Duchenne muscular dystrophy (DMD) is an X-linked muscular dystrophy known to affect one in 3600 live male births and leads to progressive proximal muscle weakness in the first years, and orthopaedic, respiratory and cardiac complications in the teens. Typically the patients would lose the ability of ambulation at around the age of 10 years and decease in young adulthood if untreated. In recent years, corticosteroid treatment has been proved to prolong ambulation, improve quality of life and survival. Moreover, it has also shown efficacy in reducing the degree of scoliosis and improving cardiopulmonary function.
In the paper by Ricotti et al,
Cerebral microbleeds (CMB) are focal haemosiderin deposits that result from minimal blood leakage from damaged small vessels, and they can be regarded as markers of pathological vascular changes. In addition to their association with small vessel disease, CMB have also been pathologically linked to cerebral amyloid angiopathy.
Stam and Vermeulen
Bleuler was of course correct that many remedies of the day were unproven and likely to be ineffective or even dangerous, and that their apparent benefits could be attributed to the enthusiasm of pioneers, suggestion and spontaneous recovery. It is fascinating to read that he was one of the first doctors to appreciate the problem of publication bias, the value of controlled trials and randomisation (even if by alternate allocation), the need for large studies,...]]>
The title of the book sounds too good in German not to quote it fully: Das Autistisch-Undisziplinierte Denken in der Medizin und seine Überwindung. This provocative title can be translated as Autistic and undisciplined thinking in medicine, and how to overcome it. In the first chapter, Bleuler asserts that many of the cognitive habits of doctors can be compared with...]]>
Many guidelines recommend urgent intervention for patients with two or more transient ischaemic attacks (TIAs) within 7 days (multiple TIAs) to reduce the early risk of stroke.
To determine whether all patients with multiple TIAs have the same high early risk of stroke.
Between April 2008 and December 2009, we included 1255 consecutive patients with a TIA from 30 Spanish stroke centres (PROMAPA study). We prospectively recorded clinical characteristics. We also determined the short-term risk of stroke (at 7 and 90 days). Aetiology was categorised using the TOAST (Trial of Org 10172 in Acute Stroke Treatment) classification.
Clinical variables and extracranial vascular imaging were available and assessed in 1137/1255 (90.6%) patients. 7-Day and 90-day stroke risk were 2.6% and 3.8%, respectively. Large-artery atherosclerosis (LAA) was confirmed in 190 (16.7%) patients. Multiple TIAs were seen in 274 (24.1%) patients. Duration <1 h (OR=2.97, 95% CI 2.20 to 4.01, p<0.001), LAA (OR=1.92, 95% CI 1.35 to 2.72, p<0.001) and motor weakness (OR=1.37, 95% CI 1.03 to 1.81, p=0.031) were independent predictors of multiple TIAs. The subsequent risk of stroke in these patients at 7 and 90 days was significantly higher than the risk after a single TIA (5.9% vs 1.5%, p<0.001 and 6.8% vs 3.0%, respectively). In the logistic regression model, among patients with multiple TIAs, no variables remained as independent predictors of stroke recurrence.
According to our results, multiple TIAs within 7 days are associated with a greater subsequent risk of stroke than after a single TIA. Nevertheless, we found no independent predictor of stroke recurrence among these patients.
The need for stroke care is escalating with an ageing population, yet methods to estimate the delivery of effective care across countries are not standardised or robust. Associations between quality and intensity of care and stroke outcomes are often assumed but have not been clearly demonstrated.
To examine variations in acute care processes across six European populations and investigate associations between the delivery of care and survival.
Data were obtained from population-based stroke registers of six centres in France, Lithuania, UK, Spain, Poland and Italy between 2004 and 2006 with follow-up for 1 year. Variations in the delivery of care (stroke unit, multidisciplinary team and acute drug treatments) were analysed adjusting for case mix and sociodemographic factors using logistic regression methods. Unadjusted and adjusted survival probabilities were estimated and stratified by levels of Organised Care Index.
Of 1918 patients with a first-ever stroke registered, 30.7% spent more than 50% of their hospital stay in a stroke unit (13.9–65.4%) among centres with a stroke unit available. The percentage of patients assessed by a stroke physician varied between 7.1% and 96.6%. There were significant variations after adjustment for confounders, in the organisation of care across populations. Significantly higher probabilities of survival (p<0.01) were associated with increased organisational care.
This European study demonstrated associations between delivery of care and stroke outcomes. The implementation of evidence-based interventions is suboptimal and understanding better ways to implement these interventions in different healthcare settings should be a priority for health systems.
