A summary of some of the recently published seminal papers in Neuroscience
Correspondence Address: Source of Support: None, Conflict of Interest: None DOI: 10.4103/0028-3886.166580
Source of Support: None, Conflict of Interest: None
Moon K, et al. Safety and efficacy of surgical resection of unruptured low-grade arteriovenous malformations from the modern decade. Neurosurgery: August 14, 2015 DOI: 10.1227/NEU.0000000000000968
The authors performed an assessment of the outcomes and complications encountered during surgical resection of low-grade brain arteriovenous malformations (bAVMs; Spetzler–Martin grade I or II) at a single high-volume neurosurgical center. They reviewed all unruptured low-grade bAVMs treated with surgery (with or without preoperative embolization) between January 2004 and January 2014. The stroke rate, mortality, and clinical and radiographic outcomes were examined. Of the 95 patients treated surgically, 85 (25 grade I, 60 grade II) met the inclusion criteria, and all achieved radiographic cure postoperatively. The authors concluded that surgical resection of low-grade unruptured bAVMs was safe, with a high rate of improvement in functional status and seizure reduction. Transient postoperative neurological deficits may occur in some patients but permanent treatment-related neurological morbidity was rare.
McCraken JD, et al. Resolution of oculomotor nerve palsy secondary to posterior communicating artery aneurysms: Comparison of clipping and coiling. Neurosurgery: August 14, 2015 DOI: 10.1227/NEU.0000000000000965
The study was performed to determine the best treatment for oculomotor nerve palsy (ONP) secondary to posterior communicating artery (PCoA) aneurysms. Data from two large academic centers was retrospectively collected over 22 years, yielding a total of 93 patients with ONP secondary to PCoA aneurysms. These patients were combined with 321 patients from the literature review for large data analyses. The onset symptoms, recovery, and time to resolution were evaluated with respect to treatment and aneurysm rupture status. The number of patients presenting with ONP were 414. Of these, 56.6% of patients treated with microsurgical clipping made a full recovery versus 41.5% of those treated with endovascular coil embolization (P = 0.02). Complete ONP occurred in 229 patients. Full recovery occurred in 47.3% of those treated with clipping but in only 20% of those who underwent coil embolization (P = 0.01). In cases with a ruptured aneurysm (n = 130), full recovery occurred in 70.9% patients who underwent surgery compared with 49.3% of those who underwent coil embolization (P = 0.014). Patients with ONP secondary to PCoA aneurysms treated with clipping showed higher rates of full ONP resolution than patients treated with coil embolization.
Jahangiri A, et al. Improved versus worsened endocrine function after transsphenoidal surgery for nonfunctional pituitary adenomas: Rate, time course, and radiological analysis. J Neurosurg. DOI: 10.3171/2015.1.JNS141543
Trans-sphenoidal surgery is frequently performed for nonfunctional pituitary adenomas (NFAs). Its influence on preoperative hypopituitarism as well as on the development of new postoperative endocrine deficits remains unclear. The authors investigated the rates of resolution of hypopituitarism and the development of additional hypofunctioning of hormones following trans-sphenoidal surgery. Over a 5-year period, 305 trans-sphenoidal surgeries for NFAs performed at the California Center for Pituitary Disorders were retrospectively reviewed. After NFA resection, endocrine normalization rates were different in different hormonal axes. The normalization rates were greater than the incidence rates for the development of new endocrinal deficits. Low preoperative gland volume hampered recovery of the hormonal hypofunctioning. The thyroid and male reproductive axes were the most commonly impaired axes that were unlikely to normalize early in the postoperative period. The patient's age and the severity of the deficiency considerably influenced the recovery. This study may be utilized in counseling patients who undergo surgery to resect their NFA and who suffer from preoperative hypopituitarism.
Brown LT, et al. Dorsal anterior cingulotomy and anterior capsulotomy for severe, refractory obsessive-compulsive disorder: A systematic review of observational studies. J Neurosurg. DOI: 10.3171/2015.1.JNS14681
The objective of this study was to perform a systematic review of the clinical efficacy and adverse effect profile of dorsal anterior cingulotomy compared with anterior capsulotomy for the treatment of severe, refractory obsessive-compulsive disorder (OCD). The authors included studies comparing objective clinical measures before and after cingulotomy or capsulotomy (surgical and radiosurgical) in patients with OCD. Only papers reporting the most current follow-up data for each group of investigators were included. This systematic review of the literature supported the efficacy of both dorsal anterior cingulotomy and anterior capsulotomy in this highly treatment-refractory population. However, the observational nature of the available data limits the ability to directly compare these procedures.
