Case report: Macrophage activation syndrome in a patient with Kabuki syndrome.

Macrophage activation syndrome (MAS), is a severe and fatal complication of various pediatric inflammatory disorders. Kabuki syndrome (KS), mainly caused by lysine methyltransferase 2D (KMT2D; OMIM 602113) variants, is a rare congenital disorder with multi-organ deficiencies. To date, there have been no reported cases of MAS in patients with KS. This report describes a case of a 22-year-old male with Kabuki syndrome (KS) who developed MAS. This unique case not only deepens the understanding of the involvement of KMT2D in immune regulation and disease, but expands the phenotype of the adult patient to better understand the natural history, disease burden, and management of patients with KS complicated with autoimmune disorders.

Central Vestibular Dysfunction in Head Injury.

OBJECTIVES: This study aims to provide an overview of dizziness post head injury in those with prominent features for central vestibular dysfunction (CVD) in comparison to those with a post-traumatic peripheral vestibular etiology. STUDY DESIGN: Retrospective. SETTING: University Health Network (UHN) Workplace Safety and Insurance Board (WSIB) database from 1988 to 2018 were evaluated for post-traumatic dizziness. METHODS: The UHN WSIB neurotology database (n = 4291) between 1998 and 2018 was retrospectively studied for head-injured workers presenting with features for CVD associated with trauma. All patients had a detailed neurotological history and examination, audiovestibular testing that included video nystagmography (VNG) and cervical vestibular-evoked myogenic potentials (cVEMPs). Imaging studies including routine brain and high-resolution temporal bone computed tomography (CT) scans and/or intracranial magnetic resonance imaging (MRI) were available for the majority of injured workers. RESULTS: Among 4291 head-injured workers with dizziness, 23 were diagnosed with features/findings denoting CVD. Complaints of imbalance were significantly more common in those with CVD compared to vertigo and headache in those with peripheral vestibular dysfunction. Atypical positional nystagmus, oculomotor abnormalities and facial paralysis were more common in those with CVD. CONCLUSION: Symptomatic post-traumatic central vestibular injury is uncommon. It occurred primarily following high-impact trauma and was reflective for a more severe head injury where shearing effects on the brain often resulted in diffuse axonal injury. Complaints of persistent imbalance and ataxia were more common than complaints of vertigo. Eye movement abnormalities were highly indicative for central nervous system injury even in those with minimal change on CT/MRI.

Examination of risk factors for postoperative vestibular symptoms in patients with cholesteatoma.

BACKGROUND: In cholesteatoma, the prognosis of tympanoplasty has been well discussed in terms of hearing outcomes and residual or recurrent lesions. Postoperative dizziness and vertigo are major complications of tympanoplasty; however, few reports are available. AIMS/OBJECTIVES: We investigated each condition of cholesteatoma postoperative vestibular risk using the STAM system and staging published by EAONO/JOS, as well as findings on bony destruction. MATERIAL AND METHODS: From April 2010 to March 2021, 156 patients (166 ears) with cholesteatoma who underwent primary microscopic tympanoplasty at our hospital were registered. Subjective vestibular symptoms were recorded the day after surgery. RESULTS: Postoperative vestibular symptoms were observed in 13.9% of subjects. All of them were stage II and had both attic and mastoid lesions. Attic (p < .05) and mastoid (p < .01) lesions were risk factors. Multivariate analysis showed that significant differences were found in past histories of vestibular symptoms (p < .05) and exposure of the dura mater (p < .01). CONCLUSIONS AND SIGNIFICANCE: In the exposed dura group, the length of the prominence of the lateral semicircular canal to the middle cranial fossa dura was significantly shorter than that of the non-exposed group (p < .01). Narrow working space and downward operation may increase vestibular risk.

Cerebellar ataxia, neuropathy and vestibular areflexia syndrome (canvas): an important cause of late-onset ataxia with unique clinical features.

