Phenotypes and clinical subgroups in vestibular migraine: a cross-sectional study with cluster analysis.

OBJECTIVE: The aim of this multicentric cross-sectional study was to collect phenotypes and clinical variability on a large sample of 244 patients enrolled in different university centers in Italy, trying to differentiate subtypes of VM. BACKGROUND: VM is one of the most frequent episodic vertigo characterized by a great clinical variability for duration of attacks and accompanying symptoms. Diagnosis is based only on clinical history of episodic vertigo in 50% of cases associated with migrainous headache or photo/phonophobia. METHODS: We enrolled in different university centers 244 patients affected by definite VM according to the criteria of the Barany Society between January 2022 and December 2022. An audiometric examination and a CNS MRI were performed before inclusion. Patients with low-frequency sensorineural hearing loss were not included, as well as patients with an MRI positive otherwise that for microischemic lesions. Patients were asked to characterize vestibular symptoms choosing among (multiple answers were allowed): internal vertigo, dizziness, visuo-vestibular symptoms/external vertigo; onset of vertigo and duration, neurovegetative, and cochlear accompanying symptoms (hearing loss, tinnitus, and fullness during attacks) were collected as well as migrainous headache and/or photo/phonophobia during vertigo; autoimmune disorders were also analyzed. A bedside examination was performed including study of spontaneous-positional nystagmus with infrared video goggles, post head shaking ny, skull vibration test, and video head impulse test. RESULTS: We included 244 subjects, 181 were females (74.2%). The age of onset of the first vertigo was 36.6 ± 14.5 while of the first headache was 23.2 ± 10.1. A positive correlation has been found between the first headache and the first vertigo. The mean duration of vertigo attacks was 11 ± 16 h. We carried on a cluster analysis to identify subgroups of patients with common clinical features. Four variables allowed to aggregate clusters: age of onset of vertigo, duration of vertigo attacks, presence of migrainous headache during vertigo, and presence of cochlear symptoms during vertigo. We identified 5 clusters: cluster 1/group 1 (23 subjects, 9.4%) characterized by longer duration of vertigo attacks; cluster 2/group 2 (52 subjects, 21.3%) characterized by absence of migrainous headache and cochlear symptoms during vertigo; cluster 3/group 3 (44 subjects, 18%) characterized by presence of cochlear symptoms during vertigo but not headache; cluster 4/group 4 (57 subjects, 23.4%) by the presence of both cochlear symptoms and migrainous headache during vertigo; cluster 5/group 5 (68 subjects, 27.9%) characterized by migrainous headache but no cochlear symptoms during vertigo. CONCLUSION: VM is with any evidence a heterogeneous disorder and clinical presentations exhibit a great variability. In VM, both symptoms orienting toward a peripheral mechanism (cochlear symptoms) and central ones (long lasting positional non-paroxysmal vertigo) may coexist. Our study is the first published trying to characterize subgroups of VM subjects, thus orienting toward different pathophysiological mechanisms.

Menière's disease patients improve specific posturographic parameters following diagnostic intratympanic injection.

PURPOSE: Evaluation of specific computerized posturographic parameters in patients with Menière's disease (MD) following the intratympanic injection of gadolinium, a contrast agent, used in radiological diagnosing. MATERIALS AND METHODS: We have observed 12 adult patients with unilateral Menière's Disease subjected to inner ear magnetic resonance imaging (MRI) examination after intratympanic gadolinium injection (ITG). The diagnoses have been performed according to the guidelines of the American Academy of otolaryngology. Before and after 24 h the ITG, all patients were subjected to the clinical evaluation and computerized posturography (CP), in 4 conditions depending on open/closed eyes and with/without foam cushion under feet. RESULTS: After ITG, in the affected ear the MRI confirmed the endolymphatic hydrops revealing a thin or even disappeared perilymphatic space. The statokinesigram showed improvement of stability only with closed eyes on a foam cushion. The CP performed 24 h after the contrast intratympanic injection showed a significant reduction of Path Length and Confidence Ellipse Area, due to an improvement of vestibular function on static balance. This improvement could be directly dependent to intratympanic pressure modification mediated by volume of contrast liquid, by "columella effect". CONCLUSIONS: This study demonstrates the absence of vestibular damage in patients undergoing intratympanic gadolinium infiltration and confirms the relationship between intratympanic pressure and vestibular stability modifications providing positive evidences for an applicative use of CP as a functional assessment to better address diagnosis and follow-up in MD patients treated with intratympanic injections.

