cover image European Journal of Neurology

European Journal of Neurology

2019 - Volume 26
Issue 5 | May 2019

Issue Information

Issue Information

Short Communication

Background and purpose

Genetic variability in has been shown to modify age of onset of Parkinson's disease (PD) among Gly2019Ser carriers in North African Arab–Berber populations. In Asian populations, the Gly2019Ser mutation is rare or absent but two other variants, Gly2385Arg and Arg1628PPro, increase PD risk. We aimed to determine whether the locus was associated with age of PD onset in both carriers and non‐carriers of risk variants in Asians.

Methods

We analyzed the association of rs2421947 genotypes with age of PD onset in 3645 Chinese samples, of which 369 carried at least one of two Asian risk variants.

Results

rs2421947 genotypes were not associated with age of PD onset in Chinese samples. We observed no heterogeneity in the effect of rs2421947 between the Asian risk variant carriers and non‐carriers.

Conclusions

rs2421947 was not associated with age of PD onset in risk variant carriers and non‐carriers in Chinese samples. Further studies in other Asian populations will be of interest.

Original Article

Background and purpose

Post‐stroke dysphagia occurs in up to three quarters of patients with acute stroke and is associated with a higher risk of respiratory infections and poor outcome. Systematic screening of dysphagia in the acute stroke unit is essential to identify patients at risk of aspiration and to provide dietary recommendations. Our study aimed to assess the impact of the systematic application of the Gugging Swallowing Screen (GUSS) in patients with acute ischaemic stroke.

Methods

This was a retrospective study of consecutive patients with acute ischaemic stroke admitted to an acute stroke unit in two time periods: pre‐GUSS (February 2014–July 2015), when the 10‐mL water‐swallowing test was systematically administered, and GUSS (August 2015–October 2016), when the GUSS test was systematically administered. Groups were compared with regard to baseline and stroke characteristics, and the occurrence of stroke‐associated pneumonia (SAP), in‐hospital death and 3‐month outcome.

Results

Of the 344 patients who were included in the study (median age 71 years), 51.7% were male with a median National Institutes of Health Stroke Scale score of 11. A total of 204 patients were included during the pre‐GUSS period and 140 during the GUSS period. Patients in the GUSS period more frequently had diabetes and partial anterior circulation syndromes, and were more frequently treated with thrombectomy. There was no difference in the occurrence of SAP between the two groups (pre‐GUSS, 12.5%; GUSS, 15.1%;  = 0.490) and no differences were found concerning in‐hospital mortality ( = 0.996), 3‐month functional independence ( = 0.647) or 3‐month mortality ( = 0.598).

Conclusions

The systematic administration of GUSS in a population of patients with acute ischaemic stroke did not reduce the occurrence of SAP, mortality or 3‐month functional dependence when compared with the systematic administration of the 10‐mL water‐swallowing test.

Letter to the Editor

Isolated bilateral fornix stroke and acute amnestic syndrome

Original Article

Background and purpose

Information on the prevalence and course of post‐stroke cognitive impairment in young stroke patients is limited. The aim was to assess a consecutive sample of acute young ischaemic stroke patients (18–55 years) for the presence and development of neuropsychological deficits.

Methods

Patients prospectively underwent a comprehensive clinical and cognitive assessment, examining general cognitive function, processing speed, attention, flexibility/executive function and word fluency within the first 3 weeks after hospital admission (median assessment at day 6) and at a 3 months’ follow‐up (FU). Cognitive dysfunction was defined in comparison to age‐standardized published norms.

Results

At baseline ( = 114), deficits were highly prevalent in processing speed (56.0%), flexibility/executive function (49.5%), attention (46.4%) and general cognitive function (42.1%). These frequencies were comparable for those with FU assessment ( = 87). In most domains, cognitive performance improved within 3 months, except for word fluency. However, in about one‐third of patients, cognitive deficits (as defined by 1.5 standard deviations below the standardized mean) were still present 3 months after stroke. At FU, 44.0% were impaired in the domain flexibility/executive function, 35.0% in processing speed and 30.0% in attention.

Conclusions

The high prevalence of cognitive deficits in acute young patients with ischaemic stroke highlights the importance of early post‐stroke cognitive assessment to capture a patient's dysfunction in a comprehensive manner and to offer adequate rehabilitation. The role of factors which promote neuropsychological deficits needs further exploration.

