Can MRI predict olfactory loss and improvement in posttraumatic olfactory dysfunction?

BACKGROUND: Although most patients with post-traumatic olfactory dysfunction (PTOD) undergo MRI, there is no consensus about its diagnostic or prognostic value. The aims were: 1) to classify the extent of post-traumatic neurodegeneration; 2) to determine its relationship with chemosensory dysfunction (smell, taste, trigeminal); and 3) to establish whether MRI can predict olfactory improvement. METHODOLOGY: We conducted a retrospective cohort study based on a series of 56 patients with PTOD. All patients underwent validated psychophysical tests of their smell, taste, and trigeminal functions, otorhinolaryngologic evaluation, and MRI. An experienced radiologist blinded to patient data evaluated 40 chemosensory-relevant brain regions according to a four-point scale (0=no lesion to 3=large lesion). Follow up data after 4 years (on average) were available in 46 patients. RESULTS: The cluster analysis showed 4 brain lesion patterns that differed in lesion localization and severity. They are associated with diagnostic categories: anosmia, hyposmia and normosmia. Two clusters were highly specific for anosmia (100% specificity)and could accurately predict this condition (100% positive predictive value). No clusters were associated with trigeminal or taste dysfunction. Regarding improvement, 72.7% of patients in the cluster with mild lesions experienced subjective and measurable olfactory improvement whereas this was only the case in 21.7-37.5% of patients with larger lesions. The odds of subjective smell improvement were 5.9 times higher in patients within the milder cluster compared to larger ones. CONCLUSIONS: The analysis of brain lesions in PTOD allows corroboration of smell test results and prediction of subjective and measurable improvement.

Focused electrical stimulation using a single current source.

OBJECTIVE: Cochlear implants, while providing significant benefits to recipients, remain limited due to broad neural activation. Focussed multipolar stimulation (FMP) is an advanced stimulation strategy that uses multiple current sources to produce highly focussed patterns of neural excitation in order to overcome these shortcomings. APPROACH: This report presents single-source multipolar stimulation (SSMPS), a novel form of stimulation based on a single current source and a passive current divider. Compared to conventional FMP with multiple current sources, SSMPS can be implemented as a modular addition to conventional (i.e. single) current source stimulation systems facilitating charge balance within the cochlea. As with FMP, SSMPS requires the determination of a transimpedance matrix to allow for focusing of the stimulation. The first part of this study therefore investigated the effects of varying the probe stimulus (e.g. current level and pulse width) on the measurement of the transimpedance matrix. SSMPS was then studied using in vitro based measurements of voltages at non-stimulated electrodes along an electrode array in normal saline. The voltage reduction with reference to monopolar stimulation was compared to tripolar and common ground stimulation, two clinically established stimulation modes. Finally, a proof of principle in vivo test of SSMPS in a feline model was performed. MAIN RESULTS: A probe stimulus of at least 40 nC is required to reliably measure the transimpedance matrix. In vitro stimulation using SSMPS resulted in a significantly greater voltage reduction compared to monopolar, tripolar and common ground stimulation. Interestingly, matching measurement and stimulation parameters did not lead to an improved focussing performance. Compared to monopolar stimulation, SSMPS resulted in reduced spread of neural activity in the inferior colliculus, albeit with increased thresholds. SIGNIFICANCE: The present study demonstrates that SSMPS successfully limits the broadening of the excitatory field along the electrode array and a subsequent reduction in the spread of neural excitation.

Cell cycle reactivation of cochlear progenitor cells in neonatal FUCCI mice by a GSK3 small molecule inhibitor.

