Enhancing Diagnostic Accuracy Through Neuroimaging Revisions in Pediatric Pseudotumor Cerebri Syndrome: A Cross-Sectional Study.

BACKGROUND: This cross-sectional study aimed to report all neuroimaging findings suggestive of raised intracranial pressure in children with pseudotumor cerebri syndrome (PTCS), before and after re-review by two neuroradiologists. METHODS: We included 48 children aged <18 years diagnosed with PTCS between 2016 and 2021. Clinical and radiological data were obtained from their medical files. Two neuroradiologists independently re-reviewed all neuroimages, and the average of their assessments was compared with the initial neuroimaging reports; an additional review was done to analyze inter- and intraclass correlation. RESULTS: The initial neuroimaging reports showed under-reporting of findings, with only 26 of 48 (54.1%) patients identified with abnormal reports. After revision, the proportion of the reported findings increased to 44 of 48 (91.6%). Distention of the perioptic space was the most commonly reported finding after revision (36.5 of 48; 76%). Flattening of the posterior globe and empty sella were initially under-reported but improved after revision. Moreover, several findings suggestive of increased intracranial pressure not mandated by Friedman criteria were identified, such as narrowing of the Meckel cave, posterior displacement of the pituitary stalk, and narrowing of the cavernous sinus. Analysis of associations between neuroimaging findings and demographic and clinical characteristics yielded no statistically significant results. The inter- and intraclass correlation results demonstrated a significant agreement between raters and within each rater's assessment (P < 0.05). CONCLUSIONS: This study highlights the impact of image revision in enhancing PTCS diagnosis. Intra- and interclass correlations underscore the reliability of the review process, emphasizing the importance of meticulous image analysis in clinical practice.

Novel association of Dandy-Walker malformation with CAPN15 variants expands the phenotype of oculogastrointestinal neurodevelopmental syndrome.

Oculogastrointestinal neurodevelopmental syndrome has been described in seven previously published individuals who harbor biallelic pathogenic variants in the CAPN15 gene. Biallelic missense variants have been reported to demonstrate a phenotype of eye abnormalities and developmental delay, while biallelic loss of function variants exhibit phenotypes including microcephaly and craniofacial abnormalities, cardiac and genitourinary malformations, and abnormal neurologic activity. We report six individuals from three unrelated families harboring biallelic deleterious variants in CAPN15 with phenotypes overlapping those previously described for this disorder. Of the individuals affected, four demonstrate radiographic evidence of the classical triad of Dandy-Walker malformation including hypoplastic vermis, fourth ventricle enlargement, and torcular elevation. Cerebellar anomalies have not been previously reported in association with CAPN15-related disease. Here, we present three unrelated families with findings consistent with oculogastrointestinal neurodevelopmental syndrome and cerebellar pathology including Dandy-Walker malformation. To corroborate these novel clinical findings, we present supporting data from the mouse model suggesting an important role for this protein in normal cerebellar development. Our findings add six molecularly confirmed cases to the literature and additionally establish a new association of Dandy-Walker malformation with biallelic CAPN15 variants, thereby expanding the neurologic spectrum among patients affected by CAPN15-related disease.

Pseudotumor cerebri syndrome in children: Clinical characteristic and re-classification.

AIM: To describe the clinical characteristics of children with pseudotumor cerebri syndrome (PTCS) who were diagnosed according to the modified Dandy criteria and to reclassify them according to the newly proposed diagnostic criteria by Freidman. METHODOLOGY: This retrospective study included the period from January 2016-to July 2021. RESULTS: 50 patients were included; 34 males and 16 females with a male to female ratio of 2.1:1. The average age at onset of symptoms was 8 years. Obesity was noticed in 6 (12%) patients; 34 (68%) had symptoms upon presentation. The most common presenting symptom was headache (28 patients; 56%), papilledema was present in 33 (66%) patients. Most patients (37; 74%) had an initial cerebrospinal fluid (CSF) pressure ≥280 mmH2O. At last follow-up, papilledema resolved in 11/32 (34.3%) patients, and headache resolved in 17/23 (74%) patients. 22/50 (44%) patients fulfilled the definite criteria proposed by Freidman, 11/50 (22%) fulfilled the probable, 10/50 (20%) were categorized as possible, and 7 (14%) patients were categorized as unmet. CONCLUSION: PTCS is a chronic condition. Managing patients who do not have papilledema or who do not meet the newly proposed higher CSF pressure is challenging. Although, applying the newly proposed criteria captured most of our patients, however, around one quarter were managed based on clinical experience. This study indicates a strong need for future guidelines tailored specifically for children, taking into consideration that the cut-off point of CSF pressure might not be similar for all populations.

