Red flags alerting a posterior cranial fossa tumor from audiovestibular perspectives - a review.

BACKGROUND: There is no comprehensive and up-to-date overview of audiovestibular approach to the posterior fossa tumors in the literature. OBJECTIVE: This paper reviewed the literature relating to tumors at the posterior cranial fossa to find red flags alerting a posterior fossa lesion from audiovestibular perspectives. METHODS: This review was developed from articles published in those journals listed on the journal citation reports. Through the PubMed database, Embase, Google Scholar, and Cochrane library, 60 articles were finally obtained based on the PRISMA guidelines for reporting reviews. RESULTS: The presence of one red flag indicates a positive predictive value of 33% for detecting a posterior fossa lesion. Clinical features, namely, 1) mid-frequency sudden sensorineural hearing loss (SNHL), 2) bilateral sudden SNHL, and 3) rebound nystagmus may indicate a posterior fossa lesion, representing one, two, and three red flags, respectively. CONCLUSION: Those with 1) mid-frequency sudden SNHL, 2) bilateral sudden SNHL, and 3) rebound nystagmus trigger one, two, and three red flags, respectively, alerting clinicians the possibility of a posterior fossa lesion, which warrant MR imaging to exclude life-threatening or treatable conditions. SIGNIFICANCE: Patients with posterior fossa tumors may have potential life-threatening outcome.

Evaluation of safety of fluoxetine for cerebellar mutism syndrome in children after posterior fossa surgery.

BACKGROUND: Cerebellar mutism syndrome (CMS) occurs in 8-29 % of children undergoing posterior fossa tumor surgery. Its main symptoms are mutism and emotional lability. Although it is always transient, recovery time can be lengthy with long-term cognitive sequelae. There is no approved drug treatment for CMS, but some drugs are used in everyday medical practice. One of these is fluoxetine, which has been used for many years in our institution. The main objective of this study was to establish the safety profile of fluoxetine in this condition. MATERIALS AND METHODS: The records of patients admitted to the pediatric intensive care unit after brain surgery at Angers University Hospital from 2010 to 2020 were reviewed. Children aged 2 years and older who underwent a posterior fossa tumor surgery and were diagnosed with CMS were included. Data on patient characteristics, prescription of fluoxetine treatment, side effects if any, and complete mutism duration were collected. RESULTS: Among 246 patients admitted to the pediatric intensive care unit for brain surgery during the study period, 23 had CMS and eight were prescribed fluoxetine. No serious adverse event related to fluoxetine was reported. Complete mutism duration did not differ significantly between the fluoxetine group and the non-fluoxetine group(p = 0.22). However, the treatment was initiated after recovery from complete mutism in half of the treated patients. CONCLUSION: This study suggests a positive safety profile of fluoxetine used in postoperative CMS. It does not answer the question of whether the treatment is effective for this indication. A randomized controlled trial based on a syndrome severity scale should be conducted to provide a more reliable assessment of the efficacy and safety of fluoxetine.

Effects of cognitive-motor intervention for pediatric posterior fossa tumor survivors: results of a pilot study.

The purpose of this prospective pilot study was to evaluate the feasibility and effects of cognitive-motor intervention on the cognitive and motor abilities of pediatric survivors of posterior fossa tumors. The study involved patients aged 7 to 18 years with cognitive deficits who had completed primary treatment for posterior fossa tumors. 25 participants (Mage=11.3 ± 2.93, 64% male; 17 medulloblastoma, 1 ependymoma, 1 desmoplastic medulloblastoma, 6 piloid astrocytoma; 22 in remission (Mmonths =45), 3 in stabilization (Mmonths=49)) were recruited from the Research Institute for Brain Development and Peak Performance. The intervention consisted of two phases with a 3-month break for home training, and a total duration of 6 months. Each phase lasted 7 weeks and included two assessment procedures (pre- and post-intervention) and 10 training sessions over a period of 5 weeks (two 3-hour sessions per week). At baseline and pre- and post-intervention, all participants underwent a battery of cognitive and motor tests. Each training session included gross motor training (GMT), graphomotor training (GT), and cognitive-motor training (CMT). Statistical analysis was performed using the Friedman test for repeated measures and post-hoc Durbin-Conover test. The results indicated significant improvements in visuospatial working memory, visual attention, eye-hand coordination, semantic verbal fluency, auditory-motor synchronization, reaction time, and a decrease in the rate of ataxia. These improvements remained stable even in the absence of direct intervention. The findings demonstrate positive effects and feasibility of the intervention and suggest the need for further research in this area including randomized controlled feasibility studies with a larger sample.

