Stroke: What's Sleep Got to Do With It?

SUMMARY: Ischemic strokes most often occur between 6 am and 12 am after awakening from sleep but up to 30% occur during sleep. Wake-up strokes (WUS) are new focal neurological deficit(s) persisting for ≥ 24 hours attributable to an ischemic event present on patient awakening. Obstructive sleep apnea (OSA) is a major risk factor for WUS because it compounds the instability of the morning environment and increases the likelihood of cardiovascular events, including hypertension, atrial fibrillation, right-to-left shunts, and stroke. Circadian-driven alterations in structural, homeostatic, and serological factors also predispose to WUS. Also, WUS patients are often not considered candidates for time-dependent intravenous thrombolysis therapy because of an uncertain onset time. However, using the tissue clock (positive diffusion weighted imaging-negative fluid-attenuated inversion recovery mismatch) dates the WUS as 3 to 4.5 hours old and permits consideration for intravenous thrombolysis and if needed mechanical thrombectomy. Given the high prevalence of moderate/severe OSA in stroke patients and its impact on stroke outcomes, screening with overnight pulse oximetry and home sleep apnea test is needed. Treating OSA poststroke remains challenging. Polysomnographic changes in sleep architecture following acute/subacute stroke may also impact upon stroke outcome.

Expansion of the dimensions in the current management of acute ischemic stroke.

Stroke is the fifth leading cause of death in the United States with a huge burden on health care. Acute ischemic stroke (AIS) accounts for 87% of all stroke. The use of thrombolytic agents in AIS treatment is well known since 1950 but no FDA approval until 1996, due to lack of strong evidence showing benefits outweigh the risk of intracranial hemorrhage. The NINDS trial led to the approval of intravenous tissue plasminogen activator treatment (IV recombinant tPA) within 3 h of stroke. Due to this limitation of 3-4.5 h. window, evolution began in the development of effective endovascular therapy (EVT). Multiple trials were unsuccessful in establishing the strong evidence for effectiveness of EVT. In 2015, MR CLEAN trial made progress and showed improved outcomes with EVT in AIS patients with large vessel occlusion (LVO), with 6-h window period. In 2018, two major trials-DAWN and DEFUSE 3-along with few other trials had shown improved outcomes with EVT and stretched window period from 6 to 24 h. AHA Stroke Council is constantly working to provide focused guidelines and recommendations in AIS management since 2013. SVIN had started the initiative "Mission Thrombectomy-2020" to increase global EVT utilization rate 202,000 procedures by 2020. Physicians are using safer and easier approach like brachial and radial approach for EVT. TeleNeurology and artificial intelligence also played a significant role in increasing the availability of IV recombinant tPA in AIS treatment in remote hospitals and also in screening, triaging and identifying LVO patients for EVT. In this review article, we aim to describe the history of stroke management along with the new technological advancements in AIS treatment.

A bibliometric analysis of top 50-most cited articles on repetitive trans-cranial magnetic stimulation (rTMS) for treatment of depression.

BACKGROUND: Citation count can be used as a key tool to assess the quality of the published literature and because of its immense advantages it is now widely used in ranking the articles on specific topics. OBJECTIVE/HYPOTHESIS: To extract and assess the top cited work on repetitive transcranial magnetic stimulation (rTMS) for depression treatment. METHODS: Scopus Library Database was searched and two independent authors produced a list of 50 most cited articles on repetitive transcranial magnetic stimulation (rTMS) for treatment of depression. All the relevant articles having key-terms within their titles, abstract and keywords were included in our search. Our list was categorized into two categories, "mixed" and "focused". RESULTS: The articles in the produced list of top 50 most cited articles on rTMS for treatment of depression belong to the time period 1993-2012 with total citation count 12078. George MS was prominent in the list. 'Biological Psychiatry' published most number of articles (n = 13) among the list. Articles were categorized on the basis of primary population and intervention into 'Focused' and 'Mixed' categories. LIMITATIONS: Articles that were published before 1993 and after 2012 on rTMS for depression couldn't made it to the final list of top-50 most cited article. CONCLUSION: We attempted to conduct a topic-specific citation analysis considering the paucity of specified bibliometrics in medical literature. Our research provides an insight on emerging trends in rTMS for depression and highlights the characteristics, quality and dynamics of frequently cited articles in the field.

Artificial intelligence as an emerging technology in the current care of neurological disorders.

