Severe Neurological Involvement Research Articles

Volume expansion mitigates Shiga toxin-producing E. coli-hemolytic uremic syndrome in children

BackgroundShiga toxin-producing E. coli-hemolytic uremic syndrome (STEC-HUS) is associated with high morbidity and relevant mortality. Previous small studies showed that volume expansion could improve the course and outcome of STEC-HUS. The aim of this single-center study was to evaluate the effect of volume expansion on the clinical course and outcome in STEC-HUS.MethodsData of pediatric patients with STEC-HUS were analyzed retrospectively. Course and outcome of patients treated with volume expansion (VE) from 2019 to 2022 (n = 38) were compared to historical controls (HC) from 2009 to 2018 (n = 111).ResultsPatients in the VE group had a significant relative median weight gain compared to HC (7.8% (3.4–11.3) vs. 1.2% (− 0.7–3.9), p < 0.0001) 48 h after admission. The need for dialysis was not reduced by VE (VE 21/38 (55.3%) vs. HC 64/111 (57.7%), p = 0.8). However, central nervous system involvement (impairment of consciousness, seizures, focal neurological deficits, and/or visual disturbances) was significantly reduced (VE 6/38 (15.8%) vs. HC 38/111 (34.2%), p = 0.039). None of the patients in the VE group died or developed chronic kidney disease (CKD) stage 5, whereas in the HC group, three patients died and three patients had CKD stage 5 at discharge.ConclusionsThis study suggests that volume expansion may be associated with the mitigation of the acute course of STEC-HUS, especially severe neurological involvement and the development of CKD. Prospective trials should lead to standardized protocols for volume expansion in children with STEC-HUS.Graphical abstractA higher resolution version of the Graphical abstract is available as Supplementary information

Post Hoc Analysis of a Phase 2/3 Study in Japanese Patients with iTTP Treated with Caplacizumab

Introduction Immune-mediated thrombotic thrombocytopenic purpura (iTTP) is a rare, life-threatening disease caused by a severe deficiency of a disintegrin and metalloproteinase with thrombospondin type 1 motif, member 13 (ADAMTS13). Caplacizumab is a von Willebrand factor-directed antibody fragment designed to treat iTTP in conjunction with therapeutic plasma exchange (TPE) and immunosuppressive therapy. Caplacizumab was approved in Europe in 2018, in the United States in 2019, and in Japan in 2022. Methods In the open-label, Phase 2/3 study (NCT04074187), Japanese patients ≥18 years old with a clinical diagnosis of iTTP and ≤1 prior TPE received caplacizumab in combination with TPE and immunosuppression for ≥30 days post-TPE and were followed for 4 weeks after the end of treatment. Patients with persistent ADAMTS13 deficiency (eg, &amp;lt;10%) were allowed treatment extension of up to 8 weeks. This post hoc analysis assessed outcomes including patient characteristics, time to platelet count recovery, time to normalization of all 3 organ damage markers (lactate dehydrogenase, cardiac troponin I, and serum creatinine), safety, time to recovery of ADAMTS13 activity, ADAMTS13 activity at end of treatment, and incidence of ADAMTS13 inhibitor elevation during treatment stratified by iTTP severity. Very severe iTTP at baseline was defined as follows: French severity score ≥3 or severe neurological involvement (eg, coma, seizures, focal deficit), or cardiac involvement (cardiac troponin level &amp;gt;2.5×ULN). Results Overall, 21 patients were enrolled and treated with ≥1 dose of caplacizumab (modified intent-to-treat population [mITT] and safety population). Of these,19 patients had confirmed iTTP (less severe iTTP, n=8; very severe iTTP, n=11; Table). Median (95% confidence interval [CI]) time to platelet count response and median (range) days of TPE was 3.28 (1.69-4.01) and 5.5 (3-15) days in patients with less severe iTTP and 3.49 (1.76-3.98) and 6.0 (4-20) days in patients with very severe iTTP, respectively. Median (95% CI) time to normalization of all 3 organ damage marker levels was 1.73 (0.79-2.94) days in patients with less severe iTTP and 8.66 (2.65-12.55) days in patients with very severe iTTP, which may reflect the fact that patients with very severe iTTP had worse organ damage at baseline. The number of patients experiencing recurrence, ≥1 major thromboembolic event, or TTP-related death in patients with less severe and very severe iTTP was 1 for each subgroup. Two patients in each disease severity subgroup had ≥1 treatment-emergent serious adverse event. Of the 19 patients with confirmed iTTP, median (95% CI) time to recovery of ADAMTS13 activity to ≥10, ≥20, and ≥60% was 14.57 (5.95-24.76),18.49 (5.95-31.75), and 47.51 (18.49-60.94) days, respectively. Patients with ADAMTS13 inhibitor levels ≥2 BU/mL at baseline (n=7) took approximately twice as long to recover ADAMTS13 activity to ≥10, ≥20, and ≥60% versus patients with baseline inhibitor levels &amp;lt;2 BU/mL. Median (range) ADAMTS13 activity level at the end of caplacizumab treatment was 62.0% (29.0%-101.0%). ADAMTS13 inhibitor elevation occurred in 9 patients (Figure). Among them, 7 patients extended caplacizumab treatment. Only 1 patient with inhibitor re-increase experienced a recurrence 2 days after discontinuing caplacizumab due to an adverse event. Conclusions These results suggest that caplacizumab in conjunction with TPE and immunosuppression is effective for patients with iTTP regardless of their baseline severity and may reduce the risk of recurrence due to inhibitor re-increase.

