cover image European Journal of Neurology

European Journal of Neurology

2016 - Volume 23
Issue 9 | September 2016

Original Article

Background and purpose

Dementia causes morbidity, disability and mortality, and as the population ages the societal burden will grow. The direct health costs and indirect costs of lost productivity and social welfare of dementia were estimated compared with matched controls in a national register based cohort study.

Methods

Using records from the Danish National Patient Registry (1997–2009) all patients with a diagnosis of Alzheimer's disease, vascular dementia or dementia not otherwise specified and their partners were identified and compared with randomly chosen controls matched for age, gender, geographical area and civil status. Direct health costs included primary and secondary sector contacts, medical procedures and medication. Indirect costs included the effect on labor supply. All cost data were extracted from national databases. The entire cohort was followed for the entire period – before and after diagnosis.

Results

In all, 78 715 patients were identified and compared with 312 813 matched controls. Patients' partners were also identified and matched with a control group. Patients had lower income and higher mortality and morbidity rates and greater use of medication. Social‐ and health‐related vulnerability was identified years prior to diagnosis. The average annual additional cost of direct healthcare costs and lost productivity in the years before diagnosis was 2082 euros per patient over and above that of matched controls, and 4544 euros per patient after the time of diagnosis.

Conclusions

Dementias cause significant morbidity and mortality, consequently generating significant socioeconomic costs.

Original Article

Background and purpose

Physicians often struggle to screen out patients who are no longer fit to drive after stroke. The agreement between the recommendations of physicians and on‐road assessors with regard to fitness to drive after stroke was investigated.

Methods

In this retrospective study, 735 patients with stroke underwent medical, visual and road tests at an official fitness‐to‐drive center of the Belgian Road Safety Institute. Physicians provided medical fitness‐to‐drive recommendations using one of three categories (favorable, reserved or unfavorable). On‐road assessors used the same three categories to make practical fitness‐to‐drive recommendations. Agreement between the medical and practical fitness‐to‐drive recommendations was calculated using the percentage of agreement and prevalence and bias adjusted kappa (PABAK). Area under the curve (AUC) was used to predict the medical and practical recommendations after stepwise logistic regression analyses.

Results

The percentage of agreement was 73% and the PABAK was 0.60 ( < 0.0001). Physicians disagreed on 92% of patients classified as unfavorable and 80% of those classified as reserved by the on‐road assessor. Previous visits to the driving center and number of comorbidities predicted medical fitness‐to‐drive recommendations (AUC = 0.68). Age, previous visits to the center, binocular acuity and driving experience constituted the best model to predict practical fitness‐to‐drive recommendations (AUC = 0.70).

Conclusions

Although there was a moderate agreement between the medical and practical fitness‐to‐drive recommendations, physicians were less likely to screen out those patients who may pose an actual risk on the road. Demographic, clinical and driving factors differently affected the medical and practical fitness‐to‐drive recommendations.

Original Article

Background

Evidence demonstrates that the T allele of the single‐nucleotide polymorphism rs405509 in the apolipoprotein E (APOE) promoter is a risk factor for Alzheimer's disease. However, it is unknown whether rs405509 T allele synergizes with the APOE ε4 allele in influencing cognition and brain structure.

Methods

We analyzed the interaction effect of the rs405509 T allele and the APOE ε4 allele on cognitive ability and brain gray matter volume among elderly people. The subjects were grouped into four groups according to APOE and rs405509 genotypes.

Results

Significant interaction effects were found between rs405509 and APOE on general mental status, memory and attention. Analysis of the whole brain gray matter showed a significantly positive interaction effect between rs405509and APOE on the right inferior temporal gyrus and right fusiform gyrus (alphasim correction < 0.001). In addition, there was a significant relationship between cognitive ability and gray matter volume.

Conclusions

The data indicate that the APOE rs405509 T homozygote modulates the effect of APOE ε4 on both cognitive performance and brain gray matter structure.

