Nasal Passageways Research Articles

A rare presentation of nasopharyngeal mass: a case report

A Thornwaldt's cyst develops in the nasopharynx, which is the region where the throat and nasal passageways converge, extending from the back of the nasal tube to above the soft palate. A painful throat, obstruction of the eustachian tube, and pus with an unpleasant taste and odour might result from an infection of the cyst. Here in our study, we report a case of a 27-year-old male presented with symptoms of nasal obstruction and voice change for the past 1 year. On zero-degree endoscopic examination, a nasopharyngeal mass was seen arising from the roof of the nasopharynx without bony erosion of skull base. Further based on his radiological investigations, heterogeneous hyperintense lesion in T1/T2 weighted images of size 5×5 mm noted in nasopharynx most likely to be the Thornwaldt’s cyst. Thus, the surgical removal of the nasopharyngeal mass has been performed through a transoral and trans nasal endoscopic technique with no remnants at the surgical site. The histopathological findings revealed respiratory-type epithelium with underlying lymphoid tissue confirming Thornwald’s cyst as diagnosis. The patient was discharged with no complications and have been periodically advised for a follow-up. The differential diagnosis should include a meningocele or meningo-encephalocele. Various therapeutic approaches, including endoscopic, transoral, or trans palatal surgical interventions, can be used for treatment of symptomatic cysts.

The Effects of the Maxillary Movements in Angle Class 2 and 3 Malocclusion Treatment on Nose Air Flow Amount, Rate, and Resistance.

Maxillary movements performed during orthognathic surgery affect the external and internal anatomy of the nose. The functional and anatomical effects may change nasal airway parameters after the surgery, and these alterations can be examined objectively by rhinomanometry. In this study, patients who underwent maxillary orthognathic surgery were divided into 3 groups based on their surgical plans: advancement (group 1), impaction and advancement (group 2), and setdown and advancement (group 3). Preoperative and postoperative rhinomanometric data including the average nasal volume, minimum cross-sectional area, average airflow resistance of the right and left nasal passageways, and an average of both nasal passages were collected. The study included 50 patients who underwent orthognathic surgery between October 2021 and October 2022. There were 20 patients each in group 1 and group 2 and 10 patients in group 3. The average nasal passage volume increased in the advancement (group 1) and impaction-advancement (group 2) groups. In addition, the advancement (group 1) group had a decreased average airflow resistance. Setdown-advancement (group 3) group did not show a positive or negative effect on nasal airway parameters. Maxillary movements during orthognathic surgery revealed no adverse effect on nasal parameters. Moreover, advancement and impaction positively affected nasal functional and anatomical parameters.

Canine-inspired Unidirectional Flows for Improving Memory Effects in Machine Olfaction.

A dog's nose differs from a human's in that air does not change direction but flows in a unidirectional path from inlet to outlet. Previous simulations showed that unidirectional flow through a dog's complex nasal passageways creates stagnant zones of trapped air. We hypothesize that these zones give the dog a "physical memory," which it may use to compare recent odors to past ones. In this study, we conducted experiments with our previously built Gaseous Recognition Oscillatory Machine Integrating Technology (GROMIT) and performed corresponding simulations in two dimensions. We compared three settings: a control setting that mimics the bidirectional flow of the human nose; a short-circuit setting where odors exit before reaching the sensors; and a unidirectional configuration using a dedicated inlet and outlet that mimics the dog's nose. After exposure to odors, the sensors in the unidirectional setting showed the slowest return to their baseline level, indicative of memory effects. Simulations showed that both short-circuit and unidirectional flows created trapped recirculation zones, which slowed the release of odors from the chamber. In the future, memory effects such as the ones found here may improve the sensitivity and utility of electronic noses.

Early Transcriptional Responses of Human Nasal Epithelial Cells to Infection with Influenza A and SARS-CoV-2 Virus Differ and Are Influenced by Physiological Temperature.

