Maarten Schrooten

Treatment Time-Specific Number Needed to Treat Estimates for Tissue Plasminogen Activator Therapy in Acute Stroke Based on Shifts Over the Entire Range of the Modified Rankin Scale

Background and Purpose— To make informed treatment decisions, patients and physicians need to be aware of the benefits and risks of a proposed treatment. The number needed to treat (NNT) for benefit and harm are intuitive and statistically valid measures to describe a treatment effect. The aim of this study is to calculate treatment time-specific NNT estimates based on shifts over the entire spectrum of clinically relevant functional outcomes. Methods— The pooled data set of the first 6 major randomized acute stroke trials of intravenous tissue plasminogen activator was used for this study. The data were stratified by 90-minute treatment time windows. NNT for benefit and NNT for harm estimates were determined based on expert generation of joint outcome distribution tables. NNT for benefit estimates were also calculated based on joint outcome distribution tables generated by a computer model. Results— NNT for benefit estimates based on the expert panel were 3.6 for patients treated between 0 and 90 minutes, 4.3 with treatment between 91 and 180 minutes, 5.9 with treatment between 181 and 270 minutes, and 19.3 with treatment between 271 and 360 minutes. The computer simulation yielded very similar results. The NNT for harm estimates for the corresponding time intervals are 65, 38, 30, and 14. Conclusions— Up to 4½ hours after symptom onset, tissue plasminogen activator therapy is associated with more benefit than harm, whereas there is no evidence of a net benefit in the 4½- to 6-hour time window. The NNT estimates for each 90-minute epoch provide useful and intuitive information based on which patients may be able to make better informed treatment decisions.

Microbleeds and the Risk of Recurrent Stroke

Background and Purpose— We studied the risk of recurrent cerebrovascular events in patients who had a transient ischemic attack or ischemic stroke and who had evidence of microbleeds on MRI. Methods— A prospective follow-up study was performed on hospitalized patients who were at least 50 years old with a transient ischemic attack or an ischemic stroke. The presence and number of microbleeds were assessed on gradient echo MRI and the presence of white matter disease on fluid-attenuated inversion recovery imaging using a semiquantitative scale. Patients were followed up by phone every 6 months. End points were intracerebral hemorrhage, ischemic stroke, and unclassified stroke. Cerebral events were adjudicated by 2 independent neurologists blinded to the presence of microbleeds. Cox regression analysis was performed. Results— A total of 487 patients with a mean age of 72 years were followed up for a median of 2.2 years (25th to 75th percentile 1.9 to 2.7 years). Microbleeds were identified in 129 patients (25.6%). Two patients developed intracerebral hemorrhage during follow-up, 32 patients developed recurrent ischemic stroke, and 3 patients had unclassified strokes. Microbleeds were not independent predictors of recurrent stroke (P=0.2) or intracerebral hemorrhage (P=0.43). Lobar microbleeds or combined lobar and deep microbleeds were independently associated with recurrent stroke (P=0.018). Conclusion— In this European cohort, patients with microbleeds who have had cerebral ischemia have a higher risk of developing new ischemic strokes than of intracerebral hemorrhage. Lobar microbleeds or combined lobar and deep microbleeds might be independent predictors of recurrent stroke.

Benefit of the Awaji diagnostic algorithm for amyotrophic lateral sclerosis: a prospective study.

Early and accurate diagnosis of amyotrophic lateral sclerosis (ALS) is important for patient care and for entry in clinical trials. Retrospective studies suggest that the use of the Awaji algorithm for the diagnosis of ALS is more sensitive for early diagnosis than the currently used revised El Escorial criteria.

