Sensorineural hearing loss in children & Cochlear Implant Kiatisak Tantavichian อ สมชาย ศรีร่มโพธิ์ทอง

Sensorineural hearing loss in children 1 non genetic SNHL 2 genetic SNHL syndromic non-syndromic

SNHL in children Permanent congenital or early onset hearing loss in the moderate to profound range (41 to 100 dB) Intervention instituted < 6 months of age lead to poor academic performance & school behavior problems

- evoked otoacoustic emissions (EOAE) 30% - 40% of children with hearing loss => health-related developmental + communicative development Early Hearing Detection& Intervention (EHDI) studies of universal newborn hearing screening - evoked otoacoustic emissions (EOAE) - automated auditory brainstem response (AABR)

National EHDI goals (a) all newborns will be screened for hearing loss < 1 month of age (b) all infants who screen positive will have a diagnostic audiologic assess < 3 months of age (c) infants identified with a hearing loss will begin receiving early intervention services < 6 months of age

EVALUATION Hx Multidisciplinary team - prenatal, birth& postnatal history & FH for hearing loss - speech or language disorders;ENT disorders & craniofacial deformities, such syndromic features ( kidney disorders, sudden death of a family member at a young age, thyroid disease, intracranial tumors, progressive blindness and cafe au lait spots ) - marital pedigree

PE HL syndromes ( auricular displacement or malformation, preauricular or branchial pits, white forelock, heterochromia irides, blue sclerae, dystopia canthorum, facial asymmetry, and cafe aulait spots ) & vision test

ECG, hemato & chem, TFT, tests for congenital infection [e.g., toxoplasmosis, syphilils,CMV], renal U/S & temporal bone imaging Childhood deafness, confirm lab within first 2 - 3 weeks of life

NONGENETIC DX

Cytomegalovirus Infection Most prevalent cause of intrauterine viral infection Direct transmission of CMV - vertically or horizontally Primary infection can lead to months or years of viral shedding in saliva, urine, semen & cervical or vaginal fluids Particular CMV => VIII th nerve

Cytomegalovirus Infection Congenital CMV infection rate - high (20% to 25%) - lower socioeconomic - mothers < 20 years of age, most of whom are unmarried (80% in one study)

Cytomegalovirus Infection Perinatally infected infants - pneumonitis, slow weight gain, adenopathy, rash, jaundice, anemia & atypical lymphocytosis shed virus in bodily secretions from birth and peri-postnatally infected infants can begin excreting virus between 3 and 12 weeks of age Definitive Dx - viral isolation from urine or saliva e.g PCR within the first 2 weeks of life

10% - 15% symptomatic CMV 90% having cytomegalic inclusion disease (CID), with involve CNS & RE system, hepatosplenomegaly, petechiae & jaundice

Cytomegalovirus Infection 90% of CMV-infected neonates who are asymptomatic at birth- improved prognosis ( neuro development), but other sequelae, including SNHL (10% to 15% of cases), can develop 2 years of age=> nearly all infants with CID - Severe mental& perceptual deficits, with severe to profound SNHL & chorioretinitis & optic atrophy in 25% to 30% of cases

Cytomegalovirus Infection Congenital CMV infection – 1/3 of sensorineural impairments in young children develop permanent CMV - related hearing impairment, which can be delayed months or years Fluctuate & progress in severity over time

Cytomegalovirus Infection Limited antiviral therapy trials (ganciclovir-treated group) After 6 months of F/U with ABR -84% improved hearing /maintained normal ABR - 59% of nontreated controls At 1 year, 21% of the treatment group did have more hearing loss full 68% of controls also showed a worsening of auditory thresholds

Congenital Toxoplasmosis

reproduce, and disseminate to infect tissues such as the CNS, eye, skeletal & cardiac muscle & placenta

Congenital Toxoplasmosis Fetal infection varies 15% in the 1st trimester 30% in 2nd trimester 60% in 3rd trimester Highest risk of severe congenital toxoplasmosis associated with primary maternal infection (weeks 10 - 24 of preg) Spiramycin administered to expectant mothers with documented primary infection during pregnancy can reduce transmission to the fetus up to 60%

