Nocturnal paroxysmal dystonia to sleep-related hypermotor epilepsy: A critical review.

Sleep-related paroxysmal motor episodes (SPMEs) have been described by various names, including nocturnal paroxysmal dystonia, nocturnal frontal lobe epilepsy (NFLE), and sleep-related hypermotor epilepsy. The underlying pathophysiology has been debated over the years, with these episodes assumed to be a form of paroxysmal dystonia or parasomnia versus a form of epilepsy. In most studies published on SPMEs and their variants (paroxysmal arousals, nocturnal paroxysmal dystonia, and episodic nocturnal wanderings) in the early 1990s, the authors speculated on the pathophysiology but did not commit to one idea. It was not until the mid-1990s that epilepsy became the leading prospect. We performed a narrative review of the major articles that have described this syndrome in a chronological fashion. We identified three eras, 1972-1993, 1994-1998, and 1999 to the present, each era marked by a landmark study. Our critical review of these early studies shows that the neurophysiological data supporting epilepsy as the sole basis for all SPME cases is very weak. In 1994-1995, a familial pattern of this syndrome was described and the term autosomal dominant NFLE was coined, with the authors claiming that all their patients had a form of frontal lobe epilepsy. With the exception of a few reference cases, the neurophysiological evidence that all patients had frontal lobe epilepsy was very weak. Compared to articles published on surgical series of frontal lobe epilepsy, the percentage of SPME cases with positive interictal/ictal electroencephalograms remained very low, seriously questioning the epileptic basis of the syndrome. Our critical review and analysis of the published literature shows that the evidence presented in favor of SPMEs being a homogenous focal epilepsy syndrome is very weak. Neurologists must recognize that SPMEs could be a form of movement disorder, parasomnia, or epilepsy. We recommend a pragmatic semiology-based classification of these episodes using the four-dimensional classification system.

Spectrum of motor responses elicited by electrical stimulation of primary motor cortex: A polygraphic study in patients with epilepsy.

OBJECTIVE: To study the neurophysiology of motor responses elicited by electrical stimulation of the primary motor cortex. METHODS: We studied motor responses in four patients undergoing invasive epilepsy monitoring and functional cortical mapping via electrical cortical stimulation using surface EMG electrodes. In addition, polygraphic analysis of intracranial EEG and EMG during bilateral tonic-clonic seizures, induced by cortical stimulation, was performed in two patients. RESULTS: (a) Electrical cortical stimulation: The motor responses were classified as clonic, jittery, and tonic. The clonic responses were characterized by synchronous EMG bursts of agonist and antagonistic muscles, alternating with silent periods. At stimulation frequencies of <20 Hz, EMG bursts were of ≤50 ms duration (Type I clonic). At stimulation frequencies of 20-50 Hz, EMG bursts were of >50 ms duration and had a complex morphology (Type II clonic). Increasing the current intensity at a constant frequency converted clonic responses into jittery and tonic contractions. (b) Bilateral tonic-clonic seizures: The intracranial EEG showed continuous fast spiking activity during the tonic phase along with interference pattern on surface EMG. The clonic phase was characterized by a polyspike-and-slow wave pattern. The polyspikes were time-locked with the synchronous EMG bursts of agonists and antagonists and the slow waves were time-locked with silent periods. INTERPRETATION: These results suggest that epileptic activity involving the primary motor cortex can produce a continuum of motor responses ranging from type I clonic, type II clonic, and tonic responses to bilateral tonic-clonic seizures. This continuum is related to the frequency and intensity of the epileptiform discharges with tonic seizures representing the highest end of the spectrum.

Nonmydriatic Retinal Photography in the Outpatient Neurology Resident Clinic.

