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.

Moyamoya disease in a primarily white, midwestern US population: increased prevalence of autoimmune disease.

BACKGROUND AND PURPOSE: Moyamoya disease is an uncommon, cerebrovascular occlusive disease of unknown pathogenesis. Previously described Moyamoya cohorts include predominantly Asian populations or ethnically diverse North American cohorts. To gain further insight into the pathogenesis of moyamoya, we examined clinical characteristics of a primarily white, Midwestern US population METHODS: Retrospective analysis of patients with angiographically confirmed moyamoya disease evaluated at our institution was performed. Prevalence of comorbidities, cerebrovascular risk factors, and autoimmune diseases were compared with the general population. RESULTS: Ninety-four patients with moyamoya were evaluated; 72.3% were female. Ethnic composition was primarily white (85%). A significantly higher prevalence of autoimmune disease was seen, particularly type 1 diabetes mellitus (8.5% versus 0.4% in the general population) and thyroid disease (17.0% versus 8.0% in the institutional general patient population). Hyperlipidemia was also increased (27.7% versus 16.3% in the general population). CONCLUSIONS: This study of a unique, primarily white, Midwestern population of moyamoya patients demonstrates a significantly higher prevalence of autoimmune disease than in the general population. This supports a possible autoimmune component to the pathogenesis of moyamoya disease.

The predictive value of serum myeloperoxidase for vasospasm in patients with aneurysmal subarachnoid hemorrhage.

Vasospasm is a major contributor to morbidity and mortality in aneurysmal subarachnoid hemorrhage (SAH), with inflammation playing a key role in its pathophysiology. Myeloperoxidase (MPO), an inflammatory marker, was examined as a potential marker of vasospasm in patients with SAH. Daily serum samples from patients with aneurysmal SAH were assayed for MPO, and transcranial Doppler (TCDs) and neurological exams were assessed to determine vasospasm. Suspected vasospasm was confirmed by angiography. Peak MPO levels were then compared with timing of onset of vasospasm, based on clinical exams, TCDs and cerebral angiography. Patients with vasospasm had a mean MPO level of 115.5 ng/ml, compared to 59.4 ng/ml in those without vasospasm, 42.0 ng/ml in those with unruptured aneurysms, and 4.3 ng/ml in normal controls. In patients who experienced vasospasm, MPO was elevated above the threshold on the day of, or at any point prior to, vasospasm in 10 of 15 events (66.7%), and on the day of, or within 2 days prior to, vasospasm in 8 of 15 events (53.3%). Elevated serum MPO correlates with clinically evident vasospasm following aneurysmal SAH. The potential utility of MPO as a marker of vasospasm is discussed.

Preoperative embolization of the external carotid artery branches as an adjunct to superficial temporal artery-to-middle cerebral artery bypass.

When technically feasible, the preferred revascularization procedure in patients with adult moyamoya disease is a superficial temporal artery-to-middle cerebral artery (STA-MCA) bypass. The caliber of the STA has been reported as a prognostic factor for a successful bypass, with smaller-caliber STA being more likely to fail. We describe a novel approach to this circumstance in which preoperative embolization of external carotid artery (ECA) branches is used to augment blood flow through a small STA as a prelude to bypass surgery. We report 2 cases: a 42-year-old female presenting with symptomatic ischemic and radiographically progressive moyamoya disease and a 23-year-old female presenting with advanced moyamoya disease secondary to diabetes. Preoperative angiography demonstrated small-caliber STAs in each case, and primary revascularization was deemed difficult. Preoperative ECA embolization was undertaken to shunt blood toward the STA, thereby increasing its flow and caliber. In both cases, angiography after embolization demonstrated a 20%-45% increase in STA size, and doppler ultrasound indicated a 14%-50% increase in flow. Subsequently, both patients underwent successful STA-MCA bypass combined with encephalomyosynangiosis without complications. Of 167 STA-MCA bypasses performed by the senior author, embolization was performed in 7 unique patients on 9 sides. ECA embolization may be a beneficial adjunct when considering a direct bypass in the setting of a small STA. It can increase blood flow through the STA, making the operation technically easier and enhancing the patency of the bypass.

CyberKnife radiosurgical rhizotomy for the treatment of atypical trigeminal nerve pain.

