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Alzheimer's disease and related dementias (ADRD) present significant challenges including cognitive and functional loss, behavioral disruption, emotional distress, and significant financial burden. These stressors are amplified in minority groups, who experience higher rates of ADRD but less frequent and later diagnosis. There is therefore a critical need to identify tangible approaches to culturally informed dementia assessment and care for patients from diverse communities. Muslim patients and particularly Muslim women are among the populations most understudied in the ADRD space. Muslim patients may hold unique religious, spiritual, and cultural beliefs and practices that can impact care-seeking for dementia symptoms, diagnostic accuracy, and treatment uptake. This paper outlines culturally informed approaches to assessing and treating Muslim women and families at each stage of ADRD care, though many recommendations extend to the broader Muslim community and others of diverse racial-ethnic backgrounds. We provide concrete suggestions for building rapport within and leveraging common family structures, respecting principles of modesty and privacy for all women including those who observe hijab or niqab, and communicating dementia diagnosis and care in the context of spiritual and ethical beliefs. While not intended as a comprehensive and prescriptive guide, this review provides important points of consideration and discussion with patients of Muslim backgrounds.

The semi-adiabatic localization by adiabatic selective refocusing (sLASER) sequence provides single-shot full intensity signal with clean localization and minimal chemical shift displacement error and was recommended by the international MRS Consensus Group as the preferred localization sequence at high- and ultra-high fields. Across-vendor standardization of the sLASER sequence at 3 tesla has been challenging due to the B 1 requirements of the adiabatic inversion pulses and maximum B 1 limitations on some platforms. The aims of this study were to design a short-echo sLASER sequence that can be executed within a B 1 limit of 15 μT by taking advantage of gradient-modulated RF pulses, to implement it on three major platforms and to evaluate the between-vendor reproducibility of its perfomance with phantoms and in vivo. In addition, voxel-based first and second order B 0 shimming and voxel-based B 1 adjustments of RF pulses were implemented on all platforms. Amongst the gradient-modulated pulses considered (GOIA, FOCI and BASSI), GOIA-WURST was identified as the optimal refocusing pulse that provides good voxel selection within a maximum B 1 of 15 μT based on localization efficiency, contamination error and ripple artifacts of the inversion profile. An sLASER sequence (30 ms echo time) that incorporates VAPOR water suppression and 3D outer volume suppression was implemented with identical parameters (RF pulse type and duration, spoiler gradients and inter-pulse delays) on GE, Philips and Siemens and generated identical spectra on the GE 'Braino' phantom between vendors. High-quality spectra were consistently obtained in multiple regions (cerebellar white matter, hippocampus, pons, posterior cingulate cortex and putamen) in the human brain across vendors (5 subjects scanned per vendor per region; mean signal-to-noise ratio > 33; mean water linewidth between 6.5 Hz to 11.4 Hz). The harmonized sLASER protocol is expected to produce high reproducibility of MRS across sites thereby allowing large multi-site studies with clinical cohorts., (© 2019 John Wiley & Sons, Ltd.)

