Background and purpose

Patient and public involvement in clinical practice guideline development is recommended to increase guideline trustworthiness and relevance. The aim was to engage multiple sclerosis (MS) patients and caregivers in the definition of the key questions to be answered in the European Academy of Neurology guideline on palliative care of people with severe MS.

Methods

A mixed methods approach was used: an international online survey launched by the national MS societies of eight countries, after pilot testing/debriefing on 20 MS patients and 18 caregivers, focus group meetings of Italian and German MS patients and caregivers.

Results

Of 1199 participants, 951 (79%) completed the whole online survey and 934 from seven countries were analysed: 751 (80%) were MS patients (74% women, mean age 46.1) and 183 (20%) were caregivers (36% spouses/partners, 72% women, mean age 47.4). Participants agreed/strongly agreed on inclusion of the nine pre‐specified topics (from 89% for ‘advance care planning’ to 98% for ‘multidisciplinary rehabilitation’), and <5% replied ‘I prefer not to answer’ to any topic. There were 569 free comments: 182 (32%) on the pre‐specified topics, 227 (40%) on additional topics (16 guideline‐pertinent) and 160 (28%) on outcomes. Five focus group meetings (three of MS patients, two of caregivers, and overall 35 participants) corroborated the survey findings. In addition, they allowed an explanation of the guideline production process and the exploration of patient‐important outcomes and of taxing issues.

Conclusions

Multiple sclerosis patient and caregiver involvement was resource and time intensive, but rewarding. It was the key for the formulation of the 10 guideline questions and for the identification of patient‐important outcomes.

Background and purpose

The aim was to assess the feasibility and safety of fast‐track hospitalizations in a selected cohort of patients with stroke.

Methods

Patients hospitalized at the Stroke Center of the University Hospital Basel, Switzerland, with an acute ischaemic stroke confirmed on magnetic resonance diffusion‐weighted imaging were included. Neurological deficits of the included patients were non‐disabling, i.e. not interfering with activities of daily living and compatible with a direct discharge home. Patients with premorbid disability were excluded. All patients were admitted to the Stroke Center for ≥24 h. Two study groups were compared – fast‐track hospitalizations (≤72 h) and long‐term hospitalizations (>72 h). The primary end‐point was a composite of any unplanned rehospitalization for any reason within 3 months since hospital discharge and a modified Rankin Scale 3–6 at 3 months. Adjustment for confounders was done using the inverse probability of treatment weights (IPTW).

Results

Amongst the 521 patients who met the inclusion criteria, fast‐track hospitalizations were performed in 79 patients (15%). In the fast‐track group, seven patients (8.9%) met the primary end‐point, compared to 37 (8.4%) in the long‐term group [odds ratio (OR) 1.06, 95% confidence interval (CI) 0.42–2.34,  = 0.88]. After weighting for IPTW, the odds of the primary end‐point remained similar between the two arms (OR 1.27, 95% CI 0.51–3.16,  = 0.61). The costs of fast‐track hospitalizations were lower, on average, by $4994.

Conclusions

Fast‐track hospitalizations including a full workup proved to be feasible, showed no increased risk and were less expensive than long‐term hospitalizations.

Abstract

Clinical practice in dystonia has greatly evolved in recent years; a synthetic review on patient management is provided here. Dystonia is a movement disorder characterized by sustained or intermittent muscle contractions causing abnormal, often repetitive, movements, postures or both. A recent classification has innovated clinical practice and serves as guidance for clinical assessment: Axis I describes clinical features, whereas Axis II indicates etiology. Dystonia presents with different syndromic aggregations with varied somatic involvement and some common features. There are five recognizable physical signs of dystonia: two main signs (dystonic postures and movements) and three additional signs ( or tricks, mirror dystonia and overflow dystonia). There is still no validation of diagnostic criteria for the different dystonia syndromes, and many cases with mild phenomenology remain undiagnosed. Patients with dystonia also present non‐motor features that are variably combined with the movement disorder. The features of the most common inherited and acquired dystonia syndromes are reviewed here. There is clear evidence of genetic–environmental interaction in the determinism of dystonia. The diagnostic process is guided by clinical examination and based on specific laboratory examinations. Symptomatic treatments are available for dystonia: botulinum neurotoxin injections are the primary choice for most focal dystonia syndromes; deep brain stimulation is useful in some generalized and non‐generalized syndromes. Additional treatment strategies are currently being assessed.

