Background and purpose

Subthalamic nucleus (STN) deep brain stimulation (DBS) improves quality of life (QoL) and motor and non‐motor symptoms in advanced Parkinson's disease (PD). However, its effect on alexithymia and its relationship to other neuropsychiatric symptoms and QoL in PD is unclear.

Methods

In this prospective, observational study of 39 patients with PD undergoing STN‐DBS, we examined the Parkinson's Disease Questionnaire‐8 (PDQ‐8), 20‐item Toronto Alexithymia Scale (TAS‐20), Hospital Anxiety and Depression Scale (HADS), Self‐Report Manic Inventory (SRMI), Apathy Evaluation Scale (AES), Unified Parkinson's Disease Rating Scale (UPDRS) activities of daily living, UPDRS motor examination and UPDRS complications (UPDRS‐II/‐III/‐IV) and levodopa‐equivalent daily dose (LEDD) pre‐operatively and at 5‐month follow‐up. Outcome changes were tested with Wilcoxon signed‐rank or paired ‐test when parametric tests were applicable and corrected for multiple comparisons. The relationship between outcome changes was explored with bivariate correlations. Additionally, partial correlations between PDQ‐8 and TAS‐20 were computed controlling for HADS, SRMI and AES change scores. Predictor analyses for PDQ‐8 improvement were calculated for all baseline parameters.

Results

The baseline prevalence of alexithymia was 17.9%. We observed significant beneficial effects of STN‐DBS on PDQ‐8, TAS‐20, HADS, UPDRS‐II, ‐III and ‐IV scores and significant LEDD reduction. The correlation between TAS‐20 and PDQ‐8 improvements remained significant after controlling for all other aforementioned outcomes. Predictor analyses for PDQ‐8 improvement were significant for PDQ‐8 and TAS‐20.

Conclusions

This is the first report of beneficial effects of STN‐DBS on alexithymia. Alexithymia was significantly associated with QoL outcome independent of anxiety, depression, mania and apathy. Our study highlights the importance of alexithymia for holistic assessments of DBS outcomes.

Background and purpose

The aim of this study was to describe the clinical and epidemiological characteristics of acute ischaemic stroke (AIS) in patients with atrial fibrillation (AF) previously treated with oral anticoagulants (OACs) according to the type of OAC prescribed. Also, to analyze the outcomes of the patients and the therapeutic approach adopted by the neurologist in the acute phase and for secondary prevention.

Methods

We performed a multicenter, observational study based on prospective registries. We included patients with AF treated with OACs admitted for AIS over a 1‐year period. Detailed clinical data and functional outcome at 3 months (modified Rankin Scale score) were collected. Patients were divided into two groups according to their pre‐AIS anticoagulant therapy: vitamin K antagonists (AIS‐VKA) and direct‐acting OACs (AIS‐DOAC).

Results

We recruited 1240 patients (80.4% AIS‐VKA and 19.6% AIS‐DOAC). In the AIS‐DOAC group, transient ischaemic attack was more frequent (18.1% vs. 10.8%;  = 0.001), symptomatic hemorrhagic transformation was less frequent (1.6% vs. 4.6%;  = 0.035) and hospital stay was shorter (median 6 vs. 7 days;  = 0.03). Intravenous thrombolysis was more commonly used in AIS‐VKA (9.2% vs. 1.6%;  < 0.001). There were no differences between the groups with respect to mechanical thrombectomy, mortality and modified Rankin Scale score at 3 months. At 3 months, 54% of patients required a DOAC as antithrombotic treatment for secondary prevention.

Conclusions

Patients with AF treated with DOACs who experienced AIS more frequently had transient symptoms (transient ischaemic attack), less symptomatic hemorrhagic transformation and a shorter mean stay than those treated with VKAs. Most patients who had been previously anticoagulated with AIS received long‐term treatment with DOACs.

Background and purpose

No prospective study has evaluated the impact of restless legs syndrome (RLS) on clinical factors in patients with migraine. We planned a prospective study to assess the impact of RLS comorbid status on clinical factors in patients with migraine.

