Brainstem auditory evoked potentials and middle ...

Journal of Clinical Neuroscience 20 (2013) 383–388

Contents lists available at SciVerse ScienceDirect

Journal of Clinical Neuroscience journal homepage: www.elsevier.com/locate/jocn

Clinical Study

Brainstem auditory evoked potentials and middle latency auditory evoked potentials in young children Jin Jun Luo a,b,⇑, Divya S. Khurana c, Sanjeev V. Kothare c,1 a

Department of Neurology, Temple University School of Medicine, Philadelphia, PA 19140, USA Department of Pharmacology, Temple University School of Medicine, Philadelphia, USA c Section of Neurology, Department of Pediatrics, St. Christopher’s Hospital for Children, Drexel University College of Medicine, Philadelphia, USA b

a r t i c l e

i n f o

Article history: Received 1 December 2011 Accepted 26 February 2012

Keywords: Auditory evoked potentials BAEP MLAEP

a b s t r a c t Measurements of brainstem auditory evoked potentials (BAEP) and middle latency auditory evoked potentials (MLAEP) are readily available neurophysiologic assessments. The generators for BAEP are believed to involve the structures of cochlear nerve, cochlear nucleus, superior olive complex, dorsal and rostral pons, and lateral lemniscus. The generators for MLAEP are assumed to be located in the subcortical area and auditory cortex. BAEP are commonly used in evaluating children with autistic and hearing disorders. However, measurement of MLAEP is rarely performed in young children. To explore the feasibility of this procedure in young children, we retrospectively reviewed our neurophysiology databank and charts for a 3-year period to identify subjects who had both BAEP and MLAEP performed. Subjects with known or identifiable central nervous system abnormalities from the history, neurologic examination and neuroimaging studies were excluded. This cohort of 93 children up to 3 years of age was divided into 10 groups based on the age at testing (upper limits of: 1 week; 1, 2, 4, 6, 8, 10 and 12 months; 2 years; and 3 years of age). Evolution of peak latency, interpeak latency and amplitude of waveforms in BAEP and MLAEP were demonstrated. We concluded that measurement of BAEP and MLAEP is feasible in children, as early as the first few months of life. The combination of both MLAEP and BAEP may increase the diagnostic sensitivity of neurophysiologic assessment of the integrity or functional status of both the peripheral (acoustic nerve) and the central (brainstem, subcortical and cortical) auditory conduction systems in young children with developmental speech and language disorders. Ó 2012 Elsevier Ltd. All rights reserved.

1. Introduction Brainstem auditory evoked potentials (BAEP) are the electrical responses recorded in the relevant auditory pathways provoked by auditory stimulation. BAEP are usually recorded for up to 10 ms, triggered by click-stimulation. The generators for waves I, II, III, IV and V of BAEP are believed to involve the structures of cochlear nerve, cochlear nucleus, superior olive complex, dorsal and rostral pons, and lateral lemniscus, respectively.1 Waves II and IV vary significantly and may vary from person to person while waves I, III and V are stable with high reproducibility, reliability and interindividual consistency. BAEP are sensitive to brainstem lesions from tumors, trauma, hemorrhage, ischemia, demyelination and metabolic insult.2,3 The unique properties of BAEP enable reliable

⇑ Corresponding author at: J.J. Luo, 3401 N. Broad Street, C525, Department of Neurology, Temple University School of Medicine, Philadelphia, PA 19140, USA. E-mail address: [email protected] (J.J. Luo). 1 Present address: Division of Epilepsy and Clinical Neurophysiology, Department of Neurology, Children’s Hospital, Harvard Medical School, Boston, MA 02115, USA. 0967-5868/$ - see front matter Ó 2012 Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.jocn.2012.02.038

