Adherence to disease-modifying therapies (DMTs) results in the reduction of the number and severity of relapses and delays the progression of multiple sclerosis (MS). Patients with lower adherence rates experience more inpatient visits and higher MS-related medical costs. Fingolimod, the first oral DMT approved by the US Food and Drug Administration, may improve the access and compliance to MS treatment when compared to injectable DMTs.
This retrospective cohort study used pharmacy claims from Medco Health Solutions, Inc., of patients who initiated DMTs between October 2010 and February 2011. Initiation was defined as no prescription fills for the same DMT in the prior 12 months. Patients without a DMT prescription fill 12 months before the index date were considered naïve users. Compliance was measured via proportion of days covered (PDC) and medication possession ratio (MPR) for 12 months post-index. Discontinuation was defined as a ≥60-day gap of index DMT supply. Cox proportional hazard models compared time to discontinuation between cohorts.
Of 1,891 MS patients (mean age: 45.7; female: 76.4%), 13.1% initiated fingolimod, 10.7% interferon beta-1b, 20.0% intramuscular interferon beta-1a, 18.8% subcutaneous interferon beta-1a, and 37.4% glatiramer acetate. Patients initiating fingolimod had highest average PDC and MPR in both experienced (fingolimod: mean PDC=0.83, 73.7% with PDC≥0.8; mean MPR=0.92, 90.5% with MPR≥0.8) and naïve DMT users (fingolimod: mean PDC=0.80, 66.7% with PDC≥0.8; mean MPR=0.90, 87.4% with MPR≥0.8). The proportion of patients discontinuing index DMT within 12 months was significantly lower for the fingolimod cohort (naïve: 31.3%; experienced: 25.7%). Adjusted results found that patients receiving self-injected DMTs discontinued significantly sooner than fingolimod users. This association was generally stronger in experienced DMT users.
Fingolimod initiators were more compliant, less likely to discontinue treatment, and discontinued later than patients who initiated self-injected DMT.
Multiple sclerosis; Compliance; Patient adherence; Medication persistence; Discontinuation; Fingolimod
Patients with Parkinson’s disease often suffer from reduced mobility due to impaired postural control. Balance exercises form an integral part of rehabilitative therapy but the effectiveness of existing interventions is limited. Recent technological advances allow for providing enhanced visual feedback in the context of computer games, which provide an attractive alternative to conventional therapy. The objective of this randomized clinical trial is to investigate whether a training program capitalizing on virtual-reality-based visual feedback is more effective than an equally-dosed conventional training in improving standing balance performance in patients with Parkinson’s disease.
Patients with idiopathic Parkinson’s disease will participate in a five-week balance training program comprising ten treatment sessions of 60 minutes each. Participants will be randomly allocated to (1) an experimental group that will receive balance training using augmented visual feedback, or (2) a control group that will receive balance training in accordance with current physical therapy guidelines for Parkinson’s disease patients. Training sessions consist of task-specific exercises that are organized as a series of workstations. Assessments will take place before training, at six weeks, and at twelve weeks follow-up. The functional reach test will serve as the primary outcome measure supplemented by comprehensive assessments of functional balance, posturography, and electroencephalography.
We hypothesize that balance training based on visual feedback will show greater improvements on standing balance performance than conventional balance training. In addition, we expect that learning new control strategies will be visible in the co-registered posturographic recordings but also through changes in functional connectivity.
Randomized clinical trial; Parkinson’s disease; Physical therapy; Balance training; Postural control; Virtual reality; Visual feedback; Electroencephalography; Posturography; Force plate
The clinical profiles of cerebellar cavernous malformations (CCMs) with and without associated developmental venous anomalies (DVAs) are not well known. The aims of this study were to analyze the clinical and radiological characteristics of CCMs and to assess the various therapeutic strategies.
A consecutive series of 41 patients with identified CCMs were retrospectively reviewed. Of these, 11 patients (26.8%) were found to have associated DVAs. We compared the clinical profile of the two groups of patients (CCMs with and without DVAs). The CCMs with DVAs cases underwent radical resection of the CCMs, and the distal radicles of the DVAs that directly drain from the CCMs were coagulated and dissected at the length of the CCMs.
There were no statistically significant differences between the two groups with regard to age, sex, location and size of lesions, multiplicity, and surgical prognosis. The patients with CCMs with DVAs did not experience any brain swelling or hemorrhagic tendency intraoperatively. The postoperative course was uneventful for all of the 36 surgical patients with the exception of two of the patients with CCMs with associated DVAs, who suffered from serious cerebellar edema, and one of these two patients underwent an emergency suboccipital decompression craniotomy. With the exception of three patients who were lost to follow-up (mean, 22.3 months), all of the CCMs patients exhibited good long-term prognosis (modified Rankin scale values of 0–2) and no reoccurrence.