Implications of DNA Methylation Classification in Diagnosing Ependymoma.

BACKGROUND: Ependymoma is a central nervous system (CNS) tumor that arises from the ependymal cells of the brain's ventricles and spinal cord. The histopathology of ependymomas is indistinguishable regardless of the site of origin, and the prognosis varies. Recent studies have revealed that the development site and prognosis reflect the genetic background. In this study, we used genome-wide DNA methylation array analysis to investigate the epigenetic background of ependymomas from different locations treated at our hospital. METHODS: Four cases of posterior fossa ependymomas and 11 cases of spinal ependymomas were analyzed. RESULTS: DNA methylation profiling using the DKFZ methylation classifier showed that the methylation diagnoses of the 2 cases differed from the histopathological diagnoses, and 2 cases could not be classified. Tumor that spread from the brain to the spinal cord was molecularly distinguishable from other primary spinal tumors. CONCLUSIONS: Although adding DNA methylation classification to conventional diagnostic methods may be helpful, the diagnosis in some cases remains undetermined. This may affect decision-making regarding treatment strategies and follow-up. Further investigations are required to improve the diagnostic accuracy of these tumors.

Preoperative 11 C-Methionine PET-MRI in Pediatric Infratentorial Tumors.

PURPOSE: MRI is the main imaging modality for pediatric brain tumors, but amino acid PET can provide additional information. Simultaneous PET-MRI acquisition allows to fully assess the tumor and lower the radiation exposure. Although symptomatic posterior fossa tumors are typically resected, the patient management is evolving and will benefit from an improved preoperative tumor characterization. We aimed to explore, in children with newly diagnosed posterior fossa tumor, the complementarity of the information provided by amino acid PET and MRI parameters and the correlation to histopathological results. PATIENTS AND METHODS: Children with a newly diagnosed posterior fossa tumor prospectively underwent a preoperative 11 C-methionine (MET) PET-MRI. Images were assessed visually and semiquantitatively. Using correlation, minimum apparent diffusion coefficient (ADC min ) and contrast enhancement were compared with MET SUV max . The diameter of the enhancing lesions was compared with metabolic tumoral volume. Lesions were classified according to the 2021 World Health Organization (WHO) classification. RESULTS: Ten children were included 4 pilocytic astrocytomas, 2 medulloblastomas, 1 ganglioglioma, 1 central nervous system embryonal tumor, and 1 schwannoma. All lesions showed visually increased MET uptake. A negative moderate correlation was found between ADC min and SUV max values ( r = -0.39). Mean SUV max was 3.8 (range, 3.3-4.2) in WHO grade 4 versus 2.5 (range, 1.7-3.0) in WHO grade 1 lesions. A positive moderate correlation was found between metabolic tumoral volume and diameter values ( r = 0.34). There was no correlation between SUV max and contrast enhancement intensity ( r = -0.15). CONCLUSIONS: Preoperative 11 C-MET PET and MRI could provide complementary information to characterize pediatric infratentorial tumors.

Characterizing the association between CSF biomarkers and risk for ventriculoperitoneal shunt following posterior fossa tumor resection in a case-control study.

