Nerve Anomalies Research Articles

Surgical treatment for congenital absence of the oval window with facial nerve anomalies

Three patients with a middle ear malformation characterized by the absence of the oval window and complicated by facial nerve anomalies were treated by surgery. Hearing ability of all the patients was improved. A variety of facial nerve anomalies were observed. Fenestration of the vestibule above the facial nerve was performed in the case of 2 of the 3 patients. In the other patient, fenestration of the scala vestibuli below the facial nerve was performed. In the case of all the 3 patients, hearing ability improved after the surgery and remained stable for a long time. Surgery for this disease has been considered difficult because of a high risk of complications. Because all the 3 patients showed excellent long-term surgical results, we suggest that fenestration of the inner ear should be considered one of the main options for the management and treatment of an absent oval window associated with facial nerve anomalies.

Difficult problems: Strabismus

Relevance: The most common ICD-9 codes used by pediatric ophthalmologists concerned strabismus. Patients that present with straight-forward unoperated strabismus do not present a challenge to most pediatric ophthalmologists. However, patients may also present with very complex strabismus that pose diagnostic and therapeutic challenges: strabismus secondary to brain injury, brain tumors, cranial nerve palsies, orbital disease or anomalies, and status post multiple extraocular muscle surgeries. This workshop will specifically deal with rarer and more atypical presentations of strabismus that present a knowledge gap to the practicing pediatric ophthalmologist.

Bilateral bifid labyrinthine facial nerve anomalies associated with agenesis of the oval window: Case report and review of the literature

Formation of the nerve commences early in gestation with the facioacoustic primordium (derived from the neural crest and otic vesicle) separating into facial and acoustic components at the end of the 4th week. By the end of the 5th gestational week, the chorda tympani has differentiated from the distal facial nerve. By the 8th week, the orientation of the facial nerve within the temporal bone has been established, with the nerve’s ultimate position and bony covering determined by development of the stapes and membranous labyrinth.

A novel homozygous HESX1 mutation causes panhypopituitarism without midline defects and optic nerve anomalies

There are many genes reported to have been associated with combined pituitary hormone deficiencies, but mutations in HESX1 strongly correlate with septo-optic dysplasia. Our aim was to determine the cause of panhypopituitarism in our patient. We studied an 8-month-old child having panhypopituitarism. The coding exons of PIT1, PROP1, LHX3, and HESX1 genes were amplified. Direct sequencing was done after denaturing HLPC. We identified a novel homozygous mutation (R160H) within the homeodomain of HESX1, which, to our knowledge, is the first to be described in humans. Neuroimaging studies revealed anterior pituitary aplasia, a normal posterior pituitary gland, and a thin pituitary stalk but no midline abnormalities. Optic nerve studies showed no pathology. This mutation is also carried in the parents of the affected child in a heterozygous pattern, suggesting an autosomal recessive inheritance. These data demonstrate that homozygous HESX1 mutation causing an R160H substitution can result in panhypopituitarism without midline defects.

Imaging of 7th and 8th Cranial Nerve Anomalies in PTCD

Free accessAbstractFirst published online August 2010Imaging of 7th and 8th Cranial Nerve Anomalies in PTCDLindsay Young, MD, presenter, Tim Booth, MD, […], Peter Roland, MD, Joe Kutz, MD, and Mario Miranda, MD+2-2View all authors and affiliationsVolume 143, Issue 2_supplhttps://doi.org/10.1016/j.otohns.2010.06.512

More About Cochlear Implantation in Children with Charge Association

CHARGE is the acronym for Coloboma, Heart malformation, Choanal Atresia, Retardation of growth and/or development, Genital and Ear anomalies. It is a rare genetic syndrome, usually with no family history. From an otological point of view, it is characterized by semicircular canal agenesia, Mondini-type cochlear hypoplasia, frequent vestibular dysfunction, and hearing impairment (ranging from transient OME to profound deafness) (Abadie et al., 2000).Speech and language delay in this syndrome is due not only to hearing problems, but also to mental retardation, facial palsy, oro-lingual motor deficit, and swallowing disorders, which often require enteral feeding or gastrostomy. Moreover, anatomical cochlear or facial nerve anomalies have been described.Due to these aggravating factors, few children affected by CHARGE have undergone cochlear implantation. However, several cochlear implantation centres, including ours, consider that children affected by this syndrome and profound hearing impairment might obtain benefit from a cochlear implant (CI), at least to improve communication, although not necessarily to develop spoken language (Bauer et al., 2002; McArdle et al., 2002; Lanson et al., 2007). This point of view was supported by a previous work about four children with CHARGE and sensorineural hearing loss: communication mode and language reception and expression progressed in a similar way in the two implanted profoundly deaf children as in the two of them with severe hearing impairment and hearing aids (Lina-Granade et al., 2006). Hence, we undertook this case study with more children and a longer follow-up, in order to have a more accurate description of the surgical particularities, fitting, and outcomes of implantation in children with CHARGE.

Unilateral situs inversus of optic disc associated with reduced binocularity and stereoacuity resembling monofixation syndrome

Situs inversus of the optic disc is a rare, usually bilateral, congenital embryological abnormality associated with high myopia, optic disc coloboma or tilted optic disc. It is characterized by emergence of the retinal vessels in an anomalous direction with dysversion of the optic disc. In this report we present a 13-year-old boy diagnosed with isolated, unilateral situs inversus of the optic disc associated with reduced binocularity and stereoacuity resembling a monofixation syndrome. The clinicians should be aware of this association and assess the binocularity in patients with unilateral optic disc or macular anomalies. Conversely, patients with reduced binocularity and stereoacuity should be carefully evaluated for macular or optic nerve anomalies, if not associated with strabismus, anisometropia and eccentric fixation. Typical fundus picture, optical coherence tomography and multifocal electro retinogram of the patient would be instructive to a clinician.

321 Congenital heart defects in CHARGE syndrome patients with CHD7 mutations

CHARGE syndrome (MIM 214800) consists of a combination of congenital malformations including Coloboma, Heart defects, Atresia of choanae, Retardation of growth and developmental delay, Genital anomalies and Ear anomalies. Diagnosis criteria have been recently refined and several other features have been described such as semi-circular canals and cranial nerve anomalies. A CHD7 gene mutation is found in 60% of patients with a clinical diagnosis of CHARGE syndrome. Although frequently found, cardiovascular malformations (CVM) are not specific.

Variations of the piriformis and sciatic nerve with clinical consequence: A review

The deep gluteal region is often encountered when performing injections, when performing surgery such as total hip replacements, or diagnosing problems of this region or lower limbs using clinical or imaging techniques. Previously, the prevalence figures of piriformis and sciatic nerve anomalies have ranged from 1.5 to 35.8% in dissected specimens. This study systematically reviews and meta-analyses the prevalence of piriformis and sciatic nerve anomalies in humans using previously published literature. A further review is conducted regarding the anatomical abnormalities present in surgical case series of procedures for patients suffering from piriformis syndrome. After pooling the results of 18 studies and 6,062 cadavers, the prevalence of the anomaly in cadavers was 16.9%; 95% confidence interval (CI) 16.0-17.9%. The prevalence of the piriformis and sciatic nerve anomaly in the surgical case series was 16.2%, 95% CI: 10.7-23.5%. The difference between the two groups was not found to be significant 0.74%; 95% CI: -5.66 to 7.13; P = 0.824. Because of the high likelihood of an anomaly being present in a patient, clinicians and surgeons should be aware of the potential complications this anomaly may have on medical or surgical interventions. Furthermore, because the prevalence of the anomaly in piriformis syndrome patients is not significantly different from what is thought to be a normal population, it indicates that this anomaly may not be as important in the pathogenesis of piriformis syndrome as previously thought.

Genetic and developmental basis of renal coloboma (papillorenal) syndrome

Renal coloboma syndrome, also known as papillorenal syndrome, is characterized by optic nerve anomalies and kidney hypodysplasia. Autosomal dominant mutations in the gene encoding the paired box transcription factor, PAX2, can be identified in nearly half of all patients with this phenotype. The primary ophthalmologic findings include congenital central retinal vasculature absence associated with abnormalities in retinal blood vessel patterning and deeply excavated optic discs. Other published findings include optic nerve hypoplasia, optic nerve cyst, optic nerve pits, retinal coloboma, microphthalmia and scleral staphyloma. Visual acuity ranges from normal to severe impairment. Up to one third of affected patients will develop end-stage renal disease. Mouse and zebrafish with Pax2/pax2a mutations provide developmentally based explanations for the observed phenotypic observations in affected patients.

