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BackgroundCLN2 disease (Neuronal Ceroid Lipofuscinosis Type 2) is an ultra-rare, neurodegenerative lysosomal storage disease, caused by an enzyme deficiency of tripeptidyl peptidase 1 (TPP1). Lack of disease awareness and the non-specificity of presenting symptoms often leads to delayed diagnosis. These guidelines provide robust evidence-based, expert-agreed recommendations on the risks/benefits of disease-modifying treatments and the medical interventions used to manage this condition.MethodsAn expert mapping tool process was developed ranking multidisciplinary professionals, with knowledge of CLN2 disease, diagnostic or management experience of CLN2 disease, or family support professionals. Individuals were sequentially approached to identify two chairs, ensuring that the process was transparent and unbiased. A systematic literature review of published evidence using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidance was independently and simultaneously conducted to develop key statements based upon the strength of the publications. Clinical care statements formed the basis of an international modified Delphi consensus determination process using the virtual meeting (Within3) online platform which requested experts to agree or disagree with any changes. Statements reaching the consensus mark became the guiding statements within this manuscript, which were subsequently assessed against the Appraisal of Guidelines for Research and Evaluation (AGREEII) criteria.ResultsTwenty-one international experts from 7 different specialities, including a patient advocate, were identified. Fifty-three guideline statements were developed covering 13 domains: General Description and Statements, Diagnostics, Clinical Recommendations and Management, Assessments, Interventions and Treatment, Additional Care Considerations, Social Care Considerations, Pain Management, Epilepsy / Seizures, Nutritional Care Interventions, Respiratory Health, Sleep and Rest, and End of Life Care. Consensus was reached after a single round of voting, with one exception which was revised, and agreed by 100% of the SC and achieved 80% consensus in the second voting round. The overall AGREE II assessment score obtained for the development of the guidelines was 5.7 (where 1 represents the lowest quality, and 7 represents the highest quality).ConclusionThis program provides robust evidence- and consensus-driven guidelines that can be used by all healthcare professionals involved in the management of patients with CLN2 disease and other neurodegenerative disorders. This addresses the clinical need to complement other information available.

BackgroundThe classic phenotype of CLN2 disease (neuronal ceroid lipofuscinosis type 2) typically manifests between ages 2 and 4 years with a predictable clinical course marked by epilepsy, language developmental delay, and rapid psychomotor decline. Atypical phenotypes exhibit variable time of onset, symptomatology, and/or progression. Intracerebroventricular-administered cerliponase alfa (rhTPP1 enzyme) has been shown to stabilize motor and language function loss in patients with classic CLN2 disease, but its impact on individuals with atypical phenotypes has not been described.MethodsA chart review was conducted of 14 patients (8 male, 6 female) with atypical CLN2 phenotypes who received cerliponase alfa. Pre- and posttreatment CLN2 Clinical Rating Scale Motor and Language (ML) domain scores were compared.ResultsMedian age at first presenting symptom was 5.9 years. First reported symptoms were language abnormalities (6 [43%] patients), seizures (4 [29%]), ataxia/language abnormalities (3 [21%]), and ataxia alone (1 [7%]). Median age at diagnosis was 10.8 years. ML score declined before treatment in 13 (93%) patients. Median age at treatment initiation was 11.7 years; treatment duration ranged from 11 to 58 months. From treatment start, ML score remained stable in 11 patients (treatment duration 11-43 months), improved 1 point in 1 patient after 13 months, and declined 1 point in 2 patients after 15 and 58 months, respectively. There were 13 device-related infections in 8 patients (57%) and 10 hypersensitivity reactions in 6 (43%).ConclusionsCerliponase alfa is well tolerated and has the potential to stabilize motor and language function in patients with atypical phenotypes of CLN2 disease.