Lacosamide (LCM) is a third-generation anti-epileptic drug (AED) for partial-onset epilepsy with minimal hepatic metabolism and drug-drug interactions. The impact of individual patient variables such as race on drug metabolism have been under-reported in AEDs and LCM has not been specifically investigated. Our aim was to assess the role race plays on serum LCM levels in the management of epilepsy. Thus, we retrospectively reviewed patients with focal seizures who received LCM and had LCM levels as part of their routine clinical care in our Level IV Epilepsy Center. Variables including age, race, gender, LCM serum levels, LCM daily dose, and concomitant AEDs were collected and analyzed. A total of 93 patients with 1-3 clinic visits yielded 122 LCM serum levels. African Americans (AA) comprised 62.3% of our serum samples. Daily LCM doses averaged 350 mg/day (range 50-1000 mg/day). Eighty-nine percent of patients took 1-2 other AEDs. Overall, AA patients had lower LCM levels (mean 6.8 μg/mL) compared to White patients (mean of 7.1 μg/mL) (p = .017) even when considering for the daily dose effect (p = .007). Analysis of co-variables did not have significant effect on LCM levels. Overall, AA patients had a weaker relationship between LCM daily dose (adjusted for weight) and serum levels as compared to White patients and require a higher LCM dose per weight to achieve similar levels. Differences in pharmacogenetics may play an important role in these findings and focus on how these variations impact seizure burden., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Objective: In the general population, injury related to seizures often involves falls, head trauma, soft tissue injuries, burns and fractures. Additionally, postictal deleterious behavior changes can by experienced by patients. We seek to identify the risk for seizure-related injury (SRI) and postictal aggression (PIA) in patients with refractory epilepsy., Methods: Self-reported SRI and PIA were gathered through a seizure questionnaire as part of the epilepsy center's seizure safety protocol. Retrospective review of questionnaire, clinical course, and demographic data was completed. Statistical analysis of variables of interest was done using nonparametric methods., Results: 126 patient questionnaires were completed over a one-year duration. Most patients reported seizure related injury (56.3 %) and postictal aggression (52.4 %). Increased disease duration was associated with seizure related injury and its severity (Kwallis p = 0.025), with number of antiepileptic drugs (AEDs) as significant factors (p = 0.012). Postictal aggression was also associated with a longer duration of epilepsy (Ranksum p = 0.037, t-test p = 0.04) and higher seizure frequency (p = 0.017). Patients who reported seizure related injury and postictal aggression were on more AEDs (p = 0.0003, p = 0.01, respectively), with first-generation AEDs being most contributory., Conclusion: The majority of patients with seizures report seizure-related injuries and postictal aggression. Duration and AED regimen are significant risk factors and screening practices can potentially guide safety measures and recommendations., Competing Interests: Declaration of Competing Interest None. We confirm that the work described has been carried out in accordance with The Code of Ethics of the World Medical Association. This study was approved by the Internal Review Board and waver of consent was obtained. The privacy rights of human subjects were always observed., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Multiple sclerosis (MS) has both an inflammatory and a neurodegenerative component, with gray matter (GM) atrophy being an important contributor to disability. Optical coherence tomography (OCT) may serve as a prognostic tool for neuroaxonal health by measuring ganglion cell inner plexiform layer (GCIPL) thickness. There is a paucity of literature regarding the effects of race on pathobiology of MS, as racial minorities are underrepresented in research studies., Objective: The aim of this paper is to compare the correlation between GM fraction (GMF) and GCIPL thickness in Caucasian Americans with MS (CAMS) and African Americans with MS (AAMS)., Methods: Fifty-nine patients with relapsing-remitting multiple sclerosis (RRMS) were included. Using a cross-sectional design, we compared the OCT (GCIPL thickness) and MRI (GMF) data of 32 CAMS and 27 AAMS patients., Results: No significant correlation was observed between GMF and GCIPL in our study group (p = 0.127, r = 0.148). CAMS exhibited a significant correlation between these measures (p = 0.0004, r = 0.434), while in AAMS these measures did not correlate significantly (p = 0.187, r = -0.201)., Conclusion: GCIPL might be a sensitive biomarker predicting GM atrophy and disability in CAMS, but not in AAMS. Larger studies are needed to investigate reliable biomarkers across races. Inclusion of AAMS in research studies is necessary to shed more light on the pathobiology of MS., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Few cross-sectional studies have investigated the correlation between neurochemical changes and multiple sclerosis (MS) fatigue, but little is known on the fatigue-related white matter differences between time points. We aim to investigate the longitudinal neurometabolite profile of white matter in MS fatigue. Forty-eight relapsing remitting multiple sclerosis (RRMS) patients with an expanded disability status scale (EDSS) ≤ 4 underwent high field 1 H-multivoxel magnetic resonance spectroscopy (MRS) at baseline and year 1. Fatigue severity was evaluated by the fatigue severity scale (FSS). Patients were divided into low (LF, FSS ≤ 3), moderate (MF, FSS = 3.1-5), and high fatigue (HF, FSS ≥ 5.1) groups. In a two-way analysis of variance (ANOVA), we observed a decline in the ratio of the sum of N-acetylaspartate (NAA) and N-acetylaspartylglutamate (NAAG) to the sum of creatine (Cr) and phosphocreatine (PCr) in the right anterior quadrant (RAQ) and left anterior quadrant (LAQ) of the MRS grid in the HF group at baseline and year 1. This decline was significant when compared with the LF group ( p = 0.018 and 0.020). In a one-way ANOVA, the fatigue group effect was significant and the ratio difference in the right posterior quadrant (RPQ) and left posterior quadrant (LPQ) of the HF group was also significant ( p = 0.012 and 0.04). Neurochemical changes in the bilateral frontal white matter and possibly parietooccipital areas were noted in the HF group at two different time points. Our findings may shed some light on the pathology of MS fatigue.