Letter to the Editor

A new case of infantile‐onset hereditary spastic paraplegia with complicated phenotype (SPG61) in a consanguineous Russian family

Original Article

Background and purpose

Randomized clinical trials involving anti‐amyloid interventions focus on the early stages of Alzheimer's disease (AD) with proven amyloid pathology, using amyloid positron emission tomography (amyloid‐PET) imaging or cerebrospinal fluid analysis. However, these investigations are either expensive or invasive and are not readily available in resource‐limited centres. Hence, the identification of cost‐effective clinical alternatives to amyloid‐PET is highly desirable. This study aimed to investigate the accuracy of combined clinical markers in predicting amyloid‐PET status in mild cognitive impairment (MCI) individuals.

Methods

In all, 406 MCI participants from the Alzheimer's Disease Neuroimaging Initiative database were dichotomized into amyloid‐PET(+) and amyloid‐PET(−) using a cut‐off of >1.11. The accuracies of single clinical markers [apolipoprotein E4 (ApoE4) genotype, demographics, cognitive measures and cerebrospinal fluid analysis] in predicting amyloid‐PET status were evaluated using receiver operating characteristic curve analysis. A logistic regression model was then used to determine the optimal model with combined clinical markers to predict amyloid‐PET status.

Results

Cerebrospinal fluid amyloid‐β (Aβ) showed the best predictive accuracy of amyloid‐PET status [area under the curve (AUC) = 0.927]. Whilst ApoE4 genotype (AUC = 0.737) and Alzheimer's Disease Assessment Scale – Cognitive Subscale (ADAS‐Cog) 13 (AUC = 0.724) independently discriminated amyloid‐PET(+) and amyloid‐PET(−) MCI individuals, the combination of clinical markers (ApoE4 carrier, age >60 years and ADAS‐Cog 13 > 13.5) improved the predictive accuracy of amyloid‐PET status (AUC = 0.827, <0.001).

Conclusions

Cerebrospinal fluid Aβ, which is an invasive procedure, is most accurate in predicting amyloid‐PET status in MCI individuals. The combination of ApoE4, age and ADAS‐Cog 13 also accurately predicts amyloid‐PET status. As this combination of clinical markers is cheap, non‐invasive and readily available, it offers an attractive surrogate assessment for amyloid status amongst MCI individuals in resource‐limited settings.

Original Article

Background and purpose

Extracranial internal carotid artery thromboembolism is one major cause of ischaemic stroke and the predictive value of non‐high‐density lipoprotein cholesterol (non‐HDLC) is superior to low‐density lipoprotein cholesterol (LDLC). This study aimed to assess the association between non‐HDLC levels and the prevalence of asymptomatic extracranial internal carotid artery stenosis (EICAS) as well as the predictive value of non‐HDLC over LDLC on EICAS presence.

Methods

The Asymptomatic Polyvascular Abnormalities Community study is a subset of the Kailuan study emphasizing asymptomatic polyvascular abnormalities in Chinese adults. A total of 5351 participants, aged ≥40, without history of cardiovascular disease were enrolled in this study. Carotid duplex ultrasonography was carried out for the detection of EICAS.

Results

Of the 5351 patients, 2.5% (131/5351) were diagnosed with EICAS (stenosis ≥50%). Univariate analysis showed that non‐HDLC is an independent indicator for asymptomatic EICAS [odds ratio (OR) 1.49, 95% confidence interval (CI) 1.17–1.91]; the same result was reached in multivariate analysis after adjustment for confounding factors (OR 1.32, 95% CI 1.00–1.75), especially for people with hypertension (OR 1.52, 95% CI 1.11–2.08), whilst non‐HDLC failed to show better predictive value of EICAS than LDLC (OR 1.45, 95% CI 1.02–2.05).

Conclusions

Non‐HDLC is an independent risk factor for EICAS prevalence, especially for hypertension patients. Although the predictive value of non‐HDLC was no better than LDLC on EICAS presence, non‐HDLC is still a powerful atherogenic factor and potential therapeutic target for EICAS.

Original Article

Background and purpose

The purpose was to evaluate the association between the left ventricular ejection fraction (LVEF) and cerebral small vessel disease (cSVD) in ischaemic stroke patients.

