Antonio Cesarani

Short form of the Dizziness Handicap Inventory: construction and validation through Rasch analysis.

A new item response scale is presented, which measures the severity of self-reported balance deficits. The scale, DHIsf, is a short form of the Dizziness Handicap Inventory. The scale was constructed and validated by Rasch analysis. Rasch analysis was applied to rescore or remove any items misfitting, redundant, or off-target, until an optimal instrument was obtained. The 25-item, 3-level Dizziness Handicap Inventory was, thus, reduced to the 13-item, 2-level DHIsf. The retained items explore the domains of eye/head movements, full body activities, and mood alterations. Data were collected from 55 outpatients (63 +/- 13 yr; 43 females) attending otoneurological rehabilitation referral at a general hospital because of complaints of dizziness or imbalance. They were fully independent in ambulation and showed no evidence of major neurological or orthopedic diseases. Objective tests included brain computed tomography, sovraaorctic Doppler sonography, craniocorpography, static posturography, and nystagmography. The findings were categorized as pathologic, borderline, or normal. At least one examination was borderline or abnormal in 42 patients. The DHIsf was well targeted on this sample, with a mean score of 5.7/13 (standard deviation, 2.8; median, 5; range, 1-13). The Rasch statistics showed that the 13 items evenly fitted a hierarchy of difficulty within a homogeneous construct. A moderate but significant variance explanation of DHIsf measures was provided by a two-way analysis of variance model, with craniocorpography and nystagmography as independent categorical variables (r2 = 0.15; P = 0.018). When the clinical tests were individually taken into account, their outcome (dichotomized as abnormal v borderline or normal) could not be predicted by either of the DHIsf measures or raw scores (logistic regression). The DHIsf compares favorably with the original Dizziness Handicap Inventory, shows some consistency with the instrumental findings, and provides original information on the severity of imbalance syndromes, as it is seen from the patients perspective.

A novel mutation within the MIR96 gene causes non-syndromic inherited hearing loss in an Italian family by altering pre-miRNA processing

The miR-96, miR-182 and miR-183 microRNA (miRNA) family is essential for differentiation and function of the vertebrate inner ear. Recently, point mutations within the seed region of miR-96 were reported in two Spanish families with autosomal dominant non-syndromic sensorineural hearing loss (NSHL) and in a mouse model of NSHL. We screened 882 NSHL patients and 836 normal-hearing Italian controls and identified one putative novel mutation within the miR-96 gene in a family with autosomal dominant NSHL. Although located outside the mature miR-96 sequence, the detected variant replaces a highly conserved nucleotide within the companion miR-96*, and is predicted to reduce the stability of the pre-miRNA hairpin. To evaluate the effect of the detected mutation on miR-96/mir-96* biogenesis, we investigated the maturation of miR-96 by transient expression in mammalian cells, followed by real-time reverse-transcription polymerase chain reaction (PCR). We found that both miR-96 and miR-96* levels were significantly reduced in the mutant, whereas the precursor levels were unaffected. Moreover, miR-96 and miR-96* expression levels could be restored by a compensatory mutation that reconstitutes the secondary structure of the pre-miR-96 hairpin, demonstrating that the mutation hinders precursor processing, probably interfering with Dicer cleavage. Finally, even though the mature miR-96 sequence is not altered, we demonstrated that the identified mutation significantly impacts on miR-96 regulation of selected targets. In conclusion, we provide further evidence of the involvement of miR-96 mutations in human deafness and demonstrate that a quantitative defect of this miRNA may contribute to NSHL.

Vestibular evoked myogenic potentials in multiple sclerosis: clinical and imaging correlations

Patients with multiple sclerosis (MS) frequently report symptoms related to vestibular disorders in the course of their disease. At present, the fundamental tests assessing vestibulospinal involvement are posturography and vestibular evoked myogenic potentials (VEMPs). While posturography cannot be performed in every subject requiring minimal stance control, VEMPs do not require any specific skill on the part of the subjects and they may be investigated in all patients able to sit. VEMPs were recorded for 40 patients (17 men, 23 women; mean age 38 years, range 17-71 years) fulfilling diagnostic criteria of clinically defined MS, by means of rarefaction clicks, recording modulation of sterno-cleido-mastoideus tonic contraction saccule-mediated modulation. VEMPs were found to be abnormal in 28 of 40 patients. In 18 of the cases the VEMPs were asymmetric, i.e., had a prolonged latency on one side. In six cases latency was increased on both sides (mean delay 4.1 ms). In four subjects VEMPs were absent on one side. C oncordance with clinical findings of presence/absence of brainstem involvement was found in 55% and with MRI findings in 65% of the cases. A bnormal VEMPs indicated brainstem dysfunction in four patients (10%) with normal MRI and no specific clinical signs.

