Publications

Patients with shunted hydrocephalus presenting with altered mental status and ventriculomegaly are generally considered to be in shunt failure requiring surgical treatment. The authors describe a case of shunted hydrocephalus secondary to a disseminated neuroectodermal tumor in a pediatric patient in whom rapid fluctuations in sodium levels due to diabetes insipidus repeatedly led to significant changes in ventricle size, with invasively confirmed normal shunt function and low intracranial pressure. This clinical picture exactly mimics shunt malfunction, requires urgent nonsurgical therapy, and underscores the importance of considering serum osmolar abnormalities in the differential diagnosis for ventriculomegaly.

Focal cortical dysplasia (FCD) causes medically intractable seizures in 5-10% of adult epilepsy patients, but patients can become seizure free through surgical resection. The authors present the utility of three-dimensional surface visualization (3DSV) that expands on existing imaging datasets to highlight surface vasculature as a tool for achieving more successful resections in patients with FCD. In this prospective series of six patients, preoperative 3DSV was performed for planning the surgical approach to the lesion and for intraoperative guidance. Reconstructions involved volume rendering of a contrast-enhanced dataset to visualize surface venous vasculature. Postoperatively, five of the six patients had complete resections, with one patient having a subtotal resection due to proximity to crucial vasculature. We report that 3DSV is a useful tool for surgical planning, since topographical relationships between lesion location and surface vasculature landmarks are less likely to change with surgical progress.

This article describes the basis for neuromodulation procedures for obsessive-compulsive disorder (OCD) and summarizes the literature on the efficacy of these interventions. Discussion includes neural circuitry underlying OCD pathology, the history and types of ablative procedures, the targets and modalities used for neuromodulation, and future therapeutic directions.

OBJECTIVES: To determine the ability of foramen ovale electrodes (FOEs) to localize epileptogenic foci after inconclusive noninvasive investigations in patients with suspected mesial temporal lobe epilepsy (MTLE).

METHODS: We identified patients with medically intractable epilepsy who had undergone FOE investigation for initial invasive monitoring at our institution between 2005 and 2012. Indications for initiating FOE investigation were grouped into four categories: (1) bilateral anterior temporal ictal activity on scalp electroencephalography (EEG), (2) unclear laterality of scalp EEG onset due to muscle artifact or significant delay following clinical manifestation, (3) discordance between ictal and interictal discharges, and (4) investigation of a specific anatomic abnormality or competing putative focus. The FOE investigation was classified as informative if it provided sufficient evidence to make a treatment decision.

RESULTS: Forty-two consecutive patients underwent FOE investigation, which was informative in 38 patients (90.5%). Of these 38 patients, 24 were determined to be appropriate candidates for resective surgery. Five were localized sufficiently for surgery, but were considered high risk for verbal memory deficit, and nine were deemed poor surgical candidates because of bilateral ictal origins. The remaining 4 of 42 patients had inconclusive FOE studies and were referred for further invasive investigation. Of the 18 patients who underwent resective surgery, 13 (72%) were seizure-free (Engel class I) at last follow-up (mean 22.5 months).

SIGNIFICANCE: More than 90% of our 42 FOE studies provided sufficient evidence to render treatment decisions. When undertaken with an appropriate hypothesis, FOE investigations are a minimally invasive and efficacious means for evaluating patients with suspected MTLE after an inconclusive noninvasive investigation.

OBJECT: Surgical treatment of moyamoya disease in the adult population commonly uses direct revascularization, the superficial temporal artery (STA) to middle cerebral artery (MCA) bypass (STA-MCA). Pial synangiosis, a method of indirect revascularization, has been used in adult patients with moyamoya when STA-MCA bypass was not technically feasible. Although the effectiveness of pial synangiosis has been well described in children, only limited reports have examined its role in adult patients with moyamoya disease. In this study the authors report on their experience with pial synangiosis revascularization for this population.

METHODS: The authors reviewed the clinical and radiographic records of all adult patients (≥ 18 years of age) with moyamoya disease who underwent cerebral revascularization surgery using pial synangiosis at a single institution.

RESULTS: From 1985 to 2010, 66 procedures (6 unilateral, 30 bilateral) were performed on 36 adult patients with moyamoya disease. The mean age at surgery was 28.3 years, and 30 patients were female. Twenty-eight patients (77.8%) presented with transient ischemic attacks (TIAs), 24 (66.7%) with stroke, and 3 (8.3%) with hemorrhage. Preoperative Suzuki stage was III or higher in 50 hemispheres (75.8%) and 3 patients had undergone prior treatments to the affected hemisphere before pial synangiosis surgery. Clinical follow-up was available for an average of 5.8 years (range 0.6-14.1 years), with 26 patients (72.2%) followed for longer than 2 years. Postoperative angiography was available for 24 patients and 46 revascularized hemispheres, and 39 (84.8%) of the 46 hemispheres demonstrated good collateral formation (Matsushima Grade A or B). Postoperative complications included 3 strokes, 5 TIAs, and 2 seizures, and there was no hemorrhage during the follow-up period. One patient required additional revascularization surgery 8 months after pial synangiosis.

CONCLUSIONS: Pial synangiosis is a safe and durable method of cerebral revascularization in adult patients with moyamoya and can be considered as a potential treatment option for moyamoya disease in adults.