Clinical Features, Familial History, and Migraine Precursors in Patients With Definite Vestibular Migraine: The VM-Phenotypes Projects.

OBJECTIVE: The aim of this work was to assess through a questionnaire the features of vertiginous episodes, accompanying symptoms, familial history, and migraine precursors in a sample of 252 subjects with a diagnosis of definite vestibular migraine. BACKGROUND: Migraine is a common neurological disorder characterized by episodic headaches with specific features. About two-thirds of cases run in families, and patients may refer symptoms occurring in infancy and childhood, defined as episodic syndromes that may be associated with migraine. Migraine is associated with episodic vertigo, called vestibular migraine, whose diagnosis mainly relies on clinical history showing a temporary association of symptoms. METHODS: In this cross-sectional multicentric study, 252 subjects were recruited in different centers; a senior specialist through a structured questionnaire assessed features of vestibular symptoms and accompanying symptoms. RESULTS: The age of onset of migraine was 23 years, while onset of vertigo was at 38 years. One hundred and eighty-four subjects reported internal vertigo (73%), while 63 subjects (25%) reported external vertigo. The duration of vertigo attacks was less than 5 minutes in 58 subjects (23%), between 6 and 60 minutes in 55 (21.8%), between 1 and 4 hours in 29 (11.5%), 5 and 24 hours in 44 (17.5%), up to 3 days in 14 (5.5%), and more than 3 days in seven (2.8%); 14 subjects (5.5%) referred attacks lasting from less than 5 minutes and up to 1 hour, nine (3.6%) referred attacks lasting from less than 5 minutes and up to 1 to 4 hours, six (2.4%) referred attacks lasting from less than 5 minutes and up to 5 to 24 hours, and five (2%) cases referred attacks lasting from less than 5 minutes and up to days. Among accompanying symptoms, patients referred the following usually occurring, in order of frequency: nausea (59.9%), photophobia (44.4%), phonophobia (38.9%), vomiting (17.8%), palpitations (11.5%), tinnitus (10.7%), fullness of the ear (8.7%), and hearing loss (4%). In total, 177 subjects referred a positive family history of migraine (70.2%), while 167 (66.3%) reported a positive family history of vertigo. In the sample, 69% of patients referred at least one of the pediatric precursors, in particular, 42.8% of subjects referred motion sickness. The age of onset of the first headache was lower in the subsample with a familial history of migraine than in the total sample. Among the pediatric precursors, benign paroxysmal vertigo - BPV, benign paroxysmal torticollis, and motion sickness were predictive of a lower age of onset of vertigo in adulthood; cyclic vomiting was predictive for vomiting during vertigo attacks in adults. CONCLUSIONS: Our results may indicate that vestibular symptoms in pediatric patients may act as a predisposing factor to develop vestibular migraine at an earlier age in adulthood.

Ultrastructural regenerating features of nasal mucosa following microdebrider-assisted turbinoplasty are related to clinical recovery.

