Raqeeb Haque

Advances in Neuroprotective Strategies: Potential Therapies for Intracerebral Hemorrhage

Intracerebral hemorrhage (ICH) is associated with higher mortality and morbidity than any other form of stroke. However, there currently are no treatments proven to improve outcomes after ICH, and therefore, new effective therapies are urgently needed. Growing insight into ICH pathophysiology has led to the development of neuroprotective strategies that aim to improve the outcome through reduction of secondary pathologic processes. Many neuroprotectants target molecules or pathways involved in hematoma degradation, inflammation or apoptosis, and have demonstrated potential clinical benefits in experimental settings. We extensively reviewed the current understanding of ICH pathophysiology as well as promising experimental neuroprotective agents with particular focus on their mechanisms of action. Continued advances in ICH knowledge, increased understanding of neuroprotective mechanisms, and improvement in the ability to modulate molecular and pathologic events with multitargeting agents will lead to successful clinical trials and bench-to-bedside translation of neuroprotective strategies.

Comparison of two minimally invasive surgery strategies to treat adult spinal deformity.

OBJECT Minimally invasive surgery (MIS) techniques are becoming a more common means of treating adult spinal deformity (ASD). The aim of this study was to compare the hybrid (HYB) surgical approach, involving minimally invasive lateral interbody fusion with open posterior instrumented fusion, to the circumferential MIS (cMIS) approach to treat ASD. METHODS The authors performed a retrospective, multicenter study utilizing data collected in 105 patients with ASD who were treated via MIS techniques. Criteria for inclusion were age older than 45 years, coronal Cobb angle greater than 20°, and a minimum of 1 year of follow-up. Patients were stratified into 2 groups: HYB (n = 62) and cMIS (n = 43). RESULTS The mean age was 60.7 years in the HYB group and 61.0 years in the cMIS group (p = 0.910). A mean of 3.6 interbody fusions were performed in the HYB group compared with a mean of 4.0 interbody fusions in the cMIS group (p = 0.086). Posterior fusion involved a mean of 6.9 levels in the HYB group and a mean of 5.1 levels in the cMIS group (p = 0.003). The mean follow-up was 31.3 months for the HYB group and 38.3 months for the cMIS group. The mean Oswestry Disability Index (ODI) score improved by 30.6 and 25.7, and the mean visual analog scale (VAS) scores for back/leg pain improved by 2.4/2.5 and 3.8/4.2 for the HYB and cMIS groups, respectively. There was no significant difference between groups with regard to ODI or VAS scores. For the HYB group, the lumbar coronal Cobb angle decreased by 13.5°, lumbar lordosis (LL) increased by 8.2°, sagittal vertical axis (SVA) decreased by 2.2 mm, and LL-pelvic incidence (LL-PI) mismatch decreased by 8.6°. For the cMIS group, the lumbar coronal Cobb angle decreased by 10.3°, LL improved by 3.0°, SVA increased by 2.1 mm, and LL-PI decreased by 2.2°. There were no significant differences in these radiographic parameters between groups. The complication rate, however, was higher in the HYB group (55%) than in the cMIS group (33%) (p = 0.024). CONCLUSIONS Both HYB and cMIS approaches resulted in clinical improvement, as evidenced by decreased ODI and VAS pain scores. While there was no significant difference in degree of radiographic correction between groups, the HYB group had greater absolute improvement in degree of lumbar coronal Cobb angle correction, increased LL, decreased SVA, and decreased LL-PI. The complication rate, however, was higher with the HYB approach than with the cMIS approach.

Less invasive surgery for treating adult spinal deformities: ceiling effects for deformity correction with 3 different techniques

