Scellig Stone

The subcallosal cingulate gyrus in the context of major depression.

The subcallosal cingulate gyrus (SCG), including Brodmann area 25 and parts of 24 and 32, is the portion of the cingulum that lies ventral to the corpus callosum. It constitutes an important node in a network that includes cortical structures, the limbic system, thalamus, hypothalamus, and brainstem nuclei. Imaging studies have shown abnormal SCG metabolic activity in patients with depression, a pattern that is reversed by various antidepressant therapies. The involvement of the SCG in mechanisms of depression and its emerging potential role as a surgical target for deep brain stimulation has focused recent interest in this area. We review anatomic and histologic attributes of the SCG and the morphologic and imaging changes observed in depression. Particular attention is given to the regional and downstream structures that could be influenced by the application of deep brain stimulation in this region.

Stimulation of Entorhinal Cortex Promotes Adult Neurogenesis and Facilitates Spatial Memory

Deep brain stimulation (DBS) is an established therapeutic modality for the treatment of movement disorders and an emerging therapeutic approach for the treatment of disorders of mood and thought. For example, recently we have shown that DBS of the fornix may ameliorate cognitive decline associated with dementia. However, like other applications of DBS, the mechanisms mediating these clinical effects are unknown. As DBS modulates neurophysiological activity in targeted brain regions, DBS might influence cognitive function via activity-dependent regulation of hippocampal neurogenesis. Using stimulation parameters analogous to clinical high-frequency DBS, here we addressed this question in mice. We found that acute stimulation of the entorhinal cortex (EC) transiently promoted proliferation in the dentate gyrus (DG). Cells generated as a consequence of stimulation differentiated into neurons, survived for at least several weeks, and acquired normal dentate granule cell (DGC) morphology. Importantly, stimulation-induced promotion of neurogenesis was limited to the DG and not associated with changes in apoptotic cell death. Using immunohistochemical approaches, we found that, once sufficiently mature, these stimulation-induced neurons integrated into hippocampal circuits supporting water-maze memory. Finally, formation of water-maze memory was facilitated 6 weeks (but not 1 week) after bilateral stimulation of the EC. The delay-dependent nature of these effects matches the maturation-dependent integration of adult-generated DGCs into dentate circuits supporting water-maze memory. Furthermore, because the beneficial effects of EC stimulation were prevented by blocking neurogenesis, this suggests a causal relationship between stimulation-induced promotion of adult neurogenesis and enhanced spatial memory.

Functional Convergence of Developmentally and Adult-Generated Granule Cells in Dentate Gyrus Circuits Supporting Hippocampus-Dependent Memory

In the hippocampus, the production of dentate granule cells (DGCs) persists into adulthood. As adult‐generated neurons are thought to contribute to hippocampal memory processing, promoting adult neurogenesis therefore offers the potential for restoring mnemonic function in the aged or diseased brain. Within this regenerative context, one key issue is whether developmentally generated and adult‐generated DGCs represent functionally equivalent or distinct neuronal populations. To address this, we labeled separate cohorts of developmentally generated and adult‐generated DGCs and used immunohistochemical approaches to compare their integration into circuits supporting hippocampus‐dependent memory in intact mice. First, in the water maze task, rates of integration of adult‐generated DGCs were regulated by maturation, with maximal integration not occurring until DGCs were five or more weeks in age. Second, these rates of integration were equivalent for embryonically, postnatally, and adult‐generated DGCs. Third, these findings generalized to another hippocampus‐dependent task, contextual fear conditioning. Together, these experiments indicate that developmentally generated and adult‐generated DGCs are integrated into hippocampal memory networks at similar rates, and suggest a functional equivalence between DGCs generated at different developmental stages.

