Phase-Amplitude Coupling Localizes Pathologic Brain with Aid of Behavioral Staging in Sleep.

Low frequency brain rhythms facilitate communication across large spatial regions in the brain and high frequency rhythms are thought to signify local processing among nearby assemblies. A heavily investigated mode by which these low frequency and high frequency phenomenon interact is phase-amplitude coupling (PAC). This phenomenon has recently shown promise as a novel electrophysiologic biomarker, in a number of neurologic diseases including human epilepsy. In 17 medically refractory epilepsy patients undergoing phase-2 monitoring for the evaluation of surgical resection and in whom temporal depth electrodes were implanted, we investigated the electrophysiologic relationships of PAC in epileptogenic (seizure onset zone or SOZ) and non-epileptogenic tissue (non-SOZ). That this biomarker can differentiate seizure onset zone from non-seizure onset zone has been established with ictal and pre-ictal data, but less so with interictal data. Here we show that this biomarker can differentiate SOZ from non-SOZ interictally and is also a function of interictal epileptiform discharges. We also show a differential level of PAC in slow-wave-sleep relative to NREM1-2 and awake states. Lastly, we show AUROC evaluation of the localization of SOZ is optimal when utilizing beta or alpha phase onto high-gamma or ripple band. The results suggest an elevated PAC may reflect an electrophysiology-based biomarker for abnormal/epileptogenic brain regions.

The Possibility of Eidetic Memory in a Patient Report of Epileptogenic Zone in Right Temporo-Parietal-Occipital Cortex.

Eidetic memory has been reported in children and in patients with synesthesia but is otherwise thought to be a rare phenomenon. Presented herein is a patient with right-sided language dominance, as proven via multiple functional imaging and neuropsychometric methods, who has a seizure onset zone in the right temporo-parietal-occipital cortex. This patient's medically refractory epilepsy and thus hyperactive cortex could possibly contribute to near eidetic ability with paired-associates learning tasks (in both short-term and long-term retention). There are reports of epilepsy negatively affecting memory, but as far as the authors are aware to date, there is limited evidence of any lesion enhancing cognitive functions (whether through direct lesion or via compensatory mechanism) that would be localized to a seizure onset zone in the dominant temporo-parietal-occipital junction.

Status Epilepticus in Post-Transplantation Hyperammonemia Involves Careful Metabolic Management.

Hyperammonemia is a condition that may result after solid organ transplantation, particularly lung transplantation. However, it is very uncommon for this presentation to occur more than 30 days post-transplantation. Hyperammonemia and the resulting encephalopathy typically manifest with altered sensorium, a clinical situation which is not often included in the differential diagnosis of presumed nonconvulsive status epilepticus (NCSE). Seizures are common among this subset of patients with hyperammonemia and may be refractory to traditional treatments. Evidence of elevated intracranial pressure by invasive monitoring and neuroimaging findings of diffuse cerebral edema are commonly reported. Here we examine the therapeutic importance of identifying the specific cause of hyperammonemic encephalopathy, a condition which may result in status epilepticus and ultimately cerebral edema or even brain death.

Mepolizumab-Induced Posterior Reversible Encephalopathy Syndrome (PRES), a new patient report.

BACKGROUND: Posterior Reversible Encephalopathy Syndrome (PRES) is a neurotoxic state characterized by seizures, headache, vision change, paresis, and altered mental status. PRES has an important place in medicine due to the wide variety of causative diseases, infections, and medications that precipitate its mysterious onset. Although exposure to medications, particularly immunosuppressants, cancer chemotherapy, and biologic drugs, is a common occurrence in patients who develop PRES, Mepolizumab has never before been associated. CASE PRESENTATION: This report of a 67-year-old male patient outlines the first reported case of Mepolizumab-induced PRES in the literature. CONCLUSIONS: Treatment of severe asthma, asthma-exacerbations, and diseases such as eosinophilic granulomatosis with polyangiitis (formerly Churg-Strauss) with Mepolizumab is rapidly gaining popularity ever since the drug's recent FDA-approval. This report aims to raise awareness of this potentially life-threatening and previously unreported side effect of Mepolizumab since early identification of the causative agent is the key to preventing the severe neurologic disability and possible death that may occur from the delayed treatment of PRES.

