Journal of the Neurological Sciences

Editorial Board

2012-02-15

Implementing clinical trials on an international platform: Challenges and perspectives

2011-11-03

Abstract: The importance of conducting medical research on a global or international platform cannot be overemphasized in current times. Sponsors are encouraging international clinical trials for a number of reasons. Globally, clinical trials are under increasing pressure to meet patient recruitment goals quickly and efficiently, at times with very limited resources. Conducting clinical trials in multiple countries increases access to potentially eligible study subjects. It is reasonable to believe that international trials will be completed more quickly and efficiently, leading to more rapid advancement in science and conservation of research-specific resources. Rapid advancement in science can reduce the burden of disease, promote health, and extend longevity for all people. In addition, generalizability, one of the major goals of translational medicine, will increase when recruiting patients from multiple countries and multiple ethnicities. Further, improvement of global health may be possible when certain types of clinical trials are conducted in countries that would not otherwise have access to an innovative drug or intervention.

Functional neuroanatomy of vocalization in patients with Parkinson's disease

I. Rektorova, M. Mikl, J. Barrett, R. Marecek, I. Rektor, T. Paus — 2011-11-11

Abstract: In Parkinson's disease (PD) both speech production and self-monitoring of voiced speech are altered.Methods: In our previous study we used functional magnetic resonance imaging (fMRI) to examine which brain areas are involved in overt reading in nine female PD patients (mean age 66.0±11.6years) compared with eight age-matched healthy female controls (mean age 62.2years±12.3). Here we performed the post-hoc seed-based functional connectivity analysis of our data to assess the functional connectivity between the periaqueductal gray matter (PAG; i.e. the core subcortical structure involved in human vocalization) and other brain regions in the same groups of PD patients and controls.Results: In PD patients as compared with controls we observed increased connectivity between PAG and basal ganglia, posterior superior temporal gyrus, supramarginal and fusiform gyri and inferior parietal lobule on the right side. In the PD group, the connectivity strength in the right putamen and the right sypramarginal gyrus was correlated with variability of pitch while the connectivity strength in the right posterior superior temporal gyrus and in the right inferior parietal lobule was correlated with speech loudness.Conclusion: We observed functional reorganization in PD patients as compared with controls in both the motor basal ganglia-thalamo-cortical circuitry and cortical areas known to be engaged in-auditory and somatosensory feedback control of voiced speech. These changes were hemisphere-specific and might either reflect effects of dopaminergic treatment or at least partially successful compensatory mechanisms involved in early-stage PD.

Visuo-spatial interference affects the identification of emotional facial expressions in unmedicated Parkinson's patients

2011-10-26

Abstract: There is evidence that visuo-spatial capacity can become overloaded when processing a secondary visual task (Dual Task, DT), as occurs in daily life. Hence, we investigated the influence of the visuo-spatial interference in the identification of emotional facial expressions (EFEs) in early stages of Parkinson's disease (PD). We compared the identification of 24 emotional faces that illustrate six basic emotions in, unmedicated recently diagnosed PD patients (16) and healthy adults (20), under two different conditions: a) simple EFE identification, and b) identification with a concurrent visuo-spatial task (Corsi Blocks). EFE identification by PD patients was significantly worse than that of healthy adults when combined with another visual stimulus.

Immunization with a new DNA vaccine for Alzheimer's disease elicited Th2 immune response in BALB/c mice by in vivo electroporation

Xiaona Xing, Sha Sha, Yu Li, Lixia Zong, Tongzi Jiang, Yunpeng Cao — 2011-10-26

Abstract: Immunization with synthetic amyloid β-protein (Aβ) peptide has resulted in preventing and clearing Aβ deposits as well as improving cognitive function in transgenic mouse models of Alzheimer's disease (AD). But similar immunization studies in humans were halted due to the risk of inducing T cell-mediated meningoencephalitis. A safe and effective vaccine for AD requires not only therapeutic levels of anti-Aβ antibodies but also the prevention of an adverse T cell-mediated, proinflammatory autoimmune response. In this study, we developed a DNA vaccine, p(Aβ3–10)10-IL-4, encoding ten tandem repeats of Aβ3–10 fused with mouse cytokine interleukin-4 (IL-4) as a molecular adjuvant. Wild-type mice were injected intramuscularly with p(Aβ3–10)10-IL-4 followed by in vivo electroporation. The p(Aβ3–10)10-IL-4 vaccine elicited high titer anti-Aβ antibodies which bound to Aβ plaque in brain tissue from a ten-month-old APP/PS1 transgenic mouse. The antibody isotype was mainly IgG1 and the IgG1/IgG2a ratio in the p(Aβ3–10)10-IL-4 group was approximately eight times greater than that of the Aβ42 group. Ex vivo cultured splenocytes isolated from mice immunized with p(Aβ3–10)10-IL-4 exhibited a low IFN-γ response and a high IL-4 response compared with the control group. These results indicate that immunization with the p(Aβ3–10)10-IL-4 vaccine induced effective anti-Aβ antibodies and elicited a Th2-polarized immune response that had a lower potential to cause an inflammatory T cell response. Thus, the DNA vaccine, p(Aβ3–10)10-IL-4, may be a safe and efficient vaccine for AD.

Cilostazol combined with aspirin prevents early neurological deterioration in patients with acute ischemic stroke: A pilot study

Tomomi Nakamura, Shinji Tsuruta, Shinichiro Uchiyama — 2011-10-20

Abstract: Recent randomized trials have shown that cilostazol is superior to aspirin for secondary stroke prevention. We hypothesized that combining cilostazol with aspirin is more effective than aspirin alone in patients with acute ischemic stroke. This randomized study compared the effects of oral aspirin alone to aspirin plus cilostazol in patients with non-cardioembolic ischemic stroke within 48h of stroke onset. NIH Stroke Scale (NIHSS) and modified Rankin Scale (mRS) scores were checked before and after 14days and 6months of drug administration. The primary and secondary endpoints were neurological deterioration or stroke recurrence (NIHSS score≥1) within 14days and 6months, respectively. For statistical analysis, on-treatment analysis was conducted. Seventy-six patients were enrolled in the study. The primary endpoint was significantly higher in the aspirin group than in the aspirin plus cilostazol group (28% vs. 6%, relative risk (RR): 0.21, 95% confidence intervals (CI): 0.05–0.87, p=0.013). Among the patients who did not reach these endpoints, the mean improvement in the NIHSS score at day 14 tended to be better (−1.8±1.2 vs. −1.2±1.0, p=0.078) and the frequency of the favorable functional status of mRS 0–1 at month 6 was significantly higher (RR: 1.48, 95% CI: 1.07–2.06, p=0.0048) in the aspirin plus cilostazol group than in the aspirin group. Patients treated with aspirin plus cilostazol during the acute phase of stroke had less neurological deterioration and more favorable functional status than those treated with aspirin alone.

