Rocco Bruno

Hearing impairment in genotyped Wolfram syndrome patients.

Objectives: Wolfram syndrome is a progressive neurodegenerative syndrome characterized by the features “DIDMOAD” (diabetes insipidus, diabetes mellitus, optic atrophy, and deafness). We sought to study the audiometric data of genotyped Wolfram syndrome patients with sensorineural hearing impairment. Methods: Pure tone threshold data of 23 Wolfram syndrome patients were used for cross-sectional analysis in subgroups (age less than 16 years or between 19 and 25 years, gender, and origin). Results: All subgroups, with 1 exception, showed a fairly similar type of hearing impairment with, on average, thresholds of about 25 dB (range, 0 to 65 dB) at 0.25 to 1 kHz, gently sloping downward to about 60 dB (range, 25 to 95 dB) at 8 kHz. The subgroup of Dutch women, which was excluded from the calculations of the average hearing thresholds, showed a higher degree of hearing impairment. Only the latter subgroup showed progression; however, contrary to the previous longitudinal analysis, progression was not significant in the present cross-sectional analysis, presumably because of the high degree of cross-subject variability. Conclusions: This unique collection of audiometric data from genotyped Wolfram syndrome patients shows no substantial progression in sensorineural hearing impairment with advancing age, no relation to the types of WFS1 mutations identified, and, with exclusion of the subgroup of Dutch female patients, no significant sex-related differences.

Clinical pharmacology of melatonin in the treatment of tinnitus: a review

PurposeWe performed a review with the purpose to summarise, analyse and discuss the evidence provided by clinical studies evaluating effectiveness of melatonin in the cure of tinnitus. Due to the fact that there is no satisfactory treatment for tinnitus, clinical research has explored new therapeutic approaches.MethodsA search of Pubmed, Medline, Embase, Central and Google Scholar was conducted to find trials published prior March 2014 on melatonin in the treatment of tinnitus. Design of the studies, randomization, allocation concealment procedures and diagnostic instruments (scales for tinnitus evaluation) were critical evaluated.ResultsFive clinical studies have been included. Three of them tested effectiveness of melatonin alone, the remaining two along with sulpiride and sulodexide respectively. Considered clinical trials adopted various experimental designs: single arm, randomised placebo-controlled and randomised placebo-controlled followed by crossover. These studies were characterised by several methodological weaknesses.ConclusionConfirmation of melatonin clinical effectiveness in the treatment of tinnitus cannot be given in the light of the biases observed in the considered evidence. Melatonin seems to improve sleep disturbance linked to tinnitus.

Prevalence of Deafness-Associated Connexin-26 (GJB2) and Connexin-30 (GJB6) Pathogenic Alleles in a Large Patient Cohort from Eastern Sicily.

Mutations in the gene encoding the gap junction protein connexin 26 (GJB2) and connexin 30 (GJB6) have been shown to be a major contributor to prelingual, sensorineural, nonsyndromic deafness.

Audiomotor Integration in Minimally Conscious State: Proof of Concept!

Patients suffering from chronic disorders of consciousness (DOC) are characterized by profound unawareness and an impairment of large-scale cortical and subcortical connectivity. In this study, we applied an electrophysiological approach aimed at identifying the residual audiomotor connectivity patterns that are thought to be linked to awareness. We measured some markers of audiomotor integration (AMI) in 20 patients affected by DOC, before and after the application of a repetitive transcranial magnetic stimulation protocol (rTMS) delivered over the left primary motor area (M1), paired to a transauricular alternating current stimulation. Our protocol induced potentiating of the electrophysiological markers of AMI and M1 excitability, paired to a clinical improvement, in all of the patients with minimally conscious state (MCS) but in none of those suffering from unresponsive wakefulness syndrome (UWS). Our protocol could be a promising approach to potentiate the functional connectivity within large-scale audiomotor networks, thus allowing clinicians to differentiate patients affected by MCS from UWS, besides the clinical assessment.

