Effectiveness of intra-thecal methotrexate in refractory Anti-N-methyl-d-aspartate receptor encephalitis.

BACKGROUND: Anti-N-methyl-d-aspartate "anti-NMDA" receptor encephalitis is one of the most common autoimmune encephalitis for which first- and second-line therapies have been recommended following international consensus. However, some refractory cases do not respond to the first- and second-line therapy and require further immune-modulatory therapies such as intra-thecal methotrexate. In this study, we reviewed six confirmed cases of refractory anti-NMDA receptor encephalitis from two tertiary centers in Saudi Arabia that required escalation of treatment and received a six-month course of intra-thecal methotrexate. The aim of this study was to evaluate the effectiveness of intra-thecal methotrexate as immunomodulatory therapy for refractory anti-NMDA receptor encephalitis. METHODS: We retrospectively evaluated six confirmed cases of refractory anti-NMDA receptor encephalitis who did not improve after first- and second-line therapy and received monthly intra-thecal methotrexate treatment course for six consecutive months. We reviewed patient demography, underlying etiologies, and compared their modified Rankin score prior to receiving intra-thecal methotrexate and six months after completing the treatment. RESULTS: Three of the six patients showed a marked response to intra-thecal methotrexate with a modified Rankin scale of 0-1 at 6-month follow-up. None of the patients experienced any side effects during or after intra-thecal methotrexate treatment, and no flareups were observed. CONCLUSION: Intra-thecal methotrexate may be a potentially effective and relatively safe escalation option for immunomodulatory therapy of refractory anti-NMDA receptor encephalitis. Future studies on intra-thecal methotrexate -specific treatment regimens may further support its utility, efficacy, and safety in treating refractory anti-NMDA receptor encephalitis.

Clinical Characteristics and Risk Factors of Neonatal Hypoxic-Ischaemic Encephalopathy and Its Associated Neurodevelopmental Outcomes During the First Two Years of Life: A Retrospective Study in Saudi Arabia.

Objective: This study aimed to determine the clinical characteristics and factors associated with neonatal hypoxic-ischaemic encephalopathy (HIE) and its neurodevelopmental outcomes. Methods: We conducted retrospective case-control research to investigate the clinical and labour-related risk factors for HIE. In addition, a single-centre cohort study was conducted on infants with HIE to describe their neurodevelopment from birth to 24 months. For this investigation, cases with a diagnosis of HIE who were born at King Abdullah Children's Specialist Hospital (KASCH), Riyadh, Saudi Arabia, between 2015 and 2019 were identified and matched with controls from the same facility (1:4). Each case's clinical information was extracted using electronic medical records. In addition, 24-month follow-up HIE cases were included in a cohort study to describe their neurodevelopmental outcomes. Results: The sample includes 60 infants diagnosed with HIE and 234 infants serving as controls, with a mean gestational age of 38.8 weeks (SD 1.6) and a predominance of males (56.4%). Around one-third of the HIE cases (36.6%) had moderate HIE (stage 2), whereas 35.1% of infants had severe HIE (stage 3), according to Sarnat staging. Compared to the control group, children with HIE were twice as likely to be born to mothers with maternal comorbidities and more likely to have prepartum and intrapartum complications. A 24-month follow-up of neurodevelopmental outcomes for HIE babies revealed that approximately 24% exhibited delays in gross motor skill development, 22% in fine motor skill development, 33% in language skill development, and 22% in social skill development. Conclusion: In the HIE group, maternal comorbidities and prepartum or intrapartum complications were more common. The severity grade of HIE can be used to predict neurodevelopmental consequences. Enhancing patient care and rehabilitation requires a minimum of 24 months of neurodevelopmental follow-up.

Congenital disorder of glycosylation with defective fucosylation 2 (FCSK gene defect): The third report in the literature with a mild phenotype.

BACKGROUND: Congenital disorders of glycosylation (CDG) are a group of heterogeneous disorders caused by abnormal lipid or protein glycosylation. Variants in the FCSK gene have been reported to cause CDG. Defective FCSK-induced CDG (FCSK-CDG) has only been reported previously in three unrelated children. METHODS: In this study, we genetically and clinically examined a 3-year-old proband with resolved infantile spasms and normal development. Standard whole-exome sequencing (WES) and Sanger sequencing were performed to identify the functional impact of the variant. RESULTS: WES revealed a rare biallelic missense variant (c.3013G>C; p.Val1005Leu) in FCSK. RT-qPCR showed a significant depletion in FCSK gene expression in the affected individual. Western blotting revealed reduced FCSK expression at the protein level compared to that in the control. Furthermore, 3D protein modeling suggested changes in the secondary structure, which might affect the overall FCSK protein function. CONCLUSION: This study broadens the mutation and phenotypic spectrum of FCSK-associated developmental disorders.

