Suppression of inner ear signal intensity on fluid-attenuated inversion recovery magnetic resonance imaging in cats with vestibular disease.

OBJECTIVES: Otitis media/interna (OMI) is the most common cause of peripheral vestibular disease in cats. The inner ear contains endolymph and perilymph, with perilymph being very similar in composition to cerebrospinal fluid (CSF). As a very-low-protein fluid, it would be expected that normal perilymph should suppress on fluid-attenuated inversion recovery (FLAIR) MRI sequences. Based on this, we hypothesized that MRI FLAIR sequences should provide a non-invasive way of diagnosing inflammatory/infectious diseases such as OMI in cats, something that has previously been demonstrated in humans and, more recently, in dogs. METHODS: This was a retrospective cohort study in which 41 cats met the inclusion criteria. They were placed into one of four groups, based on presenting complaint: clinical OMI (group A); inflammatory central nervous system (CNS) disease (group B); non-inflammatory structural disease (group C); and normal brain MRI (control group; group D). Transverse T2-weighted and FLAIR MRI sequences at the level of the inner ears bilaterally were compared in each group. The inner ear was selected as a region of interest using Horos, with a FLAIR suppression ratio calculated to account for variability in signal intensity between MRIs. This FLAIR suppression ratio was then compared between groups. Statistical analyses were performed by an experienced statistician, with a general linear model used to compare mean FLAIR suppression ratio, CSF nucleated cell count and CSF protein concentration between groups. RESULTS: The OMI group (group A) had significantly lower FLAIR suppression scores compared with all other groups. The CSF cell count was also significantly increased in the OMI (group A) and inflammatory CNS disease (group B) groups compared with the control group (group D). CONCLUSIONS AND RELEVANCE: This study demonstrates the utility of MRI FLAIR sequences in diagnosing presumptive OMI in cats, similarly to in humans and dogs. This study is relevant to practicing veterinary neurologists and radiologists in interpreting MRI findings in cats with suspected OMI.

Neuroimaging in Kabuki syndrome and another KMT2D-related disorder.

Recognition of distinct phenotypic features is an important component of genetic diagnosis. Although CHARGE syndrome, Kabuki syndrome, and a recently delineated KMT2D Ex 38/39 allelic disorder exhibit significant overlap, differences on neuroimaging may help distinguish these conditions and guide genetic testing and variant interpretation. We present an infant clinically diagnosed with CHARGE syndrome but subsequently found to have a de novo missense variant in exon 38 of KMT2D, the gene implicated in both Kabuki syndrome and a distinct KMT2D allelic disorder. We compare her brain and inner ear morphology to a retrospective cohort of 21 patients with classic Kabuki syndrome and to typical CHARGE syndrome findings described in the literature. Thirteen of the 21 Kabuki syndrome patients had temporal bone imaging (5/13 CT, 12/13 MRI) and/or brain MRI (12/13) which revealed findings distinct from both CHARGE syndrome and the KMT2D allelic disorder. Our findings further elucidate the spectrum of inner ear dysmorphology distinguishing Kabuki syndrome and the KMT2D allelic disorder from CHARGE syndrome, suggesting that these three disorders may be differentiated at least in part by their inner ear anomalies.

Clinical signs, MRI findings and outcome in dogs with peripheral vestibular disease: a retrospective study.

