Touch-screen automatisms in the digital age.

OBJECTIVE: To describe a novel set of gestural automatisms related to the use of digital screens on smartphones and tablets in patients with epilepsy. METHODS: Representative patients were selected from among those admitted to the Epilepsy Monitoring Unit at the Toronto Western Hospital between April 2016 and January 2020, and included if they exhibited automatisms clearly related to or mimicking digital device use. RESULTS: In total 5 patients were included, 4 female. All had temporal lobe epilepsy: 2 had left mesial temporal sclerosis and 3 had normal imaging. Nearly equal numbers of seizures began with right (5/9) and left (4/9) temporal onsets, with most automatisms occurring after seizure propagation to bilateral temporal involvement (6/9). Left-handed automatisms were most common (8/9). The majority of the automatisms (7/9) were perseverative on device usage prior to the seizure. CONCLUSION: Gestural automatisms appear related to the contemporary lived experience, culture, and habitual behaviour of patients with epilepsy. In the modern era, the use of smartphones and tablets are both common and habitual for many, and this case series shows that touch-screen automatisms may be added to the semiological panoply of temporal lobe seizures.

Electroencephalography Findings in Wrong Way Eyes: Unilateral Hemispheric Dysfunction Supporting Smooth Pursuit Asymmetry Hypothesis.

BACKGROUND: Conjugate horizontal eye deviation away from the side of the lesion, termed Wrong Way Eyes (WWE), is a rare manifestation of supratentorial lesions. The proposed etiologic hypotheses include seizure activity, compression of contralateral horizontal gaze pathways from mass effect or midline shift, and asymmetry of hemispheric smooth pursuit mechanisms. We present neurophysiological evidence that favors the asymmetry of hemispheric smooth pursuit hypothesis. METHODS: Electroencephalography (EEG) was performed in 2 patients with large left hemispheric supratentorial lesions, capturing fluctuating periods of (a) unresponsiveness with WWE and (b) relative alertness without WWE. One patient had 5 days of continuous EEG, and the other routine EEG. RESULTS: Neither patient had seizures. EEG showed normal right hemispheric activity during both unresponsiveness with WWE and alertness without WWE states. By contrast, more severe left hemispheric dysfunction was evident in the WWE state compared with the non-WWE state in both patients. In one patient, during the relatively alert state, right-beating nystagmus was observed, and drift of the eyes away from the side of the lesion was reliably seen to occur on eyelid closure and after ipsiversive volitional saccades. CONCLUSIONS: Seizure activity does not account for WWE. Compression of contralateral horizontal gaze pathways is also unlikely to account for WWE as that hypothetical mechanism should produce EEG abnormalities over the nonlesioned hemisphere, which were not seen. The findings suggest instead that a single dysfunctional hemisphere is sufficient to produce WWE. The repeated rightward drift of the eyes and nystagmus seen in one patient during relative alertness, and the observation of unilateral hemispheric dysfunction on EEG during unresponsiveness with WWE in both patients supports the idea that an imbalance of smooth pursuit mechanisms is most likely to account for this rare phenomenon.

A Distinct EEG Marker of Celiac Disease-Related Cortical Myoclonus.

BACKGROUND: Celiac disease is associated with motor cortex hyperexcitability and neurological manifestations including cortical myoclonus. Electroencephalography abnormalities have been described, but no distinct pattern has been reported. METHODS: We describe the neurophysiological characteristics of 3 patients with celiac-associated cortical myoclonus using electroencephalography, magnetoencephalography, and transcranial magnetic stimulation. RESULTS: Electroencephalography in all cases demonstrated lateralized low-amplitude, electropositive beta-frequency polyspike activity over the central head region, corresponding to motor cortex contralateral to the myoclonic limb. Jerk-locked back-averaging demonstrated a preceding cortical potential; magnetoencephalography source localization revealed a cortical generator in the posterior wall of the precentral gyrus for the back-averaged potential and oscillatory abnormality. In 1 patient, cerebellar inhibition of the motor cortex was physiologically normal. CONCLUSIONS: Central head oscillatory, low-amplitude, electropositive electroencephalography polyspike activity may be a distinct marker of celiac-related cortical myoclonus and is consistent with celiac-related motor cortex hyperexcitability, which may not necessarily result from cerebellar disinhibition. © 2020 International Parkinson and Movement Disorder Society.

Blood oxygen level-dependent (BOLD) response patterns with thalamic deep brain stimulation in patients with medically refractory epilepsy.