Methods

Consecutive first‐ever ischaemic stroke patients between 2010 and 2013 were included. White matter hyperintensity (WMH) volumes were rated using both the Fazekas score and quantitative methods on fluid‐attenuated inversion recovery images. As spectra of cSVD, lacunes, cerebral microbleeds (CMBs) and enlarged perivascular spaces (EPVSs) were also evaluated. To assess the dose–response relationship between LVEF and cSVD, the burdens of each radiological marker and the total cSVD score were rated.

Results

A total of 841 patients were included [median WMH volume 2.98 (1.22–10.50) ml; the frequencies of lacunes, CMBs and moderate to severe EPVSs were 38%, 31% and 35%, respectively]. In the multivariate analysis about predictors of WMH volumes, the LVEF ( = −0.052,  < 0.001) remained significant after adjusting for confounders. LVEF was also a predictor of lacunes [adjusted odds ratio (aOR) 0.978,  = 0.012], CMBs (aOR = 0.96,  < 0.001) and moderate to severe EPVSs (aOR = 0.94,  < 0.001) after adjusting for their confounders. The LVEF values were negatively correlated with the burdens of lacunes ( = 0.026), CMBs ( < 0.001) and EPVSs ( = 0.002). The total cSVD score also showed a negative association with LVEF in a dose–response manner ( < 0.001).

Conclusions

The burden of cSVD is negatively correlated with the LVEF in a dose–response manner. Our results suggest clues for further studies about determining the pathophysiology of cSVD.

Original Article

Background and purpose

Data on real‐world experience with intravenous thrombolysis (IV tPA) in wake‐up stroke (WUS) are limited. The aim of this study was to examine the efficacy and safety of IV tPA in patients with WUS included in the Austrian Stroke Unit Registry.

Methods

Data from a large nationwide stroke unit registry including initial stroke severity, vascular risk factors, comorbidities, treatment with IV tPA, symptomatic intracerebral haemorrhage (sICH) and functional outcome were extracted and analysed. Patients with WUS were compared with patients with known‐onset stroke (KOS) regarding the frequency of IV tPA treatment, neurological improvement (National Institutes of Health Stroke Scale score ≥4), sICH and 3‐month functional outcome by modified Rankin Scale score using standard statistical tests.

Results

A total of 107 895 stroke patients entered the analysis, including 12 534 with WUS and 91 899 with KOS. Altogether, 904 (7.2%) patients with WUS received IV tPA as compared with 16 694 (18.2%) patients with KOS. Patients with WUS who received IV tPA treatment had twofold higher initial National Institutes of Health Stroke Scale score (median 8 vs. median 4) as compared with patients with KOS. There was no statistical difference in functional outcome by modified Rankin Scale score 0–1 at 3 months between patients with WUS and patients with KOS treated with IV tPA (adjusted odds ratio, 1.08; 95% confidence interval, 0.9–1.31). Also, the rate of sICH did not differ (4.1% vs. 4%,  = 0.852).

Conclusions

In this large non‐randomized comparison, the safety and efficacy of IV tPA in patients with WUS in the real‐world setting seems to be comparable to patients with KOS.

Original Article

Background and purpose

The prognosis of status epilepticus (SE) depends on the time between onset and the diagnosis and start of treatment. Our aim was to design a scale with predictive value for pre‐hospital diagnosis of SE.

Methods

This was a retrospective study of 292 patients who attended the emergency department for an epileptic seizure. A total of 49 patients fulfilled the criteria for SE. We recorded the patients’ history and clinical features. Variables independently associated with SE were combined to design a clinical scale. The performance of the scale was evaluated in a validation dataset of 197 patients.

Results

A total of 50.3% of the patients were male and the mean age was 55.9 years. The following features were more prevalent in patients with SE: abnormal speech (79.6% vs. 18.9%,  < 0.001), eye deviation (69.4% vs. 14.0%,  < 0.001), automatism (22.4% vs. 6.3%,  < 0.001), hemiparesis (24.5% vs. 10.9%,  = 0.011), state of stupor/coma (46.9% vs. 4.2%,  < 0.001) and number of pre‐hospital seizures, i.e. two (34.7% vs. 4.5%,  < 0.001) or more than two (51.0% vs. 0.4%,  < 0.001). Based on these findings, we designed a scale that scored 1 point each for presence of abnormal speech, eye deviation, automatism and two seizures, and 2 points for more than two seizures. The predictive capacity of the scale for identifying SE in the validation dataset was 98.7% (95% confidence interval, 97.3%–100%) and 85.4% of patients with a score >1 had SE.