Pediatrics COVID-19 and neurological manifestations: Single tertiary centre experience.

IMPORTANCE: Coronavirus disease 2019 (COVID-19) is a severe acute respiratory syndrome that is caused by a novel coronavirus 2 (SARS-CoV-2). It originated in China late December 2019 and was declared a global pandemic on March 12, 2020. Most reports of COVID-19 cases either presented with neurological manifestations or complications involve adults. Only few cases were reported in pediatric patients. OBJECTIVE: To report COVID-19 pediatric cases with neurological manifestations and identify the wide spectrum of its manifestations. DESIGN SETTING AND PARTICIPANTS: This was a retrospective, observational case series. Data of pediatric patients infected by SARS-CoV-2 presenting with neurological manifestations at King Abdullah Specialized Children Hospital in King Abdulaziz Medical City in Riyadh were collected from May 23 to June 30, 2020. RESULTS: We encountered 5 COVID-19 cases with neurological manifestations. Three patients who were previously healthy had new-onset neurological symptoms. Symptoms and signs included encephalopathy, ataxia, headache, seizure, papilledema, ophthalmoplegia, hyporeflexia, and different clinical spectra, such as Miller Fisher syndrome, meningoencephalitis, and idiopathic intracranial hypertension. Other patients attending our center were incidentally found to be SARS-CoV-2-positive, which caused a delay in the investigations required to reach diagnosis. CONCLUSIONS AND RELEVANCE: Our cases highlight the wide clinical spectrum of neurological manifestations in COVID-19 patients. Given the paucity of information about pediatric COVID-19 cases with neurological symptoms, we here reported these cases to shed light on the association between SARS-CoV-2 and neurological presentation. Moreover, our study indicates that many investigations are being delayed and could affect diagnosis and treatment.

The Leukodystrophy Spectrum in Saudi Arabia: Epidemiological, Clinical, Radiological, and Genetic Data.

Background: Leukodystrophies (LDs) are inherited heterogeneous conditions that affect the central nervous system with or without peripheral nerve involvement. They are individually rare, but collectively, they are common. Thirty disorders were included by the Global Leukodystrophy Initiative Consortium (GLIA) as LDs. Methods: We conducted a retrospective chart review of a consecutive series of patients diagnosed with different types of LD from four large tertiary referral centers in Riyadh, Saudi Arabia. Only those 30 disorders defined by GLIA as LDs were included. Results: In total, 83 children from 61 families were identified and recruited for this study. The male-to-female ratio was 1.5:1, and a consanguinity rate of 58.5% was observed. An estimated prevalence of 1:48,780 or 2.05/100,000 was observed based on the clinical cohort, whereas a minimum of 1:32,857 or 3.04/100,000 was observed based on the local genetic database. The central region of the country exhibited the highest prevalence of LDs (48.5%). The most common LD was metachromatic leukodystrophy (MLD), and it accounted for 25.3%. The most common disorder based on carrier frequency was AGS. Novel variants were discovered in 51% of the cases, but 49% possessed previously reported variants. Missense variants were high in number and accounted for 73% of all cases. Compared with other disorders, MLD due to saposin b deficiency was more common than expected, Pelizaeus-Merzbacher-like disease was more prevalent than Pelizaeus-Merzbacher disease, and X-linked adrenoleukodystrophy was less common than expected. The mortality rate among our patients with LD was 24%. Conclusion: To the best of our knowledge, this is the largest cohort of patients with LD from Saudi Arabia. We present epidemiological, clinical, radiological, and genetic data. Furthermore, we report 18 variants that have not been reported previously. These findings are of great clinical and molecular utility for diagnosing and managing patients with LD.

Biallelic loss-of-function variants in NEMF cause central nervous system impairment and axonal polyneuropathy.

