Few studies have systematically addressed the role of epidural analgesia and caesarean delivery in predicting the post-partum disease activity in women with Multiple Sclerosis (MS).
The objective of this study was to assess the impact of epidural analgesia (EA) and caesarean delivery (CD) on the risk of post-partum relapses and disability in women with MS.
In the context of an Italian prospective study on the safety of immunomodulators in pregnancy, we included pregnancies occurred between 2002 and 2008 in women with MS regularly followed-up in 21 Italian MS centers. Data were gathered through a standardized, semi-structured interview, dealing with pregnancy outcomes, breastfeeding, type of delivery (vaginal or caesarean) and EA. The risk of post-partum relapses and disability progression (1 point on the Expanded Disability Status Sclae, EDSS, point, confirmed after six months) was assessed through a logistic multivariate regression analysis.
We collected data on 423 pregnancies in 415 women. Among these, 349 pregnancies resulted in full term deliveries, with a post-partum follow-up of at least one year (mean follow-up period 5.5±3.1 years). One hundred and fifty-five patients (44.4%) underwent CD and 65 (18.5%) EA. In the multivariate analysis neither CD, nor EA were associated with a higher risk of post-partum relapses. Post-partum relapses were related to a higher EDSS score at conception (OR=1.42; 95% CI 1.11-1.82; p=0.005), a higher number of relapses in the year before pregnancy (OR=1.62; 95% CI 1.15-2.29; p=0.006) and during pregnancy (OR=3.07; 95% CI 1.40-6.72; p=0.005). Likewise, CD and EA were not associated with disability progression on the EDSS after delivery. The only significant predictor of disability progression was the occurrence of relapses in the year after delivery (disability progression in the year after delivery: OR= 4.00; 95% CI 2.0-8.2; p<0.001; disability progression over the whole follow-up period: OR= 2.0; 95% CI 1.2-3.3; p=0.005).
Our findings, show no correlation between EA, CD and postpartum relapses and disability. Therefore these procedures can safely be applied in MS patients. On the other hand, post-partum relapses are significantly associated with increased disability, which calls for the need of preventive therapies after delivery.
Epidural analgesia; Caesarean delivery; Multiple sclerosis; Pregnancy
Stroke is one of the major causes of loss of independence, decreased quality of life and mortality among elderly people. About half of the elderly stroke patients discharged after rehabilitation in a nursing home still experience serious impairments in daily functioning one year post stroke, which can lead to difficulties in picking up and managing their social life. The aim of this study is to evaluate the effectiveness and feasibility of a new multidisciplinary transmural rehabilitation programme for older stroke patients.
A two group multicentre randomised controlled trial is used to evaluate the effects of the rehabilitation programme. The programme consists of three care modules: 1) neurorehabilitation treatment for elderly stroke patients; 2) empowerment training for patient and informal caregiver; and 3) stroke education for patient and informal caregiver. The total programme has a duration of between two and six months, depending on the individual problems of the patient and informal caregiver. The control group receives usual care in the nursing home and after discharge.
Patients aged 65 years and over are eligible for study participation when they are admitted to a geriatric rehabilitation unit in a nursing home due to a recent stroke and are expected to be able to return to their original home environment after discharge. Data are gathered by face-to-face interviews, self-administered questionnaires, focus groups and registration forms. Primary outcomes for patients are activity level after stroke, functional dependence, perceived quality of life and social participation. Outcomes for informal caregivers are perceived care burden, objective care burden, quality of life and perceived health. Outcome measures of the process evaluation are implementation fidelity, programme deliverance and the opinion of the stroke professionals, patients and informal caregivers about the programme. Outcome measures of the economic evaluation are the healthcare utilisation and associated costs. Data are collected at baseline, and after six and 12 months. The first results of the study will be expected in 2014.
International Standard Randomised Controlled Trial Register Number ISRCTN62286281, The Dutch Trial Register NTR2412
Stroke; Rehabilitation; Aftercare; Elderly persons; Discharged; Nursing home
Based upon the acquainted loss of dopaminergic neurons in the substantia nigra in Parkinson’s disease (PD), we hypothesised changes in magnetic resonance imaging signal intensities of the basal ganglia to be useful as an additional technical tool in the diagnostic work-up.
Region-of-interest analyses (substantia nigra and globus pallidus internus) of T2-weighted scans were performed in seventy subjects with PD, 170 age- and gender-matched controls and 38 patients with an atypical form of neurodegenerative Parkinsonian syndrome (N = 11 multisystem atrophy, N = 22 progressive supranuclear palsy, N = 5 corticobasal syndrome).
In patients with PD, significant changes in signal intensities within the substantia nigra were observed compared to controls at p < 0.001. For the globus pallidus internus, signal alterations in PD and progressive supranuclear palsy were found to be significant (p < 0.001) if compared to controls. Furthermore, signal changes of substantia nigra correlated with signal intensities of globus pallidus internus in the ipsilateral hemisphere in both groups. Sensitivity was 86% and specificity was 90% for the combined analysis of substantia nigra and globus pallidus internus in the complete patient sample versus controls.
Signal alterations of substantia nigra and globus pallidus internus in routine magnetic resonance imaging were useful to distinguish patients with PD from controls. In addition, signal changes in globus pallidus internus could be used to differentiate progressive supranuclear palsy patients from controls. These analyses have the potential to serve as an additional non-invasive technical tool to support the individual differential diagnosis of PD.