interpretation independent of the level of consciousness, sedative medications and general anesthesia. BAEP are a useful intraoperative monitoring tool during brainstem, acoustic nerve or posterior fossa tumor surgery,4–6 and for the prognostication of coma or stroke.7–10 Studies of BAEP are helpful in evaluating the functional status of the peripheral and central auditory pathways. Abnormalities or disappearance of the individual waveforms, and delay in the peak latencies (PL) and/or the interpeak latencies (IPL) indicate abnormalities involving either the relevant fibers and/or the generator(s) in the auditory conduction pathways.1 Therefore, BAEP are a useful tool in the evaluation of children with suspected hearing disorders involving the cochlea, acoustic nerve and brainstem.11 MLAEP are usually recorded for up to 100 ms in adults after the click-stimulation. The generators for the waveforms denoted as P0 and Na are assumed to be in the subcortical regions while those for Pa, Nb and Pb are thought to arise in the auditory cortex, or Heschl’s gyrus, of normal subjects.12–17 Measurement of the IPL of P0–Pa and/or Na–Pa waveforms of the MLAEP is the most relevant parameter in the assessment of the auditory pathway between the upper brainstem and auditory cortex. A combination of BAEP and MLAEP measurement may thus aid in the investigation of the

384

J.J. Luo et al. / Journal of Clinical Neuroscience 20 (2013) 383–388

Table 1 Measures of peak latency, interpeak latency and amplitude in brainstem auditory evoked potentials Upper limit of age group

n

I PL

III PL

V PL

I–III IPL

III–V IPL

I–V IPL

I Amp

V Amp

Ratio V/I amp

1 week 1 month 2 months 4 months 6 months 8 months 10 months 12 months 2 years 3 years Total p

7 8 13 7 9 4 3 5 23 14 93

3.37 ± 0.27 3.69 ± 0.76 3.42 ± 0.43 3.61 ± 0.57 3.45 ± 0.58 3.56 ± 0.57 3.33 ± 0.29 3.30 ± 0.18 3.23 ± 0.31 3.19 ± 0.27

4.70 ± 0.57 4.91 ± 0.21 4.67 ± 0.29 4.50 ± 0.31 4.39 ± 0.29 4.36 ± 0.24 4.13 ± 0.19 4.10 ± 0.15 4.10 ± 0.39 3.96 ± 0.25

7.01 ± 0.59 7.22 ± 0.43 6.85 ± 0.47 6.60 ± 0.38 6.35 ± 0.33 6.29 ± 0.25 6.09 ± 0.34 6.17 ± 0.21 6.21 ± 0.73 5.86 ± 0.27

3.01 ± 0.55 3.10 ± 0.31 2.99 ± 0.23 2.69 ± 0.33 2.67 ± 0.21 2.58 ± 0.11 2.46 ± 0.05 2.44 ± 0.10 2.49 ± 0.34 2.36 ± 0.21

2.32 ± 0.11 2.41 ± 0.20 2.13 ± 0.19 2.10 ± 0.12 2.01 ± 0.12 1.93 ± 0.11 1.97 ± 0.19 2.07 ± 0.14 2.11 ± 0.4 1.91 ± 0.11

5.33 ± 0.58 5.38 ± 0.47 5.14 ± 0.34 4.79 ± 0.41 4.62 ± 0.30 4.51 ± 0.05 4.43 ± 0.21 4.52 ± 0.21 4.59 ± 0.71 4.27 ± 0.21

0.42 ± 0.17 0.40 ± 0.13 0.45 ± 0.16 0.60 ± 0.20 0.54 ± 0.36 0.58 ± 0.24 0.52 ± 0.26 0.69 ± 0.32 0.61 ± 0.20 0.71 ± 0.14

0.37 ± 0.23 0.23 ± 0.10 0.33 ± 0.11 0.39 ± 0.08 0.43 ± 0.16 0.37 ± 0.21 0.52 ± 0.20 0.50 ± 0.06 0.51 ± 0.19 0.60 ± 0.24

0.92 ± 0.38 0.62 ± 0.28 0.79 ± 0.30 0.74 ± 0.23 0.97 ± 0.47 0.63 ± 0.26 1.31 ± 0.83 0.86 ± 0.41 0.91 ± 0.40 0.90 ± 0.40