We aimed to detect the causative gene in five unrelated families with recessive inheritance pattern neurological disorders involving the central nervous system, and the potential function of the NEMF gene in the central nervous system. Exome sequencing (ES) was applied to all families and linkage analysis was performed on family 1. A minigene assay was used to validate the splicing effect of the relevant discovered variants. Immunofluorescence (IF) experiment was performed to investigate the role of the causative gene in neuron development. The large consanguineous family confirms the phenotype-causative relationship with homozygous frameshift variant (NM_004713.6:c.2618del) as revealed by ES. Linkage analysis of the family showed a significant single-point LOD of 4.5 locus. Through collaboration in GeneMatcher, four additional unrelated families' likely pathogenic NEMF variants for a spectrum of central neurological disorders, two homozygous splice-site variants (NM_004713.6:c.574+1G>T and NM_004713.6:c.807-2A>C) and a homozygous frameshift variant (NM_004713.6: c.1234_1235insC) were subsequently identified and segregated with all affected individuals. We further revealed that knockdown (KD) of Nemf leads to impairment of axonal outgrowth and synapse development in cultured mouse primary cortical neurons. Our study demonstrates that disease-causing biallelic NEMF variants result in central nervous system impairment and other variable features. NEMF is an important player in mammalian neuron development.

Acute Necrotizing Encephalopathy of Childhood: A Multicenter Experience in Saudi Arabia.

Background: Acute necrotizing encephalopathy of childhood (ANEC) is a rapidly progressing encephalopathy characterized by fever, depressed level of consciousness, and seizures. Diagnosis depends on clinical presentation and characteristic neuroimaging findings of abnormal signal intensity involving the thalami as well as the supra and infra-tentorial areas. Treatment modalities are not well-established; empirical treatment with antibiotics and antiviral agents is the initial step, followed by steroids and immunoglobulin, as well as supportive care. Patients with ANEC have a variable prognosis, but mortality is very high. Methods: A retrospective chart review of patients diagnosed with ANEC in five tertiary centers from January 2015 to October 2018 was performed. Clinical and radiological findings, as well as the therapeutic approach and outcomes, were described. Results: Twelve children were included ranging in age from 10 months to 6 years. All patients presented with preceding febrile illness, altered level of consciousness, and seizure. Radiological features showed abnormal signals in the thalami, and five patients (41.7%) had brainstem involvement. All patients received empirical treatment with antibiotics and antiviral agents. Ten patients (83.3%) received intravenous immunoglobulin (IVIG) and IV Methylprednisolone therapy. Outcomes were variable ranging from good outcomes with minimal neurological deficits to poor outcomes and death in 25% of cases. Conclusion: ANEC is a rare fulminant disease in children. The treatment is challenging. Early interventions with the use of IVIG and IV Methylprednisolone may change the outcome; however, further studies are needed to establish a consensus guideline for the management.

EMC10 homozygous variant identified in a family with global developmental delay, mild intellectual disability, and speech delay.

In recent years, several genes have been implicated in the variable disease presentation of global developmental delay (GDD) and intellectual disability (ID). The endoplasmic reticulum membrane protein complex (EMC) family is known to be involved in GDD and ID. Homozygous variants of EMC1 are associated with GDD, scoliosis, and cerebellar atrophy, indicating the relevance of this pathway for neurogenetic disorders. EMC10 is a bone marrow-derived angiogenic growth factor that plays an important role in infarct vascularization and promoting tissue repair. However, this gene has not been previously associated with human disease. Herein, we describe a Saudi family with two individuals segregating a recessive neurodevelopmental disorder. Both of the affected individuals showed mild ID, speech delay, and GDD. Whole-exome sequencing (WES) and Sanger sequencing were performed to identify candidate genes. Further, to elucidate the functional effects of the variant, quantitative real-time PCR (RT-qPCR)-based expression analysis was performed. WES revealed a homozygous splice acceptor site variant (c.679-1G>A) in EMC10 (chromosome 19q13.33) that segregated perfectly within the family. RT-qPCR showed a substantial decrease in the relative EMC10 gene expression in the patients, indicating the pathogenicity of the identified variant. For the first time in the literature, the EMC10 gene variant was associated with mild ID, speech delay, and GDD. Thus, this gene plays a key role in developmental milestones, with the potential to cause neurodevelopmental disorders in humans.

Genomic testing and counseling: The contribution of next-generation sequencing to epilepsy genetics.