Different molecular expression in thymoma with ocular or generalized myasthenia gravis

2011-10-17

Abstract: Background: Increasing evidence supports a link between expressions of CD4, CD25, Foxp3, and CXCL13 in thymic hyperplasia with myasthenia gravis (MG) patients. Herein, we investigated the expressions of these molecules in thymoma patients with ocular MG (OMG) or generalized MG (GMG).Methods: A total of 58 thymoma patients with MG (23 GMG and 35 OMG) and 73 thymoma patients without MG were analyzed using immunohistochemistry for CD4, CD25, Foxp3 and CXCL13.Results: OMG was more frequent than GMG in late-onset thymoma males (P=0.037), but no difference was observed in females (P=0.128). There was no significant difference of Foxp3 expression among all types of thymoma from patients with OMG and Non-MG. Compared to patients with OMG, a decreased Foxp3 expression was seen in types AB, B1 and B2 thymoma with GMG, with the decrease in the former two types reaching significance (P=0.001, 0.043, respectively). However, a significantly increased expression of CXCL13 was observed in types B1 and B2 thymoma patients with GMG (P=0.027, 0.048, respectively, compared to those with OMG). Furthermore, the CXCL13 expression in type AB thymoma patients with GMG was higher than those with Non-MG (P=0.003).There were no differences among expressions of CD4, CD25, Foxp3, and CXCL13 in type A and B3 thymoma patients, regardless of with OMG, GMG or Non-MG.Conclusion: Differential expressions of Foxp3 and CXCL13 in various types of thymoma patients with OMG or GMG might suggest the differential immunological processes underlying the two subtype of MG.

Reversible propriospinal myoclonus due to thoracic disc herniation: Long-term follow-up

Wooyoung Jang, Joong-Seok Kim, Jin Young Ahn, Hee-Tae Kim — 2011-10-24

Abstract: PSM is a rare form of myoclonus of spinal origin. The thoracic level is considered as the myoclonic generator in most cases; however, structural abnormality in conventional magnetic resonance imaging (MRI) related to PSM is more rare. We report the case of a 23-year-old man with PSM with ventral thoracic disc herniation confirmed by conventional MRI, which completely resolved after thoracic discectomy. This case indicates that decompressive surgery might be a valid treatment option.

Reflexive and volitional saccades: Biomarkers of Huntington disease severity and progression

2011-10-24

Abstract: Background: Huntington disease (HD) is a genetic, neurodegenerative disorder characterized by chorea, behavioral co-morbidities, cognitive deficits, and eye movement abnormalities. We sought to evaluate whether reflexive and voluntary orienting prove useful as biomarkers of disease severity in HD.Methods: Eleven HD subjects were evaluated with the motor subscale of the Unified Huntington Disease Rating Scale (UHDRS) and the Montreal Cognitive Assessment. Using an infrared eye tracker, we also measured latency and error rates of horizontal and vertical saccades using prosaccade and antisaccade eye movement tasks. We calculated simple and age-controlled correlations between eye movement and clinical parameters.Results: Prosaccade latency correlated with total chorea score. HD patients with greater clinical severity were significantly slower in the prosaccade task. Antisaccade error rate also correlated with UHDRS motor score and total chorea score. HD patients with greater clinical severity as measured by either measure made significantly more errors in the antisaccade task. All these correlations remained significant even when age was taken into account.Conclusions: The results of the present age-controlled study show for the first time that both reflexive and voluntary eye motor control in HD patients decrease with increase in disease severity suggesting declines in both motor and cognitive function. Thus, relatively simple eye movement parameters (latency and error rate) obtained from simple tasks (prosaccade and antisaccade) may serve as quantitative biomarkers of sub-cortical and cortical disease severity in HD and could aid in predicting onset, distinguishing subtypes, or evaluating disease progression and novel therapies.

Clinical features and recovery patterns of acquired non-thyrotoxic hypokalemic paralysis

Akiyuki Hiraga, Ikuo Kamitsukasa, Kazuho Kojima, Satoshi Kuwabara — 2011-10-17

Abstract: Objective: To report the clinical features and recovery patterns of patients with non-thyrotoxic acquired hypokalemic paralysis.Methods: The clinical and laboratory records of 11 consecutive patients with acquired non-thyrotoxic hypokalemic paralysis were reviewed and compared with those of 3 patients with thyrotoxic periodic paralysis (TPP). The causes of potassium wasting were diarrhea (n=4), alcohol abuse (n=2), pseudoaldosteronism (n=2), primary aldosteronism (n=1), distal renal tubular acidosis associated with Sjögren's syndrome (n=1) and an unknown cause (n=1).Results: Three of the 11 patients had prominently asymmetric limb weakness, and 2 had predominant upper limb weakness. On admission, mean serum potassium and creatine kinase (CK) levels of patients with acquired hypokalemic paralysis on admission were 1.8mEq/L and 4,075U/mL, respectively, and the mean duration between admission and independent walking was 6.8days (range, 2–31days). Despite clinical recovery, 10 patients still presented with increased CK levels after several days (mean of maximum levels, 10,519U/mL). In addition, normalization of serum potassium levels in patients with acquired hypokalemic paralysis patients was much slower compared to that in patients with TPP. One patient with acquired hypokalemic paralysis developed ventricular fibrillation, whereas all 3 patients with TPP had symmetric proximal and lower limb-dominant weakness and exhibited complete recovery from paralysis as well as normalized serum potassium levels within 24h.Conclusions: In patients with acquired non-thyrotoxic hypokalemic paralysis, asymmetric or upper limb-dominant weakness of the extremities is observed. Despite clinical improvement after treatment, normalization of serum potassium and CK levels is often delayed, and therefore, careful monitoring for cardiac and renal complications is required.

External carotid artery branches involvement in reversible cerebral vasoconstriction syndrome

E. Melki, C. Denier, M. Théaudin-Saliou, M. Sachet, D. Ducreux, G. Saliou — 2011-10-17

Abstract: Reversible cerebral vasoconstriction syndrome (RCVS) is characterized by segmental vasoconstriction and dilatation of intracranial arteries, usually revealed by headaches, which spontaneously resolve in few weeks.We report a patient with RCVS, revealed by thunderclap headaches, involving both internal and external carotid artery (ECA). She received fluoxetin for depression and took a great amount of cannabis in the last months. While angio-MR, transcranial Doppler and CSF analysis were normal, cerebral angiography disclosed stenoses and dilatations of the middle cerebral artery. It also showed an involvement of maxillary arteries. Fluoxetin and cannabis were stopped. After few days, she had no more headaches. At 8th week, angiography was normalized confirming the RCVS.ECA angiogram may help reaching a diagnosis in patients with suspected RCVS when intracerebral abnormalities are minor or absent.