Original Article

Background and purpose

To compare two recently developed staging systems for amyotrophic lateral sclerosis (ALS) [King's College and Milano‐Torino staging (MITOS) systems] in an incident, population‐based cohort of patients with ALS.

Methods

Since 2009, a prospective registry has been recording all incident cases of ALS in the Emilia Romagna region in Italy. For each patient, detailed clinical information, including the ALS functional rating scale score, is collected at each follow‐up.

Results

Our study on 545 incident cases confirmed that King's College stages occurred at predictable times and were quite evenly spaced out throughout the disease course (occurring at approximately 40%, 60% and 80% of the disease course), whereas MITOS stages were mostly skewed towards later phases of the disease. In the King's College system there was a decrease in survival and an increase in deaths with escalating stages, whereas in the MITOS system survival curves pertaining to intermediate stages overlapped and the number of deaths was fairly homogenous throughout most stages.

Conclusions

The King's College staging system had a higher homogeneity (i.e. smaller differences in survival among patients in the same stage) and a higher discriminatory ability (i.e. greater differences in survival among patients in different stages), being more suitable for individualized prognosis and for measuring efficacy of therapeutic interventions.

Original Article

Background

In the context of the development of telemedicine in France to address low thrombolysis rates and limited stroke infrastructures, a star‐shaped telestroke network was implemented in Burgundy (1.6 million inhabitants). We evaluated the safety and effectiveness of this network for thrombolysis in acute ischemic stroke patients.

Methods

One hundred and thirty‐two consecutive patients who received intravenous thrombolysis during a telemedicine procedure (2012–2014) and 222 consecutive patients who were treated at the stroke center of Dijon University Hospital, France (2011–2012) were included. Main outcomes were the modified Rankin scale (mRS) score and case fatality at 3 months. Comparisons between groups were made using multivariable ordinal logistic regression and logistic regression analyses, respectively.

Results

Baseline characteristics of telethrombolysis patients were similar to those of patients undergoing thrombolysis locally except for a higher frequency of previous cancer and pre‐morbid handicap, and a trend towards greater severity at admission in the former. The distribution of mRS scores at 3 months was similar between groups, as were case‐fatality rates (18.9% in the telethrombolysis group versus 16.5%, = 0.56). In multivariable models, telethrombolysis did not independently influence functional outcomes at 3 months (odds ratio for a shift towards a worse outcome on the mRS, 1.11; 95% confidence interval, 0.74–1.66, = 0.62) or death (odds ratio, 0.86; 95% confidence interval, 0.44–1.69, = 0.66).

Conclusion

The implementation of a regional telemedicine network for the management of acute ischemic stroke appeared to be effective and safe. Thanks to this network, the proportion of patients who benefit from thrombolysis will increase. Further research is needed to evaluate economic benefits.

Original Article

Background and purpose

Theoretical considerations and the results of animal studies indicate that manual lymphatic drainage (MLD) might have an impact on intracranial pressure (ICP). There is a lack of clinically qualitative investigations on patients with severe cerebral diseases.

Methods

Between April 2013 and January 2015 a prospective observational study was performed on patients who were undergoing intracranial pressure measurement and treatment with MLD. ICP, cerebral perfusion pressure, mean arterial pressure (MAP), heart rate and oxygen saturation were recorded continuously 15 min before the procedure, during MLD (22 min) and for 15 min after the procedure. For analysis the data treatment units were divided into two groups: patients with a mean baseline ICP <15 mmHg (group 1) and patients with a mean ICP ≥15 mmHg before MLD (group 2).

Results

A total of 133 treatment units (61 patients) were analysed (group 1 = 99; group 2 = 34). The mean baseline ICP was 10.4 mmHg overall, and 8.3 mmHg and 18.6 mmHg respectively in group 1 and group 2; ICP significantly decreased during therapy with MLD and this persisted during the follow‐up period in group 2. MAP did not show any significant differences between the different periods.