Could autonomic system assessment be helpful in disorders of consciousness diagnosis? A neurophysiological study

Although patients with chronic disorders of consciousness (DOC), including unresponsive wakefulness syndrome (UWS) and minimally conscious state (MCS), show a limited repertoire of awareness signs, owing to a large-scale cortico–thalamo–cortical functional disconnectivity, an activation of some cortical areas in response to relevant stimuli has been described by means of electrophysiological and functional neuroimaging approaches. In addition, cognitive processes associated with autonomic nervous system (ANS) responses elicited by nociceptive stimuli have been identified in some DOC patients. In an attempt to identify ANS functionality markers that could be useful in differentiating UWS and MCS individuals, we measured the amplitude, latency and γ-band power (γPOW) of ultra-late laser-evoked potentials (CLEPs) and skin reflex (SR), which both express some aspects of cognitive processes related to ANS functionality, besides other ANS parameters either during a 24hh-polygraphy or following a solid-state laser repetitive nociceptive stimulation. MCS showed physiological modification of vital signs (O2 saturation, hearth rate, hearth rate variability) throughout the night and a preservation of SR-γPOW, whereas UWS did not show significant variations. Following repetitive nociceptive stimulation, MCS patients had a significant increase in CLEP-γPOW, O2 saturation, hearth rate, and hearth rate variability, whereas UWS individuals did not show any significant change (but two patients, who reached high Coma Recovery Scale-Revised scores). Hence, our work suggests that a wide-spectrum electrophysiological evaluation of ANS functionality may support DOC differential diagnosis. Interestingly, the two above-mentioned UWS patients showed MCS-like vital sign modifications and electrophysiological pain responsiveness. It is therefore hypothesizable that our approach could be helpful in identifying residual aware autonomic system-related cognitive processes even in some UWS patients. Such issue draws the attention to either DOC clinical diagnosis or adequate pain treatment in DOC patients.

Neonatal stridor and laryngeal cyst: Which comes first?

Neonatal stridor is a rare condition usually caused by laryngomalacia. Congenital laryngeal cyst represents an uncommon cause of stridor in the neonatal population and may be misinterpreted as laryngomalacia, leading to serious morbidity and mortality if diagnosis and treatment are delayed. Herein we report the case of a full‐term infant with stridor, feeding problems and failure to thrive. Initially, direct laryngoscopy diagnosed only laryngomalacia. As stridor worsened, however, and respiratory distress appeared, repeat laryngoscopy showed vallecular laryngeal cyst, visible macroscopically. The patient was successfully treated with endoscopic marsupialization. There was no evidence of recurrence at follow up after 3 months. This case highlights the importance of laryngoscopic assessment for suspected laryngeal abnormalities in infants with stridor. If symptoms worsen, endoscopy should be repeated, because congenital laryngeal cysts may not be immediately visible macroscopically.

Phonosurgery debulking and pharmacological treatment of human papillomavirus patient with recurrent respiratory papillomatosis and vocal outcomes

We are presenting this case, a 56-year-old woman, with laryngeal papillomatosis involving both vocal cords and anterior commissure, treated with cold phonosurgical debulking and laser CO 2 surgery, with respect to the mucosa of anterior commissure, and cidofovir and indolo-3-carbinolo, in order to explain the physiopathological principles of the treatment, the surgical methods and the long term results (8 years and 6 months) in absence of sequelae and vocal outcomes.

Therapeutic efficacy of the Galletti–Contrino manoeuvre for benign paroxysmal positional vertigo of vertical semicircular canals in overweight subjects