It is not rare that associated DVAs occur in CCMs. The total removal of the CCM combined with the coagulation and dissection of the distal radicles of DVA at the length of the associated CCM may result in good long-term prognosis in patients.
Cerebellum; Cavernous malformations; Developmental venous anomalies; Surgery; Prognosis
Stroke is the 4th leading cause of death and 1st leading cause of disability in Singapore. However the information on long-term post stroke outcomes for Singaporean patients was limited. This study aimed to investigate the post stroke outcomes of 5-year survival and rehospitalization due to stroke recurrence for hemorrhagic and ischemic stroke patients in Singapore. The outcomes were stratified by age, ethnic group, gender and stroke types. The causes of death and stroke recurrence were also explored in the study.
A multi-site retrospective cohort study. Patients admitted for stroke at any of the three hospitals in the National Healthcare Group of Singapore were included in the study. All study patients were followed up to 5 years. Kaplan-Meier was applied to study the time to first event, death or rehospitalization due to stroke recurrence. Cox proportional hazard model was applied to study the time to death with adjustment for stroke type, age, sex, ethnic group, and admission year. Cumulative incidence model with competing risk was applied for comparing the risks of rehospitalization due to stroke recurrence with death as the competing risk.
Totally 12,559 stroke patients were included in the study. Among them, 59.3% survived for 5 years; 18.4% were rehospitalized due to stroke recurrence in 5 years. The risk of stroke recurrence and mortality increased with age in all stroke types. Gender, ethnic group and admitting year were not significantly associated with the risk of mortality or stroke recurrence in hemorrhagic stroke. Male or Malay patient had higher risk of stroke recurrence and mortality in ischemic stroke. Hemorrhagic stroke had higher early mortality while ischemic stroke had higher recurrence and late mortality. The top cause of death among died stroke patients was cerebrovascular diseases, followed by pneumonia and ischemic heart diseases. The recurrent stroke was most likely to be the same type as the initial stroke among rehospitalized stroke patients.
Five year post-stroke survival and rehospitalization due to stroke recurrence as well as their associations with patient demographics were studied for different stroke types in Singapore. Specific preventive strategies are needed to target the high risk groups to improve their long-term outcomes after acute stroke.
Stroke; Outcomes; Recurrence; Rehospitalization; Mortality; Singapore
Stroke is the second most common cause of death and disability worldwide. It is a multi-factorial disease influenced by both environmental and genetic factors. Studies from the different ethnic regions of world have reported variable results on association of Apolioprotein E (APOE), Methylenetetrahydrofolate reductase (MTHFR), Endothelial Nitric Oxide Synthase (ENOS), Factor V Leiden (F5), Cytochrome P450 4F2 (CYP4F2), beta-fibrinogen and Phosphodiesterase 4D (PDE4D) gene in stroke. There has been substantial evidence from the European descent genetic studies showing that genetic risk of stroke varies as per specific subtypes of ischemic stroke.
This study aims to test the hypothesis that above mentioned encoding gene polymorphisms are associated with stroke and to determine whether risk varies as per specific subtypes of stroke.
The study design would be case–control study. Six hundred cases with diagnosis of stroke and 600 age and sex matched controls will be recruited. Controls will be matched in 1:1 ratio. Baseline and demographic data will be collected in standardized data collection form. Four ml of blood will be collected in EDTA coated vial and will be used for DNA isolation. Genotyping will be done by using PCR-RFLP method. For the reconfirmation of RFLP results, PCR product of each genotype in triplet for all the selected polymorphism will be sent for DNA sequencing. Data will be analyzed using conditional logistic regression to determine odds ratio associated with the above genes.
This protocol will assess the association of above mentioned gene polymorphisms with ischemic stroke in North Indian Population. This study will also helpful to determine genetic component of stroke and whether variation in genetic risk as per different subtypes of stroke.
Few studies have focused on fatigue in myasthenia gravis (MG), and fatigue in relation to the autonomic system has never been systematically explored in these patients. The study aimed to document the prevalence of MG-related fatigue in ethnic Norwegians and to examine whether MG severity is associated with symptoms of autonomic disturbance, which in turn is associated with fatigue and functional disability.
Eighty two of the 97 who fulfilled the study inclusion criteria participated in the study. Controls were 410 age- and sex-matched subjects drawn from a normative sample (n = 2136) representative of the Norwegian population. Bivariate analyses and multivariate linear regression analyses were used to assess associations between questionnaire-reported MG severity, symptoms of autonomic disturbance, fatigue (mental and physical) and functional disability.
Forty-four per cent (36/82) of patients fulfilled the criteria for fatigue compared with 22% (90/410) of controls (odds ratio 2.0; p = 0.003). Twenty-one per cent of patients (17/82) met the criteria for chronic fatigue versus 12% (48/410) of controls (odds ratio 1.96; p = 0.03). MG patients had higher total fatigue scores than controls (p < 0.001) and a high prevalence of autonomic symptoms, especially poor thermoregulation and sleep disturbance. According to multivariate analyses controlled for MG score, symptoms of autonomic disturbances were independently positively associated with fatigue (p < 0.001), and fatigue was independently negatively associated with functional level (p < 0.001).
