cover image European Journal of Neurology

European Journal of Neurology

2017 - Volume 24
Issue 10 | October 2017

Review Article

Background and purpose

Tick‐borne encephalitis (TBE) is an infection of the central nervous system (CNS) caused by tick‐borne encephalitis virus (TBEV) and transmitted by ticks, with a variety of clinical manifestations. The incidence of TBE in Europe is increasing due to an extended season of the infection and the enlargement of endemic areas. Our objectives are to provide recommendations on the prevention, diagnosis and management of TBE, based on evidence or consensus decisions.

Methods

For systematic evaluation, the literature was searched from 1970 to 2015 (including early online publications of 2016), and recommendations were based on evidence or consensus decisions of the Task Force when evidence‐based data were not available.

Recommendations

Vaccination against TBE is recommended for all age groups above 1 year in highly endemic areas (≥5 cases/100 000/year), but also for individuals at risk in areas with a lower incidence. Travellers to endemic areas should be vaccinated if their visits will include extensive outdoor activities. Post‐exposure prophylaxis after a tick bite is not recommended. A case of TBE is defined by the presence of clinical signs of meningitis, meningoencephalitis or meningoencephalomyelitis with cerebrospinal fluid (CSF) pleocytosis (>5 × 10 cells/l) and the presence of specific TBEV serum immunoglobulin M (IgM) and IgG antibodies, CSF IgM antibodies or TBEV IgG seroconversion. TBEV‐specific polymerase chain reaction in blood is diagnostic in the first viremic phase but it is not sensitive in the second phase of TBE with clinical manifestations of CNS inflammation. Lumbar puncture should be performed in all patients with suspected CNS infection unless there are contraindications. Imaging of the brain and spinal cord has a low sensitivity and a low specificity, but it is useful for differential diagnosis. No effective antiviral or immunomodulating therapy is available for TBE; therefore the treatment is symptomatic. Patients with a potentially life threatening meningoencephalitis or meningoencephalomyelitis should be admitted to an intensive care unit. In the case of brain oedema, analgosedation should be deepened; osmotherapy and corticosteroids are not routinely recommended. If intracranial pressure is increased, therapeutic hypothermia or decompressive craniectomy might be considered. Seizures should be treated as any other symptomatic epileptic seizures.

Conclusions

Tick‐borne encephalitis is a viral CNS infection that may result in long‐term neurological sequelae. Since its incidence in Europe is increasing due to broadening of endemic areas and prolongation of the tick activity season, the health burden of TBE is enlarging. There is no effective antiviral treatment for TBE, but the disease may be effectively prevented by vaccination.

Original Article

Background and purpose

Few studies have examined the association between multivitamin use and the risk of stroke incidence and mortality, and the results remain inconclusive as to whether multivitamins are beneficial.

Methods

The associations between multivitamin use and the risk of incident stroke and stroke mortality were prospectively examined in 86 142 women in the Nurses’ Health Study, aged 34–59 years and free of diagnosed cardiovascular disease at baseline. Multivitamin use and covariates were updated every 2 years and strokes were documented by review of medical records. Hazard ratios of total, ischaemic and hemorrhagic strokes were calculated across categories of multivitamin use (non‐user, past, current user) and duration (years), using Cox proportional hazards models.

Results

During 32 years of follow‐up from 1980 to 2012, 3615 incident strokes were documented, including 758 deaths from stroke. In multivariate analyses, women who were current multivitamin users did not have a lower risk of incident total stroke compared to non‐users [relative risk (RR) 1.02, 95% confidence interval (CI) 0.93–1.11], even those with longer durations of 15 or more years of use (RR 1.08, 95% CI 0.97–1.20) or those with a lower quality diet (RR 0.96, 95% CI 0.80–1.15). There was also no indication of benefit from multivitamin use for incident ischaemic or hemorrhagic strokes or for total stroke mortality.

Conclusions

Long‐term multivitamin use was not associated with reduced risk of stroke incidence or mortality amongst women in the study population, even amongst those with a lower diet quality. An effect in a less well‐nourished population cannot be ruled out.

Original Article

Background and purpose

The microrchidia family CW‐type zinc finger 2 gene () was newly identified as a causative gene of Charcot–Marie–Tooth disease (CMT) type 2Z in 2016. We aimed to describe the clinical and mutational spectrum of patients with CMT harboring mutations in Japan.

Methods

We analyzed samples from 781 unrelated patients clinically diagnosed with CMT using deoxyribonucleic acid microarray or targeted resequencing by next‐generation sequencing, and samples from 434 mutation‐negative patients were subjected to whole‐exome sequencing. We extracted variants from these whole‐exome sequencing data and classified them according to American College of Medical Genetics standards and guidelines.

Results

We identified variants in 13 patients. As the second most common causative gene of CMT type 2 after 2, variants were detected in 2.7% of patients with CMT type 2. The mean age of onset was 10.3 ± 8.7 years, and the inheritance pattern was mostly sporadic (11/13 patients, 84.6%). The clinical phenotype was typically length‐dependent polyneuropathy, and electrophysiological studies revealed sensory‐dominant axonal neuropathy. Mental retardation was identified in 4/13 patients (30.8%). p.Arg190Trp, as a mutational hotspot, was observed in eight unrelated families. We also identified two novel probably pathogenic variants, p.Cys345Tyr and p.Ala369Val, and one novel uncertain significance variant, p.Tyr332Cys.

Conclusions

Our study is the largest report of patients harboring variants. We revealed a clinical and mutational spectrum of Japanese patients with variants. More attention should be paid to cognitive impairment, and the responsible mechanism requires further research for elucidation.

Review Article

Abstract

Dystonia is characterized by excessive muscle contractions giving rise to abnormal posture and involuntary twisting movements. Although dystonia syndromes are a heterogeneous group of disorders, certain pathophysiological mechanisms have been consistently identified across different forms. These pathophysiological mechanisms have subsequently been exploited for the development of non‐invasive brain stimulation (NIBS) techniques able to modulate neural activity in one or more nodes of the putative network that is altered in dystonia, and the therapeutic role of NIBS has hence been suggested. Here all studies that applied such techniques as a therapeutic intervention in any forms of dystonia, including the few works performed in children, are reviewed and emerging concepts and pitfalls of NIBS are discussed.

Original Article

Background and purpose

We assessed the prevalence and magnitude of neuropsychiatric adverse events (NPAEs) associated with antiepileptic drugs (AEDs) among patients with brain tumour‐related epilepsy (BTRE).

Methods

This observational, prospective, multicentre study enrolled 259 patients with BTRE after neurosurgery. All patients received AED monotherapy. Efficacy was assessed through clinical diaries, whereas NPAEs were collected using the Neuropsychiatric Inventory Test‐12 questionnaire at baseline and after 5 months.

Results

Tumour localization in the frontal lobe was associated with a higher prevalence of NPAEs (odds ratio, 7.73; < 0.001). Independent of tumour localization, levetiracetam (LVT) treatment was associated with higher prevalence and magnitude of NPAEs (odds ratio, 7.94; < 0.01) compared with other AEDs. Patients with oligodendroglioma reported more NPAEs than patients with other tumour types. NPAEs were not influenced by chemotherapy, radiotherapy or steroid treatment. Evaluating non‐neurobehavioural adverse events of AEDs, no significant differences were found among AEDs, although patients treated with old AEDs had a higher prevalence of adverse events than those treated with new AEDs.

Conclusions

Both tumour localization in the frontal lobe and LVT treatment are associated with a higher risk of NPAEs in patients with BTRE. LVT is regarded as a first‐line option in patients with BTRE because of easy titration and few significant drug‐to‐drug interactions. Thus, as NPAEs lead to poor compliance and a high dropout rate, clinicians need to accurately monitor NPAEs after AED prescription, especially in patients with frontal lobe tumours receiving LVT.

Review Article

Abstract

Psychotic symptoms are common, disabling non‐motor features of Parkinson's disease (PD). Despite noted heterogeneity in clinical features, natural history and therapy response, current dogma posits that psychosis generally progresses in a stereotypic manner through a cascade of events that begins with minor hallucinations and evolves to severe hallucinations and delusions. Further, the occurrence of psychotic symptoms is believed to indicate a poor prognosis. Here we propose a classification scheme that outlines the pathogenesis of psychosis as it relates to dysfunction of several neurotransmitter systems. We hypothesize that several subtypes exist, and that PD psychosis is not consistently indicative of a progressive cascade and poor prognosis. The literature was reviewed from 1990 to 2017. An overview of the features of PD psychosis is followed by a review of data indicating the existence of neurotransmitter‐related subtypes of psychosis. We found that ample evidence exists to demonstrate the presence of multiple subtypes of PD psychosis, which are traced to dysfunction of the following neurotransmitter systems: dopamine, serotonin and acetylcholine. Dysfunction of each of these systems is recognizable through their clinical features and correlates, and the varied long‐term prognoses. Identifying which neurotransmitter system is dysfunctional may help to develop targeted therapies. PD psychosis has various subtypes that differ in clinical features, underlying pathology and pathophysiology, treatment response and prognosis. A novel classification scheme is presented that describes the clinical subtypes with different outcomes, which could lead to the development of targeted therapies. Future research should focus on testing the viability of this classification.