Mutational screening of BASP1 and transcribed processed pseudogene TPΨg-BASP1 in patients with Möbius syndrome

Möbius syndrome is a rare disorder primarily characterized by congenital facial palsy, frequently accompanied by ocular abduction anomalies and occasionally associated with orofacial, limb and musculoskeletal malformations. Abnormal development of cranial nerves V through XII underlines the disease pathogenesis. Although a genetic etiology for Möbius syndrome was proposed, molecular genetic studies to identify the causative gene(s) are scarce. In this study, we selected two candidate genes. One is BASP1 residing in a human chromosome 5p15.1-p15.2, syntenic to mouse chromosome 15qA2-qB2, to which a mouse model with facial nerve anomalies was mapped. The other is transcribed processed pseudogene TPPsig-BASP1, which is located on chromosome 13q flanking the putative locus for Möbius syndrome and might be involved in the regulation of the transcripts encoded by BASP1. Mutation analyses in nineteen patients excluded these genes as being candidates for Möbius syndrome.

Bilateral Stapedectomy: Association between First- and Second-Ear Surgical Findings and Their Effects on the Second-Ear Outcome

We assessed the association between first-ear and second-ear surgical findings in patients undergoing second-ear stapedectomy for bilateral otosclerosis and the impact of such findings on the audiometric outcome of the second ear. A retrospective chart review of all stapedectomy patients who underwent stapes surgery by one of two surgeons in a single tertiary referral institution from 1962 to 2001 was performed, and those patients who underwent bilateral stapedectomy were identified. Patient demographic data, surgical findings, procedure performed, and preoperative and postoperative audiometric data were recorded. A total of 459 patients (918 ears) underwent bilateral stapedectomy for bilateral otosclerosis during the study period, of whom 426 had complete data for analysis. The finding of a white or obliterated footplate in the second ear was significantly higher if the first ear had this disease manifestation (p < .001, chi2 test). The association between a second drill-out's being performed and a drill-out in the first operation was significant (p < .001, chi2 test). Statistical analysis identified that those who underwent a drill-out procedure had a 2.9-fold increase in unsuccessful outcome in comparison to those who did not have a drill-out (odds ratio, 2.89; 95% confidence interval, 1.41 to 5.89). Facial nerve anomalies were infrequently encountered, affecting only 23 patients, of whom 3 had bilateral abnormalities. The finding of an overhanging or dehiscent facial nerve in the second ear was significantly more likely if such an abnormality was identified during the first procedure (23% versus 2.5%; p = .005, Fisher's exact test). Second-ear hearing results are poorer in those who require a drill-out of this ear, and this is more likely to be required if a drill-out was required in the first ear, regardless of a successful outcome of the first procedure. Patients should be aware of the reduced likelihood of success in these cases and be counseled regarding risks and benefits of second-ear surgery based, in part, on the findings from the first ear. This study confirms that bilateral advanced footplate obliteration and overhanging or dehiscent facial nerves may be anticipated in patients found to have these abnormalities during first-ear stapedectomy.

Cranial nerve manifestations in CHARGE syndrome

Cranial nerve (CN) anomalies have been regarded as a major criterion for a clinical diagnosis of CHARGE syndrome for some time. However, there have been relatively few studies of the extent of this involvement. A detailed questionnaire (in French or English) was distributed to all physicians who participated in the 2001-2004 Canadian Paediatric Surveillance Program (CPSP), and who identified themselves as caring for an individual with CHARGE syndrome. Clinical data were collected from multiple sources for each individual, including evidence of CN dysfunction. Evidence for CN anomalies recorded by the clinical presentations and evidence from specialized testing, were: weak chewing and/or sucking (CN V), facial palsy (CN VII), sensorineural hearing loss (CN VIII), balance vestibular problems (CN VIII), and swallowing problems (CN IX/X). Data were analyzed as to the frequency of the CN anomalies and compared to the literature. At the time of this study, there were 99 individuals identified with CHARGE syndrome across Canada. The CHARGE syndrome diagnosis was confirmed by geneticists across the country. Gene testing was not available at the time of this study. Of these 92% exhibited symptoms of at least one CN anomaly, and 72% reported involvement of more than one. Isolated CN involvement was rare. Ascertainment was highest for CN IX/X, and lowest for VIII vestibular. The frequency of CN involvement was generally higher than that reported in the literature.

