[«Digital Postcovid Syndrome¼ - possibilities and limits in digital communication with neurological patients]. / «Digitales Postcovid-Syndrom¼ ­ Möglichkeiten und Grenzen in der digitalisierten Kommunikation mit neurologischen Patienten.

INTRODUCTION: Background: This work deals with the question of which digital touchpoints in the course of a patient journey are desired by neurological patients, important for effective treatment and easy to implement. Methodology: 100 (44 men, 56 women) patients in a neurological practice at three different locations were examined using a written questionnaire with closed questions on topics of online booking, making appointments and reminders via SMS, video consultation with the doctor and chat with the doctor or the medical practice assistant. Results: It was shown that the older a person is, the less they prefer digital booking and consultation and that the more they work, the more they prefer digital booking and consultation and the longer they live in Switzerland, the less they prefer chat advice. Data protection plays a more important role in older patients. Regarding gender no significant differences can be shown. Discussion: The results are in line with a survey conducted by the Swiss Medical Association (Foederatio Medicorum Helveticorum) of 2020, which shows that the population wants to relieve the burden on doctors in administrative tasks through the use of digital solutions considered desirable. In this study, both younger and older patients are very interested in booking appointments online and to receive an appointment reminder via text message. Since older patients tend to prefer conservative booking, a «hybrid model¼ should be offered so that both options are available.

Effectiveness, Safety and Patients' Satisfaction of Nabiximols (Sativex®) on Multiple Sclerosis Spasticity and Related Symptoms in a Swiss Multicenter Study.

Background: Cannabinoid oro-mucosal spray nabiximols is approved for patients with moderate to severe multiple sclerosis spasticity (MSS) resistant to other antispastic medications. Few real-world data are available on the effectiveness, safety and patients' satisfaction in MS patients treated with nabiximols as monotherapy. Methods: To investigate the effectiveness, tolerability and satisfaction of nabiximols in a real-life multicentric Swiss cohort as monotherapy or with stable doses of other antispastic medications, and explore clinical features which may predict treatment response. The following data were collected at treatment start (baseline) and 12 weeks thereafter: Modified Ashworth scale (MAS), scores at numerical rating scales ranging from 0 (absent) to 10 (considerable) for effect on spasticity (sNRS), pain (pNRS), gait (gNRS), urinary symptoms (uNRS), tolerability (tNRS) as assessed by the treating neurologist, and overall treatment satisfaction (TsNRS) and tolerability (tNRS) as assessed by the patient. Results: Ninety-five patients (44 relapsing remitting, 37 secondary progressive and 14 primary progressive MS; median age = 53 (IQR 45-62); female 70%; median EDSS 6 (IQR 4-6), concomitant antispastic treatments in 54% of patients) were included. From baseline to week 12, median MAS score decreased from 3.0 to 2.0 (p < 0.001). Median scores of the each NRS also significantly decreased (p < 0.001 for all comparisons). At week 12, the median TsNRS and tTS scores were 8/10 (IQR: 6-9) and 9/10 (IQR: 7-10), respectively, and 93.7% of patients continued to use nabiximols at the average dose of six sprays/day. No clinical factors, including use of nabiximols as add on vs. monotherapy, were associated with responder status. Conclusions: Our first Swiss, multicentric, observational, real-life study supports and enhances previous finding of nabiximols as monotherapy and as add-on therapy, being an effective, safe and well-tolerated treatment option for resistant MS spasticity and spasticity-related symptoms (pain, bladder dysfunction and gait).

[A Rare Cause for Median Nerve Irritation]. / Eine seltene Ursache für die Reizung des Nervus medianus.