Due to the lack of regenerative capacity of the mammalian auditory epithelium, sensory hair cell loss results in permanent hearing deficit. Nevertheless, a population of tissue resident stem/progenitor cells has been recently described. Identification of methods to trigger their activity could lead to exploitation of their potential therapeutically. Here we validate the use of transgenic mice reporting cell cycle progression (FUCCI), and stemness (Lgr5-GFP), as a valuable tool to identify regulators of cell cycle re-entry of supporting cells within the auditory epithelium. The small molecule compound CHIR99021 was used to inhibit GSK3 activity. This led to a significant increase in the fraction of proliferating sphere-forming cells, labeled by the FUCCI markers and in the percentage of Lgr5-GFP + cells, as well as a selective increase in the fraction of S-G2-M cells in the Lgr5 + population. Using whole mount cultures of the organ of Corti we detected a statistically significant increment in the fraction of proliferating Sox2 supporting cells after CHIR99021 treatment, but only rarely appearance of novel MyoVIIa +/Edu + hair cells. In conclusion, these tools provide a robust mean to identify novel regulators of auditory organ regeneration and to clarify the contribution of stem cell activity.

Radiation dose reduction in postoperative computed position control of cochlear implant electrodes in lambs - An experimental study.

OBJECTIVE: Cochlear implants (CI) are standard treatment for prelingually deafened children and postlingually deafened adults. Computed tomography (CT) is the standard method for postoperative imaging of the electrode position. CT scans accurately reflect electrode depth and position, which is essential prior to use. However, routine CT examinations expose patients to radiation, which is especially problematic in children. We examined whether new CT protocols could reduce radiation doses while preserving diagnostic accuracy. METHODS: To investigate whether electrode position can be assessed by low-dose CT protocols, a cadaveric lamb model was used because the inner ear morphology is similar to humans. The scans were performed at various volumetric CT dose-indexes CTDIvol)/kV combinations. For each constant CTDIvol the tube voltage was varied (i.e., 80, 100, 120 and 140kV). This procedure was repeated at different CTDIvol values (21mGy, 11mGy, 5.5mGy, 2.8mGy and 1.8mGy). To keep the CTDIvol constant at different tube voltages, the tube current values were adjusted. Independent evaluations of the images were performed by two experienced and blinded neuroradiologists. The criteria diagnostic usefulness, image quality and artifacts (scaled 1-4) were assessed in 14 cochlear-implanted cadaveric lamb heads with variable tube voltages. RESULTS: Results showed that the standard CT dose could be substantially reduced without sacrificing diagnostic accuracy of electrode position. The assessment of the CI electrode position was feasible in almost all cases up to a CTDIvol of 2-3mGy. The number of artifacts did not increase for images within this dose range as compared to higher dosages. The extent of the artifacts caused by the implanted metal-containing CI electrode does not depend on the radiation dose and is not perceptibly influenced by changes in the tube voltage. Summarizing the evaluation of the CI electrode position is possible even at a very low radiation dose. CONCLUSIONS: CT imaging of the temporal bone for postoperative electrode position control of the CI is possible with a very low and significantly radiation dose. The tube current-time product and voltage can be reduced by 50% without increasing artifacts. Low-dose postoperative CT scans are sufficient for localizing the CI electrode.

The pre- and post-somatic segments of the human type I spiral ganglion neurons--structural and functional considerations related to cochlear implantation.

Human auditory nerve afferents consist of two separate systems; one is represented by the large type I cells innervating the inner hair cells and the other one by the small type II cells innervating the outer hair cells. Type I spiral ganglion neurons (SGNs) constitute 96% of the afferent nerve population and, in contrast to other mammals, their soma and pre- and post-somatic segments are unmyelinated. Type II nerve soma and fibers are unmyelinated. Histopathology and clinical experience imply that human SGNs can persist electrically excitable without dendrites, thus lacking connection to the organ of Corti. The biological background to this phenomenon remains elusive. We analyzed the pre- and post-somatic segments of the type I human SGNs using immunohistochemistry and transmission electron microscopy (TEM) in normal and pathological conditions. These segments were found surrounded by non-myelinated Schwann cells (NMSCs) showing strong intracellular expression of laminin-ß2/collagen IV. These cells also bordered the perikaryal entry zone and disclosed surface rugosities outlined by a folded basement membrane (BM) expressing laminin-ß2 and collagen IV. It is presumed that human large SGNs are demarcated by three cell categories: (a) myelinated Schwann cells, (b) NMSCs and (c) satellite glial cells (SGCs). Their BMs express laminin-ß2/collagen IV and reaches the BM of the sensory epithelium at the habenula perforata. We speculate that the NMSCs protect SGNs from further degeneration following dendrite loss. It may give further explanation why SGNs can persist as electrically excitable monopolar cells even after long-time deafness, a blessing for the deaf treated with cochlear implantation.