Norwegian ethnic patients with MG have higher levels of fatigue and a higher prevalence of chronic fatigue than controls, even in patients in full remission. MG severity is highly suggestive to be associated with symptoms of autonomic disturbance, which in turn is associated with fatigue and the level of functional disability.
Myasthenia gravis; Fatigue; Autonomic nervous system; Self report; Questionnaire; Acetylcholine esterase inhibitors
In 2002, the Transverse Myelitis Consortium Working Group (TMCWG) proposed the diagnostic criteria for idiopathic acute transverse myelitis (IATM) to delimit and unify this group of patients. This study aimed to describe the conversion rate to multiple sclerosis (MS) and variables associated with conversion, and to analyze functional outcome and prognostic factors associated with functional recovery in patients who fulfilled the current TMCWG criteria for definite and possible IATM.
Eighty-seven patients diagnosed with IATM between 1989 and 2011 were retrospectively reviewed. Two patients with positive neuromyelitis optica IgG serum antibodies were excluded. Epidemiological, clinical, laboratory, magnetic resonance imaging (MRI) data and outcome of 85 patients were analyzed.
Eleven (13%) patients converted to MS after a median follow-up of 2.9 years (interquartile range 1.0-4.8). Early-age onset of symptoms was related to conversion to MS. Only 9.4% of patients with IATM were unable to walk unassisted at the end of follow-up. Urinary sphincter dysfunction (odds ratio [OR] 3.37, 95% confidence interval [CI] 1.04-10.92) and longitudinally extensive transverse myelitis (LETM) on MRI (OR 12.34, 95% CI 3.38-45.00) were associated with a poorer outcome (Rankin ≥ 2).
At least 13% of patients who fulfill the TMCWG criteria for definite and possible IATM will convert to MS. Functional recovery in IATM is poorer in patients with urinary sphincter dysfunction at admission or LETM on MRI.
Transverse myelitis; Idiopathic; Multiple sclerosis; Prognosis; Neuromyelitis optica
Silent brain infarcts are detected by neuroimaging in up to 20% of asymptomatic patients based on population studies. They are five times more frequent than stroke in general population, and increase significantly both with advancing age and hypertension. Moreover, they are independently associated with the risk of future stroke and cognitive decline.
Despite these numbers and the clinical consequences of silent brain infarcts, their prevalence in Mediterranean populations is not well known and their role as predictors of future cerebrovascular and cardiovascular events in hypertensive remains to be determined.
ISSYS (Investigating Silent Strokes in Hypertensives: a magnetic resonance imaging study) is an observational cross-sectional and longitudinal study aimed to: 1- determine the prevalence of silent cerebrovascular infarcts in a large cohort of 1000 hypertensives and to study their associated factors and 2-to study their relationship with the risk of future stroke and cognitive decline.
Cohort study in a randomly selected sample of 1000 participants, hypertensive aged 50 to 70 years old, with no history of previous stroke or dementia.
On baseline all participants will undergo a brain MRI to determine the presence of brain infarcts and other cerebrovascular lesions (brain microbleeds, white matter changes and enlarged perivascular spaces) and will be also tested to determine other than brain organ damage (heart-left ventricular hypertrophy, kidney-urine albumin to creatinine ratio, vessels-pulse wave velocity, ankle brachial index), in order to establish the contribution of other subclinical conditions to the risk of further vascular events. Several sub-studies assessing the role of 24 hour ambulatory BP monitoring and plasma or genetic biomarkers will be performed.
Follow-up will last for at least 3 years, to assess the rate of further stroke/transient ischemic attack, other cardiovascular events and cognitive decline, and their predictors.
Improving the knowledge on the frequency and determinants of these lesions in our setting might help in the future to optimize treatments or establish new preventive strategies to minimize clinical and socioeconomic consequences of stroke and cognitive decline.
Patients with carbon monoxide (CO) intoxication may develop ongoing neurological and psychiatric symptoms that ebb and flow, a condition often called delayed encephalopathy (DE). The association between morphologic changes in the brain and neuropsychological deficits in DE is poorly understood.
Magnetic resonance imaging and neuropsychological tests were conducted on 11 CO patients with DE, 11 patients without DE, and 15 age-, sex-, and education-matched healthy subjects. Differences in gray matter volume (GMV) between the subgroups were assessed and further correlated with diminished cognitive functioning.
As a group, the patients had lower regional GMV compared to controls in the following regions: basal ganglia, left claustrum, right amygdala, left hippocampus, parietal lobes, and left frontal lobe. The reduced GMV in the bilateral basal ganglia, left post-central gyrus, and left hippocampus correlated with decreased perceptual organization and processing speed function. Those CO patients characterized by DE patients had a lower GMV in the left anterior cingulate and right amygdala, as well as lower levels of cognitive function, than the non-DE patients.
