Incidence, Characteristics, and Outcomes of Stroke in Pediatric Patients with Celiac Disease.

(1) Background: Celiac disease (CD) can cause long-term inflammation and endothelial dysfunction and has been cited as a risk factor for acute ischemic stroke (AIS) in pediatric patients. However, the rate and outcomes of AIS in pediatric patients with CD has not been explored in a large population. Our objective is to explore the rate, severity, and outcomes of CD amongst pediatric AIS patients on a nationwide level. (2) Methods: The National Inpatient Sample (NIS) database was queried from 2016 to 2020 for pediatric patients with a principal diagnosis of AIS. Patients with a concurrent diagnosis of CD (AIS-CD) were compared to those without (AIS). Baseline demographics and comorbidities, clinical variables of severity, hospital complications, and the rates of tissue plasminogen activator (tPA) and mechanical thrombectomy were compared between the two groups. The main outcomes studied were mortality, discharge disposition, length of stay (LOS), and total hospital charges. (3) Results: Of 12,755 pediatric patients with a principal diagnosis of AIS, 75 (0.6%) had concurrent CD. There were no differences in the severity, discharge disposition, or mortality between the AIS-CD and AIS patients. Patients with AIS-CD were more likely to receive tPA at an outside hospital within 24 h of admission (p < 0.01) and more likely to undergo mechanical thrombectomy (p < 0.01) compared to the AIS patients. (4) Conclusions: CD patients made up only 0.6% of all pediatric AIS patients. No differences in the severity, mortality, or discharge disposition suggests a minimal to absent role of CD in the etiology of stroke. The CD-AIS patients were more likely to receive a tPA or undergo a mechanical thrombectomy; studies are needed to confirm the safety and efficacy of these interventions in pediatric patients.

Use of Intraoperative Neuromonitoring in Surgical Treatment of Acute Presentation of Chiari I Malformation: A Case Report.

Intraoperative neuromonitoring (IONM) has been used in neurosurgical procedures to assess patient safety and minimize risk of neurological deficit. However, its use in decompressive surgeries of Chiari malformation type I (CM-I) remains a topic of debate. Here we present the case of a 5-year-old girl who presented with acute right lower extremity monoplegia after accidental self-induced hyperflexion of the neck while playing. Imaging revealed 15 mm of tonsillar ectopia with cervical and upper thoracic spinal cord edema. She was taken to surgery for a suboccipital decompression with expansile duraplasty. IONM demonstrated improvement in motor evoked potentials during the decompression. Postoperatively, she had full recovery of strength and mobility. This is a case of acute weakness after mild trauma in the setting of previously asymptomatic CM-I that showed close correlation with IONM, clinical findings, and imaging. IONM during decompressive surgery for CM-I may be useful in patients who present acutely with cervical cord edema.

Significant Mortality Associated With COVID-19 and Comorbid Cerebrovascular Disease: A Quantitative Systematic Review.

We report the first quantitative systematic review of cerebrovascular disease in coronavirus disease 2019 (COVID-19) to provide occurrence rates and associated mortality. Through a comprehensive search of PubMed we identified 8 cohort studies, 5 case series, and 2 case reports of acute cerebrovascular disease in patients with confirmed COVID-19 diagnosis. Our first meta-analysis utilizing the identified publications focused on comorbid cerebrovascular disease in recovered and deceased patients with COVID-19. We performed 3 additional meta-analyses of proportions to produce point estimates of the mortality and incidence of acute cerebrovascular disease in COVID-19 patients. Patient's with COVID-19 who died were 12.6 times more likely to have a history of cerebrovascular disease. We estimated an occurrence rate of 2.6% (95% confidence interval, 1.2-5.4%) for acute cerebrovascular disease among consecutively admitted patients with COVID-19. While for those with severe COVID-19' we estimated an occurrence rate of 6.5% (95% confidence interval, 4.4-9.6%). Our analysis estimated a rate of 35.5% for in-hospital mortality among COVID-19 patients with concomitant acute cerebrovascular disease. This was consistent with a mortality rate of 34.0% which we obtained through an individual patient analysis of 47 patients derived from all available case reports and case series. COVID-19 patients with either acute or chronic cerebrovascular disease have a high mortality rate with higher occurrence of cerebrovascular disease in patients with severe COVID-19.

Acute ischemic strokes in patients with developmental disabilities: A cross-sectional analysis.

