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Neurological Disorders (neurological + disorders)
Kinds of Neurological Disorders Selected AbstractsTHE PREVALENCE OF AT-RISK FOOT IN PATIENTS WITH DIABETES MELLITUS, PATIENTS WITHOUT DIABETES MELLITUS WITH NEUROLOGICAL DISORDERS, AND SUBJECTS WITHOUT KNOWN DIABETES MELLITUS OR LOWER LIMB SENSORY LOSSJOURNAL OF AMERICAN GERIATRICS SOCIETY, Issue 1 2008Zoltan Pataky MD No abstract is available for this article. [source] Therapeutic Yield and Outcomes of a Community Teaching Hospital Code Stroke ProtocolACADEMIC EMERGENCY MEDICINE, Issue 4 2004Andrew W. Asimos MD Objectives: To describe the experience of a community teaching hospital emergency department (ED) Code Stroke Protocol (CSP) for identifying acute ischemic stroke (AIS) patients and treating them with tissue plasminogen activator (tPA) and to compare outcome measures with those achieved in the National Institute of Neurological Disorders and Stroke (NINDS) trial. Methods: This study was a retrospective review from a hospital CSP registry. Results: Over a 56-month period, CSP activation occurred 255 times, with 24% (n= 60) of patients treated with intravenous (IV) tPA. The most common reasons for thrombolytic therapy exclusion were mild or rapidly improving symptoms in 37% (n= 64), intracerebral hemorrhage (ICH) in 23% (n= 39), and unconfirmed symptom onset time for 14% (n= 24) of patients. Within 36 hours of IV tPA treatment, 10% (NINDS = 6%) of patients (n= 6) sustained a symptomatic ICH (SICH). Three months after IV tPA treatment, 60% of patients had achieved an excellent neurologic outcome, based on a Barthel Index of ,95 (NINDS = 52%), while mortality measured 12% (NINDS = 17%). Among IV tPA-treated patients, those developing SICH were significantly older and had a significantly higher mean initial glucose value. Treatment protocol violations occurred in 32% of IV tPA-treated patients but were not significantly associated with SICH (Fisher's exact test). Conclusions: Over the study period, the CSP yielded approximately one IV tPA-treated patient for every four screened and, despite prevalent protocol violations, attained three-month functional outcomes equal to those achieved in the NINDS trial. For community teaching hospitals, ED-directed CSPs are a feasible and effective means to screen AIS patients for treatment with thrombolysis. [source] The response to IV rt-PA in very old stroke patientsEUROPEAN JOURNAL OF NEUROLOGY, Issue 3 2008M. Gómez-Choco The use of rtPA in stroke patients aged >80 years remains controversial and it is debated whether there are sex-based differences in the response to rtPA. We assessed the clinical value of thrombolytic therapy in patients aged >80 years (elderly group) in comparison with a non-elderly group, and evaluated the existence of sex differences in the response to rtPA. All consecutive patients (n = 157) treated with rtPA were prospectively assessed since July 2001, including 49 elderly patients who fulfilled the National Institute of Neurological Disorders and Stroke (NINDS) criteria. Changes of the National Institute of Health Stroke Scale (NIHSS) score at 1 h, 24 h, and 7 days after rtPA administration, favourable outcome at day 90 [(modified Rankin Scale) mRS 0,1, or 2 if mRS = 2 before the stroke], symptomatic bleedings, and death rates were compared between elderly and non-elderly patients. Using logistic regression, baseline NIHSS score [odds ratio (OR) 0.59, 95% confidence interval (CI) 0.41,0.84] was an independent predictor of favourable outcome, but not sex (OR 0.72, 95% CI 0.33,1.56), or age >80 years (OR 0.74, 95% CI 0.32,1.70). The rates of clinical improvement, mortality, or symptomatic CNS bleeding were also unrelated to age and sex. In conclusion, the response to IV rtPA is not impaired in elderly stroke patients and male and female are equally responsive. [source] Ethnic Differences in Singapore's Dementia Prevalence: The Stroke, Parkinson's Disease, Epilepsy, and Dementia in Singapore StudyJOURNAL OF AMERICAN GERIATRICS SOCIETY, Issue 11 2008Suresh Sahadevan MBBS OBJECTIVES: To study the prevalence of dementia in Singapore among Chinese, Malays, and Indians. DESIGN: A two-phase, cross-sectional study of randomly selected population from central Singapore with disproportionate race stratification. SETTING: Community-based study. Subjects screened to have cognitive impairment at phase 1 in their homes were evaluated clinically for dementia at phase 2 in nearby community centers. PARTICIPANTS: Fourteen thousand eight hundred seventeen subjects aged 50 and older (67% participation rate). MEASUREMENTS: The locally validated Abbreviated Mental Test was used to screen for cognitive impairment at phase 1. Dementia was diagnosed at phase 2 as per Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria. Possible Alzheimer's disease (AD) and possible vascular dementia (VD) were diagnosed along the National Institute of Neurological and Communicative Disorders,Alzheimer's Disease and Related Disorders Association and National Institute of Neurological Disorders and Stroke,Association Internationale pour la Recherche et l'Enseignement en Neuroscienes criteria, respectively. RESULTS: The overall age- and race-standardized dementia prevalence was 1.26% (95% confidence interval (CI)=1.10,1.45). Prevalence (in 5-year age bands) was 0.08% (50,54), 0.08% (55,59), 0.44% (60,64), 1.16% (65,69), 1.84% (70,74), 3.26% (75,79), 8.35% (80,84), and 16.42% (,85). From age 50 to 69, 65% of dementia cases were VD; at older ages, 60% were AD. Logistic regression (adjusted for age, sex, education) showed that Malays had twice the risk for AD as Chinese, and Indians had more than twice the risk for AD and VD than Chinese. CONCLUSION: Singapore's dementia prevalence, primarily influenced by its Chinese majority, is lower than seen in the West. The striking interethnic differences suggest a need for a dementia incidence study and further investigation of underlying genetic and cultural differences between the three ethnic groups in relation to dementia risk. [source] 17th European Society for Neurochemistry Meeting 3rd Conference on Advances in Molecular Mechanisms of Neurological Disorders, Salamanca, Spain, 19,22 May, 2007JOURNAL OF NEUROCHEMISTRY, Issue 2007Article first published online: 25 APR 200 No abstract is available for this article. [source] Baseline Computed Tomography Changes and Clinical Outcome After Thrombolysis With Recombinant Tissue Plasminogen Activator in Acute Ischemic StrokeJOURNAL OF NEUROIMAGING, Issue 2 2001Jorge E. Mendizabal MD ABSTRACT Objective. Intravenous recombinant tissue plasminogen activator (rt-PA) is the only therapy of proven value for patients with acute ischemic stroke (AIS). Controversy exists with regard to the prognostic significance of early computed tomography (CT) changes in patients receiving rt-PA for AIS. The authors retrospectively reviewed all cases of AIS who received intravenous rt-PA for AIS in University of South Alabama hospitals between January 1996 and May 1999. A neuroradiologist, blinded to clinical outcomes, reviewed all baseline CT scans for the presence of the following signs: hyperdense middle cerebral artery (HMCA), loss of gray-white differentiation (LGWD), insular ribbon sign (IRS), parenchymal hypodensity (PH), and sulcal effacement (SE). Modified Rankin Scale (mRS) score was recorded 90 days after thrombolysis, and clinical outcome was dichotomized as favorable (0,1) or unfavorable (2,6). The authors performed both univariate and multivariate analyses to investigate the relationship between early CT signs, baseline clinical variables, and functional outcome as measured by the 90-day mRS scores. Any one early CT finding was detected in 23 (64%) patients. The frequency of specific findings were as follows: SE in 13 patients (36%), LGWD in 12 patients (33%), PH in 9 patients (25%), HMCA in 4 patients (11%), and IRS in 3 patients (8%) patients. There was no statistically significant association between the occurrence of these imaging findings and subsequent functional outcome after thrombolysis. The data suggest that the presence of subtle acute CT changes in AIS patients is not predictive of clinical outcome following administration of rt-PA as per National Institute of Neurological Disorders and Stroke protocol. [source] Neurological Disorders: Public Health ChallengesJOURNAL OF POLICY AND PRACTICE IN INTELLECTUAL DISABILITIES, Issue 1 2008Gideon Vardi M.D. [source] National Institute of Neurological Disorders and Stroke (NINDS): Advances in understanding and treating neuropathy, 24,25 October 2006; Bethesda, MarylandJOURNAL OF THE PERIPHERAL NERVOUS SYSTEM, Issue 1 2008Eva L. Feldman Abstract National Institute of Neurological Disorders and Stroke sponsored a meeting to explore the current status of basic and clinical research in peripheral neurobiology and clinical neuropathy. The goal of the workshop was to identify areas where additional research could lead to the development of new therapeutics in the next 5 years. Participants discussed the current understanding of disease mechanisms of axonal and demyelinating neuropathies, existing techniques in research, disease biomarkers, and assessment of neuropathy. Painful neuropathies were discussed at the basic scientific and clinical levels in relation to new insights into etiology and treatment. The meeting concluded with a discussion on therapeutic development in neuropathy and the need for a unified approach to multicenter trials. Short-term goals of the workshop were to form a working group for neuropathy, the Peripheral Neuropathy Study Group, and to translate new scientific findings into therapies and complete clinical trials. [source] Lack of association between progressive supranuclear palsy and arterial hypertension: A clinicopathological studyMOVEMENT DISORDERS, Issue 6 2003Carlo Colosimo MD Abstract It has been reported that up to 80% of patients clinically diagnosed as having progressive supranuclear palsy (PSP) may have arterial hypertension (HT). Because previous studies were performed on patients with presumed diagnosis of PSP, we tried to replicate these studies in a series of pathologically confirmed patients. Seventy-three patients with a neuropathological diagnosis of PSP autopsied at the Queen Square Brain Bank for Neurological Disorders in London were collected between 1989 and 1999. For the purpose of this study, patients were considered hypertensive if a blood pressure above 140/90 mm Hg was found in the clinical records. The prevalence of HT in PSP patients at the first and at the last visit during their neurological disease