CT perfusion (CTP) is rapid and accessible for emergency ischaemic stroke diagnosis. The feasibility of introducing CTP and diagnostic accuracy versus non-contrast CT (NCCT) in a tertiary hospital were assessed.
All patients presenting <9 h from stroke onset or with wake-up stroke were eligible for CTP (Siemens 16-slice scanner, 2x24 mm slabs) unless they had estimated glomerular filtration rate (eGFR)<50 ml/min or diabetes with unknown eGFR. NCCT was assessed by a radiologist and stroke neurologist for early ischaemic change and hyperdense arteries. CTP was assessed for prolonged time to peak and reduced cerebral blood flow. Technical adequacy was defined as 2 CTP slabs of sufficient quality to diagnose stroke.
Between January 2009 and September 2011, 1152 ischaemic stroke patients were admitted, 475 (41%) were <9 h/wake-up onset. Of these, 276 (58%) had CTP. Reasons for not performing CTP were diabetes with unknown eGFR (48 (10%)), known kidney disease (36 (8%)), established infarct on NCCT (27 (6%)), posterior circulation syndrome (25 (5%)) and patient motion/instability (16 (3%)). Clinician discretion excluded a further 47 (10%). CTP was more frequently diagnostic than NCCT (80% vs 50%, p<0.001). Non-diagnostic CTP was due to lacunar infarction (28 (10%)), infarct outside slab coverage (21 (8%)), technical failure (4 (1%)) and reperfusion (2 (0.7%)). Normal CTP in 86/87 patients with stroke mimics supported withholding tissue plasminogen activator. CTP technical adequacy improved from 56% to 86% (p<0.001) after the first 6 months. Median time for NCCT/CTP/arch-vertex CT angiogram (including processing and interpretation) was 12 min. No clinically significant contrast nephropathy occurred.
CTP in suspected stroke is widely applicable, rapid and increases diagnostic confidence.
The overall incidence of aneurysmal subarachnoid haemorrhage (aSAH) in western populations is around 9 per 100 000 person-years, which confers to a lifetime risk of around half per cent. Risk factors for aSAH are usually expressed as relative risks and suggest that absolute risks vary considerably according to risk factor profiles, but such estimates are lacking. We aimed to estimate incidence and lifetime risks of aSAH according to risk factor profiles.
We used data from 250 patients admitted with aSAH and 574 sex-matched and age-matched controls, who were randomly retrieved from general practitioners files. We determined independent prognostic factors with multivariable logistic regression analyses and assessed discriminatory performance using the area under the receiver operating characteristic curve. Based on the prognostic model we predicted incidences and lifetime risks of aSAH for different risk factor profiles.
The four strongest independent predictors for aSAH, namely current smoking (OR 6.0; 95% CI 4.1 to 8.6), a positive family history for aSAH (4.0; 95% CI 2.3 to 7.0), hypertension (2.4; 95% CI 1.5 to 3.8) and hypercholesterolaemia (0.2; 95% CI 0.1 to 0.4), were used in the final prediction model. This model had an area under the receiver operating characteristic curve of 0.73 (95% CI 0.69 to 0.76). Depending on sex, age and the four predictors, the incidence of aSAH ranged from 0.4/100 000 to 298/100 000 person-years and lifetime risk between 0.02% and 7.2%.
The incidence and lifetime risk of aSAH in the general population varies widely according to risk factor profiles. Whether persons with high risks benefit from screening should be assessed in cost-effectiveness studies.
Small vessel disease (mainly hypertensive arteriopathy and cerebral amyloid angiopathy (CAA)) is an important cause of spontaneous intracerebral haemorrhage (ICH), a devastating and still poorly understood stroke type. Enlarged perivascular spaces (EPVS) are a promising neuroimaging marker of small vessel disease. Based on the underlying arteriopathy distributions, we hypothesised that severe centrum semiovale EPVS are more common in lobar ICH attributed to CAA than other ICH. We evaluated EPVS prevalence, severity and distribution, and their clinical–radiological associations.
Retrospective multicentre cohort study of 121 ICH patients. Clinical information was obtained using standardised forms. Basal ganglia and centrum semiovale EPVS on T2-weighted MRI (graded 0–4 (>40 EPVS)), white-matter changes, cerebral microbleeds (CMBs) and lacunes were rated using validated scales.
Patients with probable or possible CAA (n=76) had a higher prevalence of severe (>40) centrum semiovale EPVS compared with other ICH patients (35.5% vs 17.8%; p=0.041). In logistic regression age (OR: 1.43; 95% CI 1.01 to 2.02; p=0.045), deep CMBs (OR: 3.27; 95% CI 1.27 to 8.45; p=0.014) and mean white-matter changes score (OR: 1.29; 95% CI 1.17 to 1.43; p<0.0001) were independently associated with increased basal ganglia EPVS severity; only age was associated with increased centrum semiovale EPVS severity (OR: 1.50; 95% CI 1.08 to 2.10; p=0.017).