OBJECT: Patients with atypical trigeminal neuralgia (TN) have unilateral pain in the trigeminal distribution that is dull, aching, or burning in nature and is constant or nearly constant. Studies of most radiosurgical and surgical series have shown lower response rates in patients with atypical TN. This study represents the first report of the treatment of atypical TN with frameless CyberKnife stereotactic radiosurgery (SRS). METHODS: Between 2002 and 2007, 7 patients that satisfied the criteria for atypical TN and underwent SRS were included in our study. A 6-8-mm segment of the trigeminal nerve was targeted, excluding the proximal 3 mm at the brainstem. All patients were treated in a single session with a median maximum dose of 78 Gy and a median marginal dose of 64 Gy. RESULTS: Outcomes in 7 patients with a mean age of 61.6 years and a median follow-up of 20 months are reported. Following SRS, 4 patients had complete pain relief, 2 had minimal pain relief with some decrease in the intensity of their pain, and 1 patient experienced no pain relief. Pain relief was reported within 1 week of SRS in 4 patients and at 4 months in 2 patients. After a median follow-up of 28 months, pain did not recur in any of the 4 patients who had reported complete pain relief. Complications after SRS included bothersome numbness in 3 patients and significant dysesthesias in 1 patient. CONCLUSIONS: The authors have previously reported a 90% rate of excellent pain relief in patients with classic TN treated with CyberKnife SRS. Compared with patients with classic TN, patients with atypical TN have a lower rate of pain relief. Nevertheless, the nearly 60% rate of success after SRS achieved in this study is still comparable to or better than results achieved with any other treatment modality for atypical TN.

Repeat resective surgery in complex pediatric refractory epilepsy: lessons learned.

OBJECT Resection can sometimes offer the best chance of meaningful seizure reduction in children with medically intractable epilepsy. However, when surgery fails to achieve the desired outcome, reoperation may be an option. The authors sought to investigate outcomes following resective reoperation in pediatric patients with refractory epilepsy, excluding tumoral epilepsies. Differences in preoperative workup between surgeries are analyzed to identify factors influencing outcomes and complications in this complex group. METHODS Medical records were reviewed for all pediatric patients undergoing a repeat resective surgery for refractory epilepsy at the authors' institution between 2005 and 2012. Tumor and vascular etiologies were excluded. Preoperative evaluation and outcomes were analyzed for each surgery and compared. RESULTS Ten patients met all inclusion criteria. The median age at seizure onset was 4.5 months. Preoperative MRI revealed no lesion in 30%. Nonspecific gliosis and cortical dysplasia were the most common pathologies. The majority of preoperative workups included MRI, video-electroencephalography (EEG), and SISCOM. Intracranial EEG was performed for 60% for the first presurgical evaluation and 70% for the second evaluation. The goal of surgery was palliative in 4 patients with widespread cortical dysplasia. The final Engel outcome was Class I in 50%. The rate of favorable outcome (Engel Class I-II) was 70%. The complication rate for the initial surgery was 10%. However, the rate increased to 50% with the second surgery, and 3 of these 5 complications were pseudomeningoceles requiring shunt placement (2 of the 3 patients underwent hemispherotomy). CONCLUSIONS Resective reoperation for pediatric refractory epilepsy has a high rate of favorable outcome and should be considered in appropriate candidates, even as a palliative measure. Intracranial EEG monitoring should be considered on initial workup in cases where the results of imaging or EEG studies are ambiguous or conflicting. Epilepsy secondary to cortical dysplasia, especially if the dysplasia is not seen clearly on MRI, can be difficult to cure surgically. Therefore, in these cases, as large a resection as can be safely accomplished should be done, particularly when the goal is palliative. The rate of complications, particularly pseudomeningocele ultimately requiring shunt placement, is much higher following reoperation, and patients should be counseled accordingly.

Intravenous recording of intracranial, broadband EEG.

The most direct evaluation of human brain activity has been obtained from intracranial electrodes placed either on the surface of the brain or inserted into the brain to record from deep brain structures. Currently, the placement of intracranial electrodes implies transcranial surgery, either through a burr hole or a craniotomy, but the high degree of invasiveness and potential for morbidity of such major surgical procedures limits the applicability of intracranial recording. The vascular system provides a natural avenue to reach many brain regions that currently are reached by transcranial approaches, along with deep brain structures that cannot be reached via a transcranial approach without significant risk. To determine the applicability of intravascular approaches to high-frequency intracranial monitoring, a catheter containing multiple macro- and micro-electrodes was placed into the superior sagittal sinus of anesthetized pigs in parallel with clinical, subdural electrode grids to record epileptiform activity induced by direct, cortical injection of penicillin and to record responses to electrical stimulation. Intravascular electrodes recorded epileptiform spikes with similar magnitudes and waveshapes to those obtained by surface electrodes, both for macroelectrodes and microelectrodes, including the spatiotemporal evolution of epileptiform activity, suggesting that intravascular electrodes might provide localizing information regarding seizure foci. Sinusoidal electrical stimulation showed that intravascular electrodes provide sufficient broadband fidelity to record high-frequency, physiological events that may also prove useful in localizing seizure onset zones. As intravascular techniques have transformed cardiology, so intravascular neurophysiology may transform intracranial monitoring, in general, and the treatment of epilepsy, in particular.

