Impact of tumor-associated syrinx on outcomes following resection of primary ependymomas of the spinal cord.

PURPOSE: To interrogate the association of tumor-associated syrinxes with postoperative neurological and oncological outcomes in patients surgically treated for WHO grade 2 spinal ependymomas. METHODS: Adults treated for primary spinal intramedullary ependymomas between 2000 and 2020 were identified and data were gathered on preoperative neurological exam, radiographic characteristics, operative details, and postoperative neurological outcome. Neurological status was graded on the modified McCormick Scale (MMS). Neurological worsening immediately postoperatively and at last follow-up were defined by ≥ 1 MMS grade deterioration. Decision-tree analyses were also performed to identify independent predictors of new neurological deficits. RESULTS: Seventy patients were identified; mean age 45.4 ± 12.7; 60% male. Forty-eight patients (68.6%) had tumor-associated syrinxes, were more common among males (68.8%) and cervical lesions (68.8 vs. 31.8%; P = 0.005). Postoperatively patients with syrinxes had better MMS (P = 0.035) and were less likely to require a gait aid (39.6 vs. 81.8; P = 0.002). This latter difference persisted to last follow-up (22.9 vs. 59.1%; P = 0.006). On decision-tree analysis the strongest predictors of long-term neurological worsening were advanced age (≥ 63 years) and worse baseline neurological function. Worsened neurological status in the immediate postoperative period was best predicted by thoracic localization, the presence of a hemosiderin cap, and longer craniocaudal extension. CONCLUSION: For spinal ependymomas, tumor-associated syrinxes may portend decreased risk for immediate postoperative neurologic deficits but do not predict long-term neurological outcomes (MMS) or odds of successful gross total resection. Thoracic localization appears to best predict new immediate postoperative deficits, and worse baseline neurological function and advanced age best predict long-term deficits.

Clinical characteristics and management differences for grade II and III spinal meningiomas.

PURPOSE: The majority of spinal meningiomas are grade I tumors, as defined by World Health Organization (WHO) classification making atypical (grade II) or anaplastic (grade III) tumors extremely rare lesions to encounter in clinical practice. Here, we present our institutional experience of management of grade II and III spinal meningiomas. METHODS: Following IRB approval, we queried all available institutional electronic medical records for patients undergoing surgical resection of pathology-proven spinal meningiomas, with further review of patients with grade II and III. Variables of interest included age, sex, histological type, tumor size, symptoms at baseline, treatment characteristics, symptom resolution at the last follow-up, recurrence, NF-2 status, concurrent intracranial meningioma, and mortality. Kaplan Meier curves were constructed to study time to progression/recurrence. RESULTS: A total of 188 patients undergoing surgical resection of spinal meningioma between 1988 and 2018 were identified. Among those, 172 (91.5%) patients had grade I meningioma and 16 (8.5%) patients had high grade meningiomas [grade II (15) and III (1)]. Over a median (IQR) follow-up of 8.0 years (5.1-13.0), mortality and recurrence rates were 18.8% (n = 3) and 47.1% (n = 8), respectively. In univariate analysis, adjuvant radiotherapy and thoracic segment involvement were associated with lower rates of recurrence while male sex was associated with a higher rate of recurrence. CONCLUSIONS: Results showed variations in clinical outcomes for patients with high grade spinal meningiomas, especially the recurrence. Adjuvant radiotherapy and thoracic segment involvement was associated with lower rates of recurrence while recurrence ocurred at a higher rate in males.

Comparison of narcotic pain control between stereotactic electrocorticography and subdural grid implantation.

