Botulinum Toxin Treatment for Cancer-Related Disorders: A Systematic Review.

This systematic review investigates the effect of botulinum neurotoxin (BoNT) therapy on cancer-related disorders. A major bulk of the literature is focused on BoNT's effect on pain at the site of surgery or radiation. All 13 published studies on this issue indicated reduction or cessation of pain at these sites after local injection of BoNTs. Twelve studies addressed the effect of BoNT injection into the pylorus (sphincter between the stomach and the first part of the gut) for the prevention of gastroparesis after local resection of esophageal cancer. In eight studies, BoNT injection was superior to no intervention; three studies found no difference between the two approaches. One study compared the result of intra-pyloric BoNT injection with preventive pyloromyotomy (resection of pyloric muscle fibers). Both approaches reduced gastroparesis, but the surgical approach had more serious side effects. BoNT injection was superior to saline injection in the prevention of esophageal stricture after surgery (34% versus 6%, respectively, p = 0.02) and produced better results (30% versus 40% stricture) compared to steroid (triamcinolone) injection close to the surgical region. All 12 reported studies on the effect of BoNT injection into the parotid region for the reduction in facial sweating during eating (gustatory hyperhidrosis) found that BoNT injections stopped or significantly reduced facial sweating that developed after parotid gland surgery. Six studies showed that BoNT injection into the parotid region prevented the development of or healed the fistulas that developed after parotid gland resection-parotidectomy gustatory hyperhidrosis (Frey syndrome), post-surgical parotid fistula, and sialocele. Eight studies suggested that BoNT injection into masseter muscle reduced or stopped severe jaw pain after the first bite (first bite syndrome) that may develop as a complication of parotidectomy.

The Minor's test in Frey syndrome treated with botulinum toxin: Methodology and efficacy.

In this paper, we aimed at methodologically presenting a video-case of Frey Syndrome occurred after parotidectomy, assessed by means of Minor's Test and treated with intradermic botulinum toxin A (BoNT-A) injection. Although largely described in the literature, a detailed explanation of both the procedures has not been previously elucidated. In a more original approach, we also highlighted the role of the Minor's test in identifying the most affected skin areas and new insight on the patient-tailored approach provided by multiple injections of botulinum toxin. Six months after the procedure, the patient's symptoms were resolved, and no evident signs of Frey syndrome were detectable through the Minor's test.

Not only gustatory sweating and flushing: Signs and symptoms associated to the Frey syndrome and the role of botulinum toxin A therapy.

BACKGROUND: The classic symptoms of Frey syndrome are gustatory sweating and flushing. Aims of the study were to describe prevalenceand severity of typical and atypical presentations of the disorder and to assess the effects of botulinum neurotoxin A (BoNT-A) therapy in patients with Frey syndrome after parotidectomy. METHODS: In this prospective, observational study on 18 patients, we assessed symptom severity before therapy, after 15 days, 1, 3 and 6 months' follow-up with the sweating-flushing-itch-paresthesia-pain (SFIPP) Frey scale specifically designed by the authors themselves for this study. RESULTS: Before BoNT-A injection, all patients (100%) complained gustatory sweating, 80% paresthesia, 77% gustatory flushing, 60% pain and 60% gustatory itch. The SFIPP-Frey overall score and the symptom-specific ones decreased significantly at each post-therapy control. CONCLUSIONS: The prevalence of "unusual" manifestations is not negligible. BoNT-A improves symptoms severity. The SFIPP-Frey scale may be useful to assess symptoms and to monitor post-therapy outcomes.

Temporoparietal frey syndrome: An uncommon variant of a common syndrome.

