Prognostic significance of multimodality evoked response testing in high-risk newborns

Exposure to hypoxic-ischemic events in fetal or neonatal life may lead to permanent brain damage and subsequent neurodevelopmental deficits. Clinical and diagnostic tools have been somewhat helpful in identifying an at-risk group, particularly those patients sustaining significant neurologic sequelae. In this prospective study, the prognostic significance of multimodality evoked responses in high-risk newborns was examined. A group of 44 high-risk newborns, as well as 14 healthy newborns, were tested during the newborn period with auditory brainstem responses and somatosensory evoked responses; these tests were repeated at 2 and 6 months corrected age. A neonatal neurologic examination, the Einstein Neonatal Neurobehavioral Assessment Scale, was also conducted. At 1 year corrected age, both groups were assessed in a blind fashion by a pediatric neurologist and a psychologist to determine neurodevelopmental outcome. Results indicated that somatosensory evoked response abnormalities in particular predict an abnormal neurologic status at 1 year of age. Abnormalities that persisted or worsened correlated with severe neurologic impairment, whereas an abnormal somatosensory evoked response that improved or normalized in infancy was associated with mild to moderate neurologic sequelae. Increased brainstem conduction in the auditory brainstem responses was also associated with neurologic sequelae. Normal findings from auditory brainstem responses and somatosensory evoked responses predicted normal developmental scores in all areas, as well as a normal neurologic outcome at 1 year with negative predictive powers ranging from 85–100%. Evoked response testing appears to be an important adjunct to the neurologic investigation of high-risk newborns.     

Effect of brainstem auditory evoked potential stimulus intensity variations in neonates of small for gestational age

The latencies of brainstem auditory evoked potentials were compared first in 25 small for gestational age (SGA) neonates (conceptional age less than 43 weeks) matched with 25 appropriate for gestational age (AGA) neonates, and then in the 8 younger SGA neonates (less than 37 weeks) matched with 8 AGA neonates. In this last subgroup the results showed that the I-V interval is shorter in SGA than in AGA neonates, as previously described. This shortening effect is essentially linked to a lengthening of wave I. So the results are discussed in terms of immaturity of the basal end of the cochlea, rather than of precocious development of the auditory brainstem neural function in SGA infants.     

PROGNOSTIC SIGNIFICANCE OF THE AUDITORY BRAINSTEM EVOKED RESPONSE HIGH-RISK NEONATES

The prognostic significance of the auditory brainstem evoked response (ABR) was examined in this prospective study of neonates at risk for neurodevelopmental sequelae. ABR testing was performed in the neonatal period (37 to 45 weeks conceptional age) and at two and/or six months corrected age. 34 high-risk newborns and 14 controls were followed to one year of age, when they received neurological and developmental assessments. Increased I to III and I to V interwave latencies predicted gross motor delay at one year, with a positive predictive power of 83 per cent and a specificity of 94.7 per cent. Increased brainstem conduction, dispersal of waves III to V and V/I amplitude ratio abnormalities predicted abnormal neurological findings at one year, with positive predictive values of 100, 100 and 80 per cent, respectively. A standard clinical examination of the newborn, performed on the at-risk and control infants at 40 weeks conceptional age, was not found to be strongly predictive of neurodevelopmental deficits at one year.     

Transient neurologic abnormalities and BAEPs in high-risk infants

We examined brainstem auditory evoked potentials in 2 neurodevelopmentally different groups of high-risk premature infants during the first year of life. Our 77 patients were considered at birth to be at risk for neurologic disabilities, but were found to have normal development in the second year of life. The patients were divided into 2 groups on the basis of their neurologic findings during the first year of life; 24 of the 77 patients demonstrated transient neurologic abnormalities (group I) and the remaining 53 demonstrated normal neurologic findings through the first year of life (group II). Normative data of brainstem auditory evoked potentials were obtained from 60 low-risk and neurologically normal infants. Group I patients had prolonged III-V and I-V intervals at 2 months of age or younger and poorly detectable waves VI and VII at 5 months of age or younger, compared with control subjects. Wave VI was poorly detected in group II patients only at 35-39 weeks of conceptional age. Brainstem auditory evoked potentials suggested that the patients with transient neurologic abnormalities had transient dysfunction or maturational delay in the brainstem and upper auditory pathway early in the first year of life.     

