ResearchPad - original-communication https://www.researchpad.co Default RSS Feed en-us © 2020 Newgen KnowledgeWorks <![CDATA[Newly developed stroke in patients admitted to non-neurological intensive care units]]> https://www.researchpad.co/article/elastic_article_16565 Little is known about newly developed stroke in patients admitted to the intensive care unit (ICU).ObjectiveThis study aimed to investigate characteristics and outcomes of newly developed stroke in patients admitted to the non-neurological intensive care units (ICU-onset stroke, IOS).MethodsA consecutive series of adult patients who were admitted to the non-neurological ICU were included in this study. We compared neurological profiles, risk factors, and mortality rates between patients with IOS and those without IOS.ResultsOf 18,604 patients admitted to the ICU for non-neurological illness, 218 (1.2%) developed stroke (ischemic, n = 182; hemorrhagic, n = 36). The most common neurological presentation was altered mental status (n = 149), followed by hemiparesis (n = 55), and seizures (n = 28). The most common etiology of IOS was cardioembolism (50% [91/182]) for ischemic IOS and coagulopathy (67% [24/36]) for hemorrhagic IOS. In multivariable analysis, the Acute Physiology and Chronic Health Evaluation II (APACHE II) score (adjusted odds ratio [AOR] = 1.04, 95% CI = 1.03−1.06, P < 0.001), prothrombin time (AOR = 0.99, 95% CI = 0.98−0.99, P = 0.013), cardiovascular surgery (AOR = 1.84, 95% CI = 1.34−2.50, P < 0.001), mechanical ventilation (AOR = 6.75, 95% CI = 4.87−9.45, P < 0.001), and extracorporeal membrane oxygenation (AOR = 2.77, 95% CI = 1.62−4.55, P < 0.001) were related to the development of IOS. Stroke was associated with increased 3-month mortality after hospital discharge (AOR, 2.20; 95% CI, 1.58–3.05; P < 0.001), after adjustment for APACHE II and comorbidities.ConclusionsPatients who developed IOS had characteristics of initial critical illness and managements performed in the ICU as well as neurological presentations. The occurrence of IOS was related to high morbidity and mortality.Electronic supplementary materialThe online version of this article (10.1007/s00415-020-09955-5) contains supplementary material, which is available to authorized users. ]]> <![CDATA[Meta-analysis of haematoma volume, haematoma expansion and mortality in intracerebral haemorrhage associated with oral anticoagulant use]]> https://www.researchpad.co/article/Nb7bbdcf9-ee53-456d-8da0-e298cd1a15b1

Objective

To obtain precise estimates of age, haematoma volume, secondary haematoma expansion (HE) and mortality for patients with intracerebral haemorrhage (ICH) taking oral anticoagulants [Vitamin K antagonists (VKA-ICH) or non-Vitamin K antagonist oral anticoagulants (NOAC-ICH)] and those not taking oral anticoagulants (non-OAC ICH) at ICH symptom onset.

Methods

We conducted a systematic review and meta-analysis of studies comparing VKA-ICH or NOAC-ICH or both with non-OAC ICH. Primary outcomes were haematoma volume (in ml), HE, and mortality (in-hospital and 3-month). We calculated odds ratios (ORs) using the Mantel–Haenszel random-effects method and corresponding 95% confidence intervals (95%CI) and determined the mean ICH volume difference.

Results

We identified 19 studies including data from 16,546 patients with VKA-ICH and 128,561 patients with non-OAC ICH. Only 2 studies reported data on 4943 patients with NOAC-ICH. Patients with VKA-ICH were significantly older than patients with non-OAC ICH (mean age difference: 5.55 years, 95%CI 4.03–7.07, p < 0.0001, I2 = 92%, p < 0.001). Haematoma volume was significantly larger in VKA-ICH with a mean difference of 9.66 ml (95%CI 6.24–13.07 ml, p < 0.00001; I2 = 42%, p = 0.05). HE occurred significantly more often in VKA-ICH (OR 2.96, 95%CI 1.74–4.97, p < 0.00001; I2 = 65%). VKA-ICH was associated with significantly higher in-hospital mortality (VKA-ICH: 32.8% vs. non-OAC ICH: 22.4%; OR 1.83, 95%CI 1.61–2.07, p < 0.00001, I2 = 20%, p = 0.27) and 3-month mortality (VKA-ICH: 47.1% vs. non-OAC ICH: 25.5%; OR 2.24, 95%CI 1.52–3.31, p < 0.00001, I2 = 71%, p = 0.001). We did not find sufficient data for a meta-analysis comparing NOAC-ICH and non-OAC-ICH.