1094. Comparison of Demographic and Clinical Characteristics in Survivors Vs. Decedents with Multisystem Inflammatory Syndrome in Children (MIS-C) During the COVID-19 Pandemic—CDC National Surveillance, February 2020-December 2022

Abstract Background Multisystem inflammatory syndrome in children (MIS-C) is a rare but severe complication of SARS-CoV-2. Identifying clinical and demographic characteristics associated with MIS-C mortality and description of MIS-C decedents over time may help identify children at increased risk for poor outcomes and potentially inform treatment decisions. Methods This investigation included all MIS-C cases with known outcome reported to CDC MIS-C national surveillance from February 2020─December 2022. Clinical and demographic characteristics were compared between survivors and decedents. Decedents were described over time and classified by date of MIS-C illness onset into five pandemic waves corresponding to five peaks of MIS-C activity (Figure 1): (1) 2/19/2020─6/28/2020, (2) 6/29/2020─10/17/2020, (3) 10/18/2020─7/8/2021, (4) 7/9/2021─12/7/ 2021, and (5) 12/8/2021─12/31/2022. Waves 4 and 5 were periods of predominant Delta and Omicron SARS-CoV-2 variant circulation, respectively.Figure 1.Multisystem Inflammatory Syndrome in Children (MIS-C) Decedents by Pandemic MIS-C Wave, February 19, 2020-December 31, 2022, N=76 Results Seventy-six decedents and 8,691 survivors were reported (Table). A higher proportion of decedents compared with survivors were aged 16-20 years (41% vs 9%; p&amp;lt; 0.01), from the South (55% vs 41%; p=0.01) and had MIS-C illness onset in wave 1 (18% vs 7%; p&amp;lt; .01). Half (51%) of decedents had an underlying medical condition compared with 24% of survivors (p&amp;lt; 0.01). A higher proportion of decedents than survivors had severe cardiovascular (95% vs 76%), respiratory (99% vs 36%), renal (59% vs 19%), and neurologic (30% vs 4%) involvement, and fewer had mucocutaneous (33% vs 75%). Deaths in the 16-20 age group were predominant in waves 1-4 but comprised only 15% of deaths in wave 5, when 57% of decedents were aged 0-4 years (Figure 2). Race and ethnicity of decedents varied over time. Severe cardiovascular and respiratory involvement was high ( &amp;gt;85-100%) over time in decedents; other organ manifestations varied by MIS-C wave.Table.Demographic and Clinical Characteristics of Children with Multisystem Inflammatory Syndrome in Children (MIS-C)-CDC National Surveillance, February 2020-December 2022Figure 2.Demographic Characteristics and Organ Involvement of Children with Multisystem Inflammatory Syndrome in Children (MIS-C) Who Died Stratified by Pandemic MIS-C Wave, February 19, 2020-December 31, 2022, N=76 Conclusion Older age (16-20 years), residing in the South, illness early in the pandemic, underlying medical conditions, and severe organ involvement were all significantly associated with death among children with MIS-C. MIS-C decedent characteristics are dynamic and may continue to evolve with changes in underlying population immunity, SARS-CoV-2 transmission, and variant emergence. Disclosures All Authors: No reported disclosures

