Quantitative analysis of reversible dysfunction of brain-stem midline structures caused by disturbance of basilar artery blood flow with the auditory brain-stem responses

To clarify the effects of disturbances in basilar artery blood flow, basilar artery angiospasm was induced in 2 cats and 4 guinea pigs and auditory brain-stem responses (ABRs) were continuously recorded preceding, during and following the angiospasm. The angiospasm caused specific ABR changes in that waves II (P2-N2) and III (P3-N3) were attenuated without any corresponding amplitude reduction of P4. Those changes were equivalent following stimulation of either ear. Moreover, the ABR changes gradually recovered within 5 h. On the basis of the animal experiments, 52 patients with subarachnoid hemorrhage, supratentorial tumor showing increased intracranial pressure or hydrocephalus were selected for repeated ABR examinations. ABR abnormalities similar to those observed in the animal experiment were obtained especially from the patients exhibiting grade 3 or 4 symptomatology with subarachnoid hemorrhage. In these cases, the wave III to wave IV-V amplitude ratio was significantly decreased. In some cases the ABR abnormalities and the wave III to wave IV-V amplitude ratio recovered as the clinical course improved. These results support the conclusion that specific ABR changes (wave III to wave IV-V amplitude ratio) reflect transient ischemic dysfunction of the midline portion of the brain-stem caused by disturbances of basilar artery blood flow.     

Effect of graded periods of congenital hypothyroidism on the peripheral auditory evoked activity of rats

Rats were treated with a goitrogen, propylthiouracil (PTU), from 3 days before delivery up to different ages postnatally. Peripheral auditory function was evaluated with the auditory brain-stem response (ABR) technique performed at 200 days of age. All groups of rats exposed consecutively pre- and postnatally to PTU displayed permanent auditory impairment for each stimulus modality used, as revealed by significantly prolonged wave I latencies and elevated thresholds, and the severity of these abnormalities was directly related to the duration of PTU treatment. The only congenitally hypothyroid animals not affected were those treated from 3 days before parturition up to birth and those treated for 10 days beginning at 35 days of age. These data underline the susceptibility of the developing auditory system since, while very brief perinatal PTU exposure resulted in permanent evoked response abnormalities, longer exposure in later life had no effect.     

Auditory brainstem response in hyperbilirubinemic rats: Part II.

The effect of an albumin-bilirubin solution on the auditory brainstem response (ABR) of rats was examined and compared with that of rats in which only bilirubin was administered. In albumin-bilirubin-loaded rats, the latencies of waves II and IV were prolonged and the amplitudes decreased, whereas the ABR wave I did not change significantly. The I-IV interpeak latency also was prolonged. These changes were more severe in rats loaded only with bilirubin. Mannitol injection hastened the appearance of ABR changes when only bilirubin was used, but peak levels of ABR changes were almost the same in the mannitol-injected groups. When the blood-brain barrier is intact, albumin administration is useful in hyperbilirubinemia for the prevention of damage to the central auditory pathways. The reversibility of the ABR changes were demonstrated in all bilirubin-administered groups.     

Somatosensory evoked potentials and auditory brain-stem responses in congenital hypothyroidism. II. A cross-sectional study in childhood. Correlations with hormonal levels and developmental quotients

We report the results of somatosensory evoked potentials (SEPs) and auditory brain-stem responses (ABRs) done in 48 congenital hypothyroid (CH) treated children, early detected and aged 18 months, 3 and 5-9 years of age. We report also the results of SEP and ABR done in 9 3-year-old CH children, before and after a 1 month therapy interruption to reassess the thyroid status. The more frequent abnormalities were increased wave I latencies for 18 month and 3-year-old CH children. In some children, these increases were not associated with signs of otitis media. No significant difference was seen between CH children and controls for SEP latencies and ABR and SEP interpeak latencies (IPLs). Similarly, no significant difference was seen between the two recording sessions in the 9 3-year-old CH children for ABR and SEP. On an individual basis, we observed abnormalities of central conduction time for ABR and SEP in several CH children. Moreover, significant partial correlations were found between ABR and SEP IPLs and thyroxine (T4) serum levels at diagnosis and thyrotropin (TSH) serum levels at the time of recording. There was also a significant partial correlation between N19-P22 IPLs and the practical reasoning scale of the Griffiths test considering the whole group of CH children. These results indicate that SEP might eventually be used to detect CH children at risk of presenting developmental abnormalities.     