Congenital Toxoplasmosis 75% - 80% - asymptomatic at birth 15%- eye findings 10% - severely involved Untreated neonates with subclinical infection are at high risk for later chorioretinitis with decreasing VA (up to 85% by age 20) - progressive CNS involvement with decreased intellectual function, deafness & precocious puberty

Congenital Toxoplasmosis 1 spiramycin - 1st-2nd trimester 2 pyrimethamine & sulfadiazine late second trimester may reduce the frequency of transplacental transmission & serious fetal sequelae 3 folinic acid – ameliorate bone marrow suppression Studies of prenatal treatment of infected mothers reveal a 0.6% fetal infection rate - in early pregnancy - 3.7% during the 6th to 16th wk(GA) - 20% in 16th through the 25th wk - 70% in untreated mothers

U/S fetal infection =>intracranial calcifications, ventricular dilatation, hepatic enlargement, ascites, & increased placental thickness

Congenital Toxoplasmosis S/S may be hydrocephalus, microcephaly, intracranial calcifications, chorioretinitis, strabismus, blindness, epilepsy, psychomotor, thrombocytopenia c petechiae & anemia

Congenital Toxoplasmosis PCR confirms detect T. gondii DNA Offspring of mothers with maternal infection should be treated for up to 1 year F/U - CT scans to assess CNS status? - ophthalmo. exam for chorioretinitis? - audio evaluation to detect delayed onset hearing loss?

Congenital Toxoplasmosis 15% - 25% of untreated => develope SNHL A Chicago-based study of treated infants with longitudinal ABR & behavioral audiologic tests - no hearing loss among 57 infected infants

Congenital Syphilis CS caused by transplacental transmission of spirochete Treponema pallidum may be obvious at birth or late as the fifth decade of life most likely during - primary syphilis (70% to 100%) - late stage (30%)

CS ,early-onset(first 3 months of life) associated with maternal infection early in pregnancy infants = LBW with hepatosplenomegaly & mucocutaneous & rhinitis (“snuffles”) diffuse, maculopapular, desquamating skin rash + palms & soles of the feet

Classic stigmata of congenital syphilis SNHL, interstitial keratitis, Hutchinson teeth (notched incisors), mulberry molars, Clutton joints (bilateral painless knee effusions), nasal septal perforation & saddle deformity& frontal bossing. Skeletal findings osteochondritis& periostitis of long bones

radiographic evidence (particularly in the humerus and femur) of symmetric changes- serrated metaohyseal ends thickened periosteum & metaphyseal defects of the upper medial tibia

Congenital Syphilis Offspring of seroreactive mothers should undergo scrutiny for signs of CS, in addition to histopathologic exam of the placenta or umbilical cord using fluorescent antitreponemal antibody staining techniques If maternal syphilis had been treated by an adequate regimen, the infant should be treated unless a fourfold decrease in nontreponemal maternal antibody was documented

Congenital Syphilis Prevalence hearing loss with CS = 3%- 38% - 37% of cases < age 10 - 51% between 25 - 35 years of age - 12% even later in life Audiologic follow-up

Congenital Syphilis Audiometric configuration= bilateral, flat SNHL, which can present in children as a sudden, bilateral profound impairment, usually without vertigo

Congenital Syphilis Late CS, the hearing loss can be sudden, asymmetric, fluctuating, and progressive, accompanied often by episodic tinnitus and vertigo Poor SDS are typically, loudness recruitment severe & caloric response weak to absent A positive labyrinththine fistula test may be present (Hennebert sign) & Tullio phenomenon, disequilibrium

Congenital Syphilis FTA-ABS = high sensitivity & specificity rate 98% False-positive findings => Pt. with autoimmune or drug-induced collagen vascular Dz Confirmatory tests – microhemagglutination assay for T. pallidum (MHA-TP)& the T. pallidum inhibition test (TPI), which is highly specific (99%)

Congenital Syphilis Offspring of seropositive mother should be monitored with nontreponemal antibody tests at 1, 2, 4, 6, and 12 months of age Stable or rising titers by 6 months age = indication for reevaluation & treatment Infants with neurosyphilis should have serial LP at 6-month intervals until the spinal fluid is normal

