Intraoperative neuromonitoring potentials and evidence of preserved neuronal circuitry below the anatomical and functional level in patients with complex spinal dysraphism undergoing detethering reoperations.

OBJECTIVE: Spina bifida represents one of the most common birth defects, occurring in approximately 1-2 children per 1000 live births worldwide. The functional level of patients with spina bifida is highly variable and believed to be correlated with the anatomical level of the lesion. The variable clinical picture is well established, but the correlation with anatomical level and intraoperative neuromonitoring (IONM) data has not been investigated. Furthermore, the potential for preserving function beyond the apparent clinical level has also not been investigated. The objective of this research was to determine the presence and level of intraoperative transcranial motor evoked potential (tcMEP) and triggered electromyography (tEMG) responses, and the association of these responses with preoperative clinical function and radiographic data in pediatric cases of complex tethered cord release reoperations. METHODS: A single-center retrospective review of pediatric patients with complex spinal dysraphism undergoing detethering reoperations was conducted. Preoperative demographic and clinical data, including the radiographic and clinical level of dysraphism, were collected. IONM, including tcMEPs and tEMG responses, were obtained and compared with preoperative clinical data. Descriptive analysis was performed, by patient for demographics and by case for surgeries performed. RESULTS: In 100% of 21 cases of complex detethering reoperations, representing 20 patients, intraoperative tcMEPs could be generated at (4.8%) or below (95.2%) the level of clinical function. Compared with the preoperative clinical examination, 5 cases (23.8%) demonstrated tcMEP responses that were 1 level below the clinical function level, 11 cases (52.4%) were 2 levels below, and 4 cases (19.0%) were 3 levels below. Overall, 18 of 21 cases showed tEMG responses at or below the level of clinical function; of these, 7 cases (33%) were 1 level below and 3 (14%) were ≥ 2 levels below the clinical function level. CONCLUSIONS: The presence of positive stimulation potentials below the level of clinical function in patients with complex spinal dysraphism undergoing detethering reoperations indicates a degree of preserved neuronal connectivity. These findings suggest novel future treatment approaches for these patients, including using devices targeted to stimulation of these neurological pathways.

Electrophysiology of Sensory and Motor Nerve Root Fibers in Selective Dorsal Rhizotomies.

AIMS: Spasticity remains a major impediment in the treatment of cerebral palsy (CP). The single-level selective dorsal rhizotomy (SDR) is a minimally invasive intervention that reduces spasticity in select patients. We provide a descriptive set of normative data that practitioners can utilize to help guide the single-level SDR procedure, including (1) physiological threshold values used to dissociate ventral from dorsal roots; (2) response characteristics of muscles; (3) descriptions of abnormal physiological responses; and (4) percentage of rootlets transected during surgery. METHODS: We examined data from 38 patients with CP who underwent SDR. Dorsal and ventral roots were classified based on the amplitude of electromyographic (EMG) responses, number of muscles activated, and abnormal response characteristics. RESULTS: Ventral roots activated more muscles at significantly lower stimulus thresholds and demonstrated larger EMG responses than did dorsal roots. Of the transections made, 64.72 ± 1.69% of each rootlet was transected. Ventral and dorsal roots can be readily separated based on a few key physiological characteristics including response thresholds and the spread of muscle activation. It was observed that a threshold of approximately 0.4 mA could be used to dissociate ventral and dorsal roots during surgery. CONCLUSIONS: These data illustrate the range of physiological variance observed while performing SDR in patients with spastic CP. Notably, we encountered outlier patients whose roots demonstrated aberrant response characteristics and displayed uncharacteristically low dorsal root thresholds or abnormally high ventral root thresholds. Practitioners should be prepared to individualize their threshold criteria and customize treatment on a patient-by-patient basis.

Incidence and Risk Factors for Intraoperative Seizures During Elective Craniotomy.

