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David S. Xu and Francisco A. Ponce

OBJECTIVE

The aim of this article is to review the authors’ and published experience with deep brain stimulation (DBS) therapy for the treatment of patients with Alzheimer’s disease (AD) and Parkinson’s disease dementia (PDD).

METHODS

Two targets are current topics of investigation in the treatment of AD and PDD, the fornix and the nucleus basalis of Meynert. The authors reviewed the current published clinical experience with attention to patient selection, biological rationale of therapy, anatomical targeting, and clinical results and adverse events.

RESULTS

A total of 7 clinical studies treating 57 AD patients and 7 PDD patients have been reported. Serious adverse events were reported in 6 (9%) patients; none resulted in death or disability. Most studies were case reports or Phase 1/2 investigations and were not designed to assess treatment efficacy. Isolated patient experiences demonstrating improved clinical response after DBS have been reported, but no significant or consistent cognitive benefits associated with DBS treatment could be identified across larger patient populations.

CONCLUSIONS

PDD and AD are complex clinical entities, with investigation of DBS intervention still in an early phase. Recently published studies demonstrate acceptable surgical safety. For future studies to have adequate power to detect meaningful clinical changes, further refinement is needed in patient selection, metrics of clinical response, and optimal stimulation parameters.

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Robert F. Spetzler and Francisco A. Ponce

Object

The authors propose a 3-tier classification for cerebral arteriovenous malformations (AVMs). The classification is based on the original 5-tier Spetzler-Martin grading system, and reflects the treatment paradigm for these lesions. The implications of this modification in the literature are explored.

Methods

Class A combines Grades I and II AVMs, Class B are Grade III AVMs, and Class C combines Grades IV and V AVMs. Recommended management is surgery for Class A AVMs, multimodality treatment for Class B, and observation for Class C, with exceptions to the latter including recurrent hemorrhages and progressive neurological deficits. To evaluate whether combining grades is warranted from the perspective of surgical outcomes, the 3-tier system was applied to 1476 patients from 7 surgical series in which results were stratified according to Spetzler-Martin grades.

Results

Pairwise comparisons of individual Spetzler-Martin grades in the series analyzed showed the fewest significant differences (p < 0.05) in outcomes between Grades I and II AVMs and between Grades IV and V AVMs. In the pooled data analysis, significant differences in outcomes were found between all grades except IV and V (p = 0.38), and the lowest relative risks were found between Grades I and II (1.066) and between Grades IV and V (1.095). Using the pooled data, the predictive accuracies for surgical outcomes of the 5-tier and 3-tier systems were equivalent (receiver operating characteristic curve area 0.711 and 0.713, respectively).

Conclusions

Combining Grades I and II AVMs and combining Grades IV and V AVMs is justified in part because the differences in surgical results between these respective pairs are small. The proposed 3-tier classification of AVMs offers simplification of the Spetzler-Martin system, provides a guide to treatment, and is predictive of outcome. The revised classification not only simplifies treatment recommendations; by placing patients into 3 as opposed to 5 groups, statistical power is markedly increased for series comparisons.

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Patrick P. Han, Francisco A. Ponce and Robert F. Spetzler

Object. In this study the authors quantified a subgroup of patients with Spetzler—Martin Grades IV and V arteriovenous malformations (AVMs) recommended for complete, partial, or no treatment, and calculated the retrospective hemorrhage rate for these lesions.

Methods. Between July 1997 and May 2000, 73 consecutive patients with Grades IV and V AVMs were evaluated prospectively by the cerebrovascular team at Barrow Neurological Institute. Treatment recommendations given to the patients or referring physicians were classified as complete treatment, partial treatment, and no treatment. Retrospectively, the hemorrhage rates associated with these treatment groups were also calculated.

In the prospective portion of the study (the intention-to-treat analysis), no treatment of the AVM, was recommended for 55 patients (75%) and partial treatment was recommended for seven patients (10%). Aneurysms associated with an AVM were obliterated by surgical or endovascular treatment in seven patients (10%), and complete surgical removal was recommended for four patients (5%). The overall hemorrhage rate for Grades IV and V AVMs was 1.5% per year. The annual risk of hemorrhage was 10.4% among patients who previously had received incomplete treatment, compared with patients without previous treatment.

