Meningioangiomatosis (MA) is a rare hamartomatous lesion. Only six cases of cystic MA have been reported in the literature.
We present a case of multicystic MA. A 21-year-old woman without any stigmata of neurofibromatosis type 2 presented with intractable seizures since 10 years. Brain magnetic resonance imaging revealed a well-defined, multicystic mass with heterogeneous signal intensity in the right temporal lobe. The patient underwent resection of the lesion and of the epileptogenic cortex under intraoperative electrocorticography (ECoG) assistance. Histopathological examination showed proliferation of perivascular cells that were arranged in a cuff pattern and were positive for vimentin, D2-40 and smooth muscle actin. Mutiple microcysts and enlarged perivascular spaces were present, which was similar to the structure of the arachnoid cavity. Hyalinized collagen fibers with round concentric acellular eosinophilic lamellae within areas of reactive gliosis were noted for the first time in MA. The patient was followed up without any clinical symptoms or recurrence for 2 years.
MA may originate from arachnoid and vascular tissue trapped in the cortical parenchyma during brain development, and the cysts may have resulted from the gradual accumulation of cerebrospinal fluid in the perivascular spaces of the trapped tissue. Resection of the lesion and of the epileptogenic cortex is important not only for pathological diagnosis but also for seizure control, and intraoperative ECoG assistance is recommended.
Meningioangiomatosis; Multicystic; Seizure; Hamartomatous lesion
Although common and often disabling in multiple sclerosis (MS), visual dysfunction is currently not adequately accounted for in both clinical routine and MS trials. Sloan low contrast letter acuity (SLCLA) is a standardised chart-based measure of visual function particular at low contrast and has been suggested as additional visual component to the Multiple Sclerosis Functional Composite (MSFC). Here, we evaluate the relations between SLCLA, retinal integrity, MSFC, and quality of life (QoL) in MS patients.
Cross-sectional analysis of retinal nerve fibre layer (RNFL) thickness, MSFC, SLCLA (2.5% and 1.25% contrast levels), visual evoked potentials, and QoL (Short Form (SF) 36, National Eye Institute Visual Functioning Questionnaire (NEIVFQ)) using baseline data of 92 MS patients from an ongoing prospective longitudinal trial. Relations between RNFL thickness or P100 latency and SLCLA were analysed using generalised estimating equations (GEE) accounting for intra-individual inter-eye dependencies and corrected for age, gender, and history of optic neuritis. Pearson’s correlations were used to assess relations between SLCLA, MSFC, and QoL.
SLCLA reflected RNFL thickness (p = 0.021) and P100 latency (p = 0.004) and predicted vision-related QoL, reflected by the NEIVFQ39 subscores “general vision” and “near activities” (p < 0.008 for both). SLCLA did not predict general QoL reflected by SF36. Implementing SLCLA into MSFC, thus creating a four-dimensional MSFC4, captured aspects of disability reflected by the NEIVFQ39 subscores “general vision” (r = 0.42, p < 0.0001) and “near activity” (r = 0.3, p = 0.014) which were not captured by standard MSFC3.
SLCLA at 2.5% and 1.25% contrast levels correlates with retinal morphology and P100 latency and predicts some aspects of vision-related QoL in MS. More importantly, using a prospective cross-sectional approach we provide evidence that extending the MSFC by SLCLA as an additional visual component increases the performance of MSFC to capture MS-related disability. Longitudinal data on the relation between SLCLA, MSFC, and QoL will be available in the near future.
Multiple sclerosis; Low contrast visual acuity; Sloan low contrast letter acuity; Multiple sclerosis functional composite; Quality of life; Retinal nerve fibre layer thickness
Cerebrovascular complications (CVCs) frequently occur in patients with acute infective endocarditis (IE). The aim of this study is to describe the clinical findings of CVCs and to evaluate the impact of CVCs on long-term mortality in patients with IE.
We retrospectively analyzed 144 patients who fulfilled the modified Duke’s criteria for definite left-sided IE. CVCs were classified into minor (silent cerebral embolism, TIA and stroke with an initial modified Rankin scale ≤ 2) or major (an initial modified Rankin scale ≥ 3) CVCs. Cox proportional hazards model was used for mortality analysis. Hazard ratio (HR) and 95% confidence interval (CI) were obtained.
The mean age of the 144 patients (96 males and 48 females) was 49.1 years (range 6-85 years). A CVC was found in 37 (25.7%) patients. Of these, 25 were treated with surgical therapy. The patients who underwent early surgery within 2 weeks after stroke had a statistical trend toward a higher risk of postoperative brain hemorrhage (50% versus 4.8%, P = 0.057 by Fisher exact test). The minor CVC group had a similar risk of death as the no-CVC group (P = 0.803; HR 0.856; CI 0.253-2.894), whereas the major CVC group had a higher mortality (P = 0.013; HR 2.865; CI 1.254-6.548) than the no-CVC group. In the multivariate analysis, major CVC (P = 0.002; HR 3.893; CI 1.649-9.194) was a significant predictor of mortality in IE patients, together with advanced age (P = 0.005; HR 3.138; CI 1.421-6.930) and prosthetic valve IE (P = 0.008; HR 2.819; CI 1.315-6.044).
