Patterns of subregional cerebellar atrophy across epilepsy syndromes: An ENIGMA-Epilepsy study.

OBJECTIVE: The intricate neuroanatomical structure of the cerebellum is of longstanding interest in epilepsy, but has been poorly characterized within the current corticocentric models of this disease. We quantified cross-sectional regional cerebellar lobule volumes using structural magnetic resonance imaging in 1602 adults with epilepsy and 1022 healthy controls across 22 sites from the global ENIGMA-Epilepsy working group. METHODS: A state-of-the-art deep learning-based approach was employed that parcellates the cerebellum into 28 neuroanatomical subregions. Linear mixed models compared total and regional cerebellar volume in (1) all epilepsies, (2) temporal lobe epilepsy with hippocampal sclerosis (TLE-HS), (3) nonlesional temporal lobe epilepsy, (4) genetic generalized epilepsy, and (5) extratemporal focal epilepsy (ETLE). Relationships were examined for cerebellar volume versus age at seizure onset, duration of epilepsy, phenytoin treatment, and cerebral cortical thickness. RESULTS: Across all epilepsies, reduced total cerebellar volume was observed (d = .42). Maximum volume loss was observed in the corpus medullare (dmax = .49) and posterior lobe gray matter regions, including bilateral lobules VIIB (dmax = .47), crus I/II (dmax = .39), VIIIA (dmax = .45), and VIIIB (dmax = .40). Earlier age at seizure onset ( η ρ max 2 = .05) and longer epilepsy duration ( η ρ max 2 = .06) correlated with reduced volume in these regions. Findings were most pronounced in TLE-HS and ETLE, with distinct neuroanatomical profiles observed in the posterior lobe. Phenytoin treatment was associated with reduced posterior lobe volume. Cerebellum volume correlated with cerebral cortical thinning more strongly in the epilepsy cohort than in controls. SIGNIFICANCE: We provide robust evidence of deep cerebellar and posterior lobe subregional gray matter volume loss in patients with chronic epilepsy. Volume loss was maximal for posterior subregions implicated in nonmotor functions, relative to motor regions of both the anterior and posterior lobe. Associations between cerebral and cerebellar changes, and variability of neuroanatomical profiles across epilepsy syndromes argue for more precise incorporation of cerebellar subregional damage into neurobiological models of epilepsy.

Antiganglioside antibody frequency in routine clinical care settings.

BACKGROUND AND PURPOSE: Antiganglioside antibodies (AGAs) might be involved in the etiopathogenesis of many neurological diseases, such as Miller-Fisher syndrome (MFS) and Guillain-Barré syndrome (GBS). Available comprehensive reference data regarding AGA positivity rates and cross-responsiveness among AGAs (where one line immunoblot is positive for ≥1 AGA) during routine clinical care are scant. METHODS: In this 10-year monocentric retrospective study, 3560 immunoglobulin (Ig) G and IgM line blots (GA Generic Assays' Anti-Ganglioside Dot kit) obtained using cerebrospinal fluid (CSF) and serum samples from 1342 patients were analyzed for AGA positivity in terms of 14 diagnosis categories and AGA cross-responsiveness. RESULTS: Of all 3560 line blots 158 (4.4%) and of all CSF samples 0.4% (4/924) CSF line blots were AGA positive. For serum IgG, blots with positivity rates higher than the standard deviation of 15.6% were associated with MFS (GD3, GD1a, GT1a and GQ1b) and acute motor axonal neuropathy (AMAN) (GM1, GD1a and GT1a). For serum IgM, blots with positivity rates higher than the standard deviation of 8.1% were associated with AMAN (GM2, GT1a and GQ1b), MFS (GM1, GT1a and GQ1b), multifocal motor neuropathy (MMN) (GM1, GM2 and GQ1b) and chronic inflammatory demyelinating polyneuropathy (CIDP) (GM1). Cross-responsiveness was observed in 39.6% of all positive serum AGA. CONCLUSIONS: Testing for AGAs during routine clinical care rarely led to positive findings, both in serum and even less in CSF, except for the diagnoses AMAN, MFS, MMN and CIDP. Nonspecific findings found as cross-responsiveness between different AGA samples occur frequently, impacting the positivity of most AGA subtypes.

Risk factors for nonidiopathic and idiopathic facial nerve palsies: findings of a retrospective study.

