Spontaneous Cerebrospinal Fluid Rhinorrhea in a Patient With Breast Cancer.

Despite the well documented increased risk of osteopenia in patients with breast cancer during chemotherapy and endocrine therapy, spontaneous cerebrospinal fluid rhinorrhea (CSFR) is still rare. The authors present a case of spontaneous CSFR that occurred during chemotherapy and endocrine therapy for breast cancer. The patient underwent a repair using myofascia and adipose tissue and was started on mannitol. There was no recurrence at 1-year follow-up. Therefore, clinicians should pay attention to the possibility of CSFR in patients with breast cancer, to avoid misdiagnosis.

Prolactinoma extension as a contributing factor in dopamine agonist-induced CSF rhinorrhea: a systematic review of the literature.

BACKGROUND: Dopamine agonist-induced cerebrospinal fluid (CSF) rhinorrhea is an uncommon treatment-related complication arising in 6.1% of prolactinoma patients treated with dopamine agonists. Locally invasive prolactinomas may create CSF fistulae through formation of dural and osseous skull base defects. Tumor shrinkage secondary to dopamine agonist therapy unmasks skull base defects, thus inducing CSF rhinorrhea. In these cases, repair of the leak may be achieved through collaborative surgical intervention by rhinologists and neurosurgeons. Multiple variables have been investigated as potential contributors to the risk of CSF rhinorrhea development in medically treated prolactinoma patients, with little consensus. OBJECTIVE: The primary aim of our study was the characterization of risk factors for CSF rhinorrhea development following dopamine agonist treatment. METHODS: A systematic review of the literature was conducted to identify cases of CSF rhinorrhea following dopamine agonist treatment of prolactinoma. The clinical history, radiographic findings and treatment outcomes are discussed. RESULTS: Fifty-four patients with dopamine agonist-induced CSF rhinorrhea were identified across 23 articles published from 1979 to 2019. Description of diagnostic imaging [computed tomography (CT)/magnetic resonance imaging (MRI)] was not provided for 18/54 subjects. For the 36 cases that described prolactinoma appearance on CT or MRI, invasion of the cavernous sinuses was reported in 13 (36.1%) and invasion of the sphenoid sinus was reported in 18 (50%). CONCLUSION: Based on our systematic review, we propose that CT findings of osseous erosion of the sella or the anterior skull base may predict dopamine agonist-induced CSF rhinorrhea. We recommend obtaining a thin-slice CT of the sinuses in cases with MRI evidence of sphenoid involvement.

Rhinorrhea as a Result of Alzheimer's Disease Treatment.

Pharmacists serving older individuals should be encouraged to avoid prescribing cascades by recommending medication discontinuation or dose reduction, whenever possible.

Medically induced CSF rhinorrhea following treatment of macroprolactinoma: case series and literature review.

PURPOSE: Although several reports have addressed cerebrospinal fluid (CSF) rhinorrhea following dopamine agonist (DA) therapy of macroprolactinomas, further study is warranted for this relatively uncommon entity. Toward this aim, our retrospective series and review of literature further clarifies recommendations in treatment of this rare problem. METHODS: We retrospectively reviewed all macroprolactinoma cases in our hospital for a 15-year period. Our systematic search of PubMed identified original articles and reviews of all macroprolactinoma cases with an associated medication-induced CSF leak. RESULTS: Five patients with drug-induced CSF leak were identified; four of these patients received cabergoline therapy an average of 6 weeks before the onset of rhinorrhea and then underwent surgical repair of the CSF leak. Of 35 published studies included, we identified 60 patients with medication-induced CSF leak. Medical therapy included bromocriptine in 34 patients, cabergoline in 21 patients, and use of both DAs in two patients. Three cases did include complete diagnostic and treatment data. Median time from initiation of the DA treatment to occurrence of rhinorrhea was 6 weeks. For CSF rhinorrhea, 49 patients underwent surgical repair (38 by the transnasal approach) and seven patients were treated nonoperatively. CONCLUSION: Baseline skull base erosion in macroprolactinomas in combination with subsequent tumor shrinkage induced by DA therapy may result in spontaneous CSF rhinorrhea. Therefore, such patients should be advised about and monitored for this potential setback. Once CSF leak is diagnosed, prompt treatment must be carried out to avoid infectious complications. Transnasal surgery appears the most effective therapeutic approach.