0.2052

< 0.0001

< 0.0001

< 0.0001

0.0017

< 0.0001

0.0219

0.0005

0.2871

p value indicates level of difference among the age groups. Data are given as mean ± standard deviation. I = wave I, III = wave III, V = wave V, amp = amplitude, IPL = interpeak latency, PL = peak latency.

integrity of the auditory conduction pathways, including the acoustic nerve, brainstem, subcortical and cortical areas related to auditory processing, thus assisting to differentiate various sites of abnormalities involved in children with speech and language delays.18–20 However, both BAEP and MLAEP are rarely recorded in routine clinical neurophysiologic studies of hearing and language disorders in children. The purpose of this study is to demonstrate that MLAEP are measurable, along with BAEP, in children from 1 week to 3 years of age.

BAEP

2. Methods 2.1. Subjects The data were collected from our neurophysiology databank via a retrospective review of clinic charts from January 1 2000 to December 31 2002 at St Christopher’s Hospital for Children. Data for subjects up to 3 years old who had BAEP and MLAEP with identifiable waveforms were collected. Subjects with known abnormalities such as a brain or brainstem structural lesion on neurologic

MLAEP

38 gestational week male

2 months male

6 months male

10 months female

Fig. 1. Waveforms showing brainstem auditory evoked potentials (BAEP) and middle latency auditory evoked potentials (MLAEP) in very young children.

385

J.J. Luo et al. / Journal of Clinical Neuroscience 20 (2013) 383–388

no significant effects on BAEP and MLAEP.21 Recordings were made with subjects comfortable in the recumbent position on a bed or seated in an armchair in a semi-darkened room with constant illumination intensity. The BAEP and MLAEP were obtained using a Bravo electroencephalograph (Nicolet Biomedical, Madison, WI, USA) and gold cup disk electrodes. Waveforms were recorded with the reference electrodes placed at the earlobes A1 and A2, recording at the vertex (Cz), and the ground electrode at the high forehead FPz. Stimulation with 100 ms clicks starting with rarefaction polarity was performed monaurally with contralateral masking white noise at 40 dB. The stimulation frequency was 9.1 Hz for BAEP and 5.1 Hz for MLAEP. Threshold was determined by the appearance of wave

examination and neuroimaging; a history of neurodegenerative, metabolic or congenital disorders; central nervous system (CNS) infections; encephalopathy; and those who had received chemotherapy were subsequently excluded. 2.2. Recording conditions for auditory evoked potentials A subset of children who required sedation for the study (one child under 1 year old, 19 children 1–2 years old and three children 2–3 years old) received chloral hydrate 20–50 mg/kg orally. A few of these children (n = 3) also received 0.2–0.5 mg/kg oral diazepam, when they did not respond to the initial chloral hydrate dose. Administration of these medications has been reported to have

I-III

BAEP Interpeak Latency

6

III-V I-V

5

ms

4 3 2 1 1w

1m

2m

4m

6m

8m

10m

12m

1.1-2y

Iamp

BAEP Amplitude

1.2

2.1-3y

Vamp

1 0.8

uV

0.6 0.4 0.2 0 1w

1m

2m

4m

6m

8m

10m

12m

1.1-2y

2.1-3y

Fig. 2. Graphs showing evolution of brainstem auditory evoked potentials (BAEP) in different measures in young children. The x axis represents child age: m = month, w = week, y = year, I = wave I, III = wave III, V = wave V, amp = amplitude. (This figure is available in colour at www.sciencedirect.com.)