BACKGROUND: Idiopathic (IF) and nonidiopathic facial (NIF) nerve palsies are the most common forms of peripheral facial nerve palsies. Various risk factors for IF palsies, such as weather, have been explored, but such associations are sparse for NIF palsies, and it remains unclear whether certain diagnostic procedures, such as contrast agent-enhanced cerebral magnetic resonance imaging (cMRI), are helpful in the differential diagnosis of NIF vs. IF. METHODS: In this retrospective, monocentric study over a five-year period, the medical reports of 343 patients with peripheral facial nerve palsy were analysed based on aetiology, sociodemographic factors, cardiovascular risk factors, consultation time, diagnostic procedures such as cMRI, and laboratory results. We also investigated whether weather conditions and German Google Trends data were associated with the occurrence of NIF. To assess the importance of doctors' clinical opinions, the documented anamneses and clinical examination reports were presented and rated in a blinded fashion by five neurology residents to assess the likelihood of NIF. RESULTS: A total of 254 patients (74%) had IF, and 89 patients (26%) had NIF. The most common aetiology among the NIF patients was the varicella zoster virus (VZV, 45%). Among the factors analysed, efflorescence (odds ratio (OR) 17.3) and rater agreement (OR 5.3) had the highest associations with NIF. The day of consultation (Friday, OR 3.6) and the cMRI findings of contrast enhancement of the facial nerve (OR 2.3) were also risk factors associated with NIF. In contrast, the local weather, Google Trends data, and cardiovascular risk factors were not associated with NIF. CONCLUSION: The findings of this retrospective study highlight the importance of patient history and careful inspections to identify skin lesions for the differential diagnosis of acute facial nerve palsy. Special caution is advised for hospital physicians during the tick season, as a surge in NIF cases can lead to a concomitant increase in IF cases, making it challenging to choose adequate diagnostic methods.

Shear wave elastography characterizes passive and active mechanical properties of biceps brachii muscle in vivo.

Mechanical characterization of individual muscles in their in vivo environment is not well studied. Shear wave elastography (SWE) as a non-invasive technique was shown to be promising in quantifying the local mechanical properties of skeletal muscles. This study aimed to investigate the mechanics of the biceps brachii muscle (BB) derived from SWE in relation to elbow joint position and contraction intensity during isometric contraction. 14 healthy, young subjects participated in the study and five different joint positions (60°-180° elbow angle) were investigated. Shear elastic modulus and surface electromyography (sEMG) of the BB and elbow torque were measured simultaneously, both in passive (i.e., resting) and active states during slow, sub-maximal isometric ramp contractions up to 25%, 50%, and 75% of the maximum voluntary contraction. At passive state, the shear elastic modulus of the BB increased with increasing elbow angle (p < 0.001). Maximum elbow flexion torque was produced at 60° and it decreased with increasing elbow angle (p = 0.001). During sub-maximal contractions, both elbow angle (p < 0.001) and contraction intensity (p < 0.001) had significant effects on the shear elastic modulus but only contraction intensity (p < 0.001) affected sEMG amplitude of the BB. Although torque was decreased at extended elbow positions (150°, 180°), higher active shear elastic modulus of BB muscle was found compared to flexed positions (60°, 90°). Linear regression of the BB sEMG amplitude over elbow torque showed good agreement for all joint positions (R2 between 0.69 and 0.89) while the linear agreement between shear elastic modulus of BB and elbow torque differed between flexed (R2 = 0.70 at 60° and R2 = 0.79 at 90°) and extended positions (with the lowest R2 = 0.57 at 150°). We conclude that using SWE, we can detect length-dependent mechanical changes of BB both in passive and active states. More importantly, SWE can be used to characterize active muscle properties in vivo. The present findings have critical importance for developing muscle stiffness as a measure of individual muscle force to validate muscle models and using SWE in clinical diagnostics.

Characterization of Muscle Weakness Due to Myasthenia Gravis Using Shear Wave Elastography.

Myasthenia gravis (MG) is often accompanied with muscle weakness; however, little is known about mechanical adaptions of the affected muscles. As the latter can be assessed using ultrasound shear wave elastography (SWE), this study characterizes the biceps brachii muscle of 11 patients with MG and compares them with that of 14 healthy volunteers. Simultaneous SWE, elbow torque and surface electromyography measurements were performed during rest, maximal voluntary contraction (MVC) and submaximal isometric contractions (up to 25%, 50% and 75% MVC) at different elbow angles from flexion to extension. We found that, with increasing elbow angle, maximum elbow torque decreased (p < 0.001), whereas muscle stiffness increased during rest (p = 0.001), MVC (p = 0.004) and submaximal contractions (p < 0.001). Muscle stiffness increased with increasing contraction intensities during submaximal contractions (p < 0.001). In comparison to the healthy cohort, muscle stiffness of MG patients was 2.1 times higher at rest (p < 0.001) but 8.93% lower in active state (75% MVC, p = 0.044). We conclude that (i) increased muscle stiffness shown by SWE during rest might be an indicator of MG, (ii) SWE reflects muscle weakness and (iii) SWE can be used to characterize MG muscle.