BACKGROUND: Vestibular dysfunction is relatively common in dogs, with a prevalence of 0.08% reported in primary veterinary care in the UK. There are several studies investigating how to differentiate between peripheral and central vestibular disease but only limited information regarding the possible underlying causes for peripheral vestibular dysfunction in dogs. This study therefore aimed to describe the clinical signs, magnetic resonance imaging findings (MRI), underlying causes and outcome in a large population of dogs diagnosed with peripheral vestibular disease. RESULTS: One hundred eighty-eight patients were included in the study with a median age of 6.9 years (range 3 months to 14.6 years). Neurological abnormalities included head tilt (n = 185), ataxia (n = 123), facial paralysis (n = 103), nystagmus (n = 97), positional strabismus (n = 93) and Horner syndrome (n = 7). The most prevalent diagnosis was idiopathic vestibular disease (n = 128), followed by otitis media and/or interna (n = 49), hypothyroidism (n = 7), suspected congenital vestibular disease (n = 2), neoplasia (n = 1) and cholesteatoma (n = 1). Long-term follow-up revealed persistence of head tilt (n = 50), facial paresis (n = 41) and ataxia (n = 6) in some cases. Recurrence of clinical signs was observed in 26 dogs. Increasing age was associated with a mild increased chance of diagnosis of idiopathic vestibular syndrome rather than otitis media and/or interna (P = 0.022, OR = 0.866; CI 0.765-0.980). History of previous vestibular episodes (P = 0.017, OR = 3.533; CI 1.251-9.981) was associated with an increased likelihood of resolution of the clinical signs whilst contrast enhancement of cranial nerves VII and/or VIII on MRI (P = 0.018, OR = 0.432; CI 0.251-0.868) was associated with a decreased chance of resolution of the clinical signs. CONCLUSIONS: Idiopathic vestibular disease is the most common cause of peripheral vestibular dysfunction in dogs and it is associated with advanced age. Incomplete recovery from peripheral vestibular disease is common, especially in dogs presenting with cranial nerve enhancement on MRI but less so if there is previous history of vestibular episodes.

Phenotypic expansion of KMT2D-related disorder: Beyond Kabuki syndrome.

Pathogenic variants in KMT2D, which encodes lysine specific methyltransferase 2D, cause autosomal dominant Kabuki syndrome, associated with distinctive dysmorphic features including arched eyebrows, long palpebral fissures with eversion of the lower lid, large protuberant ears, and fetal finger pads. Most disease-causing variants identified to date are putative loss-of-function alleles, although 15-20% of cases are attributed to missense variants. We describe here four patients (including one previously published patient) with de novo KMT2D missense variants and with shared but unusual clinical findings not typically seen in Kabuki syndrome, including athelia (absent nipples), choanal atresia, hypoparathyroidism, delayed or absent pubertal development, and extreme short stature. These individuals also lack the typical dysmorphic facial features found in Kabuki syndrome. Two of the four patients had severe interstitial lung disease. All of these variants cluster within a 40-amino-acid region of the protein that is located just N-terminal of an annotated coiled coil domain. These findings significantly expand the phenotypic spectrum of features associated with variants in KMT2D beyond those seen in Kabuki syndrome and suggest a possible new underlying disease mechanism for these patients.

Holoprosencephaly in Kabuki syndrome.

Kabuki syndrome is a rare, multi-systemic disorder of chromatin regulation due to mutations in either KMT2D or KDM6A that encode a H3K4 methyltransferase and an H3K27 demethylase, respectively. The associated clinical phenotype is a direct result of temporal and spatial changes in gene expression in various tissues including the brain. Although mild to moderate intellectual disability is frequently recognized in individuals with Kabuki syndrome, the identification of brain anomalies, mostly involving the hippocampus and related structures remains an exception. Recently, the first two cases with alobar holoprosencephaly and mutations in KMT2D have been reported in the medical literature. We identified a de novo, pathogenic KMT2D variant (c.6295C > T; p.R2099X) using trio whole-exome sequencing in a 2-year-old female with lobar holoprosencephaly, microcephaly and cranio-facial features of Kabuki syndrome. This report expands the spectrum of brain anomalies associated with Kabuki syndrome underscoring the important role of histone modification for early brain development.

The effect of canal diameter on audiologic results in patients with cochlear implantation with large vestibular aqueduct syndrome.