INTRODUCTION: The choice of subdural grid (SDG) or stereoelectroencephalography (sEEG) for patients with epilepsy can be complex and in some cases overlap. Comparing postoperative pain and narcotics consumption with SDG or sEEG can help develop an intracranial monitoring strategy. MATERIALS AND METHODS: A retrospective study was performed for adult patients undergoing SDG or sEEG monitoring. Numeric Rating Scale (NRS) was used for pain assessment. Types and dosage of the opioids were calculated by converting into milligram morphine equivalents (MME). Narcotic consumption was analyzed at the following three time periods: I. the first 24 h of implantation; II. from the second postimplantation day to the day of explantation; and III. the days following electrode removal to discharge. RESULTS: Forty-two patients who underwent SDG and 31 patients who underwent sEEG implantation were analyzed. After implantation, average NRS was 3.7 for SDG and 2.2 for sEEG (P < .001). After explantation, the NRS was 3.5 for SDG and 1.4 in sEEG (P < .001). Sixty percent of SDG patients and 13% of sEEG patients used more than one opioid in period III (P < .001). The SDG group had a significantly higher MME throughout the three periods compared with the sEEG group: period I: 448 (SDG) vs. 205 (sEEG) mg, P = .002; period II: 377 (SDG) vs. 102 (sEEG) mg, P < .001; and period III: 328 (SDG) vs. 75 (sEEG) mg; P = .002. Patients with the larger SDG implantation had the higher NRS (P = .03) and the higher MME at period I (P = .019). There was no correlation between the number of depth electrodes and pain control in patients with sEEG. CONCLUSIONS: Patients undergoing sEEG had significantly less pain and required fewer opiates compared with patients with SDG. These differences in perioperative pain may be a consideration when choosing between these two invasive monitoring options.

Reactivation of seizure-related changes to interictal spike shape and synchrony during postseizure sleep in patients.

OBJECTIVE: Local field potentials (LFPs) arise from synchronous activation of millions of neurons, producing seemingly consistent waveform shapes and relative synchrony across electrodes. Interictal spikes (IISs) are LFPs associated with epilepsy that are commonly used to guide surgical resection. Recently, changes in neuronal firing patterns observed in the minutes preceding seizure onset were found to be reactivated during postseizure sleep, a process called seizure-related consolidation (SRC), due to similarities with learning-related consolidation. Because IISs arise from summed neural activity, we hypothesized that changes in IIS shape and relative synchrony would be observed in the minutes preceding seizure onset and would be reactivated preferentially during postseizure slow-wave sleep (SWS). METHODS: Scalp and intracranial recordings were obtained continuously across multiple days from clinical macroelectrodes implanted in patients undergoing treatment for intractable epilepsy. Data from scalp electrodes were used to stage sleep. Data from intracranial electrodes were used to detect IISs using a previously established algorithm. Partial correlations were computed for sleep and wake periods before and after seizures as a function of correlations observed in the minutes preceding seizures. Magnetic resonance imaging (MRI) and computed tomography (CT) scans were co-registered with electroencephalography (EEG) to determine the location of the seizure-onset zone (SOZ). RESULTS: Changes in IIS shape and relative synchrony were observed on a subset of macroelectrodes minutes before seizure onset, and these changes were reactivated preferentially during postseizure SWS. Changes in synchrony were greatest for pairs of electrodes where at least one electrode was located in the SOZ. SIGNIFICANCE: These data suggest preseizure changes in neural activity and their subsequent reactivation occur across a broad spatiotemporal scale: from single neurons to LFPs, both within and outside the SOZ. The preferential reactivation of seizure-related changes in IISs during postseizure SWS adds to a growing body of literature suggesting that pathologic neural processes may utilize physiologic mechanisms of synaptic plasticity.

Brain-responsive neurostimulation in patients with medically intractable mesial temporal lobe epilepsy.

OBJECTIVE: Evaluate the seizure-reduction response and safety of mesial temporal lobe (MTL) brain-responsive stimulation in adults with medically intractable partial-onset seizures of mesial temporal lobe origin. METHODS: Subjects with mesial temporal lobe epilepsy (MTLE) were identified from prospective clinical trials of a brain-responsive neurostimulator (RNS System, NeuroPace). The seizure reduction over years 2-6 postimplantation was calculated by assessing the seizure frequency compared to a preimplantation baseline. Safety was assessed based on reported adverse events. RESULTS: There were 111 subjects with MTLE; 72% of subjects had bilateral MTL onsets and 28% had unilateral onsets. Subjects had one to four leads placed; only two leads could be connected to the device. Seventy-six subjects had depth leads only, 29 had both depth and strip leads, and 6 had only strip leads. The mean follow-up was 6.1 ± (standard deviation) 2.2 years. The median percent seizure reduction was 70% (last observation carried forward). Twenty-nine percent of subjects experienced at least one seizure-free period of 6 months or longer, and 15% experienced at least one seizure-free period of 1 year or longer. There was no difference in seizure reduction in subjects with and without mesial temporal sclerosis (MTS), bilateral MTL onsets, prior resection, prior intracranial monitoring, and prior vagus nerve stimulation. In addition, seizure reduction was not dependent on the location of depth leads relative to the hippocampus. The most frequent serious device-related adverse event was soft tissue implant-site infection (overall rate, including events categorized as device-related, uncertain, or not device-related: 0.03 per implant year, which is not greater than with other neurostimulation devices). SIGNIFICANCE: Brain-responsive stimulation represents a safe and effective treatment option for patients with medically intractable epilepsy, including patients with unilateral or bilateral MTLE who are not candidates for temporal lobectomy or who have failed a prior MTL resection.