The Cancer Genome Atlas More Details Research Network. Comprehensive, integrative genomic analysis of diffuse lower-grade gliomas. N Engl J Med 2015;372:2481-98
Diffuse low-grade and intermediate-grade gliomas (which together make up the lower-grade gliomas, World Health Organization grades II and III) have a highly variable clinical behavior that is not adequately predicted on the basis of histologic class. Some are indolent; others quickly progress to the development of a glioblastoma. The uncertainty is compounded by interobserver variability in histologic diagnosis. Mutations in isocitrate dehydrogenase (IDH), tumor protein 53 (TP53), and thalassemia/mental retardation syndrome X-linked (ATRX) and co-deletion of chromosome arms 1p and 19q have been implicated as clinically relevant markers of lower-grade gliomas. The authors performed genome-wide analyses of 293 lower-grade gliomas from adults, incorporating exome sequence, DNA copy number, DNA methylation, messenger RNA expression, microRNA expression, and targeted protein expression. These data were integrated and tested for correlation with clinical outcomes. Three molecular classes of lower-grade gliomas were identified that correlated better with the IDH, 1p/19q, and TP53 status than with the histologic class. Lower-grade gliomas with an IDH mutation either had 1p/19q codeletion or carried a TP53 mutation. Most lower-grade gliomas without an IDH mutation had molecular and clinical characteristics similar to a glioblastoma.
Douketis JD and other Bridge investigators. Perioperative bridging anticoagulation in patients with atrial fibrillation. N Engl J Med August 27, 2015;373:823-33. DOI: 10.1056/NEJMoa1501035
Patients with atrial fibrillation need an interruption in warfarin treatment for an elective operation or other elective invasive procedures. It is uncertain whether bridging anticoagulation (in the form of low-molecular-weight heparin) is necessary for these patients during the period of interruption in the warfarin treatment. The authors hypothesized that in case one does not administer a bridging anticoagulation during the period of interruption in warfarin treatment for an invasive procedure, it would not be inferior to bridging with low-molecular-weight heparin for the prevention of perioperative arterial thromboembolism. In fact, nonbridging would be superior to bridging in preventing a major bleeding.
In this randomized, double-blind, placebo-controlled trial, after perioperative interruption of warfarin therapy, patients were randomly assigned to receive bridging anticoagulation therapy with low-molecular-weight heparin (100 IU of dalteparin per kilogram of body weight) or matching placebo administered subcutaneously twice daily, from 3 days before the procedure until 24 hours before the procedure and then for 5–10 days after the procedure. Warfarin treatment was stopped 5 days before the procedure and was resumed within 24 hours after the procedure. Follow-up of patients continued for 30 days after the procedure. The primary outcomes were arterial thromboembolism (stroke, systemic embolism, or transient ischemic attack) and major bleeding. In patients with atrial fibrillation who had warfarin treatment interrupted for an elective operation or other elective invasive procedure, not administering the bridging anticoagulation did not have any significant deleterious effects in the occurrence of perioperative arterial thromboembolism, when compared with patients in whom bridging with low-molecular-weight heparin had been performed. Moreover, not bridging with low-molecular-weight heparin also decreased the risk of major bleeding.
Prust MJ, et al. Standard chemoradiation for glioblastoma results in progressive brain volume loss. Neurology 85;8:683-91
The study investigated, in patients with a glioblastoma, the effects of chemotherapy and cranial irradiation on normal brain tissue using in vivo neuroimaging. The authors used a longitudinal MRI imaging to monitor structural brain changes during standard treatment in patients newly diagnosed with a glioblastoma. They assessed volumetric and diffusion tensor imaging measures in 14 patients receiving 6 weeks of chemoradiation, followed by up to 6 months of temozolomide chemotherapy alone. They examined changes in the whole brain, gray matter (GM), white matter (WM), anterior lateral ventricle, and in the hippocampal volumes. Normal-appearing GM, WM, and hippocampal analyses were conducted within the hemisphere of lowest/absent tumor burden. Diffusion tensor imaging measures within the subventricular zone were examined. Significant and progressive treatment-associated structural brain changes occurred in patients with a glioblastoma treated with standard chemoradiation. Longitudinal neuropsychological evaluation will further characterize the functional consequences of these structural changes.
Guo J, et al. Statin treatment reduces the risk of poststroke seizures. Neurology 85;8;701-7
In this cohort study, patients with a first-ever ischemic stroke and no history of epilepsy before stroke were enrolled. After a mean follow-up period of 2.5 years, a follow-up assessment was performed to identify poststroke epilepsy. Of the 1832 enrolled patients, 63 (3.4%) had poststroke early-onset seizures and 91 (5.0%) had poststroke epilepsy. The use of statin, especially in the acute phase, may reduce the risk of poststroke early-onset seizures. In addition, statin treatment may prevent the progression of an initial poststroke seizure-induced neurodegeneration into chronic epilepsy. This study provides Class III evidence that in patients with a first-ever ischemic stroke, the early use of statins reduces the risk of early poststroke seizures.