Type I interferon signature is high in lupus and neuromyelitis optica but low in multiple sclerosis

2011-10-31

Abstract: Objective: Neuromyelitis optica (NMO) is characterized by selective inflammation of the spinal cord and optic nerves but is distinct from multiple sclerosis (MS). Interferon (IFN)-β mitigates disease activity in MS, but is controversial in NMO, with a few reports of disease worsening after IFN-β therapy in this highly active disease. In systemic lupus erythematosus (SLE), IFNs adversely affect disease activity. This study examines for the first time whether serum IFN-α/β activity and IFN-β-induced responses in peripheral blood mononuclear cells (MNC) are abnormally elevated in NMO, as they are in SLE, but contrast to low levels in MS.Methods: Serum type I IFN-α/β activity was measured by a previously validated bioassay of 3 IFN-stimulated genes (RT-PCR sensitivity, 0.1U/ml) rather than ELISA, which has lower sensitivity and specificity for measuring serum IFNs. IFN responses in PBMNC were assessed by in vitro IFN-β-induced activation of phospho-tyrosine-STAT1 and phospho-serine-STAT1 transcription factors, and MxA proteins using Western blots.Results: Serum IFN-α/β activity was highest in SLE patients, followed by healthy subjects and NMO, but was surprisingly low in therapy-naïve MS. In functional assays in vitro, IFN-β-induced high levels of P-S-STAT1 in NMO and SLE, but not in MS and controls. IFN-β-induced MxA protein levels were elevated in NMO and SLE compared to MS.Conclusions: Serum IFN activity and IFN-β-induced responses in PBMNC are elevated in SLE and NMO patients versus MS. This argues for similarities in pathophysiology between NMO and SLE and provides an explanation for IFN-induced disease worsening in NMO.

Widespread cerebral cortical mineralization in Wilson's disease detected by susceptibility-weighted imaging

Jae-Hyeok Lee, Tae-Il Yang, Mong Cho, Ki-Tae Yoon, Seung-Kug Baik, Yong-Hee Han — 2011-10-24

Abstract: Signal abnormalities of cortical gray matter, compared with the deep nuclear structures, have received less attention in Wilson's disease (WD). They nearly always accompanied white matter signal change, and commonly are associated with epilepsy and psychiatric features. We report herein two cases diagnosed as WD who, in addition to characteristic deep nuclear lesions on MR imaging, had widespread cerebral cortical paramagnetic signals dramatically detected by susceptibility-weighted imaging. T2-weighted MR images did not show any cortico-subcortical hyperintense lesions. To our knowledge, these findings have not been described before and may help to further characterize the disease.

Autonomic involvement in Parkinson's disease: Pathology, pathophysiology, clinical features and possible peripheral biomarkers

Maria G. Cersosimo, Eduardo E. Benarroch — 2011-10-17

Abstract: Autonomic nervous system involvement occurs at early stages in both Parkinson's disease (PD) and incidental Lewy body disease (ILBD), and affects the sympathetic, parasympathetic, and enteric nervous systems (ENS).It has been proposed that alpha-synuclein (α-SYN) pathology in PD has a distal to proximal progression along autonomic pathways. The ENS is affected before the dorsal motor nucleus of the vagus (DMV), and distal axons of cardiac sympathetic nerves degenerate before there is loss of paravertebral sympathetic ganglion neurons. Consistent with neuropathological findings, some autonomic manifestations such as constipation or impaired cardiac uptake of norepinephrine precursors, occur at early stages of the disease even before the onset of motor symptoms. Biopsy of peripheral tissues may constitute a promising approach to detect α-SYN neuropathology in autonomic nerves and a useful early biomarker of PD.

Neurotrophin-3 gene modified mesenchymal stem cells promote remyelination and functional recovery in the demyelinated spinal cord of rats

2011-10-14

Abstract: Multiple sclerosis (MS) is a debilitating neurodegenerative disease characterized by axonal/neuronal damage that may be caused by defective remyelination. Current therapies aim to slow the rate of degeneration, however there are no treatment options that can stop or reverse the myelin sheath damage. Bone marrow mesenchymal stem cells (MSCs) are a potential candidate for the cell implantation-targeted therapeutic strategies, but the pro-remyelination effects of MSCs when directly injected into a demyelinated cord lesion have been questioned. Neurotrophin-3 (NT-3) has been shown to serve a crucial role in the proliferation, differentiation and maturation of oligodendrocyte lineages. Here, we showed that implantation of NT-3 gene-modified MSCs via a recombinant adenoviral vector (Adv) into a region of ethidium bromide (EB)-induced demyelination in the spinal cord resulted in significant improvement of locomotor function and restoration of electrophysiological properties in rats. The morphological basis of this recovery was evidenced by robust myelin basic protein (MBP) expression and the extensive remyelination. AdvNT-3-MSC implants promote the endogenous remyelinating cells to participate directly in myelination, which was confirmed under light and electron microscopy. Our study suggested that genetically modified MSCs could be a potential therapeutic avenue for improving the efficacy of stem cell treatment for neurodegenerative diseases such as MS.

Effect of the 50bp deletion polymorphism in the SOD1 promoter on SOD1 mRNA levels in Italian ALS patients

2011-10-18

Abstract: The genetic association between homozygosity for a 50bp deletion polymorphism in the SOD1 promoter, 1684bp upstream of the ATG, and an increased age of symptom onset was observed in various populations of ALS patients. Moreover, it has been demonstrated that this deletion reduces SOD1 expression in vitro. The objective of the present study was to test whether the observed association is replicated in patients from an Italian population and to check whether the deletion correlates with reduced SOD1 mRNA expression in vivo. Genomic DNA from 235 Italian SALS cases and 245 age- and sex-matched donors from the same ethnic background was screened for the 50bp SOD1 promoter deletion by real time PCR assays. No differences were observed between ALS patients and controls for the frequency of both the alleles (D=deleted, N=non-deleted; p=0.95) and genotypes (p=0.90). Furthermore, stratification of the ALS samples showed that this variation was not associated with increased age of onset in ND and DD patients in comparison to NN patients (p=0.48). Finally, we performed real-time RT-PCR to quantify SOD1 mRNA levels in 48 patients and we did not find a relevant difference among the three sub-groups of genotypes (p=0.30). Our data suggest that the studied polymorphism does not modulate SOD1 mRNA level and disease phenotype in an Italian population.

