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Contains fulltext : 70189.pdf (Publisher’s version ) (Closed access) Age-related hearing impairment (ARHI), or presbycusis, is a very common multifactorial disorder. Despite the knowledge that genetics play an important role in the etiology of human ARHI as revealed by heritability studies, to date, its precise genetic determinants remain elusive. Here we report the results of a cross-sectional family-based genetic study employing audiometric data. By using principal component analysis, we were able to reduce the dimensionality of this multivariate phenotype while capturing most of the variation and retaining biologically important features of the audiograms. We conducted a genome-wide association as well as a linkage scan with high-density SNP microarrays. Because of the presence of genetic population substructure, association testing was stratified after which evidence was combined by meta-analysis. No association signals reaching genome-wide significance were detected. Linkage analysis identified a linkage peak on 8q24.13-q24.22 for a trait correlated to audiogram shape. The signal reached genome-wide significance, as assessed by simulations. This finding represents the first locus for an ARHI trait.

Purpose Dominant cystoid macular degeneration (DCMD) is an autosomal dominant trait of cystoid macular edema with poor visual prognosis. Until now, no efficient treatments for DCMD have been reported. The authors evaluated a somatostatin-analogue (octreotide acetate) as treatment for DCMD. Methods The authors treated four patients with early DCMD by intramuscular longacting octreotide acetate, 20 mg every 4 weeks for 1 year. In addition to general ophthalmologic examination the authors performed fluorescein angiography (FA) before and after treatment. Results Seven out of eight eyes showed improvement on FA and stabilization of visual acuity. Conclusions Somatostatin-analogues may reduce cystoid edema in DCMD and may thus prevent disease-related visual loss.

Contains fulltext : 69050.pdf (Publisher’s version ) (Open Access) Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS: MIM 270550) is a neurodegenerative disorder characterized by early-onset cerebellar ataxia with spasticity and peripheral neuropathy. This disorder, considered to be rare, was first described in the late seventies among French Canadians in the isolated Charlevoix-Saguenay region of Quebec. Nowadays, it is known that the disorder is not only limited to this region but occurs worldwide. Our objective was to identify cases of autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) in Dutch patients with recessive early-onset cerebellar ataxia by sequencing the complete SACS gene. In a Dutch cohort of 43 index patients with ataxia onset before age 25, we identified 16 index patients (total 23 patients) with mutations in the SACS gene. Nine of them had homozygous mutations, and seven of them had compound heterozygous mutations. Retrospectively, the phenotype of patients carrying mutations was remarkably uniform: cerebellar ataxia with onset before age 13 years, lower limb spasticity and sensorimotor axonal neuropathy, and cerebellar (vermis) atrophy on magnetic resonance imaging, consistent with the core ARSACS phenotype previously described. The high rate of mutations (37%) identified in this cohort of Dutch patients suggests that ARSACS is substantially more frequent than previously estimated. We predict that the availability of SACS mutation analysis as well as an increasing awareness of the characteristic ARSACS phenotype will lead to the diagnosis of many additional patients, possibly even at a younger age.

Contains fulltext : 70417.pdf (Publisher’s version ) (Closed access) OBJECTIVE: To study the audiologic outcome of bone-anchored hearing aid (BAHA) application in patients with congenital unilateral conductive hearing impairment. STUDY DESIGN: Prospective audiometric evaluation on 20 patients. SETTING: Tertiary referral center. PATIENTS: The experimental group comprised 20 consecutive patients with congenital unilateral conductive hearing impairment, with a mean air-bone gap of 50 dB. METHODS: Aided and unaided hearing was assessed using sound localization and speech recognition-in-noise tests. RESULTS: Aided hearing thresholds and aided speech perception thresholds were measured to verify the effect of the BAHA system on the hearing acuity. All patients fulfilled the criteria that the aided speech reception thresholds or the mean aided sound field thresholds were 25 dB or better in the aided situation. Most patients were still using the BAHA almost every day. Sound localization scores varied widely in the unaided and aided situations. Many patients showed unexpectedly good unaided performance. However, nonsignificant improvements of 3.0 (500 Hz) and 6.9 degrees (3,000 Hz) were observed in favor of the BAHA. Speech recognition in noise with spatially separated speech and noise sources also improved after BAHA implantation, but not significantly. CONCLUSION: Some patients with congenital unilateral conductive hearing impairment had such good directional hearing and speech-in-noise scores in the unaided situation that no overall significant improvement occurred after BAHA fitting in our setup. Of the 18 patients with a complete data set, 6 did not show any significant improvement at all. However, compliance with BAHA use in this patient group was remarkably high. Observations of consistent use of the device are highly suggestive of patient benefit. Further research is recommended to get more insight into these findings.

Contains fulltext : 70980.pdf (Publisher’s version ) (Closed access) OBJECTIVE: Evaluation of the management and survival of patients treated for temporal bone squamous cell carcinoma. STUDY DESIGN: A retrospective analysis. SETTING: Tertiary care, academic referral center. PATIENTS: Twenty-eight patients underwent primary treatment for squamous cell carcinoma of the temporal bone. INTERVENTIONS: The patients were staged using the modified Pittsburgh staging system. Patients underwent a local resection, lateral temporal bone resection, or a subtotal lateral temporal bone resection usually followed by radiotherapy. MAIN OUTCOME MEASURE: The survival rate of patients grouped by tumor size was calculated. RESULTS: Staging revealed 12 pT1, 2 pT2, 4 pT3, and 10 pT4 tumors. The mean follow-up was 34 months (2-132 mo). The Kaplan-Meier survival curves showed survival rates at 5 years of 83 and 25% for the stages pT1 and pT4, respectively. The pooled survival curves showed survival rates at 5 years of 85 and 46% for the stages pT1p/T2 and pT3/pT4, respectively. CONCLUSION: Long-term prognosis of the carcinoma of the external auditory canal mainly depends on the stage and primary treatment. Surgery may consist of a lateral temporal bone or subtotal temporal bone resection; in T3 and T4 tumors, resection may be combined with a superficial parotidectomy. If disease is diagnosed in the neck or parotid, then a neck dissection and total parotidectomy may also be performed. Additional radiotherapy should be provided in incompletely resected T1 and all T2 and T3 tumors and part of the T4 tumors. T4 tumors may be treated according to their subclassification based on the anatomic extension.

Contains fulltext : 71383.pdf (Publisher’s version ) (Closed access) OBJECTIVE: To evaluate the preliminary visual results of femtosecond laser-assisted Descemet stripping endothelial keratoplasty (FS-DSEK). METHODS: We prospectively analyzed results of 20 consecutive patients with Fuchs endothelial dystrophy or aphakic/pseudophakic bullous keratopathy who underwent FS-DSEK. Best spectacle-corrected visual acuity (BSCVA), refraction, corneal topography, and endothelial cell density were measured preoperatively and 3 and 6 months after FS-DSEK. Corneal thickness was measured using an optical coherence tomography technique. RESULTS: The average BSCVA of 11 eyes with normal visual potential significantly improved from 20/110 +/- 4 lines to 20/57 +/- 1 line at 6 months (P < .007). At 6 months, the mean (SD) hyperopic shift was 2.24 (2.3) diopters (D). Preoperative and 6 months postoperative refractive astigmatism were -0.75 (0.9) D and -1.58 (1.1) D (P = .01), but the topographic astigmatism did not change postoperatively (P = .95). Mean (SD) endothelial cell density at 6 months was 1368 (425) cells/mm(2). There was a persistent deswelling of the graft up to 3 months postoperatively. Complications included graft dislocations requiring repositioning (20%), pupillary block glaucoma (5%), epithelial ingrowth (5%), and primary graft failure (5%). CONCLUSIONS: Femtosecond laser-assisted Descemet stripping endothelial keratoplasty was effective in treating endothelial failure with minimal induced refractive astigmatism, limited improvement of BSCVA, and induction of a hyperopic shift. Endothelial cell count and dislocation rate were significant, which may be related to the surgical technique.