Lansberg MG and DEFUSE 2 study investigators. Response to endovascular reperfusion is not time-dependent in patients with salvageable tissue. Neurology 85;8:708-14
This study determined whether time to treatment modified the effect of endovascular reperfusion in stroke patients who had a perfusion–diffusion mismatch on MRI (which is an MRI hallmark of salvageable tissue). Patients from the Diffusion and Perfusion Imaging Evaluation for Understanding Stroke Evolution 2 (DEFUSE 2) cohort study with a perfusion–diffusion target mismatch were included. Reperfusion was defined as a decrease in the perfusion lesion volume of at least 50% between baseline and early follow-up. Good functional outcome was defined as a modified Rankin Scale score ≤2 at day 90. Lesion growth was defined as the difference between the baseline and the early follow-up diffusion-weighted imaging lesion volumes. Thus, the association between endovascular reperfusion and improved functional and radiologic outcomes is not time-dependent in patients with a perfusion–diffusion mismatch.
Scolding N, et al. Association of British Neurologists: Revised (2015) guidelines for prescribing disease-modifying treatments in multiple sclerosis. Pract Neurol 2015;15:273–9. DOI: 10.1136/practneurol-2015-001139
In June 1999, the Association of British Neurologists (ABN) first published guidelines for the use of licensed multiple sclerosis (MS) disease-modifying treatments (at that time, β-interferon and glatiramer acetate). This 2015 revised guideline replaces the former versions. It includes all newly approved or licensed treatments for MS and represents a consensus concerning their use. These guidelines will require future revision as other treatments receive approval (e.g., daclizumab and ocrelizumab). The authors suggest that these treatments should be reviewed at an interval of no longer than 12 months.
La Mantia L, et al. Comparative efficacy of interferon β versus glatiramer acetate for relapsing-remitting multiple sclerosis. J Neurol Neurosurg Psychiatry 2015;86:1016-20
Interferon β (INFβ) and glatiramer acetate (GA) are often used in patients with relapsing–remitting multiple sclerosis (RRMS), but their efficacy status is unknown. The authors performed a systematic search of head-to-head trials for gaining objective and reliable data to compare the two drugs using the Cochrane Collaboration methodology. They identified five randomized controlled trials (RCTs; 2858 participants) comparing directly INFβ versus GA in RRMS. Both therapies showed similar efficacy at 24 months based on their clinical (patients with relapse or progression) and one MRI activity (enhancing lesions) measure. At 3 years, evidence from a single study showed that the relapse rate was higher in the INFβ group than in the GA group. The number of participants who dropped out of the studies because of adverse events was similar in the two groups. These data support the use of these therapies, based on their similar safety and efficacy profiles, in the prevention of disease activity. Their different effects on the MRI measures and the different tolerability, however, might have a role in the therapeutic choice at the individual level.
Bonati LH and the International Carotid Stenting Study Investigators. Long-term outcomes after stenting versus endarterectomy for treatment of symptomatic carotid stenosis: The International Carotid Stenting Study (ICSS) randomised trial. Lancet 2015;385:529-38
Stenting is an alternative to endarterectomy for the treatment of carotid artery stenosis, but long-term efficacy of this procedure is uncertain. The authors report the long-term data from the randomized International Carotid Stenting Study comparing these treatments. Patients with symptomatic carotid stenosis were randomly assigned 1:1 to open treatment with stenting or endarterectomy at 50 centers worldwide. Randomization was computer-generated centrally and allocated by telephone call or fax. Major outcomes were assessed by an independent end-point committee unaware of treatment assignment. The primary end point was fatal or disabling stroke in any territory after randomization to the end of follow-up. A total of 1713 patients were assigned to stenting (n = 855) or endarterectomy (n = 858) and followed up for a median of 4.2 years (interquartile range (IQR): 3·0–5·2, maximum: 10·0). The number of fatal or disabling strokes (52 vs. 49) and cumulative 5-year risk did not differ significantly between the stenting and endarterectomy groups. Any stroke was more frequent in the stenting group than in the endarterectomy group (119 vs. 72 events), but were mainly nondisabling strokes. The distribution of modified Rankin Scale scores at 1 year, 5 years, or the final follow-up did not differ significantly between the treatment groups. The authors concluded that the long-term functional outcome and risk of fatal or disabling stroke are similar for stenting and endarterectomy procedures in the presence of symptomatic carotid stenosis.
