Preserving normal facial nerve function and improving hearing outcome in large vestibular schwannomas with a combined approach: planned subtotal resection followed by gamma knife radiosurgery

Objective

To perform planned subtotal resection followed by gamma knife surgery (GKRS) in a series of patients with large vestibular schwannoma (VS), aiming at an optimal functional outcome for facial and cochlear nerves.

Methods

Patient characteristics, surgical and dosimetric features, and outcome were collected prospectively at the time of treatment and during the follow-up.

Results

A consecutive series of 32 patients was treated between July 2010 and June 2016. Mean follow-up after surgery was 29 months (median 24, range 4–78). Mean presurgical tumor volume was 12.5 cm³ (range 1.47–34.9). Postoperative status showed normal facial nerve function (House–Brackmann I) in all patients. In a subgroup of 17 patients with serviceable hearing before surgery and in which cochlear nerve preservation was attempted at surgery, 16 (94.1%) retained serviceable hearing. Among them, 13 had normal hearing (Gardner–Robertson class 1) before surgery, and 10 (76.9%) retained normal hearing after surgery. Mean duration between surgery and GKRS was 6.3 months (range 3.8–13.9). Mean tumor volume at GKRS was 3.5 cm³ (range 0.5–12.8), corresponding to mean residual volume of 29.4% (range 6–46.7) of the preoperative volume. Mean marginal dose was 12 Gy (range 11–12). Mean follow-up after GKRS was 24 months (range 3–60). Following GKRS, there were no new neurological deficits, with facial and hearing functions remaining identical to those after surgery in all patients. Three patients presented with continuous growth after GKRS, were considered failures, and benefited from the same combined approach a second time.

Conclusion

Our data suggest that large VS management, with planned subtotal resection followed by GKRS, might yield an excellent clinical outcome, allowing the normal facial nerve and a high level of cochlear nerve functions to be retained. Our functional results with this approach in large VS are comparable with those obtained with GKRS alone in small- and medium-sized VS. Longer term follow-up is necessary to fully evaluate this approach, especially regarding tumor control.

     

Mouse choroideremia gene mutation causes photoreceptor cell degeneration and is not transmitted through the female germline

Choroideremia (CHM) is an X-linked progressive eye disorder which results from defects in the human Rab escort protein-1 (REP-1) gene. A gene targeting approach was used to disrupt the mouse chm/rep-1 gene. Chimeric males transmitted the mutated gene to their carrier daughters but, surprisingly, these heterozygous females had neither affected male nor carrier female offspring. The targeted rep-1 allele was detectable, however, in male as well as female blastocyst stage embryos isolated from a heterozygous mother. Thus, disruption of the rep-1 gene gives rise to lethality in male embryos; in female embryos it is only lethal if the mutation is of maternal origin. This observation can be explained by preferential inactivation of the paternal X chromosome in murine extraembryonic membranes suggesting that expression of the rep-1 gene is essential in these tissues. In both heterozygous females and chimeras the rep-1 mutation causes photoreceptor cell degeneration. Consequently, conditional rescue of the embryonic lethal phenotype of the rep-1 mutation may provide a faithful mouse model for choroideremia.      

Specificity and potency of N-methyl-D-aspartate glycine site antagonists and of mephenesin on the rat spinal cord in vitro.

The potency, specificity and reversibility of various presumed glycine site N-methyl-D-aspartate (NMDA) antagonists was studied on neonatal rat spinal cord using the grease gap technique. 5,7-Dichlorokynurenate was the most potent and specific glycine site antagonist among the compounds tested. On the other hand mephenesin was a weak non-specific excitatory amino acid (EAA) antagonist; reduction of the response to NMDA was not reversed by D-serine. The EAA antagonist properties of mephenesin could explain its mode of action at the cellular level. The lack of effect of D-serine alone suggests that in our experimental conditions glycine sites on spinal neurones are occupied by an endogenous ligand.     

Relation between Hypofractionated Radiotherapy,Toxicity and Outcome in Early Breast Cancer

To compare adjuvant conventional radiotherapy (C‐RT) to hypofractionated schedule (HF‐RT) in early breast cancer. Between May 2012 and September 2015, 120 patients were included in the analysis. All patients underwent conservative surgery and adjuvant RT. RT was delivered in C‐RT (50 Gy; 2 Gy/fr) or HF‐RT (42.5 Gy; 2.66 Gy/fr), followed by a tumor bed boost (10 Gy; 2 Gy/fr). RT‐induced toxicity was recorded and compared between groups. Toxicity results were graded according to the Common Terminology Criteria for Adverse Events guidelines. A multivariate analysis was performed of the factors associated with acute toxicity onset. Mild acute skin toxicity was observed in 71.7% of patients. No grade 4 toxicity was observed. From the multivariate analysis, Breast volume and RT fractionation significantly affected acute radiation‐related toxicity. No increase in late toxic effects has been reported between C‐RT and HF‐RT schedules. Overall, the 2‐year disease free survival was 94.4%. HF‐RT represents a valid adjuvant treatment option in early breast cancer patients, without negative impact on acute and late radiation sequelae, as well as tumor control.     

Which early ‘red flag’ symptoms identify children with meningococcal disease in primary care?