The diagnostic value of sensory evoked potentials in pediatric Wilson disease

We studied the sensory evoked potentials in pediatric Wilson disease to verify their subclinical neurologic involvement and to elucidate the role of cirrhosis in abnormal evoked potentials in non-neurologic Wilson disease. Thirty children (17 male, 13 female), diagnosed with Wilson disease before 18 years, were enrolled. The mean age during studies was 15.8 +/- 6.3 years, and disease duration since diagnosis was 3.0 +/- 3.3 years. In 12 neurologic Wilson disease cases, there were prolonged interpeak latencies of brainstem auditory evoked potentials III-V, I-V, somatosensory evoked potentials N13-N20 (P < 0.01 vs controls and non-neurologic cases), and P100 latency (P < 0.01 vs controls). All 12 patients had at least one abnormal evoked potential, including 91.7% brainstem auditory, 58.3% somatosensory, and 25% visual evoked potentials. In 18 non-neurologic Wilson disease cases, there were still prolonged interpeak latencies for brainstem auditory evoked potentials I-V and somatosensory evoked potentials N13-N20 (P < 0.05 vs controls), with 27.8% of them having at least one abnormal evoked potential, including 16.6% brainstem auditory, 5.6% somatosensory, and 11.1% visual evoked potentials. In those with non-neurologic Wilson disease, there were no significant differences in all the evoked potential parameters between the cirrhotic and non-cirrhotic patients.     

Multimodality evoked potentials in amyotrophic lateral sclerosis

Visual, brainstem auditory and somatosensory evoked potentials to medial nerve stimulation were recorded in 27 patients affected by amyotrophic lateral sclerosis. VEP N75, P100, N140, N75-P100 latencies and P100 amplitude, BAEP I-III, III-V and I-V interpeak-latencies were within normal limits in all ALS patients. Somatosensory evoked potentials were abnormally delayed in 8 patients: in 3 arms because of a delayed N9-N13 latency, in 9 arms because of a delayed N13-N19 latency.     

Prediction of outcome at school age in neonatal intensive care unit graduates using neonatal neurologic tools

Prediction of outcome for neonatal intensive care unit graduates is clinically useful to counsel families effectively and target those who may benefit from early interventions. Evoked potentials have proven prognostic value of neurologic outcomes in early childhood; however, their long-term predictive validity remains to be determined. The objective of this prospective study was to determine the long-term predictive value of three neonatal neurologic assessments: brainstem auditory evoked potentials, somatosensory evoked potentials, and the Einstein Neonatal Neurobehavioral Assessment Scale. Seventy-eight high-risk newborns and 28 healthy controls were recruited and were assessed in the newborn period using these tests. At 8 to 9 years of age, 42 subjects and 13 controls were re-evaluated for developmental progress using a range of psychologic, sensorimotor, and neurologic measures. Findings indicated that the somatosensory evoked potential was most accurate at predicting outcome at school age, with high specificity (83-100%) across all domains tested and good sensitivity (80-100%) for intellectual performance and sensorimotor abilities. The brainstem auditory evoked potential was limited by false-negatives, whereas the neonatal neurobehavioral assessment yielded many false-positives. This study provides new evidence that associations between neonatal somatosensory evoked potentials and developmental sequelae continue to be significant at school age.     

Evoked potentials in neonates and infants with aseptic meningitis

We investigated 4 infants with aseptic meningitis, 4–38 days of age, by repeated electroencephalography (EEG), flash-visual evoked potentials (F-VEPs), and brainstem auditory evoked potentials. The patients all had mild, acute phases and favorable outcomes at 1–2 years of age. EEGs and F-VEPs obtained within 1 month after onset all were defined as abnormal. In 3 patients, EEG findings were normal 1–2 months after onset, while F-VEP findings were normal at 9–10 months. Brainstem auditory evoked potential findings were normal, except for 1 with otitis media. Evoked potentials suggested that subclinical brain damage, especially due to cortical lesions, persisted during the first year of life in these patients clinically diagnosed with “meningitis.”     

Short-latency somatosensory and brainstem auditory evoked potentials in patients with Parkinson's disease

Short-latency somatosensory evoked potentials (SSEPs) and brainstem auditory evoked potentials (BAEPs) were recorded in 44 patients with Parkinson's disease (mean age 67.3 years) and 23 normal subjects (mean age 69.3 years). Patients with Parkinson's disease and normal subjects did not show any significant difference with regard to the interpeak latencies between N13 and N20 central conduction time (CCTs). Likewise, there were no significant differences in CCTs between patients with and without dementia. The interpeak latencies between waves I and V (I-V IPLs) in patients with Parkinson's disease were significantly longer than those of the normal subjects (p less than 0.05). In particular, patients with dementia revealed significant prolongation of I-V IPLs compared to patients without dementia and normal subjects (p less than 0.01, p less than 0.001) although no significant differences were observed between patients without dementia and normal subjects. These results show that auditory brainstem pathways are involved in Parkinson's disease patients with dementia.     

Evoked potentials in olivopontocerebellar atrophy

Pattern-reveral visual evoked potentials, far-field and cortical somatosensory evoked potentials, and auditory brainstem potentials were recorded in two patients with olivopontocerebellar atrophy. In one patient, visual evoked potentials exhibited prolonged latency and interocular latency differences in the absence of clinical visual dysfunction. Median and tibial nerve evoked cortical potentials were severely attenuated in the absence of somatosensory deficit or peripheral nerve slowing. The far-field somatosensory potentials, however, were well preserved. All components of the auditory brain-stem potentials had latencies within normal limits. In the other, more severely afflicted, patient, all visual, somatosensory, and auditory evoked potentials were abnormal.     

Short- and long-term outcome of severe neonatal nonhemolytic hyperbilirubinemia

We studied the effects of hyperbilirubinemia on brainstem auditory pathways and neurodevelopmental status in 99 full-term neonates with severe nonhemolytic hyperbilirubinemia (total serum bilirubin level = 301 to 500 micromol/L) born between 1995 and 2000. These were divided into three groups: group 1, moderate hyperbilirubinemia (n = 30; mean maximum total serum bilirubin = 320.7 micromol/L or 18.9 mg%); group 2, severe hyperbilirubinemia (n = 63; mean maximum total serum bilirubin = 369.0 micromol/L or 21.7 mg%); and group 3, super hyperbilirubinemia (n = 6; mean maximum total serum bilirubin = 457.2 micromol/L or 26.9 mg%). All received phototherapy, and three neonates also had exchange transfusion. Initial brainstem auditory evoked potentials were recorded in all at the mean age of 3.1 months (range 1-9 months). At initial assessment, only nine neonates (9.1%) had abnormal brainstem auditory evoked potentials. All except two returned to normal at 2 years. These two children had a hearing threshold at 50 nHL. We then compared serial brainstem auditory evoked potentials until 2 years for these nine cases with initial abnormal brainstem auditory evoked potentials, and nine cases with initial normal brainstem auditory evoked potentials were recruited for comparison. All 99 children had regular physical, neurologic, visual, and auditory assessments every 3 to 6 months until the age of 3 years. There was no significant correlation between demographic factors (gender, gestational age, or birthweight), maximum total serum bilirubin, and total serum bilirubin at discharge with an abnormal brainstem auditory evoked potential. There was no significant difference in the rate of brainstem auditory evoked potential abnormalities between the three groups: moderate (10%), severe (7.9%), and super (16.7%). All had normal neurodevelopmental status at 3 years. Only two children had transient mild motor delay and hypotonia, and both had normal brainstem auditory evoked potentials. There was no relationship between the abnormalities of the brainstem auditory evoked potentials and neurodevelopmental status. None of the three children receiving exchange transfusion had abnormal brainstem auditory evoked potentials or neurodevelopmental outcome. With the neurophysiologic and clinical outcomes in our cohort with severe nonhemolytic hyperbilirubinemia, we propose that the toxic effect of hyperbilirubinemia on auditory brainstem pathways might be transient provided that prompt treatment is initiated.     

