Longitudinal study of auditory brainstem response in leigh syndrome

To assess the utility of auditory brainstem response (ABR) in diagnosing brainstem changes in patients with Leigh syndrome (LS), we performed a longitudinal study of five patients with LS using both ABR and neuroimaging techniques (CT and MRI). The brainstem components of the initial ABRs we performed on the patients were abnormal in all five patients. In four of the patients, these abnormal findings preceded any clinical signs of brainstem impairment. Improvements in clinical findings were reflected in improvements in ABR findings in three patients. In one of these three patients, improvements in clinical findings were also reflected in improvements in MRI findings. In the other two patients, MRI findings showed no improvements, despite the improvements in clinical findings. In two of our patients, ABR clearly revealed functional improvements in the brainstem which were not revealed by MRI. Therefore, we conclude that ABR is an essential diagnostic technique for patients with LS.     

A comparison of the three-dimensional auditory brainstem response and the conventional auditory brainstem response in children

For measurement of neural activity in the brainstem auditory pathway, the conventional two-dimensional (2D) auditory brainstem response (ABR) does not provide a true response, because the equivalent dipoles originate from the stereoregularity pathway. It is thus necessary to use three-dimensional (3D) ABR to estimate the true response of the brainstem. We recorded 3D ABR in a group of children and adults, and compared the results with those of the conventional 2D ABR.

The subjects were 22 children (age range 3–10 years) and 10 adults with no neurological disorders, and three patients: a boy and a girl who had experienced sudden brainstem dysfunction, and a girl who had sudden deafness. 3D ABR was recorded for all subjects, and the results were displayed on a computer screen for off-line analysis using an original 3D ABR analysis program.

Four leaf-like vector segments of 3D ABR existed during the first 8 ms after stimulation. Each vector segment corresponded to a peak of the conventional ABR, and showed the original directivity. The amplitudes of waves II and IV of the 3D ABR were significantly larger than those of the conventional ABR. 3D ABR was shown to be superior to the conventional ABR in obtaining absolute amplitude. We were able to clarify the development of brainstem function using 3D ABR. In one patient in whom only one wave was obtained, 3D ABR was able to identify the wave as wave V. These results indicate that ABR is useful both for identifying the kind of wave produced and for suggesting the wave origin.     

Auditory brainstem response and somatosensory evoked potential in Machado-Joseph disease in Japanese families

To clarify physiological aspects of Machado-Joseph disease (MJD), we studied auditory brainstem response (ABR) and somatosensory evoked potential (SEP) in 17 clinically diagnosed patients with MJD aged 32-64 in Japanese families. ABR was recorded in 13 patients. In 8 patients, ABR were abnormal. In 5 patients, the latency of I wave was normal, but other waves could not be evoked. In the other 3 patients, I-III interpeak latency was prolonged. SEP was recorded in 15 patients. In SEP of median nerve, 11 patients had abnormal findings, and SEP of posterior tibial nerve revealed abnormal findings in all 15 patients. In all patients, responses from Erb's point and popliteal fossa were normal in latency, but other peaks were low in amplitude or absent, and the latency and central conduction time (CCT) were prolonged. The result of ABR indicated the involvement of the brainstem auditory pathways in MJD, and the result of SEP suggested that somatosensory pathways, particularly central pathways, would be involved in the disease process. ABR and SEP can be potential diagnostic methods for detection of subclinical abnormality in MJD 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.     

Auditory and vestibular system findings in patients with vertebrobasilar dolichoectasia

Impairment of the auditory-vestibular system has been reported in patients with vertebrobasilar dolichoectasia (VBD), but little is known about the underlying cause of the symptoms. Auditory testing (pure tone audiometry, auditory brain stem response and stapedius reflex) and vestibular tests (assessment of nystagmus, eye tracking tests, caloric test and rotational test) were performed in 23 patients with auditory-vestibular symptoms and/or cranial nerve impairment associated with VBD. Specific evidence of auditory and/or vestibular system impairment was observed in 19 cases (83%). Among patients with abnormal test findings, 47% had evidence suggesting peripheral impairment, 16% evidence suggesting central dysfunction, and 37% evidence suggesting both peripheral and central dysfunction. Although compression of the vestibulocochlear nerve plays an important role in the genesis of the auditory-vestibular dysfunction in patients with VBD, mechanism such as brain stem-cerebellar ischemia and impaired blood supply to the vestibular labyrinth may be just as important.     

Cranial nerve function in workers exposed to polychlorinated dioxins and furans

OBJECTIVE: To look for possible effects of polychlorinated dioxins and furans (PCDD/F) on cranial nerve function. MATERIAL AND METHODS: Clinical and neurophysiological examinations [visual and brainstem auditory evoked potentials (VEP and BAEP), blink reflex] in 121 PCDD/F exposed workers of one pesticide producing plant. RESULTS: BAEP abnormalities were more frequent in workers with chloracne (6 of 33 workers, 18.2%) than in those without chloracne (7 of 84, 8.3%), but this was not statistically significant (chi2: 2.33). VEP abnormalities were seen in one worker with and two without chloracne. Clinically visual functions were normal except in one worker, who was amaurotic since birth. Blink reflex abnormalities without corresponding clinical findings were observed in two patients without chloracne. CONCLUSION: Severe exposure to PCDD/F is not followed by clinical signs of cranial nerve dysfunction but may create an increased risk for abnormal BAEP findings, which were more than twice as common in workers with chloracne. Although this difference did not reach statistical significance, it cannot exclude a toxic effect of PCDD/F, as statistical significance is difficult to achieve with such small numbers of workers. In none of the workers, BAEP abnormalities were accompanied by clinical signs of hearing dysfunction.     