Brain-stem auditory evoked potential abnormalities with unilateral brain-stem lesions demonstrated by magnetic resonance imaging

We correlated the brain-stem auditory evoked potential (BAEP) abnormalities in 24 patients with discrete unilateral brain-stem lesions demonstrated by magnetic resonance imaging. In 18 patients who had BAEP abnormalities either confined to or more severe on stimulation of one ear, the lesion on magnetic resonance imaging was in the brain stem ipsilateral to the corresponding ear. Mesencephalic lesions produced amplitude abnormalities of the IV/V complex while pontine lesions resulted in abnormalities of earlier components (wave II and/or III). Prolongation of the I-III interpeak latency tended to occur with pontine lesions and of the III-V interpeak latency with mesencephalic lesions. Unilateral brain-stem lesions, particularly at the mesencephalic level, often produced BAEP abnormalities on both ipsilateral and contralateral monaural stimulation.     

Anatomical bases of binaural interaction in auditory brain-stem responses from guinea pig

There is a non-linear interaction of binaural stimulation on auditory brain-stem potentials in both human and animals. The interaction takes the form of the binaurally evoked ABR being of smaller amplitude than the sum of the monaurally evoked ABRs. In the guinea pig this interaction occurs at the time of components P4, N4 and P5. In order to investigate the generator sites of binaural interaction in the ABR, various lesions were made in the brain-stem auditory system in 29 guinea pigs. The effects of those lesions on binaural interaction were as follows: (1) unilateral lesion of lateral lemniscus or bilateral lesions of the inferior colliculi had no significant effect on binaural interaction; (2) transection of the lateral lemnisci bilaterally was associated with a loss of the component of binaural interaction associated in time with N4; (3) a lesion just lateral to the lateral superior olivary complex resulted in an attenuation of the component of binaural interaction associated in time with P4; (4) complete section of the decussating fibers of the trapezoid body or a complete unilateral lesion of the superior olivary complex led to a loss of all components of binaural interaction. These results suggest that binaural interaction in the guinea pig ABR requires the integrity of several distinct portions of the brain-stem auditory pathway, i.e., both lateral lemnisci are required for the interaction occurring at the time of N4; the brain-stem just lateral to the lateral superior olive participates in the interaction at the time of P4. The trapezoid body and superior olivary nucleus are required for binaural interaction at P4, N4 and P5.     

Anesthesia effects: auditory brain-stem response

Auditory brain-stem responses (ABRs) were measured in the awake state and with ketamine and xylazine anesthesia in adult gerbils. Surface recorded vertex-positive components of the ABR were analyzed with respect to the awake and anesthetized states as a function of stimulus frequency. ABR thresholds were not altered with ketamine/xylazine. Small increases in peak latency were associated with anesthesia for all components except wave P1. Increases in absolute latency were progressively greater for successive peaks, reaching an average shift of 0.41 msec for wave P6. Amplitude changes with anesthesia were more variable, with increases generally seen for waves P4 and P6. Significant anesthesia effects on peak latency and amplitude were independent of stimulus frequency. These data confirm previously reported ABR sensitivity to non-barbiturate anesthesia. Direct comparisons of ABR interpeak intervals or amplitude ratios from awake versus anesthetized animals must account for the effects of barbiturate and non-barbiturate agents. However, the stability of response threshold and the small magnitude of latency and amplitude changes with a ketamine and xylazine regimen demonstrate that accurate electrophysiological measures of hearing sensitivity and auditory brain-stem activity can be obtained in anesthetized animals, provided that temperature and other parameters are maintained within normal physiological limits.     

Postnatal development of auditory function in the chicken revealed by auditory brain-stem responses (ABRs)

Auditory evoked brain-stem responses (ABRs) were recorded from the surfaces of the brain of lightly anesthetized newborn (1-7 days old) and adult (7-9 weeks old) chickens as a measure of the development of auditory processing. One-day-old and older chickens showed a series of waves within 5 msec after the stimulus onset. This precocity of the ABR in chickens contrasts with the first appearance of the ABR in cats at 4 days of age. The ABR onset latency was shorter in adult chickens than in newborns. This indicates that developmental modifications of mechanical transmission in the external and middle ear or cytodifferentiation of the sensory hair cells of the basillar papilla and the neurons of the acoustic nerve continue postnatally. Within the complex wave form of the response, most of the inter-wave latencies decreased with maturation, indicating that development of the central auditory pathway also continues postnatally. One inter-wave latency (N1 to P3-4) was significantly shorter (P less than 0.05) in adults than in newborns for intense click stimuli, and even among newborns, this inter-wave latency was significantly shorter in 6- and 7-day-old specimens than in 1-3-day-old specimens. It seems likely that changes in the N1 to P3-4 inter-wave latency reflect changes in evoked activity of second order auditory neurons that are located in the nucleus angularis and nucleus magnocellularis, and that intensive developmental changes occur in these neurons during the first postnatal week. The ABR recorded in chickens is a reliable measure of functional activity in the auditory system which is reproducible between individuals and capable of demonstrating developmental changes in specific segments of the wave form.     