Background and purpose

Research indicates that patients with myotonic dystrophy type 1 (DM1) are at increased risk of cancer and early death. Family data may provide insights given DM1 phenotypic heterogeneity, the broad range of non‐muscular manifestations and the usual delays in the diagnosis of DM1.

Method

Family history data were collected from 397 genetically and/or clinically confirmed DM1 patients (respondents) enrolled in the US or UK myotonic dystrophy registries. Standardized mortality ratios were calculated for DM1 first‐degree relatives (parents, siblings and offspring) by their reported DM1 status (affected, unaffected or unknown). For cancer‐related analyses, mixed effects logistic regression models were used to evaluate factors associated with cancer development in DM1 families, including familial clustering.

Results

A total of 467 deaths and 337 cancers were reported amongst 1737 first‐degree DM1 relatives. Mortality risk amongst relatives reported as DM1‐unaffected was comparable to that of the general population [standardized mortality ratio (SMR) 0.82,  = 0.06], whilst significantly higher mortality risks were noted in DM1‐affected relatives (SMR = 2.47,  < 0.0001) and in those whose DM1 status was unknown (SMR = 1.60,  < 0.0001). In cancer risk analyses, risk was higher amongst families in which the DM1 respondent had cancer (odds ratio 1.95,  = 0.0001). Unknown DM1 status in the siblings (odds ratio 2.59,  = 0.004) was associated with higher cancer risk.

Conclusion

There is an increased risk of death, and probably cancer, in relatives with DM1 and in those whose DM1 status is unknown. This suggests a need to perform a careful history and physical examination, supplemented by genetic testing, to identify family members at risk for DM1 and who might benefit from disease‐specific clinical care and surveillance.

Background and purpose

encodes the α1 subunit of the neuronal calcium channel P/Q. mutations underlie three allelic disorders: familial hemiplegic migraine type 1 (FHM1), episodic ataxia type 2 (EA2) and spinocerebellar ataxia type 6 (SCA6). A clear‐cut genotype–phenotype correlation is often lacking since clinical manifestations may overlap. Several case reports have described cognitive and behavioral features in disorders, but studies in larger case series are lacking.

Methods

Genetically confirmed cases were retrieved from the database of the ataxia outpatient clinic of the Department of Neurology at Innsbruck Medical University. Clinical charts and neuropsychological test results were retrospectively analyzed. In addition, a review of the literature including only genetically confirmed cases was performed.

Results

Forty‐four cases were identified in our database. Delayed psychomotor milestones and poor school performance were described in seven (four FHM1, three EA2) and eight (three FHM1, five EA2) patients, respectively. Psychiatric comorbidities were diagnosed in eight patients (two FHM1, six EA2). Neuropsychological testing was available for 23 patients (11 FHM1, 10 EA2, two SCA6). Various cognitive deficits were documented in 21 cases (all patients except one SCA6). Impairments were predominantly seen in figural memory, visuoconstructive abilities and verbal fluency. In the literature, an early psychomotor delay is described in several children with EA2 and FHM1, whilst reports of cognitive and psychiatric findings from adult cases are scarce.

Conclusions

Neuropsychiatric manifestations are common in episodic disorders. In the case of otherwise unexplained developmental delay and a positive family history, mutations should be considered in the differential diagnosis.

Background and purpose

The clinical differentiation between parkinsonism in idiopathic normal pressure hydrocephalus (iNPH) and Parkinson's disease (PD) remains challenging in the initial phase. Whether an early cognitive profiling might support the differential diagnosis of early iNPH and PD was addressed.

Methods

Neuropsychological tests of 40 iNPH subjects with early symptoms resembling parkinsonism were retrospectively evaluated together with 47 PD patients (dnPD). Only neuropsychological tests performed within 1 year from the first motor symptom were included. The cognitive spectrum of iNPH and dnPD was also compared with a sample of 70 normal controls.

Results

A clear difference in the cognitive profile of iNPH, dnPD patients and normal controls was shown. 65% of iNPH subjects showed a diffuse cognitive impairment, including memory, visuospatial abilities, fronto‐executive functioning and attention, whereas only 25.5% of the dnPD patients presented an executive dysfunction. 35% of iNPH and 74.5% of PD patients performed within the normal range ( < 0.05).

Conclusion

Subjects with iNPH showed an early and diffuse alteration of cognition with respect to dnPD patients. Performing a prompt and accurate neuropsychological evaluation might support the differential diagnosis of these two conditions of parkinsonism.