Low-dose temporal bone CT in infants and young children: effective dose and image quality.

BACKGROUND AND PURPOSE: The temporal bone is ideal for low-dose CT because of its intrinsic high contrast. The aim of this study was to retrospectively evaluate image quality and radiation doses of a new low-dose versus a standard high-dose pediatric temporal bone CT protocol and to review dosimetric data from the literature. MATERIALS AND METHODS: Image quality and radiation doses were compared for 38 low-dose (80 kV/90-110 mAs) and 16 high-dose (140 kV/170 mAs) temporal bone CT scans of infants to 5-year-old children. The CT visualization quality of 23 middle and inner ear structures was subjectively graded by 3 neuroradiologists and 3 otologists by using a 5-point scale with scores 1-2 indicating insufficient and scores 3-5 indicating sufficient image quality. Effective doses of local and literature-derived protocols were calculated from dosimetric data by using NRPB-SR250 software. RESULTS: Insufficient image-quality scores were more frequent in low-dose scans versus high-dose scans, but the difference was only statistically significant for otologists (6.0% versus 3.4%, P = .004) and not for neuroradiologists (1.2% versus 0.7%, P = .84). Image quality was critical for small structures (such as the stapes or lamella at the internal auditory canal fundus). Effective doses were 0.25-0.3 mSv for low-dose scans, 1.4-1.8 mSv for high-dose scans, and 0.9-2.6 mSv for literature-derived protocols. CONCLUSIONS: The image quality of the new low-dose protocol remains diagnostic for assessing middle and inner ear anatomy despite a 3- to 8-fold dose reduction over previous and literature-derived protocols. However, image quality of small structures is critical and may be perceived as insufficient.

Assessment of speech perception and communication skills in adolescents with cochlear implants for pre- and peri-lingual deafness.

OBJECTIVE: This study aimed to assess speech perception and communication skills in adolescents between ages 8 and 18 that received cochlear implants for pre- and peri-lingual deafness. METHODS: We studied 15 adolescents, aged 12 to 23 years, with late cochlear implantation. Speech perception was assessed with the Bishop sentences test and a memory number sequence test at 3-9 years after cochlear implantation. A questionnaire completed retrospectively was used to investigate communication skills pre- and post implantation. RESULTS: Six individuals achieved grammar comprehension scores comparable to children 8-10 years old with normal hearing; only 3 individuals achieved a percentile rank higher than 50% in the memory number sequence test. The self-reported communication skills improved after cochlear implantation in all adolescents. CONCLUSIONS: Speech perception skills of adolescents with late implantation for pre- and peri-lingual deafness are typically inferior to those of children with normal hearing at the age of 10. However, when the evaluation of the cochlear implant outcome was broadened with the use of a questionnaire, many individuals reported that they participated more actively in conversations, spoke more actively to unknown individuals, and were more easily understood by others.

[Ophthalmological findings in microcephaly-lymphoedema-chorioretinal dysplasia syndrome]. / Okuläre Veränderungen beim Mikrozephalie-Lymphödem-Chorioretinale-Dysplasie-Syndrom.

BACKGROUND: Microcephaly-lymphoedema-chorioretinal dysplasia (MLCRD) is a rare syndrome characterized by microcephaly, chorioretinal dysplasia, lymphoedema and a characteristic facial phenotype. The exact mode of inheritance is uncertain, autosomal dominant, recessive and X-chromosomal cases have been reported. HISTORY AND SIGNS: A three-month-old boy with intrauterine growth retardation and microcephaly was referred to our clinic. The ophthalmic examination revealed a left eye with a persistent hyperplastic primary vitreous. On funduscopy of the right eye pale optic disc, chorioretinal dysplasia with pigmentary and atrophic changes and falciform folds were noted. General morphological changes and ophthalmological findings led to the diagnosis of MLCRD-syndrome. THERAPY AND OUTCOME: Eye examinations of the parents and the grandparents did not show any retinal changes, therefore an autosomal dominant inheritance was excluded. CONCLUSIONS: An ophthalmological examination in children with microcephaly and facial dysmorphies is essential. Parents and grandparents should also be considered for eye examination if a child has chorioretinal dysplasia and microcephaly.

