Palliation for catastrophic nonlocalizing epilepsy: a retrospective case series of complete corpus callosotomy at a single institution.

OBJECTIVE: In this study, the authors describe their 10-year single-institution experience with single-step complete corpus callosotomy (CCC) for seizure management in pediatric and adult patients with catastrophic, medically refractory, nonlocalizing epilepsy at Advent Health Orlando. METHODS: The authors conducted a retrospective observational study of patients aged 6 months to 49 years who underwent clinically indicated CCC for drug-resistant nonlocalizing epilepsy at Advent Health Orlando between July 2011 and July 2021. Follow-up ranged from 12 months to 10 years. RESULTS: Of the 101 patients (57% of whom were male) who met eligibility criteria, 81 were pediatric patients and 20 were ≥ 18 years. All patients had seizures that appeared poorly lateralized on both electroencephalograms and clinical semiological studies. Of 54 patients with drop seizures before CCC, 29 (54%) achieved stable freedom from drop seizures after CCC. Of the 101 patients, 14 (13.9%) experienced stable resolution of all types of clinical seizures (International League Against Epilepsy classes 1 and 2). The most common postoperative neurological complication was a transient disconnection syndrome, observed in 50% of patients; of those patients, 73% experienced syndrome resolution within 2 months after surgery, and all resolved by the 2-year follow-up. Formal neuropsychological test results were stable in 13 patients assessed after CCC. CONCLUSIONS: CCC is an effective and well-tolerated palliative surgical technique. In this study, drop attacks were reduced after CCC but could recur for the first time as late as 44 months after surgery. Other seizure types were also reduced postoperatively but could recur for the first time as late as 28 months after surgery. Nearly 14% of patients achieved stable and complete freedom from seizures after CCC. Re-evaluation after CCC can reveal lateralized seizure onset in some patients.

Progenitor cell therapy for acquired pediatric nervous system injury: Traumatic brain injury and acquired sensorineural hearing loss.

While cell therapies hold remarkable promise for replacing injured cells and repairing damaged tissues, cell replacement is not the only means by which these therapies can achieve therapeutic effect. For example, recent publications show that treatment with varieties of adult, multipotent stem cells can improve outcomes in patients with neurological conditions such as traumatic brain injury and hearing loss without directly replacing damaged or lost cells. As the immune system plays a central role in injury response and tissue repair, we here suggest that multipotent stem cell therapies achieve therapeutic effect by altering the immune response to injury, thereby limiting damage due to inflammation and possibly promoting repair. These findings argue for a broader understanding of the mechanisms by which cell therapies can benefit patients.

Epilepsy Surgery in Children versus Adults.

Epilepsy is one of the most common chronic neurological disorder affecting 6-7 per 1000 worldwide. Nearly one-third of patients with newly diagnosed epilepsy continue to have recurrent seizures despite adequate trial of more than two anti-seizure drugs : drug-resistant epilepsy (DRE). Children with DRE often experience cognitive and psychosocial co-morbidities requiring more urgent and aggressive treatment than adults. Epilepsy surgery can result in seizure-freedom in approximately two-third of children with improvement in cognitive development and quality of life. Understanding fundamental differences in etiology, co-morbidity, and neural plasticity between children and adults is critical for appropriate selection of surgical candidates, appropriate presurgical evaluation and surgical approach, and improved overall outcome.

Safety of Autologous Umbilical Cord Blood Therapy for Acquired Sensorineural Hearing Loss in Children.

BACKGROUND AND OBJECTIVES: Sensorineural hearing loss (SNHL) in children is associated with neurocognitive morbidity. The cause of SNHL is a loss of hair cells in the organ of Corti. There are currently no reparative treatments for SNHL. Numerous studies suggest that cord blood mononuclear cells (human umbilical cord blood, hUCB) allow at least partial restoration of SNHL by enabling repair of a damaged organ of Corti. Our objective is to determine if hUCB is a safe treatment for moderate to severe acquired SNHL in children. Subjects and. METHODS: Eleven children aged 6 months to 6 years with moderate to severe acquired SNHL were treated with intravenous autologous hUCB. The cell dose ranged from 8 to 30 million cells/kg body weight. Safety was assessed by measuring systemic hemodynamics during hUCB infusion. Infusion-related toxicity was evaluated by measuring neurologic, hepatic, renal and pulmonary function before and after infusion. Auditory function, auditory verbal language assessments and MRI with diffusion tensor imaging (DTI) were obtained before and after treatment. RESULTS: All patients survived, and there were no adverse events. No infusionrelated changes in hemodynamics occurred. No infusion-related toxicity was recorded. Five subjects experienced a reduction in auditory brainstem response (ABR) thresholds. Four of those 5 subjects also experienced an improvement in cochlear nerve latencies. Comparison of MRI with DTI sequences obtained before and after treatment revealed increased fractional anisotropy in the primary auditory cortex in three of five subjects with reduced ABR thresholds. Statistically significant (p<0.05) reductions in ABR thresholds were identified. CONCLUSIONS: TIntravenous hUCB is feasible and safe in children with SNHL.

