Clinical characteristics and NF1 gene mutation analysis of three successive generations in three different Indian families with neurofibromatosis type 1 and peripheral nerve sheath tumours.

Neurofibromatosis type 1 (NF1) is a rare autosomal-dominant disorder caused by inactivation of NF1 tumour suppressor gene, which associates in the development of peripheral nerve tumours. NF1 is an important regulator of GAP and RAS proteins, mutations in NF1 results in the impairment in this function causing specific osseous lesions in any organ of the human body. In the present study, we investigated the clinical characteristics and NF1 gene mutation analysis of 3 unrelated Indian families with neurofibromatosis type 1. All the exons of NF1 gene was PCR amplified and sequenced. The structural and functional analysis was performed using molecular modelling tools. The sequence analysis of NF1 gene revealed; in family I five novel mutations p.R103K, p.D105N, p.M108I, p.L114M, p.E116X and p.A131S was observed in exon 4. In family II one missense p.A131S mutation and one silent p.L234L mutation was detected in exon 4. While, in family III one novel frame shift p.E225Rfs∗6 mutation was identified in exon 7 resulting in the truncated protein formation. Further, the structural analysis revealed all these mutations fall in the protein kinase C domain of NF1 gene causing loss of functional GRD and CSRD domains. In conclusion, novel mutations in the exon 4 and exon 7 of NF1 gene in these families correlating with genotype-phenotype characters explaining the neurofibromatosis type 1 and peripheral nerve sheath tumours condition in these patients.

Minimally invasive transforaminal lumbar interbody fusion using bone cement-augmented pedicle screws for lumbar spondylolisthesis in patients with osteoporosis. Case series and review of literature.

BACKGROUND: Instrumentation in patients with osteoporosis is challenging. Bone cement-augmented fenestrated pedicle screw fixation is a new procedure for fixation in the osteoporotic bone; and, applying minimally invasive techniques to the above is a challenging and novel concept. AIMS: To evaluate the clinical and radiological outcome of minimally invasive spine surgery transforaminal lumbar interbody fusion (MIS-TLIF) in patients with spondylolisthesis and poor bone quality, performed with rigid instrumentation using bone cement [poly(methylmethacrylate)]-augmented fenestrated pedicle screws. SETTINGS AND DESIGN: Prospective, observational, single-center study. STATISTICAL ANALYSIS USED: Wilcoxon nonparametric test for paired samples with a level of significance of 0.05. METHODS: A clinical series of 25 patients with lumbar spondylolisthesis and osteoporosis who underwent minimally invasive TLIF with bone cement-augmented pedicle screws were included in the study. Clinical outcome and the function were assessed using the visual analog scale (VAS) score for pain and the Oswestry Disability Index (ODI). Perioperative, postoperative, and long-term complications were monitored with a mean follow-up of 18 months. RESULTS: A total of 25 (20 female and 5 male) patients were included in the study with an average age of 61.05 years. The major symptom was low back pain with radiating pain to lower limbs. The average T-score was -3.0. All the patients were followed clinically and radiologically. There was a statistically significant improvement in the VAS scores and ODI scores postoperatively. No events of cement extravasation, radiological loosening, or pulling out of screws were observed. CONCLUSIONS: Fenestrated pedicle screw fixation with bone cement augmentation in patients with osteoporosis is a well-established alternative to increase the pullout strength of screws placed in the osteoporotic bone. Applying the concept of minimally invasive surgery to this procedure makes it a more complete solution for instrumentation in osteoporotic spine. Our series is the largest in literature on spondylolisthesis and confirms the feasibility and safety of this procedure in treating spondylolisthesis in the aging population.

Dural metastases in chronic myeloid leukemia presenting as subdural hematoma.

Subdural hematoma (SDH) has been reported in 0.5-4% of all intracranial metastatic tumors. Chronic SDH has been reported in intracranial metastases from both solid and haematological malignancies. Here we report recurrent SDH in a patient with chronic myeloid leukaemia (CML) following dural metastases. An elderly male patient a known case of CML was admitted to our casualty with symptoms of headache and altered sensorium and imaging revealed a large right fronto temporo parietal chronic SDH. This was surgically managed and histopathology of the duramater and subdural membrane confirmed infiltration with leukemic cells. The pathogenesis of chronic SDH in malignancies is multifactorial and this case report throws light on leukemic infiltration of duramater as a cause for chronic SDH other than coagulopathy.