INTRODUCTION: A lesion of the median nerve due to nerve compression comparable to carpal tunnel syndrome is very common, with an incidence of 3.3 to 3.45 cases per 1000 inhabitants and year. In the present case series, we report compressions of the -median nerve due to wearing a smartwatch, which to our knowledge has not been previously reported in the literature. We -describe five patients with typical carpal tunnel symptoms and pathological sensory neurography who had been wearing a smartwatch more than 24 hours/day for several weeks to detect atrial fibrillation, and whose symptoms and electrophysiology improved after they stopped wearing it. Smartwatches can be an interesting additional gadget for diagnosing diseases such as cardiac arrhythmias. However, the tight wearing that is necessary can possibly also compress the median nerve and lead to symptoms such as the carpal tunnel syndrome. According to the manufacturer, it is important to choose the right strap size when buying and only leave the watch very tight when you need the sensors (but without feeling uncomfortable) and otherwise to tie the strap loosely, to take it off or alternate the wrist in order to avoid pain and injury.

High-Resolution 3D versus Standard-Resolution 2D T2-Weighted Turbo Spin Echo MRI for the Assessment of Lumbar Nerve Root Compromise.

Radiculopathy can be caused by nerve root irritation and nerve root compression at the level of the lateral recess or at the level of the intervertebral foramen. T2-weighted (T2w) MRI is considered essential to evaluate the nerve root and its course, starting at the lateral recess through the intervertebral foramen to the extraforaminal space. With the introduction of novel MRI acceleration techniques such as compressed SENSE, standard-resolution 2D T2w turbo spin echo (TSE) sequences with a slice-thickness of 3-4 mm can be replaced with high-resolution isotropic 3D T2w TSE sequences with sub-millimeter resolution without prolonging scan time. With high-resolution 3D MRI, the course of the nerve root can be visualized more precisely due to a detailed depiction of the anatomical situation and less partial volume effects, potentially allowing for a better detection of nerve root compromise. In this intra-individual comparison study, 55 patients with symptomatic unilateral singular nerve root radiculopathy underwent MRI with both 2D standard- and 3D high-resolution T2w TSE MRI sequences. Two readers graded the degree of lumbar lateral recess stenosis and lumbar foraminal stenosis twice on both image sets using previously validated grading systems in an effort to quantify the inter-readout and inter-sequence agreement of scores. Inter-readout agreement was high for both grading systems and for 2D and 3D imaging (Kappa = 0.823-0.945). Inter-sequence agreement was moderate for both lumbar lateral recess stenosis (Kappa = 0.55-0.577) and lumbar foraminal stenosis (Kappa = 0.543-0.572). The percentage of high degree stenosis with nerve root deformity increased from 16.4%/9.8% to 41.8-43.6%/34.1% from 2D to 3D images for lateral recess stenosis/foraminal stenosis, respectively. Therefore, we show that while inter-readout agreement of grading systems is high for both standard- and high-resolution imaging, the latter outperforms standard-resolution imaging for the visualization of lumbar nerve root compromise.

[Brivaracetam - A Good Alternative in the Acute Treatment of Trigeminal Neuralgia]. / Brivaracetam ­ eine gute Alternative in der akuten Behandlung der Trigeminusneuralgie.

Brivaracetam - A Good Alternative in the Acute Treatment of Trigeminal Neuralgia Abstract. In trigeminal neuralgia there is brief neuropathic pain in the supply area of the trigeminal nerve. A distinction is made between classic, symptomatic, and idiopathic trigeminal neuralgia. Only a few drugs are available for acute treatment. In the presented case series, we report on five patients with trigeminal neuralgia of various origins who responded well to treatment with brivaracetam. Brivaracetam binds to the synaptic vesicle protein 2A, which is also found on nerves and nerve roots. SV2 regulates the exocytotic release of neurotransmitters, which may explain the effect of brivaracetam on neuropathic pain. The use of brivaracetam can be helpful in the short-term therapy of paroxysmal pain with trigeminal neuralgia. Further studies are required to demonstrate this effect and to rule out a placebo effect.

Spiral gradient echo versus cartesian turbo spin echo imaging for sagittal contrast-enhanced fat-suppressed T1 weighted spine MRI: an inter-individual comparison study.