BACKGROUND: Perioperative seizures may affect 1% to 50% of patients undergoing craniotomy and adversely impact outcomes. However, data on intraoperative seizures are limited. This retrospective case-control study investigated the incidence and risk factors for intraoperative seizures during elective supratentorial craniotomy involving evoked potential monitoring. MATERIALS AND METHODS: Patients aged 18 years or above undergoing elective supratentorial craniotomy with evoked potential monitoring who experienced intraoperative seizures at our institution between December 2008 and March 2014 were compared with a control group generated using a random number generator. Six controls were used for each case from among the patients who underwent elective supratentorial craniotomy during the same calendar year. Multivariate analysis was conducted using logistic regression to identify the risk factors for intraoperative seizures. RESULTS: Among the 1916 patients who met the inclusion criteria, 45 (2.3%) had intraoperative seizures. The majority of seizures occurred during burr-hole placement or craniotomy, before lesion manipulation. Timing of seizures relative to motor evoked potential runs and stimulus intensity was variable. Significant risk factors for intraoperative seizures were seizure history (odds ratio [OR], 2.18; 95% confidence interval [CI], 1.07-4.46; P=0.03), diagnosis of brain tumor (OR, 2.41; 95% CI, 1.16-4.19; P=0.02), and temporal craniotomy (OR, 5.18; 95% CI, 2.03-13.25; P=0.001). Intraoperative prophylactic use of phenytoin/fosphenytoin and levetiracetam was protective against seizure (phenytoin/fosphenytoin: OR, 0.12; 95% CI, 0.04-0.35; P<0.001 and levetiracetam: OR, 0.40; 95% CI, 0.17-0.94; P=0.04). Phenytoin/fosphenytoin was more protective than levetiracetam (OR, 0.31; 95% CI, 0.10-0.99; P=0.048). CONCLUSIONS: The overall incidence of intraoperative seizures was 2.3%. Independent risk factors for intraoperative seizures were seizure history, diagnosis of intracranial tumor, and temporal craniotomy. Intraoperative prophylactic anticonvulsant use was protective.

Preoperative Facial Nerve Mapping to Plan and Guide Pediatric Facial Vascular Anomaly Resection.

Importance: Facial vascular anomalies are surgical challenges due to their vascularity and facial nerve distortion. To assist facial vascular anomaly surgical treatment, presurgical percutaneous facial nerve stimulation and recording of compound motor action potentials can be used to map the facial nerve branches. During surgery, the nerve map and continuous intraoperative motor end plate potential monitoring can be used to reduce nerve injury. Objective: To investigate if preoperative facial nerve mapping (FNM) is associated with intraoperative facial nerve injury risk and safe surgical approach options compared with standard nerve integrity monitoring (NIM). Design, Setting, and Participants: This investigation was a historically controlled study at a tertiary vascular anomaly center in Seattle, Washington. Participants were 92 pediatric patients with facial vascular anomalies undergoing definitive anomaly surgery (from January 1, 1999, through January 1, 2015), with 2 years' follow-up. In retrospective review, a consecutive FNM patient cohort after 2005 (FNM group) was compared with a consecutive historical cohort (1999-2005) (NIM group). Main Outcomes and Measures: Postoperative facial nerve function and selected surgical approach. For NIM and FNM comparisons, statistical analysis calculated odds ratios of nerve injury and operative approach, and time-to-event methods analyzed operative time. Results: The NIM group had 31 patients (median age, 3.3 years [interquartile range, 2.2-11.4 years]; 20 [65%] male), and the FNM group had 61 patients (median age, 4.4 years [interquartile range, 1.5-11.0 years]; 26 [43%] male). In both groups, lymphatic malformation resection was most common (19 of 31 [61%] in the NIM group and 32 of 61 [52%] in the FNM group), and the median anomaly volumes were similar (52.4 mL; interquartile range, 12.8-183.3 mL in the NIM group and 65.4 mL; interquartile range, 18.8-180.2 mL in the FNM group). Weakness in the facial nerve branches at 2 years after surgery was more common in the NIM group (6 of 31 [19%]) compared with the FNM group (1 of 61 [2%]) (percentage difference, 17%; 95% CI, 3%-32%). Anterograde facial nerve dissection was used more in the NIM group (27 of 31 [87%]) compared with the FNM group (28 of 61 [46%]) (percentage difference, 41%; 95% CI, 24%-58%). Treatment with retrograde dissection without identification of the main trunk of the facial nerve was performed in 21 of 61 (34%) in the FNM group compared with 0 of 31 (0%) in the NIM group. Operative time was significantly shorter in the FNM group, and patients in the FNM group were more likely to complete surgery sooner (adjusted hazard ratio, 5.36; 95% CI, 2.00-14.36). Conclusions and Relevance: Facial nerve mapping before facial vascular anomaly surgery was associated with less intraoperative facial nerve injury and shorter operative time. Mapping enabled direct identification of individual intralesional and perilesional nerve branches, reducing the need for traditional anterograde facial nerve dissection, and allowed for safe removal of some lesions after partial nerve dissection through transoral or direct excision.