Conclusions

A score >1 on the ADAN scale is a robust predictor of the diagnosis of SE in patients who experience an epileptic seizure. This scale may be a useful tool for clinical use and warrants further investigation.

Original Article

Background and purpose

To clarify whether subtyping of amnestic and non‐amnestic mild cognitive impairment (MCI) is clinically relevant in Parkinson's disease (PD) by analyzing patterns of neuroimaging and longitudinal cognitive changes.

Methods

We performed comparative analyses of cortical thickness, hippocampal volume, white matter integrity and resting‐state functional connectivity between the patients with PD with amnestic MCI (PD‐aMCI) ( = 50) and non‐amnestic MCI (PD‐naMCI) ( = 50) subtypes. Additionally, we assessed the longitudinal rate of cognitive decline in each cognitive domain over time and the rate of dementia conversion in patients with PD‐aMCI ( = 125) and PD‐naMCI ( = 61).

Results

The demographic data showed that scores in memory domains were lower in the PD‐aMCI group compared with the PD‐naMCI group. There were no significant differences in cortical thickness, hippocampal volume and white matter integrity between the two groups, although the PD‐aMCI group exhibited more cortical thinning and hippocampal atrophy relative to the control group. The PD‐aMCI group exhibited increased functional connectivity in the left posterior parietal region with the salience network relative to the PD‐naMCI group. The longitudinal cognitive assessment demonstrated that patients with PD‐aMCI exhibited a more rapid cognitive decline in frontal/executive function than those with PD‐naMCI ( = 0.022). In addition, the PD‐aMCI group had a higher risk of dementia conversion than the PD‐naMCI group.

Conclusions

This study suggests that the designation of PD‐MCI subtypes based on memory function would highlight the heterogeneity of functional correlates as well as the longitudinal cognitive prognosis.

Original Article

Background and purpose

Predicting the course of behavioural variant frontotemporal dementia (bvFTD) remains a major clinical challenge. This study aimed to identify factors that predict survival and clinical progression in bvFTD.

Methods

Consecutive patients with clinically probable bvFTD were prospectively followed up over an 8‐year period. Baseline neuropsychological variables, presence of a known pathogenic frontotemporal dementia gene mutation and a systematic visual magnetic resonance imaging assessment at baseline were examined as candidate predictors using multivariate modelling.

Results

After screening 121 cases, the study cohort consisted of 75 patients with probable bvFTD, with a mean age of 60.8 ± 8.5 years, followed up for a mean duration of 7.2 ± 3.5 years from symptom onset. Median survival time from disease onset was 10.8 years and median survival, prior to transition to nursing home, was 8.9 years. A total of 25 of the 75 patients died during the study follow‐up period. Survival without dependence was predicted by shorter disease duration at presentation (hazard ratio, 0.49,  = 0.001), greater atrophy in the anterior cingulate cortex (hazard ratio, 1.75,  = 0.047), older age (hazard ratio, 1.07,  = 0.026) and a higher burden of behavioural symptoms (hazard ratio, 1.04,  = 0.015).

Conclusions

This study provides novel clinical predictors of survival and progression in bvFTD. Our findings are likely to have an impact on prognostication and care planning in this difficult disease.

Original Article

Background and purpose

Symptoms and signs in patients with Huntington's disease are usually assessed with the Unified Huntington's Disease Rating Scale (UHDRS). Ceiling and floor effects hamper the measurement of disease progression in patients with late stage Huntington's disease and therefore the UHDRS–For Advanced Patients (UHDRS‐FAP) has been developed. The aim of this longitudinal study was to examine if the UHDRS‐FAP and UHDRS are sensitive enough to detect change over time in late stage Huntington's disease.

Methods

Forty nursing home residents and patients receiving day‐care were assessed with the UHDRS, UHDRS‐FAP and Care Dependency Scale (CDS). After 6 months, the assessment scales were completed again in 29 patients. Changes between baseline and follow‐up were calculated using paired tests. Wilcoxon signed‐rank tests were used to calculate longitudinal changes for middle and late stage patients separately.