OBJECTIVES: To compare a novel 3D spiral gradient echo (GRE) sequence with a conventional 2D cartesian turbo spin echo (TSE) sequence for sagittal contrast-enhanced (CE) fat-suppressed (FS) T1 weighted (T1W) spine MRI. METHODS: In this inter-individual comparison study, 128 patients prospectively underwent sagittal CE FS T1W spine MRI with either a 2D cartesian TSE ("TSE", 285 s, 64 patients) or a 3D spiral GRE sequence ("Spiral", 93 s, 64 patients). Between both groups, patients were matched in terms of anatomical region (cervical/thoracic/lumbar spine and sacrum). Three readers used 4-point Likert scales to assess images qualitatively in terms of overall image quality, presence of artifacts, spinal cord visualization, lesion conspicuity and quality of fat suppression. RESULTS: Spiral achieved a 67.4% scan time reduction compared to TSE. Interreader agreement was high (alpha=0.868-1). Overall image quality (4;[3,4] vs 3;[3,4], p<0.001 - p=0.002 for all readers), presence of artifacts (4;[3,4] vs 3;[3,4] p=0.027 - p=0.046 for all readers), spinal cord visualization (4;[4,4] vs 4;[3,4], p<0.001 for all readers), lesion conspicuity (4;[4,4] vs 4;[4,4], p=0.016 for all readers) and quality of fat suppression (4;[4,4] vs 4;[4,4], p=0.027 - p=0.033 for all readers), were all deemed significantly improved by all three readers on Spiral images as compared to TSE images. CONCLUSION: We demonstrate the feasibility of a novel 3D spiral GRE sequence for improved and rapid sagittal CE FS T1W spine MRI. ADVANCES IN KNOWLEDGE: A 3D spiral GRE sequence allows for improved sagittal CE FS T1W spine MRI at very short scan times.

Single shot zonal oblique multislice SE-EPI diffusion-weighted imaging with low to ultra-high b-values for the differentiation of benign and malignant vertebral spinal fractures.

PURPOSE: To investigate the diagnostic yield of low to ultra-high b-values for the differentiation of benign from malignant vertebral fractures using a state-of-the-art single-shot zonal-oblique-multislice spin-echo echo-planar diffusion-weighted imaging sequence (SShot ZOOM SE-EPI DWI). MATERIALS AND METHODS: 66 patients (34 malignant, 32 benign) were examined on 1.5 T MR scanners. ADC maps were generated from b-values of 0,400; 0,1000 and 0,2000s/mm2. ROIs were placed into the fracture of interest on ADC maps and trace images and into adjacent normal vertebral bodies on trace images. The ADC of fractures and the Signal-Intensity-Ratio (SIR) of fractures relative to normal vertebral bodies on trace images were considered quantitative metrics. The appearance of the fracture of interest was graded qualitatively as iso-, hypo-, or hyperintense relative to normal vertebrae. RESULTS: ADC achieved an area under the curve (AUC) of 0.785/0.698/0.592 for b = 0,400/0,1000/0,2000s/mm2 ADC maps respectively. SIR achieved an AUC of 0.841/0.919/0.917 for b = 400/1000/2000s/mm2 trace images respectively. In qualitative analyses, only b = 2000s/mm2 trace images were diagnostically valuable (sensitivity:1, specificity:0.794). Machine learning models incorporating all qualitative and quantitative metrics achieved an AUC of 0.95/0.98/0.98 for b-values of 400/1000/2000s/mm2 respectively. The model incorporating only qualitative metrics from b = 2000s/mm2 achieved an AUC of 0.97. CONCLUSION: By using quantitative and qualitative metrics from SShot ZOOM SE-EPI DWI, benign and malignant vertebral fractures can be differentiated with high diagnostic accuracy. Importantly qualitative analysis of ultra-high b-value images may suffice for differentiation as well.

Advanced multimodality MR imaging of a cerebral nocardiosis abscess in an immunocompetent patient with a focus on Amide Proton Transfer weighted imaging.

Cerebral nocardiosis abscess is a very rare entity in an immunocompetent patient. In this case report multiparametric and multimodality MR imaging characteristics of a pyogenic brain abscess caused by Nocardia Farcinica are discussed with a specific focus on amide proton transfer weighted imaging as a modern non-invasive, molecular MR imaging method which detects endogenous mobile protein and peptide concentration and tissue pH changes in pathologic brain lesions. The imaging characteristics are reviewed and discussed in respect to possible differential diagnoses, especially malignant tumorous lesions.