Parkinson’s disease; MRI; Substantia nigra; Globus pallidus internus; Progressive supranuclear palsy; Morphological changes
Reduced upper extremity function is one of the most common impairments after stroke and has previously been reported in approximately 70-80% of patients in the acute stage. Acute care for stroke has changes over the last years, with more people being admitted to a stroke unit as well as use of thrombolysis. The aim of the present study was to describe baseline characteristics, care pathway and discharge status in an unselected group of patients with first occasion of stroke who were at a stroke unit within 72 hours after stroke and also to investigate the frequency of impaired arm and hand function. A second aim was to explore factors associated with impaired upper extremity function and the impact of impairment on the patient’s outcome.
Patients over 18 years of age with first ever stroke, living in a geographical catchment area, being at the stroke unit within 72 hours after onset, with no prior upper extremity impairment were included. Baseline characteristics, arm and hand function within 72 hours, stroke outcome and care pathway in the acute phase were described, by gathering information retrospectively from the patients’ charts. Ischemic strokes were categorized according to the Bamford classification and the Trial of Org 10172 in Acute Stroke Treatment criteria.
Of the 969 patients with first ever stroke who were screened, 642 patients fulfilled the inclusion criteria. According to the National Institutes of Health Stroke Scale (NIHSS), the patients had a mean score of 6.0, median 3.0, at arrival to the hospital. Ischemic stroke was most frequent in the anterior circulation (87.7%). Within 72 hours after stroke onset 48.0% of the patients had impaired arm and hand function and this was positively associated with higher age (p < 0.004), longer stay in the acute care (p < 0.001) and mortality in acute care (p < 0.001). Directly admitted to the stroke unit were 89.1% of the patients and 77.1% received hospital care on same day as stroke onset. Mean length of stay in the stroke unit was 9.9 days, 56.8% of the patients were discharged directly home from the stroke unit. Mortality within 72 hours after stroke onset was 5.0%.
Impaired arm and hand function is present in 48% of the patients in a non selected population with first ever stroke, estimated within 72 hours after onset. This is less than previously reported. Impaired arm and hand function early after stroke is associated with higher age, longer stay in the acute care, and higher mortality within the acute hospital care.
Stroke recovery; Upper extremity; Paresis; Outcomes; Process assessment
Physical disability in multiple sclerosis (MS) is frequently characterized by impaired ambulation. Although walking tests have been successfully employed to assess walking ability in MS patients, data analytic procedures have predominantly relied on result-oriented parameters (e.g. total distance covered during a given amount of time), whereas process-oriented, dynamic walking patterns have mostly been ignored. This is striking, since healthy individuals have been observed to display a stereotypical U-shaped pattern of walking speed during timed walking, characterized by relatively high speed during the initial phase, subsequent slowing and final acceleration. Objective of the current study was to test the utility of the 6 min Walk (6MW) and the 12 min Walk (12MW) for revealing putatively abnormal temporal dynamic features of walking in MS.
A group of 37 MS patients was divided into subgroups with regard to their level of disability analyzed with the Expanded Disability Status Scale (EDSS; Mild MS Group, n = 20, EDSS 0 – 3.5; Moderate MS Group, n = 17, EDSS 4 – 5). Subsequently, both groups were compared to age-matched healthy controls (n = 25) on both tests with regard to result-oriented characteristics (mean walking speed), as well as dynamic features (mean decline in walking speed, degree of observed U-shape).
Both MS groups showed a significantly lower mean walking speed than healthy controls, independent of test duration. Compared to controls, the Moderate MS Group also slowed down more rapidly throughout both tests. The same pronounced decline in walking speed was observed for the Mild MS Group in case of the 12MW. Additionally, for both MS groups an attenuated U-shaped velocity pattern was observed relative to controls in the 6MW. Patients' subjective fatigue scores were more strongly correlated with the decline in walking speed than with the common parameter of mean walking speed in the 6MW.
MS patients display abnormal dynamics in their walking patterns. A pronounced linear decline in walking speed can be identified with the 12MW even in MS patients with seemingly mild disability. Similarly, the 6MW can be used to assess an abnormal walking profile. Particularly the linear decline in walking speed on this test shows a more robust association with subjective fatigue than mean walking speed. Dynamic walking parameters may hence represent valuable clinical features, serving as surrogate measures of motor fatigue. Future studies are needed to verify their prognostic value.
Multiple sclerosis; Ambulation; Walking; 6 minute walk; 6MW; 12 minute walk; 12MW; Linear trend; U-shape
This paper provides a strategy to obtain a reliable estimate of the incidence rate for Amyotrophic lateral sclerosis based on data from the National Registry of Rare Diseases (NRRD). In fact, unobserved cases may be due to the fact that “a long time” may intercour between the suspect of having the disease (onset) and the date the disease is diagnosed. Potential factors that may influence the probability of experiencing the event (diagnosis) conditionally on the onset (suspected) are investigated. Since we are treating rare diseases, the role of social and economic factors is not that obvious; latent as well as observed factors may influence the delay to diagnosis.
We use a semiparametric estimator based on the distribution of delay to diagnosis to account for potential underreporting. In particular, we propose to adopt an Horvitz-Thompson based estimator to correct the incidence figure that can be derived for the period 2007-2009 from the NRRD, Italy.