PURPOSE: To compare audiologic results according to vestibular aqueduct (VA) diameter in patients who have undergone cochlear implantation and were diagnosed with LVAS. METHODS: This was a retrospective study detailing the outcomes of 18 patients with LVAS and 18 patients undergone cochlear implants. VA diameter was assessed by magnetic resonance imaging and computed tomography. Categories of Auditory Perception (CAP) and Speech Intelligibility Rating (SIR) were assessed in all patients, and speech audiometry, including speech recognition thresholds (SRT) and word discrimination scores, was applied for all subjects who were able to perform these tests. All audiologic parameters were compared between patients with and without LVAS, and the relationship of these parameters with VA diameter was investigated. RESULTS: The control group consisted of 18 subjects (5 males, 13 females), ranging in age between 2 and 34 years (mean 13.17 ± 8.97 years). The research group consisted of 18 subjects (8 males, 10 females), ranging in age between 2 and 35 years (mean 13.28 ± 8.96 years). There was a statistically significant difference between the groups in terms of SIR and CAP pre-post differences (Mann-Whitney U test, p < 0.05), with higher averages in the LVAS group. No statistically significant correlations were found between VA diameter on computed tomography and magnetic resonance imaging and the audiologic variables collected. CONCLUSIONS: Patients with LVAS benefit from cochlear implant surgery and VA parameters do not affect audiologic parameters.

[Imaging characteristics of patients with large vestibular aqueduct syndrome and its relationship with the acoustically evoked short latency negative response].

Objective: To explore the imaging characteristics of large vestibular aqueduct syndrome (LVAS) patients and their relationship with the acoustically evoked short latency negative response (ANSR), so as to provide reference for the diagnosis of LVAS. Methods: Clinical data of 174 patients(334 ears) with LVAS diagnosed and treated by the Department of Otorhinolaryngology Head and Neck Surgery of the First Affiliated Hospital of Guangxi Medical University, from October 2009 to December 2017 were retrospectively analyzed, including 117 males and 57 females, aged from 5 months to 47 years old, with the median age of 4 years and 4 months. ABR and imaging data of patients were collected. Midpoint diameter and the outlet diameter of the vestibular aqueduct were measured on CT images, the midpoint diameter of the intraosseous parts and the extraosseous parts of enlarged endolymphatic sac(EES) were measured on MRI images. The correlation between the above measurements was analyzed by Pearson test using SPSS 17.0. According to whether ASNR was detected in ABR, the above data were divided into two groups, and the differences of the above imaging measurements were compared by the Independent-Sample Test. Results: The average midpoint diameter of the vestibular aqueduct was (1.87±0.58) mm (x±s, the following was the same), and the outlet diameter was (3.07±0.99) mm on CT; the average midpoint diameter of the intraosseous parts in enlarged endolymphatic sac(EES) was (2.39±1.37) mm, and the extraosseous parts was (2.50±2.18) mm on MRI. There was a correlation between the four measurements (P<0.05), among which the midpoint diameter of vestibular aqueduct was strongly positively correlated with the outlet diameter (r=0.760), and the remaining pairs were weakly correlated. ASNR was detected in 241 ears (72.16%,241/334) and undetected in 93 ears (27.84%, 93/334) of the 334 ears with LVAS. Midpoint diameter and the outlet diameter of the vestibular aqueduct in no ASNR group were smaller than the ASNR group, and the difference was statistically significant (t value was 2.814 and 2.754, P<0.05). There was no significant difference in the midpoint diameter of the intraosseous parts and the extraosseous parts of enlarged endolymphatic sac between the two groups, and the difference was no statistically significant(t value was 0.101 and 0.683, P>0.05). Conclusions: There is a strong positive correlation between the midpoint diameter of vestibular aqueduct and the outlet diameter in LVAS patients. There is a certain correlation between the size of vestibular aqueduct and the size of endolymphatic sac. The smaller the diameter of vestibular aqueduct, the lower the occurrence rate of ASNR.

Tumor-to-Tumor Metastasis of Hepatocellular Carcinoma to Vestibular Schwannoma.

