Recently, plasma miRNAs have been reported as biomarkers for various diseases. However, the knowledge on the association of plasma miRNAs with ischemic stroke is still lacking. In this study, we investigated whether plasma concentrations of miR-30a, miR-126 and let-7b may be biomarkers for ischemic stroke in humans.
One hundred ninety seven patients with ischemic stroke were recruited and their blood samples were collected at 24 h, 1 week, 4 weeks, 24 weeks and 48 weeks after symptoms onset, and fifty healthy volunteers were selected as control. Levels of miRNA were quantified by quantitative real-time PCR. Relative expression level of miRNA was calculated using 2-ΔΔct method. The ability to distinguish the ischemic stroke group from control group was characterized by receiver operating characteristic (ROC) curve, and the area under ROC curve (AUC) was calculated.
Circulating miR-30a and miR-126 levels were markedly down-regulated in all patients with ischemic stroke until 24 weeks. However, circulating let-7b was lower in patients with large-vessel atherosclerosis than healthy volunteers, whereas circulating let-7b had higher level in patients with other kinds of ischemic stroke until 24 weeks. Among all patients, circulating miRNAs levels returned to normal 48 weeks after symptom onset. Receiver operating characteristic (ROC) curve analysis showed that the areas under the curve (AUC) of plasma miR-30a were 0.91, 0.91, 0.92 and 0.93, the miR-126 were 0.92, 0.94, 0.93 and 0.92, and let-7b were 0.93, 0.92, 0.92 and 0.91 at 24 h, 1 w, 4 w and 24 w, respectively.
These data suggest that miR-30a, miR-126 and let-7b might be useful biomarkers for ischemic stroke in humans.
Circulating miRNA; Biomarker; Stroke
Multiple sclerosis (MS) has a major impact on the physical, psychological and social life of patients and their families. The aim of this study was to evaluate the different perceptions of patients and caregivers about management of MS, particularly about the same items, to gather information to ameliorate the care of patients.
We evaluated what MS patients and caregivers perceive as unmet needs and compared patients’ opinions with caregivers’ opinions using a multidimensional questionnaire. The questionnaire was specifically designed for the study, taking into account different aspects of the global care perceived by patients and care givers, such as information about MS, medical treatment and rehabilitation, patients’ relationships with medical staff and their psychological and social life.
We administered the questionnaire to 497 patients and 206 caregivers. Results showed that the majority of participants were satisfied with medical staff but expressed a desire that staff be more forthcoming with information about MS. As for medical treatment concerns, more patients found there to be useful a multidisciplinary approach than caregivers did. Both required psychological support for patients but patients felt a greater need for it at the time of diagnosis, whereas caregivers felt it was required post-diagnosis. Both reported significant strains on patient relationships at work but no effect on other social interactions.
A better understanding of MS patient needs, starting from the point of view of patients and caregivers, could have a great impact on quality of life and on management of the disease.
Subarachnoid hemorrhage (SAH) is a devastating cause of stroke, occurring in relatively young people. It has been suggested that some immune-mediated diseases may be associated with an increased risk of SAH.
We analysed a database of linked statistical records of hospital admissions and death certificates for the whole of England (1999–2011). Rate ratios for SAH were determined, comparing immune-mediated disease cohorts with comparison cohorts.
There were significantly elevated risks of SAH after hospital admission for the following individual immune-mediated diseases: Addison’s disease, ankylosing spondylitis, autoimmune haemolytic anaemia, Crohn’s disease, diabetes mellitus, idiopathic thrombocytopenia purpura, myxoedema, pernicious anaemia, primary biliary cirrhosis, psoriasis, rheumatoid arthritis, scleroderma, Sjogren’s syndrome, SLE and thyrotoxicosis. Elevated risks that were greater than 2-fold were found for Addison’s disease (rate ratio (RR) = 2.01, 95% confidence interval 1.3-2.97), idiopathic thrombocytopenia purpura (RR = 2.42, 1.86-3.11), primary biliary cirrhosis (RR = 2.21, 1.43-3.16) and SLE (RR = 3.76, 3.08-4.55).
Our findings strongly support the suggestion that patients with some immune-mediated diseases have an increased risk of SAH. Further studies of the mechanisms behind this association are warranted.
Modern medicine has increased the survival rate for stroke patients; however, the patient’s psychosocial adaptation after stroke onset may be related to the clinical outcomes. This study aimed to investigate patients’ acceptance of disability (AOD) and its predictors in stroke patients.
This cross-sectional study used a purposive sampling method to recruit 175 stroke patients from a hospital in southern Taiwan. A structured questionnaire gathered data on respondent demographics and disease characteristics, and included the Chinese version of the AOD Scale-Revised. Factors associated with AOD were examined by a multiple linear regression analysis.