Patients with CO intoxication in the chronic stage showed a worse cognitive and morphologic outcome, especially those with DE. This study provides additional evidence of gray matter structural abnormalities in the pathophysiology of DE in chronic CO intoxicated patients.
Carbon monoxide intoxication; Cognitive deficits; Delayed encephalopathy; Magnetic resonance imaging; Voxel-based morphometry
Multiple sclerosis (MS) is the most common cause of neurological disability in young adults worldwide and approximately half of those affected are in Europe. The assessment of differential incidence and prevalence across populations can reveal spatial, temporal and demographic patterns which are important for identifying genetic and environmental factors contributing to MS. However, study methodologies vary and the quality of the methods can influence the estimates. This study aimed to systematically review European studies of incidence and prevalence of MS and to provide a quantitative assessment of their methodological quality.
A comprehensive literature search was performed to obtain all original population-based studies of MS incidence and prevalence in European populations conducted and published between January 1985 and January 2011. Only peer-reviewed full-text articles published in English or French were included. All abstracts were screened for eligibility and two trained reviewers abstracted the data and graded the quality of each study using a tool specifically designed for this study.
There were 123 studies that met the inclusion criteria. The study estimates were highly heterogeneous, even within regions or countries. Quality was generally higher in the more recent studies, which also tended to use current diagnostic criteria. Prevalence and incidence estimates tended to be higher in the more recent studies and were higher in the Nordic countries and in northern regions of the British Isles. With rare exceptions, prevalence and incidence estimates were higher in women with ratios as high as 3:1. Few studies examined ethnicity. Epidemiological data at the national level was uncommon and there were marked geographical disparities in available data, with large areas of Europe unrepresented and other regions well-represented in the literature. Only 37% of the studies provided standardized estimates.
Despite the breadth of the literature on the epidemiology of MS in Europe, inter-study comparisons are hampered by the lack of standardization. Further research should focus on regions not yet studied and the evaluation of ethnic differences in MS prevalence and incidence. National-level studies using current diagnostic criteria, validated case definitions and similar age- and sex-standardization would allow better geographical comparisons.
Multiple sclerosis; Epidemiology; Europe; Incidence; Prevalence
Parkinson’s disease (PD), the second most common neurodegenerative disease, is characterized by loss of dopaminergic neurons in the substantia nigra. The clinical manifestations of PD encompass a variety of motor and non-motor symptoms. Mutations in the F-box protein 7 gene (FBXO7) have been identified to cause Parkinsonian-pyramidal syndrome, an autosomal recessive form of Parkinsonism. The F-box protein 42 gene (FBXO42), a paralog of the FBXO7 gene, is involved in the ubiquitin-proteasome system that may play a role in the pathogenesis of PD.
To determine whether the FBXO42 gene is associated with PD, we performed a systematic genetic analysis of the FBXO42 gene in 316 PD patients and 295 gender-, age-, and ethnicity-matched normal controls.
We identified a novel variant c.1407T>C (p.S469S) and three known single nucleotide variants, including rs2273311, rs12069239 and rs35196193 in the FBXO42 gene in PD patient group. None of the three known variants displayed statistically significant difference in either genotypic or allelic distributions between patient and control groups (all P > 0.05). Haplotype analysis showed that a common haplotype (G-C-G) for the three single nucleotide variants conferred a 1.69-fold increased risk for PD (P = 0.008 after Bonferroni correction, OR = 1.69, 95% CI = 1.06-2.71).
Our findings suggest that a haplotype of the FBXO42 gene might be associated with a higher susceptibility to PD.
Parkinson’s disease; FBXO42; FBXO7; Variants; Haplotype
The accumulation of the misfolded forms of cellular prion protein, i.e. prions (PrPSc), in the brain is one of the crucial characteristics of fatal neurodegenerative disorders, called transmissible spongiform encephalopathies (TSEs). Cellular prion protein is normally linked to the cell surface by the glycosylphosphatidylinositol (GPI) anchor. There is accumulating evidence that the GPI-anchorless prion protein may act as an accelerator of formation and propagation of prions. In the TSE affected human brain we have previously discovered a novel GPI-anchorless prion protein fragment, named PrP226*, which ends with the tyrosine 226. This fragment can be labeled specifically by the monoclonal antibody V5B2.
We developed a DELFIA based assay for quick and sensitive detection of the PrP226* fragment in human brain tissue homogenates. By calculating the ratio between the signals of native (N) and denatured (D) samples applied to the assay we were able to observe significant difference between 24 TSE affected brains and 10 control brains. The presence of PrP226* in brain tissue was confirmed by western blot.
