Focal Disorders Research Articles

GABAB Receptors: are they Missing in Action in Focal Epilepsy Research?

GABA, the key inhibitory neurotransmitter in the adult forebrain, activates pre- and postsynaptic receptors that have been categorized as GABAA, which directly open ligand-gated (or receptor-operated) ion-channels, and GABAB, which are metabotropic since they operate through second messengers. Over the last three decades, several studies have addressed the role of GABAB receptors in the pathophysiology of generalized and focal epileptic disorders. Here, we will address their involvement in focal epileptic disorders by mainly reviewing in vitro studies that have shown: (i) how either enhancing or decreasing GABAB receptor function can favour epileptiform synchronization and thus ictogenesis, although with different features; (ii) the surprising ability of GABAB receptor antagonism to disclose ictal-like activity when the excitatory ionotropic transmission is abolished; and (iii) their contribution to controlling seizure-like discharges during repetitive electrical stimuli delivered in limbic structures. In spite of this evidence, the role of GABAB receptor function in focal epileptic disorders has been attracting less interest when compared to the numerous studies that have addressed GABAA receptor signaling. Therefore, the main aim of our mini-review is to revive interest in the function of GABAB receptors in focal epilepsy research.

КЛИНИЧЕСКОЕ НАБЛЮДЕНИЕ СИНДРОМА ШИММЕЛЬПЕННИНГА–ФОЙЕРШТЕЙНА–МИМСА В СОЧЕТАНИИ С РАБДОМИОСАРКОМОЙ

The authors represent the clinical case observation of the Schimmelpenning-Feuerstein-Mims syndrome, a congenital dermatological-neurological disease, which includes an organoid epidermal nevus with a wide range of multiple organ dysfunction (neurological, skeletal, cardiovascular, ophthalmological and urological), complicated by the development of rhabdomyosarcoma in a patient. The predominant neurological manifestations of the syndrome are as follows: epilepsy, intellectual and focal disorders. The authors pay specialists’ attention to the complexity of establishing diagnosis and the importance of an interdisciplinary approach in the diagnosis and management in such kind of patients.

Corticotropin Releasing Factor Mediates KCa3.1 Inhibition, Hyperexcitability, and Seizures in Acquired Epilepsy.

Temporal lobe epilepsy (TLE), the most common focal seizure disorder in adults, can be instigated in experimental animals by convulsant-induced status epilepticus (SE). Principal hippocampal neurons from SE-experienced epileptic male rats (post-SE neurons) display markedly augmented spike output compared with neurons from nonepileptic animals (non-SE neurons). This enhanced firing results from a cAMP-dependent protein kinase A-mediated inhibition of KCa3.1, a subclass of Ca2+-gated K+ channels generating the slow afterhyperpolarizing Ca2+-gated K+ current (IsAHP). The inhibition of KCa3.1 in post-SE neurons leads to a marked reduction in amplitude of the IsAHP that evolves during repetitive firing, as well as in amplitude of the associated Ca2+-dependent component of the slow afterhyperpolarization potential (KCa-sAHP). Here we show that KCa3.1 inhibition in post-SE neurons is induced by corticotropin releasing factor (CRF) through its Type 1 receptor (CRF1R). Acute application of CRF1R antagonists restores KCa3.1 activity in post-SE neurons, normalizing KCa-sAHP/IsAHP amplitudes and neuronal spike output, without affecting these variables in non-SE neurons. Moreover, pharmacological antagonism of CRF1Rs in vivo reduces the frequency of spontaneous recurrent seizures in post-SE chronically epileptic rats. These findings may provide a new vista for treating TLE.SIGNIFICANCE STATEMENT Epilepsy, a common neurologic disorder, often develops following a brain insult. Identifying key cellular mechanisms underlying acquired epilepsy is critical for developing effective antiepileptic therapies. In an experimental model of acquired epilepsy, principal hippocampal neurons manifest hyperexcitability because of downregulation of KCa3.1, a subtype of Ca2+-gated K+ ion channels. We show that KCa3.1 downregulation is mediated by corticotropin releasing factor (CRF) acting through its Type 1 receptor (CRF1R). Congruently, acute application of selective CRF1R antagonists restores KCa3.1 channel activity, leading to normalization of neuronal excitability. In the same model, injection of a CRF1R antagonist to epileptic animals markedly decreases the frequency of electrographic seizures. Therefore, targeting CRF1Rs may provide a new strategy in the treatment of acquired epilepsy.