OBJECTIVE: Anterior nucleus of thalamus (ANT) deep brain stimulation (DBS) has shown promise as a treatment for medically refractory epilepsy. To better understand the mechanism of this intervention, we used functional magnetic resonance imaging (fMRI) to map the acute blood oxygen level-dependent (BOLD) response pattern to thalamic DBS in fully implanted patients with epilepsy. METHODS: Two patients with epilepsy implanted with bilateral ANT-DBS devices underwent four fMRI acquisitions each, during which active left-sided monopolar stimulation was delivered in a 30-s DBS-ON/OFF cycling paradigm. Each fMRI acquisition featured left-sided stimulation of a different electrode contact to vary the locus of stimulation within the thalamus and to map the brain regions modulated as a function of different contact selection. To determine the extent of peri-electrode stimulation and the engagement of local structures during each fMRI acquisition, volume of tissue activated (VTA) modeling was also performed. RESULTS: Marked changes in the pattern of BOLD response were produced with thalamic stimulation, which varied with the locus of the active contact in each patient. BOLD response patterns to stimulation that directly engaged at least 5% of the anterior nuclear group by volume were characterized by changes in the bilateral putamen, thalamus, and posterior cingulate cortex, ipsilateral middle cingulate cortex and precuneus, and contralateral medial prefrontal and anterior cingulate. SIGNIFICANCE: The differential BOLD response patterns associated with varying thalamic DBS parameters provide mechanistic insights and highlight the possibilities of fMRI biomarkers of optimizing stimulation in patients with epilepsy.

Phase-amplitude coupling within the anterior thalamic nuclei during seizures.

Cross-frequency phase-amplitude coupling (cfPAC) subserves an integral role in the hierarchical organization of interregional neuronal communication and is also expressed by epileptogenic cortex during seizures. Here, we sought to characterize patterns of cfPAC expression in the anterior thalamic nuclei during seizures by studying extra-operative recordings in patients implanted with deep brain stimulation electrodes for intractable epilepsy. Nine seizures from two patients were analyzed in the peri-ictal period. CfPAC was calculated using the modulation index and interregional functional connectivity was indexed using the phase-locking value. Statistical analysis was performed within subjects on the basis of nonparametric permutation and corrected with Gaussian field theory. Five of the nine analyzed seizures demonstrated significant cfPAC. Significant cfPAC occurred during the pre-ictal and ictal periods in three seizures, as well as the postictal windows in four seizures. The preferred phase at which cfPAC occurred differed 1) in space, between the thalami of the epileptogenic and nonepileptogenic hemispheres; and 2) in time, at seizure termination. The anterior thalamic nucleus of the epileptogenic hemisphere also exhibited altered interregional phase-locking synchrony concurrent with the expression of cfPAC. By analyzing extraoperative recordings from the anterior thalamic nuclei, we show that cfPAC associated with altered interregional phase synchrony is lateralized to the thalamus of the epileptogenic hemisphere during seizures. Electrophysiological differences in cfPAC, including preferred phase of oscillatory interactions may be further investigated as putative targets for individualized neuromodulation paradigms in patients with drug-resistant epilepsy. NEW & NOTEWORTHY The association between fast brain activity and slower oscillations is an integral mechanism for hierarchical neuronal communication, which is also manifested in epileptogenic cortex. Our data suggest that the same phenomenon occurs in the anterior thalamic nuclei during seizures. Further, the preferred phase of modulation shows differences in space, between the epileptogenic and nonepileptogenic hemispheres and time, as seizures terminate. Our data encourage the study of cross-frequency coupling for targeted, individualized closed-loop stimulation paradigms.

Long-Term Cognitive Outcomes in Patients with Autoimmune Encephalitis.

BACKGROUND: A need exists to characterise the long-term cognitive outcomes in patients who recovered from autoimmune encephalitis and to identify the modifiable factors associated with improved outcomes. METHODS: We retrospectively analysed data from patients diagnosed with autoimmune encephalitis in our outpatient autoimmune encephalitis clinic over a 5-year period, where the Montreal Cognitive Assessment (MoCA) is routinely administered. RESULTS: In total, 21 patients met the inclusion criteria, of whom 52% had persistent cognitive impairment at their latest follow-up (median delay to testing=20 months, range 13-182). Visuospatial and executive abilities, language, attention, and delayed recall were predominantly affected. Patients with status epilepticus at presentation had lower total MoCA scores at their last follow-up (median total score 21, range 15-29) compared with patients without status epilepticus at presentation (median total score 27.5, range 21-30; r 2=0.366, p=0.004). Patients who experienced delays of more than 60 days from symptom onset to initiation of treatment (either immunosuppression or tumour removal) were more likely to have a MoCA score compatible with cognitive impairment at their last follow-up (r 2=0.253, p=0.0239; z-score=-2.01, p=0.044). CONCLUSIONS: Our study suggests that the MoCA may be used to evaluate cognition in recovering patients with autoimmune encephalitis. Delays to treatment shorter than 60 days and absence of status epilepticus at onset were associated with better performance on the MoCA obtained more than 1 year after symptom onset, and may predict better long-term cognitive outcomes.