was compared with that found in a series of 21 normal controls who donated their brain to the same institution. Overall, 29 of 73 (39.7%) of the patients were recorded as having HT at the first visit during the disease course; this ratio increased to 42 of 73 (57.5%) at the last visit before death. When these figures were compared to the 21 normal controls (11 of 21 with HT, 52.4%), we were unable to find an increased prevalence of HT in PSP (odds ratio, 0.60; 95% confidence interval, 0.20,1.76). Therefore, HT does not represent an important clinical feature of this neurodegenerative disorder, although cerebrovascular disease can masquerade clinically as PSP. © 2003 Movement Disorder Society [source] Progressive supranuclear palsy combined with Alzheimer's disease: A clinicopathological study of two autopsy casesNEUROPATHOLOGY, Issue 3 2009Rieko Sakamoto We present here the clinicopathological characteristics of two autopsy-confirmed cases comorbid of progressive supranuclear palsy (PSP) and Alzheimer's disease (AD). Histopathologically, the amount and distribution of neurofibrillary tangles (NFTs) in the basal ganglia and brainstem fulfilled the pathological criteria of PSP proposed by the National Institute of Neurological Disorders and Stroke , The Society for PSP (NINDS-SPSP). The Braak stages of senile plaques and NFTs were stage C and stage V in Case 1, and stage C and stage IV in Case 2. These neuropathological findings confirmed that the two patients had combined PSP with AD. Our patients presented clinically with executive dysfunction prior to memory disturbance as an early symptom. Not only neurological symptoms such as gait disturbance, supranuclear ophthalmoplegia and pseudobulbar palsy, but emotional and personality changes and delirium were prominent. Therefore, symptoms of subcortical dementia of PSP were more predominant than AD-related symptoms in the present two patients. Comorbid PSP and AD further complicates the clinical picture and makes clinical diagnosis even more difficult. [source] Proposed neuropathological criteria for the post mortem diagnosis of multiple system atrophyNEUROPATHOLOGY & APPLIED NEUROBIOLOGY, Issue 6 2007J. Q. Trojanowski This report summarizes the recommendations of the multiple system atrophy (MSA) Working Group on Diagnostic Neuropathology Criteria for MSA that was part of an international MSA Workshop held on 26 and 27 April 2007 in Boston, MA. The workshop was supported by a grant from the National Institute of Neurological Disorders and Stroke that was intended to convene a group of international experts to revise and update criteria for the clinical and neuropathological diagnosis of MSA. The MSA Workshop recognized the glial cytoplasmic inclusions (GCIs) composed of filamentous alpha-synuclein as a defining morphological feature of MSA, and it recommends that widespread GCIs should be a criterion for the definite neuropathological diagnosis of MSA. The deliberations and recommendations of the Working Group on Diagnostic Neuropathology Criteria for MSA are summarized in this report. [source] Acute Stroke Care at Rural Hospitals in Idaho: Challenges in Expediting Stroke CareTHE JOURNAL OF RURAL HEALTH, Issue 1 2006James G. Gebhardt MD ABSTRACT:,Context: Thrombolytics are currently the most effective treatment for stroke. However, the National Institute for Neurological Disorders and Stroke criteria for initiation of thrombolytic therapy, most notably the 3-hour time limit from symptom onset, have proven challenging for many rural hospitals to achieve. Purpose: To provide a snapshot of stroke care at rural hospitals in Idaho and to investigate the experiences of these hospitals in expediting stroke care. Methods: Using a standard questionnaire, a telephone survey of hospital staff at 21 rural hospitals in Idaho was performed. The survey focused on acute stroke care practices and strategies to expedite stroke care. Findings: The median number of stroke patients treated per year was 23.3. Patient delays were reported by 77.8% of hospitals, transport delays by 66.7%, in-hospital delays by 61.1%, equipment delays by 22.2%, and ancillary services delays by 61.1%. Approximately 67% of hospitals had implemented a clinical pathway for stroke and 80.0% had provided staff with stroke-specific training. No hospitals surveyed had a designated stroke team, and only 33.3% reported engaging in quality improvement efforts to expedite stroke care. Thrombolytics (tPA) were available and indicated for stroke at 55.6% of the hospitals surveyed. Conclusions: Rural hospitals in Idaho face many difficult challenges as they endeavor to meet the 3-hour deadline for thrombolytic therapy, including limited resources and experience in acute stroke care, and many different types of prehospital and in-hospital delays. [source] JC virus persistence following progressive multifocal leukoencephalopathy in multiple sclerosis patients treated with natalizumab,ANNALS OF NEUROLOGY, Issue 3 2010Caroline F. Ryschkewitsch MT JC virus (JCV) DNA in the cerebrospinal fluid (CSF) provides the laboratory confirmatory diagnosis of progressive multifocal leukoencephalopathy (PML) in patients whose clinical symptoms and magnetic resonance imaging findings are consistent with PML. The Laboratory of Molecular Medicine and Neuroscience (LMMN), National