Особенности клинического течения диабетической ретинопатии при миопии

This review presents the results of a study of patients with diabetic retinopathy (DR) suffering from myopia. It is shown that in patients with different variants of the length of the anterior-posterior part of the eye, the contraction, development and progression of DR occurs in different ways. Thus a number of authors note that DR generally does not develop in patients with high myopia. Some attribute this to impairment of circulation in the retinal stretching of the myopic eye, others to the concentration of vascular endothelial growth factor (VEGF), which is significantly lower in eyes with a longer axis or greater myopic refraction, and others to a focal continuity disorder in the pigment epithelium layer, in which metabolic products are removed through the choroid and sclera, as a result of which local acidosis, venous statis don’t develop, and the barrier function of the vascular endothelium is not disturbed. Key words: diabetic retinopathy, myopia, anterior and posterior segment, vascular endothelial growth factor, emmetropia, hypermetropia, diabetes mellitus

FOCAL EPILEPSY AND EXECUTIVE DYSFUNCTION IN AUTISM SPECTRUM DISORDER (ASD)

Recent advances in neuroscience have allowed researchers to introduce functional neuromarkers of autism spectrum disorders (ASD) into clinical practice. Most promising are studies of brain work in milliseconds, such as quantitative EEGs, event-related potentials (ERPs), low resolution electromagnetic tomography(sLORETA), especially when it is possible to use Human Brain Index (HBI) methodology to compare test results obtained by a child with ASD with the normative database. The use of HBI methodology make possible to determine functional neuromarkers of ASD and comorbidities, such as epilepsy, impaired cognitive and emotional control or executive function (FF) disorders. Such procedure can contribute to more effective diagnosis, as well as provide personalized care for patients with ASD. In this case study we use the HBI methodology for more effective diagnosis of the child with ASD (level 2) with focal epilepsy and EF dysfunction in hope that we can provide more effective therapies which might improve her quality of life. We present the case of a 11-years-old girl with an initial diagnosis of ASD with focal epilepsy and EF dysfunction. The patient was sent to the Teaching-Reintegration Centre in Kraków with remarks that she simply could not function in everyday life. A neuropsychological examination using standardized batteries to assess the girl's cognitive, emotional and social functioning confirmed the presence of ASD (level 2), and co-occurring executive function disorders (EF). She was also analyzed from the clinical EEG perspective as well as from the QEEG/ERPs perspective and current coexistence of 3 Hz Spike-Wave Discharges on EEG and focal epilepsy was found. In the examination several episodes of 3 Hz paroxysms were found in the ventro-lateral prefrontal cortex (BA 11) in 40 min EEG recoding in Eyes open, Eyes closed as well as in task conditions. The patient’s ERPs showed that to the first stimulus (continue cue) temporal P2 wave with larger duration and longer latency was elicited in comparison to the average of the norm for her age from the Human Brain Index (HBI) normative database at Chur, Switzerland. The P30 cue was smaller in the patient than in the healthy controls from HBI and statistically significant deviations from the average were found. Also in response to NOGO stimulus no positive parietal-central P3 was observed, which appears in the ERPs of ealthy controls from HBI. The ERPs differences in the VCPT show statistically significant deviations in the patient’s brain function when compared to the ealthy controls from HBI. It should be stressed that the number of trials for the first stimulus presentation and NOGO condition were large enough for computing reliable ERPs, as it was indicated by Kropotov (2009; 2016). HBI methodology was helpful in finding functional neuromarkers of co-existence of 3 Hz Spike-Wave Discharges on EEG with focal epilepsy and EF disorder in girl with ASD (level 2). Therefore, it was possible to offer more effective rehabilitation of the disorders, which will contribute to the integration of the self system and better quality of her life.