Background and purpose

Hereditary ataxias are heterogeneous groups of neurodegenerative disorders, characterized by cerebellar syndromes associated with dysarthria, oculomotor and corticospinal signs, neuropathy and cognitive impairment.

Mutated patients showed a pure cerebellar ataxia at onset, evolving in mild spastic ataxia (alternatively) associated with dysarthria (~80% of patients), urinary urgency (~30%) and pyramidal signs (~70%). Comparing homozygotes and compound heterozygotes, we noted a difference in age at onset and Scale for the Assessment and Rating of Ataxia score between the two groups, supporting an earlier and more severe phenotype in compound heterozygotes versus homozygotes.

Methods

We set up a rapid assay for c.1529C>T using restriction enzyme analysis after polymerase chain reaction amplification. We confirmed the diagnosis with Sanger sequencing.

Results

We identified eight homozygotes and 13 compound heterozygotes, including two novel variants affecting splicing.

Conclusions

The c.1529C>T (p.Ala510Val) mutants accounted for 2.3% of cerebellar ataxia cases in Italy, suggesting that this variant should be considered as a priority test in the presence of late‐onset pure ataxia. Moreover, the heterozygous/homozygous genotype appeared to predict the onset of clinical manifestation and disease progression.

Background

Cardiovascular diseases (CVDs) are more frequent in multiple sclerosis (MS) patients when compared to controls. In particular, CVDs are linked with higher accumulation of lesions and advanced brain atrophy.

Objective

To investigate whether CVDs contribute to accelerated lesion accumulation and brain atrophy over 5 years in patients with MS.

Methods

194 MS patients and 43 controls without neurologic disease were followed for 5 years. Full physical, neurological evaluation, and structured questionnaire investigating CVD and risk factors (hypertension, hyperlipidemia, heart disease, smoking, diabetes, obesity/overweight) were collected using interview‐based questionnaire and further cross‐reference with electronic medical records. Lesion and brain atrophy outcomes were assessed with 3T MRI. ANCOVA adjusted for age, gender, and disease duration were used accordingly. False discovery rate correction was performed using Benjamini‐Hochberg correction.

Results

Patients with diagnosis of heart disease showed higher white matter and whole brain volume loss compared to those without (−4.2% vs. −0.7%, = 0.01 and −3.4% vs. −1.6%, = 0.01, respectively). The percentage lateral ventricle volume change in MS patients with hypertension was higher compared to non‐hypertensive patients (24.5% vs. 14.1%, = 0.05). Hyperlipidemia, smoking, and obesity/overweight were not associated with progression of MRI‐derived outcomes. CVDs did not contribute to larger lesion volume accrual over the 5‐year period. The presence of CVDs was not associated with MRI‐derived changes in the controls.

Conclusions

Hypertension and heart disease contribute to advanced brain atrophy in MS patients. CVDs did not contribute to additional lesion accrual. CVD comorbidities in MS patients may contribute to neurodegenerative tissue injury that can be detected with brain MRI.

Background and purpose

Vascular pathology is increasingly acknowledged as a risk factor for multiple sclerosis (MS). Vascular density (VD) is reduced in the eyes of patients with MS on optical coherence tomography (OCT) angiography. We performed a 1‐year prospective study to estimate VD variations over time and possible clinical correlates.

Methods

A total of 50 patients with MS underwent spectral domain‐OCT and OCT angiography at baseline and after 1‐year follow‐up. Mixed‐effect linear regression models were used to assess variations of each OCT measure and its relation to treatment and clinical outcomes.

Results

We observed an increase in parafovea VD (coefficient, 1.147; 95% confidence interval, 0.081–2.214; = 0.035). Reduction in parafovea VD was associated with increase in Expanded Disability Status Scale score (coefficient, −0.969; 95% confidence interval, −1.732/−0.207; = 0.013).

Conclusions

Retinal VD can improve over time in MS, particularly in patients experiencing disease stability. Longer follow‐up, inclusion of early MS cases and combination with conventional markers of MS severity (i.e. brain atrophy) are needed to better define VD as a potential new biomarker.

Background and purpose

Distal involvement of autonomic nerve fibers is critical in familial amyloid polyneuropathy (FAP) due to transthyretin (TTR) mutation. This study compares different methods for assessing autonomic foot innervation in TTR‐FAP patients.