Yu JH, et al. Association of intraplaque hemorrhage and acute infarction in patients with basilar artery plaque. Stroke. DOI: 10.1161/STROKEAHA.115.009412
The authors have studied the association of intraplaque hemorrhage in patients who develop an acute infarction due to basilar artery (BA) atherosclerosis using high-resolution magnetic resonance imaging (HRMRI). They analyzed the HRMRI and clinical data of 74 patients (all had more than 50% basilar artery stenosis) among whom 45 patients were symptomatic and 29 were asymptomatic. A high signal intensity (more than 150% of the intensity of the surrounding muscle) within a BA plaque on magnetization-prepared rapid acquisition with gradient-echo sequences was considered as diagnostic. A total of 30 (42.3%) patients had intraplaque hemorrhage. Out of these 30, 24 were symptomatic and 6 were asymptomatic. Symptomatic lesions were significantly more in the MR-positive intraplaque hemorrhage group as compared with the MR-negative group (80.0% vs. 48.8%; P < 0.01). The relative risk of an acute focal stroke in the MR-positive group was 1.64 when compared with the MR-negative group. The authors concluded that the presence of intraplaque hemorrhage within BA plaque (as diagnosed by HRMRI) was highly prevalent and was associated with acute stroke.
Gracies JM, et al. Safety and efficacy of abobotulinumtoxinA for hemiparesis in adults with upper limb spasticity after stroke or traumatic brain injury: A double-blind randomised controlled trial. Lancet Neurol. DOI: http://dx.doi.org/10.1016/S1474-4422 (15) 00216-1
The authors have conducted a randomized, double-blind, placebo-controlled study to assess the effects of abobotulinumtoxinA injection in the upper limb muscles on muscle tone, spasticity, active movement, and function. For the study, adult patients between the age of 18 and 80 years were enrolled from across 34 neurology or rehabilitation centers in Europe and in the United States. The patients had stroke or brain trauma at least 6 months prior to being enrolled and were randomly assigned to one of the three groups (abobotulinumtoxinA 500 U and 1000 U and placebo group) in a ratio of 1:1:1. The patients received a single injection session into the most hypertonic muscle group among the elbow, wrist, finger flexors, or shoulder extensors (primary target muscle group [PTMG]), and into at least two additional muscle groups from the elbow, wrist, finger flexors, or shoulder extensors. Modified Ashworth Scale (MAS) was used to assess the primary end point of change in the muscle tone in the PTMG from the baseline to 4 weeks. Physician Global Assessment (PGA) at week 4 and change in the Disability Assessment Scale (DAS) from the baseline to 4 weeks were utilized for secondary end points.
Eighty-one patients each were randomly allocated to the three groups. The mean change in the MAS score from the baseline to week 4 in the PTMG was −0.3 (SD: 0.6) in the placebo group (n = 79), −1.2 (1.0) in the abobotulinumtoxinA 500-U group (n = 80, difference: −0.9, 95% confidence interval, −1.2 to −0.6, P < 0.0001 vs. placebo), and −1.4 (1.1) in the abobotulinumtoxinA 1000-U group (n = 79, −1.1, −1.4 to −0.8, P < 0.0001 vs. placebo). The mean change from baseline to week 4 in the DAS score for the principal target of treatment was −0.5 (0.7) in the placebo group (n = 79), −0.7 (0.8) in the abobotulinumtoxinA 500-U group (n = 80; P = 0.2560 vs. placebo), and −0.7 (0.7) in the abobotulinumtoxinA 1000-U group (n = 78; P = 0.0772 vs. placebo). The mean PGA score at week 4 was 0.6 (SD: 1.0) in the placebo group (n = 78), 1.4 (1.1) in the abobotulinumtoxinA 500-U group (n = 80; P = 0.0003 vs. placebo), and 1.8 (1.1) in the abobotulinumtoxinA 1000-U group (n = 78; P < 0.0001 vs. placebo). Treatment-related adverse events occurred in two cases in the placebo group, six cases in the abobotulinumtoxinA 500-U group, and seven cases in the abobotulinumtoxinA 1000-U group, and these were mild or moderate. The authors conclude that injection of either 500 U or 1000 U of abobotulinumtoxinA provides reduction of tone and clinical benefit in hemiparesis.