A Contextual-Bandit-Based Approach for Informed Decision-Making in Clinical Trials.

Clinical trials are conducted to evaluate the efficacy of new treatments. Clinical trials involving multiple treatments utilize the randomization of treatment assignments to enable the evaluation of treatment efficacies in an unbiased manner. Such evaluation is performed in post hoc studies that usually use supervised-learning methods that rely on large amounts of data collected in a randomized fashion. That approach often proves to be suboptimal in that some participants may suffer and even die as a result of having not received the most appropriate treatments during the trial. Reinforcement-learning methods improve the situation by making it possible to learn the treatment efficacies dynamically during the course of the trial, and to adapt treatment assignments accordingly. Recent efforts using multi-arm bandits, a type of reinforcement-learning method, have focused on maximizing clinical outcomes for a population that was assumed to be homogeneous. However, those approaches have failed to account for the variability among participants that is becoming increasingly evident as a result of recent clinical-trial-based studies. We present a contextual-bandit-based online treatment optimization algorithm that, in choosing treatments for new participants in the study, takes into account not only the maximization of the clinical outcomes as well as the patient characteristics. We evaluated our algorithm using a real clinical trial dataset from the International Stroke Trial. We simulated the online setting by sequentially going through the data of each participant admitted to the trial. Two bandits (one for each context) were created, with four choices of treatments. For a new participant in the trial, depending on the context, one of the bandits was selected. Then, we took three different approaches to choose a treatment: (a) a random choice (i.e., the strategy currently used in clinical trial settings), (b) a Thompson sampling-based approach, and (c) a UCB-based approach. Success probabilities of each context were calculated separately by considering the participants with the same context. Those estimated outcomes were used to update the prior distributions within the bandit corresponding to the context of each participant. We repeated that process through the end of the trial and recorded the outcomes and the chosen treatments for each approach. We also evaluated a context-free multi-arm-bandit-based approach, using the same dataset, to showcase the benefits of our approach. In the context-free case, we calculated the success probabilities for the Bernoulli sampler using the whole clinical trial dataset in a context-independent manner. The results of our retrospective analysis indicate that the proposed approach performs significantly better than either a random assignment of treatments (the current gold standard) or a multi-arm-bandit-based approach, providing substantial gains in the percentage of participants who are assigned the most suitable treatments. The contextual-bandit and multi-arm bandit approaches provide 72.63% and 64.34% gains, respectively, compared to a random assignment.

Chronic Lymphocytic Inflammation with Pontine Perivascular Enhancement Responsive to Steroids May Extend above and below Pons and Is Associated with Other Autoimmune Diseases.

Many autoimmune diseases can affect the central nervous system, and their varying clinical presentations often confound a straightforward diagnosis. In this report, we describe a unique presentation of CLIPPERS syndrome. To our knowledge, this is the first case to demonstrate significant supratentorial involvement with symmetric and non-confluent lesions in the medial orbitofrontal cortex; additionally, this is the second case to describe an association between diagnoses of hypothyroidism and CLIPPERS.

Characterizing the electrophysiological abnormalities in visually reviewed normal EEGs of drug-resistant focal epilepsy patients.

