Background and purpose

Converging evidence suggests that migraine has, in part, a vascular basis. In turn, vascular pathology is a strong risk factor for cognitive decline. In this population‐based study, we studied cognition amongst individuals with and without migraine.

Methods

In 6708 participants of the Rotterdam Study, migraine was assessed using a validated questionnaire. Cognition was assessed by the Mini Mental State Examination (MMSE) and a dedicated cognitive test battery. Participants were classified as non‐migraineurs ( = 5399), migraineurs ( = 1021) or probable migraineurs ( = 288). Multivariable linear regression was used to cross‐sectionally evaluate the association between migraine and cognition, adjusting for age, sex and cardiovascular risk factors. Additionally, we stratified the analysis by sex and by migraine subtype.

Results

Migraineurs had higher mean MMSE scores [unstandardized regression coefficient 0.21, (95% confidence interval, 0.08; 0.34)] and global cognition [0.10 (0.04; 0.15)] than non‐migraineurs. This difference was particularly marked for migraineurs with aura [MMSE: 0.39 (0.13; 0.66); global cognition: 0.13 (0.01; 0.24)]. Migraineurs performed better on tests of executive function and fine motor skills amongst specific cognitive domains. The difference in MMSE between migraineurs and non‐migraineurs was greater in women [0.25 (0.10; 0.40)] than in men [0.13 (−0.15; 0.40)], whereas the difference in global cognition was similar in men and women [0.15 (0.04; 0.27) and 0.09 (0.02; 0.15), respectively].

Conclusions

Migraineurs, particularly migraineurs with aura, tend to score higher in cognition tests than non‐migraineurs. More studies are needed to corroborate these findings.

Background and purpose

Spasmodic dysphonia (SD), or laryngeal dystonia, is a task‐specific isolated focal dystonia of unknown causes and pathophysiology. Although functional and structural abnormalities have been described in this disorder, the influence of its different clinical phenotypes and genotypes remains scant, making it difficult to explain SD pathophysiology and to identify potential biomarkers.

Methods

We used a combination of independent component analysis and linear discriminant analysis of resting‐state functional magnetic resonance imaging data to investigate brain organization in different SD phenotypes (abductor versus adductor type) and putative genotypes (familial versus sporadic cases) and to characterize neural markers for genotype/phenotype categorization.

Results

We found abnormal functional connectivity within sensorimotor and frontoparietal networks in patients with SD compared with healthy individuals as well as phenotype‐ and genotype‐distinct alterations of these networks, involving primary somatosensory, premotor and parietal cortices. The linear discriminant analysis achieved 71% accuracy classifying SD and healthy individuals using connectivity measures in the left inferior parietal and sensorimotor cortices. When categorizing between different forms of SD, the combination of measures from the left inferior parietal, premotor and right sensorimotor cortices achieved 81% discriminatory power between familial and sporadic SD cases, whereas the combination of measures from the right superior parietal, primary somatosensory and premotor cortices led to 71% accuracy in the classification of adductor and abductor SD forms.

Conclusions

Our findings present the first effort to identify and categorize isolated focal dystonia based on its brain functional connectivity profile, which may have a potential impact on the future development of biomarkers for this rare disorder.

Background and purpose

Conventional magnetic resonance imaging (MRI) has limited value for differentiation of true tumor progression and pseudoprogression in treated glioblastoma multiforme (GBM). Perfusion weighted imaging (PWI) may be helpful in the differentiation of these two phenomena. Here interobserver variability in routine radiological evaluation of GBM patients is assessed using MRI, including PWI.

Methods

Three experienced neuroradiologists evaluated MR scans of 28 GBM patients during temozolomide chemoradiotherapy at three time points: preoperative (MR1) and postoperative (MR2) MR scan and the follow‐up MR scan after three cycles of adjuvant temozolomide (MR3). Tumor size was measured both on T1 post‐contrast and T2 weighted images according to the Response Assessment in Neuro‐Oncology criteria. PW images of MR3 were evaluated by visual inspection of relative cerebral blood volume (rCBV) color maps and by quantitative rCBV measurements of enhancing areas with highest rCBV. Image interpretability of PW images was also scored. Finally, the neuroradiologists gave a conclusion on tumor status, based on the interpretation of both T1 and T2 weighted images (MR1, MR2 and MR3) in combination with PWI (MR3).

Results

Interobserver agreement on visual interpretation of rCBV maps was good ( = 0.63) but poor on quantitative rCBV measurements and on interpretability of perfusion images (intraclass correlation coefficient 0.37 and = 0.23, respectively). Interobserver agreement on the overall conclusion of tumor status was moderate ( = 0.48).