Conclusions

Our data showed a significant reduction of ICP during therapy with craniocervical MLD in patients with severe cerebral diseases.

Original Article

Background and purpose

Previous studies have demonstrated that the components of ideal cardiovascular health (CVH) metrics are related to dementia. This study aimed to investigate the overall effects of ideal CVH metrics on cognitive functioning.

Methods

Information was collected on the seven ideal CVH metrics (smoking, body mass index, dietary intake, physical activity, blood pressure, total cholesterol and fasting blood glucose) from the Asymptomatic Polyvascular Abnormalities Community study, and cognitive functioning was assessed by the score of the Mini‐Mental State Examination (MMSE). Multivariate logistic regression and linear regression models were used to assess the relationships between ideal CVH metrics and cognitive functioning.

Results

A total of 3260 (56.7% men) patients were included in this study. After adjusting for potential confounding factors, the associations between the number or score of ideal CVH metrics and cognitive impairment remained significant [odds ratio (OR) (95% confidence interval) 0.773 (0.664–0.928) and 0.904 (0.831–0.983), respectively]. In addition, there were significant linear relationships between the number or score of CVH metrics and the score of the MMSE ( = 0.211 and 0.134 respectively, < 0.001).

Conclusions

A clear inverse association was observed between the number or score of ideal CVH metrics and cognitive impairment in a Chinese population, supporting the importance of ideal CVH metrics in prevention of dementia.

Original Article

Background and purpose

Akinetic mutism is thought to be an appropriate therapeutic end‐point in patients with sporadic Creutzfeldt−Jakob disease (sCJD). However, prognostic factors for akinetic mutism are unclear and clinical signs or symptoms that precede this condition have not been defined. The goal of this study was to identify prognostic factors for akinetic mutism and to clarify the order of clinical sign and symptom development prior to its onset.

Methods

The cumulative incidence of akinetic mutism and other clinical signs and symptoms was estimated based on Japanese CJD surveillance data (455 cases) collected from 2003 to 2008. A proportional hazards model was used to identify prognostic factors for the time to onset of akinetic mutism and other clinical signs and symptoms.

Results

Periodic synchronous discharges on electroencephalography were present in the majority of cases (93.5%). The presence of psychiatric symptoms or cerebellar disturbance at sCJD diagnosis was associated with the development of akinetic mutism [hazard ratio (HR) 1.50, 95% confidence interval (CI) 1.14–1.99, and HR 2.15, 95% CI1.61–2.87, respectively]. The clinical course from cerebellar disturbance to myoclonus or akinetic mutism was classified into three types: (i) direct path, (ii) path via pyramidal or extrapyramidal dysfunction and (iii) path via psychiatric symptoms or visual disturbance.

Conclusions

The presence of psychiatric symptoms or cerebellar disturbance increased the risk of akinetic mutism of sCJD cases with probable MM/MV subtypes. Also, there appear to be sequential associations in the development of certain clinical signs and symptoms of this disease.

Original Article

Background and purpose

There is evidence that migraine is a risk factor for stroke but little is known about this association in elderly people. Furthermore, non‐migrainous headache (NMH) has received little attention despite being the most frequently reported type of headache. Late‐life migraine and NMH were examined as candidate risk factors for stroke in a community‐dwelling elderly sample over a 12‐year follow‐up.

Methods

One thousand nine hundred and nineteen non‐institutionalized subjects aged 65+, without dementia (Diagnostic and Statistical Manual of Mental Disorders, 4th edition, DSM‐IV criteria) and with no stroke history at baseline, were drawn from the Three‐City Montpellier cohort (recruitment 1999–2001) for longitudinal analysis. Ischaemic and haemorrhagic stroke was reported at baseline and at each of the five follow‐ups, with cases validated by a panel of experts, according to ICD‐10 criteria (International Classification of Diseases, 10th revision). Migraine and NMH were determined at baseline during a neurological interview and examination using 1988 International Headache Society criteria.

