Abstract AIMS Prolonged follow-up with imaging has costs both financial and psychological. We sought to review clinical and radiological follow-up for operated dysembryoplastic neuroepithelial tumour (DNET) and ganglioglioma in our unit. METHOD Retrospective review of patients diagnosed with WHO grade 1 DNET or ganglioglioma identified from our histopathology database over the last 20 years. RESULTS 44 patients were identified (DNET n=23, ganglioglioma n=21). Mean age at first surgery was 27.2 and 22.3 respectively. The median length of follow-up was 3.45 (0.84-13.9) years for DNET, and 5.03 (0.4-12.6) years for ganglioglioma. The majority of the patients had epilepsy (39/44, 88.6%) prior to surgery. Patients with DNET had 0.58 postoperative scans per year, whilst those with ganglioglioma had 1.17 scans per year. 11 (47.8%) DNET and 9 (42.9%) ganglioglioma patients had residual tumour after first surgery. None of the DNET patients had radiological change during follow-up. 9 (43%) patients with ganglioglioma had radiological change noted at least once during follow-up. 3 (13%) patients with DNET and 4 (19%) with ganglioglioma had further surgery for ongoing seizures due to residual tumour, but not for radiological progression. CONCLUSIONS Radiological change following tumour resection did not occur for DNET whereas it was more common for gangliogliomas. A reduction in postoperative imaging in our practice could be considered for operated low grade DNET and ganglioglioma, given that for all patients the indication for reoperation was seizures rather than tumour progression.
GNAO1 (OMIM 139311) encodes a GαCNS protein responsible for regulation of GABA-B and α2-receptors, and neurotransmitter release. Mutations of GNAO1 are reported in patients with epileptic encephalopathy (EE) at times with a movement disorder (MD); some display severe hyperkinetic movements without EE, three underwent Deep Brain Stimulation (DBS) with reduction in exacerbations.1–4 (see online supplementary table 3, supporting information (SI)).
### Supplementary Material
Supplementary table 1[SP3.pdf]
We describe the MD phenomenology and course in three patients identified from neurology services in Brisbane and Glasgow with GNAO1 -related MD, highlighting effectiveness of DBS in exacerbations.
Informed consent was obtained. Four MD specialists reviewed videos (baseline, exacerbations, post-DBS) using a Proforma (SI) and reached a consensus on movement phenomenology.
All patients had global delay, central hypotonia and MD noted in early life (see online supplementary table 1, patient synopsis, SI). Patient 3 initially showed bradykinesia, rigidity and dystonia; patient 1 resting tremor. All had been diagnosed with dyskinetic Cerebral Palsy (CP), without substantive MRI findings. Medication for baseline MD had variable efficacy (see online supplementary table 2, SI). MRI demonstrated mild progressive atrophy over 6 years in two patients (see online supplementary figure 1, SI). MRI during an exacerbation revealed restricted diffusion in the internal capsules and splenium (corpus callosum) in one (figure 1).
### Supplementary Material
Supplementary figure 1[SP1.JPG]
Figure 1
Response to Deep Brain Stimulation (DBS) and MRI changes. PICU - Pediatric Intensive Care Unit.
Whole exome sequencing identified de novo heterozygous mutations in the GNAO1 gene in all three patients, confirmed with Sanger sequencing.