Conclusions

Interobserver agreement on the visual interpretation of PWI color maps was good. However, overall interpretation of MR scans (using both conventional and PW images) showed considerable interobserver variability. Therefore, caution should be applied when interpreting MRI results during chemoradiation therapy.

Background and purpose

The severity of status epilepticus (SE) has an important impact in clinical outcomes The Status Epilepticus Severity Score (STESS) is a score for predicting mortality in SE at admission. The baseline modified Rankin Scale (mRS) might be a prognostic factor for assessing the short‐tem outcomes of SE. Therefore, our aim was to evaluate the effectiveness of mRS and whether its addition to the STESS improves the prediction of mortality.

Methods

Consecutive patients with SE and aged >16 years were recruited during 3 years. Receiver operating characteristic curves and a logistic regression model were developed to estimate the scores of the new score, designated as modified STESS (mSTESS), and it was subsequently compared with the STESS.

Results

In all, 136 patients were included. Mean age was 62.01 ± 17.62 (19–95) years, and 54% were male. The capacity of the STESS to predict mortality was 74.3% (95% confidence interval 63.8%–81.8%), whilst the capacity of the mRS to predict mortality was 65.2% (95% confidence interval 54.2%–76.2%). The logistic regression model and receiver operating characteristic curves enabled the classification of mRS as follows: 0, mRS = 0; 1, mRS = 1–3; and 2, mRS > 3. These values, when added to the other items of the STESS, resulted in the mSTESS with scores between 0 and 8 points. The capacity of the mSTESS to predict mortality was 80.1%. An mSTESS > 4 established an overall accuracy of 81.8% for predicting mortality, which was considerably higher than the overall accuracy of STESS ≥ 3 (59.6%)

Conclusions

The baseline mRS was associated with high mortality risk. It is proposed to use mSTESS to improve the prediction of mortality risk in SE.

Background and purpose

Chronic syphilitic infection may lead to dementia. It is in general paresis (GP), which is the major late form of neurosyphilis, that cognitive impairment frequently occurs. The association between lipid metabolism and GP is unclear.

Methods

In this study, serum lipids were studied in 188 GP patients, in 241 syphilitic patients without neurosyphilis and in 539 healthy controls. The Mini‐Mental State Examination (MMSE) was tested in all GP patients. Thirty‐five GP patients had a follow‐up evaluation 3 months after penicillin treatment.

Results

Significantly lower apolipoprotein A‐I (apoA‐I) levels were found in GP and in syphilitic patients without neurosyphilis compared to controls. In the 25–44‐year‐old groups, the male syphilitic patients without neurosyphilis had lower serum apoA‐I levels and higher apolipoprotein B (apoB)/apoA‐I ratios compared with female patients. A follow‐up evaluation of 35 GP patients 3 months after penicillin treatment showed a significant positive correlation between increased apoA‐I levels and MMSE scores.

Conclusion

Abnormal apoA‐I metabolism may be associated with the decline of cognitive performance. Long‐term decrease of apoA‐I level and higher apoB/apoA‐I ratio may be contributing factors in syphilitic dementia. These results suggest a similar overlap between syphilitic dementia and lipid metabolism to that occurring in Alzheimer's disease.

Assessing morphological, perfusion and metabolic brain changes preceding or associated with neuropsychiatric symptoms (NPSs) will help in the understanding of pathophysiological underlying processes in Alzheimer's disease (AD). This review aimed to highlight the main findings on significant associations between neuroimaging and NPSs, the pathophysiology to elucidate possible underlying mechanisms, and methodological issues to aid future research. Research papers published from January 1990 to October 2015 were identified in the databases PsycInfo, Embase, PubMed and Medline, using key words related to NPSs and imaging techniques. In addition to a semi‐systematic search in the databases, we also performed hand searches based on reported citations identified to be of interest. Delusions, apathy and depression symptoms were particularly associated with brain changes in AD. The majority of studies disclosed an association between frontal lobe structural and/or metabolic changes and NPSs, implicating, interestingly, for all 12 NPSs studied, the anterior cingulate cortex although temporal, subcortical and parietal regions, and insula were also involved. Given the high degree of connectivity of these brain areas, frontal change correlates of NPSs may help in the understanding of neural network participation. This review also highlights crucial methodological issues that may reduce the heterogeneity of results to enable progress on the pathophysiological mechanisms and aid research on NPS treatments in AD. Based on a broad review of the current literature, a global brain pattern to support the huge heterogeneity of neuroimaging correlates of NPSs in AD and methodological strategies are suggested to help direct future research.

Background and purpose

Urinary incontinence (UI) could be an indicator of increased mortality after new‐onset stroke. The aim of the present meta‐analysis was to characterize this association.