Conclusion

This meta-analysis confirms, refines and expands findings from prior studies. We provide precise estimates of key prognostic factors and outcomes for VKA-ICH, which has larger haematoma volume, increased rate of HE and higher mortality compared to non-OAC ICH. There are insufficient data on NOACs.

Electronic supplementary material

The online version of this article (10.1007/s00415-019-09536-1) contains supplementary material, which is available to authorized users.

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<![CDATA[Cardiovascular autonomic testing in the work-up of cerebellar ataxia: insight from an observational single center study]]> https://www.researchpad.co/article/N38a65297-2ad4-4222-808f-de5693e92038

Background

Cerebellar ataxias are a heterogeneous group of disorders of both genetic and non-genetic origin. In sporadic cases, two entities are recognized: multiple system atrophy of cerebellar type (MSA-C) and SAOA (sporadic adult-onset ataxia). The presence of severe cardiovascular autonomic failure reliably distinguishes MSA-C from other ataxias, but it may appear only late in the disease course.

Objective

To evaluate the diagnostic yield of cardiovascular autonomic function tests in the work-up of cerebellar ataxia.

Methods

We applied a cardiovascular autonomic tests battery in consecutive patients with neurodegenerative cerebellar ataxia and matched healthy controls. We recorded the presence of both orthostatic hypotension (OH) and blood pressure falls non-fulfilling the criteria of OH (non-OH BP). Sporadic cases were followed-up for an eventual conversion to MSA-C.

Results

Forty-two patients were recruited, 19 of whom with sporadic disease (2 probable MSA-C, 6 possible MSA-C, 11 SAOA). Sporadic and hereditary cases showed no difference concerning ataxia severity at baseline. At head-up tilt, non-OH BP falls were detected in nine patients, but not in controls. This finding was significantly more frequent in sporadic cases (p = 0.006) and was detected in five out of seven patients that during follow-up converted to possible/probable MSA-C. Findings at standing test were normal in four out of nine cases with non-OH BP falls at head-up tilt.

Conclusions

A complete cardiovascular autonomic battery with head-up tilt can detect early signs of BP dysregulation which may be missed at bed-side tests, thus warranting its application in the first line work-up of cerebellar ataxias.

Electronic supplementary material

The online version of this article (10.1007/s00415-019-09684-4) contains supplementary material, which is available to authorized users.

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<![CDATA[Frequency and clinical features of treatment-refractory myasthenia gravis]]> https://www.researchpad.co/article/Nb2844ef5-ca09-48e8-a92e-1fd7e6010bc0

Background

To investigate the frequency and characterize the clinical features of treatment-refractory myasthenia gravis in an Austrian cohort.

Methods

Patient charts of 126 patients with generalized myasthenia gravis and onset between 2000 and 2016 were analyzed retrospectively. Patients were classified as treatment-refractory according to strict, predefined criteria. These mandated patients being at least moderately symptomatic (i.e., MGFA class III) or needing either maintenance immunoglobulins or plasma exchange therapy for at least 1 year in spite of two adequately dosed immunosuppressive drugs. Clinical features and outcome at last follow-up were compared to treatment-responsive patients.

Results

14 out of 126 patients (11.1%) met these criteria of treatment-refractory myasthenia gravis. Treatment-refractory patients had more frequent clinical exacerbations and more often received rescue treatments or a further escalation of immunosuppressive therapies. They also remained more severely affected at last follow-up. An early onset of myasthenia gravis was associated with a higher risk for a refractory course.

Conclusion

A small subgroup of patients with generalized myasthenia gravis do not respond sufficiently to standard therapies. Refractory disease has considerable implications for both patients and health care providers and highlights an unmet need for new treatment options.

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<![CDATA[Low sun exposure increases multiple sclerosis risk both directly and indirectly]]> https://www.researchpad.co/article/Nd1e0c0aa-dd33-41a8-bede-cd22cb1de34b

Objective

We aimed to study (1) to what extent the influence of low sun exposure on multiple sclerosis (MS) risk is mediated by low vitamin D levels; (2) whether low sun exposure or vitamin D deficiency act synergistically with HLA-DRB1*15:01 and absence of HLA-A*02:01.

Methods

We used two population-based case–control studies (7069 cases, 6632 matched controls). Subjects with different HLA alleles, sun exposure habits and vitamin D status were compared regarding MS risk, by calculating odds ratios (OR) with 95% confidence intervals (CI) employing logistic regression. Mediation analysis was used to identify the potential mediation effect of vitamin D on the relationship between low sun exposure and MS risk.