Cerebellar ataxia, neuropathy, vestibular areflexia syndrome (CANVAS) is a late-onset, slowly progressive disorder characterized by cerebellar ataxia, sensory neuropathy and bilateral vestibulopathy. Recently, a biallelic intronic AAGGG repeat expansion, (AAGGG)exp, in the Replication Factor C1 (RFC1) gene was identified as the cause of this disorder. In this study, we describe the phenotypic features of five patients from five different families diagnosed as CANVAS. The mean age at onset was 49.00 ± 9.05 years (between 34 and 56 years) and the most frequent presenting symptom in CANVAS was gait ataxia, followed by sensory disturbances. Persistent coughing was prominent in three patients, and it preceded the onset of ataxia and sensory symptoms in two patients. Parental consanguinity was present in three patients. Two patients showed symptoms or signs suggesting autonomic involvement. Sural nerve biopsy revealed axonal neuropathy in two patients. The mean age at onset was 49.00 ± 9.05 years (between 34 and 56 years) and the most frequent presenting symptom in CANVAS was gait ataxia, followed by sensory disturbances. Persistent coughing was prominent in three patients, and it preceded the onset of ataxia and sensory symptoms in two patients. Parental consanguinity was present in three patients. Two patients showed symptoms or signs suggesting autonomic involvement. Sural nerve biopsy revealed axonal neuropathy in two patients. Our study describes clinical findings, histopathological features and diagnostic clues of CANVAS from Turkey, a country with a high consanguineous marriage rate. Repeat expansion in the RFC1 gene should be considered in all cases with late-onset ataxia, especially when sensory disturbances, vestibular involvement and persistent coughing coexist.

Progress in protecting vestibular hair cells.

Vestibular hair cells are mechanosensory receptors that are capable of detecting changes in head position and thereby allow animals to maintain their posture and coordinate their movement. Vestibular hair cells are susceptible to ototoxic drugs, aging, and genetic factors that can lead to permanent vestibular dysfunction. Vestibular dysfunction mainly results from the injury of hair cells, which are located in the vestibular sensory epithelium. This review summarizes the mechanisms of different factors causing vestibular hair cell damage and therapeutic strategies to protect vestibular hair cells.

Sudden Otovestibular Dysfunction in 3 Metastatic Melanoma Patients Treated With Immune Checkpoint Inhibitors.

Immune-related adverse events have been described in 86%-96% of high-risk melanoma patients treated with immune checkpoint inhibitors (ICI), while in 17%-59% of cases these are classified as severe or even life-threatening. The most common immune-related adverse events include diarrhea, fatigue, hypothyroidism, and hepatitis. Bilateral uveitis and unspecific vertigo have been described in 1% of cases, respectively, in the pivotal studies of ICIs, but the affection of the vestibule-cochlear system has not been reported before. In this case series, we present 3-stage IV melanoma patients with sudden onset of otovestibular dysfunction (hearing loss and vestibulopathy), partly combined with uveitis because of ICIs. We describe detailed diagnostic work-up and therapeutic interventions and discuss possible pathogenic mechanisms of this rare and disabling event.

Usefulness of Exam Questions and Vital Signs for Predicting the Outcome of Objective Vestibular Tests.

OBJECTIVES/HYPOTHESIS: To determine the value of standard clinic screening questions and vital signs in predicting abnormal vestibular function, indicated by standard objective diagnostic tests. STUDY DESIGN: Retrospective records review. METHODS: We reviewed electronic medical records of 150 patients seen by the neurotologists or the physician assistant they supervised, in an out-patient tertiary care clinic, between June 2018 and March 2020, and subsequently referred for the complete objective vestibular test battery (VB). RESULTS: Of standard questions asked during the initial exam about vertigo, disequilibrium, lightheadedness and oscillopsia, only vertigo predicted an abnormal response on the VB. More males than females had abnormal VB responses, P < .05. Pulse was not related to VB score. Significantly more subjects with blood pressure in the range for stage 2 hypertension (blood pressure [BP] stage 2) had abnormal than normal results on the VB, P < .00001. Subjects with BP stage 2 had high rates of diabetes (34.2%) and hypertension (68.4%) as diagnosed by their primary care physicians or cardiologists. CONCLUSION: Complaints of subjective vertigo and BP in the range of hypertension stage 2 are most likely to predict abnormal findings on the VB. Therefore, during an examination of a patient who comes in complaining of dizziness, two measures may be the most useful for screening: BP in the range of hypertension type 2, when BP is taken by a nurse, and a question to determine whether or not the patient has true vertigo. LEVEL OF EVIDENCE: 3 Laryngoscope, 131:1382-1385, 2021.

Influence of Cochlear Implantation on Balance Function in Pediatrics.

