Ernesto Bruno

Body sway in diabetic neuropathy.

OBJECTIVE To evaluate the influence of peripheral neuropathy on body sway assessed by posturography. RESEARCH DESIGN AND METHODS The age-matched study subjects included 10 insulin-dependent diabetes mellitus (IDDM) patients with peripheral neuropathy (DN), 23 IDDM patients without peripheral neuropathy (D) according to the San Antonio Consensus Conference guidelines, and 21 control subjects (C). All subjects with symptoms and/or clinical signs of postural instability were excluded from the study. RESULTS The trace surface was significantly larger in the DN than in the C and D groups (P < 0.05), and the trace length was longer in the DN than in the C and D groups (P < 0.01). Mean velocity was faster in the DN than in the other two groups (P < 0.001). A direct relationship was found between the parameters of posturography and some parameters of the nerve conduction velocity. CONCLUSIONS Diabetic patients with peripheral neuropathy demonstrate a relative deficit in their ability to maintain posture. Posturography allows an early disclosure of the failure of postural control.

Postural Rearrangement in IDDM Patients With Peripheral Neuropathy

OBJECTIVE To evaluate the influence of diabetic peripheral neuropathy on postural strategy. RESEARCH DESIGN AND METHODS Static posturography and nerve conduction velocity were performed in the following age-matched subjects: 10 IDDM patients with peripheral neuropathy, 23 IDDM patients without peripheral neuropathy, and 21 control subjects. All subjects with signs or symptoms of postural instability were excluded from the study. The following posturographic parameters were drawn: 1) velocity of body sway, expressed as mean velocity and average of the SDs, 2) VFY, the parameter derived from the velocity variance and the anteroposterior mean position of the body (this parameter monitors the postural strategy pursued by the subject), and 3) fast Fourier transformation on the x (FFTX) and y (FFTY) planes, spectral analysis of the frequencies of body oscillation on frontal (x) and anteroposterior (y) planes. RESULTS Mean velocity and its SD were higher in IDDM patients with peripheral neuropathy than in control subjects and IDDM patients without peripheral neuropathy (P < 0.001). VFY was increased in IDDM patients with peripheral neuropathy versus control subjects and IDDM patients without peripheral neuropathy (P < 0.01). A direct relationship was found between parameters of posturography and some parameters of nerve conduction tests. CONCLUSIONS Diabetic patients with peripheral neuropathy demonstrate a shift from physiological ankle control to hip postural control as monitored by specific posturography analysis.

Contribution of Central Neuropathy to Postural Instability in IDDM Patients With Peripheral Neuropathy

OBJECTIVE To evaluate the contribution of central neuropathy on postural impairment observed in diabetic patients with peripheral neuropathy. RESEARCH DESIGN AND METHODS Central sensory and motor nervous propagation, nerve conduction velocity, and static posturography were assessed in the following age-matched subjects: 7 IDDM patients with peripheral neuropathy (group DN), 18 IDDM patients without peripheral neuropathy (group D), and 31 control subjects (group C). Somatosensory-evoked potentials (SEPs) during tibial nerve stimulation were recorded, and the spine-to-scalp sensory central conduction time (SCCT) was evaluated. Motor-evoked potentials (MEPs) were recorded from leg muscles during magnetic transcranial brain stimulation, and the scalp-to-spine motor central conduction time (MCCT) was evaluated. The following posturographic parameters were calculated from the statokinesigram: trace length, trace surface, velocity of body sway with its standard deviation, and VFY (a parameter derived from the velocity variance and the anteroposterior mean position of the body). RESULTS SCCT was significantly higher in the DN group than in the C and D groups (P < 0.001). MCCT was similar in all groups. Posturographic parameters were all significantly impaired in the DN group (P < 0.01). While posturographic parameters showed a direct relationship with some parameters of peripheral nerve conduction, no correlations were observed with SEP and MEP central conduction time. These results were also confirmed by logistic regression, which indicates peripheral neuropathy as the only implicating factor in postural instability (odds ratio 0.22, 95% CI 0.07–0.75) after data reduction by means of factor analysis. CONCLUSIONS Although diabetic patients with peripheral neuropathy show a delay in central sensory conduction, postural instability may be fully explained by the presence of peripheral neuropathy.