Cerebrospinal Fluid Leak Rhinorrhea after Systemic Erlotinib Chemotherapy for Metastatic Lung Cancer: A Familiar Problem from an Unfamiliar Culprit.

BACKGROUND: Cerebrospinal fluid (CSF) rhinorrhea after medical therapy for pituitary prolactinoma is a rare but well-described phenomenon. To our knowledge, no CSF leaks have been reported after targeted medical treatment of pituitary or anterior skull base metastases. We report this unusual case to raise awareness of spontaneous CSF leaks in the setting of skull base metastatic disease. CASE PRESENTATION: A 66-year-old woman presented with epidermal growth factor receptor-mutant stage IV adenocarcinoma of the lung. Headache workup revealed a large sellar and clival lesion consistent with metastatic disease. Systemic erlotinib chemotherapy was initiated with a robust positive response. Approximately 1 week after chemotherapy initiation, the patient noted clear discharge from the right nostril. Her oncologist first diagnosed her with allergic rhinitis, but she presented with meningitis 4 days after diagnosis of CSF leak and was admitted for intravenous antibiotics and definitive repair of a CSF leak via an endoscopic endonasal approach. An erosion of bone and dura was found at the dorsum sellae where tumor had regressed due to the chemotherapy. A multilayer skull base repair was made uneventfully, and she recovered fully with no leakage seen at 2-month follow-up. CONCLUSIONS: All members of the treatment team should be aware of this possibility of CSF leak after initiation of systemic chemotherapy and tumor regression and urgently refer patients for repair if a leak should develop before the development of meningitis.

[Cerebrospinal fluid rhinorrhea in primary treatment of large and giant prolactinomas with dopamine agonists]. / Nazal'naia likvoreia pri pervichnom lechenii bol'shikh i gigantskikh prolaktinom agonistami dofamina.

At present, pharmacological therapy of prolactinomas with dopamine agonists (DAs) is considered the treatment of choice. In most cases, giant prolactinomas respond to treatment with dopamine agonists and decrease in size during the first months of the treatment. One of the rare but dangerous complications of conservative treatment of prolactinomas with invasive growth is cerebrospinal fluid rhinorrhea. MATERIAL AND METHODS: We present a retrospective analysis of 15 patients with macropropactinomas who underwent surgery for cerebrospinal fluid rhinorrhea developed due to primary therapy with dopamine agonists at the Burdenko Neurosurgical Institute (BNI) in the period between 2005 and 2015. All patients had large and giant tumors (according to the classification adopted at the BNI). When cerebrospinal fluid rhinorrhea was detected, patients were hospitalized to the BNI for examination, detection of a CSF fistula, reconstruction of a defect, and resection (if possible) of the tumor. RESULTS: In the period between 2005 and 2015, 15 patients (8 males and 7 females) with prolactinomas of a large and giant size at the onset of conservative therapy underwent surgery for cerebrospinal fluid rhinorrhea at the BNI. All patients underwent transnasal reconstruction of a skull base defect, with 13 out of 15 patients undergoing simultaneous resection of the tumor. After tumor resection, reconstruction was performed using auto-fat, fascia, and glue (in 8 cases). In the remaining cases, apart from auto-fat, fascia, and glue, a mucoperiosteal flap and auto-bone were used. Fourteen patients were followe-up. In 13 cases, there was no relapse of cerebrospinal fluid rhinorrhea after skull base reconstruction. In 1 case, there was a relapse of cerebrospinal fluid rhinorrhea. CONCLUSION: Conservative treatment of patients with giant prolactinomas should be performed under regular control of ENT doctors and neurosurgeons for timely detection and surgical treatment of cerebrospinal fluid rhinorrhea.