BACKGROUND: Artificial intelligence (AI) has influenced all aspects of human life and neurology is no exception to this growing trend. The aim of this paper is to guide medical practitioners on the relevant aspects of artificial intelligence, i.e., machine learning, and deep learning, to review the development of technological advancement equipped with AI, and to elucidate how machine learning can revolutionize the management of neurological diseases. This review focuses on unsupervised aspects of machine learning, and how these aspects could be applied to precision neurology to improve patient outcomes. We have mentioned various forms of available AI, prior research, outcomes, benefits and limitations of AI, effective accessibility and future of AI, keeping the current burden of neurological disorders in mind. DISCUSSION: The smart device system to monitor tremors and to recognize its phenotypes for better outcomes of deep brain stimulation, applications evaluating fine motor functions, AI integrated electroencephalogram learning to diagnose epilepsy and psychological non-epileptic seizure, predict outcome of seizure surgeries, recognize patterns of autonomic instability to prevent sudden unexpected death in epilepsy (SUDEP), identify the pattern of complex algorithm in neuroimaging classifying cognitive impairment, differentiating and classifying concussion phenotypes, smartwatches monitoring atrial fibrillation to prevent strokes, and prediction of prognosis in dementia are unique examples of experimental utilizations of AI in the field of neurology. Though there are obvious limitations of AI, the general consensus among several nationwide studies is that this new technology has the ability to improve the prognosis of neurological disorders and as a result should become a staple in the medical community. CONCLUSION: AI not only helps to analyze medical data in disease prevention, diagnosis, patient monitoring, and development of new protocols, but can also assist clinicians in dealing with voluminous data in a more accurate and efficient manner.

Organization of Stroke Care in Pakistan.

In Pakistan, stroke is one of the major contributors to the health problem. The increasing incidence of stroke and lack of infrastructure in both urban and rural areas requires immediate attention. Multiple societies and groups have been established to highlight the growing problem, but necessary steps must be taken at the government level to improve and design a better stroke care system in the country.

Traumatic brain injury causing intestinal dysfunction: A review.

Traumatic brain injuries (TBI) and its sequelae are becoming one of the most pressing public health concerns worldwide. It is one of the leading causes of increased morbidity and mortality. The primary insult to the brain can cause ischemic brain injury, paralysis, concussions, death, and other serious complications. Brain injury also involves other systems through a secondary pathway resulting in multiple complications during and after hospitalization. The focus of our article is to assess the literature available on traumatic brain injury and intestinal dysfunctional to highlight the aspects of epidemiology, pathophysiology, and different diagnostic approaches for early diagnosis of gut dysfunction. We review studies done in both humans and animals, to better understand this underrated topic, as it costs billions of dollars to the healthcare industry because of delayed diagnosis.

Characteristics and treatment effectiveness of the nummular headache: a systematic review and analysis of 110 cases.

BACKGROUND/OBJECTIVE: Nummular headache (NH) is a primary headache disorder characterised by intermittent or continuous scalp pain, affecting a small circumscribed area of the scalp. As there are limited data in the literature on NH, we conducted this review to evaluate demographic characteristics and factors associated with complete resolution of the headache, and effectiveness of treatment options. METHODS: We performed a systematic review of cases reported through PubMed database, using Preferred Reporting Items for Systematic Reviews and Meta-Analyses protocol and 'nummular headache', 'coin-shaped headache' and 'coin-shaped cephalalgia' keywords. Analysis was performed by using χ2 test and Wilcoxon rank-sum test. For individual interventions, the response rate (RR%) of the treatment was calculated. RESULTS: We analysed a total of 110 NH cases, with median age 47 years and age of pain onset 42 years. Median duration to make correct diagnosis was 18 months after first attack. The median intensity of each attack was 5/10 on verbal rating scale over 4 cm diameter with duration of attack <30 min. Patients with NH had median three attacks per day with frequency of 9.5 days per month. 40 (57.97%) patients had complete resolution of the headache after treatment. Patients with complete resolution were younger, more likely to be female, and were more likely to have diagnosis within year. Patients with complete resolution more likely to have received treatment with onabotulinum toxin A (botulinum toxin type A (BoNT-A)), and gabapentin compared with patients without complete resolution. Most effective interventions were gabapentin (n=34; RR=67.7%), non-steroidal anti-inflammatory drugs (NSAIDs) (n=32; RR=65.6%), BoNT-A (n=12; RR=100%) and tricyclic antidepressant (n=9; RR=44.4%). CONCLUSION: Younger patients, female sex and early diagnosis were associated with complete resolution. NSAIDs, gabapentin and BoNT-A were most commonly used medications, with significant RRs.

Periventricular Hyperintensities Mimicking Multiple Sclerosis.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a small-to-medium-sized vessel disease that causes degeneration of vascular smooth muscles. The most frequently found mutation is NOTCH3 on chromosome 19, the presence of which confirms the diagnosis of CADASIL. The core features of CADASIL are migraine, ischemic events, cognitive decline, and psychiatric features. Its symptoms overlap with other diseases, most commonly with multiple sclerosis (MS). Both diseases can give fluid-attenuated inversion recovery in periventricular regions and deep white matter. CADASIL is often misdiagnosed and treated as MS due to these similarities. We present a case of a 28-year-old woman who began treatment for MS and was later confirmed with a diagnosis of CADASIL with a NOTCH3 mutation.

An Overview of Therapeutic Options in Relapsing-remitting Multiple Sclerosis.