Combined endoscopic third ventriculostomy and choroid plexus cauterization as primary treatment for infant hydrocephalus: a prospective North American series

OBJECT Combined endoscopic third ventriculostomy with choroid plexus cauterization (ETV/CPC) enhances the likelihood of shunt freedom over ETV alone, and thus avoidance of shunt-related morbidity, in hydrocephalic infants. To date, virtually all published reports describe experiences in Africa, thus hampering generalization to other parts of the world. Here, the authors report the first North American prospective series of this combined approach to treat hydrocephalus of various etiologies in infants. METHODS A prospective series of 50 boys and 41 girls (mean and median ages 4.7 and 3.2 months, respectively) with hydrocephalus underwent ETV/CPC performed by the senior author at Boston Childrens Hospital from August 2009 through March 2014. Success data were analyzed using the Kaplan-Meier method and Cox proportional hazards model. RESULTS The 91 patients treated included those with aqueductal stenosis (23), myelomeningocele (23), posthemorrhagic hydrocephalus (25), Dandy-Walker complex (6), post-infectious hydrocephalus (6), and other conditions (8). Using Kaplan-Meier survival analysis, 57% of patients required no further hydrocephalus treatment at 1 year. Moreover, 65% remained shunt free to the limit of available follow-up (maximum roughly 4 years). A Cox proportional hazards model identified the following independent predictors of ETV/CPC failure: post-infectious etiology, age at treatment younger than 6 months, prepontine cistern scarring, and prior CSF diversion. Of patients with at least 6 months of follow-up, the overall ETV/CPC success at 6 months (59%) exceeded that predicted by the ETV Success Score (45%). Complications included 1 CSF leak and 1 transient syndrome of inappropriate antidiuretic hormone secretion, and there were no deaths. CONCLUSIONS ETV/CPC is an effective, safe, and durable treatment for infant hydrocephalus in a North American population, with 1-year success rates similar to those reported in Africa and equivalent to those for primary shunt placement in North America. These findings underscore the need for prospective multicenter studies of the outcomes, quality of life, and economic impact of the procedure compared with primary shunt insertion.

Memory rescue and enhanced neurogenesis following electrical stimulation of the anterior thalamus in rats treated with corticosterone.

Deep brain stimulation has been investigated as a treatment for memory disturbance but its mechanisms remain elusive. We show that anterior thalamic nucleus (ATN) stimulation administered to corticosterone-treated rats one month prior to testing improved performance on a delayed non-matching to sample task and increased hippocampal neurogenesis. In contrast, no behavioral changes were observed in animals that were tested a few days after surgery. Results of this study suggests that the behavioral effects of ATN stimulation in corticosterone-treated animals was likely dependent on long-term plastic changes, including the development of newly borne dentate gyrus cells of sufficient functional maturity.

Anterior thalamus deep brain stimulation at high current impairs memory in rats

Deep brain stimulation (DBS) of the anterior thalamic nucleus (AN), an important relay in the circuitry of memory, is currently being proposed as a treatment for epilepsy. Despite the encouraging results with the use of this therapy, potential benefits and adverse effects are yet to be determined. We show that AN stimulation at relatively high current disrupted the acquisition of contextual fear conditioning and impaired performance on a spatial alternating task in rats. This has not been observed at parameters generating a charge density that approximated the one used in clinical practice. At settings that impaired behavior, AN stimulation induced a functional depolarization block nearby the electrode, increased c-Fos expression in cerebral regions projecting to and receiving projections from the AN, and influenced hippocampal activity. This suggests that complex mechanisms might be involved in the effects of AN DBS, including a local target inactivation and the modulation of structures at a distance. Though translating data from animals to humans has to be considered with caution, our study underscores the need for carefully monitoring memory function while selecting stimulation parameters during the clinical evaluation of AN DBS.

The pedunculopontine nucleus and movement disorders: Anatomy and the role for deep brain stimulation

The pedunculopontine nucleus (PPN) is a brainstem locomotive center that also processes sensory and behavioral information. Through its connections with basal ganglia structures and the spinal cord, the PPN may play a role in axial motor symptoms in Parkinsons disease (PD). We review the anatomical features of the PPN, its role in motor control, and its potential role as a target for PD surgery, including the results of recently published clinical studies.

