Retrospective comparison of percutaneous balloon compression and radiofrequency-thermocoagulation in the management of trigeminal neuralgia.

PURPOSE: To compare percutaneous balloon compression (PBC) and radiofrequency thermocoagulation (RFTC) for the treatment of trigeminal neuralgia. METHODS: This was a retrospective single-center analysis of data from 230 patients with trigeminal neuralgia who underwent 202 PBC (46%) and 234 RFTC (54%) from 2002 to 2019. Comparison of demographic data and trigeminal neuralgia characteristics between procedures as well as assessment of 1) initial pain relief by an improved Barrow Neurological Institute (BNI) pain intensity scale of I-III; 2) recurrence-free survival of patients with a follow-up of at least 6 months by Kaplan-Meier analysis; 3) risk factors for failed initial pain relief and recurrence-free survival by regression analysis; and 4) complications and adverse events. RESULTS: Initial pain relief was achieved in 353 (84.2%) procedures and showed no significant difference between PBC (83.7%) and RFTC (84.9%). Patients who suffered from multiple sclerosis (odds ratio 5.34) or had a higher preoperative BNI (odds ratio 2.01) showed a higher risk of not becoming pain free. Recurrence-free survival in 283 procedures was longer for PBC (44%) with 481 days compared to RFTC (56%) with 421 days (p=0.036) but without statistical significance. The only factors that showed a significant influence on longer recurrence-free survival rates were a postoperative BNI ≤ II (P=<0.0001) and a BNI facial numbness score ≥ 3 (p = 0.009). The complication rate of 22.2% as well as zero mortality showed no difference between the two procedures (p=0.162). CONCLUSION: Both percutaneous interventions led to a comparable initial pain relief and recurrence-free survival with a low and comparable probability of complications. An individualized approach, considering the advantages and disadvantages of each intervention, should guide the decision-making process. Prospective comparative trials are urgently needed.

Clinico-genetic spectrum of limb-girdle muscular weakness in Austria: A multicentre cohort study.

BACKGROUND AND PURPOSE: Hereditary myopathies with limb-girdle muscular weakness (LGW) are a genetically heterogeneous group of disorders, in which molecular diagnosis remains challenging. Our aim was to present a detailed clinical and genetic characterization of a large cohort of patients with LGW. METHODS: This nationwide cohort study included patients with LGW suspected to be associated with hereditary myopathies. Parameters associated with specific genetic aetiologies were evaluated, and we further assessed how they predicted the detection of causative variants by conducting genetic analyses. RESULTS: Molecular diagnoses were identified in 62.0% (75/121) of the cohort, with a higher proportion of patients diagnosed by next-generation sequencing (NGS) than by single-gene testing (77.3% vs. 22.7% of solved cases). The median (interquartile range) time from onset to genetic diagnosis was 8.9 (3.7-19.9) and 17.8 (7.9-27.8) years for single-gene testing and NGS, respectively. The most common diagnoses were myopathies associated with variants in CAPN3 (n = 9), FKRP (n = 9), ANO5 (n = 8), DYSF (n = 8) and SGCA (n = 5), which together accounted for 32.2% of the cohort. Younger age at disease onset (p = 0.043), >10× elevated creatine kinase activity levels (p = 0.024) and myopathic electromyography findings (p = 0.007) were significantly associated with the detection of causative variants. CONCLUSIONS: Our findings suggest that an earlier use of NGS in patients with LGW is needed to avoid long diagnostic delays. We further present parameters predictive of a molecular diagnosis that may help to select patients for genetic analyses, especially in centres with limited access to sequencing.

New-onset seizures after cranioplasty-a different view on a putatively frequently observed phenomenon.