Contains fulltext : 69802.pdf (Publisher’s version ) (Closed access) This study investigated changes of short-wavelength fundus autofluorescence (SW-AF) by retinal bleaching effects. All measurements were performed with the Heidelberg Retina Angiograph 2 (HRA 2). Initially, experimental imaging was done on a healthy eye after dark adaptation. Photopigment was bleached within the central 30 degrees of the fundus by HRA 2 excitation light. Then SW-AF imaging of this region was performed, and SW-AF of the surrounding, unbleached 25 degrees fundus region was subsequently studied by a wide-field lens. Next, another 30 degrees SW-AF image of the posterior pole was obtained after complete dark adaptation. Then an extra SW-AF examination was performed with 15 degrees temporal eccentricity, overlapping the original examination area. Finally, a successive image series was carried out on the dark-adapted eye to test for bleaching kinetics. The second and third experiments were also performed on eyes with macular dystrophies. Distinct regions of increased SW-AF were observed after strong illumination with the blue excitation light in all eyes studied. During light adaptation mean gray levels showed a saturation plateau after an initial steep increase. The resulting gray-value maps showed significant differences of pixel intensities between bleached and unbleached parts of the fundus. Two-dimensional density difference maps allowed analysis of visual pigment distribution and density in both healthy eyes and eyes with macular dystrophies. Our observations highlight the viability of objective, non-invasive evaluation of visual pigment in the healthy and diseased human retina by means of confocal fundus autofluorescence.

Contains fulltext : 69994.pdf (Publisher’s version ) (Closed access) OBJECTIVES/HYPOTHESIS: To define audiological application criteria for different implantable hearing aid devices. STUDY DESIGN: Retrospective study. METHODS: Comparisons were made between aided speech recognition scores obtained at conversational level (65 dB) in patients with the Vibrant Soundbridge (VSB) (n = 22), the Otologics middle ear transducer (MET) (n = 10), conventional hearing aids (behind-the-ears) (n = 47), and cochlear implants (CIs) (n = 123). RESULTS: In relation to hearing loss, only for mild hearing loss, speech recognition scores with VSB were comparable to that with conventional hearing aids. In the Otologics MET users, speech recognition scores were comparable with those of the conventional hearing aid users until a mean hearing loss of about 75 dB HL. At a sensorineural hearing loss of about 65 dB HL or more, the Otologics MET users have better speech recognition scores than the VSB users. For comparison with CI users, we followed a more conservative approach. In 90% of the users of a CI, speech recognition scores were better than those in: 1) patients with a conventional hearing aid and a mean hearing loss of about 95 dB HL or worse; 2) patients with an Otologics MET and a mean hearing loss of 85 dB HL or worse. CONCLUSIONS: Patients fitted with a VSB or an Otologics MET middle ear implant do not demonstrate better speech recognition scores than patients fitted with today's conventional hearing aids. Results might even been worse. However, the VSB and Otologics MET are a good option in patients with moderate (VSB) to severe (Otologics MET) sensorineural hearing loss and external otitis.

Item does not contain fulltext We present an overview of the history, development, technological advancements, current application, and future trends of cranial endoscopy. Neuroendoscopy provides a safe and effective management modality for the treatment of a variety of intracranial disorders, either tumoral or non-tumoral, congenital, developmental, and degenerative, and its knowledge, indications, and limits are fundamental for the armamentarium of the modern neurosurgeon.

Contains fulltext : 71081.pdf (Publisher’s version ) (Closed access) The treatment of lumbar spinal stenosis is either conservative or surgical decompression. Recently, an interspinous decompression device (X-Stop) has been developed as an alternative. Patients treated with an X-Stop between 2003 and 2006 are subject of this study. The SF-36 Health Survey and Zurich Questionnaires are used. The data of pre- and post-operative self-rated questionnaires are collected and analysed by independent investigators. The data were statistically analysed. A good outcome was defined when the mean score at the ZQ for satisfaction was at maximal 2.0, and the mean improvement of the severity score was at least 0.5, and also for vitality score. For relations between outcome and gender, smoking, BMI, orthopaedic co-morbidity, number of implanted X-Stops were sought. The change in SF-36 scales was related to the outcome. Sixty-five patients did undergo implantation of an X-Stop. The mean age was 64.4 +/- 10.0 years (range: 37.0-85.0 years). 31.1% Of the patients had a good outcome. A good outcome was not related to smoking, BMI, number of implanted X-Stops. However, a good outcome was related to the absence of orthopaedic co-morbidity or male gender. Patients with a good outcome had significantly a better improvement of the scales of the SF-36 concerning physical pain or impairment. The X-Stop does improve the clinical situation. However, a good outcome is achieved less often than previously reported. Probable explanations are discussed.

Contains fulltext : 51677.pdf (Publisher’s version ) (Closed access) Pharmacokinetic models can be differentiated into two groups: physiological-based models and empirical models. Traditionally the pharmacokinetics of volatile anaesthetics are described using physiological-based models together with the respective tissue-blood distribution coefficients. The compartments of the empirical model have no anatomical equivalents and are merely the product of the mathematical procedure for parameter estimation. The end expiratory concentration of volatile anaesthetics is approximately equal to the arterial concentration and, therefore, the description of the transition between plasma and effect site for volatile anaesthetics plays a central role. The most important parameter here is the k(e0) value which is a time constant and describes the time delay for the transition from the central compartment to the calculated effect compartment. The k(e0) values for sevoflurane and isoflurane are the same but the concentration balance between the end-tidal concentration and the effect compartment occurs twice as quickly with desflurane. In clinical practice volatile anaesthetics are normally combined with N(2)O and/or opioids. This results in an additive interaction between volatile anaesthetics and N(2)O but a synergistic interaction of volatile anaesthetics with opioids. However, there are relatively few investigations on the interactions between the clinically widely used combination of volatile anaesthetics, N(2)O and opioids.

Contains fulltext : 52398.pdf (Publisher’s version ) (Closed access) BACKGROUND: The surgical treatment of spinal epidural metastasis is evolving. To be a surgical candidate, a patient should have a life expectancy of at least 3 months. Estimation of survival by experienced specialists has proven to be unreliable. METHODS: The Cox proportional hazards model was used to make a prediction model. To validate the model, Efron optimism correction by bootstrapping was performed. Retrospective data of patients treated for a spinal metastasis were used. Possible predictive factors were defined based on clinical experience and the literature. Statistical methods and clinical knowledge were also used to reveal an optimal set of predictors of survival. Data from patients treated at the Department of Radiation Oncology for spinal metastasis between 1998 and 2005 were evaluated. RESULTS: The case notes of 219 patients form the base of this study. In the final model, only 5 variables were required to predict the survival of a patient with spinal metastasis: sex, location of the primary lesion, intentional curative treatment of the primary tumor, cervical location of the spinal metastasis, and Karnofsky performance score. Examples with different predictors are given. The R(2) (N) index of Nagelkerke was 0.36 (95% confidence interval [95% CI], 0.28-0.48) and the c-index 0.72 (95% CI, 0.68-0.77). CONCLUSIONS: A reliable and simple model with which to predict the survival of a patient with spinal epidural metastasis is presented. Without the need for extensive investigations, survival can be predicted and only 5 easily obtainable parameters are required.