Objectives: Cilostazol, a selective inhibitor of phosphodiesterase 3, may reduce symptomatic vasospasm and improve outcome in patients with aneurysmal subarachnoid hemorrhage considering its anti-platelet and vasodilatory effects. We aimed to analyze the effects of cilostazol on symptomatic vasospasm and clinical outcome among patients with aneurysmal subarachnoid hemorrhage (aSAH)., Patients and Methods: We searched PubMed and Embase databases to identify 1) prospective randomized trials, and 2) retrospective trials, between May 2009 and May 2017, that investigated the effect of cilostazol in patients with aneurysmal aSAH. All patients were enrolled after repair of a ruptured aneurysm by clipping or endovascular coiling within 72hours of aSAH. fixed-effect models were used to pool data. We used the I 2 statistic to measure heterogeneity between trials., Results: Five studies were included in our meta-analysis, comprised of 543 patients with aSAH (cilostazol [n=271]; placebo [n=272], mean age, 61.5years [SD, 13.1]; women, 64.0%). Overall, cilostazol was associated with a decreased risk of symptomatic vasospasm (0.31, 95% CI 0.20 to 0.48; P<0.001), cerebral infarction (0.32, 95% CI 0.20 to 0.52; P <0.001) and poor outcome (0.40, 95% CI 0.25 to 0.62; P<0.001). We observed no evidence for publication bias. Statistical heterogeneity was not present in any analysis., Conclusion: Cilostazol is associated with a decreased risk of symptomatic vasospasm and may be clinically useful in the treatment of delayed cerebral vasospasm in patients with aSAH. Our results highlight the need for a large multi-center trial to confirm the observed association., (Copyright © 2018 National Stroke Association. Published by Elsevier Inc. All rights reserved.)

Intravascular imaging has significantly contributed to the advancement of interventional cardiology. Intravascular ultrasound and optical coherence tomography have facilitated decision-making and interventional strategies in management of coronary artery lesions. Yet, applications of these modalities are limited in cerebrovascular practice. With the momentum in advancement of neuroendovascular interventions and techniques for treatment of strokes, cerebrovascular atherosclerotic diseases, aneurysms and vascular malformations, there is a need for the development of high-resolution platforms that can safely be used in cerebrovascular system, and to meet the imaging requirements in the field. In this brief review, we aim to discuss current and emerging intravascular imaging modalities and explore their potentials in field of neuroendovascular surgery.

Status epilepticus (SE) is defined as ongoing seizures lasting longer than five minutes or multiple seizures without recovery. Benzodiazepines (BZDs) are first-line agents for the management of SE. Our objective was to evaluate BZD dosing in SE patients and its effects on clinical/electrographic outcomes. A retrospective analysis was conducted from a prospective database of SE patients admitted to a university-based neurocritical care unit. The initial presentation and progression to refractory SE (RSE) and non-convulsive SE (NCSE) with coma was evaluated. Outcome measures included length of stay (LOS), rates of intubation, ventilator-dependent days, and Glasgow outcome scale (GOS). The lorazepam equivalent (LE) dosage of BZDs administered was calculated and we analysed variations in progression if 4 mg or more of LE (adequate BZDs) was administered. Among 100 patients, the median dose of LE was 3 mg (IQR: 2-5 mg). Only 31% of patients received adequate BZDs. Only 18.9% of patients with NCSE without coma received adequate BZDs (p=0.04). Among patients progressing to RSE, 75.4% had not received adequate BZDs (p=0.04) and among patients developing NCSE with coma, 80.6% did not receive adequate BZDs (p=0.07). Escalating doses of BZDs were associated with a decrease in cumulative incidences of RSE (correlation coefficient r=-0.6; p=0.04) and NCSE with coma (correlation coefficient r=-0.7; p=0.003). Outcome measures were not influenced by BZD dosing. The majority of our patients were not adequately dosed with BZDs. Inadequate BZD dosing progressed to RSE and had a tendency to lead to NCSE with coma. Our study demonstrates the need to develop a hospital-wide protocol to guide first responders in the management of SE.

Objective: To compare the outcomes of patent foramen ovale (PFO) closure vs antiplatelet agent (APA) vs oral anticoagulation therapy (OAT) for secondary prevention of stroke in patients with cryptogenic stroke, using direct and indirect evidence from existing randomized data., Methods: Relevant randomized controlled trials were identified by a systematic review. The efficacy outcome was stroke recurrence, and safety outcomes were atrial fibrillation and bleeding complications at the end of follow-up. Bayesian network meta-analysis was performed to calculate risk estimates and the rank probabilities using APA therapy as the reference., Results: In a network meta-analysis of 6 randomized controlled trials consisting of 3,497 patients (1,732 PFO closure, 1,252 APA, 513 OAT), PFO closure and OAT were associated with lower rates of recurrent stroke (odds ratio [OR] 0.30, 95% credibility interval [CrI] 0.17-0.49 and OR 0.42, 95% CrI 0.22-0.78, respectively) with equal efficacy of OR 0.70 (95% CrI 0.37-1.49). PFO closure had the highest top rank probability of atrial fibrillation and OAT had the highest risk of bleeding complications., Conclusions: These findings suggest that closure and OAT may be equally effective in recurrent stroke prevention in patients with PFO. There is an increased risk of atrial fibrillation and bleeding with closure and OAT therapy, respectively. A randomized trial is needed to identify patients who would benefit most from each strategy., (© 2018 American Academy of Neurology.)

