International Pediatric Otolaryngology Group (IPOG) Consensus Recommendations: Congenital Cholesteatoma.

OBJECTIVE: To provide recommendations to otolaryngologists and allied physicians for the comprehensive management of children who present with signs and symptoms of congenital cholesteatoma. METHODS: A two-iterative Delphi method questionnaire was used to establish expert recommendations by the members of the International Pediatric Otolaryngology Group, on the preoperative work-up, the perioperative considerations, and follow-up. RESULTS: Twenty-two members completed the survey, in 14 tertiary-care center departments representing 5 countries. The main consensual recommendations were: a precise otoscopic description of the quadrants involved, extensive audiological workup (bilateral tonal, vocal audiometry, and BERA), and a CT scan are required. Facial nerve monitoring and a combination of microscope and telescope are recommended for surgical removal. Clinical and audiological follow-up should be pursued yearly for at least 5 years. First MRI follow-up should be done at 18 months postoperatively if the removal violated the matrix. MRI follow-up duration depends on the initial extent of the cholesteatoma. CONCLUSION: The goal of preoperative and follow-up consensus from International Pediatric Otolaryngology Group participants is to help manage infants and children with congenital cholesteatoma. The operative techniques may vary, and experienced surgeons must perform these procedures.

Relative Preservation of Superior Semicircular Canal Architecture in CHARGE Syndrome.

OBJECTIVES: (1) Describe common patterns of semicircular canal (SCC) anomalies in CHARGE syndrome (CS) and (2) recognize that in CS, the architecture of the superior SCC may be relatively preserved. STUDY DESIGN: This is a retrospective review of temporal bone imaging studies. SETTING: Quaternary care center. SUBJECTS AND METHODS: A sample of 37 patients with CS. All subjects met clinical diagnostic criteria for CS. The presence/absence of anomalies of the middle ear, mastoid, temporal bone venous anatomy, inner ear, and internal auditory canal was recorded. Anomalies of each SCC were considered separately and by severity (normal, dysplasia, aplasia). RESULTS: Thirty-seven subjects (74 temporal bones) were reviewed. Thirty-four (92.0%) patients demonstrated bilateral SCC anomalies. Three (8.0%) had normal SCCs. In patients with SCC anomalies, all canals demonstrated bilateral abnormalities. Thirty-two (86.5%) patients had bilateral horizontal SCC aplasia. These 32 patients also demonstrated posterior SCC aplasia in at least 1 ear. Of 74 temporal bones, 37 (50.0%) had superior SCC dysplasia. All dysplastic superior SCCs showed preservation of the anterior limb. Complete superior SCC aplasia was found in 28 (37.8%) temporal bones. CONCLUSION: SCC anomalies occur with high frequency in CS. Complete absence of the horizontal and posterior canals is typical and usually bilateral. By contrast, the superior SCC often demonstrates relative preservation of the anterior limb.

Inner ear manifestations in CHARGE: Abnormalities, treatments, animal models, and progress toward treatments in auditory and vestibular structures.

The inner ear contains the sensory organs for hearing and balance. Both hearing and balance are commonly affected in individuals with CHARGE syndrome (CS), an autosomal dominant condition caused by heterozygous pathogenic variants in the CHD7 gene. Semicircular canal dysplasia or aplasia is the single most prevalent feature in individuals with CHARGE leading to deficient gross motor skills and ambulation. Identification of CHD7 as the major gene affected in CHARGE has enabled acceleration of research in this field. Great progress has been made in understanding the role of CHD7 in the development and function of the inner ear, as well as in related organs such as the middle ear and auditory and vestibular neural pathways. The goals of current research on CHD7 and CS are to (a) improve our understanding of the pathology caused by CHD7 pathogenic variants and (b) to provide better tools for prognosis and treatment. Current studies utilize cells and whole animals, from flies to mammals. The mouse is an excellent model for exploring mechanisms of Chd7 function in the ear, given the evolutionary conservation of ear structure, function, Chd7 expression, and similarity of mutant phenotypes between mice and humans. Newly recognized developmental functions for mouse Chd7 are shedding light on how abnormalities in CHD7 might lead to CS symptoms in humans. Here we review known human inner ear phenotypes associated with CHD7 pathogenic variants and CS, summarize progress toward diagnosis and treatment of inner ear-related pathologies, and explore new avenues for treatment based on basic science discoveries.