Methods

A total of 101 patients with migraine who were evaluated for RLS twice at 7‐year intervals in a university hospital setting were included in this study. The RLS group was defined as positive for RLS at either baseline or follow‐up and the non‐RLS group was defined as negative for RLS at both baseline and follow‐up. The Migraine Disability Assessment (MIDAS) questionnaire, Beck Depression Inventory‐II (BDI‐II), Pittsburgh Sleep Quality Index (PSQI) and Epworth Sleepiness Scale were administered to all patients.

Results

The RLS prevalence was 16.8% at baseline and 20.8% at follow‐up. Compared with the non‐RLS group ( = 27), the RLS group ( = 74) showed a significantly higher rate of smoking and higher MIDAS and BDI‐II scores at 7‐year follow‐up. A significant reduction in MIDAS and BDI‐II scores at 7‐year follow‐up compared with those at baseline was observed in the non‐RLS group, but not in the RLS group. The non‐RLS group showed a significantly lower MIDAS score at 7‐year follow‐up than the RLS group after adjusting for confounding variables such as age, gender, smoking status, Epworth Sleepiness Scale and PSQI scores using analysis of covariance. The persistent RLS group ( = 11) (positive for RLS at both baseline and follow‐up) showed a significantly higher rate of smoking and increased MIDAS, BDI‐II and PSQI scores compared with the non‐RLS group ( = 74) at 7‐year follow‐up.

Conclusion

Our prospective study showed that RLS had a significant impact on headache‐related disability in patients with migraine.

Background and purpose

Dementia in Parkinson's disease (PD) is common and disabling. Identification of modifiable risk factors for it is essential. Vascular risk factors (VRFs) may be associated with cognitive decline in early PD. Biomarkers that serve as surrogates of the long‐term effect of VRFs on PD are needed. To that end, we aimed to quantitate white matter hyperintensities (WMH) in early PD, measure associations with VRFs and examine relationships between WMH and longitudinal cognition.

Methods

Participants in the Parkinson's Progression Markers Initiative study (141 patients with PD, 63 healthy controls) with adequate baseline structural brain magnetic resonance imaging data were included. Hypertension and diabetes history, and body mass index were combined to create a vascular risk score. WMH were quantitated via automated methods. Cognition was assessed annually with a comprehensive test battery.

Results

In the PD group, vascular risk score was associated with WMH for total brain (β = 0.210;  = 0.021), total white matter (β = 0.214;  = 0.013), frontal (β = 0.220;  = 0.002) and temporal (β = 0.212;  = 0.002) regions. Annual rate of change in global cognition was greater in those with higher vascular risk score (β = −0.040;  = 0.007) and greater WMH (β = −0.029;  = 0.049). Higher temporal WMH burden was associated with great decline over time in verbal memory (β = −0.034;  = 0.031).

Conclusions

In early PD, modifiable VRFs are associated with WMH on brain magnetic resonance imaging. Temporal WMH burden predicts decline in verbal memory. WMH may serve as a surrogate marker for the effect of VRFs on cognitive abilities in PD.

Background and purpose

The aim of this study was to identify the prevalence of sleep disorders and measure the objective sleep quality in patients with seizure disorders.

Methods

Patients admitted for video electroencephalography monitoring were prospectively recruited and polysomnography was performed on the third night of monitoring.

Results

A total of 4/44 (9%) patients with epilepsy and 2/22 (9%) patients with dissociative seizures were found to have mild sleep‐disordered breathing. Three (7%) patients with epilepsy were found to have mild or moderate obstructive sleep apnea–hypopnea syndrome (OSAHS) and three (14%) patients with dissociative seizures had mild or moderate OSAHS. Most patients with sleep‐disordered breathing or OSAHS were overweight or obese. Time awake after sleep onset was high in both groups. There were no significant differences in sleep architecture between the groups except for a difference in average N3 sleep stage proportion. Periodic limb movements (PLMs) were common in both groups and 27% of patients with dissociative seizures had both high PLM rates and high arousal indices, suggesting a high prevalence of probable PLM disorder in that group (compared with 9% in the epilepsy group).

Conclusions

Our findings contradict the commonly reported high comorbidity of OSAHS and epilepsy, and question its purported clinical relevance. High rates of PLMs were found in patients with dissociative seizures. In both patient groups, high awake after sleep onset times were indicative of sleep disruption, which can have an epileptogenic effect and is known to increase dissociative tendencies.

