The Electrophysiological Findings in Spinocerebellar Ataxia Type 6: Evidence From 24 Patients.

PURPOSE: Peripheral neuropathy has been reported commonly in several spinocerebellar ataxia (SCA) types. To date, there is a lack of robust evidence for neuropathy or neuronopathy in SCA type 6 (SCA6). Here, we aim to evaluate the presence of neuropathy or neuronopathy in a cohort of SCA6 patients. METHODS: Twenty-four individuals with genetically confirmed SCA6 underwent detailed neurophysiological assessment. This included nerve conduction studies, and in some, cutaneous silent periods, blink reflexes, tilt table tests, quantitative sudomotor axon reflex tests, and somatosensory (median and tibial) evoked potentials. RESULTS: Mean age was 56.1 years (range, 22-94 years) at the time of testing. Four patients were presymptomatic of SCA6 at recruitment. The mean disease duration of symptomatic patients was 11.9 years (range, 1-40 years). Most patients (79.2%, 19/24) had no neurophysiological evidence of a peripheral neuropathy. One with impaired glucose tolerance had mild, large, and small fiber sensorimotor polyneuropathy. One elderly patient had length-dependent axonal sensorimotor polyneuropathy. Two had minor sensory abnormalities (one had type II diabetes and previous chemotherapy). One other had minor small fiber abnormalities. Ten patients (41.7%) had median neuropathies at the wrist. All somatosensory evoked potential (15/15), and most autonomic function tests (13/14) were normal. CONCLUSIONS: A large proportion of subjects (79.2%) in our cohort had no evidence of large or small fiber neuropathy. This study does not support the presence of neuropathy or neuronopathy as a common finding in SCA6 and confirms the importance of considering comorbidities as the cause of neurophysiological abnormalities.

Overview of the Clinical Approach to Individuals With Cerebellar Ataxia and Neuropathy.

Increasingly, cerebellar syndromes are recognized as affecting multiple systems. Extracerebellar features include peripheral neuropathies affecting proprioception; cranial neuropathies such as auditory and vestibular; and neuronopathies, for example, dorsal root and vestibular. The presence of such features, which in and of themselves may cause ataxia, likely contribute to key disabilities such as gait instability and falls. Based on the evolving available literature and experience, we outline a clinical approach to the diagnosis of adult-onset ataxia where a combination of cerebellar and peripheral or cranial nerve pathology exists. Objective diagnostic modalities including electrophysiology, oculomotor, and vestibular function testing are invaluable in accurately defining an individual's phenotype. Advances in MRI techniques have led to an increased recognition of disease-specific patterns of cerebellar pathology, including those conditions where neuronopathies may be involved. Depending on availability, a stepwise approach to genetic testing is suggested. This is guided by factors such as pattern of inheritance and age at disease onset, and genetic testing may range from specific genetic panels through to whole-exome and whole-genome sequencing. Management is best performed with the involvement of a multidisciplinary team, aiming at minimization of complications such as falls and aspiration pneumonia and maximizing functional status.

Seizure Forecasting Using a Novel Sub-Scalp Ultra-Long Term EEG Monitoring System.

Accurate identification of seizure activity, both clinical and subclinical, has important implications in the management of epilepsy. Accurate recognition of seizure activity is essential for diagnostic, management and forecasting purposes, but patient-reported seizures have been shown to be unreliable. Earlier work has revealed accurate capture of electrographic seizures and forecasting is possible with an implantable intracranial device, but less invasive electroencephalography (EEG) recording systems would be optimal. Here, we present preliminary results of seizure detection and forecasting with a minimally invasive sub-scalp device that continuously records EEG. Five participants with refractory epilepsy who experience at least two clinically identifiable seizures monthly have been implanted with sub-scalp devices (Minder®), providing two channels of data from both hemispheres of the brain. Data is continuously captured via a behind-the-ear system, which also powers the device, and transferred wirelessly to a mobile phone, from where it is accessible remotely via cloud storage. EEG recordings from the sub-scalp device were compared to data recorded from a conventional system during a 1-week ambulatory video-EEG monitoring session. Suspect epileptiform activity (EA) was detected using machine learning algorithms and reviewed by trained neurophysiologists. Seizure forecasting was demonstrated retrospectively by utilizing cycles in EA and previous seizure times. The procedures and devices were well-tolerated and no significant complications have been reported. Seizures were accurately identified on the sub-scalp system, as visually confirmed by periods of concurrent conventional scalp EEG recordings. The data acquired also allowed seizure forecasting to be successfully undertaken. The area under the receiver operating characteristic curve (AUC score) achieved (0.88), which is comparable to the best score in recent, state-of-the-art forecasting work using intracranial EEG.

Long-term mood, quality of life, and seizure freedom in intracranial EEG epilepsy surgery.

OBJECTIVES: To determine the long-term outcomes in patients undergoing intracranial EEG (iEEG) evaluation for epilepsy surgery in terms of seizure freedom, mood, and quality of life at St. Vincent's Hospital, Melbourne. METHODS: Patients who underwent iEEG between 1999 and 2016 were identified. Patients were retrospectively assessed between 2014 and 2017 by specialist clinic record review and telephone survey with standardized validated questionnaires for: 1) seizure freedom using the Engel classification; 2) Mood using the Neurological Disorders Depression Inventory for Epilepsy (NDDI-E); 3) Quality-of-life outcomes using the QOLIE-10 questionnaire. Summary statistics and univariate analysis were performed to investigate variables for significance. RESULTS: Seventy one patients underwent iEEG surgery: 49 Subdural, 14 Depths, 8 Combination with 62/68 (91.9%) of those still alive, available at last follow-up by telephone survey or medical record review (median of 8.2 years). The estimated epileptogenic zone was 62% temporal and 38% extra-temporal. At last follow-up, 69.4% (43/62) were Engel Class I and 30.6% (19/62) were Engel Class II-IV. Further, a depressive episode (NDDI-E > 15)was observed in 34% (16/47), while a 'better quality of life' (QOLIE-10 score < 25) was noted in 74% (31/42). Quality of life (p < 0.001) but not mood (p = 0.24) was associated with seizure freedom. SIGNIFICANCE: Long-term seizure freedom can be observed in patients undergoing complex epilepsy surgery with iEEG evaluation and is associated with good quality of life.