Background: B-cells play a pivotal role in several autoimmune diseases, including patients with immune-mediated neurological disorders (PIMND), such as neuromyelitis optica (NMO), multiple sclerosis (MS), and myasthenia gravis (MG). Targeting B-cells has been an effective approach in ameliorating both central and peripheral autoimmune diseases. However, there is a paucity of literature on the safety of continuous B-cell depletion over a long period of time., Objective: The aim of this study was to examine the long-term safety, incidence of infections, and malignancies in subjects receiving continuous therapy with a B-cell depleting agent rituximab over at least 3 years or longer., Methods: This was a retrospective study involving PIMND who received continuous cycles of rituximab infusions every 6 to 9 months for up to 7 years. The incidence of infection related adverse events (AE), serious adverse events (SAE), and malignancies were observed., Results: There were a total of 32 AE and 4 SAE with rituximab treatment. The 3 SAE were noted after 9 cycles (48 months) and 1 SAE was observed after 11 cycles (60 months) of rituximab. There were no cases of Progressive multifocal leukoencephalopathy (PML) and malignancies observed throughout the treatment period. Rituximab was well tolerated without any serious infusion reactions. Also, rituximab was found to be beneficial in treating PIMND over a 7-year period., Conclusions: This study demonstrates that long-term depletion of peripheral B-cells appears safe and efficacious in treating PIMND. Longer and larger prospective studies with rituximab are needed to carefully ascertain risks associated with chronic B-cell depletion, including malignancies. Recognizing that this is a small, retrospective study, such data nonetheless complement the growing literature documenting the safety and tolerability of B-cell depleting agents in neurological diseases.

Background and Purpose: African American (AA) patients with multiple sclerosis (MS) have been reported to have a more aggressive disease course compared to their white counterparts. We explored the relation of gray matter (GM) volume, a marker of tissue injury, and cerebrospinal fluid (CSF) IgG index in both AA and white MS patients., Methods: This was a cross-sectional study of 150 self-identified AA and 150 white patients with MS who underwent magnetic resonance imaging scan of brain and CSF sampling. Intrathecal IgG synthesis was quantified as IgG index. The Spearman test was used for univariate correlation analysis, followed by generalized linear model (GLM) to assess the effect of race on the correlation between IgG index and GM volume., Results: The GM volume was inversely related to the IgG index for the entire group (rho = -.57, P < .0004). The AA group showed a stronger correlation (rho = -.893, P < .00004), as compared to whites (rho = -.019, P = .85), between GM and IgG index. Furthermore, GLM analysis showed a significant effect of race on the relation between IgG index and GM volume (P < .0005)., Conclusions: AA patients with MS have lower GM volume and a stronger inverse correlation between GM volume and CSF IgG index, compared to the whites. These findings suggest a potentially prominent role of humoral immunity in mediating tissue injury in AA patients with MS., (Copyright © 2017 by the American Society of Neuroimaging.)

Fatigue is a common and disabling symptom in Multiple Sclerosis (MS). However, consistent neuroimaging correlates of its severity are not fully elucidated. In this article, we study the neuronal correlates of fatigue severity in MS. Forty-three Relapsing Remitting MS (RRMS) patients with MS-related fatigue (Fatigue Severity Scale (FSS) range: 1-7) and Expanded Disability Status Scale (EDSS) ≤ 4, were divided into high fatigue (HF, FSS ≥ 5.1) and low fatigue groups (LF, FSS ≤ 3). We measured T2 lesion load using a semi-automated technique. Cortical thickness, volume of sub-cortical nuclei, and brainstem structures were measured using Freesurfer. Cortical Diffusion Tensor Imaging (DTI) parameters were extracted using a cross modality technique. A correlation analysis was performed between FSS, volumetric, and DTI indices across all patients. HF patients showed significantly lower volume of thalamus, ( p = 0.02), pallidum ( p = 0.01), and superior cerebellar peduncle ((SCP), p = 0.002). The inverse correlation between the FSS score and the above volumes was significant in the total study population. In the right temporal cortex (RTC), the Radial Diffusivity ((RD), p = 0.01) and Fractional Anisotropy ((FA), p = 0.01) was significantly higher and lower, respectively, in the HF group. After Bonferroni correction, thalamic volume, FA-RTC, and RD-RTC remained statistically significant. Multivariate regression analysis identified FA-RTC as the best predictor of fatigue severity. Our data suggest an association between fatigue severity and volumetric changes of thalamus, pallidum, and SCP. Early neuronal injury in the RTC is implicated in the pathogenesis of MS-related fatigue., Competing Interests: K.Y., F.B., R.S., C.S.M., R.G., N.S.B. report no conflict of interest. O.K. received lecture fees from TEVA, Genzyme and research support from Chugai, Medimmune, and Biogen. EB received lecture fees from Biogen, TEVA, and EMD Serono and research support from Roche, Chugai, and Medimmune.