Abstract

Muscular cramp is a common symptom in healthy people, especially among the elderly and in young people after vigorous or peak exercise. It is prominent in a number of benign neurological syndromes. It is a particular feature of chronic neurogenic disorders, especially amyotrophic lateral sclerosis. A literature review was undertaken to understand the diverse clinical associations of cramp and its neurophysiological basis, taking into account recent developments in membrane physiology and modulation of motor neuronal excitability. Many aspects of cramping remain incompletely understood and require further study. Current treatment options are correspondingly limited.

Background and purpose

The P2Y12 receptor, a well‐known factor in the platelet activation pathway, plays a role in thrombosis as well as systemic inflammation. Clopidogrel, a prototype P2Y12 receptor antagonist, reportedly decreases inflammation and systemic infection. The aim of this study was to evaluate whether clopidogrel use decreases the risk of post‐stroke infection following ischaemic stroke.

Methods

A total of 1643 patients with acute ischaemic stroke (within 7 days after onset) were included for analysis between March 2010 and December 2015. Patients were categorized into two groups (clopidogrel users versus clopidogrel non‐users), and clinical characteristics and risks of post‐stroke infection were compared between the two groups. The inverse probability of treatment weighting using propensity scores for baseline imbalance adjustments was applied.

Results

Of the included patients (mean age 67.7 years; men 60.6%), 670 (40.8%) patients were clopidogrel users and 164 (10.0%) patients had post‐stroke infection. The proportion of patients with post‐stroke infection was significantly lower in clopidogrel users compared to clopidogrel non‐users (6.7% vs. 12.2%, ≤0.001). Moreover, clopidogrel users were less likely to be admitted to the intensive care unit (13.3% vs. 35.3%, =0.006). A multivariate analysis with inverse probability of treatment weighting revealed that clopidogrel users exhibited a lower risk of post‐stroke infection (odds ratio 0.56, 95% confidence interval 0.42–0.75) and intensive care unit admission (odds ratio 0.34, 95% confidence interval 0.22–0.53).

Conclusions

The study suggested that clopidogrel users exhibit a lower risk of infection and develop less severe infections after ischaemic stroke. Further prospective studies are needed.

Background and purpose

Previous studies have reported that many patients with a severe head injury are not transported to a higher‐level trauma centre where the necessary round‐the‐clock neurosurgical care is available. The aim of this study was to analyse the diagnostic value of emergency medical services (EMS) provider judgement in the identification of a head injury.

Methods

In this multicentre cohort study, all trauma patients aged 16 years and over who were transported with highest priority to a trauma centre were evaluated. The diagnostic value of EMS provider judgement was determined using an Abbreviated Injury Scale score of ≥1 in the head region as reference standard.

Results

A total of 980 (35.4%) of the 2766 patients who were included had a head injury. EMS provider judgement (Abbreviated Injury Scale score ≥1) had a sensitivity of 67.9% and a specificity of 87.7%. In the cohort, 208 (7.5%) patients had a severe head injury. Of these, 68% were transported to a level I trauma centre.

Conclusions

Identification of a head injury on‐scene is challenging. EMS providers could not identify 32% of the patients with a head injury and 21% of the patients with a severe head injury. Additional education, training and a supplementary protocol with predictors of a severe head injury could help EMS providers in the identification of these patients.

Background and purpose

Fampridine leads to significant improvements in walking in many people with multiple sclerosis (PwMS). However, a relevant proportion of PwMS does not respond to fampridine and predictors of initial drug responsiveness are unknown.

Methods

Drug response to prolonged‐release (PR)‐fampridine was assessed in 55 PwMS using the timed 25‐foot walk (T25FW), 6‐min walk test (6MWT) and 12‐item multiple sclerosis walking scale as outcome parameters. Patients were treated with PR‐fampridine and placebo for 6 weeks each in a randomized, double‐blind, placebo‐controlled trial with crossover design (NCT01576354). Possible predictors of drug responsiveness were investigated by multiple correlation analysis and binary logistic regression models. An additional longitudinal analysis followed the drug responses of 32 patients treated with PR‐fampridine over 3 years to identify potential predictors of long‐term drug responsiveness.