BACKGROUND: New-onset seizures after cranioplasty (NOSAC) are reported to be a frequent complication of cranioplasty (CP) after decompressive hemicraniectomy (DHC). There are considerable differences in the incidence of NOSAC and contradictory data about presumed risk factors in the literature. We suggest NOSAC to be a consequence of patients' initial condition which led to DHC, rather than a complication of subsequent CP. We conducted a retrospective analysis to verify our hypothesis. METHODS: The medical records of all patients ≥ 18 years who underwent CP between 2002 and 2017 at our institution were evaluated including incidence of seizures, time of seizure onset, and presumed risk factors. Indication for DHC, type of implant used, timing of CP, patient age, presence of a ventriculoperitoneal shunt (VP shunt), and postoperative complications were compared between patients with and without NOSAC. RESULTS: A total of 302 patients underwent CP between 2002 and 2017, 276 of whom were included in the outcome analysis and the incidence of NOSAC was 23.2%. Although time between DHC and CP differed significantly between DHC indication groups, time between DHC and seizure onset did not differ, suggesting the occurrence of seizures to be independent of the procedure of CP. Time of follow-up was the only factor associated with the occurrence of NOSAC. CONCLUSION: New-onset seizures may be a consequence of the initial condition leading to DHC rather than of CP itself. Time of follow-up seems to play a major role in detection of new-onset seizures.

Cranioplasty following ventriculoperitoneal shunting: lessons learned.

OBJECTIVE: Cranioplasty (CP) is considered as a straightforward and technically unchallenging operation; however, complication rates are high reaching up to 56%. Presence of a ventriculoperitoneal shunt (VPS) and timing of CP are reported risk factors for complications. Pressure gradients and scarring at the site of the cranial defect seem to be critical in this context. The authors present their experiences and lessons learned. METHODS: A consecutive series of all patients who underwent CP at the authors' institution between 2002 and 2017 were included in this retrospective analysis. Complications were defined as all events that required reoperation. Logistic regression analysis and chi-squared test were conducted to evaluate the complication rates according to suspected risk factors. RESULTS: A total of 302 patients underwent cranioplasty between 2002 and 2017. The overall complication rate was 17.5%. Complications included epi-/subdural fluid collection (7.3%) including hemorrhage (4.6%) and hygroma (2.6%), bone graft resorption (5.3%), bone graft infection (2.0%), and hydrocephalus (5.7%). Overall, 57 patients (18.9%) had undergone shunt implantation prior to CP. The incidence of epi-/subdural fluid collection was 19.3% in patients with VPS and 4.5% in patients without VPS, OR 5.1 (95% CI 2.1-12.4). Incidence of hygroma was higher in patients who underwent early CP. Patients with temporary shunt ligation for CP did not suffer from complications. CONCLUSION: CP in patients with a VPS remains a high-risk procedure. Any effort to understand the pressure dynamics and to reduce factors that may trigger the formation of a large epidural space must be undertaken.

Microvascular decompression in trigeminal neuralgia: predictors of pain relief, complication avoidance, and lessons learned.

OBJECTIVE: To analyze characteristics associated with long-term pain relief after microvascular decompression (MVD) for trigeminal neuralgia (TGN). Description of associated morbidity and complication avoidance. METHODS: One hundred sixty-five patients with TGN underwent 171 MVD surgeries at the authors' institution. Patient characteristics and magnetic resonance imaging (MRI) datasets were obtained through the hospital's archiving system. Patients provided information about pre- and post-operative pain characteristics and neurologic outcome. Favorable outcome was defined as a Barrow Neurological Institute (BNI) pain intensity score of I to III with post-operative improvement of I grade. RESULTS: Type of TGN pain with purely paroxysmal pain (p = 0.0202*) and TGN classification with classical TGN (p = 0.0372*) were the only significant predictors for long-term pain relief. Immediate pain relief occurred in 90.6% of patients with a recurrence rate of 39.4% after 3.5 ± 4.6 years. MRI reporting of a neurovascular conflict had a low negative predictive value of 39.6%. Mortality was 0% with major complications observed in 8.2% of patients. Older age was associated with lower complication rates (p = 0.0009***). Re-MVD surgeries showed improved long-term pain relief in four out of five cases. CONCLUSIONS: MVD is a safe and effective procedure even in the elderly. It has the unique potential to cure TGN if performed on a regular basis, and if key surgical steps are respected. Early MVD should be offered in case of medical treatment failure and paroxysmal pain symptoms. The presence of a neurovascular conflict on MRI is not mandatory. In case of recurrence, re-MVD is a good treatment option that should be discussed with patients. HIGHLIGHTS: • Long-term analysis of pain relief after MVD. • Positive predictors for outcome: classical TGN and purely paroxysmal pain. • Presence of neurovascular conflict in MRI is not mandatory for MVD surgery. • Analysis of complications and surgical nuances for avoidance. • MVD is a safe procedure also in the elderly.

Severe Myasthenic Manifestation of Leptospirosis Associated with New Sequence Type of Leptospira interrogans.

We report the rapid development of a myasthenic crisis as the first-time manifestation of myasthenia gravis. The symptoms developed in the course of acute leptospirosis associated with a new sequence type of Leptospira interrogans. Antibiotic treatment led to rapid amelioration of myasthenia.

Global analysis of muscle-specific kinase signaling by quantitative phosphoproteomics.

The development of the neuromuscular synapse depends on signaling processes that involve protein phosphorylation as a crucial regulatory event. Muscle-specific kinase (MuSK) is the key signaling molecule at the neuromuscular synapse whose activity is required for the formation of a mature and functional synapse. However, the signaling cascade downstream of MuSK and the regulation of the different components are still poorly understood. In this study we used a quantitative phosphoproteomics approach to study the phosphorylation events and their temporal regulation downstream of MuSK. We identified a total of 10,183 phosphopeptides, of which 203 were significantly up- or down-regulated. Regulated phosphopeptides were classified into four different clusters according to their temporal profiles. Within these clusters we found an overrepresentation of specific protein classes associated with different cellular functions. In particular, we found an enrichment of regulated phosphoproteins involved in posttranscriptional mechanisms and in cytoskeletal organization. These findings provide novel insights into the complex signaling network downstream of MuSK and form the basis for future mechanistic studies.

Current Aspects of Intraoperative High-Field (3T) Magnetic Resonance Imaging in Pediatric Neurosurgery: Experiences from a Recently Launched Unit at a Tertiary Referral Center.

OBJECTIVE: To evaluate the neurosurgical and economic effectiveness of a newly launched intraoperative high-field (3T) magnetic resonance imaging (MRI) suite for pediatric tumor and epilepsy neurosurgery. METHODS: Altogether, 148 procedures for 124 pediatric patients (mean age, 8.7 years; range, 0-18 years) within a 2.5-year period were undertaken in a 2-room intraoperative MRI (iopMRI) suite. Surgery was performed mainly for intractable epilepsy (n = 81; 55%) or pediatric brain tumors (n = 65; 44%) in the supine (n = 113; 76%) and prone (n = 35; 24%) positions. The mean time of iopMRI from draping to re-surgery was 50 minutes. RESULTS: IopMRI was applied not in all but in 64 of 148 procedures (43%); in 45 procedures (31%), iopMRI was estimated unnecessary at the end of surgery based on the leading surgeon's decision. In the remaining 39 procedures (26%), ultra-early postoperative MRI was carried out after closure with the patient still sterile in the head coil. Of the 64 procedures with iopMRI, second-look surgery was performed in 26% (in epilepsy surgery in 17%, in tumor surgery in 9%). We did not encounter any infections, wound revisions, or position-related or anesthesiology-related complications. CONCLUSIONS: We used iopMRI in less than half of pediatric tumor and epilepsy surgery for which it was scheduled initially. Therefore, high costs argue against its routine use in pediatric neurosurgery, although it optimized surgical results in one quarter of patients and met high safety standards.

A navigated, robot-driven laser craniotomy tool for frameless depth electrode implantation. An in-vivo recovery animal study.

Objectives: We recently introduced a frameless, navigated, robot-driven laser tool for depth electrode implantation as an alternative to frame-based procedures. This method has only been used in cadaver and non-recovery studies. This is the first study to test the robot-driven laser tool in an in vivo recovery animal study. Methods: A preoperative computed tomography (CT) scan was conducted to plan trajectories in sheep specimens. Burr hole craniotomies were performed using a frameless, navigated, robot-driven laser tool. Depth electrodes were implanted after cut-through detection was confirmed. The electrodes were cut at the skin level postoperatively. Postoperative imaging was performed to verify accuracy. Histopathological analysis was performed on the bone, dura, and cortex samples. Results: Fourteen depth electrodes were implanted in two sheep specimens. Anesthetic protocols did not show any intraoperative irregularities. One sheep was euthanized on the same day of the procedure while the other sheep remained alive for 1 week without neurological deficits. Postoperative MRI and CT showed no intracerebral bleeding, infarction, or unintended damage. The average bone thickness was 6.2 mm (range 4.1-8.0 mm). The angulation of the planned trajectories varied from 65.5° to 87.4°. The deviation of the entry point performed by the frameless laser beam ranged from 0.27 mm to 2.24 mm. The histopathological analysis did not reveal any damage associated with the laser beam. Conclusion: The novel robot-driven laser craniotomy tool showed promising results in this first in vivo recovery study. These findings indicate that laser craniotomies can be performed safely and that cut-through detection is reliable.

Implementation of a 7T Epilepsy Task Force consensus imaging protocol for routine presurgical epilepsy work-up: effect on diagnostic yield and lesion delineation.

OBJECTIVE: Recently, the 7 Tesla (7 T) Epilepsy Task Force published recommendations for 7 T magnetic resonance imaging (MRI) in patients with pharmaco-resistant focal epilepsy in pre-surgical evaluation. The objective of this study was to implement and evaluate this consensus protocol with respect to both its practicability and its diagnostic value/potential lesion delineation surplus effect over 3 T MRI in the pre-surgical work-up of patients with pharmaco-resistant focal onset epilepsy. METHODS: The 7 T MRI protocol consisted of T1-weighted, T2-weighted, high-resolution-coronal T2-weighted, fluid-suppressed, fluid-and-white-matter-suppressed, and susceptibility-weighted imaging, with an overall duration of 50 min. Two neuroradiologists independently evaluated the ability of lesion identification, the detection confidence for these identified lesions, and the lesion border delineation at 7 T compared to 3 T MRI. RESULTS: Of 41 recruited patients > 12 years of age, 38 were successfully measured and analyzed. Mean detection confidence scores were non-significantly higher at 7 T (1.95 ± 0.84 out of 3 versus 1.64 ± 1.19 out of 3 at 3 T, p = 0.050). In 50% of epilepsy patients measured at 7 T, additional findings compared to 3 T MRI were observed. Furthermore, we found improved border delineation at 7 T in 88% of patients with 3 T-visible lesions. In 19% of 3 T MR-negative cases a new potential epileptogenic lesion was detected at 7 T. CONCLUSIONS: The diagnostic yield was beneficial, but with 19% new 7 T over 3 T findings, not major. Our evaluation revealed epilepsy outcomes worse than ILAE Class 1 in two out of the four operated cases with new 7 T findings.

The effect of perioperative non-steroidal anti-inflammatory drugs and male sex on the recurrence rates after chronic subdural hematoma evacuation.

BACKGROUND: Drugs that inhibit blood clot formation are a risk factor for the development and recurrence of chronic subdural hematoma (cSDH). The use of non-steroidal anti-inflammatory drug (NSAID) was associated with higher bleeding rates in non-neurosurgical patients, but their influence on cranial hematomas is unclear. We sought to better describe the hazard associated with their use in cSDH patients and find additional risk factors. METHODS: We performed a retrospective analysis of patients undergoing burr hole drainage for cSDH over a period of 15 years. Demographic and surgical details were extracted from individual patient records. Patients were followed for up to 90 days with SDH recurrence requiring repeat surgery as the primary endpoint. Univariate and multivariate Cox regression models were performed to identify risk factors and their effect size. RESULTS: We included 361 patients, who underwent burr hole drainage for cSDH. Recurrences occurred in 73 patients (20.2%) after a median time period of 18 days. Sixty-six patients in our cohort were taking NSAIDs perioperatively. The recurrence rate was not higher in NSAID users compared to other patients with 18.2% and 20.7%, respectively. 23.5% of men, yet only 12.7% of women had recurrences revealing male sex as a risk factor in a uni- and multivariate regression. Not placing a drain was a risk factor for early recurrences, which resulted in a prolonged hospital stay. CONCLUSIONS: We identified male sex as a risk factor for cSDH recurrence after burr hole drainage, while perioperative NSAID use did not increase recurrence rates.

