Vincenzo Marcelli

MRI Magnetic Field Stimulates Rotational Sensors of the Brain

Vertigo in and around magnetic resonance imaging (MRI) machines has been noted for years [1, 2]. Several mechanisms have been suggested to explain these sensations [3, 4], yet without direct, objective measures, the cause is unknown. We found that all of our healthy human subjects developed a robust nystagmus while simply lying in the static magnetic field of an MRI machine. Patients lacking labyrinthine function did not. We use the pattern of eye movements as a measure of vestibular stimulation to show that the stimulation is static (continuous, proportional to static magnetic field strength, requiring neither head movement nor dynamic change in magnetic field strength) and directional (sensitive to magnetic field polarity and head orientation). Our calculations and geometric model suggest that magnetic vestibular stimulation (MVS) derives from a Lorentz force resulting from interaction between the magnetic field and naturally occurring ionic currents in the labyrinthine endolymph fluid. This force pushes on the semicircular canal cupula, leading to nystagmus. We emphasize that the unique, dual role of endolymph in the delivery of both ionic current and fluid pressure, coupled with the cupulas function as a pressure sensor, makes magnetic-field-induced nystagmus and vertigo possible. Such effects could confound functional MRI studies of brain behavior, including resting-state brain activity.

Trigeminal Stimulation Elicits a Peripheral Vestibular Imbalance in Migraine Patients

Objective.—The study explored the hypothesis that spontaneous nystagmus (Ny) in migraine patients can be triggered or modulated by painful trigeminal stimulation, providing evidence of a functional connection between vestibular and trigeminal systems.

Postural restrictions in labyrintholithiasis

Abstract Benign paroxysmal positional vertigo (BPPV) is the most frequent labyrinthopathy in humans. Treatment consists mainly of liberatory maneuvers aiming to remove otolithic debris and subsequent postural restrictions in order to prevent debris from returning into the canal. The reappearance of symptoms after an effective liberatory maneuver was studied in a group subjected to restrictions and in a second group free from restrictions. The effects of these restrictions were evaluated. No statistically significant difference was found between the groups. Accordingly, restrictions seem to have no effect upon symptom recurrence. The slight supremacy of the Semont maneuver and the prevalence of subsequent relapse compared with the Epley maneuver suggests that these maneuvers could operate on different disorders (cupulolithiasis versus canalolithiasis). Finally, late recognition of relapse in patients who undergo restrictions might even make the liberatory maneuver less effective.

Hearing Impairment in Parkinson's Disease: Expanding the Nonmotor Phenotype

The objective of this study was to evaluate hearing impairment in patients affected by Parkinsons disease compared with hearing scores observed in normal age‐ and sex‐matched controls. One hundred eighteen consecutive patients with a clinical diagnosis of Parkinsons disease were screened. Severity of motor symptoms and staging were measured with the Unified Parkinsons Disease Rating Scale (section III) and the Hoehn and Yahr scale. Audiometric evaluation consisted of a comprehensive audiologic case history and questionnaire, visual otoscopic examination, acoustic immittance measures (tympanogram and acoustic reflexes), pure tone audiometry, and measurement of brain stem auditory‐evoked potentials. Healthy age‐ and sex‐matched subjects were selected as the control group. One hundred six of 118 patients were enrolled. Pure tone audiometry revealed age‐dependent high‐frequency hearing loss in patients with Parkinsons disease compared with both normative values and values for healthy age‐ and sex‐matched controls (75/106 [71%], χ2 = 5.959, P = .02; 92/106 [86.8%] vs 60/106 [56.6%], χ2 = 23.804, P < .001, respectively). Pure tone audiometry scores correlated with Hoehn and Yahr scale scores (P < .05). Brain stem auditory‐evoked potentials were normal in all patients. Our patients with Parkinsons disease showed age‐dependent peripheral, unilateral, or bilateral hearing impairment. Whether these auditory deficits are intrinsic to Parkinsons disease or secondary to a more complex impaired processing of sensorial inputs occurring over the course of illness remains to be determined. Because α‐synuclein is located predominately in the efferent neuronal system within the inner ear, it could affect susceptibility to noise‐induced hearing loss or presbycusis. It is feasible that the natural aging process combined with neurodegenerative changes intrinsic to Parkinsons disease might interfere with cochlear transduction mechanisms, thus anticipating presbycusis.