Campbell BCV, et al. Endovascular stent thrombectomy: The new standard of care for large vessel ischaemic stroke. Lancet Neurol 2015;14:846-54
The studies published in 2013, related to endovascular treatment in ischemic stroke, had their own limitations, which were due to the selection criteria used, the fact that the devices used were of modest efficacy and of an earlier generation, and that there were often nonconsecutive enrollments and treatment delays. However, in the recent past, six trials were conducted to evaluate the efficacy of endovascular thrombectomy for ischemic strokes, and these have provided level 1 evidence for improved patient care. In a majority of patients, thrombectomy was coupled with intravenous alteplase, but even those patients who were ineligible for alteplase showed benefits using the endovascular therapy. Major vessel occlusion on imaging was a prerequisite for all these trials, and patients with large areas of irreversibly damaged brain were excluded from the study. The studies reported a low procedural complication rate with no major safety concerns. The authors concluded on the basis of the currently available data that in addition to intravenous alteplase in cases of major vessel occlusion, endovascular thrombectomy should also immediately be offered. Under these circumstances, one should not wait for the response of alteplase to occur.
NINDS Exploratory Trials in Parkinson Disease (NET-PD) FS-ZONE Investigators. Pioglitazone in early Parkinson's disease: A phase 2, multicentre, double-blind, randomised trial. Lancet Neurol 2015;14:795-803
The authors have conducted a multicentric, double-blind, randomized trial to evaluate the role of pioglitazone in the treatment of Parkinson's disease. Patients with early Parkinson's disease (210 patients) on either 1 mg/day rasagiline or 10 mg/day selegiline were enrolled from 35 sites in United States and randomly assigned (1:1:1) to either 15 mg/day pioglitazone (72 patients), 45 mg/day pioglitazone (67 patients), or placebo (71 patients). Change in the total Unified Parkinson's Disease Rating Scale (UPDRS) score between the baseline and 44 weeks was chosen as the primary outcome measure and was analyzed by intention to treat. The null hypothesis for each group was the mean change in UPDRS being 3 points less than the mean change in the placebo group. The improvement following pioglitazone adminisration not being meaningfully different from the placebo was the alternate hypothesis (of futility). The null hypothesis was rejected if there was significant evidence of futility at the one-sided alpha level of 0.10.
Based on the failure of the study to reject the null hypothesis and the adverse events occurring, the authors concluded that at the doses used in the study, pioglitazone is unlikely to modify progression in early Parkinson's disease, and any further study in a larger trial is not recommended.
Bydon M, et al. Impact of age on short-term outcomes after lumbar fusion: An analysis of 1395 patients stratified by decade cohorts. Neurosurgery 2015;77:380-5
The safety of spinal fusion in elderly patients is uncertain. The authors intended to study whether spinal instrumentation (lumbar fusion) in elderly has a higher 30-day complication rate when compared with their younger counterparts. All patients undergoing posterolateral instrumentation for lumbar fusion were identified (by using the American College of Surgeons National Surgical Quality Improvement Program). Patients were grouped into one of the four groups based on their age: <65 years, 65–75, 75–85, and >85 years. By multivariate analysis, all 30-day complications (grouped as overall composite morbidity) were compared. The overall 30-day complication rate was 11.47% among the total of 1395 patients who were identified and included in the study. The complication rate was 9.04% for <65 years and 14.05% for >65 years group. The complication rate was 9.04% for the <65 year cohort, 13.46% for the 65–75 year cohort, 16.17% for the 75–85 year group, and 4.00% for the >85 year cohort. There was no significant difference between the <65 and >65 year cohorts on multivariate analysis (odds ratio = 1.26; 95% confidence interval: 0.87–2.19). The authors concluded that although patients >65 years of age have significantly more complication rates after lumbar fusion, age is not an independent risk factor for complication occurrence.
Thomas AJ, et al. Proposal of venous drainage-based classification system for carotid cavernous fistulae with validity assessment in a multicenter cohort. Neurosurgery 2015;77:380-5
Although arterial supply is used most commonly for classifying carotid cavernous fistulae (CCF), it is the venous drainage that predominantly influences the symptoms and the treatment approach. The authors have proposed a new classification of CCFs based on venous drainage. The CCFs were classified into five types based on their venous drainage pattern. Type 1 had posterior/inferior drainage only, type 2 had posterior/inferior and anterior drainage, type 3 had anterior drainage only, type 4 had retrograde drainage into cortical veins with/without other drainage channels, and type 5 had a direct connection between the internal carotid artery and the cavernous sinus. Type 2 (27.6%) and type 3 (34.5%) were the most commonly encountered CCFs in the series, and type 1 was rare (6.9%). The proposed classification was significantly associated with symptomatology (P = 0.001). Ocular/orbital and cavernous symptoms were significantly associated with type 2 CCF (P = 0.001) and type 3 CCF with ocular/orbital symptoms only (P = 0.01). Type 4 CCF was associated with cortical symptoms with/without ocular/orbital and cavernous symptoms (P = 0.01). The new classification significantly influenced the endovascular treatment approach (P = 0.001). The endovascular inferior petrosal sinus approach was useful in type 1 and 2 CCF (P = 0.01). The endovascular superior ophthalmic vein approach was significantly associated with type 3 CCF (P = 0.01). The type 5 CCF was approached in a significant number of patients using a transarterial approach through the ICA (P = 0.01). There was a trend toward partial resolution after endovascular treatment in type 2 CCFs (P = 0.07). A significant number of patients with a minor residual fistula after treatment recovered completely or significantly improved owing to spontaneous thrombosis. The rate of complete cure in recent series has been approximately 70% or greater similar to the rate of 72% in the series. A significant residual fistula, long-standing symptoms, and a larger number of cavernous sinus-draining venous channels appear to pose a higher risk of delayed recovery after embolization.