BACKGROUND: Intracranial metastasis is a common complication of systemic malignancy. A rare subset of intracranial masses constitutes tumor-to-tumor metastasis, in which an extracranial neoplasm hematogenously spreads to an existing intracranial lesion. CASE DESCRIPTION: Here we present the unique case of a 59-year-old man with known hepatocellular carcinoma who presented with acute headaches, double vision, vertigo, and gait instability in the context of 2 years of right-sided hearing loss. Head imaging showed a heterogeneous right cerebellopontine angle mass extending into the porus acousticus with adjacent cerebellar edema. Histopathologic analysis after resection found coexisting hepatocellular carcinoma within a vestibular schwannoma. CONCLUSIONS: Tumor-to-tumor metastasis is an important consideration in the diagnostic work-up and treatment of patients with known systemic malignancy who present with a new intracranial lesion. This pathologic entity could be missed if this patient were treated with single-fraction radiosurgery such as Gamma Knife.

Extension patterns of vestibular schwannomas towards the middle ear: three new cases and review of the literature.

OBJECTIVE: Middle ear extension of vestibular schwannomas is not a common occurrence, and only a few cases have been described so far in past publications. We report three new cases of vestibular schwannomas extending to the middle ear and reviewed the literature to specify the patterns of such an extension. MATERIALS AND METHODS: We analysed databases of previously published articles to search for additional cases of middle ear extension of vestibular schwannomas and compared them to the cases we have documented. Extension patterns of the tumours were analysed, especially focusing on the extension through the round and oval windows. RESULTS AND CONCLUSION: Middle ear vestibular schwannomas are uncommon tumours and only 13 cases have been published so far. The vestibular schwannoma (internal auditory canal or intralabyrinthine) has to invade the labyrinth first (complete invasion in 88% of the cases, n = 14), before reaching the middle ear. In the majority of cases (69%, n = 11/16), internal auditory canal vestibular schwannomas or intralabyrinthine schwannomas extended in the middle ear though the round window.

Is CT or MRI the optimal imaging investigation for the diagnosis of large vestibular aqueduct syndrome and large endolymphatic sac anomaly?

BACKGROUND AND PURPOSE: We explored whether there was a difference between measurements obtained with CT and MRI for the diagnosis of large vestibular aqueduct syndrome or large endolymphatic sac anomaly, and whether this influenced diagnosis on the basis of previously published threshold values (Valvassori and Cincinnati). We also investigated whether isolated dilated extra-osseous endolymphatic sac occurred on MRI. Secondary objectives were to compare inter-observer reproducibility for the measurements, and to investigate any mismatch between the diagnoses using the different criteria. MATERIALS/METHODS: Subjects diagnosed with large vestibular aqueduct syndrome or large endolymphatic sac anomalies were retrospectively analysed. For subjects with both CT and MRI available (n = 58), two independent observers measured the midpoint and operculum widths. For subjects with MRI (± CT) available (n = 84), extra-osseous sac widths were also measured. Results There was no significant difference between the width measurements obtained with CT versus MRI. CT alone diagnosed large vestibular aqueduct syndrome or large endolymphatic sac anomalies in 2/58 (Valvassori) and 4/58 (Cincinnati), whilst MRI alone diagnosed them in 2/58 (Valvassori). There was 93% CT/MRI diagnostic agreement using both criteria. Only 1/84 demonstrated isolated extra-osseous endolymphatic sac dilatation. The MRI-based LVAS/LESA diagnosis was less dependent on which criteria were used. Midpoint measurements are more reproducible between observers and between CT/MR imaging modalities. CONCLUSION: Supplementing MRI with CT results in additional diagnoses using either criterion, however, there is no net increased diagnostic sensitivity for CT versus MRI when applying the Valvassori criteria. Isolated enlargement of the extra-osseous endolymphatic sac is rare.

Comparison among ultrasonic, electrical apparatus, and toxic chemicals for vestibular lesion in mice.

