Published online May 21, 2007
PEDIATRICS Vol. 119 No. 6 June 2007, pp. e1351-e1360 (doi:10.1542/peds.2006-3009)
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ARTICLE

Auditory Brainstem Response Abnormalities and Hearing Loss in Children With Craniosynostosis

Michael W. Church, PhDa, Leslie Parent-Jenkins, MSb, Arlene A. Rozzelle, MDc, Frances E. Eldis, PhDb and S. Nadya J. Kazzi, MDd

a Departments of Obstetrics and Gynecology
d Pediatrics, Wayne State University School of Medicine, Detroit, Michigan
b Communication Disorders Clinic
c Department of Plastic Surgery, Children's Hospital of Michigan, Detroit, Michigan


   ABSTRACT
TOP
 ABSTRACT
PATIENTS AND METHODS
 RESULTS
 DISCUSSION
 CONCLUSIONS
 REFERENCES
 
OBJECTIVES. Craniosynostosis is a devastating disorder characterized by premature closure of the cranial plates before or shortly after birth. This results in an abnormally shaped skull, face, and brain. Little is known about hearing disorders in such patients, and nothing has been published about their auditory brainstem responses. Our objective was to evaluate such patients for auditory brainstem response and hearing disorders with the long-term goal of improving patient evaluation and management.

PATIENTS AND METHODS. We evaluated the auditory brainstem responses, hearing, and brain images of children with fibroblast growth factor receptor 2 craniosynostosis (n = 11).

RESULTS. Prolongation of the auditory brainstem response I-to-III interpeak latency was a frequent characteristic of fibroblast growth factor receptor 2 craniosynostosis, occurring in 91% of our patients. Prolongation of the III-to-V interpeak latency was an occasional characteristic, occurring in 27% of our patients. Whenever the I-to-III interpeak latency was prolonged, wave II was always abnormal. Associated morbidities included sensorineural hearing loss (27%), recurrent otitis media (100%), and Arnold-Chiari malformation (27%). Cranial decompression improved the interpeak latencies of 2 children.

CONCLUSIONS. These previously undocumented auditory brainstem response abnormalities reflect abnormal neural transmission, which could cause peripheral and central auditory processing disorders. We speculate that the major pathogenic basis of the I-to-III interpeak latency and wave II abnormalities is compression of the auditory nerve as it passes through the internal auditory meatus and posterior fossa, which would explain the auditory nerve hearing loss, tinnitus, and vertigo that affect these children. Awareness of these abnormalities could lead to important advancements in the auditory and neurosurgical assessment and management of this overlooked patient group. We provide recommendations for the improved assessment and management of these patients. In particular, we recommend that auditory brainstem response diagnostics become standard clinical care for this patient group as the best way to detect auditory nerve compression.

Key Words: Apert syndrome • Arnold-Chiari malformation • auditory brainstem response • central auditory processing disorder • conductive hearing loss • craniosynostosis • Crouzon syndrome • fibroblast growth factor receptor • Jackson-Weiss syndrome • Pfeiffer syndrome • recurrent otitis media • sensorineural hearing loss • tinnitus • vertigo

Abbreviations: FGFR—fibroblast growth factor receptor • ABR—auditory brainstem response • CHL—conductive hearing loss • ROM—recurrent otitis media • SNHL—sensorineural hearing loss • IPL—interpeak latency • A-C—Arnold-Chiari • CPA—cerebellopontine angle • MVD—microvascular decompression • CAPD—central auditory processing disorder

Craniosynostosis is a birth defect characterized by premature closure of the cranial plates before or shortly after birth, resulting in a devastating condition wherein the child has an abnormally shaped skull, face, brain, low-set and posteriorly rotated ears, abnormal pinna configuration, eustachian tube dysfunction, ossicular fixation, constricted and distorted brain growth, neurodevelopmental impairments or mental retardation, hydrocephaly, cranial nerve disorders, increased intracranial pressure, hearing loss, tinnitus, vertigo, facial palsy, seizures, and blindness. Treatment consists of surgery to relieve pressure on the brain and to remodel the child's face and skull.1,2 Craniosynostosis occurs in ~1 of 2000 live births with >2000 such children being born in the United States every year.3 Most forms of craniosynostosis are caused by mutations in the fibroblast growth factor receptor (FGFR) 1, 2, or 3 genes, which influence bone and connective tissue growth. Our report involves auditory brainstem response (ABR), hearing, and brain imaging assessments of patients with the FGFR2 forms of craniosynostosis, which include Apert, Pfeiffer, Crouzon, Jackson-Weiss, and Beare-Stevenson syndromes.1,2

