromes.