Otolaryngologists' radiological assessment of nasal septum deviation symptomatology.

OBJECTIVES: Nasal Septal Deviation (NSD) is one of the most common causes of nasal obstruction. This study aims to further examine the clinical utility of imaging assessment in the workup and management of symptomatic nasal septal deviation, across all levels of medical training. STUDY DESIGN: Cross-sectional survey. METHODS: CT scans of 10 confirmed NSD patients and 36 healthy controls (HC) were mixed and emailed through anonymous REDCap surveys to otolaryngologists in the US. The HC had no reported sinonasal obstruction symptoms-NOSE (NSD: 62.2 ± 12.5; HC: 5.69 ± 5.99, p < 0.05); SNOT-22 (NSD: 31.4 ± 14.5; HC: 9.72 ± 10.76, p < 0.05). The images consisted of a coronal slice at each subject's most deviated location. Participants were instructed to choose the patients suspected to present with symptoms of sinonasal obstruction. RESULTS: 88 otolaryngologists responded to the survey. 18 were excluded due to incomplete responses. On average, they identified 64.2 ± 29.8% of symptomatic NSD subjects correctly, but misidentified 54.6 ± 34.6% of HC as symptomatic. Their decisions were strongly correlated to degree of NSD (r = 0.69, p < 0.05). There exists a significant degree of NSD among HC (38.7 ± 17.2%), which does not significantly differ from symptomatic subjects (51.0 + 18.7%, p = 0.09). Residents and fellows performed similarly, with responses correlated between levels of training (r = 0.84-0.96, p < 0.05). CONCLUSIONS: The incorporation of a substantial number of otolaryngologists, large patient sample, and blind mixing with HC gives us greater insight to the relative contribution of the extent of septal deviation to symptoms of nasal obstruction. Although NSD is a common factor contributing to nasal obstruction, the results of this study suggest that it is difficult to reliably infer obstructive symptoms based on degree of NSD on CT. LEVEL OF EVIDENCE: Three.

Magnetic resonance imaging in a large cohort of facioscapulohumeral muscular dystrophy patients: Pattern refinement and implications for clinical trials.

OBJECTIVE: Therapeutic perspectives have brought attention to the development of instruments to accurately evaluate the degree of pathology in patients with facioscapulohumeral muscular dystrophy. We aimed to analyze the type and extent of muscle involvement on magnetic resonance imaging (MRI) in a large cohort of patients representative of the broad clinical spectrum of this disease. METHODS: Pelvic and lower limb muscle MRI scans of 269 symptomatic individuals and 19 nonpenetrant gene carriers were assessed. Comparative analysis of the upper girdle scan in 181 of these subjects was also performed. RESULTS: We found a peculiar susceptibility and resistance of particular muscles. Combined involvement of abdominal and hamstring muscles with iliopsoas sparing is common in facioscapulohumeral muscular dystrophy (67% of the patients). Adductor longus and/or rectus femoris, whose involvement can go clinically undetected, are often typically affected in early disease (69% of patients younger than 45 years). The extent of lesions on lower limb MRI showed a high correlation with overall clinical severity. One-fourth of the nonpenetrant gene carriers showed abnormalities on MRI. Hyperintensities on short-tau inversion recovery sequences, markers of active disease, were found in muscles without signs of fatty replacement in 35% of patients, representing early lesions. INTERPRETATION: Our large-scale cross-sectional data provide preliminary evidence for the usefulness of MRI in clinical trials, and set the baseline for longitudinal studies. Muscle MRI can also be used for distinguishing facioscapulohumeral muscular dystrophy from other myopathies in selected cases. Finally, our results are consistent with a model that configures facioscapulohumeral muscular dystrophy as a "muscle-by-muscle" disease. Ann Neurol 2016;79:854-864.

Diagnosis of primary headache in children younger than 6 years: A clinical challenge.