Contains fulltext : 52793.pdf (Publisher’s version ) (Closed access) A cross-sectional questionnaire survey was performed. The objectives of the study were to assess the psychosocial impact of current voice complaints as perceived by student-teachers with voice complaints in comparison with student-teachers without voice complaints, and to observe the pattern of risk factors in relation to their voice handicap. Subjects in the general population without a voice-demanding profession were selected as a reference group for limited comparison with the total group of student-teachers (future professional voice users). The respondents to the questionnaires were anonymous. Among the student-teachers, 17.2% reported current voice complaints in comparison with 9.7% of the reference group, and the odds ratio was 1.94, which showed the relative risk. Student-teachers had significantly greater total Voice Handicap Index (VHI) scores than the reference group (P = 0.034). The VHI subscale scores were not significantly different (P > 0.05). Student-teachers who reported current voice complaints had a significantly higher total VHI and subscale scores than student teachers without voice complaints (P < 0.001). Of the student-teachers without voice complaints, 17.0% had VHI scores greater than the 75th percentile. These persons may be neglecting their voice handicap and probably represent the false-negative cases in the estimation of voice complaints. Logistic regression analysis of each of the given risk factors with the VHI as the independent variable showed that the perceived negative influence of the given risk factors on their voices was significantly greater with increasing VHI scores across the VHI range. A significant correlation was observed between the number of perceived risk factors and increasing VHI scores across the VHI range. An increased awareness of risk factors in relation to their voice handicap would serve to motivate student-teachers to change factors that contributed to their voice problem. Attention to all risk factors, which the subjects perceive to be a risk, would aid in effective management of their voice handicap.

Contains fulltext : 52594.pdf (Publisher’s version ) (Closed access) BACKGROUND: Our study aims to identify anatomical characteristics of glaucoma filtering blebs by means of slit lamp-adapted optical coherence tomography (SL-OCT) and to identify new parameters for the functional prognosis of the filter in the early post-operative period. METHODS: Patients with primary open-angle glaucoma, aged 18 years and older, scheduled for primary trabeculectomy at the Department of Ophthalmology, Radboud University Nijmegen Medical Centre, were considered for our study. All patients underwent standardized trabeculectomy with intra-operative application of mitomycin C. The filtering blebs were evaluated clinically and with SL-OCT on day 1 and 1, 2, 4 and 12 weeks following surgery. The resulting data were analysed and weighed against surgical success. To better understand the SL-OCT data a small comparative histologic study was performed. RESULTS: The study included 20 eyes of 20 patients. After completion of our study, 15 eyes of 15 patients (mean age+/-SD 67 +/- 16 years) were eligible for data analysis and 5 eyes missed at least one follow-up visit. Filtering surgery was considered successful (intraocular pressure < or = 21 mmHg without antiglaucomatous medication) in 11 of 15 eyes. SL-OCT frequently demonstrated multiple hypo-reflective layers within Tenon's capsule ("striping" phenomenon) in the first post-operative week. Presumably, these layers corresponded with drainage channels in the histological specimen. These channels were present in functional filters but not in the failures. In addition, the visualisation of the sclera below the filtering zone was better defined in failures compared with successful filtering blebs ("shading" phenomenon). We observed no differences in the volume and clinical aspect of the blebs in the successful group compared with the unsuccessful group. CONCLUSIONS: Successful filtering blebs show characteristic optical properties on SL-OCT. These phenomena suggest a diffusely enhanced fluid content and the presence of intra-bleb drainage channels in functional filtering blebs.

Item does not contain fulltext AIMS: To determine and compare the accuracy and reproducibility of GDx variable cornea compensation (VCC) scanning laser polarimetry (SLP) with VCC, Heidelberg retina tomograph (HRT) I confocal scanning laser ophthalmoscopy (CSLO), and clinical assessment of stereoscopic optic nerve head (ONH) photographs for diagnosing glaucoma. METHODS: One eye each of 40 healthy subjects, 48 glaucoma patients, and six patients with ocular hypertension were measured with SLP-VCC and CSLO. Simultaneous stereoscopic ONH photographs were also obtained. Sixteen photographs of healthy and glaucomatous eyes were duplicated for assessing intraobserver agreement. Four glaucoma specialists, four general ophthalmologists, four residents in ophthalmology, and four optometrists classified the ONH photographs as normal or glaucomatous. For SLP-VCC, the nerve fiber indicator (NFI) was evaluated. For CSLO, the Moorfields regression analysis (MRA) and the Bathija linear discriminant function (LDF) were used. Sensitivity, specificity, percentage of correctly classified eyes, and intra- and interobserver agreement, expressed as kappa (kappa) were calculated. RESULTS: SLP-VCC had the highest diagnostic accuracy, with a sensitivity, specificity, and overall correct classification of 91.7%, 95.0% and 93.2%, respectively. CSLO, expressed as Bathija LDF and MRA, had a diagnostic accuracy comparable to glaucoma specialists and general ophthalmologists with an overall accuracy of 89.8%, 86.4%, 86.7% and 85.2%, respectively. Residents classified the fewest eyes correctly. Intraobserver agreement for classifying the ONH photographs ranged between 0.48 (within residents) and 0.78 (within glaucoma specialists). The interobserver agreement ranged between 0.45 (between residents) and 0.74 (between glaucoma specialists). The agreement between observers and CSLO MRA (kappa, 0.68) was statistically significantly higher (p

Contains fulltext : 49790.pdf (Publisher’s version ) (Closed access) OBJECTIVE: To describe the different imaging modalities used for the diagnosis and classification of hydrocephalus, their role in defining the optimal treatment of hydrocephalus and to define the optimal preoperative diagnostics for endoscopic third ventriculocisternostomy (ETV). METHODS: An overview on available imaging modalities for hydrocephalus will be given and their pros and cons discussed. In addition, different aspects of the treatment of hydrocephalus by shunts and by ETV will be highlighted. DISCUSSION: The role of the technical aspects of performing an ETV, the role of the surgeon's philosophy, the role of the urgency of the procedure, and the role of informed consent on the requirements for the imaging of the hydrocephalus will be discussed. CONCLUSION: The authors conclude that MRI is a conditio sine qua non for ETV in elective surgical cases.

Contains fulltext : 50281thijssen.pdf (Publisher’s version ) (Closed access) Despite the social impact of repetitive strain injury (RSI), little is known about its pathophysiological mechanism. The main objective of this study was to assess the local muscle oxygenation (mVO2) and blood flow (mBF) of the forearm in individuals with RSI during isometric contractions of the forearm. We employed the non-invasive optical technique near-infrared spectroscopy to assess forearm VO2 and BF. These variables were assessed at 10%, 20%, and 40% of their individual maximal voluntary strength. Twenty-two patients with RSI symptoms in both arms (bilateral RSI) and 30 healthy age-matched subjects participated in this cross-sectional study. The results showed lower mVO2 during exercise and a reduced mBF after exercise. The results suggest that mVO2 and mVO2 are lower in the forearms of individuals with RSI compared with their controls at similar working intensities. This finding indicates that the underlying vasculature may be impaired. Although these findings contribute to the understanding of RSI, future research is necessary to further unravel the mechanisms of this area.

Contains fulltext : 50720.pdf (Publisher’s version ) (Closed access) OBJECTIVES: To report hearing impairment and vestibular and ocular features in a Dutch DFNA11 family and to compare these results to reported data on three other DFNA11 families. STUDY DESIGN: Family study. METHODS: Regression analysis was performed in relation to age to outline the development of hearing thresholds and speech recognition scores. Vestibular and ocular functions were examined. RESULTS: First symptoms of hearing impairment started between the ages of 4 and 43 years. Most of the audiograms were symmetric and flat or downsloping. The annual threshold deterioration increased from 0.2 to 2.6 dB per year at 0.25 to 8 kHz in the longitudinal analyses and in the cross-sectional analysis from 0.3 to 0.9 dB per year. The speech recognition score was quite good, deteriorating by 0.9% per year from a 90% score at the age of 36 years onward. Remarkably, extensive ocular examination including corrected visual acuity and refraction measurements, slit-lamp examination, ophthalmoscopy, Goldmann perimetry, electroretinography and electro-oculography revealed signs of subclinical retinal dysfunction. None of the patients showed the classic triad of retinitis pigmentosa. Pure-tone thresholds, phoneme recognition scores, and vestibular responses of the mutation carriers were fairly similar to previously described DFNA11 families. CONCLUSION: Even though the diverse mutations are located in different regions of the myosin VIIa gene, the cochleovestibular phenotype is fairly similar in all DFNA11 families. Surprisingly, only in this family was subclinical retinal dysfunction detected.