Neurophysiological evidence for generalized sensory neuronopathy in cerebellar ataxia with neuropathy and bilateral vestibular areflexia syndrome.

INTRODUCTION: Cerebellar ataxia with neuropathy and bilateral vestibular areflexia syndrome (CANVAS) is a recently described multisystem ataxia defined by the presence of cerebellar ataxia, bilateral vestibulopathy, and a somatosensory deficit. The characteristic clinical sign is an abnormal visually enhanced vestibuloocular reflex. The somatosensory deficit contributes to a significant level of disability in CANVAS. METHODS: This study was a neurophysiological investigation of 14 patients with CANVAS. RESULTS: Findings revealed uniformly absent sensory nerve action potentials in all limbs, abnormal blink reflexes in 13 of 14 patients, and abnormal masseter reflexes in 6 of 11 patients. Tibial H-reflexes were absent in 11 of 14 patients. Somatosensory evoked potentials were abnormal in 10 of the 11 patients tested, and brainstem auditory evoked responses were abnormal in 3 of 8. Cutaneous silent period responses were abnormal in 7 of 14 patients. CONCLUSIONS: We suggest that a sensory neuronopathy should be sought in cerebellar and/or vestibular ataxias, particularly where the degree of ataxia is out of proportion to the clinically identified cerebellar and/or vestibular dysfunction.

Patient-specific bivariate-synchrony-based seizure prediction for short prediction horizons.

This paper evaluates the patient-specific seizure prediction performance of pre-ictal changes in bivariate-synchrony between pairs of intracranial electroencephalographic (iEEG) signals within 15min of a seizure in patients with pharmacoresistant focal epilepsy. Prediction horizons under 15min reduce the durations of warning times and should provide adequate time for a seizure control device to intervene. Long-term continuous iEEG was obtained from 6 patients. The seizure prediction performance was evaluated for all possible channel pairs and for different prediction methods to find the best performing channel pairs and methods for both pre-ictal decreases and increases in synchrony. The different prediction methods involved changes in window duration, signal filtering, thresholding approach, and prediction horizon durations. Performance for each patient, for all seizures, was first compared with an analytical-Poisson-based random predictor. The performance of the top 5% of channel pairs for each patient closely matched the top 5% of analytical-Poisson-based random predictor performance indicating that patient-specific, bivariate-synchrony-based seizure prediction could be random in general (under the assumption that channel-pair prediction times are statistically independent). Analysis of the spatial patterns of performance showed no clear relationship to the seizure onset zone. For each patient the best channel pair showed better performance than Poisson-based random prediction for a selected subset of prediction thresholds. Given the caveats of comparing with this form of random prediction, alarm time surrogates were employed to assess statistical significance of a four-fold out-of-sample cross-validation analysis applied to the best channel-pairs. The cross-validation analysis obtained reasonable testing performance for most patients when performance was compared to random prediction based on alarm time surrogates. The most significant case was a patient whose testing set sensitivity and false positive rate were 0.67±0.09 and 3.04±0.29h(-1), respectively, for decreases in synchrony, an intervention time of 15min and a seizure onset period of 5min. For each testing set for this patient, performance was better than that obtained by random prediction at the significance level of 0.05 (average sensitivity of 0.47±0.05). Moreover, there were 9 seizures in each testing set which gives greater power to this cross-validation result, although the cross-validation was performed on the best channel pair selected by within-sample optimization for all seizures of the patient. Further validation with larger datasets from individual patients is needed. Improvements in prediction performance should be achievable through investigations of multivariate synchrony combined with non-linear classification methods.

Seizure detection using seizure probability estimation: comparison of features used to detect seizures.

This paper analyses seizure detection features and their combinations using a probability-based scalp EEG seizure detection framework developed by Marc Saab and Jean Gotman. Our method was evaluated on 525 h of data, including 88 seizures in 21 patients. The individual performances of the three features used by Saab and Gotman were compared to six alternative features, and combinations of these nine features were analyzed in order to find a superior detector. On a testing set with the combination of their three features, Saab and Gotman reported a sensitivity of 0.78, a false positive rate of 0.86/h, and a median detection delay of 9.8 s. Based on 10-fold cross-validation the testing performance of our implementation of their method achieved a sensitivity of 0.79, a false positive rate of 0.62/h, and a median detection delay of 21.3 s. A detector based on an alternative combination of features achieved sensitivity of 0.81, a false positive rate of 0.60/h, and a median detection delay of 16.9 s. By including filtering techniques, it was possible to achieve performance levels similar to Saab and Gotman using our implementation of their method, although this involved increases in detection delays. Of the seizure detection measures investigated, relative average amplitude, relative power, relative derivative, and coefficent of variation of amplitude provided the best performing combinations. These better-performing features can be employed together to make robust and reliable seizure detectors.