Routine scalp EEG is essential in the clinical diagnosis and management of epilepsy. However, a normal scalp EEG (based on expert visual review) recorded from a patient with epilepsy can cause delays in diagnosis and clinical care delivery. Here, we investigated whether normal EEGs might contain subtle electrophysiological clues of epilepsy. Specifically, we investigated (i) whether there are indicators of abnormal brain electrophysiology in normal EEGs of epilepsy patients, and (ii) whether such abnormalities are modulated by the side of the brain generating seizures in focal epilepsy. We analysed awake scalp EEG recordings of age-matched groups of 144 healthy individuals and 48 individuals with drug-resistant focal epilepsy who had normal scalp EEGs. After preprocessing, using a bipolar montage of eight channels, we extracted the fraction of spectral power in the alpha band (8-13 Hz) relative to a wide band of 0.5-40 Hz within 10-s windows. We analysed the extracted features for (i) the extent to which people with drug-resistant focal epilepsy differed from healthy subjects, and (ii) whether differences within the drug-resistant focal epilepsy patients were related to the hemisphere generating seizures. We then used those differences to classify whether an EEG is likely to have been recorded from a person with drug-resistant focal epilepsy, and if so, the epileptogenic hemisphere. Furthermore, we tested the significance of these differences while controlling for confounders, such as acquisition system, age and medications. We found that the fraction of alpha power is generally reduced (i) in drug-resistant focal epilepsy compared to healthy controls, and (ii) in right-handed drug-resistant focal epilepsy subjects with left hemispheric seizures compared to those with right hemispheric seizures, and that the differences are most prominent in the frontal and temporal regions. The fraction of alpha power yielded area under curve values of 0.83 in distinguishing drug-resistant focal epilepsy from healthy and 0.77 in identifying the epileptic hemisphere in drug-resistant focal epilepsy patients. Furthermore, our results suggest that the differences in alpha power are greater when compared with differences attributable to acquisition system differences, age and medications. Our findings support that EEG-based measures of normal brain function, such as the normalized spectral power of alpha activity, may help identify patients with epilepsy even when an EEG does not contain any epileptiform activity, recorded seizures or other abnormalities. Although alpha abnormalities are unlikely to be disease-specific, we propose that such abnormalities may provide a higher pre-test probability for epilepsy when an individual being screened for epilepsy has a normal EEG on visual assessment.

Creutzfeldt-Jakob Disease May Present Early With Unusual Bulbar Predominance.

INTRODUCTION: Creutzfeldt-Jakob disease (CJD) is a prion protein disorder of significant consequence and currently incurable. Diagnosis can be challenging early in the disease course. CJD can present in many ways but often fits a pattern of cognitive problems, cerebellar disturbance, behavioral/psychological changes, and perhaps myoclonus. CASE REPORT: We herein present the case of a 69-year-old White male with subacute progressive bulbar and limb weakness over ten weeks period. Early on, he was diagnosed with amyotrophic lateral sclerosis versus autoimmune-related bulbar neuropathy and treated as such. However, he continued to deteriorate clinically that prompted another admission, upon readmission, his cerebrospinal fluid RTQuick and 14-3-3 from the National Prion Disease Pathology Surveillance Center (NPDPSC) did eventually return positive. Hence he was diagnosed with CJD. CONCLUSIONS: CJD may present with progressive bulbar symptoms similar to acute inflammatory demyelinating polyradiculoneuropathy (MF variant), motor neuron disease, or autoimmune brainstem encephalitis. It becomes even higher on the differentials especially with no response to immunotherapy.

Electrophysiological Correlates of Brain Health Help Diagnose Epilepsy and Lateralize Seizure Focus.

The absence of epileptiform activity in a scalp electroencephalogram (EEG) recorded from a potential epilepsy patient can cause delays in clinical care delivery. Here we present a machine-learning-based approach to find evidence for epilepsy in scalp EEGs that do not contain any epileptiform activity, according to expert visual review (i.e., "normal" EEGs). We found that deviations in the EEG features representing brain health, such as the alpha rhythm, can indicate the potential for epilepsy and help lateralize seizure focus, even when commonly recognized epileptiform features are absent. Hence, we developed a machine-learning-based approach that utilizes alpha-rhythm-related features to classify 1) whether an EEG was recorded from an epilepsy patient, and 2) if so, the seizure-generating side of the patient's brain. We evaluated our approach using "normal" scalp EEGs of 48 patients with drug-resistant focal epilepsy and 144 healthy individuals, and a naive Bayes classifier achieved area under ROC curve (AUC) values of 0.81 and 0.72 for the two classification tasks, respectively. These findings suggest that our methodology is useful in the absence of interictal epileptiform activity and can enhance the probability of diagnosing epilepsy at the earliest possible time.

Insulinoma as a Potential Insidious Presenter in Medical Refractory Epilepsy.