BACKGROUND: The nasal mucosa plays a key role in conditioning the inhaled air and in regulating the immune response. These functions led many authors to recommend mucosal sparing techniques for the surgical management of inferior turbinate hypertrophy. However, the histological modifications of chronic diseases retain the inflammatory activity and prevent the nasal physiology restoration. It has been proved that the basal cells of the nasal mucosa are able to proliferate and to repair after cold-knife incision. The aim of this study was to demonstrate that the healing process after removal of the inferior turbinate mucosa with cold techniques results in a complete structural restoration. METHODS: A prospective study was performed in 18 patients who underwent Microdebrider inferior turbinoplasty (cold technique). Subjective and objective improvement of nasal patency was evaluated with visual analogue scale, rhinomanometry, videoendoscopy and mucociliary transport test. Pre- and post-operative biopsy specimens were taken from 7 patients to evaluate the healing process. Two samples were taken from two healthy patients as control. The specimens were processed for transmission electron microscopy analysis. RESULTS: Videoendoscopy showed reduction of lower turbinate after surgery. Nasal patency augmented and no adverse consequences were observed. After 4 months the nasal mucosa showed normal appearance, with restoration of the pseudostratified ciliated pattern, intercellular connections and normal cellular morphology. Fibrosis and submucosal edema disappeared. At longer time after operation (4 years) clinical improvement was confirmed. CONCLUSIONS: The total removal of the nasal mucosa with cold techniques results in a complete restoration of the normal structure and permanent resolution of the chronic inflammation typical of hypertrophic rhinopathy.

Vertical saccades during horizontal head impulses: a sign of posterior semicircular canal hypofunction.

Objective: We describe an uncharacteristic vestibular-ocular reflex (VOR) pattern, studied by video head impulse tests (VHIT) in patients suffering from unilateral isolated posterior semicircular canal (PSC) hypofunction. In these patients, we found an upward sliding of the eyes, followed by an oblique downward catch-up saccade during horizontal head impulse to the healthy side. Methods: We present a retrospective study of all VHIT exams presenting isolated PSC hypofunction between May 2020 and November 2022. Results: We found 37 patients, which led to the discovery of such incongruent eye movement in 19 cases; their gain data are shown and compared to the remaining 18 cases in which such an anomaly was absent. A control group of 31 healthy subjects was recruited to define the reference criteria for VHIT gain values. The correlation between the amplitude of the vertical saccade and the relative functional imbalance of the vertical semicircular canals was studied. Conclusions: We have observed that in approximately half of the subjects with isolated CSP deficiency, there is a VOR anomaly. A possible pathophysiological explanation of the unbalanced effect of vertical semicircular canal stimulation of a labyrinth during horizontal head thrust toward the opposite side is proposed. The planar incongruity of the response of the VOR described here appears more evident at the onset of the CSP deficit. Current VHIT systems do not detect this incongruent eye reflex. They can lead to an error in gain evaluation (pseudo-deficit) of the lateral semicircular canal of the healthy side and problems in performing the test (trace rejected). In the future, software for VHIT should take into account the possibility of non-coplanar ocular responses to cephalic stimuli.

The Role of Nasal Cytology and Serum Atopic Biomarkers in Paediatric Rhinitis.

A Nasal Provocation Test allows the differentiation of allergic and non-allergic rhinitis, but it is difficult and expensive. Therefore, nasal cytology is taking hold as an alternative. We carried out a cross-sectional study, including 29 patients with persistent rhinitis according to ARIA definition and negative skin prick tests. Nasal symptoms were scored from 0 to 5 using a visual analogue scale, and patients underwent blood tests to investigate blood cell count (particularly eosinophilia and basophilia), to analyze serum total and specific IgE and eosinophil cationic protein (ECP), and to perform nasal cytology. We performed a univariate logistical analysis to evaluate the association between total serum IgE, serum eosinophilia, basophils, and ECP and the presence of eosinophils in the nasal mucosa, and a multivariate logistic model in order to weight the single variable on the presence of eosinophils to level of the nasal mucosa. A statistically significant association between serum total IgE levels and the severity of nasal eosinophilic inflammation was found (confidence interval C.I. 1.08-4.65, odds ratio OR 2.24, p value 0.03). For this reason, we imagine a therapeutic trial with nasal steroids and oral antihistamines in patients with suspected LAR and increased total IgE levels, reserving nasal cytology and NPT to non-responders to the first-line therapy.