Spatio-temporal pattern of vestibular information processing after brief caloric stimulation

Processing of vestibular information at the cortical and subcortical level is essential for head and body orientation in space and self-motion perception, but little is known about the neural dynamics of the brain regions of the vestibular system involved in this task. Neuroimaging studies using both galvanic and caloric stimulation have shown that several distinct cortical and subcortical structures can be activated during vestibular information processing. The insular cortex has been often targeted and presented as the central hub of the vestibular cortical system. Since very short pulses of cold water ear irrigation can generate a strong and prolonged vestibular response and a nystagmus, we explored the effects of this type of caloric stimulation for assessing the blood-oxygen-level-dependent (BOLD) dynamics of neural vestibular processing in a whole-brain event-related functional magnetic resonance imaging (fMRI) experiment. We evaluated the spatial layout and the temporal dynamics of the activated cortical and subcortical regions in time-locking with the instant of injection and were able to extract a robust pattern of neural activity involving the contra-lateral insular cortex, the thalamus, the brainstem and the cerebellum. No significant correlation with the temporal envelope of the nystagmus was found. The temporal analysis of the activation profiles highlighted a significantly longer duration of the evoked BOLD activity in the brainstem compared to the insular cortex suggesting a functional de-coupling between cortical and subcortical activity during the vestibular response.

Vestibular Pathways Involvement in Children With Migraine: A Neuro‐Otological Study

(Headache 2010;50:71‐76)

Double-blind randomized trial on the efficacy of the Gufoni maneuver for treatment of lateral canal BPPV

The need for class I and II studies on the efficacy of liberatory maneuvers in the treatment of lateral canal benign paroxysmal positional vertigo (LC‐BPPV) motivated the present double‐blind randomized trial on the short‐term efficacy of the Gufoni liberatory maneuver (GLM).

Benign paroxysmal vertigo of childhood: A 10-year observational follow-up.

Aim The aim of this article is to explore the progression of neurological, neuro-otological and cochlear features in benign paroxysmal vertigo (BPV) in children over time and its relation with migraine, neuro-otological and cochlear disorders in adulthood. Methods From January 2002 to December 2002, 15 children with BPV were prospectively recruited and then evaluated during a 10-year observational follow-up. All patients underwent detailed neurological, neuro-otological and cochlear examinations during interictal phases. Six children were also studied during ictal periods. Results At first assessment, four children reported migraine with aura (MwA) and six children reported migraine without aura (MwoA). Neuro-otological examinations were abnormal in two of 15 children. Cochlear examinations were normal in all patients. During the 10-year follow-up, recurrent vestibular symptoms and/or MwA and/or MwoA have been observed in the children. Neuro-otological examinations were abnormal in three of 15 individuals during the interictal period, and abnormal in four out of six patients who were studied during the ictal period. Two patients developed cochlear signs and/or symptoms. Conclusions During the 10-year follow-up, a phenotype variability in BPV patients has been observed. Specifically, de novo cochlear signs and/or symptoms developed in children with BPV, suggesting that cochlear symptoms should be properly investigated in these patients over time.

Anti-GAD antibody ocular flutter: expanding the spectrum of autoimmune ocular motor disorders