Is Altered Oculomotor Control during Smooth Pursuit Neck Torsion Test Related to Subjective Visual Complaints in Patients with Neck Pain Disorders?

Subjective visual complaints are commonly reported in patients with neck pain, but their relation to objectively measured oculomotor functions during smooth pursuit neck torsion tests (SPNTs) has not yet been investigated. The aim of the study was to analyse classification accuracy of visual symptom intensity and frequency based on SPNT results. Forty-three patients with neck pain were referred by orthopaedic outpatient clinics where they were required to fill out 16-item proformas of visual complaints. Infrared video-oculography was used to measure smooth pursuit eye movements during neutral and neck torsion positions. Parameters of gain and SPNT difference (SPNTdiff) were taken into the Naïve Bayes model as classifiers, while intensity and frequency of visual symptoms were taken as predicted class. Intensity and, to a lesser degree, frequency of visual symptoms previously associated with neck pain or focal vision disorders (computer vision syndrome) showed better classification accuracy using gain at neck torsion position, indicating cervical driven visual disturbances. Moreover, SPNTdiff presented with slightly lower classification accuracy as compared to gain at neck torsion position. Our study confirmed the relationship between cervical driven oculomotor deficits and some visual complaints (concentrating to read, words moving on page, blurred vision, difficulty judging distance, sore eyes, heavy eyes, red eyes, and eyes strain).

Диагностика и лечение нисходящего оптического неврита как проявления локального вирусного энцефалита (клиническое наблюдение)

It is well known that the incidence of encephalitis and optic neuritis is relatively high worldwide. Moreover, it is associated with high mortality and disability rates. At the same time, in 45–75% of cases, optic neuritis affects the central nervous system causing its disorders of various severity. Unfortunately, for practicing ophthalmologists and neurologists it is difficult to find a relationship between optical neuritis and inflammation of the brain tissue (especially when it is limited by a certain part of the brain) which underlies the diagnosis of opticoencephalitis. In this context, an ophthalmologist who can use methods of ophthalmological diagnostics will play a more important role. The ophthalmologist will be able to arrive at a topical diagnosis and localize a level of the brain tissue lesion, which is essential for determining the disease but cannot be done by neurologist. This publication presents our own clinical observation describing the specific aspects of diagnosis and treatment of descending optic neuritis co-occurring with viral inflammation of the brain tissue. The article provides analysis of the clinical signs which both impeded and facilitated the process of making the accurate diagnosis. It should be recognized that during the process of opticoencephalitis development, its ophthalmic manifestations for a long time will not only remain a single sign of this focal neurological disorder, but will require timely initiation of etiotropic drugs, using the appropriate routes of administration, doses, and duration of treatment. Thus, it is important to be aware and prepared for detecting viral encephalitis (opticoencephalitis) even at the slightest suspicion for a descending pathway of the diagnosed inflammation of the eye tissues. Keywords: optical neuritis, encephalitis, herpes virus, markers, antibodies, vesicles, ophthalmoscopy, perimetry. For citation: Korsakova N.V., Korsakova E.I. Diagnosis and treatment of descending optic neuritis developed as a manifestation of local viral encephalitis (a clinical case). Russian Journal of Clinical Ophthalmology. 2022;22(4):273–278 (in Russ.). DOI: 10.32364/2311-7729- 2022-22-4-273-278.

Contrast-induced encephalopathy and nonconvulsive status epilepticus after diagnostic cerebral angiography in an end-stage renal disease patient

A 70-year-old man with a history of recurrent ischemic stroke and end-stage renal disease was admitted to the neurology department for a transient ischemic attack. The patient underwent transfemoral cerebral angiography with iopamidol to evaluate the status of carotid stenosis. On the same day, the patient developed drowsy mentality, global aphasia, and fever. Electroencephalography showed continuous regional rhythmic delta activities (0.5 to 1.0 Hz) without definite spatiotemporal evolution, suggestive of focal seizure disorder arising from the left temporal area and ictal-interictal continuum. Computed tomography perfusion images showed hyperperfusion in the left hemisphere. The patient was diagnosed with contrast-induced encephalopathy and associated nonconvulsive status epilepticus. The patient was treated with oral lacosamide, levetiracetam, and daily hemodialysis. The patient’s mental status recovered after 8 days of intensive care unit care.

