BACKGROUND:

Heat stress results in multiorgan failure and CNS injury. There a few case reports in the literature on the neurological consequences of heat stress.

CASE PRESENTATION:

We describe a patient with heat stress presenting with encephalopathy and bilateral cerebral, cerebellar, and thalamic lesions and intraventricular hemorrhage on MRI.

CONCLUSION:

Heat stress should be in the differential diagnosis of patients presenting with encephalopathy and elevated serum inflammatory markers especially if the history suggests a preceding episode of hyperthermia.

BACKGROUND:

Clinical-Diffusion mismatch (CDM; NIHSS score >=8 & DWI lesion volume <=25 mL) and Perfusion-Diffusion mismatch (PDM; difference >20% between initial DWI and MTT lesion volumes) have been proposed as surrogates for ischemic brains that are at risk of infarction. However, their utility to improve the selection of patients for thrombolytic treatment remains controversial. Our aim was to identify molecular biomarkers that can be used with neuroimaging to facilitate the selection of ischemic stroke patients for systemic thrombolysis.

METHODS:

We prospectively studied 595 patients with ischemic stroke within 12 h of the stroke onset. A total of 184 patients received thrombolytic treatment according to the SITS-MOST criteria. DWI and MTT volumes were measured at admission. The main outcome variable was good functional outcome at 3 months (modified Rankin scale <3). Serum levels of glutamate (Glu), IL-10, TNF-alpha, IL-6, NSE, and active MMP-9 also were determined at admission.

RESULTS:

Patients treated with t-PA who presented with PDM had higher IL-10 levels at admission (p < 0.0001). In contrast, patients with CDM had higher levels of IL-10 (p < 0.0001) as well as Glu and TNF-alpha (all p < 0.05) and lower levels of NSE and active MMP-9 (all p < 0.0001). IL-10 >= 30 pg/mL predicts good functional outcome at 3 months with a specificity of 88% and a sensitibity of 86%. IL-10 levels >=30 pg/mL independently in both patients with PDM (OR, 18.9) and CDM (OR, 7.5), after an adjustment for covariates.

CONCLUSIONS:

Serum levels of IL-10 facilitate the selection of ischemic stroke patients with CDM and PDM for systemic thrombolysis.

BACKGROUND:

Limited information has been published regarding standard quality assurance (QA) procedures for stroke registries. We share our experience regarding the establishment of enhanced QA procedures for the University of Texas Houston Stroke Registry (UTHSR) and evaluate whether these QA procedures have improved data quality in UTHSR.

METHODS:

All 5093 patient records that were abstracted and entered in UTHSR, between January 1, 2008 and December 31, 2011, were considered in this study. We conducted reliability and validity studies. For reliability and validity of data captured by abstractors, a random subset of 30 records was used for re-abstraction of select key variables by two abstractors. These 30 records were re-abstracted by a team of experts that included a vascular neurologist clinician as the "gold standard". We assessed inter-rater reliability (IRR) between the two abstractors as well as validity of each abstractor with the "gold standard". Depending on the scale of variables, IRR was assessed with Kappa or intra-class correlations (ICC) using a 2-way, random effects ANOVA. For assessment of validity of data in UTHSR we re-abstracted another set of 85 patient records for which all discrepant entries were adjudicated by a vascular neurology fellow clinician and added to the set of our "gold standard". We assessed level of agreement between the registry data and the "gold standard" as well as sensitivity and specificity. We used logistic regression to compare error rates for different years to assess whether a significant improvement in data quality has been achieved during 2008--2011.

RESULTS:

The error rate dropped significantly, from 4.8% in 2008 to 2.2% in 2011 (P < 0.001). The two abstractors had an excellent IRR (Kappa or ICC >= 0.75) on almost all key variables checked. Agreement between data in UTHSR and the "gold standard" was excellent for almost all categorical and continuous variables.

