Tension Pneumocephalus Related to Spontaneous Skull Base Dehiscence in a Patient on BiPAP

Spontaneous pneumocephalus is an uncommon phenomenon that may develop in patients with occult skull base defects. There have been reports of pneumocephalus occurring spontaneously in the setting of continuous positive airway pressure (CPAP) use (1). Tension pneumocephalus represents a neurosurgical emergency where intracranial air is trapped with increasing pressures resulting in neurological deterioration (2). Previous literature has also documented the growing understanding of how obesity, elevated intracranial pressure (ICP), obstructive sleep apnea (OSA), and cortical skull thinning are associated with spontaneous tegmen dehiscence and cerebrospinal fluid (CSF) leakage (3). Other mechanisms for spontaneous CSF leak include aberrant arachnoid granulation, congenital skull base dehiscences, increased abdominal and thoracic pressure resulting in reduced cerebral venous drainage, and age-related cortical thinning. In this report, we present the case of a bilevel positive airway pressure (BiPAP) user with an undiagnosed spontaneous tegmen dehiscence who developed spontaneous tension pneumocephalus

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

Surgical repair of spontaneous cerebrospinal fluid (CSF) leaks: A systematic review

Objectives To review the safety and efficacy of surgical management for spontaneous cerebrospinal fluid (CSF) leaks of the anterior and lateral skull base. Data Sources A systematic review of English articles using MEDLINE. Review Methods Search terms included spontaneous, CSF, cerebrospinal fluid, endoscopic, middle fossa, transmastoid, leak, rhinorrhea. Independent extraction of articles by 3 authors. Results Patients with spontaneous CSF leaks are often obese (average BMI of 38 kg/m2) and female (72%). Many patients also have obstructive sleep apnea (∼45%) and many have elevated intracranial pressure when measured by lumbar puncture. In addition to thinning of the skull base, radiographic studies also demonstrate cortical bone thinning. Endoscopic surgical repair of anterior skull base leaks and middle cranial fossa (MCF) approach for repair of lateral skull base leaks are safe and effective with an average short‐term failure rate of 9% and 6.5%, respectively. Long‐term failure rates are low. One randomized trial failed to show improved success of anterior leak repairs with the use of a lumbar drain (LD) (95% with vs. 92% without; P = 0.2). In a large retrospective cohort of MCF lateral skull base repairs, perioperative LD use was not necessary in >94% of patients. Conclusions Spontaneous CSF leaks are associated with female gender, obesity, increased intracranial hypertension, and obstructive sleep apnea. Endoscopic repair of anterior skull base leaks and MCF or transmastoid approaches for lateral skull base leaks have a high success rate of repair. In most cases, intraoperative placement of lumbar drain did not appear to result in improved success rates for either anterior or lateral skull base leaks. Level of Evidence 2a, Systematic Review

Outpatient management of cholesteatoma with canal wall reconstruction tympanomastoidectomy

Objectives The postoperative wound infection rate for canal wall reconstruction (CWR) tympanomastoidectomy with mastoid obliteration in the treatment of chronic otitis media with cholesteatoma has been reported to be 3.6%. Postoperative administration of 24–48 hours of intravenous antibiotics has been recommended. We aim to determine the infection rate of CWR with postoperative outpatient oral antibiotics. Study Design Institutional review board—approved retrospective case review. Setting Tertiary referral center. Patients: Retrospective review of consecutive patients who underwent CWR tympanomastoidectomy with mastoid obliteration at a single institution from 2014 to 2016. Main Outcome Measure: Patient characteristics (age, sex) were calculated. Rate of postoperative complications and infections within 1 month of surgery were calculated. Comparison to previous published infection rates with postoperative intravenous antibiotics. Results 51 patients underwent CWR followed by outpatient oral antibiotics with a mean age of 25.9 years (16 patients were less than 10 years old). There were no postoperative wound infections. Outpatient antibiotics showed non-inferiority to IV antibiotic historic controls (0% vs. 3.6%; 95% confidence interval [CI], 0–6.09%; p = 0.03). One patient had small postoperative wound dehiscence with CSF leak that was managed conservatively. One patient developed Clostridium difficile colitis on postoperative day 2. Conclusions The infection rate after CWR tympanomastoidectomy with use of outpatient antibiotics is low and is non-inferior to a historic cohort treated with inpatient intravenous antibiotics. A larger randomized controlled trial is warranted. Level of Evidence 4

Middle Cranial Fossa (MCF) Approach without the use of Lumbar Drain for the Management of Spontaneous Cerebral Spinal Fluid (CSF) Leaks