### MD phenomenology
Dominant baseline MD varied between patients; agreed features included …
MMPs (matrix metalloproteinases), ADAMs (a disintegrin and metalloproteinase) and TIMPs (tissue inhibitors of metalloproteinases) are implicated in invasion and angiogenesis: both are tissue remodeling processes involving regulated proteolysis of the extracellular matrix, growth factors and their receptors. The expression of these three groups and their correlations with clinical behaviour has been reported in gliomas but a similar comprehensive study in meningiomas is lacking. In this study, we aimed to evaluate the patterns of expression of 23 MMPs, 4 TIMPs, 8 ADAMs, selective growth factors and their receptors in 17 benign meningiomas using a quantitative real-time polymerase chain reaction (qPCR). Results indicated very high gene expression of 13 proteases, inhibitors and growth factors studied: MMP2 and MMP14, TIMP-1, -2 and -3, ADAM9, 10, 12, 15 and 17, EGF-R, EMMPRIN and VEGF-A, in almost every meningioma. Expression pattern analysis showed several positive correlations between MMPs, ADAMs, TIMPs and growth factors. Furthermore, our findings suggest that expression of MMP14, ADAM9, 10, 12, 15 and 17, TIMP-2, EGF-R and EMMPRIN reflects histological subtype of meningioma such that fibroblastic subtype had the highest mRNA expression, transitional subtype was intermediate and meningothelial type had the lowest expression. In conclusion, this is the first comprehensive study characterizing gene expression of 8 ADAMs in meningiomas. These neoplasms, although by histological definition benign, have invasive potential. Taken together, the selected elevated gene expression pattern may serve to identify targets for therapeutic intervention or indicators of biological progression and recurrence.
Summary Objective The risk of premature death is increased in patients with intractable epilepsy. The effect of vagus nerve stimulation ( VNS ) on mortality remains unclear. In a previous study by Annegers et al., mortality was raised, comparable to similar intractable cohorts. Our aim was to calculate standardized mortality ratios ( SMR s), identify epilepsy‐related deaths, and estimate sudden unexpected death in epilepsy ( SUDEP) rates in patients treated with VNS for epilepsy. Methods All United Kingdom patients undergoing VNS between January 1, 1995 and December 31, 2010 at King's College Hospital, London were flagged through the national Medical Research Information Service. Analysis was performed in relation to all deaths occurring by December 31, 2010. Deceased patients were identified from the national death register, and additional information on cause and circumstances of death sought where appropriate to allow for classification of deaths. Results The cohort consisted of 466 patients, with 2993.83 person‐years of follow‐up and a median observation period of 5.9 years. Twenty‐nine deaths occurred, 27 with the device active. SMR was 7.1 (95% confidence interval [CI] 4.8–10.3) for the active device; 12 deaths were considered epilepsy related, including 10 definite or probable SUDEP and one fatal near SUDEP . Definite/probable and fatal near SUDEP occurred at a rate of 3.7/1,000 person‐years. SMR s decreased from 10.5 (5.6–19.5) in the first 2 years after implantation to 5.9 (3.7–9.5) thereafter, although CIs overlapped. SUDEP rates did not alter over time. Significance SMR s and SUDEP rate in this study are comparable to other cohorts with intractable epilepsy, with SUDEP an important cause of death. VNS does not appear to lower the risk of premature death overall. There was a clear trend with lower SMR after 2 years of implantation, although CIs overlapped. SUDEP rates, however, did not change.
To examine the outcome of vagus nerve stimulation (VNS) for drug-resistant epilepsy using data from a National Health Service VNS clinic.Clinical records of patients implanted with VNS for epilepsy between1995 and 2010 were examined. Patients were selected for study who had at least one year of therapeutic stimulation (minimum 1 mA stimulator current) and follow-up by our service with analysable electronic records, providing continuous assessment of seizure control during available follow-up. Seizure status at each attendance was assessed and graded 1-4 (1=seizure free or <5 seizures/year; 2 =≥50%reduction in seizure frequency; 3=<50% reduction; 4=no improvement compared to baseline). Responders were those whose grades improved consistently (Grades 1,2 and 3).Of 464 patients, 171 fulfilled the inclusion criteria and were divided into three groups: a) Responders (n = 81); b) non-responders (n = 80) and c) others (n = 10), the latter showing a late step-wise change (six improved; four deteriorated). After initial ramping up of current, groups were very stable over subsequent periods varying from one to 12 years (median 3.8 years). Sixteen patients died, 10 of non-epilepsy causes with 6 epilepsy-related deaths. There was a significant relation between epilepsy-related deaths and response (p < 0.00001). Patients with longer time as non-responders had more likelihood of suffering an epilepsy death than responders, though numbers were small.This study shows that meaningful data can be obtained retrospectively from routine clinic records. In this cohort about half of patients treated with VNS responded and the response generally remaining stable over time.
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