Progressive encephalomyelitis with rigidity and myoclonus: Resolution after thymectomy

Progressive encephalomyelitis with rigidity and myoclonus (PERM) is a disorder of subacute onset presenting with widespread rigidity, painful spasms, and prominent myoclonus.1 PERM is probably related to stiff-person syndrome (SPS). In both conditions, most patients have anti-glutamic acid decarboxylase (anti-GAD) antibodies, and both can be paraneoplastic. However, PERM differs from SPS by the presence of brainstem and long tract signs and its aggressive course. Initially, PERM was considered as uniformly fatal.2 More recently, partial improvement of PERM has been reported in rare cases.3,4 We describe a patient with PERM and glycine receptor antibodies who completely recovered after resection of a thymoma. ### Classification of evidence. This case report provides Class IV evidence that thymectomy for a thymoma resulted in resolution of PERM. ### Case report. On September 15, 2008, a 49-year-old farmer without significant medical history developed pain in his right leg, which became intolerable within 5 days. Lumbosacral spine MRI was normal. He then developed involuntary, painful extension spasms of the right leg, left arm stiffness, speech and swallowing difficulties, intermittent diplopia, dry mouth, constipation, urinary retention, and excessive sweating. He could no longer fully open his mouth, and was referred to our hospital with a tentative diagnosis of tetanus, 8 days after onset. On admission, he was …

Benefits of intensive insulin therapy on neuromuscular complications in routine daily critical care practice: a retrospective study

IntroductionIntensive insulin therapy (IIT) reduced the incidence of critical illness polyneuropathy and/or myopathy (CIP/CIM) and the need for prolonged mechanical ventilation (MV ≥ 14 days) in two randomised controlled trials (RCTs) on the effect of IIT in a surgical intensive care unit (SICU) and medical intensive care unit (MICU). In the present study, we investigated whether these effects are also present in daily clinical practice when IIT is implemented outside of a study protocol.MethodsWe retrospectively studied electrophysiological data from patients in the SICU and MICU, performed because of clinical weakness and/or weaning failure, before and after routine implementation of IIT. CIP/CIM was diagnosed by abundant spontaneous electrical activity on electromyography. Baseline and outcome variables were compared using Students t-test, Chi-squared or Mann-Whitney U-test when appropriate. The effect of implementing IIT on CIP/CIM and prolonged MV was assessed using univariate analysis and multivariate logistic regression analysis (MVLR), correcting for baseline and ICU risk factors.ResultsIIT significantly lowered mean (± standard deviation) blood glucose levels (from 144 ± 20 to 107 ± 10 mg/dl, p < 0.0001) and significantly reduced the diagnosis of CIP/CIM in the screened long-stay patients (125/168 (74.4%) to 220/452 (48.7%), p < 0.0001). MVLR identified implementing IIT as an independent protective factor (p < 0.0001, odds ratio (OR): 0.25 (95% confidence interval (CI): 0.14 to 0.43)). MVLR confirmed the independent protective effect of IIT on prolonged MV (p = 0.002, OR:0.40 (95% CI: 0.22–0.72)). This effect was statistically only partially explained by the reduction in CIP/CIM.ConclusionsImplementing IIT in routine daily practice in critically ill patients evoked a similar beneficial effect on neuromuscular function as that observed in two RCTs. IIT significantly improved glycaemic control and significantly and independently reduced the electrophysiological incidence of CIP/CIM. This reduction partially explained the beneficial effect of IIT on prolonged MV.

Association of Apolipoprotein E ε2 With White Matter Disease but Not With Microbleeds

Background and Purpose— Apolipoprotein E (apoE) alleles (ϵ2 and ϵ4) are associated with cerebral amyloid angiopathy, in which white matter disease and microbleeds are prominent features. The role of apoE in patients with microbleeds or white matter disease but no evidence of cerebral amyloid angiopathy has not been elucidated. We studied apoE alleles in relation to white matter disease and microbleeds in patients with transient ischemic attack or ischemic stroke. Methods— We obtained brain MRI scans and apoE genotypes in 334 transient ischemic attack or ischemic stroke patients. Microbleeds were scored on a gradient echo MRI and white matter disease was examined on fluid attenuated inversion recovery MRI using a semiquantitative rating scale. Results— Patients with moderate to severe white matter disease more frequently carried apoE ϵ2 alleles (25.2% versus 11.3%, P=0.001), but not apoE ϵ4 (26.6% in apoE ϵ4 carriers versus 25.9%; P=0.98). Adjustment for traditional risk factors did not modify this relationship (odds ratio, 2.9; 95% confidence interval, 1.5 to 5.3). There was no association between the presence of microbleeds and the apoE ϵ4 or apoE ϵ2 alleles. Conclusions— ApoE alleles do not exert a major influence on the development of microbleeds, but apoE ϵ2 may be associated with development of moderate to severe white matter disease in transient ischemic attack and stroke patients.