386

J.J. Luo et al. / Journal of Clinical Neuroscience 20 (2013) 383–388

V on audiometry, using a series of clicks at 70, 50, 30 and 10 dB intensity. The stimulation intensity was set at 60 dB above the hearing threshold. Band-pass was set at 100–3000 Hz for BAEP and 30–250 Hz for MLAEP. Four thousand sweeps were averaged and 10 ms were recorded for BAEP, while 1000 sweeps were averaged and 70 ms recorded for MLAEP. 2.3. Data acquisition and analysis For BAEP, the PL of waves I, III and V; IPL of waves I–III, III–V and I–V; the amplitudes of wave I and V; and the ratios of the amplitudes of waves V and I (V/I) were measured. For MLAEP, the PL and amplitude of P0 and Na were defined by waveform appearance 5–15 ms following stimulus onset with opposite polarity. Pa latency was defined by waveform appearance 10–40 ms following stimulus onset with the same polarity as P0. The PL of the individual waves and the IPL between the waves were measured. Since the waveforms of Nb and Pb were unreliably recorded in children younger than the age of 4 years,15,22 they were not included in this study. Statistical Analysis System (SAS) software (Cary, NC, USA) was used to analyze the data. One-way ANOVA was used to evaluate the difference among age groups for each variable and for the comparison of the ipsilateral with the contralateral recordings. A value of p < 0.05 was considered statistically significant. 3. Results One hundred and thirty-three children up to 3 years of age who had both BAEP and MLAEP recordings were initially identified. Of

these, 93 subjects who fulfilled the inclusion criteria were included in this study. They were distributed in various age groups from one week to 3 years (Table 1). BAEP and MLAEP could be detected as early as 38 weeks gestational age and became easily recorded after the age of 2 months (Fig. 1). The PL of waves I, III and V; the IPL of waves I–III, III–V and I–V; the amplitudes of waves I and V; and the ratios of the amplitudes of waves V and I (V/I) for BAEP are shown in Table 1. The individual PL of waveforms I, III and V and the IPL of I–III, III–V and I–V were observed to be longer at birth, shortening continuously until the age of 3 years with significant statistical differences (Fig. 2, Table 1). The amplitudes of both wave I and wave V increased with age (p = 0.02 and 0.0005, respectively), however, without significant change in the ratios of V/I (p = 0.29). The interlateral measures of PL of P0, Na and Pa, and IPL of P0– Na, Na–Pa and P0–Pa of MLAEP are shown in Fig. 3 and Tables 2 and 3. Significant shortening of the PL of P0 and Na and IPL of P0–Na was also observed with age; however, no significant changes in Pa latency were observed.

4. Discussion In this study we demonstrated that MLAEP can be measured in young children (Fig. 1). A combination of measurements of BAEP and MLAEP may aid in the neurophysiologic assessment of children with auditory processing disorders and language delays at a young age. To the best of our knowledge, there are no serial data of MLAEP in children younger than 2 years reported in the literature.

Fig. 3. Graphs showing evolution of middle latency auditory evoked potentials (MLAEP) in different measures in young children. The x axis represents child age: m = month, w = week, y = year, Na = wave Na, P0 = wave P0, Pa = wave Pa. (This figure is available in colour at www.sciencedirect.com.)

387

J.J. Luo et al. / Journal of Clinical Neuroscience 20 (2013) 383–388

In agreement with previous reports on BAEP, our results showed a decrease in PL of waves I, III, and V, in IPL of I–III, III–V and I–V, and an increase in the amplitude of wave I and V with age (Fig. 2, Table 1).23,24 These changes probably reflect developmental hierarchy or the stages of maturation of the CNS. It is well known that myelination in the nervous system facilitates conduction velocity. The waveforms of P0, Na and Pa in MLAEP in young children are highly reproducible and more readily recordable than previously expected (Fig. 1). These waveforms originate in generators located in discrete anatomic locations. Human studies suggest that the generators for P0 and Na are likely located in the upper brainstem involving the structures of the inferior colliculus and medial geniculate body.25,26 It is currently accepted that P0 and Na are generated in the subcortical region while Pa is generated in the auditory cortex. The PL of P0 and Na and the IPL of P0–Na in MLAEP shortened with age in the period of 6–12 months of life (Fig. 3, Tables 2 and 3), which may be related to myelination in the brainstem. These age-related changes have been well documented in both peripheral nerve conduction studies and studies of central nerve conduction of somatosensory evoked potentials (SSEP) and visual evoked potentials (VEP).27–29 Myelination and cytoarchitectural and axonal maturation are believed to be the key components responsible for these changes.30 Allison and colleagues observed a ‘‘U’’ type of trend in the latencies of SSEP and VEP from a study on 286 normal subjects aged from 4 to 95 years.31 The early decrease in the latencies correlated with maturation of myelination with age. Significantly increased detectability of both Na and Pa