Background Criteria defined by the International headache Society are commonly used for the diagnosis of the different headache types in both adults and children. However, some authors have stressed some limits of these criteria when applied to preschool age. Objective Our study aimed to describe the characteristics of primary headaches in children younger than 6 years and investigate how often the International Classification of Headache Disorders (ICHD) criteria allow a definitive diagnosis. Methods This retrospective study analysed the clinical feature of 368 children younger than 6 years with primary headache. Results We found that in our patients the percentage of undefined diagnosis was high when either the ICHD-II or the ICHD-III criteria were used. More than 70% of our children showed a duration of their attacks shorter than 1 hour. The absence of photophobia/phonophobia and nausea/vomiting significantly correlate with tension-type headache (TTH) and probable TTH. The number of first-degree relatives with migraine was positively correlated to the diagnosis of migraine in the patients ( p < 0.001). Conclusions Our study showed that the ICHD-III criteria are difficult to use in children younger than 6 years. The problem is not solved by the reduction of the lowest duration limit for the diagnosis of migraine to 1 hour, as was done in the ICHD-II.

Role of the Attachment Style in Determining the Association Between Headache Features and Psychological Symptoms in Migraine Children and Adolescents. An Analytical Observational Case-Control Study.

OBJECTIVE: We aimed to study the role of attachment style on headache severity and psychological symptoms in migraineurs children/adolescents. Moreover, we investigated the association between attachment style, migraine severity, and psychological symptoms. BACKGROUND: Attachment theory suggests that early interpersonal relationships may be important determinants of psychopathology and pain management. In particular, individuals with insecure attachment styles have been shown to experience more pain than people with secure attachment style. Few studies focused on headache and data on attachment style in pediatric headache are scarce. METHODS: We studied 90 migraineurs (mean age 12.2 ± 2.6 years; female: 54, male: 36). Patients were divided in two groups according to headache attack frequency: (1) high frequency (HF) patients, having from weekly to daily episodes and (2) low frequency (LF) patients, showing ≤3 episodes per month. According to headache attack intensity, patients were classified in two groups: (1) mild pain (MP), allowing the patient to continue his/her daily activities and (2) severe pain (SP), leading to interruption of patient activities or forcing the child to go to bed. The psychological screening was assessed by SAFA Anxiety, Depression, and Somatization questionnaires. Attachment style was measured by the semi-projective test Separation Anxiety Test. Patients were divided into "secure," "avoidant," "ambivalent," and "disorganized/confused" attachment patterns. RESULTS: We found a significant relationship between the attachment style and migraine features. The ambivalent attachment was the most common style among patients reporting high attack frequency (51%) and severe pain intensity (50%). Anxiety (SAFA-A Tot: F = 23.3, P < .001), depression (SAFA-D Tot: F = 11.8, P < .001), and somatization (SAFA-S Tot: F = 10.1, P < .001) were higher in patients with ambivalent attachment style. Moreover, our results showed an association between high attack frequency and high anxiety levels, in children with ambivalent attachment style (F = 6.7, P < .002). CONCLUSIONS: Ambivalent attachment style may be a common vulnerability factor that impacts on pain severity, anxiety, depression, and somatization symptoms in young migraineurs. In particular, the present study provides the first evidence of the role of insecure attachment on the relationship between pain severity and psychological symptoms in migraine children.

Pain and the alpha-sleep anomaly: a mechanism of sleep disruption in facioscapulohumeral muscular dystrophy.