Could vagus nerve stimulation influence bone remodeling?

OBJECTIVES: To investigate the effect of vagus nerve stimulation (VNS) on the bone mineral density (BMD) in epileptic patients. METHODS: A prospective cohort study was conducted on individuals with refractory seizures who underwent VNS surgery between January 2012 and December 2018. BMD was measured preoperatively and between 6 months and one year after surgery. RESULTS: Twenty-one patients (mean age (±SD)=23.6±12.3 years) were recruited for the implantation of a VNS device. The mean absolute increase in lumbar BMD in the 21 patients was 0.04±0.04 g/cm2 resulting in an overall percent increase from baseline of 4.7±6.1%. BMD increased by an amount ≥ the least significant change (LSC) for the lumbar spine in 13 patients (61.9%). The lumbar Z score also increased in these patients from -1.22±1.15 to -0.88±1.22, P=0.006). Pre and Post VNA femoral BMD was measured in only 11 patients and, of those 3 showed a significant increase in BMD, 1 a significant decrease and 7 no change. CONCLUSION: The implantation of a VNS was associated with an increase in lumbar BMD. This study could lead to a new application for VNS in the treatment of osteoporosis.

The clinical characteristics of primary headache and associated factors in children: A retrospective descriptive study.

BACKGROUND: Headache is the most encountered manifestation of pain in childhood. The purpose of this study was to investigate the incidence and clinical characteristics of primary headaches. Further, the factors associated with primary headache were examined. MATERIALS AND METHODS: A retrospective study was conducted among young children and adolescents over 3 years at a tertiary referral teaching hospital in North Jordan. Relevant patient information was obtained by reviewing patients' medical records. RESULTS: This study included 194 children (95 males, 99 females). The incidence rate of primary headache in the current study was 2.815 per 1000 children visited pediatric clinic. The mean age of patients at the time of headache onset was 10 years, and about half of them were males (95/194; 49%). Approximately 30% (56/194) had a family history of headache. Migraine headaches were the most commonly reported types (87/194; 44.8%) and only 17/194; 8.7% suffered from tension type headaches. Approximately, 40% (84/194) of patients reported severe headache and a third of them (67/194; 34.5%) complained of daily headaches. Pain location was reported as bilateral in most patients (153/194; 78.9%). About one fifth (41/194; 21.1%) stated that their headache was precipitated by sleep deprivation. Abnormal serum level of vitamin D and family history of headache were significantly associated with primary headache (p < 0.001). CONCLUSIONS: These findings highlight the importance of early detection and management of headaches among pediatric population. In addition, screening vitamin D status should be encouraged for children presented with primary headaches.

Congenital insensitivity to pain with anhidrosis syndrome: A series from Jordan.

OBJECTIVES: To present the clinical picture, the associated complications and the genetic findings of Jordanian patients diagnosed with Congenital insensitivity to pain with anhidrosis (CIPA). PATIENTS AND METHODS: This is a retrospective study including 7 patients diagnosed with CIPA presenting to Jordan University Hospital neurology clinic between 2001 and 2017. RESULTS: Among five families, seven patients were diagnose with CIPA and followed for a period ranging from one month to 6 years. The initial symptom observed in all patients was high fever in the first few days after birth, decreased sensation to pain and decreased sweating were later noted. Poor weight gain, microcephaly and global developmental delay were present in most cases. All patients had tongue ulcerations. Fingers/toes ulcerations were present in 6/7 (86.0 %), hip joint dislocation in 3/7 (43.0 %), chronic arthritis and joint swelling in 6/7 (86.0 %), corneal ulcers in 4/7 (57.1 %) and kidney amyloidosis in 1/7 (13.0 %) of all patients. Death occurred in 4/7 (57.1 %) patients. Consanguinity was present in all families. Mutation analysis revealed three variants in NTRK1 gene. The frameshift (c.1860_1861insT; p.Pro621fs) mutation was common in our series. One patient carried a novel missense mutation (c.2170 G > A; p.Gly724Ser). The third missense mutation (C2125 G > T; p.Val709Leu) was reported in a previous study in one patient. CONCLUSION: This cohort reveals a severe CIPA phenotype necessitating thorough multidisciplinary care and follow up.

