Diagnosis and treatment of Chiari malformation type 1 in children: the International Consensus Document

Malformació de Chiari 1; Nens; SiringomieliaMalformación de Chiari 1; Niños; SiringomieliaChiari 1 malformation; Children; SyringomyeliaBackground Chiari malformation type 1 (CM1) is a rare condition where agreed classification and treatment are still missing. The goal of this study is to achieve a consensus on the diagnosis and treatment of CM1 in children. Methods A multidisciplinary panel formulated 57 provisional statements based on a review of the literature. Thirty-four international experts (IE) participated in a Delphi study by independently rating each statement on a 4-point Likert scale (“strongly disagree,” “disagree,” “agree,” “strongly agree”). Statements that were endorsed (“agree” or “strongly agree”) by < 75% of raters were re-formulated, or new statements were added, and another Delphi round followed (up to a maximum of three). Results Thirty-five IE were contacted and 34 agreed to participate. A consensus was reached on 30/57 statements (52.6%) after round 1. Three statements were added, and one removed. After round 2, agreement was reached on 56/59 statements (94.9%). Finally, after round 3, which took place during the 2019 Chiari Consensus Conference (Milan, Italy), agreement was reached on 58/59 statements (98.3%) about four main sections (Definition and Classification, Planning, Surgery, Isolated Syringomyelia). Only one statement did not gain a consensus, which is the “definition of radiological failure 24 month post-surgery.” Conclusions The consensus document consists of 58 statements (24 on diagnosis, 34 on treatment), serving clinicians and researchers following children with CM1. There is a clear need for establishing an international network and registry and to promote collaborative studies to increase the evidence base and optimize the long-term care of this patient population.Open access funding provided by Università Cattolica del Sacro Cuore within the CRUI-CARE Agreement

Tethered cord: natural history, surgical outcome and risk for Chiari malformation 1 (CM1): A review of 110 detethering

The surgical results of this series of occult spina bifida seem better than the natural history registered in the long pre-operative period in terms of neurological deterioration. The major contribution to this result is attributed to neurophysiological monitoring that lowers the risks of permanent damage and increases the percentage of effective detethering. The present series of TCS, due to conus and filar lipoma, documents that CM1 is a really rare association occurring in less than 6% of the patients, despite the low position of conus. The detethering procedure did not influence the tonsillar position, thus excluding the correlation between the tethering and the tonsillar descent. The genetic alteration documented in a girl reinforces the hypothesis of a rare complex polymaformative picture deserving multiple procedures according to the prevailing clinical symptoms

Quantitation of normal metabolite concentrations in six brain regions by <i>in-vivo</i> ¹ H-MR spectroscopy

This study examined the concentrations of brain metabolites visible to <i>in-vivo</i> ¹ H-Magnetic Resonance Spectroscopy ( ¹ H-MRS) at 1.5 T in a sample of 28 normal subjects. Quantitation was attempted for inositol compounds, choline units, total creatine and N-acetyl moieties, using open-source software. Six brain regions were considered: frontal and parietal white matter, medial temporal lobe, thalamus, pons and cerebellum. Absolute concentrations were derived using tissue water as an internal reference and using an external reference; metabolite signal intensity ratios with respect to creatine were also calculated. The inter-individual variability was smaller for absolute concentrations (internal reference) as compared to that for signal intensity ratios. Significant regional variability in concentration was found for all metabolites, indicating that separate normative values are needed for different brain regions. The values obtained in this study can be used as reference in future studies, provided the same methodology is followed; it is confirmed that despite unsuccessful attempts in the past, smaller coefficients of variation can indeed be obtained through absolute quantification

Brain Tumors in NF1 Children: Influence on Neurocognitive and Behavioral Outcome

Neurofibromatosis type-1 (NF1) is a monogenic tumor-predisposition syndrome creating a wide variety of cognitive and behavioral abnormalities, such as decrease in cognitive functioning, deficits in visuospatial processing, attention, and social functioning. NF1 patients are at risk to develop neurofibromas and other tumors, such as optic pathway gliomas and other tumors of the central nervous system. Few studies have investigated the impact of an additional diagnosis of brain tumor on the cognitive outcome of children with NF1, showing unclear results and without controlling by the effect of surgery, radio- or chemotherapy. In the present mono-institutional study, we compared the behavioral and cognitive outcomes of 26 children with neurofibromatosis alone (NF1) with two age-matched groups of 26 children diagnosed with NF1 and untreated optic pathway glioma (NF1 + OPG) and 19 children with NF1 and untreated other central nervous system tumors (NF1 + CT). NF1 + CT and NF1 + OPG showed significantly impaired cognitive abilities compared to NF1 group, with weaknesses in visuo-spatial abilities, visual scanning and verbal working memory, while general verbal abilities are preserved. Moreover, NF1 + OPG patients present more frequent internalizing problems and increased oppositional-deviant behaviors. These results suggest that the co-diagnosis of a brain tumor in NF1 children may partially worsen the cognitive and emotional outcome

Periventricular heterotopia in a male child with USP9X missense variant

The ubiquitin-specific protease USP9X has been found to play a role in multiple aspects of neural development including processes of neuronal migrations. In males, hemizygous partial loss of function variants in USP9X lead to a clinical phenotype primarily characterized by intellectual disability, hypotonia, speech and language impairment, behavioral disturbances accompanied by additional clinical features with variable expressivity. Structural brain abnormalities are reported in all cases where neuro-imaging was performed. The most common radiological features described include hypoplasia/agenesis of the corpus callosum, widened ventricles, white matter disturbances, and cerebellar hypoplasia. Here we report a child harboring a missense variant in USP9X presenting with the classical neurodevelopmental phenotype and a previously unreported radiological picture of periventricular heterotopia. This case expands the phenotypic landscape of this emergent condition and supports the critical role of USP9X in neuronal migration processes

Anti-Cyclic Citrullinated Peptide Antibody Index in the Cerebrospinal Fluid for the Diagnosis and Monitoring of Rheumatoid Meningitis

Rheumatoid meningitis (RM) is a rare but often aggressive neurological complication of rheumatoid arthritis. The diagnosis of RM, besides the clinical, radiological, and laboratory criteria, usually requires a cerebral biopsy. Based on the two cases presented in this paper, we propose a new laboratory marker. Cerebrospinal fluid and serum anti-cyclic citrullinated peptide (CCP) IgG were measured, and the intrathecal synthesis of anti-CCP antibodies (anti-CCP antibody index) was calculated using the hyperbolic function. The anti-CCP antibody index was positive in both cases at first diagnosis and progressively decreased after treatments. Together with clinical and radiological criteria, the calculation of the anti-CCP intrathecal synthesis, more than the simple measurement of serum or cerebrospinal fluid anti-CCP antibody titers, may represent a useful tool for RM diagnosis and, possibly, for treatment response