Results

Low sun exposure increased MS risk directly as well as indirectly, by affecting vitamin D status. The direct effect, expressed as OR, was 1.26 (95% CI 1.04–1.45) and the indirect effect, mediated by vitamin D deficiency, was 1.10 (95% CI 1.02–1.23). Of the total effect, nearly 30% was mediated by vitamin D deficiency. There was a significant interaction between low sun exposure and vitamin D deficiency (attributable proportion due to interaction 0.3, 95% CI 0.04–0.5) accounting for about 12% of the total effect. Further, both factors interacted with HLA-DRB1*15:01 to increase MS risk.

Interpretation

Our findings indicate that low sun exposure acts both directly on MS risk as well as indirectly, by leading to low vitamin D levels. The protective effect of sun exposure thus seems to involve both vitamin D and non-vitamin D pathways, which is of relevance for prevention, in particular for those with a genetic susceptibility to MS.

Electronic supplementary material

The online version of this article (10.1007/s00415-019-09677-3) contains supplementary material, which is available to authorized users.

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<![CDATA[Clinical and imaging correlates of EEG patterns in hospitalized patients with encephalopathy]]> https://www.researchpad.co/article/N8e74b5fc-3139-41ea-8bc8-3ee5949edb86

To identify the relationship between pathologic electroencephalographic (EEG) patterns, clinical and neuroradiological abnormalities, and outcome in hospitalized patients with acute encephalopathy. This 5-year cohort study was performed at an academic tertiary care center. EEGs in 154 patients with altered mental status were classified according to five predefined patterns: Isolated continuous slowing of background activity (theta, theta/delta, and delta activity) and patterns with slowing background activity with episodic transients [i.e., triphasic waves (TWs) or frontal intermittent delta activity (FIRDA)]. Clinical characteristics, blood tests and neuroimaging were compared among groups. Associations between EEG patterns and structural and non-structural abnormalities were calculated. Glasgow Outcome Score >3 at discharge was defined as favorable and 1–3 as unfavorable outcome. In multivariable analyses, theta was associated with brain atrophy (OR 2.6, p = 0.020), theta/delta with intracerebral hemorrhages (OR 6.8, p = 0.005), FIRDA with past cerebrovascular accidents (OR 2.7, p = 0.004), TWs with liver or multi-organ failure (OR 6, p = 0.004; OR 4, p = 0.039), and delta activity with alcohol/drug abuse with or without intoxication, and HIV infection (OR 3.8, p = 0.003; OR 9, p = 0.004). TWs were associated with death (OR 4.5, p = 0.005); theta/delta with unfavorable outcomes (OR 2.5, p = 0.033), while patients with FIRDA had favorable outcomes (OR 4.8, p = 0.004). In encephalopathic patients, well-defined EEG patterns are associated with specific pathological conditions and outcomes, suggesting that mechanistic hypotheses underlie these abnormal EEG patterns. To clarify the respective contributions of non-structural and structural abnormalities to encephalopathy reflected in specific EEG patterns, prospective studies using continuous EEG monitoring during the acute onset of encephalopathy are needed.

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<![CDATA[Association of PROtein and CAloric Intake and Clinical Outcomes in Adult SEPTic and Non‐Septic ICU Patients on Prolonged Mechanical Ventilation: The PROCASEPT Retrospective Study]]> https://www.researchpad.co/article/Ncfff6fe7-6704-4e42-8372-953e6eb85f81

Abstract

Background

The optimal nutritional support for critically ill septic patients remains unknown. This study evaluates the associations of macronutrient intake during the first week of intensive care unit (ICU) admission and long‐term clinical outcomes in septic and non‐septic patients.

Methods

Prolonged mechanically ventilated patients were retrospectively studied. The association of protein (low: <0.8 g/kg/d, medium: 0.8–1.2 g/kg/d, high >1.2 g/kg/d) and energy intake (<80%, 80%–110%, 110% of target) during days 1–3 and 4–7 after ICU admission and 6‐month mortality was analyzed for septic and non‐septic patients separately.