Evidence for consolidation of neuronal assemblies after seizures in humans.

The establishment of memories involves reactivation of waking neuronal activity patterns and strengthening of associated neural circuits during slow-wave sleep (SWS), a process known as "cellular consolidation" (Dudai and Morris, 2013). Reactivation of neural activity patterns during waking behaviors that occurs on a timescale of seconds to minutes is thought to constitute memory recall (O'Keefe and Nadel, 1978), whereas consolidation of memory traces may be revealed and served by correlated firing (reactivation) that appears during sleep under conditions suitable for synaptic modification (Buhry et al., 2011). Although reactivation has been observed in human neuronal recordings (Gelbard-Sagiv et al., 2008; Miller et al., 2013), reactivation during sleep has not, likely because data are difficult to obtain and the effect is subtle. Seizures, however, provide intense and synchronous, yet sparse activation (Bower et al., 2012) that could produce a stronger consolidation effect if seizures activate learning-related mechanisms similar to those activated by learned tasks. Continuous wide-bandwidth recordings from patients undergoing intracranial monitoring for drug-resistant epilepsy revealed reactivation of seizure-related neuronal activity during subsequent SWS, but not wakefulness. Those neuronal assemblies that were most strongly activated during seizures showed the largest correlation changes, suggesting that consolidation selectively strengthened neuronal circuits activated by seizures. These results suggest that seizures "hijack" physiological learning mechanisms and also suggest a novel epilepsy therapy targeting neuronal dynamics during post-seizure sleep.

Drug-resistant focal epilepsy in women of childbearing age: Reproduction and the effect of epilepsy surgery.

OBJECTIVE: Women with epilepsy (WWE) have lower birth rates than expected. The reasons for this are multifactorial and involve a complex interaction between reproductive endocrine and psychosocial factors. The effect of epilepsy surgery on reproduction in women with drug-resistant focal epilepsy has not previously been studied. METHODS: Adult women of childbearing age (18-45years old) with drug-resistant focal epilepsy who had undergone a focal cortical resection between 1997 and 2008 at the Mayo Clinic in Rochester, MN were included in the study. Patients who had a history of hysterectomy or tubal ligation or who were menopausal at the time of surgery were excluded. Data on prior pregnancies and births, epilepsy history, surgical treatment, hormonal dysfunction, and socioeconomic status were obtained using a retrospective chart review. Associations between various clinical and demographic variables with changes in pregnancies and births from pre- to postsurgery were assessed using Chi-square or Fisher's exact test for categorical variables and Wilcoxon rank sum test for continuous variables. All tests were 2-sided, and p-values less than 0.05 were considered statistically significant. All analyses were performed using SAS software version 9.2 (SAS INC, Cary NC). RESULTS: One hundred and thirteen women (average age: 30.5years) were included in the study. Average length of follow-up was 5.7years (SD-3.90). Sixty-four patients (57.5%) were nulliparous at the time of surgery. Sixty-one patients (54%) had never been married. Average number of pregnancies per patient prior to surgery was 0.93, and average number of births prior to surgery was 0.73. After surgery, a total of 17 women had a total of 35 pregnancies and 25 births. The average number of pregnancies and births after surgery was 1.27 and 0.96, respectively. Infertility was reported in one patient postoperatively. Patients who were younger at the time of surgery experienced a greater change in the number of pregnancies and births after surgery (p=0.0036 and 0.0060, respectively). Patients who received fewer antiepileptic drug medication trials by the time of surgery also had a greater change in the number of births after surgery (p=0.0362). Seizure onset localization and lateralization, presurgical seizure frequency, age at seizure onset, duration of epilepsy, and postoperative seizure outcome were not statistically significant factors. CONCLUSION: The present retrospective observational study provides additional evidence for the importance of early surgical treatment in women with drug-resistant focal epilepsy. Patients who had received fewer medications prior to surgery were more likely to experience an increase in births following surgery. The significance of these findings requires further investigation but may support a role for earlier surgical intervention in the management of drug-resistant focal epilepsy.