Methods

Three groups of seven TTR‐FAP patients were included, according to disease severity: clinically asymptomatic, moderate or advanced neuropathy. The autonomic investigation included the eutectic mixture of local anesthetics test and laser Doppler flowmetry for vasomotor aspects and the Sudoscan® (measuring electrochemical skin conductance) and Neuropad® test for sudomotor aspects. Somatic innervation was assessed by performing nerve conduction studies, quantitative sensory testing [including vibration, cold and warm detection threshold (WDT) measurements] and laser evoked potentials.

Results

The results of all neurophysiological tests varied according to TTR‐FAP severity ( ≤ 0.01, Kruskal–Wallis test), except for the eutectic mixture of local anesthetics test and laser Doppler flowmetry variables. In addition, the sudomotor tests (Sudoscan or Neuropad) or WDT measurement provided early markers of neuropathy in two of the seven asymptomatic carriers. Finally, all neurophysiological results correlated with the Neuropathy Impairment Score ( values between −0.88 and −0.66,  < 0.005, Spearman test), except the cold detection threshold.

Conclusions

The Neuropad test could be used to detect TTR‐FAP onset, but confirmation requires electrochemical skin conductance and WDT measurement. The Sudoscan technique, but not the Neuropad test (at least assessed at a fixed time point), could be valuable to follow the progression of the neuropathy. Follow‐up investigation should also include large‐fiber investigation (e.g. nerve conduction studies and vibration detection threshold). Conversely, reliable tests for assessing vasomotor disturbances in limb extremities of TTR‐FAP patients are still awaited.

Background and purpose

Hemodialysis (HD) may have some adverse effects on the nervous system. Headache is the most commonly reported neurological symptom amongst HD patients. Our aim was to determine the frequency, clinical characteristics and triggering factors of HD‐related headache (HRH) and to evaluate preventive strategies for reducing HRH.

Method

In all, 494 patients were included. Comparative controls (CC) were classified within the same patients without headache. Arterial systolic/diastolic blood pressure, blood urea nitrogen (BUN) and creatinine were correlated before/after one HD. The urea reduction ratio during the dialysis session was determined.

Results

A total of 175 patients (35.4%) with a mean age of 57.3 ± 15.7 years were diagnosed with HRH. HRH was more common in males (<0.001). Headache was started a mean of 2.90 ± 0.86 h after the HD. The common localization of pain was reported to be bifrontal in 41.7% ( = 73). The mean duration of headache was 6.22 ± 7.8 h, with a duration of ≤4 h reported by 64.0% of patients. The mean Visual Analog Scale score was 5.64 ± 2.05. The differences between pre/post‐dialysis BUN values were 94.6 ± 31.1 in HRH patients and 86.8 ± 28.5 in the CC group ( = 0.006). The systolic blood pressure difference between the pre/post‐dialysis measurements was 22.4 ± 16.5 mmHg in HRH patients and 12.8 ± 19.4 mmHg in CC( < 0.001). Patients with HRH had significantly higher mean systolic and diastolic blood pressure pre‐dialysis values (systolic,  = 0.002; diastolic,  < 0.001). The differences in systolic/diastolic blood pressure between pre/post‐dialysis were higher in the HRH group ( < 0.001,  = 0.001, respectively).

Conclusion

Regulating the frequency and timing of dialysis may provide better management in HRH with high BUN levels and high pre‐dialysis blood pressure.

Background and purpose

People with multiple sclerosis (MS) have to face important decisions with regard to their medical treatment. The aim of this study was to evaluate whether a targeted cognitive training reduces framing effects and thus improves medical judgments.

Methods

This was a randomized, double‐blind, cross‐over study enrolling patients with relapsing‐remitting MS and healthy controls (HCs). Participants were randomly assigned to training order A (first week, numerical training; second week, control training) or B (reverse order). The primary endpoint was changed in a framing task score (framing effect). In the framing task, participants evaluated the success of fictive medications on a 7‐point scale. Medications were described in either positive or negative terms.

Results

A total of 37 patients and 73 HCs performed either training order A ( = 56) or B ( = 54). The framing effect decreased after the numerical training regardless of training order. No such decrease was found after the control training. Mean change in framing effect was −0.3 ± 0.8 after the numerical training and 0.03 ± 0.6 after the control training. This specific effect of training type was comparable between groups.

Conclusion

Judgments of medical information improve in both patients with relapsing‐remitting MS and HCs after a targeted numerical training. Thus, a specific cognitive intervention may help patients making informed decisions.

