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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.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.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.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.

Background and objectives Multifocal motor neuropathy (MMN) is a rare neuropathy and detailed descriptions of larger patient cohorts are scarce. The objective of this study was to evaluate epidemiological, clinical, and laboratory features of MMN patients and their response to treatment in Austria and to compare these data with those from the literature. Methods Anonymized demographic and clinical data about MMN patients until 31.12.2017 were collected from registered Austrian neurologists. Exploratory statistics on clinical and laboratory features as well as treatment regimens and responses were performed. Results 57 Patients with MMN were identified, resulting in a prevalence of 0.65/100.000. Mean age of onset was 44.1 ± 13.1 years, the diagnostic delay 5.5 ± 8.4 years. In 77% of patients, symptom onset was in the upper limbs, and in 92%, it occurred in distal muscles. Proximal onset was never observed in the lower limbs. At the final follow-up, the majority of patients had atrophy (88%) in affected regions. Definite motor conduction blocks (CB) were found in 54 patients. Anti-GM1-IgM antibodies were present in 43%. Treatment with intravenous immunoglobulins improved muscle strength and INCAT score initially, but at last follow-up, both scores deteriorated to values before treatment. Discussion The findings of the present study corroborate the previous findings in MMN. Onset typically occurs in the upper limbs and mostly distal, CBs are found in the majority of cases, while anti-GM1-IgM antibodies are detected in only approximately 40%. Our study underlines that the initial good response to treatment fades over time.

Most patients with myasthenia gravis (MG) need long-term immunosuppressive therapy. However, conventional agents may have intolerable side effects, take too long or fail to achieve disease control. Rituximab (RTX) has emerged as an off-label treatment for refractory MG, but data on its use are still sparse. We conducted a retrospective nationwide study contacting all Austrian neurologists to provide anonymized data of all adult MG patients treated with RTX and minimum follow-up of 3 months. The Myasthenia Gravis Foundation of America Postintervention Status scale was used to assess outcomes. 34 (60.7%) of a total of 56 patients were women. Median (IQR) age at diagnosis of MG and start of RTX were 41.5 (24.3; 65.8) and 47.5 (33; 71) years, respectively. Antibodies (ab) against acetylcholine receptor (AchR) and muscle-specific tyrosine kinase (MuSK) were present in 69.6% and 25% of patients, respectively (seronegative: 5.4%). Before RTX, 47 (83.9%) patients had had plasma exchange, immune adsorption or immunoglobulins. Three months after RTX, 14 of 53 (26.4%) patients were in remission. At last follow-up after a median of 20 (10; 53) months, remission was present in 42.9% of patients and another 25% had minimal manifestations. Remission was more frequent in patients with MuSK ab vs. those with AchR ab (71.4% vs. 35.9%, p = 0.022). RTX was safe. The presence of MuSK ab independently predicted remission after RTX. In this retrospective study on RTX for MG, the largest to date, RTX appeared safe, efficacious and fast acting. Benefit from RTX was greatest in MuSK ab + MG.

Epileptic seizures, especially status epilepticus can produce MRI changes. In contrast to convulsive status epilepticus (CSE), permanent parenchymal loss is not well documented with nonconvulsive status epilepticus (NCSE) and the observed MRI changes are transient. We describe a patient with non-lesional right-sided temporal lobe epilepsy with complex partial seizures and repeated episodes of untreated complex partial status epilepticus (CPSE). Diffusion-weighted MRI exhibited marked and extended signal changes within the right temporal, frontal, insular and cingulate regions. The affected areas are considered propagation pathways of temporal lobe epilepsies. After admission, the patient was treated with i.v. antiepileptic drugs. Behavioral, EEG and MRI signal changes resolved. An atrophy of the right temporal lobe not seen in the pre-status MRI examinations was observed 6 weeks after the resolution of MRI hyperintensities. Prior episodes of CPSE had been correctly treated and remained without permanent brain damage. This case report is in favour of immediate and aggressive treatment of partial NCSE in order to avoid irreversible parenchymal loss.