BACKGROUND: The funduscopic examination is an essential component of the neurologic examination. However, examination of the ocular fundus with a direct ophthalmoscope is often difficult. Nonmydriatic ocular fundus photography allows direct visualization of the ocular fundus with high-quality photographs. We used nonmydriatic ocular fundus photography to improve patient care and funduscopy skills of residents in the Neurology Resident Clinic. METHODS: At the time of triage, funduscopic photographs of all new neurology resident clinic patients were taken. The images were imported into the hospital's imaging software. The residents completed a full neurologic examination, including a funduscopic examination with a handheld ophthalmoscope. At the time of staffing the patients with the attendings, the residents received immediate feedback and teaching on retina photograph evaluation. RESULTS: A total of 255 patients were enrolled. Of those, 230 (90%) had at least one high-quality funduscopic photograph. Retinal photographs were normal in 161 (70%). Out of the 69 abnormal photographs, only 7% of abnormalities were detected by the residents. Ninety-three percent of residents found the retinal photographs useful. CONCLUSIONS: Nonmydriatic ocular fundus photography improved the care in patients presenting to a Neurology resident clinic and facilitated residents in recognizing funduscopic findings. Its benefits are clear when one considers (1) the high risk of negative patient outcomes and possible medicolegal consequences due to missed findings, (2) the ease of incorporating retinal photographs into the patients' medical records, and (3) the benefit of improving resident education in regard to the ophthalmologic examination.

EEG based oculographic analysis of epileptic nystagmus.

Epileptic nystagmus (EN) is a subtle seizure semiology, most commonly seen in seizures originating in the posterior cortical regions. EN is broadly categorized into type I and type II. Type I EN consists of contralateral repetitive saccadic eye movements alternating with post-saccadic slow drifts with an overall contralateral deviation. Type II EN is characterized by ipsilateral slow drift alternating with contralateral corrective saccades. In this article, we report a method to perform oculographic analysis of eye movements using EEG only. We used this method to classify the type of EN in three patients with parieto-occipital seizures. In all three patients, the ictal EEG demonstrated repetitive saccadic eye movements, directed contralateral to the seizure onset zone. With prolonged time constant, we were able to identify this eye movement pattern as EN with distinct slow and fast phases. We were able to further characterize the type of EN as type I and type II. In all three patients, the direction of EN (direction of fast phase or saccades) was contralateral to the seizure onset zone. EN can be easily missed on video-electroencephalography (vEEG) recordings because of various reasons. Our study demonstrates a systematic method of eye movement analysis on EEG, which can be used to not only identify EN as seizure semiology but also classify it, without requiring additional electrodes.

Rejuvenating classical brain electrophysiology source localization methods with spatial graph Fourier filters for source extents estimation.

EEG/MEG source imaging (ESI) aims to find the underlying brain sources to explain the observed EEG or MEG measurement. Multiple classical approaches have been proposed to solve the ESI problem based on different neurophysiological assumptions. To support clinical decision-making, it is important to estimate not only the exact location of the source signal but also the extended source activation regions. Existing methods may render over-diffuse or sparse solutions, which limit the source extent estimation accuracy. In this work, we leverage the graph structures defined in the 3D mesh of the brain and the spatial graph Fourier transform (GFT) to decompose the spatial graph structure into sub-spaces of low-, medium-, and high-frequency basis. We propose to use the low-frequency basis of spatial graph filters to approximate the extended areas of brain activation and embed the GFT into the classical ESI methods. We validated the classical source localization methods with the corresponding improved version using GFT in both synthetic data and real data. We found the proposed method can effectively reconstruct focal source patterns and significantly improve the performance compared to the classical algorithms.

Multi-Modal Electrophysiological Source Imaging With Attention Neural Networks Based on Deep Fusion of EEG and MEG.