Background and purpose

In spinocerebellar ataxia type 3/Machado–Joseph disease (SCA3/MJD), the length of CAG repeat expansions in shows an inverse correlation with age at onset (AO). Recently, a formula for predicting AO based on CAG expansion was developed for European carriers. We tested this formula in SCA3/MJD carriers from distinct origins and developed population‐specific models to predict AO.

Methods

This was a parametric survival modelling study.

Results

The European formula (EF) was tested in 739 independent SCA3/MJD carriers from South Brazil, Taiwan and the Portuguese Azorean islands, and it largely underestimated AO in South Brazilian and Taiwanese test cohorts. This finding challenged the universal use of the EF, leading us to develop and validate population‐specific models for AO prediction. Using validation cohorts, we showed that Brazilian and Taiwanese formulas largely outperformed the EF in a population‐specific manner. Inversely, the EF was more accurate at predicting AO among Portuguese Azorean patients. Hence, specific prediction models were required for each SCA3/MJD ethnic group.

Conclusions

Our data strongly support the existence of as yet unknown factors that modulate AO in SCA3/MJD in a population‐dependent manner, independent of CAG expansion length. The generated models are made available to the scientific community as they can be useful for future studies on SCA3/MJD carriers from distinct geographical origins.

Background and purpose

Body mass index (BMI), hyperglycaemia and type 2 diabetes and their interactive effects are associated with brain volume atrophy in ageing. It remains to be established if these risk factors are particularly concerning in individuals with high or low brain volumes.

Methods

Demographics, venous blood and magnetic resonance imaging data were collected for 494 healthy community‐living adults aged 53–78 (mean 65) years, as part of the Personality and Total Health Through Life study. Associations between BMI, blood glucose, diabetes status and brain volume (whole brain, grey matter, white matter and subcortical structures) were investigated using quantile regression.

Results

Quantile regression revealed vulnerability to BMI × glucose interactions particularly in lower volumes and significant main effects for type 2 diabetes particularly in higher volumes. Diabetes was most strongly associated with brain volumes. The association between BMI, blood glucose and diabetes was not consistent across the full range of brain volumes.

Conclusion

Explicit investigation of the upper and lower boundaries of brain volume distributions was valuable. We found evidence of protective reserve from higher brain volumes and that a combination of high BMI and higher blood glucose was particularly concerning for individuals with lower brain volumes.

Background and purpose

Patients suffering from basilar artery occlusion (BAO) and treated with intravenous thrombolysis are, in some centers, started on adjunct anticoagulation in hyperacute settings. We aimed to assess the outcome of such patients and to compare low‐molecular weight heparin (LMWH) and unfractionated heparin (UFH) in this context.

Methods

We examined 211 patients with angiography‐proven BAO treated with intravenous thrombolysis and either adjunct UFH or LMWH. Main outcome variables were rate of symptomatic intracranial hemorrhage (sICH) according to European Cooperative Acute Stroke Study II criteria and modified Rankin Scale (mRS) at 3 months.

Results

The overall rate of sICH was 11.4% and driven by the UFH group (13.3%). None of the LMWH group developed sICH. Recanalization rate did not significantly differ between the LMWH and UFH groups. An additional propensity analysis was made to balance anticoagulation groups regarding baseline characteristics. Propensity analysis showed a significant difference in sICH rate (0.0% vs. 14.8%, =0.044) in favor of LMWH. Independent outcome (mRS score 0–2) was achieved in a total of 31.0% and in 44.8% and 29.1% in the LMWH and UFH group, respectively (=0.09). Propensity analysis showed a significant difference in the risk of ending up bedridden or dead (mRS score 5–6; 34.5% vs. 63.0%, =0.033) in favor of LMWH.

Conclusions

Our study showed a lower rate of sICH and a shift towards improved outcome in thrombolysed patients with BAO treated with LMWH as compared with UFH.

Background and purpose

Diphenylarsinic acid (DPAA) intoxication caused by drinking contaminated well water was found in Kamisu, Japan. The symptoms indicated cerebellar–brainstem and temporo‐occipital involvement. However, it remains unclear how it affects the human brain. To elucidate the effect of DPAA on the human brain, we analyzed cerebral blood flow (CBF) data after the drinking of DPAA‐contaminated water was stopped and investigated the correlation between DPAA exposure level and CBF by single‐photon emission computed tomography (CBF‐SPECT).