The incidence estimates obtained by adopting the proposed approach are about 1 case per 100000 inhabitants and despite they let recovering a good part of underreporting, they are still far from ALS incidence international ranges between 1.5 and 2.5. However, by looking only at northern Italy, the incidence estimates we can derive are coherent with those known internationally.
These results confirm the existence of substantial differences in reporting accuracy, and point out where the system of data collection must be improved. In particular, when reliable individual characteristics will be available, they could be employed to refine the proposed estimator.
Delay to diagnosis; Horvitz-Thompson; Incidence estimate; Rare diseases; Reverse hazard
Nerve damage in leprosy often causes disabilities and deformities. Prednisolone is used to treat nerve function impairment (NFI). However, optimal dose and duration of prednisolone treatment has not been established yet. Besides treating existing NFI it would be desirable to prevent NFI. Studies show that before NFI is clinically detectable, nerves often show subclinical damage. Within the ‘Treatment of Early Neuropathy in LEProsy’ (TENLEP) study two double blind randomized controlled trials (RCT) will be carried out: a trial to establish whether prednisolone treatment of 32 weeks duration is more effective than 20 weeks in restoring nerve function in leprosy patients with clinical NFI (Clinical trial) and a trial to determine whether prednisolone treatment of early sub-clinical NFI can prevent clinical NFI (Subclinical trial).
Two RCTs with a follow up of 18 months will be conducted in six centers in Asia. In the Clinical trial leprosy patients with recent (< 6 months) clinical NFI, as determined by Monofilament Test and Voluntary Muscle Test, are included. The primary outcomes are the proportion of patients with restored or improved nerve function. In the Subclinical trial leprosy patients with subclinical neuropathy, as determined by Nerve Conduction Studies (NCS) and/or Warm Detection Threshold (WDT), and without any clinical signs of NFI are randomly allocated to a placebo group or treatment group receiving 20 weeks prednisolone. The primary outcome is the proportion of patients developing clinical NFI. Reliability and normative studies are carried out before the start of the trial.
This study is the first RCT testing a prednisolone regimen with a duration longer than 24 weeks. Also it is the first RCT assessing the effect of prednisolone in the prevention of clinical NFI in patients with established subclinical neuropathy. The TENLEP study will add to the current understanding of neuropathy due to leprosy and provide insight in the effectiveness of prednisolone on the prevention and recovery of NFI in leprosy patients. In this paper we present the research protocols for both Clinical and Subclinical trials and discuss the possible findings and implications.
Netherlands Trial Register: NTR2300
Clinical Trial Registry India: CTRI/2011/09/002022
Leprosy; Prednisolone; Nerve function impairment; Subclinical neuropathy
Recombinant factor VIIa (rFVIIa) may be used for rapid hemostasis in life-threatening hemorrhage. In warfarin-associated intracerebral hemorrhage (wICH), FVIIa use is controversial and may carry significant thromboembolic risks. We compared incidence of baseline thromboembolic risk factors and thromboembolism rates in wICH patients treated with additional rFVIIa to those treated with standard therapy of fresh frozen plasma (FFP) and vitamin K alone.
We identified 45 consecutive wICH patients treated with additional rFVIIa over 5-year period, and 34 consecutive wICH patients treated with standard therapy alone as comparison group. We compared the incidence of post-hemorrhage cardiac and extra-cardiac thromboembolic complications between two treatment groups, and used logistic regression to adjust for significant confounders such as baseline thromboembolic risk factors. We performed secondary analysis comparing the quantity of FFP transfused between two treatment cohorts.
Both rFVIIa-treated and standard therapy-treated wICH patients had a high prevalence of pre-existing thromboembolic diseases including atrial fibrillation (73% vs 68%), deep venous thrombosis (DVT) or pulmonary embolism (PE) (22% vs 18%), coronary artery disease (CAD) (38% vs 32%), and abnormal electrocardiogram (EKG) (78% vs 85%). Troponin elevation following wICH was prevalent in both groups (47% vs 41%). Clinically significant myocardial infarction (MI), defined as troponin > 1.0 ng/dL, occurred in 13% of rFVIIa-treated and 6% of standard therapy-treated patients (p=0.52). Past history of CAD (p=0.0061) and baseline abnormal EKG (p=0.02) were independently associated with clinically significant MI following wICH while rFVIIa use was not. The incidences of DVT/PE (2% vs 9%; p=0.18) and ischemic stroke (2% vs 0%; p=0.38) were similar between two treatment groups. Recombinant FVIIa-treated patients had lower mean INR at 3 (p=0.0001) and 6 hours (p<0.0001) and received fewer units of FFP transfusion (3 vs 5; p=0.003).
Pre-existing thromboembolic risk factors as well as post-hemorrhage troponin elevation are prevalent in wICH patients. Clinically significant MI occurs in up to 13% of wICH patients. rFVIIa use was not associated with increased incidence of clinically significant MI or other venous or arterial thromboembolic events in this wICH cohort.
Activated recombinant factor VII; Intracerebral hemorrhage; Thromboembolism; Warfarin
Many Polio survivors have reduced mobility, pain and fatigue, which make access to conventional forms of aerobic exercise difficult. Inactivity leads to increased risk of health problems, many of which are prevalent among Polio survivors. Aerobic exercise programmes in Polio survivors should utilise stable muscle groups and should be designed to minimise exacerbation of pain and fatigue. A home-based arm ergometry aerobic exercise programme may represent an affordable and accessible exercise modality, incorporating exercise prescription principles in this group.