The process of reconstructing underlying cortical and subcortical electrical activities from Electroencephalography (EEG) or Magnetoencephalography (MEG) recordings is called Electrophysiological Source Imaging (ESI). Given the complementarity between EEG and MEG in measuring radial and tangential cortical sources, combined EEG/MEG is considered beneficial in improving the reconstruction performance of ESI algorithms. Traditional algorithms mainly emphasize incorporating predesigned neurophysiological priors to solve the ESI problem. Deep learning frameworks aim to directly learn the mapping from scalp EEG/MEG measurements to the underlying brain source activities in a data-driven manner, demonstrating superior performance compared to traditional methods. However, most of the existing deep learning approaches for the ESI problem are performed on a single modality of EEG or MEG, meaning the complementarity of these two modalities has not been fully utilized. How to fuse the EEG and MEG in a more principled manner under the deep learning paradigm remains a challenging question. This study develops a Multi-Modal Deep Fusion (MMDF) framework using Attention Neural Networks (ANN) to fully leverage the complementary information between EEG and MEG for solving the ESI inverse problem, which is termed as MMDF-ANN. Specifically, our proposed brain source imaging approach consists of four phases, including feature extraction, weight generation, deep feature fusion, and source mapping. Our experimental results on both synthetic dataset and real dataset demonstrated that using a fusion of EEG and MEG can significantly improve the source localization accuracy compared to using a single-modality of EEG or MEG. Compared to the benchmark algorithms, MMDF-ANN demonstrated good stability when reconstructing sources with extended activation areas and situations of EEG/MEG measurements with a low signal-to-noise ratio.

Semiology and Neurophysiology of Clonic Seizures: A Report of 39 Patients.

Background and Objectives: Clonic seizures are currently defined as repetitive and rhythmic myoclonic contractions of a specific body part, producing twitching movements at a frequency of 0.2-5 Hz. There are few studies in the literature that have reported a detailed analysis of the semiology, neurophysiology, and lateralizing value of clonic seizures. In this article, we aim to report our findings from a retrospective review of 39 patients. Methods: We identified 39 patients (48 seizures) from our center who had been admitted with clonic seizures between 2016 and 2022. We performed a retrospective review of their video-EEG recordings for semiology and ictal EEG findings. Seventeen patients also had simultaneous surface-EMG (sEMG) electrodes placed on affected body parts, which were analyzed as well. Results: The most common initial affected body parts were face, arm, and hand. In most of the cases, seizures propagated from lower face to upper face and distal hand to proximal arm. The most common seizure-onset zone was the perirolandic region, and the most common EEG seizure pattern was paroxysmal rhythmic monomorphic activity. The lateralizing value for EEG seizure onset to contralateral hemisphere in unilateral clonic seizures (n = 39) was 100%. All seizures recorded with sEMG electrodes demonstrated synchronous brief tetanic contractions of agonists and antagonists, alternating with synchronous silent periods. Arrhythmic clonic seizures were associated with periodic epileptiform discharges on the EEG, whereas rhythmic clonic seizures were associated with paroxysmal rhythmic monomorphic activity. Overall, the most common etiology was cerebrovascular injuries, followed by tumors. Discussion: Clonic seizures are characterized by synchronized brief tetanic contractions of agonist and antagonistic muscles alternating with synchronized silent periods, giving rise to the visible twitching. The most common seizure onset zone is in the perirolandic region, which is consistent with the symptomatogenic zone being in the primary motor area. The lateralizing value of unilateral clonic seizures for seizure onset in the contralateral hemisphere is 100%.

County-Level Socio-Environmental Factors Associated With Stroke Mortality in the United States: A Cross-Sectional Study.

We used machine learning methods to explore sociodemographic and environmental determinants of health (SEDH) associated with county-level stroke mortality in the USA. We conducted a cross-sectional analysis of individuals aged ≥15 years who died from all stroke subtypes between 2016 and 2020. We analyzed 54 county-level SEDH possibly associated with age-adjusted stroke mortality rates/100,000 people. Classification and Regression Tree (CART) was used to identify specific county-level clusters associated with stroke mortality. Variable importance was assessed using Random Forest analysis. A total of 501,391 decedents from 2397 counties were included. CART identified 10 clusters, with 77.5% relative increase in stroke mortality rates across the spectrum (28.5 vs 50.7 per 100,000 persons). CART identified 8 SEDH to guide the classification of the county clusters. Including, annual Median Household Income ($), live births with Low Birthweight (%), current adult Smokers (%), adults reporting Severe Housing Problems (%), adequate Access to Exercise (%), adults reporting Physical Inactivity (%), adults with diagnosed Diabetes (%), and adults reporting Excessive Drinking (%). In conclusion, SEDH exposures have a complex relationship with stroke. Machine learning approaches can help deconstruct this relationship and demonstrate associations that allow improved understanding of the socio-environmental drivers of stroke and development of targeted interventions.