Background: The diagnostic accuracy of cerebrospinal fluid oligoclonal bands (CSF-OCB) detected by isoelectric focusing (IEF) in patients with multiple sclerosis (MS) was evaluated in our study., Methods: Three hundred and twenty-one patients with MS and other central nervous system (CNS) immune mediated disorders were assessed (CIMD). Cerebrospinal fluid and matched serum samples were examined for the presence of OCB by IEF-IB (isoelectric focusing with immunoblotting)., Results: Isolated oligoclonal bands (ISO-OCB) were the only predictor of MS diagnosis independent of age, gender and CSF-OCB. ISO-OCB ≥ 3.5 detected by IEF yielded a sensitivity of 98% and specificity of 87% in distinguishing MS from MS mimickers., Conclusions: For the neurologist, a score of ≥ 4 ISO-OCB supports the diagnosis of MS. On the other hand, ISO-OCB ≤3 favors CIMD. Further studies with larger population samples are warranted to confirm these findings.

Multiple sclerosis (MS) is considered a primary autoimmune disease; however, this view is increasingly being challenged in basic and clinical science arenas because of the growing body of clinical trials' data showing that exclusion of immune cells from the CNS only modestly slows disease progression to disability. Accordingly, there is significant need for expanding the scope of potential disease mechanisms to understand the etiology of MS. Concomitantly, the use of a broader range of pre-clinical animal models for characterizing existing efficacious clinical treatments may elucidate additional or unexpected mechanisms of action for these drugs that augment insight into MS etiology. Herein, we explore the in vivo mechanism of action of dimethyl fumarate, which has been shown to suppress oxidative stress and immune cell responses in psoriasis and MS. Rather than studying this compound in the context of an experimental autoimmune-induced attack on the CNS, we have used a genetic model of hypomyelination, male rumpshaker (rsh) mice, which exhibit oligodendrocyte metabolic stress and startle-induced subcortical myoclonus during development and into adulthood. We find that myoclonus is reduced 30-50% in treated mutants but we do not detect substantial changes in metabolic or oxidative stress response pathways, cytokine modulation, or myelin thickness (assessed by anova). All procedures involving vertebrate animals in this study were reviewed and approved by the IACUC committee at Wayne State University., (© 2017 International Society for Neurochemistry.)

Sjogren's syndrome is a chronic autoimmune disorder which affects the exocrine glands with lymphocytic infiltration, and occasionally involves central nervous system. It is usually rare and manifests as a lesion in the trigeminal nerve. Our case discusses the involvement of the oculomotor and abducens nerves along with the prevalence of such cases as seen on literature review. We describe a case of a middle aged woman who presented with ophthalmoplegic symptoms. The symptoms resolved in response to steroid therapy and serum analysis was positive for anti SSA antibodies. Increasing use of imaging modalities has enabled identifying cranial nerve enhancements easily. Correlating this to serum analysis, as in our case; has helped identify more cases of third and sixth cranial nerve involvement than was previously known to occur with primary Sjogren's syndrome., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Background and Purpose: Conventional MRI techniques do not necessarily provide information about multiple sclerosis (MS) disease pathology or progression. Nonconventional MRI techniques, including proton magnetic resonance spectroscopy ( 1 H-MRS), are increasingly used to improve the qualitative and quantitative specificity of MR images. This study explores potential correlations between MRI measures of disease and disability progression as measured by the Expanded Disability Status Scale (EDSS), Functional Systems (FS), and ambulation index scores in a unique cohort of MS patients treated with glatiramer acetate that has been closely monitored for over 20 years., Methods: This was a multicenter, open-label, cross-sectional MRI substudy among participants in the GA-9004 open-label extension of the 36-month, double-blind GA-9001 study, timed to coincide with the prospectively planned 20-year clinical exam., Results: Of 64 patients who participated in the MRI substudy, results are presented for the 39 patients (61%) who had a 1 H-MRS assessment at 20 years of treatment. Both total N-acetylaspartate relative to total creatinine (tNAA/tCr) concentration ratio and T1 lesion volume were found to be robustly associated with disability levels with different statistical approaches. Gray matter (GM) volume was found to be a more consistent parameter than white matter (WM) volume for disability allocation. The elastic net algorithm showed a trade-off between WM and GM volumes for disability estimation when different disability definitions were used., Conclusions: Among patients with MS receiving long-term glatiramer acetate therapy, consistent effects on disability levels indicated by EDSS and pyramidal FS score thresholds were found for tNAA/tCr concentration ratio and T1 lesion volume., (© 2016 The Authors. Journal of Neuroimaging published by Wiley Periodicals, Inc. on behalf of American Society of Neuroimaging.)