Congenital Syphilis The treatment of choice = high dose parenteral penicillin Systemic corticosteroids (oral prednisone) may be effective in stabilizing or improving hearing in approximately 50% of patients with syphilitic deafness SDS may show greater improvement than pure tone thresholds

Neonatal Sepsis Meningitis = common outcome hearing loss should be ruled out by ABR in all survivors of neonatal meningitis Group streptococcal (GBS) major pathogen - 80% presenting during the 1st week of life GBS associated include hearing loss, vision problems& developmental delay

Neonatal Sepsis Risk increases with prolonged labor +early membrane rupture, preterm delivery & maternal intrapartum fever Positive maternal vaginal & rectal cultures within 5 weeks (35 to 37 weeks of GA) of expected delivery => intrapartum antibiotics Most neonatal infections involve maternal-to-infant transmission of organisms during labor& delivery

Herpes Simplex Encephalitis HSV-1 & HSV-2 serotypes( most recurrent genital herpes) An initial clinical episode of genital herpes during pregnancy should be treated with oral acyclovir, but recurrent episodes during pregnancy should not be treated

Herpes Simplex Encephalitis risk of transmission from infected mother to neonate is high =>near time of delivery (30%- 50%) - Delivery by cesarean section serves to minimize the infant’s exposure to HSV if the mother has symptomatic infection

Herpes simplex encephalitis (HSE) 1:2,500 to 1:20,000 live births Incubation period up to 4 wks, neonatal herpes simplex meningoencephalitis (HSE) during the 2nd-3rd postpartum wks Nonspecific clinical findings can coexist with abnormal CSF results in > 90% of patients Neonatal HSV present with - mucocutaneous involvement or disseminated infection - 1/4 - 1/3 + meningoencephalitis

Herpes Simplex Encephalitis EEG& imaging studies, CT& MRI detect focal meningoencephalitis & the only definitive DX brain biopsy

Herpes Simplex Encephalitis In children with focal encephalitis of uncertain cause should addition to acyclovir, until a definitive Dx has been reached Recommended therapy for all infants having evidence of neonatal herpes - IV acyclovir (20 mg/kg body weight) q 8 hrs - 21 days (disseminated disease) - 14 days for isolated involvement of the skin and mucous membranes

Rubella Rubella virus - transmitted by a respiratory route congenital rubella triad of deafness, congenital cataracts & heart defects

Sequelae infants with prenatal rubella infection Up to 90% during 1st GA < 11 wks 50% GA 11- 20 wks may acquire the infection (25% to 50%) => primarily hearing loss 3rd trimester (> GA 20th wk) => unlikely to occur

Congenital rubella syndrome (CRS) Now includes cataracts or congenital glaucoma, congenital heart disease (e.g. patent ductus arteriosus or peripheral pulmonary artery stenosis), hearing loss & pigmentary retinopathy

Rubella Associated purpura, jaundice, microcephaly, splenomegaly, mental retardation, meningoencephalitis, or radiologic evidence of long bone lucency Hearing loss, the most prevalent disability in CRS,

Rubella Most infants with asymptomatic congenital rubella manifest sequelae by age 5 years & hearing loss is the most common finding SNHL :variable in severity & asymmetric & audiogram => most commonly( 500- 2,000 Hz)

Mumps and Measles Spread by respiratory droplets During viremia, 12 to 25 days after exposure, salivary glands & meninges can be involved 20% of mumps - asymptomatic 40% to 50% limited primarily to respiratory S/S Typical parotitis ( 30% to 40% of cases) & aseptic meningitis

Mumps and Measles 5/10,000 pts with mumps => hearing loss, sudden in onset - 80% => unilateral, often + tinnitus, vertigo, N/V most common patients < 5 years and >20 years of age 15% - 25% of survivors => neurologic sequelae +SNHL EIA & radial hemolysis antibody tests, can also confirm DX

Mumps and Measles most common patients < 5 years and >20 years of age 15% - 25% of survivors => neurologic sequelae +SNHL