BACKGROUND AND OBJECTIVE: Patients with profound Sensorineural Hearing Loss (SNHL) are susceptible to vestibular disturbances following Cochlear Implant (CI) surgery. This study aimed to evaluate vestibular dysfunctions following unilateral CI in the congenitally deaf children. METHODS: This was a cross-sectional study conducted on 24 children (mean age: 10.56 ± 5.49 years old) who underwent unilateral CI and 24 age-matched controls (mean age: 11.13 ± 6.21 years old). Vestibular functions were assessed by Vestibular Evoked Myogenic Potential (VEMP) and Computerized Dynamic Posturography (CDP). The VEMP test was performed for otolith's function (especially saccule) evaluation. Sensory Organization Test (SOT) protocol of CDP was also utilized to differentiate the role of various sensory systems contributing to postural stability. In addition, total equilibrium score was calculated. The variables were comparatively assessed between the two groups. RESULTS: The mean p13-n23 amplitude in the CI users was significantly lower than the controls (p<0.05). However, the two groups showed no significant difference in cVEMP latency values (p>0.05). The SOT analysis revealed that 45.83% (11/24) of the CI subjects had some kind of sensory abnormalities: 7 cases (29.17%) vestibular, 2 cases (8.33%) visual, 2 cases (8.33%) vestibular and somatosensory involvements. Furthermore, total equilibrium score was significantly reduced in implanted group than the controls (p<0.001). At least, 70.59% (12/24) CI patients showed abnormal values in the CDP or cVEMP examinations. CONCLUSION: This study shows functional vestibular impairments in children who underwent CI. These patients showed significantly increased postural instability which was more evident in dynamic conditions. These findings provide the basis for better pre-operative counseling and postoperative vestibular rehabilitation to CI recipients.

Subjective Visual Vertical Testing in Patients With Chronic Suppurative Otitis Media.

OBJECTIVE: To analyze the results of the subjective visual vertical test using the "bucket method" in patients with chronic suppurative otitis media (CSOM). STUDY DESIGN: Cross-sectional, controlled study. SETTING: Outpatient otology clinic in a tertiary care hospital. SUBJECTS AND METHODS: Patients had CSOM, defined as the presence of chronic infection or inflammation of the middle ear cleft, associated with a perforation of the tympanic membrane, frequent or intractable middle ear suppuration, with or without cholesteatoma. Controls were selected using a nonprobability, purposive sampling method. We excluded patients with neurologic or metabolic diseases, cognitive deficits, otosclerosis, vestibular migraine, Ménière's disease, past use of ototoxic medication, or head and neck cancer. The volunteers were subjected to the subjective visual vertical test using the "bucket method." The results obtained in our study and control groups were analyzed using nonparametric tests. RESULTS: Our study comprised 51 patients with CSOM and 50 controls. In the CSOM group, we observed that 72.5% of the patients had vestibular symptoms in the past year, and 70.5% had abnormalities identified in at least 1 vestibular function test. The subjective visual vertical test revealed that patients with CSOM (with and without cholesteatoma) had significantly higher deviations of the true vertical as compared with controls (CSOM, 3.66°; controls, 0.76°; P < .001). CONCLUSION: Our results revealed that CSOM was associated with high rates of vestibular symptoms, abnormal vestibular function tests, and abnormal subjective vertical visual results.

Clinical signs, MRI findings and outcome in dogs with peripheral vestibular disease: a retrospective study.