Objective: To determine the efficacy and morbidity of repairing spontaneous cerebrospinal fluid (CSF) leaks with the middle cranial fossa (MCF) approach without the use of a lumbar drain (LD), as perioperative use of LD remains controversial. Study Design: Retrospective review from 2003 to 2015. Setting: University of Iowa Hospitals and Clinics and Indiana University Health Center. Patients: Those with a confirmed lateral skull base spontaneous CSF leaks and/or encephaloceles. Intervention: MCF approach for repair of spontaneous CSF leak and/or encephalocele without the use of lumbar drain. Assessment of patient age, sex, body mass index (BMI), and medical comorbidities. Main Outcome Measure: Spontaneous CSF leak patient characteristics (age, sex, BMI, obstructive sleep apnea) were collected. Length of stay (LOS), hospital costs, postoperative complications, CSF leak rate, and need for LD were calculated. Results: Sixty-five operative MCF repairs were performed for spontaneous CSF leaks on 60 patients (five had bilateral CSF leaks). CSF diversion with LD was used in 15 of 60 patients, mostly before 2010. After 2010, only three of 44 patients (6.7%) had postoperative otorrhea requiring LD. The use of LD resulted in significantly longer LOS (3.6 ± 1.6 versus 8.7 ± 2.9 d) and hospital costs ($29,621). There were no postoperative complications in 77% (50 of 65) of cases. Three cases required return to the operating room for complications including frontal subdural hematoma (1), subdural CSF collection (1), and tension pneumocephalus (1). No patients experienced long-term neurologic sequelae or long-term CSF leak recurrence with an average length of follow-up of 19.5 months (range 3–137 mo). The average patient BMI was 37.5 ± 8.6 kg/m2. The average age was 57.5 ± 11.4 years and 68% were female. Obstructive sleep apnea was present in 43.3% (26 of 60) of patients. Conclusion: The morbidity of the MCF craniotomy for repair of spontaneous CSF leaks is low and the long-term efficacy of repair is high. Universal use of perioperative lumbar drain is not indicated and significantly increases length of stay and hospital costs. Obesity and obstructive sleep apnea are highly associated with spontaneous CSF leaks

Defective Tmprss3-Associated Hair Cell Degeneration in Inner Ear Organoids

Mutations in the gene encoding the type II transmembrane protease 3 (TMPRSS3) cause human hearing loss, although the underlying mechanisms that result in TMPRSS3-related hearing loss are still unclear. We combined the use of stem cell-derived inner ear organoids with single-cell RNA sequencing to investigate the role of TMPRSS3. Defective Tmprss3 leads to hair cell apoptosis without altering the development of hair cells and the formation of the mechanotransduction apparatus. Prior to degeneration, Tmprss3-KO hair cells demonstrate reduced numbers of BK channels and lower expressions of genes encoding calcium ion-binding proteins, suggesting a disruption in intracellular homeostasis. A proteolytically active TMPRSS3 was detected on cell membranes in addition to ER of cells in inner ear organoids. Our in vitro model recapitulated salient features of genetically associated inner ear abnormalities and will serve as a powerful tool for studying inner ear disorders

Progress in Modeling and Targeting Inner Ear Disorders with Pluripotent Stem Cells

Sensorineural hearing loss and vestibular dysfunction are caused by damage to neurons and mechanosensitive hair cells, which do not regenerate to any clinically relevant extent in humans. Several protocols have been devised to direct pluripotent stem cells (PSCs) into inner ear hair cells and neurons, which display many properties of their native counterparts. The efficiency, reproducibility, and scalability of these protocols are enhanced by incorporating knowledge of inner ear development. Modeling human diseases in vitro through genetic manipulation of PSCs is already feasible, thereby permitting the elucidation of mechanistic understandings of a wide array of disease etiologies. Early studies on transplantation of PSC-derived otic progenitors have been successful in certain animal models, yet restoration of function and long-term cell survival remain unrealized. Through further research, PSC-based approaches will continue to revolutionize our understanding of inner ear biology and contribute to the development of therapeutic treatments for inner ear disorders

Improved autologous cortical bone harvest and viability with 2Flute otologic burs

Objectives To determine if 2Flute (Stryker Corporation, Kalamazoo, MI) otologic burs improve the size, cellular content, and bone healing of autologous cortical bone grafts harvested during canal wall reconstruction (CWR) tympanomastoidectomy with mastoid obliteration. Study Design Institutional review board-approved prospective cohort study. Methods Human autologous cortical bone chips were harvested using various burs (4 and 6 mm diameter; multiflute, and 2Flute [Stryker Corporation]) from patients undergoing CWR tympanomastoidectomy for the treatment of chronic otitis media with cholesteatoma. Bone chip size, cell counts, cellular gene expression, and new bone formation were quantified. Results Bone chips were significantly larger when harvested with 2Flute (Stryker Corporation) bur compared to multiflute burs at both 6 mm diameter (113 ± 14 μm2 vs. 66 ± 8 μm2; P < 0.05) and 4 mm diameter (70 ± 8 μm2 vs. 50 ± 3 μm2; P < 0.05). After 2 weeks in culture, cell numbers were significantly higher when harvested with 2Flute (Stryker Corporation) bur compared to multiflute burs at both 6 mm diameter (48.7 ± 3 vs. 31.8 ± 3 cells/μg bone; P < 0.05) and 4 mm diameter (27.6 ± 1.2 vs. 8.8 ± 1.2 cells/μg bone; P < 0.05). Bone-derived cells express osteoblast markers (alkaline phosphatase, osteocalcin). Cultured cells are able to form new bone in culture, and bone formation is facilitated by the presence of bone chips. Conclusion Use of 2Flute (Stryker Corporation) otologic burs for human autologous cortical bone harvest results in more viable bone fragments, with larger bone chips and more osteoblasts. Future studies are needed to determine if this leads to improved bone healing

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