Methods

A systematic search retrieved all studies exploring the post‐stroke period and comparing death among patients suffering from UI with those without UI. Hazard ratios (HRs) were extracted or estimated from the published proportion of deaths. Various meta‐analyses pooled unadjusted HRs, HRs adjusted for confounders and HRs stratified by subgroups of strokes (ischaemic or haemorrhagic), using models with random effects. Heterogeneity was explored through stratification of studies and meta‐regression of predefined parameters.

Results

The meta‐analysis included 24 studies. UI increased the mortality among the general stroke patients in pooled unadjusted (HR, 5.1; 95% CI, 3.9–6.7) and adjusted (HR, 2.2; 95% CI, 1.8–2.7) analyses. This association was also found among ischaemic (HR, 8.5; 95% CI, 4.6–15.7) and haemorrhagic (HR, 3.9; 95% CI, 1.4–11.3) subgroups of strokes. Studies including indwelling catheters, published more than 10 years ago or with the highest quality on the selection criteria of the Newcastle–Ottawa Quality Assessment scale were associated with a greater effect of UI on mortality. Funnel plots showed a clear asymmetry for adjusted associations. After correcting for this potential publication bias, the pooled HRs still demonstrated a positive association between UI and mortality.

Conclusions

Urinary incontinence indicates high risk of death after a new‐onset stroke. Validity of the analyses on adjusted models is limited by an obvious publication bias.

Background and purpose

Dopamine agonists in Parkinson's disease (PD) are associated with impulse control disorders (ICDs) and other compulsive behaviours (together called ICD behaviours). The frequency of ICD behaviours reported as adverse events (AEs) in long‐term studies of rotigotine transdermal patch in PD was evaluated.

Methods

This was a analysis of six open‐label extension studies up to 6 years in duration. Analyses included patients treated with rotigotine for at least 6 months and administered the modified Minnesota Impulse Disorders Interview. ICD behaviours reported as AEs were identified and categorized.

Results

For 786 patients, the mean (±SD) exposure to rotigotine was 49.4 ± 17.6 months. 71 (9.0%) patients reported 106 ICD AEs cumulatively. Occurrence was similar across categories: 2.5% patients reported ‘compulsive sexual behaviour’, 2.3% ‘buying disorder’, 2.0% ‘compulsive gambling’, 1.7% ‘compulsive eating’ and 1.7% ‘punding behaviour’. Examining at 6‐month intervals, the incidence was relatively low during the first 30 months; it was higher over the next 30 months, peaking in the 54–60‐month period. No ICD AEs were serious, and 97% were mild or moderate in intensity. Study discontinuation occurred in seven (9.9%) patients with ICD AEs; these then resolved in five patients. Dose reduction occurred for 23 AEs, with the majority (73.9%) resolving.

Conclusions

In this analysis of >750 patients with PD treated with rotigotine, the frequency of ICD behaviour AEs was 9.0%, with a specific incidence timeline observed. Active surveillance as duration of treatment increases may help early identification and management; once ICD behaviours are present rotigotine dose reduction may be considered.

Background and purpose

Charcot‐Marie‐Tooth disease (CMT) type 1A is characterized by uniformly reduced nerve conduction velocity (NCV) that is fully penetrant since the first years of life, remains fairly stable through the life and does not correlate with disability whereas compound muscular action potential (CMAP) amplitude does. The aim of the present study was to analyze the large amount of electrophysiological data collected in the ascorbic acid trial in Italy and the UK (CMT‐TRIAAL/CMT‐TRAUK) and to use these data to gain insights into the pathophysiology of NCV in CMT1A.

Methods

Baseline electrophysiological data from 271 patients were analysed. Electrophysiological recordings were taken from the motor ulnar, median and peroneal nerves and the sensory ulnar nerve. Distal motor latency (DML), motor (MNCV) and sensory (SNCV) nerve conduction velocity, and amplitudes of CMAPs and sensory action potentials were assessed. Electrophysiological findings were correlated with age of patients at examination and the Charcot–Marie−Tooth Examination Score (CMTES).

Results

NCV was markedly and uniformly reduced. CMAP amplitudes were overall reduced but more severely in lower limbs. DML decreased and MNCV and SNCV increased with age of the patients, whereas CMAP amplitudes worsened with age and also correlated with CMTES.

Conclusions

This is the largest sample of electrophysiological data obtained so far from CMT1A patients. Axonal degeneration as assessed by means of CMAP amplitude reflected clinical impairment and was consistent with a slowly progressive length‐dependent neuropathy. All patients typically had markedly slowed NCV that did, however, slightly increase with age of the patients. The improvement of NCV might depend on myelin thickness remodelling that occurs during the adult life of CMT1A patients.

Background and purpose

Chronic periodontitis (ChP) and lacunar infarct (LI) are two common diseases amongst the elderly. Although several studies have shown an association between ischaemic stroke and ChP, little is known about the relationship between ChP and LI. The study aims to investigate whether ChP is associated with the presence of lacunar stroke.