Melatonin Influences Human Balance

In order to evaluate a possible correlation between melatonin, the cerebellum and, consequently, human balance, a double-blind pilot study was performed in 5 subjects with random administration of different doses of melatonin. Before and 1 h after a single administration, a complete otoneurological examination was performed. This first pilot study revealed that melatonin had effects on human equilibrium although these effects were not dosage related and were different in individual subjects. On the basis of these results, a second study was performed. Fourteen healthy volunteers were investigated before and 1 h after administration of a single dose of 10 mg melatonin. The otoneurological examination was restricted to the evaluation of: horizontal saccades, horizontal sinusoidal smooth pursuit, eyes open, eyes closed and head retroflexed static posturography. All subjects showed a decrease in posturographic performances, especially in the simplest test (eyes open) and half of them (6 out of 13) showed also impairment of eye movements. These results confirm the role of melatonin in the control of sensorimotor performances, and the cerebellar receptors might be correlated with the control of human balance.

The treatment of acute vertigo

Abstract.Vertigo and dizziness are very common symptoms in the general population. The aim of this paper is to describe the physical and pharmacological treatment of symptoms characterized by sudden onset of rotatory vertigo. Acute vertigo can be subdivided into two main groups: (1) spontaneous vertigo and (2) provoked vertigo, usually by postural changes, generally called paroxysmal positional vertigo (PPV). Sudden onset of acute vertigo is usually due to acute spontaneous unilateral vestibular failure. It can be also fluctuant as, e.g., in recurrent attacks of Ménière’s disease. Pharmacotherapy of acute spontaneous vertigo includes Levo-sulpiride i.v. , 50 mg in 250 physiologic solution, once or twice a day, methoclopramide i.m., 10 mg once or twice a day, or tiethilperazine rectally, once or twice a day, to reduce neurovegetative symptoms; diazepam i.m., 10 mg once or twice a day, to decrease internucelar inhibition, sulfate magnesium i.v., two ampoules in 500 cc physiological solution, twice a day, or piracetam i.v., one ampoule in 500 cc physiological solution, twice a day, to decrease vestibular damage. At the onset of the acute symptoms, patients must lie on their healthy side with the head and trunk raised 20°. The room must be quiet but not darkened. If the patient is able to swallow without vomiting, it is important to reduce nystagmus and stabilize the visual field with gabapentine, per os, 300 mg twice or three times a day. The first step of the physical therapy of acute vertigo is vestibular electrical stimulation, that is to say, a superficial paravertebral electrical stimulation of neck muscles, aimed to reduce antigravitary failure and to increase proprioceptive cervical sensory substitution. PPV is a common complaint and represents one of the most common entities in peripheral vestibular pathology. While the clinical picture is well known and widely described, the etiopathogenesis of PPV is still a matter of debate. Despite the different interpretation of PPV etiopathogenesis, the maneuvers described by Semont, Epley, or Lempert and their modifications are undoubtedly effective. For this reason the first therapeutic approach in acute provoked vertigo must be by means of one of these kinds of treatments.

Chronic cerebrospinal venous insufficiency in Meniere disease

Objectives The aim of this study was to focus on patients suffering from cochleo-vestibular disorder with and without Ménière disease (MD) in order to verify whether chronic cerebrospinal drainage abnormalities could play a role in the etiopathogenesis of endolymphatic hydrops. Methods Fifty-two volunteers were enrolled and subdivided into two groups: 24 definite MD and 28 not-MD. Both magnetic resonance venography imaging with contrast-enhanced imaging of the venous cerebrospinal system (MRV) and venous echo-color Doppler (ECD) were performed. Results MRV showed abnormalities in 83% of MD and 57% of not-MD subjects (p < 0.001). Asymmetrical cervical venous flow, assessed by MRV, was confirmed by ECD in 62.5% of MD but in only 21.5% of not-MD subjects (p<0.001). Conclusion Chronic cerebrospinal venous insufficiency might be the anatomical background, which provides a predisposing factor for the development of endolymphatic hydrops in MD patients.

Gluten sensitivity in Meniere's disease.

Wheat is one of the most common food allergens found in patients with Menieres disease (MD). Gluten from wheat has been identified to have a etiopathogenetic role in celiac disease, IgE hypersensitivity to wheat disease, and recently to gluten sensitivity. The aim of this study was to verify the incidence of gliadin prick test response in patients affected by MD.