EPVS are common in ICH. Different mechanisms may account for EPVS according to their anatomical distribution. Severe centrum semiovale EPVS may be secondary to, and indicative of, CAA with value as a new neuroimaging marker. By contrast, basal ganglia EPVS severity is associated with markers of hypertensive arteriopathy.
Epilepsy surgery within the temporal lobe of the language dominant hemisphere bears the risk of postoperative verbal memory decline. As surgical procedures have become more tailored, the question has arisen, which type of resection within the temporal lobe is more favourable for memory outcome. Since the hippocampus (HC) is known to play an essential role for long-term memory, we examined whether HC sparing resections help to preserve verbal memory functions.
We retrospectively analysed neuropsychological data (prior to and 1 year after surgery) of patients undergoing either HC sparing resections (HC-S, N=65) or resections including the hippocampus (HC-R, N=62).
Prior to surgery, the HC-R group showed worse memory performance as compared to HC-S patients. Both patient groups revealed further deterioration over time, but in verbal learning HC-R patients demonstrated a stronger decline. Predictors for verbal learning decline were left-sided surgery, better preoperative performance, higher age at surgery, hippocampus resection, and lower preoperative IQ. In patients with spared HC, resection of the left-sided parahippocampal gyrus was rather accompanied by a decline in verbal learning performance. For visual memory, better preoperative performance best predicted deterioration after surgery. Seizure outcome was comparable between the two groups (HC-S: 66%, HC-R: 65% Engel 1a).
Temporal lobe resections within the language dominant hemisphere can be accompanied by a decline in verbal memory performance, even if the HC is spared. Yet, HC sparing surgery is associated with a benefit in verbal learning performance. These results can help when counselling patients prior to epilepsy surgery.
Degeneration of dopaminergic neurons in the substantia nigra (SN) pars compacta is the primary cause of idiopathic Parkinson's disease (iPD). In early stages of disease in particular, presentation of symptoms is non-specific leading to difficulties in differentiating between iPD and atypical parkinsonian syndromes (aPS). The aim of this study was to evaluate the feasibility of three-dimensional magnetic resonance spectroscopic imaging (MRSI) of the SN region for differentiation between iPD and aPS.
20 patients with iPD, 10 with aPS and 22 controls were examined on a 3 T MR scanner using three-dimensional MRSI with a voxel size of 0.252 ml and an echo time of 30 ms. Excitation volume was positioned in such a way that in each hemisphere 1 voxel defines the rostral and 1 voxel the caudal SN region. Using a fully automatic spectra evaluation, the metabolite ratios of N-acetyl aspartate/creatine (NAA/Cr) were calculated.
In all cases spectra with good quality were obtained. Differences in rostral to caudal NAA/Cr ratios were significant between controls and iPD patients, as well as between iPD and aPS patients (p<0.001 for both). For controls, rostral NAA/Cr was greater than caudal, whereas in iPD patients this ratio was reversed. aPS patients showed similar ratios as controls.
Typical reversed rostral to caudal NAA/Cr ratios in iPD patients suggests that they could be linked to specific pathology of neuronal loss in the SN pars compacta. Therefore, the results suggest that MRSI may support the differential diagnosis of patients with clinically unclassifiable parkinsonian syndromes who do not yet fulfil the established clinical criteria.
To study the prevalence of and associated factors for cognitive impairment and dementia in community dwelling Chinese from Singapore.
This study includes Chinese subjects from the Epidemiology of Dementia in Singapore (EDIS) study, aged ≥60 years, who underwent comprehensive examinations, including cognitive screening with the locally validated Abbreviated Mental Test and Progressive Forgetfulness Questionnaire. Screen positive participants subsequently underwent extensive neuropsychological testing and cerebral MRI. Cognitive impairment no dementia (CIND) and dementia were diagnosed according to internationally accepted criteria. The prevalence of cognitive impairment and dementia were computed per 5 year age categories and gender. To examine the relationship between baseline associated factors and cognitive impairment, we used logistic regression models to compute odd ratios with 95% CI.
1538 Chinese subjects, aged ≥60 years, underwent cognitive screening: 171 (15.2%) were diagnosed with any cognitive impairment, of whom 84 were CIND mild, 80 CIND moderate and seven had dementia. The overall age adjusted prevalence of CIND mild was 7.2%; CIND moderate/dementia was 7.9%. The prevalence increased with age, from 5.9% in those aged 60–64 years to 31.3% in those aged 75–79 years and 44.1% in those aged ≥80 years. Multivariate analysis revealed age, diabetes and hyperlipidaemia to be independently associated with cognitive impairment.