Results

A total of 110 (5.4%) cases of migraine and 179 (8.9%) cases of NMH were identified at baseline. During the median 8.8‐year follow‐up, incident stroke was observed in 1.9% of baseline migrainers, 6.2% of NMH and 3.6% of those with no lifetime history of headache. Cox proportional hazard models indicated that migraine was not a risk factor for stroke; however, NMH sufferers were twice as likely to have a stroke (hazard ratio 2.00, 95% confidence interval 1.00–3.93, = 0.049).

Conclusions

This study is one of the first to suggest that late‐life NMH rather than migraine could be an independent risk factor for stroke and a warning sign. The incidence of stroke in elderly migrainers, seldom reported, is particularly low.

Original Article

Background and purpose

Studies on cognitive decline in myotonic dystrophy type 1 (DM1) are characterized by conflicting results. The purpose of the present study was to analyse possible decline in classical/adult onset DM1 at a 5‐year follow‐up and to explore the correlation with disease‐related and demographic factors.

Methods

Patients with DM1 ( = 37) were examined with a comprehensive neuropsychological test battery yielding measures on memory, attention, verbal, visuospatial and executive functions. Assessment of muscle impairment and CTG repeat expansion size was performed.

Results

A majority of the participants (65%) performed worse at follow‐up. Compared to normative data, patients scored significantly worse on tests measuring memory, attention, visuospatial construction and verbal ability. Neither CTG repeat size nor muscle impairment related to cognitive decline. However, age at onset and disease duration were correlated with the number of tests in which performance was below 1 SD at both baseline and follow‐up examination.

Conclusions

Measurements show that classical/adult onset DM1 is characterized by cognitive decline. Both earlier onset and longer duration of the disease are indicative of more cognitive deficits.

Letter to the Editor

Reply to ‘Hitting two birds with one stone: daily scheduled opiods in preventing migraine and migraine‐related epilepsy (migralepsy)’

CME Article

Background and purpose

The influence of temporal patterns of intracerebral haemorrhage (ICH) on the outcome of heparin‐treated patients with cerebral venous sinus thrombosis (CVST) has not been examined systematically.

Methods

Temporal patterns of ICH and their influence on survival without disability (modified Rankin Scale score ≤1 point) at hospital discharge were examined in 141 consecutive hospital‐admitted patients with acute CVST who were treated with intravenous unfractionated heparin.

Results

Of all 141 patients (median age 40 years; 73% women), 59 (42%) had ICH at the time of diagnosis (early ICH). Of these, seven (12%) subsequently had extension of ICH and 13 (22%) had additional ICHs at other locations (delayed ICH). Of 82 patients without early ICH, nine (11%) later had delayed ICH. After a median hospital stay of 26 days, 107 patients (76%) were discharged without disability. Patients with early ICH were less likely to survive without disability until discharge than those without early ICH [63% vs. 85%; risk ratio (RR) 0.73; = 0.005]. The association was attenuated after adjusting for age, sex and impaired consciousness on admission (RR 0.83; = 0.03). Taking temporal patterns of ICH into account, early ICH with subsequent complication (extension or delayed ICH) had a larger influence on survival without disability (RR 0.57; 95% confidence interval 0.35–0.95) than early ICH without complications (RR 0.78; 95% confidence interval 0.67–0.91).

Conclusions

Heparin‐treated CVST patients were less likely to survive without disability when ICH was present on admission. This association may largely be driven by subsequent extension of haemorrhage or additionally occurring delayed haemorrhage.

Original Article

Background and purpose

The interictal electroencephalogram (EEG) has an important role in the classification and treatment of epilepsy. In busy EEG laboratories, valuable resources are used in order to comply with current recommendations regarding the length of EEG recordings. Our aim was to examine the time to first interictal epileptiform discharge (IED) in standard and sleep‐deprived EEGs.