Recurrent meningitis in children: etiologies, outcome, and lessons to learn.

PURPOSE: Recurrent meningitis in children is a rare condition. However, its early recognition is important in order to prevent serious complications. This study aims to review cases of recurrent meningitis in children. METHODS: This is a retrospective study that included children diagnosed with recurrent meningitis and who were followed at child neurology clinic at the Jordan University Hospital from January 2001 to June 2017. RESULTS: Thirteen patients were included (nine males and four females). Age of first episode of meningitis ranged from 2 months to 9.5 years. The delay in diagnosis of the underlying cause after the first episode ranged from 6 months to 2.5 years. Underlying causes included inner ear malformation in one patient, skull fractures in two, and dermal sinuses (thoracic spinal and occipital dermal sinus) in two patients. No identifiable cause was found in eight patients. Streptococcus pneumoniae was identified in four (31%) patients, Staphylococcus aureus in two (15%), and no organism was isolated in seven (54%). Three patients (23.1%) developed neurological sequel including developmental delay, limb spasticity, and epilepsy. Two patients had sensorineural hearing loss related to meningitis, and two patients had sensorineural hearing loss mostly related to their original disease. CONCLUSION: A detailed history, examination, and thorough investigations are necessary to determine the underlying cause of recurrent meningitis. In addition, in patients with positive CSF bacterial culture, finding the underlying etiology is very likely.

Congenital insensitivity to pain and anhydrosis due to a rare mutation and that is complicated by inflammatory bowel disease and amyloidosis: a case report.

Patients with congenital insensitivity to pain and anhydrosis syndrome are at risk for renal amyloidosis and inflammatory bowel disease. Physicians caring for such patients should be aware of these complications.

Dandy-Walker malformation, genitourinary abnormalities, and intellectual disability in two families.

We report on two families, each with documented consanguinity and two affected with overlapping features of Dandy-Walker malformation, genitourinary abnormalities, intellectual disability, and hearing deficit. This phenotype shares similar findings with many well-known syndromes. However, the clinical findings of this syndrome categorize this as a new syndrome as compared with the phenotype of already established syndromes. Due to parental consanguinity, occurrence in siblings of both genders and the absence of manifestations in obligate carrier parents, an autosomal recessive pattern of inheritance is more likely. The authors believe that these families suggest a novel autosomal recessive cerebello-genital syndrome. Array CGH analyses of an affected did not show pathological deletions or duplications.

Intracranial Hypertension in Children: Etiologies, Clinical Features, and Outcome.

This retrospective study aimed to describe the clinical presentations, possible causes, and outcomes of children with idiopathic intracranial hypertension who presented to the authors' clinic. The mean age at onset of symptoms in the authors' cohort of 19 children was 6 years (range: 7 months to 12 years). Most patients (90%) were under 11 years old and (84.2%) symptomatic. The probable cause was identified in 7/19 (37.0%) patients. The most common cause was vitamin D deficiency (26.3%). Other associated probably coincidental comorbidities included sinusitis (5/19, 26.3%), hypophosphatasia (1/19), Pyle disease (1/19), and measles vaccine (1/19). Apart from 2 patients who required lumboperitoneal shunt, the cerebrospinal fluid pressure returned to normal in all patients within a period of 6 weeks to 1 year (average, 5 months). Of those who followed up with the authors' ophthalmologist, 30.7% developed optic atrophy or pallor; 75% of these patients had previous ocular comorbidities.

