Enlarging the spectrum of cluster headache: Extracranial autonomic involvement revealed by voice analysis.

BACKGROUND: People with cluster headache (CH) are frequently burdened by misdiagnosis or diagnostic delay. The peculiar somatic and behavioral changes characterizing patients with CH are not useful to improve diagnostic accuracy. In our clinical experience, we noticed a typical voice quality with low and croaking tone in patients with CH. In this cross-sectional study, we evaluated, by digital voice analysis, whether it is possible to identify typical voice quality characterizing patients with CH compared with healthy controls (HCs). Furthermore, to investigate whether putative differences in voice characteristics could be underpinned by constitutional aspects or pathological processes of vocal cords, subjects underwent a videolaryngostroboscopy. Smoking habits and alcohol consumption were specifically investigated. METHODS: After conducting digital recording of the voices from both patients with CH and HCs in a soundproof insulated cabin in the laboratory of the Audiology Department, a set of voice parameters was analyzed. We included the measures of fundamental frequency, calculations of jitter and shimmer, and noise-to-harmonics ratios as well as quantities related to the spectral tilt (i.e., H1-H2, H1-A1, H1-A2, and H1-A3) in 20 patients with CH and in 13 HCs. A videolaryngostroboscopy was performed in all subjects. RESULTS: Patients with CH, explored during the cluster bout period, showed significantly lower second harmonic (H1-H2) values compared with HCs (-6.9 ± 7.6 vs. 2.1 ± 6.7, p = 0.002), usually characterizing the so-called creaky voice. By using a laryngoscopy investigation, a significantly higher prevalence of mild to moderate vocal cord edema and laryngopharyngeal reflux signs were found in patients with CH (100% of patients with CH vs. 15% of HC, p < 0.001). CONCLUSION: Creaky phonation is a "physiological mode of laryngeal operation" usually underpinned by shortened and thickened vocal folds. Creaky voice phonation can be due to a vocal fold's reduced capability to become slack or flaccid secondary to vocal cord edema underpinned by laryngopharyngeal reflux affecting the phonatory mechanisms in patients with CH. The laryngopharyngeal reflux may represent a dysautonomic sign related to the increased parasympathetic tone during in-bout period, reinforcing the hypothesis of an extracranial autonomic dysfunction as part of CH clinical picture.

X-Linked Sensorineural Hearing Loss: A Literature Review.

Sensorineural hearing loss is a very diffuse pathology (about 1/1000 born) with several types of transmission. X-linked hearing loss accounts for approximately 1% - 2% of cases of non-syndromic forms, as well as for many syndromic forms. To date, six loci (DFNX1-6) and five genes (PRPS1 for DFNX1, POU3F4 for DFNX2, SMPX for DFNX4, AIFM1 for DFNX5 and COL4A6 for DFNX6) have been identified for X-linked non-syndromic hearing loss. For the syndromic forms, at least 15 genes have been identified, some of which are also implicated in non-syndromic forms. Moreover, some syndromic forms, presenting large chromosomal deletions, are associated with mental retardation too. This review presents an overview of the currently known genes related to X-linked hearing loss with the support of the most recent literature. It summarizes the genetics and clinical features of X-linked hearing loss to give information useful to realize a clear genetic counseling and an early diagnosis. It is important to get an early diagnosis of these diseases to decide the investigations to predict the evolution of the disease and the onset of any other future symptoms. This information will be clearly useful for choosing the best therapeutic strategy. In particular, regarding audiological aspects, this review highlights risks and benefits currently known in some cases for specific therapeutic intervention.

Mutational analysis for GJB2, GJB6, and GJB3 genes in Campania within a universal neonatal hearing screening programme.

OBJECTIVE: To determine the incidence of GJB2 and GJB3 mutations and of two deletions upstream of the GJB6 gene in infants of the Campania region of southern Italy. DESIGN: DNA samples from non-syndromic hearing-impaired infants enrolled in a neonatal screening programme for sensorineural hearing loss were analysed by PCR and by direct sequencing. The audiological features of infants with biallelic GJB2 mutations were also examined to identify genotype-phenotype correlations. STUDY SAMPLE: Molecular analyses were carried out in 129 affected and five unaffected infants. RESULTS: A genetic etiology of hearing loss was identified in 28% of infants, including several at environmental risk of hearing loss. Neither GJB6 nor GJB3 (a gene not previously investigated in the Campania population) mutations were found. CONCLUSIONS: This study confirms the importance of universal neonatal hearing screening. The identification of a genetic cause in infants at environmental risk indicates that such infants should be included when investigating etiology. We confirm that also in our geographical area, c.35delG homozygotes tend to have severe symmetrical hearing loss, whereas hearing impairment is milder in compound heterozygotes.

