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A review of published articles examining the effects of manganese exposure to workers and community residents shows adverse neurologic outcomes. Innovative biomarkers, including those from neuroimaging, were incorporated into many of these studies to assess both manganese exposure and neurologic outcomes. A variety of health effects were evaluated, including cognitive and motor impairments. Studies of community participants residing near manganese point sources show variability in outcomes, reflecting the complexities of exposure measurement, individual absorption, and assessment of neurologic effects. The aging population provides insight into the impacts of chronic exposure in younger populations.

BACKGROUND AND PURPOSE: Digital subtraction myelography performed with the patient in the lateral decubitus position has the potential for increased sensitivity over prone-position myelography in the detection of spinal CSF-venous fistulas, a well-established cause of spontaneous intracranial hypotension. We report on the safety of performing routine, consecutive-day right and left lateral decubitus digital subtraction myelography in these patients. MATERIALS AND METHODS: In this retrospective case series, all patients undergoing consecutive-day lateral decubitus digital subtraction myelography for suspected spinal CSF leak between September 2018 and September 2019 were identified. Chart review was performed to identify any immediate or delayed adverse effects associated with the procedures. Procedural parameters were also analyzed due to inherent variations associated with the positive-pressure myelography technique that was used. RESULTS: A total of 60 patients underwent 68 pairs of consecutive-day lateral decubitus digital subtraction myelographic examinations during the study period. No major adverse effects were recorded. Various minor adverse effects were observed, including pain requiring analgesics (27.2%), nausea/vomiting requiring antiemetics (8.1%), and transient neurologic effects such as syncope, vertigo, altered mental status, and autonomic dysfunction (5.1%). Minor transient neurologic effects were correlated with increasing volumes of intrathecal saline injectate used for thecal sac prepressurization. CONCLUSIONS: In patients with spontaneous intracranial hypotension and suspected spontaneous spinal CSF leak, consecutive-day lateral decubitus digital subtraction myelography demonstrates an acceptable risk profile without evidence of neurotoxic effects from cumulative intrathecal contrast doses. Higher intrathecal saline injectate volumes may correlate with an increased incidence of minor transient periprocedural neurologic effects.

The COVID-19 pandemic has been met with studies on risk factors, characteristics, and clinical course. Among these characteristics are neurologic symptoms, which may provide improved insight into the mechanisms of this novel virus and the brain's susceptibility to infectious diseases. This article aims to discuss 1) findings related to neurologic complications, 2) how they connect to and are bidirectionally impacted by bioimmunology, 3) how this combination of biological mechanisms impact and are impacted by psychosocial stressors, and 4) the importance of considering potential neurodegenerative consequences of COVID-19. Longitudinal studies on neuropathology and cognition are critical to avoiding premature conclusions related to long-term neurologic effects.

Introduction: Recent research has observed the ability of coronavirus disease 2019 (COVID-19) to spread in the brain from the respiratory system. The associated neurological disorder includes encephalopathies, inflammatory syndromes, stroke, peripheral neuropathies, and various other central nervous system disorders. This study aims to highlight the long-term neurological sequelae in patients with COVID-19 disease. Methods: This long-term study was carried out in the COVID-19 unit of a tertiary care hospital in Pakistan from July 2020 to July 2021. After obtaining informed consent, we enrolled 1000 patients who recovered from COVID-19 and were discharged. The participants were followed up after 30 and 90 days. Results: At the time of enrollment, there were 602 (60.2%) males and 398 (39.8%) females. The most common neurological symptom on 30-day follow-up was headache (8.8%), followed by insomnia. The most common neurological symptom on day 90 follow-up was insomnia (5.07%), followed by an altered sense of smell (3.3%). Conclusion: COVID-19 tends to produce a wide range of neurological symptoms, ranging from headache to anosmia to increased risk of stroke, that complicates clinical management. Potential neurologic effects and drug interactions have been reported secondary to the medications used to treat COVID-19. In light of the aforementioned facts, COVID-19 could potentially have a long-term effect on the brain. Therefore, it is important that the clinicians must be aware of the potential neurologic complications. Lastly, proper follow-up is recommended that would aid in timely recognition and management of the neurological disorder.

Experimental investigations have shown that drug abuse initiates a cascade of pathophysiological events including toxic and hypoxic-ischemic injury on neurons, microglia and astrocytes, which finally lead to widespread disturbances in the brain. There are many reports about the psychiatric and neurologic effects of multiple drug abuse, but only a few clinical studies reporting possible correlation between recreational illicit drugs and gliomas. In this paper we present the case of a 40 years-old male patient, with a long history (almost ten years) of multiple drug abuse, including cocaine, heroin, marijuana, ethnobotanical drugs and nicotine, who was diagnosed and surgically treated for a supratentorial secondary giant cell glioblastoma (sgcGB) developed in a diffuse astrocytoma NOS. Depending on the type of the illicit drug used by the patient and the moment of life he used them, the morphological features identified in the histological samples of our patient confirmed the gliomagenesis effect of chronic multiple drug abuse, but also its inhibitory effects on tumour cells growth. This was due to the fact that although the tumour was large in size and caused brain sub-falcine herniation, the patient reported the onset of seizures only late in the evolution. In conclusion, the diagnosis of a brain tumour should take into consideration not only patient's clinical and imaging data, but also his lifestyle, especially his addiction to recreational drugs.