Rééducation de la part fonctionnelle de l’amblyopie dans un Morning Glory syndrome

Morning Glory syndrome, characterized by an enlarged dysplasic optic disc with glial tissue, is one of the congenital anomalies of the optic nerve. This syndrome is rare, prevalent in the girls, and generally unilateral. It can be revealed with nystagmus, strabismus, or amblyopia. We report the clinical observation of a 2.5-year-old girl, referred for the diagnosis of Morning Glory syndrome in the left eye with severe amblyopia (1/10 Rossano 1/20) and esotropia. This syndrome has associated central nervous system anomalies with a basal encephalocele. Treated with functional amblyopia therapy, visual acuity was 7/10 Rossano 1/2 after 1 year. Rehabilitation on functional amblyopia in organic optic nerve anomalies is essential. A child with a Morning Glory syndrome, detected during the period of sensory maturation, must be treated with occlusion therapy, followed by maintenance treatment. This part of the treatment can prevent deep amblyopia. Moreover, regular ophthalmologic follow-up to detect complications of retinal detachment and multidisciplinary follow-up to detect a cytogenetic disease, CHARGE syndrome, or association with endocrine and central nervous system anomalies are necessary. The author recommends occlusion therapy for children with Morning Glory syndrome or other organic asymmetric optic nerve anomalies, during the period of amblyopia reversibility. Most patients' vision improves after treatment. This case is an illustration.

Choroidal Neovascularization in Congenital Disorders of the Optic Nerve

Choroidal neovascularization is one of the most important visual losses seen in developed countries and is usually associated with age-related macular degeneration in the older age group. Choroidal neovascular membranes seen at a young age may be associated with pathologic myopia and ocular histoplasmosis; the idiopathic group also has an important place. Congenital optic nerve diseases are an important but rare disease group that makes peripapillary choroidal neovascularization in the young age group. Under these headings, besides isolated congenital optic nerve anomalies such as tilted disc, optic disc drusen, optic pit, and myelinated nerve fiber; anomalies showing serious neurological deficits such as optic disc coloboma, morning glory anomaly, optic nerve hypoplasia can also be counted. In this review, pathophysiology and treatment of the togetherness of optic nerve diseases and the neovascular membrane will be evaluated.

Blindness Caused by Deficiency in AE3 Chloride/Bicarbonate Exchanger

BackgroundVision is initiated by phototransduction in the outer retina by photoreceptors, whose high metabolic rate generates large CO2 loads. Inner retina cells then process the visual signal and CO2. The anion exchanger 3 gene (AE3/Slc4a3) encodes full-length AE3 (AE3fl) and cardiac AE3 (AE3c) isoforms, catalyzing plasma membrane Cl−/HCO3 − exchange in Müller (AE3fl) and horizontal (AE3c) cells. AE3 thus maintains acid-balance by removing photoreceptor-generated CO2 waste.Methodology/Principal FindingsWe report that Slc4a3−/− null mice have inner retina defects (electroretinogram b-wave reduction, optic nerve and retinal vessel anomalies). These pathologic features are common to most human vitreoretinal degenerations. Immunobloting analysis revealed that Na+/HCO3 − co-transporter (NBC1), and carbonic anhydrase II and CAXIV, protein expression were elevated in Slc4a3 −/− mouse retinas, suggesting compensation for loss of AE3. TUNEL staining showed increased numbers of apoptotic nuclei from 4–6 months of age, in Slc4a3 −/− mice, indicating late onset photoreceptor death.Conclusions/SignificanceIdentification of Slc4a3 as underlying a previously unrecognized cause of blindness suggests this gene as a new candidate for a subset of hereditary vitreoretinal retinal degeneration.

Role of CT and MRI in the preoperative evaluation of auditory brainstem implantation in patients with congenital inner ear pathology

The purpose of this study was to evaluate the reliability of computed tomography (CT) and magnetic resonance imaging (MRI) in characterising cochlear nerve anomalies in auditory brainstem implant candidates with congenital hearing loss. Seventeen patients affected by congenital sensorineural hearing loss were examined by CT and MRI. Inner ear malformations eligible for auditory brainstem implants were classified according to the Casselman classification. All patients subsequently received auditory brainstem implants. Suspected congenital anomalies were confirmed by CT and MRI in all 17 patients. There were 5/17 bilateral cochlear nerve aplasias and 12/17 cochleovestibular anomalies. Of these, 5/12 patients had a common cochleovestibular cavity, 2/12 had bilateral cochlear aplasia and cochlear nerve agenesis, 1/12 had type I incomplete partition, 2/12 had type II incomplete partition and 2/12 had cochlear hypoplasia. Preoperative CT and MRI assessment of patients with sensorineural hearing loss is reliable. MRI provided additional information, identifying the possible absence of cochlear nerve and excluding other central nervous system (CNS) diseases.

CHARGE syndrome.