Usefulness of intraoperative insular electrocorticography in modified functional hemispherectomy.

BACKGROUND: The insular cortex is not routinely removed in modified functional hemispherectomy due to the risk of injury to the main arteries and to deep structures. Our study evaluates the safety and usefulness of applying intraoperative electrocorticography (ECoG) on the insular during the hemispherectomy. METHODS: We included all patients who underwent insular ECoG during a modified functional hemispherectomy from 2012 to 2015. After the surgery, the decision for further resection of the insular cortex was made based on the presence of electrographic seizures on ECoG. RESULTS: The study included 19 patients (age, 6.4 ± 4.7 years, mean ± standard deviation). Electrographic seizures were identified in 5 patients (26.3%). Sixteen of the 19 patients (84.2%) became seizure-free with a follow-up duration of 3.1 ± 0.6 years and no vascular complication occurred. CONCLUSIONS: Intraoperative insular ECoG monitoring can be performed safely while providing a tailored approach for insular resection during modified hemispherectomy.

Technical descriptions of four hemispherectomy approaches: From the Pediatric Epilepsy Surgery Meeting at Gothenburg 2014.

Hemispherectomy is a complex multistep procedure with a steep learning curve. Several surgical approaches have been developed, but each requires considerable practice to master. Four experienced pediatric neurosurgeons, who participated in the 2014 Gothenburg Pediatric Epilepsy Surgery Meeting, provided succinct technical summaries of four hemispherectomy approaches: modified functional hemispherectomy, peri-insular hemispherotomy, parasagittal hemispherotomy, and endoscopic-assisted hemispherotomy. No clinical or outcome data are included. Our intention is to reduce the slope and length of the learning curve for surgeons and to improve the understanding of the technical details of hemispherectomy surgery by nonsurgeonmembers of epilepsy teams.

CortiQ-based Real-Time Functional Mapping for Epilepsy Surgery.

PURPOSE: To evaluate the use of the cortiQ-based mapping system (g.tec medication engineering GmbH, Austria) for real-time functional mapping (RTFM) and to compare it to results from electrical cortical stimulation mapping (ESM) and functional magnetic resonance imaging (fMRI). METHODS: Electrocorticographic activity was recorded in 3 male patients with intractable epilepsy by using cortiQ mapping system and analyzed in real time. Activation related to motor, sensory, and receptive language tasks was determined by evaluating the power of the high gamma frequency band (60-170 Hz). The sensitivity and specificity of RTFM were tested against ESM and fMRI results. RESULTS: "Next-neighbor" approach demonstrated [sensitivity/specificity %] (1) RTFM against ESM: 100.00/79.70 for hand motor; 100.00/73.87 for hand sensory; -/87 for language (it was not identified by the ESM); (2) RTFM against fMRI: 100.00/84.4 for hand motor; 66.70/85.35 for hand sensory; and 87.85/77.70 for language. CONCLUSIONS: The results of the quantitative "next-neighbor" RTFM evaluation were concordant to those from ESM and fMRI. The RTFM correlates well with localization of hand motor function provided by ESM and fMRI, which may offer added localization in the operating room and guidance for extraoperative ESM mapping. Real-time functional mapping correlates with fMRI language activation when ESM findings are negative. It has fewer limitations than ESM and greater flexibility in activation paradigms and measuring responses.

Autologous bone marrow mononuclear cells reduce therapeutic intensity for severe traumatic brain injury in children.