Is Skull-Vibration-Induced Nystagmus Modified with Aging?

BACKGROUND: Despite clinical practice utilizing the Dumas test (SVINT), some questions remain unanswered, including the age-related changes in frequency (FN) and slow-phase angular velocity (SPAV). This study aims to retrospectively evaluate their variations in subjects affected by unilateral peripheral vestibular loss (UPVL). METHODS: We evaluated the selected samples based on the results of the SVINT, the results of the vestibular-evoked potentials (C-VEMP and O-VEMP), and the results of the head impulse test (HIT) and we compared the results against the age of the patients. We calculated the timing between the onset of UPVL and clinical evaluation in days. The presence or absence of VEMP indicated the UPVL severity. UPVL and BPPV patients with spontaneous or pseudo-spontaneous nystagmus were compared. RESULTS: Statistical analysis showed changes in the FN and SPAV depending on age and the side of the application of the stimulus. We also observed that, in the UPVL, the severity of the disease modifies the SPAV, but not the frequency. CONCLUSIONS: The SVINT is a simple, reliable, and straightforward test that, if evaluated instrumentally, can show significant differences with aging. Further studies need to be performed to refine the clinical significance of the test and clarify its physiological background.

Unmasking the 'Asymptomatic' COVID-19: A Nose Question.

The new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus has high infectivity, often masked by asymptomatic carriers, which allows it to spread rapidly and become a pandemic. Attempts to slow the pandemic at this stage depend on the ability to unmask asymptomatic carriers. The rapid diagnosis of active coronavirus disease 2019 (COVID-19) infection is one of the cornerstones of pandemic control, as the nasal cavity is the main gateway for SARS-CoV-2 entry and altered sense of smell is a feature of the current virus. In the present study, we therefore tested the olfactory threshold coupled with heart-lung parameters in subjects undergoing traditional molecular testing, resulting in a significantly different score between asymptomatic subjects and healthy controls. In total, 82% of asymptomatic positives showed olfactory impairment; of these, 46% had severe hyposmia and 7% had anosmia, while in the control 9% had severe hyposmia and 0% had anosmia, respectively, which agrees with heart rate, breathing rate, and blood pressure parameter variations. The olfactory test coupled with physiological parameters may help to identify asymptomatic people. In conclusion, our results suggest that most asymptomatic individuals could be unmasked by mass olfactory rapid threshold screening and then referred to traditional slower diagnostic tests.

COVID-19 Smell Impairment and Crosstalk with Hypoxia Physiology.

Since its apomorphic appearance in 2019, severe acute respiratory syndrome Coronavirus type 2 (SARS-CoV-2) nowadays circulates as a plesiomorphic human virus in several synapomorphic variants. The respiratory tract is the most important site of infection, the viral effects in the lungs are well described, and more than half of the patients could develop shortness of breath and dyspnea and require ventilatory support. The physiological sign of this condition is the decrease in the partial pressure of oxygen in the blood, leading to acute hypoxia, which could be a factor in the disease. In severe patients, we recorded several physiological parameters: breath frequency (BF), partial pressure of oxygen in the blood (pO2), partial pressure of carbon dioxide in the blood (pCO2), hemoglobin (Hb), heart rate (HR), and blood pressure in correlation with the olfactory threshold. We found significant correlations between reduced olfactory threshold with pO2 and hemoglobin levels, changes in heart rate, and increased HR and pCO2. These results suggest that COVID-19 causes an impaired sense of smell that decreases in threshold corresponding to the disease severity.

Effect of tonsillectomy in a child with obesity and obstructive sleep apnea: A case report and review of the literature.