OBJECTIVES/HYPOTHESIS: To describe a previously unreported variant of Frey syndrome. Gustatory sweating is a common complication of parotidectomy and typically directly overlies the surgical site or parotid bed. In some instances, the sweating may occur beyond the parotid bed or involve tissue that was undisturbed during the procedure. STUDY DESIGN: Retrospective case series. METHODS: All cases of temporoparietal Frey syndrome in a single surgeon's experience were reviewed. RESULTS: Seven patients were found to have temporoparietal Frey syndrome. Three patients had concomitant first bite syndrome. Three patients had some form of reconstruction at time of surgery. The mean time to onset of symptoms was 11.5 months, with a range of 7 to 21 months. Four patients did not require any treatment for their symptoms, but two patients required intradermal Botox injections for symptomatic relief. DISCUSSION: This study describes a previously unreported variant of Frey syndrome with symptoms occurring distal to the parotid gland. This likely develops either by regeneration of severed postganglionic fibers into sympathetic targets distally along the course of the auriculotemporal nerve or by regeneration into fibers of the sympathetic plexus traveling along the superficial temporal artery. LEVEL OF EVIDENCE: Laryngoscope, 129:2071-2075, 2019.

Tratamiento de la hiperhidrosis secundaria a síndrome de Frey con toxina botulínica. A propósito de un caso / Treatment of hyperhydrosis secondary to Frey syndrome with botulinum toxin. Apropos of a case

El síndrome aurículo-temporal o síndrome de Frey, es una entidad caracterizada por sudoración y enrojecimiento de la piel del territorio inervado por el nervio aurículo-temporal en relación con la masticación. Se presenta el caso de un paciente diagnosticado de hiperhidrosis hemifacial secundaria a síndrome de Frey, remitido desde otorrinolaringología a consulta de rehabilitación para valoración de tratamiento. Se decide tratamiento con toxina botulínica tipo A, con buena respuesta. Se hace una breve revisión del tratamiento con toxina botulínica en el síndrome de Frey, resaltando su efectividad y facilidad de aplicación

Auriculotemporal syndrome, or Frey syndrome, is characterised by sweating and redness of the skin in the area innervated by the auriculotemporal nerve during chewing. We report the case of a patient diagnosed with hemifacial hyperhidrosis secondary to Frey syndrome who was referred by the otorhinolaryngology service to the rehabilitation service for treatment assessment. The patient was treated with botulinum toxin with good response. We provide a brief review of botulinum toxin treatment in Frey syndrome, highlighting its effectiveness and ease of application

Botulinum toxin therapy: functional silencing of salivary disorders.

Botulinum toxin (BTX) is a neurotoxic protein produced by Clostridium botulinum, an anaerobic bacterium. BTX therapy is a safe and effective treatment when used for functional silencing of the salivary glands in disorders such as sialoceles and salivary fistulae that may have a post-traumatic or post-operative origin. BTX injections can be considered in sialoceles and salivary fistulae after the failure of or together with conservative treatments (e.g. antibiotics, pressure dressings, or serial aspirations). BTX treatment has a promising role in chronic sialadenitis. BTX therapy is highly successful in the treatment of gustatory sweating (Frey's syndrome), and could be considered the gold standard treatment for this neurological disorder.

Botulinum toxin therapy in Frey's syndrome: a retrospective study of 440 treatments in 100 patients.

OBJECTIVE: Frey's syndrome is characterised as sweating, redness and warmth of the parotideal area and is often treated with botulinum toxin A. The objective of this retrospective study was to prove whether the toxin dosage and time-to-treatment intervals change after repeated botulinum toxin injections. STUDY DESIGN/METHODS: The charts of patients, who were treated for Frey's syndrome during the last 16 years, were assessed. Three brands of botulinum toxin A were available for therapy. The Minor test was used to confirm the sweating before each treatment and to determine the toxin dosage. Constant amount of botulinum toxin was injected per cm2 of the affected area. Patients consulted our department for the next treatment as soon as they felt disturbed by recurring sweating and when the sweating was objectively evident in the Minor test. Time intervals between treatments and injected toxin dosages were assessed. RESULTS: In total, 100 patients received 440 treatments in 16 years. Repeated injections, median 4.0, were carried out in 70.5% of patients. Median time interval to the first injection was 2.8 years. Median time interval between treatments was 12.0 months and showed to be steady (anova, P = .49, F = 1.01). CONCLUSION: Duration of effect of botulinum toxin on Frey's syndrome was long-lasting and stable with no significantly different time intervals between treatments. The extent of the sweating area did not vary significantly after repeated treatments and required a constant dose of botulinum toxin A.

