X-linked hypophosphatemia (XLH) is the most common monogenic disorder causing hypophosphatemia. This case-note review documents the clinical features and the complications of treatment in 59 adults (19 male, 40 female) with XLH. XLH is associated with a large number of private mutations; 37 different mutations in the PHEX gene were identified in this cohort, 14 of which have not been previously reported. Orthopaedic involvement requiring surgical intervention (osteotomy) was frequent. Joint replacement and decompressive laminectomy were observed in those older than 40 years. Dental disease (63%), nephrocalcinosis (42%), and hearing impairment (14%) were also common. The rarity of the disease and the large number of variants make it difficult to discern specific genotype-phenotype relationships. A new treatment, an anti-FGF23 antibody, that may affect the natural history of the disease is currently being investigated in clinical trials.Electronic supplementary materialThe online version of this article (10.1007/s10545-018-0147-6) contains supplementary material, which is available to authorized users.

In a certain group of patients with syringomyelia, even with the advent of sophisticated magnetic resonance imaging (MRI), no associated abnormality or cerebrospinal fluid (CSF) block is easily identified. This type of syringomyelia is often termed idiopathic. Current literature has less than 10 reports of arachnoid webs to be the causative factor. We present our experience in the management of two cases of syringomyelia secondary to arachnoid webs. Both our patients presented with progressive neurological deterioration with MRI scans demonstrating cervical/thoracic syrinx without Chiari malformation or low-lying cord. There was no history of previous meningitis or trauma. Both patients underwent myelography that demonstrated dorsal flow block implying CSF obstruction. Cord displacement/change in caliber was also noted and this was not evident on MRI scans. Both patients underwent thoracic laminectomy. After opening the dura, thickened/abnormal arachnoid tissue was found that was resected thus widely communicating the dorsal subarachnoid space. Postoperatively at 6 months, both patients had significant symptomatic improvement with follow-up MRI scans demonstrating significant resolution of the syrinx. In patients with presumed idiopathic syringomyelia, imaging studies should be closely inspected for the presence of a transverse arachnoid web. We believe that all patients with idiopathic symptomatic syringomyelia should have MRI CSF flow studies and/or computed tomography (CT) myelography to identify such arachnoid abnormalities that are often underdiagnosed. Subsequent surgery should be directed at the establishment of normal CSF flow by laminectomy and excision of the offending arachnoid tissue.

The authors report their experience in successfully treating a 4-year-old girl who presented with sudden onset of quadriparesis that lasted for 20 days. Magnetic resonance (MR) imaging of the spine revealed an intramedullary cystic lesion extending from C-4 to C-6. A C4-6 laminectomy was performed followed by a median myelotomy. The cyst was decompressed and most of the cyst wall was excised. The histopathological findings were consistent with those of an arachnoid cyst. By postoperative Day 3, power had gradually returned to normal in all her limbs. On follow-up reviews at 2 and 17 months, the results of her neurological examinations remained normal. Follow-up MR imaging of the spine at 17 months revealed an intramedullary residual cystic lesion extending from C-5 to C-6, without any mass effect. An intramedullary arachnoid cyst should be considered in the differential diagnosis of an intramedullary cystic lesion.

All our patients experienced significant and sustained clinical improvement. Anterior cervical osteophytectomy consistently leads to improvement in symptomatic ACH patients without recurrence. Early referral to a neurosurgical multi-disciplinary team (MDT) is indicated in ACH related dysphagia, once conservative management has failed.

Brain tumours kill more children and adults under 40 than any other cancer. Around half of primary brain tumours are glioblastoma multiforme (GBMs) where treatment remains a significant challenge. GBM survival rates have improved little over the last 40 years, thus highlighting an unmet need for the identification/development of novel therapeutic targets and agents to improve GBM treatment. Using archived and fresh glioma tissue, we show that in contrast to normal brain or benign schwannomas GBMs exhibit re-expression of FANCD2, a key protein of the Fanconi Anaemia (FA) DNA repair pathway, and possess an active FA pathway. Importantly, FANCD2 expression levels are strongly associated with tumour grade, revealing a potential exploitable therapeutic window to allow inhibition of the FA pathway in tumour cells, whilst sparing normal brain tissue. Using several small molecule inhibitors of the FA pathway in combination with isogenic FA-proficient/deficient glioma cell lines as well as primary GBM cultures, we demonstrate that inhibition of the FA pathway sensitises gliomas to the chemotherapeutic agents Temozolomide and Carmustine. Our findings therefore provide a strong rationale for the development of novel and potent inhibitors of the FA pathway to improve the treatment of GBMs, which may ultimately impact on patient outcome.