Magnetic resonance imaging-guided laser interstitial thermal therapy for previously treated hypothalamic hamartomas.

OBJECTIVE Hypothalamic hamartomas (HHs) are associated with gelastic seizures and the development of medically refractory epilepsy. Magnetic resonance imaging-guided laser interstitial thermal therapy (MRg-LITT) is a minimally invasive ablative treatment that may have applicability for these deep-seated lesions. Here, the authors describe 3 patients with refractory HHs who they treated with MRg-LITT. METHODS An institutional review board-approved prospective database of patients undergoing Visualase MRg-LITT was retrospectively reviewed. Demographic and historical medical data, including seizure and medication histories, previous surgeries, procedural details, and surgical complications, along with radiological interpretation of the HHs, were recorded. The primary outcome was seizure freedom, and secondary outcomes included medication reduction, seizure frequency, operative morbidity, and clinical outcome at the latest follow-up. RESULTS All 3 patients in the multi-institutional database had developed gelastic seizures related to HH at the ages of 7, 7, and 9 years. They presented for further treatment at 25, 28, and 48 years of age, after previous treatments with stereotactic radiosurgery in all cases and partial hamartoma resection in one case. One ablation was complicated by a small tract hemorrhage, which was stable on postoperative imaging. One patient developed hyponatremia and experienced weight gain, which were respectively managed with fluid restriction and counseling. At the most recent follow-up at a mean of 21 months (range 1-32 months), one patient was seizure free while another had meaningful seizure reduction. Medication was reduced in one case. CONCLUSIONS Adults with gelastic seizures despite previous treatments can undergo MRg-LITT with reasonable safety and efficacy. This novel therapy may provide a minimally invasive alternative for primary and recurrent HH as the technique is refined.

Outcomes following myxopapillary ependymoma resection: the importance of capsule integrity.

OBJECT While extent of resection has been shown to correlate with outcomes after myxopapillary ependymoma (MPE) resection, the effect of capsular violation has not been well studied. The role of adjuvant radiation also remains controversial. In this paper the authors' goals were to evaluate outcomes following resection of MPE based on intraoperative capsular violation and to explore the role of adjuvant radiotherapy in cases of capsular violation. METHODS A retrospective review of patients undergoing resection of MPE at 2 academic institutions between 1990 and 2013 was performed. Cases with dissemination at presentation, less than 12 months of follow-up, or incomplete records were excluded. Extent of resection was defined as en bloc if all visible tumor was removed without capsular violation, gross-total resection (GTR) if all visible tumor was removed, but with capsular violation, and subtotal resection (STR) if a known residual was left at the time of surgery. Postoperative MR images were reviewed to confirm the extent of resection. Primary outcomes were progression-free survival (PFS) and overall recurrence rates. The effects of extent of resection, capsular violation, and adjuvant radiotherapy on recurrence rates and PFS were analyzed using Kaplan-Meier statistics. Associations between recurrence and preoperative variables were evaluated using Fisher exact methods and t-tests where appropriate. RESULTS Of the 107 patients reviewed, 58 patients (53% were male) met inclusion criteria. The mean age at surgery was 40.8 years (range 7-68 years). The median follow-up was 51.5 months (range 12-243 months). Extent of resection was defined as en bloc in 46.5% (n = 27), GTR in 34.5% (n = 20), and STR in 18.9% (n = 11). No recurrences were noted in the en bloc group, compared with 15% (n = 3) and 45% (n = 5) in the GTR and STR groups. En bloc resection was achieved most frequently in tumors involving the conus. Twelve patients (20%) underwent adjuvant radiotherapy following either STR or GTR. The overall recurrence rate was 13.8% (n = 8), and the 5-year PFS was 81%. Capsular violation was associated with a higher recurrence rate (p = 0.005). Adjuvant radiotherapy showed a nonsignificant trend of lower recurrence rates (16.7% vs 31.6%, p = 0.43) and longer PFS at 5 years (83.3% vs 49.9%, p = 0.16) in cases of capsular violation. CONCLUSIONS A strong correlation between capsular violation and recurrence was found following removal of MPE and should be assessed when defining extent of resection in future studies. Although the use of adjuvant radiotherapy in cases of capsular violation showed a trend toward improved PFS, further investigation is needed to establish its role as salvage therapy also appears to be effective at halting disease progression.