BACKGROUND: Recalcitrant hydrocephalus necessitating permanent cerebrospinal fluid (CSF) diversion is a known complication after resection of a posterior fossa tumor (PFT). Various CSF contents, such as protein and other markers, have been variably correlated with the need for permanent CSF diversion. This study aims to evaluate which CSF laboratory values are associated with permanent CSF diversion following PFT resection in adults. METHODS: This study queried our multi-institutional database (Central Nervous System Tumor Outcome Registry at Emory; CTORE) consisting of 617 adult patients with PFT resections from 2006 to 2021. Retrospective data was collected from the 89 patients of this cohort that required EVD placement. Patients were stratified into two groups: those that required a shunt following EVD removal (n = 30) and those that did not (n = 40). CSF variables collected included glucose, protein, nucleated cell count, and presence of infection. An unadjusted logistic regression was performed to assess exposures associated with shunt requirement and unadjusted odds ratios (ORs) and their associated 95 % confidence intervals (CIs) were obtained. RESULTS: Immediately following surgery, no CSF variables were significantly associated with shunt placement. Except for post-operative CSF being not-clear (OR: 4.15 (1.47-12.56), p = 0.009) and CSF glucose (OR: 0.97 (1.03-1.07), p = 0.031) all other variables were not significantly associated with shunt at time point 2. CONCLUSION: In our retrospective analysis, most routinely collected CSF values were not associated with permanent CSF diversion via a ventriculoperitoneal shunt following PFT resection. Further research is needed to identify other potential predictive markers.

Development of Chromosome 1q+ Specific Treatment for Highest Risk Pediatric Posterior Fossa Ependymoma.

PURPOSE: There are no effective treatment strategies for children with highest-risk posterior fossa group A ependymoma (PFA). Chromosome 1q gains (1q+) are present in approximately 25% of newly diagnosed PFA tumors, and this number doubles at recurrence. Seventy percent of children with chromosome 1q+ PFA will die because of the tumor, highlighting the urgent need to develop new therapeutic strategies for this population. EXPERIMENTAL DESIGN: In this study, we utilize 1q+ PFA in vitro and in vivo models to test the efficacy of combination radiation and chemotherapy in a preclinical setting. RESULTS: 5-fluorouracil (5FU) enhances radiotherapy in 1q+ PFA cell lines. Specifically, 5FU increases p53 activity mediated by the extra copy of UCK2 located on chromosome 1q in 1q+ PFA. Experimental downregulation of UCK2 resulted in decreased 5FU sensitivity in 1q+ PFA cells. In in vitro studies, a combination of 5FU, retinoid tretinoin (ATRA), and radiation provided the greatest reduction in cellular proliferation and greatest increase in markers of apoptosis in 1q+ PFA cell lines compared with other treatment arms. Similarly, in vivo experiments demonstrated significant enhancement of survival in mice treated with combination radiation and 5FU and ATRA. CONCLUSIONS: These results are the first to identify a chromosome 1q+ specific therapy approach in 1q+ PFA. Existing phase I studies have already established single-agent pediatric safety and dosages of 5FU and ATRA, allowing for expedited clinical application as phase II trials for children with high-risk PFA.

Language outcomes in children who underwent surgery for the removal of a posterior fossa tumor: A systematic review.

BACKGROUND: Children who underwent posterior fossa tumor removal may have spoken or written language impairments. The present systematic review synthesized the literature regarding the language outcomes in this population. Benefits of this work were the identification of shortcomings in the literature and a starting point toward formulating guidelines for postoperative language assessment. METHODS: A systematic literature search was conducted, identifying studies with patients who had posterior fossa surgery before 18 years of age. Included studies were narratively synthesized to understand language outcomes by language function (e.g., phonology, morphosyntax) at a group and individual level. Furthermore, the influence of several mediators (e.g., postoperative cerebellar mutism syndrome (pCMS), tumor type) was investigated. A critical evaluation of the language assessment tools was conducted. RESULTS: The narrative synthesis of 66 studies showed that a broad spectrum of language impairments has been described, characterized by a large interindividual heterogeneity. Patients younger at diagnosis, receiving treatment for a high-grade tumor and/or radiotherapy and diagnosed with pCMS seemed more prone to impairment. Several gaps in language assessment remain, such as a baseline preoperative assessment and the assessment of pragmatics and morphosyntax. Further, there were important methodological differences in existing studies which complicated our ability to accurately guide clinical practice. CONCLUSION: Children who had posterior fossa surgery seem to be at risk for postoperative language impairment. These results stress the need for language follow-up in posterior fossa tumor survivors.

National multicentered retrospective review of clinical and intraoperative factors associated with the development of cerebellar mutism after pediatric posterior fossa tumor resection.