Bacterial Meningitis & Vaccine Development 1990, newer Hib conjugate vaccines - administration to infants >2 months of age have decreased the incidence of invasive Hib Dz - contraindicated for infants < 6 weeks of age to avoid inducing immunologic tolerance, rendering the child unresponsive to subsequent doses permanent neurologic sequelae, including SNHL, in 10% to 15% of survivors

Bacterial Meningitis & Vaccine Development Children < 2 years => mortality rate high (25%) & high incidence of SNHL heptavalent pneumococcal vaccine is recommend for all children aged 2 to 23 mo.& also for patients having cochlear implant SX

Postmeningitic Hearing Loss: incidence 15%- 20%, most = permanent, bilateral, often asymmetric, severe to profound losses - unilateral losses - 1/3 Onset early in the clinical course and does not appear to be ameliorated by any specific antibiotic

Postmeningitic Hearing Loss Dexamethasone - administered 2 hrs before initiate ATB therapy - preventing moderate to severe hearing loss in pediatric patients with Hib meningitis but not in cases of pneumococcal etiology

Anoxia and Hypoxia 2 yrs age 35% had SNHL 4 yrs age 53% : SNHL Losses with onset > age 2 were less severe than later onset losses Neonates with chronic hypoxemia related to persistent fetal circulation experience a 20% incidence of SNHL, - ¾ moderate to severe range - ¼ is profound

Hyperbilirubinemia Manifestations of chronic postkernicteric - bilirubin encephalopathy, athetosis, intellectual deficits, gaze disturbance & limitation of upward gaze & SNHL ABR changes reflective of hearing loss prolongation of wave V latency compared with the previous ABR

Noise-Induced Hearing Loss Often accompanied by tinnitus Typically, initial + 3,000 -6,000 Hz “notch” audiometric configuration

Genetic SNHL

Autosomal-Dominant Syndromic Hearing Impairment

Branchio-Oto-Renal Syndrome - External ear anomalies : preauricular pits (82%), preauricular tags, auricular malformations (32%), microtia & EAC narrowing - Middle ear anomalies: ossicular malformation , facial nerve dehiscence, absence of the oval window & reduction in size of the middle ear cleft - Inner ear anomalies : cochlear hypoplasia & dysplasia Enlargement of the cochlear or vestibular aqueducts may be hypoplasia of the lateral semicircular canal

Branchio-Oto-Renal Syndrome Hearing impairment is the most common feature of BOR syndrome (close to 90%) - conductive (30%) - sensorineural (20%) - mixed (50%) :Severe: 1/3 of persons Progressive: 1/4

Branchio-Oto-Renal Syndrome Branchial anomalies occur in laterocervical fistulas, sinuses & cysts & renal anomalies ranging from agenesis to dysplasia (25% of persons) Less common => lacrimal duct aplasia, short palate & retrognathia

Neurofibromatosis Type II development of bilateral vestibular schwannomas & other intracranial & spinal tumors (schwannomas, meningiomas, gliomas, and ependymomas)

DX criteria :NF type II (1) bilateral vestibular schwannomas that usually develop by 2nd decade of life; or (2) FH of NFII in a first-degree relative, plus one of the following: (a) unilateral vestibular schwannomas at <30 yrs of age (b) any two of meningioma, glioma, schwannoma, or juvenile posterior subcapsular lenticular opacities/juvenile cortical cataract

Neurofibromatosis Type II Hearing loss is usually high frequency SNHL and vertigo, tinnitus & facial nerve paralysis + imaging studies (MRI) Treatment of schwannomas usually => surgery gamma knife is considered in select cases Auditory brain stem implants

DX:Stickler Syndrome (1) congenital vitreous anomaly (2) any three of (a) myopia with onset < 6 yrs (b) rhegmatogenous retinal detachment or paravascular pigmented lattice degeneration (c) joint hypermobility with abnormal Beighton score (d) SNHL (audiometric confirmation) (e) midline clefting

Stickler Syndrome Other - craniofacial anomalies like midfacial flattening, mandibular hypoplasia, short upturned nose, or a long philtrum Micrognathia= common => Robin sequence with cleft palate (28–65%) , limited to a submucous cleft