Polymorphisms in the vitamin D receptor gene and multiple sclerosis risk: A meta-analysis of case–control studies

Jian Huang, Zheng-Fu Xie — 2011-10-28

Abstract: Background: The vitamin D receptor (VDR) polymorphisms have been reported to be associated with multiple sclerosis (MS), however, evidence remains conflicting. A meta-analysis was conducted to investigate this association.Methods: We searched Pubmed, Medline and Embase databases for case–control studies evaluating the association between the VDR Apa-I, Bsm-I, Fok-I, Taq-I polymorphisms and MS risk. Data were extracted using standardized forms and odds ratios (OR) with 95% confidence intervals (CI) were calculated.Results: 11 case–control studies involving a total of 2599 cases and 2816 controls were included in this meta-analysis. Available data did not suggest an association between any of the VDR polymorphisms and the risk for MS. For Taq-I, which is the most investigated VDR polymorphism with 8 studies (2472 cases and 2446 controls), the combined OR was 1.12 (95% CI: 1.00–1.26) for the dominant model (tt+Tt vs. TT), 1.03(95% CI: 0.88–1.20) for the recessive model (tt vs. Tt+TT), and 1.04 (95% CI: 0.78–1.38) for the homozygote model (tt vs. TT). ORs for other VDR polymorphisms were similar.Conclusion: The VDR Apa-I, Bsm-I, Fok-I and Taq-I polymorphisms are not associated with MS risk.

Trends in comorbid sickle cell disease among stroke patients

Bruce Ovbiagele, Robert J. Adams — 2011-10-12

Abstract: Background: Stroke is a major complication of sickle cell disease (SCD). In an era of chronic red cell transfusions for stroke prophylaxis in children and greater life expectancy, nationwide data on stroke rates among pediatric and adult patients with SCD are scarce. We evaluated recent time trends in stroke hospitalization among children (0–17years) and adults (>17years) with SCD in the United States.Methods: Data were obtained from the Nationwide Inpatient Sample. Pediatric (n=26,380) and adult (n=9,638,507) patients admitted to hospitals between 1997 and 2006 with a primary stroke discharge diagnosis (identified by the International Classification of Diseases, Ninth Revision procedure codes) were included. Time trends in the proportion of stroke patients with SCD were computed.Results: Pediatric stroke patients with co-morbid SCD constituted 8.7% in 1997 vs. 4.8% in 2006 (p=0.04), with 81 fewer actual hospitalizations. Adult stroke patients with SCD were 0.3% in 1997 vs. 0.5% in 2006 (p=0.01), with 157 more actual hospitalizations. Factors that changed substantially and significantly across the decade among pediatric stroke patients with SCD included a drop in ischemic stroke type (74.2% vs. 56.3%) and a rise in comorbid hypertension (1.5% vs. 11.5%), while among adult stroke patients with SCD there was a rise in other stroke type (20.4% vs. 35.6%).Conclusions: In an era of increasing prophylactic red cell transfusions, the proportion of SCD diagnoses among pediatric stroke patients significantly decreased in the United States. The rise in SCD diagnoses among adult stroke patients is possibly due to a cohort effect, but further study is needed.

Modifiable lifestyle behaviours account for most cases of subarachnoid haemorrhage: A population-based case–control study in Australasia

2011-10-13

Abstract: Background: Smoking, hypertension and alcohol excess are the major causal risk factors for subarachnoid haemorrhage (SAH) that are modifiable. We aimed to explore the hypothesis that other modifiable lifestyle factors, such as diet, may also underpin a substantial proportion of the population attributable risk (PAR) of SAH.Methods: In a multi-centre, population-based, case–control study, information on smoking status, history of hypertension, physical activity, dietary intake, alcohol consumption, body mass index, and family history of SAH, were obtained from 432 incident SAH cases and 473 frequency-matched community-based SAH-free controls without SAH. Multivariate analysis was used to identify significant risk factors and associated PARs for SAH, reported with 95% confidence intervals (CI).Results: Smoking and history of hypertension accounted for 30% (95%CI 23–37%) and 21% (10–30%) of SAH, respectively. Additionally, 25% (11–37%) of SAH was attributed to drinking skim or reduced fat milk, 15% (5–24%) to eating fruit less than once weekly, and 13% (5–21%) to eating either the fat on meat or skin on chicken >4 times weekly. Alcohol excess was not associated with SAH.Conclusions: Smoking cessation and blood pressure control are the most important strategies to prevent SAH. However, drinking skimmed/reduced fat milk, eating fruits regularly, and removing the fat from meats and skin from chicken before consumption may also reduce the burden of SAH.

Objective home-based gait assessment in spinocerebellar ataxia

S.H. Subramony, S. Kedar, E. Murray, E. Protas, H. Xu, T. Ashizawa, A. Tan — 2011-10-24

Abstract: We investigated the utility of home-based gait monitor assessment in patients with spinocerebellar ataxia (SCA). Nineteen patients with different forms of SCA were examined using a step activity monitor (SAM), clinical scales and common tests of functional motor performance including the scale for assessment and rating of ataxia (SARA), disease staging, a timed 25 foot walk test and a 9 hole peg-board test. The patient wore the SAM bracelet on his/her ankle for seven 24 hour periods at home. The objective monitor measurements were highly associated with disease duration and with the functional stage of disease (P<0.01). Monitor measurements were significantly correlated to SARA scores with the exception of the percent of steps expended in moderate and high speeds of activity. Fewer monitor measures had significant correlations with walk and peg board scores. The objective SAM outputs also possessed high internal consistency, high intraclass correlation coefficients and could be fitted to a single factor by factor analysis. We conclude that the SAM is a simple and cost effective method for obtaining data on gait parameters over extended periods in patients with SCA. The SAM has validity and reliability and can generate unbiased, continuous data that takes into account daily variations in physical performance.