Results

A total of 423 patients were investigated. Of these, 297 had sepsis. In the sepsis group, medium protein intake at days 4–7 was associated with lower 6‐month mortality (hazard ratio [HR]: 0.646, 95% confidence interval [CI]: 0.418‐0.996, P=0.048) compared with high intake. In the non‐sepsis group, early high and late low protein intake were associated with higher 6‐month mortality (HR: 3.902, 95% CI: 1.505‐10.115, P=0.005; HR: 2.642, 95% CI: 1.128‐6.189, P=0.025) compared with low and high protein intake, respectively. For energy intake, late energy intake of >110% was associated with decreased mortality in septic patients (HR: 0.400, 95% CI: 0.222‐0.721, P=0.002), whereas in non‐septic patients, late medium energy intake (80%–110%) was associated with better survival (HR: 0.379, 95% CI: 0.175‐0.820, P=0.014), both compared with low energy intake.

Conclusion

Divergent associations of macronutrient intake were found; early high protein intake in non‐septic patients, but not in septic patients, was found to be associated with higher 6‐month mortality.

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<![CDATA[A Comparative Analysis of Equations to Estimate Patient Energy Requirements Following Cardiopulmonary Bypass for Correction of Congenital Heart Disease]]> https://www.researchpad.co/article/N7f08289e-f049-4326-ad97-522a45e2014e

Abstract

Background

No consensus exists on the optimal method to estimate resting energy expenditure (REE) in critically ill children following cardiopulmonary bypass (CPB). This study assesses the accuracy of REE estimation equations in children with congenital heart disease following CPB and tests the feasibility of using allometric scaling as an alternative energy prediction equation.

Methods

A retrospective analysis of a pediatric cohort following CPB (n = 107; median age 5.2 months, median weight 5.65 kg) who underwent serial measures (median 5 measurements) of REE using indirect calorimetry for 72 hours following CPB. We estimated REE using common estimation methods (Dietary Reference Intake, Harris Benedict, Schofield, World Health Organization [WHO]) as well as novel allometric equations. We compared estimated with measured REE to determine accuracy of each equation using overall discrepancy, calculated as a time‐weighted average of the absolute deviation.

Results

All equations incorrectly estimated REE at all time points following CPB, with overestimation error predominating. WHO had the lowest discrepancy at 10.7 ± 8.4 kcal/kg/d. The allometric equation was inferior, with an overall discrepancy of 16.9 ± 10.4. There is a strong nonlinear relationship between body surface area and measured REE in this cohort, which is a key source of estimation error using linear equations.

Conclusion

In a cohort of pediatric patients with congenital heart disease following CPB, no currently utilized clinical estimation equation reliably estimated REE. Allometric scaling proved inferior in estimating REE in children following CPB. Indirect calorimetry remains the ideal method of determining REE after CPB until nonlinear methods can be derived due to overestimation using linear equations.

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<![CDATA[A Single Urine Sodium Measurement May Validly Estimate 24‐hour Urine Sodium Excretion in Patients With an Ileostomy]]> https://www.researchpad.co/article/Nc7dababf-5555-43ac-a0e9-f909b5d7585a

Abstract

Background

Sodium deficiency in patients with an ileostomy is associated with chronic dehydration and may be difficult to detect. We aimed to investigate if the sodium concentration in a single spot urine sample may be used as a proxy for 24‐hour urine sodium excretion.

Methods

In a prospective observational study with 8 patients with an ileostomy and 8 volunteers with intact intestines, we investigated the correlations and agreements between spot urine sodium concentrations and 24‐hour urine sodium excretions. Spot urine samples were drawn from every micturition during 24 hours, and relevant blood samples were drawn. All participants documented their food and fluid intakes.

Results

There was a high and statistically significant correlation between 24‐hour natriuresis and urine sodium concentrations in both morning spot samples (n = 8, Spearman's rho [ρ] = 0.78, P = 0.03) and midday spot samples (n = 8, ρ = 0.82, P = 0.02) in the patients with an ileostomy. The agreement between methods was fair (bias = −1.5, limits of agreement = −32.3 to 29.4). There were no statistically significant associations for evening samples or for samples from volunteers with intact intestines independently of time of day.

Conclusion

A single spot urine sodium sample obtained in the morning or midday may estimate 24‐hour urine sodium excretion in patients with an ileostomy and thus help to identify sodium depletion.