Results

The motor and cognitive score of the UHDRS‐FAP deteriorated during 6 months’ follow‐up, whilst the motor and cognitive score of the UHDRS did not show change. Two functional domains of the UHDRS and the CDS also declined. The behavioral score significantly improved with both rating scales in late stage patients.

Conclusions

Our results suggest that the UHDRS‐FAP motor and cognitive score, the functional domains of the UHDRS, and the CDS can detect disease progression in late stage Huntington's disease. Therefore, the use of these scores in nursing homes is recommended to optimize care by monitoring disease progression and by evaluating the effect of interventions in clinical care. Psychiatric symptoms seem to fade away as the disease progresses.

Original Article

Background and purpose

Neuropsychological testing plays a key role in various clinical contexts. Even though a substantial number of adults suffer neurological disorders such as early‐onset dementia, stroke, traumatic brain injury or multiple sclerosis, most normative data do not include persons below 65. The aim of this study was to produce updated norms for the Mini‐Mental State Examination, the Free and Cued Selective Reminding Test, the Trail Making Test, verbal fluency tasks and the Digit Symbol Substitution Test for middle‐aged and older adults.

Methods

The sample consisted of 51 879 participants aged 45–70 years from the CONSTANCES study. Norms are presented in percentiles stratified on age, education and gender.

Results

The results illustrated the effect of age in all tests considered. For tests involving speed processing, the impact of age was observed including in tight age range categories (5 years). The results also showed the well‐known effect of education and an effect of gender in tests involving verbal memory and speed processing.

Conclusions

The norms provided allow the variability of the cognitive performances of middle‐aged to older populations to be understood, with a high precision in age categories. The tests considered are broadly used in neuropsychological practice and should be helpful in a variety of clinical contexts.

Original Article

Background and purpose

Cognitive impairment, slow walking speed and motoric cognitive risk syndrome (MCR) have separately been associated with an increased risk for mortality in the short term. The aim of the study was to examine the association of MCR and its components [i.e. subjective cognitive complaint (SCC) and slow walking speed] with short‐, medium‐ and long‐term mortality in older community‐dwellers.

Methods

In all, 3778 participants from the Epidémiologie de l'Ostéoporose (EPIDOS) study were selected. MCR was defined as the combination of slow walking speed and SCC in participants without major neurocognitive disorders. Deaths were prospectively recorded using mail, phone calls, questionnaires and/or the French national death registry at 5, 10, 15 and 19 (end of follow‐up period) years.

Results

Over the follow‐up of 19 years, 80.5% ( = 3043) participants died. Slow walking speed and MCR were associated with mortality [hazard ratio (HR) 1.20 with  = 0.004 for slow walking speed and HR = 1.26 with  = 0.002 for MCR at 10 years; HR = 1.27 with  ≤ 0.001 for slow walking speed and HR = 1.22 with  = 0.001 for MCR at 15 years; HR = 1.41 with  ≤ 0.001 at 19 years for slow walking speed and MCR]. There was no association between SCC and mortality. Kaplan–Meier distributions of mortality showed that participants with MCR and slow walking speed died earlier compared to healthy participants and those with SCC ( < 0.001).

Conclusions

Slow walking speed and MCR were associated with an increased risk for mortality at the medium and long term, whereas no association was found with SCC.

Original Article

Background and purpose

Subjective memory impairment (SMI) and amnestic mild cognitive impairment (aMCI) are thought to represent the pre‐dementia stages of Alzheimer's disease (AD). SMI is considered a more advanced pre‐clinical status prior to aMCI. Understanding the neuromechanism of SMI will have great benefits for monitoring the disease progression of AD. The study aims to explore whether SMI shows alterations of white matter (WM) integrity similar to the patterns of aMCI.

Methods

The atlas‐based analyses were performed to investigate the diffusion changes in the major WM tracts amongst 22 individuals with normal cognition (NC), 22 SMI patients and 25 aMCI patients. The correlations between the altered diffusion metrics and cognitive performance in the SMI and aMCI groups were assessed.