Human brain atlas-based multimodal MRI analysis of volumetry, diffusimetry, relaxometry and lesion distribution in multiple sclerosis patients and healthy adult controls: Implications for understanding the pathogenesis of multiple sclerosis and consolidation of quantitative MRI results in MS

2011-10-05

Abstract: Multiple sclerosis (MS) is the most common immune-mediated disabling neurological disease of the central nervous system. The pathogenesis of MS is not fully understood. Histopathology implicates both demyelination and axonal degeneration as the major contributors to the accumulation of disability. The application of several in vivo quantitative magnetic resonance imaging (MRI) methods to both lesioned and normal-appearing brain tissue has not yet provided a solid conclusive support of the hypothesis that MS might be a diffuse disease.In this work, we adopted FreeSurfer to provide standardized macrostructure or volumetry of lesion free normal-appearing brain tissue in combination with multiple quantitative MRI metrics (T2 relaxation time, diffusion tensor anisotropy and diffusivities) that characterize tissue microstructural integrity. By incorporating a large number of healthy controls, we have attempted to separate the natural age-related change from the disease-induced effects. Our work shows elevation in diffusivity and relaxation times and reduction in volume in a number of normal-appearing white matter and gray matter structures in relapsing–remitting multiple sclerosis patients. These changes were related in part with the spatial distribution of lesions. The whole brain lesion load and age-adjusted expanded disability status score showed strongest correlations in regions such as corpus callosum with qMRI metrics that are believed to be specific markers of axonal dysfunction, consistent with histologic data of others indicating axonal loss that is independent of focal lesions. Our results support that MS at least in part has a neurodegenerative component.

The factors associated with a functional outcome after ischemic stroke in diabetic patients: The Fukuoka Stroke Registry

2011-10-12

Abstract: Background: The prognosis in ischemic stroke is poor in diabetic patients. However, scant research has so far been done on the predisposing factors associated with poor outcomes.Methods: We prospectively investigated the background characteristics and prognosis at 3months in 241 consecutive diabetic patients having their first ischemic stroke (153 males, 88 females, mean age±SD, 71±10years). Poor functional outcome was defined as modified Rankin scale ≥3 at 3months after onset.Results: Univariate analysis showed that age, dementia, initial National Institutes of Health Stroke Scale (NIHSS) score, systolic blood pressure on admission, proteinuria, stroke subtype, and prior use of angiotensin receptor blocker (ARB) were significantly related to an outcome at 3months after onset. A multivariate logistic regression analysis showed that age (odds ratio (OR) 1.07, 95% confidence interval (CI) 1.01 to 1.13, p=0.017, per 1-year increase), NIHSS score (OR 1.22, 95% CI 1.12 to 1.35, p<0.001, per 1-score increase), and proteinuria (OR 4.22, 95% CI 1.71 to 10.92, p=0.002) were significantly and independently associated with poor clinical outcome after ischemic stroke in diabetic patients. Conversely, prior use of ARB (OR 0.28, 95% CI 0.09 to 0.79, p=0.023) was associated with a better outcome.Conclusions: In diabetic patients, proteinuria was independently associated with a poor clinical outcome after ischemic stroke, whereas the prior use of ARB appeared to be beneficial.

Effects of highly active antiretroviral therapy on cognitive functions in severely immune-compromised HIV-seropositive patients

Yahaya O. Obiabo, Olubunmi A. Ogunrin, Abayomi S. Ogun — 2011-10-13

Abstract: Objective: This study assessed the effects of highly active antiretroviral therapy on the cognitive performances of HIV seropositive patients with severe immune depression.Methods: It is a prospective longitudinal interventional study of 69 anti-retroviral naïve HIV-seropositive adult patients with CD4 levels≤350/μl. The cognitive assessment was done at initiation and 12months after anti-retroviral treatment using the Community Screening Instrument for Dementia (CSID) and the computer-assisted Iron Psychology (FePsy). The impact of therapy on CD4 levels and cognitive scores of the patients before and after therapy were compared and tested for statistical significance using Student t test and one-way ANOVA.Results: The mean age of the patients was 36.6±8.8years. There was a significant increase in CD4 levels of the patients from 144.75±88.92 at baseline to 295.91±148.79 after 12months of HAART (p<0.0001). There were significant improvements in their cognitive scores (p<0.05) in all cognitive domains tested but the finger tapping task (motor speed) did not show any improvement (p>0.05). Combination ARV drugs with efavirenz did not significantly improve attention and choice reaction time.Conclusion: Highly active antiretroviral therapy significantly improved the CD4 levels and cognitive performances of treated HIV positive patients in all tested domains with the exception of motor speed.

Cerebral oxygen metabolism in patients with early Parkinson's disease

2011-10-05

Abstract: Aim: Decreased activity of the mitochondrial electron transport chain (ETC) has been implicated in the pathogenesis of Parkinson's disease (PD). This model would most likely predict a decrease in the rate of cerebral oxygen consumption (CMRO2). To test this hypothesis, we compared CMRO2 and cerebral blood flow (CBF) PET scans from PD patients and healthy controls.Materials and methods: Nine early-stage PD patients and 15 healthy age-matched controls underwent PET scans for quantitative mapping of CMRO2 and CBF. Between-group differences were evaluated for absolute data and intensity-normalized values.Results: No group differences were detected in regional magnitudes of CMRO2 or CBF. Upon normalization using the reference cluster method, significant relative CMRO2 decreases were evident in widespread prefrontal, parieto-occipital, and lateral temporal regions. Sensory-motor and subcortical regions, brainstem, and the cerebellum were spared. A similar pattern was evident in normalized CBF data, as described previously.Conclusion: While the data did not reveal substantially altered absolute CMRO2 in brain of PD patients, employing data-driven intensity normalization revealed widespread relative CMRO2 decreases in cerebral cortex. The detected pattern was very similar to that reported in earlier CBF and CMRglc studies of PD, and in the CBF images from the same subjects. Thus, the present results are consistent with the occurrence of parallel declines in CMRO2, CBF, and CMRglc in spatially contiguous cortical regions in early PD, and support the hypothesis that ETC dysfunction could be a primary pathogenic mechanism in early PD.

New novel mutation of the ATP7B gene in a family with Wilson disease

2011-11-10

Abstract: Wilson disease (WD) is an autosomal recessive disorder of copper metabolism. The WD gene codes for a copper transporting P-type ATPase (ATP7B) are located on chromosome 13q14.3. Mutation of this gene disrupts copper homeostasis, resulting in the accumulation of copper in the liver, brain, kidneys and corneas and copper toxication at these sites. Since the detection of the WD gene in 1993, approximately 300 disease-specific muations have been identified. We recently evaluated a Korean family with WD. The proband, a 17-year-old boy, visited our hospital due to abnormal behaviors including generalized slow movement, dysphagia, drooling and ataxia. Laboratory results revealed decreases in serum copper and ceruloplasmin and an increase in urinary excretion of copper. He had liver cirrhosis, brain lesions and Kayser–Fleischer corenal rings. Molecular genetic analysis of the ATP7B gene demonstrated that he was heterozygous for deletion mutation c.2697_2723del27 in exon 11. Further study of family members revealed that his father and younger brother had the same mutation. The c.2697_2723del27 deletion mutation in exon 11 has not yet been reported as a causative muation of WD and is an in-frame deletion not expected to lead to a frame shift. Therefore, we report a novel mutation of the ATP7B gene in a family with WD.