OBJECTIVE: To measure the presence of the alpha-sleep anomaly in facioscapulohumeral muscular dystrophy (FSHD) and to evaluate the association between the sleep electroencephalogram (EEG) pattern and the presence of musculoskeletal pain. DESIGN: Cross-sectional study. SETTING: Sleep laboratory. SUBJECTS: Fifty-five consecutive adult FSHD patients, 26 women and 29 men, age 49.6 ± 15.1 years (range 18-76). INTERVENTIONS: Questionnaires and polysomnography. OUTCOME MEASURES: Patients were asked to indicate if in the 3 months before the sleep study they presented persisting or recurring musculoskeletal pain. Patients who reported pain were asked to fill in the Italian version of the Brief Pain Inventory and the McGill Pain questionnaire, and a 101-point visual analog scale (VAS) for pain intensity. Polysomnographic recordings were performed. EEG was analyzed by means of Fast Fourier Transform. Four power spectra bands (δ 0-4 Hz, θ 4-8 Hz, α 8-14 Hz, ß 14-32 Hz) were computed. Sleep macrostructure parameters and alpha/delta EEG power ratio during non rapid eye movement (NREM) sleep were compared between patients with and without pain. RESULTS: Forty-two patients in our sample reported chronic pain. VAS mean score was 55.2 ± 23.8 (range 10-100), pain rating index score was 13.8 ± 10.2, and present pain intensity was 2.5 ± 0.8. The statistical analysis documented an increased occurrence of the alpha and beta rhythms during NREM sleep in FSHD patients with pain. Significant correlations were observed between the alpha/delta power ratio during NREM sleep and pain measures. CONCLUSIONS: Chronic musculoskeletal pain is frequent in FSHD patients, and it represents a major mechanism of sleep disruption.

Intraoperative delineation of p16+ oropharyngeal carcinoma of unknown primary origin with fluorescence lifetime imaging: Preliminary report.

BACKGROUND: This study evaluated whether fluorescence lifetime imaging (FLIm), coupled with standard diagnostic workups, could enhance primary lesion detection in patients with p16+ head and neck squamous cell carcinoma of the unknown primary (HNSCCUP). METHODS: FLIm was integrated into transoral robotic surgery to acquire optical data on six HNSCCUP patients' oropharyngeal tissues. An additional 55-patient FLIm dataset, comprising conventional primary tumors, trained a machine learning classifier; the output predicted the presence and location of HNSCCUP for the six patients. Validation was performed using histopathology. RESULTS: Among the six HNSCCUP patients, p16+ occult primary was surgically identified in three patients, whereas three patients ultimately had no identifiable primary site in the oropharynx. FLIm correctly detected HNSCCUP in all three patients (ROC-AUC: 0.90 ± 0.06), and correctly predicted benign oropharyngeal tissue for the remaining three patients. The mean sensitivity was 95% ± 3.5%, and specificity 89% ± 12.7%. CONCLUSIONS: FLIm may be a useful diagnostic adjunct for detecting HNSCCUP.

CD8(+) T cells in facioscapulohumeral muscular dystrophy patients with inflammatory features at muscle MRI.

Facioscapulohumeral muscular dystrophy (FSHD) is an inherited disease, and although strongly suggested, a contribution of inflammation to its pathogenesis has never been demonstrated. In FSHD patients, we found by immunohistochemistry inflammatory infiltrates mainly composed by CD8(+) T cells in muscles showing hyperintensity features on T2-weighted short tau inversion recovery magnetic resonance imaging (T2-STIR-MRI) sequences. Therefore, we evaluated the presence of circulating activated immune cells and the production of cytokines in patients with or without muscles showing hyperintensity features on T2-STIR-MRI sequences and from controls. FSHD patients displaying hyperintensity features in one or more muscles showed higher CD8(+)pSTAT1(+), CD8(+)T-bet(+) T cells and CD14(+)pSTAT1(+), CD14(+)T-bet(+) cells percentages and IL12p40, IFNγ and TNFα levels than patients without muscles displaying hyperintense features and controls. Moreover, the percentages of CD8(+)pSTAT1(+), CD8(+)T-bet(+) and CD14(+)pSTAT1(+) cells correlated with the proportion of muscles displaying hyperintensity features at T2-STIR sequences. These data indicate that circulating activated immune cells, mainly CD8(+) T cells, may favour FSHD progression by promoting active phases of muscle inflammation.