[Brivaracetam-A good alternative for the treatment of muscle cramps]. / Brivaracetam ­ eine gute Alternative zur Behandlung von Muskelkrämpfen.

BACKGROUND: Muscle cramps are suddenly occurring involuntary, mostly painful contractions of a single muscle, rarely of a muscle group. They can be idiopathic or occur in various neuromuscular diseases and can sometimes substantially impair the quality of life due to the frequency and strength. Only a few drugs are available for the effective treatment of cramps. RESULTS: In this case series we report on five patients with cramps of different origin who responded well to treatment with brivaracetam. DISCUSSION: Brivaracetam is actually used for the treatment of epileptic seizures. It binds to the synaptic vesicle protein 2A (SV2A), which also occurs in nerves and nerve roots. The SV2A regulates the exocytotic release of neurotransmitters, which could explain the effect of brivaracetam on muscle cramps. CONCLUSION: Further studies are needed to demonstrate the effect of brivaracetam on muscle cramps.

Nine Hole Peg Test and Transcranial Magnetic Stimulation: Useful to Evaluate Dexterity of the Hand and Disease Progression in Amyotrophic Lateral Sclerosis.

OBJECTIVE: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease with involvement of the upper and lower motor neurons. Since the loss of fine motor skills is one of the earliest signs of ALS, the hypothesis was tested if the nine hole PEG test (NHPT) and transcranial magnet stimulation (TMS) with resting-motor threshold (RMT) could be useful in monitoring disease progression. METHODS: We examined 28 ALS patients and 27 age-matched healthy controls. ALS patients and healthy controls underwent the nine hole peg test (NHPT) and TMS with RMT. Measurements in patients were repeated after three and six months. RESULTS: At baseline, the median NHPT durations were 1,4-fold longer (p < 0.001), and TMS scores showed a significant 0.8-fold smaller score in ALS patients compared with healthy controls (p < 0.001). The comparison of three and six months versus baseline revealed significant differences for NHPT durations and ALSFRS-R in patients, whereas TMS scores did not significantly differ in the patients. CONCLUSION: NHPT seems to be a good tool to evaluate dexterity of the hand and the progression of the disease in ALS patients. TMS RMT to the hand muscles seems to be poorly qualified to evaluate the dexterity of the hand function and the course of the disease.

[Genetics of Amyotrophic Lateral Sclerosis]. / Genetik der amyotrophen Lateralsklerose.

Genetics of Amyotrophic Lateral Sclerosis Abstract. In recent years, the knowledge of gene mutation that can lead to amyotrophic lateral sclerosis (ALS), frontotemporal dementia, or a FTD-ALS complex has been drastically improvedwith the help of next-generation sequencing (NGS), so that many new genes and their molecular genetic mechanisms and symptoms of the patients could be described. For example it was found that in the same family with the same gene mutation patients with ALS, FTD or another neurodegenerative disease can be found. The knowledge about the genes does not only contribute to the understanding of these diseases, but should help develop new therapeutic possibilities.

Investigation of Neurodegenerative Processes in Amyotrophic Lateral Sclerosis Using White Matter Fiber Density.

In the current work two novel parameters, fiber density (FD) and mean diffusion signal (MDS) are investigated for evaluating neurodegenerative processes in amyotrophic lateral sclerosis (ALS). The MDS provides a measure of the FD but is derived directly from the diffusion signal. Using tract-based spatial statistics (TBSS), pathological changes across the entire white matter and changes in the parameters over time were evaluated. The results were related to those obtained using the fractional anisotropy (FA) value. A widespread pattern of significantly decreased FD and MDS values was observed. A strong trend towards statistical significance was seen in similar white matter structures using TBSS analysis based on the FA value. Longitudinal analysis of the FD values demonstrated continuing deterioration of the same fiber tracts that were shown to be impaired in the group analysis. The findings suggest that MDS and in particular FD show great promise for evaluating microstructural white matter changes in ALS and may be more sensitive than the more commonly used FA value.

Amide Proton Transfer Weighted Imaging Shows Differences in Multiple Sclerosis Lesions and White Matter Hyperintensities of Presumed Vascular Origin.