This is a prospective, single blinded, randomised controlled trial. There are two arms; exercise intervention using arm ergometers and control. Polio survivors meeting eligibility criteria will be recruited and randomly allocated to intervention or control groups. Participants allocated to the intervention group will receive a small arm ergometer and a polar heart rate monitor. They will carry out a home-based moderate intensity (50-70% HRMax) aerobic exercise programme for eight weeks, following instruction by the treating physiotherapist. Assessments will occur at baseline and after eight weeks and will include tests of physical fitness, activity, energy cost of walking, fatigue and quality of life. Clinically feasible assessment tools including the Six Minute Arm Test, the Physical Activity Scale for People with Physical Disabilities questionnaire, the Physiological Cost Index, Fatigue Severity Scale and the SF-36v2 will be utilised.
The efficacy of a home-based arm ergometry programme in Polio survivors will be examined. No previous trial has examined such a programme using a wide range of outcome measures pertinent to Polio survivors. This study will provide new information on the impact of arm ergometry on physical fitness, activity, body composition, fatigue, pain, muscle strength, and health related quality of life. Also, the study will provide information, which at present is lacking, on safety of aerobic exercise in Polio, as potential negative outcomes of activity including loss of muscle strength, increased pain and fatigue will be closely monitored.
Clinicaltrials.gov identifier: NCT01271530
Poliomyelitis; Arm Ergometry; Physical fitness; Fatigue
To explore current status and choices regarding diagnosis and treatment of Parkinson’s disease (PD) among physicians, general neurologists and movement disorders specialists in China via a national survey.
The cross-sectional questionnaire-based survey was conducted from November, 2010 to July, 2011. Six hundreds and twelve doctors from different cities in China were recruited for this study.
68.6% (n=420) and 23.9% (n=146) of doctors have read the national and international guidelines, respectively. There was a larger proportion of movement disorders specialists reading the guidelines, in contrast to physicians and general neurologists (P<0.001). Up to 76.4% (n=465) and 81.8% (n=498) of doctors would choose standard oral levodopa test and conventional MRI(with T1 and T2), respectively; Whereas susceptibility weighed imaging(SWI)(16.1%; n=98), transcranial sonography (TCS) (1.8%; n=11) and functional neuroimaging test, such as single photon emission computed tomography(SPECT) (10.2%; n=62) and positron emission tomography(PET)(13.3%; n=81) were less used for suspected patients with PD in clinical practice. Doctors at different levels or from different hospitals and cities would choose different medication for motor complications and non-motor symptoms of patients with PD, in addition to initial drug selection for newly diagnosed PD. Doctors who had read the guidelines had significantly better knowledge of medication selections for PD under specific circumstances.
Compared with commonly employed standard oral levodopa test and conventional MRI, SWI complements MRI, TCS and functional neuroimaging were less performed for diagnosis of PD in clinical practice in China. The choices of diagnostic methods and therapeutic strategy of PD vary among physicians, general neurologists and movement disorders specialists. Guideline awareness is markedly beneficial to reasonable PD medications strategy in China.
Parkinson’s disease; National survey; Clinical practice guideline; Medication
Behavioral changes in patients with amyotrophic lateral sclerosis (ALS) mirror those found in frontotemporal dementia (FTD). Considering the high rate of neuropsychiatric symptoms found in ALS patients, this paper examines whether caregiver burden is associated with behavioral changes over and above the physical disability of patients with ALS, and if the presence of caregivers’ depression, anxiety and stress also impacts on caregiver burden.
140 caregivers of patients with ALS participated in a postal survey investigating patients’ neuropsychiatric symptoms (Cambridge Behaviour Inventory Revised CBI-R), motor function (Amyotrophic Lateral Sclerosis Functional Rating Scale Revised - ALSFRS-R), caregiver burden (Zarit Burden Interview), and caregiver mood (Depression, Anxiety and Stress Scale- DASS21). Seventy four percent of them were caregivers of patients with limb onset and 25.7% were caregivers of patients with bulbar onset.
Moderate to severe behavioral changes were reported in 10-40% of patients with ALS. The levels of depression, anxiety and stress in the caregivers reached 20%. Burden was high in 48% of the caregivers. The strongest predictor of high caregiver burden was ALS patients’ abnormal behavior rather than physical disability, with an odds ratio of 1.4, followed by caregivers’ stress.
Our study has identified that behavioral changes (e.g. disinhibition, impulsivity) and caregiver stress have greater impact on caregiver burden than level and pattern of physical disability.
ALS; Behavioral changes; FTD; Caregiver burden
In patients with relapsing–remitting multiple sclerosis (RRMS), subcutaneous (sc) interferon (IFN)β-1a and IFNβ-1b have been shown to reduce relapse rates. A formulation of IFNβ-1a has been produced without fetal bovine serum and without human serum albumin as an excipient (not currently approved for use in the US). The objectives of this study were to evaluate tolerability, injection-site redness, subject-reported satisfaction with therapy, and clinical safety and efficacy of the serum-free formulation of IFNβ-1a versus IFNβ-1b in IFNβ-treatment-naïve patients with RRMS. The objectives of the extension phase were to evaluate long-term safety and tolerability of IFNβ-1a.