Contains fulltext : 50690.pdf (Publisher’s version ) (Closed access) PURPOSE: Yoked prism spectacles (eccentric viewing spectacles [EVS]) facilitate eccentric viewing in patients with bilateral central scotomas. This study was conducted to evaluate the long-term success and patient satisfaction of this type of low-vision aid. METHODS. In this retrospective cross-sectional study, we reviewed the low-vision rehabilitation records of all patients who received EVS since 1993. With an 18-item survey, 191 patients were questioned about the wearing characteristics, advantages, and disadvantages of the EVS. Descriptive and nonparametric statistics were applied to compare regular users with those persons who no longer use the EVS. RESULTS: The response rate was 83.2% and the average follow-up time was 4.5 years. Forty percent of all patients still used the EVS. The main disadvantages of these spectacles, mentioned mainly by the nonusers, included the heavy weight (41%), perception of curved lines (46%), dizziness during walking (46%), and poor cosmetic appearance (25%). Many successful long-term users considered the EVS suitable for home activities (86%) and walking in the street (70%) and reported that this device reduced eccentric viewing (77%), created better vision in the center of their visual field (67%), and helped with recognition of objects and faces (64%). CONCLUSIONS: The prescription of EVS aids eccentric viewing in patients with dense central scotomas. Although associated with a number of disadvantages and side effects, 40% of the patients continued to use EVS. The results of this study indicate that patients who experience difficulties with eccentric fixation are most likely to benefit from these low-vision aids. A thorough explanation of the advantages and disadvantages of the EVS is important to prevent unnecessary disappointments.

Item does not contain fulltext BACKGROUND: In circumscribed choroidal hemangiomas (CCH) a long observation period and decreased visual acuity before treatment are risk factors for poor visual outcome. Therefore, we studied the use of limited, single spot photodynamic therapy (PDT) with Visudyne for the timely treatment of CCH. METHODS: Six consecutive patients with CCH, and metamorphopsia but (near) normal visual acuity were treated with PDT, using a single spot covering only the most prominent part of the tumour, and a radiance exposure of 50 J/cm(2). Start of treatment was 6 min following a 1-min infusion with Visudyne (6 mg/m(2) BSA), using a diode laser (692 nm). RESULTS: In all patients, the metamorphopsia disappeared, the OCT images returned to a normal foveal contour, and visual acuity remained 20/20 or improved to 20/20. In five patients, the tumour became ultrasonographically undetectable; in three after one PDT session, in one patient after two and in another patient after three PDT sessions. The last patient had a residual tumour height of 1.2 mm, but no metamorphopsia, a normal foveal contour on OCT, and fluorescein angiography showed no residual leakage. CONCLUSION: The present series demonstrates that single spot PDT might be an effective treatment for CCH with a visual acuity > or =20/30, without serious side-effects during a follow-up of at least 18 months.

Contains fulltext : 50908.pdf (Publisher’s version ) (Closed access) Assessment of initial disease severity after subarachnoid haemorrhage (SAH) remains difficult. The objective of the study is to identify biochemical markers of brain damage in peripheral blood after SAH. Hospital admission S100beta, glial fibrillary acidic protein (GFAP) and neuron-specific enolase (NSE) serum levels were analysed in 67 patients with SAH. Disease severity was determined by using the World Federation of Neurological Surgeons (WFNS) scale and the Fisher CT (computerized tomography) grading scale. Mean astroglial serum concentrations taken at hospital admission were increased (S100beta 2.8-fold and GFAP 1.8-fold) compared with the upper limit of normal laboratory reference values (P95). The mean NSE concentration was within normal limits. S100beta (P < 0.001) and GFAP (P =0.011) but not NSE levels were higher in patients who were in coma at the time of hospital admission compared with patients who were not. Similarly S100beta and GFAP but not NSE serum levels increased with higher WFNS scores, raised intracranial pressure and higher CT Fisher grade scores. Concerning the location of the aneurysm, S100beta and GFAP serum levels were within normal limits after a perimesencephalic type of haemorrhage and significantly increased after aneurysmal type SAH. Increased glial (S100beta and GFAP) but not neuronal (NSE) protein serum concentrations are found after SAH, associated to the clinical severity of the initial injury.

Purpose Several types of inborn errors of the O-glycan biosynthesis are known, leading to clinically very distinct phenotypes. Children with O-mannosyl glycan biosynthesis defects commonly present as a severe form of congenital muscular dystrophy with decreased alpha-dystroglycan staining, congenital eye anomalies, and brain migration defects. Alpha-dystroglycan is an O-mannosylated glycoprotein with additional mucin type O-glycans. Methods Based on overlapping clinical features with O-mannosyl glycan defects, especially with muscle-eye-brain disease, the authors performed a muscle biopsy in a child with severe congenital hypotonia, high myopia, partial pachygyria, mental retardation, cutis laxa, and an inborn error affecting the biosynthesis of both mucin type O-glycans and N-linked glycans. Results The histology showed no signs of muscle dystrophy, but a mild myopathy with slight increase in the muscle fiber diameter variability and type I fiber predominance. No significant decrease in the alpha-dystroglycan staining was detected; therefore, in spite of the phenotypic similarities the authors could not confirm the role of abnormal dystroglycan in the etiology of the muscle weakness and the developmental anomalies. Conclusions High myopia, muscle weakness, and cortical neuronal migration abnormalities are common in disorders of O-mannosylation and also observed in the authors’ patient. However, compared to the severe generalized defect observed in mannosyl glycan defects, in this child the cerebral white matter and cerebellum were spared, and no muscle dystrophy could be confirmed. This is the first description of high myopia in cutis laxa syndrome in combination with congenital disorders of glycosylation.

Contains fulltext : 50873.pdf (Publisher’s version ) (Closed access) BACKGROUND: The present preliminary study documents the effects of a selective nerve root block (SNB) with short or long acting local anaesthetic compared with baseline measurements in patients with chronic low back pain radiating to the leg with maximum pain in one dermatome (L4). METHODS: Ten consecutive patients underwent 20 controlled SNBs at L4 with ropivacaine 0.25% and lidocaine 1% in a prospective, randomized, double blind, crossover fashion. Baseline measurements included sensory function (assessed by pinprick on both unaffected and painful leg) and pain (Verbal Numeric Rating Scale; VNRS, 0-10). A change in size of areas with altered sensory function >10% and a VNRS change of 2 points were considered clinically significant. P-values

Contains fulltext : 49730.pdf (Publisher’s version ) (Closed access) Pain is the major presenting symptom of chronic pancreatitis. Patients with chronic pancreatitis experience substantial impairments in health-related quality of life. Pain may be considered as the most important factor affecting the quality of life. The pathogenesis of pancreatic pain is poorly understood. The cause of pain in chronic pancreatitis is probably multifactorial. This article discusses the various hypotheses that have been suggested to underlie pain. Special attention is paid to the concept of autonomous central sensitisation and hyperalgesia as a cause of pain. Strict abstinence from alcohol is the first step of chronic pancreatic pain management. As a second step, it is important to exclude treatable complications of chronic pancreatitis, such as pseudocysts. Symptomatic treatment with analgesics is often unavoidable in patients with chronic pancreatitis. Acetaminophen, non-steroidal anti-inflammatory drugs and eventually opioids are suitable. Several trials have been performed with pancreatic enzymes, but a meta-analysis demonstrated no significant benefit in terms of pain relief. The treatment of chronic pancreatic pain requires a multidisciplinary approach that tailors the various therapeutic options to meet the need of the individual patient.