Auditory brain-stem responses in blepharospasm

The auditory brain-stem response (ABR) has been reported to detect abnormalities in both the auditory pathways and in adjacent structures. Ten of 35 consecutive patients with blepharospasm were found to have abnormal ABRs involving poor form and delayed peak latency of positive components III or V. Abnormal ABRs in approximately 30% of patients with essential blepharospasm suggest pathology in the brain-stem of a substantial proportion of patients with this form of cranial-cervical dystonia.     

Clinical evidence supporting a subthalamic origin of the P15 wave of the somatosensory evoked potentials to median nerve stimulation

Both somatosensory (SSEPs) and brain-stem auditory evoked potentials (BAEPs) were recorded in 3 patients with localized lesions in the thalamus or brain-stem. In one patient with a right thalamic cystic tumour there was a significant interhemispheric difference in the central conduction time (CCT), but the N14-P15 interval was not affected on either side and BAEPs showed normal wave latencies and interpeak latencies (IPLs). The second patient had a colloid cyst of the third ventricle in which central herniation had occurred resulting in 'locked-in' syndrome. The P15 peak was absent on one side and markedly prolonged in latency on the other. BAEPs showed neither wave IV nor V on either side. The third patient had compression of the right posterior rostral pons by a metastatic tumour, resulting in significant prolongation of the CCT on the side of the tumour because of increase in the N14-P15 interval. Both I-V and III-V interpeak latencies were significantly prolonged bilaterally without prolongation in I-III IPL in this case. There was a correlation between the electrophysiological abnormalities of P15 and of BAEP wave V. These results suggest that the origin of the P15, which is usually recorded as a far-field potential, may be in the subthalamus or the upper part of the brain-stem.     

Functioning of the brain-stem auditory pathway in non-retarded autistic individuals

Functioning of auditory brain-stem pathways was examined in non-retarded autistic individuals (14-28 years of age). Functioning was assessed by recording ERPs (event-related brain potentials) generated by these auditory pathways. These ERPs were evoked by click stimuli and occurred within the first 8 msec following the onset of the click. To assess the ability of these early auditory pathways to process sensory stimuli of varying characteristics, we systematically varied click intensity, rate of stimulation, ear of stimulation, and polarity of clicks. The results show that non-retarded autistic individuals have normal functioning of the brain-stem auditory pathways which generate these ERPs: every autistic subject had normal ERPs. So, disorder in auditory brain-stem pathways which generate these ERPs is not necessary for autism to occur. The dysfunctioning neural systems directly responsible for autism in non-retarded individuals must be sought elsewhere. Ten of the autistic subjects in this study, whom we found to have normal auditory brain-stem ERPs, had previously been found to have abnormalities in longer latency cognitive ERP components (Courchesne et al. 1984, 1985). We conclude, therefore, that those abnormalities in longer latency components are not the downstream consequences of abnormalities in the structures generating the auditory brain-stem ERPs recorded in the present study.     

Response enhancement and reduction of the auditory brain-stem response in a forward-masking paradigm

Alterations in the probe evoked auditory brain-stem response (ABR) were evaluated in 15 normal-hearing subjects using several stimulus configurations in a tone-on-tone forward-masking paradigm. The stimulus parameters manipulated in the study included: masker frequency; relative intensity of the masker; overall intensity of the masker-probe pair; and masker rise-fall time. Latency increases for waves III and V and an amplitude reduction for wave III were observed under some stimulus conditions. These changes were interpreted in terms of partial forward-masking effects. The masking effects were shown: to be maximal for masker frequencies in close proximity to the probe; to increase with increasing level of masker; to be independent of the overall level of the masker-probe pair; and, to decrease with increasing rise-fall time of the masker. Collectively, the forward-masking effects were interpreted as peripheral in origin, although, an additional brain-stem locus was not ruled out. In contrast, the same stimuli which increased wave III and V latencies and reduced wave III amplitude produced a robust amplitude increment in wave V which was termed enhancement. Wave V enhancement was shown: to be maximal for masker frequencies in close proximity to the probe; to decrease with increasing masker level; and, to decrease with faster rise-fall times of the masker. The processes mediating wave V enhancement are not clear, however, it was concluded that wave V enhancement probably reflects the resultant of a complex central neuronal interaction, presumably in the vicinity of the wave V generator(s).     