Obstructive sleep apnea (OSA) is an increasingly recognized disorder in children. Adenotonsillectomy is the primary surgical treatment for OSA in children with adenotonsillar hypertrophy (ATH). We present the case of an obese 4-year-old boy hospitalized for severe desaturation during sleep and severe ATH. Nasal steroid therapy proved ineffective with persistent symptoms. Polygraphy documented severe OSA with an apnea-hypopnea index (AHI) equal to 11. Tonsillectomy resulted in prompt symptom improvement and a substantial reduction of the AHI (2.2). In this case, tonsillectomy alone resulted effective in treating OSA, despite obesity. We concluded that the presence of obesity should not postpone/exclude surgical treatment of preschool children for whom ATH is the most important cause of OSA.

Spontaneous nystagmus in benign paroxysmal positional vertigo.

OBJECTIVE: The purpose of this study was to evaluate the presence and eventually to study the features of spontaneous nystagmus (Ny) in our patients with diagnosis of benign paroxysmal positional vertigo (BPPV). PATIENTS AND METHODS: We retrospectively reviewed the clinical records of patients who presented with vertigo spells and were managed at our tertiary care referral center. Patients with only idiopathic BPPV presenting with typical vertigo spells and positioning Ny characteristic of the disease were included in this study. To investigate the positioning Ny, we studied the patients in the sitting position, during the head shaking test, and during the Dix-Hallpike test and the McClure-Pagnini test (Ny provoked by rotation of the head in a supine patient). Ny responses in all patients were observed using infrared videoscopy. RESULTS: We managed 412 patients affected by BPPV. Of the 412 patients, 292 (70.87%) were diagnosed to be having posterior canal-BPPV and 110 (26.99%) patients had horizontal canal-BPPV (HC-BPPV). The remaining 10 patients (2.44%) were identified to have anterior canal-BPPV. Spontaneous Ny in sitting position was observed, by infrared videoscopy, only in the patients affected by HC-BPPV. CONCLUSION: Spontaneous Ny in BPPV can be observed with infrared videoscopy in patients affected by HC-BPPV. The origin of this Ny is most likely due to a natural inclination of horizontal semicircular canal with respect to the horizontal plane. This Ny stops after flexion of the head in neutral position, and for this reason, it should be considered as a seemingly spontaneous Ny. This Ny, in our experience, is observed in most HC-BPPV patients but does not indicate the need for a different management protocol or any different prognostic value of HC-BPPV.

MRI With Intratympanic Gadolinium: Comparison Between Otoneurological and Radiological Investigation in Menière's Disease.

Objectives/hypothesis: To compare findings obtained using both magnetic resonance imaging plus intratympanic gadolinium and audiovestibular testing for Menière's disease. Study design: Retrospective cohort study. Methods: Patients with definite unilateral Menière's disease (n = 35) diagnosed according to 2015 Barany Criteria were included. Three-dimensional real inversion recovery (3D-real-IR) MRI was executed 24 h after intratympanic gadolinium injection to assess the presence and degree of endolymphatic hydrops. Pure tone audiometry, bithermal caloric test, head impulse test, ocular, and cervical VEMPs using air-conducted sound were performed to evaluate the level of hearing and vestibular loss. The results were compared to verify precision of the method in providing correct diagnoses. Results: Different degrees of endolymphatic hydrops were observed in the MRI of the cochlea and vestibule in the affected ears of Menière's disease patients, even though it was impossible to radiologically distinguish the two otolithic structures separately. The correlation between the degree of linked alterations between instrumental and MRI testing was statistically significant. In particular, an 83% correspondence with audiometry, a 63% correspondence for cVEMPs and 60% correspondence for cVEMPs were seen. While for HIT the accordance was 70 and 80% for caloric bithermal test. Conclusions: MRI using intratympanic gadolinium as a contrast medium has proved to be a reliable and harmless method, even though there is an objective difficulty in disclosing macular structures. The study revealed that there is no complete agreement between instrumental values and MRI due to the definition of the image and fluctuation of symptoms. The present work highlights the greater (but not absolute) sensitivity of otoneurological tests while MRI, although not yet essential for diagnosis, is certainly important for understanding the disease and its pathogenic mechanisms.