OBJECTIVES: The devastating effect of traumatic brain injury is exacerbated by an acute secondary neuroinflammatory response, clinically manifest as elevated intracranial pressure due to cerebral edema. The treatment effect of cell-based therapies in the acute post-traumatic brain injury period has not been clinically studied although preclinical data demonstrate that bone marrow-derived mononuclear cell infusion down-regulates the inflammatory response. Our study evaluates whether pediatric traumatic brain injury patients receiving IV autologous bone marrow-derived mononuclear cells within 48 hours of injury experienced a reduction in therapeutic intensity directed toward managing elevated intracranial pressure relative to matched controls. DESIGN: The study was a retrospective cohort design comparing pediatric patients in a phase I clinical trial treated with IV autologous bone marrow-derived mononuclear cells (n = 10) to a control group of age- and severity-matched children (n = 19). SETTING: The study setting was at Children's Memorial Hermann Hospital, an American College of Surgeons Level 1 Pediatric Trauma Center and teaching hospital for the University of Texas Health Science Center at Houston from 2000 to 2008. PATIENTS: Study patients were 5-14 years with postresuscitation Glasgow Coma Scale scores of 5-8. INTERVENTIONS: The treatment group received 6 million autologous bone marrow-derived mononuclear cells/kg body weight IV within 48 hours of injury. The control group was treated in an identical fashion, per standard of care, guided by our traumatic brain injury management protocol, derived from American Association of Neurological Surgeons guidelines. MEASUREMENTS AND MAIN RESULTS: The primary measure was the Pediatric Intensity Level of Therapy scale used to quantify treatment of elevated intracranial pressure. Secondary measures included the Pediatric Logistic Organ Dysfunction score and days of intracranial pressure monitoring as a surrogate for length of neurointensive care. A repeated-measure mixed model with marginal linear predictions identified a significant reduction in the Pediatric Intensity Level of Therapy score beginning at 24 hours posttreatment through week 1 (p < 0.05). This divergence was also reflected in the Pediatric Logistic Organ Dysfunction score following the first week. The duration of intracranial pressure monitoring was 8.2 ± 1.3 days in the treated group and 15.6 ± 3.5 days (p = 0.03) in the time-matched control group. CONCLUSIONS: IV autologous bone marrow-derived mononuclear cell therapy is associated with lower treatment intensity required to manage intracranial pressure, associated severity of organ injury, and duration of neurointensive care following severe traumatic brain injury. This may corroborate preclinical data that autologous bone marrow-derived mononuclear cell therapy attenuates the effects of inflammation in the early post-traumatic brain injury period.

Microscopic versus open approach to craniosynostosis: a long-term outcomes comparison.

The purpose of this retrospective study was to evaluate the long-term outcomes of using the microscopic minimally invasive approach for the treatment of nonsyndromic craniosynostosis. During the last 10 years, 180 consecutive patients with nonsyndromic craniosynostosis were treated: 67 patients were treated with microscopic minimally invasive approach, and 113 were treated with the open approach. In the microscopic group, there was 1 intraoperative complication (1.5%). There were 10 postoperative complications (14.9%), of which 9 required major reoperations and 1 required a minor procedure. The major complications occurred in 7 unicoronal patients (58.3%) and 2 metopic patients (25.0%). In the open-approach group, there were 8 complications (7.1%), 2 patients required major reoperations and 6 required minor procedures. Chi-squared test showed that there was no statistically significant difference in the overall complication rate between the microscopic and open approaches. However, in the unicoronal patients, the complication rate was significantly higher in the microscopic group (P < 0.001). In conclusion, the microscopic approach is our treatment of choice in nonsyndromic patients with sagittal and lambdoidal craniosynostosis. We no longer use the microscopic approach in patients with unicoronal or metopic craniosynostosis because of the high complication rate.

Is it time to replace the Wada test and put awake craniotomy to sleep?

The question we address here is whether the invasive presurgical brain mapping approaches of direct cortical stimulation and of the Wada procedure can be replaced by noninvasive functional neuroimaging methods (functional magnetic resonance imaging [fMRI], magnetoencephalography [MEG], transcranial magnetic stimulation and [TMS]). First, we outline the reasons for contemplating such a replacement. Second, we present evidence to the effect that the efficacy of the invasive and noninvasive methods, while suboptimal, is comparable. Third, we discuss additional advantages of noninvasive presurgical brain mapping and conclude that there are no longer compelling reasons for opting for invasive mapping in many if not most cases provided that the non-invasive methods are available.

Autologous bone marrow mononuclear cell therapy for severe traumatic brain injury in children.