Factors contributing to the yield of asymmetric bilateral implantation of intracranial electrodes.

OBJECTIVE: To determine the outcome of implanting fewer electrodes over the hemisphere with less supporting presurgical localizing data. METHODS: We retrospectively reviewed our epilepsy surgery database at Mayo Clinic, Rochester, Minnesota, between January 1, 1999, and December 31, 2011, to identify patients who had an asymmetric number of electrode contacts implanted in each hemisphere for seizure localization. We scored each presurgical noninvasive data point (0, 0.5, or 1) to predict the likelihood of identifying seizure onset in the hemisphere with fewer intracranial electrode contacts (HFEC). An aggregate score was obtained for each patient. RESULTS: Thirteen (37%) of 35 patients had HFEC-onset seizures on intracranial electroencephalography (iEEG). The following factors predicted HFEC-onset seizures: (1) temporal lobe epilepsy (p = 0.02); (2) interictal scalp electroencephalographic discharges at the HFEC (p = 0.04); and (3) both interictal and ictal scalp EEG discharges at the HFEC (p = 0.01). The median (range) aggregate score was 2 (1-3) for patients with HFEC-onset seizures recorded on iEEG and 1 (0-3) for patients without HFEC-onset seizures (p = 0.001). Using this scoring model, the odds ratio of identifying HFEC-onset seizures on iEEG was 6.4 for each one-point increment in the aggregate score. The area under the receiver operating characteristic curve for this model was 0.84, suggesting excellent ability of the aggregate score to discriminate between patients with and without HFEC-onset seizures on iEEG. SIGNIFICANCE: Implanting electrodes on the basis of limited supporting presurgical data may be useful in selected patients, especially those with temporal lobe epilepsy, interictal scalp discharges involving the HFEC, or both interictal and ictal scalp discharges involving the HFEC. In addition, our proposed scoring system may be helpful in selecting patients with complicated epilepsy for implantation of an asymmetric number of intracranial electrodes in the hemispheres.

Increased cortical extracellular adenosine correlates with seizure termination.

OBJECTIVE: Seizures are currently defined by their electrographic features. However, neuronal networks are intrinsically dependent on neurotransmitters of which little is known regarding their periictal dynamics. Evidence supports adenosine as having a prominent role in seizure termination, as its administration can terminate and reduce seizures in animal models. Furthermore, microdialysis studies in humans suggest that adenosine is elevated periictally, but the relationship to the seizure is obscured by its temporal measurement limitations. Because electrochemical techniques can provide vastly superior temporal resolution, we test the hypothesis that extracellular adenosine concentrations rise during seizure termination in an animal model and humans using electrochemistry. METHODS: White farm swine (n = 45) were used in an acute cortical model of epilepsy, and 10 human epilepsy patients were studied during intraoperative electrocorticography (ECoG). Wireless Instantaneous Neurotransmitter Concentration Sensor (WINCS)-based fast scan cyclic voltammetry (FSCV) and fixed potential amperometry were obtained utilizing an adenosine-specific triangular waveform or biosensors, respectively. RESULTS: Simultaneous ECoG and electrochemistry demonstrated an average adenosine increase of 260% compared to baseline, at 7.5 ± 16.9 s with amperometry (n = 75 events) and 2.6 ± 11.2 s with FSCV (n = 15 events) prior to electrographic seizure termination. In agreement with these animal data, adenosine elevation prior to seizure termination in a human patient utilizing FSCV was also seen. SIGNIFICANCE: Simultaneous ECoG and electrochemical recording supports the hypothesis that adenosine rises prior to seizure termination, suggesting that adenosine itself may be responsible for seizure termination. Future work using intraoperative WINCS-based FSCV recording may help to elucidate the precise relationship between adenosine and seizure termination.

Network oscillations modulate interictal epileptiform spike rate during human memory.