Electrophysiological and olfactometric evaluation of long-term COVID-19.

COVID-19 is a public health emergency with cases increasing globally. Its clinical manifestations range from asymptomatic and acute respiratory disease to multiple organ dysfunction syndromes and effects of COVID-19 in the long term. Interestingly, regardless of variant, all COVID-19 share impairment of the sense of smell and taste. We would like to report, as far as we know, the first comprehensive neurophysiological evaluation of the long-term effects of SARS-CoV-2 on the olfactory system with potential-related neurological damage. The case report concerns a military doctor, with a monitored health history, infected in April 2020 by the first wave of the epidemic expansion while on military duty in Codogno (Milan). In this subject, we find the electrophysiological signal in the periphery, while its correlate is absent in the olfactory bulb region than in whole brain recordings. In agreement with this result is the lack of metabolic signs of brain activation under olfactory stimulation. Consequently, quantitative and qualitative diagnoses of anosmia were made by means of olfactometric tests. We strongly suggest a comprehensive series of olfactometric tests from the first sign of COVID-19 and subsequent patient assessments. In conclusion, electrophysiological and metabolic tests of olfactory function have made it possible to study the long-term effects and the establishment of neurological consequences.

Otitis media with effusion: The role of Helicobacter Pylori in its pathogenesis.

BACKGROUND: Otitis Media with Effusion (OME) is the most common disease of the middle ear. Different factors play a role in its pathogenesis, such as viral and bacterial infections, allergy, morphological and functional changes of nasal passage, Eustachian Tube (ET), and cleft palate. This study aims to investigate the Helicobacter Pylori presence in middle ear effusions from patients with OME through RT-PCR and compare our results with results from other published articles. METHODS: The study was carried out from October 2007 to February 2009, in the Department of Otorhinolaryngology of SS. Annunziata Hospital, Chieti, Italy. 132 consecutive patients with OME were included in the study. Fluid in the middle ear was assessed for the presence of Helicobacter Pylori through RT-PCR. RESULTS: 132 consecutive patients with OME were included in the study. The patients were between ages 8 and 78 (median 50); 62 were males (47%), 70 were females (53%), and 53 patients had bilateral OME (40%). 185 samples were collected from 132 patients. Of the 185 samples taken from the ear, 21 (11.35%) were not adequate for the correct execution of the DNA extraction procedure. The remaining 167 samples, subjected to RT-PCR, did not show in any case an increase in fluorescence linked to the FAM fluorophore, thus demonstrating the complete absence of Helicobacter Pylori. CONCLUSION: Based on the results obtained, we can affirm that although a third of the cases of OME is correlated to the presence of reflux, Helicobacter Pylori does not seem to play any role in the pathophysiology of OME as it cannot be found in endo-tympanic exudate.

Congenital Hairy Polyp Causing Severe Upper Airway Obstruction in a Newborn: A Case Report.

BACKGROUND Hairy polyps are rare tumors mainly comprising fatty tissues covered by skin and hair follicles, with varied localizations and sizes. Early excision of the polyps by surgery is an effective treatment resulting in a permanent cure. We present a case of successful management of severe obstruction of the oropharynx in a newborn who presented with a large mass of congenital hairy polyp. CASE REPORT A vaginally delivered infant, weighing 3 kg, presented immediately after birth with cyanosis symptoms, failure of the first cry, and respiratory distress signs. The newborn was born to a mother with an uneventful pregnancy. Screening tests during the pregnancy reported no congenital anomalies. The newborn's hematological and biochemical test results were normal. After presenting these symptoms, the newborn was immediately intubated and put on a nasogastric feeding tube, which revealed a small portion of a polyp-like mass. A computed tomography (CT) scan further confirmed a large pedunculated mass, measuring 3×2 cm, arising from the soft palate, and obstructing the oropharynx. Histopathological examination confirmed the presence of a hairy polyp. The polyp was wholly removed transorally using the Covidien LigaSure device without the need for endoscopy. This procedure allowed safe extubation, and the baby was discharged home without symptoms 4 days after birth. CONCLUSIONS This case sheds light on the importance of considering hairy polyp in the differential diagnosis of pharyngeal mass with respiratory distress in pediatric patients. This report also describes our experience using the LigaSure surgical device without needing endoscopic visualization to successfully resect the hairy polyp without complications.