Carotid artery stenosis typically causes hemispheric neurologic effects by atheroembolism. Nonhemispheric symptoms, such as syncope, are generally not attributable to extracranial carotid disease. This report describes a 62-year-old woman with severe bilateral carotid artery stenosis, right vertebral artery occlusion, and severe left vertebral artery stenosis who presented with transient loss of consciousness and unilateral weakness when upright. Her symptoms resolved after right carotid endarterectomy. Whereas vertebrobasilar insufficiency alone can cause syncope, in the case of severe multivessel cerebrovascular disease, unilateral carotid revascularization was successful in treating the patient's transient loss of consciousness, suggesting global cerebral hypoperfusion as the cause. Keywords: Carotid stenosis, Vertebrobasilar, Hypoperfusion, Positional

BackgroundPolymer coating embolism due to vascular medical device use is an increasingly recognized iatrogenic complication. This phenomenon has been linked with various adverse effects including neuroinflammation, acute ischemic stroke, cerebral hemorrhage, and death. Notably, procedure- and device-specific risks of this complication are poorly investigated. In this study, we evaluate the detectable frequency of intra-arterial polymer coating delamination among patients who underwent endovascular thrombectomy for treatment of acute ischemic stroke due to large vessel occlusion.MethodsNinety-two cerebral thrombectomy specimens were retrospectively analyzed for the presence of polymer coating particulates. Histologic findings were correlated with demographic and procedural details and patient outcomes.ResultsEvidence of polymer coating deposition was found in 30 of 92 extracted thrombi (33%). No correlation between intrathrombus polymer deposition and use of a specific thrombectomy device such as a stent retriever, aspiration catheter, or guide catheter was found. However, heterogeneous patterns of device use suggest a number of culprit devices. A trend toward longer procedure times and multiple thrombectomy passes was noted in positive cases. Intrathrombus polymer deposition was not associated with adverse clinical outcomes as measured by the 90-day modified Rankin Scale (mRS); however, small sample size and follow-up intervals limit interpretation. Ninety-day outcomes based on mRS may not fully capture the clinical effects of acute and/or delayed intracerebral polymer complications.ConclusionIn light of documented adverse neurologic effects, the frequency of intrathrombus polymer particulates indicates the need for consensus testing methods and large-scale long-term prospective clinical device trials, with inclusion of relevant endpoints to better assess biomaterial and device risks to patients.

Chronic alcohol use induces silent changes in the structure and function of the central and peripheral nervous systems that eventually result in irreversible, debilitating repercussions. Once identified, nutritional supplementation and cessation measures are critical in preventing further neurologic damage. The proposed mechanisms of neuronal injury in chronic alcohol abuse include direct toxic effects of alcohol and indirect effects, including those resulting from hepatic dysfunction, nutritional deficiencies, and neuroinflammation. Clinical manifestations include cerebellar ataxia, peripheral neuropathy and Wernicke-Korsakoff encephalopathy. Continued exploration of the pathophysiologic mechanisms may lead to the discovery of early interventions that can prevent permanent neurologic injury.

Coronavirus disease 2019 (COVID-19) grew to pandemic proportions in 2020. Research has shown that the causative virus, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), uses the angiotensin-converting enzyme II (ACE-II) receptor to attack host cells. These ACE-II receptors are present essentially in all organs, acting as a route of entry for SARS-CoV-2 to cause a wide variety of manifestations. There is growing research showing the neurologic effects of COVID-19. There have been several cases of encephalopathy, stroke, and encephalitis associated with COVID-19, however, intraventricular hemorrhages (IVH) have rarely been reported. Here we present a case of an IVH in the setting of COVID-19. A 32-year-old male with no past medical history, and not taking any medications, presented to the emergency room after acute onset loss of consciousness. Inflammatory markers were elevated, and computerized tomographic (CT) of the head and chest showed an intraventricular hemorrhage and bilateral interstitial infiltrates, respectively. Although possibly coincidental, this may represent a rare extrapulmonary fatal manifestation of COVID-19. With the growing evidence of neurologic presentations in patients with COVID-19, clinicians should maintain a high index of suspicion for COVID-19 to cause fatal extrapulmonary manifestations.

Research on neurologic effects of air pollution has focused on neurodevelopment or later-life neurodegeneration; other effects throughout adulthood have received less attention. We examined air pollution levels and neurologic symptoms among 21,467 adults in US Gulf Coast states. We assigned exposure using Environmental Protection Agency estimates of daily ambient particulate matter 2.5 (PM(2.5)) and ozone. Gulf Long-term Follow-up Study participants reported neurologic symptoms at enrollment (2011–2013). We estimated cross-sectional associations between each air pollutant and prevalence of “any” neurologic, central nervous system (CNS), or peripheral nervous system (PNS) symptoms. Ambient PM(2.5) was consistently associated with prevalence of neurologic symptoms. The highest quartile of 30-day PM(2.5) was associated with any neurologic symptom (prevalence ratio [PR] = 1.16; 95% confidence interval [CI] = 1.09, 1.23) and there were increasing monotonic relationships between 30-day PM(2.5) and each symptom category (P-trend ≤ 0.01). Associations with PM(2.5) were slightly stronger among nonsmokers and during colder seasons. The highest quartile of 7-day ozone was associated with increased prevalence of PNS symptoms (PR = 1.09; 95% CI = 1.00, 1.19; P-trend = 0.03), but not with other outcomes. Ozone concentrations above regulatory levels were suggestively associated with neurologic symptoms (PR = 1.06; 95% CI = 0.99, 1.14). Mutual adjustment in co-pollutant models suggests that PM(2.5) is more relevant than ozone in relation to prevalence of neurologic symptoms.