Shear Wave Elastography in Bruxism-Not Yet Ready for Clinical Routine.

Ultrasound shear wave elastography (SWE) is an emerging modality for the estimation of stiffness, but it has not been studied in relation to common disorders with altered stiffness, such as bruxism, which affects almost one-third of adults. Because this condition could lead to an increased stiffness of masticatory muscles, we investigated SWE in bruxism according to a proof-of-principle and feasibility study with 10 patients with known bruxism and an age- and gender-matched control group. SWE of the left and right masseter muscles was estimated under three conditions: relaxed jaw, 50% of the subjective maximal bite force, and maximal jaw opening. Rejecting the null hypothesis, SWE was significantly increased during relaxed jaw (bruxism 1.92 m/s ± 0.44; controls 1.66 m/s ± 0.24), whereas for maximal mouth opening, the result was vice versa increased with 2.89 m/s ± 0.93 for bruxism patients compared with 3.53 m/s ± 0.95 in the healthy control, which could be due to limited jaw movement in chronic bruxism patients (bruxism 4.46 m/s ± 1.17; controls 5.23 m/s ± 0.43). We show that SWE in bruxism is feasible and could be of potential use for diagnostics and monitoring, though we also highlight important limitations and necessary methodological considerations for future studies.

Diagnosis of Froin's Syndrome by Parallel Analysis of Ventriculoperitoneal Shunt and Lumbar Cerebrospinal Fluid in a Patient with Cervical Spinal Stenosis.

Elevated protein levels in cerebrospinal fluid (CSF) can occur in various pathologies and are sometimes difficult to interpret. We report a 62-year-old male patient with subacute neurological deterioration, progressive tetraparesis, and cytoalbumin dissociation in the lumbar CSF. The patient had a pre-existing cervical spinal stenosis with mild tetraparesis. Based on the initial cytoalbumin dissociation (protein 938 mg/dL, 4 leucocytes/µL), Guillain-Barré syndrome was initially considered. For further diagnosis, a CSF sample was taken from a pre-existing ventriculoperitoneal shunt, which showed a normal protein and cell count considering the patient's age (protein 70 mg/dL, 1 leucocyte/µL). In conclusion, we suggest that intermediate aggravation of tetraparesis was due to pneumonia with septic constellation, and the cytoalbumin dissociation was interpreted as Froin's syndrome (FS) due to spinal stenosis. In this unique case, we were able to prove the -often suspected- case of FS by parallel analysis of ventriculoperitoneal shunt and lumbar CSF. The triad of xanthochromia, high protein levels, and marked coagulation was first described by Georges Froin and occurs in various processes leading to severe spinal stenosis. The altered composition of lumbar CSF might be due to impaired CSF circulation; however, the exact mechanisms of this phenomenon require further investigation.

Ultrasound of the Biceps Muscle in Idiopathic Parkinson's Disease with Deep Brain Stimulation: Rigidity Can Be Quantified by Shear Wave Elastography.

Rigidity in Parkinson's disease (PD) is assessed by clinical scales, mostly the Unified Parkinson's Disease Rating Scale of the Movement Disorders Society (MDS-UPDRS). While the MDS-UPDRS-III ranges on an integer from 0 to 4, we investigated whether muscle ultrasound shear wave elastography (SWE) offers a refined assessment. Ten PD patients (five treated with deep brain stimulation (DBS) and levodopa, five with levodopa only) and ten healthy controls were included. Over a period of 80 min, both the SWE value and the item 22b-c of the MDS-UPDRS-III were measured at 5 min intervals. The measurements were performed bilaterally at the biceps brachii muscle (BB) and flexor digitorum profundus muscle in flexion and passive extension. Rigidity was modified and tracked under various therapeutic conditions (with and without medication/DBS). The feasibility of SWE for objective quantification was evaluated by correlation with the UPDRS-III: considering all positions and muscles, there was already a weak correlation (r = 0.01, p < 0.001)­in a targeted analysis, the BB in passive extension showed a markedly higher correlation (r = 0.494, p < 0.001). The application of dopaminergic medication and DBS resulted in statistically significant short-term changes in both clinical rigidity and SWE measurements in the BB (p < 0.001). We conclude that rigidity is reflected in the SWE measurements, indicating that SWE is a potential non-invasive quantitative assessment tool for PD.

Patterns of subregional cerebellar atrophy across epilepsy syndromes: An ENIGMA-Epilepsy study.