Research on hearing disorders in craniosynostosis patients is rather limited. Studies on Apert syndrome patients have described incidences of conductive hearing loss (CHL) because of recurrent otitis media (ROM) and congenital stapes fixation.4–8 There are no reports of ABR findings or sensorineural hearing loss (SNHL) in Apert syndrome patients. The literature on hearing loss in Pfeiffer syndrome is also limited. Investigators have found mild CHL and middle ear abnormalities,9 problems with middle ear effusion,10,11 and some instances of SNHL.11,12 There are no studies reporting ABR findings in Pfeiffer syndrome. The literature on hearing loss in Crouzon syndrome is even sparser. A case study found SNHL in one 13-year-old Crouzon child.13 Another study found instances of CHL (21%), mixed hearing loss (11%), and SNHL (21%).14 There are no reports of ABR or ROM findings in Crouzon patients. We found no literature on ABR or hearing disorders in Jackson-Weiss or Beare-Stevenson syndrome patients.

In testing an infant with Apert syndrome with ABRs, we noticed that he had abnormally prolonged wave I-to-III interpeak latencies (IPLs). We wanted to see if our finding was a common feature of craniosynostosis and if this ABR abnormality was associated with certain brain abnormalities and hearing losses. This article presents findings from a case series of FGFR2 craniosynostosis patients and discusses the clinical significance and possible pathogenic bases of our findings.


   PATIENTS AND METHODS
TOP
 ABSTRACT
 PATIENTS AND METHODS
RESULTS
 DISCUSSION
 CONCLUSIONS
 REFERENCES
 
All of the subjects (n = 11) were patients of the Communication Disorders Clinic, Children's Hospital of Michigan. An informed consent, approved by the Wayne State University Human Investigation Committee, was obtained from a parent or legal guardian. Standard ABR recording procedures were used and collected on Bio-logic sensory evoked potential equipment using THD-39 headphones (Telephonics Corp, Farmington, NY) or insert earphones.15 Stimulus clicks (0.1 millisecond in duration, 23.3 clicks per second) were 75 dB of peak equivalent sound pressure level unless otherwise stated. Brain electrical activity (100- to 3000-Hz bandpass filter) was recorded by an active electrode placed on the upper forehead, a reference electrode on the earlobe of the stimulated ear, and a ground electrode on the left frontal area of the forehead.15 The ABR I-to-III and III-to-V IPLs for each patient were compared with published norms for infants and young children15–17 and norms for subjects ≥12 years of age.18 ABR latencies from normal-hearing children in our clinic compare favorably with these published norms. For example, normal-hearing 1-year-old children in our clinic had I-to-III IPLs of 2.32 ± 0.14 milliseconds (n = 20) as compared with the published norm of 2.31 ± 0.15 milliseconds (n = 47).15–17 The respective III-to-V IPLs were 2.04 ± 0.08 and 2.01 ± 0.22 milliseconds. Each patient's IPLs were expressed as standard deviates (z scores) to determine their percentile ranking. IPLs that were in the upper 5th percentile (P ≤ .05) were considered to be significantly prolonged. Subjects received on multiple occasions a standard battery of age-appropriate hearing tests, including pure tone or behavioral audiometry, tympanometry, otoscopy, otoacoustic emissions, and sometimes ABR audiometry (latency-intensity profiles). Normal hearing was defined as –10 to +15 dB of hearing level across all of the frequencies.19,20 Standard criteria for defining ROM were used.19,20 Brain imaging included MRI and computed tomography scans.


   RESULTS
TOP
 ABSTRACT
 PATIENTS AND METHODS
 RESULTS
DISCUSSION
 CONCLUSIONS
 REFERENCES
 
Apert Case 1
This term black male infant had head circumference and body weight below the 10th percentile. Dysmorphic features included craniosynostosis, polydactyly, and syndactyly of the feet. The ABRs, obtained at 8 days postpartum, had significant prolongations of the wave I-to-III IPLs. The left- and right-ear I-to-III IPLs of 3.90 and 3.84 milliseconds were prolonged by 4.50 and 4.27 SDs in comparison with the age-matched norm (mean ± SD) of 2.704 ± 0.266 milliseconds (P < .001). In contrast, this infant's left- and right-ear wave III-to-V IPLs of 2.64 and 2.76 milliseconds were within normal limits of the age-matched norm of 2.379 ± 0.246 milliseconds.

