Characteristics and Clinical Management Strategy of Petrous Apex Cholesterol Granulomas.

Purpose: To evaluate the clinical characteristics of petrous apex cholesterol granulomas (PACG) and assess outcomes after different treatment strategies. Method: A consecutive case series of 34 patients with a PACG. Main outcomes were PACG growth, symptoms, and the outcomes of different treatment strategies: wait-and-scan (WS) and surgical drainage. Results: Thirty-four patients were analyzed; mean follow-up time was 7.1 years. Twenty-one patients (61.7%) showed symptoms, mostly more than one. Most symptoms reported were cranial nerve palsy (58.8%) and headache (35.3%). Twenty-one patients (61.8%) received solely wait-and-scan (WS), and thirteen patients (38.2%) underwent surgery, five of whom (38.5%) after an initial WS period. In the solely WS group, one (4.8%) developed new symptoms, and two (9.5%) reported symptom progression despite a stable granuloma size. Two (9.5%) showed granuloma growth on follow-up scans without symptom progression. Surgery consisted of drainage. Eleven (84.6%) of these thirteen patients reported partial recovery; one (7.7%) reported no recovery; and one (7.7%) reported full recovery of reported symptoms related to PACG. Among the patients with cranial nerve involvement, 7.7% showed full recovery after surgery; 84.6% showed partial recovery; and 7.7% did not recover. Adverse events occurred in five out of 13 patients who underwent surgery, all with full recovery. Conclusions: This study confirms that PACG are slow-growing lesions with a low risk of adverse events. Solely using wait-and-scan strategy is a safe option for patients without symptoms, with acceptable symptoms without symptom progression, and with asymptomatic growth. Surgical treatment can be considered in patients with symptom progression or symptomatic growth.

Sensorineural Hearing Impairment Recovery after Transmastoidal Surgery for a Petrous Apex Cholesterol Granuloma: A Case Report.

Cholesterol granulomas are the most common primary lesions of the petrous apex. Although their benign character, impingement of critical neurovascular structures can cause significant symptomatology such as hearing impairment. We present unique results after treatment of a cholesterol granuloma located in the petrous apex causing sensorineural hearing impairment. A transmastoidal approach was performed using an intraoperative computed tomography-guided navigation system. The video, which is included for reference, illustrates clear drainage of the cyst and drain positioning. The hearing improved completely in the lower frequencies at 500 and 1000 Hz and with a 19 dB improvement in overall bone conduction in the affected ear.

An Adolescent With a Retropharyngeal Swelling: To Drain or Not to Drain?: Keeping a Broad Vision During the COVID-19 Pandemic.

CASE PRESENTATION: An 18-year-old patient with a history of COVID-19 (1 month previously) was admitted with malaise and complaints of a stiff neck, a left-sided cervical mass, headache, and difficulty in swallowing and breathing, which had been present for 4 days. Two days after the onset of the first symptoms, a painless skin rash on the legs, arms, palms of both hands, and soles of both feet developed. Despite 2 days of treatment with antibiotics (amoxicillin/clavulanic acid, 500/125 mg three times daily orally), symptoms progressed. On presentation, the patient was alert and oriented, there were no neurologic disorders, and all symptoms related to the recent COVID-19 infection had subsided. His medical history was negative for sexually transmitted diseases, and the patient had received all vaccines except for meningococcus and COVID-19.

Diagnosis, treatment and prognosis of otomastoiditis induced by Fusobacterium necrophorum: A retrospective multicentre cohort study.

OBJECTIVES: Otomastoiditis caused by the anaerobic Fusobacterium necrophorum (F. necrophorum) often induces severe complications, such as meningitis and sinus thrombosis. Early diagnosis is difficult, partly because little is known about specific early signs. Comprehensive research about clinically chosen antimicrobial therapy has not been done yet and prognostic information about otomastoiditis caused by F. necrophorum is scarce. More knowledge about this subject is required. METHODS: In this retrospective cohort study, we included all cases of otomastoiditis caused by F. necrophorum treated in two university medical centres in the Netherlands during the past 10 years. Data was gathered from patient records and analysed using independent sample T-tests and Chi2-tests. RESULTS: This study reveals that otomastoiditis caused by F. necrophorum potentially induces neurological sequelae. Thereby, 80% of all included patients (n = 16) needed readmission within six months due to recurrence or complications of otomastoiditis caused by F. necrophorum. Mean (range) of age, CRP and temperature were 4.5 years (0.9-29.3), 243 mg/L (113-423) and 40 °C (37-41). All patients were hospitalized and treated with antibiotics, mostly metronidazole (n = 13/16) and a ß -lactam (n = 15/16). Additional treatment contained low molecular weight heparin (83%, n = 10/12), dexamethasone (78%, n = 7/9) and/or surgery (80%, n = 12/16, whereof 9/12 mastoidectomy). CONCLUSIONS: Patients and/or their parents need to be informed about this potential unfortunate prognosis when otomastoiditis caused by F. necrophorum is diagnosed. To improve early diagnosis, otomastoiditis caused by F. necrophorum should be suspected and therefore immediately cultured when a) young children present with otomastoiditis, with b) high CRP values, and/or c) vomiting and decreased consciousness.