Our results demonstrate that PrP226* is present in small quantities in healthy human brain, whereas in degenerated brain it accumulates in prion aggregates, proportionally to PrPSc. Samples with high D/N ratio generally comprised more proteinase K resistant PrP, while no correlation was found between the quantity of PrP226* and standard classification of Creutzfeldt-Jakob disease (CJD).
In the present study we show that the PrP226* fragment accumulates in prion aggregates and after being released from them by a denaturation procedure, could serve as a proteinase K digestion independent biomarker for human TSEs. The PrP226* assay described in this paper offers a tool to follow and study this unique anchorless PrP fragment in various parts of human brain and possibly also in other tissues and body fluids.
Transmissible spongiform encephalopathies; Creutzfeldt-Jakob disease; GSS; Prion; V5B2; Immunoassay; DELFIA; Anchorless PrP; PrP fragment; Proteinase K
Wilson’s disease (WD) is a genetic disorder which can be controlled fairly well with decupuration therapy. However, symptoms, on rare occasions, can worsen even when WD is being treated. Herein, we report a case involving unusual neurological deterioration during decupuration therapy for WD.
A 28-year-old man was diagnosed with WD 13 years prior to his clinical visit; however, his drug compliance has been poor over the years. He was treated with trientine because tremors and dysarthria have presented in recent years. However, dysarthria and dystonia developed in his limbs, which were worse on the right side and had been aggravated for several weeks despite good drug compliance. His symptoms were fluctuating. It was initially misdiagnosed as dystonia; although, it turned out to be a seizure due to cortical degeneration. These symptoms were completely resolved with antiepileptic drugs. Moreover, the cortical enhancement of bifrontal degeneration has disappeared on the MRI.
This case showed unusual epileptic neurologic deterioration due to cortical degeneration during decupuration therapy. Seizures in WD can easily be mistaken as part of dystonia. However, the fluctuating symptoms suggest a seizure.
Wilson’s disease; Seizure; Dystonia; Cortical lesion: MRI
Among the patients with established coronary artery diseases, obese patients tend to have a more favorable prognosis, which is called as obesity paradox. Interestingly, mildly obese patients who underwent coronary revascularization had a lower risk of bleeding. In this context, we have investigated the association between obesity and hemorrhagic transformation (HTf) after acute ischemic stroke.
A total of 365 patients with first-ever acute ischemic stroke were included in this study. Demographic, clinical and radiological information was collected and HTf was evaluated through follow-up T2*-weighted gradient-recalled echo MRI performed usually within 1 week after occurrence of stroke. Body mass index was calculated, and obesity was defined using the World Health Organization Western Pacific Regional Office criteria.
The HTf was identified in 59 patients (16.2%). As the severity of obesity increased, the occurrence of HTf decreased. Compared with the normal weight group and after controlling possible confounders including acute and previous treatment, stroke severity and subtype, the risk of HTf decreased significantly in the obese group (odds ratio, 0.39; 95% confidence interval, 0.17-0.87).
The better outcome for HTf seen in obese patients suggests the existence of a “bleeding-obesity paradox” in acute ischemic stroke.
Obesity; Hemorrhagic transformation; Bleeding-obesity paradox; Ischemic stroke; Body mass index
Itch is a frequent complaint reported by patients and is usually ascribed to dermatological or metabolic causes. In neurological disorders, however, it is a very unusual symptom and thus its neurological aetiology is likely to be overlooked. There are only very few reports about permanent itch related to lesions of the central nervous system. To our knowledge we report the first case of episodic itch associated with a central nervous lesion.
A 74-year-old female suffered from long-standing episodes of itch of the dermatomes C2 to C6 on the right side that was refractory to any treatment. On occurrence it propagated in a proximal to distal fashion. Between the episodes the patient was asymptomatic. MRI of the cervical spine uncovered a spinal glioma that matched the location of the symptoms. Treatment with gabapentin led to a prompt reduction of the symptoms.
Patients with intractable pruritus and dermatomal presentation ought to undergo neurological examination and spinal cord imaging. Thus, ongoing frustrating and sometimes even harmful treatment trials could be avoided.
Itch; Spine; Glioma; MRI; Gabapentin
Despite heart failure being a substantial risk factor for stroke, few studies have evaluated the predictive value of heart dysfunction for all-cause mortality in patients with acute ischemic stroke, in particular in the elderly. The aim of this study was to investigate whether impaired heart function in elderly patients can predict all-cause mortality after acute ischemic stroke or transient ischemic attack (TIA).
A prospective long-term follow-up analysis was performed on a hospital cohort consisting of n = 132 patients with mean age 73 ± 9 years, presenting with acute ischemic stroke or transient ischemic attack, without atrial fibrillation. All patients were examined by echocardiography during the hospital stay. Data about all-cause mortality were collected at the end of the follow-up period. The mean follow-up period was 56 ± 22 months.