Subsequent brain imaging indicated an Arnold-Chiari (A-C) malformation with herniated cerebellar tonsils and enlarged lateral ventricles but "with no evidence of brainstem morphologic abnormality." Cranial surgery was done at 22 months of age to relieve intracranial pressure. During recovery, he was given another ABR series, which indicated that he continued to have abnormally prolonged I-to-III IPLs. Specifically, the I-to-III IPLs from the left and right ears were 2.83 and 3.07 milliseconds (Fig 1), which were significantly prolonged by 3.21 and 4.38 SDs in comparison with the age-matched norm of 2.168 ± 0.206 milliseconds (P < .001). Wave II was absent in both ears. In contrast, this child's left- and right-ear III-to-V IPLs of 1.89 and 1.71 milliseconds compared favorably with the age-matched norm of 1.959 ± 0.195 milliseconds. A comparison of the left ear presurgery and postsurgery I-to-III IPLs indicates the prolongation decreased from 4.50 to 3.21 SDs. Thus, there was an improvement in the left-ear I-to-III IPL after decompression surgery. In contrast, the right-ear I-to-III IPL showed no improvement. Hearing tests indicated no SNHL or permanent CHL.


Figure 1
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  		FIGURE 1 Right-ear ABR taken from Apert case 1 after cranial surgery. The I-to-III IPL was significantly prolonged, and wave II was absent; the III-to-V IPL was within normal limits. The left-ear ABR was highly similar.

 
Apert Case 2
Brain imaging of this black female infant showed enlarged lateral ventricles. She had a history of ROM with no SNHL or permanent CHL. ABRs were collected at 6 months of age. The 2.89- and 2.83-millisecond I-to-III IPLs for the right and left ears were prolonged by 2.11 (P = .017) and 1.84 SDs (P = .033), respectively. Visual inspection suggested that wave II latency was also prolonged in both ears. In contrast, the III-to-V IPLs for both ears were within normal limits. Fig 2 shows the right-ear ABR. The left-ear ABR was similar.


Figure 2
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  		FIGURE 2 Right-ear ABR taken from Apert case 2. The I-to-III IPL and wave II were significantly prolonged, whereas the III-to-V IPL was within normal limits. The left-ear ABR was highly similar.

 
Apert Case 3
This white male has brachycephaly and plagiocephaly, enlarged third and fourth ventricles, and required a ventricular shunt. Brain imaging indicated no A-C malformation at 1 month of age, but by 29 months of age, a Chiari I malformation had developed. He is globally delayed and has central sleep apnea. He had a moderate mixed hearing loss (SNHL + CHL) in the right ear as evidenced by ABR audiometry, normal hearing in the left ear, and a history of ROM. ABRs were collected at 22 months. The 2.77- and 2.83-millisecond I-to-III IPLs for the left and right ears were prolonged by 2.92 and 3.21 SDs, respectively (P < .001). In contrast, the III-to-V IPLs were within normal limits. Fig 3 shows the right-ear ABRs. The left-ear ABRs were highly similar. Wave II was absent in both the left- and right-ear ABR traces.


Figure 3
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  		FIGURE 3 A, Right-ear ABR taken from Apert case 3. The I-to-III IPL was significantly prolonged, and wave II was absent; the III-to-V IPL was within normal limits. The left-ear ABR was highly similar. Shown are 2 ABR traces demonstrating replication. B, Sound field audiogram responses to warble stimuli (WW) indicated mild hearing loss in the better ear. ABR audiometry subsequently indicated a moderate high-frequency SNHL component to the hearing loss in the right ear.

 
Apert Case 4
Brain imaging of this white male infant indicated shortening of the posterior fossa, elongation of the middle cranial fossa, a foreshortened anterior cranial fossa, moderate enlargement of the lateral ventricles, and no A-C malformation. The Bayley Scales of Infant Development found delayed motor (1st percentile) and cognitive skills (5th percentile). He had mild-to-moderate CHL because of scarring from repeated myringotomies and ROM. ABRs were collected at 3 years of age. The 2.95-millisecond I-to-III IPL for the left ear was prolonged by 3.95 SDs (P < .001), whereas the III-to-V IPL was within normal limits. The left-ear ABR also showed poor morphology and no wave II. In contrast, both the I-to-III and III-to-V IPLs for the right ear were within normal limits, the ABR had excellent morphology, and wave II was normal and clearly defined (Fig 4).