The Cardiofaciocutaneous Syndrome: From Genetics to Prognostic-Therapeutic Implications.

Cardiofaciocutaneous (CFC) syndrome is one of the rarest RASopathies characterized by multiple congenital ectodermal, cardiac and craniofacial abnormalities with a mild to severe ocular, gastrointestinal and neurological involvement. It is an autosomal dominant syndrome, with complete penetrance, caused by heterozygous pathogenic variants in the genes BRAF, MAP2K1/MEK1, MAP2K2/MEK2, KRAS or, rarely, YWHAZ, all part of the RAS-MAPK pathway. This pathway is a signal transduction cascade that plays a crucial role in normal cellular processes such as cell growth, proliferation, differentiation, survival, metabolism and migration. CFC syndrome overlaps with Noonan syndrome, Costello syndrome, neurofibromatosis type 1 and Legius syndrome, therefore making the diagnosis challenging. Neurological involvement in CFC is more severe than in other RASopathies. Phenotypic variability in CFC patients is related to the specific gene affected, without a recognized genotype-phenotype correlation for distinct pathogenic variants. Currently, there is no specific treatment for CFC syndrome. Encouraging zebrafish model system studies suggested that, in the future, MEK inhibitors could be a suitable treatment of progressive phenotypes of CFC in children. A multidisciplinary care is necessary for appropriate medical management.

Wolfram Syndrome: A Rare Genetic disorder affecting Multiple Organ Systems

Wolfram syndrome is a rare neurological disorder characterised by four main symptoms: diabetes mellitus, optic atrophy, deafness, and diabetes insipidus. It is caused by alterations in the CISD2 and WFS1 genes, which encode important proteins involved in cellular processes. Wolfram syndrome type 1 (WS1) has an earlier onset of diabetes and more severe neurological and ocular involvement compared to WS2. The diagnosis of Wolfram syndrome is based on the presence of early-onset diabetes and progressive optic atrophy. Genetic analysis, such as sequencing of the WFS1 gene, is used to confirm the diagnosis. The prevalence of Wolfram syndrome varies across populations, with a carrier frequency of 1 in 354. Individuals with Wolfram syndrome may experience a range of complications, including neurological abnormalities, urinary tract problems, depression, and an increased risk of suicide. The pathophysiology of Wolfram syndrome involves endoplasmic reticulum stress and unfolded protein responses, leading to cellular dysfunction and apoptosis. A differential diagnosis includes other genetic and mitochondrial disorders with similar symptoms. Although there is no cure for Wolfram syndrome, careful clinical observation and supportive therapy can help manage the symptoms and improve the quality of life for affected individuals.

Associations of the cerebrospinal fluid lymphocyte population with a clinical presentation of tick-borne encephalitis

