Identification and examination of all patients with multifocal motor neuropathy (MMN) in the Netherlands to document the clinical spectrum and response to IV immunoglobulin (IVIg) and to determine ...correlates of outcome.
A national cross-sectional descriptive study was performed. Ninety-seven patients were identified; 88 participated. Logistic regression analysis was used to study determinants of outcome.
Age at onset was younger in men than in women (38 vs 45 years, p = 0.05). Onset of weakness was in distal arm (61%) or distal leg (34%), and occasionally in the upper arm (5%). Initial diagnosis was motor neuron disease in one-third of patients. Brisk, but not pathologic, reflexes in weakened muscles were found in 8%. Conduction blocks were most frequently detected in the ulnar (80%) and median (77%) nerves, but occasionally only between Erb and axilla (6%), or in the musculocutaneous nerve (1%). Ninety-four percent responded to IVIg therapy: nonresponders had longer disease duration before the first treatment (p = 0.03). Seventy-six percent received IVIg maintenance treatment at the time of this study (median duration 6 years; range 0-17): the median dose increased over the years from 12 to 17 g per week (p < 0.01). Independent determinants of more severe weakness and disability were axon loss (p < 0.001; p < 0.0001) and longer disease duration without IVIg (p = 0.03; p = 0.07).
The results of this study may help aid recognition the clinical picture of MMN. Early IVIg treatment may help to postpone axonal degeneration and permanent deficits.
This study provides Class IV evidence that IVIg improves muscle strength of patients with MMN and disability (defined as an increase of >or=1 Medical Research Council grade in at least 2 muscle groups without decrease in other muscle groups) in 94% (95% confidence interval, 86.8%-97.4%) of patients.
Purpose
To demonstrate that mapping pelvis conductivity at 3T with deep learning (DL) is feasible.
Methods
210 dielectric pelvic models were generated based on CT scans of 42 cervical cancer ...patients. For all dielectric models, electromagnetic and MR simulations with realistic accuracy and precision were performed to obtain
B1+ and transceive phase (ϕ±). Simulated
B1+ and ϕ± served as input to a 3D patch‐based convolutional neural network, which was trained in a supervised fashion to retrieve the conductivity. The same network architecture was retrained using only ϕ± in input. Both network configurations were tested on simulated MR data and their conductivity reconstruction accuracy and precision were assessed. Furthermore, both network configurations were used to reconstruct conductivity maps from a healthy volunteer and two cervical cancer patients. DL‐based conductivity was compared in vivo and in silico to Helmholtz‐based (H‐EPT) conductivity.
Results
Conductivity maps obtained from both network configurations were comparable. Accuracy was assessed by mean error (ME) with respect to ground truth conductivity. On average, ME < 0.1 Sm−1 for all tissues. Maximum MEs were 0.2 Sm−1 for muscle and tumour, and 0.4 Sm−1 for bladder. Precision was indicated with the difference between 90th and 10th conductivity percentiles, and was below 0.1 Sm−1 for fat, bone and muscle, 0.2 Sm−1 for tumour and 0.3 Sm−1 for bladder. In vivo, DL‐based conductivity had median values in agreement with H‐EPT values, but a higher precision.
Conclusion
Anatomically detailed, noise‐robust 3D conductivity maps with good sensitivity to tissue conductivity variations were reconstructed in the pelvis with DL.