IE can give rise to various forms of CVC, most frequently, acute ischemic brain lesions. In our study, major CVC was associated with high risk of mortality although total CVC was not significantly related to the risk of death in patients with IE.
Infective endocarditis; Cerebrovascular complication; Stroke
To determine the incidence rate and to describe other basic epidemiological data of primary brain tumours in a population-based study in Georgia, performed between March 2009 and March 2011.
Active case ascertainment was used to identify brain tumour cases by searching neuroradiology scan reports and medical records from all participating medical institutions, covering almost 100% of the neurooncology patients in the country.
A total of 980 new cases were identified during the two-year period. For a population of almost 4.5 million, the overall annual incidence rate was 10.62 per 100,000 person-years, age-standardized to the year 2000 US population (ASR). Non-malignant tumours constituted about 65.5% of all tumours. Males accounted for 44% and females for 56% of the cases. Among classified tumours, age-standardized incidence rates by histology were highest for meningiomas (2.65/100,000), pituitary adenoma (1.23/100,000) and glioblastomas (0.51/100,000). ASR were higher among females than males for all primary brain tumours (10.35 vs. 9.48/100,000) as well as for main histology groups except for neuroepithelial, lymphomas and germ cell tumours.
The annual incidence rate of all primary brain tumours in Georgia, though comparable with some European registry data, is low in comparison with the 2004–2005 Central Brain Tumor Registry of the United States (CBTRUS) database, which may reflect variations in reporting and methodology. The higher percentage of unclassified tumours (37.8%) probably also affects the discrepancies between our and CBTRUS findings. However, the most frequently reported tumour was meningioma with a significant predominance in females, which is consistent with CBTRUS data.
Epidemiology; Incidence; Primary brain tumours; Brain tumour registry; Meningioma; Glioblastoma
Natalizumab, a highly specific α4-integrin antagonist, , has recently been registered across the Middle East and North Africa region. It improves clinical and magnetic resonance imaging (MRI) outcomes and reduces the rate of relapse and disability progression in relapsing-remitting multiple sclerosis (MS). Natalizumab is recommended for patients who fail first-line disease-modifying therapy or who have very active disease. Progressive multifocal leukoencephalopathy is a rare, serious adverse event associated with natalizumab.
We aim to develop regional recommendations for the selection and monitoring of MS patients to be treated with natalizumab in order to guide local neurological societies.
After a review of available literature, a group of neurologists with expertise in the management of MS met to discuss the evidence and develop regional recommendations to guide appropriate use of natalizumab in the region.
Disease breakthrough is defined as either clinical (relapse or disability progression) or radiological activity (new T2 lesion or gadolinium-enhancing lesions on MRI), or a combination of both. Natalizumab is recommended as an escalation therapy in patients with breakthrough disease based on its established efficacy in Phase III studies. Several factors including prior immunosuppressant therapy, anti-John Cunningham virus (JCV) antibody status and patient choice will affect the selection of natalizumab. In highly active MS, natalizumab is considered as a first-line therapy for naive patients with disabling relapses in association with MRI activity. The anti-JCV antibody test is used to assess anti-JCV antibody status and identify the risk of PML. While seronegative patients should continue treatment with natalizumab, anti-JCV antibody testing every 6 months and annual MRI scans are recommended as part of patient monitoring. In seropositive patients, the expected benefits of natalizumab treatment have to be weighed against the risks of PML. Clinical vigilance and follow-up MRI scans remain the cornerstone of monitoring. After 2 years of natalizumab therapy, monitoring should include more frequent MRI scans (every 3–4 months) for seropositive patients, and the risk-benefit ratio should be reassessed and discussed with patients.
Recommendations have been developed to guide neurologists in the Middle East and North Africa on patient selection for natalizumab treatment and monitoring.
Multiple sclerosis; Natalizumab; Progressive multifocal leukoencephalopathy; Recommendations; Risk stratification
Spatial neglect is a frequent and debilitating consequence of acquired brain injury and currently has no widely accepted standard of care. While previous interventions for spatial neglect have targeted patients’ overt spatial deficits (e.g., reduced contralesional visual scanning), far fewer have directly targeted patients’ non-spatial deficits (e.g., sustained attention deficits). Considering that non-spatial deficits have shown to be highly predictive of long-term disability, we developed a novel computer based training program that targets both sustained (tonic) and moment-to-moment (phasic) aspects of non-spatial attention (Tonic and Phasic Alertness Training, TAPAT). Preliminary studies demonstrate that TAPAT is safe and effective in improving both spatial and non-spatial attention deficits in the post-acute recovery phase in neglect patients. The purpose of the current trial (referred to as the REmediation of SPatial Neglect or RESPONSE trial) is to compare TAPAT to an active control training condition, include a larger sample of patients, and assess both cognitive and functional outcomes.