Pediatric Acute Otitis Media in the Era of Pneumococcal Vaccination.

Objectives (1) Describe longitudinal trends in annual prevalence of hospital admission for pediatric acute otitis media (AOM) and complications of AOM (CAOM) since introduction of pneumococcal vaccination in 2000 and (2) describe the longitudinal trend of prevalence of hospital admission for pneumococcal meningitis in children with AOM-related diagnoses in the postvaccination era. Study Design Retrospective analysis of Kids' Inpatient Database from 2000 to 2012. Setting Community, nonrehabilitation hospitals. Subjects and Methods To determine annual prevalence of admission for AOM/CAOM, nationally weighted frequencies of children aged <21 years with acute suppurative otitis media, acute mastoiditis, suppurative labyrinthitis, and/or acute petrositis were collected. The frequency of coexisting pneumococcal meningitis diagnoses among these patients was also collected. Trend analysis of prevalences of admission for AOM/CAOM and for pneumococcal meningitis occurring in the setting of AOM/CAOM from 2000 to 2012 was performed. Results Between 2000 and 2012, annual prevalence of admission for AOM/CAOM decreased from 3.956 to 2.618 per 100,000 persons ( P < .0001) (relative risk reduction 34%). Declines in admission prevalence were most pronounced in children <1 year of age (from 22.647 to 8.715 per 100,000 persons between 2000 and 2012, P < .0001) and 1 to 2 years of age (from 13.652 to 5.554 per 100,000 persons between 2000 and 2012, P < .0001). For all ages, the admission prevalence for pneumococcal meningitis and concomitant AOM/CAOM decreased (from 1.760 to 0.717 per 1,000,000 persons, P < .0001) over the study period. Conclusions The prevalence of hospital admission for pediatric AOM/CAOM has declined since the advent of pneumococcal vaccination. Admission rates for pneumococcal meningitis with AOM/CAOM have similarly declined.

Radioprotective Effect of Aminothiol PrC-210 on Irradiated Inner Ear of Guinea Pig.

Radiotherapy of individuals suffering with head & neck or brain tumors subserve the risk of sensorineural hearing loss. Here, we evaluated the protective effect of Aminothiol PrC-210 (3-(methyl-amino)-2-((methylamino)methyl)propane-1-thiol) on the irradiated inner ear of guinea pigs. An intra-peritoneal or intra-tympanic dose of PrC-210 was administered prior to receiving a dose of gamma radiation (3000 cGy) to each ear. Auditory Brainstem Responses (ABRs) were recorded one week and two weeks after the radiation and compared with the sham animal group. ABR thresholds of guinea pigs that received an intra-peritoneal dose of PrC-210 were significantly better compared to the non-treated, control animals at one week post-radiation. Morphologic analysis of the inner ear revealed significant inflammation and degeneration of the spiral ganglion in the irradiated animals not treated with PrC-210. In contrast, when treated with PrC-210 the radiation effect and injury to the spiral ganglion was significantly alleviated. PrC-210 had no apparent cytotoxic effect in vivo and did not affect the morphology or count of cochlear hair cells. These findings suggest that aminothiol PrC-210 attenuated radiation-induced cochlea damage for at least one week and protected hearing.

A semi-supervised Support Vector Machine model for predicting the language outcomes following cochlear implantation based on pre-implant brain fMRI imaging.

INTRODUCTION: We developed a machine learning model to predict whether or not a cochlear implant (CI) candidate will develop effective language skills within 2 years after the CI surgery by using the pre-implant brain fMRI data from the candidate. METHODS: The language performance was measured 2 years after the CI surgery by the Clinical Evaluation of Language Fundamentals-Preschool, Second Edition (CELF-P2). Based on the CELF-P2 scores, the CI recipients were designated as either effective or ineffective CI users. For feature extraction from the fMRI data, we constructed contrast maps using the general linear model, and then utilized the Bag-of-Words (BoW) approach that we previously published to convert the contrast maps into feature vectors. We trained both supervised models and semi-supervised models to classify CI users as effective or ineffective. RESULTS: Compared with the conventional feature extraction approach, which used each single voxel as a feature, our BoW approach gave rise to much better performance for the classification of effective versus ineffective CI users. The semi-supervised model with the feature set extracted by the BoW approach from the contrast of speech versus silence achieved a leave-one-out cross-validation AUC as high as 0.97. Recursive feature elimination unexpectedly revealed that two features were sufficient to provide highly accurate classification of effective versus ineffective CI users based on our current dataset. CONCLUSION: We have validated the hypothesis that pre-implant cortical activation patterns revealed by fMRI during infancy correlate with language performance 2 years after cochlear implantation. The two brain regions highlighted by our classifier are potential biomarkers for the prediction of CI outcomes. Our study also demonstrated the superiority of the semi-supervised model over the supervised model. It is always worthwhile to try a semi-supervised model when unlabeled data are available.