Alpha-1 adrenergic antagonists induced severe rhinitis in patients with benign prostatic hyperplasia.

The standard gold care medications for benign prostatic hyperplasia (BPH) are the alpha-1-adrenergic antagonists, they are an effective medications and are generally well tolerated. However, at this time, no data have been published concerning the development of severe rhinorrhea with a great impact on quality of life in patients treated with alpha-1-adrenergic antagonists. We report two men with BPH treated with two different alpha-adrenergic antagonists; alfuzosin and doxazocin. The naranjo quality scale documented a probable adverse drug reaction (score 7) between rhinorrhea and treatment with alpha-1-adrenergic antagonists. In conclusion we reported that alpha-1-adrenergic antagonists are able to induce rhinorrhea in patients with BPH.

Alcohol-induced respiratory symptoms are common in patients with aspirin exacerbated respiratory disease.

BACKGROUND: A large percentage of patients with aspirin exacerbated respiratory disease (AERD) report the development of alcohol-induced respiratory reactions, but the true prevalence of respiratory reactions caused by alcoholic beverages in these patients was not known. OBJECTIVE: We sought to evaluate the incidence and characteristics of alcohol-induced respiratory reactions in patients with AERD. METHODS: A questionnaire designed to assess alcohol-induced respiratory symptoms was administered to patients at Brigham and Women's Hospital and Scripps Clinic. At least 50 patients were recruited into each of 4 clinical groups: (1) patients with aspirin challenge-confirmed AERD, (2) patients with aspirin-tolerant asthma (ATA), (3) patients with aspirin tolerance and with chronic rhinosinusitis, and (4) healthy controls. Two-tailed Fisher exact tests with Bonferroni corrections were used to compare the prevalence of respiratory symptoms among AERD and other groups, with P ≤ .017 considered significant. RESULTS: The prevalence of alcohol-induced upper (rhinorrhea and/or nasal congestion) respiratory reactions in patients with AERD was 75% compared with 33% with aspirin-tolerant asthma, 30% with chronic rhinosinusitis, and 14% with healthy controls (P < .001 for all comparisons). The prevalence of alcohol-induced lower (wheezing and/or dyspnea) respiratory reactions in AERD was 51% compared with 20% in aspirin-tolerant asthma and with 0% in both chronic rhinosinusitis and healthy controls (P < .001 for all comparisons). These reactions were generally not specific to one type of alcohol and often occurred after ingestion of only a few sips of alcohol. CONCLUSION: Alcohol ingestion causes respiratory reactions in the majority of patients with AERD, and clinicians should be aware that these alcohol-induced reactions are significantly more common in AERD than in controls who are aspirin tolerant.

Case report: management of persistent dural anastomotic dehiscence in a patient treated with bevacizumab.

A 55-year-old woman with recurrent glioblastoma multiforme on palliative chemotherapy including Avastin, an angiogenesis inhibitor, presents with several episodes of bacterial meningitis secondary to a persistent cerebrospinal fluid (CSF) leak. Anastomotic dehiscence of the dura mater in the region of the previous craniotomy sites was evident. Attempts to repair the cranial CSF leak with external ventricular drain and ventriculoperitoneal shunt were unsuccessful. This patient underwent repair of the dural defects with a radial forearm free fascial flap, with consequent resolution of the CSF leak.A literature search was performed, and the available data on angiogenesis inhibitors and anastomotic dehiscence was reviewed, specifically focusing on delayed anastomotic dehiscence in patients receiving Avastin (bevacizumab). Although the potential complications of anastomotic dehiscence in patients receiving angiogenesis inhibitors are well documented, there is comparatively little documentation in the literature regarding delayed wound or anastomotic dehiscence. Twenty such cases were found cited in the literature; however, only one study was found which specifically considered angiogenesis inhibitors within the context of central nervous system malignancies.

