Background and purpose

Continued care in patients with encephalitis and prolonged status epilepticus (SE) is controversial. Limited data are available on the functional and cognitive outcomes.

Methods

In a prospective cohort study from 2007 to 2016, patients with acute encephalitis and SE were reviewed. Long‐term outcomes including motor disability (modified Rankin Scale, mRS), daily living skills (activities of daily living, ADL), cognitive ability (modified Telephone Interview for Cognitive Status, TICS‐M) and epilepsy sequelae were evaluated in survivors at the 12‐month follow‐up.

Results

At the 12‐month follow‐up, 72 patients were recruited who got a median score of 14 on the total ADL. 68% patients remained independent in their daily activities (mRS ≤ 2). Post‐SE symptomatic epilepsy was observed in 49% of patients. Sixty‐two patients achieved a median score of 40 on the TICS‐M and 14 on the TICS‐M Memory. Patients with autoimmune encephalitis were less prone to post‐SE symptomatic epilepsy (18% vs. 58%, = 0.005) but had lower TICS‐M Memory score than those with viral encephalitis (8.5 vs. 15, = 0.017). Compared to non‐refractory status epilepticus (non‐RSE), patients with RSE had a longer stay in the neurocritical care unit (39 vs. 26, = 0.002), more in‐hospital complications and post‐SE symptomatic epilepsy (67% vs. 33%, = 0.005). Long‐term outcomes including ADL, mRS and TICS‐M were not significantly different between patients with RSE and non‐RSE or between patients with long (≥4 h) and short (<4 h) duration of SE.

Conclusions

Survival with favorable functional recovery was promising after prolonged RSE in patients with acute encephalitis.

Background and purpose

Diagnosis of pharyngeal dysphagia caused by myasthenia gravis (MG) based on clinical examination alone is often challenging. Flexible endoscopic evaluation of swallowing (FEES) combined with Tensilon (edrophonium) application, referred to as the FEES‐Tensilon test, was developed to improve diagnostic accuracy and to detect the main symptoms of pharyngeal dysphagia in MG. Here we investigated inter‐ and intra‐rater reliability of the FEES‐Tensilon test and analyzed the main endoscopic findings.

Methods

Four experienced raters reviewed a total of 20 FEES‐Tensilon test videos in randomized order. Residue severity was graded at four different pharyngeal spaces before and after Tensilon administration. All interpretations were performed twice per rater, 4 weeks apart (a total of 160 scorings). Intra‐rater test–retest reliability and inter‐rater reliability levels were calculated.

Results

The most frequent FEES findings in patients with MG before Tensilon application were prominent residues of semi‐solids spread all over the hypopharynx in varying locations. The reliability level of the interpretation of the FEES‐Tensilon test was excellent regardless of the rater's profession or years of experience with FEES. All four raters showed high inter‐ and intra‐reliability levels in interpreting the FEES‐Tensilon test based on residue clearance (kappa = 0.922, 0.981). The degree of residue normalization in the vallecular space after Tensilon application showed the highest inter‐ and intra‐rater reliability level (kappa = 0.863, 0.957) followed by the epiglottis (kappa = 0.813, 0.946) and pyriform sinuses (kappa = 0.836, 0.929).

Conclusion

Interpretation of the FEES‐Tensilon test based on residue severity and degree of Tensilon clearance, especially in the vallecular space, is consistent and reliable.

Background and purpose

The aim was to investigate the association between step time variability and related brain structures in accordance with fall status in people with multiple sclerosis (PwMS).

Methods

The study included 225 PwMS. Whole‐brain magnetic resonance imaging was performed with a high‐resolution 3.0 T magnetic resonance scanner in addition to volumetric analysis based on 3D T1‐weighted images using the FreeSurfer image analysis suite. Step time variability was measured with an electronic walkway. Participants were defined as ‘fallers’ (at least two falls during the previous year) and ‘non‐fallers’.