We will employ a multi-site, longitudinal, blinded randomized controlled trial (RCT) design with a target sample of 114 patients with spatial neglect. Patients will either perform, at their home, the experimental TAPAT training program or an active control computer games condition for thirty minutes/day, five days a week, over three months. Patients will be assessed on a battery of cognitive and functional outcomes on three occasions: a) immediately before training, b) within forty-eight hours post completion of total training, and c) after a three-month no-contact period post completion of total training, to assess the longevity of potential training effects.
The strengths of this protocol are that it tests an innovative, in-home administered treatment that targets a fundamental deficit in neglect, employs highly sensitive computer-based assessments of cognition as well as functional outcomes, and incorporates a large sample size (relative to other neglect treatment studies) in an RCT design.
ClinicalTrials.gov identifier, NCT01965951
Hemispatial neglect; Rehabilitation; Non-spatial attention; Stroke; Computer-based cognitive training
Chronic inflammatory demyelinating polyradiculoneuropathy is a rare acquired immune-mediated progressive or relapsing disorder causing peripheral neuropathic disease of duration more than two months. Many individuals with chronic inflammatory demyelinating polyradiculoneuropathy fail to make a long-term recovery with current treatment regimes. The aim of this study was to prospectively review the literature to determine the effectiveness of therapies for chronic inflammatory demyelinating polyradiculoneuropathy.
Articles published from January 1990 to December 2012 were searched for studies to treat adults with chronic inflammatory demyelinating polyradiculoneuropathy. Peer-reviewed full-text articles published in English were included.
Nine placebo-controlled double-blinded randomised trials were reviewed to treat subjects with chronic inflammatory demyelinating polyradiculoneuropathy exhibiting various degrees of effectiveness. The most effect treatments were; three randomised controlled trials using intravenous immunoglobulin, a study comparing pulsed dexamethasone and short term prednisolone and rituximab all showed promising results and were well tolerated.
IVIg and corticosteroids remain first line treatments for CIDP. Therapies using monoclonal antibodies, such as Rituximab and Natalizumab offer the most promise for treatment of Chronic inflammatory demyelinating polyradiculoneuropathy however they also need further research, as does the use of stem cell therapy for treating Chronic inflammatory demyelinating polyradiculoneuropathy. Large randomised controlled trials and better patient selection are required to address responsiveness of CIDP patients to conventional treatments to elucidate mechanisms of action and future directions for therapeutic improvement.
Chronic inflammatory demyelinating polyneuropathy; Peripheral neuropathy; Anti-myelin associated glycoprotein; Autoimmune diseases; Treatment; Plasmapheresis; IVIg; Corticosteroids
Subcortical hypodensities of presumed vascular etiology (SHPVO) are a clinical, radiological and neuropathological syndrome with a still largely unexplained pathophysiology. Parallel to the clinical heterogeneity, there is also recognised cerebral topographical diversity with undetermined etiological implications. Our aim is to assess clinical and neurosonological predictors of SHPVO according to their location.
Cross sectional analysis of consecutive patients that underwent neurosonologic evaluation and head CT within one month, during a one year period. We excluded patients with absent temporal sonographic window, any pathology with a possible confounding effect on cerebral arterial pulsatility, atrial fibrillation and other etiologies of white matter diseases. The mean pulsatility index (PI) of both middle cerebral arteries was measured in the middle third of the M1 segment; intima media thickness was evaluated in the far wall of both common carotid arteries. SHPVO were rated by analysis of head CT in deep white matter (DWMH), periventricular white matter (PVWMH) and basal ganglia (BGH). We conducted a multivariate ordinal logistic regression model including all clinical, demographic and ultrasonographic characteristics to determine independent associations with SHPVO.
We included 439 patients, mean age 63.47 (SD: 14.94) years, 294 (67.0%) male. The independent predictors of SHPVO were age (OR = 1.067, 95% CI: 1.047-1.088, p < 0.001 for DWMH; OR = 1.068, 95% CI: 1.049-1.088, p < 0.001 for PVWMH; OR = 1.05, 95% CI: 1.03-1.071, p < 0.001 for BGH), hypertension (OR = 1.909, 95% CI: 1.222-2.981, p = 0.004 for DWMH; OR = 1.907, 95% CI: 1.238-2.938, p = 0.003 for PVWMH; OR = 1.775, 95% CI: 1.109-2.843, p = 0.017 for BGH) and PI (OR = 17.994, 95% CI: 6.875-47.1, p < 0.001 for DWMH; OR = 5.739, 95%CI: 2.288-14.397, p < 0.001 for PVWMH; OR = 11.844, 95% CI: 4.486-31.268, p < 0.001 for BGH) for all locations of SHPVO.
Age, hypertension and intracranial pulsatility are the main independent predictors of SHPVO across different topographic involvement and irrespective of extracranial atherosclerotic involvement.
White matter lesions; Ischemic leukoencephalopathy; Small vessel disease; Transcranial doppler; Neurosonology; Stroke; Atherosclerosis
Recurrent TIAs are thought to signal a high stroke risk. The aim of this study is to examine if repeated ischemic events increase the risk of recurrent ipsilateral stroke among patients with symptomatic 50-99% carotid stenosis.