Previously seizures have been reported as presenting neurological manifestation with COVID-19 infection. There is a growing literature on the delayed neurologic effects of COVID-19 infection. Here, we report a case with insidious onset of focal impaired awareness seizures associated with left temporal epileptiform interictal and ictal discharges consistent with focal epilepsy; occurring within a short time frame of the diagnosis of COVID-19 infection. This may be possibly a post COVID-19 inflammatory syndrome manifesting as new onset focal epilepsy with focal non-motor seizures with impaired awareness. As implicated by presentation with seizure as in our case, longterm follow-up studies are warranted to further investigate if the patients who acquire COVID-19 infection are at increased risk of developing epilepsy as a delayed manifestation.

This chapter deals with neurologic complications of drug abuse, i.e., use of illicit drugs or the prescription or over-the-counter drugs for purposes other than those for which they are meant, or excessive amounts of substances that are normally consumed in moderation and includes the problems of drug addiction and withdrawal. Most of the adverse effects are now covered under the broad term of substance use disorders. Drugs that are frequently abused include opioids, psychostimulants such as cocaine, and sedatives and hypnotics such as benzodiazepines. Therapeutic uses of marijuana compounds as well as adverse effects of illicit use are also described. Pathomechanisms of neurologic disorders due to drug or substance abuse are discussed. Some are primary effects, whereas others such as falls with CNS trauma are secondary to other adverse effects such as seizures. Cognitive impairment, CNS infections, and stroke are other complications of illicit drug use.

Introduction Insofar, use of programmed cell death-1 (PD-1) immune checkpoint inhibitors in oncology has been linked with several immune-mediated neurologic effects. However, grade 3 to 4 adverse events such as myasthenic crisis have been vanishingly rare. Case presentation: We present herein a unique patient with Hodgkin lymphoma who developed late-onset double-seronegative myasthenia gravis syndrome followed by myasthenic crisis after 16 weeks of therapy with nivolumab. One day prior to this event, she developed ptosis, diplopia, bulbar symptoms of dysphagia, dysarthria, orthopnea as well as extremity weakness. She required intubation, mechanical ventilation, plasmapheresis and steroid therapy. Management and outcome: She gradually achieved a near-complete resolution of neurologic symptoms over the next several weeks. On a follow-up visit eight weeks later, she only has some residual diplopia. Restaging scans showed a continued decrease in size of the mediastinal mass, without abnormal uptake. She remains on prednisone 10 mg orally daily. Discussion Prompt recognition of this rare phenomenon, immediate discontinuation of checkpoint inhibitor therapy and subsequent management with immunosuppressive therapy are necessary steps in order to minimize the considerable rates of morbidity and mortality.

Background Cardiac arrest (CA) is the most common cause of acute neurologic insult in children. Many survivors have significant neurocognitive deficits at 1 year of recovery. Epoxyeicosatrienoic acids (EETs) are multifunctional endogenous lipid signaling molecules that are involved in brain pathobiology and may be therapeutically relevant. However, EETs are rapidly metabolized to less active dihydroxyeicosatrienoic acids by soluble epoxide hydrolase (sEH), limiting their bioavailability. We hypothesized that sEH inhibition would improve outcomes after CA in an infant swine model. Male piglets (3–4 kg, 2 weeks old) underwent hypoxic-asphyxic CA. After resuscitation, they were randomized to intravenous treatment with an sEH inhibitor (TPPU, 1 mg/kg; n = 8) or vehicle (10% poly(ethylene glycol); n = 9) administered at 30 min and 24 h after return of spontaneous circulation. Two sham-operated groups received either TPPU (n = 9) or vehicle (n = 8). Neurons were counted in hematoxylin- and eosin-stained sections from putamen and motor cortex in 4-day survivors. Results Piglets in the CA + vehicle groups had fewer neurons than sham animals in both putamen and motor cortex. However, the number of neurons after CA did not differ between vehicle- and TPPU-treated groups in either anatomic area. Further, 20% of putamen neurons in the Sham + TPPU group had abnormal morphology, with cell body attrition and nuclear condensation. TPPU treatment also did not reduce neurologic deficits. Conclusion Treatment with an sEH inhibitor at 30 min and 24 h after resuscitation from asphyxic CA does not protect neurons or improve acute neurologic outcomes in piglets.

Deep brain stimulation (DBS) is an effective therapy as an alternative to pharmaceutical treatments for Parkinson's disease (PD). Aside from factors such as instrumentation, treatment plans, and surgical protocols, the success of the procedure depends heavily on the accurate placement of the electrode within the optimal therapeutic targets while avoiding vital structures that can cause surgical complications and adverse neurologic effects. Although specific surgical techniques for DBS can vary, interventional guidance with medical imaging has greatly contributed to the development, outcomes, and safety of the procedure. With rapid development in novel imaging techniques, computational methods, and surgical navigation software, as well as growing insights into the disease and mechanism of action of DBS, modern image guidance is expected to further enhance the capacity and efficacy of the procedure in treating PD. This article surveys the state-of-the-art techniques in image-guided DBS surgery to treat PD, and discusses their benefits and drawbacks, as well as future directions on the topic.

Neurologic complications of lymphoid cancer can be challenging to recognize and treat. The nervous system can be affected directly by hematogenous or local spread of lymphoma. Indirect neurologic effects of lymphoma include paraneoplastic syndromes and vascular complications. Lymphoma treatments can also cause neurologic complications. Early identification and treatment are crucial to stabilize or reverse neurologic deficits, prevent further nervous system injury, and optimize overall oncologic therapy. This article provides an overview of the different neurologic complications of lymphoma and its treatments, in addition to presenting case studies that emphasize commonly encountered clinical scenarios.