This randomized, parallel-group, open-label study was conducted at 27 clinical sites in the US. Eligible patients aged 18–60 years were randomized to receive either IFNβ-1a, titrated to 44 μg sc three times weekly (tiw) (n = 65), or IFNβ-1b, titrated to 250 μg sc every other day (n = 64) over 12 weeks. Following this, all patients received IFNβ-1a 44 μg tiw for 82–112 weeks. Primary endpoint was mean change in patient-reported pain, as assessed by visual analog scale (VAS) diary pain score (from 0 mm [no pain] to 100 mm [worst possible pain]) at the injection site, from pre-injection to 30 min post-injection over the first 21 full-dose injections. Secondary assessments included proportion of patients pain-free as recorded by VAS diary and the Short-Form McGill Pain questionnaire VAS.
A total of 129 patients were included in the intent-to-treat analysis. Mean (standard deviation) change in VAS diary pain score was not significantly different between groups, although numerically lower with IFNβ-1a versus IFNβ-1b from pre-injection to immediately post-injection (1.46 [2.93] vs. 4.63 [10.57] mm), 10 min post-injection (0.70 [1.89] vs. 1.89 [5.75] mm), and 30 min post-injection (0.67 [2.32] vs. 1.14 [4.94] mm). Proportion of patients pain-free at all time periods post-injection was also not significantly different between groups. Adverse events were consistent with the known safety profiles of these treatments.
In IFNβ-treatment-naïve patients with RRMS, both the serum-free formulation of IFNβ-1a and IFNβ-1b treatments were generally accompanied by low-level injection-site pain and were well tolerated.
Randomized controlled trial; Interferonβ-1a; Interferonβ-1b; Relapsing–remitting multiple sclerosis; Subcutaneous injections; Injection-site pain; Pain measurement
Little is known about the long-term success of non-drug therapies for treating dementia, especially whether the effects are sustained after therapy ends. Here, we examined the effects of a one-year multimodal therapy 10 months after patients completed the therapy.
This randomised, controlled, single-blind, longitudinal trial involved 61 patients (catamnesis: n = 52) with primary degenerative dementia in five nursing homes in Bavaria, Germany. The highly standardised intervention, MAKS, consisted of motor stimulation, practice of activities of daily living (ADLs), and cognitive stimulation. Each group of 10 patients was treated for 2 h, 6 days a week for 12 months. Control patients received standard nursing home care. At baseline, at the end of therapy (month 12), and 10 months thereafter (month 22), cognitive functioning was assessed using the cognitive subscale of the Alzheimer’s Disease Assessment Scale, and the ability to perform ADLs was assessed using the Erlangen Test of Activities of Daily Living.
During the therapy phase, the MAKS patients maintained their cognitive function and ability to carry out ADLs. After the end of therapy, both the control and the MAKS groups deteriorated in both their cognitive function (control, p = 0.02; MAKS, p < 0.001) and their ability to carry out ADLs (control, p < 0.001; MAKS, p = 0.001). However, in a confound-adjusted multiple regression model, the ability of the MAKS group to perform ADLs remained significantly higher than that of the control group even 10 months after the end of therapy (H0: βMAKS + βMAKS month 22 = 0; χ2 = 3.8568, p = 0.0496). Cohen’s d for the difference between the two groups in ADLs and cognitive abilities 10 months after the end of therapy was 0.40 and 0.22, respectively.
A multimodal non-drug therapy of dementia resulted in stabilisation of the ability to perform ADLs, even beyond the end of therapy. To prevent functional decline for as long as possible, therapy should be performed continuously until the benefit for the patient ends. Follow-up studies on larger numbers of patients are needed to definitively confirm these results.
http://www.isrctn.com Identifier: ISRCTN87391496
Dementia; Non-drug-therapy; RCT; Follow-up study; Nursing home
Posterior reversible encephalopathy syndrome (PRES) has been increasingly identified in patients with systemic lupus erythematosus (SLE) owing to the advance in neuroimaging techniques. Prompt diagnosis is pivotal to improve its outcome. To analyze the clinical and radiographic profile of PRES in patients with SLE and search for the appropriate treatment strategy PRES in SLE.
SLE patients who fulfilled the diagnostic criteria for PRES from August 2008 to January 2011 were evaluated at baseline, and followed to determine clinical outcomes. Data were analysis on clinical characteristics, laboratory abnormalities, treatment details, and outcomes.
Ten episodes of PRES in patients with SLE were identified. All patients were female, mean age of onset was 22.93 ± 2.48 years, and SLEDAI at the onset of PRES were 25.8 ± 5.7. All cases had acute onset of headache, altered mental status, stupor, vomiting, cortical blindness and seizures. Neurological symptoms were the initial manifestation of SLE in three cases. Head magnetic resonance imaging (MRI) demonstrated posterior white matter edema involving the parietal, temporal and occipital lobes, which were more conspicuous on T2 weighted spin echo and diffusion-weighted MR imaging (DWI) than on computed tomography (CT) scan. Complete clinical and radiographic recovery was observed in 8 patients after prompt treatment with corticosteroids.
PRES might be due to lupus per se besides other traditional causative factors such as hypertension. PRES might be an underestimated variant of “reversible neurological deficits” in SLE. Prompt recognition and timely management is important to prevent permanent neurological deficits.