Presentación infrecuente de síndrome de Frey bilateral, tratado con toxina botulínica / An unusual presentation of bilateral Frey syndrome treated with botulinum toxin

El síndrome de Frey o síndrome auriculotemporal, incluye sudoración facial al estímulo gustatorio, más frecuentemente después de cirugía de la glándula parótida. Describimos el caso de un síndrome de Frey bilateral, después de una cirugía unilateral de la glándula parótida, y su tratamiento exitoso con toxina botulínica tipo A. Se trata de una mujer de 54 años de edad, remitida para tratamiento a nuestro servicio de rehabilitación por referir sudoración en la mejilla durante la masticación, 2 años después de cirugía de la glándula parótida. En la valoración con el test de iodo/almidón, se observó un área de sudoración en ambas mejillas, mayor en la homolateral a la cirugía. Ambas áreas fueron tratadas con toxina botulínica, 50 unidades en cada una con un total de 100 unidades reconstituidas en 2 ml de solución salina estéril. A los 6 meses y al año de seguimiento, la paciente sigue asintomática. Nuestra paciente presentaba una forma inusual de síndrome de Frey y fue tratada con éxito con toxina botulínica. No hemos encontrado casos similares en la literatura de aparición en la edad adulta. La patofisiología del síndrome queda todavía por esclarecer (AU)

Frey syndrome, also known as auriculotemporal syndrome, includes facial gustatory sweating, mainly after surgery of the parotid gland. We describe a case of bilateral Frey syndrome after unilateral surgery and its subsequent successful treatment with type A botulinum toxin. A 54-year-old woman was referred for treatment to our physical medicine and rehabilitation department 2 years after parotid gland surgery complaining of sweating while eating in her ipsilateral cheek. When the affected area was assessed with the iodine and starch test, a hyperhydrotic area was revealed in both cheeks, which was greater in the ipsilateral cheek to surgery. Both areas were treated with botulinum toxin, 50 units in each, with a total of 100 units reconstituted with 2 ml sterile saline solution. Injections were performed following recommended protocols every 1 cm2. At 6 months and 1 year of follow up, the patient was asymptomatic. Our patient had an unusual form of Frey syndrome and was successfully treated with botulinum toxin. To the best of our knowledge, this is the first reported case of bilateral Frey syndrome beginning in adulthood. Further research is warranted to clarify the pathophysiology of this syndrome (AU)

Efficacy and safety of botulinum toxin type A for treatment of Frey's syndrome: evidence from 22 published articles.

Frey's syndrome (FS) is an unavoidable sequela following the surgery of the parotid gland. Although several treatment methods are available, their efficacy is short term or accompanied by unacceptable complications. In the past two decades, botulinum toxin type A (BTXA) has been widely used to treat FS. Although several systematic reviews have been reported recently, they were conflicting and with obvious deficiencies. Thus, we performed an objectively systematic review to determine whether BTXA is an effective and safe treatment for FS. A literature retrieval covering PubMed, Web of Science, Ovid, Embase and Cochrane library was performed on 16 January, 2015. Proportion meta-analysis and corresponding 95% confidence interval (CI) were performed to evaluate the efficacy and safety of BXTA in treatment of FS. A total of 499 records were retrieved and 22 articles with 23 studies were included after scrutiny by two independent authors. Statistical analyses regarding the effective rate, incidence of complications were used to estimate the efficacy and safety of BTXA. Our results suggested that the effective rate of BTXA for treatment of FS is 98.5% (95% CI = 0.971-0.994) and the incidence of complication is 3.6% (95% CI = 0.017-0.061). In conclusion, our study supports that BTXA produces meaningful benefits on the treatment of patients with FS. However, owing to lack of strong evidence, future studies with well-designed inclusion criteria and multicenter randomized controlled trials are needed to give more credible evidence, if possible.

Bilateral gustatory sweating in the submandibular region after bilateral neck dissection successfully treated with botulinum toxin.