OBJECTIVE: Lesion procedures for psychiatric indications have a history that spans more than a century. This review provides a brief history of psychiatric surgery and addresses the most recent literature on lesion surgery for the treatment of anxiety and mood disorders.

METHODS: Relevant data described in publications from the early 1900 s through the modern era regarding lesion procedures for psychiatric indications, both historical and current use, are reported.

RESULTS: The early procedures of Burkhardt, Moniz, and Freeman are reviewed, followed by descriptions of the more refined techniques of Leksell, Knight, Foltz, White, and Kelly. The application of lesion procedures to obsessive-compulsive disorder, mood disorders, and addiction are discussed.

CONCLUSIONS: Lesioning procedures have informed modern deep brain stimulation targets. Recent lesioning studies demonstrate the efficacy and durability of these procedures in severely disabled patients. Judicious application of these techniques should continue for appropriately selected patients with severe, refractory psychiatric disorders.

OBJECT: Recurrence after endovascular coiling of intracranial aneurysms is reported in up to 42% of cases and is attributed to the lack of endothelialization across the neck. In this study the authors used a novel tissue engineering approach to promote endothelialization by seeding endothelial progenitor cells (EPCs) within a fibrin polymer injected endovascularly into the aneurysm.

METHODS: Experimental aneurysms were created in New Zealand White rabbits and were left untreated, surgically clipped, or embolized with platinum coils, fibrin biopolymer alone, or fibrin combined with autologous cultured EPCs.

RESULTS: In aneurysms treated with EPCs, a confluent monolayer of endothelial cells with underlying neointima was demonstrated across the neck at 16 weeks posttreatment, which was not observed with aneurysms treated using the other methods.

CONCLUSIONS: This novel technique may address reasons for the limited durability of standard coil embolization and provides further avenues for the development of improved devices for the care of patients with aneurysms.

OBJECTIVE: The posterior meningeal artery (PMA) normally arises from the vertebral artery; however, its origin varies considerably as the result of its embryological development. This gains clinical significance when associated with vascular pathology.

CLINICAL PRESENTATION: A 65-year-old man presented to his local hospital with a sudden-onset, severe headache. Computed tomography of the head revealed diffuse subarachnoid hemorrhage, mostly in the left posterior fossa. A computed tomographic angiogram demonstrated an anomalous origin of the PMA from the posteroinferior cerebellar artery (PICA). Cerebral angiography showed the PICA to be enlarged, with a reduced caliber at the takeoff of the PMA, which is consistent with possible dissection.

INTERVENTION: The patient was taken to the operating room for trapping of the dissecting segment of the PMA. A clip was placed across the PMA at its origin from the PICA, and the vessel was coagulated and transected. The PICA was wrapped in muslin gauze.

CONCLUSION: The variable origin of the PMA and PICA may be the result of the persistence of embryological anastomoses between the arteries, with regression of the normal channel. Physical stress at the junction of the anomalous PMA and the PICA may have contributed to the abnormality of the PMA, consistent with possible dissection. Because the PMA has multiple anastomoses with the arteries of the falx cerebri, the proximal PMA may be occluded with no compromise to its vascular territory.

Drug targeting of adult stem cells has been proposed as a strategy for regenerative medicine, but very few drugs are known to target stem cell populations in vivo. Mesenchymal stem/progenitor cells (MSCs) are a multipotent population of cells that can differentiate into muscle, bone, fat, and other cell types in context-specific manners. Bortezomib (Bzb) is a clinically available proteasome inhibitor used in the treatment of multiple myeloma. Here, we show that Bzb induces MSCs to preferentially undergo osteoblastic differentiation, in part by modulation of the bone-specifying transcription factor runt-related transcription factor 2 (Runx-2) in mice. Mice implanted with MSCs showed increased ectopic ossicle and bone formation when recipients received low doses of Bzb. Furthermore, this treatment increased bone formation and rescued bone loss in a mouse model of osteoporosis. Thus, we show that a tissue-resident adult stem cell population in vivo can be pharmacologically modified to promote a regenerative function in adult animals.

Treatment of large defects requires the harvest of fresh living bone from the iliac crest. Harvest of this limited supply of bone is accompanied by extreme pain and morbidity. This has prompted the exploration of other alternatives to generate new bone using traditional principles of tissue engineering, wherein harvested cells are combined with porous scaffolds and stimulated with exogenous mitogens and morphogens in vitro and/or in vivo. We now show that large volumes of bone can be engineered in a predictable manner, without the need for cell transplantation and growth factor administration. The crux of the approach lies in the deliberate creation and manipulation of an artificial space (bioreactor) between the tibia and the periosteum, a mesenchymal layer rich in pluripotent cells, in such a way that the body's healing mechanism is leveraged in the engineering of neotissue. Using the "in vivo bioreactor" in New Zealand White rabbits, we have engineered bone that is biomechanically identical to native bone. The neobone formation followed predominantly an intramembraneous path, with woven bone matrix subsequently maturing into fully mineralized compact bone exhibiting all of the histological markers and mechanical properties of native bone. We harvested the bone after 6 weeks and transplanted it into contralateral tibial defects, resulting in complete integration after 6 weeks with no apparent morbidity at the donor site. Furthermore, in a proof-of-principle study, we have shown that by inhibiting angiogenesis and promoting a more hypoxic environment within the "in vivo bioreactor space," cartilage formation can be exclusively promoted.