Systemic lupus erythematosus; Neuropsychiatric lupus; Posterior reversible encephalopathy syndrome
As low and middle-income countries such as Vietnam experience the health transition from infectious to chronic diseases, the morbidity and mortality from stroke will rise. In line with the recommendation of the Institute of Medicine’s report on “Promoting Cardiovascular Health in the Developing World” to “improve local data”, we sought to investigate patient characteristics and clinical predictors of mortality among stroke inpatients at Da Nang Hospital in Vietnam.
A stroke registry was developed and implemented at Da Nang Hospital utilizing the World Health Organization’s Stroke STEPS instrument for data collection.
754 patients were hospitalized for stroke from March 2010 through February 2011 and admitted to either the intensive care unit or cardiology ward. Mean age was 65 years, and 39% were female. Nearly 50% of strokes were hemorrhagic. At 28-day follow-up, 51.0% of patients with hemorrhagic stroke died whereas 20.3% of patients with ischemic stroke died. A number of factors were independently associated with 28-day mortality; the two strongest independent predictors were depressed level of consciousness on presentation and hemorrhagic stroke type. While virtually all patients completed a CT during the admission, evidence-based processes of care such as anti-thrombotic therapy and carotid ultrasound for ischemic stroke patients were underutilized.
This cohort study highlights the high mortality due in part to the large proportion of hemorrhagic strokes in Vietnam. Lack of hypertension awareness and standards of care exacerbated clinical outcomes. Numerous opportunities for simple, inexpensive interventions to improve outcomes or reduce recurrent stroke have been identified.
Hemorrhage; Ischemia; Mortality; Risk factors; Stroke
The purpose of this study was to examine associations between cardiovascular risk factors and cognitive ability in middle aged and elderly Lithuanian urban population.
Data from the survey performed in the framework of the HAPIEE (Health, Alcohol, Psychosocial Factors in Eastern Europe) study were presented. A random sample of 7,087 individuals aged 45–72 years was screened in 2006–2008.
The scores of immediate recall and delayed verbal recall, cognitive speed and attention were significantly lower in men than in women; yet numerical ability scores were higher in men. Significant associations between lowered cognitive functions and previous stroke (in male OR = 2.52; 95% CI = 1.75-3.64; in female OR = 2.45; 95% CI = 1.75, 3.64) as well as ischemic heart disease history (among male OR = 1.28; 95% CI = 1.03-1.60) have been determined. Higher level of physical activity in leisure time (among female OR = 1.32; 95% CI = 1.03-1.69), poor self-rated health (among male OR = 1.57; 95% CI = 1.15-2.14) and poor quality of life (in male OR = 1.67; 95% CI = 1.07-2.61; in female OR = 2.81; 95% CI = 1.92-4.11) were related to lowered cognitive function.
The findings of the study suggest that associations between cardiovascular risk factors and lowered cognitive function among healthy middle-aged and elderly adults strongly depend on gender.
The burden of cognitive impairment among school children from developing communities is under reported due to lack of culturally appropriate screening tools. The objective of this study was to validate a culturally modified short form of the McCarthy Scales of Children Abilities (MSCA) in school children aged 6–8 years from varied backgrounds.
One hundred and one children aged 6–8 years attending mainstream classes were enrolled cross-sectionally from three schools: one rural and two urban. Two assessments were conducted on each child and the Short form MSCA was compared to an independent assessment by the educational psychologist.
When comparing the results of the MSCA to local standard at -2SD, -1.5 SD and -1SD the sensitivity rates ranged from 17 to 50% with lower sensitivity at -2SD cut-off point. Specificity rates had less variation ranging from 95% to 100%. The number of children identified with cognitive impairment using -2SD, -1.5SD and -1SD below the mean for MSCA as a cut-off point were 3(3%), 7(7%) and 13(13%) respectively while the psychologist identified 18 (18%). The overall mean score on MSCA was 103 (SD 15). The rural children tended to score significantly lower marks compared to their peers from urban areas, mean (SD) 98(15) and 107(15) respectively, p=0.006. There was no difference in the mean (SD) scores between boys and girls, 103(17) and 103(15) respectively, p=0.995.
The culturally modified short form MSCA showed high specificity but low sensitivity. Prevalence of cognitive impairment among 6 to 8 year children was 3%. This figure is high when compared to developed communities.
To investigate to what extent Alzheimer's Disease (AD) affects Resting State activity, the possible impairment of independent electrophysiological parameters was determined in Eye-open and Eye-closed Conditions. Specifically, Flash-Visual Evoked Potential (F-VEP) and quantitative EEG (q-EEG) were examined to establish whether abnormalities of the former were systematically associated with changes of the latter.
Concurrently recorded F-VEP and q-EEG were comparatively analysed under Eye-open and Eye-closed Conditions in 11 Controls and 19 AD patients presenting a normal Pattern-Visual Evoked Potential (P-VEP). Between Condition differences in latencies of P2 component were matched to variations in spectral components of q-EEG.
P2 latency increased in 10 AD patients with Abnormal Latency (AD-AL) under Eye-closed Condition. In these patients reduction of alpha activity joined an increased delta power so that their spectral profile equated that recorded under Eye-open Condition. On the opposite, in Controls as well as in AD patients with Normal P2 Latency (AD-NL) spectral profiles recorded under Eye-open and Eye-closed Conditions significantly differed from each other. At the baseline, under Eye-open Condition, the spectra overlapped each other in the three Groups.