This is a secondary analysis of the ANSYSCAP study, where we analyzed recurrent ipsilateral ischemic stroke before carotid endarterectomy in 230 consecutive patients with symptomatic 50-99% carotid stenosis. Here, we further analyzed the patients according to if they were clinically stable, unstable or highly unstable – respectively defined as having 0, 1 or ≥2 additional ipsilateral events within 7 days before and/or after the ischemic cerebrovascular event for which the patient sought health care (the presenting event).
Of the 230 included patients, 155 (67%) were clinically stable, 47 (20%) were clinically unstable and 28 (12%) were clinically highly unstable. Eighteen patients suffered a stroke within 7 days; of these patients, 12 (67%) were clinically stable. The risk of recurrent ipsilateral ischemic stroke within 7 days was equally high for clinically stable (8%), unstable (9%) and highly unstable (7%) patients. Fourteen patients had 3–11 additional ipsilateral events; of these patients, only one suffered a recurrent ipsilateral ischemic stroke.
The seemingly clinical stable symptomatic 50-99% carotid stenosis patients without additional ipsilateral events have a high risk of recurrent stroke. Patients without additional events should undergo preoperative evaluation and carotid endarterectomy in the same expedient manner as patients with additional events.
Stroke; Carotid stenosis; Risk
Despite remarkable advances in genetic testing, many adults with syndromic epilepsy remain without a molecular diagnosis. The challenge in providing genetic testing for this patient population lies in the extensive genetic heterogeneity associated with epilepsy. Even for the subset of epilepsy patients that present with a defining feature, such as microcephaly, the number of possible genes that would require interrogation by Sanger sequencing is extensive and often prohibitively expensive.
We report a family of French Canadian descent with four adult children affected with severe intellectual disability, epilepsy and microcephaly born to consanguineous parents and evaluated by the Genetics Service to provide informed genetic counseling to unaffected family members regarding possible recurrence risks. We used whole-exome sequencing (WES) of DNA from one affected sibling as a first-line diagnostic tool and compared the prioritization of variants using two strategies: 1) focusing on genes with homozygous variants; and, 2) focusing on genes associated with microcephaly. Both approaches prioritized the same homozygous novel frameshift mutation (p.Arg608Serfs*26) in WDR62, a gene known to cause autosomal recessive primary microcephaly. Sanger sequencing confirmed the presence of the homozygous mutation in the other three affected siblings.
WES and subsequent filtering of the rare variants in a single affected family member led to the rapid and cost-effective identification of a novel homozygous frameshift mutation in WDR62, thereby explaining the severe neurodevelopmental disorder in this family and facilitating genetic counseling. Our findings support WES as an effective first-line diagnostic tool in families presenting with rare genetically heterogeneous neurological disorders.
Primary microcephaly; Epilepsy; Whole-exome sequencing; WDR62
A 6-month phase 2 study of fingolimod demonstrated efficacy and safety in Japanese patients with relapsing-remitting multiple sclerosis (MS). Here we report a 6-month observational extension that evaluated efficacy and safety in patients who received fingolimod continuously for 12 months or who switched from placebo to fingolimod.
Of 147 patients who completed the 6-month core study, 143 entered the extension. Those originally randomized to placebo were re-randomized to fingolimod 1.25 mg or 0.5 mg. During the extension, all patients were switched to open-label fingolimod 0.5 mg.
Magnetic resonance imaging (MRI) and relapse outcomes were maintained or improved in patients treated with fingolimod for 12 months versus those treated for 6 months. No new safety events were reported over 12 months of treatment. Infections occurred in similar proportions of continuously treated and switched patients, while cardiac and liver adverse events occurred in fewer continuously treated than switched patients. Four patients were aquaporin-4 (AQP4) antibody-positive, three of whom showed rapid disease exacerbations within 10 days of fingolimod initiation.
Continuous fingolimod treatment for up to 12 months was associated with maintained or improved efficacy and a manageable safety profile, consistent with that previously seen. Results in a small number of patients suggest lack of benefit in AQP4 antibody-positive patients. Meaningful statistical interpretation was limited by the small sample size in each treatment group, owing to the number of patients who completed the core study.
Aquaporin 4; Fingolimod; Longitudinally extensive spinal cord lesions; Multiple sclerosis; Phase 2 study
Perceived disability after stroke may persist long-term even among young individuals with mild stroke and may be related to age-related expectations of health and recovery. Thus, in order to appreciate the magnitude of perceived disability in a younger stroke population studies are needed to explore perceived health-related differences between young individuals with stroke and a matched general population. Further, to provide long-term measures by health care, relevant to the same young individuals with stroke, their perceived long-term functioning and disability associated with health need to be explored.
The generic questionnaire EQ-5D was used to compare ratings of global health and disability between young individuals living in the community up to 6 years after stroke (n = 150) and an age and geographically matched general population (n = 2661). Stroke related medical data were retrieved from medical records and the study specific questionnaire, the MYS-questionnaire, was used to assess self-rated disability associated with global health.
Among the young individuals 79% had suffered a mild stroke, 45% rated a low global health compared to 15% of the matched general population and a higher proportion rated problems in mobility, self-care, usual activities and anxiety/depression. Among the young individuals with stroke, limitations and restrictions in leisure activities, work, reading as well as low level of physical activity, utilizing personal care provider or personal assistance and tiredness were negatively associated with self-rated global health (R square 0.60).