Clinical characteristics and an evaluation of predictors for a favourable outcome of Mycobacterium abscessus otomastoiditis: a systematic review and meta-analysis of individual participant data.

BACKGROUND: Otomastoiditis caused by Mycobacterium abscessus is rare, but its incidence has increased over the past decades and its optimal treatment remains unknown. This study aims to summarise the clinical and therapeutic features and find characteristics of patients with M. abscessus otomastoiditis associated with favourable treatment outcomes. METHODS: We searched MEDLINE, Embase and Web of Science to identify studies including patients with M. abscessus otomastoiditis. A 1-stage individual patient data (IPD) meta-analysis was conducted. A 2-level mixed-effects linear regression model was provided for antimycobacterial treatment duration. RESULTS: Twenty-three studies reported a total of 85 patients. Children possess a unique clinical profile including a history of ear infections, tympanostomy tube placement and antibiotic treatment. Antimycobacterial treatment was administered for 26 (interquartile range [IQR]: 15-35) weeks. Macrolides were prescribed in 98.8% of the cases. Surgery was performed in 80.5% of the cases, of which, 47.1% required revision surgery. Otalgia was a significant predictor (ß = 9.3; P = .049) of antimycobacterial treatment duration. CONCLUSIONS: Mastoid surgery (regularly requiring revision) and a multidrug regimen for a minimum of 6 months, including a minimum of 3 active agents, are most often needed to attain cure. The presence of otalgia significantly extends the treatment duration of M. abscessus otomastoiditis.

The medium to long-term effects of two-duct ligation for excessive drooling in neurodisabilities, a cross-sectional study.

OBJECTIVES: This study aims to evaluate the medium to long-term (1-12 years) effectiveness of two-duct ligation (2-DL) in patients with nonprogressive neurodisabilities. METHODS: Main outcomes included a Visual Analogue Scale (VAS), Drooling Severity (DS) and Drooling Frequency (DF), collected at baseline, 32 weeks postintervention and 1-12 years postintervention. Secondary outcomes were adverse events (AEs), and satisfaction. RESULTS: Forty-two patients were analyzed (mean age 17 years, mean baseline VAS 82). VAS decreased significantly from baseline to long-term (n = 30. Mean difference -36.5, CI -47.0 to -26.0, p ≤ 0.001; -26.1, CI -36.2 to -15.9, p ≤ 0.001). However, long-term VAS significantly increased compared to VAS at 32 weeks (+10.4, CI 1.0-19.8, p = 0.031). Out of 42 patients, 64% would recommend 2-DL to peers. CONCLUSION: There is a significant subjective 2-DL effect on drooling severity in the medium to long-term as reported by patients and caregivers, but there is also a certain degree of recurrence in this time span, and 33% of the patients required subsequent treatment. However, the majority of patients and/or caregivers would recommend 2-DL to peers.

Surgery versus botulinum neurotoxin A to reduce drooling and improve daily life for children with neurodevelopmental disabilities: a randomized controlled trial.

AIM: To compare the effect of bilateral submandibular duct ligation and botulinum neurotoxin A (BoNT-A) on drooling severity and its impact on daily life and care in children and adolescents with moderate-to-severe drooling. METHOD: This was a randomized, interventional, controlled trial in which 53 children and adolescents (31 males, 22 females, mean age 11y, range 8-22y, SD 2y 10mo) with cerebral palsy (58.5%) or other non-progressive developmental disorders (41.5%) were randomized to BoNT-A (n=26) or bilateral submandibular duct ligation (n=27). A parent questionnaire on the severity of drooling in specific positions and daily activities and the impact of drooling on daily life and care was filled out at baseline and 8 and 32 weeks posttreatment. RESULTS: Both BoNT-A and bilateral submandibular duct ligation had a positive effect on daily care, damage to electronic equipment and/or furniture, social interactions, and self-esteem. However, bilateral submandibular duct ligation had a significant greater and longer-lasting short- (8wks) and medium-term (32wks) effect on daily care, reducing damage to electronic devices, and improving social interactions and satisfaction with life in general. INTERPRETATION: This randomized controlled trial confirms reduced drooling by both BoNT-A and bilateral submandibular duct ligation, but provides new evidence on improved well-being through a reduction in drooling. Even though there is a greater risk of complications and morbidity after bilateral submandibular duct ligation, compared to BoNT-A there was a significantly greater and longer-lasting positive effect on most outcomes. What this paper adds Bilateral botulinum neurotoxin A (BoNT-A) and submandibular duct ligation had a positive effect on the well-being of individuals with moderate-to-severe drooling. Bilateral submandibular duct ligation had a greater effect on the impact of drooling during daily care than BoNT-A. Bilateral submandibular duct ligation reduced damage to electronic devices and improved social interactions and satisfaction with life.