Conclusions. The hemorrhage risk of 1.5% per year, which was associated with Grades IV and V AVMs appears to be lower than that reported for Grades I through III AVMs. The authors recommend that no treatment be given for most Grades IV and V AVMs. No evidence indicates that partial treatment of an AVM reduces a patient's risk of hemorrhage. In fact, partial treatment may worsen the natural history of an AVM. The authors do not support palliative treatment of AVMs, except in the specific circumstances of arterial or intranidal aneurysms or progressive neurological deficits related to vascular steal. Complete treatment is warranted for patients with progressive neurological deficits caused by hemorrhage of the AVM. This selection process plays a significant role in the relatively low combined morbidity and mortality rates for Grade IV and Grade V AVMs (17 and 22%, respectively) reported by the cerebrovascular group in both retrospective and prospective studies.

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Francisco A. Ponce and Andres M. Lozano

Object

The number of citations a published article receives is a measure of its impact in the scientific community. This study identifies and characterizes the current 100 top-cited articles in journals specifically dedicated to neurosurgery.

Methods

Neurosurgical journals were identified using the Institute for Scientific Information Journal Citation Reports. A search was performed using Institute for Scientific Information Web of Science for articles appearing in each of these journals. The 100 top-cited articles were selected and analyzed.

Results

The 100 most cited manuscripts in neurosurgical journals appeared in 3 of 13 journals dedicated to neurosurgery. These included 79 in the Journal of Neurosurgery, 11 in the Journal of Neurology, Neurosurgery and Psychiatry, and 10 in Neurosurgery. The individual citation counts for these articles ranged from 287 to 1515. Seventy-seven percent of articles were published between 1976 and 1995. Representation varied widely across neurosurgical disciplines, with cerebrovascular diseases leading (43 articles), followed by trauma (27 articles), stereotactic and functional neurosurgery (13 articles), and neurooncology (12 articles). The study types included 5 randomized trials, 5 cooperative studies, 1 observational cohort study, 69 case series, 8 review articles, and 12 animal studies. Thirty articles dealt with surgical management and 12 with nonsurgical management. There were 15 studies of natural history of disease or outcomes after trauma, 11 classification or grading scales, and 10 studies of human pathophysiology.

Conclusions

The most cited articles in neurosurgical journals are trials evaluating surgical or medical therapies, descriptions of novel techniques, or systems for classifying or grading disease. The time of publication, field of study, nature of the work, and the journal in which the work appears are possible determinants of the likelihood of citation and impact.

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Francisco A. Ponce and Andres M. Lozano

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Francisco A. Ponce, Kelly D. Foote and Andres M. Lozano

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Francisco A. Ponce and Andres M. Lozano

Object

The authors undertook a study to estimate the relative academic impact of neurosurgical departments in Canada and the US using the h index, a measure of the number of citations received by a collection of work.

Methods

The study included 99 departments of neurosurgery with residency programs participating in the US National Residency Matching Program, and the 14 analogous Canadian programs. Three types of h indices were determined—one reflecting the cumulative work attributed to a neurosurgical department, h(c); one restricted to the cumulative work published over the past 10 years, h(10); and one limited to work published in 2 major North American neurosurgical journals, hNS(10). For an article to be included, attribution to a neurosurgical department had to appear in the address field in the database Thomson's ISI Web of Science. The three h indices were compared with each other, and their relation to other measures such as size of the department, degrees held by the faculty, and research funding was examined.

Results

Significant correlations were found between the citation indices and faculty size, number of publications and the types of degrees held by the faculty, and funding by the US NIH. Three types of authorship were identified: neurosurgeon, nonclinician researcher, and nonneurosurgeon clinical affiliate. The degree to which the latter 2 nonneurosurgeon categories contributed to the departmental h index varied among departments and can confound interdepartmental comparison. Limiting articles to those published in neurosurgical journals appeared to correct for the influence of nonneurosurgeons in departmental impact and reflect neurosurgeon-driven scholarship.