Canadian epileptologists' counseling of drivers amidst guideline inconsistencies.

BACKGROUND: Epilepsy is a common medical condition for which physicians perform driver fitness assessments. The Canadian Medical association (CMA) and the Canadian Council of Motor transportation administrators (CCMTA) publish documents to guide Canadian physicians' driver fitness assessments. OBJECTIVES: We aimed to measure the consistency of driver fitness counseling among epileptologists in Canada, and to determine whether inconsistencies between national guidelines are associated with greater variability in counseling instructions. METHODS: We surveyed 35 epileptologists in Canada (response rate 71%) using a questionnaire that explored physicians' philosophies about driver fitness assessments and counseling practices of seizure patients in common clinical scenarios. Of the nine scenarios, CCMTA and CMA recommendations were concordant for only two. Cumulative agreement for all scenarios was calculated using Kappa statistic. Agreement for concordant (two) vs. discordant (seven) scenarios were split at the median and analyzed using the Wilcoxon signed rank sum test. RESULTS: Overall the agreement between respondents for the clinical scenarios was not acceptable (Kappa=0.28). For the two scenarios where CMa and CCMta guidelines were concordant, specialists had high levels of agreement with recommendations (89% each). A majority of specialists disagreed with CMa recommendations in three of seven discordant scenarios. The lack of consistency in respondents' agreement attained statistical significance (p<0.001). CONCLUSIONS: Canadian epileptologists have variable counseling practices about driving, and this may be attributable to inconsistencies between CMa and CCMta medical fitness guidelines. This study highlights the need to harmonize driving recommendations in order to prevent physician and patient confusion about driving fitness in Canada.

Ipsilateral preictal alpha rhythm attenuation (IPARA): An EEG sign of side of seizure onset in temporal lobe epilepsy.

PURPOSE: Identification of the seizure onset zone is critically important for outlining the surgical plan in the treatment of pharmacoresistant focal epilepsy. In patients with temporal lobe epilepsy (TLE), bilateral ictal scalp EEG changes frequently occur and can make lateralization of the seizure onset zone difficult. We investigated the incidence and clinical utility of unilateral preictal alpha rhythm attenuation as a lateralizing sign of seizure onset in TLE. METHODS: Scalp EEG recordings of the seizures acquired during presurgical video-EEG monitoring of 57 consecutive patients with TLE were reviewed retrospectively. Included patients had interictal baseline recordings demonstrating symmetrical posterior alpha rhythm and seizures occurring during wakefulness. RESULTS: We identified a total of 649 seizures in the 57 patients, of which 448 seizures in 53 patients fulfilled the inclusion criteria. Among the 53 included patients, 7 patients (13.2%) exhibited a distinct attenuation of the posterior alpha rhythm prior to the first ictal EEG changes, in 26 of 112 (23.2%) included seizures. Preictal alpha rhythm attenuation in these seizures was ipsilateral to the ultimately determined side of seizure onset (based on video-EEG or intracranial EEG findings) in 22 (84.6%) of these seizures and bilateral in 4 (15.4%), and occurred on average 5.9 ± 2.6 s prior to ictal EEG onsets. CONCLUSION: Our findings suggest that in some patients with TLE lateralized preictal attenuation of the posterior alpha rhythm may be a useful indicator of side of seizure onset, presumably due to early disruption of thalamo-temporo-occipital network function, likely mediated through the thalamus.

Hyperventilation-induced focal seizures in adults: think autoimmune encephalitis.

Case reports have described rare patients with autoimmune encephalitis in whom focal seizures could be reliably provoked by hyperventilation. With the hypothesis that this phenomenon may have diagnostic significance, all cases of hyperventilation-induced focal seizures identified during ~10,000 consecutive routine electroencephalography (EEG) studies were reviewed, and corresponding diagnoses established. Seven EEG recordings, in six patients, contained focal hyperventilation-induced seizures, each of temporal lobe onset. All patients were diagnosed with autoimmune encephalitis, in two cases after EEG; five had voltage-gated potassium channel complex autoantibodies. Although rare, a hyperventilation-induced focal seizure during EEG in an adult should raise concern for autoimmune encephalitis.