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<![CDATA[Analysis of autonomic outcomes in APOLLO, a phase III trial of the RNAi therapeutic patisiran in patients with hereditary transthyretin-mediated amyloidosis]]> https://www.researchpad.co/article/N5262ba07-0fc8-48a3-ba27-e4c09f7c3ebf

Hereditary transthyretin-mediated (hATTR) amyloidosis is a progressive, debilitating disease often resulting in early-onset, life-impacting autonomic dysfunction. The effect of the RNAi therapeutic, patisiran, on autonomic neuropathy manifestations in patients with hATTR amyloidosis with polyneuropathy in the phase III APOLLO study is reported. Patients received patisiran 0.3 mg/kg intravenously (n = 148) or placebo (n = 77) once every 3 weeks for 18 months. Patisiran halted or reversed polyneuropathy and improved quality of life from baseline in the majority of patients. At baseline, patients in APOLLO had notable autonomic impairment, as demonstrated by the Composite Autonomic Symptom Score-31 (COMPASS-31) questionnaire and Norfolk Quality of Life-Diabetic Neuropathy (Norfolk QOL-DN) questionnaire autonomic neuropathy domain. At 18 months, patisiran improved autonomic neuropathy symptoms compared with placebo [COMPASS-31, least squares (LS) mean difference, − 7.5; 95% CI: − 11.9, − 3.2; Norfolk QOL-DN autonomic neuropathy domain, LS mean difference, − 1.1; − 1.8, − 0.5], nutritional status (modified body mass index, LS mean difference, 115.7; − 82.4, 149.0), and vasomotor function (postural blood pressure, LS mean difference, − 0.3; − 0.5, − 0.1). Patisiran treatment also led to improvement from baseline at 18 months for COMPASS-31 (LS mean change from baseline, − 5.3; 95% CI: − 7.9, − 2.7) and individual domains, orthostatic intolerance (− 4.6; − 6.3, − 2.9) and gastrointestinal symptoms (− 0.8; − 1.5, − 0.2). Rapid worsening of all study measures was observed with placebo, while patisiran treatment resulted in stable or improved scores compared with baseline. Patisiran demonstrates benefit across a range of burdensome autonomic neuropathy manifestations that deteriorate rapidly without early and continued treatment.

Electronic supplementary material

The online version of this article (10.1007/s00415-019-09602-8) contains supplementary material, which is available to authorized users.

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<![CDATA[ω‐3 Fatty‐Acid Enriched Parenteral Nutrition in Hospitalized Patients: Systematic Review With Meta‐Analysis and Trial Sequential Analysis]]> https://www.researchpad.co/article/Nc7c4f4fb-159f-4de0-9987-cf0556d174f7

Abstract

This systematic review and meta‐analysis investigated ω‐3 fatty‐acid enriched parenteral nutrition (PN) vs standard (non‐ω‐3 fatty‐acid enriched) PN in adult hospitalized patients (PROSPERO 2018 CRD42018110179). We included 49 randomized controlled trials (RCTs) with intervention and control groups given ω‐3 fatty acids and standard lipid emulsions, respectively, as part of PN covering ≥70% energy provision. The relative risk (RR) of infection (primary outcome; 24 RCTs) was 40% lower with ω‐3 fatty‐acid enriched PN than standard PN (RR 0.60, 95% confidence interval [CI] 0.49‐0.72; P < 0.00001). Patients given ω‐3 fatty‐acid enriched PN had reduced mean length of intensive care unit (ICU) stay (10 RCTs; 1.95 days, 95% CI 0.42‐3.49; P = 0.01) and reduced length of hospital stay (26 RCTs; 2.14 days, 95% CI 1.36‐2.93; P < 0.00001). Risk of sepsis (9 RCTs) was reduced by 56% in those given ω‐3 fatty‐acid enriched PN (RR 0.44, 95% CI 0.28‐0.70; P = 0.0004). Mortality rate (co‐primary outcome; 20 RCTs) showed a nonsignificant 16% reduction (RR 0.84, 95% CI 0.65‐1.07; P = 0.15) for the ω‐3 fatty‐acid enriched group. In summary, ω‐3 fatty‐acid enriched PN is beneficial, reducing risk of infection and sepsis by 40% and 56%, respectively, and length of both ICU and hospital stay by about 2 days. Provision of ω‐3‐enriched lipid emulsions should be preferred over standard lipid emulsions in patients with an indication for PN.

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<![CDATA[MR-imaging pattern is not a predictor of occult atrial fibrillation in patients with cryptogenic stroke]]> https://www.researchpad.co/article/N7bec16a9-6f53-4de0-9dc9-4c2c4129674d

Background

To date, insertable cardiac monitors (ICMs) are the most effective method for the detection of occult atrial fibrillation (AF) in cryptogenic stroke. The overall detection rate after 12 months, however, is low and ranges between 12.4 and 33.3%, even if clinical predictors are considered. Ischemic stroke patients due to cardiogenic embolism present with particular lesion patterns. In patients with cryptogenic stroke, MR-imaging pattern may be a valuable predictor for AF.