In present study, the overall prevalence of cognitive impairment and dementia in Chinese was 15.2%, which is in the same range as the prevalence reported in Caucasian and other Asian populations.
Cerebral microbleeds (MBs), defined as haemorrhagic microvascular lesions or microangiopathy in the brain, have traditionally been considered clinically silent. Recent studies, however, suggest that MBs are associated with a decline in cognitive function.
To determine whether an association between MBs and cognitive function exists, we conducted a systematic review of the literature using the Cochrane Library, MEDLINE, EMBASE and the China National Knowledge Infrastructure database. We also searched the reference lists of relevant studies and review articles.
A total of seven studies were included. Qualitative meta-analysis of two studies suggested that the presence of MBs was significantly associated with cognitive impairment, while quantitative meta-analysis revealed an association between MBs and cognitive dysfunction in two studies (OR 3.06, 95% CI1.59 to 5.89) and implicated MBs as important in cognitive function decline in three other studies (standardised mean difference –1.06, 95% CI –2.10 to –0.02). MBs in the frontal or temporal region and the basal ganglia might also be related to cognitive dysfunction.
These results suggest that rather than being clinically silent, cerebral MBs might be a factor inducing cognitive function decline.
To assess the current use of glucocorticoids (GCs) in Duchenne muscular dystrophy in the UK, and compare the benefits and the adverse events of daily versus intermittent prednisolone regimens.
A prospective longitudinal observational study across 17 neuromuscular centres in the UK of 360 boys aged 3–15 years with confirmed Duchenne muscular dystrophy who were treated with daily or intermittent (10 days on/10 days off) prednisolone for a mean duration of treatment of 4 years.
The median loss of ambulation was 12 years in intermittent and 14.5 years in daily treatment; the HR for intermittent treatment was 1.57 (95% CI 0.87 to 2.82). A fitted multilevel model comparing the intermittent and daily regiments for the NorthStar Ambulatory Assessment demonstrated a divergence after 7 years of age, with boys on an intermittent regimen declining faster (p<0.001). Moderate to severe side effects were more commonly reported and observed in the daily regimen, including Cushingoid features, adverse behavioural events and hypertension. Body mass index mean z score was higher in the daily regimen (1.99, 95% CI 1.79 to 2.19) than in the intermittent regimen (1.51, 95% CI 1.27 to 1.75). Height restriction was more severe in the daily regimen (mean z score –1.77, 95% CI –1.79 to –2.19) than in the intermittent regimen (mean z score –0.70, 95% CI –0.90 to –0.49).
Our study provides a framework for providing information to patients with Duchenne muscular dystrophy and their families when introducing GC therapy. The study also highlights the importance of collecting longitudinal natural history data on patients treated according to standardised protocols, and clearly identifies the benefits and the side-effect profile of two treatment regimens, which will help with informed choices and implementation of targeted surveillance.
A 54-year-old healthy man was admitted to our hospital with acute dysarthria and mild impairment in swallowing and tongue movements, which he had noticed 2 days before. He was not taking any drugs, and his medical history was unremarkable except for mild hypertension (145/95 mm Hg). He denied prior trauma, fever, facial pain, headache or any other symptoms.
Physical examination showed mild dysarthria and left-sided tongue deviation when the patient poked his tongue out, which was consistent with left hypoglossal nerve palsy (
Biochemical analyses and complete blood cell count were normal. Microbiological and immunological studies, respectively, excluded active viral infection and immune disorders. A cranial angiographic MRI, performed 2 weeks after onset of symptoms, showed an arterial dissection located at the distal segment of the left internal carotid artery,...]]>
Patients eligible for this study were referred to the outpatient department or day clinic for neurology at the Academic Medical Center (AMC) in Amsterdam for the first time and with neurological symptoms which could not be explained by neurological disease (FNS group). Patients with the following...]]>
The diagnosis of adult-onset primary dystonia (AOPD) is mainly clinical, but requires the exclusion of any secondary causes. AOPD is characterised by sustained involuntary muscle contraction resulting in one or more body parts moved away from their neutral position. No other neurological sign is observed, apart from tremor. The 1998 Movement Disorder Society Consensus on Tremor states indeed that tremor and dystonia can be associated, defining the tremor affecting a dystonic body part as ‘dystonic tremor’, and the tremor affecting a non-dystonic body part as ‘tremor associated with dystonia’.