Results

Severity of walking disability was positively correlated with enhanced responses to PR‐fampridine. The strongest single predictor of drug responsiveness was poor 6MWT performance at baseline, which was positively correlated with enhanced drug response in the 6MWT ( = −0.541;  < 0.001). A multivariable logistic regression model including 6MWT and T25FW baseline performances predicted PR‐fampridine responder status with an accuracy of 85.5% (specificity, 90.0%; sensitivity, 73.3%), with a threshold of 211 m in the 6MWT best separating responders from non‐responders. Enhanced drug responsiveness after 3 years correlated with decline in walking endurance during this period ( = −0.634;  = 0.001).

Conclusions

Initial walking impairment is a good predictor of therapeutic responsiveness to PR‐fampridine. Valid predictors of patients’ responsiveness to PR‐fampridine are essential for patient stratification and optimization of multiple slcerosis treatment.

Background and purpose

In contrast to anterior circulation stroke (ACS), there is no evidence from randomized trials that mechanical thrombectomy (MT) with modern stent retrievers or thromboaspiration is safe and effective in posterior circulation stroke (PCS).

Methods

The present analysis was based on the prospective multicentre Registry on Revascularization in Ischemic Stroke Patients (REVASK) in Germany. Demographic data, periprocedural times and complications, recanalization rates, and functional outcome at discharge and after 3 months were compared between 139 consecutive patients with PCS (84.9% basilar artery, 16.5% vertebral artery and 4.3% posterior cerebral artery occlusion) and 961 patients with ACS treated with MT.

Results

Compared to ACS, PCS patients were significantly younger (65 vs. 69 years, = 0.021) and had a lower median National Institutes of Health Stroke Scale (NIHSS) score at baseline (12 vs. 15, = 0.024). Patients with PCS had a significantly longer time delay between symptom onset and both start and end of the MT procedure. Successful recanalization and thrombectomy passes did not significantly differ between the two groups. No symptomatic intracranial haemorrhage occurred in PCS compared to 3% in ACS ( = 0.010). The median NIHSS score at discharge was 3 in PCS and 4 in ACS. Favourable functional outcome at 3 months (modified Rankin Scale 0–2 38.0% vs. 42.6%, = 0.392) and mortality (33.7% vs. 30.8%, = 0.539) did not differ significantly between PCS and ACS.

Conclusions

The study suggests that MT in PCS shows a lower risk of symptomatic intracranial haemorrhage and similar effectiveness compared to ACS. PCS patients also seem to benefit from MT started beyond 6 h after symptom onset.

Background and purpose

The aim of the study was to evaluate the metabolic correlates of () genotype in amyotrophic lateral sclerosis (ALS) and to investigate the role of ε2 as a risk factor for cognitive impairment.

Methods

A total of 159 ALS cases underwent and ALS‐related genes analysis, neuropsychological assessment and cerebral F‐2‐fluoro‐2‐deoxy‐D‐glucose positron emission tomography. The genotype was regressed against whole brain metabolism as assessed by F‐2‐fluoro‐2‐deoxy‐D‐glucose positron emission tomography, with age, sex, education, type of onset and status as covariates.

Results

Brain metabolism was significantly positively correlated with genotype from ε2/ε2 to ε3/ε4 in the left prefrontal [Brodmann area (BA) 10], orbitofrontal (BAs 11, 45, 47) and anterior cingulate (BA 32) cortices. There was a tendency to a relative hypometabolism going towards the ε2/ε2 extreme.

Conclusions

We found a highly significant, relatively lower metabolism in association with the ε2 allele in extra‐motor areas typically affected in frontotemporal dementia (left prefrontal, orbitofrontal and anterior cingulate cortices), strengthening the finding of a role of ε2 as a risk factor for cognitive impairment in ALS. Our data suggested a link between cholesterol homeostasis and neurodegeneration.

Background and purpose

Data from randomly controlled trials have indicated that a decompressive hemicraniectomy is more clinically effective than medical treatment in the management of space‐occupying brain oedema post middle cerebral artery infarction. This economic evaluation compares the impact of the two options in the UK. No recent study has conducted an economic evaluation on this topic for the UK.

Method

A cost–utility analysis over a time period of 1 year was used, measuring benefits in terms of quality adjusted life years (QALYs) and costs in pound sterling, discounted to 2015 prices. The evaluation was from the perspective of the National Health Service, the largest healthcare provider in the UK.