Results

In all, 105 PwMS were defined as fallers and had a greater step time variability compared to non‐fallers [5.6% (SD = 3.4) vs. 3.4% (SD = 1.5); 0.001]. MS fallers exhibited a reduced volume in the left caudate and both cerebellum hemispheres compared to non‐fallers. On using a linear regression analysis no association was found between gait variability and related brain structures in the total cohort and the non‐fallers group. However, the analysis found an association between the left hippocampus and left putamen volumes with step time variability in the faller group: = 0.031, 0.048, respectively, controlling for total cranial volume, walking speed, disability, age and gender. Nevertheless, according to the hierarchical regression model, the contribution of these brain measures to predict gait variability was relatively small compared to walking speed.

Conclusions

An association between low left hippocampal, putamen volumes and step time variability was found in PwMS with a history of falls, suggesting that brain structural characteristics may be related to falls and increased gait variability in PwMS.

Background and purpose

Some symptoms of multiple sclerosis (MS) affect driving. In a recent study, performance on five cognitive tests predicted the on‐road test performance of individuals with relapsing‐remitting MS with 91% accuracy, 70% sensitivity and 97% specificity. However, the accuracy with which the battery will predict the driving performance of a different cohort that includes all types of MS is unknown.

Methods

Participants ( = 118; 48 ± 9 years of age; 97 females) performed a comprehensive off‐road evaluation that lasted about 3 h and a standardized on‐road test that lasted approximately 45 min over a 2‐day period within the same week. Performance on the five cognitive tests was used to predict participants’ performance on the standardized on‐road test.

Results

Performance on the five tests together predicted outcome of the on‐road test with 82% accuracy, 42% sensitivity and 90% specificity.

Conclusions

The accuracy of predicting the on‐road performance of a new MS cohort using performance on the battery of five cognitive tests remained very high (82%). The battery, which was administrable in <45 min and cost ~$150, was better at identifying those who actually passed the on‐road test (90% specificity). The sensitivity (42%) of the battery indicated that it should not be used as the sole determinant of poor driving‐related cognitive skills. A fail performance on the battery should only imply that more comprehensive testing is warranted.

Background and purpose

Pain is highly prevalent in Parkinson's disease (PD), impacting patients’ ability, mood and quality of life. Detecting the presence of pain in its multiple modalities is necessary for adequate personalized management of PD. A 14‐item, PD‐specific, patient‐based questionnaire (the King's Parkinson's Disease Pain Questionnaire, KPPQ) was designed corresponding to the rater‐based KPP Scale (KPPS). The present multicentre study was aimed at testing the validity of this screening tool.

Methods

First, a comparison between the KPPQ scores of patients and matched controls was performed. Next, convergent validity, reproducibility (test–retest) and diagnostic performance of the questionnaire were analysed.

Results

Data from 300 patients and 150 controls are reported. PD patients declared significantly more pain symptoms than controls (3.96 ± 2.56 vs. 2.17 ± 1.39;  < 0.0001). The KPPQ convergent validity was high with KPPS total score ( = 0.80) but weak or moderate with other pain assessments. Test–retest reliability was satisfactory with kappa values ≥0.65 except for item 5, Dyskinetic pains ( = 0.44), and the intraclass correlation coefficient (ICC) for the KPPQ total score was 0.98.

After the scores of the KPPS were adapted for screening (0, no symptom; ≥1, symptom present), a good agreement was found between the KPPQ and the KPPS (ICC = 0.88). A strong correlation ( = 0.80) between the two instruments was found. The diagnostic parameters of the KPPQ were very satisfactory as a whole, with a global accuracy of 78.3%–98.3%.

Conclusions

These results suggest that the KPPQ is a useful, reliable and valid screening instrument for pain in PD to advance patient‐related outcomes.

Background and purpose

To assess long‐term treatment effectiveness of disease‐modifying therapy (DMT) initiated early in disease course versus later treatment start.

Methods

We included all Danish patients with multiple sclerosis (MS) treated with DMT through two nationwide population‐based MS registries. Patients were categorized as early treated if treatment started within 2 years after the first MS symptom ( = 2316) and later treated if treatment started between 2 and 8 years after clinical onset ( = 1479). We compared time from treatment start to progression to an Expanded Disability Status Scale (EDSS) score of 6 and mortality between cohorts as hazard ratio (HR) using a Cox proportional hazards model with adjustment for stabilized inverse probability of treatment weights. Several sensitivity analyses were conducted.