Bimodal strategy for excellent audiological rehabilitation in a subject with a novel nonsense mutation of the SLC26A4 gene: A case report.

Sensorineural hearing loss is a heterogeneous disease caused by mutations in many genes. However, in the presence of enlarged vestibular aqueduct, it is frequently associated with mutations in the solute carrier family 26 member 4 (SLC26A4), a gene causative of a syndromic form (Pendred) as well as a non-syndromic form of hearing loss (DFNB4). We describe a clinical case presenting bilateral sensorineural hearing loss and enlarged vestibular aqueduct in which a novel homozygous SLC26A4 mutation was identified. Despite a late diagnosis of hearing loss, a peculiar rehabilitation therapy strategy was identified that provided excellent results.

Phenotypic and genetic characterization of a family carrying two Xq21.1-21.3 interstitial deletions associated with syndromic hearing loss.

BACKGROUND: Sensorineural hearing impairment is a common pathological manifestation in patients affected by X-linked intellectual disability. A few cases of interstitial deletions at Xq21 with several different phenotypic characteristics have been described, but to date, a complete molecular characterization of the deletions harboring disease-causing genes is still missing. Thus, the aim of this study is to realize a detailed clinical and molecular analysis of a family affected by syndromic X-linked hearing loss with intellectual disability. RESULTS: Clinical analyses revealed a very complex phenotype that included inner ear malformations, vestibular problems, choroideremia and hypotonia with a peculiar pattern of phenotypic variability. Genomic analysis revealed, for the first time, the presence of two close interstitial deletions in the Xq21.1-21.3, harboring 11 protein coding, 9 non-coding genes and 19 pseudogenes. Among these, 3 protein coding genes have already been associated with X-linked hearing loss, intellectual disability and choroideremia. CONCLUSIONS: In this study we highlighted the presence of peculiar genotypic and phenotypic details in a family affected by syndromic X-linked hearing loss with intellectual disability. We identified two, previously unreported, Xq21.1-21.3 interstitial deletions. The two rearrangements, containing several genes, segregate with the clinical features, suggesting their role in the pathogenicity. However, not all the observed phenotypic features can be clearly associated with the known genes thus, further study is necessary to determine regions involved.

Abnormal thalamic function in patients with vestibular migraine.

OBJECTIVE: To investigate the functional response of neural pathways associated with vestibular stimulation in patients with vestibular migraine (VM). METHODS: Twelve patients with VM underwent whole-brain blood oxygen level-dependent (BOLD) fMRI during ear irrigation with cold water. The functional response of neural pathways to this stimulation in patients with VM was compared with age- and sex-matched patients with migraine without aura and healthy controls. Secondary analyses explored associations between BOLD signal change and clinical features of migraine in patients. RESULTS: We observed a robust cortical and subcortical pattern of BOLD signal change in response to ear irrigation across all participants. Patients with VM showed a significantly increased thalamic activation in comparison with both patients with migraine without aura and healthy controls. The magnitude of thalamic activation was positively correlated with the frequency of migraine attacks in patients with VM. CONCLUSIONS: We provide novel evidence for abnormal thalamic functional response to vestibular stimulation in patients with VM. These functional abnormalities in central vestibular processing may contribute to VM pathophysiology.

Exclusion of TNFRSF11B as Candidate Gene for Otosclerosis in Campania Population.

The etiology of otosclerosis is unknown. The etiopathogenesis of otosclerosis seems similar to that occurring in Paget's disease of bone, for which mutations or polymorphisms in several genes have been identified. Among these, TNFRSF11B gene encoding the osteoprotegerin is produced at high levels in the normal inner ear and at low level in active otosclerotic stapes footplates. The aim of this work was to verify the presence of a correlation between the rs2073618 (N3K) polymorphism in the TNFRSF11B gene and otosclerosis. Mutational screening in the TNFRSF11B gene was performed by direct sequencing. SNPs analysis was performed by PCR and by specific restriction enzyme assay with HpaI. The significance of the association was analyzed by statistical specific software. No causative mutation has been identified but the data suggested a strong correlation between the rs2073618 (N3K) polymorphism and otosclerosis. This correlation, however, has been excluded in a case-control study. This study excluded the association between the N3K polymorphism and otosclerosis in Campania region population.