Double-Blind Randomized Trial on the Efficacy of the Forced Prolonged Position for Treatment of Lateral Canal Benign Paroxysmal Positional Vertigo.

OBJECTIVES/HYPOTHESIS: 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 forced prolonged position (FPP). STUDY DESIGN: Double-blind, randomized controlled trial. METHODS: Two hundred twenty-one patients with unilateral LC-BPPV met the inclusion criteria for a multicentric study. Patients were randomly assigned to treatment by FPP (116 subjects) or sham treatment (105 subjects). Subjects were followed up at 24 hours with the supine roll test by blinded examiners. RESULTS: Among the sample, 67.4% and 32.6% of the patients showed respectively geotropic and apogeotropic variant of LC-BPPV. At the 24-hour follow-up, the effectiveness of FFP compared to the sham maneuver was, respectively, 57.8% versus 12.4% (P < .0001) in the total sample, 76.9% versus 11.3% (P < .0001) in the geotropic variant group, and 60.5% versus 17.6% (P = .0003) in the apogeotropic variant group, including resolution or transformation to geotropic variant. CONCLUSIONS: FPP proved highly effective compared to the sham maneuver. The present class 2 study of the efficacy of the FPP changes the level of recommendation of the method for treating LC-BPPV into a strong one. LEVEL OF EVIDENCE: 2 Laryngoscope, 131:E1296-E1300, 2021.

New Insight on Motor Behavior: The Link Between the Hopping Task and the Tracing Performance as Hint of Gross and Fine Motor Functions.

The gross motor coordination tasks are thought to be likely not linked to the fine motor coordination tasks. The authors aimed to investigate this matter through a network analysis linking graphomotor (by tablet PC tracing), gross coordination (by Körperkoordinationstest für Kinder items), and strength (by handgrip) parameters in school children. Interestingly, the authors found that "Hopping" was the strongest central node, with linkages to "Quality" and "Speed" on tracing test. Handgrip strength did not link to gross coordination and graphomotor parameters, except with "Pressure." Graphomotor performances suggested substantial peculiarities in developmental trajectories. Sport participation did not influence gross coordination nor graphomotor performances. The authors suggest considering the functional link between hopping and graphomotricity both in planning physical education and in understanding coordination impairments, through the developmental trajectories.

A new pharmacological approach based on remdesivir aerosolized administration on SARS-CoV-2 pulmonary inflammation: A possible and rational therapeutic application.