Methods

This is an MRI-based, retrospective, observational, comparative, single-center study of 104 patients who underwent ICM implantation after cryptogenic stroke. The findings were compared to a reference group with related stroke etiology, i.e., 166 patients with embolic stroke due to AF detected for the first time by long-term ECG. Lesion patterns were evaluated with regard to affected territories, distribution (cortical, lacunar, scattered), lesion volume, and lesion size (diameter of the lesion size > 20 mm).

Results

The MR-imaging analysis of acute ischemic lesions yielded no association between AF and lesion size or volume, arterial vessel distribution, or the number of affected territories. There was no significant difference between the cohorts regarding ischemic patterns (cortical lesions, scattered lesions, and lacunar infarcts). An important clinical inference of our findings is that 10% (2 of 20) of cases in the ICM group in whom AF was detected had a lacunar infarct pattern. Similar results were shown in cases of ischemic stroke patients with AF detected for the first time by long-term ECG, with 10.9% (16 of 147) of them showing lacunar infarcts. The analysis of chronic MRI lesions revealed no differences between the groups in the rate of chronic lesions, arterial vessel distribution, or the number of affected territories. Left atrial size (LA size) and the presence of atrial runs in long-term ECG were independently associated with AF.

Conclusions

In this MRI-based analysis of patients with cryptogenic stroke who had received ICM implantation, the detection rate of AF in patients with ICM was not related to the imaging pattern. In addition, the lacunar infarct pattern should not be an exclusion criterion for ICM insertion in patients with cryptogenic stroke. ICM insertion in patients with cryptogenic stroke should not be evaluated solely on the basis of reference to infarct patterns.

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<![CDATA[Unexpected emergence from the vegetative state: delayed discovery rather than late recovery of consciousness]]> https://www.researchpad.co/article/Nd8bc048d-5a48-44be-a163-e0d68c494d35

Background

The vegetative state, also known as the unresponsive wakefulness syndrome, is one of the worst possible outcomes of acquired brain injury and confronts rehabilitation specialists with various challenges. Emergence to (minimal) consciousness is classically considered unlikely beyond 3–6 months after non-traumatic or 12 months after traumatic etiologies. A growing body of evidence suggests that these timeframes are too narrow, but evidence regarding chances of recovery is still limited.

Objective

To identify the moment of recovery of consciousness in documented cases of late emergence from a vegetative state.

Methods

Four cases of apparent late recovery of consciousness, identified within a prospective cohort study, were studied in-depth by analyzing medical, paramedical and nursing files and interviewing the patients’ families about their account of the process of recovery.

Results

All patients were found to have shown signs of consciousness well within the expected time frame (5 weeks–2 months post-ictus). These behaviors, however, went unnoticed or were misinterpreted, leading to a diagnostic delay of several months to over 5 years. Absence of appropriate diagnostics, the use of erroneous terminology, sedative medication but also patient-related factors such as hydrocephalus, language barriers and performance fluctuations are hypothesized to have contributed to the delay.

Conclusions

Delayed recognition of signs of consciousness in patients in a vegetative state may not only lead to suboptimal clinical care, but also to distorted prognostic figures. Discriminating late recovery from the delayed discovery of consciousness, therefore, is vital to both clinical practice and science.

Electronic supplementary material

The online version of this article (10.1007/s00415-019-09542-3) contains supplementary material, which is available to authorized users.

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<![CDATA[Scapular dyskinesis in myotonic dystrophy type 1: clinical characteristics and genetic investigations]]> https://www.researchpad.co/article/N50a93d6d-1c1e-40de-ac18-229221f81bb8

Objective

To study scapular winging or other forms of scapular dyskinesis (condition of alteration of the normal position and motion of the scapula) in myotonic dystrophy type 1 (DM1), which is generally considered to be a distal myopathy, we performed an observational cohort study.

Methods

We performed a prospective cohort study on the clinical features and progression over time of 33 patients with DM1 and pronounced, mostly asymmetric scapular winging or other forms of scapular dyskinesis. We also explored if scapular dyskinesis in DM1 has the same genetic background as in facioscapulohumeral muscular dystrophy type 1 (FSHD1).