Autoimmune Encephalitis and Autoantibodies: A Review of Clinical Implications.

BACKGROUND: Autoimmune encephalitis (AE) is a common cause of encephalitis. We review the most recent evidence on this neuroimmune condition and autoantibody testing currently available. CONTENT: Clinical criteria, neuroimaging and electroencephalography can facilitate the diagnosis of AE prior to obtaining autoantibody testing results, and lead to a diagnosis of AE even in the absence of a recognized antibody. Early treatment of AE has been found to correlate with improved long-term functional and cognitive outcomes. We suggest a clinical approach to diagnosis based on the predominant area of nervous system involvement and the results of ancillary testing that are widely available. We also propose a 2-tiered approach to the acute management of probable or definite AE. We, finally, provide guidance on the long-term management of AE-a challenging and understudied area. SUMMARY: Much work remains to be done to improve the care of patients with AE. As understanding of the pathophysiology and predisposing factors underlying this condition steadily increases, a more evidence-based, targeted approach to the treatment of AE is still desired. Nonetheless, looking at the progress made over the past 2 decades, since the discovery of the first autoantibodies associated with AE, one cannot help but feel optimistic about the road ahead.

Brain Connectivity Changes in Postconcussion Syndrome as the Neural Substrate of a Heterogeneous Syndrome.

Background: Postconcussion syndrome (PCS) or persistent symptoms of concussion refers to a constellation of symptoms that persist for weeks and months after a concussion. To better capture the heterogeneity of the symptoms of patients with PCS, we aimed to separate patients into clinical subtypes based on brain connectivity changes. Methods: Subject-specific structural and functional connectomes were created based on diffusion weighted and resting state functional magnetic resonance imaging, respectively. Following an informed dimensionality reduction, a Gaussian mixture model was used on patient-specific structural and functional connectivity matrices to find potential patient clusters. For validation, the resulting patient subtypes were compared in terms of cognitive, neuropsychiatric, and postconcussive symptom differences. Results: Multimodal analyses of brain connectivity were predictive of behavioral outcomes. Our modeling revealed two patient subtypes: mild and severe. The severe subgroup showed significantly higher levels of depression, anxiety, aggression, and a greater number of symptoms than the mild patient subgroup. Conclusion: This study suggests that structural and functional connectivity changes together can help us better understand the symptom severity and neuropsychiatric profiles of patients with PCS. This work allows us to move toward precision medicine in concussions and provides a novel machine learning approach that can be applicable to other heterogeneous conditions.

Ovarian resection in anti-N-methyl-D-aspartate receptor encephalitis: A comparison of surgical approaches.

Background: For patients with anti-N-methyl-D-aspartate receptor encephalitis (NMDARE) and ovarian teratoma, "conservative" surgical approaches (complete or partial unilateral oophorectomy or bilateral partial oophorectomies) are associated with clinical improvement. "Aggressive" ovarian resections (complete bilateral oophorectomy or "blind" ovarian resections without pre-operative evidence of teratoma) are also reported, although the evidence supporting these approaches is unclear. Objective: To compare the one-year functional outcomes of patients with NMDARE who underwent conservative vs. aggressive ovarian resections. Methods: Patients with NMDARE undergoing ovarian resection between January 1st, 2012 and December 31st, 2021 were retrospectively identified from three North American tertiary care centers. Primary outcome was a modified Rankin Scale score of 0-2 one year after ovarian resection. Fisher exact and Wilcoxon rank sum tests were used to compare demographic features, disease characteristics, and functional outcomes between the two surgical groups. A fixed-effects meta-analysis of studies reporting functional outcomes based on surgical approach was also performed. Results: Twenty-three patients were included. Eight underwent aggressive surgical management. There was a non-significant trend toward an association between aggressive surgical management and younger age-at-onset, higher baseline disease severity, and longer delays to treatment. There was no difference between "aggressive" (3/8, 38%) and "conservative" (11/15, 73%) management groups in achieving the primary outcome (OR95% = <0.1-1.9; p = 0.18). Findings were similar when considering data from 52 patients in two published studies (RR = 0.74; CI95% = 0.48-1.13; p = 0.16). Conclusions: Aggressive ovarian resection was not associated with improved outcomes in patients with NMDARE in this series. Group differences may have contributed, recognizing that patients who underwent aggressive resection tended to be sicker, with procedures performed later in the disease course. Based on available evidence, we advocate for function-sparing resection in patients with imaging-confirmed/suspected teratoma, and repeated multi-modal imaging in at-risk patients with NMDARE refractory to conventional treatment.