Institute of Neurological Disorders and Stroke (NINDS), National Institutes of Health (NIH), made the confirmatory laboratory diagnosis in 35 multiple sclerosis (MS) patients treated with natalizumab. Thirteen patients had 3 or more CSF samples taken from weeks to months following PML diagnosis. Seven of the 13 patients demonstrated persistence of JCV DNA in the CSF even though all patients experienced immune reconstitution inflammatory syndrome (IRIS), 11 patients had plasma exchange, and 2 had immunoabsorption. Specific anti-JCV antibody was measured in plasma/sera samples from 25 of the 35 patients. Most of the samples showed moderate to high or rising antibody levels from the time of PML diagnosis. However, plasma from 1 patient at or near the time of PML diagnosis had a titer considered seronegative and 2 other plasma samples from patients had titers considered at baseline for seropositivity. In several PML cases, viral persistence and neurological deficits have continued for several years, indicating that once initiated, JCV infection may not entirely clear, even with IRIS. Ann Neurol 2010;68:384,391 [source] Local institutional review board (IRB) review of a multicenter trial: Local costs without local contextANNALS OF NEUROLOGY, Issue 2 2010Bernard Ravina MD, MSCE Multicenter clinical research involves parallel Institutional Review Board (IRB) reviews based on the premise that local review reflects aspects of the research environment. We examined the costs and effects of local IRB review of the consent and protocol in a multicenter clinical trial in Parkinson disease. Seventy-six percent of changes to the consent reflected standard institutional language, with no substantive changes to the protocol. The costs of this process exceeded $100,000. These findings support initiatives by the Office of Human Research Protections (OHRP) and the National Cancer Institute (NCI) to facilitate centralized reviews. This may be an opportune time for the National Institute of Neurological Disorders and Stroke (NINDS) to adopt a central review model. ANN NEUROL 2010;67:258,260 [source] Why ischemic stroke patients do not receive thrombolytic treatment: results from a general hospitalACTA NEUROLOGICA SCANDINAVICA, Issue 3 2009J. S. P. Van Den Berg Objectives,,, To determine the proportion of patients with an ischemic stroke that received intravenous (IV) thrombolytic treatment, and reasons why patients are not treated. Methods,,, A prospective registry of all patients with an ischemic stroke admitted to our emergency department (ED). Results,,, A total of 286 patients with an ischemic stroke were admitted. Eighty-one patients were admitted within 3 h of onset of neurological deficit, of which 28 received IV thrombolysis. In 25 patients no thrombolytic treatment was given because of the presence of the National Institute of Neurological Disorders and Stroke (NINDS) exclusion criteria, and one patient refused treatment. No thrombolytic treatment was given to 27 patients because of mild neurological deficit or rapid clinical improvement, and after 3 months all these patients were independently living at home without nursing help. Despite a public campaign to gain awareness concerning stroke, the majority of the patients arrived too late at the ED for thrombolytic treatment. Conclusions,,, A large proportion of the patients with an ischemic stroke are admitted too late to receive IV thrombolysis. More needs to be done to increase both public and medical awareness of stroke as a treatable emergency. [source] Step-forward Randomization in Multicenter Emergency Treatment Clinical TrialsACADEMIC EMERGENCY MEDICINE, Issue 6 2010Wenle Zhao PhD Abstract The authors present a new centralized randomization method for multicenter emergency treatment clinical trials. With this step-forward method, treatment randomization for the next subject is performed immediately after the enrollment of the current subject. This design ensures the readiness of the treatment assignment for each subject at the point of study enrollment, and it simultaneously provides effective control on treatment assignments balance and distributions of covariates. The authors also discuss procedures of the step-forward randomization method along with its implementation for two National Institute of Neurological Disorders and Stroke,funded multicenter acute stroke trials, one double-blinded and one open-labeled. Advantages and limitations are presented based on experience gained in these two trials. ACADEMIC EMERGENCY MEDICINE 2010; 17:659,665 © 2010 by the Society for Academic Emergency Medicine [source] Neurological disorders in complex humanitarian emergencies and natural disastersANNALS OF NEUROLOGY, Issue 3 2010Farrah J. Mateen MD Complex humanitarian emergencies include the relatively acute, severe, and overwhelming health consequences of armed conflict, food scarcity, mass displacement, and political strife. Neurological manifestations of complex humanitarian emergencies are important and underappreciated consequences of emergencies in populations worldwide. This review critically assesses the existing knowledge of the range of neurological disorders that accompany complex humanitarian emergencies and natural disasters in both the acute phase of crisis and the "long shadow" that follows. Ann Neurol 