The mean AOD score was 71.72, which indicated a lower level of disease acceptance (range, 32-128). Our findings showed that patients who reported no religious beliefs, shorter disease duration, recurrent stroke episodes, and poorer physical functioning also reported lower levels of disability acceptance. These factors accounted for 38.2% of the variance in AOD among participants.
The findings are beneficial to healthcare providers by identifying those stroke patients with predisposition of having lower disability acceptance, which could then facilitate the provision of appropriate rehabilitation interventions within six months after the diagnosis of stroke to support their adaptation process.
Acceptance of disability; Stroke; Taiwan
Pediatric multiple sclerosis (MS) is a rare disorder with significant consequences. Quantitative MRI measurements may provide significant insights, however multicenter collaborative studies are needed given the small numbers of subjects. The goal of this study is to demonstrate feasibility and evaluate lesion volume (LV) characteristics in a multicenter cohort of children with MS.
A common MRI-scanning guideline was implemented at six member sites of the U.S. Network of Pediatric MS Centers of Excellence. We included in this study the first ten scans performed at each site on patients meeting the following inclusion criteria: pediatric RRMS within 3 years of disease onset, examination within 1 month of MRI and no steroids 1 month prior to MRI. We quantified T2 number, T2-LV and individual lesion size in a total of 53 MRIs passing quality control procedures and assessed gadolinium-enhancing lesion number and LV in 55 scans. We studied MRI measures according to demographic features including age, race, ethnicity and disability scores, controlling for disease duration and treatment duration using negative binomial regression and linear regression.
The mean number of T2 lesions was 24.30 ± 19.68 (range:1–113) and mean gadolinium-enhancing lesion count was 1.85 ± 5.84, (range:0–32). Individual lesion size ranged from 14.31 to 55750.60 mm3. Non-white subjects had higher T2–LV (unadjusted pT2-LV = 0.028; adjusted pT2-LV = 0.044), and maximal individual T2-LV (unadjusted pMax = 0.007; adjusted pMax = 0.011) than white patients. We also found a trend toward larger mean lesion size in males than females (p = 0.07).
Assessment of MRI lesion LV characteristics is feasible in a multicenter cohort of children with MS.
Mucopolysaccharidosis type III (MPS III) is an autosomal recessive disorder caused by deficiency of a specific enzyme leading to heparan sulfate (HS) accumulation within cells and to eventual progressive cerebral and systemic organ abnormalities. Different enzyme deficiencies comprise the MPS III subcategories (A, B, C, D). Since neuropathological manifestations are common to all MPS III types, determining blood-brain barrier (BBB) condition may be critical to understand potential additional disease mechanisms.
We investigated BBB integrity in various brain structures of post-mortem tissues from an eleven year old Caucasian female with MPS III A and from a twenty four year old Caucasian female with MPS III D. Control tissues were obtained post-mortem from three Caucasians without neurological deficits: a twelve year old male, a twenty four year old female, and a twenty seven year old female. BBB capillary ultrastructure (electron microscopy) and capillary functional integrity (IgG leakage, tight junction proteins, and lysosomal accumulation within endothelium) were examined.
Compromised BBB integrity was found in both MPS III cases. Major study findings were: (1) capillary endothelial and pericyte cell damage; (2) mucopolysaccharide bodies in a majority of endothelial cells and pericytes rupturing cell membranes; (3) severe extracellular edema; (4) IgG microvascular leakage and reductions of occludin and claudin-5 with variations between MPS III types; (5) extensive lysosomal accumulation in capillary endothelium.
These new findings of BBB structural and functional impairment, although from only two cases, MPS III A and III D, may have implications for disease pathogenesis and should be considered in treatment development for MPS III.
Mucopolysaccharidosis type III; Patients; Blood-brain barrier; Endothelial cells; Pericytes; Lysosomal accumulation
Cerebral vasculopathy have been described in Fabry disease, in which altered cerebral blood flow, vascular remodelling or impairment of endothelial function could be involved. Our study aims to evaluate these three possibilities in a group of Fabry patients, and compare it to healthy controls.
Cerebral hemodynamics, vascular remodelling and systemic endothelial function were investigated in 10 Fabry patients and compared to data from 17 healthy controls. Transcranial Doppler was used to study blood flow velocity of intracranial arteries and cerebral vasomotor reactivity. For the study of vascular remodelling and endothelial function, intima-media thickness of common carotid arteries, flow-mediated dilation in brachial artery and serum levels of soluble VCAM-1, TNF-α, high-sensitive CRP and IL-6 were measured. Differences between groups were evaluated using appropriate tests.