Vestibular compensation: analysis of postural re-arrangement as a control index for unilateral vestibular deficit.

&NA; Patients with an acute unilateral vestibular lesion show an impaired balance control.The initial presentation is vertigo followed by postural instability; but with time, the global balance functions can be completely restored by a process called vestibular compensation. The aim of our study was to evaluate short and long‐term variations of postural parameters in 20 patients affected by vestibular neuritis (VN), and to compare these patients to 20 normal individuals using computerized static posturography (CSP) along with patient feedback throughout the spectral frequency analysis. This analysis showed in patients with no residual dizziness a frequency shift of body sway from low to middle frequencies as a probable expression of the compensatory strategies used by the central nervous system. On the other hand, patients with persistence of postural instability did not show any frequency shift. Our results seem to provide an early index of a proper occurring compensation so that we can adjust therapeutic protocols according to each patients functional modifications.

Connexin 26 (GJB2) mutations, causing KID Syndrome, are associated with cell death due to calcium gating deregulation.

The autosomic dominant KID Syndrome (MIM 148210), due to mutations in GJB2 (connexin 26, Cx26), is an ectodermal dysplasia with erythematous scaly skin lesions, keratitis and severe bilateral sensorineural deafness. The Cx26 protein is a component of gap junction channels in epithelia, including the cochlea, which coordinates the exchange of molecules and ions. Here, we demonstrate that different Cx26 mutants (Cx26D50N and Cx26G11E) cause cell death in vitro by the alteration of intra-cellular calcium concentrations. These results help to explain the pathogenesis of both the hearing and skin phenotypes, since calcium is also a potent regulator of the epidermal differentiation process.

Early and Phasic Cortical Metabolic Changes in Vestibular Neuritis Onset

Functional brain activation studies described the presence of separate cortical areas responsible for central processing of peripheral vestibular information and reported their activation and interactions with other sensory modalities and the changes of this network associated to strategic peripheral or central vestibular lesions. It is already known that cortical changes induced by acute unilateral vestibular failure (UVF) are various and undergo variations over time, revealing different cortical involved areas at the onset and recovery from symptoms. The present study aimed at reporting the earliest change in cortical metabolic activity during a paradigmatic form of UVF such as vestibular neuritis (VN), that is, a purely peripheral lesion of the vestibular system, that offers the opportunity to study the cortical response to altered vestibular processing. This research reports [18F]fluorodeoxyglucose positron emission tomography brain scan data concerning the early cortical metabolic activity associated to symptoms onset in a group of eight patients suffering from VN. VN patients’ cortical metabolic activity during the first two days from symptoms onset was compared to that recorded one month later and to a control healthy group. Beside the known cortical response in the sensorimotor network associated to vestibular deafferentation, we show for the first time the involvement of Entorhinal (BAs 28, 34) and Temporal (BA 38) cortices in early phases of symptomatology onset. We interpret these findings as the cortical counterparts of the attempt to reorient oneself in space counteracting the vertigo symptom (Bas 28, 34) and of the emotional response to the new pathologic condition (BA 38) respectively. These interpretations were further supported by changes in patients’ subjective ratings in balance, anxiety, and depersonalization/derealization scores when tested at illness onset and one month later. The present findings contribute in expanding knowledge about early, fast-changing, and complex cortical responses to pathological vestibular unbalanced processing.

Role of p63 and the Notch pathway in cochlea development and sensorineural deafness

The ectodermal dysplasias are a group of inherited autosomal dominant syndromes associated with heterozygous mutations in the Tumor Protein p63 (TRP63) gene. Here we show that, in addition to their epidermal pathology, a proportion of these patients have distinct levels of deafness. Accordingly, p63 null mouse embryos show marked cochlea abnormalities, and the transactivating isoform of p63 (TAp63) protein is normally found in the organ of Corti. TAp63 transactivates hairy and enhancer of split 5 (Hes5) and atonal homolog 1 (Atoh1), components of the Notch pathway, known to be involved in cochlear neuroepithelial development. Strikingly, p63 null mice show morphological defects of the organ of Corti, with supernumerary hair cells, as also reported for Hes5 null mice. This phenotype is related to loss of a differentiation property of TAp63 and not to loss of its proapoptotic function, because cochleas in mice lacking the critical Bcl-2 homology domain (BH-3) inducers of p53- and p63-mediated apoptosis—Puma, Noxa, or both—are normal. Collectively, these data demonstrate that TAp63, acting via the Notch pathway, is crucial for the development of the organ of Corti, providing a molecular explanation for the sensorineural deafness in ectodermal dysplasia patients with TRP63 mutations.