Results

The cost–utility analysis found an incremental cost effectiveness of £116 595.10 for every QALY gained if patients were offered a decompressive hemicraniectomy compared to the best medical treatment.

Discussion

This is above the National Institute for Health and Care Excellence (NICE) ‘cost‐effective’ threshold of £20 000–£30 000 per QALY, but lower mortality rates associated with the surgical alternative raises ethical considerations for healthcare providers in the UK.

Background and purpose

Migraine has long been associated with unsteadiness and dizziness but postural control has not been studied in the ictal state. Here, the stability of upright stance during migraine attacks was measured.

Methods

Static balance was assessed prospectively in migraine patients ( = 30) during quiet stance for 40 s on a posturographic force platform. Recordings were performed both ictally and in the pain‐free interval. Subjects were assessed under four different conditions yielding different visual and proprioceptive feedback environments. Both ictal and interictal data were compared with age‐matched healthy controls ( = 30).

Results

Postural instability increased significantly under all experimental conditions during migraine attacks. Whilst standing on a foam pad with eyes closed, median sway area was 353 mm in control subjects, 318 mm in migraineurs in the pain‐free period and 618 mm in the ictal state. However, Romberg and vestibular Romberg quotients were not altered during migraine attacks. Spectral analyses of postural sway also showed similar profiles in migraineurs and controls. The severity of headache was inversely correlated to Romberg quotients.

Conclusions

The demonstrated pattern of balance disorder during migraine attacks suggests a transient cerebellar dysfunction. Our findings also indicate that intense headache induces a re‐weighting of sensory processing toward less dependence on visual and proprioceptive information.

Background and purpose

The therapeutic scenario of X‐linked adrenoleukodystrophy (X‐ALD) is rapidly changing. Whereas the disease is well characterized in men, the condition remains to be fully clarified in women carrying ATP binding cassette subfamily D member 1 () variants. Specifically, data on clinical progression are needed, in order to recommend any appropriate management. The objective of this study was to outline the natural history of a cohort of untreated heterozygous female carriers.

Methods

Longitudinal data from a single‐center population of 60 carriers were retrospectively reviewed. Demographics, anthropometrics, serum very long chain fatty acid (VLCFA) levels, clinical parameters and the Adult ALD Clinical Score (AACS) were collected from every recorded visit in a 7‐year period and analyzed to define the phenotype modifications, to determine factors associated with clinical features, and to estimate the annual progression rate and the subsequent sample size for interventional trials.

Results

Thirty‐two patients were eligible for the study, and 59.4% were symptomatic at baseline. Clinical severity worsens with age which increases risk of symptom onset, the cut‐off of 41 years being crucial for phenoconversion. VLCFA levels were not predictive and did not change over time. Symptomatic carriers were followed up for 3.45 ± 2.1 years. The AACS increased at an annual rate of 0.24 points. The estimated sample size for 30% reduction in annual progression at 80% power was 272.

Conclusions

This study provides data on the natural disease progression of untreated heterozygous female carriers, demonstrating the relevance of aging. The estimated annual increase of the AACS will be useful for future interventional studies.

The International League against Epilepsy (ILAE) proposed a diagnostic scheme for psychogenic non‐epileptic seizure (PNES). The debate on ethical aspects of the diagnostic procedures is ongoing, the treatment is not standardized and management might differ according to age group. The objective was to reach an expert and stakeholder consensus on PNES management. A board comprising adult and child neurologists, neuropsychologists, psychiatrists, pharmacologists, experts in forensic medicine and bioethics as well as patients’ representatives was formed. The board chose five main topics regarding PNES: diagnosis; ethical issues; psychiatric comorbidities; psychological treatment; and pharmacological treatment. After a systematic review of the literature, the board met in a consensus conference in Catanzaro (Italy). Further consultations using a model of Delphi panel were held. The global level of evidence for all topics was low. Even though most questions were formulated separately for children/adolescents and adults, no major age‐related differences emerged. The board established that the approach to PNES diagnosis should comply with ILAE recommendations. Seizure induction was considered ethical, preferring the least invasive techniques. The board recommended looking carefully for mood disturbances, personality disorders and psychic trauma in persons with PNES and considering cognitive‐behavioural therapy as a first‐line psychological approach and pharmacological treatment to manage comorbid conditions, namely anxiety and depression. Psychogenic non‐epileptic seizure management should be multidisciplinary. High‐quality long‐term studies are needed to standardize PNES management.