BACKGROUND: Cerebellar mutism (CM) is characterized by a significant loss of speech in children following posterior fossa (PF) surgery. The biological origin of CM remains unclear and is the subject of ongoing debate. Significant recovery from CM is less likely than previously described despite rigorous multidisciplinary neuro-rehabilitational efforts. METHODS: A national multi-centered retrospective review of all children undergoing PF resection in four midsized Canadian academic pediatric institutions was undertaken. Patient, tumor and surgical factors associated with the post-operative development of CM were reviewed. Retrospective identification of PF surgery patients including those developing and those that did not (internal control). RESULTS: The study identified 258 patients across the 4 centers between 2010 and 2020 (mean age 6.73 years; 42.2% female). Overall, CM was experienced in 19.5% of patients (N = 50). Amongst children who developed CM histopathology included medulloblastoma (35.7%), pilocytic astrocytoma (32.6%) and ependymoma (17.1%). Intraoperative impression of adherence to the floor of the 4th ventricle was positive in 36.8%. Intraoperative abrupt changes in blood pressure and/or heart rate were identified in 19.4% and 17.8% of cases. The clinical resolution of CM was rated to be complete, significant resolution, slight improvement, no improvement and deterioration in 56.0%, 8.0%, 20.0%, 14.0% and 2.0%, respectively. In the cohort of children who experienced post-operative CM as compared to their no-CM counterpart, proportionally more tumors were felt to be adherent to the floor of the 4th ventricle (56.0% vs 49.5%), intraoperative extent of resection was a GTR (74% vs 68.8%) and changes in heart rate were noted (≥ 20% from baseline) (26.0% vs 15.9%). However, a multiple regression analysis identified only abrupt changes in HR (OR 5.97, CI (1.53, 23.1), p = 0.01) to be significantly associated with the development of post-operative CM. CONCLUSION: As a devastating surgical complication after posterior fossa tumor surgery with variable clinical course, identifying and understanding the operative cues and revising intraoperative plans that optimizes the child's neurooncological and clinical outcome are essential.

Complications following resection of primary and recurrent pediatric posterior fossa ependymoma.

OBJECTIVE: Extent of resection (EOR) is the most important modifiable prognostic variable for pediatric patients with posterior fossa ependymoma. An understanding of primary and recurrent ependymoma complications is essential to inform clinical decision-making for providers, patients, and families. In this study, the authors characterize postsurgical complications following resection of primary and recurrent pediatric posterior fossa ependymoma in a molecularly defined cohort. METHODS: The authors conducted a 20-year retrospective single-center review of pediatric patients undergoing resection of posterior fossa ependymoma at the Hospital for Sick Children in Toronto, Canada. Complications were dichotomized into major and minor groups; EOR was compared across complication categories. The association between complication occurrence with length of stay (LOS) and mortality was also assessed using multivariable regressions. RESULTS: There were 60 patients with primary resection included, 41 (68%) of whom were alive at the time of data collection. Gross-total resection was achieved in 33 (58%) of 57 patients at primary resection. There were no 30-day mortality events following primary and recurrent ependymoma resection. Following primary resection, 6 patients (10%) had posterior fossa syndrome (PFS) and 36 (60%) developed cranial neuropathies, 56% of which recovered within 1 year. One patient (1.7%) required a tracheostomy and 9 patients (15%) required gastrostomy tubes. There were 14 ventriculoperitoneal shunts (23%) inserted for postoperative hydrocephalus. Among recurrent cases, there were 48 recurrent resections performed in 24 patients. Complications included new cranial neuropathy in 10 patients (21%), of which 5 neuropathies resolved within 1 year. There were no cases of PFS following resection of recurrent ependymoma. Gastrostomy tube insertion was required in 3 patients (6.3%), and 1 patient (2.0%) required a tracheostomy. Given the differences in the location of tumor recurrence, a direct comparison between primary and recurrent resection complications was not feasible. Following multivariate analysis adjusting for sex, age, molecular status, and EOR, occurrence of major complications was found to be associated with prolonged LOS but not mortality. CONCLUSIONS: These results detail the spectrum of postsurgical morbidity following primary and recurrent posterior fossa ependymoma resection. The crude complication rate following resection of infratentorial recurrent ependymoma was lower than that of primary ependymoma, although a statistical comparison revealed no significant differences between the groups. These results should serve to inform providers of the morbidity profile following surgical management of posterior fossa ependymoma and inform perioperative counseling of patients and their families.