OBJECTIVE: Patients with developmental disabilities (DD) are frequently excluded from acute ischemic stroke (AIS) randomized control trials. We sought to evaluate the impact of having DD on this patient cohort. METHODS: The National Inpatient Sample was analyzed to explore the impact of AIS and treatment on discharge dispositions in patients with DD. Clinical characteristics, treatments, and outcomes were compared to fully-abled patients with AIS. RESULTS: 1,605,723 patients with AIS were identified from 2010-2019, of whom 4094 (0.30%) had a DD. AIS patients with DD were younger (60.31 vs 70.93 years, p < 0.01), less likely to be Caucasian (66.37%vs 68.09%, p = 0.01), and had higher AIS severity (0.63 vs 0.58, p < 0.01). Tissue plasminogen activator (tPA) was administered in 99,739 (6.2%) fully-abled patients and 196 (4.79%) of patients with DD (p < 0.01). Endovascular thrombectomy (EVT) was performed in 21,066 (1.31%) of fully-abled patients and 35 (0.85%) of patients with DD (p < 0.01). The presence of developmental disabilities were predictive of lower rates of tPA (OR:0.71,CI:0.56-0.87,p < 0.01) and EVT (OR:0.24,CI:0.16-0.36,p < 0.01). In a propensity score-matched cohort of all AIS patients who underwent EVT, there was no difference in functional outcome (p = 0.41), in-hospital mortality (0.10), and LOS (p = 0.79). CONCLUSION: AIS patients with DD were less likely to receive tPA and EVT compared to fully-abled patients. Individuals with DD had higher mortality and worse discharge disposition. There was no significant difference in post-EVT outcomes between fully-abled patients and patients with developmental disabilities. In the absence of prospective clinical trials, population based cross-sectional analyses such as the present study provide valuable clinical insight.

Intravenous thrombolysis for treatment of pediatric acute ischemic stroke: Analysis of 20 years of population-level data in the United States.

BACKGROUND AND AIMS: Although intravenous thrombolysis (IVT) represents standard-of-care treatment for acute ischemic stroke (AIS) in eligible adult patients, definitive evidence-based guidelines and randomized clinical trial data evaluating its safety and efficacy in the pediatric population remain absent from the literature. We aimed to evaluate the utilization and outcomes of IVT for the treatment of pediatric AIS using a large national registry. METHODS: Weighted hospitalizations for pediatric (<18 years of age) AIS patients were identified in the National Inpatient Sample during the period of 2001 to 2019. Complex sample statistical methods were performed to assess unadjusted and adjusted outcomes in patients treated with IVT or other medical management. RESULTS: Among 13,901 pediatric AIS patients, 270 (1.9%) were treated with IVT monotherapy (median age 12.8 years). IVT-treated patients developed any intracranial hemorrhage (ICH) at a rate of 5.6% (n = 15), and 71.9% (n = 194) experienced favorable functional outcomes at discharge (to home or to acute rehabilitation). Following propensity-score adjustment for age, acute stroke severity, infarct location, and etiological/comorbid conditions, IVT was not associated with an increased risk of any ICH (5.6% vs 5.4%, p = 0.931; adjusted odds ratio (aOR) = 1.01, 95% confidence interval (CI) = 0.48-2.14, p = 0.971), nor with favorable functional outcome (71.9% vs 74.5%, p = 0.489; aOR = 0.88, 95% CI = 0.60-1.29, p = 0.511) in comparison with other medical therapy. CONCLUSIONS: Twenty years of population-level data in the United States demonstrate that pediatric AIS patients treated with IVT experienced high rates of favorable outcomes without an increased risk of hemorrhagic transformation.

Responsive Neurostimulation Targeting the Anterior, Centromedian and Pulvinar Thalamic Nuclei and the Detection of Electrographic Seizures in Pediatric and Young Adult Patients.

Background: Responsive neurostimulation (RNS System) has been utilized as a treatment for intractable epilepsy. The RNS System delivers stimulation in response to detected abnormal activity, via leads covering the seizure foci, in response to detections of predefined epileptiform activity with the goal of decreasing seizure frequency and severity. While thalamic leads are often implanted in combination with cortical strip leads, implantation and stimulation with bilateral thalamic leads alone is less common, and the ability to detect electrographic seizures using RNS System thalamic leads is uncertain. Objective: The present study retrospectively evaluated fourteen patients with RNS System depth leads implanted in the thalamus, with or without concomitant implantation of cortical strip leads, to determine the ability to detect electrographic seizures in the thalamus. Detailed patient presentations and lead trajectories were reviewed alongside electroencephalographic (ECoG) analyses. Results: Anterior nucleus thalamic (ANT) leads, whether bilateral or unilateral and combined with a cortical strip lead, successfully detected and terminated epileptiform activity, as demonstrated by Cases 2 and 3. Similarly, bilateral centromedian thalamic (CMT) leads or a combination of one centromedian thalamic alongside a cortical strip lead also demonstrated the ability to detect electrographic seizures as seen in Cases 6 and 9. Bilateral pulvinar leads likewise produced reliable seizure detection in Patient 14. Detections of electrographic seizures in thalamic nuclei did not appear to be affected by whether the patient was pediatric or adult at the time of RNS System implantation. Sole thalamic leads paralleled the combination of thalamic and cortical strip leads in terms of preventing the propagation of electrographic seizures. Conclusion: Thalamic nuclei present a promising target for detection and stimulation via the RNS System for seizures with multifocal or generalized onsets. These areas provide a modifiable, reversible therapeutic option for patients who are not candidates for surgical resection or ablation.