Administration of edaravone, a free radical scavenger, during t-PA infusion can enhance early recanalization in acute stroke patients — A preliminary study

2011-10-04

Abstract: Background and purpose: The aim of the present study was to investigate whether administration of edaravone during t-PA infusion can enhance early recanalization in acute stroke patients.Methods: This trial was undertaken as a multicenter, single blind, randomized, open-labeled study. Acute stroke patients with M1 or M2 occlusion within 3h of onset were studied prospectively. The subjects were randomly allocated to edaravone (Edaravone group: when t-PA was intravenously infused, intravenous edaravone (30mg) was started at the same time) and no edaravone (Non-Edaravone group). Early recanalization within 1h after t-PA infusion and neurological recovery 24h after t-PA infusion were compared between the two groups.Results: 40 patients (23 men, 17 women; mean age, 76.4±8.2years, median 79years) were enrolled; 23 patients were assigned to the Edaravone group and 17 to the Non-Edaravone group. Early recanalization was more frequently observed in the Edaravone group than in the Non-Edaravone group (56.5% vs. 11.8%, P=0.0072). Eight patients who underwent endovascular therapy immediately after t-PA infusion were excluded, and neurological recovery was analyzed. Remarkable and good recoveries were more frequently observed in the Edaravone group than in the Non-Edaravone group (80.1% vs. 45.5%, P=0.0396).Conclusion: Early recanalization and good neurological recovery were more frequently observed in the Edaravone group than in the Non-Edaravone group. These results demonstrate that administration of edaravone during t-PA infusion should enhance early recanalization in acute stroke patients.

Lack of association between vitamin D levels and bone mineral density in patients with multiple sclerosis

2011-10-12

Abstract: Background: There is conflicting evidence regarding the association of vitamin D status with bone mineral density (BMD) in adult patients with multiple sclerosis (MS). We evaluated cross-sectionaly the determinants (including vitamin D levels) of low BMD in patients with relapsing-remitting MS (RRMS).Methods: The BMD at lumbar level (L2-L4) and femoral neck was measured in consecutive adult, ambulatory, RRMS patients by dual-energy X-ray absorptiometry. Blood samples were collected for total serum calcium, phosphorus, magnesium, 25-hydroxyvitamin D3 and parathormone. Osteopenia and osteoporosis were defined according to the World Health Organization operational BMD definition. MS severity was assessed using the EDSS-score. Cross-sectional associations were evaluated using Spearman's correlation-coefficient and multiple linear regression models.Results: A total of 119 patients were evaluated (mean age 39.2±10.4years; 40% men). Osteopenia at lumbar spine (L2-L4) and femoral neck was present in 26% (95%CI: 18%–35%) and 50% (95%CI: 41%–60%) of the patients respectively. Osteoporosis was documented at lumbar spine and femoral neck of 3% (95%CI: 0%-8%) and 11% (95%CI: 6%–18%) of the study population respectively. There was no correlation (p>0.1) of 25-hydroxyvitamin D3 levels with any of BMD measurements (including Z- and T-scores) both in lumbar spine and in femoral neck. Increasing MS duration and increasing dosage of intravenous corticosteroids were independently and negatively associated with both lumbar spine and femoral neck BMD.Conclusions: We documented no correlation between vitamin D levels and decreased BMD at femoral neck and lumbar spine in RRMS patients. Vitamin D insufficiency appears not to be the underlying cause of secondary osteoporosis in MS.

Blood–brain barrier permeability derangements in posterior circulation ischemic stroke: Frequency and relation to hemorrhagic transformation

2011-09-26

Abstract: Background: Early disruption of the blood–brain barrier (BBB) due to severe ischemia can be detected by MRI T2* permeability imaging. In middle cerebral artery (MCA) infarction, pretreatment T2* permeability derangements have been found in 22% of patients and are powerful predictors of hemorrhagic transformation after revascularization therapy. The frequency, clinical correlates, and relation to hemorrhagic transformation of permeability derangements in posterior circulation have not been previously explored, and may differ as ischemia volume and collateral status are different between vertebrobasilar and MCA infarcts.Methods: We analyzed clinical and pretreatment MRI data on consecutive patients undergoing recanalization therapy for acute vertebrobasilar ischemia at a medical center November 2001 through September 2009. Pretreatment MRI permeability images were derived from perfusion source imaging acquisitions. Permeability abnormality was detected as persisting increased signal intensity at later time points in perfusion MRI acquisition, indicating local accumulation of contrast caused by BBB leakage.Results: Among the 14 patients meeting study entry criteria, mean age was 71.1years and median pretreatment NIHSS was 20.5. Permeability imaging abnormality was present in 1 of the 14 patients (7%). Among 14 patients, post-treatment parenchymal hematoma occurred in one and more minor degrees of hemorrhagic transformation in four. The one patient with pretreatment permeability abnormality was the patient to develop post-treatment parenchymal hematoma (Fisher's exact test, P=0.07).Conclusion: Pretreatment permeability abnormality, an indicator of BBB derangements, is an infrequent finding in acute posterior circulation ischemic stroke and may be associated with an increased risk of parenchymal hematoma development undergoing recanalization therapy.

Nationwide survey on the epidemiology of syringomyelia in Japan

2011-09-26

Abstract: Background: Syringomyelia is a rare disease characterized by abnormal fluid-filled cavities within the spinal cord, and is associated with Chiari malformations, arachnoiditis, or spinal cord tumors. The widespread availability of magnetic resonance imaging (MRI) in Japan has allowed for easy identification of syrinxes. The aim of this study was to survey the clinicoepidemiological characteristics of syringomyelia in Japan.Methods: A 2-stage postal survey was conducted in late 2009. The first survey aimed to estimate the number of patients with syringomyelia, and the second survey aimed to elucidate clinicoepidemiological characteristics. Diagnosis of syringomyelia was based on the findings of MRI or computed tomographic myelography.Results: In the first survey, we received 2133 responses from 2937 randomly selected departments and collected data of 1215 syringomyelia patients (543 men and 672 women). The total response rate for the first survey was 73%. The estimated prevalence of ambulatory syringomyelia patients in Japan was 1.94 per 100000. In the second survey, the proportion of asymptomatic syringomyelia patients was 22.7%. Chiari type I malformations and idiopathic syringomyelia were the first and second most common etiologies.Conclusions: Our nationwide survey indicated that widespread MRI availability has contributed to the diagnosis of both asymptomatic and idiopathic cases.

Audiovestibular loss in anterior inferior cerebellar artery territory infarction: A window to early detection?