Serotype-dependent recombinant adeno-associated vector (AAV) infection of Epstein\u2013Barr virus-positive B-cells, towards recombinant AAV-based therapy of focal EBV\u2009+\u2009lymphoproliferative disorders

BackgroundB-cell proliferative disorders, such as post-transplant lymphoproliferative disease (PTLD), are increased among persons afflicted by T-cell compromise. Most are Epstein–Barr virus (EBV) + and can first present with a focal lesion. Direct introduction of oncolytic viruses into localized tumors provides theoretical advantages over chemotherapy, immunotherapy and radiation therapy by reducing systemic toxicity. Despite extensive study as a vehicle for gene therapy, adeno-associated viruses (AAV) have rarely been applied to human cancer research due to technical and theoretical obstacles. Moreover, human B-cells have historically been described as resistant to AAV infection. Nonetheless, advances using different recombinant (r)AAV serotypes with unique tropisms to deliver cytotoxic therapy suggested a localized anti-tumor approach was feasible.MethodsAs a prelude to the development of a therapeutic vehicle, the ability of fifteen distinct EGFP-bearing rAAV serotypes to transduce human B-cells, including primary, immortalized, and B-cell tumor lines ± EBV was assessed by confocal microscopy, flow cytometry and subsequently cell viability assay.ResultsRank order analysis revealed augmented transduction by rAAV6.2 and closely related virions. EBV infection of EBV-negative B-cell tumor lines and EBV immortalization of primary B-cells increased susceptibility to rAAV6.2 transduction. As a proof of concept, transduction by rAAV6.2 encoding herpes simplex virus type 1 (HSV1)-thymidine kinase (TK) eliminated TK-negative rhabdomyosarcoma cells and diminished viability of transduced B-cell lines upon incubation with ganciclovir.ConclusionsrAAV serotypes differentially transduce human B-cell lines reversing the dogma that human B-cells are refractory to AAV infection. EBV + B-cells display increased susceptibility to rAAV6.2 infection, uncovering a new method for improved nucleic acid transfer into transfection-resistant B-cell lines. The introduction of a functional suicide gene into the rAAV6.2 genome identifies a candidate vector for the development of rAAV-based oncolytic therapy targeting focal EBV-bearing B-lymphoproliferative disorders.

Deep brain stimulation in primary Meige’s syndrome: a successful case report

Introduction: Meige’s Syndrome is a rare focal dystonia disorder characterized mainly by blepharospasm and orofacial dystonia. Dystonia is identified as a movement disorder, with abnormal involuntary movements and postures, caused by sustained or intermittent muscle contractions. Its pathophysiology is not fully elucidated, but it is known that its evolution is due to an abnormal excitability of the sensorimotor cortex and the interneural pathways of the brainstem, a genetic predisposition and environmental factors. Treatment includes various interventions, ranging from conservative approaches to invasive surgical procedures. Oral medications such as anticholinergics, dopamine antagonists and GABA receptor agonists shows positive results, also botulinum A injection can be used as treatment. If any of those conservative alternatives are not providing the required results, deep brain stimulation (DBS) of globus pallidus interna (GPi) provides an invasive neuromodulation that has been presenting improvement of symptoms in individuals with previous failure in other forms of treatment. Objectives: The purpose of this case report is to show the effectiveness of treatment with deep brain stimulation of GPi in a patient with Meige Syndrome that has undergone several other approaches previously. Because it is a surgical procedure, there are risks of adverse effects, but most of them can be minimized or even stopped by the correct programming of the intracerebral electrodes. This case report shows that the deep brain stimulation of Gpi is more efficient than other treatments when well indicated, besides having a better index of improvement when compared to the stimulation of the subthalamic nucleus. The authors do not have any conflict of interests. Case report: A 66-years-old man started suffering involuntary contractions of the orofacial muscles associated with blepharospasm that impaired his quality of life. He was diagnosed with Meige syndrome by a neurologist specialized in movement disorders. Before starting the treatment, he was extremely depressed with suicidal ideas and his psycho-affective relationship with family deteriorated since those symptoms started. Therefore, he was under follow-up with a psychologist and psychiatrist, who prescribed antidepressants Duloxetin 30 mg 12/12 oral and Nortriptyline 25 mg 12/12 oral. The patient was unresponsive to the conventional treatment. He had pharmacological treatment with Levodopa, Trazodone and Lorazepam without benefits. He also underwent several botulinum toxin applications for one year and two eyelid lift surgeries, also without success. He was referred to a functional neurosurgeon, who proceeded with the Gpi-DBS implantation in the patient, in February 2021, with an ActivRC generator. The surgery was performed with the patient awake and bilateral microrecording was used to help locate the target. After 4 weeks of surgery and correct programming of the electrodes - 3387 from Medtronic, 130 Hz, 90 PW, 2.5 mA, 1.5 mm2 contact area and 1.5 mm interelectrode spacing, with rechargeable battery -, the patient evolved with an improvement of 80% of the symptoms he presented before the surgical procedure.