2010;68:282,294 [source] Autoantibodies in gluten ataxia recognize a novel neuronal transglutaminaseANNALS OF NEUROLOGY, Issue 3 2008Marios Hadjivassiliou MD Objective Gluten sensitivity typically presents as celiac disease, a chronic, autoimmune-mediated, small-intestinal disorder. Neurological disorders occur with a frequency of up to 10% in these patients. However, neurological dysfunction can also be the sole presenting feature of gluten sensitivity. Development of autoimmunity directed toward different members of the transglutaminase gene family could offer an explanation for the diversity in manifestations of gluten sensitivity. We have identified a novel neuronal transglutaminase isozyme and investigated whether this enzyme is the target of the immune response in patients with neurological dysfunction. Methods Using recombinant human transglutaminases, we developed enzyme-linked immunosorbent assays and inhibition assays to analyze serum samples of patients with gluten-sensitive gastrointestinal and neurological disorders, and various control groups including unrelated inherited or immune conditions for the presence and specificity of autoantibodies. Results Whereas the development of anti-transglutaminase 2 IgA is linked with gastrointestinal disease, an anti-transglutaminase 6 IgG and IgA response is prevalent in gluten ataxia, independent of intestinal involvement. Such antibodies are absent in ataxia of defined genetic origin or in healthy individuals. Inhibition studies showed that in those patients with ataxia and enteropathy, separate antibody populations react with the two different transglutaminase isozymes. Furthermore, postmortem analysis of brain tissue showed cerebellar IgA deposits that contained transglutaminase 6. Interpretation Antibodies against transglutaminase 6 can serve as a marker in addition to human leukocyte antigen type and detection of anti-gliadin and anti-transglutaminase 2 antibodies to identify a subgroup of patients with gluten sensitivity who may be at risk for development of neurological disease. Ann Neurol 2008;64:332,343 [source] Development of a Disposable Magnetically Levitated Centrifugal Blood Pump (MedTech Dispo) Intended for Bridge-to-Bridge Applications,Two-Week In Vivo EvaluationARTIFICIAL ORGANS, Issue 9 2010Eiki Nagaoka Abstract Last year, we reported in vitro pump performance, low hemolytic characteristics, and initial in vivo evaluation of a disposable, magnetically levitated centrifugal blood pump, MedTech Dispo. As the first phase of the two-stage in vivo studies, in this study we have carried out a 2-week in vivo evaluation in calves. Male Holstein calves with body weight of 62.4,92.2 kg were used. Under general anesthesia, a left heart bypass with a MedTech Dispo pump was instituted between the left atrium and the descending aorta via left thoracotomy. Blood-contacting surface of the pump was coated with a 2-methacryloyloxyethyl phosphorylcholine polymer. Post-operatively, with activated clotting time controlled at 180,220 s using heparin and bypass flow rate maintained at 50 mL/kg/min, plasma-free hemoglobin (Hb), coagulation, and major organ functions were analyzed for evaluation of biocompatibility. The animals were electively sacrificed at the completion of the 2-week study to evaluate presence of thrombus inside the pump, together with an examination of major organs. To date, we have done 13 MedTech Dispo implantations, of which three went successfully for a 2-week duration. In these three cases, the pump produced a fairly constant flow of 50 mL/Kg/min. Neurological disorders and any symptoms of thromboembolism were not seen. Levels of plasma-free Hb were maintained very low. Major organ functions remained within normal ranges. Autopsy results revealed no thrombus formation inside the pump. In the last six cases, calves suffered from severe pneumonia and they were excluded from the analysis. The MedTech Dispo pump demonstrated sufficient pump performance and biocompatibility to meet requirements for 1-week circulatory support. The second phase (2-month in vivo study) is under way to prove the safety and efficacy of MedTech Dispo for 1-month applications. [source] Hypocretin/orexin and narcolepsy: new basic and clinical insightsACTA PHYSIOLOGICA, Issue 3 2010S. Nishino Abstract Narcolepsy is a chronic sleep disorder, characterized by excessive daytime sleepiness (EDS), cataplexy, sleep paralysis and hypnagogic hallucinations. Both sporadic (95%) and familial (5%) forms of narcolepsy exist in humans. The major pathophysiology of human narcolepsy has been recently discovered based on the discovery of narcolepsy genes in animals; the genes involved in the pathology of the hypocretin/orexin ligand and its receptor. Mutations in hypocretin-related genes are rare in humans, but hypocretin ligand deficiency is found in a large majority of narcolepsy with cataplexy. Hypocretin ligand deficiency in human narcolepsy is probably due to the post-natal cell death of hypocretin neurones. Although a close association between human leucocyte antigen (HLA) and human narcolepsy with cataplexy suggests an involvement of autoimmune mechanisms, this has not yet been proved. Hypocretin deficiency is also found in symptomatic cases of narcolepsy and EDS with various neurological conditions, including immune-mediated