Results

The diffusion tensor metrics of SMI were intermediate between the NC and aMCI groups. The aMCI group presented disrupted integrity in multiple WM tracts, including the left anterior thalamic radiation, right corticospinal tract and left cingulum of the hippocampus (CgH), compared to the NC group. The left CgH showed diffusion alterations in the SMI group. In the aMCI group, the mean diffusivity of the left CgH was negatively correlated with episodic memory, whilst the radial diffusivity of the right corticospinal tract was negatively correlated with executive function. No significant relationship was found in the SMI group.

Conclusion

The study suggested that SMI patients might present detectable WM integrity changes in the left CgH before exhibiting objective cognitive dysfunction, which may provide novel insights into the pathological mechanisms of AD.

Original Article

Background and purpose

We previously reported that certain optical coherence tomography (OCT) measures were sensitive and reliable in identifying idiopathic intracranial hypertension (IIH). This prospective study aimed to define OCT measures that allow differentiation of IIH with and without papilledema, thereby helping clinical decision‐making.

Methods

Eight patients with IIH with papilledema, nine without papilledema and 19 with other neurological diseases were included. OCT measures were obtained before lumbar puncture and within 2 h, 1, 3 and 6 months after lumbar puncture with cerebrospinal fluid (CSF) removal.

Results

All patients with papilledema had increased retinal nerve fiber layer (RNFL) thickness and elevated CSF pressure. All patients without papilledema had normal RNFL but elevated CSF pressure. After CSF removal, reduced RNFL thickness was registered in all eight patients with IIH with papilledema. No significant change in RNFL thickness after CSF removal was observed in IIH without papilledema or in patients with other neurological diseases, although reduced CSF pressure was documented. RNFL thickness tended to be normal in patients with IIH with papilledema at 3–6 months after CSF removal. All patients with IIH showed increased rim area and rim thickness, but reduced optic cup volume regardless of RNFL thickness or papilledema.

Conclusions

Retinal nerve fiber layer thickness is sensitive for monitoring acute IIH and evaluating treatment effect. Increased rim area and rim thickness and decreased optic cup volume are reliable parameters that indicate persistently increased CSF pressure and risk of relapse. OCT measures are sensitive and reliable for diagnosing subtle IIH even in the absence of papilledema.

Original Article

Background and purpose

There are no recommendations regarding how to treat cardioembolic recurrent strokes when patients are well anticoagulated. We evaluated the safety and efficacy of combining oral anticoagulation (OAC) with percutaneous left atrial appendage closure (LAAC) in patients with well‐anticoagulated atrial fibrillation (AF) with recurrent strokes.

Methods

In an explorative, prospective, observational study, LAAC was performed in patients with AF with at least two ischaemic strokes in the previous year, despite good anticoagulation using the Amplatzer Cardiac Plug (St Jude Medical, St Paul, MN, USA) or Amulet Abbot device (Abbot Vascular, Santa Clara, CA, USA). We recorded age, type of AF, CHADS‐VASC and HAS‐BLED scores, types of OAC and risk factors. After closure, treatment with aspirin (100 mg/day) was continued for 3 months in combination with indefinite OAC. Clinical status, recurrent embolisms and bleeding complications were recorded during follow‐up.

Results

A total of 19 patients were included (mean age, 72.1 ± 9.6 years; mean CHADS‐VASC score, 5.3 ± 1.48; mean number of previous strokes, 2.78 ± 1.15). Thirteen had spontaneous echocardiographic contrast and all had dilatation of the left atrium. Eighteen patients had a multilobulated left atrial appendage, 17 with ‘chicken‐wing’ morphology and one patient had a left atrial appendage thrombus. There were no complications during the procedure. Only one patient had a transient ischaemic attack and no major bleeding occurred during a mean follow‐up of 17.4 ± 11.5 months.

Conclusion

Combination therapy with indefinite OAC plus LAAC in patients with AF with recurrent strokes despite good anticoagulation should be considered in order to prevent a new stroke.

Original Article

Background and purpose

In patients with Parkinson's disease (PD) with motor fluctuations, total daily OFF time is comprised of both end‐of‐dose time and the time taken to turn ON with medication. However, little is known about the impact of delays in ON time.