Endovascular Thrombectomy for Pediatric Acute Ischemic Stroke.

BACKGROUND: Evidence regarding the utilization and outcomes of endovascular thrombectomy (EVT) for pediatric ischemic stroke is limited, and justification for its use is largely based on extrapolation from clinical benefits observed in adults. METHODS: Weighted discharge data from the National Inpatient Sample were queried to identify pediatric patients with ischemic stroke (<18 years old) during the period of 2010 to 2019. Complex samples statistical methods were used to characterize the profiles and clinical outcomes of EVT-treated patients. Propensity adjustment was performed to address confounding by indication for EVT based on disparities in baseline characteristics between EVT-treated patients and those medically managed. RESULTS: Among 7365 pediatric patients with ischemic stroke identified, 190 (2.6%) were treated with EVT. Utilization significantly increased in the post-EVT clinical trial era (2016-2019; 1.7% versus 4.0%; P<0.001), while the use of decompressive hemicraniectomy decreased (2.8% versus 0.7%; P<0.001). On unadjusted analysis, 105 (55.3%) EVT-treated patients achieved favorable functional outcomes at discharge (home or to acute rehabilitation), while no periprocedural iatrogenic complications or instances of contrast-induced kidney injury were reported. Following propensity adjustment, EVT-treated patients demonstrated higher absolute but nonsignificant rates of favorable functional outcomes in comparison with medically managed patients (55.3% versus 52.8%; P=0.830; adjusted hazard ratio, 1.01 [95% CI, 0.51-2.03]; P=0.972 for unfavorable outcome). Among patients with baseline National Institutes of Health Stroke Scale score >11 (75th percentile of scores in cohort), EVT-treated patients trended toward higher rates of favorable functional outcomes compared with those treated medically only (71.4% versus 55.6%; P=0.146). In a subcohort assessment of EVT-treated patients, those administered preceding thrombolytic therapy (n=79, 41.6%) trended toward higher rates of favorable functional outcomes (63.3% versus 49.5%; P=0.060). CONCLUSIONS: This cross-sectional evaluation of the clinical course and short-term outcomes of pediatric patients with ischemic stroke treated with EVT demonstrates that EVT is likely a safe modality which confers high rates of favorable functional outcomes.

Failed Emergence After Pediatric Epilepsy Surgery: Is Propofol-Related Infusion Syndrome to Blame?

Propofol infusion syndrome was first reported in the literature by Bray in 1998. He described a series of fatal outcomes after a presenting constellation of symptoms observed in pediatric patients who had received prolonged propofol infusions. Profound metabolic acidosis and bradycardia are the disease's hallmark features, which can further develop expeditiously to rhabdomyolysis, renal failure, and heart failure. It has been subsequently theorized that a triggering mechanism or a precipitating factor sets up the progressive physiologic spiral which can ensue. The name of the disease was expanded to Propofol Related Infusion Syndrome (PRIS), as propofol alone was no longer considered the culprit. The disease process is rare and can present with an insidious onset in some cases, causing much speculation of whether there is a proper grasp of the disease entity in its entirety as currently reported. The case discussed in this article depicts an adverse neurologic outcome following a craniotomy for temporal lobectomy in a child with lesional epilepsy. Since there was no obvious causative factor for these findings, PRIS became a diagnosis that was robustly discussed among the involved services.

Cerebral Venous Sinus Thrombosis in COVID-19 Infection: A Case Series and Review of The Literature.