Methods

An age‐ and gender‐matched case–control study of 62 cases (subjects diagnosed with LI) and 60 controls is reported. Clinical periodontal measures (probing pocket depth, recession, clinical attachment level, full mouth plaque score and full mouth gingival bleeding on probing score) were assessed, and associated risk factors for periodontitis and lacunar stroke were ascertained by means of a structured questionnaire.

Results

Chronic periodontitis showed a strong association with LI after adjusting for common vascular risk factors (odds ratio 4.20; 95% confidence interval 1.81–10.20; = 0.001). Likewise, severe ChP and LI also tended to be significantly associated, independent of other vascular covariates (odds ratio 3.53; 95% confidence interval 1.07–12.77; = 0.04).

Conclusions

Chronic periodontitis was independently associated with the presence of LI after adjusting for well‐known vascular risk factors for lacunar stroke. Further observational studies are necessary to investigate the pathophysiological mechanisms that can explain this relationship.

Background and purpose

The term hereditary spastic paraplegia (HSP) covers a spectrum of genetically heterogeneous disorders in which lower limb spasticity is the common clinical feature. Many patients with childhood‐onset HSP are mistakenly diagnosed with cerebral palsy (CP).

Methods

A group of as yet molecularly undiagnosed HSP patients were analyzed using SpastoPlex a customized target re‐sequencing panel able to investigate the coding regions of 72 genes linked to HSP, spastic ataxias or related motor diseases.

Results

Our investigations identified loss‐of‐function mutations in /SPG52 in four children (three families) who had previously received a diagnosis of diplegic/quadriplegic CP. The patients presented spastic paraparesis, mild facial dysmorphisms, moderate‐to‐severe intellectual disability and severe speech delay. Two patients manifested febrile seizures and childhood‐onset focal seizures. In all the patients, brain magnetic resonance imaging (MRI) showed a peculiar hypoplastic posterior corpus callosum, often associated with ventriculomegaly, white matter loss and cerebral atrophy.

Conclusion

Adaptor protein 4 (AP‐4) deficiency disorders should be suspected in children with spastic paraparesis, cognitive deficit and absent speech accompanied by suggestive MRI features. Seizures might be amongst the clinical manifestations of the syndrome.

Background and purpose

Our aim was to update previous European Federation of Neurological Societies guidelines on neurostimulation for neuropathic pain, expanding the search to new techniques and to chronic pain conditions other than neuropathic pain, and assessing the evidence with the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system.

Methods

A systematic review and meta‐analysis of trials published between 2006 and December 2014 was conducted. Pain conditions included neuropathic pain, fibromyalgia, complex regional pain syndrome (CRPS) type I and post‐surgical chronic back and leg pain (CBLP). Spinal cord stimulation (SCS), deep brain stimulation (DBS), epidural motor cortex stimulation (MCS), repetitive transcranial magnetic stimulation (rTMS) and transcranial direct electrical stimulation (tDCS) of the primary motor cortex (M1) or dorsolateral prefrontal cortex (DLPFC) were assessed. The GRADE system was used to assess quality of evidence and propose recommendations.

Results

The following recommendations were reached: ‘weak’ for SCS added to conventional medical management in diabetic painful neuropathy, CBLP and CRPS, for SCS versus reoperation in CBLP, for MCS in neuropathic pain, for rTMS of M1 in neuropathic pain and fibromyalgia and for tDCS of M1 in neuropathic pain; ‘inconclusive’ for DBS in neuropathic pain, rTMS and tDCS of the DLPFC, and for motor cortex tDCS in fibromyalgia and spinal cord injury pain.

Conclusions

Given the poor to moderate quality of evidence identified by this review, future large‐scale multicentre studies of non‐invasive and invasive neurostimulation are encouraged. The collection of higher quality evidence of the predictive factors for the efficacy of these techniques, such as the duration, quality and severity of pain, is also recommended.

Background and purpose

Approximately 9000 people in the UK are affected by Huntington's disease (HD). People with HD require ongoing health and social care support. There is a knowledge gap about costs of health and social care use associated with HD in the UK. This paper estimates the economic cost in the UK.

Methods

Data on UK patients for the year 2013 were extracted from the European Huntington's Disease Network REGISTRY study, a full clinical dataset, including the full medical history and medication history for patients with HD. National unit costs for the price year 2013 were applied to health and social care services.

Results

Data were available for 131 people. The mean annual cost per person with HD was £21 605. The largest proportion of this cost (65%) was due to informal care (£14 085).

Conclusions

Informal care was the largest driver of costs across all stages of HD; thus there is a need to also consider the needs of carers when planning services for people with HD.