Results

The cohort included patients with congenital (n = 3), infantile (n = 6) and adult-onset DM1 (n = 24). Scapular girdle examination showed moderate shoulder girdle weakness (mean MRC 3) and atrophy of trapezius, infraspinatus, and rhomboid major, seemingly similar as in FSHD1. Shoulder abduction and forward flexion were limited (50–70°). In five patients, scapular dyskinesis was the initial disease symptom; in the others it appeared 1–24 years after disease onset. Follow-up data were available in 29 patients (mean 8 years) and showed mild to severe increase of scapular dyskinesis over time. In only three patients, DM1 coexisted with a FSHD mutation. In all other patients, FSHD was genetically excluded. DM2 was genetically excluded in nine patients. The clinical features of the patients with both DM1 and FSHD1 mutations were similar to those with DM1 only.

Conclusion

Scapular dyskinesis can be considered to be part of DM1 in a small proportion of patients. In spite of the clinical overlap, FSHD can explain scapular dyskinesis only in a small minority. This study is expected to improve the recognition of shoulder girdle involvement in DM1, which will contribute to the management of these patients.

Electronic supplementary material

The online version of this article (10.1007/s00415-019-09494-8) contains supplementary material, which is available to authorized users.

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<![CDATA[Fascial nomenclature: Update on related consensus process]]> https://www.researchpad.co/article/Nc3adc18b-1458-4ae6-a2e2-0a94182fb3b5

The term fascia is increasingly used not only by anatomists but also by other professionals and authors in different health‐oriented fields. This goes along with an inconsistent usage of the term, in which many different tissues are included by different authors causing an increasing amount of confusion. The Fascia Research Society acted to address this issue by establishing a Fascia Nomenclature Committee (FNC) with the purpose of clarifying the terminology relating to fascia. This committee conducted an elaborate Delphi process to foster a structured consensus debate among different experts in the field. This process led to two distinct terminology recommendations from the FNC, defining the terms “a fascia” and “the fascial system.” This article reports on the process behind this proposed terminology as well as the implications for inclusion and exclusion of different tissue types to these definitions. Clin. Anat. 32:929–933, 2019. © 2019 The Authors. Clinical Anatomy published by Wiley Periodicals, Inc. on behalf of American Association of Clinical Anatomists.

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<![CDATA[How satisfied are cervical dystonia patients after 3 years of botulinum toxin type A treatment? Results from a prospective, long-term observational study]]> https://www.researchpad.co/article/N1f371596-6036-483d-b693-c4af9165e4b1

Background

Patients with cervical dystonia (CD) typically require regular injections of botulinum toxin to maintain symptomatic control. We aimed to document long-term patient satisfaction with CD symptom control in a large cohort of patients treated in routine practice.

Methods

This was a prospective, international, observational study (NCT01753349) following the course of adult CD treated with botulinum neurotoxin type A (BoNT-A) over 3 years. A comprehensive clinical assessment status was performed at each injection visit and subjects reported satisfaction in two ways: satisfaction with symptom control at peak effect and at the end of treatment cycle.

Results

Subject satisfaction remained relatively stable from the first to the last injection visit. At 3 years, 89.9% of subjects reported satisfaction with symptom control at peak effect and 55.6% reported satisfaction with symptom control at end of treatment cycle. By contrast, objective ratings of CD severity showed an overall reduction over 3 years. Mean ± SD Toronto Western Spasmodic Rating Scale (TWSTRS) Total scores (clinician assessed at end of treatment cycle) decreased from 31.59 ± 13.04 at baseline to 24.49 ± 12.43 at 3 years (mean ± SD reduction from baseline of − 6.97 ± 11.56 points). Tsui scale scores also showed gradual improvement; the percent of subjects with a tremor component score of 4 reduced from 12.4% at baseline to 8.1% at 3 years.

Conclusions

Despite objective clinical improvements over 3 years, subject satisfaction with symptom control remained relatively constant, indicating that factors other than symptom control also play a role in patient satisfaction.

Electronic supplementary material

The online version of this article (10.1007/s00415-019-09527-2) contains supplementary material, which is available to authorized users.

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<![CDATA[The occurrence of seizures after ischemic stroke does not influence long-term mortality; a 26-year follow-up study]]> https://www.researchpad.co/article/5c0abea9d5eed0c484522d22

Objective

Epileptic seizures are a common complication after stroke. The relation between occurrence of seizures after stroke and long-term mortality remains elusive. We aimed to assess whether seizures in an early or late phase after ischemic stroke are an independent determinant of long-term mortality.

Methods

We prospectively included and followed 444 ischemic stroke patients with a first-ever supratentorial brain infarct for at least 2 years after their stroke regarding the occurrence of seizures. The final follow-up for mortality is from April 2015 (follow-up duration 24.5–27.8 years, mean 26.0 years, SD 0.9 years). We compared patients with early-onset seizures with all seizure-free patients, whereas the patients with late-onset seizures were compared with the 1-week survivors without any seizures. We used Cox-regression analyses to correct for possible confounding factors.