ObjectiveTo compare the Galletti–Contrino manoeuvre with the more widely used Semont–Toupet in overweight subjects presenting with benign paroxysmal positional vertigo (BPBV) of vertical semicircular canals (posterior and anterior canals).Study designProspective cohort study.Patients204 patients (BMI range 25–30) with a diagnosis of BPPV of vertical semicircular canals were randomly divided in two groups treated with two different maneuvers: Galletti–Contrino (Group A) and Semont–Toupet manoeuvre (Group B). The results were compared with those obtained from a control group (204 non-overweight subjects with BPV of vertical semicircular canals.)InterventionGalletti Contrino/ Semont Toupet manoeuvres.Main outcome measure(s)Liberatory nystagmus or vertigo after maximum 2 maneuvers. Vertigo and dizziness intensity scores (Visual analogue scale VAS 0–10) from day 0 to day 5 following the repositioning manoeuvre were also recorded in responsive patients.ResultsWhile in non-overweight subjects no significant difference comparing the effectiveness of the two manoeuvres was found, liberatory nystagmus and vertigo were more frequently observed after Galletti Contrino manoeuvre in overweight subjects; this difference was statistically significant when posterior canals were involved (P < 0.03). Vertigo and dizziness VAS scores reduced significantly from day 0 to day 5 after therapy in all groups. A more significant reduction of dizziness VAS was recorded in patients undergoing Galletti–Contrino manoeuvre at days 4–5 (P < 0.005).ConclusionGalletti–Contrino manoeuvre seems to be significantly more effective than Semont–Toupet manoeuvre in the treatment of BPPV of posterior semicircular canal and may be preferential in patients with limited body movements.

Reducing the rate of misdiagnosis in patients with chronic disorders of consciousness: Is there a place for audiovisual stimulation?

BACKGROUND The patients with chronic Disorders of Consciousness (DoC) mostly present with extremely challenging differential diagnosis. The advanced analysis of electroencephalographic (EEG) signals induced by brain stimulation paradigms may provide an appropriate approach to differentiate patients with DoC, besides the clinical assessment. OBJECTIVE This study was performed with an objective of identifying residual brain network perturbations following an innovative, non-invasive audiovisual stimulation protocol, which could be related to behavioral responsiveness in patients with DoC. METHODS The study comprised of ten healthy controls (HC), seven patients with Minimally Conscious State (MCS), and nine patients with Unresponsive Wakefulness Syndrome (UWS). Both synchronous as well as asynchronous transorbital and transauricolar alternating current were employed as stimuli and their effects were measured in terms of functional and effective connectivity. RESULTS A more noticeable deterioration of long range connectivity patterns were found in patients with UWS than in those with MCS, with an exception of two patients with UWS, who showed connectivity values similar to those of MCS patients. CONCLUSION The audiovisual stimulation paradigm used in the present study may be employed as a supportive bedside tool for improving the differential diagnosis in patients with DoC.

Twist and turn into chronic disorders of consciousness: Potential role of the auditory stapedial reflex

BACKGROUND Patients suffering from chronic disorders of consciousness (DOC), including minimally conscious state (MCS) and unresponsive wakefulness syndrome (UWS), typically show an awareness impairment paralleled by a significant reflex hyper-excitability, which depend on the cortical deafferentation following brain-damage-induced thalamocortical system deterioration. Nonetheless, recent studies have shown a residual preservation of cortico-subcortical pathways that may sustain residual fragments of awareness in some DOC patients. OBJECTIVE The aim of our study was to assess whether the cortical modulation of auditory stapedial reflex (ASR) could be a marker of a higher degree of brain network connectivity, which is a fundamental prerequisite for awareness generation and maintenance. METHODS We applied a repetitive transcranial magnetic stimulation (rTMS) protocol over the primary auditory area and measured the neuromodulation effects on ASR threshold (ASRt) in a DOC sample and a healthy control group (HC). RESULTS We observed an ASRt reduction in all the HC and MCS individuals, in parallel to a better sound-induced motor responsiveness in MCS sample, while all the UWS patients, but two, did not show any significant ASRt modulation. CONCLUSION We hypothesize that our conditioning protocol may have entrained and potentiated some spared cortico-subcortical networks that sustained the clinical and electrophysiological amelioration we found. Our data electrophysiologically demonstrate for the first time that primary the auditory area can influence ASR elicitation, and such finding may support the DOC differential diagnosis.