in MLAEP has been observed as a function of age in children.15,22 In agreement with those reports, our study confirms the evolution in BAEP and MLAEP with increasing age in young children. Measurement of the Pa latency and P0–Pa IPL can provide information on the integrity or functional status of auditory processing in the subcortical and cortical areas. However, it may be age limited because of the absence of Nb and Pb in MLAEP before the age of 4 years.15,22 Interestingly, the IPL of P0–Pa and Na–Pa were found to be initially prolonged with ageing (Fig. 3, Table 3) which might be due to a hierarchy of acoustic synaptic maturation in the auditory cortex or, alternatively, increase in the distance of the pathway paralleled to increase in cephalic size. An additional explanation is that acquisition of development may be diversely distinct in different segments of the auditory pathway within the brainstem, acoustic cortex and/or its adjacent subcortical white matter. The observation that waveforms of Nb and Pb could not be recorded in early life, but become reliably evoked after the age of 4 years, supports this notion.15,22 Multiple pathophysiologic conditions may affect MLAEP recordings. The amplitude of MLAEP waveforms may vary significantly depending on the subject’s age, medication and functional status.15,22,32–35 Changes in body temperature, stimulation or recording paradigm can also influence the recordings.36–39 Prolonged Pa latency is seen in the elderly.40 Of note, these results are all from studies conducted in adults. Whether the effects of those factors on MLAEP in young children are the same as in adults remains to be elucidated. Therefore, it is recommended that individual neurophysiologic laboratories should establish their own normative data based on their recording conditions.

Table 2 Measures of peak latency in middle latency auditory evoked potentials Upper limit of age group

P0-i

P0-c

Na-i

Na-c

Pa-i

Pa-c

1 week 1 month 2 months 4 months 6 months 8 months 10 months 12 months 2 years 3 years

8.01 ± 1.51 7.85 ± 3.58 7.17 ± 0.36 7.06 ± 0.51 6.96 ± 0.32 6.72 ± 0.24 6.58 ± 0.42 8.33 ± 3.32 7.01 ± 2.03 6.51 ± 1.53

8.02 ± 1.00 9.96 ± 1.71 8.20 ± 0.45 8.36 ± 0.74 7.50 ± 0.34 7.79 ± 0.66 7.37 ± 0.35 8.38 ± 2.48 7.70 ± 1.87 6.87 ± 0.59

14.25 ± 3.81 15.63 ± 2.92 12.90 ± 1.60 12.46 ± 1.21 11.40 ± 1.59 11.20 ± 1.38 11.43 ± 2.96 12.04 ± 3.02 11.30 ± 2.78 9.91 ± 1.91

14.74 ± 2.84 16.80 ± 1.86 15.09 ± 1.49 14.36 ± 1.08 13.14 ± 1.12 12.37 ± 1.47 12.79 ± 2.63 12.95 ± 1.46 12.90 ± 2.39 11.51 ± 2.22

20.69 ± 2.98 23.80 ± 2.12 22.50 ± 2.97 24.30 ± 4.50 23.12 ± 3.46 19.60 ± 0.85 19.83 ± 0.40 20.67 ± 3.41 20.66 ± 4.95 19.80 ± 6.99

21.28 ± 3.41 23.37 ± 3.08 23.15 ± 2.82 25.02 ± 3.36 21.56 ± 1.86 20.85 ± 1.04 20.58 ± 1.96 19.25 ± 1.46 20.82 ± 4.72 20.76 ± 6.31

p (1) p (2)

0.7945

0.0136 0.004

0.0024

0.0002 0.0003

0.4965

0.4312 0.8294

p (1) value indicates level of difference among the age groups. p (2) value indicates level of difference between the ipsilateral and contralateral measures of the age groups. Data are presented as mean ± SD. c = contralateral, i = ipsilateral, Na = wave Na, P0 = wave P0, Pa = wave Pa.