Methods

The DPAA‐exposed inhabitants ( = 78) were divided into 35 symptomatic and 43 asymptomatic subjects and compared with 38 healthy controls. The DPAA concentration in nails or hair and well water was measured using a high‐performance liquid chromatography system and coupled plasma mass spectrometry after adequate extraction treatment. CBF‐SPECT data, obtained within 1 year after the drinking of contaminated well water was stopped, were analyzed by statistical parametric mapping. We also examined the relationship between variations in CBF‐SPECT signals and variations in DPAA concentrations in the hair or nails of the subjects.

Results

Compared with control subjects, CBF in symptomatic DPAA‐exposed subjects was significantly lower in the occipital lobe, including the cuneus and inferior occipital gyri. The DPAA concentration in the nails or hair of subjects was inversely and significantly related to their CBF.

Conclusion

These data suggest that CBF‐SPECT may be useful as a clinical marker to infer the effect of accumulated DPAA on the brain.

Background and purpose

We aimed to estimate the prevalence of perceived cognitive impairment (PCI) and explore its associations with lifestyle and disease characteristics in a large international cohort of people with multiple sclerosis (MS).

Methods

This study was a cross‐sectional analysis. Participants rated their cognitive function over the preceding 4 weeks using four questions in a subscale within the Multiple Sclerosis Quality of Life questionnaire (MSQOL‐54). These questions assessed perceived concentration, attention and memory by the patient and family/friends. Four definitions of PCI were derived, ranging from lowest to highest specificity. Associations with PCI were assessed by log‐binomial regression.

Results

The prevalence of PCI in our sample ranged from 41.0% (95% confidence interval, 39.0–43.0) using the least‐specific definition to 11.6% (95% confidence interval, 10.3–12.9) using the most specific definition. A number of factors were associated with PCI, increasing in magnitude as the definition specificity increased, including positive associations for smoking and body mass index, whereas physical activity, dietary quality and use of vitamin D/omega‐3 supplements were inversely associated with PCI.

Conclusions

Our study reports associations between healthy lifestyle behaviours and PCI in people with MS. Although reverse causality is a potential explanation for our findings, previous studies have shown comparable associations with healthy lifestyle and MS onset and progression. Subject to external validation, these results suggest benefits realized from a healthy lifestyle in people with MS.

Background and purpose

Treatments for progressive‐onset multiple sclerosis (MS) are lacking. To improve the disease management for progressive‐onset MS, the differences between relapse‐onset MS and progressive‐onset MS in patient‐reported disability, progression and symptoms were examined.

Methods

A total of 1985 participants of the Australian Multiple Sclerosis Longitudinal Study were included. Associations between onset type and outcomes were assessed with negative binomial regression.

Results

The severity of 17 of the 19 outcomes was significantly higher for progressive‐onset MS patients than relapse‐onset MS patients, including perspectives from disability, progression over the last year, fatigue, sensory, walking difficulties, pain, balance, spasticity, sexual dysfunction, bladder, bowel, anxiety, depression and the European quality of life (EQ‐5D) (<0.05; adjusted mean ratio ranged from 1.11 to 1.52). The differences between the two onset types were most pronounced early in the disease process and reduced with increasing MS duration, and the interaction was significant for disability, progression over the last year, walking difficulties, bladder problems, bowel problems and spasticity.

Conclusion

Participants with progressive‐onset MS were significantly worse off on nearly all patient‐reported outcomes than relapse‐onset MS participants, and the differences were most pronounced early in the disease course, highlighting the importance of early intervention for those with progressive‐onset MS.

Background

An engineered glove measuring finger motor performance previously showed ability to discriminate early‐stage multiple sclerosis (MS) patients from healthy controls (HCs). Radiologically isolated syndrome (RIS) classifies asymptomatic subjects with brain magnetic resonance imaging (MRI) abnormalities suggestive of multiple sclerosis.

Methods

Seventeen asymptomatic subjects with RIS and 17 HCs were assessed. They performed finger‐to‐thumb opposition sequences at their maximal velocity, metronome‐paced bimanual movements and conventional and diffusion tensor MRI.

Results

Subjects with RIS showed lower ( = 0.005) maximal velocity and higher ( = 0.006) bimanual coordination impairment than HCs. In RIS, bimanual coordination correlated with T2‐lesion volume, fractional anisotropy and radial diffusivity in the white matter.