Influenza A (IAV) and SARS-CoV-2 (SCV2) viruses represent an ongoing threat to public health. Both viruses target the respiratory tract, which consists of a gradient of cell types, receptor expression, and temperature. Environmental temperature has been an understudied contributor to infection susceptibility and understanding its impact on host responses to infection could help uncover new insight into severe disease risk factors. As the nasal passageways are the initial site of respiratory virus infection, in this study we investigated the effect of temperature on host responses in human nasal epithelial cells (hNECs) utilizing IAV and SCV2 in vitro infection models. We demonstrate that temperature affected SCV2, but not IAV, viral replicative fitness and that SCV2-infected cultures were slower to mount an infection-induced response, likely due to suppression by the virus. Additionally, we show that that temperature not only changed the basal transcriptomic landscape of epithelial cells, but that it also impacted the response to infection. The induction of interferon and other innate immune responses was not drastically affected by temperature, suggesting that while the baseline antiviral response at different temperatures remained consistent, there may be metabolic or signaling changes that affect how well the cultures were able to adapt to new pressures, such as infection. Finally, we show that hNECs responded differently to IAV and SCV2 infection in ways that give insight into how the virus is able to manipulate the cell to allow for replication and release. Taken together, these data give new insight into the innate immune response to respiratory infections and can assist in identifying new treatment strategies for respiratory infections.

Deviated Nasal Septum in Left Side Nose: A Case Report

Introduction: When the thin wall that separates your right and left nasal passageways, your nasal septum, is moved to one side, you have a deviated septum. A disorder that is present at birth can create a deviated septum. A deviated septum can form during prenatal development and become visible at birth in some situations.
 Main Symptoms and Important Clinical Findings: One or both nostrils are blocked. This obstruction (blockage) can make breathing via the nose or nostrils difficult. Nosebleeds. Pain in the face. During sleep, there is a lot of noise. The nasal cycle is something to be aware of. A preference for sleeping on one side over the other.
 Patient Information: A patient is 45year old, having chief complete is shortness of breath, chest pain, fatigue, coughing, and weakness. Patient admitted to the hospital on date 12-7-21.
 Clinical Findings: The Patient appeared to be awake and oriented with an individual on general inspection. Nasal bleeding, congestion, loss of smell, runny lose or post-nasal drip headache patients with clinical symptoms that are very similar to those of our case have lately been described.
 Medical Management: Decongestants are drugs that assist keep the airways on both sides of your nose open by reducing nasal tissue swelling. Antihistamines are antihistamines, which assist to avoid allergy symptoms such as a stuffy or runny nose—steroid nasal spray.
 Nursing Management: Administered fluid replacement (DNS and RL), maintained intake and output charts, and monitored hourly vital signs.
 Conclusion: Nasal obstruction is a prevalent complaint among patients when the septum has deviated, stressing the need for more effective procedures to aid physicians in recommending surgical therapy when a patient has a nasal septum deviation.

Correlation of brachycephaly grade with level of exophthalmos, reduced airway passages and degree of dental malalignment' in Persian cats.

For many years, there has been a trend to breed cats with an increasing degree of brachycephalic head features, which are known to have a severe impact on the animals’ health and welfare. The direct relation between different grades of brachycephaly and their negative implications have not been researched in this species. The aim of this study was therefore to establish correlations between the different grades of brachycephaly and reduced upper respiratory airways, exophthalmos of the eye globes and malalignment of the teeth in Persian cats. Sixty-nine Persian cats of various skull dimensions and ten Domestic shorthair cats were recruited for the study. The cats’ skulls were examined using three-dimensional reconstructions created from Computed Tomography datasets. Brachycephaly was graded using established craniometric measurements (facial index, cranial index, skull index, craniofacial angle). The flow area of the nasal passageways at different locations, the amount of the eye globe not supported by the bony orbit and the axial deviation of the teeth were quantified and evaluated for a correlation with the grade of brachycephaly. The results of this study clearly show that increased grades of brachycephaly in Persian cats resulted in larger extra-orbital parts of the ocular bulbs. The brachycephalic skull dimension also resulted in a lower height of the naso-osseal aperture, while other areas of the nasal airways were not correlated with the severity of brachycephaly. Persian cats showed a significantly increased occurrence of premolar tooth displacement in the upper jaw with increasing brachycephaly grades. It was interesting to note that the measured values had a broad range and values of some individual Persian cats showed an overlap with those of Domestic shorthair cats.