INTRODUCTION: Currently, next-generation sequencing (NGS) technology is more accessible and available to detect the genetic causation of diseases. Though NGS technology benefited some clinical phenotypes, for some clinical diagnoses such as seizures and epileptic disorders, adaptation occurred slowly. The genetic diagnosis was mainly based on epilepsy gene panels and not on whole exome and/or genome sequencing. METHOD: We retrospectively analyzed 420 index cases, referred for NGS over a period of 18 months, to investigate the challenges in diagnosing epilepsy. RESULT: Of the 420 cases, 65 (15%) were referred due to epilepsy with one third having a positive family history. The result of the NGS was 14 positive cases (21.5%), 16 inconclusive cases (24%), and 35 (53%) negative cases. No gene has been detected twice in the inconclusive and positive groups. Comparative genomic hybridization has been performed for all 30 NGS negative cases and four cases with pathogenic variants (deletion in 15q11.213.1, deletion of 2p16.3, deletion in Xq22.1, and deletion in 17p13.3) were identified. CONCLUSION: These findings have implications for our understanding of the approach to genetic testing and counseling of patients affected with seizures and epilepsy disorders. The overall diagnostic yield of exome/genome sequencing in our cohort was 23%. The main characteristic is genetic heterogeneity, supporting NGS technology as a suitable testing approach for seizures and epilepsy disorders. Genetic counseling for newly identified disease-causing variants depends on the pedigree interpretation, within the context of disease penetrance and variable expressivity.

Epilepsy in Propionic Acidemia: Case Series of 14 Saudi Patients.

Propionic acidemia is an inborn error of metabolism that is inherited in an autosomal recessive manner. It is characterized by a deficient propionyl-CoA carboxylase due to mutations in either of its beta or alpha subunits. In the literature, there is a clear association between propionic acidemia and epilepsy. In this cohort, we retrospectively reviewed the data of 14 propionic acidemia patients in Saudi Arabia and compared the findings to those of former studies. Six of the 14 (43%) patients developed epileptic seizure, mainly focal seizures. All patients were responsive to conventional antiepileptic drugs as their seizures are controlled. The predominant electroencephalographic (EEG) findings were diffuse slowing in 43% and multifocal epileptiform discharges in 14% of the patients. In 1 patient, burst suppression pattern was detected, a pattern never before reported in patients with propionic acidemia. Brain magnetic resonance imaging (MRI) findings mainly consisted of signal changes of the basal ganglia (36%), generalized brain atrophy (43%), and delayed myelination (43%).The most common genotype in our series is the homozygous missense mutation in the PCCA gene (c.425G>A; p. Gly142Asp). However, there is no clear genotype-seizure correlation. We conclude that seizure is not an uncommon finding in patients with propionic acidemia and not difficult to control. Additional studies are needed to further elaborate on genotype-seizure correlation.

Further Delineation of the Clinical Phenotype of Cerebellar Ataxia, Mental Retardation, and Disequilibrium Syndrome Type 4.

BACKGROUND: Cerebellar ataxia, mental retardation, and disequilibrium syndrome (CAMRQ) is a heterogeneous group of genetic disorders that have been grouped by shared clinical features; all of these features are transmitted via an autosomal recessive mechanism. Four variants of this syndrome have been identified so far, and each one differs in terms of both clinical and genotypical features. CAMRQ4 is a rare genetic disorder characterized by mental retardation, ataxia or an inability to walk, dysarthria and, in some patients, quadrupedal gait. METHODS: We investigated three Saudi families with CAMRQ4. Blood samples were collected from the affected patients, their parents, and healthy siblings. DNA was extracted from whole blood, and whole-exome sequencing was performed. Findings were confirmed by segregation analysis, which was performed on other family members. RESULTS: Thus far, 17 patients have been affected by CAMRQ4. Genetic analysis of all patients, including our current patients, showed a mutation in the aminophospholipid transporter, class I, type 8A, member 2 gene (ATP8A2). A series of common phenotypical features have been reported in these patients, with few exceptions. Ataxia, mental retardation, and hypotonia were present in all patients, consanguinity in 90% and abnormal movements in 50%. Moreover, 40% achieved ambulation at least once in their lifetime, 40% had microcephaly, whereas 30% were mute. Magnetic resonance imaging (MRI) of the brain was normal in 60% of patients. CONCLUSIONS: We described the largest cohort of patients with CAMRQ4 syndrome and identified three novel mutations. CAMRQ4 syndrome should be suspected in patients presenting with ataxia, intellectual disability, hypotonia, microcephaly, choreoathetoid movements, ophthalmoplegia, and global developmental delay, even if brain MRI appears normal.