Cephalometric findings in facioscapulohumeral muscular dystrophy patients with obstructive sleep apneas.

PURPOSES: The purposes of the study are: (1) to establish if cephalometry and upper airway examination may provide tools for detecting facioscapulohumeral (FSHD) patients at risk for obstructive sleep apnea syndrome (OSAS); and (2) to correlate cephalometry and otorhinolaryngologic evaluation with clinical and polysomnographic features of FHSD patients with OSAS. METHODS: Patients were 13 adults affected by genetically confirmed FSHD and OSAS, 11 men, with mean age 47.1 ± 12.8 years (range, 33-72 years). All underwent clinical evaluation, Manual Muscle Test, Clinical Severity Scale for FSHD, Epworth Sleepiness Scale, polysomnography, otorhinolaryngologic evaluation, and cephalometry. RESULTS: Cephalometric evidence of pharyngeal narrowing [posterior airways space (PAS) < 10 mm] was present in only one patient. The mandibular planus and hyoid (MP-H) distance ranged from 6.5 to 33.1 mm (mean, 17.5 ± 7.8 mm). The mean length of soft palate (PNS-P) was 31.9 ± 4.8 mm (range, 22.2 to 39.7 mm). No patient presented an ANB angle > 7°. There was no significant correlation between cephalometric measures, clinical scores, and PSG indexes. PAS and MP-H were not related to the severity of the disease. CONCLUSIONS: Upper airway morphological evaluation is of poor utility in the clinical assessment of FSHD patients and do not allow to predict the occurrence of sleep-related upper airway obstruction. This suggests that the pathogenesis of OSAS in FSHD is dependent on the muscular impairment, rather than to the anatomy of upper airways.

The Impact of COVID-19 on Head and Neck Cancer Treatment: Before and During the Pandemic.

OBJECTIVES: To describe the impact that the coronavirus disease 2019 (COVID-19) pandemic had on the presentation of patients with head and neck cancer in a single tertiary care center. STUDY DESIGN: Retrospective cohort study. SETTING: Academic institution. METHODS: We performed a retrospective review of patients with newly diagnosed head and neck squamous cell carcinoma (HNSCC) who presented as new patients between September 10, 2019, and September 11, 2020. Patients presenting during the 6 months leading up to the announcement of the pandemic (pre-COVID-19 period) on March 11, 2020, were compared to those presenting during the first 6 months of the pandemic (COVID-19 period). Demographics, time to diagnosis and treatment, and tumor characteristics were analyzed. RESULTS: There were a total of 137 patients analyzed with newly diagnosed malignancies. There were 22% fewer patients evaluated during the COVID-19 timeframe. The groups were similar in demographics, duration of symptoms, time to diagnosis, time to surgery, extent of surgery, and adjuvant therapy. There was a larger proportion of tumors classified as T3/T4 (61.7%) in the COVID-19 period vs the pre-COVID-19 period (40.3%) (P = .024), as well as a larger median tumor size during the COVID-19 period (P = .0002). There were no differences between nodal disease burden (P = .48) and distant metastases (P = .42). CONCLUSION: Despite similar characteristics, time to diagnosis, and surgery, our findings suggest that there was an increase in primary tumor burden in patients with HNSCC during the early COVID-19 pandemic.

A standardized clinical evaluation of patients affected by facioscapulohumeral muscular dystrophy: The FSHD clinical score.

To define numerically the clinical severity of facioscapulohumeral muscular dystrophy (FSHD), we developed a protocol that quantifies muscle weakness by combining the functional evaluation of six muscle groups affected in this disease. To validate reproducibility of the protocol, 69 patients were recruited. Each patient was evaluated by at least five neurologists, and an FSHD severity score was given by each examiner. The degree of agreement among clinicians' evaluations was measured by kappa-statistics. Nineteen subjects received a score between 0 and 1, 9 had a score between 2 and 4, 20 received a score between 5 and 10, and 8 had a score between 11 and 15. Of the 13 subjects with D4Z4 alleles within the normal range (ranging from 10 to 150 repeats), 12 obtained a score of 0 and only 1 had a score of 1. Kappa-statistics showed a very high concordance for all muscle groups. We developed a simple, reliable, easily used tool to define the clinical expression of FSHD. Longitudinal studies will assess its sensitivity and utility in measuring changes for widespread use.