Marijuana-based treatment for refractory epilepsy shows promise in surveys, case series, and clinical trials. However, literature on their EEG effects is sparse. Our objective is to analyze the effect of marijuana on EEG in a 24-year-old patient with idiopathic generalized epilepsy treated with cannabis. We blindly reviewed 3 long-term EEGs-a 24-hour study while only on antiepileptic drugs, a 72-hour EEG with Cannabis indica smoked on days 1 and 3 in addition to antiepileptic drugs, and a 48-hour EEG with combination C indica/sativa smoked on day 1 plus antiepileptic drugs. Generalized spike-wave discharges and diffuse paroxysmal fast activity were categorized as interictal and ictal, based on duration of less than 10 seconds or greater, respectively. Data from three studies concatenated into contiguous time series, with usage of marijuana modeled as time-dependent discrete variable while interictal and ictal events constituted dependent variables. Analysis of variance as initial test for significance followed by time series analysis using Generalized Autoregressive Conditional Heteroscedasticity model was performed. Statistical significance for lower interictal events (analysis of variance P = 0.001) was seen during C indica use, but not for C indica/sativa mixture (P = 0.629) or ictal events (P = 0.087). However, time series analysis revealed a significant inverse correlation between marijuana use, with interictal (P < 0.0004) and ictal (P = 0.002) event rates. Using a novel approach to EEG data, we demonstrate a decrease in interictal and ictal electrographic events during marijuana use. Larger samples of patients and EEG, with standardized cannabinoid formulation and dosing, are needed to validate our findings.

To examine retinal structure injury in African-Americans (AA) with Multiple Sclerosis (MS) compared to Caucasians (CA) with MS, we used spectral domain optical-coherence tomography (OCT) in this cross sectional study. The peripapillary retinal nerve fiber layer (pRNFL) and macular volume of 234 MS patients (149 CA; 85 AA) and 74 healthy controls (60 CA; 17 AA) were measured. Intra-retinal segmentation was performed to obtain retinal nerve fiber (RNFL), ganglion cell (GCL), inner plexiform (IPL), inner nuclear (INL), outer plexiform (OPL), outer nuclear (ONL), retinal pigment epithelium (RPE), and photoreceptor (PR) layer volumes. Study was approved by IRB, and informed consent obtained from all participants. We found that pRNFL was thicker in AA v. CA healthy controls (100.9 vs 97.00μm, p=0.004). Compared to HC, MS patients demonstrated thinner pRNFL (p<0.0001), and lower TMV (p<0.001), macular RNFL (p<0.0001), GCL (p<0.0001), and IPL (p<0.0001). AAMS patients had thinner pRNFL (87.2 vs 90.0μm, and lower TMV (8.2 vs 8.4mm(3), p=0.0001), RNFL (0.73 vs 0.79mm(3), p=0.0001), and GCL (0.94 vs 0.98mm(3), p=0.007) than CAMS patients. Sub-analysis of patients without history of AON showed thinner pRNFL (88.9 vs 93.1µm) and TMV (8.2 vs. 8.5mm(3), p<0.0001) in AAMS compared to CAMS patients. In conclusion, this cross-sectional study provides evidence supporting greater retinal structure injury in AAMS compared to CAMS patients, irrespective of history of AON. Our findings are consistent with other studies demonstrating a more severe CNS tissue injury in AAMS patients., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Introduction: The value of biomarkers in early diagnosis and development of therapeutics in Parkinson's disease (PD) is well established., Methods: We used proton magnetic resonance spectroscopy in a prospective, longitudinal study of 23 patients with early PD, naïve to dopaminergic therapy, and six age-matched healthy controls to examine the temporal changes in metabolic profile of substantia nigra over a period of 3 months., Results: N-acetyl aspartate to creatine ratio at month 3 was compared with baseline values in the PD and control groups, as well as the side-to-side difference of the ratio at baseline. By month 3, n-acetyl aspartate to creatine ratio had decreased by 4.4% in patients with PD (P = 0.024), without a concomitant change in healthy controls. The side-to-side asymmetry was significantly higher in the PD group (16.7%) vs. healthy controls (1.6%, P = 0.0024)., Conclusion: Estimation of change in the n-acetyl aspartate to creatine ratio appears to be a fast, quantifiable, and reliable marker of dopaminergic neuronal viability in PD., (© 2015 International Parkinson and Movement Disorder Society.)