Table 3 Measures of interpeak latency in middle latency auditory evoked potentials Upper limit of age group

P0–Na-i

P0–Na-c

Na–Pa-i

Na–Pa-c

P0–Pa-i

P0–Pa-c

1 week 1 month 2 months 4 months 6 months 8 months 10 months 12 months 2 years 3 years

6.24 ± 2.35 6.67 ± 1.21 5.73 ± 1.58 5.40 ± 1.55 4.44 ± 1.32 4.48 ± 1.15 4.85 ± 2.59 3.71 ± 0.81 4.29 ± 1.58 3.40 ± 0.52

6.72 ± 2.10 6.84 ± 1.71 6.89 ± 1.54 6.00 ± 0.97 5.64 ± 0.84 4.57 ± 1.06 5.41 ± 2.36 5.09 ± 0.43 5.19 ± 2.05 4.64 ± 1.89

6.44 ± 2.30 8.17 ± 2.03 9.59 ± 2.44 12.01 ± 3.82 11.92 ± 2.29 8.40 ± 2.22 8.40 ± 2.55 8.63 ± 4.84 9.32 ± 4.46 9.80 ± 6.60

6.55 ± 1.30 6.24 ± 2.78 8.42 ± 2.33 10.86 ± 2.69 8.65 ± 1.09 8.48 ± 1.21 7.79 ± 2.14 7.09 ± 1.69 7.90 ± 3.67 9.42 ± 6.46

12.68 ± 1.78 14.84 ± 1.48 15.32 ± 2.89 17.22 ± 5.01 16.15 ± 3.23 12.88 ± 1.09 13.25 ± 0.21 12.34 ± 4.52 13.62 ± 4.78 13.16 ± 6.65

13.26 ± 2.45 13.15 ± 1.74 14.89 ± 2.64 16.92 ± 3.45 14.07 ± 1.69 13.05 ± 1.28 13.21 ± 1.62 12.17 ± 1.74 13.02 ± 4.69 14.11 ± 6.46

p (1) p (2)

0.001

0.0957 0.0012

0.5377

0.5894 0.0651

0.6032

0.7103 0.5545

p (1) value indicates level of difference among the age groups. p (2) value indicates level of difference between the ipsilateral and contralateral measures of the age groups. Data are presented as mean ± SD. c = contralateral, i = ipsilateral, Na–Pa = interpeak latency of Na–Pa, P0–Na = interpeak latency of P0–Na, P0–Pa = interpeak latency of P0–Pa.