Farahmand D, et al. A double-blind randomized trial on the clinical effect of different shunt valve settings in idiopathic normal pressure hydrocephalus. J Neurosurg. DOI: 10.3171/2015.1.JNS141301
The authors have conducted a prospective, double-blind, randomized, controlled double-center study to determine if gradual reduction of opening pressure of a shunt system has any effect on the signs and symptoms in cases of idiopathic normal pressure hydrocephalus (iNPH). Sixty-eight patients implanted with a ventriculoperitoneal shunt with an adjustable Codman Medos valve were randomly assigned to either of the two groups, namely the 20-4 group (valve setting initially set to 20 cm of H2O and gradually reduced to 4 cm of H2O over a 6-month period), and the 12 group (valve pressure kept constant at 12 cm of H2O throughout the 6-month study period). All cases were clinically evaluated preoperatively using four tests, and postoperatively also at 1, 2, 3, 4 and 6 months. Fifty-five patients were able to complete the study. Significant improvement was seen in both the groups after shunt placement, with maximum improvement seen in the first postoperative evaluation. There was no significant difference either preoperatively or at any point of time in the postoperative period and follow-up. Clinically significant improvement was seen in the first 3 months, with no significant improvement thereafter, in both the groups. The authors concluded that gradual reduction of valve pressure (20 cm of H2O to 4 cm of H2O) did not improve outcome when compared with fixed valve setting (12 cm of H2O).
Scheller C, et al. Prophylactic nimodipine treatment for cochlear and facial nerve preservation after vestibular schwannoma surgery: A randomized multicenter Phase III trial. J Neurosurg. DOI: 10.3171/2015.1.JNS142001
The authors have conducted a prospective, randomized, multicenter phase III trial to ascertain whether prophylactic nimodipine and hydroxyethyl starch improves facial nerve and cochlear nerve preservation following vestibular schwannoma (VS) surgery. 112 patients, who underwent VS surgery in seven departments of neurosurgery, were randomly assigned to either of the two groups, namely the treatment group (n = 56) and the control group (n = 56). The treatment group received parenteral nimodipine (1–2 mg/h) and hydroxyethyl starch (hematocrit: 30%–35%) from the day prior to surgery till the seventh day after surgery. The control group received neither of these drugs. There was no significant difference in either facial nerve function (35 [67.3%] of 52 [treatment group] compared with 34 [72.3%] of 47 [control group]; P = 0.745) or hearing preservation (11 [23.4%] of 47 [treatment group] compared with 15 [31.2%] of 48 [control group]; P = 0.530) 12 months after surgery. The tumor size was significantly larger in the treatment group. The risk of deterioration of facial nerve function was adjusted nearly the same in both groups (OR: 1.07 [95% CI: 0.34–3.43], P = 0.91). In contrast, the risk for postoperative hearing loss was adjusted two times lower in the treatment group compared with the control group (OR: 0.49 [95% CI: 0.18–1.30], P = 0.15). The authors conclude that there was no statistically significant difference in both the groups and thus no significant effects of the treatment.
Fereshtehnejad SM, et al. New clinical subtypes of Parkinson disease and their longitudinal progression: A prospective cohort comparison with other phenotypes. JAMA Neurol 2015;72:863-73
There is a wide variability of symptoms in Parkinson disease (PD) patients suggesting that the disease can be divided into different subtypes. This study was undertaken to identify these subtypes depending on the baseline characteristic and the progression over a period of time. A total of 113 PD patients were recruited from two movement disorder centers in Quebec, Canada, and different motor/nonmotor clinical features were noted. Seventy-six patients were reassessed after a mean period of 4.5 years. Three subtypes of PD, mainly motor/slow progression, diffuse/malignant, and intermediate, were identified based on mild cognitive impairment, orthostatic hypotension, rapid eye movement sleep behavior disorder, anxiety, depression, and Unified Parkinson Disease Rating Scale Part II and Part III scores at baseline. The diffuse/malignant subtype had a rapid progression in comparison with other phenotypes despite having subjects of a similar age and disease duration. The authors concluded that patients with PD should be screened at the baseline visits to identify features of diffuse/malignant subtypes, namely orthostatic hypotension, mild cognitive impairment, and rapid eye movement sleep behavior disorder.