Posterior drooling in children with cerebral palsy and other neurodevelopmental disorders.

AIM: To evaluate the effect of botulinum neurotoxin A (BoNT-A) injections, submandibular gland excision (SMGE), and bilateral submandibular duct ligation (2DL) for the control of posterior drooling in children with neurological impairment. METHOD: In a retrospective cohort, children with neurological impairment (e.g. cerebral palsy) treated between 2000 and 2016 were identified. Mean age at time of surgery was 9 years (range 1-21y). The primary outcome was posterior drooling severity by a visual analogue scale (VAS; 0-10) at baseline, 8-weeks, and 32-weeks follow-up. The secondary outcome was lower respiratory tract infections during the follow-up period. RESULTS: Ninety-two patients (out of 475; 47 males, 45 females) were identified. They were undergoing three different treatments: BoNT-A (n=63), SMGE (n=16), and 2DL (n=13). A significant reduction in VAS over time was observed in the total group of 92 patients. After SMGE, VAS decreased significantly from 6.82 (SD 3.40) at baseline to 2.29 (SD 1.93) at 8 weeks, and 2.17 (SD 2.58) at 32 weeks (F[2.34]=11.618, p<0.001). There was no significant decrease after both BoNT-A and 2-DL. INTERPRETATION: Posterior drooling is an unfamiliar, potentially life-threatening condition that is treatable with medication, BoNT-A injections, or surgery. Although all treatments reduced signs and symptoms of posterior drooling, there is a greater effect after SMGE compared to BoNT-A and 2-DL. What this paper adds Submandibular gland excision has better results for posterior drooling than botulinum toxin A or submandibular duct ligation.

Repeated onabotulinum neurotoxin A injections for drooling in children with neurodisability.

AIM: To evaluate the effect of repeated onabotulinum neurotoxin A injections for the treatment of drooling in children with neurodisabilities. METHOD: This was a retrospective cohort study, in which the first, second, and third onabotulinum neurotoxin A injection were compared within children treated between 2000 and 2020. Primary outcomes included drooling quotient, visual analogue scale (VAS), and treatment success defined as ≥50% reduction in drooling quotient and/or VAS 8 weeks after treatment. Each outcome was obtained at baseline and 8 weeks posttreatment. RESULTS: Seventy-seven children were included (mean age at first injection: 8y 3mo, SD 3y 7mo, range 3-17y; 44 males, 33 females; 51.9% with cerebral palsy, 45.5% wheelchair-bound). The objective (drooling quotient) and subjective (VAS) effect after the second injection was lower compared to the first injection. The third injection showed less objective and significantly less subjective effect compared to the first injection. An overall success rate of 74.0%, 41.6%, and 45.8% were found for the first, second, and third injection respectively. INTERPRETATION: Although onabotulinum neurotoxin A remained effective throughout the entire treatment course, there is less effect of subsequent onabotulinum neurotoxin A injections compared to the first. Although there might be a loss of effect after repeated injections, there is continued improvement for most children. What this paper adds Repeated injections show a diminished treatment effect after the second injection. A continued improvement is seen in most patients.

Cost-effectiveness of botulinum neurotoxin A versus surgery for drooling: a randomized clinical trial.