Contains fulltext : 51141.pdf (Publisher’s version ) (Open Access) BACKGROUND: Frequent active opening of the eustachian tube (ET) allows ventilation of the middle ear and equilibration of pressure changes. Active opening is accomplished by the contraction of the paratubal muscles during swallowing. Because a disturbance of the ventilatory function of the ET may contribute to the development of otitis media with effusion, it is important to investigate ET function. Sonotubometry can be used to detect whether the ET can open or not during swallowing acts. METHODS: We developed a sonotubometer to test ET ventilatory function in 36 healthy adults. The width of the test signal frequency was between 5500 and 8500 Hz (centre frequency of 7000 Hz) and the loudness was 95 dB. To test reproducibility, testing took place in two sessions of 10 swallowing acts each. RESULTS: Opening of the ET could be registered in 91.6 per cent of the subjects in at least one of the two measurements. The first and the second measurements were highly correlated, with a Spearman's coefficient of 0.907. CONCLUSION: We confirmed that there is generally a good ventilatory ET function in otologically healthy adults, although, in a few cases, ET opening was not registered. Furthermore, we confirmed that our sonometric test equipment had acceptable reproducibility. Sonotubometry is a promising method for assessing ventilatory ET function. Research is ongoing to test the discriminative power of sonotubometry in children with various otological conditions.

Contains fulltext : 50194.pdf (Publisher’s version ) (Closed access) Median entrapment neuropathy or carpal tunnel syndrome is uncommon in children. The majority of cases are related to genetic conditions which result in skeletal dysplasia or altered connective tissue characteristics, direct injury to the median nerve caused by intensive sports or trauma, or hereditary neuropathy with liability to pressure palsies. This report describes a 10-year-old patient with Alagille syndrome who presented with poor fine motor skills because of an entrapment neuropathy of the median nerve at the wrist. This condition was probably caused by intermittent external compression at the wrists due to years of rubbing both wrists and hands to relieve pruritus. To our knowledge, median neuropathy has never been associated with Alagille syndrome, although severe pruritus is considered a major symptom and many patients exhibit widespread scratching and rubbing.

Contains fulltext : 51125.pdf (Publisher’s version ) (Closed access) The performance of continuous bilateral sciatic nerve blocks under ultrasonographic control using stimulating catheters is described in a 4-year-old child with VACTERL syndrome. Ultrasound showed an abnormal vascular and nerve supply to the lower limbs. The use of ultrasound guidance made successful continuous sciatic nerve blocks possible in a child in whom the traditional method of nerve localisation was unlikely to succeed for anatomical reasons.

Contains fulltext : 51311.pdf (Publisher’s version ) (Open Access) Stem cells have been recognized and intensively studied for their potential use in restorative approaches for degenerative diseases and traumatic injuries. In the central nervous system (CNS), stem cell-based strategies have been proposed to replace lost neurons in degenerative diseases such as Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis (Lou Gehrig's disease), or to replace lost oligodendrocytes in demyelinating diseases such as multiple sclerosis. Stem cells have also been implicated in repair of the adult spinal cord. An impact to the spinal cord results in immediate damage to tissue including blood vessels, causing loss of neurons, astrocytes, and oligodendrocytes. In time, more tissue nearby or away from the injury site is lost due to secondary injury. In case of relatively minor damage to the cord some return of function can be observed, but in most cases the neurological loss is permanent. This review will focus on in vitro and in vivo studies on the use of bone marrow stromal cells (BMSCs), a heterogeneous cell population that includes mesenchymal stem cells, for repair of the spinal cord in experimental injury models and their potential for human application. To optimally benefit from BMSCs for repair of the spinal cord it is imperative to develop in vitro techniques that will generate the desired cell type and/or a large enough number for in vivo transplantation approaches. We will also assess the potential and possible pitfalls for use of BMSCs in humans and ongoing clinical trials.

Objectives: We compared classroom performance of children with a cochlear implant (CI) with that of their normal-hearing peers in mainstream education. Methods: Thirty-two CI children in mainstream education, congenitally or prelingually deaf, participated in this study, as did 37 hearing classmates. Their teachers filled out 2 questionnaires: the Assessment of Mainstream Performance (AMP) and the Screening Instrument for Targeting Educational Risk (SIFTER). A high Fletcher index and open-set speech perception scores were obtained. Results: The children with CIs scored above average on the AMP and sufficiently well in all but one area (communication) of the SIFTER questionnaire. Class rankings did not differ significantly between the CI students and their normal-hearing peers. Overall, the normal-hearing group outperformed the CI group. The classroom performance of CI children correlated negatively with duration of deafness and age at implantation. All longitudinal audiological data of the CI children showed improvement in open-set speech recognition. Conclusions: Although the results are encouraging, the CI group scored significantly less well than their normal-hearing peers on most questionnaire domains of both the AMP and the SIFTER. The most important variables for the outcome in this study were age at implantation and duration of deafness.

Contains fulltext : 51217.pdf (Publisher’s version ) (Open Access) The aim of this study was to test the efficacy of shortterm transcutaneous electrical nerve stimulation (TENS) treatment in chronic pain with respect to pain intensity and patients' satisfaction with treatment results. We therefore performed a randomised controlled trial comparing TENS and sham TENS. Patients, researchers and therapists were blinded for treatment allocation. One hundred and sixty-three patients with chronic pain referred to the Pain Centre entered the study. Conventional TENS and sham TENS were applied in the segments of pain, for a period of ten days. Outcome measures were pain intensity (visual analogue scale) and patients' satisfaction with treatment result (yes or no). The proportions of patients satisfied with treatment result differed significantly for TENS compared to sham TENS (58 and 42.7% respectively, chi(2)=3.8, p=0.05). However, no differences in pain intensity were found for patients treated with TENS or sham TENS. Only for patients satisfied with treatment results pain intensity gradually decrease equally both for TENS and sham TENS with repeated treatment application.

Item does not contain fulltext Treatment of patients with prolactinomas consists primarily of dopamine agonists (DA). Cerebrospinal fluid (CSF) leakage has sporadically been reported in patients with macroprolactinomas treated with short-acting DA such as bromocriptine. Little is known on the incidence of this complication in patients treated with the long-acting D2 specific DA cabergoline. We report three patients with CSF leakage shortly after initiation of cabergoline treatment for macroprolactinoma. All three patients responded rapidly to cabergoline (CAB) by shrinkage of the tumor and release of the optic chiasm compression. The CSF leakage occurred within 10 days after initiation of treatment. CAB treatment was not discontinued. In one patient the CSF leakage ceased spontaneously, with no additional therapy. The second patient had a surgical repair of the CSF fistula, permitting cabergoline to be continued without a recurrence of the CSF leakage. The third patient refused surgical repair of the sellar defect. In this patient the cabergoline dosage was temporarily decreased with no effect on the CSF leakage. Four years later, the CSF leakage is unchanged in this patient, whilst no other complications occurred during the follow-up. No infectious complications occurred in these three patients. In conclusion, patients with large, invasive macroprolactinomas are at risk of CSF leakage during medical treatment with CAB. It is advisable to warn these patients for occurrence of this complication and to monitor them closely especially during the first months of treatment.

Contains fulltext : 50306.pdf (Publisher’s version ) (Closed access) PURPOSE: To test human CRB1 heterozygotes for possible clinical or functional retinal changes and to evaluate whether a patient with Leber congenital amaurosis (LCA) with CRB1 mutations not consistent with previously described CRB1 phenotypes carried a modifier allele in another LCA gene. METHODS: Seven unrelated heterozygous carriers of CRB1 mutations underwent phenotyping by full eye examinations (indirect ophthalmoscopy and slit lamp biomicroscopy) and functional testing (standard full-field electroretinography [ERG] and multifocal ERG). For genotyping of the LCA patients and their parents, denaturing high-performance liquid chromatography (dHPLC) analyses were performed, followed by sequence analysis of CRB1, followed by sequence analysis of the AIPL1 and CRX genes to identify a putative modifier effect in a patient with an atypical CRB1 phenotype. RESULTS: Reduced full-field ERG b-wave amplitudes were observed with scotopic -2 dB flash (140 microV; P < 0.05), normal full-field cone ERGs, and significant regional retinal dysfunction on mfERG in five of seven carriers of CRB1 mutations. A known AIPL1 mutation (p. R302L) was identified as a potential modifier allele in a patient with LCA carrying two CRB1 mutations and with a prominent maculopathy. CONCLUSIONS: In human heterozygotes of CRB1 mutations (parents of offspring with LCA), distinctive regional retinal dysfunctions were found by multifocal ERG measurements that were consistent with the focal histologic abnormalities reported for the two CRB1 knockout mice models. This phenotypic finding may identify CRB1 carriers and point to the causal gene defect in affected LCA offspring, significantly facilitating the molecular diagnostic process. Evidence suggests a modifier allele in AIPL1 in a patient with LCA with prominent atrophic macular lesions and homozygous defects in CRB1.