CONCLUSIONS:

Establishment of a rigorous data quality assurance for our UTHSR has helped to improve the validity of data. We observed an excellent IRR between the two abstractors. We recommend training of chart abstractors and systematic assessment of IRR between abstractors and validity of the abstracted data in stroke registries.

BACKGROUND:

Flu-like symptoms (FLS) are common side effects of interferon beta (IFN-beta) treatment in patients with Multiple Sclerosis (PwMS) and are associated with post-injection cytokine surge. We hypothesized that vitamin D3 supplementation would ameliorate FLS by decreasing related serum cytokines' levels.

METHODS:

In a randomized, double blind study of 45 IFNbeta-treated PwMS, 21 patients were assigned to 800 IU of vitamin D3 per day (low dose), while 24 patients received 4,370 IU per day (high dose) for one year. FLS were assessed monthly by telephonic interviews. Serum levels of 25-hydroxy-D (25-OH-D), calcium, PTH, IL-17, IL-10 and IFN-gamma were measured periodically. EDSS, relapses, adverse events and quality of life (QoL) were documented.

RESULTS:

25-OH-D levels increased to a significantly higher levels and PTH levels decreased in the high dose group. There was no significant change in FLS. IL-17 levels were significantly increased in the low dose group, while patients receiving high dose vitamin D had a heterogeneous IL-17 response. No significant differences in relapse rate, EDSS, QoL, serum IL-10 and IFNgamma were found. Hypercalcemia or other potential major adverse events were not observed.

CONCLUSION:

Vitamin D supplementation to IFN-beta treated PwMS, at the doses used, seems safe and associated with dose-dependent changes in IL-17 serum levels, while not affecting IFN-beta related FLS.Trial registration: ClinicalTrials.gov ID: NCT01005095.

BACKGROUND:

The aim of this study was to assess the effectiveness of neuroendoscopy compared with non-neuroendoscopic procedures for treating patients with arachnoid membrane cysts in the lateral ventricles.

METHODS:

The medical records of 28 patients with arachnoid membrane cysts in the lateral ventricles who were treated with neuroendoscopy and 39 such patients treated with non-neuroendoscopic techniques using classic treatment procedures were reviewed. The neuroendoscopic approach combined craniotomy, corticectomy, lesion resection and cyst ventriculostomy or cyst cisternostomy to restore normal cerebrospinal fluid circulation. The non-neuroendoscopic techniques included craniotomy, corticectomy, and lesion resection performed under a microscope. Clinical outcomes of symptoms and cyst size change on imaging were compared between the two treatment groups during follow-up (range: 1--5 years).

RESULTS:

Patients in the neuroendoscopy group had significantly less blood loss (P < 0.001) and shorter operative time (P < 0.001), better marked improvement in symptoms (64.3% vs. 5.1%, respectively), and a higher total resection rate (92.9% vs. 66.7%; P = 0.011) compared with the patients in the non-neuroendoscopy group. In the neuroendoscopy group there was no cyst recurrence whereas in the non-neuroendoscopy group 8 (20.5%) patients had cyst recurrence. However, all patients in the neuroendoscopy group had postoperative transient fever and 8 (28.6%) patients had subdural fluid accumulation which was treated and subsequently resolved during follow-up. These symptoms did not occur in the non-neuroendoscopy group.

CONCLUSION:

We found that neuroendoscopic therapy for arachnoid cysts in the lateral ventricles was more efficacious than non-neuroendoscopic methods. Our results indicate that neuroendoscopy may produce better clinical outcomes than non-neuroendoscopic procedures in treating patients with arachnoid cysts in the lateral ventricles.

BACKGROUND:

A debate surrounding multiple sclerosis epidemiology has centred on time-related incidence increases and the need of monitoring. The purpose of this study is to reassess multiple sclerosis incidence in the European Economic Area.

METHODS:

We conducted a systematic review of literature from 1965 onwards and integrated elements of original research, including requested or completed data by surveys authors and specific analyses.