Experimental observation of increased fluctuations in an order parameter before epochs of extended brain synchronization.

The identification of epileptic seizure precursors has potential clinical relevance. It is conjectured that seizures may be represented by dynamical bifurcations and that an adequate order parameter to characterize brain dynamics is the phase difference in the oscillatory activity of neural systems. In this study, the critical point hypothesis that seizures, or more generally periods of widespread high synchronization, represent bifurcations is empirically tested by monitoring the growth of fluctuations in the putative order parameter of phase differences between magnetoencephalographic and electroencephalographic signals in nearby brain regions in patients with epilepsy and normal subjects during hyperventilation. Implications of the results with regard to epileptic phenomena are discussed.

Selective enhancement of rapid eye movement sleep by deep brain stimulation of the human pons.

Animal studies suggest that rapid eye movement (REM) sleep is governed by the interaction of REM-promoting and REM-inhibiting nuclei in the pontomesencephalic tegmentum. The pedunculopontine nucleus is proposed to be REM promoting. Using polysomnography, we studied sleep in five parkinsonian patients undergoing unilateral pedunculopontine nucleus deep brain stimulation (DBS). We demonstrated a near doubling of nocturnal REM sleep between the DBS "off" and DBS "on" states, without significant changes in other sleep states. This represents the first demonstration that DBS can selectively modulate human sleep, and it supports an important role for the pedunculopontine nucleus region in modulating human REM sleep. Ann Neurol 2009;66:110-114.

Dravet syndrome and deep brain stimulation: seizure control after 10 years of treatment.

Dravet syndrome is a genetically determined severe epilepsy associated with cognitive decline and ataxia. The many types of seizures seen in these patients are typically pharmacoresistant. Here we describe two adults with Dravet syndrome who were treated with thalamic deep brain stimulation (DBS) and followed for 10 years. One patient with partial onset seizures received DBS at age 19 and showed a marked improvement in seizure control after DBS insertion and stimulation. The other patient with generalized onset seizures received DBS at age 34 and did not show any immediate benefit. No side effects or changes in cognition were observed in either of the patients. This is the first report of (short- and) long-term results in Dravet patients treated with thalamic DBS. We speculate that the results of DBS for epilepsy in patients with Dravet syndrome may be related to age at initiation of DBS treatment and seizure type.

Searching for autoimmune encephalitis: Beware of normal CSF.

OBJECTIVE: To determine the prevalence of cerebrospinal fluid (CSF) markers associated with inflammation (i.e., elevated white blood cell count, protein concentration, and CSF-specific oligoclonal bands) in patients with early active autoimmune encephalitis (AE). METHODS: CSF characteristics, including WBC count, protein concentration, and oligoclonal banding, were analyzed in patients diagnosed with AE at two tertiary care centers. RESULTS: Ninety-five patients were included in the study. CSF white blood cell counts and protein levels were within normal limits for 27% (CI95%: 19-37) of patients with AE. When results of oligoclonal banding were added, 14% (CI95%: 6-16) of patients with AE had "normal" CSF. The median CSF white blood cell count was 8 cells/mm3 (range: 0-544) and the median CSF protein concentration was 0.42 g/L (range: 0.15-3.92). CONCLUSIONS: White blood cell counts and protein levels were within normal limits in the CSF of a substantial proportion of patients with early active AE. Inclusion of CSF oligoclonal banding identified a higher proportion of patients with an inflammatory CSF profile, especially when CSF was sampled early in the disease process.

Memory enhancement induced by hypothalamic/fornix deep brain stimulation.

Bilateral hypothalamic deep brain stimulation was performed to treat a patient with morbid obesity. We observed, quite unexpectedly, that stimulation evoked detailed autobiographical memories. Associative memory tasks conducted in a double-blinded "on" versus "off" manner demonstrated that stimulation increased recollection but not familiarity-based recognition, indicating a functional engagement of the hippocampus. Electroencephalographic source localization showed that hypothalamic deep brain stimulation drove activity in mesial temporal lobe structures. This shows that hypothalamic stimulation in this patient modulates limbic activity and improves certain memory functions.

Neurologic injuries in hockey.

Ice hockey is a fast contact sport played on an ice surface enclosed by rigid boards. There is an intrinsic risk for injury in hockey, with many injuries potentially affecting the nervous system. This article provides an overview of neurologic injuries occurring in hockey as reported in the scientific literature. Among all injuries, a small but real risk for catastrophic cervical spinal cord injury and a high incidence of concussion emerge as the two most important neurologic issues.