Prevalence of Obstructive Sleep Apnea (OSA) in Spontaneous Cerebrospinal Fluid (CSF) Leaks: A Prospective Cohort Study

Objective: To determine the prevalence of obstructive sleep apnea (OSA) in a prospective cohort of patients with spontaneous CSF (sCSF) leaks of the temporal bone. Study Design: Prospective cohort study. Setting: Tertiary referral center. Patients: Consecutive sCSF leak patients (21) over a 3-year period. Four patients presented with a history of OSA and 17 patients were prospectively offered polysomnogram (PSG) testing during the initial clinic encounter. Intervention: Level I PSG. Main Outcome Measures: Patient characteristics (age, sex, body mass index), apnea hypopnea index (AHI), presence of snoring, and presence of hypoxia (oxygen saturation 5 min). OSA was defined as mild (AHI ≥5 and <15/h), moderate (AHI ≥15 and <30/h), and severe (AHI ≥30/h). Results: The prevalence of OSA in sCSF leak patients is 83.3%. PSG studies were performed on 18 of the 21 patients. There were 15 women and 6 men with an average age (standard deviation) of 56.3 (11.2) years and an average body mass index of 35.3 (7.7) kg/m2. Objectively, the AHI ranged from mild to severe (range = 5.7–92, median = 19.8). Snoring was present in 61% of patients and hypoxia was present in 39% of patients. sCSF leak patients with OSA were significantly older than sCSF leak patients without OSA (56.7 [8.3] versus 42.7 [14.5] yr, p = 0.03). Conclusions: OSA is highly prevalent among patients with sCSF leaks. All patients with sCSF leaks should undergo formal PSG testing. Future studies are needed to determine the role of OSA in the development of sCSF leaks

The role of obesity, sleep apnea, and elevated intracranial pressure in spontaneous cerebrospinal fluid leaks

Purpose of review Spontaneous cerebrospinal fluid (sCSF) leaks often occurs in middle age, obese females. Here we investigate the role of obesity, idiopathic intracranial hypertension (IIH), and obstructive sleep apnea (OSA) in the pathophysiology of sCSF leaks. Recent findings The association of obesity and sCSF leaks has been well established in many studies. It has now been revealed that sCSF leak patients have thinner calvariums along with the skull base. An intracranial process likely leads to calvarium and skull base thinning in sCSF leaks patients since this occurs independent of extracranial bone thinning and independent of obesity. OSA, which is known to cause spikes in intracranial pressure (ICP), has been found to be significantly prevalent in the sCSF population and has been shown to lead to both calvarial and skull base thinning. Chronically elevated ICP (IIH) has also been shown to impact calvarial and skull base thicknesses. Summary The incidence of sCSF leaks has increased in recent decades along with an increasing rate of obesity. OSA and IIH, which are obesity-related factors and cause transient and chronic elevations in ICP, have now been implicated as critical factors leading to calvarial and skull base thinning and resultant sCSF leaks

CHRONIC TRANSPLANT REJECTION: PROBLEMS, DISCOVERIES, SOLUTIONS

poster abstractOrgan transplantation has become an increasingly important remedy in helping extend the lives of patients with organ failures or deficien-cies. Although the survival rates of organ recipients have dramatically increased in the short term (1-5 years), long-term (5+ years) survival rates have not improved significantly. Additionally, increasingly un-healthy lifestyles have contributed to a dramatic increase in the need for organ transplants, while organ supply has only slightly increased, resulting in a constantly increasing gap between organ demand and organ supply. Dr. Raymond Johnson, an IU Health Physician, discov-ered a new T cell subset that is resistant to medications routinely used to prevent transplant rejection. This discovery is important because it can be used to develop mechanism-specific diagnostic blood tests for chronic rejection and, potentially, new drugs to treat chronic trans-plant rejection. However, innovations developed in faculty labs often face multiple hurdles in reaching the market place. As participants in the Innovation-to-Technology Central (ITEC) program, our unique multidisciplinary team of students investigated Dr. Raymond Johnson’s discovery by conducting literature research and expert interviews on organ transplantation and rejection and pharmaceutical drugs used in preventing acute transplant rejection. Through our research and our interviews, we were able to further document the dire need for meth-ods for increasing survival rates of transplanted organs. Most im-portantly, we have conducted preliminary market research and devel-oped several commercialization strategy recommendations based on comparable innovation analysis and precedent biotechnology start-up strategies. We anticipate that our research will provide Dr. Johnson with new information and perspectives to help seek venture capitalists to invest in his research, which holds the promise to change the lives of thousands of transplant recipients each year. Funding provided by IUPUI’s Innovation-to-Enterprise Central (ITEC)