The diagnostic and prognostic utility of repetitive nerve stimulation in patients with myasthenia gravis.

Repetitive nerve stimulation (RNS) is a standard test for the diagnosis of myasthenia gravis (MG), where decrement of compound muscle action potentials (CMAP) corresponds to clinical muscle fatigability. Our aim was to ascertain the diagnostic and prognostic utility of RNS in MG patients. This study included MG patients treated between 01/2000 and 12/2016, with an observational period of at least one year and a minimum of two neurological examinations. Clinical and electrophysiological data were retrospectively gathered from patient records, and CMAP decrement was correlated with autoantibody titers and clinical disease severity at different time points. Ninety-four patients were included, with 88.3% of the cohort testing positive for acetylcholine receptor autoantibodies (AChR-Abs). RNS sensitivity was higher in patients with generalized disease (71.6%) than in purely ocular MG (38.5%). CMAP decrement did not significantly correlate with AChR-Ab titers, nor with clinical symptom severity at the time of testing or last follow up. However, there was a significant correlation between CMAP decrement and the worst recorded clinical status on a group level. RNS testing is more sensitive in generalized disease and AChR-Ab positive patients, but our data do not support RNS as a tool for long-term outcome prediction. Future studies with a prospective study design could help to overcome a number of limiting factors discussed in our study.

Technical Note: Advantages of a 2-Room Intraoperative 3-Tesla Magnetic Resonance Imaging Operating Suite for Performing Laser Interstitial Thermal Therapy in Pediatric Epilepsy and Tumor Surgery.

OBJECTIVE: Magnetic resonance thermography-guided laser interstitial thermal therapy (LITT) provides a minimally invasive treatment option in children with central nervous system tumors or medically intractable epilepsy. However, transporting anesthetized children between an operating room (OR) and a radiologic suite creates logistical challenges. Thus we describe advantages of using a 2-room intraoperative magnetic resonance imaging (MRI) concept for LITT. METHODS: Patients were pinned in a head frame that doubles as the lower part of the MRI head coil. Preoperative MRI was performed for accurate neuronavigation, after which laser fibers were stereotactically implanted. Transport between OR and MRI was achieved by sliding the top of the OR table onto a trolly. RESULTS: We performed 12 procedures in 11 children, mean age 7.1 years (range: 2 to 14 years). Ten children suffered from medically intractable epilepsy, and 1 child had a pilocytic midbrain astrocytoma. Two fibers were placed in 8 and 1 fiber in 4 procedures. Mean entry point and target errors were 2.8 mm and 3.4 mm, respectively. Average transfer time from OR to MRI and vice versa was 9 minutes (±1 minute, 40 seconds). Altogether, 50% of the seizure patients were seizure free (Engel grade I) at 22 months' follow-up time. One hemorrhagic event, which could be managed nonoperatively, occurred. We recorded no surgical site or intracranial infections. CONCLUSIONS: All LITT procedures were successfully carried out with head frame in the sterile environment. The intraoperative MRI suite proved to be advantageous for minimally invasive procedures, especially in young children resulting in short transports while maintaining high accuracy and safety.

Intraoperative magnetic resonance imaging in epilepsy surgery: systematic review of the literature and meta-analysis.