Cochlear active mechanisms in young normal-hearing subjects affected by Williams syndrome: Time-frequency analysis of otoacoustic emissions

The aim of this study was to investigate the functionality of cochlear active mechanisms in normal-hearing subjects affected by Williams syndrome (WS). Transient evoked otoacoustic emissions (TEOAEs) were recorded in a group of young WS subjects and a group of typically developing control subjects, all having normal-hearing thresholds and normal middle-ear functionality. We also analysed the narrow-band frequency components of TEOAEs, extracted from the broad-band TEOAE recordings by using a time-frequency analysis algorithm based on the Wavelet transform. We observed that TEOAEs and the frequency components extracted from TEOAEs measured in WS subjects had significantly lower energy compared to the controls. Also, the narrow-band frequency components of TEOAEs measured in WS subjects had slightly increased latency compared to the controls. Overall, results would suggest a subtle (i.e., sub-clinical) dysfunction of the cochlear active mechanisms in WS subjects with otherwise normal hearing. Also, results point out the relevance of using otoacoustic emissions in the audiological evaluation and monitoring of WS subjects to early identify possible subtle auditory dysfunctions, before the onset of mild or moderate hearing loss that could exacerbate language or cognitive impairments associated with WS.

Risk factors for idiopathic sudden sensorineural hearing loss and their association with clinical outcome

BACKGROUND Sudden sensorineural hearing loss (ISSHL) is idiopathic in 85% of cases and cochlear micro-thrombosis has been hypothesized as pathogenic mechanism. The role of thrombophilia and cardiovascular risk factors in ISSHL is controversial and whether these risk factors influence the clinical outcome of ISSHL is unknown. METHODS and patients To investigate the role of thrombophilia and cardiovascular risk factors in ISSHL and to evaluate their influence on clinical outcome of the disease, 118 patients with a first episode of ISSHL and 415 healthy controls were investigated. Thrombophilia screening included measurements of antithrombin, protein C, protein S, factor V Leiden, prothrombin G20210A, antiphospholipid antibodies, fibrinogen, factor VIII and homocysteine. RESULTS Deficiencies of antithrombin, protein C or S taken together, high factor VIII and hyperhomocysteinemia were significantly associated with ISSHL (OR [95%CI]: 7.55 [1.05-54.47], 2.91 [1.31-6.44] and 2.69 [1.09-6.62], respectively), whereas no association was found with the remaining thrombophilia markers. A 2-fold increased risk of poor clinical outcome was observed for every 5 μmol/L increase of fasting homocysteine levels (adjusted OR [95%CI]) 2.13 [1.02-4.44]) until levels of approximately 15 μmol/L, then the risk increased slowly. Cardiovascular risk factors (arterial hypertension, hyperlipidemia, diabetes and smoking) were associated with an increased risk of ISSHL (OR [95%CI] 1.88 [1.17-3.03]) and with a poor clinical outcome (OR [95%CI] 2.22 [0.93-5.26]). CONCLUSIONS Hyperhomocysteinemia, high factor VIII and, with more uncertainty, deficiencies of antithrombin, protein C or S and cardiovascular risk factors increase the risk of ISSHL. Hyperhomocysteinemia and cardiovascular risk factors are associated with a poor clinical outcome of ISSHL.

Audiological findings in Williams syndrome: A study of 69 patients

The aim of this study was to investigate, in a clinical setting, the auditory function of a group of individuals affected by Williams syndrome (WS). Sixty‐nine patients with WS, aged 2–30, underwent comprehensive audiological testing including air/bone conduction behavioral audiometry, speech audiometry, tympanometry and measurement of the acoustic reflex, transient evoked otoacoustic emissions and brainstem auditory evoked responses. Hearing loss, defined by a pure‐tone average above 15 dB HL, affected 22.6% of the patients studied with traditional audiometry and was mostly slight in severity. Hearing loss was conductive in 9.4% of patients, mainly children with otitis media with effusion, and sensorineural in 13.2% of patients. However, 30% of the ears studied had a hearing impairment in the high frequency range (high‐frequency pure‐tone audiometry above 15 dB HL), higher in participants above 15 years (46.15%) than in the younger ones (23.45%). Contralateral stapedial reflexes were present in all patients with A‐type tympanograms. Transient otoacoustic emissions were absent in 44% of the ears of patients with normal hearing. Brainstem auditory evoked responses fell within normal ranges thus confirming the absence of retrocochlear dysfunction. Although hearing loss does not seem to be frequent, a cochlear fragility, especially in the high frequency range, related to outer hair cells is characteristic of WS. Therefore we strongly recommend monitoring patients affected by WS using annual audiometric tests and performing otoacoustic emissions in order to identify a subclinical cochlear dysfunction which might benefit from an audiological follow up before the possible onset of hearing loss.