Ariño H, et al. Paraneoplastic neurological syndromes and glutamic acid decarboxylase antibodies. JAMA Neurol. DOI http://dx.doi.org/10.1001/jamaneurol. 2015.0749
Antibodies to the synaptic enzyme glutamic acid decarboxylase (GAD-abs) have been considered as sensitive biomarkers for stiff person syndrome. In this paper, the authors have looked into the causal association of paraneoplastic syndromes (PNS) and GAD65-abs. Fifteen cases fulfilling the criteria of definite or possible PNS with GAD65-abs but without concomitant onconeuronal antibodies were compared with 106 cases with GAD65-abs and no cancer (control). GAD65-abs patients with PNS were more frequently male, older, and more often associated with neuronal cell surface antibodies. Most common associated tumors were present in the lung and thymus. The authors concluded that patients having GAD-abs were more likely to have underlying cancer if their clinical presentation was that of classical PNS or if they had clinical presentations different from that seen in stiff person syndrome or cerebellar ataxia, or if the patient had coexisting neuronal cell-surface antibodies.
Zange L, et al. Phosphorylated α-synuclein in skin nerve fibres differentiates Parkinson's disease from multiple system atrophy. Brain 2015;138(Pt 8):2310-21
Parkinson disease (PD) and multiple system atrophy (MSA) are both characterized by the accumulation of the phosphorylated SNCA (∝-synuclein) gene. Clinically differentiating between them is, therefore, challenging. The pre- and postmortem studies in patients with PD have demonstrated ∝--synuclein deposition in cutaneous nerve fibers, but there is no premortem study in MSA patients. In this study, 10 patients each, respectively, of PD and MSA were recruited. Six patients with essential tremor (ET) were also recruited as controls. All patients underwent a clinical examination, autonomic function testing, single-photon emission computerized tomography, and 3-mm punch biopsy of the skin. Immunohistochemistry was done using anti-pSNCA, anti-ubiquitin carboxyl-terminal esterase L1 (UCHL1), and anti-tyrosine hydroxylase (TH) antibodies. All PD patients expressed phosphorylated SNCA in their sympathetic skin nerve fibers. In contrast, none of the MSA and ET patients had phosphorylated SNCA in their skin biopsy. Skin biopsy assessment of phosphorylated SNCA can be a definite and reliable tool for differentiating between PD and MSA patients.
Jacobsen JH, et al. Why musical memory can be preserved in advanced Alzheimer's disease. Brain 2015;138:2438-50
Musical memory is less involved in Alzheimer's disease (AD) patients. The hypothesis is that areas responsible for this memory are intact until late stages of dementia have set in. To prove this hypothesis, a 7-tesla functional magnetic resonance imaging (MRI) study was done on 32 (16 male and 16 female) healthy young human subjects. The brain response to unknown music excerpts was analyzed. A role of the caudal anterior cingulate and the ventral presupplementary motor area was found in the neural encoding of memory related to unknown music. In the second part of the study, three biomarkers of AD were analyzed in the region of interest (caudal anterior cingulate and the ventral presupplementary motor area) in 20 AD patients and 34 healthy controls. As compared with the other parts of brain, these areas showed minimal cortical atrophy and minimal disruption of glucose metabolism. The only exception was the amyloid accumulation, which was similar to other areas of the brain. This finding explains the relative preservation of musical memory in AD patients.
Silberstein SD, et al. Per cent of patients with chronic migraine who responded per onabotulinumtoxinA treatment cycle: PREEMPT. J Neurol Neurosurg Psychiatry. 2015;86:996-1001
Onabotulinumtoxin A has been approved for use in chronic migraine patients. It is not clear, however, whether the patients who fail to respond after the first injection respond to the second or subsequent injection. This study was a pooled data from the “Phase III Research Evaluating Migraine Prophylaxis Therapy” (PREEMPT) study. The end point of the study was ≤50% reduction in headache-days or ≤5-point improvement in the headache impact test (HIT) score. The study was conducted in two phases (phase 1: double-blind randomized, and phase 2: open-label). Among the 688 treated group, ≤50% reduction in headache-days was seen in 49.3% patients after cycle 1, in 11.6% after cycle 2, and in 10.3% after cycle 3. Similarly, ≤5-point improvement in the HIT score was seen in 56.3% patients after cycle 1, 14.5% patients after cycle 2, and 7.7% patients after cycle 3. This study concluded that a significant proportion of patients suffering from chronic migraine are likely to improve in the subsequent cycles of treatment if they fail to respond in the first cycle.