BACKGROUND: Insulinoma as a cause of epileptic seizure has been thoroughly described but often not considered in differentials for previously established diagnoses of seizure disorder. Hypoglycemic symptoms can mimic neurological disorders such as epilepsy. CASE PRESENTATION: A 52-year-old woman presented with a history of epilepsy on anti-epileptic drugs (AEDs) developed repeated episodes consisting of seizures and neuropsychiatric symptoms with no predisposing factors for epilepsy at age 52. She had received full AED treatment before the possibility of hypoglycemia was considered. Following a clinical diagnosis of insulinoma, distal pancreatectomy was performed, and her seizures did not occur again. CONCLUSION: The early diagnosis of insulinoma requires vigilance, not only for hypoglycemia in patients with neuropsychiatric symptoms, but also for the possible masking effects of a history of epilepsy and preceding AED usage.

Developing Strategies for Sustainable Medical Equipment Maintenance in Under-Resourced Settings.

Engineering technology plays a pivotal role in the delivery of health care in under-resourced countries by providing an infrastructure to improve patient outcomes. However, sustainability of these technologies is difficult in these settings oftentimes due to limited resources or training. The framework presented in this editorial focuses on establishing medical and laboratory equipment sustainability in developing countries and is comprised of four steps: 1) establishing reliable in-country relationships with stakeholders, 2) identifying needs for sustainable solutions locally, 3) exploring potential solutions and assessing their effort-to-impact ratios, and 4) working with strategic partners to implement solutions with clear performance metrics. By focusing on the sustainability of donated equipment instead of the equipment itself, this method presented distinguishes itself from other philanthropic endeavors in the field by seeking to establish preventive maintenance habits that can impact clinical outcomes of a community long term. Application of this methodology is reported in the Original Research Article "A Low-Cost Humidity Control System to Protect Microscopes in a Tropical Climate" by Asp et. al.

Fingolimod-associated macular edema controlled with nepafenac non-steroidal anti-inflammatory opthalmologic applications.

BACKGROUND: Fingolimod, an immunomodulatory agent, is used for the treatment of relapsing-remitting multiple sclerosis (RRMS). Fingolimod-associated macular edema (FAME) is a known complication with an incidence of 0.4%. The current recommendation for treatment of FAME is cessation of fingolimod. There are few case reports with management of FAME with steroid eye drops. CASE PRESENTATION: A 38-year-old Caucasian female patient with history of relapsing-remitting multiple sclerosis (RRMS) and treated with fingolimod developed Fingolimod-associated macular edema (FAME). Nevertheless, FAME was successfully treated with nonsteroidal anti-inflammatory eye drops without discontinuation of fingolimod. CONCLUSION: FAME may be managed with non-steroidal eye drops without discontinuation of fingolimod in appropriate patient monitored with close follow up.

Thalamic aphasia secondary to glioblastoma multiforme.

BACKGROUND: Thalamic aphasia is an unusual clinical presentation of brain neoplasm with few cases reported. Herein, we present a case of an adult woman with thalamic aphasia due to glioblastoma of the thalamus. CASE PRESENTATION: A 57-year-old female patient presented with difficulty walking, slow speech and cognition and altered mental status. At baseline, she was conversant and interactive. Physical examination showed right hemiparesis in addition to word finding difficulties, an impaired naming of objects and semantic paraphasia but preserved repetition and comprehension. The remaining neurological exam was otherwise unremarkable. Brain CT and brain MRI scans showed a left thalamic lesion that is centrally necrotic and peripherally enhancing suggestive of a high-grade neoplasm. Eventually, histopathological examination of brain biopsy confirmed the diagnosis of glioblastoma multiforme. Thalamic aphasia was proposed as an explanation for the neurological symptoms observed in this patient. CONCLUSIONS: This patient demonstrates an unusual presentation of glioblastoma multiforme as thalamic aphasia. It may also point to the potential contribution of the understanding of how thalamic aphasia evolves to characterize the role of the thalamus in language functions.

Acquired intercostal lung herniation: conservative management may lead to continuation of symptoms and other adverse consequence.