Association of Obstructive Sleep Apnea With Calvarial and Skull Base Thinning

Importance: Spontaneous cerebrospinal fluid leaks (sCSF-L) of the temporal bone are associated with obesity, calvarial thinning, and obstructive sleep apnea (OSA), and the incidence has doubled in the past decade. It is currently unknown if OSA is independently associated with skull thinning. Objective: To determine if patients with OSA have thinner skulls than patients without OSA. Design, Setting, and Participants: A retrospective cohort study of patients who underwent a level 1 polysomnogram (PSG) and also had high-resolution computed tomographic (CT) imaging of the head from January 2010 to March 2017 at Indiana University was carried out. Patients with moderate to severe OSA (apnea-hypopnea index [AHI]≥25/h) and without OSA (AHI<5/h) were matched for age and body mass index (BMI, calculated as weight in kilograms divided by height in meters squared). Interventions: Measurement of calvarial thickness, extracranial zygoma thickness, skull base height and tegmen dehiscence (>4 mm) when blinded to OSA status. Main Outcomes and Measures: Primary outcomes were calvarial, skull base, and zygoma thickness differences between patients with OSA vs those without OSA. Results: A total of 22 933 patients had a PSG and 1012 also had head CT imaging. Of the 1012 patients with both PSG and CT, the mean (SD) age was 50.8 (16.2) years and 624 (61.7%) were women. Those patients with moderate to severe OSA (56) and without OSA (58) were matched for mean (SD) age (50.3 [6.5] vs 49.8 [6.1] years]) and BMI (37.4 [8.1] vs 38.6 [6.8]). Patients with OSA had thinner mean (SD) calvaria (2.73 [0.67] vs 2.47 [0.52] mm; difference, -0.26 mm; 95% CI, -0.49 to -0.04; Cohen d, 0.44) and thinner skull bases (5.03 [1.40] vs 4.32 [1.28] mm; difference, -0.71; 95% CI, -1.23 to -0.19; Cohen d, 0.53). The mean (SD) extracranial zygoma thickness was the same (4.92 [0.87] vs 4.84 [0.84] mm; difference, -0.07 mm; 95% CI, -0.39 to 0.24). The tegmen mastoideum was dehiscent in nearly twice as many patients with OSA as those without (37% vs 20%; difference, 17%; 95% CI, 0.4-32). Conclusions and Relevance: Obstructive sleep apnea was independently associated with intracranial bone (calvaria and skull base) thinning and not with extracranial (zygoma) thinning. These findings support a possible role of OSA in the pathophysiologic development of sCSF-L

Middle Cranial Fossa Repair of Temporal Bone Spontaneous CSF Leaks With Hydroxyapatite Bone Cement

Objectives To determine the safety and effectiveness of the middle cranial fossa (MCF) approach in repairing spontaneous cerebrospinal fluid (sCSF) leaks. Study Design Retrospective cohort study. Methods Patient with sCSF leaks repaired by MCF approach between January 1, 2014 and August 31, 2019 were included. Demographic information, clinical and surgical findings, and postoperative outcomes were recorded. Results The cohort (n = 45) included 24 tegmen repairs by multilayer reconstruction using hydroxyapatite cement and 21 cases of multilayer repair without hydroxyapatite cement. Ten MCF repairs were performed on patients ≥65 years old. Twenty (53%) ears had multiple tegmen defects (range, 1–9 tegmen defects) and 78% of patients had ≥1 encephaloceles. All sCSF leaks were resolved with one surgical intervention. There were no major intracranial complications. Transient expressive aphasia occurred in 2 patients. Medical complications occurred in four patients. There were no short-term postoperative CSF leaks with bone cement reconstruction and two postoperative leaks without bone cement. One resolved with lumbar drain (LD) and the other resolved without treatment. The average (SD) length of stay (LOS) with bone cement was shorter than in patients without bone cement (2.54 [0.83] days vs. 3.52 [1.99] days, P < .05). There have been no long-term CSF leak recurrences with an average (SD) follow-up of 13.5 (12.9) months (range 0.25–46 months). Conclusions MCF approach for sCSF repairs demonstrate efficacious outcomes, particularly with tegmen reconstruction using hydroxyapatite cement. The approach exhibited no serious adverse events and few complications requiring intervention. Therefore, MCF is a safe and effective approach to resolve sCSF leaks

