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.

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.

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.

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.

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.

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.

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.

Missense mutations of CACNA1A are a frequent cause of autosomal dominant nonprogressive congenital ataxia.

BACKGROUND: Mutations in the CACNA1A gene, encoding the pore-forming CaV2.1 (P/Q-type) channel α1A subunit, localized at presynaptic terminals of brain and cerebellar neurons, result in clinically variable neurological disorders including hemiplegic migraine (HM) and episodic or progressive adult-onset ataxia (EA2, SCA6). Most recently, CACNA1A mutations have been identified in patients with nonprogressive congenital ataxia (NPCA). METHODS: We performed targeted resequencing of known genes involved in cerebellar dysfunction, in 48 patients with congenital or early onset ataxia associated with cerebellar and/or vermis atrophy. RESULTS: De novo missense mutations of CACNA1A were found in four patients (4/48, ∼8.3%). Three of them developed migraine before or after the onset of ataxia. Seizures were present in half of the cases. CONCLUSION: Our results expand the clinical and mutational spectrum of CACNA1A-related phenotype in childhood and suggest that CACNA1A screening should be implemented in this subgroup of ataxias.

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.

Upper girdle imaging in facioscapulohumeral muscular dystrophy.

BACKGROUND: In Facioscapulohumeral muscular dystrophy (FSHD), the upper girdle is early involved and often difficult to assess only relying on physical examination. Our aim was to evaluate the pattern and degree of involvement of upper girdle muscles in FSHD compared with other muscle diseases with scapular girdle impairment. METHODS: We propose an MRI protocol evaluating neck and upper girdle muscles. One hundred-eight consecutive symptomatic FSHD patients and 45 patients affected by muscular dystrophies and myopathies with prominent upper girdle involvement underwent this protocol. Acquired scans were retrospectively analyzed. RESULTS: The trapezius (100% of the patients) and serratus anterior (85% of the patients) were the most and earliest affected muscles in FSHD, followed by the latissimus dorsi and pectoralis major, whilst spinati and subscapularis (involved in less than 4% of the patients) were consistently spared even in late disease stages. Asymmetry and hyperintensities on short-tau inversion recovery (STIR) sequences were common features, and STIR hyperintensities could also be found in muscles not showing signs of fatty replacement. The overall involvement appears to be disease-specific in FSHD as it significantly differed from that encountered in the other myopathies. CONCLUSIONS: The detailed knowledge of single muscle involvement provides useful information for correctly evaluating patients' motor function and to set a baseline for natural history studies. Upper girdle imaging can also be used as an additional tool helpful in supporting the diagnosis of FSHD in unclear situations, and may contribute with hints on the currently largely unknown molecular pathogenesis of this disease.

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.

Different molecular signatures in magnetic resonance imaging-staged facioscapulohumeral muscular dystrophy muscles.

BACKGROUND: Facioscapulohumeral muscular dystrophy (FSHD) is one of the most common muscular dystrophies and is characterized by a non-conventional genetic mechanism activated by pathogenic D4Z4 repeat contractions. By muscle Magnetic Resonance Imaging (MRI) we observed that T2-short tau inversion recovery (T2-STIR) sequences identify two different conditions in which each muscle can be found before the irreversible dystrophic alteration, marked as T1-weighted sequence hyperintensity, takes place. We studied these conditions in order to obtain further information on the molecular mechanisms involved in the selective wasting of single muscles or muscle groups in this disease. METHODS: Histopathology, gene expression profiling and real time PCR were performed on biopsies from FSHD muscles with different MRI pattern (T1-weighted normal/T2-STIR normal and T1-weighted normal/T2-STIR hyperintense). Data were compared with those from inflammatory myopathies, dysferlinopathies and normal controls. In order to validate obtained results, two additional FSHD samples with different MRI pattern were analyzed. RESULTS: Myopathic and inflammatory changes characterized T2-STIR hyperintense FSHD muscles, at variance with T2-STIR normal muscles. These two states could be easily distinguished from each other by their transcriptional profile. The comparison between T2-STIR hyperintense FSHD muscles and inflammatory myopathy muscles showed peculiar changes, although many alterations were shared among these conditions. CONCLUSIONS: At the single muscle level, different stages of the disease correspond to the two MRI patterns. T2-STIR hyperintense FSHD muscles are more similar to inflammatory myopathies than to T2-STIR normal FSHD muscles or other muscular dystrophies, and share with them upregulation of genes involved in innate and adaptive immunity. Our data suggest that selective inflammation, together with perturbation in biological processes such as neoangiogenesis, lipid metabolism and adipokine production, may contribute to the sequential bursts of muscle degeneration that involve individual muscles in an asynchronous manner in this disease.

An integrated video-analysis software system designed for movement detection and sleep analysis. Validation of a tool for the behavioural study of sleep.

OBJECTIVE: The aim of the present study was to develop and validate a software tool for the detection of movements during sleep, based on the automated analysis of video recordings. This software is aimed to detect and quantify movements and to evaluate periods of sleep and wake. METHODS: We applied an open-source software, previously distributed on the web (Zoneminder, ZM), meant for video surveillance. A validation study was performed: computed movement analysis was compared with two standardised, 'gold standard' methods for the analysis of sleep-wake cycles: actigraphy and laboratory-based video-polysomnography. RESULTS: Sleep variables evaluated by ZM were not different from those measured by traditional sleep-scoring systems. Bland-Altman plots showed an overlap between the scores obtained with ZM, PSG and actigraphy, with a slight tendency of ZM to overestimate nocturnal awakenings. ZM showed a good degree of accuracy both with respect to PSG (79.9%) and actigraphy (83.1%); and had very high sensitivity (ZM vs. PSG: 90.4%; ZM vs. actigraphy: 89.5%) and relatively lower specificity (ZM vs. PSG: 42.3%; ZM vs. actigraphy: 65.4%). CONCLUSIONS: The computer-assisted motion analysis is reliable and reproducible, and it can allow a reliable esteem of some sleep and wake parameters. The motion-based sleep analysis shows a trend to overestimate wakefulness. SIGNIFICANCE: The possibility to measure sleep from video recordings may be useful in those clinical and experimental conditions in which traditional PSG studies may not be performed.

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.