Objectives: To assess the ability of 3D amide proton transfer weighted (APTw) imaging based on magnetization transfer analysis to discriminate between multiple sclerosis lesions (MSL) and white matter hyperintensities of presumed vascular origin (WMH) and to compare APTw signal intensity of healthy white matter (healthy WM) with APTw signal intensity of MSL and WHM. Materials and Methods: A total of 27 patients (16 female, 11 males, mean age 39.6 years) with multiple sclerosis, 35 patients (17 females, 18 males, mean age 66.6 years) with small vessel disease (SVD) and 20 healthy young volunteers (9 females, 11 males, mean age 29 years) were included in the MSL, the WMH, and the healthy WM group. MSL and WMH were segmented on fluid attenuated inversion recovery (FLAIR) images underlaid onto APTw images. Histogram parameters (mean, median, 10th, 25th, 75th, 90th percentile) were calculated. Mean APTw signal intensity values in healthy WM were defined by "Region of interest" (ROI) measurements. Wilcoxon rank sum tests and receiver operating characteristics (ROC) curve analyses of clustered data were applied. Results: All histogram parameters except the 75 and 90th percentile were significantly different between MSL and WMH (p = 0.018-p = 0.034). MSL presented with higher median values in all parameters. The histogram parameters offered only low diagnostic performance in discriminating between MSL and WMH. The 10th percentile yielded the highest diagnostic performance with an AUC of 0.6245 (95% CI: [0.532, 0.717]). Mean APTw signal intensity values of MSL were significantly higher than mean values of healthy WM (p = 0.005). The mean values of WMH did not differ significantly from the values of healthy WM (p = 0.345). Conclusions: We found significant differences in APTw signal intensity, based on straightforward magnetization transfer analysis, between MSL and WMH and between MSL and healthy WM. Low AUC values from ROC analyses, however, suggest that it may be challenging to determine type of lesion with APTw imaging. More advanced analysis of the APT CEST signal may be helpful for further differentiation of MSL and WMH.

In-vivo evaluation of neuronal and glial changes in amyotrophic lateral sclerosis with diffusion tensor spectroscopy.

Diffusion tensor spectroscopy (DTS) combines features of magnetic resonance spectroscopy and diffusion tensor imaging and permits evaluating cell-type specific properties of microstructure by probing the diffusion of intracellular metabolites. This exploratory study investigates for the first time microstructural changes in the neuronal and glial compartments of the brain of patients with amyotrophic lateral sclerosis (ALS) using DTS. To this end, the diffusion properties of the neuronal metabolite tNAA (N-acetylaspartate + N-acetylaspartylglutamate) and the predominantly glial metabolites tCr (creatine + phosphocreatine) and tCho (choline-containing compounds) were evaluated in the primary motor cortex of 24 ALS patients and 27 healthy controls. Significantly increased values in the diffusivities of all three metabolites were found in ALS patients relative to controls. Further analysis revealed more pronounced microstructural alterations in ALS patients with limb onset than with bulbar onset relative to controls. This observation may be related to the fact that the spectroscopic voxel was positioned in the part of the motor cortex where the motor functions of the limbs are represented. The higher diffusivities of tNAA may reflect neuronal damage and/or may be a consequence of mitochondrial dysfunction in ALS. Increased diffusivities of tCr and tCho are in line with reactive microglia and astrocytes surrounding degenerating motor neurons in the primary motor cortex of ALS patients. This pilot study demonstrates for the first time that cell-type specific microstructural alterations in the brain of ALS patients may be explored in vivo and non-invasively with DTS. In conjunction with other microstructural magnetic resonance imaging techniques, DTS may provide further insights into the pathogenic mechanisms that underlie neurodegeneration in ALS.

Further analysis of KIFAP3 gene in ALS patients from Switzerland and Sweden.

