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Objective: To define the prevalence of psychiatric symptoms of anxiety and depression in patients at the time of their first seizure presentation to a neurologist. Methods: Our pilot study uses a cohort approach with multimodal data (clinical, social, structural [3T magnetic resonance imaging], and functional [electroencephalogram]). We screened 105 patients referred to the Halifax First Seizure Clinic between 2014 and 2016 and 51 controls. All participants completed two screening questionnaires: Neurological Disorders Depression Inventory for Epilepsy and Generalized Anxiety Disorder 7-Item. After applying the exclusion criteria, the study population consisted of 57 patients with unprovoked first seizure and 31 controls. The prevalence of anxiety and depression was based on cutoff scores of >15 and >14 respectively. Results: Unprovoked first seizure patients showed higher prevalence of depression (33%) compared with control (6%) with an odds ratio (OR) of 2.75 (95% confidence interval [CI], 0.72-10.5). There was no significant difference in the prevalence of anxiety between control subjects (9.7%) and unprovoked first seizure patients (23%). Subcategory analysis conducted after diagnosis confirmation revealed significantly increased OR of depression in patients diagnosed with new-onset epilepsy (OR, 11.6; 95% CI, 2.1-64.0) and newly diagnosed epilepsy (OR, 20.0; 95% CI,2.2-181), but not first seizure only patients (OR, 2.2; 95% CI,0.28-17.6) compared with control. Conclusions: Our study supports a bidirectional relationship between the first seizure and depression. Prevalence rate of depression increased with duration of undiagnosed epilepsy at the time of first clinical assessment.

Epilepsy is a neurologic condition which often occurs with other neurologic and psychiatric disorders. The relation between epilepsy and these conditions is complex. Some population-based studies have identified a bidirectional relation, whereby not only patients with epilepsy are at increased risk of suffering from some of these neurologic and psychiatric disorders (migraine, stroke, dementia, autism, depression, anxiety disorders, Attention deficit hyperactivity disorder (ADHD), and psychosis), but also patients with these conditions are at increased risk of suffering from epilepsy. The existence of common pathogenic mechanisms has been postulated as a potential explanation of this phenomenon. To reassess the relationships between neurological and psychiatric conditions in general, and specifically autism, depression, Alzheimer's disease, schizophrenia, and epilepsy, a recent meeting brought together basic researchers and clinician scientists entitled “Epilepsy as a Network Disorder.” This was the fourth in a series of conferences, the “Fourth International Halifax Conference and Retreat”. This manuscript summarizes the proceedings on potential relations between Epilepsy on the one hand and autism and depression on the other. A companion manuscript provides a summary of the proceedings about the relation between epilepsy and Alzheimer's disease and schizophrenia, closed by the role of translational research in clarifying these relationships. The review of the topics in these two manuscripts will provide a better understanding of the mechanisms operant in some of the common neurologic and psychiatric comorbidities of epilepsy.

Purpose A first seizure can result in significant uncertainty, fear and apprehension. One of the key roles of the clinician in the setting of first seizure is to provide accurate, timely information and counselling. Method We review the numerous components to be considered when counselling an adult patient after a first seizure. Results We provide a framework and manner to provide that counselling. We focus on an individualized approach and provide recommendations and information on issues of diagnosis, etiology, prognosis, the role and importance of medical testing, lifestyle considerations, driving, medication and other key counselling considerations. Conclusion Accurate, timely counselling can allay fears and anxieties, remove misconceptions and reduce the risk for injury in seizure recurrence.

Multiple sclerosis (MS) is characterized by demyelinated and inflammatory lesions in the brain and spinal cord that are highly variable in terms of cellular content. Here, we used imaging mass cytometry (IMC) to enable the simultaneous imaging of 15+ proteins within staged MS lesions. To test the potential for IMC to discriminate between different types of lesions, we selected a case with severe rebound MS disease activity after natalizumab cessation. With post-acquisition analysis pipelines we were able to: (1) Discriminate demyelinating macrophages from the resident microglial pool; (2) Determine which types of lymphocytes reside closest to blood vessels; (3) Identify multiple subsets of T and B cells, and (4) Ascertain dynamics of T cell phenotypes vis-à-vis lesion type and location. We propose that IMC will enable a comprehensive analysis of single-cell phenotypes, their functional states and cell-cell interactions in relation to lesion morphometry and demyelinating activity in MS patients., eLife digest It takes an army of immune cells to defend the body against infection. But sometimes the body’s immune system mistakenly attacks its own cells and chronic inflammatory conditions develop. In multiple sclerosis – also known as “MS” – a horde of immune cells infiltrate the brain and spinal cord, forming lesions which strip nerve cells of their insultation, a protective fatty material called myelin. Nerve cells become damaged, scarred and exposed, and this interferes with messages between the brain and other parts of the body. Advanced imaging techniques have revolutionized the diagnosis of multiple sclerosis by capturing lesions as they develop in the brain and spinal cord. Researchers have also focused their efforts on understanding how immune cells activated in the blood stream invade the central nervous system. To better understand how a mistaken immune response leads to nerve damage in multiple sclerosis, a forensic examination of which immune cells accumulate in brain tissue to form lesions is needed. Standard techniques for analyzing whole tissue samples are however limited by design, capable of detecting only a few cell markers in one section of tissue. Ramaglia et al. have now validated a new imaging technique for looking at an array of cell types in brain tissue in a single sample. The technique – called imaging mass cytometry (or IMC for short) – was used to look at post-mortem brain tissue from a multiple sclerosis patient with an acute form of the illness. The tissue examined had multiple sclerosis lesions present. Different types of immune cells were simultaneously identified and characterized using a panel of antibodies which recognize the signature proteins each immune cell makes when active. The state of the underlying myelin content of the tissue was also characterized. The imaging approach could distinguish between the immune cells of the brain (known as resident microglia) and a type of white blood cell summoned as part of the immune response (infiltrating macrophages). The analysis showed that, in the particular patient examined, microglia are abundant in active lesions in multiple sclerosis; also, different subsets of white blood cells were detected. Measuring how far different immune cells had migrated from nearby blood vessels added insights as to how immune cells move through the brain and which cells may have arrived first. Altogether, Ramaglia et al. have shown that IMC can be used as a discovery tool to gain a deeper understanding of multiple sclerosis lesions and immune cells active in the inflamed brain. Further work will apply this now validated imaging approach to large cohorts of multiple sclerosis patients.

