The added value of brain MR spectroscopy in children with Crigler-Najjar syndrome type-I: correlation with demographic, neurodevelopmental, and laboratory findings.

OBJECTIVE: The aim of this study is to demonstrate the role of proton magnetic resonance spectroscopy (1H-MRS) in the detection of brain microstructural changes in patients with Crigler-Najjar syndrome type-I (CNs-I), and its correlation with demographic, neurodevelopmental and laboratory findings. METHODS: Prospective study was conducted on 25 children with CNs-I and 25 age and sex-matched children, who served as control. They underwent multivoxel 1H-MRS of basal ganglion at echo time 135-144 ms. N-acetyl aspartate/Creatine (NAA/Cr) and Choline (Ch)/Cr were calculated and correlated with demographic, clinical, and laboratory findings of patients with CNs-I. RESULTS: There was a significant difference in NAA/Cr and Ch/Cr between patients and controls. The cut-off value for NAA/Cr and Ch/Cr used to differentiate patients from controls were 1.8 and 1.2 with an area under the curve (AUC) of 0.91 and 0.84 respectively. There was a significant difference in MRS ratios between patients with neurodevelopmental delay (NDD) and patients without NDD. The cut-off values for NAA/Cr and Ch/Cr used to differentiate between patients with NDD and patients without NDD were 1.47 and 0.99, with AUC of 0.87 and 0.8 respectively. The NAA/Cr and Ch/Cr were well correlated with family history (p = 0.006 and p < 0.001) respectively, consanguinity (p < 0.001 and p = 0.001), neurodevelopmental delay (p = 0.001 and p = 0.004), serum bilirubin level (r = -0.77, p < 0.001), (r = -0.49, p = 0.014), phototherapy (p < 0.001 and p = 0.32), blood transfusion (p < 0.001 and p = 0.001) respectively. CONCLUSION: 1H-MRS can be a useful tool in the detection of neurological changes in patients with CNs-I; NAA/Cr and Ch/Cr parameters are well correlated with demographic, clinical, and laboratory findings. ADVANCES IN KNOWLEDGE: Our study is the first report on using MRS in assessing neurological manifestations in CNs. 1H-MRS can be a useful tool in the detection of neurological changes in patients with CNs-I.

Clinical characteristics, outcome, and predictors of neurological sequelae of persistent congenital hyperinsulinism: A single tertiary center experience.

AIM: Congenital hyperinsulinism (CHI) is a heterogeneous disease with variable genetic etiology, histopathology, and clinical phenotype. This study aims to describe the clinical characteristics of persistent CHI and evaluate long-term neurological outcome and its risk factors in a cohort of Egyptian children. METHODS: Clinical, genetic, and biochemical data of 42 patients with CHI were collected. Patients were invited for neurological assessment, electroencephalogram, and magnetic resonance imaging of the brain. RESULTS: ABCC8 mutation was found in (61%) of cases who underwent genetic testing (17/28). Five cases with homozygous biparental ABCC8 mutation responded to combined diazoxide and octreotide without needing surgery. Seven out of twenty-one patients who had pancreatectomy (33%) developed diabetes after a median period of 4.8 (range:1-10) years following surgery. Fifty-five percent of our patients had neurodevelopmental impairment at follow-up. Logistic regression analysis has shown that delayed referral to tertiary centre for more than 8 days, delayed diagnosis of CHI for more than 14 days and hospital admission for more than 30 days, are significant predictors of unfavorable neurological sequelae in CHI; (OR = 12.7 [2.56], p = 0.001), (OR = 12.7 [2.9-56], p = 0.001), and (OR = 3.8 [0.14.5], p = 0.043), respectively. CONCLUSIONS: ABCC8 mutation was the commonest genetic mutation underlying CHI in this study group. CHI cases with biparental homozygous ABCC8 mutation may show response to combined octreotide and diazoxide therapy. More than half of our patients had neurodevelopmental impairment at follow-up. Delayed referral to expert centre, delayed diagnosis and longer hospital stay are significant predictors of neurological disability in CHI cases.

Diffusion Tensor Imaging of Microstructural Changes in the Gray and White Matter in Patients With Crigler-Najjar Syndrome Type I.

PURPOSE: This study aimed to evaluate the role of diffusion tensor imaging of microstructural changes in gray and white matter in Crigler-Najjar syndrome type I. PATIENT AND METHODS: A prospective study was conducted on 10 patients with Crigler-Najjar syndrome type I and 10 age- and sex-matched children who underwent diffusion tensor imaging of the brain. Mean diffusivity (MD) and fractional anisotropy (FA) of gray and white matter were measured. RESULTS: There was a significantly higher MD of the gray matter regions including the globus pallidus, thalamus, caudate head, substantia nigra, and dentate nucleus in patients versus controls (P = 0.007, 0.001, 0.014, 0.003, and 0.002), respectively. The areas under the curve (AUC) of MD of the globus pallidus and thalamus used to differentiate patients from controls were 0.93 and 0.925, respectively. There was a significant difference in MD of the frontal white matter and posterior limb of the internal capsule in patients versus controls (P = 0.001 and 0.02), respectively. The AUCs of MD of these regions used to differentiate patients from controls were 0.82 and 0.8. There was a significant difference in FA of the frontal white matter and posterior limb of the internal capsule in patients versus controls (P = 0.006 and 0.006), respectively. The AUCs of FA of these regions were 0.83 and 0.85, respectively. The MD of the globus pallidus correlated with serum bilirubin (r = 0.87 and P = 0.001). CONCLUSION: Diffusion tensor imaging can detect microstructural changes of deep gray matter and some regions of white matter in Crigler-Najjar syndrome type I.

Seizure outcome and epilepsy patterns in patients with cerebral palsy.

PURPOSE: The aim of the present study was to investigate epilepsy patterns and outcomes in patients with cerebral palsy (CP) and identify the variables that determine remission. METHODS: This was a retrospective cohort study. We followed 107 CP patients aged 1-16 years with newly diagnosed epilepsy. The patients were categorized according to their remission outcome, uninterrupted freedom of seizure for 2 years or longer, and 4 epilepsy patterns: A) sustained freedom from seizures before 6 months of treatment; B) delayed but sustained seizure freedom; C) relapsing-remitting course; and D) seizure freedom never attained. The variables were analysed for their prognostic relevance to the outcomes RESULTS: A total of 107 patients were included; their mean age at epilepsy diagnosis was 4.2 years (SD 2.5). By the end of the 8-year follow up, 19.6% 26.1%, 31.7%, and 22.4% were in sustained remission, terminal remission, relapse, and no remission respectively. Pattern A was identified in 6.5% of the patients, pattern B in 27.1%, pattern C in 43.9%, and pattern Din 22.4%. Univariate analysis revealed that the type of CP, mobility, and number of seizure types, are among the other factors that significantly affected remission. CONCLUSION: A total of 45% of patients with CP and epilepsy achieved remission (with and without antiepileptics) but after a relatively long treatment duration. Remission was affected by patient- and epilepsy-related factors. More studies are required to further evaluate these factors.