In this cohort, 58% of patients with acute ischemic stroke or TIA had heart dysfunction. Survival analysis showed that heart dysfunction did not predict all-cause mortality in this cohort. Furthermore, in multivariate regression analysis age (HR 5.401, Cl 1.97-14.78, p < 0.01), smoking (HR 3.181, Cl 1.36-7.47, p < 0.01), myocardial infarction (HR 2.826, Cl 1.17-6.83, p < 0.05) were independent predictors of all-cause mortality.
In this population with acute ischemic stroke or TIA and without non-valvular atrial fibrillation, impaired heart function does not seem to be a significant predictor of all-cause mortality at long-term follow-up.
Echocardiography; Heart failure; Mortality; Stroke; TIA
Diabetes constitutes a risk factor for stroke that also aggravates stroke prognosis. Several prognostic models have been developed for the evaluation of neurologic status, severity, short-term functional outcome and mortality of stroke patients. IScore is a novel tool recently developed in order to predict mortality rates within 30 days and 1 year after ischemic stroke and diabetes is not included in the scoring scale of IScore. The aim of the present study was to evaluate and compare IScore validity in ischemic stroke patients with and without diabetes.
This prospective study included 312 consecutive Caucasian patients with type 2 diabetes and 222 Caucasian patients without diabetes admitted for ischemic stroke in a tertiary Greek hospital. Thirty-day and 1-year IScores were individually calculated for each patient and actual mortality was monitored at the same time intervals. IScore’s predictive ability and calibration was evaluated and compared for ischemic stroke patients with and without diabetes. The performance of IScore for predicting 30 and 1-year mortality between patients with and without diabetes was assessed by determining the calibration and discrimination of the score. The area under the receiver operating characteristic curve was used to evaluate the discriminative ability of IScore for patients with and without diabetes, whereas the calibration of IScore was assessed by the Hosmer–Lemeshow goodness-of fit statistic.
Baseline population characteristics and mortality rates did not differ significantly for both cohorts. IScore values were significantly higher for patients with diabetes at 30 days and 1 year after ischemic stroke and patients with diabetes presented more frequently with lacunar strokes. Based on ROC curves analysis IScore’s predictive ability for 30 day mortality was excellent, without statistically significant difference, for both cohorts. Predictive ability for 1 year mortality was also excellent for both groups with significantly better ability for patients with diabetes especially at high score values. Calibration of the model was good for both groups of patients.
IScore accurately predicts mortality in acute ischemic stroke Caucasian patients with and without diabetes with higher efficacy in predicting 1 year mortality in patients with diabetes especially with high scores.
IScore; Stroke; Ischemic stroke; Ischemic stroke mortality; Diabetes
Stroke is the fourth leading cause of death in the U.S. and stroke mortality rates differ substantially by ethnic group. The impact of adherence to the USDA dietary guidelines on risk for fatal stroke among different ethnic groups has not previously been examined.
A prospective cohort design was used to examine associations between adherence with dietary recommendations for fruit and vegetable intake and risk for stroke mortality among 174,888 men and women representing five ethnic groups; African American, Native Hawaiian, Japanese American, Latino, and Caucasian. Dietary intake was assessed using a mailed quantitative food frequency questionnaire. Associations were examined using Cox proportional hazards models.
There was no evidence that ethnicity modified associations between fruit and vegetable intake and stroke mortality. When data for different ethnicities were combined, a reduced risk for fatal stroke was observed among women who were adherent with the USDA dietary recommendations for vegetable intake, although this result did not reach statistical significance (RR = 0.84, 95% CI = 0.68-1.04). No associations were observed among men.
The results of this study do not provide evidence that dietary intake of fruits and vegetables differentially impacts risk for stroke mortality among different ethnic groups.
Fruits; Vegetables; Stroke mortality; Ethnicity
Among patients with relapsing-remitting multiple sclerosis, relapses are associated with increased disability and decreased quality of life. Relapses are commonly treated with corticosteroids or left untreated. We aimed to better understand patient perceptions of the adequacy of corticosteroids in resolving relapse symptoms.
We examined self-reported data from 4482 participants in the North American Research Committee on Multiple Sclerosis (NARCOMS) Registry regarding evaluation, treatment, and recovery from relapses. Pearson’s chi-square test was used to analyze categorical variables, while logistic regression was used to assess factors associated with patients’ perceptions.
Forty percent (1775/4482) of respondents were simply observed for disease worsening, whereas 25% (1133/4482) were treated with intravenous methylprednisolone (IVMP) and 20% (923/4482) with oral corticosteroids; additional treatments included adrenocorticotropic hormone, plasmapheresis, intravenous immunoglobulin, and others. Among patients who responded to questions about their most recent relapse, 32% (363/1123) of IVMP-treated and 34% (301/895) of oral corticosteroid-treated patients indicated their symptoms were worse one month after treatment than pre-relapse, as did 39% (612/1574) of observation-only patients; 30% (335/1122) of IVMP-treated patients indicated their treatment made relapse symptoms worse (13% [145/1122]) or had no effect (17% [190/1122]), as did 38% (340/894) of oral corticosteroid-treated patients (worse, 13% [116/894]; no effect, 25% [224/894]) and 76% (1162/1514) of observation-only patients (worse, 17% [264/1514]; no change, 59% [898/1514]).