Complications in pediatric osseointegrated implantation.

OBJECTIVE: To report an accurate complication rate in pediatric osseointegrated implants in a large cohort of patients from a major center and to characterize the complications observed. SETTING: Tertiary care pediatric hospital. STUDY DESIGN: Case series with chart review of all consecutive patients receiving otologic osseointegrated implants at Cincinnati Children's Hospital since 2001. SUBJECTS AND METHODS: All patients undergoing osseointegrated implant placement were identified at Cincinnati Children's Hospital, and complication rates were tabulated and stratified to major and minor based on the need for surgical revision. Evaluations of syndromic and body mass index associations were performed, along with evaluation of length of follow-up. RESULTS: Forty-three patients were identified with 88 implants placed. Eighteen (42%) children had a diagnosis of a craniofacial syndrome. Overall, 19 (41.9%) returned to the operating suite, with a complication rate of 46.1%. A long duration of follow-up was obtained, and with this was identified an increasing risk of complications over time. Also identified was a significantly increased complication risk associated with a craniofacial syndrome. Body mass index was not found to be associated with complications. CONCLUSION: Osseointegrated implants require frequent maintenance care from the surgeon. Complication rates are higher for children with a diagnosis of a craniofacial syndrome, and the risk of a complication increases significantly over a prolonged period of time.

Analysis of hearing preservation after endolymphatic mastoid sac surgery for Meniere's disease.

OBJECTIVES/HYPOTHESIS: Comparison of audiometric outcomes between patients with definite Meniere's disease who underwent endolymphatic mastoid sac surgery (EMSS) following failed medical therapy and patients who underwent medical therapy only. STUDY DESIGN: Retrospective chart review of 456 consecutive patients between 1997 and 2006. METHODS: Outcome measures were changes in pure-tone average (PTA), word recognition score (WRS), and speech reception threshold (SRT). RESULTS: Of 58 qualified patients, 29 who underwent EMSS after failing medical therapy showed a 4 dB decrease in PTA, a 2% increase in WRS, and a 2 dB decrease in SRT. Twenty-nine patients treated with medical therapy only demonstrated a 1 dB PTA increase, 2% WRS improvement, and 2 dB SRT improvement. No significant difference was noted between the medically and surgically managed patients in terms of changes in PTA (P = .34) or WRS (P = .95) after treatment. Of all patients in the study, 60% had no clinically significant change in hearing, whereas 24% improved and 16% worsened. The distribution of post-treatment hearing changes between the medical and surgical groups was statistically insignificant (P = .17). CONCLUSIONS: The changes in PTA and WRS among patients with Meniere's disease managed with medical therapy or EMSS were not statistically significant. Although performing EMSS to treat the vertigo of Meniere's disease does not appear to be associated with an increased risk of deteriorating auditory function after treatment, surgery also does not confer an increased likelihood of stabilizing or improving hearing.

Surgical management of otologic disease in pediatric patients with Turner syndrome.