Eleven patients being evaluated with intracranial electroencephalography for medically resistant temporal lobe epilepsy participated in a visual recognition memory task. Interictal epileptiform spikes were manually marked and their rate of occurrence compared between baseline and three 2 s periods spanning a 6 s viewing period. During successful, but not unsuccessful, encoding of the images there was a significant reduction in interictal epileptiform spike rate in the amygdala, hippocampus, and temporal cortex. During the earliest encoding period (0-2000 ms after image presentation) in these trials there was a widespread decrease in the power of theta, alpha and beta band local field potential oscillations that coincided with emergent focal gamma frequency activity. Interictal epileptiform spike rate correlated with spectral band power changes and broadband (4-150 Hz) desynchronization, which predicted significant reduction in interictal epileptiform spike rate. Spike-triggered averaging of the field potential power spectrum detected a burst of low frequency synchronization 200 ms before the interictal epileptiform spikes that arose during this period of encoding. We conclude that interictal epileptiform spikes are modulated by the patterns of network oscillatory activity that accompany human memory offering a new mechanistic insight into the interplay of cognitive processing, local field potential dynamics and interictal epileptiform spike generation.

Resection of cervical ependymoma.

Intramedullary ependymomas are surgically curable tumors. However, their surgical resection poses several challenges. In this intraoperative video we illustrate the main steps for the surgical resection of a cervical intramedullary ependymoma. These critical steps include: adequate exposure of the entire length of the tumor; use of the intraoperative ultrasound; identification of the posterior median sulcus and separation of the posterior columns; Identification of the plane between the spinal cord and the tumor; mobilization and debulking of the tumor and disconnection of the vascular supply (usually from small anterior spinal artery branches). Following these basic steps a complete resection can be safely achieved in many cases. The video can be found here: http://youtu.be/QMYXC_F4O4U.

Implantation accuracy of novel polyimide stereotactic electroencephalographic depth electrodes-a human cadaveric study.

Introduction: Stereoelectroencephalography (sEEG) is a minimally invasive procedure that uses depth electrodes stereotactically implanted into brain structures to map the origin and propagation of seizures in epileptic patients. Implantation accuracy of sEEG electrodes plays a critical role in the safety and efficacy of the procedure. This study used human cadaver heads, simulating clinical practice, to evaluate (1) neurosurgeon's ability to implant a new thin-film polyimide sEEG electrode according to the instructions for use (IFU), and (2) implantation accuracy. Methods: Four neurosurgeons (users) implanted 24 sEEG electrodes into two cadaver heads with the aid of the ROSA robotic system. Usability was evaluated using a questionnaire that assessed completion of all procedure steps per IFU and user errors. For implantation accuracy evaluation, planned electrode trajectories were compared with post-implantation trajectories after fusion of pre- and postoperative computer tomography (CT) images. Implantation accuracy was quantified using the Euclidean distance for entry point error (EPE) and target point error (TPE). Results: All sEEG electrodes were successfully placed following the IFU without user errors, and post-implant survey of users showed favorable handling characteristics. The EPE was 1.28 ± 0.86 mm and TPE was 1.61 ± 0.89 mm. Long trajectories (>50 mm) had significantly larger EPEs and TPEs than short trajectories (<50 mm), and no differences were found between orthogonal and oblique trajectories. Accuracies were similar or superior to those reported in the literature when using similar experimental conditions, and in the same range as those reported in patients. Discussion: The results demonstrate that newly developed polyimide sEEG electrodes can be implanted as accurately as similar devices in the marker without user errors when following the IFU in a simulated clinical environment. The human cadaver ex-vivo test system provided a realistic test system, owing to the size, anatomy and similarity of tissue composition to that of the live human brain.

Surgical management of malignant melanotic nerve sheath tumors: an institutional experience and systematic review of the literature.