CHARGE syndrome was initially defined as a non-random association of anomalies (Coloboma, Heart defect, Atresia choanae, Retarded growth and development, Genital hypoplasia, Ear anomalies/deafness). In 1998, an expert group defined the major (the classical 4C's: Choanal atresia, Coloboma, Characteristic ears and Cranial nerve anomalies) and minor criteria of CHARGE syndrome. Individuals with all four major characteristics or three major and three minor characteristics are highly likely to have CHARGE syndrome. However, there have been individuals genetically identified with CHARGE syndrome without the classical choanal atresia and coloboma. The reported incidence of CHARGE syndrome ranges from 0.1–1.2/10,000 and depends on professional recognition. Coloboma mainly affects the retina. Major and minor congenital heart defects (the commonest cyanotic heart defect is tetralogy of Fallot) occur in 75–80% of patients. Choanal atresia may be membranous or bony; bilateral or unilateral. Mental retardation is variable with intelligence quotients (IQ) ranging from normal to profound retardation. Under-development of the external genitalia is a common finding in males but it is less apparent in females. Ear abnormalities include a classical finding of unusually shaped ears and hearing loss (conductive and/or nerve deafness that ranges from mild to severe deafness). Multiple cranial nerve dysfunctions are common. A behavioral phenotype for CHARGE syndrome is emerging. Mutations in the CHD7 gene (member of the chromodomain helicase DNA protein family) are detected in over 75% of patients with CHARGE syndrome. Children with CHARGE syndrome require intensive medical management as well as numerous surgical interventions. They also need multidisciplinary follow up. Some of the hidden issues of CHARGE syndrome are often forgotten, one being the feeding adaptation of these children, which needs an early aggressive approach from a feeding team. As the child develops, challenging behaviors become more common and require adaptation of educational and therapeutic services, including behavioral and pharmacological interventions.

Optical Coherence Tomography of the Optic Nerve Head

Optical coherence tomography may be a new technique for quantitative 3-dimensional assessment of the optic nerve head for diagnosis of optic nerve anomalies and diseases such as the glaucomas. The purpose of the present study was to examine its reproducibility. The clinical noninterventional study included 10 randomly chosen eyes of 10 healthy individuals who underwent 24 optical coherence tomographic examinations with the high-resolution and fast scan program, interactively corrected or uncorrected. The pupils were not dilated. All examinations were performed by 3 examiners independently of one another. The coefficient of variation was calculated as the ratio of the mean of the standard deviations divided by the mean of the means. The coefficients of variation for redetermination of optic disc area, ranging between 0.047 and 0.119, were lowest for the manually corrected fast scan mode and highest for the uncorrected fast scan mode. For remeasurements of the neuroretinal rim area, the best mean coefficient of variation was 0.073+/-0.026 (corrected fast scan mode). In healthy eyes, the morphometric measurements of the optic nerve head by optical coherence tomography show a relatively high reproducibility with mean coefficients of variation lower than 10% for remeasurements of the optic disc and neuroretinal rim area. With undilated pupils, reproducibility is better with the fast scan mode with interactive correction of the outlining of the optic disc border than it is with the high-resolution mode.

Leading causes of blindness and visual impairment in the region of Eastern Herzegovina

Visual impairment and blindness are serious social and health problems in the world. 1992 classification of visual disorders by World Health Organization has recently been implemented. The goal of this study was to determine common causes of visual impairment and blindness in the region of Eastern Herzegovina. In this population based study we have analyzed medical records stored in the regional Association of Visually Impaired and Blind Persons of the Republic of Srpska (Trebinje, Bileća, Foca, Eastern Sarajevo). The analysis included sex and age distribution of registered population, classification and leading causes of visual disability and blindness. RESULTS There are 298 registered persons with visual disability and blindness in the region of Eastern Herzegovina and Eastern Sarajevo. The prevalence of visual impairment and blindness in the aforementioned region is 0.1%. Among the studied population, there are more males than females with visual disability or blindness (56% versus 44%). Most (78%) of registered persons are blind, and only 22% are visualy impaired. 43% of registered population are in the IV category and only 8.38% are registered in the II category. Only 2% of registered population are children. Common causes of visual disability and blindness in the region of Eastern Herzegovina are: glaucoma (22%), cataract (17%), myopia alta (13%), diabetic retinopathy (12%) and ocular trauma (11). Common causes of children's visual impairment include. optic nerve anomalies, congenital cataract and premature retinopathy. Compared with literature data, common causes of blindness and visual impairment in the region of Eastern Herzegovina do not differ significantly from those in other regions. Registration is based on the WHO model, but it is possible only by performing active epidemiological studies.