The new zoonotic coronavirus (SARS-CoV-2) responsible for coronavirus disease (COVID-19) is a new strain of coronavirus not previously seen in humans and which appears to come from bat species. It originated in Wuhan, Hubei Province, China, and spread rapidly throughout the world, causing over 5,569,679 global cases and 351,866 deaths in almost every country in the world, including Europe, particularly Italy. In general, based on existing data published to date, 80.9% of patients infected with the virus develop mild infection; 13.8% severe pneumonia; 4.7% respiratory failure, septic shock or multi-organ failure; 3% of these cases are fatal. Critical patients have been shown to develop acute respiratory distress syndrome (ARDS) and hospitalization in intensive care units. The average age of patients admitted to hospital is 57-79 years, with one third half with an underlying disease. Asymptomatic infections have also been described, but their frequency is not known. SARS-CoV-2 transmission is mainly airborne from one person to another via droplets. The data available so far seem to indicate that SARS-CoV-2 is capable of producing an excessive immune reaction in the host. The virus attacks type II pneumocytes in the lower bronchi through the binding of the Spike protein (S protein) to viral receptors, of which the angiotensin 2 conversion enzyme (ACE2) receptor is the most important. ACE2 receptor is widely expressed in numerous tissues, including the oropharynx and conjunctiva, but mostly distributed in ciliated bronchial epithelial cells and type II pneumocytes in the lower bronchi. The arrival of SARS-CoV-2 in the lungs causes severe primary interstitial viral pneumonia that can lead to the "cytokine storm syndrome", a deadly uncontrolled systemic inflammatory response triggered by the activation of interleukin 6 (IL-6), whose effect is extensive lung tissue damage and disseminated intravascular coagulation (DIC), that are life-threatening for patients with COVID-19. In the absence of a therapy of proven efficacy, current management consists of off-label or compassionate use therapies based on antivirals, antiparasitic agents in both oral and parenteral formulation, anti-inflammatory drugs, oxygen therapy and heparin support and convalescent plasma. Like most respiratory viruses can function and replicate at low temperatures (i.e. 34-35 °C) and assuming viral thermolability of SARS-CoV-2, local instillation or aerosol of antiviral (i.e. remdesivir) in humid heat vaporization (40°-41 °C) in the first phase of infection (phenotype I, before admission), both in asymptomatic but nasopharyngeal swab positive patients, together with antiseptic-antiviral oral gargles and povidone-iodine eye drops for conjunctiva (0,8-5% conjunctival congestion), would attack the virus directly through the receptors to which it binds, significantly decreasing viral replication, risk of evolution to phenotypes IV and V, reducing hospitalization and therefore death.

Smell and Taste in Severe CoViD-19: Self-Reported vs. Testing.

One of the most striking reported symptoms in CoViD-19 is loss of smell and taste. The frequency of these impairments and their specificity as a potential central nervous system function biomarker are of great interest as a diagnostic clue for CoViD-19 infection as opposed to other similar symptomatologic diseases and because of their implication in viral pathogenesis. Here severe CoViD-19 was investigated by comparing self-report vs. testing of smell and taste, thus the objective severity of olfactory impairment and their possible correlation with other symptoms. Because a significant discrepancy between smell and taste testing vs. self-report results (p < 0.001) emerges in our result, we performed a statistical analysis highlighting disagreement among normosmia (p < 0.05), hyposmia, severe hyposmia, and anosmia (p < 0.001) and, in hypogeusia and severe hypogeusia, while no differences are observed in normogeusia and ageusia. Therefore, we analyzed the olfactory threshold by an objective test revealing the distribution of hyposmic (34%), severe hyposmic (48%), and anosmic (13%) patients in severe CoViD-19. In severe CoViD-19 patients, taste is lost in 4.3% of normosmic individuals, 31.9% of hyposmic individuals, 46.8% of severe hyposmic individuals, and 17% of anosmic individuals. Moreover, 95% of 100 CoViD-19 patients objectively tested were affected by smell dysfunction, while 47% were affected by taste dysfunction. Furthermore, analysis by objective testing also highlighted that the severity of smell dysfunction in CoViD-19 subjects did not correlate with age and sex. In conclusion, we report by objective testing that the majority of CoViD-19 patients report severe anosmia, that most of the subjects have olfactory impairment rather than taste impairment, and, finally, that the olfactory impairment correlate with symptom onset and hospitalization (p < 0.05). Patients who exhibit severe olfactory impairment had been hospitalized for about a week from symptom onset; double time has taken place in subjects with normosmia. Our results may be limited by the relatively small number of study participants, but these suggest by objective testing that hyposmia, severe hyposmia, and anosmia may relate directly to infection severity and neurological damage. The smell test assessment could be a potential screening symptom that might contribute to the decision to test suspected cases or guide quarantine instructions, further therapeutic approach, and evaluation of neurological damage.

Corrigendum: Clinical Features of Headache in Patients With Diagnosis of Definite Vestibular Migraine: The VM-Phenotypes Projects.

[This corrects the article DOI: 10.3389/fneur.2018.00395.].