Contains fulltext : 47623.pdf (Publisher’s version ) (Closed access) OBJECTIVES: To perform genetic analysis and to analyze cochleovestibular impairment features in a newly identified Dutch family with nonsyndromic autosomal dominant hearing impairment (DFNA9). STUDY DESIGN: Genetic analysis was performed using microsatellite markers and single nucleotide polymorphisms. Audiometric data were collected and analyzed longitudinally. Results were compared with those obtained in previously identified P51S COCH mutation carriers (n = 74). Special attention was also given to a comparison of age-related features such as progressive hearing loss and vestibular impairment. SETTING: Tertiary referral center. PATIENTS: G88E COCH mutation carriers from a Dutch family. MAIN OUTCOME MEASURES: The study of clinical features of a DFNA9 family carrying a G88E COCH mutation and to compare this to the symptoms of those carrying a P51S/COCH mutation. RESULTS: Pure-tone thresholds, phoneme recognition scores, and vestibular responses of the G88E mutation carriers were essentially similar to those previously established in the P51S mutation carriers. Hearing started to deteriorate in G88E mutation carriers from age 46 to 49 years and onward, whereas deterioration of vestibular function started from approximately age 46 years. In the P51S mutation carriers, vestibular impairment started earlier, at approximately age 34 years. However, the difference in age of onset with the G88E mutation carriers was not significant. Remarkably, the proportion of patients who developed complete vestibular areflexia within the age range of 40 to 56 years was significantly lower for the G88E mutation carriers than for the P51S mutation carriers. CONCLUSION: Apart from a significantly lower frequency of vestibular areflexia between the ages of 40 and 56 years, there are no phenotypic differences between carriers of the G88E and P51S mutations in the COCH gene.

OBJECTIVE: To evaluate the safety and performance of a synthetic dural sealant as an adjunct to standard surgical dural repair techniques to prevent cerebrospinal fluid (CSF) leakage. METHODS: This study was designed as a prospective, nonrandomized, single-center clinical trial. The dural sealant is a synthetic absorbable hydrogel. Consecutive series of patients scheduled for elective cranial and intradural spinal surgery were included until a total of 50 applications were achieved. It was used primarily as an adjunct to ensure watertight dural closure. The end point was defined as no leak with the Valsalva maneuver after dural sealant application. The patients were followed up for 3 months after surgery to check for CSF leakage, standard laboratory and neurological examinations, and possible adverse advents. RESULTS: Of the 49 patients, 46 were included and treated with the dural sealant because of spontaneous leak (n = 34; 69%) or leak after the Valsalva maneuver (n = 12; 25%). There was no leak in the other patients (n = 3; 6%). After application of the dural sealant, there was no leak in all 46 patients (100%). Of the 46 patients included, there was one case of overt CSF leak. One patient had a pseudomeningocele. There were no adverse events other than those related to the disease or to the surgical procedure itself. CONCLUSION: The dural sealant, a synthetic absorbable hydrogel, is a useful adjunct to achieve watertight dural closure. Application resulted in 100% closure of intraoperative CSF leaks. There are no evident adverse effects.

Item does not contain fulltext OBJECTIVE: To study the impact of introducing a blood loss chart as a means to support treatment selection in women with dysfunctional uterine blood loss. STUDY DESIGN: Retrospective chart review, prospective observational study, and decision modelling. RESULTS: Introduction of a blood loss chart resulted in a 50% reduction of re-treatments within 1 year (from 25% to 12.5%). The use of the blood loss chart resulted in a slightly higher expected value and lower costs, which is reflected in a more favourable cost/quality adjusted life year (QALY) ratio. CONCLUSION: The use of a blood loss chart as an aid in treatment selection in women with dysfunctional uterine blood loss is feasible. Although its use requires an extra outpatient visit, the associated extra costs are off-set by its impact on initial treatment selection, and, in particular, on the probability of re-treatment within 1 year of follow-up.

Contains fulltext : 47504.pdf (Publisher’s version ) (Closed access) OBJECTIVE: To identify EEG derivations that yield high signal-to-noise ratios (SNRs) of the auditory steady-state response (ASSR) in infants aged 0 to 5 months. DESIGN: The ASSR was recorded simultaneously from 10 EEG derivations in a monopolar montage in 20 sleeping infants. Stimuli were tones of 0.5 or 2 kHz that were 100% amplitude modulated and 20% frequency modulated, presented at 65 dB SPL for 4.4 minutes in either the right or the left ear. An amplitude modulation frequency of 90 Hz (left ear) or 94 Hz (right ear) was used. From the 10 measured monopolar derivations, all 45 bipolar derivations were calculated mounting up to 55 EEG derivations. EEG derivations were selected in the preferred set if they had the largest SNRs within subjects and if they were obtained significantly more frequently across subjects than was expected by chance (Monte Carlo simulation and Wilcoxon signed ranks test). RESULTS: The preferred derivations are both mastoids ipsilateral to the stimulated ear with Cz as common reference. These derivations improved SNRs compared with each of several conventional EEG derivations (excluding the preferred derivations) between 16 and 69% (500 Hz, left ear), 9 and 132% (500 Hz, right ear), 31 and 193% (2 kHz, left ear), and 3 and 105% (2 kHz, right ear). In contrast to results reported earlier for adults, high SNRs were not found at the inion-Cz derivation in these infants. CONCLUSIONS: High SNRs were obtained in infants aged younger than 6 months if the ASSR was recorded from the mastoids ipsilateral to the ear of stimulation referenced to Cz.

Contains fulltext : 47792.pdf (Publisher’s version ) (Closed access) Nail-patella syndrome (NPS) is characterized by developmental defects of dorsal limb structures, nephropathy, and glaucoma and is caused by heterozygous mutations in the LIM homeodomain transcription factor LMX1B. In order to identify possible genotype-phenotype correlations, we performed LMX1B mutation analysis and comprehensive investigations of limb, renal, ocular, and audiological characteristics in 106 subjects from 32 NPS families. Remarkable phenotypic variability at the individual, intrafamilial, and interfamilial level was observed for different NPS manifestations. Quantitative urinanalysis revealed proteinuria in 21.3% of individuals. Microalbuminuria was detected in 21.7% of subjects without overt proteinuria. Interestingly, nephropathy appeared significantly more frequent in females. A significant association was established between the presence of clinically relevant renal involvement in an NPS patient and a positive family history of nephropathy. We identified normal-tension glaucoma (NTG) and sensorineural hearing impairment as new symptoms associated with NPS. Sequencing of LMX1B revealed 18 different mutations, including six novel variants, in 28 families. Individuals with an LMX1B mutation located in the homeodomain showed significantly more frequent and higher values of proteinuria compared to subjects carrying mutations in the LIM domains. No clear genotype-phenotype association was apparent for extrarenal manifestations. This is the first study indicating that family history of nephropathy and mutation location might be important in precipitating individual risks for developing NPS renal disease. We suggest that the NPS phenotype is broader than previously described and that NTG and hearing impairment are part of NPS. Further studies on modifier factors are needed to understand the mechanisms underlying phenotypic heterogeneity.