Somatosensory evoked potentials and auditory brain-stem responses in congenital hypothyroidism. I. A longitudinal study before and after treatment in six infants detected in the neonatal period

We report the results of a longitudinal study of auditory brain-stem responses (ABRs) and somatosensory evoked potentials (SEPs) performed in 6 children with congenital hypothyroidism. These infants were detected by the Quebec Network for Genetic Medicine and treated early. ABRs and SEPs were recorded both before and 2 weeks after the initiation of therapy and at 6 months of age. Before treatment, for SEP, we found increased wave N19, P22 latencies and N13-N19, N19-P22 interpeak latencies (IPLs) in congenital hypothyroid (CH) children. For ABR, there were increased wave I latencies with normal I-V IPLs. Substitutive therapy improved these abnormalities although this improvement was more evident after a shorter period of time for ABRs than for SEPs. Even at 6 months, 2 CH children still showed increased N13-N19 IPLs. Both had very low serum T4 levels at the time of diagnosis and one had also a very small knee surface area, both criteria indicating a severe hypothyroidism. It will be interesting to verify if initial and persisting increase of N13-N19 IPL is associated with later neuropsychological problems.     

Hemicraniectomy for massive cerebral infarction: Evoked potentials as presurgical prognostic factors.

In patients with massive hemispheric infarctions, mortality exceeds 80% with medical therapy alone. In certain conditions hemicraniectomy may result in meaningful survival. We studied presurgical clinical and electrophysiological parameters that may serve as prognostic factors to assess efficacy of decompressive surgery. We evaluated 26 consecutive patients with severe focal neurological deficit, deterioration of consciousness, and massive hemispheric infarction by cranial computerized tomography who underwent hemicraniectomy. Clinical examination included pupillary size and reaction, and determination of level of consciousness on an hourly basis. Median nerve somatosensory evoked potentials and brainstem auditory evoked potentials were obtained before and after hemicraniectomy. Outcome was assessed by using the Barthel Index. Clinical and evoked potential data were correlated with the outcome. Fisher's Exact Test was applied to establish statistical significance. With surgery 18 of 26 patients survived on an average intensive care treatment of 29.6 (+/-27.5) days. Barthel Index at discharge was 61.7 (+/-24.4) in survivors. Presurgical pupillary reaction, level of consciousness, and somatosensory evoked potentials were not found to correlate with outcome. In contrast, presurgical brainstem auditory evoked potentials showed a significant correlation with survival (P<.05). All patients with good outcomes (Barthel Index >/=60: n=12, 46.1%) had normal brainstem auditory evoked potentials before surgery. Clinical parameters did not reliably forecast prognosis in patients with massive cerebral infarction treated with hemicraniectomy.     

Auditory brainstem responses in congenital heart disease

To evaluate the effect of chronic hypoxemia on brainstem maturation, auditory brainstem responses were examined in 70 children (32 with and 38 without cyanosis) who had congenital heart disease. Ninety-one age-matched normal children served as controls. At 1–3 months of age, the I–V interpeak latencies of cyanotic infants (mean ± S.D.; 5.17 ± 0.17 ms) were more prolonged than were those of controls (4.95 ± 0.11 ms) and those without cyanosis (4.84 ± 0.22 ms; P < .05; P < .01). At 4–11 months of age, the I–V interpeak latencies of cyanotic infants (4.85 ± 0.13 ms) were more prolonged than were those of controls (4.67 ± 0.19 ms) and those not experiencing cyanosis (4.5 ± 0.17 ms; P < .05; P < .01). In the cyanotic children, there was a significant negative correlation between the I–V interpeak latency and oxygen partial pressure (P < .01) or oxygen saturation (P < .05). Three of the 70 patients (4.3%) with congenital heart disease had absent auditory brainstem response. These data indicate that chronic hypoxemia may be one of the factors in retarded brainstem maturation.     