neurological disorders, such as Guillain,Barre syndrome, MA2-positive paraneoplastic syndrome and neuromyelitis optica (NMO)-related disorder. The findings in symptomatic narcoleptic cases may have significant clinical relevance to the understanding of the mechanisms of hypocretin cell death and choice of treatment option. The discoveries in human cases lead to the establishment of the new diagnostic test of narcolepsy (i.e. low cerebrospinal fluid hypocretin-1 levels for ,narcolepsy with cataplexy' and ,narcolepsy due to medical condition'). As a large majority of human narcolepsy patients are ligand deficient, hypocretin replacement therapy may be a promising new therapeutic option, and animal experiments using gene therapy and cell transplantations are in progress. [source] Randomized trial of botulinum toxin injections into the salivary glands to reduce drooling in children with neurological disordersDEVELOPMENTAL MEDICINE & CHILD NEUROLOGY, Issue 2 2008S M Reid MClinEpi BAppSc (physio) The primary aim of this randomized, controlled trial was to assess the effectiveness of botulinum toxin A (BoNT-A) injections into the submandibular and parotid glands on drooling in children with cerebral palsy (CP) and other neurological disorders. Secondary aims were to ascertain the duration of any such effect and the timing of maximal response. Of the 48 participants (27 males, 21 females; mean age 11y 4mo [SD 3y 3mo], range 6-18y), 31 had a diagnosis of CP and 15 had a primary intellectual disability; 27 children were non-ambulant. Twenty-four children randomized to the treatment group received 25 units of BoNT-A into each parotid and submandibular gland. Those randomized to the control group received no treatment. The degree and impact of drooling was assessed by carers using the Drooling Impact Scale questionnaire at baseline and at monthly intervals up to 6 months postinjection/baseline, and again at 1 year. Maximal response was at 1 month at which time there was a highly significant difference in the mean scores between the groups. This difference remained statistically significant at 6 months. Four children failed to respond to the injections, four had mediocre results, and 16 had good results. While the use of BoNT-A can help to manage drooling in many children with neurological disorders, further research is needed to fully understand the range of responses. [source] Modulation of spatial attention in a child with developmental unilateral neglectDEVELOPMENTAL MEDICINE & CHILD NEUROLOGY, Issue 4 2003Veronika B Dobler MD Attentional neglect of left space is one of the most striking acquired neurological disorders of adulthood. Recent evidence indicates a link between left spatial neglect and general right-hemisphere impairments in sustained attention and alertness. Poor sustained attention and alertness is also a central feature of other disorders, particularly childhood attention-deficit-hyperactivity disorder (ADHD). Here we present the case of a 7-year-old male showing that frank neglect can be present in children with sustained attention problems without a clear aetiological event, or obvious structural brain abnormalities as indicated by a normal MRI. Experimental amelioration of the neglect through left-hand movement and externally alerting stimulation by uninformative sounds further suggest close similarities to the adult disorder. We suggest that such distortions of spatial attention may be more common in childhood than previously thought. [source] Role of mitogen-activated protein kinase cascades in P2Y receptor-mediated trophic activation of astroglial cells ,DRUG DEVELOPMENT RESEARCH, Issue 2-3 2001Joseph T. Neary Abstract The trophic actions of extracellular nucleotides and nucleosides on astroglial cells in the central nervous system may be important in development as well as injury and repair. Here we summarize recent findings on the signal transduction mechanisms and gene expression that mediate the trophic effects of extracellular ATP on astrocyte cultures, with a particular emphasis on mitogenesis. Activation of ATP/P2Y receptors leads to the stimulation of mitogen-activated protein kinase (MAPK) cascades, which play a crucial role in cellular proliferation, differentiation, and survival. Inhibition of ERK and p38, members of two distinct MAPK cascades, interferes with the ability of extracellular ATP to stimulate astrocyte proliferation, thereby indicating their importance in mitogenic signaling by P2Y receptors. Signaling from P2Y receptors to ERK involves phospholipase D and a calcium-independent protein kinase C isoform, PKC; this pathway is independent of the phosphatidylinositol-phospholipase C / calcium pathway which is also coupled to P2Y receptors. Pharmacological studies suggest that astrocytes may express an as-yet uncloned P2Y receptor that recruits a novel MEK activator in the ERK cascade. Extracellular ATP can also potentiate fibroblast growth factor (FGF)-2-induced proliferation, and studies on interactions between ATP and FGF-2 signaling pathways have revealed that although ATP does not activate cRaf-1, the first protein kinase in the ERK cascade, it can reduce cRaf-1 activation by FGF-2. As intermediate levels of Raf activity stimulate the cell cycle, the partial inhibition of FGF-induced Raf activity by ATP may contribute to