The Role of the Cerebellum in Visual-Spatial Memory in Pediatric Posterior Fossa Tumor Survivors.

The cerebellum is involved in motor and non-motor functions. Cerebellar lesions can underlie the disruption of various executive functions. The violation of executive functions in cerebellar lesions is a serious problem, since children, after completing treatment, must return to school, finish their education, and get a profession. One of the important executive functions is working memory, which contributes to academic success. Deficits of verbal working memory in cerebellar tumors have been studied, in contrast to visual-spatial working memory. To assess this issue, 101 patients who survived cerebellar tumors and 100 healthy control subjects performed a visual-spatial working memory test. As a result, in children who survived cerebellar tumors, visual-spatial working memory is impaired compared to the control group. Moreover, with age, and hence the time since the end of treatment, the number of elements that children can retain in visual-spatial working memory increases, but still remains smaller compared to the control group. Our findings complement the idea of cerebellar involvement in visual-spatial working memory and suggest that it is disrupted by cerebellar lesions in children.

Oculomotor Impairments in Children After Posterior Fossa Tumors Treatment.

Posterior fossa tumors (PFT) are the most common pediatric brain tumors, and the study of the somatic and cognitive status of PFT survivors still remains a critical problem. Since cerebellar damage can affect eye movement centers located in the vermis and hemispheres, such patients suffer from disturbances in visual perception, visual-spatial functions, reading, etc. Our investigation aimed at describing oculomotor impairments in PFT survivors linked to core oculomotor functions assessed through eye tracking method: gaze holding, reflexive saccades, and organization of voluntary saccades and their dependency on age at tumor diagnosis. Also, we investigated the relationship between oculomotor functions and ataxia measured with International Cooperative Ataxia Rating Scale (ICARS). A total of 110 children (patients and age-matched healthy controls, aged 9-17 years old) participated in the study. We found that the earlier the child had a tumor, the more impaired gaze holding (p = 0.0031) and fewer isometric saccades (p = 0.035) were observed at the time of examination. The above-mentioned functions in healthy controls improved with age. Visual scanning was also impaired compared to controls but was not related to age at diagnosis. A positive correlation between ICARS scores and number of hypermetric saccades (r = 0.309, p = 0.039), but no correlation with the number of hypometric saccades (r = - 0.008, p = 0.956). Furthermore, number of hypometric saccades did not differ between patients and controls (p = 0.238). Thus, primarily hypermetric saccades can be considered a prominent oculomotor symptom of cerebellar tumors. Our study provides basis for new methods of PFT diagnosis and rehabilitation procedure evaluation, both playing essential roles in modern pediatric neurooncology.

Thirty-day surgical morbidity and risk factors in pediatric brain tumor surgery: a 10-year nationwide retrospective study.

OBJECTIVE: Pediatric neuro-oncological surgery is often associated with significant risk; however, comprehensive data on surgical morbidity remain limited. The purpose of this study was therefore to provide national population-based data on both the incidence and characteristics of poor postoperative outcomes following pediatric intracranial neuro-oncological surgery. Additionally, the authors aimed to evaluate key risk factors for poor postoperative outcomes including overall morbidity, significant morbidity, and the most frequent types of morbidity. METHODS: The authors conducted a registry-based, nationwide, retrospective study including all children receiving surgical treatment for a CNS tumor over a 10-year period. Patients were identified using the Danish Childhood Cancer Registry, and 30-day morbidity was assessed through manual review of electronic health records. Significant morbidity was defined as complications in need of treatment under general anesthesia, ICU admission, or persistent neurological deficits at 30 days following surgery or death. Risk factors including sex, age, tumor location, tumor malignancy grade, and preoperative hydrocephalus were investigated using multivariate logistic regression analysis. RESULTS: A total of 349 children undergoing 473 tumor procedures were included, with an overall morbidity rate of 66.0% and a significant morbidity rate of 34.2%. The most frequent complications included neurological deficits (41.4%) and CSF-related morbidity consisting of CSF leaks, pseudomeningoceles, and postoperative hydrocephalus. Highly significant associations between infratentorial tumor location and both significant morbidity (OR 1.26, 95% CI 1.11-1.43; p < 0.001) and neurological deficits (OR 1.38, 95% CI 1.21-1.57; p < 0.001) were identified. In addition, younger age was revealed as a major risk factor of both postoperative CSF leakage and CSF-related morbidity in general. CONCLUSIONS: In this large, population-based cohort, the authors show that postoperative morbidity is frequent, occurring in about two-thirds of all patients, largely driven by neurological deficits and CSF-related complications. In addition, infratentorial tumor location and younger age emerged as key risk factors for poor postoperative outcomes.