Overall, patients with relapsing multiple sclerosis who receive treatment report better outcomes than those who are simply observed. However, a sizeable percentage of patients feel that their symptoms following corticosteroid treatment are worse than pre-relapse symptoms and that treatment had no effect or worsened symptoms. Patient perceptions of relapse treatment deserve more attention, and more effective treatment options are needed.
Multiple sclerosis; Relapses; Corticosteroids; Methylprednisolone; Prednisone
OnabotulinumtoxinA has demonstrated significant benefit in adult focal spasticity. This study reviews the injection patterns (i.e., muscle distribution, dosing) of onabotulinumtoxinA for treatment of adult spasticity, as reported in published studies.
A systematic review of clinical trials and observational studies published between 1990 and 2011 reporting data on muscles injected with onabotulinumtoxinA in adult patients treated for any cause of spasticity.
28 randomized, 5 nonrandomized, and 37 single-arm studies evaluating 2,163 adult patients were included. The most frequently injected upper-limb muscles were flexor carpi radialis (64.0% of patients), flexor carpi ulnaris (59.1%), flexor digitorum superficialis (57.2%), flexor digitorum profundus (52.5%), and biceps brachii (38.8%). The most frequently injected lower-limb muscles were the gastrocnemius (66.1% of patients), soleus (54.7%), and tibialis posterior (50.5%). The overall dose range reported was 5–200 U for upper-limb muscles and 10–400 U for lower-limb muscles.
The reviewed evidence indicates that the muscles most frequently injected with onabotulinumtoxinA in adults with spasticity were the wrist, elbow, and finger flexors and the ankle plantar flexors. OnabotulinumtoxinA was injected over a broad range of doses per muscle among the studies included in this review, but individual practitioners should be mindful of local regulatory approvals and regulations.
Botulinum toxin; OnabotulinumtoxinA; Spasticity; Muscles; Injection patterns
Multiple sclerosis is a chronic, incurable, demyelinating disease that requires long-term treatment. Rates of non-adherence to prescribed therapy of up to 50% have been reported for chronic diseases. Strategies to improve treatment adherence are therefore of the utmost importance. This study will evaluate the effect of using electronic and paper diaries on treatment adherence to interferon beta-1b in patients with a first clinical isolated syndrome (CIS) or relapsing-remitting multiple sclerosis (RRMS). Here we report on the study design and results of baseline assessments.
Patients were recruited into a prospective national multicenter cohort study for an observational period of 2 years. At the start of the study, patients opted to use a digital (DiD) or paper diary (PD) to document self-administered injections of interferon beta-1b. Adherence to treatment will be assessed on the dropout rate at the end of the observation period and on the regularity of injections every other day at 6-month intervals. Patient-related health outcomes will also be evaluated.
700 patients with a mean age of 38.3 (SD 10.3) years and a mean duration of disease since diagnosis of 3.6 (SD 5.9) years were enrolled. 383 patients opted for the digital diary, 192 of which included an injection reminder. Significantly more male than female patients opted for the DiD. Only gender was identified as a factor influencing the decision for DiD or PD. Based on rating scales, a significantly higher proportion of women had depressive comorbidities at baseline.
Demographic characteristics of the two cohorts were similar at baseline. More women chose a paper diary, and more had depression at baseline. These imbalances will be addressed in the analysis of the study as possible confounders influencing long-term treatment adherence in the digital and paper diary cohorts.
ClinicalTrials.gov Identifier: NCT00902135.
Adherence; Interferon beta-1b; Non-interventional study; Electronic diary; Multiple sclerosis; Immunomodulation
Professionals in Japan tend to regard the individual contexts of persons with spinal cord injury (SCI) as the cause of their passive participation in self-care activities or self-management. However, the meaning of self-care involves variables that interrelate with sociocultural factors. Thus, it is necessary to uncover its meaning in the perceptions of persons with cervical spinal cord injury (CSCI) in order not only to implement better rehabilitation but also to understand the sociocultural constraints that determine the injured person’s attitudes to self-care and long-term health outcomes.
Semi-structured interviews with 29 CSCI participants from fourteen municipalities of Osaka, Hyogo, and Ehime prefectures were conducted. Participants contributed diverse perspectives on rehabilitation, lay-professional and family relationships, health promotion, and body conceptions. Interviews were recorded, transcribed and analyzed using the grounded theory approach to inter-relate categories and to develop theoretical constructions.