["Floaterectomy"--pars-plana-vitrectomy for vitreous opacities]. / "Floaterektomie"--Pars-Plana-Vitrektomie wegen Glaskörpertrübungen.

BACKGROUND: Patients suffer from vitreous opacities, despite good visual acuity. The lack of objective measurements may make it difficult to justify the indication for vitreous surgery. PATIENTS AND METHODS: We analysed retrospectively the outcome of 90 eyes/ 67 patients, age 20 - 86 years (mean 60 +/- 19) after pars plana vitrectomy (ppv) for vitreous opacities. Follow-up was 6 - 40 months (mean 19 +/- 9). Additional pathologies (except cataract) possibly affecting the functional outcome were present in 33 % (uveitis 8 %, premacular membrane 10 %, other 15 %). The technique consisted of a standard 3-port vitrectomy (44 % 25-gauge, 46 % 20-gauge). In 78 % ppv was combined with phacoemulsification + IOL implantation. RESULTS: Mean preoperative visual acuity was 0.6, postoperative 1.0 (+ 2.3 lines, p > 0.0001). One eye lost 2 lines. Peripheral retinal tears occurred in 11 %. Long-term complications (12 - 31 months) consisted of premacular membrane formation (1), luxation of the IOL/capsular bag. Secondary interventions included YAG capsulotomy (4) and glaucoma surgery (1). 94 % of all patients (98 % if additional pathologies were excluded) were satisfied with the outcome. CONCLUSIONS: Pars plana vitrectomy for vitreous opacities is safe and effective. Careful patient selection is crucial.

[Stem-cell-based approaches for treating inner ear diseases]. / Stammzellbasierte Ansätze zur Therapie von Innenohrerkrankungen.

The capacity of stem cells to regenerate lost tissue cells has gained recognition among physicians. Despite the successful use of blood stem cells for treating blood cancers, other stem cell types have not yet been widely introduced into clinical practice. Therapy options involving stem cells for inner ear diseases consequently have not been implemented. Nonetheless, several reports have recently been published describing the generation of morphologically and immunologically distinctive inner ear cell types-such as hair cells, supporting cells, and spiral ganglion neurons-from stem cells. Although promising, all of these studies still lack functional results regarding hearing restoration or vestibular function.

Changes on diffusion-weighted MRI with focal motor status epilepticus: case report.

Transient imaging abnormalities, including changes on diffusion-weighted imaging (DWI), may be seen in focal status epilepticus. The changes on DWI provide am insight into the pathophysiology. We report a 53-year-old man with focal motor status epilepticus involving the left hand, arm and face with focal slowing on EEG. The apparent diffusion coefficients (ADC) were higher in the affected hemisphere than on the other side. At 10 days and 6 weeks after the end of the seizures, we saw normal ADCs and atrophy of the affected hemisphere. We conclude that the MRI findings indicate both cytotoxic and vasogenic oedema during seizure activity and subsequent loss of brain parenchyma.

[Ocular barostress and barotrauma. A study of 15 scuba divers]. / Okuläre Druckbelastung und Barotrauma. Studie an 15 Sporttauchern.

BACKGROUND: During SCUBA-diving, relative changes of the pressure in the diving mask, compared to the environmental pressure, are transmitted to the eye and to the periocular tissue. Barotrauma results from lack of pressure equilibration. MATERIAL AND METHODS: In 15 divers (6 experienced, 9 beginners) the pressure difference (delta-p) between inside and outside of the diving mask was measured every second during recreational SCUBA-diving. Data were transmitted wireless to a modified standard diving computer. An overall dive time of 323 minutes was analysed. RESULTS: Mean delta-p was 14.8 mbar (-44 to , std.dev. +/- 9), it was not dependent on the diving depth (r2 = 0.0004). Delta-p oscillated between 0 and 25 mbar (0-19 mm Hg), parallel to respiration. Negative delta-p values were 9.5 times more frequent in beginners than in experienced divers. Negative pressure peaks (changes > or = 10 mbar for more than 6 sec) occurred in the beginner group exclusively (p = 0.01). CONCLUSIONS: During SCUBA diving, ocular tissues undergo oscillating changes of environmental pressure, parallel to respiration. This may be important in eyes with previous surgery. Pressure peaks, leading to severe ocular barotrauma, are easily avoidable.