the enhancing effect of ATP on FGF-2-induced astrocyte proliferation. Activation of P2Y receptors also leads to nuclear signaling, and the use of DNA arrays has shown that treatment of astrocytes with extracellular ATP results in the up- and downregulation of a number of genes; studies to determine which of these genes are regulated by MAPKs are now in progress. Elucidation of the components of MAPK pathways linked to P2Y receptors and subsequent changes in gene expression may provide targets for a new avenue of drug development aimed at the management of astrogliosis which occurs in many types of neurological disorders and neurodegeneration. Drug Dev. Res. 53:158,165, 2001. Published 2001 Wiley-Liss, Inc. [source] Aluminum induces chromosome aberrations, micronuclei, and cell cycle dysfunction in root cells of Vicia fabaENVIRONMENTAL TOXICOLOGY, Issue 2 2010Min Yi Abstract Aluminum (Al) exists naturally in air, water, and soil, and also in our diet. Al can be absorbed into the human body and accumulates in different tissues, which has been linked to the occurrence of Alzheimer's disease and various neurological disorders. By using Vicia cytogenetic tests, which are commonly used to monitor the genotoxicity of environmental pollutants, cytogenetic effects of aluminum (AlCl3) were investigated in this study. Present results showed that Al caused significant increases in the frequencies of micronuclei (MN) and anaphase chromosome aberrations in Vicia faba root tips exposed to Al over a concentration-tested range of 0.01,10 mM for 12 h. The frequency of micronucleated cells was higher in Al-treated groups at pH 4.5 than that at pH 5.8. Similarly, AlCl3 treatment caused a decrease in the number of mitotic cells in a dose- and pH-dependent manner. The number of cells in each mitotic phase changed in Al-treated samples. Mitotic indices (MI) decreased with the increases of pycnotic cells. Our results demonstrate that aluminum chloride is a clear clastogenic/genotoxic and cytotoxic agent in Vicia root cells. The V. faba cytogenetic test could be used for the genotoxicity monitoring of aluminum water contamination. © 2009 Wiley Periodicals, Inc. Environ Toxicol, 2010. [source] Gene therapy in epilepsyEPILEPSIA, Issue 1 2009Véronique Riban Summary Results from animal models suggest gene therapy is a promising new approach for the treatment of epilepsy. Several candidate genes such as neuropeptide Y and galanin have been demonstrated in preclinical studies to have a positive effect on seizure activity. For a successful gene therapy-based treatment, efficient delivery of a transgene to target neurons is also essential. To this end, advances have been made in the areas of cell transplantation and in the development of recombinant viral vectors for gene delivery. Recombinant adeno-associated viral (rAAV) vectors in particular show promise for gene therapy of neurological disorders due to their neuronal tropism, lack of toxicity, and stable persistence in neurons, which results in robust, long-term expression of the transgene. rAAV vectors have been recently used in phase I clinical trials of Parkinson's disease with an excellent safety profile. Prior to commencement of phase I trials for gene therapy of epilepsy, further preclinical studies are ongoing including evaluation of the therapeutic benefit in chronic models of epileptogenesis, as well as assessment of safety in toxicological studies. [source] Psychoses of epilepsy in Babylon: The oldest account of the disorderEPILEPSIA, Issue 9 2008Edward H. Reynolds Summary We have previously published translations of Babylonian texts on epilepsy and stroke, which we believe to be the oldest detailed accounts of these neurological disorders from the second millennium BC. We now present a short Babylonian text, which clearly describes what are today known as interictal or schizophrenia-like psychoses of epilepsy. The text includes many of the classical symptoms of the syndrome, for example, paranoid delusions, hallucinations and mood disorders, as well as religiosity and hyposexuality, which have only been crystallized in the twentieth century. The Babylonians were remarkably good observers of human disease and behavior but had little or no understanding of pathology or brain function. Although they recognized many natural causes of disease, epilepsy and behavior disorders were attributed to supernatural, usually evil forces, the forerunner of the Greek concept of the Sacred Disease. [source] Study of laryngopharyngeal pathology in Thoroughbred horses in southern CaliforniaEQUINE VETERINARY JOURNAL, Issue 9 2009S. DIAB Summary Reasons for performing study: There is increasing anecdotal evidence among horse owners, trainers and equine clinicians of a high prevalence of subepiglottic ulcers, suggested to have a negative effect on racing performance. Objectives: To provide a prevalence study and pathological characterisation of laryngopharyngeal lesions with emphasis in the subepiglottic area and, in particular, subepiglottic ulcers. Methods: The study was carried out on 91 Thoroughbred racehorses received for post mortem examination from 4 major Southern California racetracks. The most common reason for submission was catastrophic musculoskeletal injury, but others include sudden death, laminitis, colic, colitis, neurological