Results

The median follow‐up time of 3795 patients was 7.0 (range 0.6–19.5) years for the EDSS score of 6 outcome and 10.4 (range 1.2–20.1) years for the mortality outcome. Patients with later treatment start showed a 42% increased hazard rate of reaching an EDSS score of 6 compared with the early‐treated patients [HR, 1.42; 95% confidence interval (CI), 1.18–1.70; < 0.001]. When stratified by sex, the increased hazard among later‐treated women persisted (HR, 1.53; 95% CI, 1.22–1.93; < 0.001), whereas the HR was lower in men (1.25; 95% CI, 0.93–1.69; = 0.15). Mortality was increased by 38% in later starters (HR, 1.38; 95% CI, 0.96–1.99; = 0.08).

Conclusions

Patients who started treatment with DMT later reached an EDSS score of 6 more quickly compared with patients who started early and the delay showed a tendency to shorten time to death. Our results support the use of early treatment.

Background and purpose

There is debate as to whether the apparent rebound after fingolimod discontinuation is related to the discontinuation itself or whether it is due to the natural course of highly active multiple sclerosis (MS). Our aim was to survey the prevalence of severe reactivation and rebound after discontinuation of fingolimod in a cohort of Italian patients with MS.

Methods

Patients with relapsing–remitting MS who were treated with fingolimod for at least 6 months and who stopped treatment for reasons that were unrelated to inefficacy were included in the analysis.

Results

A total of 100 patients who had discontinued fingolimod were included in the study. Fourteen patients (14%) had a relapse within 3 months after fingolimod discontinuation, and an additional 12 (12%) had a relapse within 6 months. According to this study's criteria, 10 patients (10%) had a severe reactivation. Amongst these patients, five (5%) had a reactivation that was considered to be a rebound.

Conclusions

The present study showed that more than 26% of patients are at risk of having a relapse within 6 months after fingolimod discontinuation. Nevertheless, the risk of severe reactivations and rebound is lower than has been previously described.

Background and purpose

There is a lack of age‐specific evidence regarding the efficacy and safety of dual antiplatelet therapy (DAPT). A systematic review and meta‐analysis was conducted for dual versus mono antiplatelet therapy in elderly patients with ischaemic stroke (IS) or transient ischaemic attack (TIA).

Methods

PubMed, Embase and the Cochrane Central Register of Controlled Trials were searched for relevant studies. Risk ratios (RRs) for the outcomes of stroke recurrence, major bleeding and intracranial bleeding were calculated based on the DerSimonian and Laird random effects model. Subgroup analyses were conducted.

Results

In seven multicentre, randomized controlled trials comprising 24 873 patients with IS or TIA, aged 65 years or older, a significant reduction in the risk of recurrent stroke was observed using DAPT in comparison with aspirin monotherapy [RR 0.79, 95% confidence interval (95% CI) 0.69–0.91; =0.001]. DAPT was not associated with a significant reduction in recurrent stroke compared with clopidogrel monotherapy (RR 1.01, 95% CI 0.93–1.10;  = 0.800). In addition, the results from two studies showed that DAPT significantly increased the risk of major bleeding and intracranial bleeding in elderly patients over younger patients (RR 2.18, 95% CI 1.02–4.69; and RR 2.13, 95% CI 1.18–3.86, respectively).

Conclusions

For stroke prevention in elderly patients with IS or TIA, DAPT is superior to aspirin monotherapy but appears to be equivalent to clopidogrel monotherapy, and is accompanied by an increased risk of bleeding. The balance between the benefits and risks of DAPT is important to consider when choosing antiplatelet strategy.

Background and purpose

The clinical course and optimal treatment strategy for asymptomatic extracranial carotid artery aneurysms (ECAAs) are unknown. We report our single‐center experience with conservative management of patients with an asymptomatic ECAA.