Hyung Lee — 2011-10-14

Abstract: Acute audiovestibular loss is a common neurotological condition that is characterized by sudden onset of severe prolonged (lasting days) vertigo and hearing loss and is diagnosed by the presence of canal paresis to caloric stimulation and sensorineural hearing loss on pure tone audiogram. Before 2000, papers on anterior inferior cerebellar artery (AICA) territory infarction focused mostly on associated brainstem and cerebellar findings, without a detailed description of neurotological findings. Since 2000, several reports have demonstrated that acute audiovestibular loss is an important sign for the diagnosis of AICA territory infarction. To date, at least eight subgroups of AICA infarction have been identified according to the pattern of neurotological presentations, among which the most common pattern of audiovestibular dysfunction is the combined loss of auditory and vestibular functions. Because audiovestibular loss may occur in isolation before ponto-cerebellar infarction involving AICA distribution, audiovestibular loss may serve as a window to prevent the progression of acute audiovestibular loss into more widespread areas of infarction in posterior circulation (mainly in the AICA territory). Clinician should keep in mind that acute audiovestibular loss may herald impending AICA territory infarction, especially when patients had basilar artery occlusive disease presumably close to the origin of the AICA on brain MRA, even if other central signs are absent and MRI does not demonstrate acute infarction.

Poor concurrence between disabilities as described by patients and established assessment tools three months after stroke: A mixed methods approach

Malin Tistad, Charlotte Ytterberg, Kerstin Tham, Lena von Koch — 2011-09-21

Abstract: Background: Disability/problems, one phenomenon underlying people's need for health care services, can be viewed both from the perspectives of people with stroke (felt problems), and the health professionals (assessed problems).Objective: The aim was to describe felt problems three months after stroke and to explore the concurrence between felt problems and assessed problems.Method: The patients (n=203) received care in the stroke units at Karolinska University Hospital, Sweden. Felt problems, drawn from an open question, were categorized. Results from established assessment tools: Katz Extended Index of ADL (KI); Barthel Index (BI) and Stroke Impact Scale (SIS) represented assessed problems. Items/domains in the assessment tools that corresponded to the categories of felt problems were identified and comparisons performed.Result: The category Fatigue had the largest number of felt problems (n=58, 28%). Fourteen out of the 24 categories of felt problems had corresponding items/domains in the assessment tools. KE/BI failed to identify 16–57% and SIS 0–33% of the felt problems.Conclusion: There was a substantial lack of concurrence between felt and assessed problems. The results indicate that the use of standardized instruments should be complemented by a dialog if health services are to be based on problems experienced by the patients.

Clinical and pathological effects of intrathecal injection of mesenchymal stem cell-derived neural progenitors in an experimental model of multiple sclerosis

2011-10-03

Abstract: Multiple sclerosis (MS) is associated with irreversible disability in a significant proportion of patients. At present, there is no treatment to halt or reverse the progression of established disability. In an effort to develop cell therapy-based strategies for progressive MS, we investigated the pre-clinical efficacy of bone marrow mesenchymal stem cell-derived neural progenitors (MSC-NPs) as an autologous source of stem cells. MSC-NPs consist of a subpopulation of bone marrow MSCs with neural progenitor and immunoregulatory properties, and a reduced capacity for mesodermal differentiation, suggesting that this cell population may be appropriate for clinical application in the CNS. We investigated whether MSC-NPs could promote repair and recovery after intrathecal injection into mice with EAE. Multiple injections of MSC-NPs starting at the onset of the chronic phase of disease improved neurological function compared to controls, whereas a single injection had no effect on disease scores. Intrathecal injection of MSC-NPs correlated with reduced immune cell infiltration, reduced area of demyelination, and increased number of endogenous nestin-positive progenitor cells in EAE mice. These observations suggest that MSC-NPs may influence the rate of repair through effects on endogenous progenitors in the spinal cord. This study supports the use of autologous MSC-NPs in MS patients as a means of promoting CNS repair.

Macrocephaly–capillary malformation syndrome: Three new cases

2011-10-26

Abstract: Overgrowth syndromes can be associated with asymmetry, obesity and various vascular malformations. Macrocephaly–Capillary Malformation (M–CM) is a more recently defined overgrowth syndrome characterized by cutaneous capillary malformation occurring in association with macrocephaly with tendency to progressive enlargement, abnormalities of somatic growth with body asymmetry including brain asymmetry, developmental delay, typical face with full cheeks, nevus flammeus of the nose and/or philtrum and upper lip, joint laxity, thickened subcutaneous tissue and 2/3 syndactyly of the toes. We evaluated three patients who demonstrated characteristic features of the disorder. Patients seen in the Genetic clinic of a tertiary care center were subjects of the analysis. We present three cases of overgrowth syndrome with common features of macrocephaly, capillary malformation, dysmorphic face and abnormal neurocognitive profile. These features are consistent with the newly defined M–CM syndrome. This condition must be differentiated from other overgrowth syndromes for appropriate surveillance for known complications and genetic counseling. We discuss the diagnostic criteria for the disorder and also recommend to include typical face with full cheeks, nevus flammeus of the nose and/or philtrum and upper lip, considering it as minor criterion on the basis of findings in present cases. One of the cases had bluish white iris which has not been described earlier.

‘Noteomielite’ accompanied by acute amaurosis (1844). An early case of neuromyelitis optica

S. Jarius, B. Wildemann — 2011-10-13

Abstract: So far, only very little is known about the early history of neuromyelitis optica (Devic's syndrome). Here, we discuss a then widely recognized but now forgotten 1844 report by the Genoese physician Giovanni Battista Pescetto (1806–1884) on a 42-year-old man, who simultaneously developed acute amaurosis and cervical myelitis. Pescetto's report represents the earliest account of a case of neuromyelitis optica in the Western literature known so far.

POEMS syndrome with prominent acute axonal lesions

S. Mathis, L. Magy, R. Kaboré, F. Faugeras, L. Richard, J.-M. Vallat — 2011-10-07

Abstract: Polyneuropathy is a common presenting component of POEMS syndrome whose symptoms are attributed to an overproduction of vascular endothelial growth factor (VEGF). We report two female patients with POEMS syndrome presenting as a severe predominantly axonal neuropathy. A nerve biopsy was performed for these patients; pathological data confirmed unusual numerous acute axonal lesions associated with other classical signs of POEMS syndrome. POEMS syndrome is usually associated with demyelinating neuropathy (and secondary axonal loss); however, prominent axonal neuropathy (with acute axonal lesions on nerve biopsy) can also be observed in this disease. These observations illustrate the heterogeneity of peripheral nervous system involvement in POEMS syndrome.