Flooding and heavy rainfall have been associated with waterborne infectious disease outbreaks, however, it is unclear to which extent they pose a risk for public health. Here, risks of infection from ...exposure to urban floodwater were assessed using quantitative microbial risk assessment (QMRA). To that aim, urban floodwaters were sampled in the Netherlands during 23 events in 2011 and 2012. The water contained Campylobacter jejuni (prevalence 61%, range 14- >103 MPN/l), Giardia spp. (35%, 0.1–142 cysts/l), Cryptosporidium (30%, 0.1–9.8 oocysts/l), noroviruses (29%, 102–104 pdu/l) and enteroviruses (35%, 103–104 pdu/l). Exposure data collected by questionnaire, revealed that children swallowed 1.7 ml (mean, 95% Confidence Interval 0–4.6 ml) per exposure event and adults swallowed 0.016 ml (mean, 95% CI 0–0.068 ml) due to hand-mouth contact. The mean risk of infection per event for children, who were exposed to floodwater originating from combined sewers, storm sewers and rainfall generated surface runoff was 33%, 23% and 3.5%, respectively, and for adults it was 3.9%, 0.58% and 0.039%. The annual risk of infection was calculated to compare flooding from different urban drainage systems. An exposure frequency of once every 10 years to flooding originating from combined sewers resulted in an annual risk of infection of 8%, which was equal to the risk of infection of flooding originating from rainfall generated surface runoff 2.3 times per year. However, these annual infection risks will increase with a higher frequency of urban flooding due to heavy rainfall as foreseen in climate change projections.
•Urban flooding was measured for enteric pathogens to assess risks for public health.•Health risks were quantified for flooding of different urban drainage systems.•The annual risk of infection for flooding originating from combined sewers was 8%.
Background and purpose
Natural history studies in spinal muscular atrophy (SMA) have primarily focused on infants and children. Natural history studies encompassing all age groups and SMA types are ...important for the interpretation of treatment effects of recently introduced survival motor neuron gene‐augmenting therapies.
Methods
We conducted a cross‐sectional study to investigate muscle strength, Hammersmith Functional Motor Scale (Expanded) score and the patterns of muscle weakness in relation to age and SMA type.
Results
We included 180 patients with SMA types 1–4 in the age range 1–77.5 years with median disease duration of 18 (range 0–65.8) years. With the exception of the early phases of disease in which children with SMA types 2 and 3 may achieve new motor skills and show a temporary increase in muscle strength, cross‐sectional data suggested that declining muscle strength and loss of motor skills over time are characteristic of all SMA types. Mean loss of strength was at least 1 point on the Medical Research Council score and 0.5 point on the Hammersmith Functional Motor Scale (Expanded) score per year. Trend lines compatible with deterioration of motor function and muscle strength started in childhood and continued into adulthood. The age at loss of specific motor skills was associated with disease severity. Triceps, deltoid, iliopsoas and quadriceps were the weakest muscles in all patients. Hierarchical cluster analysis did not show a segmental distribution of muscle weakness as suggested previously.
Conclusions
Progressive muscle weakness and loss of motor function are characteristic of all SMA types and all ages.
To examine the effect of multidisciplinary ALS care on the quality-of-life (QoL) in patients with ALS and their caregivers.
In a cross-sectional study, 208 patients with ALS and their caregivers were ...interviewed. QoL was assessed using the 36-item Short Form Health Survey (SF-36) and two visual analogue scales (VAS). Criteria for multidisciplinary ALS care were: an ALS team headed by a consultant in rehabilitation medicine and consisting of at least a physical therapist, occupational therapist, speech pathologist, dietician and a social worker; use of the Dutch ALS consensus guidelines for ALS care; and at least six incident ALS patients per year.
Clinical characteristics and functional loss of the 133 patients receiving multidisciplinary ALS care and the 75 patients receiving general ALS care were similar. The percentage of patients with adequate aids and appliances was higher in those with multidisciplinary ALS care (93.1 vs 81.3%, p = 0.008), whereas the number of visits to professional caregivers was similar in both groups. Patients in the multidisciplinary ALS care group had a better mental QoL on the SF-36 Mental Summary Score than those in the general care group (p = 0.01). The difference in QoL was most pronounced in the domains of Social Functioning and Mental Health, and was independent of the presence of aids and appliances. No significant differences were found in the SF-36 Physical Summary Score, VAS, or in QoL of caregivers of patients with ALS.
High standard of care improves mental quality-of-life in patients with ALS.
Using ultrasonography we found multiple sites with nerve enlargement along the course of the brachial plexus, median, ulnar, and radial nerves in the majority of 21 patients with multifocal motor ...neuropathy. Sonography and electrophysiologic studies showed more abnormalities than expected on purely clinical grounds. Moreover, sonography revealed nerve enlargement without clinical or electrophysiologic abnormalities.