In tick-borne encephalitis (TBE), lymphocytes infiltrating central nervous system are indispensable for the infection control, but also potentially immunopathogenic. To clarify their roles, we have evaluated cerebrospinal fluid (CSF) count of the main lymphocyte populations (considered as a proxy of the brain parenchyma lymphocytic infiltrate) in TBE patients and analyzed if they associate with clinical presentation, blood-brain barrier disruption and intrathecal antibody synthesis.We have studied CSF from 96 adults with TBE (50 with meningitis, 40 with meningoencephalitis, 6 with meningoencephalomyelitis), 17 children and adolescents with TBE and 27 adults with non-TBE lymphocytic meningitis. Th CD3+CD4+, Tc CD3+CD8+, double positive T CD3+CD4+CD8+, B CD19+ and NK CD16+/56+ cells were counted cytometrically with a commercial fluorochrome-stained monoclonal antibody set. The associations between the counts and fractions of these cells and clinical parameters were analyzed with non-parametric tests, p<0.05 considered significant.The TBE patients had lower pleocytosis with similar proportions of the lymphocyte populations compared to non-TBE meningitis. The different lymphocyte populations correlated positively with one another, as well as with CSF albumin, IgG and IgM quotients. The higher pleocytosis and expansion of Th, Tc and B cells associated with a more severe disease and neurologic involvement: Th with encephalopathy, myelitis and weakly with cerebellar syndrome, Tc with myelitis and weakly with encephalopathy, B with myelitis and with at least moderately severe encephalopathy. The double-positive T lymphocytes associated with myelitis, but not with other forms of CNS involvement. The fraction of double positive T cells decreased in encephalopathy and the fraction of NK in patients with neurologic deficits. In children with TBE, Tc and B counts were increased at the expense of Th lymphocytes in comparison with adults.The concerted intrathecal immune response, involving the main lymphocyte populations, increases with the clinical severity of TBE, with no evidently protective or pathogenic elements distinguishable. However, the particular populations including B, Th and Tc cells associate with different, though overlapping, spectra of CNS manifestations, suggesting they may be specifically related to TBE manifesting as myelitis, encephalopathy and cerebellitis. The double-positive T and NK cells do not expand evidently with severity and may be most closely associated with the protective anti-TBEV response.

Characteristics of enterovirus infection associated neurologic disease associated in a pediatric population in Spain

IntroductionEnteroviruses are a type of RNA-strained virus with more than 100 different genotypes. Infection can be asymptomatic, and, if any, symptoms can range from mild to severe. Some patients can develop neurological involvement, such as aseptic meningitis, encephalitis, or even cardiorespiratory failure. However, in children, the risk factors for developing severe neurological involvement are not well understood. The aim of this retrospective study was to analyze some characteristics associated with severe neurological involvement in children hospitalized for neurological disease after enterovirus infection. Methodsretrospective observational study analyzing clinical, microbiological and radiological data of 174 children hospitalized from 2009 to 2019 in our hospital. Patients were classified according to the World Health Organization case definition for neurological complications in hand, foot and mouth disease. ResultsOur findings showed that, in children between 6 months old and 2 years of age, the appearance of neurological symptoms within the first 12h from infection onset—especially if associated with skin rash—was a significant risk factor for severe neurological involvement. Detection of enterovirus in cerebrospinal fluid was more likely in patients with aseptic meningitis. By contrast, other biological samples (e.g., feces or nasopharyngeal fluids) were necessary to detect enterovirus in patients with encephalitis. The genotype most commonly associated with the most severe neurological conditions was EV-A71. E-30 was mostly associated with aseptic meningitis. ConclusionsAwareness of the risk factors associated with worse neurological outcomes could help clinicians to better manage these patients to avoid unnecessary admissions and/or ancillary tests.

JAK Inhibition in Aicardi-Goutières Syndrome: a Monocentric Multidisciplinary Real-World Approach Study

The paradigm type I interferonopathy Aicardi-Goutières syndrome (AGS) is most typically characterized by severe neurological involvement. AGS is considered an immune-mediated disease, poorly responsive to conventional immunosuppression. Premised on a chronic enhancement of type I interferon signaling, JAK1/2 inhibition has been trialed in AGS, with clear improvements in cutaneous and systemic disease manifestations. Contrastingly, treatment efficacy at the level of the neurological system has been less conclusive. Here, we report our real-word approach study of JAK1/2 inhibition in 11 patients with AGS, providing extensive assessments of clinical and radiological status; interferon signaling, including in cerebrospinal fluid (CSF); and drug concentrations in blood and CSF. Over a median follow-up of 17 months, we observed a clear benefit of JAK1/2 inhibition on certain systemic features of AGS, and reproduced results reported using the AGS neurologic severity scale. In contrast, there was no change in other scales assessing neurological status; using the caregiver scale, only patient comfort, but no other domain of everyday-life care, was improved. Serious bacterial infections occurred in 4 out of the 11 patients. Overall, our data lead us to conclude that other approaches to treatment are urgently required for the neurologic features of AGS. We suggest that earlier diagnosis and adequate central nervous system penetration likely remain the major factors determining the efficacy of therapy in preventing irreversible brain damage, implying the importance of early and rapid genetic testing and the consideration of intrathecal drug delivery.