Purpose Batten disease or neuronal ceroid lipofuscinosis is the most prevalent neurodegenerative disorder of childhood. Previously reported perioperative complications in children with Batten disease have come mainly from single case reports. The primary aim of the current study was to investigate perioperative complications of patients with Batten disease in the largest cohort known to date. The secondary objective was to characterize the anesthetic management including the use of propofol and to assess its association with adverse events. Method We conducted a single center, retrospective descriptive study by querying the hospital's electronic medical record to identify patients with a diagnosis of Batten disease or ICD10 E75.4 who received anesthetic care from December 2014 to May 2019. Results Thirty-five patients who underwent a total of 93 anesthetic encounters (range 1-11) were included in the analysis. A total of 29 adverse events were identified. Hypotension (N = 6, 6.5%) and bradycardia (N = 7, 7.5%) requiring treatment with medications were the most common adverse events. Other adverse events include oxygen desaturation (N = 4, 4.3%), seizures (N = 4, 4.3%), unanticipated hospital or ICU admission (N = 1, 1.1%), PACU phase 1 stay > 120 min (N = 2, 2.2%), hypothermia (N = 4, 4.3%), agitation (N = 1, 1.1%), and laryngospasm requiring treatment (N = 1, 1.1%). The number of preoperative anti-epileptic drugs (AEDs) had a positive correlation with the rate of perioperative adverse events. There was no statistical relationship of adverse events with intraoperative use of propofol (odds ratio 1.03, 95% CI 0.42-2.51). Conclusions The majority of these patients were managed without clinically significant perioperative complications. As previously reported, bradycardia, hypotension, and hypothermia were the most common adverse events. Routine avoidance of propofol in patients with Batten disease does not appear warranted., Author(s): Yoshikazu Yamaguchi [sup.1] [sup.5], Reagan Lyman [sup.2], Emily De Los Reyes [sup.3] [sup.4], Stephani S. Kim [sup.1], Joshua C. Uffman [sup.1] [sup.5], Joseph D. Tobias [sup.1] [sup.4] [sup.5] Author [...]

Background La Crosse virus (LACV) is the most common neuroinvasive arboviral infection in children in the United States. However, data regarding predictors of disease severity and neurologic outcome are limited. Additionally, long-term neurologic and neurobehavioral outcomes remain relatively sparse. Methods This was a single-center, retrospective cohort study, followed by recruitment for a cross-sectional analysis of long-term neurobehavioral outcomes, among children aged 0–18 years with proven or probable LACV neuroinvasive disease (LACV-ND) between January 2009 and December 2018. Case ascertainment was assured by International Classification of Diseases , Ninth and Tenth Revision , Clinical Modification codes cross-referenced with laboratory results detecting LACV. Demographics, diagnostics, radiographs, and outcomes were evaluated. Recruitment of patients with prior diagnosis of LACV-ND occurred from January 2020 to March 2020, with assessment performed by validated pediatric questionnaires. Results One-hundred fifty-two children (83 males; median age, 8 years [interquartile range, 5–11.5 years]) were diagnosed with proven (n = 61 [47%]) and probable (n = 91 [60%]) LACV-ND. Sixty-five patients (43%) had severe disease. Altered mental status (AMS) (odds ratio [OR], 6.36 [95% confidence interval {CI}, 2.03–19.95]; P =.0002) and seizures at presentation (OR, 10.31 [95% CI, 3.45–30.86]; P =.0001) were independent predictors of severe disease. Epileptiform discharges on electroencephalogram (EEG) were independently associated with epilepsy diagnosis at follow-up (OR, 13.45 [95% CI, 1.4–128.77]; P =.024). Fifty-four patients were recruited for long-term neurobehavioral follow-up, with frequent abnormal assessments identified (19%–54%) irrespective of disease severity. Conclusions Severe disease was observed frequently among children with LACV-ND. Seizures and AMS at presentation were independent predictors of severe disease. EEG may help determine long-term epilepsy risk. Long-term neurobehavioral issues are frequent and likely underrecognized among children with LACV-ND. [ABSTRACT FROM AUTHOR]

Intravenous ribavirin saved a child dying of La Crosse encephalitis (LE) after testing of a brain tissue sample revealed the presence of the virus. LE is spread by mosquitos and is endemic in the midwestern and mid-Atlantic states. Less than 20% of patients will develop severe illness. In this unusual case, there were no anti-LE antibodies in the blood, which is how the diagnosis is usually made. Herpes simplex encephalitis was suspected, but the child failed to respond to acyclovir treatment. After diagnosis, the FDA gave emergency permission to use ribavirin., ABBREVIATIONS. CNS, central nervous system; LE, La Crosse encephalitis; HSE, herpes simplex encephalitis; ICP, intracranial pressure; IgM, immunoglobulin M; IgG, immunoglobulin G; FDA, Food and Drug Administration; CSF, cerebrospinal fluid; [...]