Background Metals have been shown to have a wide range of neurologic effects across the life course, but most studies consider neurodevelopment or neurodegenerative diseases in older adults. We investigated exposure to metals during adulthood in association with subclinical neurologic endpoints, considering the metals individually and as a mixture, and potential interactions among exposures. Methods We measured blood levels of cadmium, lead, mercury, manganese, and selenium in 1007 Gulf state residents and estimated cross-sectional associations between ranked levels of blood metals and the presence of self-reported neurologic symptoms. Single pollutant models were mutually adjusted for other metals and we used quantile g-computation to evaluate associations with exposure to the combined mixture. In stratified analyses, we assessed heterogeneity by smoking and blood selenium. Results The highest quartile of cadmium was associated with a higher prevalence of central nervous system symptoms (prevalence ratio [PR] = 1.50; 95% confidence interval [CI] = 1.13, 1.99), with stronger associations among nonsmokers (PR = 1.63; 95% CI = 1.11, 2.38) and those with low selenium (PR = 2.29, 95% CI = 1.50, 3.49). Selenium also modified associations between lead and peripheral nervous system symptoms, with increased symptoms in the low selenium group at all quartiles of exposure (P-trend = 0.07). Conversely, those with the highest co-exposure to mercury and selenium had reduced neurologic symptoms (PR = 0.73, 95% CI = 0.55, 0.96). Results of the mixture analysis were consistent with single chemical results. Conclusions Cadmium exhibited the most consistent relationship with increased neurologic symptoms, though lead was an important exposure in subgroup analyses. Selenium may modify subclinical neurotoxic effects of metals at non-occupational levels in adults.

Electricity injuries are a global health problem, especially in low-income countries. The present case report involves a 4-year-old girl with quadriparesis following a low-voltage electrical injury. She was alert and her vital signs were normal on admission. The results of her examination were normal, except for decreased muscle power of the limbs, which was significantly improved during observation in the emergency ward and the subsequent follow-up. Clinical evidence suggested the diagnosis of transient neurologic effects associated with the electrical injury. Some degrees of neurological impairment are often observed in patients after electrical damage. Given the multiorgan dysfunction observed in many electrical injury patients, it is recommended to perform neurological examinations, if possible, at the first visit and follow-ups.

Bronchopulmonary dysplasia (BPD) is among the most common and consequential morbidities in very preterm infants. This chapter reviews the evidence for pharmacological agents that have been shown in randomized controlled trials, or meta-analyses, to reduce the risk of developing BPD in very preterm infants. Caffeine and vitamin A are the only medications shown in high-quality randomized trials to safely reduce the risk of BPD. Systemic dexamethasone is an effective therapy, but for many very preterm infants the risk of adverse long-term neurologic effects, including cerebral palsy, outweighs the benefits. For those at high risk of developing BPD, dexamethasone initiated after the first 7 days of age may be appropriate. Systemic hydrocortisone therapy beginning in the first week of life has been shown to reduce the risk of death or BPD, but may not prevent BPD in surviving very preterm infants nor produce long-term improvement in neurodevelopment.

Background: Styrene is an established neurotoxicant at occupational levels, but effects at levels relevant to the general population have not been studied. We examined the neurologic effects of environmental styrene exposure among U.S. Gulf coast residents. Methods: We used National Air Toxics Assessment (NATA) 2011 estimates of ambient styrene concentrations to assign exposure levels for 21,962 non-diabetic Gulf state residents, and additionally measured blood styrene concentration in a subset of participants (n = 874). Neurologic symptoms, as well as detailed covariate information, were ascertained via telephone interview. We used log-binomial regression to estimate prevalence ratios (PR) and 95% confidence intervals (95% CI) for cross-sectional associations between both ambient and blood styrene levels and self-reported neurologic symptoms. We estimated associations independently for ten unique symptoms, as well as for the presence of any neurologic, central nervous system (CNS), or peripheral nervous system (PNS) symptoms. We also examined heterogeneity of associations with estimated ambient styrene levels by race and sex. Results: One-third of participants reported at least one neurologic symptom. The highest quartile of estimated ambient styrene was associated with one or more neurologic (PR, 1.12; 95% CI: 1.07,1.18), CNS (PR, 1.17; 95% CI: 1.11,1.25), and PNS (PR, 1.16; 95% CI: 1.09,1.25) symptom. Results were less consistent for biomarker analyses, but blood styrene level was suggestively associated with nausea (PR, 1.78; 95% CI: 1.04, 3.03). In stratified analyses, we observed the strongest effects among non-White participants. Conclusions: Increasing estimated ambient styrene concentration was consistently associated with increased prevalence of neurologic symptoms. Associations between blood styrene levels and some neurologic symptoms were suggestive. Environmental styrene exposure levels may be sufficient to elicit symptomatic neurotoxic effects. Keywords: Air pollution, Nervous system, Styrene, Biomarker, Neurologic