Original Article

Background and purpose

Brain connectivity analysis has been widely used to investigate brain plasticity and recovery‐related indicators of patients with stroke. However, results remain controversial because of interindividual variability of initial impairment and subsequent recovery of function. In this study, we aimed to investigate the differences in network plasticity and motor recovery‐related indicators according to initial severity.

Methods

We divided participants (16 males and 14 females, aged 54.2 ± 12.0 years) into groups of different severity by Fugl‐Mayer Assessment score, i.e. moderate (50–84), severe (20–49) and extremely severe (<20) impairment groups. Longitudinal resting‐state functional magnetic resonance imaging data were acquired at 2 weeks and 3 months after onset. The differences in network plasticity and recovery‐related indicators between groups were investigated using network distance and graph measurements.

Results

As the level of impairment increased, the network balance was more disrupted. Network balance, interhemispheric connectivity and network efficiency were recovered at 3 months only in the moderate impairment group. However, this was not the case in the extremely severe impairment group. A single connection strength between the ipsilesional primary motor cortex and ventral premotor cortex was implicated in the recovery of motor function for the extremely severe impairment group. The connections of the ipsilesional primary motor cortex–ventral premotor cortex were positively associated with motor recovery as the patients were more severely impaired.

Conclusions

Differences in plasticity and recovery‐related indicators of motor networks were noted according to impairment severity. Our results may suggest meaningful implications for recovery prediction and treatment strategies in future stroke research.

Original Article

Background and purpose

Elevated serum uric acid (UA) is known to be associated with stroke. However, there is little information on the association between serum UA levels and cerebral microbleed (CMB), a precursor of stroke. Therefore, we investigated the association between UA and CMB in a general population taking into consideration sex‐related differences.

Methods

The subjects in this cross‐sectional study consisted of 2686 individuals of 40–79 years of age (1403 men and 1283 women) who underwent regular health screenings, including brain magnetic resonance imaging, at Seoul National University Hospital Health Promotion Center. Subjects were categorized into three groups according to tertiles of UA levels by sex. The presence and location of CMB were assessed by gradient‐recalled echo magnetic resonance imaging.

Results

The prevalence of CMB was 3.8%. In multivariate logistic regression analysis by sex, the highest tertile of UA in male subjects was independently associated with the presence of CMB compared with the lowest tertile of UA (adjusted odds ratio, 2.46; = 0.013). Meanwhile, the highest tertile of UA in female subjects was inversely associated with CMB compared with the lowest tertile of UA (adjusted odds ratio, 0.39; = 0.040).

Conclusions

High serum UA value was associated with higher prevalence of CMB in male, but lower prevalence of CMB in female subjects.

Letter to the Editor

Thalamotomy for paroxysmal kinesigenic dyskinesias in a multiplex family

Original Article

Background and purpose

To compare the performance of neuroimaging techniques, i.e. high‐resolution ultrasound (HRUS) and magnetic resonance imaging (MRI), when applied to the brachial plexus, as part of the diagnostic work‐up of chronic inflammatory demyelinating neuropathy (CIDP) and multifocal motor neuropathy (MMN).

Methods

Fifty‐one incident, treatment‐naive patients with CIDP ( = 23) or MMN ( = 28) underwent imaging of the brachial plexus using (i) a standardized MRI protocol to assess enlargement or T2 hyperintensity and (ii) bilateral HRUS to determine the extent of nerve (root) enlargement.

Results

We found enlargement of the brachial plexus in 19/51 (37%) and T2 hyperintensity in 29/51 (57%) patients with MRI and enlargement in 37/51 (73%) patients with HRUS. Abnormal results were only found in 6/51 (12%) patients with MRI and 12/51 (24%) patients with HRUS. A combination of the two imaging techniques identified 42/51 (83%) patients. We found no association between age, disease duration or Medical Research Council sum‐score and sonographic nerve size, MRI enlargement or presence of T2 hyperintensity.