Spontaneous intracranial hypotension-hypovolemia associated with tacrolimus.

There is little precedent for a medication-induced spontaneous intracranial hypotension/cerebrospinal fluid (CSF) hypovolemia (SIH). This case history of a woman with low CSF pressure, orthostatic headache, and radiographic findings consistent with SIH but without a detectable leak was notable for its association, both onset and resolution, with the use of the calcineurin inhibitor tacrolimus (FK506). A literature review for potential causes of a tacrolimus-induced CSF hypotension suggests many potential mechanisms of action, including effects on blood brain barrier and dural compliance, and supports further vigilance for this condition in the medically complex setting of tacrolimus use.

Mometasone furoate nasal spray is safe and effective for 1-year treatment of children with perennial allergic rhinitis.

OBJECTIVE: Perennial allergic rhinitis (PAR) affects children at a young age. Current guidelines recommend intranasal corticosteroids as the first-line treatment in patients with moderate-to-severe or persistent disease or in those who have congestion. In this study, the long-term safety and efficacy of mometasone furoate nasal spray (MFNS) were assessed in children with PAR. METHODS: In this multicenter, active-controlled, evaluator-blind, 12-month study, 255 children aged 6-11 years with a >or=1-year history of PAR were randomized to receive once-daily MFNS 100 microg (n=166) or the active comparator beclomethasone dipropionate (BDP) 168 microg (n=85). Changes from baseline in overall PAR symptoms and response to treatment were rated at each visit. Cosyntropin stimulation testing, as well as tonometry and slit lamp procedures, were performed. Safety variables were assessed. RESULTS: A total of 137 subjects in the MFNS group and 68 in the BDP group completed treatment. The mean reductions in physician- and subject-rated overall condition of PAR at week 52 were -42.1% and -39.7%, respectively, for MFNS, compared with -44.0% and -39.0%, respectively, for BDP. A total of 94% and 100% of MFNS and BDP subjects, respectively, reported adverse events (AEs), which were mostly mild or moderate. The most frequently reported treatment-related AEs in both groups were epistaxis, headache, and pharyngitis. Response to cosyntropin was normal and no posterior subcapsular cataracts were observed in either group. Although no significant changes in intraocular pressure were observed with MFNS, one subject receiving BDP demonstrated this effect. CONCLUSIONS: Treatment with MFNS 100 microg once daily for 1 year was well tolerated in children 6-11 years old, with negligible systemic exposure and no evidence of suppression of the hypothalamic-pituitary-adrenal axis or ocular changes.

Cerebrospinal fluid leakage as complication of treatment with cabergoline for macroprolactinomas.

Treatment of patients with prolactinomas consists primarily of dopamine agonists (DA). Cerebrospinal fluid (CSF) leakage has sporadically been reported in patients with macroprolactinomas treated with short-acting DA such as bromocriptine. Little is known on the incidence of this complication in patients treated with the long-acting D2 specific DA cabergoline. We report three patients with CSF leakage shortly after initiation of cabergoline treatment for macroprolactinoma. All three patients responded rapidly to cabergoline (CAB) by shrinkage of the tumor and release of the optic chiasm compression. The CSF leakage occurred within 10 days after initiation of treatment. CAB treatment was not discontinued. In one patient the CSF leakage ceased spontaneously, with no additional therapy. The second patient had a surgical repair of the CSF fistula, permitting cabergoline to be continued without a recurrence of the CSF leakage. The third patient refused surgical repair of the sellar defect. In this patient the cabergoline dosage was temporarily decreased with no effect on the CSF leakage. Four years later, the CSF leakage is unchanged in this patient, whilst no other complications occurred during the follow-up. No infectious complications occurred in these three patients. In conclusion, patients with large, invasive macroprolactinomas are at risk of CSF leakage during medical treatment with CAB. It is advisable to warn these patients for occurrence of this complication and to monitor them closely especially during the first months of treatment.