SARS-CoV-2, the virus responsible for novel Coronavirus (COVID-19) infection, has recently been associated with a myriad of hematologic derangements; in particular, an unusually high incidence of venous thromboembolism has been reported in patients with COVID-19 infection. It is postulated that either the cytokine storm induced by the viral infection or endothelial damage caused by viral binding to the ACE-2 receptor may activate a cascade leading to a hypercoaguable state. Although pulmonary embolism and deep venous thrombosis have been well described in patients with COVID-19 infection, there is a paucity of literature on cerebral venous sinus thrombosis (cVST) associated with COVID-19 infection. cVST is an uncommon etiology of stroke and has a higher occurrence in women and young people. We report a series of three patients at our institution with confirmed COVID-19 infection and venous sinus thrombosis, two of whom were male and one female. These cases fall outside the typical demographic of patients with cVST, potentially attributable to COVID-19 induced hypercoaguability. This illustrates the importance of maintaining a high index of suspicion for cVST in patients with COVID-19 infection, particularly those with unexplained cerebral hemorrhage, or infarcts with an atypical pattern for arterial occlusive disease.

Case 271: Metronidazole-induced Encephalopathy.

HistoryAn 11-year-old boy taking oral antibiotics for Fusobacterium meningitis diagnosed 3 months earlier presented to the emergency department with a 1-week history of intermittent emesis, dizziness, and vertigo and a 1-day history of wobbly gait and bilateral lower extremity paresthesia without confusion. His metabolic profile was normal. Contrast material-enhanced MRI of the brain was performed.

Case 271.

History An 11-year-old boy taking oral antibiotics for Fusobacterium meningitis diagnosed 3 months earlier presented to the emergency department with a 1-week history of intermittent emesis, dizziness, and vertigo and a 1-day history of wobbly gait and bilateral lower extremity paresthesia without confusion. His metabolic profile was normal. Contrast material-enhanced MRI of the brain was performed, and selected images are shown ( Fig 1 - 4 ). Figure 1a: (a) Axial fluid-attenuated inversion recovery (repetition time msec/echo time msec, 11 000/125) MRI and (b) axial turbo spin-echo T2-weighted (3000/80) MRI of the brain through the cerebellum at presentation. (c) Axial fluid-attenuated inversion recovery (6000/120) MRI and (d) axial turbo spin-echo T2-weighted (5545/100) MRI through the same level of the cerebellum obtained 6 weeks earlier. Figure 1b: (a) Axial fluid-attenuated inversion recovery (repetition time msec/echo time msec, 11 000/125) MRI and (b) axial turbo spin-echo T2-weighted (3000/80) MRI of the brain through the cerebellum at presentation. (c) Axial fluid-attenuated inversion recovery (6000/120) MRI and (d) axial turbo spin-echo T2-weighted (5545/100) MRI through the same level of the cerebellum obtained 6 weeks earlier. Figure 1c: (a) Axial fluid-attenuated inversion recovery (repetition time msec/echo time msec, 11 000/125) MRI and (b) axial turbo spin-echo T2-weighted (3000/80) MRI of the brain through the cerebellum at presentation. (c) Axial fluid-attenuated inversion recovery (6000/120) MRI and (d) axial turbo spin-echo T2-weighted (5545/100) MRI through the same level of the cerebellum obtained 6 weeks earlier. Figure 1d: (a) Axial fluid-attenuated inversion recovery (repetition time msec/echo time msec, 11 000/125) MRI and (b) axial turbo spin-echo T2-weighted (3000/80) MRI of the brain through the cerebellum at presentation. (c) Axial fluid-attenuated inversion recovery (6000/120) MRI and (d) axial turbo spin-echo T2-weighted (5545/100) MRI through the same level of the cerebellum obtained 6 weeks earlier. Figure 2a: (a) Axial fast spin-echo T1-weighted MRI (496/8) and (b) axial reconstruction of three-dimensional fast field-echo T1-weighted contrast-enhanced (7 mL of gadobutrol, Gadavist; Bayer Healthcare Pharmaceuticals, Berlin, Germany) MRI (7.98/3.72) of regions similar to those in Figure 1 . Figure 2b: (a) Axial fast spin-echo T1-weighted MRI (496/8) and (b) axial reconstruction of three-dimensional fast field-echo T1-weighted contrast-enhanced (7 mL of gadobutrol, Gadavist; Bayer Healthcare Pharmaceuticals, Berlin, Germany) MRI (7.98/3.72) of regions similar to those in Figure 1 . Figure 3a: (a) Axial diffusion-weighted MRI (3090/71) and (b) axial apparent diffusion coefficient map (3090/71) of regions similar to those in Figure 1 . Figure 3b: (a) Axial diffusion-weighted MRI (3090/71) and (b) axial apparent diffusion coefficient map (3090/71) of regions similar to those in Figure 1 . Figure 4: Three-dimensional maximum intensity projection image (25/3.45) of the posterior cerebral circulation obtained with MR angiography of the head.