Objective: The intricate neuroanatomical structure of the cerebellum is of longstanding interest in epilepsy, but has been poorly characterized within the current cortico-centric models of this disease. We quantified cross-sectional regional cerebellar lobule volumes using structural MRI in 1,602 adults with epilepsy and 1,022 healthy controls across twenty-two sites from the global ENIGMA-Epilepsy working group. Methods: A state-of-the-art deep learning-based approach was employed that parcellates the cerebellum into 28 neuroanatomical subregions. Linear mixed models compared total and regional cerebellar volume in i) all epilepsies; ii) temporal lobe epilepsy with hippocampal sclerosis (TLE-HS); iii) non-lesional temporal lobe epilepsy (TLE-NL); iv) genetic generalised epilepsy; and (v) extra-temporal focal epilepsy (ETLE). Relationships were examined for cerebellar volume versus age at seizure onset, duration of epilepsy, phenytoin treatment, and cerebral cortical thickness. Results: Across all epilepsies, reduced total cerebellar volume was observed (d=0.42). Maximum volume loss was observed in the corpus medullare (dmax=0.49) and posterior lobe grey matter regions, including bilateral lobules VIIB (dmax= 0.47), Crus I/II (dmax= 0.39), VIIIA (dmax=0.45) and VIIIB (dmax=0.40). Earlier age at seizure onset (ηρ2max=0.05) and longer epilepsy duration (ηρ2max=0.06) correlated with reduced volume in these regions. Findings were most pronounced in TLE-HS and ETLE with distinct neuroanatomical profiles observed in the posterior lobe. Phenytoin treatment was associated with reduced posterior lobe volume. Cerebellum volume correlated with cerebral cortical thinning more strongly in the epilepsy cohort than in controls. Significance: We provide robust evidence of deep cerebellar and posterior lobe subregional grey matter volume loss in patients with chronic epilepsy. Volume loss was maximal for posterior subregions implicated in non-motor functions, relative to motor regions of both the anterior and posterior lobe. Associations between cerebral and cerebellar changes, and variability of neuroanatomical profiles across epilepsy syndromes argue for more precise incorporation of cerebellum subregions into neurobiological models of epilepsy.

Shear-Wave-Elastography in Neurofibromatosis Type I.

Ultrasound shear wave elastography (SWE) is an increasingly used imaging modality that expands clinical ultrasound by measuring the elasticity of various tissues, such as the altered elasticity of tumors. Peripheral nerve tumors are rare, have been well-characterized by B-mode-ultrasound, but have not yet been investigated with SWE. Given the lack of studies, a first step would be to investigate homogeneous peripheral nerve tumors (PNTs), histologically neurofibromas or schwannomas, which can occur in multiple in neurofibromatosis type 1 and 2 (NF1 and 2), respectively. Hence, we measured shear wave velocity (SWV) in 30 PNTs of 11 patients with NF1 within the median nerve. The SWV in PNTs ranged between 2.8 ± 0.8 m/s and correlated with their width and approximate volume but not with their length or height. Furthermore, we determined the extent to which PNTs alter the SWV of the median nerve for three positions of the wrist joint: neutral (zero-degree), individual maximal flexion and maximal extension. Here, SWV was decreased in NF1 patients compared to age- and sex-matched controls (p = 0.029) during maximal wrist extension. We speculate that the presence of PNTs may have a biomechanical impact on peripheral nerves which has not been demonstrated yet.

Resection of dominant fusiform gyrus is associated with decline of naming function when temporal lobe epilepsy manifests after the age of five: A voxel-based lesion-symptom mapping study.

OBJECTIVE: To determine patients' characteristics and regions in the temporal lobe where resections lead to a decline in picture naming. METHODS: 311 patients with left hemispheric dominance for language were included who underwent epilepsy surgery at the Epilepsy Center of Erlangen and whose picture naming scores (Boston Naming Test, BNT) were available preoperatively and 6-months postoperatively. Surgical lesions were mapped to an averaged template based on preoperative and postoperative MRI using voxel-based lesion-symptom mapping (VBLSM). Postoperative brain shifts were corrected. The relationship between lesioned brain areas and the presence of a postoperative naming decline was examined voxel-wise while controlling for effects of overall lesion size at first in the total cohort and then restricted to temporal lobe resections. RESULTS: In VBLSM in the total sample, a decline in BNT score was significantly related to left temporal surgery. When only considering patients with left temporal lobe resections (n = 121), 40 (33.1%) significantly worsened in BNT postoperatively. VBLSM including all patients with left temporal resections generated no significant results within the temporal lobe. However, naming decline of patients with epilepsy onset after 5 years of age was significantly associated with resections in the left inferior temporal (extent of BNT decline range: 10.8- 14.4%) and fusiform gyrus (decline range: 12.1-18.4%). SIGNIFICANCE: Resections in the posterior part of the dominant fusiform and inferior temporal gyrus was associated with a risk of deterioration in naming performance at six months after surgery in patients with epilepsy onset after 5 years of age but not with earlier epilepsy onset.