A novel nonsense mutation in the TITF-1 gene in a Japanese family with benign hereditary chorea

2011-10-07

Abstract: A Japanese family with a novel nonsense mutation in the TITF-1 gene (p.Y98X) is described. The proband showed severe generalized chorea, delayed motor development, subnormal intelligence, congenital hypothyroidism, bronchial asthma, and a history of pulmonary infection, all of which are characteristic features of Brain–Thyroid–Lung syndrome. On the other hand, her brother and mother showed a mild benign hereditary chorea (BHC) phenotype with congenital hypothyroidism. Intrafamilial phenotypic variation is common in BHC/Brain–Thyroid–Lung syndrome and suggests the existence of other genetic or environmental factors regulating TITF-1 function. Although choreic movement in BHC/Brain–Thyroid–Lung syndrome is recognized as non-progressive, the proband showed re-exacerbation of choreic movement at puberty. The dopamine agonist, ropinirole hydrochloride, reduced her choreic movements, suggesting that levodopa and/or dopamine agonists may compensate for underdeveloped dopaminergic pathways in this disorder.

Reactivation of type 1 herpes simplex virus and varicella zoster virus in an immunosuppressed patient with acute peripheral facial weakness

2011-09-19

Abstract: We describe a 26-year-old man treated with azathioprine for myasthenia gravis who developed acute left-sided peripheral facial weakness. Brain magnetic resonance imaging (MRI) revealed enhancement in the left geniculate ganglion and in the intracanalicular and tympanic segments of the facial nerve. Analysis of cerebrospinal fluid (CSF) and serum revealed intrathecal synthesis of anti-varicella zoster virus (VZV) IgG antibody. Although previous analyses of saliva, blood mononuclear cells, serum antibodies, middle ear fluid, and auricular and geniculate zone skin scrapings have shown that a small but definite proportion of patients with idiopathic peripheral facial palsy (“Bell's palsy”) have the Ramsay Hunt syndrome zoster sine herpete (RHS ZSH), this is the first confirmation of RHS ZSH by intrathecal synthesis of anti-VZV IgG antibody. In addition, herpes simplex virus (HSV)-1 DNA was found in saliva of the patient on 3 consecutive days. Simultaneous reactivation of two alphaherpesviruses (HSV-1 and VZV) in our immunosuppressed patient underscores the need to consider opportunistic infection as a cause of facial weakness.

Multiple biomarkers for oxidative stress in patients with brain disorders

Hirokazu Tsukahara, Yosuke Fujii, Yuko Hayashi, Tsuneo Morishima — 2011-11-07

To the Editor: Reactive oxygen species are involved in human disorders of various kinds. In the Journal, Grosso and coworkers presented biological evidence that patients with epileptic encephalopathy have enhanced oxidative stress compared to those with idiopathic epilepsy syndromes, those who are seizure-free or with sporadic seizures, and healthy controls. They measured blood levels of F2-isoprostanes, advanced oxidative protein products, and non-protein binding iron in the subjects. All are appropriate biomarkers for assessing oxidative stress in humans.

Pratik D. Bhattacharya — 2011-10-19

The clinical and research applications and utilization of diffusion MRI have expanded rapidly over the last few years. In the current scenario, this book is an indispensible addition to the growing scientific literature in the field of MR imaging. The book is a wonderful compendium, for anybody: whether a basic scientist or a clinician with an academic interest in the use of this novel technique as a non-invasive and easily accessible method to understand tissue biology.

Why people get lost: the psychology and neuroscience of spatial cognition, Paul A. Dudchenko, Oxford University Press, pages, $54.95, ISBN: 978-0-19-921086-2; 299

Ilana R. Yurkiewicz, Jack W. Tsao — 2011-10-24

Who hasn't felt one or more of these symptoms? Getting lost is a universal experience, writes University of Stirling lecturer Paul A. Dudchenko in the first chapter of his book, unambiguously titled Why People Get Lost, that reviews experimental evidence to delve into the reasons that might be. “Being lost,” he defines, “means being unable to find one's way.” Thus, his work addresses the psychological aspects of our ability to navigate our environment, along with the neural correlates that underlie them. Dudchenko presents a series of questions that neatly frames the organization of the book. Do people have an internal sense of direction? Where is it in the brain? How does it develop? Do certain brain disorders hinder cognitive mapping? The first chapter closes with a spoiler. Our brains concoct an internal representation of our external surroundings, vulnerable to error accumulation when we are inattentive or in unfamiliar territory. This error disorients our innate mental compass. In other words, we become lost.

Ilana R. Yurkiewicz, Jack W. Tsao — 2011-10-19

Judge a book by its cover, and Oxford Care Manuals look very similar: the series of medical guides are all conveniently pocket-sized and publicize themselves as targeting a readership of health professionals and related members of a clinical care team. What distinguishes each book is subject matter. For a fastidiously comprehensive, well-organized guide to a common debilitating condition of geriatric patients, look no further than Dementia Care, by Jonathan Waite, Rowan H. Harwood, Ian R. Morton, and David J. Connelly.

Brett T. Monson, Jack W. Tsao — 2011-10-19

Brains: How They Seem to Work, written by Dr. Dale Purves, a professor of Neurobiology, Psychology, Neuroscience, and Philosophy at Duke University, provides not only information concerning how the brain works but also fascinating historical context from the author's work throughout his career in academia. Information presented by the author briefly covers topics in the peripheral nervous system, neural development, and the central nervous system before providing a thorough analysis of the brain's visual systems.

Kumar Rajamani — 2011-10-20

Evidence Based Medicine is defined as the explicit and judicious use of current best evidence in making decisions about care of individual patients. (Sackett et al. BMJ 1996, 312:76). If we have to offer our patients consistently the best care, and increasingly in these times at the optimal individual and societal costs, then there is need for a thoughtful integration of the best external clinical evidence from systematic research. This book provides that help to both the beginner at the start of his or her quest in field of vascular neurology (residents and fellows) as well as the established clinician who treats and manages stroke patients with problems both simple and complex. The topics for the fifteen chapters are well chosen and deal with high impact and common issues. Each of these is written by the acknowledged world experts in that field and the ‘transatlantic’ duo of editors must be complimented for this. The style is easy to read, each of the chapters is well arranged and the tables in particular are very informative. I especially liked the key points colorfully highlighted at the end of each chapter, which gives the reader a succinct ‘bite-sized’ review of all the important points covered in the chapter. The references at the end of each chapter are exhaustive and readily available – unlike some other books which recently have fallen prey to the fad of providing them separately online – which for me takes away from the continuity of reading. For this, I must compliment the designers of the book.

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2012-02-15