BACKGROUND: It is quite rare for lung to herniate between a patient's ribs, most often seen after surgery; it is, however, also rarely seen in other situations, notably during coughing fits situations such as coughing spells. There is minor controversy in the literature regarding management, namely, a question of whether to manage conservatively or with surgical correction, since this is such a rare entity physicians, may face difficulty in knowing how to proceed. Here, we provide evidence supporting acquired lung herniation management to be repaired surgically, and early, while at the same time medically optimizing the patient's risk factors for further herniation events or intercostal muscle tears. PRESENTATION: We report a 79-year-old man who suffered a right-sided lung herniation as a result of vigorous coughing, he initially was managed conservatively, and symptoms worsened but then underwent surgical repair which was associated with a suitable outcome. CONCLUSION: Lung herniation will may resolve on its own and prompt correction should be considered instead of conservative management. We recommend early surgical repair for all intercostal lung herniations, even if they are asymptomatic, to prevent complications or extension of the defect into the abdominal wall. Surgery may offer the best results, with low morbidity and no mortality reported to date.

Unsupervised machine-learning classification of electrophysiologically active electrodes during human cognitive task performance.

Identification of active electrodes that record task-relevant neurophysiological activity is needed for clinical and industrial applications as well as for investigating brain functions. We developed an unsupervised, fully automated approach to classify active electrodes showing event-related intracranial EEG (iEEG) responses from 115 patients performing a free recall verbal memory task. Our approach employed new interpretable metrics that quantify spectral characteristics of the normalized iEEG signal based on power-in-band and synchrony measures. Unsupervised clustering of the metrics identified distinct sets of active electrodes across different subjects. In the total population of 11,869 electrodes, our method achieved 97% sensitivity and 92.9% specificity with the most efficient metric. We validated our results with anatomical localization revealing significantly greater distribution of active electrodes in brain regions that support verbal memory processing. We propose our machine-learning framework for objective and efficient classification and interpretation of electrophysiological signals of brain activities supporting memory and cognition.

Author Correction: Pupil size reflects successful encoding and recall of memory in humans.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Cerebral Air Embolism after Esophagogastroduodenoscopy: Insight on Pathophysiology, Epidemiology, Prevention and Treatment.

BACKGROUND: Air embolism is an extremely rare complication that can follow gastrointestinal endoscopy. The most accepted treatment of cerebral air embolism (CAE) is hyperbaric oxygen (HBO). Limited evidence suggests that lidocaine may have a neuroprotective effect. The exact mechanism does not appear to be well elucidated. METHODS: We conducted a literature search using multiple combinations of keywords from PubMed and Ovid Medline databases according to the PRISMA guidelines. We included articles with cases of air embolism caused by an esophagogastroduodenoscopy (EGD). We excluded cases related to other procedures e.g. colonoscopy, endoscopic retrograde cholangiopancreatography, cholangioscopy, Kasai procedure, bronchoscopy, laparoscopy or thoracoscopy. We were able to identify 30 cases of CAE associated with EGD. We included our experience in treating one patient with CAE after elective EGD. RESULTS: Given the results of our literature search and this patient's characteristics, we chose to treat our patient with HBO and lidocaine infusion. Our case series consists of 31 patients of post EGD CAE, the mean age was 63.7 ± 11.14 years, 38.7% of the patients were women (n = 12). 38.7% of the cases underwent esophageal dilatation (n = 12), while 19.35% had EGD biopsy (n = 6), 9.6% had variceal ligation (n = 3), and 3.22% had variceal banding (n = 1). In 20 out of 31 cases, echocardiography has been documented, 20% of those patients (n = 4) had patent foramen ovale. HBO was used in treatment of 48% of cases (n = 15), among the included patients, 61% survived (n = 19). Our patient showed significant neurological improvement. CONCLUSIONS: Despite the rare incidence of CAE during or after EGD, physicians should be aware of this potential complication. In patients who develop sudden acute neurological symptoms, early diagnosis and intervention may prevent devastating neurological injury and death. The most accepted emergent treatment for CAE includes HBO, consideration of lidocaine, and work-up of source of the air embolism.

Arteriopathy of Unknown Etiology: Pathologic, Radiologic, and Cytogenetic Investigations.