Machine learning based liver disease diagnosis: A systematic review

The computer-based approach is required for the non-invasive detection of chronic liver diseases that are asymptomatic, progressive, and potentially fatal in nature. In this study, we review the computer-aided diagnosis of hepatic lesions in view of diffuse- and focal liver disorders. This survey mainly focuses on three image acquisition modalities: ultrasonography, computed tomography, and magnetic resonance imaging. We present the insightful analysis with pros and cons for each preliminary step, particularly preprocessing, attribute analysis, and classification techniques to accomplish clinical diagnostic tasks. In preprocessing, we explore and compare commonly used denoising, deblurring and segmentation methods. Denoising is mainly performed with nonlinear models. In contrast, deep neural networks are frequently applied for deblurring and automatic segmentation of region-of-interest. In attribute analysis, the most common approach comprises texture properties. For classification, the support vector machine is mainly utilized across three image acquisition modalities. However, comparative analysis shows the best performance is obtained by deep learning-based convolutional neural networks. Considering biopsy samples or pathological factors such as overall stage, margin, and differentiation can be helpful for improving the prediction performance. In addition, technique breakthrough is expected soon with advances in machine learning models to address data limitation problems and improve the prediction performance.

A-33 Pediatric Intraindividual Variability: Examining Dispersion across Cognitive Domains

Abstract Objective Intraindividual variability (IIV), defined as variability in performance across different cognitive domains within an individual, has been studied in adults and found to be linked to sex, age, and mean cognitive performance, and associated with developmental disorders (e.g., ADHD), focal disorders, and cognitive decline. In contrast, IIV in children is thought to be related to cognitive development rather than impairment, but has not been well studied with relation to differences across sex, age, diagnoses, or mean cognitive performance. Method Participants included 426 children/young adults (ages 3–25; M = 11.75, SD = 4.01; 62.3% male) referred for neuropsychological evaluation at a hospital-based outpatient clinic. A battery of tests was administered measuring several domains, including intelligence, academics, attention, executive functions, language, memory, visual motor integration, and fine motor skills. Intraindividual standard deviation (ISD) and maximum deviation (MD) were used as measures of IIV. Results Sex was not related to ISD or MD, ts(423) = −1.15 – -0.09, ps = 0.251–0.930. Age, measured categorically, was not related to ISD, F(3) = 0.07, p = 0.974, but was related to MD, F(3) = 3.45, p = 0.017 with children age 3–5 having lower MD. ADHD diagnosis was not related to ISD or MD, ts(417) = −1.25 – −1.19, ps = 0.211–0.234. An inverse relationship was observed between mean cognitive performance and ISD, F(1) = 36.43, p < 0.001, and MD, F(1) = 25.92, p < 0.001. Conclusions The current study did not replicate differences in IIV based on sex or diagnosis of ADHD in children. However, differences based on age and mean cognitive performance are consistent with previous literature, suggesting that IIV may reflect differences in cognitive development, secondary to both skill and age, in children.