BACKGROUND: Vestibular dysfunction is relatively common in dogs, with a prevalence of 0.08% reported in primary veterinary care in the UK. There are several studies investigating how to differentiate between peripheral and central vestibular disease but only limited information regarding the possible underlying causes for peripheral vestibular dysfunction in dogs. This study therefore aimed to describe the clinical signs, magnetic resonance imaging findings (MRI), underlying causes and outcome in a large population of dogs diagnosed with peripheral vestibular disease. RESULTS: One hundred eighty-eight patients were included in the study with a median age of 6.9 years (range 3 months to 14.6 years). Neurological abnormalities included head tilt (n = 185), ataxia (n = 123), facial paralysis (n = 103), nystagmus (n = 97), positional strabismus (n = 93) and Horner syndrome (n = 7). The most prevalent diagnosis was idiopathic vestibular disease (n = 128), followed by otitis media and/or interna (n = 49), hypothyroidism (n = 7), suspected congenital vestibular disease (n = 2), neoplasia (n = 1) and cholesteatoma (n = 1). Long-term follow-up revealed persistence of head tilt (n = 50), facial paresis (n = 41) and ataxia (n = 6) in some cases. Recurrence of clinical signs was observed in 26 dogs. Increasing age was associated with a mild increased chance of diagnosis of idiopathic vestibular syndrome rather than otitis media and/or interna (P = 0.022, OR = 0.866; CI 0.765-0.980). History of previous vestibular episodes (P = 0.017, OR = 3.533; CI 1.251-9.981) was associated with an increased likelihood of resolution of the clinical signs whilst contrast enhancement of cranial nerves VII and/or VIII on MRI (P = 0.018, OR = 0.432; CI 0.251-0.868) was associated with a decreased chance of resolution of the clinical signs. CONCLUSIONS: Idiopathic vestibular disease is the most common cause of peripheral vestibular dysfunction in dogs and it is associated with advanced age. Incomplete recovery from peripheral vestibular disease is common, especially in dogs presenting with cranial nerve enhancement on MRI but less so if there is previous history of vestibular episodes.

Evidence a shared mechanism mediates ipsi- and contralesional compensatory saccades and gait after unilateral vestibular deafferentation.

The study objective was to understand how the contralesional labyrinth contributes to gaze and gait stability after unilateral vestibular deafferentation (UVD). Head impulse testing (vHIT) was completed in 37 individuals [22 women (59%); age 52.13 ± 11.59 yr, mean ± SD] with UVD from vestibular schwannoma resection. Compensatory saccades (CS) and vestibulo-ocular reflex (VOR) gain were analyzed for both ipsilesional and contralesional impulses. Gait speed (10-m walk test) and endurance (2-min walk test) were collected for 35 individuals. CS were recruited during contralesional head rotation regardless of VOR gain on either the ipsilesional [ρ = 0.21 (-0.14, 0.57); Spearman rank (95% confidence interval)] or contralesional side [ρ = -0.04 (-0.42, 0.35)]. Additionally, the latency of these CS (151.19 ± 52.41 ms) was similar to that of CS generated during ipsilesional rotation (165.65 ± 21.62 ms; P = 0.159). CS recruited during ipsilesional vHIT were of a higher velocity (P < 0.001) and greater frequency (P < 0.001) compared with contralesional CS. VOR gain asymmetry was significantly correlated with gait speed [ρ = -0.37 (-0.73, -0.01)], yet individual VOR gain was not correlated [ipsilesional: ρ = 0.17 (-0.20, 0.55); contralesional: ρ = -0.18 (-0.52, 0.15)]. Our data reveal CS are recruited at similar latencies without correlation to VOR gain or direction of head rotation, and that the central integration of ipsilesional and contralesional vestibular afference correlates with gait. Together, our data suggest the brain considers vestibular afference from both sides when generating related behavioral output after UVD.NEW & NOTEWORTHY After unilateral vestibular deafferentation, compensatory saccades (CS) have similar latencies regardless of the direction of head rotation, and those CS generated during contralesional head rotation are unrelated to extent of vestibular loss. Additionally, the extent of asymmetry in residual vestibular function, not the extent of vestibular loss, correlates with gait speed. Our data suggest a common mechanism is responsible for the generation of CS and restoration of gait speed in vestibular compensation.

Descripción de los trastornos del equilibrio en la Unidad de Otoneurología del Hospital Clínico Herminda Martín / Description of balance disorders in the otoneurology unit of the Hospital Clinico Herminda Martin