Multiple Sclerosis (MS) is characterized by demyelinated and inflammatory lesions in the brain and spinal cord. Lesions contain immune cells with variable phenotypes and functions. Here we use imaging mass cytometry (IMC) to enable the simultaneous imaging of 15+ proteins within 11 staged MS lesions. Using this approach, we demonstrated that the majority of demyelinating macrophage-like cells in active lesions were derived from the resident microglial pool. Although CD8+ T cells predominantly infiltrated the lesions, CD4+ T cells were also abundant but localized closer to blood vessels. B cells with a predominant switched memory phenotype were enriched across all lesion stages and were found to preferentially infiltrate the tissue as compared to unswitched B cells which localized to the vasculature. We propose that IMC will enable a comprehensive analysis of single-cell phenotypes, their functional states and cell-cell interactions in relation to lesion morphometry and demyelinating activity in the MS brain.

Assessment of a first seizure (FS) presentation requires a comprehensive and systematic approach to address the complexity of this condition and all of the open questions with regards to accurate interpretation of the initial event, necessary diagnostic steps, prognosis and need for antiepileptic drugs (AED). Counseling about key life style issues and safety considerations in daily life are a major component in the first meeting; which should allow enough time to help to create trust in this vulnerable situation. “Treatment” in this review is therefore used in a holistic way and is not restricted to medication only. Pharmacological treatment of a FS aims to restore normal neuronal function and helps to suppress further seizures. Choosing pharmacological intervention must be guided by incorporating all available clinical information, structural–functional relationships, the underlying pathology, which may specifically include a treatable systematic disease, and the individual's requirements and inclination. Pharmacological treatment should always be considered if the index seizure is not the “first seizure” but actually reflects newly diagnosed epilepsy. AED treatment after a FS is also reasonable, if additional functional and structural tests suggest an epileptic process or if comorbid medical conditions exist (e.g. polytrauma, anticoagulation in an elderly patient with prior stroke) in which any further seizure would lead to additional harm. A comprehensive systematic approach incorporating 10 key principles is presented.

Background:Seizures while driving are a well known occurrence in established epilepsy and have significant impact on driving privileges. There is no data available on patients who experience their first (diagnosed) seizure while driving (FSWD).Method:Out of 311 patients presenting to the Halifax First Seizure Clinic between 2008 and 2011, 158 patients met the criteria of a first seizure (FS) or drug-naïve, newly diagnosed epilepsy (NDE). A retrospective chart review was conducted. FSWD was evaluated for 1) prevalence, 2) clinical presentation, 3) coping strategies, and 4) length of time driving before seizure occurrence.Results:The prevalence of FSWD was 8.2%. All 13 patients experienced impaired consciousness. Eleven patients had generalized tonic-clonic seizures, one starting with a déjà-vu evolving to visual aura and a complex partial seizure; three directly from visual auras. Two patients had complex partial seizures, one starting with an autonomic seizure. In response to their seizure, patients reported they were i) able to actively stop the car (n=4, three had visual auras), ii) not able to stop the car resulting in accident (n=7), or iii) passenger was able to pull the car over (n=2). One accident was fatal to the other party. Twelve out of 13 patients had been driving for less than one hour.Discussion:FSWD is frequent and possibly underrecognized. FSWD often lead to accidents, which occur less if preceded by simple partial seizures. Pathophysiological mechanisms remain uncertain; it is still speculative if complex visuo-motor tasks required while driving play a role in this scenario.

Objective: “Epilepsy in the elderly (EE)” is considered a homogeneous, benign syndrome in patients aged > 60 years, with cerebrovascular disease as the most frequent etiology. We challenge this concept by comparing EE and middle-aged adults with epilepsy (MAE). Methods: We compared: 1) seizure dynamics, 2) MRI lesions, 3) EEG findings and 4) treatment course in EE and MAE at the Halifax First Seizure Clinic. Results: 48 EE patients aged > 60.2 years (median 66.9 years). 31 MAE patients aged 50.2 – 59.6 years (median 55.1 years). Seizure dynamics in EE/MAE included first seizure in 50/54.8%, new onset epilepsy (new seizures within 12 months) in 43.8/35.5%, newly diagnosed epilepsy (seizures for >> 12 months) in 9.6/6.3%. First seizure evolved into new onset epilepsy in 12.5/3.2%. MRI in EE/MAE was normal in 22.5/27.6% or showed microangiopathy (25/38.5%), atrophy (10/15.4%), tumors (7.5/11.5%), vascular malformations (7.5/3.8%), hippocampal pathologies (0/3.8%), infarcts (12.5/0%). EEG in EE/MAE was normal in 64.4/65.5% or showed diffuse (6.6/3.5%) or focal slowing (8.8/7%), generalized (4.3/13.7%) or focal (15.4/10.4%) epileptiform activity. At 12 months, 87% of EE and 93.8% of MAE were seizure-free. Conclusions: EE and MAE show similar heterogeneity. We propose an etiology-driven classification of epilepsy syndromes in the aging brain.