The AESOP robot system for video-assisted rigid endoscopic laryngosurgery

Surgeons may occasionally encounter difficulty in visualizing the whole larynx with a direct laryngoscope. In such cases, rigid endoscopic laryngosurgery using a direct laryngoscope is an optimal solution. Multidirectional examination of the larynx using rigid endoscopes during direct laryngoscopy, leads to better control and management of the ventricle, inferior surface of the vocal fold and subglottis, and the anterior commissure. Currently, 0°, 30°, 70° and 120° angled rigid telescopes are used worldwide. Our experience in telescopic endolaryngeal surgery provided us the opportunity to work with AESOP 3000 (automated endoscope system for optimal positioning), coupling a robotic arm to a rigid endolaryngeal telescope. The use of this device allows the surgeon to control the field of view and operate with both hands. A total of 20 patients presenting a laryngeal lesion were randomly selected and included in this study undergoing a robot-assisted procedure. Three of 20 patients presented a difficult laryngeal exposure with direct laryngoscopy due to a rigid, short neck (1 male, 1 female) and prominent teeth (1 male). We used Karl Storz Hopkins II long rigid endoscopes having 0°, 30° and 70° direction of view, a Storz Xenon 300 cold light, a Storz Tricam SL camera, the Kleinsasser direct laryngoscope. The instruments we used are all commercially available for microlaryngeal surgery and included upward curved instruments in case of difficult laryngeal exposure. The operative equipment was the same for all procedures. We evaluated the acquisition of skills in controlling the AESOP 3000, the feasibility of a single surgeon performing procedures with this machine, and any advantages that it might offer to endolaryngeal surgery. The use of robotic devices improves the precision of surgical procedures, offering surgeons a more comfortable working position, particularly for longer procedures, and without an assistant to hold the camera.

Posturography frequency analysis of sound-evoked body sway in normal subjects.

Sound-evoked activation of the vestibular system has been suggested for a long time, and myogenic potentials have been recorded at the level of different muscular groups while a high intensity sound was applied. The aim of this study was to analyse sound-evoked postural responses in normal subjects and to correlate them with the activation of the vestibular system. Body sway was measured by posturography and elaborated through spectral frequency analysis in 40 healthy volunteers in the basal condition and after applying a sound stimulus monoaurally. Spectral frequency analysis results showed a significant increase, in presence of stimulus, of body sway at low and middle frequencies only on the lateral plane and in the closed-eyes condition. As it seems that these frequency ranges are mainly under vestibular control, our results suggest that sound activates specifically the vestibular system, and posturography during sound stimulation represents an alternative approach to assess vestibular function.

Experimental and clinical aspects of the efferent auditory system

The discovery of active mechanisms in the cochlea and the efferent auditory pathways from the brain to the cochlea demonstrated the existence of a modulation of the auditory input in the central nervous system (CNS). Otoacoustic emissions (OAEs) are weak signals that can be recorded in the ear canal and are considered a byproduct of an active process from the outer hair cells (OHCs) to the basilar membrane. The efferent auditory system plays an inhibitory role on the activity of OHCs; its stimulation reduces auditory nerve response, basilar membrane motility and OAEs amplitude. Indirect stimulation by contralateral sound is also inhibitory; a reduction of OAEs amplitude can be recorded and such an effect disappears after olivocochlear bundle section. The efferent system seems to play a role in detection of signals in noise, protection in noise-induced cochlear damage, development of hearing and processing of complex auditory signals. With respect to clinical application, OAEs suppression after contralateral auditory stimulation seems to be the only objective and non-invasive method for evaluation of the functional integrity of the medial efferent system, and, therefore, for evaluation of the structures lying along its course, at least up to the level of inferior colliculi.