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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Neuroimaging features of epidermal nevus syndrome.

Epidermal nevus syndrome is a kind of neurocutaneous syndrome that is associated with epidermal nevus and a variety of congenital CNS disorders. Clinical presentations include seizures, paresis, mental retardation, and developmental delay. We report three cases with MR imaging and magnetoencephalography findings; one patient underwent ictal and interictal single photon emission CT. Both structural and functional imaging studies indicated that the frontal lobes had lesser involvement or were intact. One patient underwent hemispherectomy because of the medically intractable seizure. He remained seizure free with topiramate monotherapy.

Nonsynostotic scaphocephaly: the so-called sticky sagittal suture.

OBJECT: Scaphocephaly is a common craniofacial abnormality that results from craniosynostosis of the sagittal suture. The authors have treated a group of infants who presented with nonsynostotic scaphocephaly, or a so-called sticky sagittal suture. The purpose of this study was to describe these patients with nonsynostotic scaphocephaly, the natural history of the disease, and its treatment. METHODS: At the University of Texas-Houston Medical School between 1996 and 2002, nine patients presented with nonsynostotic scaphocephaly. When the abnormality in patients was diagnosed prior to 12 months of age, the majority (seven of eight) were successfully managed by molding helmet therapy. The only child in this group in whom this therapy failed to correct the deformity was noted on repeated computerized tomography scanning to have true sagittal synostosis, which required surgical correction. One child with nonsynostotic scaphocephaly, who presented after 1 year of age, required surgical correction followed by postoperative molding helmet therapy. CONCLUSIONS: Patients with nonsynostotic scaphocephaly appear to have sagittal synostosis. If treated early (at < 12 months of age), head shape in these patients can be normalized by molding helmet therapy. Surgery is reserved for older patients (> 12 months of age) or those with sagittal synostosis.

Localization of ictal and interictal bursting epileptogenic activity in focal cortical dysplasia: agreement of magnetoencephalography and electrocorticography.

Focal cortical dysplasia (FCD) is often associated with severe partial epilepsy. In such cases, interictal frequent rhythmic bursting epileptiform activity (FBREA) on both scalp electroencephalography (EEG) and electrocorticography (ECoG) is generally accepted to be identical to the ictal epileptiform activity. We used magnetoencephalography (or Magnetic Source Imaging (MSI)) to determine the epileptogenic zone in a 6-year-old patient with histopathologically proven FCD and normal magnetic resonance imaging (MRI). MSI was used to localize the sources of both ictal activity and FRBEA, which was then compared with ECoG findings. The intracranial sources of both types of activity co-localized in the left inferior frontal and superior temporal gyri. The location and extent of the epileptogenic area determined by MSI was essentially identical to that determined directly through extra-operative ECoG. In the absence of structural abnormalities detectable on MRI, the noninvasive method of MSI provided valuable information regarding the location and extent of the primary epileptogenic area. This was critical for pre-surgical planning regarding placement of intracranial electrodes and for risk-benefit evaluation.

Somatosensory evoked magnetic fields in hemimegalencephaly.

Somatosensory maps were determined in three patients with hemimegalencephaly using magnetic resonance imaging (MRI) and magnetoencephalography (MEG). MRIs were characterized by thickened gray matter with clearly aberrant lamination patterns. Somatosensory Evoked Fields (SEFs), as measured by MEG, were absent from the affected hemisphere in the two patients with severe cortical lamination defects. The third patient presented with relatively preserved cortical lamination in the frontal lobe and clear cortical SEFs in this region, indicating somatotopical reorganization. These findings suggest that the presence and location of MEG-derived somatosensory maps reflect the severity of the cortical lamination defects in hemimegalencephaly.

Multimodality neuroimaging evaluation improves the detection of subtle cortical dysplasia in seizure patients.

The purpose of this study is to investigate if multimodality neuroimaging evaluation increases the detection of subtle focal cortical dysplasia as part of an epilepsy surgery evaluation. Three patients with normal magnetic resonance imaging and histopathological findings of focal cortical dysplasia were reviewed. Their magnetoencephalography recordings were performed on whole-head magnetoencephalography system. Magnetic resonance images were re-evaluated with special inspection in limited regions guided by magnetoencephalography spike localization. Two patients had ictal and interictal single photon emission computed tomography study after administration of Tc99m ECD. In two patients we found tiny focal abnormalities including slightly increased cortical thickness and blurred gray-white matter junction at the locations of interictal events after re-evaluation of the MR images indicating focal cortical dysplasia. The third patient showed focal atrophic change. All patients are seizure free after surgery. Both ictal and interictal single photon emission computed tomography showed hyperperfusion in the dysplastic cortex regions. Multimodality neuroimaging study can improve the detection of focal cortical dysplasia. Normal magnetic resonance images should be re-evaluated for subtle signs of focal cortical dysplasia especially when magnetoencephalography recording demonstrate focal epileptic discharges.