Characteristics of enterovirus infection associated neurologic disease in a pediatric population in Spain

IntroductionEnteroviruses are a type of RNA-strained virus with more than 100 different genotypes. Infection can be asymptomatic, and, if any, symptoms can range from mild to severe. Some patients can develop neurological involvement, such as aseptic meningitis, encephalitis, or even cardiorespiratory failure. However, in children, the risk factors for developing severe neurological involvement are not well understood. The aim of this retrospective study was to analyze some characteristics associated with severe neurological involvement in children hospitalized for neurological disease after enterovirus infection. Methodsretrospective observational study analyzing clinical, microbiological and radiological data of 174 children hospitalized from 2009 to 2019 in our hospital. Patients were classified according to the World Health Organization case definition for neurological complications in hand, foot and mouth disease. ResultsOur findings showed that, in children between 6 months old and 2 years of age, the appearance of neurological symptoms within the first 12h from infection onset—especially if associated with skin rash—was a significant risk factor for severe neurological involvement. Detection of enterovirus in cerebrospinal fluid was more likely in patients with aseptic meningitis. By contrast, other biological samples (e.g., feces or nasopharyngeal fluids) were necessary to detect enterovirus in patients with encephalitis. The genotype most commonly associated with the most severe neurological conditions was EV-A71. E-30 was mostly associated with aseptic meningitis. ConclusionsAwareness of the risk factors associated with worse neurological outcomes could help clinicians to better manage these patients to avoid unnecessary admissions and/or ancillary tests.

Atypical presentation of West Nile encephalitis

West Nile virus (WNV) causes both sporadic infection and outbreaks that may be associated with severe neurologic involvement. The infection is transmitted to humans mainly by mosquito bites, and the virus is preserved in a cycle in which birds are the main host. The typical involvement of the central nervous system is completely indistinguishable from meningitis and encephalitis related to other pathogens. In this report we described the atypical presentation of a WNV meningoencephalitis in a 81-y.o. female patient, showing psychiatric manifestations at the onset. Anamnestic information was essential to progress to the correct diagnosis. Targeted search for the causative agent of meningoencephalitis was perfected after learning that the patient lived in an area adjacent to a nature reserve.

Changes in Distribution of Severe Neurologic Involvement in US Pediatric Inpatients With COVID-19 or Multisystem Inflammatory Syndrome in Children in 2021 vs 2020

Changes in Distribution of Severe Neurologic Involvement in US Pediatric Inpatients With COVID-19 or Multisystem Inflammatory Syndrome in Children in 2021 vs 2020

Severe Influenza-Associated Neurological Disease in Australian Children: Seasonal Population-Based Surveillance 2008-2018.

Influenza-associated neurological disease (IAND) is uncommon but can result in death or neurological morbidity in children. We aimed to describe the incidence, risk factors, and outcome of children with IAND from seasonal influenza in Australia. We analyzed national, population-based, surveillance data for children aged ≤ 14 years with severe influenza and neurological involvement, over 11 Australian influenza seasons, 2008-2018, by the Australian Paediatric Surveillance Unit. There were 633 laboratory-confirmed cases of severe influenza reported. Of these, 165 (26%) had IAND. The average annual incidence for IAND was 3.39 per million children aged ≤ 14 years. Compared to cases without neurological complications, those with IAND were more likely to have a pre-existing neurological disease (odds ratio [OR] 3.03, P < .001), but most children with IAND did not (n = 135, 82%). Children with IAND were more likely to receive antivirals (OR 1.80, P = .002), require intensive care (OR 1.79, P = .001), require ventilation (OR 1.99; P = .001), and die (OR 2.83, P = .004). IAND is a preventable cause of mortality, predominantly in otherwise well children. Incidence estimates validate previous sentinel site estimates from Australia. IAND accounted for a quarter of all severe influenza, is associated with intensive care unit admission, and accounted for half of all influenza deaths.