The negative effects of stroke, on self-rated global health among young individuals living in the community, appear to be substantial, multi factorial and long-standing which call for interdisciplinary research collaborations and team measures by health care long-term.
Community; Disability; Health; Stroke; Young
This study aimed to comprehensibly investigate potential contributing factors to fear of falling (FOF) among people with idiopathic Parkinson’s disease (PD).
The study included 104 people with PD. Mean (SD) age and PD-duration were 68 (9.4) and 5 (4.2) years, respectively, and the participants’ PD-symptoms were relatively mild. FOF (the dependent variable) was investigated with the Swedish version of the Falls Efficacy Scale, i.e. FES(S). The first multiple linear regression model replicated a previous study and independent variables targeted: walking difficulties in daily life; freezing of gait; dyskinesia; fatigue; need of help in daily activities; age; PD-duration; history of falls/near falls and pain. Model II included also the following clinically assessed variables: motor symptoms, cognitive functions, gait speed, dual-task difficulties and functional balance performance as well as reactive postural responses.
Both regression models showed that the strongest contributing factor to FOF was walking difficulties, i.e. explaining 60% and 64% of the variance in FOF-scores, respectively. Other significant independent variables in both models were needing help from others in daily activities and fatigue. Functional balance was the only clinical variable contributing additional significant information to model I, increasing the explained variance from 66% to 73%.
The results imply that one should primarily target walking difficulties in daily life in order to reduce FOF in people mildly affected by PD. This finding applies even when considering a broad variety of aspects not previously considered in PD-studies targeting FOF. Functional balance performance, dependence in daily activities, and fatigue were also independently associated with FOF, but to a lesser extent. Longitudinal studies are warranted to gain an increased understanding of predictors of FOF in PD and who is at risk of developing a FOF.
Fear of falling; Physical therapy; Parkinson’s disease; Postural Balance; Rehabilitation
Machado-Joseph disease (MJD), also named spinocerebellar ataxia type 3 (SCA3) is the most common autosomal dominant ataxia worldwide. Although nystagmus is one of the most frequently reported ocular alterations in MJD patients its behaviour during the course of the disease, namely in its early stages, has only recently started to be investigated. The main goal of this work was to characterize the frequency of nystagmus in symptomatic and presymptomatic carriers of the MJD mutation, and investigate its usefulness as an early indicator of the disease.
We conducted an observational study of Azorean MJD family members, comprising a total of 158 subjects which underwent neurological evaluation. Sixty eight were clinically and molecularly diagnosed with MJD, 48 were confirmed asymptomatic carriers and 42 were confirmed non-carriers of the MJD mutation. The frequency of nystagmus was calculated for the 3 groups.
Nystagmus was present in 88% of the MJD patients. Seventeen percent of the at-risk subjects with a carrier result in the molecular test and none of the 42 individuals who received a non-carrier test result displayed nystagmus (p < 0.006). Although not reaching statistical significance, symptomatic subjects showing nystagmus had a tendency for a higher length of the CAG tract in the expanded allele, when compared to individuals who did not have nystagmus.
The frequency of nystagmus in asymptomatic carriers and its absence in non-carriers of the mutation, suggests that nystagmus may appear before gait disturbance and can thus be considered an early sign of MJD.
Spinocerebellar ataxia; Presymptomatic subjects; Clinical trials
Capsular warning syndrome (CWS) is rare (1.5% of TIA presentations) but has a poor prognosis (7-day stroke risk of 60%). Up to date, the exact pathogenic mechanism of CWS has not been fully understood. We report the clinical presentations and high-resolution MRI (HR MRI) findings of two cases with capsular warning symptoms.
Case 1 was a 63-year-old man with a history of hypertension with recurrent episodes of left hemiparesis and dysarthria lasting 10 ~ 30 minutes. Case 2 was a 54-year-old woman with repetitive episodes of transient left hemiparesis and dysarthria lasting about 10 minutes. Capsular infarctions on DWI were demonstrated in the territory of a lenticulostriate artery in both 2 patients. HR MRI disclosed atherosclerotic plaques on the ventral wall of the MCA where enticulostriate arteries were arisen from, although traditional digital subtraction angiography showed normal. Aggressive medical therapy with dual antithrombotic agents and statin was effective in these two cases.
Our HR MRI data offer an insight into the pathophysiology of CWS which might be caused by atherosclerotic plaque in non-stenotic MCA wall. HR MRI might be a useful modality for characterizing atherosclerotic plaques in the MCA and detecting the pathophysiology of the CWS.
Capsular warning syndrome; High-resolution MRI; Middle cerebral artery; Atherosclerotic plaque
Multiple sclerosis (MS) is a stressful condition; depression, anxiety, pain and fatigue are all common problems. Mindfulness based interventions (MBIs) mitigate stress and prevent relapse in depression and are increasingly being used in healthcare. However, there are currently no systematic reviews of MBIs in people with MS. This review aims to evaluate the effectiveness of MBIs in people with MS.