Relationship of cranial ultrasonography, visual and auditory evoked responses with neurodevelopmental outcome

Sixty-two preterm infants were followed up with flash visual evoked responses (VERs), brainstem auditory evoked responses (BAERs) and neurodevelopmental assessments for 18 months after term. Cranial ultrasonography showed that 18 infants developed intraventricular haemorrhage (IVH) during the newborn period and four of six infants with grade III or IV haemorrhage had absent VERs at term. The mean latency of the VER in the infants with IVH was significantly shorter than that of infants without IVH. There was no correlation between the degree of ventricular dilatation at term and the latency of the VER. Six months after term the four infants with previously absent VERs had normal responses, though there was still a significant difference between the latencies of infants with and without IVH. At 12 and 18 months of age these differences had disappeared. BAERs were not significantly different in the infants with and without IVH, and there was no difference in the VERs or BAERs of infants with neurodevelopmental delay and those developing normally. Neither flash VERs nor BAERs provide a good prognostic indicator of future neurodevelopmental disability or outcome.     

The importance of brain stem evoked potentials in the diagnosis of neurosurgical patients]

The technique of Brainstem Electric Response Audiometry (BERA) is a non-invasive electrophysiologic method used in comatose patients for localization of areas of neuronal and synaptic dysfunction not evident in clinical evaluation. This test has a diagnostic and prognostic value in detection of abnormalities and evaluation of comatose head-injured patients at a reversible clinical stage. In contrast to most clinical signs, brainstem auditory evoked potentials are independent of levels of consciousness, analgesics, sedatives. This test is aetiologically non-specific and must be carefully integrated into the clinical situation. Generators of brainstem auditory evoked potentials are located in the auditory nerve (waves I and II) and brainstem (waves III-V). Patients in acute posttraumatic coma are assessed by means of Glasgow Coma Score (GCS), which is reliable in forecasting a favourable outcome. Patients with a score 8 points have an unfavourable outcome in 16%. Brainstem auditory evoked potentials are reliable predictors of unfavourable outcome. Subsequent brainstem auditory evoked potential testing provides relevant prognostic information, since improvement of graded brainstem auditory evoked potentials indicates a favourable outcome. Progressive deterioration of brainstem auditory evoked potentials indicates irreversible damage and is associated with unfavourable outcome, whereas singular abnormal evoked potentials may result from reversible neuronal dysfunction. The absence of waves III-V associated with the end EEG activity is the proof of brain death. Serial BERA monitoring has been used to evaluate progressive clinical syndromes, such as "uncal herniation" and evolving brain death. The use of serial BERA recordings appeared to improve the outcome predictions in comparison with single BERA tests. A combination of brainstem auditory evoked potentials, somatosensory and visual evoked potentials (multimodality evoked potentials-MEP) provides more information for management of a patient than a single evoked potential modality. The main goal to use BERA is early detection of secondary deterioration in comatose patients suffering from intracranial lesions. The results of brainstem auditory evoked potentials and clinical examination of patients obtained within the acute phase after head injury may indicate increased intracranial pressure (ICP) and incipient transtentorial herniation but do not always predict outcome (GOS). The outcome can be better evaluated later, 3-6 days after head injury. In summary, BERA is a non-invasive, safe and objective method of evaluating patients after severe head injury and adds valuable information for assessment of their outcome.     