A series of studies suggests that susceptibility to ALS may be influenced by variants in multiple genes. While analyses of the 10% of cases of familial origin have identified more than 33 monogenic ALS-causing genetic defects, little is known about genetic factors that influence susceptibility or phenotype in sporadic ALS (SALS). We and others conducted a genome-wide association study (GWAS) in a cohort of 1014 ALS cases from Western Europe, England and the United States, and identified an intronic single nucleotide polymorphism (SNP) rs1541160 in the KIFAP3 gene that was statistically associated with improved survival. We have now completed an additional survival analysis examining the impact of the rs1541160 genotype in a cohort of 264 ALS and progressive bulbar palsy (PBP) cases. In the combined cohort of 264 patients, the CC, CT and TT genotypes for rs1541160 were detected, respectively, in 8.3% (22), 41.7% (110) and 50.0% (132). This study does not show an influence of KIFAP3 variants on survival in the studied Swiss and Swedish cohort. There was a difference in survival between the US and English patients and the patients from the Netherlands. The effect of KIFAP3 variants may be population specific, or the rs1541160 association reported previously may have been a false-positive.

Intraneural hemorrhage in traumatic oculomotor nerve palsy.

Isolated traumatic oculomotor nerve palsy without internal ophthalmoplegia is a rare condition after closed head trauma. The nerve strain leads to intraneural edema with nerve swelling on T2-weighted magnetic resonance (MR) images and traumatic disruption of the blood peripheral nerve barrier with contrast enhancement on T1-weighted MR images. In this patient, susceptibility-weighted MR imaging allowed the direct visualization of the intraneural hemorrhage after suspected traumatic diffuse neuronal axonal injury.

Motor Unit Number Index (MUNIX) detects motor neuron loss in pre-symptomatic muscles in Amyotrophic Lateral Sclerosis.

OBJECTIVE: Motor Unit Number Index (MUNIX) is a quantitative neurophysiological measure that provides an index of the number of lower motor neurons supplying a muscle. It reflects the loss of motor neurons in patients with Amyotrophic Lateral Sclerosis (ALS). However, it is unclear whether MUNIX also detects motor unit loss in strong, non-wasted muscles. METHODS: Three centres measured MUNIX in 49 ALS patients every three months in six different muscles (abductor pollicis brevis, abductor digiti minimi, biceps brachii, tibialis anterior, extensor digitorum brevis, abductor hallucis) on the less affected side. The decline of MUNIX in initially non-wasted, clinically strong muscles (manual muscle testing, MMT grade 5) was analysed before and after onset of weakness. RESULTS: In 49 subjects, 151 clinically strong muscles developed weakness and were included for analysis. The average monthly relative loss of MUNIX was 5.0% before and 5.6% after onset of weakness. This rate of change was significantly higher compared to ALS functional rating scale (ALSFRS-R) and compound muscle action potential (CMAP) change over 12months prior to the onset of muscle weakness (p=0.024). CONCLUSION: MUNIX is an electrophysiological marker that detects lower motor neuron loss in ALS, before clinical weakness becomes apparent by manual muscle testing. SIGNIFICANCE: This makes MUNIX a good biomarker candidate for disease progression and possibly pharmacodynamics responds.

Distribution Of fasciculations in healthy adults after exercise: An ultrasound study.

INTRODUCTION: Ultrasound has become a reliable method to detect fasciculations. There is disagreement as to whether fasciculations above the knee should raise the suspicion of a disorder even if there are no other signs of lower motor neuron abnormality. METHODS: Using ultrasonography, 3 arm and 3 leg muscles were investigated for 120 s, 45 min after 90-min handball training or a 5,000 meter run in a group of 25 men and 25 women handball players and 7 men who are amateur runners. RESULTS: All athletes had fasciculations in muscles above the knee. There were no fasciculations in the upper limb muscles in the runner group. In 21 men and 18 women handball players between 1 to 17 fasciculations in 2 min were detected. The number of fasciculations in the rectus femoris was 4-fold higher in the runners compared with the handball players (ratio 0.24; P = 0.037). CONCLUSIONS: Fasciculations may occur in muscles above the knee in healthy subjects. The distribution of fasciculations primarily depends on the exercised muscles. Muscle Nerve, 2016 Muscle Nerve 54: 132-135, 2016 Muscle Nerve 54: 132-135, 2016.