Contains fulltext : 49086.pdf (Publisher’s version ) (Closed access) We used quantitative sensory testing (QST) to gain further insight into mechanisms underlying pain in CRPS 1. Specific goals were: (1) to identify altered patterns of sensory processing some 8 years after diagnosis, (2) to document differences in sensory processing between 'warm' and 'cold' diagnostic subgroups, (3) to determine relationships between changed sensory processing and disease progression regarding pain. The study was performed on a cohort of patients (n=47) clinically diagnosed with CRPS 1 of one upper extremity approximately 8 years previously. Pain was quantified by VAS and MacGill Pain Questionnaire (MPQ), and all subjects underwent electrical and mechanical QST. Cold patients (n=13) had poorer MPQ scores than warm ones (n=34), and more pain on electrical stimulation. Their evoked pain increased with disease progression and correlated with clinical pain measures. For both diagnostic subgroups, thresholds to pressure pain were lower on the affected extremity and with disease progression. Eight years after original diagnosis, cold CRPS 1 patients have poorer clinical pain outcomes and show persistent signs of central sensitisation correlating with disease progression. The latter is not the case for warm CRPS 1 patients. Both diagnostic subgroups show greater pressure hyperalgesia on the affected limb and with disease progression. QST may prove useful in the subdiagnosis of CRPS 1 and in quantifying its progression, with both applications warranting further investigation for clinical and research use.

Contains fulltext : 48525.pdf (Publisher’s version ) (Open Access) The results obtained by percutaneous cervical cordotomy (PCC) were analysed in 43 terminally ill cancer patients treated in our institution from 1998 to 2001. We wished to determine whether there is still a place for PCC in the actual clinical situation with its wide choice of pain therapies. All patients had severe unilateral pain due to cancer, resistant to opioids and co-analgesics. Following PCC, mean pain intensity was reduced from Numeric Rating Scale (NRS) 7.2 to 1.1. At the end of life, pain had increased to NRS 2.9. Initially following PCC a good result (NRS

Item does not contain fulltext PURPOSE: To report unusual vitelliform fundus findings in three cases of paraneoplastic retinopathy associated with metastasised cutaneous or uveal melanoma and in one case, a unique immunoreactivity response. PATIENTS AND METHODS: Observational case series. The histories of three patients with MAR-like paraneoplastic retinopathy were reviewed. Electroretinography, Goldmann perimetry, fluorescein angiography, and in one case optical coherence tomography, immunohistochemistry and Western blotting were performed. RESULTS: All patients revealed similar paraneoplastic vitelliform retinal abnormalities. Symptoms in two cases differed from the classical MAR syndrome. In one case, western blotting and immunohistochemistry demonstrated antibodies against 120-kDa, a soluble photoreceptor protein. No immunoreactivity to retinal bipolar cells was detected. CONCLUSION: The clinical, electrophysiological, and immunological findings in our patients suggest a melanoma associated paraneoplastic origin, like in MAR syndrome. However contrary to MAR syndrome, this paraneoplastic vitelliform retinopathy exhibits a peculiar fundus picture, consisting of serous macular detachment and nummular vitelliform lesions in the posterior pole. This could be an unusual presentation of MAR or a separate paraneoplastic entity.

Contains fulltext : 48927.pdf (Publisher’s version ) (Closed access) OBJECTIVE: To present the course of tympanic membrane pathology in childhood and young adulthood after otitis media (OM) in early life. STUDY DESIGN: Prospective follow-up study. SETTING: Community study of a birth cohort. PATIENTS: Three hundred fifty-eight subjects with a positive and negative history of OM (OM+ or OM-) or ventilation tube insertion (VT+ or VT-) derived from a birth cohort that had been followed-up from preschool to adult age. METHODS: Standardized otomicroscopic examination performed at ages 8 and 18 years. MAIN OUTCOME MEASURES: Tympanic membrane abnormalities (i.e., tympanosclerosis, atrophy, atelectasis and retraction pockets of the pars tensa, and retraction of the pars flaccida). RESULTS: At the age of 8 years, tympanic membrane pathology was highly prevalent in the both OM+ subcohorts (OM+VT+, 92% and OM+VT-, 46%), whereas in the OM- ears (11%), tympanic membrane abnormalities were rare. In the subsequent 10-year period, many tympanic membrane abnormalities disappeared spontaneously, although the prevalence of tympanosclerosis remained substantial in the OM+VT+ cohort. CONCLUSION: The natural course of most tympanic membrane pathology associated with OM in early life is favorable over time, suggesting an intrinsic repair capacity of the tympanic membrane. Tympanosclerosis, the most prevalent sequelae of OM and treatment with VT, however, shows little tendency of resolution.

Contains fulltext : 48086.pdf (Publisher’s version ) (Open Access) Previous studies have shown an increased risk of retinal vein occlusion (RVO) in patients with hypertension, hypercholesterolemia and diabetes mellitus. Literature on the association between thrombophilic factors and RVO consists of small studies and case reports. The objective was to determine the relationship between thrombophilic risk factors and RVO. Thrombophilic risk factors analyzed were hyperhomocysteinemia, MTHFR gene mutation, factor V Leiden mutation, protein C and S deficiency, antithrombin deficiency, prothrombin gene mutation, anticardiolipin antibodies and lupus anticoagulant. For all currently known thrombophilic risk factors odds ratios for RVO were calculated as estimates of relative risk. The odds ratios were 8.9 (95% CI 5.7 - 13.7) for hyperhomocysteinemia, 3.9 (95% CI 2.3 - 6.7) for anticardiolipin antibodies, 1.2 (95% CI 0.9 - 1.6) for MTHFR, 1.5 (95% CI 1.0 - 2.2) for factor V Leiden mutation and 1.6 (95% CI 0.8 - 3.2) for prothrombin gene mutation. In conclusion, regarding thrombophilic risk factors and RVO there is only evidence for an association with hyperhomocysteinemia and anticardiolipin antibodies, factors that are known as risk factors for venous thrombosis as well as for arterial vascular disease. The minor effect of factor V Leiden mutation and the protrombin gene mutation (risk factors for venous thrombosis only) suggests that atherosclerosis might be an important factor in the development of CRVO.

Objective Disturbance of any of the ET functions may contribute to the development of otitis media. Sonotubometry measures the ventilatory function using sound. The qualities of sonotubometry as a test for eustachian tube ventilatory function have been studied by various investigators. The development of the method is described in the review, and a summary of the study results is provided to make an estimate of the diagnostic potential of this eustachian tube function test. Data sources The English-language literature on the topic was searched systematically by Medline and Pubmed using the following key words: ventilatory function, eustachian tube, sonotubometry, and function test. There were no limits for the year of publication. Study selection Articles that described the method itself (validity, reproducibility, diagnostic value) were studied in detail. Data extraction All the articles described in study selection were used for this review. Conclusions The technique of sonotubometry has been improved gradually over the years. The results of sonotubometry are at least as good as those of other function tests. However, because the results still tend to be ambiguous in children and otitis media is most common in this population, the reproducibility and application of sonotubometry must be evaluated further. Sonotubometry has great advantages over other function tests, but it is not used routinely to assess eustachian tube ventilatory function because its value for clinical practice has not yet been adequately demonstrated. The review showed that sonotubometry can be improved further and that efforts to do so seem justified because it forms a particularly promising method to assess eustachian tube function in children with suspected eustachian tube disease.