Surgical outcomes and predictors of stroke in a North American white and African American moyamoya population.

BACKGROUND: The majority of moyamoya surgical series have been confined to Asian and pediatric populations. Few have studied demographics, risk factors, and outcomes in adult North American populations. OBJECTIVE: To examine outcomes after revascularization for moyamoya in white and African American adults and to assess for predictors of recurrent stroke. METHODS: A retrospective review of 75 non-Asian patients undergoing 110 procedures at the Mayo Clinic was performed. Demographics, known moyamoya associations, cerebrovascular risk factors, and autoimmune diseases were recorded. Primary outcomes for vascular events were assessed with Kaplan-Meier analysis. Fisher exact methods were used to evaluate for associations with recurrent events. RESULTS: Mean age was 42 years, and mean follow-up was 47 months. Seventy-one of the 75 patients were white. The majority had bilateral disease (n = 49). Perioperative ischemic events occurred in 5 patients (4.5%). The 5- and 10-year event rates were 5.8% and 9.9%. Significant associations were found with a history of thyroid disease (P = .05) and recurrent stroke. A trend was also found between hypertension and autoimmune disease with recurrent stroke. CONCLUSION: Outcomes were favorable with revascularization in this subset with moyamoya. A significant association between a history of thyroid disease and recurrent stroke was found. Additionally, high prevalences of autoimmune disease, hypertension, and thyroid disease were found in our cohort, suggesting that they may play a role in the pathophysiology and progression of moyamoya disease in this population. A new classification for moyamoya is proposed based on these data.

Seizure outcomes after corpus callosotomy for drop attacks.

BACKGROUND: Medically intractable epilepsy involving drop attacks can be difficult to manage and negatively affect quality of life. Most studies investigating the effect of corpus callosotomy (CC) on seizures have been limited, focusing on the pediatric population or drop seizures alone, with little attention to other factors influencing seizure outcome. OBJECTIVE: To assess seizure outcomes after CC in adults and children. METHODS: Retrospective analysis was performed on all patients who underwent CC (anterior two thirds, 1- or 2-stage complete) at our institution between 1990 and 2011. Change in frequency after CC was assessed for drop seizures and other seizure types. Multiple factors were evaluated for impact on seizure outcome. RESULTS: Fifty patients met inclusion criteria. The median age was 1.5 years at seizure onset and 17 years at time of surgery. Anterior two-thirds CC was performed in 28 patients, 1-stage complete in 17, and 2-stage complete in 5. All 3 groups experienced a significant decrease in drop seizures (P < .001, P < .001, and P = .020, respectively), with 40% experiencing complete resolution, and 64% dropping at least 1 frequency category. Other seizure types significantly decreased in anterior two-thirds CC and 1-stage complete (P = .0035, P = .001, respectively). Younger age at surgery correlated with better seizure outcomes (P = .043). CONCLUSION: CC for medically refractory generalizing epilepsy is effective for both drop seizures and other seizure types. CC should be considered soon after a patient has been deemed medically refractory because earlier age at surgery results in lower risk and better outcome.

Intracranial phosphaturic mesenchymal tumor, mixed connective tissue variant presenting without oncogenic osteomalacia.

BACKGROUND: Phosphaturic mesenchymal tumor, mixed connective tissue variant (PMTMCT) is a rare tumor typically occurring in soft tissues and bone, causing oncogenic (tumor-induced) osteomalacia (TIO) through secretion of the phosphaturic hormone, fibroblast growth factor-23 (FGF-23). Rare tumors identical to PMTMCT occur without known TIO. Intracranial localization of PMTMCT is extremely rare, with only two cases reported in the literature. We present a very unusual case of a patient with an intracranial PMTMCT that presented with neurologic changes without osteomalacia. CASE DESCRIPTION: A 67-year-old woman presented with progressive incontinence, apathy, and abulia after having undergone a total knee replacement 1 month earlier. Imaging disclosed a large left frontal anterior fossa mass. She underwent uncomplicated surgical resection of this tumor. Surprisingly, histopathology suggested PMTMCT. Reverse transcription polymerase chain reaction (RT-PCR) assay demonstrating FGF-23 expression in the tumor confirmed the diagnosis. Serum FGF-23 levels postoperatively were normal and she had no clinical or laboratory evidence of osteomalacia or phosphaturia. CONCLUSION: This report should serve to alert clinicians to the possibility that PMTMCT can be included in the differential diagnosis of intracranial masses even in the absence of tumor-induced osteomalacia.