Stephen J. Haines

Vagus nerve stimulation (VNS) for treatment-resistant depressions: A multicenter study

BACKGROUND Vagus Nerve Stimulation (VNS) delivered by the NeuroCybernetic Prosthesis (NCP) System was examined for its potential antidepressant effects. METHODS Adult outpatients (n = 30) with nonpsychotic, treatment-resistant major depressive (n = 21) or bipolar I (n = 4) or II (n = 5; depressed phase) disorders who had failed at least two robust medication trials in the current major depressive episode (MDE) while on stable medication regimens completed a baseline period followed by NCP System implantation. A 2-week, single-blind recovery period (no stimulation) was followed by 10 weeks of VNS. RESULTS In the current MDE (median length = 4.7 years), patients had not adequately responded to two (n = 9), three (n = 2), four (n = 6), or five or more (n = 13) robust antidepressant medication trials or electroconvulsive therapy (n = 17). Baseline 28-item Hamilton Depression Rating Scale (HDRS(28)) scores averaged 38.0. Response rates (> or =50% reduction in baseline scores) were 40% for both the HDRS(28) and the Clinical Global Impressions-Improvement index (score of 1 or 2) and 50% for the Montgomery-Asberg Depression Rating Scale. Symptomatic responses (accompanied by substantial functional improvement) have been largely sustained during long-term follow-up to date. CONCLUSIONS These open trial results suggest that VNS has antidepressant effects in treatment-resistant depressions.

Long-Term Follow-Up Data from the Shunt Design Trial

Background: A previously reported multicenter randomized trial assessed whether 2 new shunt valve designs would reduce shunt failure rates compared to differential pressure valves. The study did not show a significant difference in the time to first shunt failure. Patients entered the trial between October 1, 1993, and October 31, 1995. The primary results were based on the patients’ status as of October 31, 1996 (a minimum follow-up of 1 year). This report describes the late complications based on the patients’ most recent follow-up. Methods: Three hundred and forty-four hydrocephalic children at 12 North American and European centers were randomized to 1 of 3 valves: a standard differential pressure valve; a Delta valve (PS Medical-Medtronic) or a Sigma valve (NMT Cordis). Patients were followed until their first shunt failure. Shunt failure was defined as shunt surgery for obstruction, overdrainage, loculation or infection. If the shunt did not fail, follow-up was continued until August 31, 1999. Results: One hundred and seventy-seven patients had shunt failure. Shunt obstruction occurred in 131, overdrainage in 13, loculated ventricles in 2 and infection in 29. The overall shunt survival was 62% at 1 year, 52% at 2 years, 46% at 3 years, 41% at 4 years. The survival curves for the 3 valves were similar to those from the original trial and did not show a survival advantage for any particular valve. Conclusions: Prolonged follow-up to date does not alter the primary conclusions of the trial: there does not appear to be one valve that is clearly the best for the initial treatment of pediatric hydrocephalus.

Repairing holes in the head: a history of cranioplasty.

Cranioplasty is almost as ancient as trephination, yet its fascinating history has been neglected. There is strong evidence that Incan surgeons were performing cranioplasty using precious metals and gourds. Interestingly, early surgical authors, such as Hippocrates and Galen, do not discuss cranioplasty and it was not until the 16th century that cranioplasty in the form of a gold plate was mentioned by Fallopius. The first bone graft was recorded by Meekeren, who in 1668 noted that canine bone was used to repair a cranial defect in a Russian man. The next advance in cranioplasty was the experimental groundwork in bone grafting, performed in the late 19th century. The use of autografts for cranioplasty became popular in the early 20th century. The destructive nature of 20th century warfare provided an impetus to search for alternative metals and plastics to cover large cranial defects. The metallic bone substitutes have largely been replaced by modern plastics. Methyl methacrylate was introduced in 1940 and is currently the most common material used. Research in cranioplasty is now directed at improving the ability of the host to regenerate bone. As modern day trephiners, neurosurgeons should be cognizant of how the technique of repairing a hole in the head has evolved.

A New Classification for Facial Pain

PURPOSEA patient-oriented classification scheme for facial pains commonly encountered in neurosurgical practice is proposed. CONCEPTThis classification is driven principally by the patient’s history. RATIONALEThe scheme incorporates descriptions for so-called “atypical” trigeminal neuralgias and facial pains but minimizes the pejorative, accepting that the physiology of neuropathic pains could reasonably encompass a variety of pain sensations, both episodic and constant. Seven diagnostic labels result: trigeminal neuralgia Types 1 and 2 refer to patients with the spontaneous onset of facial pain and either predominant episodic or constant pain, respectively. Trigeminal neuropathic pain results from unintentional injury to the trigeminal nerve from trauma or surgery, whereas trigeminal deafferentation pain results from injury to the nerve by peripheral nerve ablation, gangliolysis, or rhizotomy in an intentional attempt to treat either trigeminal neuralgia or other facial pain. Postherpetic neuralgia follows a cutaneous herpes zoster outbreak (shingles) in the trigeminal distribution, and symptomatic trigeminal neuralgia results from multiple sclerosis. The final category, atypical facial pain, is synonymous with facial pain secondary to a somatoform pain disorder. Atypical facial pain can be suspected but not diagnosed by history and can be diagnosed only with detailed and objective psychological testing. CONCLUSIONThis diagnostic classification would allow more rigorous and objective natural history and outcome studies of facial pain in the future.