An optimization method for surgical reduction of hypertrophied inferior turbinate

Surgical reductions of the hypertrophied inferior turbinate (HIT) can improve nasal obstruction. However, there is currently a lack of personalized and objective methods to guide surgical operations, which results in the excessive or inadequate resection of HIT. In this study, we proposed an optimizing method based on homotopy deformation to determine the resected amount and shape of the tissue by matching the flow resistance in the two nasal passageways. The simulation results obtained using computational fluid dynamics showed that after such an optimization procedure, the most obstructed nasal side could have a similar air flux as the less obstructed side. A 35% and a 56% less tissue resection in the optimizing operation compared to that in the total turbinectomy could well balance the air flow between the two nasal cavities in the simulations for patients 1 and 2 with unilateral nasal obstruction respectively. Compared with the optimization operation, the total turbinectomy made a more aggressive resection of HIT, which could worsen the air conditioning capacity of the nose. A sensitivity test indicated that in the optimization operation, the most constricted region in the nasal cavity should be adequately enlarged. However, more tissue resection than is required for the optimization operation did not improve the flow in the obstructed side strikingly. Simulations of the optimization operation in both nasal cavities for a patient with bilateral nasal obstruction were also performed. The flow rate could reach the normal level and be well balanced in the two sides after such an optimization procedure.

In the nose, not the sella: Case report of an ectopic pituitary adenoma

Abstract Background and importance Ectopic pituitary adenomas presenting in the nasal and paranasal sinuses are very rare. We report a patient with a large ectopic nonfunctioning pituitary macroadenoma involving the nasal passageways, ethmoid sinus, and extending through the cribriform plate extradurally to the anterior fossa with no involvement of the sella turcica. The patient presented with epistaxis and denied any visual disturbances or other associated clinical presentations that would demonstrate extensive cranial nerve involvement. Ectopic pituitary adenomas should be considered in the differential diagnosis of a nasal mass involving the nasal sinuses, even if there is no communication with the sella. Clinical presentation The patient is a 46-year-old male who presented with complete nasal obstruction. MRI revealed a large bilateral nasal mass extending into the anterior fossa through the cribriform plate. On nasal endoscopy, the patient was found to have a large mass occluding the entire nasal cavity. Subsequently, an endoscopic endonasal resection was performed. Conclusion This case represents a rare presentation of an ectopic pituitary adenoma. The extensive tumor involvement of the nasal passageways, ethmoid sinuses, and the anterior fossa with the absence of cranial nerve involvement are notable. Histopathologic confirmation of the ectopic pituitary tumor was made after complete endoscopic endonasal removal.

Distribution of methicillin-resistant coagulase-positive staphylococci (MRCoPS) in a surgical unit and cystotomy operation sites in a veterinary teaching hospital.

This study aimed to investigate the spread of methicillin-resistant coagulase-positive staphylococci (MRCoPS) among veterinary staff, hand-touch sites and surgical tissue during cystotomy operations on cats and dogs that were patients, and to analyze the genetic relatedness and antimicrobial resistance profiles of the isolates. Human and environmental samples were obtained from the nasal passageways of 12 surgeons and veterinary assistants and from 29 hand-touch sites of instruments in operative units and subjected to bacterial isolation and enumeration. Swab samples were collected in triplicate from 29 dogs and three cats at the site of incision, from the incision area, from the peritoneum during surgery and from the peritoneum before suture. MRCoPS were identified by mecA gene detection and characterized by their antibiogram profile, SCCmec type and pulsed-field gel electrophoresis. Twenty-four staphylococci were isolated, derived from one veterinary assistant, 12 operating room floor areas and hand-touch sites, three dogs and one cat. Methicillin-resistant S. pseudintermedius (MRSP) was found on an electric clipper and rebreathing circuits in the operating room. Three dogs were positive for MRSP during surgery, and one methicillin-resistant S. aureus (MRSA) was detected in a cat. All MRCoPS were resistant to doxycycline, erythromycin, clindamycin and enrofloxacin, but no patients developed surgical site infections. According to their genotypic patterns, the clones obtained from the environment and human sources differed from the animal clones. Despite intensive hygienic management, a variety of MRCoPS clones were present within the surgical unit and during surgery.