Systematic searches were carried out in seven major databases, using both subject headings and key words. Papers were screened, data extracted, quality appraised, and analysed by two reviewers independently, using predefined criteria. Study quality was assessed using the Cochrane Collaboration risk of bias tool. Perceived stress was the primary outcome. Secondary outcomes include mental health, physical health, quality of life, and health service utilisation. Statistical meta-analysis was not possible. Disagreements were adjudicated by a third party reviewer.
Three studies (n = 183 participants) were included in the final analysis. The studies were undertaken in Wales (n = 16, randomised controlled trial - (RCT)), Switzerland (n = 150, RCT), and the United States (n = 17, controlled trial). 146 (80%) participants were female; mean age (SD) was 48.6 (9.4) years. Relapsing remitting MS was the main diagnostic category (n = 123, 67%); 43 (26%) had secondary progressive disease; and the remainder were unspecified. MBIs lasted 6–8 weeks; attrition rates were variable (5-43%); all employed pre- post- measures; two had longer follow up; one at 3, and one at 6 months. Socio-economic status of participants was not made explicit; health service utilisation and costs were not reported. No study reported on perceived stress. All studies reported quality of life (QOL), mental health (anxiety and depression), physical (fatigue, standing balance, pain), and psychosocial measures. Statistically significant beneficial effects relating to QOL, mental health, and selected physical health measures were sustained at 3- and 6- month follow up.
From the limited data available, MBIs may benefit some MS patients in terms of QOL, mental health, and some physical health measures. Further studies are needed to clarify how MBIs might best serve the MS population.
Multiple sclerosis; Mindfulness; Stress management
Tortuous blood vessels are commonly seen in the cerebral arteries. The association between vertebrobasilar artery tortuosity and vascular vertigo remains obscure.
We describe two patients with vascular vertigo who had bilateral curving and spiral looping in multiple segments of the vertebral arteries and also exhibited basilar artery tortuosity. Both patients had cerebrovascular risk factors and exhibited clinical features of vertigo with high severity, slow recovery, and recurrent tendencies. Contrast enhanced magnetic resonance angiography of the neck showed bilateral tortuosity in the V2 segments and spiral twisting in the V4 segments of the vertebral arteries, and basilar artery curving. No obvious sign of atherosclerotic stenosis was found in the vertebrobasilar arteries and no abnormalities were observed in the internal carotid arteries. Transcranial Doppler ultrasound showed decreased blood flow in tortuous vertebrobasilar arteries. Brainstem auditory evoked potentials showed that the interpeak latencies (IPL) of waves III-IV were prolonged, with a ratio of IPL III-V/IPL I-III > 1.
Vertebrobasilar tortuosity in combination with cerebrovascular risk factors may lead to vascular vertigo in these patients.
Vertebral artery; Basilar artery; Tortuosity; Vertigo
Cathepsin D C224T polymorphism has been reported to associate with AD susceptibility. But the results were inconsistent. This study aimed to assess the relationship between C224T polymorphism and AD risk.
The relevant studies were identified by searching PubMed, Embase, Web of Science, Google Scholar and Wan fang electronic databases updated on July 2013. The relationship between Cathepsin D C224T polymorphism and AD risk was evaluated by ORs and 95% CIs.
A total of 25 case-control studies including 5,602 cases and 11,049 controls were included in the meta-analysis. There was no association between C224T polymorphism and AD risk with all the studies were pooled in the meta-analysis (CT vs. CC: OR = 1.125, 95% CI = 0.974-1.299, P = 0.109; CT + TT vs. CC: OR = 1.136, 95% CI = 0.978-1.320, P = 0.094). Furthermore, when stratified by ethnicity, age of onset and APOEϵ4 status, significant association did not found in all subgroups.
The present meta-analysis suggested that the Cathepsin D C224T polymorphism was not associated with AD susceptibility.
Cathepsin D; AD; Polymorphism; Meta-analysis
Long-term persistence to treatment for chronic disease is difficult for patients to achieve, regardless of the disease or medication being used. The objective of this investigation was to examine treatment persistence with glatiramer acetate (GA) relative to available disease-modifying therapies (DMT) for multiple sclerosis (MS) over 12-, 24- and 36-month periods.
Data from Clinformatics™ for DataMart affiliated with OptumInsight was used to identify patients using DMT between 2001 and 2010. Patients with 12, 24, and 36 months of follow-up were included. Persistence was defined as continuous use of the same DMT for the duration of follow-up regardless of treatment gaps. Regimen changes including re-initiation of therapy following gaps of 15 days or more, switching therapy, and DMT discontinuation were investigated. Descriptive statistics were used to summarize the results.