OBJECTIVE: Malignant melanotic nerve sheath tumors are rare tumors characterized by neoplastic melanin-producing Schwann cells. In this study, the authors report their institution's experience in treating spinal and peripheral malignant melanotic nerve sheath tumors and compare their results with the literature. METHODS: Data were collected from 8 patients who underwent surgical treatment for malignant melanotic nerve sheath tumors between 1996 and 2023 at Mayo Clinic and 63 patients from the literature. Time-to-event analyses were performed for the combined group of 71 cases to evaluate the risk of recurrence, metastasis, and death based on tumor location and type of treatment received. Unpaired 2-sample t-tests and Fisher's exact tests were used to determine statistical significance between groups. RESULTS: Between 1996 and 2023, 8 patients with malignant melanotic nerve sheath tumors underwent surgery at the authors' institution, while 63 patients were identified in the literature. The authors' patients and those in the literature had the same mean age at diagnosis (43 years). At the authors' institution, 5 patients (63%) experienced metastasis, 6 patients (75%) experienced long-term recurrence, and 5 patients (62.5%) died. In the literature, most patients (60.3%) were males, with a peak incidence between the 4th and 5th decades of life. Nineteen patients (31.1%) were diagnosed with Carney complex. Nerve root tumors accounted for most presentations (n = 39, 61.9%). Moreover, 24 patients (38.1%) had intradural lesions, with 54.2% (n = 13) being intramedullary and 45.8% (n = 11) extramedullary. Most patients underwent gross-total resection (GTR) (n = 41, 66.1%), followed by subtotal resection (STR) (n = 12, 19.4%), STR with radiation therapy (9.7%), and GTR with radiation therapy (4.8%). Sixteen patients (27.6%) experienced metastasis, 23 (39.7%) experienced recurrence, and 13 (22%) died. Kaplan-Meier analyses showed no significant differences among treatment approaches in terms of recurrence-free, metastasis-free, and overall survival (p > 0.05). Similar results were obtained when looking at the differences with respect to intradural versus nerve root location of the tumor (p > 0.05). CONCLUSIONS: Malignant melanotic nerve sheath tumors are rare tumors with a high potential for malignancy. They carry a dismal prognosis, with a pooled local recurrence rate of 42%, distant metastasis rate of 27%, and mortality rate of 26%. The findings from this study suggest a trend favoring the use of GTR alone or STR with radiation therapy over STR alone. Mortality was similar regardless, which highlights the need for the development of effective treatment options to improve survival in patients with melanotic schwannomas.

Pathological and physiological high-frequency oscillations in focal human epilepsy.

High-frequency oscillations (HFO; gamma: 40-100 Hz, ripples: 100-200 Hz, and fast ripples: 250-500 Hz) have been widely studied in health and disease. These phenomena may serve as biomarkers for epileptic brain; however, a means of differentiating between pathological and normal physiological HFO is essential. We categorized task-induced physiological HFO during periods of HFO induced by a visual or motor task by measuring frequency, duration, and spectral amplitude of each event in single trial time-frequency spectra and compared them to pathological HFO similarly measured. Pathological HFO had higher mean spectral amplitude, longer mean duration, and lower mean frequency than physiological-induced HFO. In individual patients, support vector machine analysis correctly classified pathological HFO with sensitivities ranging from 70-98% and specificities >90% in all but one patient. In this patient, infrequent high-amplitude HFO were observed in the motor cortex just before movement onset in the motor task. This finding raises the possibility that in epileptic brain physiological-induced gamma can assume higher spectral amplitudes similar to those seen in pathologic HFO. This method if automated and validated could provide a step towards differentiating physiological HFO from pathological HFO and improving localization of epileptogenic brain.

Temporal encephalocele: An epileptogenic focus confirmed by direct intracranial electroencephalography.

Several studies have suggested the epileptogenic potential of temporal encephaloceles. However, there is limited literature describing the results of intracranial EEG monitoring for patients with temporal encephaloceles. We describe a 19 year-old right-handed woman with drug-resistant epilepsy who presented with seizure onset at age 16 in the setting of a left temporal encephalocele where the seizure onset zone was confirmed to be the encephalocele via stereo EEG (sEEG). She had focal impaired awareness seizures occurring weekly that would progress to focal to bilateral tonic-clonic seizures monthly. Imaging showed a left anterior inferior temporal lobe encephalocele and a left choroidal fissure cyst that were stable on repeat imaging. Prolonged scalp recorded video EEG recorded seizures that showed either near simultaneous onset in the bitemporal head regions or a transitional left temporal sharp wave followed by maximum evolution in the left temporal region. Invasive monitoring with sEEG electrodes targeting primarily the left limbic system with one electrode directly in the encephalocele captured seizures with onset in the left temporal pole encephalocele. A limited resection was performed based on the results of the sEEG and except for one seizure in the immediate postop period in the setting of infection, patient remains seizure free at her 4 month follow up. This report describes a case of drug-resistant focal epilepsy where sEEG monitoring confirmed a temporal encephalocele to be the seizure onset zone without simultaneous onset at mesial temporal or other neocortical structures that were sampled. Our findings support the potential for epileptogenicity within an encephalocele with direct intracranial monitoring.

