Drop attack

Abstract: Objective To delineate the epileptology, a key part of the SYNGAP1 phenotypic spectrum, in a large patient cohort. Methods Patients were recruited via investigators9 practices or social media. We included patients with (likely) pathogenic SYNGAP1 variants or chromosome 6p21.32 microdeletions incorporating SYNGAP1. We analyzed patients9 phenotypes using a standardized epilepsy questionnaire, medical records, EEG, MRI, and seizure videos. Results We included 57 patients (53% male, median age 8 years) with SYNGAP1 mutations (n = 53) or microdeletions (n = 4). Of the 57 patients, 56 had epilepsy: generalized in 55, with focal seizures in 7 and infantile spasms in 1. Median seizure onset age was 2 years. A novel type of drop attack was identified comprising eyelid myoclonia evolving to a myoclonic-atonic (n = 5) or atonic (n = 8) seizure. Seizure types included eyelid myoclonia with absences (65%), myoclonic seizures (34%), atypical (20%) and typical (18%) absences, and atonic seizures (14%), triggered by eating in 25%. Developmental delay preceded seizure onset in 54 of 56 (96%) patients for whom early developmental history was available. Developmental plateauing or regression occurred with seizures in 56 in the context of a developmental and epileptic encephalopathy (DEE). Fifty-five of 57 patients had intellectual disability, which was moderate to severe in 50. Other common features included behavioral problems (73%); high pain threshold (72%); eating problems, including oral aversion (68%); hypotonia (67%); sleeping problems (62%); autism spectrum disorder (54%); and ataxia or gait abnormalities (51%). Conclusions SYNGAP1 mutations cause a generalized DEE with a distinctive syndrome combining epilepsy with eyelid myoclonia with absences and myoclonic-atonic seizures, as well as a predilection to seizures triggered by eating.

Abstract: We studied the effectiveness of anterior callosotomy in 43 patients whose follow-up period averaged 39 months. These patients had intractable generalized seizures, characterized by a combination of seizure patterns, most frequently drop attacks with generalized tonic-clonic, generalized tonic, and absence seizures. Overall, drop attacks were the most frequent (31/43 or 72%) and the most disabling seizure pattern (27/43 or 63%); they were also the most likely to benefit from anterior callosotomy (70%). Patients with lateralized changes tended to have a better result than did those without lateralization, but patients with synchronous and symmetrical spike and wave discharges also benefited. The preoperative intelligence quotient and the etiological factors were not predictors of outcome. There was a correlation between the extent of section and the results; patients with section of the anterior two thirds had a better result, compared with those who had section of the anterior half.

Abstract: Carotid sinus massage was carried out on 130 consecutive patients referred for investigation of dizziness, syncope or unexplained falls. Carotid sinus syndrome was diagnosed in 33 for whom no other cause of symptoms was identified. Right-sided hypersensitivity was more frequent than left-sided. Thirty per cent identified a prodrome before syncope and 30% had retrograde amnesia for the event. In 52%, symptoms were precipitated by head movement and in 48% by vagal stimuli. Seven described 'drop attacks' but symptoms were reproduced with carotid sinus massage during head-up tilt. Injuries, including fractured neck of femur, were sustained by the majority. Carotid sinus massage should be performed routinely on all elderly patients who have symptoms of unexplained dizziness, falls or syncope. Cardiac pacing relieves syncopal symptoms in those with a predominant cardio-inhibitory response and recurrent syncope.

Abstract: Eighty patients underwent anterior corpus callosotomy for treatment of generalized seizures. The patients' mean age was 18.3 years (range 4 to 53 years); the mean age at seizure onset was 5.27 years (range 0.1 to 27 years). The mean intelligence quotient (IQ) of 41 testable patients was 71.12 (range less than 30 to 114). The seizure outcome was as follows: 13% were seizure-free, 65% were significantly improved, and 22% were unchanged. Ten patients subsequently underwent a second operation to complete the callosal sectioning which resulted in additional seizure improvement in only five of them. Five complications resulted from 90 operations: two epidural hematomas, one delayed subdural hematoma, one bone-flap infection, and one postcallosotomy disconnection syndrome; two patients died. A younger age at onset of seizures, a higher IQ, and generalized tonic-clonic, atonic, complex-partial, and mixed seizure types were associated with improved seizure outcome.