Introduction of a Pediatric Neurology Hospitalist Service With Continuous Electroencephalography Monitoring at a Children's Hospital.

Hospitalists, specializing in inpatient medicine, are increasingly being utilized in the hospital setting to improve efficiency, decrease costs and length of stay, and potentially improve outcomes. With these goals in mind and with the purpose of addressing the specific needs of patients on the inpatient pediatric neurology service, we established a pediatric neurohospitalist service in 2009. The primary purpose of this article is to describe the structure and the rationale for a pediatric neurohospitalist service with continuous electroencephalography at a pediatric teaching hospital and to discuss the categories of disease seen by the inpatient neurology service.

Posterior reversible encephalopathy syndrome: incidence and associated factors in a pediatric critical care population.

BACKGROUND: Posterior reversible encephalopathy syndrome may occur frequently and be underrecognized in children and young adults admitted to a pediatric critical care unit. METHODS: Patients <21 years of age with the diagnosis of posterior reversible encephalopathy syndrome were reviewed in this retrospective cohort study conducted over a 30-month period. RESULTS: There were 2588 admissions to pediatric critical care unit, 226 neurology service consultations, and 10 patients diagnosed with posterior reversible encephalopathy syndrome (incidence of 1 in 259 pediatric critical care unit admissions, 0.4%). The majority of posterior reversible encephalopathy syndrome patients (9/10) presented with generalized tonic and or clonic seizures. Apart from hypertension and cytotoxic medication use, anemia, a previously unreported risk factor, was found in all 10 (100%) patients with posterior reversible encephalopathy syndrome. One-year follow up available in eight patients showed no residual neurological deficits attributable to posterior reversible encephalopathy syndrome with significant resolution of white matter signal abnormalities on neuroimaging. CONCLUSION: Our case cohort includes an estimation of incidence of posterior reversible encephalopathy syndrome in children and young adults with 1-year follow-up and anemia as a potential previously unreported risk factor.

Anti-N-methyl-d-aspartate encephalitis with ovarian cystadenofibroma.

We report the case of an adolescent girl with anti-N-methyl-D-aspartate-receptor (NMDAR) encephalitis who presented with focal seizures and hemichorea, followed by agitation, speech disturbance, mutism, and autonomic dysfunction. The institution of immunotherapy and removal of an ovarian cystadenofibroma led to full resolution of her symptoms with disappearance of serum NMDAR antibodies. This is the first report linking ovarian cystadenofibroma to anti-NMDAR encephalitis.

Blood transfusion in sickle cell disease leading to posterior reversible encephalopathy syndrome (PRES).

Children with sickle cell disease have a very high risk of lifelong neurologic morbidity and mortality. Cerebrovascular accidents are a known complication in children with sickle cell disease. Posterior reversible encephalopathy syndrome is a constellation of acute neurologic findings increasingly recognized in pediatric critical care population with evidence of vasogenic edema on brain imaging possibly due to cerebral vascular endothelial cell dysfunction. This report, for the first time, describes a young adult with sickle cell disease who developed posterior reversible encephalopathy syndrome following blood transfusion.

Facial palsy and idiopathic intracranial hypertension in twins with cystic fibrosis and hypovitaminosis A.

Facial nerve palsies are uncommon in infants. We report on 10-week-old monozygotic twins, diagnosed with cystic fibrosis by newborn screening, who developed facial palsy and increased intracranial pressure. Cranial imaging and cerebrospinal fluid analysis produced normal results. Levels of serum vitamin A were below normal range. Low levels of vitamin A are associated with facial nerve paralysis, and are at least partly implicated in the development of increased intracranial pressure in infants with cystic fibrosis.

Treatment of infantile spasms.

Infantile spasms are associated with a diverse range of conditions, and treatment options are available. However, outcomes remain generally poor, particularly for those with symptomatic etiologies. First-line therapy is considered to be hormonal (adrenocorticotropic hormone; ACTH), which some evidence suggests is more effective when started early. However, side effects may place limits on its use acutely and long-term. There is additional evidence for vigabatrin, specifically for infantile spasms secondary to tuberous sclerosis complex. In refractory cases, candidacy for surgical management should be explored, along with new-generation anticonvulsants (eg, topiramate, zonisamide) and the ketogenic diet. There is urgent need for further treatment trials comparing anticonvulsants with ACTH and a satisfactory animal model for the study of spasms.