BACKGROUND: Severe traumatic brain injury (TBI) in children is associated with substantial long-term morbidity and mortality. Currently, there are no successful neuroprotective/neuroreparative treatments for TBI. Numerous preclinical studies suggest that bone marrow-derived mononuclear cells (BMMNCs), their derivative cells (marrow stromal cells), or similar cells (umbilical cord blood cells) offer neuroprotection. OBJECTIVE: To determine whether autologous BMMNCs are a safe treatment for severe TBI in children. METHODS: Ten children aged 5 to 14 years with a postresuscitation Glasgow Coma Scale of 5 to 8 were treated with 6×10 autologous BMMNCs/kg body weight delivered intravenously within 48 hours after TBI. To determine the safety of the procedure, systemic and cerebral hemodynamics were monitored during bone marrow harvest; infusion-related toxicity was determined by pediatric logistic organ dysfunction (PELOD) scores, hepatic enzymes, Murray lung injury scores, and renal function. Conventional magnetic resonance imaging (cMRI) data were obtained at 1 and 6 months postinjury, as were neuropsychological and functional outcome measures. RESULTS: All patients survived. There were no episodes of harvest-related depression of systemic or cerebral hemodynamics. There was no detectable infusion-related toxicity as determined by PELOD score, hepatic enzymes, Murray lung injury scores, or renal function. cMRI imaging comparing gray matter, white matter, and CSF volumes showed no reduction from 1 to 6 months postinjury. Dichotomized Glasgow Outcome Score at 6 months showed 70% with good outcomes and 30% with moderate to severe disability. CONCLUSION: Bone marrow harvest and intravenous mononuclear cell infusion as treatment for severe TBI in children is logistically feasible and safe.

Microscopic minimally invasive approach to nonsyndromic craniosynostosis.

PURPOSE: The purpose of this retrospective study was to present the results of the authors' microscopic minimally invasive approach in the treatment of nonsyndromic craniosynostosis. METHODS: From 2001 to 2007, the authors treated a cohort of 67 infants with nonsyndromic sagittal, unicoronal, bicoronal, and metopic craniosynostosis, either with the microscopic (n = 40) or the open (n = 27) approach. In the microscopic approach, incisions were placed over the premature suture, and using a surgical microscope, the appropriate synostectomy was performed. The open approach used a traditional coronal incision with cranial vault reconstruction. Both groups of patients had postoperative molding helmet therapy. Finally, anthropometric measurements were used to evaluate the treatment results. The measurement used for the patients with sagittal and bicoronal craniosynostoses was the divergence from the norm of the age-adjusted cephalic index. The (FZr-EUl/FZl-EUr) and (FZr-EUr)/(FZl-EUl) were used for the patients with unicoronal craniosynostosis. The divergence from the norm of age-adjusted (FTr-FTl)/(Tr-Tl) was used for the patients with metopic craniosynostosis. (FZr = right frontozygomaticus, EUl = left eurion, FZl = left frontozygomaticus, Eur = right eurion, FTr = right frontotemporale, FTl = left frontotemporale, Tr = tragion, Tl = left tragion). RESULTS: The median surgical times for microscopic and open approaches were 108 and 210 minutes, the volumes of blood loss were 75 and 220 mL, the durations of hospital stay were 2 and 4 days, the numbers of helmet were 2 and 1, and the durations of helmet therapy were 10.5 and 8 weeks, respectively. The analysis of variance for repeated measures showed that there was no statistically significant difference between the 2 groups in any of the craniosynostoses. CONCLUSIONS: The treatment outcomes from the microscopic minimally invasive approach to craniosynostosis are equal to those seen with the open approach. The microscopic approach results in less operative time, blood loss, and hospitalization.

Modern approaches to pediatric brain injury therapy.

Each year, pediatric traumatic brain injury (TBI) accounts for 435,000 emergency department visits, 37,000 hospital admissions, and approximately 2,500 deaths in the United States. TBI results in immediate injury from direct mechanical force and shear. Secondary injury results from the release of biochemical or inflammatory factors that alter the loco-regional milieu in the acute, subacute, and delayed intervals after a mechanical insult. Preliminary preclinical and clinical research is underway to evaluate the benefit from progenitor cell therapeutics, hypertonic saline infusion, and controlled hypothermia. However, all phase III clinical trials investigating pharmacologic monotherapy for TBI have shown no benefit. A recent National Institutes of Health consensus statement recommends research into multimodality treatments for TBI. This article will review the complex pathophysiology of TBI as well as the possible therapeutic mechanisms of progenitor cell transplantation, hypertonic saline infusion, and controlled hypothermia for possible utilization in multimodality clinical trials.

