关键词： neurological intensive care unit   thrombocytopenia   valproic acid  

摘要： What is known and objective Thrombocytopenia is a common laboratory abnormality among critically ill patients under neurological intensive care unit (NCU) care. Valproic acid (VPA), a widely used antiepileptic drug, is one of the common causes of drug-induced thrombocytopenia. The purpose of this study was to estimate the incidence and risk factors of thrombocytopenia after intravenous VPA therapy among the patients admitted to NCU. Methods We retrospectively reviewed the medical records of patients who were treated with intravenous VPA during their NCU stay between January 2014 and December 2018. We studied the frequency of thrombocytopenia and further evaluated the risk of thrombocytopenia in these patients. Results Among the 283 patients (181 male [64.0%], mean age: [61.0 +/- 14.9] years) who were treated with intravenous VPA, thrombocytopenia was observed in 104 patients (36.7%). Thrombocytopenia was associated with several risk factors, including lower baseline platelet counts (<200 x 10(9)/L);aetiologies other than intracranial or subarachnoid haemorrhage;longer use of VPA (more than 3 days);higher daily dose of VPA (more than 1000 mg/d);concurrent use of VPA with other antiepileptic drugs;infection;and the use of mechanical ventilation. Multivariate analysis found several independent risk factors of thrombocytopenia with intravenous VPA therapy, including lower baseline platelet counts, aetiologies other than intracranial or subarachnoid haemorrhage, use of VPA for more than 3 days and infection. What is new and conclusion Thrombocytopenia is common in NCU patients. Because several clinical and laboratory factors are associated with thrombocytopenia, careful use of VPA should be considered in patients with these risk factors.

关键词： COVID-19   Stroke   ACE2   Taste   Smell   Encephalopathy   Tropism   SARS-CoV-2  

摘要： A subset of patients withcoronavirus 2disease (COVID-19) experience neurological complications. These complications include loss of sense of taste and smell, stroke, delirium, and neuromuscular signs and symptoms. The etiological agent of COVID-19 isSARS-CoV-2(severe acute respiratory syndrome coronavirus 2), an RNA virus with a glycoprotein-studded viral envelope that uses ACE2 (angiotensin-converting enzyme 2) as a functional receptor for infecting the host cells. Thus, the interaction of the envelope spike proteins with ACE2 on host cells determines the tropism and virulence ofSARS-CoV-2. Loss of sense of taste and smell is an initial symptom of COVID-19 because the virus enters the nasal and oral cavities first and the epithelial cells are the receptors for these senses. Stroke in COVID-19 patients is likely a consequence of coagulopathy and injury to cerebral vascular endothelial cells that cause thrombo-embolism and stroke. Delirium and encephalopathy in acute and post COVID-19 patients are likely multifactorial and secondary to hypoxia, metabolic abnormalities, and immunological abnormalities. Thus far, there is no clear evidence that coronaviruses cause inflammatory neuromuscular diseases via direct invasion of peripheral nerves or muscles or via molecular mimicry. It appears that most of neurologic complications in COVID-19 patients are indirect and as a result of abystanderinjury to neurons.

关键词： Phosphodiesterase   cAMP   cGMP   Neurological disorders   PDE4 inhibitors   Central nervous system  

摘要： Phosphodiesterases (PDE) are a diverse family of enzymes (11 isoforms so far identified) responsible for the degradation of cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) which are involved in several cellular and biochemical functions. Phosphodiesterase 4 (PDE4) is the major isoform within this group and is highly expressed in the mammalian brain. An inverse association between PDE4 and cAMP levels is the key mechanism in various pathophysiological conditions like airway inflammatory diseases-chronic obstruction pulmonary disease (COPD), asthma, psoriasis, rheumatoid arthritis, and neurological disorders etc. In 2011, roflumilast, a PDE4 inhibitor (PDE4I) was approved for the treatment of COPD. Subsequently, other PDE4 inhibitors (PDE4Is) like apremilast and crisaborole were approved by the Food and Drug Administration (FDA) for psoriasis, atopic dermatitis etc. Due to the adverse effects like unbearable nausea and vomiting, dose intolerance and diarrhoea, PDE4 inhibitors have very less clinical compliance. Efforts are being made to develop allosteric modulation with high specificity to PDE4 isoforms having better efficacy and lesser adverse effects. Interestingly, repositioning PDE4Is towards neurological disorders including Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), multiple sclerosis (MS) and sleep disorders, is gaining attention. This review is an attempt to summarize the data on the effects of PDE4 overexpression in neurological disorders and the use of PDE4Is and newer allosteric modulators as therapeutic options. We have also compiled a list of on-going clinical trials on PDE4 inhibitors in neurological disorders.