Under Eye-closed Condition AD patients may present a significant change in both F-VEP latency and EEG rhythm modulation. The presence of concurrent changes of independent parameters suggests that the neurodegenerative process can impair a control system active in Eye-closed Condition which the electrophysiological parameters depend upon. F-VEP can be viewed as a reliable marker of such impairment.
Alzheimer's disease; F-VEP; q-EEG; Resting state; Eye-closed; Eye-open; Dementia
It is difficult for neurosurgeons to perceive the complex three-dimensional anatomical relationships in the sellar region.
To investigate the value of using a virtual reality system for planning resection of sellar region tumors. The study included 60 patients with sellar tumors. All patients underwent computed tomography angiography, MRI-T1W1, and contrast enhanced MRI-T1W1 image sequence scanning. The CT and MRI scanning data were collected and then imported into a Dextroscope imaging workstation, a virtual reality system that allows structures to be viewed stereoscopically. During preoperative assessment, typical images for each patient were chosen and printed out for use by the surgeons as references during surgery.
All sellar tumor models clearly displayed bone, the internal carotid artery, circle of Willis and its branches, the optic nerve and chiasm, ventricular system, tumor, brain, soft tissue and adjacent structures. Depending on the location of the tumors, we simulated the transmononasal sphenoid sinus approach, transpterional approach, and other approaches. Eleven surgeons who used virtual reality models completed a survey questionnaire. Nine of the participants said that the virtual reality images were superior to other images but that other images needed to be used in combination with the virtual reality images.
The three-dimensional virtual reality models were helpful for individualized planning of surgery in the sellar region. Virtual reality appears to be promising as a valuable tool for sellar region surgery in the future.
Dextroscope; Three-dimensional reconstructionm; Transsphenoidal approach; Sellar tumor; Surgery simulation
We report a female patient with familial Creutzfeldt-Jakob disease with V180I mutation (fCJD with V180I), who was serially followed up with magnetic resonance imaging (MRI) and electroencephalogram (EEG) for up to four years.
At 6 months after the onset, diffusion-weighted images (DWI) and fluid-attenuated inversion recovery (FLAIR) of brain MRI revealed an increased signal intensity in the bilateral frontal, temporal, and parietal cerebral cortex with left dominancy except for the occipital lobe. However, her follow-up MRI at four years showed the high-signal regions spreading to the occipital cerebral cortex in DWI and FLAIR images, and bilateral frontal cerebral white matter in FLAIR images. EEG showed a progressive and general slow high-voltage rhythm from 7–8 to 3–5 c/s over four years, without evidence of periodic synchronous discharge. These findings correspond to the symptom progression even after akinetic mutism at 18 months.
We suggest that serial MRI and EEG examinations are useful for early diagnosis of fCJD with V180I and for monitoring disease progression.
Familial Creutzfeldt-Jakob disease; V180I; Magnetic resonance imaging; Electroencephalogram
Reduction of retinal nerve fibre layer (RNFL) thickness was shown as part of the neurodegenerative process in a range of different neurodegenerative pathologies including Alzheimer′s disease (AD), idiopathic Parkinson’s disease (PD), spinocerebellar ataxia (SCA) and multiple system atrophy (MSA). To further clarify the specificity of RNFL thinning as a potential marker of neurodegenerative diseases we investigated RNFL thickness in Hereditary Spastic Paraplegia (HSP), an axonal, length-dependent neurodegenerative pathology of the upper motor neurons.
Spectral domain optical coherence tomography (OCT) was performed in 28 HSP patients (clinically: pure HSP = 22, complicated HSP = 6; genetic subtypes: SPG4 = 13, SPG5 = 1, SPG7 = 3, genetically unclassified: 11) to quantify peripapillary RNFL thickness. Standardized examination assessed duration of disease, dependency on assistive walking aids and severity of symptoms quantified with Spastic Paraplegia Rating Scale (SPRS).
HSP patients demonstrated no significant thinning of global RNFL (pglobal = 0.61). Subgroup analysis revealed significant reduction in temporal and temporal inferior sectors for patients with complex (p<0.05) but not pure HSP phenotypes. Two of three SPG7-patients showed severe temporal and temporal inferior RNFL loss. Disease duration, age and severity of symptoms were not significantly correlated with global RNFL thickness.
Clinically pure HSP patients feature no significant reduction in RNFL, whereas complex phenotypes display an abnormal thinning of temporal and temporal inferior RNFL. Our data indicate that RNFL thinning does not occur unspecifically in all neurodegenerative diseases but is in HSP restricted to subtypes with multisystemic degeneration.
Hereditary spastic paraplegia (HSP); Spastic paraplegia rating scale (SPRS); Eye; Retinal nerve fibres; Optical coherence tomography (OCT)
The autophagic vacuolar myopathies (AVM) are a group of inherited myopathies defined by the presence of autophagic vacuoles in pathological muscle specimens. AVM can be categorized into three groups: acid maltase deficiency, myopathies characterized by autophagic vacuoles with unique sarcolemmal features, and rimmed vacuolar myopathies (RVM). While the pathogeneses of these conditions are still being elucidated, some drugs (e.g., chloroquine, its analog, hydroxychloroquine, and colchicine) can also cause AVM. Minocycline is a disease-modifying anti-rheumatic drug that may be used in the treatment of rheumatoid arthritis (RA). Here, we describe the first case of minocycline-associated AVM with rimmed vacuole formation.