A Prospective Study of Arterial Spin Labelling in Paediatric Posterior Fossa Tumour Survivors: A Correlation with Neurocognitive Impairment.

AIMS: Posterior fossa tumours (PFTs), which account for two-thirds of paediatric brain tumours, are successfully treated in about 70% of patients, but most survivors experience long-term cognitive impairment. We evaluated arterial spin labelling (ASL), a common, non-invasive magnetic resonance imaging (MRI) technique, as a biomarker of cognitive impairment in a paediatric PFT survivor population. MATERIALS AND METHODS: Sixty participants were prospectively analysed. PFT survivors were at least 5 years post-treatment and had been treated as appropriate for their age and type of tumour. Group 1 had received radiotherapy and Group 2 had not. Group 3 were healthy controls matched to Group 1 for age, sex and handedness. All participants underwent cognitive assessment and multimodal MRI, including an ASL perfusion sequence. We used semi-quantitative ASL methods to assess differences in mean perfusion in the thalamus, caudate, putamen and hippocampus. RESULTS: Statistically, no significant associations between cognitive data and radiation doses were identified. Compared with healthy controls, Group 1 patients had significantly lower overall mean perfusion values (20-30% lower, depending on the cerebral structure) and Group 2 had slightly lower mean perfusion values (5-10% lower). Perfusion values did not correlate with total prescribed irradiation doses nor with doses received by different cerebral structures. Episodic and semantic memory test scores were significantly lower in Group 1 and correlated with lower mean absolute perfusion values in the hippocampus (P < 0.04). CONCLUSIONS: These preliminary results indicate that radiotherapy affects the perfusion of specific cerebral structures and identify perfusion as a potential biomarker of hippocampus-dependent memory deficit.

Preoperative word-finding difficulties in children with posterior fossa tumours: a European cross-sectional study.

PURPOSE: Posterior fossa tumour surgery in children entails a high risk for severe speech and language impairments, but few studies have investigated the effect of the tumour on language prior to surgery. The current crosslinguistic study addresses this gap. We investigated the prevalence of preoperative word-finding difficulties, examined associations with medical and demographic characteristics, and analysed lexical errors. METHODS: We included 148 children aged 5-17 years with a posterior fossa tumour. Word-finding ability was assessed by means of a picture-naming test, Wordrace, and difficulties in accuracy and speed were identified by cut-off values. A norm-based subanalysis evaluated performance in a Swedish subsample. We compared the demographic and medical characteristics of children with slow, inaccurate, or combined slow and inaccurate word finding to the characteristics of children without word-finding difficulties and conducted a lexical error analysis. RESULTS: Thirty-seven percent (n = 55) presented with slow word finding, 24% (n = 35) with inaccurate word finding, and 16% (n = 23) with both slow and inaccurate word finding. Children with posterior fossa tumours were twice as slow as children in the norming sample. Right-hemisphere and brainstem location posed a higher risk for preoperative word-finding difficulties, relative to left-hemisphere location, and difficulties were more prevalent in boys than in girls. The most frequent errors were lack of response and semantically related sideordinated words. CONCLUSION: Word-finding difficulties are frequent in children with posterior fossa tumours, especially in boys and in children with right-hemisphere and brainstem tumours. Errors resemble those observed in typical development and children with word-finding difficulties.