No relevant differences were observed in cerebral hemodynamic parameters, intima-media thickness or flow-mediated dilation. There was a trend for low serum levels of IL-6 and high serum levels of TNF-α and high-sensitive CRP in Fabry patients; plasma concentrations of soluble VCAM-1 were significantly higher in Fabry disease patients than in healthy volunteers (p = 0.02).
In our sample, we did not find relevant alterations of cerebral hemodynamics in Fabry disease patients. Increased levels of plasmatic endothelial biomarkers seem to be the most important feature indicative of possible vascular dysfunction in Fabry disease patients.
Fabry disease; Hemodynamics; Chemokines; Endothelium
Leptin and adipocyte-fatty acid binding protein (A-FABP) are produced by white adipose tissue and may play a role in chronic inflammation in Multiple Sclerosis (MS). To assess leptin and A-FABP in relapsing and progressive forms of MS.
Adipokine levels were measured in untreated adult relapsing-remitting MS (RRMS), secondary progressive MS (SPMS), primary progressive MS (PPMS) and Healthy control (HC). Pediatric-onset MS (POMS) and pediatric healthy controls (PHC) were also assessed. Leptin and A-FABP levels were measured in serum by ELISA. Groups were compared using linear mixed-effects model.
Excluding two patients with Body Mass Index (BMI) > 50, a significant difference in leptin level was found between RRMS and HC controlling for age (p = 0.007), SPMS and HC controlling for age alone (p = 0.002), or age and BMI (p = 0.007). A-FABP levels were higher in SPMS than HC (p = 0.007), controlling for age and BMI. Differences in A-FABP levels between POMS and PHC was observed after controlling for age (p = 0.019), but not when BMI was added to the model (p = 0.081).
Leptin and A-FABP levels are highest in SPMS compared to HC, suggesting a role in pathogenesis of this disease subtype. A-FABP levels are increased in POMS patients and may play a role in the early stages of disease.
41. multiple sclerosis; 132. Autoimmune disease; 175. Neuroendocrinology
Vertebral artery origin (VAO) stenosis is occasionally observed in patients who have acute ischemic stroke. We investigated the long-term outcomes and clinical significance of VAO stenosis in patients with acute ischemic stroke.
We performed a prospective observational study using a single stroke center registry to investigate the risk of recurrent stroke and vascular outcomes in patients with acute ischemic stroke and VAO stenosis. To relate the clinical significance of VAO stenosis to the vascular territory of the index stroke, patients were classified into an asymptomatic VAO stenosis group and a symptomatic VAO stenosis group.
Of the 774 patients who had acute ischemic stroke, 149 (19.3%) of them had more than 50% stenosis of the VAO. During 309 patient-years of follow-up (mean, 2.3 years), there were 7 ischemic strokes, 6 hemorrhagic strokes, and 2 unknown strokes. The annual event rates were 0.97% for posterior circulation ischemic stroke, 4.86% for all stroke, and 6.80% for the composite cardiovascular outcome. The annual event rate for ischemic stroke in the posterior circulation was significantly higher in patients who had symptomatic VAO stenosis than in patients who had asymptomatic stenosis (1.88% vs. 0%, p = 0.046). In a multivariate analysis, the hazard ratio, per one point increase of the Essen Stroke Risk Score (ESRS) for the composite cardiovascular outcome, was 1.46 (95% CI, 1.02-2.08, p = 0.036).
Long-term outcomes of more than 50% stenosis of the VAO in patients with acute ischemic stroke were generally favorable. Additionally, ESRS was a predictor for the composite cardiovascular outcome. Asymptomatic VAO stenosis may not be a specific risk factor for recurrent ischemic stroke in the posterior circulation. However, VAO stenosis may require more clinical attention as a potential source of recurrent stroke when VAO stenosis is observed in patients who have concurrent ischemic stroke in the posterior circulation.
Sturge-Weber syndrome is a congenital neurocutaneous disorder characterized by facial port-wine stain, leptomeningeal angioma, and neurological disorders. Sturge-Weber syndrome can coexist with other disorders in a few patients; however, muscular abnormalities have not been reported in patients with Sturge-Weber syndrome.
A Chinese girl presented with extensive port-wine stains, congenital bilateral glaucoma, and leptomeningeal angiomatosis. The neurocutaneous symptoms were consistent with the diagnostic criteria of Sturge-Weber syndrome. Meanwhile, episodes of rhabdomyolysis were supported by the recurrent symptoms as follows: exercise intolerance, hyperCKmia, elevated serum myoglobin, and renal failure. Myopathological features and high level of blood long-chain acyl-carnitine indicated that episodes of rhabdomyolysis might be caused by lipid metabolic myopathy. Causative mutations were not found in the CPT2, ACADVL, and GNAQ gene.