OBJECTIVES: Previous reports suggest that patients with Turner syndrome have a predisposition for acute and chronic otitis media. However, the role of early or aggressive surgical management of otologic disease has not been explored in the pediatric population. With respect to otitis media in pediatric Turner syndrome patients, we examined (1) the impact of timing and (2) the type of surgical intervention in the treatment of disease. METHODS: Retrospective 10-year review of patients with Turner syndrome and chronic otitis and its surgical management at a single pediatric tertiary institution. RESULTS: One hundred and seventy-eight patients with Turner syndrome were evaluated at our institution from 1997 to 2007. Thirty-two (18.0%) were diagnosed with middle ear disease. Eighteen (10.1%) were referred to otolaryngology for evaluation. Average age at presentation was 4.7 years (range: 1 month to 12 years). The 18 patients referred to otolaryngology required a mean of 16 clinic visits each for otologic symptoms. A mean of 6.7 pressure equalization tubes (PET) were required per patient (range: 0-25). Middle ear effusions (n=14, 78%) along with tympanic membrane retractions and/or perforations (n=10, 55.6%) were the most common otoscopic findings. Patients with tympanic membrane retractions (8/18) required a higher average number of PET (9.1) and cumulatively underwent a total of five tympanoplasty-type procedures. Six ears had evidence of cholesteatoma. Two patients underwent myringoplasty, 6 patients underwent tympanoplasty (33.3%, mean age 11.6 years), and 3 patients (16.7%, mean age 9.4 years) underwent tympanomastoidectomy. Revision procedures were common. Older age at first PET placement was significantly correlated with the need for later tympanoplasty and/or tympanomastoidectomy operations (p<0.036). Tympanoplasty or tympanomastoidectomy patients had their first PET placed on average at 5.2 years as compared to 2.6 years in those not requiring tympanoplasty or tympanomastoidectomy operations. CONCLUSIONS: Recurrent and chronic otitis media is common in patients with Turner syndrome. Once established, disease is recalcitrant and leads to multiple surgical procedures. Early PET insertion is advocated to offset the future necessity of more extensive tympanic procedures.

Macrophage inflammatory proteins in cytomegalovirus-related inner ear injury.

OBJECTIVE: Inner ear inflammation triggered by CMV infection may play a role in CMV-related auditory pathogenesis. The purpose of the study was to determine if a virally encoded macrophage inflammatory protein played a role in CMV-related hearing loss. DESIGN: Mutagenesis was performed with deletion of a guinea pig CMV macrophage inflammatory protein. Intracochlear inoculations were performed on three groups of animals (n = 18). Group 1 received sterile viral media, Group 2 received wild-type CMV virus, and Group 3 received "knockout" (KO) virus with a deleted immunomodulation gene. Baseline and postinoculation ABRs were obtained. ELISA and PCR were performed and temporal bones examined. SUBJECTS: Eighteen guinea pigs. RESULTS: The KO group had significantly better hearing than the WT group. There were no significant differences between the KO and sham groups. The WT group had significant hearing loss at all frequencies. Inflammation and fibrosis were noted in the WT temporal bones only. CONCLUSIONS: Virally encoded macrophage inflammatory proteins appear to play a significant role in CMV-related hearing loss.

Controversies in aural atresia repair.

PURPOSE OF REVIEW: To discuss recent controversies regarding the management of aural atresia. RECENT FINDINGS: Management of unilateral atresia is less controversial. Candidacy for successful repair is based on high-resolution computed tomography findings and atresia grading. The bone-anchored hearing aid is a viable alternative strategy for hearing improvement. Stability of hearing results following atresia repair improves with the number of atresiaplasties performed. Development of image-guided surgery may provide benefit in atresia surgery. New unrecognized rare complications of aural atresia and atresia repair including salivary fistula and middle ear cholesteatoma are now being recognized and are manageable. SUMMARY: Management of aural atresia continues to be difficult and surrounded by controversy. New studies and cases series may shed light on these management issues.

The effect of cidofovir on cytomegalovirus-induced hearing loss in a Guinea pig model.

OBJECTIVE: To evaluate the utility of therapy with the cyclic cogener of the anti-cytomegalovirus (CMV) agent cidofovir against CMV-induced hearing loss in a guinea pig model. DESIGN: Thirty-six guinea pigs were randomly divided into 4 groups of 9. All groups underwent auditory brainstem response testing on days 0, 4, 7, 14, 21, and 28. Group 1 received no intervention. Group 2 underwent sham surgery consisting of unilateral round window injection of 25 microL of sterile viral media on day 0. Groups 3 and 4 underwent round window injection of 1.7 x 10(5) plaque-forming units of guinea pig CMV on day 0. Group 4 received antiviral treatment with intraperitoneal injection of cidofovir (20 mg/kg) on days 1 and 5 after inoculation. SETTING: An animal research facility. SUBJECTS: Thirty-six weanling Hartley guinea pigs. RESULTS: Of the animals who received guinea pig CMV and no cidofovir treatment, 4 of 9 (day 4) and 5 of 9 (days 7 and 28) demonstrated a hearing loss of at least 30 dB. In contrast, none of the animals in the untreated, sham surgery, or cidofovir-treated groups had a hearing loss of greater than 20 dB. This difference was statistically significant for day 4 (P = .04, 1-tailed Fisher exact test), day 7 (P = .01), and day 28 (P = .01). Histologic evaluation of hearing-impaired animals revealed inflammatory infiltrates, particularly in the scala tympani. Fibrosis of the basal turn of the cochlea was observed in 7 of 9 untreated animals and 1 of 9 treated animals. CONCLUSION: Cidofovir therapy prevents CMV-induced hearing loss and associated histologic changes in guinea pigs.