关键词： adenosine deaminase type 2   Divry van Bogaert syndrome   livedo racemosa   livedo reticularis   Sneddon syndrome  

摘要： Livedo is a net-like violaceous skin pattern. It can be classified as physiological or pathological. The physiological livedo reticularis usually appears in cold conditions, whereas the pathological and irregular livedo, which persists in warm temperatures, is often labeled as 'livedo racemosa'. Some neurological pathologies are associated with livedo, most commonly those with an inflammatory component or those derived from systemic disorders. The present review summarizes the most important central and peripheral neurological diseases in pediatric and adult age groups associated with livedo, providing physicians with an overview of the clinical presentation, etiology, diagnosis and management of these conditions.

关键词： COVID-19   neurological symptoms   long-term effects   novel therapies   biomarkers  

摘要： Despite the increasing large population of COVID-19(+)infected patients, knowledge of the disease remains limited. Understanding the effects and long-term implications of COVID-19 will be paramount to implementing the right public health measures and developing future preventive and effective treatments. In this article, we discuss currently available information with COVID-19-related neurological complications, possible routes of virus infection into the central nervous system, and hypothesis about virus-induced cytokine storm syndrome, long-term outcomes, as well as ongoing clinical studies of novel therapies and biomarkers for COVID-19. Understanding the effects of COVID-19 on neurological systems is crucial for properly diagnosing and caring for the disease. We need to be prepared that COVID-19 could cause long-lasting debilitations after the infection has cleared. Investigating long-term effects of the disease will yield insight for providing comprehensive care to the survivors. Understanding these risks will also lead to better treatments as well as inform policies to create a system capable of caring for those affected by COVID-19 long after the pandemic has subsided.

关键词： at-risk neonates   Hammersmith Neonatal Neurological Examination   neurodevelopmental disability  

摘要： Background and Objectives: Hammersmith Neonatal Neurologic Examination (HNNE) is used to identify term and preterm infants at risk of neurodevelopmental disability. The test is recommended at corrected term age in preterm;and around 2 weeks postnatal age in term neonates. As the current trend is to discharge based on physiological stability, it may not be feasible to perform HNNE at recommended age. The authors investigated whether predictive ability of the test for neurodevelopmental disability remained unchanged if performed early (before discharge). Methods: The authors enrolled preterm and at-risk term neonates. HNNE PE was performed before discharge in all infants. The test was repeated in preterm infants at 40 weeks postmenstrual age and in term neonates at 2 weeks of age (HNNE RA). Neurodevelopmental disability was assessed at 1 year of age. Results: HNNE PE was done in 125 neonates (103 preterm, 22 term neonates). HNNE RA was done in 58% infants. Neurodevelopmental disability was assessed in 84 (67%) of infants. Neurodevelopmental disability was noted in 14/84 (16.6%) babies. The receiver operating characteristic curve of raw scores showed that area under the curve for HNNE PE (0.71) and HNNE RA (0.66) were similar. The sensitivity, specificity, positive predictive value, negative predictive value, positive likelihood ratio, and negative likelihood ratio for both the tests were similar for a cutoff optimality score of 32.5. HNNE PE could be performed up to 4 weeks earlier than HNNE RA with the same predictive ability for neurodevelopmental disability. Conclusions: HNNE PE was as reliable as HNNE RA in predicting neurodevelopmental disability at 1 year of age. Completion of the test is assured and provides several weeks lead time for early intervention.

关键词： discharge disposition   neurological condition   outcomes  

摘要： Objective To study characteristics and outcomes of patients with stroke, traumatic brain injury (TBI), and epilepsy with discharge against medical advice (DAMA). Data Sources/Study Setting Retrospective analysis of the 2013 Nationwide Readmissions Database, a nationally representative inpatient administrative dataset. Study Design Associations between predictors and DAMA at index admission were analyzed using adjusted logistic models. We examined 30-day all-cause readmissions. Data Collection Methods Patients aged >= 18 years at index admission for International Classification of Diseases-9 diagnosis code of epilepsy, TBI, or stroke were included. Principal Findings Discharge against medical advice occurred in 1998/58278 patients (3.43 percent) in the epilepsy group, 1762/211 213 (0.83 percent) in the stroke group, and 1289/74 652 (1.73 percent) in the TBI group. Factors consistently associated with increased likelihood of DAMA included lower age, male sex, non-Medicare and nonprivate insurance, lower socioeconomic status, and behavioral risk factors (smoking history, alcohol history, and drug use). The crude 30-day all-cause readmission rate for those with DAMA from their index admission was 16.4 percent for the stroke cohort, 13.9 percent for epilepsy, and 13.4 percent for TBI. DAMA at index admission was significantly associated with increased risk of 30-day all-cause readmission among all groups (adjusted odds ratio 1.79, 95% CI: 1.65-1.94,P < .0001). Conclusions Age, sex, insurance status, socioeconomic status, and behavioral factors were associated with DAMA in neurological patients. Further research is needed to develop interventions to reduce DAMA in high-risk groups.