OBJECT Minimally invasive surgery (MIS) options for the treatment of adult spinal deformity (ASD) have advanced significantly over the past decade. However, a wide array of options have been described as being MIS or less invasive. In this study the authors investigated a multiinstitutional cohort of patients with ASD who were treated with less invasive methods to determine the extent of deformity correction achieved. METHODS This study was a retrospective review of multicenter prospectively collected data in 85 consecutive patients with ASD undergoing MIS surgery. Inclusion criteria were as follows: age older than 45 years; minimum 20° coronal lumbar Cobb angle; and 1 year of follow-up. Procedures were classified as follows: 1) stand-alone (n = 7); 2) circumferential MIS (n = 43); or 3) hybrid (n = 35). RESULTS An average of 4.2 discs (range 3-7) were fused, with a mean follow-up duration of 26.1 months in this study. For the stand-alone group the preoperative Cobb range was 22°-51°, with 57% greater than 30° and 28.6% greater than 50°. The mean Cobb angle improved from 35.7° to 30°. A ceiling effect of 23° for curve correction was observed, regardless of preoperative curve severity. For the circumferential MIS group the preoperative Cobb range was 19°-62°, with 44% greater than 30° and 5% greater than 50°. The mean Cobb angle improved from 32° to 12°. A ceiling effect of 34° for curve correction was observed. For the hybrid group the preoperative Cobb range was 23°-82°, with 74% greater than 30° and 23% greater than 50°. The mean Cobb angle improved from 43° to 15°. A ceiling effect of 55° for curve correction was observed. CONCLUSIONS Specific procedures for treating ASD have particular limitations for scoliotic curve correction. Less invasive techniques were associated with a reduced ability to straighten the spine, particularly with advanced curves. These data can guide preoperative technique selection when treating patients with ASD.

Complications, outcomes, and need for fusion after minimally invasive posterior cervical foraminotomy and microdiscectomy

BACKGROUND CONTEXT Posterior cervical foraminotomy (PCF) with or without microdiscectomy (posterior cervical discectomy [PCD]) is a frequently used surgical technique for cervical radiculopathy secondary to foraminal stenosis or a laterally located herniated disc. Currently, these procedures are being performed with increasing frequency using advanced minimally invasive techniques. Although the safety and efficacy of minimally invasive PCF/PCD (MI-PCF/PCD) have been established, reports on long-term outcome and need for secondary surgical intervention at the index or adjacent level are lacking. PURPOSE To determine the rates of complications, long-term outcomes, and need for secondary surgical intervention at the index or adjacent level after MI-PCF and microdiscectomy. STUDY DESIGN Retrospective analysis of a prospective cohort. PATIENT SAMPLE Seventy patients treated with MI-PCF and/or MI-PCD for cervical radiculopathy. OUTCOME MEASURES Visual Analog Scale for neck/arm (VASN/A) pain and Neck Disability Index (NDI). METHODS Ninety-seven patients underwent MI-PCF with or without MI-PCD between 2002 and 2011. Adequate prospective follow-up was available for 70 patients (95 cervical levels). The primary outcome assessed was need for secondary surgical intervention at the index or adjacent level. The secondary outcomes assessed included complications and improvements in NDI and VASN/A scores. All complications were reviewed. Mixed-model analyses of variance with random subject effects and autoregressive first-order correlation structures were used to test for differences among NDI, VASA, and VASN measurements made over time while accounting for the correlation among repeated observations within a patient. All statistical hypothesis tests were conducted at the 5% level of significance. RESULTS Patients were followed for a mean of 32.1 months. Of 70 patients operated, there were 3 (4.3%) complications (1 cerebrospinal fluid leak, 1 postoperative wound hematoma, and 1 radiculitis), none of which required a secondary operative intervention. Five patients required an anterior cervical discectomy and fusion (eight total levels fused) on average 44.4 months after the index surgery. Of those, five (5.3%) were at the index level and three (2.1%) were at adjacent levels. Neck Disability Index scores improved significantly (p<.0001) immediately postoperatively and continued to decrease gradually with time. Visual Analog Scale for neck/arm scores improved significantly (p<.0001) from baseline immediately postoperatively but tended to plateau with time. CONCLUSIONS Minimally invasive PCF with or without MI-PCD is an excellent alternative for cervical radiculopathy secondary to foraminal stenosis or a laterally located herniated disc. There is a low rate (1.1% per index level per year) of future index site fusion and a very low rate (0.9% per adjacent level per year) of adjacent-level disease requiring surgery.