388

J.J. Luo et al. / Journal of Clinical Neuroscience 20 (2013) 383–388

Abnormalities of either disappearance of the individual waveforms or delay in PL and/or IPL indicate abnormalities involving either the generator and/or the relevant fibers in the auditory conduction pathways. Measurement of MLAEP may assist in identifying hearing dysfunction secondary to subcortical lesions, specifically involving the quadrigeminal plate or the diencephalon, in the presence of a normal BAEP.20 Therefore, measurement of MLAEP, along with the BAEP, may increase the sensitivity of neurophysiologic diagnoses. In conclusion, our findings demonstrated that MLAEP are measurable in young children, including those younger than 1 year of age. Use of the MLAEP, along with the BAEP, may increase the diagnostic sensitivity in neurophysiologic assessment of the integrity or functional status of both the peripheral (acoustic nerve) and the central (brainstem, subcortical and cortical) auditory conduction systems of young children with developmental speech and language disorders. Acknowledgments The authors thank the staff at the Section of Neurology, Department of Pediatrics, St. Christopher’s Hospital for Children for their help and support in data collection, and Jie Feng, PhD, for statistical assistance. References 1. Scherg M, von Cramon D. A new interpretation of the generators of BAEP waves I-V: results of a spatio-temporal dipole model. Electroencephalogr Clin Neurophysiol 1985;62:290–9. 2. Burkard RF, Don M. The auditory brainstem response. In: Burkard RF, Don M, Eggermont JJ, editors. Auditory evoked potentials. Basic principles and clinical application. Philadelphia: Lippincott Williams & Wilkins; 2007, p. 229–50. 3. Legatt AD. Brainstem auditory evoked potentials: methodology, interpretation, and clinical application. In: Aminoff MJ, editor. Electrodiagnosis in clinical neurology. 5th ed. Philadelphia: Elsevier Churchill Livingstone; 2005. p. 489–523. 4. Hall JW. New Handbook of auditory evoked responses. Boston: Allyn and Bacon; 2007. p. 750. 5. Legatt AD. Mechanisms of intraoperative brainstem auditory evoked potential changes. J Clin Neurophysiol 2002;19:396–408. 6. Moller AR. Intraoperative neurophysiological monitoring. 2nd ed. Totowa, New Jersey: Humana Press; 2006. p. 356. 7. de Sousa LC, Colli BO, Piza MR, et al. Auditory brainstem response: prognostic value in patients with a score of 3 on the Glasgow Coma Scale. Otol Neurotol 2007;28:426–8. 8. Su YY, Xiao SY, Haupt WF, et al. Parameters and grading of evoked potentials: prediction of unfavorable outcome in patients with severe stroke. J Clin Neurophysiol 2010;27:25–9. 9. Young GB, Wang JT, Connolly JF. Prognostic determination in anoxic-ischemic and traumatic encephalopathies. J Clin Neurophysiol 2004;21:379–90. 10. Zhang Y, Su YY, Haupt WF, et al. Application of electrophysiologic techniques in poor outcome prediction among patients with severe focal and diffuse ischemic brain injury. J Clin Neurophysiol 2011;28:497–503. 11. Wong V, Wong SN. Brainstem auditory evoked potential study in children with autistic disorder. J Autism Dev Disord 1991;21:329–40. 12. Deiber MP, Ibañez V, Fischer C, et al. Sequential mapping favours the hypothesis of distinct generators for Na and Pa middle latency auditory evoked potentials. Electroenceph Clin Neurophysiol 1988;71:187–97. 13. Ibanez V, Deiber MP, Fischer C. Middle latency auditory evoked potentials in cortical lesions. Critical of interhemispheric asymmetry. Arch Neurol 1989;46:1325–32.