Evaluation of nasal airway patency by analysis of breathing sounds

Conclusions: A simple non-invasive method, based on acoustic analysis of breathing signals, revealed a potential for objective evaluation of differences between the patency of nasal passageways. Objectives: To examine whether acoustic signals of nasal breathing contain information that can differentiate between obstructed and patent nasal passageways. Method: A technical study aimed to examine measurements of nasal airflow acoustic signals, taken, non-invasively, simultaneously from both external sides of the nostrils. The signals were acquired for several breathing cycles, with different respiratory efforts, before and after application of a nasal decongestant to the (narrower) side that yielded lower amplitudes. Data processing of the expiratory phase yielded the power spectrum density (PSD), which was used to compute the ratio of PSD areas between the signals from both sides of the nose. The study group was composed of 20 healthy volunteers. Results: PSD changes were noted in accordance with the rise in expiratory efforts. The ratio of PSD areas between the two sides of the nasal cavity, calculated for maximal expiratory efforts, correlated well with the side that was treated with nasal decongestant in 18 out of the 20. Changes in the opposite direction were noted in two examinees.

30 Allogeneic stem cell transplantation from alternative stem cell sources in myelodysplastic syndromes

The location of stem cells within the adult CNS makes them impractical for surgical removal and autologous transplantation. Their limited availability and histocompatibility issues further restrict their use. In contrast, olfactory neuroepithelium (ONe) located in the nasal passageways has a continuous regenerative capability and can be biopsied readily. To investigate the potential of human ONe to provide viable populations of pluripotent cells, ONe was harvested from cadavers 6–18 h postmortem, dissociated, plated and fed every 3–4 days. Heterogeneous populations of neurons, glia, and epithelia were identified with lineage-specific markers. After several weeks, 5–10% of the cultures produced a population of rapidly dividing cells, which in turn, produced neurospheres containing at least two subpopulations based on neuronal and glial specific antigens. Most contained one or more neuronal markers; a few were positive for A2B5 and/or GFAP. To determine if growth modulators would affect the neurosphere forming cells, they were exposed to dibutyryl–cAMP. The nucleotide reduced cell division and increased process formation. Although the cells had been passaged more than 70 times, their viability remained constant as shown by the MTT viability index. Donor age or sex were not limiting factors, because neurospheres have been established from cadavers of both sexes from 50 to 95 years old at time of death. The ex vivo expansion of these cells will provide a patient-specific population of cells for immunological, genetic and pharmacological evaluation. Our long-term goal is to determine the utility of these cells to facilitate CNS repair.

Nosehouse: heat-conserving ventilators based on nasal counterflow exchangers

Small birds and mammals commonly minimize respiratory heat loss with reciprocating counterflow exchangers in their nasal passageways. These animals extract heat from the air in an exhalation to warm those passageways and then use that heat to warm the subsequent inhalation. Although the near-constant volume of buildings precludes direct application of the device, a pair of such exchangers located remotely from each other circumvents that problem. A very simple and crudely constructed small-scale physical model of the device worked well enough as a heat conserver to suggest utility as a ventilator for buildings.

The impact of nasal surgery on air-conditioning of the nasal airways

Air-conditioning in the nasal passageways is one of the most important functions of the upper airways. By means of in-vivo-measurements and numerical simulation, the air-conditioning function of the nose has been extensively investigated. Less well known is the effect of nasal surgery on the nasal climate. The following study presents a summary of the effect of various rhino-surgical operations, i.e. turbinoplasty, septoplasty, septorhinoplasty, repair of septal perforations, functional and radical sinus surgery, on the air-conditioning function of the nose. Nasal and sinonasal interventions have been demonstrated to be associated with increased nasal heating and humidification when the mucosal lining is preserved. Radical interventions with reduction of turbinate tissue cause reduced nasal warming and moistening within the nasal airway, with increased risk of nasal dryness and crusting. Although the impact of the nasal cycle and the airflow distribution within the nasal cavity on nasal temperature and humidity distribution is not fully understood yet, too much widening of the nasal cavity by sinunasal interventions has carefully to be avoided.