The formation and regression of a flow-related cerebral artery aneurysm.

The authors report a patient with an aneurysm of the right cerebral posterior communicating artery (PCoA) developing after thrombotic pseudo-occlusion of the right internal carotid artery (ICA). The aneurysm regressed spontaneously subsequent to ipsilateral ICA endarterectomy and reversal of blood flow in the PCoA. The formation and regression of the aneurysm was well documented by repeat cerebral digital subtraction angiography studies, computed tomography and magnetic resonance imaging. The authors conclude that the formation and regression of this 'flow-related' aneurysm was associated with hemodynamic changes in blood flow of the right PCoA and the right ICA.

Central and peripheral pressure measurements with the Goldmann tonometer and Tono-Pen after photorefractive keratectomy for myopia.

To compare the accuracy of Goldmann tonometry with that of the Tono-Pen(R) in measuring intraocular pressure (IOP) after photorefractive keratectomy (PRK). Eye Clinic, Cantonal Hospital, Lucerne, Switzerland.Thirty-five eyes (25 patients) had PRK for a mean myopia of -6.2 diopters +/- 2.6 (SD). Intraocular pressure (IOP) measurements were performed first with the Goldmann tonometer and then with the Tono-Pen in 2 corneal locations: centrally in the usual manner and temporally. For the temporal measurements, the patient was directed to gaze nasally as the tonometer was placed perpendicular to the temporal portion of the cornea and with the rim of the tonometer positioned just inside the limbus of the cornea. Subsequently, similar measurements were made with the Tono-Pen. Measurements were performed before and 1 and 3 months after PRK. Preoperative IOPs measured centrally and temporally were similar. After PRK, the central pressure readings with the Goldmann tonometer and the Tono-Pen were between 1.8 and 2.3 mm Hg lower than those measured temporally. The differences were statistically significant (P <.0001). Central corneal pressure readings obtained with either the Goldmann tonometer or the Tono-Pen after myopic PRK are inaccurate. Measurements over the temporal part of the cornea are likely more reliable.

[Prognostic factors and results after surgical treatment of idiopathic macular holes, stage 2 and 3]. / Prognostische Faktoren und Resultate nach operativer Behandlung idiopathischer Macula foramina Stadium 2 und 3.

PURPOSE: To determine prognostic factors, functional outcome and subjective rating after surgery for macular holes stage 2 and 3. METHODS: We studied 53 eyes of 49 patients undergoing vitreous surgery for macular holes stage 2 (46%) and 3 (54%). Mean follow-op was 114 weeks (32-204, std.dev. +/- 48), mean age 68.9 years (44-89, std.dev. +/- 6.8). 72% were female, 11% were pseudophakic, 19% phakic, 70% had a combined procedure (pars plana vitrectomy, phacoemulsification and IOL). Surgery consisted in a pars plana vitrectomy, peeling of epiretinal membranes and ILM, internal tamponade with SF6 (98%) resp. Si-oil in one case. Patients had to keep face-down position 6 x 20 minutes per day. RESULTS: The hole was completely closed in 90.6%. Anatomical failures included, 86% had an increase of VA, 41% = 5 lines (Final VA median 20/30, max. 20/20). No further increase of the retinal function occurred after 6 months. The visual result did not correlate with the duration of symptoms. 84% were satisfied with the outcome, subjective rating was not correlated with final VA or change of VA. 19% showed postoperative typical peripheral visual field defects. Visual field loss was not correlated with perioperative IOP elevation. CONCLUSION: Macular hole surgery has a high functional success rate. Postoperative visual field defects are an important problem.