Need for arthrodesis following facetectomy for spinal peripheral nerve sheath tumors: an institutional experience and review of the current literature.

OBJECTIVE: Spinal peripheral nerve sheath tumors (PNSTs) are a group of rare tumors originating from the nerve and its supporting structures. Standard surgical management typically entails laminectomy with or without facetectomy to gain adequate tumor exposure. Arthrodesis is occasionally performed to maintain spinal stability and mitigate the risk of postoperative deformity, pain, or neurological deficit. However, the factors associated with the need for instrumentation in addition to PNST resection in the same setting remain unclear. METHODS: An institutional tumor registry at a tertiary care center was queried for patients treated surgically for a primary diagnosis of spinal PNST between 2002 and 2016. An analysis focused on patients in whom a facetectomy was performed during the resection. The addition of arthrodesis at the index procedure comprised the primary outcome. The authors also recorded baseline demographics, tumor characteristics, and surgery-related variables. Logistic regression was used to identify factors associated with increased risk of fusion surgery. RESULTS: A total of 163 patients were identified, of which 56 (32 had facetectomy with fusion, 24 had facetectomy alone) were analyzed. The median age was 48 years, and 50% of the cohort was female. Age, sex, and race, as well as tumor histology and size, were evenly distributed between patients who received facetectomy alone and those who had facetectomy and fusion. On univariate analysis, total versus subtotal facetectomy (OR 9.0, 95% CI 2.01-64.2; p = 0.009) and cervicothoracic versus other spinal region (OR 9.0, 95% CI 1.51-172.9; p = 0.048) were significantly associated with increased odds of performing immediate fusion. On multivariable analysis, only the effect of total facetectomy remained statistically significant (OR 6.75, 95% CI 1.47-48.8; p = 0.025). CONCLUSIONS: The authors found that total facetectomy and cervicothoracic involvement may be highly associated with the need for concomitant arthrodesis at the time of index surgery. These findings may help surgeons to determine the best surgical planning for patients with PNST.

Subependymal Giant Cell Astrocytoma: Associated Hyperproteinorrhachia Causing Shunt Failures and Nonobstructive Hydrocephalus - Report of Successful Treatment with Long-term Follow-up.

Subependymal giant cell astrocytomas (SEGAs) are histologically benign tumors most frequently associated with tuberous sclerosis complex (TSC). Despite their benign histopathological appearance, they may cause unfavorable outcomes due to their intraventricular location. Rarely, SEGA may be associated with hyperproteinorrhachia (high levels of proteins in the cerebrospinal fluid [CSF]), which causes malresorptive, communicating hydrocephalus; certainly, this scenario makes shunt obstruction likely in this patient population. In this report, we illustrate the case of hyperproteinorrhachia in an SEGA patient with known TSC, who presented repeatedly with shunt failure from proteinaceous shunt obstruction. Subsequent surgical resection of the main intraventricular lesion resulted in a dramatic drop in the CSF protein levels and has since prevented further shunt failures. Different treatment concepts and possible pathophysiology are discussed and the pertinent literature is reviewed.

The genetic landscape of familial congenital hydrocephalus.

OBJECTIVE: Congenital hydrocephalus is an important birth defect, the genetics of which remains incompletely understood. To date, only 4 genes are known to cause Mendelian diseases in which congenital hydrocephalus is the main or sole clinical feature, 2 X-linked (L1CAM and AP1S2) and 2 autosomal recessive (CCDC88C and MPDZ). In this study, we aimed to determine the genetic etiology of familial congenital hydrocephalus with the assumption that these cases represent Mendelian forms of the disease. METHODS: Exome sequencing combined, where applicable, with positional mapping. RESULTS: We identified a likely causal mutation in the majority of these families (21 of 27, 78%), spanning 16 genes, none of which is X-linked. Ciliopathies and dystroglycanopathies were the most common etiologies of congenital hydrocephalus in our cohort (19% and 26%, respectively). In 1 family with 4 affected members, we identified a homozygous truncating variant in EML1, which we propose as a novel cause of congenital hydrocephalus in addition to its suggested role in cortical malformation. Similarly, we show that recessive mutations in WDR81, previously linked to cerebellar ataxia, mental retardation, and disequilibrium syndrome 2, cause severe congenital hydrocephalus. Furthermore, we confirm the previously reported candidacy of MPDZ by presenting a phenotypic spectrum of congenital hydrocephalus associated with 5 recessive alleles. INTERPRETATION: Our study highlights the importance of recessive mutations in familial congenital hydrocephalus and expands the locus heterogeneity of this condition. Ann Neurol 2017;81:890-897.

Autozygome-guided exome sequencing in retinal dystrophy patients reveals pathogenetic mutations and novel candidate disease genes.

Retinal dystrophy (RD) is a heterogeneous group of hereditary diseases caused by loss of photoreceptor function and contributes significantly to the etiology of blindness globally but especially in the industrialized world. The extreme locus and allelic heterogeneity of these disorders poses a major diagnostic challenge and often impedes the ability to provide a molecular diagnosis that can inform counseling and gene-specific treatment strategies. In a large cohort of nearly 150 RD families, we used genomic approaches in the form of autozygome-guided mutation analysis and exome sequencing to identify the likely causative genetic lesion in the majority of cases. Additionally, our study revealed six novel candidate disease genes (C21orf2, EMC1, KIAA1549, GPR125, ACBD5, and DTHD1), two of which (ACBD5 and DTHD1) were observed in the context of syndromic forms of RD that are described for the first time.