Longitudinal clinicoelectrophysiologic study of a case of Lafora disease proven by skin biopsy

A longitudinal clinicoelectrophysiologic study was undertaken of a 15-year 2-month-old girl with Lafora disease who was diagnosed by skin biopsy and an immunohistochemical method with antisera against Lafora bodies. From age 10 years 5 months, 4 months after onset, EEG disclosed progressive deterioration of background activity and incremental increase in epileptic discharges. Photosensitivity was unique: Occipital spikes and diffuse spike-wave discharges were provoked by low-frequency repetitive photic stimuli but without elicitation of myoclonic seizures. Photosensitivity completely disappeared after age 13 years 10 months. High-voltage somatosensory evoked potentials (SEPs) and high-voltage flash visual evoked potentials (F-VEPs) were seen before age 13. After age 13, progressive prolongation of I-III and I-V interpeak latencies of auditory brainstem responses (ABRs), progressive prolongation of latencies of photoevoked eyelid microvibrations, delayed latencies of pattern-reversal visual evoked potentials, and a decrease in the V/I amplitude ratio of ABRs and the previously high F-VEP amplitudes were observed.     

A Longitudinal Study Of Brainstem Auditory Evoked Potentials Of Preterm Infants

Brainstem auditory evoked potentials (BAEPs) of nine 'healthy' preterm infants were recorded at weekly intervals between 32 and 36 weeks conceptional age to study the relationship between stimulus intensity and central transmission time through the subcortical auditory pathway (i.e. the interval latency between peak I and peak V) as a function of conceptional age. Stimulus intensities of 70, 80 and 90 dB nHTL were used. Changes in click intensity produced changes in the absolute latency of all BAEP peaks, but the interval latency I to V remained constant. The absolute latencies and interval latencies reflected maturity, but varied widely between these preterm infants. The peak V latency and the I to V interval latency decreased with increasing conceptional age. Exponential regression analysis suggested that, above 70 dB nHTL, the time-constant of the calculated exponential function most likely represents maturation and function of the central subcortical pathway, and may give an indication of the infants' development.     

Cerebrotendinous xanthomatosis: 11-year treatment with chenodeoxycholic acid in five patients. An electrophysiological study

We report the electrophysiological follow-up of five cerebrotendinous xanthomatosis patients treated for 11 years with chenodeoxycholic acid (CDCA). Nerve conduction velocity (NCV) was reduced in three cases. P100 latency of visual evoked potentials was delayed in four cases, interpeaks I–III and I–V of brainstem auditory evoked potentials (BAEPs) was increased in two and interpeak N13–20 of upper limb somatosensory evoked potentials (SEPs) was slowed in one. After 4 months of therapy with CDCA, NCV was normal and did not show any significant change during the 11 years of observation. Central motor conduction time of motor evoked potentials (MEPs) and N24–P40 interpeak latency of lower limb SEPs were increased in five and four cases, respectively, in spite of 2/3-year treatment with CDCA. Improvement of evoked potentials, especially of MEPs and SEPs, was slower and continued over the whole 11-year period. The size of xanthomas slightly decreased in some patients during treatment and the clinical manifestations stabilized, avoiding progressive worsening, but there was no significant improvement in neurological deficit. Two sisters of patients who never took CDCA showed progressive worsening of clinical manifestations, upper limb SEPs and BAEPs.     

Electrophysiologic study of Fisher syndrome

Electrophysiologic studies were performed on a 6-year-old girl with Fisher syndrome. We recorded several evoked potentials in this patient: visual evoked potentials, auditory brainstem responses, auditory evoked potentials, short-latency somatosensory evoked potentials, blink reflex elicited by photic stimuli (photo-evoked eyelid microvibration), blink reflex elicited by auditory stimuli (auditory evoked eyelid microvibration), and motor nerve conduction velocity. In our study, photo-evoked eyelid microvibration response was not obtainable; laterality was indicated in visual evoked potential and electroencephalographic studies, and the remaining evoked potentials demonstrated normal responses. The results obtained from the brainstem reflex (photo-evoked eyelid microvibration) suggest that the pathologic focus of Fisher syndrome is located in the midbrain, particularly in the pretectum. It is expected that the combined use of these electrophysiologic techniques may facilitate differentiation between Fisher and Guillain-Barré syndromes.