BACKGROUND: The vestibular lesion (VL) is required to examine the physiological function of the vestibular system in animals. Toxic chemicals or electrical apparatus have been used for the VL, however, they are not ideal as they have low specificity, and can result in unintended damage, and systemic toxic effect. NEW METHOD: Localized vibration-induced VL, using an ultrasonicator, is expected to overcome the problems associated with chemical and electrical lesions. Thus, we examined the effect of the ultrasonication on the VL from the aspects of both the physiological function and histology in the present study. RESULTS: and Comparison with Existing Method(s) Complete VL, which was evaluated by deterioration of swimming skills, righting reflex, and body stability, was induced using an ultrasonicator or electrical apparatus. Histological evaluation shows that hair cell layers in the saccule and utricle were completely destroyed in both methods Furthermore, significant drop in body mass was observed in VL. However, abscess at the cranial base was observed in VL induced by the electrical apparatus in ICR mice. Complete chemically-induced VL was observed in C57BL/6J but not ICR mice, and systemic leakage of the toxic chemicals (arsenic) was not detectable even 1day after surgery. CONCLUSIONS: Compared to the electrical apparatus, the ultrasonicator is useful for inducing VL in ICR and C57BL/6J mice, as it results in less non-specific damage. Toxic chemicals can be used for inducing VL in C57BL/6J mice; however, this method does not ensure complete disruption of the hair cells in the saccule and utricle.

Incidental findings on magnetic resonance imaging of the internal auditory meatus performed to investigate audiovestibular symptoms.

OBJECTIVE: To determine the frequency of incidental findings found on magnetic resonance imaging scans of the internal auditory meatus performed to investigate audiovestibular symptoms, and to determine how to best manage these when found. METHOD: A retrospective review was conducted of internal auditory meatus magnetic resonance imaging scans during a three-month period in the radiology department at a UK district general hospital. RESULTS: A total of 109 scans were reviewed. Of these, 92.7 per cent showed no retrocochlear pathology, 0.9 per cent showed vestibular schwannoma, 6.4 per cent revealed vascular loops, and 2.8 per cent showed incidental findings that warranted further action and investigation. Of the scans, 40.4 per cent showed other incidental pathologies such as age-related ischaemic changes, and sinus disease that required no further intervention. Of the magnetic resonance imaging scans reviewed, 49.5 per cent were entirely normal. CONCLUSION: Almost half of the scans investigating audiovestibular symptoms showed incidental findings. Otolaryngologists should have an understanding of the significance of the most commonly encountered incidental findings, and should counsel patients appropriately and refer them onward when necessary.

Complications of microsurgery of vestibular schwannoma.

BACKGROUND: The aim of this study was to analyze complications of vestibular schwannoma (VS) microsurgery. MATERIAL AND METHODS: A retrospective study was performed in 333 patients with unilateral vestibular schwannoma indicated for surgical treatment between January 1997 and December 2012. Postoperative complications were assessed immediately after VS surgery as well as during outpatient followup. RESULTS: In all 333 patients microsurgical vestibular schwannoma (Koos grade 1: 12, grade 2: 34, grade 3: 62, and grade 4: 225) removal was performed. The main neurological complication was facial nerve dysfunction. The intermediate and poor function (HB III-VI) was observed in 124 cases (45%) immediately after surgery and in 104 cases (33%) on the last followup. We encountered disordered vestibular compensation in 13%, permanent trigeminal nerve dysfunction in 1%, and transient lower cranial nerves (IX-XI) deficit in 6%. Nonneurological complications included CSF leakage in 63% (lateral/medial variant: 99/1%), headache in 9%, and intracerebral hemorrhage in 5%. We did not encounter any case of meningitis. CONCLUSIONS: Our study demonstrates that despite the benefits of advanced high-tech equipment, refined microsurgical instruments, and highly developed neuroimaging technologies, there are still various and significant complications associated with vestibular schwannomas microsurgery.

Posterior semicircular canal dehiscence: CT prevalence and clinical symptoms.