Cabergoline-induced CSF rhinorrhea in patients with macroprolactinoma. Report of three cases.

induces the macroprolactinoma shrinkage. Endoscopic transsphenoidal surgery offers a safe, minimally invasive and efficient management of this complication, which allows to regularly perform the following steps of the therapeutical strategy against the prolactinoma.

Comparison of nasal mucosal responsiveness to neuronal stimulation in non-allergic and allergic rhinitis: effects of capsaicin nasal challenge.

BACKGROUND: Neuronal involvement has been implicated in the pathophysiology of non-allergic and allergic rhinitis, contributing to the typical exacerbation of these conditions upon exposure to non-specific environmental irritants. OBJECTIVES: To determine if non-allergic and allergic rhinitis are characterized by increased responsiveness of the nasal mucosa to sensorineural stimulation. METHODS: Nasal challenges with capsaicin and its vehicle were performed in three groups of subjects -- non-allergic rhinitics, perennial allergic rhinitics, and healthy controls -- and resultant symptom scores, glandular secretion reflected by lactoferrin levels, and plasma extravasation reflected by albumin levels in nasal lavage fluid were compared. RESULTS: Capsaicin-sensitive nerve stimulation produced increases in symptom scores and lactoferrin levels which were similar among the three groups of subjects. On the other hand, only the group of subjects with allergic rhinitis demonstrated a significant capsaicin-induced increase in albumin levels and a trend in total protein levels. CONCLUSIONS: We conclude that non-allergic rhinitis is not characterized by increased responsiveness of capsaicin-sensitive nerve fibres; while allergic rhinitis is marked by hyperresponsiveness manifested as increased albumin leakage in nasal fluids. This may reflect the activity of an axonal reflex to sensorineural stimulation.

Post-exercise nasal vasoconstriction and hyporeactivity: possible involvement of neuropeptide Y.

Neuropeptide Y (NPY) is co-localized with noradrenaline (NA) in perivascular sympathetic nerve and is a vasoconstrictor. Pre-treatment with exogenous NPY markedly reduced nasal airway obstruction and rhinorrhea induced by the irritant capsaicin in control subjects. The aim of the present experiments was to study the time course variations of plasma concentrations of NA and NPY during and after intense exercise in 17 healthy volunteers. In parallel, changes in nasal airway resistance (NAR) were recorded. Nasal obstruction and rhinorrhea induced by capsaicin were compared after 30 min of rest and after 30 min of exercise. Both subjective and objective NAR were significantly reduced (p < 0.05) for over 15 min after the end of exercise. Plasma levels of NPY remained increased for more than 15 min after exercise whereas NA returned to basal values within less than 10 min. The increases of NAR and mucus production evoked by capsaicin were markedly attenuated for 30 min after exercise (p < 0.05). Variations of plasma NPY concentrations over time correlated better with post-exercise nasal vasoconstriction and hyporeactivity to capsaicin than NA. These observations suggest that endogenous NPY could be involved in the prolonged post-exercise nasal vasoconstriction and acts as a modulator of nasal airways reactivity.

Bromocriptine-induced cerebrospinal fluid fistula in patients with macroprolactinomas: report of three cases and a review of the literature.

Bromocriptine therapy for macroprolactinoma induced cerebrospinal fluid (CSF) rhinorrhea in three patients. The tumor had extended well beyond the sella turcica and caused bony erosion in all the cases. All three patients responded to bromocriptine therapy rapidly. CSF fistula occurred concomitantly with the reduction of tumor size and caused meningitis in two of the patients. Withdrawal of bromocriptine resulted in cessation of the leakage. One of the patients underwent transsphenoidal repair. Two patients refused surgery. This potentially lethal complication encountered in these three cases demonstrates the need for close supervision of macroprolactinoma patients with skull base erosion placed under bromocriptine therapy.