Stereo-EEG localization of midline onset seizures on scalp EEG.

PURPOSE: The objective of this study was to describe the sEEG-defined seizure onset zone (SOZ), seizure semiology, presurgical evaluations, surgical intervention and outcome in patients with midline onset noninvasive phase I monitoring. METHODS: A single center sEEG database was reviewed to identify patients with seizures onset predominantly involving midline electrodes (FZ, CZ, PZ, OZ) on scalp EEG. Data abstracted included clinical factors, seizure semiology graded into lobar segmentation, imaging and electrographic findings, sEEG plan, interventions, and outcome. RESULTS: Twelve patients were identified (8 males, median age of sEEG 28 years) out of 100 cases of sEEG performed from January 2015-September 2019. "Frontal lobe" seizure semiology was the most common. sEEG-defined SOZ were frontal (5), diffuse (1), multifocal (1), frontal and insular (1), frontal and cingulate (1), insular (1), cingulate (1), and mesial temporal (1). CZ and/or FZ scalp EEG changes were present for all patients with SOZ involving the frontal, cingulate, and insular regions. PZ/OZ scalp involvement was present in one patient with mesial temporal SOZ. Four patients underwent a definitive resective or ablative surgery, and the remaining patients underwent a palliative intervention. Of those with follow-up information available, 8/11 had seizure reduction by ≥ 50%, including 4 with an Engel I outcome. No clinical factors were associated with outcome. CONCLUSIONS: SOZ for midline onset seizures from noninvasive phase I monitoring was most commonly in the frontal, cingulate, and insular regions. A complex cortical network between these regions may explain overlap in semiology and scalp EEG findings. While the number rendered seizure-free was limited, a significant proportion experienced a reasonably favorable outcome justifying use of sEEG to identify surgical options in these patients.

Spatiotemporal neuronal correlates of seizure generation in focal epilepsy.

PURPOSE: Focal seizures are thought to reflect simultaneous activation of a large population of neurons within a discrete region of pathologic brain. Resective surgery targeting this focus is an effective treatment in carefully selected patients, but not all. Although in vivo recordings of single-neuron (i.e., "unit") activity in patients with epilepsy have a long history, no studies have examined long-term firing rates leading into seizures and the spatial relationship of unit activity with respect to the seizure-onset zone. METHODS: Microelectrode arrays recorded action potentials from neurons in mesial temporal structures (often including contralateral mesial temporal structures) in seven patients with mesial temporal lobe epilepsy. KEY FINDINGS: Only 7.6% of microelectrode recordings showed increased firing rates before seizure onset and only 32.4% of microelectrodes showed any seizure-related activity changes. Surprisingly, firing rates on the majority of microelectrodes (67.6%) did not change throughout the seizure, including some microelectrodes located within the seizure-onset zone. Furthermore, changes in firing rate before and at seizure onset were observed on microelectrodes located outside the seizure-onset zone and even in contralateral mesial temporal lobe. These early changes varied from seizure to seizure, demonstrating the heterogeneity of ensemble activity underlying the generation of focal seizures. Increased neuronal synchrony was primarily observed only following seizure onset. SIGNIFICANCE: These results suggest that cellular correlates of seizure initiation and sustained ictal discharge in mesial temporal lobe epilepsy involve a small subset of the neurons within and outside the seizure-onset zone. These results further suggest that the "epileptic ensemble or network" responsible for seizure generation are more complex and heterogeneous than previously thought and that future studies may find mechanistic insights and therapeutic treatments outside the clinical seizure-onset zone.

Strategies to decrease the risk of ventricular catheter infections: a review of the evidence.

The use of antibiotic-coated external ventricular catheters has been controversial among practitioners; although several papers have documented decreased adherence of microbes to catheters treated with antibiotics, there is no universally accepted practice standard for the use of coated catheters for the prevention of clinical infection. In this paper, we review the in vivo and in vitro evidence for antibiotic-coated catheters.