OBJECTIVE: To estimate the prevalence of and symptoms associated with posterior semicircular canal dehiscence (PSCD) compared to superior semicircular canal dehiscence (SSCD) and nondehiscent semicircular canals (NDSC). STUDY DESIGN: Retrospective review. SETTING: Academic tertiary referral center. PATIENTS: Review of 412 temporal bone CT scans and associated patient records, excluding patients with prior mastoid or skull base surgery. INTERVENTION(S): CT images (0.625 mm thick) were reviewed in the planes of the semicircular canals. Patient demographics and symptoms were tabulated and analyzed. MAIN OUTCOME MEASURE(S): Prevalence of PSCD and SSCD; degree of hearing loss; presence or absence of aural fullness, autophony, tinnitus, pulsatile tinnitus, disequilibrium, vertigo, and Tullio phenomenon. RESULTS: Review of the 412 CT scans revealed 5 cases of PSCD (1.2%) and 20 cases of SSCD (4.9%). All patients with PSCD were male, aged 16 to 73 years. One patient with PSCD reported tinnitus, autophony, disequilibrium, vertigo, and Tullio phenomenon; 2 patients reported only tinnitus and aural fullness, and 1 patient had no symptoms. PSCD was commonly associated with SSCD. There were no significant differences in symptoms between PSCD patients and the other groups. There were, however, statistically significant differences between SSCD patients and NDSC patients in the rates of autophony, tinnitus, and disequilibrium. CONCLUSION: The prevalence of PSCD in patients undergoing temporal bone CT scans is considerably less than SSCD (1.2% versus 4.9%), and the 2 conditions commonly coexist. Given the small numbers in our study, we were not able to demonstrate any distinguishable clinical features for the PSCD patients.

[The clinical application of gene chips combined with CT examination in the diagnosis of large vestibular aqueduct syndrome patients].

OBJECTIVE: To explore the feasibility and superiority of the gene chip method and temporal bone CT in diagnosis of large vestibular aqueduct syndrome. METHOD: One hundred and eighty-eight cases of deaf students in Guangzhou were selected,the microarray detection of the SLC26A4 gene locus was performed,and the 26 cases of students with detected SLC26A4 gene mutations received temporal bone CT imaging. RESULT: Among the detected 26 cases of patients with hearing loss, IVS7-2A>G homozygous mutation was found in 7 cases, 17 cases were heterozygous mutation, 2168A>G heterozygous mutation presented in three cases, including one case of IVS7-2A>G and 2168A>G compound heterozygous mutations. Temporal bone CT findings of 25 cases among the 26 patients showed bilateral large vestibular aqueduct,among which 9 cases exhibited bilateral cochlear malformations, and 1 case was normal. CONCLUSION: Among the different SLC26A4 gene mutations, IVS7-2A>G point mutation rates the highest, followed by 2168A>G. Most of the CT examination prompted the expansion of the vestibular aqueduct. Deafness gene chip hotspot detection of SLC26A4 gene mutations can diagnose such patients before CT examination,which can be used for screening people with high risk of deafness prenatal screening. The early detection and early diagnosis can guide proper precautionary measures in advance to prevent the occurrence of prelingual deafness.

The association between semicircular canal dehiscence and Chiari type I malformation.

OBJECTIVE: To investigate the association between semicircular canal dehiscence (SCD) and Chiari type I malformation (CM-I). DESIGN: Retrospective case series. SETTING: Military tertiary referral center. PATIENTS: Adult patients with SCD. INTERVENTION: Review of records of patients diagnosed as having SCD for the radiologic diagnosis of CM-I and presenting symptoms. MAIN OUTCOME MEASURES: The prevalence of CM-I among patients with SCD and the presenting symptoms of patients with SCD with and without a coexistent CM-I. RESULTS: Of 32 patients diagnosed as having SCD, 30 underwent magnetic resonance imaging of the brain. Seven patients (23%; 95% confidence interval [CI], 12%-41%) were found to have a CM-I. Chiari type I malformation was associated with superior SCD in 3 of 26 patients (12%; 95% CI, 3%-30%). Of 10 patients with bilateral superior SCD, 2 (20%; 95% CI, 5%-52%) had a CM-I. Five of 6 patients (83%; 95% CI, 42%-99%) had a CM-I with unilateral or bilateral posterior SCD. Twenty-nine records were reviewed for presenting symptoms, and no significant difference was observed between patients with SCD alone and those with an associated CM-I (P = .09-.64). CONCLUSIONS: Among patients with SCD, the prevalence of CM-I is elevated. This association is especially marked in patients with posterior SCD. This finding suggests a relationship between CM-I and SCD, particularly with posterior SCD.