INTRODUCTION: Intraoperative magnetic resonance imaging (iopMRI) is increasingly incorporated into neurosurgery to improve outcomes. However, its usefulness in epilepsy surgery remains debated. To elucidate its current role, we conducted a systematic review of the data published to date. EVIDENCE ACQUISITION: We performed a systematic review of the available literature using the PubMed, Scopus, and Embase database. Only articles detailing the usefulness of iopMRI in quantifiable measures were included. Different aspects of iopMRI in epilepsy surgery were analyzed and two meta-analyses summarizing its impact on extent of resection and seizure outcomes performed. EVIDENCE SYNTHESIS: A total of 33 articles met the inclusion criteria, comprising a total of 1313 patients, both children and adults operated under iopMRI guidance. The mean rate of return to surgery was 29.2% in 30 articles reporting this number. Eleven publications were eligible for meta-analysis of seizure outcome in patients with refractory epilepsy, who had undergone surgery with iopMRI (N.=294) compared to controls (N.=298). Eight articles described the impact of iopMRI on the radiological extent of resection. In both regards, usage of iopMRI improved outcomes in our meta-analysis with an OR of 3.8 and 4.75, respectively. CONCLUSIONS: This work presents the first meta-analysis of the value of iopMRI in epilepsy surgery. Its use resulted in an improvement of the desired extent of resection and led to a better seizure outcome compared to conventional surgery. Understanding its benefits might help improve surgical strategies in traditional, open epilepsy surgery.

Diamond knife dissection technique for nerve preservation during resection of large vestibular schwannomas.

Facial and cochlear nerve preservation in large vestibular schwannomas is a major challenge. Bimanual pincers or plate-knife dissection techniques have been described as crucial for nerve preservation. The authors demonstrate a recently applied diamond knife dissection technique to peel the nerves from the tumor capsule. This technique minimizes the nerve trauma significantly, and complete resection of a large vestibular schwannoma without any facial nerve palsy and hearing preservation is possible. The authors illustrate this technique during surgery of a 2.6-cm vestibular schwannoma in a 27-year-old male patient resulting in normal facial function and preserved hearing postoperatively. The video can be found here: https://stream.cadmore.media/r10.3171/2021.7.FOCVID21104.

Incidence and clinical spectrum of rhabdomyolysis in general neurology: a retrospective cohort study.

The objective of this retrospective cohort study was to evaluate demographic, clinical and laboratory characteristics of patients with rhabdomyolysis as defined by a serum creatine kinase (sCK) activity > 950 U/L. A total of 248 patients were recruited from the Department of Neurology, Medical University of Vienna, between 01/2000 and 12/2017, with a median sCK activity of 2,160 U/l (IQR 1,342-4,786). Seizures (31.9%), illicit drugs/alcohol (9.7%) and exercise (8.5%) were the most common trigger factors. Rhabdomyolysis incidence rates in specific neurological diseases as estimated by the ratio between rhabdomyolysis cases and the total number of cases with the corresponding disease were highest in myopathies (49.8/1,000 person-years, 95% CI 32.3-67.4), followed by epilepsy (16.4/1,000 person-years, 95% CI 12.8-20.0) and stroke (11.9/1,000 person-years, 95% CI 8.4-15.4). The half-life of sCK activity was 1.5 days in the total cohort. In myopathies, sCK activity was significantly higher as compared to other disease entities 7 days after the peak measurement (p = 0.0023). Acute kidney injury (AKI) developed in 18 patients (7.3%) with no AKI-related deaths during the study period. In conclusion, rhabdomyolysis occurred in a broad range of neurological entities but was associated with a favorable prognosis in most cases rarely resulting in AKI and death.

Subgroup stratification and outcome in recently diagnosed generalized myasthenia gravis.