Katanin p80 regulates human cortical development by limiting centriole and cilia number.

Katanin is a microtubule-severing complex whose catalytic activities are well characterized, but whose in vivo functions are incompletely understood. Human mutations in KATNB1, which encodes the noncatalytic regulatory p80 subunit of katanin, cause severe microlissencephaly. Loss of Katnb1 in mice confirms essential roles in neurogenesis and cell survival, while loss of zebrafish katnb1 reveals specific roles for katnin p80 in early and late developmental stages. Surprisingly, Katnb1 null mutant mouse embryos display hallmarks of aberrant Sonic hedgehog signaling, including holoprosencephaly. KATNB1-deficient human cells show defective proliferation and spindle structure, while Katnb1 null fibroblasts also demonstrate a remarkable excess of centrioles, with supernumerary cilia but deficient Hedgehog signaling. Our results reveal unexpected functions for KATNB1 in regulating overall centriole, mother centriole, and cilia number, and as an essential gene for normal Hedgehog signaling during neocortical development.

Mondini malformation associated with diastematomyelia and presenting with recurrent meningitis.

The authors report the case of 5-year-old girl who presented with 4 episodes of recurrent meningitis. Her initial workup revealed a lumbosacral dermoid sinus associated with diastematomyelia and a tethered cord. Therefore, a surgical repair to correct the anomaly was performed. However, another episode of meningitis occurred after surgery, and a subsequent temporal bone scan revealed the presence of left Mondini dysplasia. To the authors' knowledge, this is the first report of Mondini dysplasia in association with diastematomyelia.

Loss of CHSY1, a secreted FRINGE enzyme, causes syndromic brachydactyly in humans via increased NOTCH signaling.

We delineated a syndromic recessive preaxial brachydactyly with partial duplication of proximal phalanges to 16.8 Mb over 4 chromosomes. High-throughput sequencing of all 177 candidate genes detected a truncating frameshift mutation in the gene CHSY1 encoding a chondroitin synthase with a Fringe domain. CHSY1 was secreted from patients' fibroblasts and was required for synthesis of chondroitin sulfate moieties. Noticeably, its absence triggered massive production of JAG1 and subsequent NOTCH activation, which could only be reversed with a wild-type but not a Fringe catalytically dead CHSY1 construct. In vitro, depletion of CHSY1 by RNAi knockdown resulted in enhanced osteogenesis in fetal osteoblasts and remarkable upregulation of JAG2 in glioblastoma cells. In vivo, chsy1 knockdown in zebrafish embryos partially phenocopied the human disorder; it increased NOTCH output and impaired skeletal, pectoral-fin, and retinal development. We conclude that CHSY1 is a secreted FRINGE enzyme required for adjustment of NOTCH signaling throughout human and fish embryogenesis and particularly during limb patterning.

Griscelli syndrome type 2: a rare and lethal disorder.

Griscelli syndrome is a rare autosomal recessive disorder. It is characterized by pigment dilution and variable immune deficiency leading to increased susceptibility to certain infections and a tendency to develop a life-threatening hemophagocytic syndrome known as the accelerated phase. Griscelli syndrome is now classified into 3 types based on the genetic and molecular features. Primary neurological presentation without the accelerated phase is rare in type 2. In this article, the authors report a boy who was presented with seizures and diffuse white matter involvement unaccompanied by the other features of the accelerated phase. Mutation analysis in family members revealed the presence of a missense mutation in Rab27a gene. In addition to the rare presentation, this is the first case of Griscelli syndrome to be reported from Jordan.

Ataxia-telangiectasia complicated by craniopharyngioma--a new observation.

Ataxia-telangiectasia is a rare autosomal recessive neurodegenerative disorder with high incidence of malignancy including leukemias, lymphomas, and solid tumors. Central nervous system tumors in ataxia telangiectasia include medulloblastomas and gliomas. We describe a 13-year-old girl with ataxia telangiectasia who developed craniopharyngioma and non-Hodgkin's lymphoma. To our knowledge, this is the first case of ataxia telangiectasia complicated by craniopharyngioma in the English literature.