Alternative sites for intraoperative monitoring of cranial nerves X and XII during intracranial surgeries.

During intracranial surgeries, cranial nerve (CN) X is most commonly monitored with electromyographic endotracheal tubes. Electrodes on these endotracheal tubes may be displaced from the vocal folds during positioning, and there is a learning curve for their correct placement. Cranial nerve XII is most commonly monitored with electrodes in the dorsum of the tongue, which are also prone to displacement because of their proximity to the endotracheal tube. A retrospective review was conducted of a consecutive series of 83 skull base surgeries using alternative sites for monitoring CN X and XII. On-going (spontaneous) and evoked electromyography (EMG) were obtained from the cricothyroid muscle for CN X and submental genioglossus for CN XII. Stimulation of CN X or XII evoked specific compound motor action potentials from these muscles, and well-defined on-going EMG was observed during tumor resection in the vicinity of CN X and XII. Volume-conducted responses from the adjacent platysma muscle during CN VII stimulation were identified by concomitant responses from the orbicularis oris and oculi. In conclusion, during skull base surgeries, CN X may be monitored with electrodes in the cricothyroid muscle and CN XII with electrodes in the submental genioglossus. These alternative sites are less prone to displacement of electrodes compared with the more commonly used EMG endotracheal tube and electrodes in the dorsum of the tongue. The cricothyroid muscle should not be used when the recurrent laryngeal nerve is at risk.

Intraoperative neurophysiological monitoring technology: recent advances and evolving uses.

Intraoperative neurophysiological monitoring has evolved over the last 25 years to become an important component of many types of orthopedic and neurosurgical procedures. From its foundations in VIII cranial nerve surgeries and scoliosis corrections surgeries, intraoperative neurophysiological monitoring has expanded to incorporate nearly all spine procedures and many involving the brain and brainstem. Fundamental to this growth in the use of intraoperative neurophysiological monitoring has been the development of the technology used to perform the neurophysiological tests. Advancements in electronics and computer technology have resulted in significant improvements in the capacity, ease of use, quality and reliability of the equipment as well as the quality of and control over the acquired data. These technological advancements have resulted in remarkable improvements in not only the quality and availability of intraoperative neurophysiological monitoring, but also, as a consequence, patient care, and have arguably propelled the expansion of the use that intraoperative neurophysiological monitoring has seen over the last 10 years.

GAT-3 transporters regulate inhibition in the neocortex.

The role of GAT-3 transporters in regulating GABA(A) receptor-mediated inhibition was examined in the rat neocortex using an in vitro slice preparation. Pharmacologically isolated GABA(A) receptor-mediated responses were recorded from layer V neocortical pyramidal cells, and the effects of SNAP-5114, a GAT-3 GABA transporter-selective antagonist, were evaluated. Application of SNAP-5114 resulted in a reversible increase in the amplitude of an evoked GABA(A) response in most cells examined, although no effect on the decay time was observed. Examination of the spontaneous output of inhibitory interneurons revealed a reversible increase in the frequency and amplitude of spontaneous inhibitory synaptic currents as a consequence of GAT-3 inhibition. This effect of GAT-3 inhibition on spontaneous inhibitory events was action potential-dependent because no such increases were observed when SNAP-5114 was applied in the presence of TTX. These results demonstrate that GAT-3 transporters regulate inhibitory interneuron output in the neocortex. The increase in inhibitory interneuron excitability resulting from application of SNAP-5114 suggests that inhibition of GAT-3 transporter function results in a reduction in ambient GABA levels, possibly by a reduction in carrier-mediated GABA release via the GAT-3 transporter.