Conclusions

The h index may be useful in evaluating output across neurosurgery departments.

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Francisco A. Ponce and Andres M. Lozano

Object

The term “citation classic” has been used in reference to an article that has been cited more than 400 times. The purpose of this study is to identify such articles that pertain to clinical neurosurgery.

Methods

A list of search phrases relating to neurosurgery was compiled. A topic search was performed using the Institute for Scientific Information Web of Science for phrases. Articles with more than 400 citations were identified, and nonclinical articles were omitted. The journals, year of publication, topics, and study types were analyzed.

Results

There were 106 articles with more than 400 citations relating to clinical neurosurgery. These articles appeared in 28 different journals, with more than half appearing in the Journal of Neurosurgery or the New England Journal of Medicine. Fifty-three articles were published since 1990. There were 38 articles on cerebrovascular disease, 21 on stereotactic and functional neurosurgery, 21 on neurooncology, 19 on trauma, 4 on nontraumatic spine, 2 on CSF pathologies, and 1 on infection. There were 29 randomized trials, of which 86% appeared in the New England Journal of Medicine, Lancet, or the Journal of the American Medical Association, and half concerned the prevention or treatment of stroke. In addition, there were 16 prospective studies, 15 classification or grading systems, and 7 reviews. The remaining 39 articles were case series, case reports, or technical notes.

Conclusions

More than half of the citation classics identified in this study have been published in the past 20 years. Case series, classifications, and reviews appeared more frequently in neurosurgical journals, while randomized controlled trials tended to be published in general medical journals.

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James J. Zhou, Tsinsue Chen, S. Harrison Farber, Andrew G. Shetter and Francisco A. Ponce

OBJECTIVE

The field of deep brain stimulation (DBS) for epilepsy has grown tremendously since its inception in the 1970s and 1980s. The goal of this review is to identify and evaluate all studies published on the topic of open-loop DBS for epilepsy over the past decade (2008 to present).

METHODS

A PubMed search was conducted to identify all articles reporting clinical outcomes of open-loop DBS for the treatment of epilepsy published since January 1, 2008. The following composite search terms were used: (“epilepsy” [MeSH] OR “seizures” [MeSH] OR “kindling, neurologic” [MeSH] OR epilep* OR seizure* OR convuls*) AND (“deep brain stimulation” [MeSH] OR “deep brain stimulation” OR “DBS”) OR (“electric stimulation therapy” [MeSH] OR “electric stimulation therapy” OR “implantable neurostimulators” [MeSH]).

RESULTS

The authors identified 41 studies that met the criteria for inclusion. The anterior nucleus of the thalamus, centromedian nucleus of the thalamus, and hippocampus were the most frequently evaluated targets. Among the 41 articles, 19 reported on stimulation of the anterior nucleus of the thalamus, 6 evaluated stimulation of the centromedian nucleus of the thalamus, and 9 evaluated stimulation of the hippocampus. The remaining 7 articles reported on the evaluation of alternative DBS targets, including the posterior hypothalamus, subthalamic nucleus, ventral intermediate nucleus of the thalamus, nucleus accumbens, caudal zone incerta, mammillothalamic tract, and fornix. The authors evaluated each study for overall epilepsy response rates as well as adverse events and other significant, nonepilepsy outcomes.

CONCLUSIONS

Level I evidence supports the safety and efficacy of stimulating the anterior nucleus of the thalamus and the hippocampus for the treatment of medically refractory epilepsy. Level III and IV evidence supports stimulation of other targets for epilepsy. Ongoing research into the efficacy, adverse effects, and mechanisms of open-loop DBS continues to expand the knowledge supporting the use of these treatment modalities in patients with refractory epilepsy.

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Editorial

Cardiac standstill

Giuseppe Lanzino and Philipp Taussky