Long-term treatment effectiveness of molding helmet therapy in the correction of posterior deformational plagiocephaly: a five-year follow-up.

OBJECTIVE: To evaluate the long-term effectiveness of helmet therapy in the correction of deformational plagiocephaly and to assess the early occlusal abnormalities seen in these patients. DESIGN: A prospective study with blinded measurements. PATIENTS: Twenty-eight patients with deformational plagiocephaly who were treated with molding helmet therapy with at least 5 years of follow-up. INTERVENTIONS: The average length of molding helmet treatment was 6.2 months. At the time of this follow-up evaluation, the mean interval since completing the molding helmet therapy was 5.6 years. MAIN OUTCOME MEASURES: Anthropometric measurements of cranial asymmetry included cranial vault asymmetry (CVA), orbitotragial depth asymmetry (OTDA), and cranial base asymmetry (CBA). A dental examination was also performed. RESULTS: At the completion of therapy, the most improvement was seen in the measurement of CBA, followed by CVA and OTDA. However, in evaluating the long-term stability of molding treatment, OTDA tended to continue improving after the initial treatment, while CBA and CVA appeared to regress, although none of the changes reached statistically significant levels. In dental measurements, all the dental midline and chin deviations were toward the unaffected side with respect to occipital deformation. CONCLUSION: This study demonstrated that helmet remodeling with the dynamic orthotic cranioplasty band is effective in the correction of cranial asymmetry, with some nonstatistically significant changes in long-term cranial vault symmetry. Dental observations indicated the possibility of occlusal abnormalities that may affect dental, especially orthodontic, diagnosis and treatment planning.

Cell therapies for traumatic brain injury.

Preliminary discoveries of the efficacy of cell therapy are currently being translated to clinical trials. Whereas a significant amount of work has been focused on cell therapy applications for a wide array of diseases, including cardiac disease, bone disease, hepatic disease, and cancer, there continues to be extraordinary anticipation that stem cells will advance the current therapeutic regimen for acute neurological disease. Traumatic brain injury is a devastating event for which current therapies are limited. In this report the authors discuss the current status of using adult stem cells to treat traumatic brain injury, including the basic cell types and potential mechanisms of action, preclinical data, and the initiation of clinical trials.

When epilepsy interferes with word comprehension: findings in Landau-Kleffner syndrome.

Landau-Kleffner syndrome is characterized by a regression in receptive language. The factors that affect the clinical expression of this syndrome remain unclear. This study presents neuroimaging findings in 2 patients showing different clinical evolutions. Linguistic regression persisted in 1 patient and evolved positively in the other. In patient A (with severe linguistic regression) there was an overlap between areas engaged during word recognition and those involved in generating the epileptiform activity; in patient B (with better linguistic evolution), receptive language was predominantly represented in the right hemisphere (unaffected). Patient A underwent multiple subpial transections. The 2-year follow-up indicated linguistic improvement, absence of epileptiform activity, and activation of the left temporal cortex during word comprehension. These results suggest that the resolution of the linguistic deficit in Landau-Kleffner syndrome may be modulated by the language-specific cortex freed from interfering epileptiform activity or by reorganization of the receptive language cortex triggered by the epileptic activity.

Corpus callosotomy: a palliative therapeutic technique may help identify resectable epileptogenic foci.

Corpus callosotomy has a long history as a palliative treatment for intractable epilepsy. Identification of a single epileptogenic zone is critical to performing successful resective surgery. We describe three patients in which corpus callosotomy allowed recognition of unapparent seizure foci, leading to subsequent successful resection. We retrospectively reviewed our epilepsy surgery database from 2003 to 2005 for children who had a prior callosotomy and were candidates for focal resection. All underwent magnetic resonance imaging and scalp video electroencephalograph monitoring, and two had magnetoencephalography, electrocorticography and/or intracranial video electroencephalograph monitoring. The children were 8 and 9 years old, and seizure onset varied from early infancy to early childhood. One child had a history of head trauma preceding seizure onset, one had a large intracerebral infarct and dysplastic cortex in the contralateral frontal lobe, and the other had an anterior temporal lobe resection without improvement in seizure frequency. After medical management failed, callosotomy was performed with the expectation of decreasing the seizure types affecting both hemispheres. Following transection of the callosal fibers, a single focus was recognized and resected, with resultant dramatic improvement in seizure control. In medically refractory epilepsy, where rapid secondary bisynchrony is suspected but the electroencephalograph is non-localizing, callosotomy should be considered as a means of treating generalized seizure types, but may also assist in identifying potentially operable seizure foci. Study limitations include its retrospective nature and cohort size. The findings, however, suggest the need for prospective, systematic, well-controlled studies of the use of corpus callostomy in this intractable patient population.