Further delineation of the phenotypic spectrum of ISCA2 defect: A report of ten new cases.

Iron-Sulfur Cluster (ISC) biogenesis is a vital cellular process required to produce various ISC-containing proteins. These ISC proteins are responsible for essential functions such as glycine cleavage and the formation of lipoic acid, an essential cofactor of respiratory chain complexes. Defects in ISC biogenesis lead to multiple mitochondrial dysfunction syndromes including: ISCA2 with infantile onset leukodystrophy. Recently, a founder mutation, c.229G > A, p.Gly77Ser in ISCA2 was reported to cause Multiple Mitochondrial Dysfunction Syndrome type 4. In a retrospective review of children diagnosed with the ISCA2 defect, we were able to identify ten new patients who were not reported previously with the identical founder mutation. High CSF glycine levels and elevated glycine peaks on MR spectroscopy were demonstrated in all tested probands. All patients were between 3 and 7 months of age with a triad of neurodevelopmental regression, nystagmus and optic atrophy and leukodystrophy. MRI findings were typical in the patients with diffuse, abnormal white matter signal in the cerebrum, cerebellum, brain stem and spinal cord. The patients ended up in a vegetative state, and often premature death due to respiratory infections. We alert clinicians to consider the ISCA2 defect as a differential diagnosis of infantile onset leukodystrophies affecting the brain as well as the spinal cord, especially in the presence of elevated CSF glycine or elevated glycine peaks in MR spectroscopy.

Retrospective review of pediatric status epilepticus in 116 Saudi patients: predictors of outcome.

BACKGROUND: Status epilepticus (SE) is a common, life-threatening condition. Multiple factors are used to predict its outcome and evaluate its risks, and there have been only a few studies in Saudi Arabia. OBJECTIVES: Investigate predictors of SE outcome. DESIGN: Retrospective chart review study. SETTING: Tertiary center, Riyadh. PATIENTS AND METHODS: We reviewed all pediatric cases (age 14 years or younger) of SE admitted between January 2005 and December 2015, collecting data on age, sex, date of birth, developmental status, pre-existing neurological diseases, SE etiology, Glasgow Outcome Scale (GOS) scores, and electroencephalogram (EEG) findings. The outcome was categorized as poor based on any decrease in baseline GOS score or moderate-to-severe developmental delay in young children; otherwise outcome was considered good. MAIN OUTCOME MEASURE: Outcome of SE. RESULTS: One hundred and sixteen patients (54% boys) with ages from 1 month to 10 years were included in the analysis. Fifty-five (47.4%) had a poor outcome. The overall mortality rate related to SE was 2.6%. Four patients had an SE duration of more than 24 hours. Univariate and multivariate analysis revealed that poor outcome was related to symptomatic SE etiology and a history of epilepsy. Age, sex, SE duration, and EEG findings were not predictors of poor outcome. CONCLUSION: Pediatric status epilepticus is highly associated with neurological morbidity. The main pre.dictor of outcome is underlying symptomatic etiology of SE and to a lesser degree the presence of a history of epilepsy. Duration does not seem to play a major role. LIMITATIONS: The main limitation is the retrospective chart review nature of the study with possible bias.

Mutation in SLC6A9 encoding a glycine transporter causes a novel form of non-ketotic hyperglycinemia in humans.

Glycine cleavage system (GCS) catalyzes the degradation of glycine and disruption of its components encoded by GLDC, AMT and GCSH are the only known causes of glycine encephalopathy, also known as non-ketotic hyperglycinemia (NKH). In this report, we describe a consanguineous family with one child who presented with NKH, but harbored no pathogenic variants in any of the three genes linked to this condition. Whole-exome sequencing revealed a novel homozygous missense variant in exon 9 of SLC6A9 NM_201649.3: c.1219 A>G (p.Ser407Gly) that segregates with the disease within the family. This variant replaces the highly conserved S407 in the ion-binding site of this glycine transporter and is predicted to disrupt its function. In murine model, knockout of Slc6a9 is associated with equivalent phenotype of NKH, namely respiratory distress and hypotonia. This is the first demonstration that mutation of the glycine transporter can be associated with NKH in humans.

Worsening of Seizures After Asparagine Supplementation in a Child with Asparagine Synthetase Deficiency.