Background and purpose

Cluster headache (CH) is characterized by severe, unilateral attacks of pain and a high nocturnal attack burden. It remains unknown whether perturbations of sleep are solely present during the CH bout. Therefore, we aimed to investigate differences in sleep between the bout and remission period in patients with episodic CH and, secondly, to compare patients in the two phases with controls.

Methods

Patients with episodic CH (aged 18–65 years), diagnosed according to the International Classification of Headache Disorders 2nd edition, were admitted for polysomnography at the Danish Center for Sleep Medicine in bout and in remission. The macrostructure of sleep, including arousals, breathing parameters, limb movements and periodic limb movements, was compared with 25 age‐, sex‐ and body mass index‐matched healthy controls.

Results

There were no differences in any of the sleep parameters for patients in bout ( = 32) compared with patients in remission ( = 23). Attacks were unrelated to sleep stages, presence of apnea episodes, periodic limb movements, limb movements and arousals. In bout, patients had longer sleep latency (18.8 vs. 11.7 min,  < 0.05) and rapid eye movement sleep latency (1.7 vs. 1.2 h,  < 0.05) than controls and sleep efficiency was lower (82.5% vs. 86.5%,  < 0.05). Patients in remission only had a longer sleep latency compared with controls (17.5 vs. 11.7 min,  < 0.01).

Conclusions

The results support the presence of a continuing or slowly recovering disturbance of sleep outside the bout rather than a disturbance occurring secondary to attacks. Further, we confirm that there is no relation between CH attacks and specific sleep stages or between CH and breathing parameters.

Background and purpose

We aimed to determine the prevalence of epilepsy in patients with multiple sclerosis (MS) at diagnosis, the risk of developing epilepsy after the diagnosis of MS and the relative risk of mortality associated with epilepsy.

Methods

We used the UK Clinical Practice Research Data‐link to identify 2526 patients with incident MS and 9980 age‐, sex‐ and index year‐matched non‐MS controls from 1997 to 2006. Logistic regression was used to estimate odds ratios [95% confidence interval (CI)] for epilepsy and Cox regression was used to estimate hazard ratios (HRs) (95% CI) for epilepsy and mortality.

Results

Patients with incident MS were on average 45 years old and 70.9% were female. At diagnosis, the prevalence of epilepsy in patients with MS was 1.30% compared with 0.57% in non‐MS controls. At diagnosis, MS was associated with an adjusted odds ratio (95% CI) of 2.11 (1.36–3.27) for pre‐existing epilepsy. Among epilepsy‐free patients, the cumulative probabilities of developing epilepsy, first recorded within 10 years of the index date, were 2.77% for patients with MS and 0.90% for controls. MS was associated with an adjusted HR (95% CI) of 6.01 (2.94–12.29) for epilepsy. Among patients with MS, epilepsy was associated with an HR (95% CI) of 2.23 (1.02–4.84) for all‐cause mortality.

Conclusions

This population‐based study found an increased prevalence of epilepsy in patients with MS at diagnosis when compared with non‐MS controls and the risk of developing epilepsy was also higher following the MS diagnosis. Patients with MS with epilepsy had a higher risk of mortality compared with those without.

Background and purpose

Adiponectin is a cytokine linking energy metabolism and immune system. After being assembled, adiponectin circulates as oligomers of different molecular weight, i.e. low, medium and high (HMW) molecular weight. These have the most potent biological effects. Multiple sclerosis (MS) is an autoimmune disease of the human central nervous system. The aim of this study was to characterize the expression levels of both total adiponectin and its oligomerization state in the serum from 99 patients with MS at baseline (i.e. not influenced by therapies). We also investigated the potential relationships between adiponectin and disease progression and severity.

Methods

Adiponectin was quantified and visualized by enzyme‐linked immunosorbent assay, western blotting and fast protein liquid chromatography. During the follow‐up (3.6 ± 2.20 years), the patients were evaluated using total annualized relapse rate and Expanded Disability Status Scale score.