A diagnostic paradigm for childhood idiopathic sensorineural hearing loss.

OBJECTIVE: Our objective was to determine the diagnostic yield of laboratory testing, radiological imaging, and GJB2 mutation screening in a large cohort of patients with differing severities of idiopathic sensorineural hearing loss (SNHL). DESIGN AND SETTING: We undertook a retrospective study of patients presenting with SNHL at our institution from 1993 to 2002. RESULTS: Laboratory testing had an extremely low yield. Patients with unilateral SNHL had a significantly higher imaging yield than those with bilateral. The diagnostic yield of GJB2 screening was significantly higher in patients with severe to profound SNHL than in those with less severe SNHL. However, a relatively large number of patients with mild to moderate SNHL had positive GJB2 screens. CONCLUSIONS: Based on diagnostic yields, we propose a cost-effective stepwise diagnostic paradigm to replace the more commonly used and costly simultaneous testing approach. EBM RATING: C.

Functional magnetic resonance imaging: contemporary and future use.

PURPOSE OF REVIEW: Functional magnetic resonance imaging is a relatively new neuroimaging technique that is being used in both research and clinical applications. Increasing work has been done to elucidate the auditory cortex. RECENT FINDINGS: Current studies focus on enhancing the sensitivity of functional magnetic resonance imaging in studying the auditory cortex and subcortical pathways in response to tonal stimulation, to evaluate the integrity of the auditory cortex before cochlear implantation, and as a screening tool for hearing impairment in the young child. SUMMARY: Recent work has been encouraging: silent functional magnetic resonance imaging techniques allow for better evaluation of the auditory cortex with less confounding scanner noises. Functional magnetic resonance imaging can be safely and reproducibly performed in hearing-impaired children and in the preoperative evaluation of candidates for cochlear implantation.

Genomic organization and expression analysis of the murine Fam3c gene.

Previously, we identified FAM3C as a candidate gene for autosomal recessive nonsyndromic hearing loss locus 17 (DFNB17). This gene has since been found to be a member of a cytokine-like gene family, but its function has not been determined. The purpose of this study was thus to elucidate the gene structure and pattern of expression, providing information that might allow a hypothesis to be developed about FAM3C function of in the inner ear. To do this we analyzed its mouse ortholog, Fam3c. Fam3c was found to be ubiquitously expressed in all analyzed tissues, and had two major transcript variants presumed to result from an alternative use of two distinct polyadenylation signals. In situ hybridization experiments revealed a predominant Fam3c pattern of expression in the nonsensory epithelium of the growing semicircular canals at embryonic day (E) 15.5. This expression pattern resembles the known pattern of the Nkx5 homeobox genes. Analysis of the Fam3c promoter region demonstrated a putative Nkx5.1 binding site. Based on our findings, we hypothesize that Fam3c may be a downstream target gene for the Nkx5.1 transcription factor, and may thus be involved in cell differentiation and proliferation during inner ear embryogenesis. Additionally, analyses of putative amino acid sequences of FAM3C orthologous proteins showed that their primary and secondary structures and overall topology were highly conserved. Further study is underway to determine the role of FAM3C in inner ear development.

Genotypic and phenotypic correlations of DFNB1-related hearing impairment in the Midwestern United States.