Summary Purpose: In temporal lobe epilepsies an asymmetric termination (AST) of the clonic phase of secondary generalized tonic–clonic seizures (sGTCS) reliably lateralizes the side of seizure onset. The last clonic activity occurs ipsilateral to the side of the seizure onset zone. We compared the prevalence and lateralizing value of AST in sGTCS of frontal and temporal lobe origin as well as in primary generalized tonic–clonic seizures (pGTCS). Methods: We analyzed 177 seizures in 84 consecutive patients. Forty-one patients had temporal lobe epilepsy (TLE), 24 frontal lobe epilepsy (FLE), and 19 had nonfocal (primary) generalized epilepsies (GE). All patients underwent intensive video-EEG (electroencephalography) monitoring, high-resolution magnetic resonance imaging (MRI), neuropsychological testing, and single photon emission computed tomography/positron emission tomography (SPECT/PET) when feasible. Two investigators blinded for diagnosis, EEG, and imaging data assessed frequency and side of the last clonic jerk. Results: AST occurred in 63% of patients with TLE (47% of seizures), in 71% with FLE (60% of seizures), and in 42% with GE (21% of seizures). These results were not significant for patients, but significant for seizures in TLE versus GE and in FLE versus GE (p

Antiepileptic drugs (AEDs) like phenytoin (PHE), carbamazepine (CBZ), barbiturates and valproic acid (VPA) interfere with folic acid absorption and metabolism, which in turn can be the cause of adverse pregnancy outcome. To study the prophylactic effect of folic acid supplementation with regard to spontaneous abortion and preterm delivery (fetal demise after week 20 of gestational age) in pregnant women receiving AED therapy, as well as benefits of most common dosage and preconceptional commencement. Prospective examination of 104 patients, registered in EURAP from 1999–2004 at a single center and a retrospective analysis of data from our epilepsy databank completed with medical records and patients interviews of the Department of Neurology of Innsbruck University Hospital from 1971 to 1999. 388 pregnancies in 244 patients were analyzed. Pregnancies with folic acid supplementation showed significant reduction of spontaneous abortion. With regard to monotherapies, in the group of women taking VPA, supplementation of folic acid had significant benefit. Other examined monotherapies (CBZ, PHE, and PB) known to interfere with folic acid showed no significant results. This study confirms the prophylactic effect of folic acid supplementation on spontaneous abortion. For AED therapy, folic acid supplementation should be part of the therapy of every pregnant epileptic woman, especially for those treated with VPA.

We describe a case of frontal lobe epilepsy with rare nocturnal generalized tonic-clonic seizures and repeated prolonged episodes of altered behavior lasting 1 to 2 days. The changes consisted of poor organizational strategies, impaired set shifting, emotional indifference, reduced motivation, and impairment of emotional decision making. Memory and consciousness were undisturbed, as she was able to follow her profession as a teacher. During the episode, the EEG was marked by right frontal rhythmical spikes and waves with spread to the homologous left region. Behavioral abnormalities and EEG changes were successfully treated with intravenous diazepam. The clinical representation can be ascribed to alterations of prefrontal-subcortical circuits, especially the anterior cingulate and orbitofrontal circuits. This unique case is classified as simple partial nonconvulsive status epilepticus with prefrontal disturbances as the sole manifestation.

Summary: Purpose: Genital automatisms (GAs) are rare clinical phenomena during or after epileptic seizures. They are defined as repeated fondling, grabbing, or scratching of the genitals. The anatomic correlates of GAs have been discussed controversially. The aim of this investigation was to assess the localizing and lateralizing value of GAs. Methods: The authors studied 207 consecutive patients with intractable seizures referred to a University Hospital for presurgical evaluation between 1998 and 2002: 135 had temporal lobe epilepsy (TLE); 23, frontal lobe epilepsy (FLE); 29, generalized epilepsies (GEs); and 20 had extratemporal or multifocal epilepsy. Results: Twenty-three (11%) of 207 patients showed GAs in 42 (3%) of 1,299 seizures. GAs occurred significantly more often in men (17 of 93, 18%) than in women (six of 114, 5%; p = 0.0037). Twenty-one (16%) of 135 patients with TLE performed GAs, one (4%) of 23 with FLE and one (3%) of 29 with GE. GAs were associated with unilateral hand automatisms in 16 (70%) of 23 and with periictal urinary urge in five (22%) of 23. All patients had amnesia for the performance of GAs. Conclusions: GAs appear in the ictal or postictal period with impaired consciousness. Men exhibit GAs significantly more often than do women. GAs do not localize or lateralize per se, but may localize seizure onset in the presence of periictal urinary urge or unilateral hand automatisms. They show a tendency to occur more often in TLE. Key Words: Genital automatisms— Sexual seizure symptoms—Video-EEG seizures—Presurgical epilepsy evaluation.