Figure 4
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  		FIGURE 4 A, Left- and right-ear ABRs from Apert case 4. The right-ear ABR wave latencies were within normal limits (right). In contrast, the left-ear ABR had a significantly prolonged I-to-III IPL, an absent wave II, and a normal III-to-V IPL (left). B, Air-conduction audiograms indicated mild-to-moderate hearing losses in both ears (right ear, O; left ear, X). This child would not tolerate a bone oscillator for bone-conduction audiograms.

 
Apert Case 5
This 26-year-old black man is the father of Apert case 1. He has a history of ROM but otherwise normal hearing. His right-ear ABR had I-to-III and III-to-V IPLs of 3.07 and 2.54 milliseconds, which were 6.40 and 4.86 SDs above the respective norms of 2.11 ± 0.15 and 1.86 ± 0.14 milliseconds (P < .001). The right-ear wave II was not clearly defined (Fig 5). Left-ear ABRs were not possible in this patient because of impacted earwax. Brain images were not available.


Figure 5
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  		FIGURE 5 Right-ear ABR from Apert case 5. There were significant prolongations of both the I-to-III and III-to-V IPLs and an absent wave II. These ABRs were evoked by 90-dB clicks.

 
Apert Case 6
This 16-year-old white male has mild bilateral high frequency SNHL, a history of ROM, attention-deficit/hyperactivity disorder, language delay, a slightly deformed posterior fossa, and an arachnoid cystic area posterior to the cerebellar vermis. This teenager had right-ear ABR I-to-III and III-to-V IPLs that were within normal limits, and the wave II was clearly defined (Fig 6). The left-ear ABR was highly similar (data not shown). This is our only patient with all of the IPLs within normal limits.


Figure 6
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  		FIGURE 6 A, The right-ear ABR from Apert case 6 had I-to-III and III-to-V IPLs that were within normal limits. The left-ear ABR was highly similar. These ABRs were evoked by 90-dB clicks. B, Air-conduction audiograms indicated mild hearing loss bilaterally (right ear, O; left ear, X). Bone conduction indicated mild high-frequency SNHL (right ear, [). These ABRs were evoked by 90-dB clicks.

 
Apert Case 7
This black male infant, born after 36 weeks of gestation, had meconium aspiration and received mechanical ventilation for 6 days. Brain imaging indicated decreased anterior-posterior diameter, midface hypoplasia, mild enlargement of the lateral ventricles, a cavum septum pellucidum and vergae, prominent Virchow-Robin spaces bilaterally, and no A-C malformation. He had normal hearing in both ears. He had an ABR test at 2.5 months of age. The left-ear I-to-III IPL of 3.42 milliseconds was prolonged by 4.17 SDs (P < .001). Wave II was poorly defined in both the left- and right-ear ABRs. In contrast, the left-ear III-to-V IPL of 2.48 milliseconds was just barely within the upper range of normalcy, being prolonged by 1.64 SDs (P = .0505; Fig 7). A temporary CHL in the right ear, because of middle ear fluid, prevented the right-ear IPLs from being scored.


Figure 7
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  		FIGURE 7 The left-ear ABR from Apert case 7 had a significant prolongation of the I-to-III IPL and a dysmorphic wave II, whereas the III-to-V IPL was within normal limits.

 
Pfeiffer Case 1
Brain imaging of this white male infant indicated a small brainstem, malformed posterior fossa, a normal fourth ventricle with malformed third and lateral ventricles, suspected aqueduct stenosis, absent septum pellucidum, cortical dysplasia, optic nerve and chiasm hypoplasia, pituitary hypoplasia, and no A-C malformation. He had normal hearing in both ears. He was ABR-tested at 3 months of age during recovery from anesthesia for his presurgery brain imaging. The I-to-III IPLs of 3.48 and 3.30 milliseconds for the left and right ears were prolonged by 4.45 and 3.61 SDs, respectively (P < .001). The III-to-V IPL of 2.36 milliseconds for the left ear was within normal limits. In contrast, the right-ear III-to-V IPL of 2.60 milliseconds was prolonged by 2.20 SDs (P = .014). Wave II was essentially absent from both the left- and right-ear ABR traces (Fig 8).


Figure 8
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  		FIGURE 8 The left and right-ear ABRs from Pfeiffer case 1 had significant prolongations of the I-to-III IPL and absent wave II. The III-to-V IPL was significantly prolonged only in the right ear.