OBJECTIVE: To determine the genotypic and phenotypic correlations of hearing impairment (HI) in a midwestern US population related to autosomal recessive nonsyndromic hearing loss locus 1 (DFNB1). DESIGN: A retrospective review. SETTING: Tertiary care children's hospital. PATIENTS: A total of 160 consecutive children diagnosed with idiopathic sensorineural hearing loss. MAIN OUTCOME MEASURES: GJB2 genotype and audiometric phenotype. RESULTS: The prevalence of subjects with HI having biallelic GJB2-related mutations was 15.3% (24/157). Of these 24 patients, 9 (38%) were homozygous 35delG, 6 (25%) had other biallelic nonsense mutations, and 9 (38%) had a missense mutation of at least 1 allele. The allelic prevalence of 35delG was 8.6% (27/314) in the study population and 48% (23/48) in the DFNB1 group. The M34T allele mutation was next most prevalent at 2.2% (7/314) in the study population and 10% (5/48) in the DFNB1 group. Severe to profound HI occurred in 59% of DFNB1 subjects. Genotypes with biallelic nonsense mutations had a high risk of severe to profound HI (88%). DFNB1-related HI was usually bilateral, symmetric, nonprogressive, and had flat audiograms. However, asymmetric HI (22%), sloping audiograms (26%), and even borderline-normal hearing in 1 ear was observed, and these were associated with the presence of at least 1 missense mutation. Two novel mutations, K15T and L90V, were identified. A subject presenting to our clinic with severe to profound HI had a 40% risk of biallelic GJB2 mutation. CONCLUSIONS: Our population represents a consecutively enrolled clinic population with sensorineural hearing loss. In our DFNB1-related HI cohort, the 35delG mutation and severe to profound HI rates were lower than previously reported. Our missense mutation and M34T allelic prevalence rates were higher than expected and were associated with a less severe hearing loss. The presence of biallelic nonsense mutations was associated with severe to profound hearing loss in nearly 90% of cases. Mild asymmetric HI and sloping audiograms were more often associated with missense mutations.

Meningioma involving Meckel's cave: transpetrosal surgical anatomy and clinical considerations.

Meningiomas originating in Meckel's cave (MC) are uncommon lesions that represent 1% of all intracranial meningiomas. Innovations in skull base surgery have enabled resection of these lesions with less morbidity, but require an intimate knowledge of both lesional pathology and regional microneuroanatomy. To review the surgical and clinical considerations involved in the management of MC meningiomas, we retrospectively reviewed data from patients who underwent transpetrosal resection of primary MC meningiomas between 1984 and 1998. Of 146 patients who underwent transpetrosal removal of meningiomas, 7 were believed to have tumors originating in MC. All 7 patients presented with trigeminal dysfunction, facial pain, and/or headache. Complete tumor removal was achieved in 5 of the 7 patients. Facial hypoesthesia or anesthesia, paralysis of cranial nerve VI, and ophthalmoplegia were among the postoperative complications encountered. Meningiomas of MC represent treatable lesions whose diagnosis requires prompt imaging of patients with trigeminal dysfunction and symptoms of facial pain and headache.

Clinical and audiological features in auditory neuropathy.

OBJECTIVE: To medically and audiologically characterize a population of children diagnosed as having auditory neuropathy (AN). STUDY DESIGN: Retrospective medical chart review. SETTING/SUBJECTS: We identified 22 patients from a pediatric otology clinic in a tertiary care pediatric hospital setting. RESULTS: A genetic factor in AN is suggested by our identification of 3 families with 2 affected children and 2 other children with family histories that were positive for hearing loss. Clinical features common among our population included a history of hyperbilirubinemia (n = 11 [50%]), prematurity (n = 10 [45%]), ototoxic drug exposure (n = 9 [41%]), family history of hearing loss (n = 8 [36%]), neonatal ventilator dependence (n = 8 [36%]), and cerebral palsy (n = 2 [9%]). Full clinical and audiological data were available for 18 of the 22 children, including otoacoustic emissions, auditory brainstem responses with cochlear microphonics, and age-appropriate audiometric findings. Significantly, 9 of these 18 patients showed improvement in behavioral thresholds over time, indicating that a subset of children with AN may recover useful hearing levels. Also significant was the success of cochlear implantation in 4 children. CONCLUSIONS: Management of AN in children requires serial clinical and audiometric evaluations, with a prominent role for behavioral testing. Prematurity, genetics, and hyperbilirubinemia appear to be significant factors in the development of AN; hyperbilirubinemia can be associated with spontaneous improvement of hearing thresholds. For those children not benefiting from amplification or FM systems, cochlear implantation remains a potentially successful method of habilitation.