Methods

Standard and sleep‐deprived EEG recordings with IEDs were retrospectively reviewed during a 2‐year period. Bedside EEGs and long‐term video‐EEGs were excluded. IED latency according to EEG type, age group and inpatient/outpatient status was analyzed with the Kaplan−Meier estimator.

Results

The study group included 684 patients, 372 (54%) males, aged 0.2–89 years. Standard ( = 316) and sleep‐deprived ( = 368) EEGs were performed in 245 inpatients and 439 outpatients. The EEG was requested in 96% of the inpatients following a seizure. Most IEDs were recorded whilst the patients were awake (43%) or drowsy (34%). Ninety percent of the IEDs were recorded within 18.5 min, earlier in standard (14.6 vs. 21.3 min) ( = 0.024) EEGs and in inpatients (14 vs. 21.3 min) ( = 0.002). IED latency was unaffected by age.

Conclusions

Electroencephalogram type and admission status may be used for individual determination of the duration of EEG recording. Reducing the duration of standard and sleep‐deprived EEGs may be considered especially in inpatients.

Review Article

Abstract

The use of carbamazepine (CBZ) and oxcarbazepine (OXC) as first‐line antiepileptic drugs in the treatment of focal epilepsy is limited by hyponatremia, a known adverse effect. Hyponatremia occurs in up to half of people taking CBZ or OXC and, although often assumed to be asymptomatic, it can lead to symptoms ranging from unsteadiness and mild confusion to seizures and coma. Hyponatremia is probably due to the antidiuretic properties of CBZ and OXC that are, at least partly, explained by stimulation of the vasopressin 2 receptor/aquaporin 2 pathway. No known genetic risk variants for CBZ‐ and OXC‐induced hyponatremia exist, but likely candidate genes are part of the vasopressin water reabsorption pathway.

Letter to the Editor

Antecedent ADHD and risk of dementia: is there a role for air pollution exposures? A reply to Golimstok . (2011). Author's reply

Letter to the Editor

Long‐term efficacy of pregabalin in stiff person syndrome

Short Communication

Background and purpose

The clinical predictors of health‐related quality of life (HRQoL) in multiple sclerosis (MS) have mainly been studied in patients with long‐standing disease. The objective of this study was to investigate the longitudinal association among HRQoL and clinical characteristics in early MS.

Methods

Relapsing MS patients within 12 months of clinical onset were enrolled in a neuroprotection trial of riluzole versus placebo as an add‐on to weekly interferon with up to 36 months of follow‐up. Serial clinical measures included Short Form‐36 (SF‐36) as the measure of HRQoL, MS Functional Composite (as a measure of disability), Modified Fatigue Impact Scale, Patient Health Questionnaire‐9 (as a measure of depression) and a cognitive battery. Multivariable linear regression analyses assessed cross‐sectional associations. Mixed model regressions with mutual adjustments were used to assess the longitudinal association of HRQoL components and clinical, cognitive and demographic variables.

Results

Forty‐three patients were enrolled within 7.5 ± 4.9 months of clinical onset (72% female, mean age 36 years). The baseline severity of fatigue and depression predicted subsequent changes in SF‐36 Physical Component Summary (PCS) ( values of 0.001 and 0.021, respectively). In longitudinal analyses, changes in disability and depression were associated with changes in SF‐36 PCS ( values of 0.002 and 0.009, respectively), whereas changes in cognitive function and fatigue were associated with changes in SF‐36 Mental Component Summary ( values of 0.037 and 0.001, respectively). A 1‐unit increase in MS Functional Composite was associated with a 7.1‐point increase in SF‐36 PCS (95% CI, 2.6–11.6).

Conclusions

Fatigue, depression, cognition and disability are independently associated with HRQoL in early MS.

Letter to the Editor

Plasma uric acid and risk of ischaemic stroke in women

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