The spread of radiofrequency electromagnetic fields (RF-EMF) is rising and health effects are still under investigation. RF-EMF promote oxidative stress, a condition involved in cancer onset, in several acute and chronic diseases and in vascular homeostasis. Although some evidences are still controversial, the WHO IARC classified RF-EMF as "possible carcinogenic to humans", and more recent studies suggested reproductive, metabolic and neurologic effects of RF-EMF, which are also able to alter bacterial antibiotic resistance. In this evolving scenario, although the biological effects of 5G communication systems are very scarcely investigated, an international action plan for the development of 5G networks has started, with a forthcoming increment in devices and density of small cells, and with the future use of millimeter waves (MMW). Preliminary observations showed that MMW increase skin temperature, alter gene expression, promote cellular proliferation and synthesis of proteins linked with oxidative stress, inflammatory and metabolic processes, could generate ocular damages, affect neuro-muscular dynamics. Further studies are needed to better and independently explore the health effects of RF-EMF in general and of MMW in particular. However, available findings seem sufficient to demonstrate the existence of biomedical effects, to invoke the precautionary principle, to define exposed subjects as potentially vulnerable and to revise existing limits. An adequate knowledge of pathophysiological mechanisms linking RF-EMF exposure to health risk should also be useful in the current clinical practice, in particular in consideration of evidences pointing to extrinsic factors as heavy contributors to cancer risk and to the progressive epidemiological growth of noncommunicable diseases.

Objective To describe the treatment of sinonasal aspergillosis with topical 1% clotrimazole solution in dogs with cribriform plate lysis. Materials and methods This retrospective study includes data retrieval from medical records of dogs with sinonasal aspergillosis and cribriform plate lysis that underwent topical treatment with 1% clotrimazole solution. Results Five dogs with sinonasal aspergillosis, cribriform plate lysis diagnosed on CT scans, and normal neurologic examinations were treated with a single (n=3) or multiple (n=2) infusions of clotrimazole solution. No dogs developed clinical neurologic disease after therapy. Clinical significance In this study, a topical clotrimazole solution was not associated with adverse neurologic effects in neurologically normal dogs with sinonasal aspergillosis and cribriform plate lysis.

Background The chemicals benzene, toluene, ethylbenzene, and xylenes (BTEX) are neuroactive. Exposures often co-occur because they share common sources. We examined neurologic effects of environmental BTEX exposure among U.S. Gulf coast residents taking into account concomitant exposures. Methods We measured blood concentrations of BTEX in 690 Gulf state residents. Neurologic symptoms were ascertained via telephone interview. We used log-binomial regression to estimate associations between blood BTEX levels and self-reported neurologic symptoms independently for the presence of any neurologic, central (CNS), or peripheral nervous system (PNS) symptoms. We estimated associations in single chemical models mutually adjusted for co-occurring BTEX and used weighted quantile sum regression to model associations between the combined BTEX mixture and neurologic symptoms. Results Half (49%) of participants reported at least one neurologic symptom. Each BTEX chemical was associated with increased CNS and PNS symptoms in single-chemical models comparing the highest to lowest quartile of exposure. After adjusting for coexposures, benzene was associated with CNS symptoms among all participants (PR = 2.13, 95% CI: 1.27, 3.57) and among nonsmokers (PR = 2.30, 95% CI: 1.35, 3.91). After adjusting for coexposures, associations with toluene were apparent only for reporting multiple PNS symptoms (PR = 2.00, 95% CI: 0.96, 4.16). In mixture analyses, a one-quartile increase in BTEX exposure was associated with neurologic symptoms (OR = 1.47, 95% CI: 1.11, 1.98). The weighted quantile sum index weighted benzene most heavily, which was consistent with single chemical analyses. Conclusions Increasing blood benzene concentration was associated with increased prevalence of CNS symptoms. In this sample, BTEX-associated neurologic effects are likely driven by exposure to benzene and, to a lesser extent, toluene.

The blood–brain barrier (BBB) is a complex anatomic and physiologic structure made up of associated structures known as the neurovascular unit (NVU). The NVU protects the sensitive central nervous system (CNS) from molecules with potential toxic or unwanted neurologic effects. These protective mechanisms have prevented introduction of therapeutic drugs for treatment of diseases of the CNS; however, extensive study of the BBB has identified a wide variety of opportunities to exploit it in future drug development. Efforts to accurately measure the ability of medications to cross the NVU into positions of therapeutic benefit are varied and are, in many ways, complementary. Certain drug modifications opened the door to enhanced therapeutics, but also to unexpected CNS toxicities and unanticipated concentrations and toxicities in systemic organ systems. Osmotic BBB disruption with intra-arterial mannitol has been well characterized and clinically applied for years as a successful method for delivery of CNS therapeutics across the NVU. Preclinical analysis, clinical applications of drug delivery and safety, and therapeutic benefit with minimal toxicities have evolved over the years thanks to preclinical and translational studies of the effects of BBB disruption. Future developments will shed light on opportunities for targeted drug delivery using known pathways through the NVU, with continued emphasis on specificity, safety, and therapeutic benefit.

We present a case of a child with Aicardi-Goutières Syndrome (AGS) undergoing general anesthesia for placement of a laparoscopic gastrostomy tube. AGS is a rare genetic leukodystrophy that can affect most organ systems with extensive neurologic effects. These changes potentially have great anesthetic implications. We describe our anesthetic management and discuss these implications. The patient had a prolonged duration of action of rocuronium and an otherwise uneventful anesthetic course.