Conclusions

These findings point out the relevance of fine hand measures as a robust marker of subclinical disability.

Background and purpose

Besides a distinct spectrum of demyelinating syndromes, encephalitis was observed in patients with myelin oligodendrocyte glycoprotein antibodies (MOG‐abs).

Methods

The clinical records of 690 patients with idiopathic demyelinating diseases of the central nervous system seen in our center from June 2015 to December 2017 were retrospectively reviewed. All underwent serum aquaporin 4 antibody (AQP4‐ab) and MOG‐ab detection by cell‐based assays as a routine diagnostic approach. Patients with MOG‐abs or AQP4‐abs who had ever experienced an encephalitis‐like illness during the disease course were identified. Whether diagnoses of possible or definite autoimmune encephalitis could be reached with regard to these particular episodes of encephalitis was determined. The incidence and clinical features of encephalitis in anti‐MOG disease are described in detail and compared with those in anti‐AQP4 disease.

Results

Amongst the 690 patients, 87 were MOG‐ab‐positive whilst 140 were AQP4‐ab‐positive. 20.7% (18/87) of the MOG‐ab‐positive patients had typical presentations of encephalitis. Unique cortical lesions (72.2%, 13/18) were observed; fever (55.6%), intracranial hypertension (41.2%) and cerebrospinal fluid pleocytosis (64.7%) were common during MOG‐ab‐associated encephalitis. Sixteen of the 18 patients fulfilled the criteria of definite autoimmune encephalitis (specific disease with MOG‐ab) during encephalitis, and five patients overlapped with anti‐‐methyl‐‐aspartate‐receptor encephalitis (NMDARE). Only 3.6% (5/140) of the AQP4‐ab‐positive patients had encephalitis, and none overlapped with NMDARE. The Expanded Disability Status Scale scores and the Cerebral Functional System Scores at last follow‐up were lower in patients with MOG‐ab‐associated encephalitis than in those with AQP4‐ab‐associated encephalitis.

Conclusions

Encephalitis should be recognized as an important clinical component in anti‐MOG diseases.

Background and purpose

The aim of this study was to analyse the clinical and prognostic features of myelin oligodendrocyte glycoprotein (MOG) antibody‐associated demyelination with different onset phenotypes.

Methods

A total of 52 MOG‐IgG‐seropositive patients were divided into four groups: (i) optic neuritis (ON) at onset (MOG‐ON,  = 23), (ii) transverse myelitis (TM) at onset (MOG‐TM,  = 12), (iii) pure brain symptoms at onset (MOG‐ON‐TM,  = 14) and (iv) both ON and TM at onset ( = 3). This final group was not included in further analyses. Data were collected through medical records and regular follow‐up.

Results

Median age at presentation was 24 (range, 3–63) years in the whole cohort (50% female). MOG‐ON‐TM patients had the youngest age of onset across the three groups. Patients with MOG‐TM tended to relapse more frequently and had a longer interval to first relapse than was observed in MOG‐ON and MOG‐ON‐TM patients. High MOG‐IgG titres were associated with increased cerebrospinal fluid leukocytes. The likelihood of harbouring transient, low MOG‐IgG titres was higher in the MOG‐TM group than in the other groups. After a median disease duration of 20 months, most but not all cases had a favourable outcome, with 8% developing severe visual deficit, 2% becoming wheelchair‐dependent and 6% developing cognitive impairment. The onset phenotype appeared to be an important predictor of disability type. Having high MOG‐IgG titres (odds ratio, 0.168,  = 0.027) or female gender (odds ratio, 0.270,  = 0.067) was associated with a lower likelihood of complete recovery.

Conclusions

Onset phenotype may influence long‐term presentation, MOG‐IgG status as well as outcome. Further large and prospective studies are needed to better clarify the clinical implications of the first demyelinating event.

Background and purpose

The recent literature suggests that a cardiac origin in ischaemic stroke is more frequent than previously assumed. However, it is not always clear which patients benefit from additional cardiac investigations if obvious cardiac pathology is absent.

Methods

A single‐center retrospective observational study was performed with 7454 consecutive patients admitted to the intensive care unit after cardiac surgery in the period 2006–2015 and who had postoperative brain imaging. Cerebral imaging was studied for the occurrence of stroke including subtype and involved vascular territory. It was assumed that all perioperative thromboembolic strokes are of cardiac origin. Data obtained from a hospital cohort of consecutive patients who received a diagnosis of ischaemic stroke were used for comparison.