Heart rate variability in facioscapulohumeral muscular dystrophy.

Facioscapulohumeral muscular dystrophy (FSHD) is the third most frequent form of muscular dystrophy. Heart rate variability (HRV) analysis is a means of evaluating the activity of the autonomic nervous system. The aim of this study was to evaluate HRV in FSHD patients. Fifty-five consecutive FSHD patients were enrolled (31 men, age 26-72 years). Muscular impairment was measured using a clinical severity scale (CSS). Patients were compared with a control group of 55 healthy subjects, matched for age and sex. HRV was analyzed in the time domain and in the frequency domain. Patients showed increased spectral power of the low-frequency band. Spectral power of the high-frequency band was inversely correlated with CSS score. FSHD is associated with a slight increase in sympathetic output and with a decrease in parasympathetic output. These modifications become more evident with the progression of the disease and could increase the risk of arrhythmias and other cardiovascular events.

EEG microstate complexity for aiding early diagnosis of Alzheimer's disease.

The dynamics of the resting brain exhibit transitions between a small number of discrete networks, each remaining stable for tens to hundreds of milliseconds. These functional microstates are thought to be the building blocks of spontaneous consciousness. The electroencephalogram (EEG) is a useful tool for imaging microstates, and EEG microstate analysis can potentially give insight into altered brain dynamics underpinning cognitive impairment in disorders such as Alzheimer's disease (AD). Since EEG is non-invasive and relatively inexpensive, EEG microstates have the potential to be useful clinical tools for aiding early diagnosis of AD. In this study, EEG was collected from two independent cohorts of probable AD and cognitively healthy control participants, and a cohort of mild cognitive impairment (MCI) patients with four-year clinical follow-up. The microstate associated with the frontoparietal working-memory/attention network was altered in AD due to parietal inactivation. Using a novel measure of complexity, we found microstate transitioning was slower and less complex in AD. When combined with a spectral EEG measure, microstate complexity could classify AD with sensitivity and specificity > 80%, which was tested on an independent cohort, and could predict progression from MCI to AD in a small preliminary test cohort of 11 participants. EEG microstates therefore have potential to be a non-invasive functional biomarker of AD.

Abnormal sexual behavior during sleep.

INTRODUCTION: Automatic, uncontrolled, and unaware sexual behaviors during sleep have occasionally been described. The clinical and polysomnographic features of nocturnal sexual behavior allow it to be considered a distinct parasomnia named "sexsomnia". Recently, abnormal sexual behaviors during sleep have been evaluated in the forensic medical context because violent behaviors can be associated with this parasomnia. AIM: To describe the clinical and polysomnographic findings in three patients who referred to our sleep laboratory for sleep disorders and who reported episodes of sleep-related sexual activation. MAIN OUTCOME MEASURES: We analyzed video-polysomnographic recordings, sleep structure, sleep microstructure, and sleep-related respiratory events. METHODS: The patients were three males aged 42, 32, and 46 years. All had unremarkable medical, neurological, and psychiatric histories. All underwent full-night polysomnography. RESULTS: Each patient presented a distinct sleep disorder: one had severe obstructive sleep apnea syndrome (OSAS), one presented clinical and polysomnographic features of non-rapid eye movement (NREM) sleep parasomnia (somnambulism), and the third presented clinical and polysomnographic features of rapid eye movement behavior disorder. CONCLUSIONS: In our patients, the clinical and polysomnographic findings suggest that abnormal nocturnal sexual behavior can occur in association with distinct sleep disorders, characterized by different pathophysiologic mechanisms and distinctive treatments. Abnormal sexual behaviors during sleep should be investigated with polysomnography in order to define their pathophysiology and to establish appropriate treatments.