Four main themes emerged from the data: rehabilitation for independence in ADLs; detachment from the body and self; embodiment; and self-management. From the participants’ point of view, rehabilitation programs in Japan aim at improving body functions for ADL performance, but provide little health education. These rehabilitation values might hinder some participants from developing self-esteem for their bodies. Moreover, socially-shaped family caregivers’ active engagement in the participants’ self-care allowed many participants to entirely rely on them for care. Through embodiment, participants found that self-care was not merely a means of independence in ADLs but also of self-management to enhance health and well-being, requiring collaborative relationships with caregivers.
Personal factors such as low motivation for self-care might be in part a reflection of social expectations of dependence for persons with CSCI. However, the shift in the meaning of self-care from ADLs to self-management implies more active participation in health care needs, shaped through social exchanges. Not only personal factors but also sociocultural factors influence the injured person’s valuation of self-care. There is a need for further research to better understand sociocultural influences on illness behaviors among persons with CSCI, so that clinical and community practice can develop accordingly.
Self-care; Self-management; Rehabilitation; Illness behavior; Health promotion; Spinal cord injury
Limited data are available on the outcome of antiepileptic drug treatment response in patients of Chinese Han ethnicity with newly diagnosed epilepsy. We sought to explore the prognosis with antiepileptic drug treatment and to identify the predictors of poor drug control of seizures in these patients.
For at least 2 years, we prospectively followed up a cohort of patients with newly diagnosed epilepsy and analyzed the response to each antiepileptic drug. Cumulative risk for seizure relapse after initial remission achieved was estimated. The patients were divided into two groups (poor and good control) and compared for clinical characteristics.
A total of 180 patients were included. Early remission was reached in 125 (69.44%) patients, 19 (10.56%) patients entered late remission, while 36 (20%) patients failed to achieve remission. The relapse rates were 19.5% at 2 years and 31.9% at 3 years of the follow-up. The response rates of the first throughout the fourth treatment regimens were 60.0%, 16.1%, 2.8%, and 0.6%, respectively. Multiple seizure types and changes in seizure type during treatment were significantly (p = 0.013 and 0.047, respectively) associated with a poor control.
The prognosis of the majority of patients with newly diagnosed epilepsy is good and the clinical pattern of epilepsy during treatment is complex. The chances of seizure control declines with each subsequent treatment regimen. The prognosis for patients with multiple seizure types and seizure type changes during treatment is unfavorable.
Antiepileptic drugs; Clinical pattern; Drug-resistant epilepsy; Prognosis; Risk factors
Only a few case reports and case series dealing with oral and dental health care are available in literature until now. The aim of the present pilot study was to determine the status of dental health in comparison to matched controls and to heighten the neurologists’ and dentists’ awareness of the oral aspects of the disease.
42 Huntington’s disease (HD) participants were scored according to the Unified Huntington’s Disease Rating Scale. The dental status was assessed by using the well established score for decayed, missing, and filled teeth (DMFT) and the dental plaque score (Silness-Loe plaque index).
Compared to controls HD participants showed significantly more decayed teeth and more plaques in both plaque indices. A higher motor impairment and a lower functional status of the patients lead to a worsening in dental status.
Possible reasons for our findings are discussed. Apart from local oral complications general complications may also occur. Thus, as a consequence, we would encourage patients, caregivers, neurologists, and the dentists to ensure regular preventive dental examinations and dental treatments of individuals with Huntington’s disease even in the premanifest stage of this disease.
Ropinirole prolonged release (RPR) is a once-daily formulation. However, there may be individual pharmacokinetic differences so that multiple dosing may be preferred in some individuals. This study compares once-daily and twice-daily RPR in patients with Parkinson’s disease.
This study was an open-label crossover study. We enrolled Parkinson’s disease patients on dopamine agonist therapy with unsatisfactory control such as motor fluctuation, dyskinesia and sleep-related problems. Agonists were switched into equivalent dose of RPR. Subjects were consecutively enrolled into either once-daily first or twice-daily first groups, and received the same amount of RPR in a single and two divided dosing for 8 weeks respectively in a crossover manner without a washout period.
The primary outcome was a questionnaire of the preference completed by patients in the last visit. The secondary outcome measures included the Unified Parkinson’s Disease Rating Scale part 3 (mUPDRS), Hoehn and Yahr stage (H&Y); sleep questionnaire including overall quality of sleep, nocturnal off symptoms and early morning symptoms; Epworth Sleep Scale (ESS); compliances and patient global impression (PGI).
A total of 82 patients were enrolled and 61 completed the study. 31 patients preferred twice-daily regimen, 17 preferred the once-daily regimen, and 13 had no preference. Their mean mUPDRS, H&Y, ESS, sleep quality, compliance and adverse events were not statistically different in both regimens. PGI-improvement on wearing off defined was better in twice-daily dosing regimen.
RPR is a once-daily formulation, but multiple dosing was preferred in many patients. Multiple dosing of RPR might be a therapeutic option if once-daily dosing is unsatisfactory.
This study is registered with ClinicalTrials.gov, number
Parkinson’s disease; Motor control; Movement disorders; Dopamine agonist