Background: Parkinson's disease (PD) is a neurodegenerative disorder associated with dopaminergic cell loss and α-synuclein aggregation in Lewy bodies, which has been demonstrated in the retina., Methods: We performed a spectral-domain optical coherence tomography (OCT) study in patients with PD and healthy controls to measure the peripapillary retinal nerve fiber layer thickness and macular volume. Intra-retinal segmentation was performed to measure the volume of the retinal nerve fiber (RNFL), ganglion cell (GCL), inner plexiform (IPL), inner nuclear (INL), outer plexiform (OPL), and outer nuclear (ONL) layers. Analysis was carried out blinded to the clinical status of study participants., Results: 101 PD and 46 healthy control eyes were included in the study. In PD patients, peripapillary retinal nerve fiber layer was not significantly thinner (96.95 μm vs 94.42 μm, p=0.08) but macular volume was (8.58 mm3 vs 8.33 mm3, p=0.0002). Intra-retinal segmentation showed that PD subjects have reduced GCL, IPL, INL and ONL volumes. In contrast, the OPL volume was significantly increased (0.81 mm3 vs 0.78 mm3 p=0.0214)., Conclusions: Thickening of the OPL is a novel finding which may correspond to the localization of α-synuclein in the OPL of PD patients. We hypothesize that the enlargement of the OPL may represent a potential biomarker of α-synuclein aggregation in PD. This may have significant clinical implications., (Copyright © 2015. Published by Elsevier B.V.)

Background: Several studies have shown a relationship between spinal cord atrophy and clinical disability in patients with multiple sclerosis (MS)., Objectives: We examined the correlation between cervical cord cross-sectional area at the C2 vertebral level (CSA-C2) and the expanded disability status scale (EDSS) in patients with relapsing-remitting and progressive forms of MS. The latter included both secondary and primary progressive MS patients., Methods: A total of 150 patients with MS were recruited from the Wayne State University MS clinic. Ninety-three had relapsing-remitting MS and 57 patients had progressive MS. MRI scan of the cervical cord was obtained for each patient. Correlation studies and multivariate regression analysis was performed, blinded to clinical status., Results: The mean age was 41.3 year old, 64.6% were women, mean disease duration was 11.2 years, CSA-C2 was 80.2mm(2) and mean EDSS was 3.8. There was significant correlation between CSA-C2 and EDSS (r -0.75, p<0.0001). Sub-group analysis showed CSA-C2 was 68.6mm(2) and 87.3mm(2) in the progressive and relapsing-remitting groups, respectively (p<0.0001). Multivariable regression showed that CSA-C2 was a significant predictor of disability independent of disease duration, and phenotype., Conclusions: Our study demonstrates that CSA-C2 has a strong correlation with clinical disability in both RRMS and progressive MS. Greater spinal cord atrophy was seen in patients with progressive than relapsing-remitting MS. CSA-C2, disease duration, and phenotype are independent predictors of disability., (Copyright © 2014. Published by Elsevier B.V.)

Tick-borne diseases are prevalent throughout the world and present a diagnostic challenge owing to their nonspecific clinical symptoms. Many tick-borne diseases involve the central and peripheral nervous systems. Early diagnosis or at least suspicion of a tick-borne cause is necessary to institute early empiric treatment. After a brief review of tick biology, we present the most common tick-borne diseases. A brief discussion of epidemiology, the transmission route, and pathogenesis is followed by a discussion of the clinical manifestations, diagnosis and treatment options when available. The review emphasizes the infectious causes with a significant neurological manifestation.

Objective: To investigate a novel method to enhance radiosensitivity of gliomas via modification of metabolite flux immediately before radiotherapy. Malignant gliomas are highly glycolytic and produce copious amounts of lactic acid, which is effluxed to the tumor microenvironment via lactate transporters. We hypothesized that inhibition of lactic acid efflux would alter glioma metabolite profiles, including those that are radioprotective. H magnetic resonance spectroscopy (MRS) was used to quantify key metabolites, including those most effective for induction of low-dose radiation-induced cell death., Methods: We inhibited lactate transport in U87-MG gliomas with alpha-cyano-4-hydroxycinnamic acid (ACCA). Flow cytometry was used to assess induction of cell death in treated cells. Cells were analyzed by MRS after ACCA treatment. Control and treated cells were subjected to low-dose irradiation, and the surviving fractions of cells were determined by clonogenic assays., Results: MRS revealed changes to intracellular lactate on treatment with ACCA. Significant decreases in the metabolites taurine, glutamate, glutathione, alanine, and glycine were observed, along with inversion of the choline/phosphocholine profile. On exposure to low-dose radiation, ACCA-pretreated U-87MG cells underwent rapid morphological changes, which were followed by apoptotic cell death., Conclusion: Inhibition of lactate efflux in malignant gliomas results in alterations of glycolytic metabolism, including decreased levels of the antioxidants taurine and glutathione and enhanced radiosensitivity of ACCA-treated cells. Thus, in situ application of lactate transport inhibitors such as ACCA as a novel adjunctive therapeutic strategy against glial tumors may greatly enhance the level of radiation-induced cell killing during a combined radio- and chemotherapeutic regimen.