The global pandemic of SARS-CoV-2 has been known to have diverse neurologic complications among adult patients. The neurologic effects of SARS-CoV-2 in the pediatric population is poorly described, especially in those with rare underlying neurologic conditions. We describe the first known case of SARS-CoV-2 in a pediatric patient with refractory opsoclonus-myoclonus syndrome. A 25-month-old female with progressive opsoclonus-myoclonus syndrome secondary to metastatic neuroblastoma status-post resection and chemotherapy presented with worsening opsoclonus, tremor, and breakthrough seizures. She had no fever or respiratory symptoms at presentation. Urine catecholamines were unchanged, with low suspicion for tumor recurrence. She was found to have SARS-CoV-2 via nasopharnygeal PCR assay. She received intravenous immunoglobulin and dexamethasone therapy with improvement in opsoclonus-myoclonus syndrome symptoms and was discharged home at her neurologic baseline. Patients with opsoclonus-myoclonus syndrome may present with exacerbation of symptoms in the context of SARS-CoV-2. This case describes a sentinel report of a child with opsoclonus-myoclonus syndrome presenting with worsening symptoms with concomitant SARS-CoV-2. Improvement in symptoms was achieved with standard of care therapies.

The development of drugs to treat psychosis is a fascinating nexus for understanding mechanisms underlying disorders of mind and movement. Although the risk of drug-induced extrapyramidal syndromes has been mitigated by the acceptance of less potent dopamine antagonists, expansive marketing and off-label use has increased the number of susceptible people who may be at risk for these neurologic effects. Clinicians need to be familiar with advances in diagnosis and management, which are reviewed herein. A better understanding of drug-induced effects on the motor circuit may improve patient safety, enhance antipsychotic effectiveness, and provide insights into mechanisms underlying antipsychotic activity in parallel brain circuits.

The management of depression during pregnancy is complicated by the risks to the mother and the fetus by both the disease state itself as well as the medications used to treat it. Serotonin reuptake inhibitors, which include the selective serotonin reuptake inhibitors (SSRIs), are commonly used medications for the treatment of depression and other mood disorders. SSRIs readily cross the placenta and can affect fetal 5-hydroxytryptamine levels. Research into the effects of SSRIs on neonates has shown conflicting results, likely confounded by the fact that maternal depression itself may also lead to adverse outcomes for the neonate. This review aims to discuss the link between markers of fetal central nervous damage and maternal SSRI use, evaluate the literature reporting various short- and long-term neurologic effects in neonates after maternal use of SSRIs, and develop recommendations for the management of and parental counseling about various adverse neurologic outcomes of SSRI use during pregnancy.

Current medical countermeasures for organophosphate (OP)-induced status epilepticus (SE) are not effective in preventing long-term morbidity and there is an urgent need for improved therapies. Rat models of acute intoxication with the OP, diisopropylfluorophosphate (DFP), are increasingly being used to evaluate therapeutic candidates for efficacy in mitigating the long-term neurologic effects associated with OP-induced SE. Many of these therapeutic candidates target neuroinflammation and oxidative stress because of their implication in the pathogenesis of persistent neurologic deficits associated with OP-induced SE. Critical to these efforts is the rigorous characterization of the rat DFP model with respect to outcomes associated with acute OP intoxication in humans, which include long-term electroencephalographic, neurobehavioral, and neuropathologic effects, and their temporal relationship to neuroinflammation and oxidative stress. To address these needs, we examined a range of outcomes at later times post-exposure than have previously been reported for this model. Adult male Sprague-Dawley rats were given pyridostigmine bromide (0.1 mg/kg, im) 30 min prior to administration of DFP (4 mg/kg, sc), which was immediately followed by atropine sulfate (2 mg/kg, im) and pralidoxime (25 mg/kg, im). This exposure paradigm triggered robust electroencephalographic and behavioral seizures that rapidly progressed to SE lasting several hours in 90% of exposed animals. Animals that survived DFP-induced SE (~70%) exhibited spontaneous recurrent seizures and hyperreactive responses to tactile stimuli over the first 2 months post-exposure. Performance in the elevated plus maze, open field, and Pavlovian fear conditioning tests indicated that acute DFP intoxication reduced anxiety-like behavior and impaired learning and memory at 1 and 2 months post-exposure in the absence of effects on general locomotor behavior. Immunohistochemical analyses revealed significantly increased expression of biomarkers of reactive astrogliosis, microglial activation and oxidative stress in multiple brain regions at 1 and 2 months post-DFP, although there was significant spatiotemporal heterogeneity across these endpoints. Collectively, these data largely support the relevance of the rat model of acute DFP intoxication as a model for acute OP intoxication in the human, and support the hypothesis that neuroinflammation and/or oxidative stress represent potential therapeutic targets for mitigating the long-term neurologic sequelae of acute OP intoxication.

Hip resurfacing arthroplasty (HRA) has a long clinical history and has utilized a variety of bearing material combinations with mixed clinical success. This paper reviews the local and systemic consequences of metal-on-metal hip resurfacing implants. Local tissue reactions cover a spectrum from no clinically adverse effects to adverse complications leading to revision associated with pain, osteolysis, or pseudotumor formation. Factors affecting the local tissue response to any implant include surgical, implant and patient factors. Metal particle size, shape and volume are important to the response around metal-on-metal implants. Surgical placement, particularly of the acetabular component, is important to the generation of wear debris. The number of patients with a sensitivity to the cobalt or chromium constituents of metal-on-metal implants is thought to be low and the cause and effect between patient sensitivity and implant failure is considered to be uncertain. Systemic toxicity from chronic exposure to the ions from metal-on-metal implants is still extremely rare although studies into potential cardiac or neurologic effects have suggested that subtle changes may be present that warrant continued and larger follow-up studies of longer-term cohorts.