Neurological manifestations in thrombotic microangiopathy: Imaging features, risk factors and clinical course.

Background and purposeThrombotic microangiopathy (TMA) is a group of microvascular occlusive disorders that presents with neurological involvement in up to 87% of the cases. Although the central nervous system (CNS) is an important target organ in TMA, the role of neurological manifestations in the disease clinical course is not well established. In this study, we described the neurological manifestations and CNS radiological aspects in patients with a first, acute TMA event. We also examined the association between severe neurological involvement and adverse clinical outcomes in TMA.MethodsA cohort of patients diagnosed with a first TMA event between 1995 and 2016 was included, their medical charts and imaging tests were retrospectively evaluated.ResultsA total of 49 patients were included, 85.7% were women and the mean age was 36.5 years-old (SD 13.0). Neurological manifestations were described in 85.7% of the patients, most of them (88%) were considered severe and consisted of confusion, compromised sensorimotor function, stupor, seizures, and personality change. Imaging tests were performed in 62% of the patients with neurological manifestations and detected acute CNS lesions, such as posterior reversible encephalopathy syndrome, hemorrhagic and ischemic stroke were observed, in 7 (27%) of them. While the need for intensive care unit admission was greater and longer among patients with severe neurological manifestations, the number of plasma exchange sessions, the total duration of hospitalization and in-hospital death were similar between groups.ConclusionsSevere neurological manifestations are common in first TMA events and are responsible for a worse disease presentation at admission. While the effect of neurological manifestations on acute TMA clinical course seems to be modest, these manifestations may have an important impact on the development of chronic cognitive impairment, which highlights the need for proper diagnosis and treatment.

Neurological manifestations in mevalonate kinase deficiency: A systematic review.

Mevalonate kinase deficiency (MKD) is a monogenic auto-inflammatory disease. Its manifestations range from partial MKD to mevalonic aciduria (MVA). All patients display a periodic fever, and MVA patients additionally exhibit severe neurological involvement. The objective of this work was to describe neurological manifestations of MKD. A systematic literature review was performed from January 1990 to January 2022. Forty-five patients from 18 case reports and five cohort studies were included in the analysis. In cohort studies, the most-reported manifestations were headaches (41%) and fatigue (31%). Serious involvements including ataxia and developmental delay were described less than 1% of patients but 22-31% of case reports. They consistently appeared in the first years of life. Retinal dystrophy was frequently reported (31%) in case reports. Other manifestations, including uveitis, aseptic meningitis, and stroke remained rare. Severe neurological manifestations are rare in MKD but are responsible for major functional disabilities. They are present at onset and never appear at follow-up of patients with mild MKD. Conversely, headaches and fatigue are frequent symptoms that should be investigated. Visual examinations should be performed on the appearance of visual symptoms. The efficacy of anti-IL-1β therapy on neurological manifestations should be further investigated.

Operative treatment of the young cerebral palsy hip.

Hip dysplasia, subluxation, and eventual hip dislocation are commonly encountered in the cerebral palsy population secondary to spasticity and loss of motor control, especially in those patients with more severe neurologic involvement. The treatment of hip disorders in these patients should take into account the degree of limb and hip involvement, pain severity, and overall functioning. Conservative management focuses on mitigating spasticity and preserving range of motion in order to provide an environment in which the femoral head remains concentrically reduced in the acetabulum. However, operative management, consisting of soft tissue or tendon releases, femoral or pelvic osteotomies, or hip salvage procedures, is sometimes necessary to treat the painful, subluxated, or dislocated hip. Radiographic hip surveillance in the pediatric cerebral palsy population is used to guide operative treatment. Long term hip containment is generally improved when surgical intervention is performed in the earlier stages of dysplasia. Younger patients who demonstrate progressive hip subluxation despite conservative measures may be carefully selected to undergo soft tissue procedures. Bony reconstruction, with adjunctive soft tissue procedures, is often necessary to better contain the proximal femur in patients above the age of four years.