Proton magnetic resonance spectroscopy (1H-MRS) studies of schizophrenia suggest an effect of the disease or of antipsychotic medications on brain N-acetyl aspartate (NAA), a marker of neuronal viability. We studied in rat the effect of haloperidol on NAA, glutamate, and glutamine in several brain regions where metabolite reductions have been reported in chronically medicated patients with schizophrenia. Two groups of 16 rats each were treated with haloperidol depo (38 mg/kg/month) and vehicle for 6 months and were killed. Concentrations of metabolites were determined by high-resolution magic angle proton magnetic resonance spectroscopy (HR-MAS 1H-MRS) at 11.7 T in ex-vivo punch biopsies from the following brain regions: medial frontal and cingulate cortex, striatum, nucleus accumbens, dorsal and ventral hippocampus, amygdala, and temporal cortex. Factorial ANOVA of NAA concentrations revealed no significant effect of drug group (F(1,212) = 1.5; p = 0.22) or a group by brain region interaction (F(7,212) = 1.0; p = 0.43). There was a significant main effect of region (F(7,212) = 17.8; p < 0.001) with lower NAA in the striatum. A prolonged exposure to the dopamine D2 receptor blockade effects of haloperidol does not result in changes in NAA, glutamate, glutamine, and other metabolites in the proton spectrum. These results are consistent with the only other two studies of the effect of antipsychotic drugs on NAA in the rat brain. The documented lower NAA in chronically treated schizophrenia patients is most likely not a simple effect of antipsychotic medications.

Recent studies suggest exaggerated responses in the limbic system of patients with generalized social anxiety disorder in response to threat/anxiety-related social situations and aversive conditioning, processes mediated by the glutamatergic system. This single-voxel, high-field 1H-magnetic resonance spectroscopy study examined concentrations of glutamate, and other metabolites, in the anterior cingulate cortex and occipital cortex (control region) of 10 medication-naive patients with generalized social anxiety and 10 matched healthy comparison subjects. Glutamate (relative to creatine) levels were significantly higher in patients than controls in the anterior cingulate, but not occipital, cortex. Anterior cingulate glutamate/creatine levels were also correlated with intensity of social anxiety symptoms. These findings provide new evidence of glutamate's involvement in the neural mechanism underlying social phobia.

Increasing evidence suggests that mood disorders are associated with a reduction in regional CNS volume and neuronal and glial cell atrophy or loss. Lithium, a mainstay in the treatment of mood disorders, has recently been demonstrated to robustly increase the levels of the cytoprotective B-cell lymphoma protein-2 (bcl-2) in areas of rodent brain and in cultured cells. In view of bcl-2's antiapoptotic and neurotrophic effects, the present study was undertaken to determine if lithium affects neurogenesis in the adult rodent hippocampus. Mice were chronically treated with lithium, and 5-bromo-2-deoxyuridine (BrdU) labeling of dividing cells was conducted over 12 days. Immunohistochemical analysis was undertaken 1 day after the last injection, and three-dimensional stereological cell counting revealed that lithium produced a significant 25% increase in the BrdU-labeled cells in the dentate gyrus. Double-labeling immunofluorescence studies were undertaken to co-localize BrdU-positive cells with neuron-specific nuclear protein and showed that approximately 65% of the cells were double-labeled. These results add to the growing body of evidence suggesting that mood stabilizers and antidepressants exert neurotrophic effects and may therefore be of use in the long-term treatment of other neuropsychiatric disorders.

The purpose of this study was to examine the relation between glucose metabolism and glutamate concentration in the human brain, in both the normal and diseased state. Regional values of glucose metabolism measured with 2-deoxy-2[F-18]fluoro-D-glucose positron emission tomography (FDG PET) studies and single-voxel proton magnetic resonance spectroscopy (1H MRS) measurements of the glutamate/ glutamine/gamma-aminobutyric acid (Glx) tissue concentration were determined in multiple brain regions in 11 patients (5 girls and 6 boys, mean age 7.5 years) with medically intractable partial epilepsy. FDG PET and 1H MRS studies were performed in the interictal state in seven patients and in the ictal/periictal state in four patients. Regions of interest were identified in epileptic cortex (determined by intracranial and/or scalp electroencephalography) and in contralateral normal brain regions. Lower glucose metabolism and lower Glx concentrations were found in the epileptic focus than in the contralateral normal cortex in all seven patients examined in the interictal state, whereas higher glucose metabolism and higher Glx concentrations were observed in the epileptic focus in the four patients who had ictal/periictal studies. Significant correlations were found between the values of cerebral glucose utilization and Glx concentration in epileptic brain region, in nonepileptic brain regions, and in epileptic and nonepileptic regions combined. These results demonstrate a significant relation between glucose metabolism and glutamate/glutamine concentration in normal and epileptic cerebral cortex. This relation is maintained in both the interictal and ictal states.