Gustatory sweating (or chorda tympani syndrome) in the submandibular region is a rare complication of cervical surgery. We report a 66-year-old patient who had been referred for the management of a squamous cell carcinoma of the mobile tongue. She was treated by bilateral neck dissection and bilateral resection of the submandibular glands. Bilateral gustatory sweating in the submandibular region developed 10 years later and was successfully treated with bilateral injections of botulinum toxin type A.

Use of scopolamine patches in patients treated with parotidectomy.

The antimuscarinic effect of scopolamine causes a reduction of salivary secretion, so it can be used successfully in postoperative parotid surgery. The aim of this article was to demonstrate the efficiency of postoperative use of scopolamine transdermal patch in reduction of complications due to the presence of saliva in the surgical spaces.

Role of medical thermography in treatment of Frey's syndrome with botulinum toxin A.

Frey syndrome classically causes gustatory sweating and facial flushing. We describe 2 cases in which medical thermography was used to investigate the symptoms. Images were taken after patients chewed a sialagogue and 2 weeks later they were given injections of botulinum toxin A. Images taken 4 weeks after treatment showed a considerable reduction in sweating and facial flushing, which was supported by the results of quality of life questionnaires completed before and after treatment. Medical thermography is much cleaner than the Minor's starch iodine test. It identifies areas of gustatory sweating, changes in temperature, and vascular changes, which potentially enable treatment to be targeted accurately.

Facial blanching due to neurotoxins: proposed mechanisms.

BACKGROUND: The effect of perceived facial blanching with neurotoxin therapy has been described in the literature and has been used to treat the undesirable facial flushing of Frey's syndrome. Patients rarely report it as a complication after cosmetic injection, but it can be distressing. OBJECTIVES: To elucidate the proposed mechanism(s) of this unusual vasculocutaneous phenomenon, we reviewed normal physiologic responses to heat stress and the role of cholinergic neurotransmission in modulating cutaneous vascular tone in the context of the literature. MATERIALS/METHODS: We report a case of a 32-year-old woman who complained of white patches on her forehead at sites of abobotulinumtoxinA injections administered 2 weeks before presentation. RESULTS: Acetylcholine is a primary mediator of cutaneous vasodilatation; certain co-transmitters modulate its effect. Chemical denervation by botulinum toxin (BoNT) appears to interfere with these normal signaling pathways and can provide symptomatic relief to patients with undesirable facial flushing. Conversely, it may create an unwanted cosmetic effect in patients who desire isolated muscle paresis. CONCLUSIONS: Skin sites injected with BoNT type A may not experience the expected decrease in cutaneous vessel tone associated with higher body temperature. The exact mechanism remains unclear.

Botulinum toxin for Frey's syndrome: a closer look at different treatment responses.

OBJECTIVE: Botulinum toxin is a widely accepted, effective treatment for Frey's syndrome. While some patients need only one injection, others require repeated treatments. We aimed to describe the clinical features of patients with a more challenging treatment course. DESIGN: Literature review and retrospective analysis of eight consecutive patients treated at a university hospital. SUBJECTS: These patients' treatment responses were categorised (using our own system) and compared with those of 25 published cases. RESULTS: Combined analysis identified no significant correlation between treatment response and age, gender or the extent of primary salivary gland surgery. There was no significant correlation between botulinum toxin dosage and time between treatments. CONCLUSION: Frey's syndrome should be viewed as a dynamic process in which the stimulus for aberrant reinnervation of parasympathetic nerve fibres can be reduced, in some patients, with higher botulinum toxin dose injections to the treated areas. However, responses are unpredictable, and relapses may occur at different time points and in different areas.

[Successful treatment of diabetic gustatory hyperhidrosis with topical glycopyrrolate]. / Vellykket behandling af diabetisk gustatorisk hyperhidrose med lokalappliceret glykopyrrolat.

Gustatory hyperhidrosis is a condition characterised by excessive craniofacial sweating in relation to food intake and is associated with diabetic neuropathy. The existing guidelines for treatment of this condition include antiperspirants, oral anticholinergic treatment, ionophoresis, botulinum toxin injections and endothoracic surgery. In this case a patient with diabetes suffering from gustatory hyperhidrosis was treated successfully with topical glycopyrrolate, an anticholinergic agent applied directly on the affected area.