Background

Symptoms are part of the initial evaluation of children with acute illness, and are often used to help identify those who may have serious infections. Meningococcal disease is a rapidly progressive infection that needs to be recognised early among children presenting to primary care.

Aim

To determine the diagnostic value of presenting symptoms in primary care for meningococcal disease.

Design of study

Data on a series of presenting symptoms were collected using a parental symptoms checklist at point of care for children presenting to a GP with acute infection. Symptom frequencies were compared with existing data on the pre-hospital features of 345 children with meningococcal disease.

Setting

UK primary care.

Method

The study recruited a total of 1212 children aged under 16 years presenting to their GP with an acute illness, of whom 924 had an acute self-limiting infection, including 407 who were reported by parents to be febrile. Symptom frequencies were compared with those reported by parents of 345 children with meningococcal disease. Main outcome measures were diagnostic characteristics of individual symptoms for meningococcal disease.

Results

Five symptoms have clinically useful positive likelihood ratios (LR+) for meningococcal disease: confusion (LR+ = 24.2, 95% confidence interval [CI] = 11.5 to 51.3), leg pain (LR+ = 7.6, 95% CI = 4.9 to 11.9), photophobia (LR+ = 6.5, 95% CI = 3.8 to 11.0), rash (LR+ = 5.5, 95% CI = 4.3 to 7.1), and neck pain/stiffness (LR+ = 5.3, 95% CI = 3.5 to 8.3). Cold hands and feet had limited diagnostic value (LR+ = 2.3, 95% CI = 1.9 to 3.0), while headache (LR+ = 1.0, 95% CI = 0.8 to 1.3), and pale colour (LR+ = 0.3, 95% CI = 0.2 to 0.5) did not discriminate meningococcal disease in children.

Conclusion

This study confirms the diagnostic value of classic ‘red flag’ symptoms of neck stiffness, rash, and photophobia, but also suggests that the presence of confusion or leg pain in a child with an unexplained acute febrile illness should also usually prompt a face-to-face assessment to exclude meningococcal disease. Telephone triage systems and primary care clinicians should consider these as ‘red flags’ for serious infection.     

Dermoscopy of lentigo maligna melanoma: report of 125 cases

Background Lentigo maligna melanoma (LMM) is the most common subtype of melanoma on the face. Its presentation may be quite subtle, particularly in early stages, and delayed diagnosis is common. Few dermoscopic studies have been performed and the main dermoscopic features of LMM were defined by Stolz and coworkers in 2000. Objectives To investigate classical as well as new dermoscopic features in a large series of LMM in a white‐skinned population, in order to evaluate their diagnostic value. Methods One hundred and twenty‐five consecutive histopathology‐proven LMMs were analysed retrospectively based on medical records, clinical and dermoscopic photographs by three independent observers for the presence of 19 predefined criteria. Results At least one of the classical Stolz criteria was present in 87% of cases (hyperpigmented follicular opening, annular‐granular pattern, pigmented rhomboidal structures, obliterated hair follicles). Three original criteria were also present at a relatively high frequency: increased density of the vascular network (58%), red rhomboidal structures (40%), target‐like patterns (41%). Darkening at dermoscopic examination (when compared with naked‐eye examination) was observed in 25% of lesions. Classical dermoscopic features of extrafacial melanoma (atypical pigment network, irregularly distributed globules, dots, streaks and pseudopods) and vertical growth phase‐associated dermoscopic criteria (ulceration, blue papular areas and black structureless areas) were rarely seen. A large number of colours, pigmented rhomboidal structures, obliterated hair follicles and red rhomboidal structures were significantly more frequent in invasive LMMs. In contrast, in situ melanomas were more often associated with one or two colours and few distinctive dermoscopic features. Conclusions We present herein, in a large series of LMM, confirmation of the diagnostic value of the classical Stolz dermoscopic criteria and describe four additional original criteria, mainly vascular. A correlation between the presence of some dermoscopic features and thicker tumoral invasion has also been demonstrated.     

Effects of amygdala-hippocampal stimulation on interictal epileptic discharges

Deep brain stimulation (DBS) of different nuclei is being evaluated as a treatment for epilepsy. While encouraging results have been reported, the effects of changes in stimulation parameters have been poorly studied. Here the effects of changes of pulse waveform in high frequency DBS (130 Hz) of the amygdala-hippocampal complex (AH) are presented. These effects were studied on interictal epileptic discharge rates (IEDRs). AH-DBS was implemented with biphasic versus pseudo monophasic charge balanced pulses, in two groups of patients: six with temporal lobe epilepsy (TLE) associated with hippocampal sclerosis (HS) and six with non lesional (NLES) temporal epilepsy. In patients with HS, IEDRs were significantly reduced with AH-DBS applied with biphasic pulses in comparison with monophasic pulse. IEDRs were significantly reduced in only two patients with NLES independently to stimulus waveform. Comparison to long-term seizure outcome suggests that IEDRs could be used as a neurophysiological marker of chronic AH-DBS and they suggest that the waveform of the electrical stimuli can play a major role in DBS. We concluded that biphasic stimuli are more efficient than pseudo monophasic pulses in AH-DBS in patients with HS. In patients with NLES epilepsy, other parameters relevant for efficacy of DBS remain to be determined.