INTRODUCCIÓN: Los trastornos del equilibrio constituyen un grupo heterogéneo de patologías. Son patologías frecuentes en medicina, representando una carga asistencial significativa en los distintos niveles de atención. En ese sentido, los estudios de frecuencia son una herramienta para entender patrones de enfermedad, como también la evaluación y planificación de una red asistencial. Material y método: Estudio descriptivo transversal sobre pacientes que asistieron al policlínico de otoneurología del Hospital Clínico Herminda Martin con motivo de consulta síntomas vestibulares durante el año 2018. Resultados: 183 pacientes cumplieron con los criterios de inclusión y exclusión, 78% (n=143) del sexo femenino y 22% (n=40) del masculino. Con una edad promedio de 58 años. El diagnóstico otoneurológico más frecuente fue vértigo posicional paroxístico benigno 34,97% (n=64), seguido de migraña vestibular 7,1% (n=13), enfermedad de Ménière 5,46% (n=10) y neuritis vestibular 4,37% (n=8). En 26,78% (n=49) no se logró un diagnóstico definitivo. Los trastornos de origen central representaron un 3,83% (n=7) y aquellos de origen no otoneurológico un 17,49% (n=32). Discusión: Los datos de frecuencia de los distintos trastornos del equilibrio registrados en el policlínico de otoneurología del Hospital Clínico Herminda Martin, son similares a la literatura internacional. Los trastornos vestibulares periféricos son los más frecuentes, de los cuales destaca el vértigo posicional paroxístico benigno representando el 34,97% del total de casos. Dentro de las causas otoneurológicas, la migraña vestibular fue la segunda causa en nuestro medio con un 7,1% del total de casos.

INTRODUCTION: Balance disorders are a heterogeneous group of diseases. They are a frequent medical condition, representing a significant healthcare burden at the different levels of care. Thus, frequency studies are a tool to understand disease patterns, as well as the evaluation and planning of a healthcare network. Material and method: Cross-sectional study of patients who attended the otoneurology out-patient clinic of the Hospital Clinico Herminda Martin with chief complaint of vestibular symptoms during 2018. Results: 183 patients met the inclusion and exclusion criteria, 143 (78%) were female and 40 (22%) male. With an average age of 58 years. The most frequent otoneurological diagnosis was benign paroxysmal positional vertigo 34.97% (n=64), followed by vestibular migraine 7.1% (n=13), Ménière's disease 5.46% (n=10) and vestibular neuritis 4.37% (n=8). In 26.78% (n=49) a definitive diagnosis was not achieved. Disorders of central origin represented 3.83% (n=7) and non-otoneurological origin 17.49% (n=32). Discussion: The frequency data of the balance disorders registered in the otoneurology out-patient clinic are similar to the international literature, peripheral vestibular disorders are the most frequent, of which benign paroxysmal positional vertigo stands out, representing 34.97% of the total cases. Among the otoneurological causes, vestibular migraine was the second cause in our study with 7.1% of the total cases

Tumor-to-Tumor Metastasis of Hepatocellular Carcinoma to Vestibular Schwannoma.

BACKGROUND: Intracranial metastasis is a common complication of systemic malignancy. A rare subset of intracranial masses constitutes tumor-to-tumor metastasis, in which an extracranial neoplasm hematogenously spreads to an existing intracranial lesion. CASE DESCRIPTION: Here we present the unique case of a 59-year-old man with known hepatocellular carcinoma who presented with acute headaches, double vision, vertigo, and gait instability in the context of 2 years of right-sided hearing loss. Head imaging showed a heterogeneous right cerebellopontine angle mass extending into the porus acousticus with adjacent cerebellar edema. Histopathologic analysis after resection found coexisting hepatocellular carcinoma within a vestibular schwannoma. CONCLUSIONS: Tumor-to-tumor metastasis is an important consideration in the diagnostic work-up and treatment of patients with known systemic malignancy who present with a new intracranial lesion. This pathologic entity could be missed if this patient were treated with single-fraction radiosurgery such as Gamma Knife.

Audiological and vestibular measurements in Behçet's disease.

INTRODUCTION: Behçet's disease (BD) is a vasculitis that involves all small vessels and influences the multiple systems of the human body. This study aimed to evaluate the audio-vestibular system involvement of patients with BD and healthy individuals. MATERIALS AND METHODS: This study was designed as a prospective case-control blinded study. Thirty-one patients with BD and 31 healthy individuals were included. All the subjects were evaluated via pure tone audiometry (PTA), video head impulse test (vHIT), post head shake nystagmus test (PHSNT) and dizziness handicap inventory (DHI) to check for audio-vestibular system involvement. RESULTS: Patients with BD showed higher PTA scores in both speech and high frequencies. The vHIT revealed pathological saccades, particularly in horizontal canals (right ear: p = 0.002, left ear: p = 0.039). The gain values of the patients were slightly lower than those of the control group; however, gain and gain asymmetry differed significantly in a few canals. In the spontaneous nystagmus test and PHSNT, pathological nystagmus was detected to be significantly higher in the patient group than control group (p = 0.001); but the saccade presence in vHIT and nystagmus in PHNT did not differ among the patients (p = 0.106). In addition, the DHI scores of the patients group were higher than those of the control group (p < 0.001). No correlation was found between disease duration and saccade presence. CONCLUSION: The vHIT was used preliminary for evaluating the vestibular system in BD. This study showed the influence of BD on the audio-vestibular system, in particular isolated horizontal canal involvement was discovered in patients with BD. LEVEL OF EVIDENCE: Level III b.