Results

Total adiponectin is statistically higher in patients with MS compared with matched controls (12.18 vs. 10.02 μg/mL, =0.001). Interestingly, the adiponectin oligomerization state is altered in MS, with an increase of HMW oligomers. In addition, patients with MS with higher levels of adiponectin at baseline have significantly higher risk of progression and severity (Multiple Sclerosis Severity Score, 3.84 vs. 2.44, =0.001). No statistical difference in adiponectin expression was found between active and inactive patients with MS and among the different forms of disease.

Conclusions

This study demonstrated that adiponectin and its HMW oligomers are greatly involved in MS autoimmune disorder representing a potential biomarker to predict worse MS prognosis and severity. Further studies are required to clarify the molecular mechanisms underlying the properties of adiponectin and HMW oligomers in MS.

Background and purpose

Our objective was to study the association between the presence of a neurological disease and the comorbidity burden as well as healthcare utilization (HCU).

Methods

Using baseline data from the Canadian Longitudinal Study on Aging (CLSA), we examined the burden of five neurological conditions. The CLSA is a population‐based study of approximately 50 000 individuals, aged 45–85 years at baseline. We used multivariable Poisson regression to identify correlates of comorbidity burden and HCU.

Results

The lifetime prevalence of five neurological diseases is presented: epilepsy, Parkinson's disease/parkinsonism, stroke/transient ischaemic attack, multiple sclerosis and migraine. We found the somatic and psychiatric comorbidity burden to be higher in those individuals with a neurological disease (an 18–45% mean increase in the number of chronic conditions) as compared with the comparison group without a neurological disease, except for Parkinson's disease/parkinsonism. The presence of a neurological disease was associated with only a modest increase in the probability of visiting a general practitioner but was associated with a greatly increased probability of visiting a medical specialist (up to 68% more likely) or an emergency department (up to 79% more likely) and an overnight hospitalization (up to 108% more likely).

Conclusions

We found striking associations between our neurological diseases and increased comorbidity burdens and HCU. These findings are important for informing public policy planning as well as driving avenues for future research. The present study established the CLSA as an important research platform for the study of neurological conditions in an aging general population.

Background and purpose

Treatment options in primary progressive multiple sclerosis (PPMS) are scarce and, with the exception of ocrelizumab, anti‐inflammatory agents have failed to show efficacy in ameliorating disability progression. The aim of this study was to investigate a potential effect of anti‐inflammatory disease‐modifying treatment on disability outcomes in PPMS.

Methods

Using MSBase, a large, international, observational database, we identified patients with PPMS who were either never treated or treated with a disease‐modifying agent. Propensity score matching was used to select subpopulations with similar baseline characteristics. Expanded Disability Status Scale (EDSS) outcomes were compared with an intention‐to‐treat and an as‐treated approach in paired, pairwise‐censored analyses.

Results

Of the 1284 included patients, 533 were matched (treated, = 195; untreated = 338). Median on‐study pairwise‐censored follow‐up was 3.4 years (quartiles 1.2–5.5). No difference in the hazard of experiencing 3‐month confirmed EDSS progression events was observed between the groups [hazard ratio (HR), 1.0; 95% confidence interval (CI), 0.6–1.7, = 0.87]. We did not find significant differences in the hazards of confirmed EDSS improvement (HR, 1.0; 95% CI, 0.6–1.6, = 0.91) or reaching a confirmed EDSS step ≥7 (HR, 1.1; 95% CI, 0.7–1.6, = 0.69).

Conclusion

Our pooled analysis of disease‐modifying agents suggests that these therapies have no substantial effect on short‐ to medium‐term disability outcomes in PPMS.

Background and purpose

Early pharmacological deep vein thrombosis (DVT) prophylaxis is recommended by guidelines, but rarely started within 48 h. We aimed to analyze the effect of early (within 48 h) versus late (>48 h) DVT prophylaxis on hematoma expansion (HE) and outcome in patients with spontaneous intracerebral hemorrhage (ICH).

Methods

We analyzed 134 consecutive patients admitted to a tertiary neurointensive care unit with diagnosed spontaneous ICH, without previous anticoagulation, severe coagulopathy, hematoma evacuation, early withdrawal of therapy or ineligibility for DVT prophylaxis according to our institutional protocol. Significant late HE was defined as ≥6 mL increase of hematoma volume between neuroimaging within 48 h and day 3–6. Multivariate analysis was performed to identify risk factors for late HE, poor 3‐month outcome (modified Rankin Scale score ≥ 4) and mortality.