Results

Thromboembolic stroke occurred in 135 cardiac surgery patients in 56 (41%) of whom the posterior cerebral circulation was involved. In the control group, 100 out of 503 strokes (20%) were located in the posterior cerebral circulation. The relative risk for a posterior location for stroke after cardiac surgery compared to patients with ischaemic stroke without prior cardiac surgery was 2.09; 95% confidence interval 1.60–2.72.

Conclusions

Thromboembolic stroke after cardiac surgery occurs twice as often in the posterior cerebral circulation compared to ischaemic strokes in the general population. If confirmed in general stroke cohorts, the consequence of this finding may be that in patients with an ischaemic stroke that involves the posterior cerebral circulation the chance of a cardiac origin is increased and therefore might trigger additional cardiac investigations such as long‐term heart rhythm monitoring or echocardiography.

Background and purpose

The aim was to investigate the brain microstructural abnormalities in epilepsy patients with postictal generalized electroencephalographic suppression (PGES) using a cortical surface‐based analysis.

Methods

According to the video‐electroencephalography records of epilepsy patients with generalized convulsive seizures, 30 patients with PGES (PGES+) and 21 patients without PGES (PGES−) were recruited. High‐resolution T1‐weighted images were acquired from each patient and 30 matched healthy control subjects. Cortical thickness was compared amongst the three groups using FreeSurfer software.

Results

Patients with PGES showed reduced cortical thickness in the right paracentral lobule, inferior parietal lobule, supramarginal gyrus and middle temporal lobe compared with patients without PGES. In relation to healthy control subjects, the PGES+ group presented reduced cortical thickness in the right superior parietal lobule and supramarginal gyrus, whilst the PGES− group presented reduced cortical thickness in the left precuneus, precentral gyrus, lateral occipital gyrus, parahippocampal gyrus, superior parietal lobule and right caudal middle frontal gyrus.

Conclusions

Patients with PGES exhibited characteristic brain microstructural abnormalities, corroborating the PGES mechanisms at the brain level. The right‐sided predominance of the detected PGES‐related cortical thinning was the same as that of sudden unexpected death in epilepsy (SUDEP) cases and patients at high risk for SUDEP, implying that PGES and SUDEP may share a common abnormal brain substrate that is involved in the pathophysiology of these conditions.

Abstract

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Abstract

Stroke is the cause of about 10% of all epilepsy and 55% of newly diagnosed seizures among the elderly. Although recent advances in acute stroke therapy have improved longevity, there has been a consequent rise in the prevalence of stroke‐related epilepsy (STRE). Many clinical studies make a distinction between early (within 7 days of onset of stroke) and late (beyond 7 days of onset of stroke) seizures based on presumed pathophysiological differences. Although early seizures are thought to be the consequence of local metabolic disturbances without altered neuronal networks, late seizures are thought to occur when the brain has acquired a predisposition for seizures. Overall, STRE has a good prognosis, being well controlled by antiepileptic drugs. However, up to 25% of cases become drug resistant. STRE can also result in increased morbidity, longer hospitalization, greater disability at discharge and greater resource utilization. Additional controlled trials are needed to explore the primary and secondary prevention of STRE as well as to provide high‐quality evidence on efficacy and tolerability of antiepileptic drugs to guide treatment of STRE. Robust pre‐clinical and clinical prediction models of STRE are also needed to develop treatments to prevent the transformation of infarcted tissue into an epileptic focus.

Abstract

Multiple sclerosis (MS) is the commonest non‐traumatic disabling disease to affect young adults. The incidence of MS is increasing worldwide, together with the socioeconomic impact of the disease. The underlying cause of MS and mechanisms behind this increase remain opaque, although complex gene–environment interactions almost certainly play a significant role. The epidemiology of MS indicates that low serum levels of vitamin D, smoking, childhood obesity and infection with the Epstein–Barr virus are likely to play a role in disease development. Changes in diagnostic methods and criteria mean that people with MS can be diagnosed increasingly early in their disease trajectory. Alongside this, treatments for MS have increased exponentially in number, efficacy and risk. There is now the possibility of a diagnosis of ‘pre‐symptomatic MS’ being made; as a result potentially preventive strategies could be studied. In this comprehensive review, MS epidemiology, potential aetiological factors and pathology are discussed, before moving on to clinical aspects of MS diagnosis and management.