Anatomy of the posterior Fossa: a comprehensive description for pediatric brain tumors.

Posterior fossa tumors are the most common pediatric brain tumors, and present unique challenges in terms of their location and surgical management. The posterior fossa comprehends complex anatomy and represents the smallest and deepest of the three cranial base fossae. An in-depth understanding of posterior fossa anatomy is crucial when it comes to the surgical resection of pediatric brain tumors. Mastering the knowledge of posterior fossa anatomy helps the neurosurgeon in achieving a maximal and safe volumetric resection, that impacts in both overall and progression free survival. With the advancements in microsurgery, the telovelar approach has emerged as the workhorse technique for the resection of posterior fossa tumors in pediatric patients. This approach involves meticulously dissecting of the natural clefts present in the cerebellomedullary fissure, making a comprehensive understanding of the underlying anatomy key for its success.

Preserved Auditory Steady State Response and Envelope-Following Response in Severe Brainstem Dysfunction Highlight the Need for Cross-Checking.

OBJECTIVES: Commercially available auditory steady state response (ASSR) systems are widely used to obtain hearing thresholds in the pediatric population objectively. Children are often examined during natural or induced sleep so that the recorded ASSRs are of subcortical origin, the inferior colliculus being often designated as the main ASSR contributor in these conditions. This report presents data from a battery of auditory neurophysiological objective tests obtained in 3 cases of severe brainstem dysfunction in sleeping children. In addition to ASSRs, envelope-following response (EFR) recordings designed to distinguish peripheral (cochlear nerve) from central (brainstem) were recorded to document the effect of brainstem dysfunction on the two types of phase-locked responses. DESIGN: Results obtained in the 3 children with severe brainstem dysfunctions were compared with those of age-matched controls. The cases were identified as posterior fossa tumor, undiagnosed (UD), and Pelizaeus-Merzbacher-Like Disease. The standard audiological objective tests comprised tympanograms, distortion product otoacoustic emissions, click-evoked auditory brainstem responses (ABRs), and ASSRs. EFRs were recorded using horizontal (EFR-H) and vertical (EFR-V) channels and a stimulus phase rotation technique allowing isolation of the EFR waveforms in the time domain to obtain direct latency measurements. RESULTS: The brainstem dysfunctions of the 3 children were revealed as abnormal (weak, absent, or delayed) ABRs central waves with a normal wave I. In addition, they all presented a summating and cochlear microphonic potential in their ABRs, coupled with a normal wave I, which implies normal cochlear and cochlear nerve function. EFR-H and EFR-V waveforms were identified in the two cases in whom they were recorded. The EFR-Hs onset latencies, response durations, and phase-locking values did not differ from their respective age-matched control values, indicating normal cochlear nerve EFRs. In contrast, the EFR-V phase-locking value and onset latency varied from their control values. Both patients had abnormal but identifiable and significantly phase-locked brainstem EFRs, even in a case with severely distorted ABR central waves. ASSR objective audiograms were recorded in two cases. They showed normal or slightly elevated (explained by a slight transmission loss) thresholds that do not yield any clue about their brainstem dysfunction, revealing the method's lack of sensitivity to severe brainstem dysfunction. CONCLUSIONS: The present study, performed on 3 sleeping children with severe brainstem dysfunction but normal cochlear responses (cochlear microphonic potential, summating potential, and ABR wave I), revealed the differential sensitivity of three auditory electrophysiological techniques. Estimated thresholds obtained by standard ASSR recordings (cases UD and Pelizaeus-Merzbacher-Like Disease) provided no clue to the brainstem dysfunction clearly revealed by the click-evoked ABR. EFR recordings (cases posterior fossa tumor and UD) showed preserved central responses with abnormal latencies and low phase-locking values, whereas the peripheral EFR attributed to the cochlear nerve was normal. The one case (UD) for which the three techniques could be performed confirms this sensitivity gradient, emphasizing the need for applying the Cross-Check Principle by avoiding resorting to ASSR recording alone. The entirely normal EFR-H recordings observed in two cases further strengthen the hypothesis of its cochlear nerve origin in sleeping children.