We report the first case that Sturge-Weber syndrome coexists with episodes of rhabdomyolysis associated with lipid metabolic myopathy.
Sturge-Weber syndrome; Rhabdomyolysis; Port-wine stains; Lipid metabolic myopathy
Infections are the leading cause of death in the acute phase following spinal cord injury and qualify as independent risk factor for poor neurological outcome (“disease modifying factor”). The enhanced susceptibility for infections is not stringently explained by the increased risk of aspiration in tetraplegic patients, neurogenic bladder dysfunction, or by high-dose methylprednisolone treatment. Experimental and clinical pilot data suggest that spinal cord injury disrupts the balanced interplay between the central nervous system and the immune system. The primary hypothesis is that the Spinal Cord Injury-induced Immune Depression Syndrome (SCI-IDS) is 'neurogenic’ including deactivation of adaptive and innate immunity with decreased HLA-DR expression on monocytes as a key surrogate parameter. Secondary hypotheses are that the Immune Depression Syndrome is i) injury level- and ii) severity-dependent, iii) triggers transient lymphopenia, and iv) causes qualitative functional leukocyte deficits, which may endure the post-acute phase after spinal cord injury.
SCIentinel is a prospective, international, multicenter study aiming to recruit about 118 patients with acute spinal cord injury or control patients with acute vertebral fracture without neurological deficits scheduled for spinal surgery. The assessment points are: i) <31 hours, ii) 31–55 hours, iii) 7 days, iv) 14 days, and v) 10 weeks post-trauma. Assessment includes infections, concomitant injury, medication and neurological classification using American Spinal Injury Association impairment scale (AIS) and neurological level. Laboratory analyses comprise haematological profiling, immunophenotyping, including HLA-DR expression on monocytes, cytokines and gene expression of immune modulators. We provide an administrative interim analysis of the recruitment schedule of the trial.
The objectives are to characterize the dysfunction of the innate and adaptive immune system after spinal cord injury and to explore its proposed 'neurogenic’ origin by analyzing its correlation with lesion height and severity. The trial protocol considers difficulties of enrolment in an acute setting, and loss to follow up. The administrative interim analysis confirmed the feasibility of the protocol. Better understanding of the SCI-IDS is crucial to reduce co-morbidities and thereby to attenuate the impact of disease modifying factors to protect neurological “outcome at risk”. This putatively results in improved spinal cord injury medical care.
DRKS-ID: DRKS00000122 (German Clinical Trials Registry)
Spinal cord injury; Immune paralysis; Lesion height dependency; High-dose methylprednisolone treatment; Infections
A large number of longitudinal studies of population-based ageing cohorts are in progress internationally, but the insights from these studies into the risk and protective factors for cognitive ageing and conditions like mild cognitive impairment and dementia have been inconsistent. Some of the problems confounding this research can be reduced by harmonising and pooling data across studies. COSMIC (Cohort Studies of Memory in an International Consortium) aims to harmonise data from international cohort studies of cognitive ageing, in order to better understand the determinants of cognitive ageing and neurocognitive disorders.
Longitudinal studies of cognitive ageing and dementia with at least 500 individuals aged 60 years or over are eligible and invited to be members of COSMIC. There are currently 17 member studies, from regions that include Asia, Australia, Europe, and North America. A Research Steering Committee has been established, two meetings of study leaders held, and a website developed. The initial attempts at harmonising key variables like neuropsychological test scores are in progress.
The challenges of international consortia like COSMIC include efficient communication among members, extended use of resources, and data harmonisation. Successful harmonisation will facilitate projects investigating rates of cognitive decline, risk and protective factors for mild cognitive impairment, and biomarkers of mild cognitive impairment and dementia. Extended implications of COSMIC could include standardised ways of collecting and reporting data, and a rich cognitive ageing database being made available to other researchers. COSMIC could potentially transform our understanding of the epidemiology of cognitive ageing, and have a world-wide impact on promoting successful ageing.
Cohort studies; Cognitive ageing; Data harmonisation; Dementia; International consortium; Mild cognitive impairment
A visual pursuit response is reportedly observed in ~20-30% of subjects in vegetative state (VS/UWS) and predicts better outcome; it is a key marker of evolution into the minimally conscious state (MCS). The probability of observing a positive response, however, has proven variable during the day, with comparable timing of the minima and maxima in VS/UWS and MCS. We verified if measures of sympathetic/parasympathetic balance are possible independent variables on which the occurrence of a pursuit response could depend and be predicted.