Methods

This was a single‐visit pilot study of fluctuating patients with PD attending a routine appointment. During a single visit, adult patients with idiopathic PD who were treated with levodopa for at least 1 year completed a questionnaire evaluating the time waiting for ON and the symptoms experienced while waiting to turn ON. Patients then completed a 5‐day home time‐to‐ON diary, where they documented how long it took to turn ON following their first morning dose of levodopa in 5‐min increments.

Results

A total of 151 consecutive patients completed the study survey, of whom 97 (64.2%) experienced motor fluctuations. Of the patients experiencing motor fluctuations, 54 (56%) reported delays in ON time (latency >30 min) following their first morning dose of levodopa. Half (51%) reported that they had experienced delayed ON at least once in the previous week and 21% reported having delayed ON during all seven mornings of the previous week. In addition, 10% of patients reported having dose failures on four or more mornings during the previous week. The most common symptoms experienced while waiting for ON were slowness (94.8%), fatigue (87.6%), reduced dexterity (82.5%), problems in walking (66.0%) and problems with balance (59.8%).

Conclusion

Early‐morning OFF problems such as delays in time to ON and dose failures are common in levodopa‐treated patients with PD.

Letter to the Editor

Myelin oligodendrocyte glycoprotein antibody associated disease: about the importance of diagnostic assays and selection of the target population in retrospective studies

Letter to the Editor

Response to ‘Myelin oligodendrocyte glycoprotein antibody associated disease: about the importance of diagnostic assays and selection of the target population in retrospective studies’

Editorial

Abstract

Click to view the accompanying paper in this volume.

Review Article

Abstract

Corticobasal degeneration (CBD) is a neurodegenerative condition characterized by 4R tau protein deposition in several brain regions that clinically manifests itself as a heterogeneous atypical parkinsonism typically expressed in adulthood. The prototypical clinical phenotype of CBD is corticobasal syndrome (CBS). Important insights into the pathophysiological mechanisms underlying motor and higher cortical symptoms in CBS have been gained by using advanced neuroimaging and neurophysiological techniques. Structural and functional neuroimaging studies often show asymmetric cortical and subcortical abnormalities, mainly involving perirolandic and parietal regions and basal ganglia structures. Neurophysiological investigations including electroencephalography and somatosensory evoked potentials provide useful information on the origin of myoclonus and on cortical sensory loss. Transcranial magnetic stimulation demonstrates heterogeneous and asymmetric changes in the excitability and plasticity of primary motor cortex and abnormal hemispheric connectivity. Neuroimaging and neurophysiological abnormalities in multiple brain areas reflect asymmetric neurodegeneration, leading to asymmetric motor and higher cortical symptoms in CBS.

Review Article

Background and purpose

Multiple sclerosis (MS) is a demyelinating and neurodegenerative disease of the central nervous system (CNS) that can be tracked through biomarkers of disease status. We investigated the effects of exercise on MS biomarkers associated with CNS status including imaging, blood–brain barrier (BBB) function and neurotrophic factors.

Methods

We conducted open‐dated searches of Scopus, Medline, EMBASE and the Cochrane Library. We included studies written in English describing interventions of exercise that measured one or more of the biomarkers associated with MS published up to October 2018.

Results

We located a total of 3012 citations through searches in electronic databases. Of these, 16 studies were eligible for review; six studies focused on magnetic resonance imaging (MRI) markers, nine studies focused on neurotrophic factors and three studies focused on BBB function markers. It is of note that two studies included both neurotrophic factor and BBB function markers and are therefore included across categories of biomarkers in this review. The existing evidence from MRI studies confirmed that exercise training can improve CNS integrity and function. There is evidence of a positive effect of exercise training on modulation of BBB permeability markers and brain‐derived neurotrophic factor.

Conclusions

Exercise successfully improves MRI outcomes and peripheral biomarkers (i.e. brain‐derived neurotrophic factor) in people with MS. This suggests that exercise can be recommended as an adjuvant therapy for MS treatment. This conclusion is tempered by some methodological limitations including small sample sizes and high drop‐out rates in the reviewed studies.

Corrigenda

Subclinical motor impairment assessed with an engineered glove correlates with magnetic resonance imaging tissue damage in radiologically isolated syndrome

Corrigenda

Depression in multiple sclerosis: effect of brain derived neurotrophic factor Val66Met polymorphism and disease perception

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