PROSPECTIVE ERROR RECORDING IN SURGERY: AN ANALYSIS OF 1108 ELECTIVE NEUROSURGICAL CASES

OBJECTIVESurgical error is common and contributes to complications for patients, necessitating detailed prospective collection and analysis of error data that emphasizes prevention. METHODSOne neurosurgeon prospectively recorded errors and complications for consecutive patients undergoing elective neurosurgical procedures. Each error was scored for type, severity, preventability, and consequence. RESULTSBetween May 2000 and August 2006, 1108 elective cases were studied, comprising 76.1% cranial, 22.7% spinal, and 1.2% other procedures. There were 2684 errors in 87.1% of cases. The most common errors were technical (27.8%), contamination (25.3%), equipment failure or missing equipment (18.2%), or related to delay (12.5%). Of the errors, 22.6% were considered major and 77.4% were minor, with 2.7% of errors substantially impacting the clinical course of the patient. Of all errors, 78.5% were deemed preventable. Of the complications, 16.7% were related to errors, of which 80.6% were major errors. Of the error-related complications, 74.2% were declared preventable. A propensity for error was identified with cranial procedures and patients with higher American Society of Anesthesiologists scores (P < 0.01). CONCLUSIONSurgical errors are common, often preventable, and frequently lead to clinical impact. In addition, the type of procedure and characteristics of the patient are important factors to consider when addressing surgical error. For individual surgeons to maintain quality control and contribute to the safety of the health care system, they must track and analyze errors to ensure that systems may be developed to prevent their occurrence.

Reopening of an obstructed third ventriculostomy: long-term success and factors affecting outcome in 215 infants

OBJECT The role of reopening an obstructed endoscopic third ventriculostomy (ETV) as treatment for ETV failure is not well defined. The authors studied 215 children with ETV closure who underwent successful repeat ETV to determine the indications, long-term success, and factors affecting outcome. METHODS The authors retrospectively reviewed the CURE Childrens Hospital of Uganda database from August 2001 through December 2012, identifying 215 children with failed ETV (with or without prior choroid plexus cauterization [CPC]) who underwent reopening of an obstructed ETV stoma. Treatment survival according to sex, age at first and second operation, time to failure of first operation, etiology of hydrocephalus, prior CPC, and mode of ETV obstruction (simple stoma closure, second membrane, or cisternal obstruction from arachnoid scarring) were assessed using the Kaplan-Meier survival method. Survival differences among groups were assessed using log-rank and Wilcoxon methods and a Cox proportional hazards model. RESULTS There were 125 boys and 90 girls with mean and median ages of 229 and 92 days, respectively, at the initial ETV. Mean and median ages at repeat ETV were 347 and 180 days, respectively. Postinfectious hydrocephalus (PIH) was the etiology in 126 patients, and nonpostinfectious hydrocephalus (NPIH) in 89. Overall estimated 7-year success for repeat ETV was 51%. Sex (p = 0.46, log-rank test; p = 0.54, Wilcoxon test), age (< vs > 6 months) at initial or repeat ETV (p = 0.08 initial, p = 0.13 repeat; log-rank test), and type of ETV obstruction (p = 0.61, log-rank test) did not affect outcome for repeat ETV (p values ≥ 0.05, Cox regression). Those with a longer time to failure of initial ETV (> 6 months 91%, 3-6 months 60%, < 3 months 42%, p < 0.01; log-rank test), postinfectious etiology (PIH 58% vs NPIH 42%, p = 0.02; log-rank and Wilcoxon tests) and prior CPC (p = 0.03, log-rank and Wilcoxon tests) had significantly better outcome. CONCLUSIONS Repeat ETV was successful in half of the patients overall, and was more successful in association with later failures, prior CPC, and PIH. Obstruction of the original ETV by secondary arachnoid scarring was not a negative prognostic factor, and should not discourage the surgeon from proceeding. Repeat ETV may be a more durable solution to failed ETV/CPC than shunt placement in this context, especially for failures at more than 3 months after the initial ETV. Some ETV closures may result from an inflammatory response that is less robust at the second operation.

Cranial sutures: a multidisciplinary review

IntroductionProgress in cranial suture research is shaping our current understanding of the topic; however, emphasis has been placed on individual contributing components rather than the cranial sutural system as a whole. Improving our holistic view helps further guide clinicians who treat cranial sutural abnormalities as well as researchers who study them.Materials and methodsInformation from anatomy, anthropology, surgery, and computed modeling was integrated to provide a perspective to interpret suture formation and variability within the cranial functional and structural system.ResultsEvidence from experimental settings, simulations, and evolution suggest a multifactorial morphogenetic process associated with functions and morphology of the sutures. Despite molecular influences, the biomechanical cranial environment has a main role in both the ontogenetic and phylogenetic suture dynamics.ConclusionsFurthering our holistic understanding of the intricate cranial sutural system promises to expand our knowledge and enhance our ability to treat associated anomalies.