Cohorts of GA users with 12 months (n = 12,144), 24 months (n = 7,386) and 36 months (n = 4,693) of follow-up were identified. Persistence rates with GA were 80% for all time periods; discontinuation rates declined over time while switching increased modestly. In contrast, the full DMT-treated cohorts showed persistent rates of 68.3% at 12 months (n = 35,312), 53.9% at 24 months (n = 21,927), and 70.1% at 36 months (n = 14,343). As with these full DMT-treated cohorts, the proportion of GA users remaining on their initial therapy without a gap of 15 days or more decreased with length of follow-up. However, the proportion of GA users with a gap in treatment who re-initiated GA increased over time (64.4% at 12 months; 75.1% at 24 months, and 80.1% at 36 months) while those in the full DMT-treated cohorts re-initiated therapy at rates of only 50-60%.
Persistence rates for GA were 80% for the 12-, 24- and 36-month time periods in contrast with the full DMT-treated cohorts whose persistence rates never exceeded 70.0%. Although there were more gaps in therapy of 15 days or more with all DMT over time, the proportion of GA users re-initiating therapy increased with follow-up contributing to the steady persistence. Therapy persistence is essential to achieve the desired outcomes in MS.
Multiple sclerosis; Disease-modifying therapy; Persistence; Treatment gaps; Therapy re-initiaton; Therapy switching; Therapy discontinuation
We sought to characterize the cognitive function and neuropsychiatric symptoms in cerebral radionecrosis (CRN) patients who have received conformal radiation for nasopharyngeal carcinoma.
A total of 40 patients treated with radiotherapy (RT) that developed CRN (RT + CRN), 40 patients treated with radiotherapy that did not have CRN (RT-No-CRN), and 36 newly diagnosed untreated nasopharyngeal carcinoma patients (No-RT) were recruited. The cognitive function and neuropsychiatric symptoms were evaluated with Montreal cognitive assessment (MoCA), the mini-mental state examination (MMSE), activity of daily living scale (ADL), neuropsychiatric inventory (NPI), Hamilton depression scale (HAMD) and Hamilton anxiety scale (HAMA).
The RT + CRN group had the lowest mean MMSE, MoCA and ADL scores, while highest mean NPI, HAMD and HAMA scores among the three patient groups (P < 0.05). Thirty (75%) of the RT + CRN patients were deemed cognitively impaired by the MoCA compared with 9 (22.5%) by the MMSE (χ
= 22.064; P < 0.001). Eighty-two percents of subject in RT + CRN group experienced neuropsychiatric symptoms within the past 4 weeks. Irritability, anxiety, depression and agitation in the RT + CRN group were of the most significantly frequent among the 3 groups.
The CRN patients generally have manifestations in cognitive and psychological impairment, which have their typical characteristics, and should be considered in CRN treatment and rehabilitation. The MoCA classifies more CRN patients as cognitively impaired than the MMSE, justifying further studies of the MoCA as an appropriate screen for CRN.
Cerebral radionecrosis; Nasopharyngeal carcinoma; Cognitive impairment; Neuropsychiatric symptom
Infection is the most important complication after acute stroke. This is substantially based on a stroke-induced immunosuppression. Heart rate variability (HRV) represents the autonomic nervous system activity in connection with stroke-induced immunomodulation and infections. We demonstrated in a feasibility study that HRV indices obtained in patients without acute post-stroke infections can predict infections in the subsequent sub-acute phase.
The study PRED-SEP is a prospective observational study. Adult patients with acute ischemic infarction in the territory of the middle cerebral artery and severe neurological deficit (National Institutes of Health Stroke Scale: NIHSS ≥ 8) are recruited. Primary endpoint is the development of infections, secondary endpoints are SIRS and severe sepsis in the sub-acute phase (day 3–5) after stroke and the functional outcome after 3 months. Infection is defined according to the PANTHERIS study and comprises pneumonia, urinary tract infection and infections without determined focus. SIRS and severe sepsis are defined according to German Sepsis Society guidelines. Functional outcome is measured by lethality and neurological scores (modified Rankin Scale, Barthel Index). Prognostic factors are HRV risk indices calculated from selected intervals of 24 h ECG measurements within 48 hours after symptom onset. It is planned to recruit 240 patients.
HRV risk indices (predictors) will be calculated according to standards and procedures previously developed and published by the authors. The predictive effects of HRV indices on infections will be estimated by fitting logistic regression models and estimating odds ratios with 95% confidence intervals. A prespecified modelling procedure will be applied to estimate unadjusted and confounder adjusted odds ratios. Secondary endpoints will be analysed in the same way. The functional outcome scales will be dichotomized. The association between HRV indices and pro- and anti-inflammatory markers will be quantified by calculating the appropriate correlation coefficients according to scale (Person or Spearman).
Since a general prophylactic antibiotic treatment after stroke is not recommended, results of this study could have essential implications for an early identification and hence, timely appropriate treating of stroke-induced infections.
Prädiktoren für die Sepsis - Pred Sep, German Clinical Trials Register:
Stroke; Infection; Pneumonia; Autonomic nervous system; Heart rate variability
Abnormalities in nocturnal blood pressure dipping are well known for its relationship to cardiovascular diseases. Cerebral microbleeds are frequently observed in patients with hypertension and are known to be potent risk factors for stroke. However, there are scanty reports about the relationship between nocturnal dipping and cerebral microbleeds.