Methods

A search in our hospital records from 1998 to 2013 revealed 20 patients [mean age 52 (SD 12.5) years] with 23 ECAAs, defined as a 150% or more fusiform dilation or any saccular dilatation compared with the healthy internal carotid artery. None of the aneurysms were treated and we had no pre‐defined follow‐up schedule for these patients. The primary study end‐point was the yearly rate for ipsilateral ischemic stroke. Secondary end‐points were ipsilateral transient ischemic attack, any stroke‐related death, other symptoms related to the aneurysm or growth defined as any diameter increase.

Results

The ECAA was either fusiform ( = 6; mean diameter 10.2 mm) or saccular ( = 17; mean diameter 10.9 mm). Eleven (55%) patients with 13 ECAAs received antithrombotic medication. During follow‐up [median 46.5 (range 1–121) months], one patient died due to ipsilateral stroke and the ipsilateral cerebral stroke rate was 1.1 per 100 patient‐years (95% confidence interval, 0.01–6.3). Three patients had ECAA growth, two of whom were asymptomatic and one was the patient who suffered a stroke.

Conclusions

In this retrospective case series of patients with an asymptomatic ECAA, the risk of cerebral infarction is small but not negligible. Conservative management seems justified, in particular in patients without growth. Large prospective registry data are necessary to assess follow‐up imaging strategies and the role of antiplatelet therapy.

Background and purpose

Antibodies to glycine receptors (GlyR‐Abs) were first defined in progressive encephalopathy with rigidity and myoclonus (PERM) but were subsequently identified in other clinical presentations. Our aim was to assess the clinical associations of all patients identified with GlyR‐Abs in Queensland, Australia, between April 2014 and May 2017 and to compare these to cases reported in the literature.

Methods

A literature review identified the clinical features of all published GlyR‐Ab‐positive cases through online databases. A case series was undertaken via collection of clinical information from all patients diagnosed or known to immunology, pathology or neurological services in Queensland during the study period of 3 years.

Results

In all, 187 GlyR‐Ab‐positive cases were identified in the literature. The majority (47.6%) had PERM, 22.4% had epilepsy, but the remaining 30% included mixed phenotypes consisting of cerebellar ataxia, movement disorders, demyelination and encephalitis/cognitive dysfunction. By contrast, in our series of 14 cases, eight had clinical presentations consistent with seizures and epilepsy and only three cases had classical features of PERM. There was one case each of global fatiguable weakness with sustained clonus, laryngeal dystonia and movement disorder with hemiballismus and tics. The rate of response to immune therapy was similar in all groups.

Conclusion

Antibodies to glycine receptors are linked to a spectrum of neurological disease. The results of the literature review and our case series suggest a greater relationship between GlyR‐Abs and epilepsy than previously reported.

Background and purpose

Recommendations for using fluorodeoxyglucose positron emission tomography (FDG‐PET) to support the diagnosis of dementing neurodegenerative disorders are sparse and poorly structured.

Methods

Twenty‐one questions on diagnostic issues and on semi‐automated analysis to assist visual reading were defined. Literature was reviewed to assess study design, risk of bias, inconsistency, imprecision, indirectness and effect size. Critical outcomes were sensitivity, specificity, accuracy, positive/negative predictive value, area under the receiver operating characteristic curve, and positive/negative likelihood ratio of FDG‐PET in detecting the target conditions. Using the Delphi method, an expert panel voted for/against the use of FDG‐PET based on published evidence and expert opinion.

Results

Of the 1435 papers, 58 papers provided proper quantitative assessment of test performance. The panel agreed on recommending FDG‐PET for 14 questions: diagnosing mild cognitive impairment due to Alzheimer's disease (AD), frontotemporal lobar degeneration (FTLD) or dementia with Lewy bodies (DLB); diagnosing atypical AD and pseudo‐dementia; differentiating between AD and DLB, FTLD or vascular dementia, between DLB and FTLD, and between Parkinson's disease and progressive supranuclear palsy; suggesting underlying pathophysiology in corticobasal degeneration and progressive primary aphasia, and cortical dysfunction in Parkinson's disease; using semi‐automated assessment to assist visual reading. Panellists did not support FDG‐PET use for pre‐clinical stages of neurodegenerative disorders, for amyotrophic lateral sclerosis and Huntington disease diagnoses, and for amyotrophic lateral sclerosis or Huntington‐disease‐related cognitive decline.