Intraventricular thrombolysis speeds blood clot resolution: Results of a pilot, prospective, randomized, double-blind, controlled trial

OBJECTIVEAnimal models and clinical studies suggest that intraventricular thrombolysis improves clot resolution and clinical outcomes among patients with intraventricular hemorrhage. However, this intervention may increase the rates of rebleeding and infection. To assess the safety and efficacy of intraventricular thrombolysis, we conducted a pilot, randomized, double-blind, controlled, multicenter study. METHODSPatients with intraventricular hemorrhage requiring ventriculostomy were randomized to receive intraventricular injections of normal saline solution or urokinase (25,000 international units) at 12-hour intervals. Injections continued until ventricular drainage was discontinued according to prespecified clinical criteria. Head computed tomographic scans were obtained daily, for quantitative determinations of intraventricular hemorrhage volumes. The rate of clot resolution was estimated for each group. RESULTSTwelve subjects were enrolled (urokinase, seven patients; placebo, five patients). Commercial withdrawal of urokinase precluded additional enrollment. The urokinase and placebo groups were similar with respect to age (49.6 versus 55.2 yr, P = 0.43) and presenting Glasgow Coma Scale scores (7.14 versus 8.00, P = 0.72). Randomization to the urokinase treatment arm (P = 0.02) and female sex (P = 0.008) favorably affected the clot resolution rate. The sex-adjusted clot half-life for the urokinase-treated group was reduced 44.6%, compared with the value for the placebo group (4.69 versus 8.48 d). CONCLUSIONIntraventricular thrombolysis with urokinase speeds the resolution of intraventricular blood clots, compared with treatment with ventricular drainage alone.

The probability of sudden death from rupture of intracranial aneurysms: A meta-analysis

OBJECTIVE To estimate the proportion of patients with aneurysmal subarachnoid hemorrhage (SAH) who die before receiving medical attention. METHODS We performed a systematic literature review. RESULTS Eighteen population-based studies between 1965 and 2001 described the incidence of death from SAH before the patients received medical attention. The combined overall risk of sudden death was 12.4% (95% confidence interval, 11–14%). Patient level analysis was possible for two studies. No significant association between age and sudden death was identified. Aneurysms in the posterior circulation had an estimated probability of sudden death of 44.7% (95% confidence interval, 7.4–86%). Statistical sensitivity analysis was performed to examine some possible causes for the heterogeneity between the studies. Study factors statistically associated with a higher rate of sudden death include origin in England, computed tomographic scans not available for diagnosis, inclusion of patients with SAH from arteriovenous malformations, lower or not stated rate of autopsy for deaths in the community, and a higher rate of patients with confirmed aneurysms. CONCLUSION The combined overall estimated risk of sudden death was 12.4% for aneurysmal SAH and 44.7% for posterior circulation aneurysms. However, there are several sources of heterogeneity or possible bias in the reported studies. Further information on patient and aneurysm characteristics is required.

Antibiotic prophylaxis for cerebrospinal fluid shunts: a metanalysis.

The value of antibiotic prophylaxis for clean neurosurgical procedures without the implantation of a foreign body has been conclusively demonstrated. Attempts to confirm its efficacy for cerebrospinal fluid shunt operations have produced confusing and inconclusive results. The objective of this study was to combine the results of high-quality controlled trials of antibiotic prophylaxis for cerebrospinal fluid shunt operations and to determine if there is evidence for the efficacy of this policy. Randomized clinical trials identified from presentations at national meetings and in the published literature were subjected to a metanalysis. The pooled data suggest a statistically significant effect favoring antibiotic prophylaxis (approximately a 50% reduction in infection risk when antibiotic prophylaxis is used). The effect is strongly related to the baseline infection rate when prophylaxis is not used and disappears when the baseline infection rate is at or below about 5%.