Fourteen subjects in VS/UWS and sixteen in MCS for more than one year were studied. A mirror was used to test the pursuit response for a total 231 useful trials. Non-invasive measures of the sympathetic/parasympathetic functional state (Heart rate variability descriptors nuLF and peakLF) used in the study of responsiveness in VS/UWS and MCS subjects were recorded and processed by descriptive statistics and advanced Support Vector Machine (SVM).
A pursuit response was observed in 33% and 78.2% of subjects in VS or MCS, respectively. Incidence was higher at HRV nuLF values in the 20–60 range and peakLF values at 0.06-0.12 Hz (76.6%) and at nuLF values in the 10–60 range and peakLF values at 0.05-0.10 Hz (80.7%) in the VS and MCS, respectively. The SVM generated model confirmed the results in the training leave one out and 10 fold cross validation tests (81% and 81.4%).
The pursuit response incidence depends to a relevant extent on the sympathetic/parasympathetic balance and autonomic functional state. Extensive monitoring appears advisable.
Disorder of consciousness; Visual pursuit response; Vegetative state; Minimally conscious state; Central autonomic system; Heart rate variability; Support vector machine
Bone marrow-derived endothelial stem cells participate in vascular repairs. Numbers of circulating endothelial progenitor cells (cEPCs) are associated with atherosclerosis. Fibrinogen plays a key role in atherosclerosis. Objective was to assess if cEPC counts were associated with atherosclerotic intracranial artery stenosis (IAS).
Three hundred subjects (108 patients with stroke and IAS (IAS), 120 control patients with stroke without IAS (CP), and 72 healthy controls (HC)) were retrospectively analyzed. cEPCs were identified and counted by flow cytometry using CD34, CD133 and KDR. Plasma fibrinogen was measured by immunoturbidimetry. cEPC counts were compared between the three groups.
cEPC numbers were significantly higher in IAS (0.059 ± 0.031%) than in CP (0.026 ± 0.012%) (P < 0.001) and HC (0.021 ± 0.011%) (P < 0.001), but without difference between CP and HC (P = 0.401). Multiple logistic regression analysis showed that cEPC levels (OR 3.31, 95%CI 1.26-8.87, P = 0.025; IAS vs. CP) were independent markers of IAS after adjustment for hypertension, diabetes and smoking. No significant correlation between cEPC counts and plasma fibrinogen levels was observed (P > 0.05).
cEPC numbers were associated with degrees of IAS. This measurement may be useful for non-invasive evaluation of atherosclerotic IAS.
Intracranial artery stenosis; Atherosclerosis; Circulating endothelial progenitor cells; Fibrinogen
The Stroke burden is increasing in many populations where health institutions may experience more patients. We wanted to examine whether incidence rates and absolute number of hospitalized stroke patients remained stable in Denmark during a 13 years period where exposure to major stroke risk factors decreased, changes in stroke treatment was implemented, and the age of the population increased.
The Danish National Patient Register was used to identify all subjects 25 years of age or above admitted with a first time stroke in Denmark from 1997–2009. Incidence rates (IRs) and age-adjusted Poisson regression analyses were used to examine trends in age-, gender- and stroke subtype (ischaemic or unspecified).
During the 13-year observation period there were 53.5 million person-years at risk (PY) and a total of 84,626 male and 84,705 female stroke patients were admitted to Danish hospitals. The IRs of hospitalized strokes per 1000 PY was 3.21 (95% confidence interval [CI] 3.16-3.27) in 1997, 3.85 (95% CI 3.79-3.91) in 2003 and 3.22 (95% CI 3.16-3.28) in 2009, respectively.
Incidence rate ratios of hospitalized stroke events adjusted for age in the period 2007–2009 compared to 1997–2000 were 0.89 (95% CI 0.87- 0.91) for men and 0.92 (95% CI 0.90-0.94) for women.
The incidence of hospitalized unspecified strokes decreased from 1997 to 2009 whereas there was a steep rise in incidence for hospitalization with specified ischemic stroke during this period.
This study found a constant rate of stroke hospitalization in Denmark from 1997–2009. The overall rate of hospitalized strokes adjusted for age decreased during this period.
Stroke; Temporal trends; Epidemiology
Primary intraosseous cavernous hemangioma is a rare bony tumor. To date, only 9 cases of multiple lesions and 2 cases with a dural tail sign have been reported.