OBJECTIVE: To describe disease outcomes of myasthenia gravis (MG) subgroups and which factors influence outcomes by reviewing individual patient records of a representative cohort. METHODS: We performed a retrospective analysis of 199 patients with generalized MG and disease onset after the year 2000 who were treated at 2 tertiary referral centers in Austria. We stratified patients as early- and late-onset acetylcholine receptor antibody-positive, muscle-specific tyrosine kinase (MuSK) antibody-positive, and seronegative patients and patients with thymoma regardless of antibody status. We evaluated patients' symptom severity and treatment regimens and the occurrence of life-threatening events at yearly time points for up to 10 years. RESULTS: Minimal manifestation status or better was eventually achieved and sustained for >1 year by 125 (63%) patients. Forty percent (66 of 165 patients) showed an early response to treatment, which predicted a benign disease course later on. In contrast, 19% of patients, who remained symptomatic for 2 years after disease onset despite immunosuppressive therapy, were more treatment resistant in the following years. The strongest predictor of outcome was the diagnostic subgroup. Patients with MuSK-MG had a much better outcome than previously reported. CONCLUSION: Our data give an update on the disease course of generalized MG in the new century. Diagnostic subgroups and response to treatment within the first 2 years help to predict the long term outcome.

No association between proton pump inhibitor use and ALS risk: a nationwide nested case-control study.

The use of proton pump inhibitors (PPIs) has been proposed as a potential risk factor for neurodegenerative diseases, but little is known regarding its role in amyotrophic lateral sclerosis (ALS). We therefore aimed to assess the association of PPI use with the subsequent risk of ALS, and performed a register-based nationwide nested case-control study, including 2,484 ALS cases diagnosed during July 2006-December 2013 in Sweden and 10 population controls per case that were individually matched to the case by sex, age, and area of residence. Dispenses and cumulative defined daily doses (cDDDs) of PPIs were extracted from the Swedish Prescribed Drug Register. The association of PPI use with the risk of ALS was assessed using conditional logistic regression, after applying different lag windows to avoid reverse causation. ALS patients were more likely to be dispensed with PPIs before diagnosis than controls. However, previous PPI use was not associated with an increased risk of ALS (OR = 1.08, 95% CI 0.97-1.19), and there was no dose-response relationship between cDDDs of PPIs and ALS risk (p = 0.0874), after excluding dispenses during the year before ALS diagnosis. The results were similar after excluding dispenses during the 2 or 3 years before ALS diagnosis.

Frequency and clinical features of treatment-refractory myasthenia gravis.

BACKGROUND: To investigate the frequency and characterize the clinical features of treatment-refractory myasthenia gravis in an Austrian cohort. METHODS: Patient charts of 126 patients with generalized myasthenia gravis and onset between 2000 and 2016 were analyzed retrospectively. Patients were classified as treatment-refractory according to strict, predefined criteria. These mandated patients being at least moderately symptomatic (i.e., MGFA class III) or needing either maintenance immunoglobulins or plasma exchange therapy for at least 1 year in spite of two adequately dosed immunosuppressive drugs. Clinical features and outcome at last follow-up were compared to treatment-responsive patients. RESULTS: 14 out of 126 patients (11.1%) met these criteria of treatment-refractory myasthenia gravis. Treatment-refractory patients had more frequent clinical exacerbations and more often received rescue treatments or a further escalation of immunosuppressive therapies. They also remained more severely affected at last follow-up. An early onset of myasthenia gravis was associated with a higher risk for a refractory course. CONCLUSION: A small subgroup of patients with generalized myasthenia gravis do not respond sufficiently to standard therapies. Refractory disease has considerable implications for both patients and health care providers and highlights an unmet need for new treatment options.

Phenotypic variability of GABRA1-related epilepsy in monozygotic twins.

Variants in GABRA1 have been associated with different epilepsies ranging from mild generalized forms to epileptic encephalopathies. Despite the broad clinical spectrum, phenotypes were found to be largely concordant within families. Contrary to this observation, we report monozygotic twin sisters with generalized epilepsy due to the c.541C>T; p.(Pro181Ser) de novo variant in GABRA1. One experienced juvenile absence seizures promptly responding to first-line medication, whereas the second developed severe treatment-refractory epilepsy with febrile, absence, atonic, and tonic-clonic seizures indicating marked intrafamilial variability in GABRA1-related epilepsy. Moreover, we provide a molecular characterization of the novel variant based on recently published structural data.