Experimental investigation of nasal airflow

The airway geometry of the nasal cavity is manifestly complex, and the manner in which it controls the airflow to accomplish its various physiological functions is not fully understood. Since the complex morphology and inaccessibility of the nasal passageways precludes detailed in-vivo measurements, either computational simulation or in-vitro experiments are needed to determine how anatomical form and function are related. The fabrication of a replica model of the nasal cavity, of a high optical clarity and derived from in-vivo scan data is described here, together with characteristics of the flow field investigated using particle image velocimetry (PIV) and flow visualization. Flow visualization is shown to be a capable and convenient technique for identifying key phenomena. Specifically the emergence of the jet from the internal nasal valve into the main cavity, how it impacts on the middle turbinate, and the large enhancement of dispersion that accompanies the initial appearance of flow instability are revealed as particularly significant features. The findings from the visualization experiments are complemented by PIV imaging, which provides quantitative detail on the variations in velocity in different regions of the nasal cavity. These results demonstrate the effectiveness of the cavity geometry in partitioning the flow into high shear zones, which facilitate rapid heat transfer and humidification from the nasal mucosa, and slower zones affording greater residence times to facilitate olfactory sensing. The experimental results not only provide a basis for comparison with other computational modelling but also demonstrate an alternative and flexible means to investigate complex flows, relevant to studies in different parts of the respiratory or cardiovascular systems.

Análisis del flujo aéreo en la cavidad nasal mediante Mecánica de Fluidos Computacional

ObjectiveThis study represents an attempt to simulate the complex three-dimensional airflow pattern in the human nasal passageways. Materials and MethodsIn the present study the computational Fluid Dynamics (CFD) have been used. The CFD solved numerically the flow governing equations. The CFD demonstrated to be a very efficient tool for researching on nasal flow. ResultsBy means of CT scan, an anatomic accurate three-dimensional representation of the human nasal cavity was obtained. Based on this model the influence of the inspiration and at the expiration at the flow pattern has been reviewed. The flow pattern is visualized by the velocity, pressure and turbulence intensity fields. ConclusionsThe flow patterns show the channel effect of turbinates and the influence of the breathing phase.

Morphological variation and airflow dynamics in the human nose

Airflow dynamics are recognized as being important to the functioning of the human nose in conditioning and filtering inspired air, yet these dynamics are poorly understood. Despite considerable research on airflow dynamics by otolaryngologists, respiratory physiologists, and toxicologists, major disagreements remain about the nature of airflow in the human nose. Specifically, there is little consensus about the character of nasal airflow regimes (laminar or turbulent) and about the major pathways of airflow through the internal chamber. Additionally, a number of features in the human nose have been argued to enhance airflow turbulence, thus increasing the exposure of moving air to the nasal mucosa and facilitating heat and moisture exchange in cold and/or dry climates. These features include: an inferior orientation of the nares; a nasal sill that is high relative to the floor of the internal nasal chamber; a nasal valve that is small in cross-sectional area relative to that of the internal chamber; and large, projecting conchae. The claim that these features affect airflow dynamics has never been tested. To clarify the nature of human nasal airflow and to test these claims of functional significance to nasal variation, we studied airflow across physiological flow rates using water and dye flowing through anatomically accurate acrylic models of human nasal air passageways (with adjustment of water flow rates to maintain dynamic similarity). The models were derived from direct casting of the nasal passageways of 10 Caucasian ("leptorrhine") cadavers (six male, four female). Measures of naris angle, nasal sill height, nasal valve area relative to internal chamber cross-sectional area, and relative projection of the inferior and middle turbinates were taken directly on the resulting casts. The relationships between aspects of nasal morphology and turbulent air flow were evaluated by examining the flow regimes (laminar, semiturbulent, or turbulent) at varying flow rates, with the expectation that the greater the development of the proposed turbulence-enhancing features the slower the flow rate at which flow would shift from one regime to another. Flow characteristics (both flow regimes and principal pathways) were highly variable within our sample. The relative projection of the inferior turbinate was the only variable that significantly affected the flow rate at which flow became turbulent. However, more projecting turbinates appear to laminate flow rather than to induce turbulence. Nostril orientation was moderately correlated with flow dynamics (with more inferiorly directed nares producing turbulence at slower flow rates), but this correlation was not statistically significant. Relative nasal valve area and nasal sill height were unrelated to turbulence in our models.