Zika virus (ZIKV) is an arthropod-borne virus that belongs to the Flaviviridae family. Although most cases are mild or go undetected, rare severe neurologic effects, including congenital ZIKV syndrome (CZS) and Guillain-Barre syndrome, have been identified. The serious neurologic complications associated with ZIKV prompted the declaration of the public health emergency of international concern by the World Health Organization. Overall, transmission occurred throughout South and Central America as well as the Caribbean, affecting 48 countries and territories from March 2015 to March 2017. Long-term management of CZS requires a comprehensive combination of supportive services throughout early development.

Clozapine is an atypical antipsychotic drug prescribed for treatment-resistant schizophrenia. The risk of adverse hematologic, cardiovascular, and neurologic effects has tempered its use, and reports of overdoses remain rare. We report a case of accidental acute clozapine intoxication in a clozapine-naïve patient, who presented with symptoms mimicking acute stroke and later developed status epilepticus. Clozapine intoxication is a rare presentation in the emergency department with potential for iatrogenic harm if not correctly identified.

Background Piglets are used to study neurologic effects of deep hypothermic circulatory arrest (DHCA), but no studies have compared human and swine electroencephalogram (EEG) responses to DHCA. The importance of isoelectricity before circulatory arrest is not fully known in neonates. We compared the EEG response to DHCA in human neonates and piglets. Methods We recorded 2 channel, left and right centroparietal, subdermal EEG in 10 neonatal patients undergoing operations involving DHCA and 10 neonatal piglets that were placed on cardiopulmonary bypass and underwent a simulated procedure using DHCA. EEG waveforms were analyzed for the presence and extent of burst suppression and isoelectricity by automated moving window analysis. The patients were monitored with 16-channel array EEG for 48 hours postoperatively and underwent postoperative brain magnetic resonance imaging. Results After induction of anesthesia, humans and piglets both displayed slowing or brief suppression, then mild burst suppression, and then severe burst suppression during cooling. All piglets subsequently achieved isoelectricity at 22.4° ± 6.9°C, whereas only 1 human did at 20.2°C. Piglets and humans emerged from severe, mild, and then brief suppression patterns during rewarming. Among the patients, there were no seizures during postoperative monitoring and 1 instance of increased white matter injury on postoperative magnetic resonance imaging. Conclusions Our data suggest that current cooling strategies may not be sufficient to eliminate all EEG activity before circulatory arrest in humans but are sufficient in swine. This important difference between the swine and human response to DHCA should be considered when using this model.

The elderly, especially women, are at risk for severe side effects from antipsychotic medication. There are a number of reasons for this. This paper lists the reasons, the nature of the effects, and provides clinical recommendations for prevention and treatment.

Xenon has been shown to have positive neurologic effects in various pre-clinical models. This study systematically reviewed the randomized-controlled trials (RCTs) investigating neurologic and cognitive outcomes associated with the clinical use of xenon. We searched PubMed, CENTRAL, EMBASE, CINAHL, elibrary.ru (for Russian studies), Google Scholar (for Russian studies), and Wanfang (for Chinese studies) for appropriate RCTs comparing neurologic or cognitive outcomes after clinical use of xenon with control treatment or with other anesthetic agents. Seventeen RCTs met the inclusion criteria. Two studies investigated the effects of xenon plus therapeutic hypothermia to treat neonatal asphyxia or out-of-hospital cardiac arrest. Compared with therapeutic hypothermia alone, xenon and therapeutic hypothermia reduced cerebral white matter abnormalities after cardiac arrest but had no effect on neurocognitive outcome and mortality. Xenon had no added value when used to treat neonatal asphyxia. Thirteen RCTs compared neurocognitive effects of xenon with other anesthetic agents in surgical patients. While xenon may be associated with improved short-term (< three hours) cognitive outcome, no medium-term (six hours to three months) advantage was observed, and longer-term data are lacking. No differences in biochemical (S-100β, neuron-specific enolase) and neuropsychologic (attentional performance) outcomes were found with xenon compared with other anesthetic drugs. Finally, two studies suggest that brief, intermittent administration of sub-anesthetic doses of xenon to patients during the acute phase of substance withdrawal may improve neurocognitive outcomes. Despite promising pre-clinical results, the evidence for positive clinical neurologic and cognitive outcomes associated with xenon administration is modest. Nevertheless, there is some evidence to suggest that xenon may be associated with better neurologic outcomes compared with the standard of care therapy in certain specific clinical situations. More clinical trials are needed to determine any potential benefit linked to xenon administration.

In this case, a patient is envenomated by his friend’s exotic pet snake. The patient rapidly develops signs of neurotoxicity, including blurred vision, ptosis, and difficulty swallowing. He ultimately develops respiratory arrest and bradycardia. In this chapter, we review some of the toxins that can cause progressive neurologic symptoms including botulinum toxin, neurotoxic snakes in the US, and some of the exotic snakes that can cause neurologic effects.

Since the worldwide introduction of antiretroviral therapy (ART) in human immunodeficiency virus type 1, HIV-1-positive mothers, together with HIV-1 testing prior to pregnancy, caesarian birth and breastfeeding cessation with replacement feeding, a reduction of HIV-1 mother-to-child transmission (MTCT) has been observed in the last few years. As such, an increasing number of children are being exposed in utero to ART. Several questions have arisen concerning the neurological effects of ART exposure in utero, considering the potential effect of antiretroviral drugs on the central nervous system, a structure which is in continuous development in the fetus and characterized by great plasticity. This review aims at discussing the possible neurological impairment of children exposed to ART in utero, focusing attention on the drugs commonly used for HIV-1 MTCT prevention, clinical reports of ART neurotoxicity in children born to HIV-1-positive mothers, and neurologic effects of protease inhibitors (PIs), especially ritonavir-“boosted” lopinavir (LPV/r) in cell and animal central nervous system models evaluating the potential neurotoxic effect of ART. Finally, we present the findings of a meta-analysis to assess the effects on the neurodevelopment of children exposed to ART in utero.