Here, we present a case of multiple cavernous hemangiomas of the skull with dural tail sign in a 24-year-old man. No abnormalities were observed in the right orbit by craniography, but frontal bone destruction was unintentionally discovered. Computed tomography and magnetic resonance imaging demonstrated multiple intraosseous lesions that destroyed the surrounding bone and intracranial extension. Total resection of the two lesions and cranioplasty were performed. Histological examination confirmed the lesions as a cavernous hemangioma.
Cavernous hemangioma is a rare bony tumor that should be considered in the differential diagnosis of skull tumors. Resection of all lesions should be performed on patients with multiple cavernous hemangiomas, and these patients should have regular follow-up examinations. Based on this case, and our literature review, we found that outcomes are usually very good.
Cavernous hemangiomas; Skull; Orbit
The Observational Skills Assessment Score (OSAS) measures amount and quality of use of the affected hand in children with unilateral Cerebral Palsy (CP) in bimanual activities and could therefore be a valuable addition to existing assessment tools. The OSAS consists of tasks that are age appropriate and require use of the affected hand.
To measure the agreement and reliability of the OSAS a convenience sample of two groups of 16 children with unilateral spastic CP (2.5-6 and 12–16 years old), performed age specific bimanual tasks in 2 measurement sessions. Three experienced raters took part in testing and 8 in scoring. Intra class correlation (ICC) values for intra- and inter-rater reliability, and the mean and standard deviation of the differences between measurements were calculated. For test-retest reliability beside ICC scores, Smallest Detectable Differences (SDDs) were calculated in 16 older and 10 younger children.
Generally, there seems to be good agreement between repeated measurements of the OSAS, as indicated by the small SDDs on most scales for quality of movement, compared to the range of their scales. This indicates potentially good sensitivity to change if used for patient evaluation purposes. The exceptions were the ‘quality of reach’ score for all tasks, and all quality scores for the stacking blocks task for the young children. As used in the present study, the OSAS has good discriminative capacity within patient populations as indicated by the high ICCs for most quality scores. Measuring the amount of use does not seem to be useful for either discrimination or evaluation.
In general, the OSAS seems to be a reliable tool for assessing the quality of use of the affected hand in bimanual activities in younger and older children with unilateral CP. Some modifications may improve its usefulness and efficiency.
Cerebral palsy; Upper limb; Bimanual performance; Outcome assessment; Reliability
Data on encephalitis in Thailand have not been completely described. Etiologies remain largely unknown. We prospectively analyzed 103 Thai patients from 27 provinces for the causes of encephalitis using clinical, microbiological and neuroimaging indices; caseswithout a diagnosis were evaluated for autoimmune causes of encephalitis.
Patients with encephalitis and/or myelitis were prospectively studied between October 2010 and August 2012. Cases associated with bacterial, rickettsial and mycobacterial diseases were excluded. Herpes viruses 1-6 and enteroviruses infection was diagnosed using PCR evaluation of CSF; dengue and JE viruses infection, by serology. The serum of test-negative patients was evaluated for the presence of autoantibodies.
103 patients were recruited. Fifty-three patients (52%) had no etiologies identified. Twenty-five patients (24%) were associated with infections. Immune encephalitis was found in 25 (24%); neuropsychiatric lupus erythematosus (4), demyelinating diseases (3), Behcet’s disease (1) and the remaining had antibodies to NMDAR (5), ANNA-2 (6), Yo (2), AMPA (1), GABA (1), VGKC (1) and NMDA coexisting with ANNA-2 (1). Presenting symptoms in the autoimmune group included behavioral changes in 6/25 (versus 12/25 in infectious and 13/53 in unknown group) and as psychosis in 6/25 (versus 0/25 infectious and 2/53 unknown). Seizures were found in 6/25 autoimmune, 4/25 infectious and 19/53 unknown group. Two patients with anti-ANNA-2 and one anti-Yo had temporal lobe involvement by magnetic resonance imaging. Two immune encephalitis patients with antibodies to NMDAR and ANNA-2 had ovarian tumors.
Autoantibody-associated encephalitis should be considered in the differential diagnosis and management algorithm regardless of clinical and neuroimaging features.
Encephalitis; Autoimmune encephalitis; Paraneoplastic encephalitis; Limbic encephalitis
Besides the defining involvement of upper and lower motor neurons, the involvement of extramotor structures has been increasingly acknowledged in amyotrophic lateral sclerosis (ALS).
Here we investigated a group of 14 mildly to moderately affected ALS patients and 14 age-matched healthy control participants using cortical thickness analysis. Cortical thickness was determined from high resolution 3D T1 magnetic resonance images and involved semiautomatic segmentation in grey and white matter, cortical alignment and determination of thickness using the Laplace method. In addition to a whole-cortex analysis a region of interest approach was applied.