Merkler AE, et al. Temporal relationship between infective endocarditis and stroke. Neurology 2015;85:512-6
This was a retrospective study to ascertain the temporal relationship between stroke and infective endocarditis (IE). A total of 17,926 patients of IE were studied between July 2007 and June 2011. Ischemic and hemorrhagic strokes were identified from the data in discrete 1-month periods beginning from 6 months before to 6 months after the diagnosis of IE. The odds of developing a stroke were compared with the odds of developing stroke in the corresponding 1-month period 2 years earlier. Out of the studied patients, 2275 patients developed strokes. Ischemic stroke was seen in 82.5%, hemorrhagic stroke in 13.7%, and both in 3.8%. The highest risk of stroke was found in the 1-month period after the diagnosis of IE. The overall risk of stroke was high in the 4-month period before and in the 5-month after the diagnosis of IE. On an individual basis, ischemic stroke followed the same pattern; however, hemorrhagic strokes had only a modest increase in risk in the 1-month period after the diagnosis of IE, while rest of the associations were found to be concordant. The increased risk of stroke after an established IE suggests bacteremia and an embolic phenomenon; however, the increased risk before the diagnosis of IE points toward the role of inflammatory mechanisms in the pathogenesis of stroke.
Wang X and CHANCE investigators. Effect of clopidogrel with aspirin on functional outcome in TIA or minor stroke: CHANCE substudy. Neurology 2015;85:573-9
This was a randomized, double-blind, placebo-controlled trial that compared clopidogrel plus aspirin and aspirin alone in patients with acute high-risk TIA or minor ischemic stroke who were followed for 90 days. A total of 5170 patients were included, out of whom 36 were lost to follow-up. Randomization allotted 2569 patients in aspirin plus placebo group and 2562 patients in clopidogrel plus aspirin group. Patients received clopidogrel plus aspirin (clopidogrel at an initial dose of 300 mg, followed by 75 mg per day for 90 days, plus aspirin at a dose of 75 mg per day for the first 21 days) or placebo plus aspirin (75 mg per day for 90 days). Patients who had a National Institutes of Health Stroke (NIHS) score of ≤3, or patients with TIA with an ABCD2 (age, blood pressure, clinical features, duration) score of 4 or more were included. The 90-day functional outcome was measured by modified Rankin Scale (mRS), and quality of life was measured by EuroQol-5 Dimension (EQ-5D). On analysis, a statistically significant difference was found in functional outcome favoring the clopidogrel plus aspirin group in terms of mobility and activity. There was an overall statistically significant difference in terms of no new stroke/nondisabling stroke in favor of the clopidogrel plus aspirin group. This study suggests that the combination of clopidogrel and aspirin appears to be superior to aspirin alone in improving poor functional outcome, in reducing the rate of disabling stroke, and in further decreasing the risk of stroke.
Schlaeger R, et al. Association between thoracic spinal cord gray matter atrophy and disability in multiple sclerosis. JAMA Neurol 2015;72:897-904
A cross-sectional study was done to establish an association, if any, between disability due to multiple sclerosis (MS) and the disease type with areas of lower thoracic cord gray matter (GM) and white matter (WM) involvement. A total of 142 patients (out of whom, 99 had relapsing MS [RMS] and 43 had progressive MS [PMS]) along with 20 healthy individuals were recruited between July 2013 and March 2014. The participants were subjected to clinical assessment in the form of Expanded Disease Status Scale (EDSS), timed 25-Foot Walk Test (T25FW), 9-Hole Peg Test (9-HPT), and power assessment of hip flexion. Participants underwent imaging in the form of “phase-sensitive inversion recovery” (PSIR) at C2/C3, C3/C4, T8/T9, and T9/T10 intervertebral disc levels. Participants also underwent T1-weighted, T2-weighted, and fluid-attenuated inversion recovery (FLAIR) images of the brain and spinal cord. The study found an inverse correlation between the EDSS and the T25FW scores with GM area at all the cord levels studied. It was also found that the mean GM areas at all cord levels studied were significantly lower in the PMS patients when compared with RMS patients. Statistical analysis also found that lower thoracic WM involvement was next only to cervical WM involvement in contributing toward the overall EDSS score. Also, there was an increasing probability of patients developing PMS as their cord WM area decreased. Brain gray matter volume, as well as cervical and lower thoracic gray matter volume, emerged as the best predictors of the course of the disease.
The present study indicates that thoracic cord WM area correlates with the disease severity and clinical status in patients with MS. WM loss is more severe in patients with PMS when compared with RMS.