Measurements of brain-stem auditory evoked potentials in infancy,childhood, and adolescence

Brain-stem auditory evoked potentials (BAEPs) were measured in 38 patients between 3 months and 18 years of age. In patients with blunt head injuries (N=28; 73.7%) no significant correlation between BAEP changes and final outcome could be established until day 36 with the exception of wave III changes in 3 children. Because various BAEP abnormalities occurred in all outcome groups and the nature of the changes was transient, we conclude that within this age group there must be a higher resistance to various lesions until irreversible impairment of brain-stem function results. In spite of this result, continuous BAEP recording in this age group appears useful, since this noninvasive investigation represents an objective assessment of topical brain-stem function.     

Edematous changes in the central nervous system of zitter rats with genetic spongiform encephalopathy

The pathogenesis of progressive spongy degeneration in zitter rats with genetic spongiform encephalopathy was examined histopathologically and biochemically in the context of edematous change in the central nervous system (CNS). Histopathological studies revealed that vacuolation in the CNS of zitter rats progressed with aging and the severity of spongy degeneration was markedly divergent in different areas in the CNS. Edematous change was confirmed by a consistently higher water content in the brain of zitter rats than in that of normal SD/J rats at all ages. Furthermore, a close relationship between spongy degeneration and edematous change in the CNS was demonstrated by regional measurement of specific gravity (SPGR) of brain tissues and quantification of the spongy degeneration by computer-image analysis. The brain regions with lighter SPGR were more severely affected by spongy degeneration. These results suggest that edematous change is related to the pathogenesis of spongy degeneration in the CNS of the zitter rat.     

Neurophysiological abnormalities in adolescents with type I Crigler-Najjar syndrome.

We report neurophysiological abnormalities in two adolescents with type I Crigler-Najjar syndrome, an autosomal recessive disorder characterized by severe unconjugated hyperbilirubinemia. Electroencephalograms (EEGs) demonstrated frequent generalized single and polyspikes, and background slowing. Normal pattern reversal evoked responses (PRVERs) and normal central brain-stem auditory evoked responses (BAERs) were recorded in both patients. These findings differ from the EEG triphasic wave pattern seen in the EEG in hepatic encephalopathy and the central BAER abnormalities seen in many infants with kernicterus. Thus these findings most likely result from complex multifactorial processes and are not simply the result of the hyperbilirubinemia which is common to all 3 conditions.     

Auditory brain-stem responses in hydrocephalic patients

Auditory brain-stem response (ABR) was measured in 40 patients (80 ears) with confirmed hydrocephalus. Eighty-eight percent of these patients showed some form of ABR abnormality. Responses indicative of brain-stem dysfunction consisted of prolonged I-V interwave latency (38%), reduced V/I amplitude ratio (33%), and abnormalities in wave-shape of components III (27%) and V (53%). In addition, 70% of the patients had elevated ABR thresholds; 45% had responses in excess of 20 dB HL and the remaining 25% had no ABR activity. The etiology of the hydrocephalus, head circumference and brain-stem symptoms were not associated with particular ABR abnormalities. Communicating hydrocephalus correlated significantly with both prolonged I-V conduction time and absence of ABR activity, compared with non-communicating hydrocephalus. Four of the 9 patients retested showed ABR improvement on follow-up; one patient showed deterioration. The results were compared to our prior studies of ABR in 60 post-meningitic patients and in 100 severely neurologically impaired institutionalized children in whom the incidence of intrinsic brainstem abnormalities was one-third and two-thirds that of the hydrocephalic group, respectively. The results of this study suggest that ABR can be used to document clinically unsuspected brain-stem pathology that may accompany hydrocephalus. Auditory brain-stem dysfunction is likely to complicate the assessment of hearing sensitivity in hydrocephalic patients.     