Results

Patients had a median Glasgow Coma Scale score of 14 [interquartile range (IQR), 10–15], ICH volume of 11 (IQR, 5–24) mL and were 71 (IQR, 61–76) years old. A total of 56% ( = 76) received early DVT prophylaxis, 37% ( = 50) received late DVT prophylaxis and 8 (6%) had unknown bleeding onset. Patients with early DVT prophylaxis had smaller ICH volume [9.5 (IQR, 4–18.5) vs. 17.5 (IQR, 8–29) mL,  = 0.038] and were more often comatose (26% vs. 10%,  = 0.025). Significant late HE [ = 5/134 (3.7%)] was associated with larger initial ICH volume ( = 0.02) and lower thrombocyte count ( = 0.03) but not with early DVT prophylaxis ( = 0.36). Early DVT prophylaxis was not associated with worse outcome.

Conclusion

Significant late HE is uncommon and DVT prophylaxis within 48 h of symptom onset may be safe in selected patients with ICH.

Background and purpose

The clinical manifestation of dystonic spasms in blepharospasm (BSP) patients may be heterogeneous. Whether the varying phenomenology of eyelid spasms becomes manifest sequentially during the course of the disease or aggregates in separate clusters according to different disease courses is still unclear. For this purpose, the clinical features in BSP patients were evaluated longitudinally over a 5‐year period and also the blink reflex recovery cycle was tested in a subgroup of BSP patients.

Methods

Sixty BSP patients were videotaped at time 0 and after approximately 5 years of follow‐up. Two experts in movement disorders, who were blinded to the video order, reviewed the videotapes and scored the severity of BSP using the Blepharospasm Severity Rating Scale. Changes in the R2 recovery index were also evaluated in 18 patients twice, i.e. upon enrolment and at the follow‐up.

Results

The severity of BSP worsened significantly over the 5‐year follow‐up period owing to the appearance or the increased duration and frequency of prolonged spasms. It was also found that the blink reflex recovery cycle worsened at follow‐up in comparison with the baseline.

Conclusions

This study shows that the disease progression of BSP is characterized by the appearance or worsening of prolonged spasms. Prolonged spasms are accompanied by changes in the excitability of brainstem interneurons. Aging‐related effects may exacerbate the pathophysiological mechanisms underlying spasms.

Background and purpose

Rituximab, a chimeric anti‐CD20 monoclonal antibody, has been used in polyneuropathy associated with anti‐myelin‐associated glycoprotein (anti‐MAG) antibody polyneuropathy with controversial results. Herein, two patients with anti‐MAG antibody neuropathy and concurrent chronic lymphocytic leukemia (CLL) are reported, who dramatically responded to obinutuzumab, a novel glycoengineered humanized anti‐CD20 monoclonal antibody.

Methods

Patient 1 was an 82‐year‐old man with severe demyelinating sensory‐motor neuropathy. He was wheelchair‐bound, with loss of sensation up to the knees. He had a CLL, immunoglobulin M (IgM) lambda monoclonal gammopathy, with anti‐MAG antibodies >70 000 Bühlmann titer units (BTU). Patient 2 was an 84‐year‐old woman with demyelinating neuropathy, paresthesias and gait instability. She had CLL and IgM kappa paraprotein with anti‐MAG antibodies >70 000 BTU. Both patients were treated with obinutuzumab intravenously at 100 mg on day +1, 900 mg +2, then at 1000 mg on days 8 and 15 of cycle 1 and day 1 of cycles 2–6; chlorambucil was given orally at 0.5 mg/kg on days 1 and 15 of cycles 1–6.

Results

Patient 1 at cycle 6 was able to stand, gait was possible with monolateral support, hypoesthesia and strength improved. M‐protein and IgM level decreased. In patient 2, already after three cycles, the monoclonal component disappeared and there was dramatic improvement of symptoms and gait normalization. At the end of therapy anti‐MAG antibody titer decreased to 5462 BTU. Neurophysiology also improved.

Conclusions

In our patients, obinutuzumab was effective as a first‐line treatment of anti‐MAG antibody polyneuropathy. CLL might have had a role in the response to therapy, but the associations might be considered in future trials.

Abstract

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