Comparison of Feline Nasal Cavity Dimensions Measured by Acoustic Rhinometry and Nasal Casts

The goal of this study was to evaluate the relationship between feline nasal cavity geometry determined in vivo by acoustic rhinometry (AR(in vivo)) and by nasal cavity casts. Cast cross-sectional areas were measured by acoustic rhinometry (AR(cast)), a fluid-displacement method (FDM), and slicing. A volume comparison between AR(in vivo) and AR(cast) was studied in cats with varying degrees of nasal obstruction after application of phenylpropanolamine, saline, or compound 48/80. After measurements of AR(in vivo), impression material was injected into the nasal cavity to produce casts. Subsequently, the cross-sectional areas of the nasal impressions were measured by AR(cast) and FDM using ethanol. All casts were weighed to determine exact volume. Six casts also were sliced into segments of equal thickness for determination of cross-sectional area. Cast volume determined by AR(cast) was consistent with results obtained using FDM and weight. Volumes of the first 3 cm determined by AR(in vivo) ranged between 78 +/- 9% of cast volumes determined by AR(cast) for decongested cavities and 16 +/- 15% for congested cavities. AR(in vivo) does not reflect cast geometry, probably because of (1) underestimation by AR because of methodological problems caused by the cavity geometry, (2) deformation of compliant structures within the nasal passageways resulting from the casting procedure, and/or (3) the casting material reaches parts of the nasal cavity not accessible to sound, e.g., sinuses or recesses. Nevertheless, this study does not preclude the use of AR as a sensitive method suited to evaluate relative changes in nasal volume caused by experimental challenges of the nasal mucosa. Compared with AR(in vivo), casts still may be of use but it is less sensitive to measure relative changes after experimental challenge.

Tourette Syndrome: The Neurology of a Tic

Tourette Syndrome: The Neurology of a Tic

Risk Factors for Epistaxis during Nasotracheal Intubation

We performed a study to confirm which risk factors are significantly associated with epistaxis during nasotracheal intubation. One hundred patients who underwent nasotracheal intubation were included. Risk factors for epistaxis were analysed using the multiple logistic regression analysis with stepwise variable selection method. Epistaxis was most likely to occur if transit of the tube through the nasal passage was difficult (P=0.0001, odds ratio 625, 95% confidence interval 3.14-14.26). On the other hand, age and gender, obesity, smoking, tube size, repeated attempts of intubation, and intubation performed with the aid of Magillforceps were not significantly related with risk of epistaxis. The presence of nasal anatomical abnormalities also did not correlate significantly with epistaxis. Strategies to ensure smooth transit of the tube through the nasal passageways are essential to reduce the incidence of epistaxis.

Poor sleep and daytime somnolence in allergic rhinitis: significance of nasal congestion.

Patients with allergic rhinitis frequently present with symptoms of nasal congestion, runny nose, sneezing, daytime somnolence and fatigue associated with decreased cognitive performance and impaired quality of life. Recent research has suggested that daytime somnolence in allergic rhinitis can be attributed to chronic inflammation of the nasal mucosa leading to nasal congestion and obstructed nasal passageways resulting in disturbed sleep. Treating daytime somnolence due to allergic rhinitis requires a reduction in obstruction caused by nasal congestion. Currently available therapy for allergic rhinitis includes topical corticosteroids, sedating and nonsedating antihistamines, topical cromolyn sodium (sodium cromoglycate), decongestants, immunotherapy and topical ipratropium bromide. The effectiveness of antihistamines in patients with allergic rhinitis has long been established. However, results of placebo-controlled trials investigating the effects of azelastine on sleep and daytime somnolence have produced conflicting results. Sleep improved with azelastine therapy, but there was a lack of evidence that azelastine significantly affected daytime sleepiness, sleep severity and nasal congestion. Sedating antihistamines exacerbate daytime somnolence and should be avoided in patients with allergic rhinitis. In a separate study, desloratadine failed to benefit sleep, but did not worsen daytime somnolence. Topical nasal cromolyn sodium is inconvenient to use and is unlikely to have a major effect on nasal congestion. Decongestants do decrease nasal congestion but the effect this has on sleep has not been adequately studied. Recent research has shown that topical corticosteroids are an effective treatment for alleviating nasal congestion secondary to allergic rhinitis. However, few studies have assessed the effect of topical corticosteroids on daytime fatigue and sleep. In 20 patients with allergic rhinitis and symptoms of daytime sleepiness, flunisolide significantly improved sleep quality and congestion but daytime sleepiness was not significantly improved. A similar study with fluticasone propionate showed improvement in nasal congestion and sleep but there was no significant change in objective sleep measurements recorded on polysomnography. Further research involving objective measures of sleep quality is necessary to determine the efficacy of medications in the treatment of allergic rhinitis associated with fatigue and daytime somnolence.