Genotype/phenotype correlation in 325 individuals referred for a diagnosis of tuberous sclerosis complex in the United States.

Tuberous sclerosis complex is an autosomal dominant neurocutaneous disorder marked by hamartoma growth in multiple organ systems. We performed mutational analyses on 325 individuals with definite tuberous sclerosis complex diagnostic status. We identified mutations in 72% (199/257) of de novo and 77% (53/68) of familial cases, with 17% of mutations in the TSC1 gene and 50% in the TSC2 gene. There were 4% unclassified variants and 29% with no mutation identified. Genotype/phenotype analyses of all observed tuberous sclerosis complex findings in probands were performed, including several clinical features not analyzed in two previous large studies. We showed that patients with TSC2 mutations have significantly more hypomelanotic macules and learning disability in contrast to those with TSC1 mutations, findings not noted in previous studies. We also observed results consistent with two similar studies suggesting that individuals with mutations in TSC2 have more severe symptoms. On performing meta-analyses of our data and the other two largest studies in the literature, we found significant correlations for several features that individual studies did not have sufficient power to conclude. Male patients showed more frequent neurologic and eye symptoms, renal cysts, and ungual fibromas. Correlating genotypes with phenotypes should facilitate the disease management of tuberous sclerosis complex.

Microscopic approach to craniosynostosis.

The purpose of this study is to describe a minimally invasive approach using a microscope and the subsequent helmet therapy. The authors have treated 14 patients with the microscopic technique between May 2001 and November 2003. In this group of patients, there were 3 females and 11 males with an average age of 10.5 weeks and a range of 4 to 28 weeks. The study included 8 patients with sagittal synostosis and 6 patients with other synostoses. In the latter group, there were 3 patients with metopic, one with unicoronal, one with bicoronal, and one with lambdoidal. The approach used limited incisions over the affected sutures. The craniotomy/craniectomy was completed using a 5-mm burr. Postoperative helmet therapy was begun within 2 weeks after surgery. In patients with sagittal synostosis, a mean of 1.5 helmets for a duration of 11.4 weeks was used. In the other groups of patients with craniosynostosis, a mean of 2.3 helmets for a duration of 13.5 weeks was used. A microscopic variation to the "minimally invasive" approach to craniosynostosis is presented. It provides excellent visualization, illumination, and control of the surgical field. When compared with traditional surgery, it results in shorter hospitalization and operative time and decreased blood loss. The authors note that critical to this approach is the postoperative helmet therapy. Early results are encouraging.

Integrating sensory and motor mapping in a comprehensive MEG protocol: clinical validity and replicability.

Considerable evidence supports the idea of magnetoencephalography (MEG) being a valuable noninvasive tool for presurgical mapping of sensory and motor functions. In this study, we test the validity and replicability of a new experimental paradigm for simultaneous sensory and motor mapping using MEG recordings. This comprehensive sensorimotor protocol (CSSMP), where external mechanic stimulation serves as a cue for voluntary movements, allows the recording of sensory and motor cortical responses during a single activation task. The stability and replicability of MEG-derived recordings during this paradigm were tested in a group of eight neurologically normal volunteers and six patients with perirolandic lesions. We found that a common sensorimotor cortical network, engaging sensory (S1, S2) and motor (M1) areas, was reliably activated in all subjects and patients and that the results remained exceptionally stable over time. Additionally, the clinical validity of the MEG-derived maps of activation was tested through intraoperative electrocortical stimulation mapping in the group of patients. The MEG-derived anatomical maps for specific sensory (S1) and motor (M1) responses were verified, by direct cortical mapping, and confirmed with the patient's surgical outcome. The results of this validation study show that the so-called CSSMP is a reliable and reproducible method for assessing simultaneously sensory and motor areas. This method minimizes methodological problems and improves our knowledge of the spatiotemporal organization of the sensorimotor cortical network and helps to optimize the surgical management of patients with perirolandic lesions.