14. Jacobson GP, Privitera M, Neils JR, et al. The effects of anterior temporal lobectomy (ATL) on the middle-latency auditory evoked potential (MLAEP). Electroenceph Clin Neurophysiol 1990;75:230–41. 15. Kraus N, Smith DI, Reed NL, et al. Auditory middle latency responses in children: effects of age and diagnostic category. Electroenceph Clin Neurophysiol 1985;62:343–51. 16. Shehata-Dieler W, Shimizu H, Soliman SM, et al. Middle latency auditory evoked potentials in temporal lobe disorders. Ear Hear 1991;12:377–88. 17. Manjunath NK, Srinivas R, Nirmala KS, et al. Shorter latencies of components of middle latency auditory evoked potentials in congenitally blind compared to normal sighted subjects. Int J Neurosci 1998;95:173–81. 18. Vitte E, Tankéré F, Bernat I, et al. Midbrain deafness with normal brainstem auditory evoked potentials. Neurology 2002;58:970–3. 19. Báez-Martín MM, Cabrera-Abreu I. Mid-latency auditory evoked potential. Rev Neurol 2003;37:579–86. 20. Kimiskidis VK, Lalaki P, Papagiannopoulos S, et al. Sensorineural hearing loss and word deafness caused by a mesencephalic lesion: clinicoelectrophysiologic correlations. Otol Neurotol 2004;25:178–82. 21. Schwender D, Klasing S, Madler C, et al. Effects of benzodiazepines on midlatency auditory evoked potentials. Can J Anaesth 1993;40:1148–54. 22. Daunderer M, Feuerecker MS, Scheller B, et al. Midlatency auditory evoked potentials in children: effect of age and general anaesthesia. Br J Anaesth 2007;99:837–44. 23. Guilhoto LM, Quintal VS, da Costa MT. Brainstem auditory evoked response in normal term neonates. Arq Neuropsiquiatr 2003;61:906–8. 24. Scaioli V, Brinciotti M, Di Capua M, et al. A multicentre database for normative brainstem auditory evoked potentials (BAEPs) in children: methodology for data collection and evaluation. Open Neurol J 2009;3:72–84. 25. Fischer C, Bognar L, Turjman F, et al. Auditory evoked potentials in a patient with a unilateral lesion of the inferior colliculus and medial geniculate body. Electroencephalogr Clin Neurophysiol 1995;96:261–7. 26. Fischer C, Bognar L, Turjman F, et al. Auditory early- and middle-latency evoked potentials in patients with quadrigeminal plate tumors. Neurosurgery 1994;35:45–51. 27. Dorfman LJ, Bosley TM. Age-related changes in peripheral and central nerve conduction in man. Neurology 1979;29:38–44. 28. Dustman RE, Beck EC. The effects of maturation and aging on the wave form of visually evoked potentials. Electroenceph Clin Neurophysiol 1969;26:2–11. 29. Doria-Lamba L, Montaldi L, Grosso P, et al. Short latency evoked somatosensory potentials after stimulation of the median nerve in children: normative data. J Clin Neurophysiol 2009;26:176–82. 30. Moore JK, Guan YL. Cytoarchitectural and axonal maturation in human auditory cortex. JARO 2001;2:297–311. 31. Allison T, Hume Al, Wood CC, et al. Developmental and aging changes in somatosensory, auditory and visual evoked potentials. Electroenceph Clin Neurophysiol 1984;58:14–24. 32. Amenedo E, Diaz F. Effects of aging on middle-latancy auditory evoked potentials: a cross sectional study. Biol Psychiat 1998;43:210–9. 33. Onofrj M, Thomas A, Iacono D, et al. Age-related changes of evoked potentials. Neurophysiol Clin 2001;31:83–103. 34. Rodriguez RA. Human auditory evoked potentials in the assessment of brain function during major cardiovascular surgery. Semin Cardiothorac Vascul Anesth 2004;8:85–99. 35. Buchwald JS, Rubinstein EH, Schwafel J, et al. Midlatency auditory evoked responses: differential effects of a cholinergic agonist and antagonist. Electroenceph Clin Neurophysiol. 1991;80:303–9. 36. Desmedt JE, Cheron G. Somatosensory evoked potentials to finger stimulation in healthy octogenarians and in young adults: wave forms, scalp topography and transit times of parietal and frontal components. Electroenceph Clin Neurophysiol 1980;50:404–12. 37. Borgmann C, Roß B, Draganova R, et al. Human auditory middle latency responses: influence of stimulus type and intensity. Hear Res 2001;158:57–64. 38. Neves IF, Gonçalves IC, Leite RA, et al. Middle latency response study of auditory evoked potentials’ amplitudes and lantencies audiologically normal individuals. Braz J Otorrinolaringol 2007;73:69–74. 39. Onitsuka T, Ninomiya H, Sato E, et al. Differential characteristics of the middle latency auditory evoked magnetic responses to interstimulus intervals. Clinical Neurophysiol 2003;114:1513–20. 40. Woods DL, Clayworth CC. Age-related changes in human middle latency auditory evoked potentials. Electroenceph Clin Neurophysiol 1986;65:297–303.