Feasibility, effectiveness, and satisfaction achieved by the transdisciplinary intervention of a clinical-hospital ethics committee. A qualitative and quantitative study.

A clinical ethics committee (CEC) has educational, regulatory, advisory, mediation, and reflexive functions. As any health care service, the consults with the CEC should be subjected to review and quality improvement. The study objectives were to assess the feasibility, effectiveness, and satisfaction with the bioethical recommendations made by the CEC and assess their impact on the treating team and the patient's family. Descriptive, retrospective, qualitative, and quantitative study of clinical cases submitted to the hospital's CEC between January 1st, 2013 and December 31st, 2017 using data from the CEC minute book, medical records, registries from the Office for Remote Communication, and semi-structured interviews with health care team members. A total of 108 cases (106 patients) were analyzed: 73 cases with survey and registries and 35 with registries only. The main most frequent reasons for consultation were adequacy of therapeutic effort (46/42.6%), severe neurological involvement (15/13.9%), patient's quality of life (11/10.2%), patient-family-health system conflict (7/6.5%), and family's refusal of treatment (6/5.6%). High levels of satisfaction (> 95%) and moderate levels of feasibility (> 74%) and effectiveness (> 85%) were observed. In only 50/108 cases (46.3%), the consultation with the CEC was registered in the medical record, 44% of health care providers stated that the consultation had a positive impact on the patient and their family. Results helped to establish improvement opportunities, especially in terms of documentation and communication in the consultation process.

Expression of lncRNAs NEAT1 and lnc-DC in Serum From Patients With Behçet’s Disease Can Be Used as Predictors of Disease

Background: Behçet’s disease (BD) is a chronic autoimmune disease. The early diagnosis of BD is very important to avoid serious and/or fatal complications such as eye damage, severe neurological involvement, and large vessel occlusion. New, sensitive biomarkers would aid in rapid diagnosis, the monitoring of disease activity, and the response to treatment. Methods: This study’s aim is to identify two immune system-related BD biomarkers. We measured long non-coding RNAs (lncRNAs) NEAT1 (nuclear-enriched abundant transcript 1), and lnc-DC (lncRNA in dendritic cells) in serum by real-time polymerase chain reaction (RT-PCR) in 52 BD patients and 52 controls. We analyzed the association between NEAT1 and lnc-DC and the clinical parameters of BD. Receiver operating characteristic (ROC) curve analysis was performed to explore the diagnostic performance of the studied genes. Results: Compared to controls, the significant upregulation of NEAT1 {median [interquartile range (IQR)] = 1.68 (0.38–7.7), p < 0.0001} and downregulation of lnc-DC [median (IQR) = 0.2 (0.12–1.39), p = 0.03] were detected in the sera collected from BD patients. Higher serum expression levels of NEAT1 and lnc-DC were significantly associated with the following clinical presentations: cutaneous lesions, vascular manifestations, articular manifestations, neurological manifestations, and higher disease activity score. Also, high NEAT1 levels were significantly associated with a negative pathergy test, while higher lnc-DC was significantly associated with a positive family history. ROC curves showed that NEAT1 and lnc-DC levels in serum could be used as predictors of BD with high specificity and fair sensitivity. NEAT1 had an area under the curve (AUC) of 0.692 (95% CI: 0.591–0.794, p = 0.001), and lnc-DC had an AUC of 0.615 (95% CI: 0.508–0.723, p = 0.043). Conclusion: Serum lncRNAs NEAT1 and lnc-DC are biomarkers for BD.

Severe Neurological Manifestations of Multisystem Inflammatory Syndrome in Adults (MIS-A)

Introduction; Multi-system inflammatory syndrome (MIS) is a para infectious or post infectious extra-pulmonary complication of COVID-19. Neurological complications are better described in children with multi-system inflammatory syndrome (MIS) in children (MIS-C). There is a paucity of literature about severe neurological manifestations of multi-system inflammatory syndrome in adults (MIS-A). Methods; Over a 22-month period, from June 2020 to December 2021, over 3450 COVID patients were admitted to our institution including 900 patients in the medical and COVID ICUs. Ten patients (1.1%) presented to us with MIS-A with severe neurological manifestations. Results; Severe neurological manifestations included transverse myelitis, COVID encephalitis, acute encephalopathy, status epilepticus and rhabdomyolytic myopathy. Our cohort had a high morbidity and mortality rate. Conclusions; Most patients with MIS-A had severe neurological involvement and a poor outcome.