Stickler Syndrome SNHL is more common in the older age groups SS type I have either normal hearing or only a mild impairment - SS type II fall in between - SS type III tend to have moderate-to-severe hearing loss

Stickler Syndrome Ocular findings in SS are its most prevalent feature Most => myopic others= vitreoretinal degeneration, retinal detachment, cataract, & blindness

Waardenburg Syndrome WS type I => SNHL, white forelock, pigmentary disturbances of the iris, & dystopia canthorum, displacement of the inner canthi & lacrimal puncti Other = synophrys, broad nasal root, hypoplasia of the alae nasi, patent metopic suture & square jaw

Waardenburg Syndrome WS type II is distinguished from WS type I by the absence of dystopia canthorum WS type III (Klein-Waardenburg syndrome) by WS type I + hypoplasia or contracture of the upper limbs WS type IV (Waardenburg-Shah syndrome) & involves the association of WS with Hirschsprung disease

WS: congenital hearing impairment WS type I : 36% to 66.7% WS type II : 57% to 85% Most commonly, the loss affects persons with more than one pigmentation abnormality & profound, bilateral, and stable Audiogram = variable, with low-frequency loss (more common)

Treacher-Collins Syndrome Abnormalities of craniofacial development Maldevelopment of the maxilla & mandible, with abnormal canthi placement, ocular colobomas, choanal atresia & CHL secondary to ossicular fixation

Autosomal-Recessive Syndromic Hearing Impairment

Pendred Syndrome associate congenital deafness with thyroid goiter 7.5 to 10 per 100,000 persons, up to 10% of hereditary deafness develop in second decade

Pendred Syndrome usually prelingual , bilateral & profound, although it can be progressive Radiologic studies : - temporal bone anomaly, either dilated vestibular aqueducts (DVAs) or - Mondini dysplasia

Jervell and Lange-Nielsen Syndrome Congenital deafness, prolonged QT interval & syncopal attacks The dominant disease(Romano-Ward syndrome) does not include the deafness phenotype The recessive disease is Jervell and Lange-Nielsen syndrome (JLNS)

Jervell and Lange-Nielsen Syndrome congenital, bilateral & severe to profound The prolonged QT interval can lead to ventricular arrhythmias, syncopal episodes & death in childhood Effective treatment with beta-adrenergic blockers reduces mortality from 71% to 6%

Usher Syndrome SNHL, retinitis pigmentosa & often vestibular dysfunction Prevalence 4.4/ 100,000 USA - 3% to 6% of congenitally deaf persons carrying this DX - cause of 50% of deaf-blindness in the United States

Usher Syndrome :types I, II and III Type I = severe-to-profound SNHL, vestibular dysfunction, retinitis pigmentosa type II = moderate-to-severe congenital SNHL, with uncertainty related to progression, no vestibular dysfunction, and retinal degeneration that begins in the third to fourth decade type III = progressive hearing loss, variable vestibular dysfunction, and variable onset of retinitis pigmentosa

X-Linked Syndromes

Alport Syndrome symmetric, high-frequency SNHL that can be detected by late childhood & progresses => all frequencies hematuric nephritis, hearing impairment & ocular changes

Alport Syndrome Diagnostic criteria include at least three of the following four characteristics (1) positive FH of hematuria with or without CRF (2) progressive high-tone SN deafness (3) typical eye lesion (anterior lenticonus, and/or macular flecks) (4) histologic changes of the glomerular BM of the kidney controlling high BP & restricting salt, protein & phosphate in the diet => dialysis and kidney transplant may be necessary

Mitochondrial Syndromes multisystemic, with hearing loss present in 70% of affected persons

Autosomal-Recessive Nonsyndromic Hearing Impairment usually prelingual & severe to profound across all frequencies

PATIENT MANAGEMENT Team of health care Inheritance patterns, audiometric characteristics, syndromic vs nonsyndromic features are necessary Directed at providing appropriate amplification as soon as possible Cochlear implantation => option for persons with severe-to-profound deafness Deaf culture consider themselves