Polymorphisms in complement component 3 (C3F) and complement factor H (Y402H) increase the risk of postoperative neurocognitive dysfunction following carotid endarterectomy

Background Up to 28% of patients undergoing carotid endarterectomy (CEA) are estimated to experience neurocognitive dysfunction following surgery. The complement cascade plays a central role in ischaemia-reperfusion injury. The authors investigated the effect of common polymorphisms in the complement component 3 (C3F) and complement factor H (CFH Y402H) genes on incidence of neurocognitive dysfunction post-CEA. Methods This study examined a nested cohort of prospectively recruited patients receiving elective CEA, who were genotyped for the C3F or Y402H polymorphisms. Each patient underwent a standard battery of eight neuropsychometric tests before, and 1 day and 30 days after, surgery. Results 57 of 142 (40%) CEA patients had at least one copy of the C3F allele (C3F+), and 17 of 137 (12%) patients had two copies of the CFH Y402H allele (Y402H++). At postoperative day 1, patients were three times (OR 3.05, p=0.045) or six times (OR 6.41, p=0.006) more likely to experience moderate-to-severe neurocognitive dysfunction if they carried the C3F+ or Y402H++ genotype, respectively. Patients with both risk genotypes had an almost eightfold risk of dysfunction (OR 7.67, p=0.046). Right-hand-dominant C3F+ subjects undergoing right-side CEA performed significantly worse on tests of visuospatial function than C3F– subjects. At day 30, C3F+ and Y402H++ genotypes trended towards significance as predictors of dysfunction (p=0.07 and p=0.22, respectively). Conclusion The C3F and Y402H polymorphisms are strong independent predictors of moderate-to-severe neurocognitive dysfunction at 1 day following CEA. Furthermore, patients undergoing right-sided CEA are predisposed to deficits associated with cortex ipsilateral to the operative carotid artery.

Intraoperative magnesium infusion during carotid endarterectomy: a double-blind placebo-controlled trial.

OBJECT Recent data from both experimental and clinical studies have supported the use of intravenous magnesium as a potential therapy in the setting of cerebral ischemia. This study assessed whether intraoperative magnesium therapy improves neuropsychometric testing (NPT) following carotid endarterectomy (CEA). METHODS One hundred eight patients undergoing CEA were randomly assigned to receive placebo infusion or 1 of 3 magnesium-dosing protocols. Neuropsychometric testing was performed 1 day after surgery and compared with baseline performance. Assessment was also performed on a set of 35 patients concurrently undergoing lumbar laminectomy to serve as a control group for NPT. A forward stepwise logistic regression analysis was performed to evaluate the impact of magnesium therapy on NPT. A subgroup analysis was then performed, analyzing the impact of each intraoperative dose on NPT. RESULTS Patients treated with intravenous magnesium infusion demonstrated less postoperative neurocognitive impairment than those treated with placebo (OR 0.27, 95% CI 0.10-0.74, p = 0.01). When stratified according to dosing bolus and intraoperative magnesium level, those who were treated with low-dose magnesium had less cognitive decline than those treated with placebo (OR 0.09, 95% CI 0.02-0.50, p < 0.01). Those in the high-dose magnesium group demonstrated no difference from the placebo-treated group. CONCLUSIONS Low-dose intraoperative magnesium therapy protects against neurocognitive decline following CEA.

Cost minimization in treatment of adult degenerative scoliosis

OBJECT Back pain is an increasing concern for the aging population. This study aims to evaluate if minimally invasive surgery presents cost-minimization benefits compared with open surgery in treating adult degenerative scoliosis. METHODS Seventy-one patients with adult degenerative scoliosis received 2-stage, multilevel surgical correction through either a minimally invasive spine surgery (MIS) approach with posterior instrumentation (n = 38) or an open midline (Open) approach (n = 33). Costs were derived from hospital and rehabilitation charges. Length of stay, blood loss, and radiographic outcomes were obtained from electronic medical records. Functional outcomes were measured with Oswestry Disability Index (ODI) and visual analog scale (VAS) surveys. RESULTS Patients in both cohorts were similar in age (Age(MIS) = 65.68 yrs, Age(Open) = 63.58 yrs, p = 0.28). The mean follow-up was 18.16 months and 21.82 months for the MIS and Open cohorts, respectively (p = 0.34). MIS and Open cohorts had an average of 4.37 and 7.61 levels of fusion, respectively (p < 0.01). Total inpatient charges were lower for the MIS cohort (

Regenerating motor bridge axons refine connections and synapse on lumbar motoneurons to bypass chronic spinal cord injury.

269,807 vs

Isoflurane Preconditioning Affords Functional Neuroprotection in a Murine Model of Intracerebral Hemorrhage

391,889, p < 0.01), and outpatient rehabilitation charges were similar (

Transforaminal nerve root stimulation: a technical report.

41,072 vs