disorders, pleuropneumonia and arytenoid chondropathy. Laryngopharyngeal specimens were collected and examined grossly; selected cases were also examined histopathologically. Results: Thirteen horses (14.3%) had at least one type of laryngopharyngeal abnormality, 7 horses (7.7%) had lesions in the subepiglottic soft tissues, including 4 subepiglottic ulcers, 2 soft palate ,kissing lesions' and one 'subepiglottic scar'. Eight horses (8.8%) had lesions elsewhere in the laryngopharynx, including mucosal ulcerations, arytenoid chondropathy, epiglottic entrapment and partial absence of arytenoid cartilage. Conclusions and potential relevance: Lesions in the subepiglottic area were among the most prevalent in this study, suggesting that an important percentage of laryngopharyngeal abnormalities may be missed during routine endoscopy of the standing horse, which often does not include the examination of subepiglottic tissues. Pathologically, subepiglottic ulcers were chronic-active with viable hyperplastic epithelial margins, suggesting that proper healing and re-epithelialisation should occur with appropriate treatment. In most cases, the lesions observed do not necessarily indicate a clinical problem and more extensive prevalence studies and correlation between abnormalities found and performance are needed to assess the clinical relevance of subepiglottic soft tissue lesions accurately. [source] Role of macrophage activation in the pathogenesis of Alzheimer's disease and human immunodeficiency virus type 1-associated dementiaEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 6 2000Smits The structure and function of neurons are changed not only during development of the central nervous system but also in certain neurological disorders, such as Alzheimer's disease and human immunodeficiency virus type 1 (HIV-1) -associated dementia. Immunological activation and altered production of neurotoxins and neurotrophins by brain macrophages are thought to play an important role in neuronal structure and function. This review describes the clinical and pathological features of both Alzheimer's disease and HIV-1-associated dementia and tries to interpret the role of the macrophage and astrocytes therein. The consequences of activation of macrophages by amyloid-, in Alzheimer's disease and HIV infection of macrophages in HIV-1-associated dementia and the similarities between these diseases will be discussed. Although the neuropathology of Alzheimer's disease and HIV-1-associated dementia differs, Alzheimer's disease is a cortical dementia and HIV-1-associated dementia is a subcortical dementia, the process of macrophage activation and the resulting pathways leading to neurotoxicity seem very similar. In both Alzheimer's disease and HIV-1-associated dementia, interaction of macrophages and astrocytes appear to play an important role. [source] Psychological assessment of malingering in psychogenic neurological disorders and non-psychogenic neurological disorders: relationship to psychopathology levelsEUROPEAN JOURNAL OF NEUROLOGY, Issue 10 2009M. Van Beilen Background and purpose:, It remains unknown whether psychological distress causes malingering in patients with psychogenic symptoms. Methods:, We studied 26 patients with psychogenic neurological disorders on psychopathology and malingering in comparison with 26 patients with various neurological conditions and 18 matched healthy controls (HC). Results:, Psychogenic patients showed the highest levels of psychological complaints and malingering, but non-psychogenic neurological patients also showed significantly more psychological distress and malingering compared with HC. Psychological distress was related to the degree of malingering, in both patient groups. Conclusion:, This data does not formally support a causal relationship between psychological distress and psychogenic neurological disorders, but suggests that a part of the psychological complaints is a general result of having an illness. The clinical implication of this study is that psychological distress is not sufficient for diagnosing functional complaints. Also, if a patient scores normal on a test for malingering, this does not mean that he or she is not suffering from psychogenic symptoms. [source] Detection and analysis of Borna disease virus in Chinese patients with neurological disordersEUROPEAN JOURNAL OF NEUROLOGY, Issue 3 2009Q. Li Background and purpose:, Borna disease virus (BDV) is a neurotropic RNA virus that is known to cause neurological disturbances in various animal species, potentially even humans. However, the association between BDV infection and human neurological disorders remains unclear. Methods:, Between August 2005 and March 2006, 65 patients with neurological disorders were enrolled into our study. The presence of BDV p24 RNA from peripheral blood mononuclear cells (PBMCs) was investigated by using nested reverse transcriptase PCR (RT-PCR) assay. Results:, Borna disease virus p24 RNA was detected from PBMCs in six patients with viral encephalitis by using nested RT-PCR assay. However, BDV p24 RNA was not detected in patients with multiple sclerosis or peripheral nerve diseases. Conclusion:, There might be possible associations between BDV infection and human viral encephalitis. [source] | ||||||||||||||||||||||||||||||||||||||||