Clinical Reasoning: A 12-Year-Old Girl With Acute-Onset Diplopia, Dizziness, and Upbeat Nystagmus.

We report a case of a 12-year-old girl who presented with acute-onset diplopia, dizziness, and upbeat nystagmus. On examination, she had right internuclear ophthalmoplegia with right eye hypertropia and exotropia and impaired convergence. In addition, she also had spontaneous primary position symmetric upbeat nystagmus. In this report, we discuss the clinical approach with meticulous neuro-ophthalmologic examination and neuroanatomic localization in pediatric patients with acute-onset diplopia.

Epileptic negative myoclonus in herpes simplex virus encephalitis.

Epileptic negative myoclonus (ENM) is a rarely reported clinical seizure semiology. It is defined as a brief interruption of tonic muscle activity in association with an epileptiform discharge on the EEG (spike or sharp wave) without preceding myoclonia. The diagnosis of ENM requires a polygraphic recording with EEG and surface EMG electrodes covering the affected body part(s), while the muscles have tonic activity. Historically, ENM has been reported in a variety of chronic epilepsy syndromes such as benign epilepsy with centrotemporal spikes, progressive myoclonic epilepsy syndromes, symptomatic partial epilepsy syndromes due to structural pathologies, cryptogenic epilepsies, etc. In this paper, we report a patient with herpes simplex virus encephalitis who presented with multiple different seizure types including ENM. The patient showed significant improvement after treatment with acyclovir.

Pseudonystagmus in progressive supranuclear palsy.

Ocular oscillations often have critical role in diagnostic algorithm of neurodegenerative disorders. Nystagmus, if present in parkinsonian syndrome, suggests cerebellar involvement that is typical of multiple system atrophy. We found vertical jerky oscillations of the eyes during oculographic assessments using head-fixed corneal curvature trackers in six patients with progressive supranuclear palsy. The oscillations were eliminated by adequate head stabilization of the patients. Although this phenomenon gave the initial impression of "downbeat nystagmus", the oscillations were phase locked and frequency matched with subtle jerky head oscillations. We interpreted such jerky eye oscillations as "pseudonystagmus" representing the vestibulo-ocular reflex in response to involuntary subtle jerky head oscillations in our patients. This study further emphasizes the importance of head stabilization during instrumented or clinical assessment of gaze holding.

A descriptive study of eye and head movements in versive seizures.

BACKGROUND: Versive seizures, consisting of forced, involuntary, sustained and unnatural turning of eyes and head toward one side, lateralize to the hemisphere contralateral to the direction of the eye and head turn. The characteristics of eye and head movements in version have been rarely and incompletely studied in spontaneous epileptic seizures as opposed to direct cortical stimulation studies. METHODS: We performed a single center retrospective analysis of a cohort of 28 patients with 43 seizures, who had been admitted to the adult epilepsy monitoring unit at University Hospitals Cleveland Medical Center between January 2009 and August 2020. We only included patients with clear, high-resolution seizure videos and interpretable EEG. RESULTS: The eye movements were conjugate and contralateral to the hemisphere of seizure onset in 100% of the focal-onset seizures. The eye movements were saccadic in 89.3% with a predominant vector in oblique upward direction in 86.8% of the seizures. Head deviation was present in 100% of the seizures and the eyes and head deviated in the same direction in 97.6% of the seizures. In addition to deviation along the horizontal meridian, there was a vertical component to the head deviation as well, as evidenced by movement of the chin upward along the vertical axis in 93% of the seizures, thus indicating strong activation of the sternocleidomastoid muscle ipsilateral to the hemisphere of seizure onset. Concomitant facial motor activity ipsilateral to the direction of version was seen in 93% of the seizures. The most common pattern was a clonic superimposed on tonic facial contraction. DISCUSSION: Version remains a reliable and highly lateralizing sign. The majority of the eye movements during version occur in a saccadic fashion rather than one smooth movement, mostly in an oblique upward direction. Head deviation is very closely associated with eye deviation, thus indicating a common symptomatogenic zone for both, which is most likely the frontal eye field. A high concurrence of ipsilateral facial motor activity with version is likely because of close proximity of the frontal eye field to the face area in the primary motor cortex.