RESULTS:

The review of 5323 documents yielded ten studies for age- and sex-specific analyses, and 21 studies for time-trend analysis of single data sets. After 1985, the incidence of multiple sclerosis ranged from 1.12 to 6.96 per 100,000 population, was higher in females, tripled with latitude, and doubled with study midpoint year. The north registered increasing trends from the 1960s and 1970s, with a historic drop in the Faroe Islands, and fairly stable data in the period 1980-2000; incidence rose in Italian and French populations in the period 1970-2000, in Evros (Greece) in the 1980s, and in the French West Indies in around 2000.

CONCLUSIONS:

We conclude that the increase in multiple sclerosis incidence is only apparent, and that it is not specific to women. Monitoring of multiple sclerosis incidence might be appropriate for the European Economic Area.

BACKGROUND:

Cerebral palsy (CP) results from a static brain lesion during pregnancy or early life and remains the most common cause of physical disability in children (1 in 500). While the brain lesion is static, the physical manifestations and medical issues may progress resulting in altered motor patterns. To date, there are no prospective longitudinal studies of CP that follow a birth cohort to track early gross and fine motor development and use Magnetic Resonance Imaging (MRI) to determine the anatomical pattern and likely timing of the brain lesion. Existing studies do not consider treatment costs and outcomes. This study aims to determine the pathway(s) to motor outcome from diagnosis at 18 months corrected age (c.a.) to outcome at 5 years in relation to the nature of the brain lesion (using structural MRI).

METHODS:

This prospective cohort study aims to recruit a total of 240 children diagnosed with CP born in Victoria (birth years 2004 and 2005) and Queensland (birth years 2006--2009). Children can enter the study at any time between 18 months to 5 years of age and will be assessed at 18, 24, 30, 36, 48 and 60 months c.a. Outcomes include gross motor function (GMFM-66 & GMFM-88), Gross Motor Function Classification System (GMFCS); musculoskeletal development (hip displacement, spasticity, muscle contracture), upper limb function (Manual Ability Classification System), communication difficulties using Communication and Symbolic Behaviour Scales-Developmental Profile (CSBS-DP), participation using the Paediatric Evaluation of Disability Inventory (PEDI), parent reported quality of life and classification of medical and allied health resource use and determination of the aetiology of CP using clinical evaluation combined with MRI. The relationship between the pathways to motor outcome and the nature of the brain lesion will be analysed using multiple methods including non-linear modelling, multilevel mixed-effects models and generalised estimating equations.

DISCUSSION:

This protocol describes a large population-based study of early motor development and brain structure in a representative sample of preschool aged children with CP, using direct clinical assessment. The results of this study will be published in peer reviewed journals and presented at relevant international conferences.Trial registration: ACTRN1261200169820.

BACKGROUND:

The anticonvulsants pregabalin and gabapentin are both indicated for the treatment of peripheral neuropathic pain. The decision on which treatment provides the best alternative, should also take into account all aspects of costs and outcomes associated with the two therapeutic options. The objective of this study was to examine the cost -- effectiveness of the two agents in the management of patients with painful diabetic neuropathy or post -- herpetic neuralgia, under the third party payer perspective in Greece.

METHODS:

The analysis was based on a dynamic simulation model which estimated and compared the costs and outcomes of pregabalin and gabapentin in a hypothetical cohort of 1,000 patients suffering from painful Diabetic Peripheral Neuropathy (DPN) or Post-Herpetic Neuralgia (PHN). In the model, each patient was randomly allocated an average pretreatment pain score, measured using an eleven-point visual analogue scale (0 -- 10) and was "run through" the model, simulating their daily pain intensity and allowing for stochastic calculation of outcomes, taking into account medical interventions and the effectiveness of each treatment.