OBJECTIVE: Asparagine synthetase deficiency is an autosomal recessive neurometabolic disorder characterized clinically by severe congenital microcephaly, global developmental delay, intractable epilepsy, and motor impairment in the form of spastic quadriparesis. Diagnosis is confirmed by findings of low cerebral spinal fluid or plasma asparagine in addition to a mutation of the subsequently in ASNS gene. There is no documented trial of asparagine as a treatment for this disorder. PATIENT DESCRIPTION: We present a child with asparagine synthetase deficiency whose mental status improved slightly from a vegetative state to a minimally conscious state after starting asparagine supplementation. He subsequently became irritable, developed sleep disturbance, and experienced worsening seizures, requiring discontinuation of the asparagine supplements. CONCLUSIONS: Asparagine supplementation may be not effective in controlling the seizures in asparagine synthetase deficiency, and it is likely to make them worse.

Asparagine Synthetase Deficiency: New Inborn Errors of Metabolism.

BACKGROUND: Asparagine synthetase deficiency (ASD) is a newly identified neurometabolic disorder characterized by severe congenital microcephaly, severe global developmental delay, intractable seizure disorder, and spastic quadriplegia. Brain MRI showed brain atrophy, delayed myelination, and simplified gyriform pattern. METHODS: We report ASD deficiency in a 2- and 4-year-old sibling. On them, we described clinical, biochemical, and molecular findings, and we compared our results with previously reported cases. RESULTS: We identified a homozygous novel missense mutation in ASNS gene in both probands and we demonstrated low CSF and plasma asparagine in both patients. CONCLUSIONS: Clinicians should suspect ASD deficiency in any newborn presented with severe congenital microcephaly followed by severe epileptic encephalopathy and global developmental delay. CSF asparagine level is low in this disorder while plasma may be low.

Hereditary neurometabolic causes of infantile spasms in 80 children presenting to a tertiary care center.

BACKGROUND: Infantile spasms are a devastating infantile epileptic syndrome with multiple etiologies. Hereditary neurometabolic disorders are rarely recognized causes of infantile spasms. The aim of this study was to identify hereditary neurometabolic disorders when they were the cause of infantile spasms in patients presenting to a tertiary care center in Saudi Arabia. METHODOLOGY: We conducted a retrospective review of children presenting to the Pediatric Department of King Abdulaziz Medical City in Riyadh, Saudi Arabia over a 15-year interval. RESULTS: Eighty patients with infantile spasms were identified. A hereditary neurometabolic disorder was diagnosed in 10 patients (12.5%). Of these patients, two had a Leigh-like disorder and one patient had each of the following diagnoses: ethylmalonic aciduria, nonketotic hyperglycinemia, hyperinsulinemic hypoglycemia, leukodystrophy, short-chain acyl-coenzyme A dehydrogenase deficiency, molybdenum cofactor deficiency, primary carnitine deficiency, and neonatal hypoglycemia due to panhypopituitarism. This article is the first to report the association of the last three conditions with infantile spasms. Compared with the other etiologies, the hereditary neurometabolic disorder group had a strong history of similar disease in the same family (P = 0.002), and most of the patients were born of consanguineous parents (P = 0.021). In addition, a typical hypsarrhythmia pattern was more common in the hereditary neurometabolic disorder group (P = 0.003). Furthermore, this group had a poor response to therapy (P = 0.04). Otherwise, there were no significant differences regarding the type of spasms, neuroimaging or outcome; however, there was a trend toward poorer outcomes and death in the hereditary neurometabolic disorder group. CONCLUSION: Hereditary neurometabolic disorders are relatively common causes of infantile spasms in this subpopulation of Saudi patients. An early diagnosis via proper metabolic and genetic testing has significant implications for applying specific treatments and for facilitating proper family counseling.

Pseudotumor cerebri in a child receiving peritoneal dialysis: Recovery of vision after lumbo-pleural shunt.

A 9-year-old boy with end-stage renal disease who was receiving continuous ambulatory peritoneal dialysis (CAPD) presented with acute visual loss and was found to have papilledema. Neuroimaging and cerebrospinal fluid (CSF) analysis were normal. The lumbar puncture opening pressure was 290 mm of water so the diagnosis of pseudotumor cerebri (PTC) was entertained. Medical treatment was not an option because of renal insufficiency; neither was lumbo-peritoneal shunting, because of the peritoneal dialysis. After a lumbo-pleural shunt was placed, there was marked improvement in symptoms. The lumbo-pleural shunt is a reasonable option for treatment for PTC in patients on CAPD who require a CSF divergence procedure.