Carbon monoxide exposure remains a public health concern worldwide. Despite the burden that carbon monoxide exerts, significant controversy exists regarding optimal treatment of exposed persons. Particular controversy around neurologic effects of carbon monoxide exposure, how best to evaluate for neurocognitive dysfunction, and effects the fetus of pregnant women. This review focuses on the mechanism of injury from carbon monoxide, and summarizes the data regarding neurocognitive dysfunction and fetal effects of exposure.

Adverse drug effects often complicate the care of critically ill patients. Therefore, each patient's medical history, maintenance medication, and new therapies administered in the intensive care unit must be evaluated to prevent unwanted neurologic adverse effects. Optimization of pharmacotherapy in critically ill patients can be achieved by considering the need to reinitiate home medications, and avoiding drugs that can decrease the seizure threshold, increase sedation and cognitive deficits, induce delirium, increase intracranial pressure, or induce fever. Avoiding medication-induced neurologic adverse effects is essential in critically ill patients, especially those with neurologic injury.

Approximately 3.4 million children worldwide are affected with human immunodeficiency virus (HIV)/AIDS with more than 90% of them residing in sub-Saharan Africa, according to the World Health Organization. A significant proportion of the children eligible for treatment with antiretroviral therapy are not currently receiving it. Neurologic manifestations of HIV are common in both adults and children. There is a large spectrum of neurologic conditions that may be caused by the virus; however, early invasion of the central nervous system by the virus, affecting the developing fetal and infant brain, is believed to result in the most common primary HIV-related central nervous system complication, HIV encephalopathy. This article summarizes the spectrum of neuro-HIV in children, focuses on the neurocognitive and behavioral sequelae, reviews the effects of treatment on the primary neurologic effects of the disease, and discusses the specific challenges of identifying and managing these problems in resource-limited contexts, such as those found on the African continent.

Preclinical and clinical studies have demonstrated the adverse consequences of untreated pain and stress on brain development in the preterm infant. Sucrose has widely been implemented as standard therapy for minor procedural pain. Anesthetics are commonly utilized in preterm infants during major surgery. Pharmacologic agents (benzodiazepines and opioids) have been examined in clinical trials of preterm infants requiring invasive mechanical ventilation. Controversy exists regarding the safety and long-term impact of these interventions. Ongoing multidisciplinary research will help define the impact of these agents and identify potential alternative therapies.

Alzheimer's disease (AD) is a neurodegenerative disease that is a great public health problem worldwide. The cause and mechanism of AD are not well understood. Inhalational anesthetics have been suggested to induce neurotoxicity, leading to memory deficits and the progression of AD. However, recent data have shown that inhalational anesthetics may protect against neurotoxicity and are not associated with an increased risk of AD. We used a Drosophila model to directly investigate the neurologic effects of the inhalational anesthetic sevoflurane on AD. Five- to six-day-old control and AD-transgenic flies were exposed to 2.1% or 3% sevoflurane 4 and 16 times for 1 hour each time. Electroretinograms (ERG), retinal immunohistochemistry, climbing ability, and survival were analyzed after sevoflurane treatment. The data were evaluated using Student's t-test or a one-way ANOVA with a supplementary Fisher's LSD (Least Significant Difference) test. Statistical significance was set at p

Squirrel monkeys (Saimiri spp) are one of the most consistently used New World primates in biomedical research and are increasingly being used in neuroscience research, including models of drug abuse and addiction. Spontaneous neurologic disease in the squirrel monkey is uncommonly reported but includes various infectious diseases as well as cerebral amyloidosis. Hypernatremia is an extremely serious condition of hyperosmolarity that occurs as a result of water loss, adipsia, or excess sodium intake. Neurologic effects of hypernatremia reflect the cellular dehydration produced by the shift of water from the intracellular fluid space into the hypertonic extracellular fluid space. Severe hypernatremia may result in cerebrocortical laminar necrosis (polioencephalomalacia) in human patients as well as in a number of domestic species, including pigs, poultry, and ruminants. We report the clinical, histopathologic, and immunohistochemical findings of polioencephalomalacia in 13 squirrel monkeys. Polioencephalomalacia in these animals was associated with hypernatremia that was confirmed by serum levels of sodium greater than 180 mmol/L (reference range, 134.0–154.0 mmol/L [mEq/L]). All animals had concurrent diseases or experimental manipulation that predisposed to adipsia. Immunohistochemical investigation using antibodies to neuronal nuclei (NeuN), CNPase, Iba-1, and CD31 revealed necrosis of predominantly cerebral cortical layers 3, 4, and 5 characterized by neuronal degeneration and loss, oligodendrocytic loss, microglial proliferation, and vascular reactivity. The squirrel monkey is exquisitely sensitive to hyperosmolar metabolic disruption and it is associated with laminar cortical necrosis.

5-fluorouracial (5-FU) is an antimetabolite chemotherapy drug. 5-FU has many adverse effects like any other chemotherapy agent as it has effects not only on cancer cells, but healthy cell as well. Serious side effects which are uncommon (occurring in about 1% of patients) and will be the focus of this paper are cardiac effects, hyperammonemia or encephalopathy and neurologic effects. There are many other side effects associated with 5-FU. In this paper we will discuss the rare side effects and alternatives on what to do if they occur during treatment based on case reports.