AIM: This study compared the cost-effectiveness of botulinum neurotoxin A (BoNT-A) injections with two-duct ligation of the submandibular glands as treatment for severe drooling after one treatment cycle. METHOD: The study was part of a larger, partly single-blinded, randomized clinical trial (trialregister.nl identifier NTR3537). Data were collected between 2012 and 2017. Evaluation was at 32 weeks after one treatment cycle. Fifty-seven patients with cerebral palsy or other neurological, non-progressive disorders and severe drooling classified as having a drooling frequency ≥3 or a drooling severity ≥2, in whom conservative treatment was deemed ineffective, were randomized to treatment by BoNT-A or two-duct ligation. An incremental cost-effectiveness ratio (ICER) was calculated using the success rates as the measure of benefit. Treatment success was defined as a decrease ≥50% from baseline to 32 weeks in the subjective visual analogue scale for the severity of drooling or the objective drooling quotient. RESULTS: Fifty-three patients were analysed (22 females, 31 males; mean age 11y, range 8-22y). Average costs for one treatment cycle, which included one BoNT-A injection, were €1929 (standard error 62) for BoNT-A and €3155 (standard error 99) for two-duct ligation. Treatment success was in favour of two-duct ligation (63% vs 27%; number needed to treat 3). The ICER was €34 per 1% gain in treatment success in favour of two-duct ligation versus BoNT-A. INTERPRETATION: The additional cost of two-duct ligation is to some extent offset by a larger treatment success rate compared with BoNT-A. WHAT THIS PAPER ADDS: Botulinum neurotoxin A (BoNT-A) is less expensive per percentage of success than two-duct ligation. The additional cost of two-duct ligation over BoNT-A is offset by greater treatment success.

Submandibular duct ligation after botulinum neurotoxin A treatment of drooling in children with cerebral palsy.

AIM: To assess: (1) the effect on drooling of bilateral submandibular duct ligation as surgical therapy after the administration of submandibular botulinum neurotoxin A (BoNT-A) for excessive drooling and (2) the predictive value of treatment success with BoNT-A on treatment success after bilateral submandibular duct ligation. METHOD: This was a within-participant retrospective observational study in which 29 children with severe drooling (15 males, 14 females) received BoNT-A treatment at a mean age of 9 years 6 months (SD 2y 5mo), followed by bilateral submandibular duct ligation at a mean age of 10 years 11 months (SD 2y 4mo). Fifteen children were diagnosed with cerebral palsy (CP), with 12 children classified in Gross Motor Function Classification System levels IV and V. The 14 children without CP had non-progressive developmental disorders. The primary drooling severity outcomes were the Visual Analogue Scale (VAS; subjective assessment) and drooling quotient (objective assessment). Measurements were taken before each intervention and again at 8 and 32 weeks. RESULTS: The VAS was significantly lower after bilateral submandibular duct ligation at follow-up compared to BoNT-A treatment (mean difference -33, p≤0.001; 95% confidence interval [CI]=-43.3 to -22.9). The mean drooling quotient did not significantly differ between BoNT-A treatment and bilateral submandibular duct ligation at follow-up (3.3, p=0.457; 95% CI=-4.35 to 9.62) or between 8 and 32 weeks (4.7, p=0.188; 95% CI=-2.31 to 11.65). INTERPRETATION: BoNT-A treatment and bilateral submandibular duct ligation are both effective treatment modalities for drooling. At 32-week follow-up, subjective drooling severity after bilateral submandibular duct ligation was significantly lower compared to previous BoNT-A injections in participants. However, treatment success with BoNT-A is no precursor to achieving success with bilateral submandibular duct ligation. WHAT THIS PAPER ADDS: Bilateral submandibular duct ligation is an effective therapy for drooling after treatment with botulinum neurotoxin A (BoNT-A). Treatment success with BoNT-A is not a predictor of successful therapy with bilateral submandibular duct ligation.

Bilateral Vocal Cord Paralysis Due to an Immune-related Adverse Event of Nivolumab: A Case Report.

Nivolumab is an anti-programmed death-1 inhibitor used in the treatment of cancer. Nivolumab has recently been approved as an adjuvant treatment for patients with stage IIIB, IIIC, and completely resected stage IV melanoma in the Netherlands. Despite the promising results of nivolumab, there is a wide variation in toxic side effects. A nivolumab-induced bilateral vocal cord paralysis (BVCP) was not reported. In this case, we present a nivolumab-induced BVCP. A 75-year-old man received nivolumab as adjuvant therapy for stage III melanoma. After the first cycle of nivolumab, this patient developed immune-related hepatitis and colitis. During admission, the patient became respiratory insufficient as a result of a BVCP. This case report describes immune-related hepatitis, colitis, and BVCP after the first cycle of nivolumab in the treatment of stage IIIb melanoma. Follow-up has not yet shown improvement in the mobility of the vocal cords.

An evaluation of predictors for success of two-duct ligation for drooling in neurodisabilities.