Conclusions

Brachial plexus sonography could complement MRI in the diagnostic work‐up of patients with suspected CIDP and MMN. Our results indicate that combined imaging studies may add value to the current diagnostic consensus criteria for chronic inflammatory neuropathies.

EAN Guidelines/CME Article

Background and purpose

Current guidelines on cerebral venous thrombosis (CVT) diagnosis and management were issued by the European Federation of Neurological Societies in 2010. We aimed to update the previous European Federation of Neurological Societies guidelines using a clearer and evidence‐based methodology.

Method

We followed the Grading of Recommendations, Assessment, Development and Evaluation system, formulating relevant diagnostic and treatment questions, performing systematic reviews and writing recommendations based on the quality of available scientific evidence.

Results

We suggest using magnetic resonance or computed tomographic angiography for confirming the diagnosis of CVT and not routinely screening patients with CVT for thrombophilia or cancer. We recommend parenteral anticoagulation in acute CVT and decompressive surgery to prevent death due to brain herniation. We suggest preferentially using low‐molecular‐weight heparin in the acute phase and not direct oral anticoagulants. We suggest not using steroids and acetazolamide to reduce death or dependency. We suggest using antiepileptics in patients with an early seizure and supratentorial lesions to prevent further early seizures. We could not make recommendations concerning duration of anticoagulation after the acute phase, thrombolysis and/or thrombectomy, therapeutic lumbar puncture, and prevention of remote seizures with antiepileptic drugs. We suggest that, in women who have suffered a previous CVT, contraceptives containing oestrogens should be avoided. We suggest that subsequent pregnancies are safe, but use of prophylactic low‐molecular‐weight heparin should be considered throughout pregnancy and puerperium.

Conclusions

Multicentre observational and experimental studies are needed to increase the level of evidence supporting recommendations on the diagnosis and management of CVT.

Letter to the Editor

Comment on ‘Efficacy and feasibility of antidepressants for the prevention of migraine in adults: a meta‐analysis’

Letter to the Editor

Response to Dr Voring .

Review Article

Abstract

Neuroimaging plays a significant role in the diagnosis of intracranial tumours, especially brain gliomas, and must consist of an assessment of location and extent of the tumour and of its biological activity. Therefore, morphological imaging modalities and functional, metabolic or molecular imaging modalities should be combined for primary diagnosis and for following the course and evaluating therapeutic effects. Magnetic resonance imaging (MRI) is the gold standard for providing detailed morphological information and can supply some additional insights into metabolism (MR spectroscopy) and perfusion (perfusion‐weighted imaging) but still has limitations in identifying tumour grade, invasive growth into neighbouring tissue and treatment‐induced changes, as well as recurrences. These insights can be obtained by various positron emission tomography (PET) modalities, including imaging of glucose metabolism, amino acid uptake and nucleoside uptake. Diagnostic accuracy can benefit from coregistration of PET results and MRI, combining high‐resolution morphological images with biological information. These procedures are optimized by the newly developed combination of PET and MRI modalities, permitting the simultaneous assessment of morphological, functional, metabolic and molecular information on the human brain.

Letter to the Editor

Stimulus‐sensitive myoclonus with trigeminal neuralgia

Original Article

Background and purpose

Rapid eye movement sleep behaviour disorder (RBD) is related to striatal dopamine depletion. This study was performed to confirm whether clinically probable RBD (cpRBD) in patients with Parkinson's disease (PD) is associated with a specific pattern of striatal dopamine depletion.

Methods

A prospective survey was conducted using the RBD Screening Questionnaire (RBDSQ) in 122 patients with PD who had undergone dopamine transporter (DAT) positron emission tomography scan.

Results

Patients with cpRBD (RBDSQ ≥ 7) exhibited greater motor deficits, predominantly in the less‐affected side and axial symptoms, and were prescribed higher levodopa‐equivalent doses at follow‐up than those without cpRBD (RBDSQ ≤ 4), despite their similar disease and treatment durations. Compared to patients without cpRBD, those with cpRBD showed lower DAT activities in the putamen, particularly in the less‐affected side in all putaminal subregions, and a tendency to be lower in the ventral striatum. In addition, greater motor deficits in patients with cpRBD than in those without cpRBD remained significant after controlling for DAT binding in the putamen and other confounding variables.

Conclusions

These results demonstrated that the presence of RBD in patients with PD is associated with different patterns of both motor deficit distribution and striatal DAT depletion, suggesting that the presence of RBD represents a distinct PD subtype with a malignant motor parkinsonism.

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