 
Crouzon Case 1
This white male infant, aged 12 months, had mild lateral ventricle asymmetry and ventriculomegaly, a very distorted cortex, myelination appropriate with chronological age, and distortion of the posterior fossa with the brainstem shifted to the left of midline, suggesting that the right-ear auditory nerve was stretched. The craniocervical junction showed a C1 ring closely juxtaposed to the occiput and a rotary deformity at the C1 to C2 level. The skull base angle was quite distorted and measured 13°. This child had normal hearing. The left-ear ABR had I-to-III and III-to-V IPLs that were within normal limits. In contrast, the right-ear I-to-III IPL of 3.60 milliseconds was prolonged by 8.64 SDs (P < .001), and the wave II was distorted. The right-ear III-to-V IPL was within normal limits (Fig 9).


Figure 9
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  		FIGURE 9 The left-ear ABR from Crouzon case 1 had IPLs that were within normal limits. The right-ear ABR had a prolonged I-to-III IPL, a prolonged and dysmorphic wave II, but a normal III-to-V IPL.

 
Crouzon Case 2
This white female subject, aged 15 years, had mild lateral ventricular dilation with unusual configuration of the frontal horns but no dilation of the other ventricles, slightly smaller right cerebellar hemisphere, asymmetry of both cortices, brain parenchyma showing good gray-white matter differentiation with no focal areas of abnormality, no gross intracranial abnormalities, midface and nasal septum deviated posteriorly to the left, and mild calvarium asymmetry with left frontal and right occipital plagiocephaly. She had mild-moderate SNHL ≤2 kHz in the left ear and mild SNHL ≤2 kHz in the right ear. She had no permanent CHL, a history of ROM, and persistence of otitis media into adolescence. This patient's wave IV/V complex was dominated by the wave IV peak with the wave V appearing as a shoulder on the downslope of the wave complex. The left-ear I-to-III IPL of 2.30 milliseconds was within the normal limits of 2.11 ± 0.15 milliseconds, whereas the III-to-V IPL of 2.30 milliseconds was prolonged by 3.14 SDs (P = .002) compared with the age-matched norm of 1.86 ± 0.14 milliseconds. The reverse situation occurred in the right ear, where the I-to-III IPL of 2.54 milliseconds was prolonged by 2.87 SDs (P = .002), and the III-to-V IPL of 2.06 was within normal limits. The left- and right-ear I-to-V IPLs of 4.60 milliseconds were prolonged by 3.00 SDs (P = .001) compared with the age-matched norm of 3.94 ± 0.22 milliseconds. Wave II was prolonged in the right ear with a latency of 3.21 milliseconds compared with a left-ear latency of 2.80 milliseconds, despite normal wave I latencies of 1.62 and 1.68 milliseconds, respectively (Fig 10).


Figure 10
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  		FIGURE 10 A, The left-ear ABR from Crouzon case 2 had a I-to-III IPL that was within normal limits but a III-to-V IPL that was prolonged. The right-ear ABR had the reverse situation with the I-to-III IPL and wave II prolonged and with the III-to-V IPL within normal limits. Both ears had equally prolonged I-to-V IPLs. B, Audiograms indicated mild SNHL ≤2 kHz in the right ear and mild-to-moderate SNHL ≤2 kHz in the left ear (air conduction: right ear, O; left ear, X; bone conduction: right ear, [; left ear,]).

 
Jackson-Weiss Case 1
This black male child, aged 4 years 2 months, had mild sleep apnea, midface retrusion, hypertelorism, exophthalmia, left lateral ventriculomegaly, a thin and dysmorphic corpus callosum, a small posterior fossa, mildly diminished cerebrospinal fluid flow at the posterior aspect of the foramen magnum, an A-C malformation, and markedly abnormal calvarium shape. The cervical spine had expansion of the spinal cord from C2 to C7 with septations. Mild subluxation was seen between C1 and C2. There was incomplete fusion of the anterior arch of the C1 ring. He had a visual loss of unknown origin in the left eye. He had a history of ROM but otherwise normal hearing.

He had a Chiari decompression surgery before his first ABR test. For this first ABR test, the left-ear I-to-III IPL of 3.01 milliseconds was prolonged by 5.93 SDs (P < .001), and the right-ear I-to-III IPL of 2.42 milliseconds was prolonged by 2.00 SDs (P = .023). In contrast, the left-ear III-to-V IPL of 1.59 milliseconds was actually significantly shorter than normal by –2.29 SDs (P = .011), and the right-ear III-to-V IPL of 1.95 milliseconds was within normal limits. Wave II was absent in both ears (Fig 11). This child had a repeat Chiari decompression surgery followed by another ABR test. The left- and right-ear I-to-III IPLs of 3.07 and 2.48 milliseconds were essentially unchanged, whereas the left- and right-ear III-to-V IPLs of 1.06 and 1.65 milliseconds were now noticeably shorter by 0.47 and 0.30 milliseconds, respectively.