Multiple sclerosis (MS) is a chronic disorder of the central nervous system (CNS). MS affects 2.1 million individuals every year and is also considered a major cause of economic health burden around the world. Genetics and environmental factors both play a role in the pathogenesis of MS by activating the immune response and causing inflammation. Patients with MS can have various clinical courses, but the most common pattern seen is relapsing-remitting multiple sclerosis (RRMS). Multiple therapeutic options have been studied to prevent RRMS patients from frequent relapses. The oldest and most frequently used medication for MS is interferon beta, either used alone or as add-on therapy with other drugs. Newer treatment options that have been recently approved to control MS symptoms and suppress the inflammation are glatiramer acetate and siponimod. Infusion therapies consisting of monoclonal antibodies and immunosuppressive drugs have also been studied in the recent past. Some trials have been conducted on the use of stem cells for RRMS patients. We have briefly discussed all treatment options and the response of RRMS patients in multiple trials.

Dravet Syndrome: An Overview.

Dravet syndrome (DS), also known as severe myoclonic epilepsy of infancy (SMEI), is one of the rare early childhood intractable epileptic encephalopathies associated with pleomorphic seizure activity, cognitive decline, motor, and behavioral abnormalities. The convulsive seizure is the most common type seen in DS. After the first episode of seizure-like activity, behavioral disorders and cognitive decline are progressive and long-lasting. The most common etiology identified in patients with DS is a de-novo genetic mutation alpha-1 subunit of voltage-gated calcium channel gene (SCN1A). DS is diagnosed clinically and if unclear, genetic testing is recommended. DS treatment options include anti-epileptic drugs and cannabinoids; ketogenic diet therapy and surgical options such as the deep brain and vagal nerve stimulation. Due to drug-refractory epilepsy in DS, many more therapies are being investigated to increase the longevity of patients.

Recent Advances and Therapeutic Options in Lambert-Eaton Myasthenic Syndrome.

Lambert-Eaton Myasthenic Syndrome (LEMS) is an autoimmune-mediated neurological disorder that manifests as muscle fatigue, diminished tendon reflexes, with symptoms of cholinergic overactivity. It can be associated with certain neoplastic conditions, the most common being small cell lung carcinoma (SCLC). The basic pathophysiology involved is antibody-mediated targeting of voltage-gated calcium channels (VGCC), which decreases the release of acetylcholine in the synaptic junction. Multiple treatment options have been introduced in the past and, recently, a new drug, amifampridine, has been approved by the Food and Drug Administration (FDA) for the treatment of weakness associated with these patients. We summarize this newly introduced drug with a brief description of other treatment options available.

Juvenile Parkinson Disease.

Juvenile Parkinson's disease (JPD) is a rare movement disorder that presents before the age of 21 years. Kufor-Rekab syndrome (KRS) is one of the distinct types of JPD caused by the ATP13A2 mutation and inherited as an autosomal recessive. The pathogenesis of KRS is related to an interrelated metabolism of ATP13A2 with Mn+2 and Zn+2, bioenergetics of mitochondria, autophagy lysosomal dysfunction, and synuclein metabolism. Clinically, KRS has a variable phenotype and may present with pyramidal or extrapyramidal symptoms and cognitive impairment. Early diagnosis of KRS is important as most of these patients are levodopa-responsive and genetic counseling and screening is important for the whole family. We present a case of a 16-year-old boy who presented with tremors and walking difficulty. His physical examination showed an expressionless face, decrease in eye blink frequency, and slow vertical saccadic eye movements. His movements were slow. All laboratory investigations were normal, except the genetic study, which led to the diagnosis of KRS.

Non-Traumatic Pneumocephalus and Sub-Dural Empyema as a Complication of Chronic Sinusitis.

Infectious sinusitis is extremely common in children, and persistent infection can lead to many complications. The most dangerous and commonly reported complications are intracranial. These intracranial complications include pneumocephalus, cerebral abscess, subdural empyema, meningitis, cellulitis, orbital abscess, and cavernous sinus thrombosis. Pneumocephalus is the presence of air in the cranium and sometimes it can lead to intracranial infection and localized pus collection in the potential space between meninges. Herein, we report a case of a 12-year-old girl who presented to a pediatric emergency in a confused and disoriented state. The cerebrospinal fluid (CSF) analysis provided a picture of bacterial meningitis, but her CT scan showed pneumocephalus and subdural empyema. This case report will help clinicians overcome this diagnostic challenge using the appropriate imaging and treatment modalities to prevent neurological sequelae.

Spondyloepiphyseal Dysplasia Congenita: A Rare Cause of Respiratory Distress.

Spondyloepiphysal dysplasia (SED) is an inheritable dysplasia of the bone due to a defect in collagen. It has a prevalence of 3.4 per million. It has two important types, congenita and tarda, which are differentiated by the age presentation and heritage mode. SED congenita can present a significant reduction in the upper segment to a lower segment ratio. Collagen mutation results in abnormal growth and development of spine and limb bones. The complex pattern of craniofacial anomalies is due to defective ossification and connective tissue problem. We here present the case of a three-hour-old girl with a short trunk and craniofacial anomalies that brought in respiratory distress to the neonatal intensive care unit. This condition is rare and thus poses a major diagnostic challenge at an early stage.