Results

Kaplan–Meier analysis showed significantly higher mortality for the patients with early-onset seizures (p = 0.002) but after correction for known risk factors for (long term) mortality early-onset seizures had no independent influence on long-term mortality (HR 1.09; 95% CI 0.64–1.85). In patients with late-onset seizures, no significant influence from late-onset seizures on long-term mortality was found (univariate p = 0.717; multivariate HR 0.81; 95% CI 0.54–1.20).

Conclusion

Both early-onset and late-onset seizures do not influence long-term mortality after ischemic stroke.

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<![CDATA[The clinical significance of 10-m walk test standardizations in Parkinson’s disease]]> https://www.researchpad.co/article/5c0abea3d5eed0c484522bec

Background

The 10-m walk test (10MWT) is a widely used measure of gait speed in Parkinson’s disease (PD). However, it is unclear if different standardizations of its conduct impact test results.

Aim of the study

We examined the clinical significance of two aspects of the standardization of the 10MWT in mild PD: static vs. dynamic start, and a single vs. repeated trials. Implications for fall prediction were also explored.

Methods

151 people with PD (mean age and PD duration, 68 and 4 years, respectively) completed the 10MWT in comfortable gait speed with static and dynamic start (two trials each), and gait speed (m/s) was recorded. Participants then registered all prospective falls for 6 months.

Results

Absolute mean differences between outcomes from the various test conditions ranged between 0.016 and 0.040 m/s (effect sizes, 0.06–0.14) with high levels of agreement (intra-class correlation coefficients, 0.932–0.987) and small standard errors of measurement (0.032–0.076 m/s). Receiver operating characteristic curves showed similar discriminate abilities for prediction of future falls across conditions (areas under curves, 0.70–0.73). Cut-off points were estimated at 1.1–1.2 m/s.

Conclusions

Different 10MWT standardizations yield very similar results, suggesting that there is no practical need for an acceleration distance or repeated trials when conducting this test in mild PD.

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<![CDATA[Progressive myoclonus epilepsy in Gaucher Disease due to a new Gly–Gly mutation causing loss of an Exonic Splicing Enhancer]]> https://www.researchpad.co/article/5c69ee06d5eed0c48414f60c

Background

Patients with Gaucher Disease (GD) exhibit three phenotypes, including type 1 (non-neuronopathic), type 2 (acute neuronopathic), and type 3 (subacute neuronopathic).

Aim

Identifying which GBA changes represent benign polymorphisms and which may result in disease-causing mutations is essential for diagnosis and genotype/phenotype correlations but is often challenging.

Results

Here, we describe a patient with type 3 GD, presenting with drug-resistant epilepsy, who bears a set of GBA polymorphic variants including the novel c.363A > G (Gly82Gly) synonymous mutation. In silico predictions, mRNA and functional studies revealed that the new Gly82Gly mutation causes skipping of GBA exon 4, leading to a severe reduction of the wild type GBA mRNA. This is the first report of a synonymous change causing GD through loss of an exonic splicing enhancer sequence.

The synonymous mutation is in trans with the Asn188Ser missense mutation, thus making the Asn188Ser responsible for the patient’s phenotype and strengthening the association of Asn188Ser with the particular neurological phenotype of type 3 GD.

Conclusion

We strengthen the association of Asn188Ser with the type 3 GD phenotype and progressive myoclonus epilepsy. Our data confirm that in silico predictions and mRNA analysis are mandatory in discriminating pathological mutations from the background of harmless polymorphisms, especially synonymous changes.

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<![CDATA[Characterisation of tissue-type metabolic content in secondary progressive multiple sclerosis: a magnetic resonance spectroscopic imaging study]]> https://www.researchpad.co/article/5c0abec4d5eed0c484523186

Proton magnetic resonance spectroscopy yields metabolic information and has proved to be a useful addition to structural imaging in neurological diseases. We applied short-echo time Spectroscopic Imaging in a cohort of 42 patients with secondary progressive multiple sclerosis (SPMS). Linear modelling with respect to brain tissue type yielded metabolite levels that were significantly different in white matter lesions compared with normal-appearing white matter, suggestive of higher myelin turnover (higher choline), higher metabolic rate (higher creatine) and increased glial activity (higher myo-inositol) within the lesions. These findings suggest that the lesions have ongoing cellular activity that is not consistent with the usual assumption of ‘chronic’ lesions in SPMS, and may represent a target for repair therapies.

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