Presenilin-1 and intracellular calcium stores regulate neuronal glutamate uptake.

Glutamate uptake by high affinity glutamate transporters is essential for preventing excitotoxicity and maintaining normal synaptic function. We have discovered a novel role for presenilin-1 (PS1) as a regulator of glutamate transport. PS1-deficient neurons showed a decrease in glutamate uptake of approximately 50% compared to wild-type neurons. Gamma-secretase inhibitor treatment mimicked the effects of PS1 deficiency on glutamate uptake. PS1 loss-of-function, accomplished by PS1 deficiency or gamma-secretase inhibitor treatment, caused a corresponding decrease in cell surface expression of the neuronal glutamate transporter, EAAC1. PS1 deficiency is known to reduce intracellular calcium stores. To explore the possibility that PS1 influences glutamate uptake via regulation of intracellular calcium stores, we examined the effects of treating neurons with caffeine, thapsigargin, and SKF-96365. These compounds depleted intracellular calcium stores by distinct means. Nonetheless, each treatment mimicked PS1 loss-of-function by impairing glutamate uptake and reducing EAAC1 expression at the cell surface. Blockade of voltage-gated calcium channels, activation and inhibition of protein kinase C (PKC), and protein kinase A (PKA) all had no effect on glutamate uptake in neurons. Taken together, these findings indicate that PS1 and intracellular calcium stores may play a significant role in regulating glutamate uptake and therefore may be important in limiting glutamate toxicity in the brain.

Dynamic influences on coincidence detection in neocortical pyramidal neurons.

The firing rate of neocortical pyramidal neurons is believed to represent primarily the average arrival rate of synaptic inputs; however, it has also been found to vary somewhat depending on the degree of synchrony among synaptic inputs. We investigated the ability of pyramidal neurons to perform coincidence detection, that is, to represent input timing in their firing rate, and explored some factors that influence that representation. We injected computer-generated simulated synaptic inputs into pyramidal neurons during whole-cell recordings, systematically altering the phase delay between two groups of periodic simulated input events. We explored how input intensity, the synaptic time course, inhibitory synaptic conductance, and input jitter influenced the firing rate representation of input timing. In agreement with computer modeling studies, we found that input synchronization increases firing rate when intensity is low but reduces firing rate when intensity is high. At high intensity, the effect of synchrony on firing rate could be switched from reducing to increasing firing rate by shortening the simulated excitatory synaptic time course, adding inhibition (using the dynamic clamp technique), or introducing a small input jitter. These opposite effects of synchrony may serve different computational functions: as a means of increasing firing rate it may be useful for efficient recruitment or for computing a continuous parameter, whereas as a means of decreasing firing rate it may provide gain control, which would allow redundant or excessive input to be ignored. Modulation of dynamic input properties may allow neurons to perform different operations depending on the task at hand.

Synaptically evoked GABA transporter currents in neocortical glia.

The presence, magnitude, and time course of GABA transporter currents were investigated in electrophysiologically characterized neocortical astrocytes in an in vitro slice preparation. On stimulation with a bipolar-tungsten stimulating electrode placed nearby, the majority of cells tested displayed long-lasting GABA transporter currents using both single and repetitive stimulation protocols. Using subtype-specific GABA transporter antagonists, long-lasting GABA transporter currents were identified in neocortical astrocytes that originated from at least two subtypes of GABA transporters: GAT-1 and GAT-2/3. These transporter currents displayed slow rise times and long decay times, contrasting the time course observed for glutamate transporter currents, and are indicative of a long extracellular time course of GABA as well as a role for glial GABA transporters during synaptic transmission.