Figure 11
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  		FIGURE 11 The left- and right-ear ABRs from Jackson-Weiss case 1 had significant prolongations of the I-to-III IPLs that were more dramatic in the left ear. Wave II was absent bilaterally. The left-ear III-to-V IPL was shorter than normal, whereas the right-ear III-to-V IPL was within normal limits.

 
Summary
Table 1 illustrates that prolonged I-to-III IPLs, SHNL, and ROM are common characteristics of FGFR2 craniosynostosis. There was a frequent occurrence of left-right asymmetry with the I-to-III and III-to-V IPL prolongations and the SNHL, which were often worse in 1 ear. The occurrence and severity of I-to-III IPL prolongations did not always correspond with the presence and severity of SNHL or the presence of an A-C malformation.


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  		TABLE 1 Summary of ABR Abnormalities and Hearing Losses in FGFR2 Craniosynostosis

 

   DISCUSSION
TOP
 ABSTRACT
 PATIENTS AND METHODS
 RESULTS
 DISCUSSION
CONCLUSIONS
 REFERENCES
 
Prolongation of the ABR I-to-III IPL was a frequent characteristic of our FGFR2 craniosynostosis patients, occurring in 10 (91%) of 11 patients. Prolongation of the III-to-V IPL was an occasional characteristic, occurring in 3 (27%) of 11 patients. Prolongation of the I-to-III IPL signifies slowed neural transmission times between the distal portion of the auditory nerve (wave I) and the cochlear nucleus (wave III). Prolongation of the III-to-V IPL indicates slowed neural transmission times between the cochlear nucleus and the lateral lemniscus/inferior colliculus (wave V).21 Wave II (proximal portion of the auditory nerve) was absent, prolonged, or dysmorphic in all 16 of the ears (100%) with prolonged I-to-III IPLs, suggesting that this portion of the auditory nerve was frequently compromised. Thus, these patients can have both upper and lower brainstem and auditory nerve dysfunctions. Our patients frequently had asymmetric ABR results. This is consistent with the asymmetric craniofacial features, brain morphology, and cranial nerve disorders that occur in these patients. The prolonged IPLs improved in 2 patients after posterior fossa decompression.

Neurologic/Neurosurgical Implications
Although prolonged IPLs have never been described in craniosynostosis patients before, IPL prolongations have been observed in patients with either A-C malformations or vascular compression of the auditory nerve. These 2 groups provide clues to the pathogenic origins of the IPL prolongations in our craniosynostosis children.

A-C Malformation and the ABR
I-to-III IPL prolongations are sometimes seen in A-C malformation patients. Increased posterior fossa pressure and brainstem deformation from cerebellar herniation are likely causes of their I-to-III IPL prolongations.22–24 Three (27%) of our 11 craniosynostosis patients had A-C malformations. Our patients fell into 3 groups: (1) 1 patient (9%) had normal I-to-III IPLs and no A-C malformation; (2) 3 patients (27%) had both prolonged I-to-III IPL and A-C malformation; and (3) 7 patients (64%) had prolonged I-to-III IPLs but no A-C malformation. Thus, most of our patients had prolonged I-to-III IPLs in the absence of an A-C malformation. One patient had normal brainstem morphology despite an A-C malformation. One infant had a stretched auditory nerve that likely caused his I-to-III IPL prolongation by making neurotransmission time longer. One patient showed a moderate improvement (shortening) in his left-ear I-to-III IPL, and a second patient showed shortening of the III-to-V IPLs in both ears after posterior fossa decompression surgery. However, their postsurgical I-to-III IPLs were still abnormally prolonged, and their wave IIs were still absent. So whereas A-C malformation, increased intracranial pressure, deformed brainstem, and stretched auditory nerve can be involved in I-to-III IPL prolongation, they did not explain most of our cases.

Vascular Compression and the ABR
Vascular compression of cranial nerves in the cerebellopontine angle (CPA) can cause facial spasms, auditory nerve hearing loss, vertigo, tinnitus, and other disorders. Patients with vascular compression along the auditory nerve have I-to-III IPL prolongations and absent or distorted wave IIs. Microvascular decompression (MVD) surgery is often successful in resolving or ameliorating the hearing loss, vertigo, tinnitus, facial spasms, and other CPA symptoms, as well as improving the patients' ABR abnormalities.25–29 Thus, auditory nerve compression merits consideration as a major source of the I-to-III IPL prolongations and absent and/or dysmorphic wave IIs in our craniosynostosis patients.