Diagnosis of Anosmia and Hyposmia: A Systematic Review

BackgroundAnosmia and hyposmia have many etiologies, including trauma, chronic sinusitis, neoplasms, and respiratory viral infections such as rhinovirus and SARS-CoV-2. We aimed to systematically review the literature on the diagnostic evaluation of anosmia/hyposmia.MethodsPubMed, EMBASE, and Cochrane databases were searched for articles published since January 1990 using terms combined with Medical Subject Headings (MeSH). We included articles evaluating diagnostic modalities for anosmia, written in the English language, used original data, and had two or more patients.ResultsA total of 2065 unique titles were returned upon the initial search. Of these, 226 abstracts were examined, yielding 27 full-text articles meeting inclusion criteria (Level of evidence ranging from 1 to 4; most level 2). The studies included a total of 13,577 patients. The most utilized diagnostic tools were orthonasal smell tests (such as the Sniffin? Sticks and the UPSIT, along with validated abridged smell tests). Though various imaging modalities (including MRI and CT) were frequently mentioned in the workup of olfactory dysfunction, routine imaging was not used to primarily diagnose smell loss.ConclusionThe literature includes several studies on validity and reliability for various smell tests in diagnosing anosmia. Along with a thorough history and physical, validated orthonasal smell tests should be part of the workup of the patient with suspected olfactory dysfunction. The most widely studied modality was MRI, but criteria for the timing and sequence of imaging modalities was heterogenous

Nasal Bone Fractures and the Use of Radiographic Imaging: An Otolaryngologist Perspective

Objective To determine radiologic preferences of practicing otolaryngologists regarding isolated nasal bone fractures. Study design An 8-question survey on isolated nasal bone fractures was designed. Setting Surveys were sent to all otolaryngology residency program directors for distribution among residents and faculty. Additional surveys were distributed to private practice otolaryngology groups. Results 140 physicians responded to the survey. 57% of the respondents were practicing otolaryngologists (75% with 10+ years of experience), while 43% of respondents were residents-in-training. 56% of respondents treated 1–5 nasal bone fractures per month. 80% of all respondents reported imaging being performed prior to consultation. If imaging was obtained before consultation, plain films and computed tomography (CT) maxillofacial/sinus scans were the most frequent modalities. 33% of residents and 70% of practicing otolaryngologists report imaging as ‘rarely’ or ‘never’ helpful in guiding management. 42% of residents and 20% of practicing otolaryngologists report asking for imaging when it wasn't already obtained. Decreased use of radiography was associated with greater years in practice and higher frequency of fractures treated. Conclusions and relevance Otolaryngologists seldom request imaging to evaluate and treat isolated nasal bone fractures. When ordered, imaging is utilized more often among residents-in-training and non-otolaryngology consulting physicians. This study highlights an opportunity to educate primary care and emergency room providers as well as otolaryngology residents on the value of comprehensive physical exam over radiographic imaging in the work-up of isolated nasal fractures. In addition, widespread adoption of a “no x-ray policy” in this setting may result in better resource utilization

Cerebrospinal Fluid Leaks From the Lateral Ventricle: A Case Series

OBJECTIVES: Describe the diagnosis and management of lateral skull base (LSB) cerebrospinal fluid (CSF) leaks originating from the lateral ventricle. STUDY DESIGN: Retrospective case review. SETTING: Tertiary referral academic center. PATIENTS: Patients with CSF leaks with direct communication to the lateral ventricle on preoperative imaging. INTERVENTION: Surgical repair via the middle cranial fossa (MCF) approach. MAIN OUTCOME MEASURES: CSF leak patient characteristics (age, sex, body mass index [BMI]) and postoperative course (complications and CSF leak resolution) were collected. RESULTS: Three patients had CSF leaks from the lateral ventricle and all patients demonstrated encephalomalacia of the temporal lobe on preoperative imaging. Encephalomalacia resulted from trauma in one case (age 5) and neurodegeneration in two cases (age 77 and 84). BMI ranged from 16.3 to 26.6 mg/kg2 and follow-up ranged from 4 to 21 months. Two patients presented with preoperative meningitis and all patients had resolution of CSF leaks after MCF repair. With the exception of the higher rate of meningitis, patient presentations did not differ from other spontaneous CSF leaks through middle fossa defects. There were no minor or major postoperative complications. CONCLUSIONS: CSF leaks from the lateral ventricle represent a rare subset of LSB CSF leaks and can occur in non-obese patients secondary to temporal lobe encephalomalacia. The MCF approach allows for repair of the dura and skull base in this cohort of patients with high-flow CSF leaks and loss of brain parenchyma