BACKGROUND: Drooling is dependent on various clinical variables. However, while drooling proves refractory to two-duct ligation in 40% of patients, predictors for treatment success are sparse and to date there is little evidence why some respond well while others are non-responders. We aim to find predictors for treatment success and study the effectiveness of two-duct ligation for drooling in neurodisabilities. METHODS: Fifty-four patients with moderate to severe drooling who had undergone two-duct ligation were screened for inclusion. Four patients were excluded due to missing or unreliable primary outcomes. The average age at the time of surgery was 12 years. Predictors were evaluated for treatment success which was defined as ≥ 50% visual analog scale for severity of drooling and/or drooling quotient reduction from baseline. Treatment effect was measured after 8 and 32 weeks compared to baseline. RESULTS: Age (more mature), adequate posture (no anteflexion), and normal speech are predictors for treatment success. Compared to baseline, drooling quotient was significantly lower at 8 (difference 18.6%, 95% confidence interval 12.3-24.9%) and 32 weeks (difference 10.1%, 95% confidence interval 3.9-16.4%). Compared to baseline, visual analog scale was significantly lower at 8 (difference 45.0, 95% confidence interval 37.0-52.9) and 32 weeks (difference 32.9, 95% confidence interval 25.0-40.7). CONCLUSIONS: Age, adequate posture, and a normal speech are predictors for treatment success, are easily determined pre-operatively, and help the clinician providing patient-specific probability of treatment success. There is a significant subjective and objective decrease of drooling after two-duct ligation.

Unsuccessful submandibular duct surgery for anterior drooling: Surgical failure or parotid gland salivation?

OBJECTIVES: To evaluate if drooling recurrence after surgery of the submandibular ducts is due to surgical failure or other variables. METHODS: Historic cohort with prospective collected data of all patients with severe drooling who underwent unsuccessful submandibular duct surgery with subsequent re-intervention between 2003 and 2018. A reference cohort was used for comparison of clinical variables. RESULTS: Six males and 4 females were included (cerebral palsy n = 8, neurodevelopmental disorders n = 2). All patients underwent submandibular gland surgery as a primary intervention (duct ligation n = 8, submandibular duct relocation n = 2) followed by re-intervention (submandibular gland excision n = 7, parotid duct ligation n = 3). One patient underwent tertiary surgery (parotid duct ligation after re-intervention by submandibular gland excision). Three patients were successful after re-intervention. No difference was found between both re-intervention techniques. There was significantly more severe dental malocclusion (50% vs. 21%, P value = 0.047) and severe speech disorders (80% vs. 42%, P value = 0.042) in the current cohort when compared to the reference cohort. CONCLUSION: Recurrence of drooling surgery is most likely not caused by surgical failure of the primary intervention, because re-intervention (submandibular gland excision) did not lead to more success. Dysarthria and dental malocclusion might negatively influence treatment outcome.

Randomized controlled trial comparing botulinum vs surgery for drooling in neurodisabilities.

OBJECTIVE: To compare the effect of submandibular duct ligation (2-DL) and submandibular botulinum neurotoxin type A (BoNT-A) for drooling in children and adolescents with neurodevelopmental disabilities. METHODS: A randomized, interventional, controlled, and partly single-blinded study was performed in which submandibular BoNT-A was compared with 2-DL to treat excessive drooling. Main outcomes included a Visual Analog Scale (VAS), drooling quotient (DQ), drooling severity (DS) scale and drooling frequency (DF) scale. Each was obtained at baseline, and 8 and 32 weeks post treatment. RESULTS: Fifty-seven patients (mean age: 11 years, mean baseline VAS score 7.9, mean baseline DQ 27.3%) were randomized to the 2-DL or BoNT-A group. Four patients were excluded from analyses, leaving 53 patients for intention-to-treat analyses. Response to treatment, defined as a ≥50% reduction in DQ or VAS score, was higher for 2-DL after 32 weeks (63.0% vs 26.9%, p = 0.008). Both VAS score (24.5, p < 0.001) and DQ (-9.3%, p = 0.022) were significantly lower at follow-up after 2-DL vs BoNT-A. The total number of adverse events (p = 0.088, 40.7% vs 19.2%) and postoperative complaints was higher (p < 0.001, mean 9.6 vs 3.6 days) for 2-DL than for BoNT-A. CONCLUSION: The 2-DL procedure is a more effective treatment for drooling than botulinum toxin, but carries a slightly greater risk of complications and morbidity. TRIALREGISTERNL IDENTIFIER: NTR3537. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that for children and adolescents with neurodevelopmental disabilities and severe drooling, 2-DL compared to a one-time intraglandular BoNT-A injection is more effective at reducing drooling at 32 weeks.