BACKGROUND Dissections occur when the intima is injured and an intramural hematoma develops between the intima and the media. There are a multitude of factors which contribute to arterial aneurysms and dissections, that could be infectious, genetic, traumatic, or environmental, but there are still cases for which the etiology is not determined. CASE REPORT We describe a patient who presented with arterial aneurysms and dissections that involved multiple vessels over the course of 10 years. We also reviewed the literature on possible risk factors, triggers, and genetic disorders that may predispose patients to developing arterial aneurysms and dissections. CONCLUSIONS To the best of our knowledge, this is the first report of this unusual pattern of presentation for idiopathic vasculopathy causing multiple dissections and aneurysms in a young patient. Idiopathic vasculopathy resulting in aneurysm and dissection is not an entirely uncommon entity; most cases of disparate dissection are not linked with a causal mechanism, although genetic influence is often heavily suspected, but it unfortunately often cannot be proven. We reviewed the available literature for a better understanding of pathologic, radiologic, and cytogenetic investigations of arteriopathy of unknown cause.

Occlusive radiation cerebral vasculopathy implies medical complexity: a case report.

BACKGROUND: Cranial irradiation is one of the main treatment modalities for central nervous system tumors. It carries many complications, one being occlusive radiation vasculopathy of large vessels. It is an underrecognized etiology for stroke, especially in the younger population. The pathophysiological process is controversial, but there is much literature supporting the theory of its being a secondary form of moyamoya disease. CASE PRESENTATION: A 31-year-old Caucasian man with a history of pineal blastoma at the age of 3 years, which was treated with resection, radiotherapy, and chemotherapy, presented to our institution with right M1 stroke. Further assessment by computed tomographic perfusion study with acetazolamide demonstrated steal phenomenon of the right middle cerebral artery territory (type III response) with a small internal region of matched cerebral blood volume defect (that is, infarct core). Coincidentally, he was found to have multiple brain masses consistent with meningiomas. Occlusive radiation vasculopathy was the most likely culprit of the patient's stroke. The patient was treated medically with "baby" acetylsalicylic acid and clopidogrel for 3 months, then continued only on baby acetylsalicylic acid. CONCLUSION: Late-onset occlusive radiation vasculopathy is a potentially severe iatrogenic manifestation of radiotherapy that requires a high index of suspicion as an etiology of stroke in young population, especially those with coexistent meningioma that might be a strong indicator for occlusive radiation vasculopathy as the stroke culprit. We reviewed the available literature to better understand the pathogenesis, clinical presentation, and treatment options of occlusive radiation vasculopathy. Applying perfusion studies with acetazolamide measures the cerebrovascular reserve in patients with occlusive radiation vasculopathy, which could help in determining the appropriate available treatment option.

Idiopathic intracranial hypertension presenting with isolated unilateral facial nerve palsy: a case report.

BACKGROUND: Idiopathic intracranial hypertension, also known as pseudotumor cerebri, is a disorder characterized by increased intracranial pressure of unclear pathogenesis in the absence of other structural and obstructive lesions that is predominantly, although not exclusively, seen in obese women of childbearing age. Patients with idiopathic intracranial hypertension commonly present with a headache, transient visual obscurations, and intracranial noises with some cranial nerves occasionally involved, most commonly CN VI. We report idiopathic intracranial hypertension presenting with isolated complete unilateral facial nerve palsy, as the sole cranial nerve involved, which is a presentation rarely reported in the literature. CASE PRESENTATION: A 40-year-old Hispanic woman with a history of obesity and hypertension presented to our emergency department complaining of bifrontal headache for 3 days associated with nausea, vomiting, transient visual disturbances, and a picture of right-sided cranial nerve VII palsy. Her neurologic examination including other cranial nerves was otherwise normal, but a fundus examination revealed bilateral grade II papilledema. Imaging studies ruled out structural and obstructive lesions as possible causes of her symptoms and lumber puncture results were unremarkable except for an increased opening pressure. She was then started on prednisone and acetazolamide. Two days later, she reported a dramatic improvement in both headache and facial nerve palsy. CONCLUSIONS: Idiopathic intracranial hypertension should be suspected in obese young women presenting with headache and transient visual complaints and some cranial nerve abnormalities. Idiopathic intracranial hypertension is a diagnosis of exclusion and imaging studies should always be performed to rule out other structural and obstructive lesions. In this case report, we aimed to draw attention to the possibility of idiopathic intracranial hypertension presenting with unilateral cranial nerve VII palsy as the only cranial nerve involved, which needs a high index of suspicion by clinicians. The mechanisms of cranial nerve VII palsy in idiopathic intracranial hypertension are not well understood and prompt further investigation.