Neurogenic Laryngeal Disorders

The larynx is critical to performing complex tasks of airway protection, phonation, respiration, and deglutition. Various focal and systemic neurologic disorders impact the larynx, causing deficits that lead to dysfunction in voice, speech, breathing, and swallowing function. The most common hyperfunctional neurolaryngeal disorders include spasmodic dysphonia (laryngeal dystonia), essential vocal tremor, and muscle tension dysphonia. Some hypofunctional neurolaryngeal disorders include parkinsonian disorders, neuromuscular junction diseases, and myopathies. A multidisciplinary approach involving evaluation by neurologists, voice-trained otolaryngologists and speech-language pathologists is often key to diagnosis and treatment of these challenging and sometimes lifelong disorders. Botulinum toxin injection into the laryngeal musculature is currently the gold-standard treatment for both spasmodic dysphonia and vocal tremor. However, much research is being conducted to advance less invasive and more definitive medical and surgical treatment interventions. This review contains 3 figures, 11 videos, 6 tables and 29 references Keywords: laryngeal neurophysiology, laryngeal dystonia, adductor spasmodic dysphonia, abductor spasmodic dysphonia, essential vocal tremor, hyperfunctional voice disorders, hypofunctional voice disorders, botulinum toxin injection

Evaluation of Eeg Pattern and Seizure Types of Genetic Dysmorphic Syndromes: Report of 50 Patients and Review of the Literature

Many chromosomal anomalies manifest with epilepsy. Only few typical EEG and seizure type have been identified in genetic syndromes. Identification of typical seizure and EEG findings of certain genetic syndromes may serve as a guide for genetic analysis. This study aims to find typical EEG paterns of spesific genetic syndromes. The study enrolled 50 patients aged 0-16 years with a diagnosis of epilepsy and genetic syndrome in between 2014-2017 at the Dr. Behçet UZ Children’s Hospital Pediatric Neurology and Medical Genetics departments. Patients' characteristics and dysmorphic features were retrieved from Medical Genetic outpatient clinic patient files, while seizure type, epileptic syndromic classification, EEG and brain MRI findings, age at onset and frequency of seizure were determined from pediatric neurology follow-ups. Fifty patients (29 girls) with a mean age of 6.52 ±3.67 years (max=16, min=1) were enrolled. Twenty-two patients had microdeletion-duplication (44%), 12 had chromosomal anomalies (24%) and 16 had monogenic syndrome (32%). Pathology was present in the EEGs of 40 patients (80%). Focal epileptic disorder was determined in 28 subjects (56%), epileptic encephalopathy in 7 (14%), and generalized epileptic disorder in 5 (10%) Identification of seizure type and EEG pattern specific to each genetic dysmorphic syndrome may give clues to clinicians in recognizing these syndromes. However, in order to detect other specific EEG patterns, there is a need for multicentre studies with more patients.

On seizure semiology.

The clinical expression of seizures represents the main symptomatic burden of epilepsy. Neural mechanisms of semiologic production in epilepsy, especially for complex behaviors, remain poorly known. In a framework of epilepsy as a network rather than as a focal disorder, we can think of semiology as being dynamically produced by a set of interconnected structures, in which specific rhythmic interactions, and not just anatomical localization, are likely to play an important part in clinical expression. This requires a paradigm shift in how we think about seizure organization, including from a presurgical evaluation perspective. Semiology is a key data source, albeit with significant methodological challenges for its use in research, including observer bias and choice of semiologic categories. Better understanding of semiologic categorization and pathophysiological correlates is relevant to seizure classification systems. Advances in knowledge of neural mechanisms as well as anatomic correlates of different semiologic patterns could help improve knowledge of epilepsy networks and potentially contribute to therapeutic innovations.