Antibodies directed against glutamic acid decarboxylase (GAD) have been described in patients with progressive cerebellar ataxia [1] and in a few patients affected by primarily oculomotor disorders [2]. The abnormal eye movements described with anti-GAD antibodies, so far, range from nystagmus (up/down-beat, periodic alternating nystagmus) [2, 3] to opsoclonus [4], but ocular flutter has never been reported. A 69-year-old woman was admitted to our hospital for a 10-month progressive oscillopsia, blurred vision and gait imbalance with significant impairment of daily activities (such as reading a book, watching television and leaving home alone). Neurological examination showed ocular flutter, characterized by intermittent bursts of horizontal conjugate saccades without an intersaccadic interval. The eye oscillations were independent of eye position and occurred during fixation (voluntary and guided changes in gaze position), regardless of gaze direction, with eyes open or closed. The patient had full range of eye motion and did not report diplopia. Unsteadiness with severe retropropulsion was also evident. The remaining neurologic examination was normal. Analysis of ocular movements using video-oculography revealed bursts of rapid horizontal, symmetric movements without intersaccadic interval (Fig. 1a). Results of electrophysiological examinations, such as somatosensory and visual evoked potentials, nerve conduction study and electroencephalography, were normal. Routine blood cell counts and biochemistry were normal. Serological tests, cultures, and polymerase chain reactions performed on blood and cerebrospinal fluid (CSF) samples were negative for viral, bacterial, and fungal infections. Brain magnetic resonance imaging showed no abnormality. Results of screening examinations for neoplasms, including abdominal ultrasonography, computed tomography of the abdomen and chest, as well as whole-body positron emission tomography, were all unremarkable. CSF examination revealed normal protein concentration and no cells, isoelectric focusing showed two oligoclonal bands and the immunoglobulin G index was within the normal range. The patient tested negative for anti-gliadin, paraneoplastic antibodies (anti-Ri, anti-Hu, anti-Yo, antiMa2, anti-CV2 and anti-amphiphysin), anti-LGI1, antiCaspr2, antiganglioside Q1b and anti-NMDA receptor in the serum and CSF. Antibodies against GAD65 were measured by radioimmunoassay. GAD65 antibody titre was increased in serum (2,378 IU/mL, normal value \1 IU/mL) and in CSF (55.7 IU/mL, normal value \1 IU/mL), with an intrathecal synthesis index of 10.64 (normal range 0.7–1.3). An intravenous immunoglobulin (IVIg) treatment (400 mg/kg/day for 5 days) in six cycles once a month was started. The symptoms gradually resolved and continued to improve after the last administration of IVIg and at the same time serum GAD65 antibody titre decreased significantly (Fig. 1c). To avoid clinical relapses, azathioprine 200 mg orally daily was added to the last cycle of IVIg (Fig. 1c). R. Dubbioso F. Manganelli R. Iodice M. Esposito L. Santoro (&) Department of Neuroscience, Reproductive Sciences and Odontostomatology, University of Naples ‘‘Federico II’’, Via Sergio Pansini, 5, 80131 Naples, Italy e-mail: lusantor@unina.it

Clinical presentation and disease course of Usher Syndrome because of mutations in MYO7A or USH2A

Purpose: To evaluate differences in the visual phenotype and natural history of Usher syndrome caused by mutations in MYO7A or USH2A, the most commonly affected genes of Usher syndrome Type I (USH1) and Type II (USH2), respectively. Methods: Eighty-eight patients with a clinical diagnosis of USH1 (26 patients) or USH2 (62 patients) were retrospectively evaluated. Of these, 48 patients had 2 disease-causing mutations in MYO7A (10 USH1 patients), USH2A (33 USH2 patients), and other USH (5 patients) genes. Clinical investigation included best-corrected visual acuity, Goldmann visual field, fundus photography, electroretinography, and audiologic and vestibular assessments. Longitudinal analysis was performed over a median follow-up time of 3.5 years. Results: Patients carrying mutations in MYO7A had a younger age of onset of hearing and visual impairments than those carrying mutations in USH2A, leading to an earlier diagnosis of the disease in the former patients. Longitudinal analysis showed that visual acuity and visual field decreased more rapidly in subjects carrying MYO7A mutations than in those carrying USH2A mutations (mean annual exponential rates of decline of 3.92 vs. 3.44% and of 8.52 vs. 4.97%, respectively), and the former patients reached legal blindness on average 15 years earlier than the latter. Conclusion: The current study confirmed a more severe progression of the retinal disease in USH1 patients rather than in USH2 patients. Furthermore, most visual symptoms (i.e., night blindness, visual acuity worsening) occurred at an earlier age in USH1 patients carrying mutations in MYO7A.