Spectrum of Ocular Findings in Closed Head Injuries, Correlation With Severity of Neurological Involvement, and Treatment Outcome: A Hospital-Based Cross-Sectional Study.

Purpose: To study the various ocular findings in patients with closed head injuries, to find any association with the degree of neurological involvement, and to analyze the treatment outcome after the necessary intervention.Setting: Tertiary referral hospital in Eastern India.Design: Prospective observational study.Methods: Patients with closed head injuries attending our Outpatient department as well as referred from the Neurosurgery department for ophthalmic evaluation between October 2017 and September 2019 were recruited for the study. All patients meeting the inclusion criteria were examined by an experienced ophthalmologist. The Glasgow coma scale (GCS) was applied to grade the neurological involvement by the neurosurgery team. Ocular findings were recorded and necessary imaging was requested. Appropriate neurosurgery consultations were done in patients with neurological findings. All ocular injuries were managed as per institutional protocol. Descriptive statistics were used for analysis with p< 0.05 taken as statistically significant.Results: A total of 207 patients (414 eyes) were included in the study. The mean age was 33.82 years, with the prevalence of male patients (82.12%). The most common cause of head injury was RTA (57.01%) followed by assault (11.59%). The majority of patients (53.14%) were classified as having moderate, 46.37% patients with mild, and 0.48% with severe neurological involvement as per GCS scoring. Isolated ocular findings were seen in 70.04% of patients while 29.95% of patients had both neurological and ophthalmic features. Ocular adnexal involvement was observed in 38.6%, anterior segment involvement in 86%, neuro-ophthalmic manifestations in 33.3%, and posterior segment involvement in 38.6% of patients. Ocular signs were resolved over due course of time in 48.8% of patients, completely resolved in 28%, while there was no improvement in 6.28% of patients. The final best-corrected visual acuity of >6/18 was achieved in 51.69% of patients. Statistical significance was observed in the correlation between the GCS scoring and general ocular findings (p= 0.02) as well as a relative afferent pupillary defect (p=0.003). The association between age > 50 years and neuro-ophthalmic features was not found to be statistically significant (p=0.56).Conclusion: Poor visual acuity at presentation, optic canal fractures, the presence of multiple fractures of orbital walls, no improvement in vision within 48 hours of starting intravenous corticosteroids, were indicators of a poor visual prognosis in this study. The GCS, neuro-deficit, and ocular signs contribute significantly to the prediction of outcomes. Prompt treatment and referral can lead to a good resolution of symptoms and signs.

Therapy-type related long-term outcomes in mucopolysaccaridosis type II (Hunter syndrome) – Case series

Mucopolysaccharidosis type II (MPS II, Hunter syndrome) is a rare, X-linked recessive multisystem lysosomal storage disease due to iduronate-2-sulfatase enzyme deficiency. We presented three unrelated Slovenian patients with the severe form of MPS II that received three different management approaches: natural course of the disease without received specific treatment, enzyme replacement therapy (ERT), and hematopoietic stem cell transplantation (HSCT). The decision on the management depended on disease severity, degree of cognitive impairment, and parent's informed decision. The current benefits of MPS II treatments are limited. The lifelong costly intravenous ERT brings significant benefits but the patients with severe phenotypes and neurological involvement progress to cognitive decline and disability regardless of ERT, as demonstrated in published reviews and our case series. The patient after HSCT was the only one of the three cases reported to show a slowly progressing cognitive development. The type of information from the case series is insufficient for generalized conclusions, but with advanced myeloablative conditioning, HSCT may be a preferred treatment option in early diagnosed MPS II patients with the severe form of the disease and low disease burden at the time of presentation.