ALS patients showed regions of significant cortical thinning in the pre- and postcentral gyri bilaterally. Further regions of cortical thinning included superior and inferior parietal lobule, angular and supramarginal gyrus, insula, superior frontal, temporal and occipital regions, thus further substantiating extramotor involvement in ALS. A relationship between cortical thickness of the right superior frontal cortex and clinical severity (assessed by the ALS functional rating scale) was also demonstrated.
Cortical thickness is reduced in ALS not only in motor areas but in widespread non-motor cortical areas. Cortical thickness is related to clinical severity.
ALS; Cortical thickness; MRI
Glatiramer acetate (GA) and interferon-beta (IFN-β) are disease-modifying therapies (DMTs) for multiple sclerosis that are administered through subcutaneous (SC) or intramuscular (IM) injections. Skin reactions associated with DMTs are common and may influence patient’s health-related quality of life (QoL). We aimed to determine the prevalence of cutaneous adverse events associated with long-term DMT use, and to assess the impact of cutaneous adverse events on QoL.
A cross-sectional study among patients with multiple sclerosis who had been treated with their first DMT for at least 2 years. Cutaneous events were assessed from photographs of injection-sites by dermatologists blinded for DMT. Generic and dermatology-specific health-related QoL were assessed using validated patient-reported questionnaires.
A total of 229 patients were enrolled, of whom 156 (68%) had at least one skin reaction. The prevalence of cutaneous adverse events was higher for SC DMTs (75-82%) compared to IM DMT (41%) (P < 0.001). Erythema and lipoatrophy were the most common skin reactions, observed in 156 (68%) and 45 (20%) patients, respectively. Dermatology-specific, but not generic, QoL was significantly lower among patients with skin reactions compared to those without.
The prevalence of cutaneous adverse events was high in long-term DMT-treatment. Patients with cutaneous adverse events had a lower perceived dermatology-specific QoL.
Skin reactions; MS; Quality of life; Glatiramer acetate; Interferon-beta; Injections
Although small calcifications of the dura and the transverse sinus occur frequently, large, single intracranial calcifications originating from the transverse sinus and the neighbouring dura are rare.
A 47-year-old man was admitted to the hospital for a right occipital headache that had persisted for two weeks. There was no neurological deficit. Normal skull X-ray and computed tomography (CT) scans revealed an irregular, calcified, intracranial lesion of approximately 4.4 × 4.0 × 2.5 cm in volume in the right occipital region. Via surgery, a bone-hard, poorly vascularised, pink mass originating from the right transverse sinus and the convex dura of the right cerebellar hemisphere, as well as the cerebellar tentorium, was completely removed. Pathological examination yielded a diagnosis of fibrous connective tissue with hyaline degeneration, calcification and ossification with no indication of neoplasia or inflammation.
We report a rare case of massive calcification and ossification of the transverse sinus and the neighbouring dura mimicking meningioma. Degenerative calcification and ossification may serve as a rare differential diagnosis of diseases, such as meningiomas, in the transverse sinus and the neighbouring dura.
Intracranial calcification; Intracranial ossification; Transverse sinus; Dura
Although muscle weakness is a hallmark of facioscapulohumeral muscular dystrophy (FSHD), the molecular mechanisms that lead to weakness in FSHD remain largely unknown. Recent studies suggest aberrant expression of genes involved in skeletal muscle development and sarcomere contractility, and activation of pathways involved in sarcomeric protein degradation. This study will investigate the contribution of sarcomeric protein dysfunction to the pathogenesis of muscle weakness in FSHD.
Evaluation of sarcomeric function using skinned single muscle fiber contractile studies and protein analysis in muscle biopsies (quadriceps femoris and tibialis anterior) from patients with FSHD and age- and gender-matched healthy controls. Patients with other forms of muscular dystrophy and inflammatory myopathy will be included as disease controls to assess whether results are due to changes specific for FSHD, or a consequence of muscle disease in general. A total of 56 participants will be included. Extensive clinical parameters will be measured using MRI, quantitative muscle studies and physical activity assessments.
This study is the first to extensively investigate muscle fiber physiology in FSHD following an earlier pilot study suggesting sarcomeric dysfunction in FSHD. The results obtained in this study will increase the understanding of the pathophysiology of muscle weakness in FSHD, and possibly identify novel targets for therapeutic intervention.
Facioscapulohumeral muscular dystrophy; Oculopharyngeal muscular dystrophy; Sporadic inclusion body myositis; Skeletal muscle; Sarcomere; Myofilament
With an increased life expectancy for the general population as well as for those ageing with chronic diseases, there are major challenges to the affected individuals and their families, but also to health care and societal planning. Most important, an increasing proportion of older people remain living in their ordinary homes despite health decline and disability. However, little is known about the home and health situation of people ageing with Parkinson’s disease (PD), and older people are often excluded from PD-research.