Conclusions

Despite limited formal evidence, panellists deemed FDG‐PET useful in the early and differential diagnosis of the main neurodegenerative disorders, and semi‐automated assessment helpful to assist visual reading. These decisions are proposed as interim recommendations.

Abstract

Click to view the accompanying paper in this volume.

Abstract

Click to view the accompanying paper in this volume.

Abstract

Idiopathic intracranial hypertension (IIH) is positively associated with obesity, mostly in young women. The global increase in obesity may influence the burden of IIH. Using the PubMed, Embase, MEDLINE and Web of Science databases, a meta‐analysis and systematic review of epidemiological studies of IIH were performed up to June 2017. Temporal changes in IIH incidence were measured, and incidence rates of IIH were correlated with country‐specific World Health Organization obesity rates. Prevalence data and shunting rates of IIH were recorded. The quality of epidemiological studies was assessed using the Standards of Reporting of Neurological Disorders (STROND) criteria. In 15 identified studies, there were 889 patients (87% women), mean age 29.8 years. The incidence of IIH ranged from 0.03 to 2.36 per 100 000 per year. The pooled incidence of IIH was 1.20 per 100 000 per year although there was very high heterogeneity ( 98%). The incidence rates of IIH were correlated with country‐specific prevalence of obesity (Spearman's correlation 0.82, < 0.01). The prevalence of IIH was rarely recorded. A shunting procedure was reported in 8% of patients. STROND criteria were variably reported, median of 26.5 of 43 (range 16–35). IIH is a public health concern as increased obesity prevalence is associated with increased incidence of IIH. A better quality of epidemiological studies is required to improve understanding of IIH and inform health policy for IIH management.

Background and purpose

Intracranial hemorrhage (ICH) is the most feared complication in patients treated with oral anticoagulants due to non‐valvular atrial fibrillation. Non‐vitamin K oral anticoagulants (NOACs) reduce the risk of ICH compared with vitamin K antagonists (VKAs). We performed a systematic review and meta‐analysis to evaluate the risk of fatal NOAC‐related ICH compared with VKA‐related ICH.

Methods

We calculated the corresponding risk ratios (RRs) in each included study to express the relative risk of fatal ICH amongst all patients receiving oral anticoagulation with either NOACs or VKAs. We additionally evaluated the mortality rates in NOAC‐related ICH in patients treated with and without NOAC‐specific reversal agents (idarucizumab and factor Xa inhibitors antidote). Case fatality was evaluated at 30–90 days following symptom onset.

Results

Our literature search identified six eligible studies (four randomized controlled trials and two open‐label trials of NOAC‐specific reversal agents). In pairwise analyses, NOACs were found to have a lower risk of fatal ICH compared with VKAs [RR, 0.46; 95% confidence interval (CI), 0.36–0.58] with no heterogeneity ( = 0%) across included randomized controlled trials. However, the case fatality rate was similar in NOAC‐related and VKA‐related (RR, 1.00; 95% CI, 0.84–1.19) ICH with no evidence of heterogeneity ( = 0%). In the indirect analysis, the case fatality rate of NOAC‐related ICH in patients treated with specific reversal agents was lower compared with the remainder of the patients [17% (95% CI, 11–24%) vs. 41% (95% CI, 34–49%); < 0.001].

Conclusions

Non‐vitamin K oral anticoagulants halve the risk of fatal ICH in patients with non‐valvular atrial fibrillation compared with VKAs, whereas indirect comparisons indicate that NOAC‐specific reversal agents may be associated with a lower case fatality rate in NOAC‐related ICH.

Abstract

Click to view the accompanying paper in this volume.

Abstract

Click to view the accompanying paper in this volume.