Low-Dose Recombinant Tissue-Type Plasminogen Activator Enhances Clot Resolution in Brain Hemorrhage: The Intraventricular Hemorrhage Thrombolysis Trial

Background and Purpose— Patients with intracerebral hemorrhage and intraventricular hemorrhage have a reported mortality of 50% to 80%. We evaluated a clot lytic treatment strategy for these patients in terms of mortality, ventricular infection, and bleeding safety events, and for its effect on the rate of intraventricular clot lysis. Methods— Forty-eight patients were enrolled at 14 centers and randomized to treatment with 3 mg recombinant tissue-type plasminogen activator (rtPA) or placebo. Demographic characteristics, severity factors, safety outcomes (mortality, infection, bleeding), and clot resolution rates were compared in the 2 groups. Results— Severity factors, including admission Glasgow Coma Scale, intracerebral hemorrhage volume, intraventricular hemorrhage volume, and blood pressure were evenly distributed, as were adverse events, except for an increased frequency of respiratory system events in the placebo-treated group. Neither intracranial pressure nor cerebral perfusion pressure differed substantially between treatment groups on presentation, with external ventricular device closure, or during the active treatment phase. Frequency of death and ventriculitis was substantially lower than expected and bleeding events remained below the prespecified threshold for mortality (18% rtPA; 23% placebo), ventriculitis (8% rtPA; 9% placebo), symptomatic bleeding (23% rtPA; 5% placebo, which approached statistical significance; P=0.1). The median duration of dosing was 7.5 days for rtPA and 12 days for placebo. There was a significant beneficial effect of rtPA on rate of clot resolution. Conclusions— Low-dose rtPA for the treatment of intracerebral hemorrhage with intraventricular hemorrhage has an acceptable safety profile compared to placebo and historical controls. Data from a well-designed phase III clinical trial, such as CLEAR III, will be needed to fully evaluate this treatment. Clinical Trial Registration— Participant enrollment began before July 1, 2005.

Anticonvulsant prophylaxis in neurological surgery

&NA; Seizures complicate many neurosurgical diseases and, in many situations, their prevention is desirable. In an attempt to arrive at a rational approach to the purely prophylactic administration of anticonvulsants, existing data pertaining to four topics were examined: the danger posed by a single seizure, the incidence of seizures in a given disease state, the ability of anticonvulsant medication to prevent seizures, and the risks and benefits associated with pharmacological intervention. In general, where the risk of seizure exceeds 10 to 15% or where a single seizure may have diastrous consequences, anticonvulsant prophylaxis is recommended. (Neurosurgery 17:510‐517, 1985)

Craniocerebral aspergillosis of sinonasal origin in immunocompetent patients: Clinical spectrum and outcome in 25 cases. Comments

OBJECTIVE:Craniocerebral aspergillosis of sinonasal origin has been reported mainly in immunocompromised patients with high mortality, and it has been described very infrequently in immunocompetent hosts. This retrospective study focuses on clinical outcome in relation to anatomic locations of invasive aspergillosis of sinonasal origin in immunocompetent patients with emphasis on our preliminary experience with use of preoperative orally administered itraconazole. METHODS:Medical records of patients treated in two tertiary care hospitals from 1991 to 2003 were reviewed retrospectively. All patients had radiological evidence of disease in the paranasal sinuses with or without intracranial extension. The study cohort was divided into three types on the basis of area of involvement revealed by computed tomographic or magnetic resonance imaging scans of brain. All patients underwent surgical intervention and treatment with antifungal therapy. Preoperative orally administered itraconazole therapy was used in four patients on the basis of neuroradiological features. Clinical outcome was assessed with the Glasgow Outcome Scale, and univariate analysis of prognostic factors was performed with 95% confidence interval (P = 0.05). RESULTS:Mean patient age was 36.5 years (range, 14–74 yr) with a male preponderance (male-to-female ratio, 23:2). Nasal stuffiness (n = 13), headaches (n = 10), proptosis (n = 9), and nasal discharges (n = 7) were major presenting clinical features. Radiological data were obtained by computed tomographic (n = 25) and magnetic resonance imaging (n = 20) scans of the brain, and diagnoses were established by histopathological analysis (n = 20) or/and fungal cultures (n = 15). Preoperative orally administered itraconazole was given in four patients with intracerebral aspergillosis. Overall mortality was 28% and was highest in patients with Type 1 aspergillosis (66.7%). Type 3 aspergillosis and use of preoperative itraconazole remained statistically significant prognostic factors. CONCLUSION:Craniocerebral aspergillosis in immunocompetent hosts has three patterns of presentation that seem to correlate with clinical outcomes. Intracerebral aspergillosis (Type 1) is associated with the worst clinical outcome. Patients with orbital and cranial base aspergillosis (Type 3) had good recovery. Intracranial extradural aspergillosis (Type 2) remained intermediate on the Glasgow Outcome Scale. Preoperative orally administered itraconazole therapy may improve clinical outcome in patients with intracerebral aspergillosis. Prospective clinical studies are required to make firm clinical therapeutic recommendations.