Epidemiology and clinical characteristics of Klebsiella spp. meningitis in France

ObjectivesTo describe the epidemiology of Klebsiella spp. meningitis in France with respect to clinical and bacteriological data. MethodsWe performed a four-year multicenter, retrospective, observational study. The primary objective was to provide a clinical description of patients with Klebsiella spp. meningitis. Secondary objectives were to compare community-acquired meningitis and healthcare-associated meningitis and to analyze factors associated with mortality. ResultsWe enrolled 131 patients with Klebsiella spp. meningitis. Eighty-two (62.6%) infections were reported following neurosurgery. Twenty-eight strains (21.4%) were resistant to third-generation cephalosporins (3GC). The median [IQR] cellularity was 980/mm3 [116–5550], the median protein level was 5.67 [1.62–9] g/L and the median CSF glucose level was 2.5 [0–3.4] mmol/L. The in-hospital mortality rate was 23.6%. Community-acquired meningitis isolates were more frequently susceptible to 3GC than isolates from healthcare-associated meningitis (89.2% versus 72%; P=0.04). Comorbidities reported for patients with community-acquired meningitis were mainly diabetes mellitus and liver cirrhosis. In multivariate analysis, focal neurological disorder at the time of diagnosis was the only factor associated with in-hospital mortality (P=0.01). ConclusionsPurulent meningitis caused by Klebsiella spp. needs to be considered in patients with community-acquired meningitis and preexisting conditions, as well as in case of meningitis following neurosurgical procedures.

Dementia, Subtype of Seizures, and the Risk of New Onset Seizures: A Cohort Study.

Seizure disorders have been identified in patients suffering from different types of dementia. However, the risks associated with the seizure subtypes have not been characterized. To compare the occurrence and risk of various seizure subtypes (focal and generalized) between patients with and without a dementia diagnosis. Data from 40.7 million private insured patient individual electronic health records from the U.S., were utilized. Patients 60 years of age or more from the Optum Insight Clinformatics-data Mart database were included in this study. Using ICD-9 diagnoses, the occurrence of generalized or focal seizure disorders was identified. The risk of new-onset seizures and the types of seizures associated with a dementia diagnosis were estimated in a cohort of 2,885,336 patients followed from 2005 to 2014. Group differences were analyzed using continuity-adjusted chi-square and hazard ratios with 95%confidence intervals calculated after a logistic regression analysisResults:A total of 79,561 patient records had a dementia diagnosis, and 56.38%of them were females. Patients with dementia when compared to those without dementia had higher risk for seizure disorders [Hazard ratio (HR) = 6.5 95%CI = 4.4-9.5]; grand mal status (HR = 6.5, 95%CI = 5.7-7.3); focal seizures (HR = 6.0, 95%CI = 5.5-6.6); motor simple focal status (HR = 5.6, 95%CI = 3.5-9.0); epilepsy (HR = 5.0, 95%CI = 4.8-5.2); generalized convulsive epilepsy (HR = 4.8, 95%CI = 4.5-5.0); localization-related epilepsy (HR = 4.5, 95%CI = 4.1-4.9); focal status (HR = 4.2, 95%CI = 2.9-6.1); and fits convulsions (HR = 3.5, 95%CI = 3.4-3.6). The study confirms that patients with dementia have higher risks of generalized or focal seizure than patients without dementia.