Contains fulltext : 48452.pdf (Publisher’s version ) (Closed access) OBJECTIVE: To evaluate the benefit of a bone-anchored hearing aid contralateral routing of sound hearing aid (BAHA CROS hearing aid) in 29 patients with unilateral inner ear deafness. STUDY DESIGN: Prospective clinical follow-up study. SETTING: Tertiary referral center. PATIENTS: Thirty patients were recruited. There were 19 patients with a history of acoustic neuroma surgery and 11 patients with unilateral inner ear deafness due to other causes; 1 patient was excluded. The first 21 patients had also participated in a previous evaluation. INTERVENTION: Audiometric measurements were taken before intervention, when fitted with a conventional CROS, and after BAHA implementation. Patients' subjective benefit was quantified with four different hearing aid-specific instruments: the Abbreviated Profile of Hearing Aid Benefit, the Glasgow Hearing Aid Benefit Profile, the International Outcome Inventory for Hearing Aids, and the Single-Sided Deafness questionnaire. MAIN OUTCOME MEASURES: The same instruments were used at a mean long-term follow-up of 1 year after BAHA implantation. RESULTS: Sound localization in an audiologic test setting was no different from chance level. The main effect of the BAHA CROS that was found was the "lift the head shadow" effect in the speech-in-noise measurements. All instruments also showed positive results in favor of the BAHA CROS at long-term follow-up. CONCLUSIONS: The poor sound-localization results in an audiologic test setting illustrated the inability of patients with unilateral inner ear deafness to localize sounds. The speech-in-noise measurements demonstrated the efficacy of the BAHA CROS to lift the head shadow. Patients were still satisfied at 1-year follow-up, according to the four instruments.

Objective: Persistent exposure of the unprotected spinal cord to amniotic fluid and the uterine wall can lead to progressive damage of neural tissue in case of a myelomeningocele (two-hit hypothesis). The aim of this study was to evaluate whether in utero repair of an experimental neural tube defect in a fetal lamb could protect neural tissue from secondary injury and save neurologic functions after birth. Methods:In 19 fetal lambs, a neural tube defect was created at 79 days’ gestation. In 12 lambs the defect was covered either with a novel, molecular defined collagen-based biocompatible and biodegradable matrix (UMC) or with a small intestinal submucosa (SIS) biomatrix (Cook®) or by closing the skin over the defect. Results: All lambs with the defect covered showed no or minor neurologic morbidity in contrast to the lambs with the defect uncovered in which major neurologic morbidity was seen. Conclusions:These results demonstrate that long-term exposure of the open spinal cord to the intrauterine environment can lead to damage of neural tissue and, consequently loss of neurologic functions and that coverage of the defect can lead to a better neurologic outcome. Furthermore, we could show that a UMC biomatrix and an SIS biomatrix are useful for in utero coverage of a surgically created neural tube defect in our model.

Contains fulltext : 48821.pdf (Publisher’s version ) (Closed access) Joubert syndrome is a genetically heterogeneous disorder. The diagnostic criteria include episodic hyperventilation, abnormal eye movements, psychomotor retardation, hypotonia, ataxia, and the characteristic neuro-imaging findings (molar-tooth sign). Many of these clinical features have been observed in new-borns with mitochondrial disorders as well. Congenital brain malformations, including cerebellar hypoplasia, have been described in pyruvate dehydrogenase deficiency. Malformations of the vermis and the cerebellar peduncles, with the lack of axonal decussations, however, are characteristic for Joubert syndrome but unique in patients with mitochondrial disorders. Here, we describe a child with Joubert syndrome presenting with primary lactic acidemia, decreased pyruvate oxidation rates, decreased ATP production, and a mildly decreased pyruvate dehydrogenase complex activity measured in a fresh muscle biopsy. Sequence analysis of the PDHc E1 alpha gene and the PDHX genes revealed no mutations. The patient received continuous feeding through a feeding tube for two years and showed a significant clinical improvement with a complete resolution of the chronic lactic acidemia. A second muscle biopsy revealed significantly decreased pyruvate oxidation rates and ATP production, but a normal pyruvate dehydrogenase complex activity. We suggest that the described mitochondrial dysfunction in our patient is secondary to an underlying mutation leading to Joubert syndrome.

Contains fulltext : 48133.pdf (Publisher’s version ) (Closed access) OBJECTIVE: A randomized controlled trial was reported recently, in which simple decompression and anterior subcutaneous transposition were compared for treatment of ulnaropathy at the elbow. Clinically, both surgical options seem to be equally effective. The objective of this study is to compare the costs, from a societal standpoint, of simple decompression versus anterior subcutaneous transposition in Euros. METHODS: Published and unpublished data from a randomized controlled trial that compared simple decompression and anterior subcutaneous transposition were used. The investigators tabulated the actual costs incurred for professional fees, use of the operating room, duration of sick leave, reintervention, and treatment of complications directly related to the surgical treatment. RESULTS: The total costs per group and per patient were statistically significantly less for those treated with simple decompression. The total median costs per patient were 1124 Euros for simple decompression and 2730 Euros for anterior subcutaneous transposition. The main difference was in the costs related to sick leave, which is significantly shorter for simple decompression. There also was a statistically significant difference in operation time in favor of simple decompression. A remarkable finding was that paid workers in both treatment groups returned to work much later than unpaid workers. CONCLUSION: Although clinically equally effective, simple decompression was associated with lower cost than anterior subcutaneous transposition for the treatment of ulnar neuropathy at the elbow. Compared with anterior subcutaneous transposition, we recommend simple decompression for the treatment of idiopathic ulnar neuropathy at the elbow.

Item does not contain fulltext Mutation of the spastin gene is the single most common cause of pure hereditary spastic paraparesis. In patients with an unexplained sporadic upper motor neuron (UMN) syndrome, clinical distinction between primary lateral sclerosis and sporadic hereditary spastic paraparesis may be problematic. To investigate whether spastin mutations are present in patients with primary lateral sclerosis and sporadic hereditary spastic paraparesis, we screened the spastin gene in 99 Dutch patients with an unexplained, apparently sporadic, adult-onset UMN syndrome. We found 6 mutations, of which 4 were novel, in the subgroup of 47 patients with UMN symptoms restricted to the legs (13%). Another novel spastin mutation was found in a patient with a rapidly progressive spinal and bulbar UMN syndrome that progressed to amyotrophic lateral sclerosis. In the patients with arm or bulbar UMN symptoms and slow progression, no spastin mutations were found. Our study shows that spastin mutations are a frequent cause of apparently sporadic spastic paraparesis but not of primary lateral sclerosis. 5 p.

Contains fulltext : 58020.pdf (Publisher’s version ) (Closed access) OBJECTIVE: To report a successful stapedectomy for stapedial fixation in a patient with Stickler syndrome type I (COL2A1). SETTING: University Hospital Department for Otology, Pathology, Ophthalmology and Clinical Genetics. STUDY DESIGN: A clinical and genetic evaluation of a mother and daughter focusing mainly on the otological, ophthalmological, histological and genetical aspects. INTERVENTION: A stapedectomy was performed successfully. RESULTS: Hearing impairment improved after stapedectomy. Postoperatively a shift in high-frequency threshold wa seen related to the stapedectomy. A new mutation in COL2A1 gene was dectected. CONCLUSION: Stapedial fixation can be the cause of hearing impairment in Stickler syndrome type I (COL2A1). The hearing impairment can be improved by stapes surgery.

Contains fulltext : 57890.pdf (Publisher’s version ) (Open Access) The Auditory Steady-State Response (ASSR) was recorded in 20 awake adults with normal hearing on ten EEG channels simultaneously to find derivations with the best signal-to-noise ratios (SNRs). Stimuli were 20% frequency modulated tones of 0.5 and 2 kHz at 20 dB SL, 100% amplitude modulated at 90 or 94 Hz, and presented one at a time to one ear. ASSR recordings using a set of at least three channels improved SNRs significantly by an average of between 6% (500 Hz right ear) to 118% (2 kHz right ear) above the SNRs from the conventional channels. Assuming that the recording time was proportional to 1/(SNR)2, this translates into a recording time of 89% (500 Hz right ear) to 21% (2 kHz right ear) of that for conventional single-channel recording. The three channels comprised the electrode positions inion, right mastoid, and left mastoid. All three electrode positions were referenced to Cz. Adding a fourth channel (Pz-Cz) increases the number of participants with significant responses from the 500 Hz right ear stimulus from 13 to 17. Electrode position F4 and other commonly used positions such as the forehead and right earlobe made significantly less contribution to test efficiency.