A 75-year-old woman suffering from RA has been continuously treated with minocycline (200 mg/day) for the past 7 years. During this time, she developed a myopathy that predominantly affected her lower limbs. Histological studies of biopsied muscle revealed scattered atrophic myofibers with rimmed vacuoles that contained pigment granules. Histochemical staining revealed that the pigment comprised both iron and melanin, which is consistent with type II minocycline-induced cutaneous pigmentation. Under electron microscopy, autophagic vacuoles were consistently observed in association with numerous collections of pigment granules.
This is the first report of minocycline-induced pigmentation in skeletal muscle. The strong association between autophagic vacuoles and the accumulation of minocycline-induced pigments suggest that long-term minocycline treatment induced pigment accumulation, leading to elevation of autophagic activity and RVM. It might also be possible that minocycline directly activated autophagy, as the observed pigments are known to form complexes containing minocycline and/or its metabolites. As long-term minocycline treatment is expected to be used more widely in the future, we must draw attention to this adverse effect.
Minocycline; Autophagic vacuole; Rimmed vacuolar myopathy; Minocycline-induced pigmentation; Rheumatoid arthritis
Cognitive change is prevalent in patients with amyotrophic lateral sclerosis (ALS), but still lack a widely accepted and sensitive screening method. In this study, we try to find a sensitive screening battery for detecting subtle cognitive deficits in patients with ALS.
Eighty consecutive ALS patients and 57 matched normal controls underwent the Mini-Mental Status Examination (MMSE), the verbal fluency test (VFT), the Stroop Color Word Interference Test (CWT), and the prospective memory (PM) tests, including event-based (EBPM) and time-based (TBPM).
The patients did not differ from the controls in the MMSE, the VFT and the CWT. By contrast, statistically significant differences were found in the PM tests (EBPM: P=0.043; TBPM: P<0.001). More interestingly, TBPM was more sensitive than EBPM in the early-phase patients.
Prefrontal lobar dysfunction does exist among ALS patients and may spread from the medial to the lateral region. The PM tests seem more sensitive in ALS patients with frontotemporal dysfunction than are the classical cognitive measures.
Stroke represents one of the most costly and long-term disabling conditions in adulthood worldwide and there is a need to determine the effectiveness of rehabilitation programs in the late phase after stroke. Limited scientific support exists for training incorporating rhythm and music as well as therapeutic riding and well-designed trials to determine the effectiveness of these treatment modalities are warranted.
A single blinded three-armed randomized controlled trial is described with the aim to evaluate whether it is possible to improve the overall health status and functioning of individuals in the late phase of stroke (1-5 years after stroke) through a rhythm and music-based therapy program or therapeutic riding. About 120 individuals will be consecutively and randomly allocated to one of three groups: (T1) rhythm and music-based therapy program; (T2) therapeutic riding; or (T3) control group receiving the T1 training program a year later. Evaluation is conducted prior to and after the 12-week long intervention as well as three and six months later. The evaluation comprises a comprehensive functional and cognitive assessment (both qualitative and quantitative), and questionnaires. Based on the International classification of functioning, disability, and health (ICF), the outcome measures are classified into six comprehensive domains, with participation as the primary outcome measure assessed by the Stroke Impact Scale (SIS, version 2.0.). The secondary outcome measures are grouped within the following domains: body function, activity, environmental factors and personal factors. Life satisfaction and health related quality of life constitute an additional domain.
A total of 84 participants were randomised and have completed the intervention. Recruitment proceeds and follow-up is on-going, trial results are expected in early 2014.
This study will ascertain whether any of the two intervention programs can improve overall health status and functioning in the late phase of stroke. A positive outcome would increase the scientific basis for the use of such interventions in the late phase after stroke.
Clinical Trials.gov Identifier: NCT01372059
Acute symptomatic hypoglycaemia is a differential diagnosis in patients presenting with stroke-like neurological impairment, but few textbooks describe the full brain imaging appearances. We systematically reviewed the literature to identify how often hypoglycaemia may mimic ischaemic stroke on imaging, common patterns and relationships with hypoglycaemia severity, duration, clinical outcome and add two new cases.
We searched EMBASE and Medline databases for papers reporting imaging in adults with symptomatic hypoglycaemia. We analysed the clinical presentation, outcome, brain imaging findings, duration and severity of hypoglycaemia, time course of lesion appearance, including two new cases.
We found 42 papers describing computed tomography or magnetic resonance imaging in 65 patients, plus our two cases with symptomatic hypoglycaemia. Imaging abnormalities on computed tomography and magnetic resonance were uni or bilateral, cortical or sub-cortical. Thirteen (20%) mimicked cortical or lacunar stroke. Acute lesions had restricted diffusion on magnetic resonance or low attenuation on computed tomography, plus swelling; older lesions showed focal atrophy or disappeared, as with ischaemic stroke. The association between the depth or duration of hypoglycaemia, the severity or extent of neurological deficit, and the imaging abnormalities, was weak.
Imaging abnormalities in patients with hypoglycaemia are uncommon but very variable, weakly associated with neurological deficit, and about a fifth mimic acute ischaemic stroke. Blood glucose testing should be routine in all patients with acute neurological impairment and hypoglycaemia should be included in the differential diagnosis of imaging appearances in patients presenting with acute stroke.
Hypoglycaemia; Ischaemic stroke; MRI; CT; Lesions