Paget’s Disease of Bone Affecting Site With Orthopedic Hardware

Introduction: Paget’s disease of bone is a focal disorder of accelerated bone remodeling which leads to bone hypertrophy, cortical expansion and abnormal bone architecture. Either a single bone (monostotic) or multiple bones (polyostotic) can be affected. Although it has been suggested to be caused by a chronic slow viral infection of the bone, a cause and effect relationship has not been clearly established. Therefore, the etiology of Paget’s disease remains an uncertain and controversial topic of discussion. Case Description: A 62-year-old African American male with a past medical history of a left tibial fracture presented with worsening left leg pain for the past 6 months. He denied any recent traumatic events, falls or strenuous physical activity. Since the pain started, his ambulation had been significantly affected requiring the use of a cane for gait stability. His left tibial fracture occurred over 20 years ago after landing on another person’s foot while playing basketball. It was surgically treated with intramedullary nailing and metal rod insertion into the canal of the tibia. Since then, he remained an active person with no physical limitations or ailments until the recent developments that brought him to clinic. A left leg CT-Scan ordered for evaluation of the tibial hardware revealed cortical thickening, marrow expansion and coarse trabeculae throughout the majority of the tibia consistent with Paget’s disease. The hardware was intact with no peri-hardware lucency to suggest loosening or infection. His laboratory workup showed a normal alkaline phosphatase level (94 U/L; normal range 40 - 115 U/L) and low 25-OH Vitamin D level of 14. A Radionuclide Bone Scan done for evaluation of location and extent of bone disease resulted in diffusely abnormal uptake present in the left tibia with no other locations of suspicious uptake. After his 25-OH Vitamin D levels were replenished, a dose of Zoledronic acid IV infusion was given with significant improvement of pain several months after. Discussion: Paget’s disease of bone is the second most common bone disease after osteoporosis. Affected skeletal sites develop a disorganized mosaic of woven and lamellar bone more susceptible to deformities and fractures than normal bone. It is often asymptomatic, but classical features include bone pain experienced either at rest or with motion, cutaneous erythema and warmth. The goal of medical therapy is to relieve symptoms and to prevent future complications with high potency bisphosphonates. Although it is well known that Paget’s disease increase the risk of fractures, this case brings up an interesting take about the possibility of fractures managed with hardware placement increasing the risk of Paget’s disease in the involved site.

Localization of Epileptic Foci Based on Simultaneous EEG–fMRI Data

Combining functional magnetic resonance imaging (fMRI) and electroencephalography (EEG) enables a non-invasive investigation of the human brain function and evaluation of the correlation of these two important modalities of brain activity. This paper explores recent reports on using advanced simultaneous EEG–fMRI methods proposed to map the regions and networks involved in focal epileptic seizure generation. One of the applications of EEG and fMRI combination as a valuable clinical approach is the pre-surgical evaluation of patients with epilepsy to map and localize the precise brain regions associated with epileptiform activity. In the process of conventional analysis using EEG–fMRI data, the interictal epileptiform discharges (IEDs) are visually extracted from the EEG data to be convolved as binary events with a predefined hemodynamic response function (HRF) to provide a model of epileptiform BOLD activity and use as a regressor for general linear model (GLM) analysis of the fMRI data. This review examines the methodologies involved in performing such studies, including techniques used for the recording of EEG inside the scanner, artifact removal, and statistical analysis of the fMRI signal. It then discusses the results reported for patients with primary generalized epilepsy and patients with different types of focal epileptic disorders. An important matter that these results have brought to light is that the brain regions affected by interictal epileptic discharges might not be limited to the ones where they have been generated. The developed methods can help reveal the regions involved in or affected by a seizure onset zone (SOZ). As confirmed by the reviewed literature, EEG–fMRI provides information that comes particularly useful when evaluating patients with refractory epilepsy for surgery.

Asymptomatic active Paget bone disease: a case report

Paget’s disease (osteitis deformans) of bone is a focal skeletal disorder that can be mono- or polyostotic. Paget's disease might be asymptomatic as with normal biomarkers, or it can be symptomatic such as bony enlargement or deformity. The diagnosis can be made by laboratory findings and specific findings in radiology or radionuclide scan, and it is sometimes confirmed by bone biopsy.In this report, we present the case of a 37-year-old man whose initial symptoms indicated sacroiliitis, which led to the suspicion of ankylosing spondylitis. Following other diagnostic evaluations and based on imaging features and bone biopsy, active Paget’s bone disease without abnormal biochemical markers was diagnosed. The laboratory diagnosis tests were normal. Other biomarkers including procollagen type I N-terminal propeptide (PINP), serum C-telopeptide (CTx), urinary N-telopeptide (NTx), and urinary hydroxyproline, are not routinely checked.The patient also showed a coincidence of unilateral idiopathic gynecomastia. A single dose of 5 mg of zoledronic acid intravenously was prescribed, and the patient was followed for six months. Paget's bone disease can occur without any change in biochemical markers. In such cases, the response to treatment can becontrolled by improving the clinical picture or evaluating the correct imaging findings.