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder of motor neurons that results in progressive muscle weakness and limits survival to 2-5 years after disease onset. Intermediate CAG ...repeat expansions in ataxin 2 (ATXN2), the causative gene of spinocerebellar ataxia type 2 (SCA2), have been implicated in sporadic ALS. We studied ATXN2 in a large cohort of patients with sporadic and familial ALS.
We determined ATXN2 CAG repeat size in 1,948 sporadic and familial ALS cases and 2,002 controls from Belgium and the Netherlands.
In controls, the maximal ATXN2 repeat size was 31. In sporadic ALS, a significant amount of longer repeat sizes (≥ 32, range 32-39) were encountered (in 0.5% or 10/1,845 ALS cases, vs 0% in controls, p = 0.0006). Receiver operating characteristic analysis showed that a cutoff of ≥ 29 appeared optimal to discriminate ALS from control (p = 0.036, odds ratio OR 1.92, 95% confidence interval CI 1.04-3.64). A meta-analysis with the previously published results from the United States showed that the association between a repeat length of ≥ 29 and ALS became stronger (p < 0.0001, OR 2.93, 95% CI 1.73-4.98). In unexplained familial ALS, we found an intermediate repeat expansion of 31 and a homozygous repeat expansion of 33 each in 1.1% of families. The phenotype of patients with ALS with expanded repeat sizes ranged from rapidly progressive typical ALS to slowly progressive ALS with reduced sensory nerve action potentials.
Our data reveal a novel genetic overlap between ALS and SCA2.
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 (n = 23) or MMN (n = 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.
•Prenatal psychopathology was associated with child hair cortisone.•Prenatal stress, especially long-lasting stress, was associated with child cortisone.•Prenatal psychopathology and stress were not ...associated with offspring cortisol.
Intrauterine exposures such as maternal psychopathology and stress are known to influence the physical and mental health of the offspring. One of the proposed pathways underlying these associations is dysregulated hypothalamic-pituitary-adrenal (HPA) axis activity in the offspring. This study examined the relation of perinatal maternal symptoms of psychopathology and stress with offspring HPA axis activity at 6 years as measured by hair cortisol and cortisone concentrations.
The study was part of the population-based Generation R Study, a prospective population-based cohort from fetal life onwards. 2546 children and their mothers formed the study population. Perinatal maternal psychopathology and stress were assessed by questionnaires in the second and third trimester. Principal components for both psychopathology and stress were created to reduce the number of explanatory variables. Child hair samples for cortisol and cortisone measurements were collected at the age of 6. Linear regression analysis, adjusted for covariates, was used to examine associations between maternal psychopathology and stress and child hair cortisol and cortisone levels.
The maternal psychopathology principal component was associated with higher child hair cortisone (adjusted B = 0.24, 95%CI 0.08;0.40, p-value < 0.01). Effect estimates of the individual dimensions ranged from 0.97 (95%CI 0.21;1.73, p-value = 0.01) for interpersonal sensitivity to 1.67 (95%CI 0.86;2.47, p-value < 0.01) for paranoid ideation. In addition, children exposed to intrauterine stress, as measured by the principal component, had higher hair cortisone levels (adjusted B = 0.54, 95%CI 0.21;0.88, p-value < 0.01). Exposure to maternal psychopathology and stress was not associated with offspring hair cortisol. Stratification by child sex resulted in associations between maternal symptoms of psychopathology during pregnancy and child hair cortisone levels in boys and associations between maternal symptoms of stress during pregnancy and child hair cortisone levels in girls.
Our results suggest that maternal psychopathology and stress during pregnancy are associated with long-term HPA axis activity of the offspring. The association of maternal psychopathology and stress during pregnancy with offspring hair cortisone levels is a novel finding. Future studies should examine whether these psychophysiological differences between exposed and non-exposed children underlie offspring morbidity associated with maternal psychopathology and stress during pregnancy.
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