Latency alterations of the auditory brainstem response in audiogenic seizure-prone Long-Evans rats

Audiogenic seizure susceptibility in the normally seizure-resistant Long-Evans rat may result from altered processing in the auditory pathway. Representative waveform latencies of the auditory brainstem responses (ABR) were recorded to examine generator alterations at different levels of the auditory neuraxis. Male Long-Evans rats primed for audiogenic seizures (AGS) on PND 14 with a 10 kHz pure tone at 120 dB SPL for 8 min were tested for AGS on PND 28 with 120 dB SPL continuous white noise. Primed subjects displayed wild running culminating in clonic convulsions. Following behavioral testing at 4-6 months, vertex recordings of ABR waves Ia-VI were made in anesthetized subjects using pure tone stimulus bursts. AGS subjects showed marginally elevated ABR thresholds. Shorter ABR wave latencies were elicited in AGS subjects for peripheral and central auditory components with stimulus intensities above 50 dB PeSPL at 8 and 40 kHz. Interpeak intervals were reduced for waves Ia-V and III-V in AGS subjects. These results reveal that intense sound stimulation during a sensitive period of development later reduces processing time at higher intensity levels.     

Brain-stem auditory evoked potentials and blink reflex in friedreich's ataxia

Summary The brain-stem involvement in Friedreich's ataxia (FA) was studied by using brain-stem auditory evoked potentials (BAEPs) and the blink reflex. Ten out of 18 patients had abnormal BAEPs, the main abnormality being complete absence of responses and disappearance of wave V. Combined degeneration of the peripheral and central acoustic pathways probably accounts for these findings. The blink reflex was abnormal in 50% of the cases. The outstanding abnormality was bilateral delay of late responses with normal early response, which could be correlated with the known pallor of the descending trigeminal tracts. In contrast with BAEP findings, blink reflex abnormalities did not correlate with either the age of patients or the severity and duration of the disease. These data suggest a difference in susceptibility to degeneration between the auditory system and neuronal system subserving the blink reflex. We conclude that systematic BAEP and blink reflex recording is useful in the electrophysiological evaluation of FA patients.     

Otoacoustic emission in patients with neurological disorders who have auditory brainstem response abnormality

Otoacoustic emissions (OAEs) were evaluated in 51 ears of 30 patients with a severe auditory brainstem response (ABR) waveform abnormality. Thirteen ears showed no ABR to click sound of higher intensity than 100 dBSPL (group 1). Fourteen ears exhibited only wave V or a decreased amplitude pattern of ABR (group 2). Twenty-four ears showed a predominant wave I or no wave III pattern (group 3). Almost all the ears with absent ABR showed no OAE, which strongly suggested hearing loss of cochlear origin, although one patient with alternating hemiplegia of childhood exhibited definite OAEs and auditory reactions without ABR. One patient with mitochondrial myopathy, encephalopathy, lactic acidosis, and strokelike episodes (MELAS) and her mother in group 2 had OAE abnormalities, which also suggested mild to severe hearing impairment. When OAEs are present, an accompanying ABR abnormality may be produced by brainstem dysfunction of the underlying disorder such as Pelizaeus-Merzbacher disease. There was a significant relationship (chi-square test P<0.001) between the positivity of the distortion product OAE response and the clinical auditory reactions in 24 patients, although their ABR abnormalities did not reflect hearing impairment directly. Careful examination of both audiometry and OAEs might be necessary for further assessment of the hearing function in pediatric patients with neurological disorders and specific auditory nerve disease.     

Brain-stem auditory evoked potentials in children with brain-stem or cerebellar dysfunction

Brain-stem auditory evoked potentials (BAEPs) were recorded in 23 children who had signs of brain-stem or cerebellar dysfunction. In patients with brain-stem gliomas, BAEPs were abnormal in all except one, in whom involvement of the brain-stem auditory pathway was limited to the midbrain tectum. The BAEPs were normal in neuronal ceroid lipofuscinosis, but abnormal bilaterally in inheritable leukoencephalopathies. All patients with Leigh's encephalopathy had BAEP abnormalities; in two, abnormalities occurred before the appearance of lesions on computed tomographic scan. Patients with Friedreich's ataxia and giant axonal dystrophy had abnormal BAEPs, but the test was normal in a child with similar neurologic findings with vitamin E deficiency. Patients with diffuse metabolic encephalopathies had variable findings. Thus, BAEP abnormalities are nonspecific for various disease processes but are frequently seen in neoplastic and neurodegenerative diseases, with primary white matter or extensive brain-stem involvement.