Association of Intracranial Hypertension With Calvarial and Skull Base Thinning

Objective: Determine if patients with increased opening pressure (OP) on lumbar puncture (LP) have thinner calvaria and skull bases. Study Design: Retrospective cohort study. Setting: Tertiary referral center. Patients: Patients (≥18 yr of age) who had a recorded OP on LP and high-resolution computed tomography imaging of the head. Patient age, sex, body mass index were calculated. Intracranial hypertension (IH) was defined with an OP≥25 cm-H2O and low intracranial pressure with an OP<15 cm-H2O. Intervention: Measurement of calvarial, zygoma, and skull base thickness when blinded to OP with three-dimensional slicer and radiologic calipers. Main Outcome Measures: Association of calvarial, skull base, and zygoma thickness with OP and age. Results: Fifty-eight patients were included with a mean (SD) age of 53.1 (16.2) years and average (SD) body mass index of 30.1 (9.1) kg/m2. Patients with IH had thinner mean (SD) calvaria (3.01 [0.81] versus 2.70 [0.58] mm; p = 0.036) and skull bases (5.17 [1.22] versus 4.60 [1.42] mm; p = 0.043) when compared with patients without IH. The mean (SD) extracranial zygoma thickness was similar between the two groups (5.09 [0.76] versus 5.00 [0.73] mm; p = 0.56). General linear model regression demonstrated advancing age was associated with increasing calvarial thickness in patients without IH and calvarial thinning in patients with IH (p = 0.038). Conclusion: IH is independently associated with intracranial bone (calvaria and skull base) thinning and not extracranial (zygoma) thinning. Skull thinning occurs with IH and advancing age. These findings support a possible role of increased ICP in the pathophysiologic development of spontaneous cerebrospinal fluid leaks

Calvarium Thinning in Patients with Spontaneous Cerebrospinal Fluid Leaks of the Anterior Skull Base

Objectives/Hypothesis Patients with spontaneous cerebrospinal fluid leaks (sCSF-L) of the temporal bone have isolated calvarial and skull base thinning that is independent of obesity. This study determines if anterior skull base (ASB) sCSF-L patients also have calvarial thinning. Study Design Retrospective Cohort Study. Methods This was a retrospective cohort study of ASB sCSF-L patients compared to nonobese (body mass index [BMI] < 30 kg/m2) and obese (BMI ≥ 30) control groups. Twenty-one patients in the ASB sCSF-L group and 25 patients in each control group were included. Calvarium and extracranial zygoma thicknesses were measured bilaterally with blinded, standardized, volumetric analysis. Results ASB sCSF-L patients had a mean (SD) age of 50.43 (10.19) years, an average (SD) BMI of 38.81 (8.92) kg/m2, and most were female (85.71%). The calvarium in patients with ASB sCSF-L was significantly thinner than the nonobese (2.55 mm [0.77] vs. 2.97 [0.67] mm; P = .006; 95% confidence intervals [CI], 0.12–0.30; Cohen d, 0.58) and obese control groups (2.55 [0.77] vs. 2.92 [0.76] mm; P = .02; 95% CI, 0.05–0.34; Cohen d, 0.66). The calvarium thickness of the nonobese patients was not significantly different from the obese patient controls (2.97 [0.67] vs. 2.92 [0.76] mm, P = .9). The extracranial zygoma was not significantly different among the groups (analysis of variance, P = .33). Conclusions ASB sCSF-L patients have isolated calvarial thinning that is independent of obesity. Like lateral skull base sCSF-L patients, these data suggest that the additional obesity-associated intracranial process contributes to skull thinning