RESULTS:

Pregabalin demonstrated a reduction in days with moderate to severe pain when compared to gabapentin. During the 12 weeks the pregabalin arm demonstrated a 0.1178 (SE 0.0002) QALY gain, which proved to be 0.0063 (SE 0.0003) higher than that in the gabapentin arm. The mean medication cost per patient was higher for the pregabalin arm when compared to the gabapentin arm (i.e. [euro sign]134.40) over the 12 week treatment period. However, this higher cost was partially offset by the reduced direct medical costs (i.e. the cost of specialist visits, the cost of diagnostic tests and the other applied interventions). Comparing costs with respective outcomes, the ICERs for pregabalin versus gabapentin were [euro sign]13 (95%CI: 8 -- 18) per additional day with no or mild pain and [euro sign]19,320 (95%CI: 11,743 -- 26,755) per QALY gained.

CONCLUSIONS:

Neuropathic pain carries a great disease burden for patients and society and, is also, associated with a significant economic burden. The treatment of pain associated with DPN and PHN with pregabalin is a cost-effective intervention for the social security in Greece compared to gabapentin. Thus, these findings need to be taken into consideration in the decision -- making process when considering which therapy to use for the treatment of neuropathic pain.

We report a case of childhood onset, generalized dystonia due to slowly progressive bilateral striatal necrosis associated with anti-N-methyl-D-aspartate receptor (NMDAR) antibodies. This clinical phenotype has not been previously associated with NMDA receptor autoimmunity.An eighteen year old man presented with a history of childhood-onset, progressive generalized dystonia. Clinical examination revealed a pure generalized dystonia with no cognitive or other neurological findings. Magnetic resonance imaging showed bilateral high T2 signal striatal lesions, which were slowly progressive over a period of nine years. New parts of the lesion showed restricted water diffusion suggesting cytotoxic oedema. Positron emission tomography of the brain showed frontal hypermetabolism and cerebellar hypometabolism. Antibodies against the NR1 subunit of the NMDA receptor were detected in the patient's serum and cerebrospinal fluid. There was no neoplasia or preceding infection or vaccination.This is the first report of chronic progressive bilateral striatal necrosis associated with anti-NMDAR antibodies. Our findings expand the clinical spectrum of disease associated with anti-NMDAR antibodies and suggest that these should be included in the work-up of dystonia with striatal necrosis.

Frontotemporal dementia (FTD) is recognised as a clinically and morphologically heterogeneous group of interrelated neurodegenerative conditions. One of the subtypes within this disease spectrum is the behavioural variant FTD (bvFTD). This is known to be a varied disorder with a mixture of tau-positive and tau-negative underlying pathologies. The other subtypes include semantic dementia (SD), which generally exhibits tau-negative pathology, and progressive non-fluent aphasia (PNFA), which is usually tau-positive. As the clinical presentation of these subtypes may overlap, a specific diagnosis can be difficult to attain and today no specific biomarker can predict the underlying pathology. Neurofilament light chain protein (NFL), a cytoskeletal constituent of intermediate filaments, is thought to reflect neuronal and axonal death when appearing in the cerebrospinal fluid (CSF). NFL has been shown to be elevated in CSF in patients with FTD compared with AD and controls. Our hypothesis was that the levels of NFL also differ between the subtypes of FTD and may indicate the underlying pathological subtype.We retrospectively analysed data from previous CSF analyses in 34 FTD cases (23 bvFTD, seven SD, four PNFA), 20 AD cases, and 26 healthy controls. A separate group of 10 neuropathologically verified and subtyped FTD cases (seven tau-negative, three tau-positive) were also analysed.NFL levels were significantly higher in FTD compared with both AD (p<0.001) and controls (p<0.001). The NFL levels of SD and bvFTD were significantly higher (p<0.001) compared with AD. The biomarker profiles of PNFA and AD were similar. In the neuropathologically verified FTD cases, NFL was higher in the tau-negative than in the tau-positive cases (exact p=0.017).The marked NFL elevation in some but not all FTD cases is likely to reflect the different underlying pathologies. The highest NFL values found in the SD group as well as in the neuropathologically verified tau-negative cases may be of subtype diagnostic value, if corroborated in larger patient cohorts. In bvFTD, a mixture of tau-positive and tau-negative underlying pathologies could possibly explain the intermediate NFL values.