First Attack and Clinical Presentation of Hemiplegic Migraine in Pediatric Age: A Multicenter Retrospective Study and Literature Review.

Background: Data on clinical presentation of Hemiplegic Migraine (HM) are quite limited in the literature, particularly in the pediatric age. The aim of the present study is to describe in detail the phenotypic features at onset and during the first years of disease of sporadic (SHM) and familial (FHM) pediatric hemiplegic migraine and to review the pertinent literature. Results: Retrospective study of a cohort of children and adolescents diagnosed with hemiplegic migraine, recruited from 11 Italian specialized Juvenile Headache Centers. Forty-six cases (24 females) were collected and divided in two subgroups: 32 SHM (16 females), 14 FHM (8 females). Mean age at onset was 10.5 ± 3.8 y (range: 2-16 y). Mean duration of motor aura was 3.5 h (range: 5 min-48 h). SHM cases experienced more prolonged attacks than FHM cases, with significantly longer duration of both motor aura and of total HM attack. Sensory (65%) and basilar-type auras (63%) were frequently associated to the motor aura, without significant differences between SHM and FHM. At follow-up (mean duration 4.4 years) the mean frequency of attacks was 2.2 per year in the first year after disease onset, higher in FHM than in SHM cases (3.9 vs. 1.5 per year, respectively). A literature review retrieved seven studies, all but one were based on mixed adults and children cohorts. Conclusions: This study represents the first Italian pediatric series of HM ever reported, including both FHM and SHM patients. Our cohort highlights that in the pediatric HM has an heterogeneous clinical onset. Children present fewer non-motor auras as compared to adults and in some cases the first attack is preceded by transient neurological signs and symptoms in early childhood. In SHM cases, attacks were less frequent but more severe and prolonged, while FHM patients had less intense but more frequent attacks and a longer phase of active disease. Differently from previous studies, the majority of our cases, even with early onset and severe attacks, had a favorable clinical evolution.

Isolation and characterization of mesoangioblasts from facioscapulohumeral muscular dystrophy muscle biopsies.

Facioscapulohumeral muscular dystrophy (FSHD) is the third most frequent inherited muscle disease. Because in FSHD patients the coexistence of affected and unaffected muscles is common, myoblasts expanded from unaffected FSHD muscles have been proposed as suitable tools for autologous cell transplantation. Mesoangioblasts are a new class of adult stem cells of mesodermal origin, potentially useful for the treatment of primitive myopathies of different etiology. Here, we report the isolation and characterization of mesoangioblasts from FSHD muscle biopsies and describe morphology, proliferation, and differentiation abilities of both mesoangioblasts and myoblasts derived from various affected and unaffected muscles of nine representative FSHD patients. We demonstrate that mesoangioblasts can be efficiently isolated from FSHD muscle biopsies and expanded to an amount of cells necessary to transplant into an adult patient. Proliferating mesoangioblasts from all muscles examined did not differ from controls in terms of morphology, phenotype, proliferation rate, or clonogenicity. However, their differentiation ability into skeletal muscle was variably impaired, and this defect correlated with the overall disease severity and the degree of histopathologic abnormalities of the muscle of origin. A remarkable differentiation defect was observed in mesoangioblasts from all mildly to severely affected FSHD muscles, whereas mesoangioblasts from morphologically normal muscles showed no myogenic differentiation block. Our study could open the way to cell therapy for FSHD patients to limit muscle damage in vivo through the use of autologous mesoangioblasts capable of reaching damaged muscles and engrafting into them, without requiring immune suppression or genetic correction in vitro. Disclosure of potential conflicts of interest is found at the end of this article.