Pathogenic Bases
Although we analyzed a small population, we can make several generalizations about the pathogenic bases and neurologic implications of our ABR findings. First, A-C and brainstem malformations or stretched auditory nerves contribute to the abnormally prolonged I-to-III IPLs in some craniosynostosis patients. However, we speculate that the major pathogenic sources of the I-to-III IPL prolongations are the vascular, bony, and connective tissue problems that often afflict such patients around the skull, cranial nerves, and brainstem. In particular, the high prevalence of wave II abnormalities in our patients strongly suggests a compression of the auditory nerve by vascular, bony, or connective tissues as it passes through the internal auditory meatus and/or the posterior fossa. Second, the auditory nerve, facial nerve, and internal auditory branch of the basilar artery transmit collectively through the internal auditory meatus and posterior fossa. The causes of deafness, tinnitus, vertigo, and hemifacial spasms in craniosynostosis patients are currently unknown. Thus, one implication from our study is that auditory and facial nerve compressions are the major pathogenic sources of these morbidities. If true, I-to-III IPL prolongations and wave II abnormalities could be important predictors of auditory nerve hearing loss, tinnitus, vertigo, hemifacial spasms, and reduced basilar artery perfusion. Third, MVD surgery could preserve or restore the integrity of the auditory and facial nerves, the basilar artery, and associated brainstem functions.

Neurologic and Neurosurgical Recommendations
We recommend that craniosynostosis patients undergo ABR evaluation with separate testing for each ear, that they be periodically evaluated with ABRs during their life span to provide early detection of developing neurologic dysfunction that may not be apparent by brain imaging or other evaluations, that patients with wave II abnormalities be assessed for facial nerve and basilar artery disorders, that the region around the internal auditory meatus be examined for possible surgical intervention, and that ABRs be gathered both presurgically and postsurgically to assess the need, extent, and success of cranial, posterior fossa, and MVD surgeries. It is likely that the severity of an IPL prolongation reflects the degree of brainstem and cranial nerve pathology and should, therefore, be useful in predicting clinical signs of cranial nerve, brainstem, and CPA syndromes. Assessing craniosynostosis patients for I-to-III and III-to-V IPL prolongations could thereby aid in the decision to have neurosurgery, particularly when neurologic signs are subtle or progressing.

Hearing Implications
Three (27%) of 11 craniosynostosis patients had SNHL. This is comparable to the findings of others.12–14 Of the 20 ears with ABR results, our data fell into 4 groups regarding SNHL. First, 2 (10%) of 20 ears had neither SNHL nor prolonged I-to-III IPLs and were, therefore, ostensibly normal. Second, 3 (15%) of 20 ears had SNHL in the absence of I-to-III IPL prolongation. The source of SNHL in these ears was purely sensory (cochlear) in origin. Third, 13 (65%) of 20 ears had no SNHL but still had prolonged I-to-III IPLs. These ears likely had a purely neural abnormality located at the proximal portion of the auditory nerve. Fourth, 2 (10%) of 20 ears had both SNHL and prolonged IPLs. The pathogenic basis of the SNHL in these ears could be auditory nerve or cochlear dysfunction or both. Some patients with A-C malformation, after posterior fossa decompression surgery, experienced recovery from SNHL,23,30,31 as well as improvements in the ABR I-to-III IPL.22–24 Thus, increased intracranial pressure can be a pathogenic factor in some cases of SNHL.23

Two patients (18%) had permanent CHL. The CHL in craniosynostosis patients can be caused by internal auditory canal abnormalities, stapedial fixation, Eustachian tube dysfunction, tympanic membrane pathology, or ossicular erosion secondary to ROM and repeated myringotomies.4–8 In our patients, both cases of permanent CHL were because of tympanic membrane scarring secondary to ROM and repeated myringotomies. None had internal auditory canal abnormalities or stapedial fixation. Previous studies of craniosynostosis patients report a high prevalence of CHL, but this seems to be primarily from temporary otitis media episodes rather than permanent middle ear pathology. Of the 7 patients old enough to have adequate otitis media histories, all (100%) had ROM, and all of the older patients showed a persistence of ROM into late childhood and adolescence. Two pathogenic sources of ROM in craniofacial syndrome children are immune deficiencies and Eustachian tube dysfunction.19,20

We can make some generalizations about the hearing implications of our findings:

  1. The I-to-III and III-to-V IPL prolongations suggest auditory nerve and lower and upper brainstem dysfunctions. These dysfunctions can cause auditory nerve and central auditory processing disorders (CAPDs). CAPD can cause or exacerbate learning disorders, attention-deficit/hyperactivity disorder, and language delays and can compromise sound localization, auditory timing, and speech comprehension in the presence of competing sounds. An IPL prolongation may, therefore, predict the presence and severity of CAPD and its comorbidities. We recommend that craniosynostosis patients be assessed and managed accordingly.
  2. SNHL and I-to-III IPL prolongation do not always coexist in craniosynostosis patients. The SNHL in these patients can be either cochlear or auditory nerve in origin. Testing should be done to determine whether the SNHL is cochlear or neural in origin and to manage the patient accordingly (eg, hearing aid or MVD).
  3. Craniosynostosis patients will very likely have asymmetric SNHL and CHL in addition to asymmetric IPLs.
  4. For those with permanent hearing losses, hearing aids were recommended for only 1 patient. Others did not need them, because their hearing losses were unilateral or <25 dB in the amplifiable range.
  5. A-C malformation patients can show progressive hearing loss with aging and a persistence of pediatric ROM into adolescence.6–8,23 A high incidence and a persistence of ROM into adolescence are common in craniofacial syndromes.19,20,32,33 Thus, craniosynostosis patients should be assessed throughout their life span to provide early detection and management of progressive hearing loss and the persistence of ROM beyond childhood.

Unexplained Observations
We had 2 puzzling observations for which we have no explanation: (1) one patient had a III-to-V IPL that was significantly shorter than normal, and (2) despite prolonged I-to-III IPLs and absent/dysmorphic wave IIs, the amplitudes and morphologies of waves III and V were relatively unaffected in many instances. The same is true for the vascular compression patients studied by M.B. Moller, MD, PhD, and A.R. Moller, PhD (written communication, 2006).


   CONCLUSIONS
TOP
 ABSTRACT
 PATIENTS AND METHODS
 RESULTS
 DISCUSSION
 CONCLUSIONS
REFERENCES
 
The ABR abnormalities of prolonged IPLs and absent/dysmorphic wave IIs in our craniosynostosis patients are previously undocumented observations that could change our perception of the disease process and lead to important clinical and research advances. For example, we hypothesize that the major pathogenic basis of these ABR abnormalities is a compression of the auditory nerve as it passes through the internal auditory meatus and posterior fossa. We further speculate that auditory and facial nerve compression and reduced basilar artery blood flow underlie the morbidities of auditory nerve deafness, tinnitus, vertigo, hemifacial spasms, and brainstem disorders. MRI tractography or functional brain imaging may be needed to investigate this nerve compression hypothesis, because conventional MRI was not able to image these nerves. We speculate that MVD surgery could prevent or reverse these cranial nerve morbidities and greatly improve the quality of life for these patients. We hypothesize that brainstem compression, A-C malformation, and a stretched auditory nerve can be occasional pathogenic sources of prolonged I-to-III and III-to-V IPLs and that posterior fossa decompression can ameliorate these conditions. The ABR should, therefore, be useful in evaluating the need and appraising the benefits of cranial, posterior fossa, and MVD surgery. We further hypothesize that craniosynostosis patients will have an inordinate prevalence of auditory nerve and CAPDs. The presence of these disorders should be investigated and managed. Finally, the ABR may be the best way to diagnosis auditory and facial nerve compression in craniosynostosis children. Others have concluded that the ABR is more useful than brain imaging for detecting vascular compression of the auditory nerve in tinnitus, vertigo, and hemifacial spasm patients (A.R. Moller, PhD, written communication, 2006). Thus, ABR diagnostics should be a standard part of neurologic, neurosurgical, and hearing evaluations for all craniosynostosis and other patients at risk for auditory nerve, facial nerve, and brainstem compression.


   ACKNOWLEDGMENTS
 
We thank Karen Piggott, AUD, and Smita Somne, MS, for collecting data on 2 patients, as well as Seetha Shankaran, MD (Director, Neonatal/Perinatal Medicine, Children's Hospital of Michigan) for reviewing our article.


   FOOTNOTES
 
Accepted Nov 21, 2006.

Address correspondence to Michael W. Church, PhD, C. S. Mott Center for Human Growth and Development, 275 E Hancock, Detroit, MI 48201. E-mail: mchurch{at}med.wayne.edu

The authors have indicated they have no financial relationships relevant to this article to disclose.


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PEDIATRICS (ISSN 1098-4275). ©2007 by the American Academy of Pediatrics




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