We recruited consecutive patients with both hypertension and ischemic stroke within 7 days after symptom onset, and those with cardioembolism were excluded. We applied 24-hour ambulatory blood pressure monitoring two weeks after stroke onset, and we used brain MRI to detect cerebral microbleeds. Various blood pressure parameters such as mean 24-hour blood pressure, awake/sleep blood pressure, and morning surge were compared between cerebral microbleeds (+) vs. (-) groups. Subjects were further classified according to nocturnal dipping status and were analyzed by logistic regression to determine its association with cerebral microbleeds with adjustment for age, gender, and cardiovascular risk factors.
A total of 162 patients (100 males, age 65.33 ± 10.32 years) were included. Cerebral microbleeds were detected in 65 patients (40.1%). Most ambulatory blood pressure parameters except morning surge were significantly higher in those who had cerebral microbleeds. After adjusting for the confounding factors, the reverse dippers were prone to have cerebral microbleeds (odds ratio, 3.81; 95% confidential interval, 1.36-10.65; p-value = 0.01).
Cerebral microbleeds are independently associated with reverse dipping on ambulatory blood pressure monitoring in hypertensive stroke patients.
Ambulatory blood pressure monitoring; Cerebral microbleeds; Cerebrovascular disease; Cerebral ischemia; Hypertension
Painful ophthalmoplegia with normal cranial imaging is rare and confined to limited etiologies. In this study, we aimed to elucidate these causes by evaluating clinical presentations and treatment responses.
Cases of painful ophthalmoplegia with normal cranial MRI at a single center between January 2001 and June 2011 were retrospectively reviewed. Diagnoses of painful ophthalmoplegia were made according to the recommendations of the International Headache Society.
Of the 58 painful ophthalmoplegia cases (53 patients), 26 (44.8%) were diagnosed as ocular diabetic neuropathy, 27 (46.6%) as benign Tolosa-Hunt syndrome (THS), and 5 (8.6%) as ophthalmoplegic migraine (OM). Patients with ocular diabetic neuropathy were significantly older (62.8 ± 7.8 years) than those with benign THS (56.3 ±12.0 years) or OM (45.8 ± 23.0 years) (p < 0.05). Cranial nerve involvement was similar among groups. Pupil sparing was dominant in each group. Patients with benign THS and OM responded exquisitely to glucocorticoid treatment with resolved diplopia, whereas patients with ocular diabetic neuropathy didn’t (p < 0.05). Patients with OM recovered more rapidly than the other groups did (p < 0.05). Overall, most patients (94.8%) recovered completely during the follow-up period.
Ocular diabetic neuropathy and benign THS accounted for most of the painful ophthalmoplegias in patients with normal cranial imaging. Patient outcomes were generally good.
Headache; Ocular diabetic neuropathy; Ophthalmoplegic migraine; Painful ophthalmoplegia; Tolosa-Hunt syndrome
In a subset of children with unilateral Cerebral Palsy (CP) a discrepancy between capacity and performance of the affected upper limb can be observed. This discrepancy is known as Developmental Disregard (DD). Though the phenomenon of DD has been well documented, its underlying cause is still under debate. DD has originally been explained based on principles of operant conditioning. Alternatively, it has been proposed that DD results from a diminished automaticity of movements, resulting in an increased cognitive load when using the affected hand. To investigate the amount of involved cognitive load we studied Event-Related Potentials (ERPs) preceding task-related motor responses during a single-hand capacity and a dual-hand performance task. It was hypothesised that children with DD show alterations related to long-latency ERP components when selecting a response with the affected upper limb, reflecting increased cognitive load in order to generate an adequate response and especially so within the dual-hand task.
Fifteen children with unilateral CP participated in the study. One of the participants was excluded due to major visual impairments. Seven of the remaining participants displayed DD. The other seven children served as a control group. All participants performed two versions of a cue-target paradigm, a single-hand capacity and a dual-hand performance task. The ERP components linked to target presentation were inspected: the mid-latency P2 component and the consecutive long-latency N2b component.
In the dual-hand performance task children with DD showed an enhancement in mean amplitude of the long-latency N2b component when selecting a response with their affected hand. No differences were found regarding the amplitude of the mid-latency P2 component. No differences were observed regarding the single-hand capacity task. The control group did not display any differences in ERPs linked to target evaluation processes between both hands.
These electrophysiological findings show that DD is associated with increased cognitive load when movements are prepared with the affected hand during a dual-hand performance task. These findings confirm behavioural observations, advance our insights on the neural substrate of DD and have implications for therapy.
Unilateral cerebral palsy; Developmental disregard; EEG; Event-related potentials; Cognitive load
The Mulvihill-Smith Syndrome was first recognized in 1975. After the recognition of the Mulvihill-Smith Syndrome, ten cases have been described.
This article describes the eleventh case of this syndrome in a male patient, 24 years-old with short stature and microcephaly with mild cognitive impairment, deafness and allergic conjunctivitis. The patient was hospitalized several times for repeated infections, and the presence of multiple melanocytic nevi on his skin was noticed.
Based on the entire set of signs and symptoms presented in our study, it was diagnosed the patient with Mulvihill-Smith Syndrome.
Case reports; Rare diseases; Neurology