The overall aim of the present project is to generate knowledge on home and health dynamics in people with PD, with an explicit attention to PD-specific symptomatology. We will concentrate on aspects of home and health captured by state-of-the-art methodology from gerontology as well as PD-research, health science and rehabilitation. This study protocol describes a longitudinal cohort survey study that includes a baseline data collection and a 3-year follow-up. Both data collection waves include self-administered questionnaires, structured interviews, clinical assessments and observations during home visits effectuated by research staff with project-specific training. In order to arrive at a follow-up sample of N=160, 250 participants identified by PD specialist nurses are being recruited from three hospitals in southern Sweden. With no lower or upper age limit, only those diagnosed with PD since at least one year were included. The exclusion criteria were: difficulties in understanding or speaking Swedish and/or cognitive difficulties/other reasons making the individual unable to give informed consent or to take part in the majority of the data collection. The data collection targets environmental factors such as assistive devices, social support, physical environmental barriers, accessibility problems and perceived aspects of home. A broad variety of instruments tap PD-specific problems (e.g. freezing of gait, fear of falling) and health-related issues such as general self-efficacy, body functions, activities and participation.
This project will produce knowledge to the benefit of the development of health care and societal planning that targets people ageing with PD, ultimately promoting activity and participation and an increase of the number of healthy life years for this sub-group of the population.
Activities of daily living; Falls; Housing; P-E fit; Walking
Locomotor training using robots is increasingly being used for rehabilitation to reduce manpower and the heavy burden on therapists, and the effectiveness of such techniques has been investigated. The robot suit Hybrid Assistive Limb (HAL) has been developed to rehabilitate or support motor function in people with disabilities. The HAL provides motion support that is tailored to the wearer’s voluntary drive. We performed a pilot clinical trial to investigate the feasibility of locomotor training using the HAL in chronic stroke patients, and to examine differences between two functional ambulation subgroups.
Sixteen stroke patients in the chronic stage participated in this study. All patients were trained with the HAL over 16 sessions (20–30 min/day within 2 days/week). Primary outcomes were walking speed, cadence, and number of steps recorded during a 10-meter walk test (10MWT). Berg balance scale (BBS) and timed up and go (TUG) were also measured. All outcome measures were evaluated without wearing HAL assistance before and after the intervention in all patients as well as in the dependent ambulatory and independent ambulatory subgroups.
All participants completed the intervention with no adverse events. Gait speed, cadence, number of steps during the 10MWT, and BBS increased significantly from 0.41 m/s to 0.45 m/s (P = 0.031), from 68.6 steps/min to 72.0 steps/min (P = 0.020), from 37.5 steps to 33.1 steps (P = 0.017), and from 40.6 to 45.4 (P = 0.004) respectively. The TUG test score improved, although this difference was not statistically significant. The findings in the dependent ambulatory subgroup primarily contributed to the significant differences observed in the group as a whole.
This pilot study showed that locomotor training using the HAL is feasible for chronic stroke patients. Randomized controlled trials are now required to demonstrate the effectiveness of HAL-based rehabilitation over conventional therapies.
Several reports have described that individual periodic leg movements during sleep (PLMS) activities are associated with autonomic nervous system activity occurring shortly before each PLMS activity. Nevertheless, no study has investigated dynamic changes of autonomic nervous system activity before the onset of PLMS. This study detected changes in heart rate variability (HRV) at the onset of the period with PLMS using complex demodulation method.
This study enrolled 14 patients diagnosed as having idiopathic PLMS disorder (PLMD). In periods with and without PLMS during sleep stage 2, HRV-related variables and the spectral power of fluctuation of a high frequency (HF) band (FHFB) were analyzed and compared. The changes of those parameters during transition from the period without PLMS to that with PLMS were explored.
Spectral power in the low frequency (LF) band and very low frequency (VLF) band were higher in the period with PLMS. Additionally, the average frequency in FHFB was higher. The frequency in this band fluctuated during the period with PLMS with remarkable elevation of FHFB. Moreover, spectral powers in FHFB, LF, and VLF were remarkably elevated shortly before the beginning of the period with PLMS (FHFB, -65 s; LF, -53 s; and VLF, -45 s).
Elevation of sympathetic nervous system activity and mean frequency fluctuation in an HF band can occur several tens of seconds before the period with PLMS. Dynamic changes in the autonomic nervous system activity might be related to the vulnerability to PLMS occurrence during the night.