Peripheral Vestibular System Histopathologic Changes following Head Injury without Temporal Bone Fracture.

OBJECTIVE: Vestibular symptoms such as dizziness and vertigo are common after head injury and may be due to trauma to the peripheral vestibular system. The pathophysiology of peripheral vestibular symptoms following head injury without temporal bone (TB) fracture, however, is not well understood. Herein, we investigate the histopathology of the peripheral vestibular system of patients who sustained head injury without a TB fracture. STUDY DESIGN: Otopathology study. SETTING: Otopathology laboratory. SUBJECTS AND METHODS: TB of subjects with a history of head injury without TB fractures were included and evaluated by light microscopy. Specimens were assessed for qualitative and quantitative characteristics, such as number of Scarpa's ganglion cells in the superior and inferior vestibular nerves, vestibular hair cell and/or dendrite degeneration in vestibular end organs, presence of vestibular hydrops, and obstruction of the endolymphatic duct. RESULTS: Five cases (n = 5 TBs) had evidence of vestibular pathology. There was a decrease of 48.6% (range, 40%-59%) in the mean count of Scarpa's ganglion cells as compared with that of normative historical age-matched controls. Moderate to severe degeneration of the vestibular membranous labyrinth was identified in the posterior, superior, and lateral canals in several cases (50%, n = 4 TBs). The maculae utriculi and sacculi showed mild to severe degeneration in 2 cases. Additional findings include vestibular hydrops (25%, n = 2 TBs) and blockage of the endolymphatic duct (n = 1 TB). CONCLUSIONS: Otopathologic analysis of patients with a history of head injury without TB fracture demonstrated peripheral vestibular otopathology. Future studies are necessary to determine if otopathology findings are directly attributable to head injury.

Kabuki syndrome: international consensus diagnostic criteria.

BACKGROUND: Kabuki syndrome (KS) is a clinically recognisable syndrome in which 70% of patients have a pathogenic variant in KMT2D or KDM6A. Understanding the function of these genes opens the door to targeted therapies. The purpose of this report is to propose diagnostic criteria for KS, particularly when molecular genetic testing is equivocal. METHODS: An international group of experts created consensus diagnostic criteria for KS. Systematic PubMed searches returned 70 peer-reviewed publications in which at least one individual with molecularly confirmed KS was reported. The clinical features of individuals with known mutations were reviewed. RESULTS: The authors propose that a definitive diagnosis can be made in an individual of any age with a history of infantile hypotonia, developmental delay and/or intellectual disability, and one or both of the following major criteria: (1) a pathogenic or likely pathogenic variant in KMT2D or KDM6A; and (2) typical dysmorphic features (defined below) at some point of life. Typical dysmorphic features include long palpebral fissures with eversion of the lateral third of the lower eyelid and two or more of the following: (1) arched and broad eyebrows with the lateral third displaying notching or sparseness; (2) short columella with depressed nasal tip; (3) large, prominent or cupped ears; and (4) persistent fingertip pads. Further criteria for a probable and possible diagnosis, including a table of suggestive clinical features, are presented. CONCLUSION: As targeted therapies for KS are being developed, it is important to be able to make the correct diagnosis, either with or without molecular genetic confirmation.

Outcomes of cochlear implantations for mumps deafness: A report of four pediatric cases.

Mumps virus occasionally causes bilateral hearing loss. We report 4 cases of bilateral mumps deafness in whom cochlear implantations (CI) were performed. The age at the onset of hearing loss was 1-9 years. CI surgery was performed within 6 months from the onset of hearing loss in 3 cases and after 9 years in the other case, showing good speech perception in the early intervention cases and a poor outcome after later implantation. Early CI surgery is highly recommended in sudden onset deafness by mumps in childhood.