Body temperature and outcome after stroke thrombolysis

Aims –  We studied whether baseline body temperature and temperature increases after stroke adversely affect outcome after thrombolysis with intravenous tissue plasminogen activator (IV tPA).

Quality Control of Motor Unit Number Index (MUNIX) Measurements in 6 Muscles in a Single-Subject “Round-Robin” Setup

Background Motor Unit Number Index (MUNIX) is a neurophysiological measure that provides an index of the number of lower motor neurons in a muscle. Its performance across centres in healthy subjects and patients with Amyotrophic Lateral Sclerosis (ALS) has been established, but inter-rater variability between multiple raters in one single subject has not been investigated. Objective To assess reliability in a set of 6 muscles in a single subject among 12 examiners (6 experienced with MUNIX, 6 less experienced) and to determine variables associated with variability of measurements. Methods Twelve raters applied MUNIX in six different muscles (abductor pollicis brevis (APB), abductor digiti minimi (ADM), biceps brachii (BB), tibialis anterior (TA), extensor dig. brevis (EDB), abductor hallucis (AH)) twice in one single volunteer on consecutive days. All raters visited at least one training course prior to measurements. Intra- and inter-rater variability as determined by the coefficient of variation (COV) between different raters and their levels of experience with MUNIX were compared. Results Mean intra-rater COV of MUNIX was 14.0% (±6.4) ranging from 5.8 (APB) to 30.3% (EDB). Mean inter-rater COV was 18.1 (±5.4) ranging from 8.0 (BB) to 31.7 (AH). No significant differences of variability between experienced and less experienced raters were detected. Conclusion We provide evidence that quality control for neurophysiological methods can be performed with similar standards as in laboratory medicine. Intra- and inter-rater variability of MUNIX is muscle-dependent and mainly below 20%. Experienced neurophysiologists can easily adopt MUNIX and adequate teaching ensures reliable utilization of this method.

Voxel-based lesion-symptom mapping of stroke lesions underlying somatosensory deficits.

The aim of this study was to investigate the relationship between stroke lesion location and the resulting somatosensory deficit. We studied exteroceptive and proprioceptive somatosensory symptoms and stroke lesions in 38 patients with first-ever acute stroke. The Erasmus modified Nottingham Sensory Assessment was used to clinically evaluate somatosensory functioning in the arm and hand within the first week after stroke onset. Additionally, more objective measures such as the perceptual threshold of touch and somatosensory evoked potentials were recorded. Non-parametric voxel-based lesion-symptom mapping was performed to investigate lesion contribution to different somatosensory deficits in the upper limb. Additionally, structural connectivity of brain areas that demonstrated the strongest association with somatosensory symptoms was determined, using probabilistic fiber tracking based on diffusion tensor imaging data from a healthy age-matched sample. Voxels with a significant association to somatosensory deficits were clustered in two core brain regions: the central parietal white matter, also referred to as the sensory component of the superior thalamic radiation, and the parietal operculum close to the insular cortex, representing the secondary somatosensory cortex. Our objective recordings confirmed findings from clinical assessments. Probabilistic tracking connected the first region to thalamus, internal capsule, brain stem, postcentral gyrus, cerebellum, and frontal pathways, while the second region demonstrated structural connections to thalamus, insular and primary somatosensory cortex. This study reveals that stroke lesions in the sensory fibers of the superior thalamocortical radiation and the parietal operculum are significantly associated with multiple exteroceptive and proprioceptive deficits in the arm and hand.

Supranuclear gaze palsy in glycine receptor antibody-positive progressive encephalomyelitis with rigidity and myoclonus.

explanations for this common feature are disruption of the basal ganglia input–output circuitry because of the white matter abnormalities or, alternatively, direct involvement of the basal ganglia through local hypomyelination or demyelination. In conclusion, dystonia can be a prominent feature of TACH and possibly of other Pol III–related leukodystrophies. Larger genotype–phenotype correlation studies are necessary to establish the frequency of dystonia in Pol III–related leukodystrophies and whether the presence of dystonia can be correlated to specific mutation types.