Residual symptoms and long-term outcomes after all-cause autoimmune encephalitis in adults.

BACKGROUND AND OBJECTIVES: To evaluate residual symptoms after all-cause autoimmune encephalitis in a real-life outpatient setting and compare long-term outcome measures. A secondary objective was to identify correlates of poor outcomes. METHODS: We analyzed patients referred to the Neuroimmunology clinic for evaluation of autoimmune encephalitis for whom standardized data were collected. We compared the prevalence of symptoms at the latest follow-up to presentation and calculated symptom improvement rates. We compared the Modified Rankin Scale (mRS) to the Clinical Assessment Scale for Autoimmune Encephalitis (CASE). Non-parametric Wilcoxon rank sum tests and Fisher's exact tests were used to compare clinical attributes between patients with and without poor outcomes. RESULTS: We evaluated 54 patients from 2017 to 2021 of whom 33 met inclusion criteria (average age 47±20 years, 57% females, 55% seropositive). By latest follow-up, 94% improved compared to presentation but six patients (18%) had poor outcomes as defined by an mRS ≥3. The most common residual symptoms were cognitive and mood dysfunction. The highest improvement rates were in alertness and psychosis while the lowest were in motor function and ataxia. CASE had moderate correlation with mRS (r2 = 0.53 [95%CI:0.23,0.74, p = 0.0015) but it captured more nuances than mRS at both presentation and follow-up. Older age and higher post-treatment CASE score correlated with poor outcomes. DISCUSSION: Most autoimmune encephalitis patients experience symptom improvement post-treatment. The CASE score was more representative of the wide symptomatic spectrum of autoimmune encephalitis and correlated with poor outcomes. However, CASE did not capture patients with dysautonomia, sleep dysfunction, or death.

Confounders in the Interpretation of Paraneoplastic and Neuronal Autoantibody Panels.

The recent discovery of several neuronal autoantibodies linked to neurologic syndromes that are fully or partially responsive to immunosuppressive therapy has revolutionized neuroimmunology and expanded the scope of classical paraneoplastic and antibody-related syndromes. A great deal of understanding of the techniques of neuronal antibody testing, the sensitivity and specificity of serum and cerebrospinal fluid sampling, and the value of the specific type and titer of each antibody is imperative. This article provides an overview of neuronal antibody and paraneoplastic panel testing with emphasis on how to differentiate clinically relevant from clinically irrelevant results and the downstream implications of those results.

Concurrent Atlantoaxial Septic Arthritis and Septic Thrombosis of the Ophthalmic Vein due to Staphylococcus aureus: A Case Report and Review of the Literature.

Atlantoaxial joint septic arthritis and superior ophthalmic vein thrombosis are uncommon manifestations of Staphylococcus aureus infection. A 68-year-old man presented with acute-onset neck pain and diplopia. Imaging studies revealed atlantoaxial septic arthritis and right superior ophthalmic vein thrombosis. Blood cultures grew methicillin-susceptible S. aureus. We review the literature describing these 2 uncommon manifestations of a common pathogen.