Vestibular function in severely retarded children in relation to their motor disabilities

We examined vestibular functions of thirty-one severely retarded children with caloric test and rotation nystagmus test, in combination with auditory brainstem response (ABR) recordings and measurement of brainstem width on cranial CT scans. The laterality of vestibular response was over 20% in most of the bedridden cases and was under 20% who could move. Abnormal findings in ABR had no relationship with the degree of motor disabilities, but decreased width of brainstem on CT scan showed some relationship with the degree of motor disabilities. We conclude that vestibular function tests are useful to predict future motor development in severely retarded children.     

Hereditary neuronal intranuclear inclusion disease with autonomic failure and cerebellar degeneration

BACKGROUND: Neuronal intranuclear inclusion disease (NIID), a multiple-system degeneration, occurs usually as a sporadic disorder with onset in childhood. The disease has been found in monozygotic twins and in siblings. In 2 previously described families, the disorder has affected 2 generations. OBJECTIVE: To investigate the clinical, anatomical, and electrophysiological characteristics of NIID that affect the central nervous system and the central and peripheral components of the autonomic nervous system in 2 successive generations of a family. DESIGN: Case report. SETTING: Tertiary care hospital. PATIENTS: A 53-year old woman and her sons, aged 28 and 25 years. Symptoms began in childhood in 2 of the 3 cases, and consisted of urinary and fecal incontinence, erectile dysfunction in the men, and recurrent orthostatic hypotension. METHODS: We used results of clinical neurological evaluations; cranial magnetic resonance imaging; skeletal muscle and sphincter electromyography (EMG); peripheral nerve conduction and bulbocavernosus reflex studies; autonomic function tests; brainstem, visual, somatosensory, and motor evoked potentials; auditory and vestibular testing; metabolic and molecular genetic testing; and muscle and rectal biopsy with immunohistochemistry. RESULTS: We found variable degrees of ocular dysmetria in 2 cases, ataxic dysarthria and limb ataxia in 1, and hyperreflexia in 2. Magnetic resonance imaging revealed cerebellar atrophy in all 3 cases and diffuse cerebral cortical atrophy in 1. Results of peripheral nerve conduction studies were normal. Sphincter EMG findings were abnormal in 2 of the 3 cases, and results of autonomic function tests were abnormal in the same 2. The EMG in 1 case revealed a chronic neurogenic pattern in the distal limb muscles. Metabolic and molecular genetic testing revealed no abnormal findings. Results of the muscle biopsy were negative, but results of the rectal biopsy revealed eosinophilic ubiquitinated intranuclear inclusions in neurons. CONCLUSION: Transmission of NIID in 2 generations presenting with autonomic failure and cerebellar ataxia was hereditary.     

The maturation of the auditory brainstem response compared to peripheral nerve conduction velocity in preterm and full-term infants

The maturation of the auditory brainstem response in preterm and full-term infants is compared with that of nerve conduction velocity. There is a linear relationship between wave I latency, the peripheral component of the response, and nerve conduction velocity, but the negative correlation is not high. A poor negative correlation exists between the I-V interval, an index of brainstem transmission, and nerve conduction velocity. The factors governing the maturation of central transmission along the auditory pathway in the brainstem are not related to myelination of peripheral nerves. Abnormal nerve conduction velocities are not related to any particular abnormal brainstem response in a stable external environment.     

Unilateral multiple cranial nerve palsies mimicking Garcin syndrome as an atypical symptom of brainstem encephalitis: a case report]

We report a 56-year-old Japanese man who was admitted because of dysphagia and left side facial dysesthesia. On admission, his general conditions were unremarkable. Neurological examination revealed that he was alert and well oriented. He exhibited left-side cranial nerve involvement such as the trigeminal(sensory and motor), glossopharyngeal and potential vagal nerve palsy. He exhibited neither long-tract signs, such as motor weakness, sensory disturbance in his exremities and pathological reflex, nor ataxia. By a few days after admission, his symptoms had worsened. Vertigo and diplopia appeared, and his consciousness level became drowsy. Bilateral third and sixth nerves, left fourth, fifth, eighth, ninth and tenth nerves were involved. Results of laboratory tests and CSF studies were within normal. Results of examination of the skull base X-ray and MRIs of the brain were normal. Administration of corticosteroid and intravenous administration of a high dose of gamma-globulin were not effective. His symptoms gradually recovered three months after admission. Based on clinical symptoms and results of physiological examination, i.e., an involvement of his consciousness and abnormal findings in blink reflex test that suggest involvement of the brainstem, he was diagnosed as having brainstem encephalitis. Although the exact pathophysiological mechanisms were unclear, it is clinically important to note that an atypical brainstem encephalitis may present a subacute progressive appearance of unilateral multiple cranial nerve palsies mimicking Garcin syndrome.     

Normalization of poor auditory brainstem response in infants and children

In these past 10 years, the usefulness of auditory brainstem response (ABR) has been demonstrated in the clinical evaluation of audiological or neurological disorders, and the absence of an ABR is commonly accepted as consistent with a peripheral hearing loss caused by middle or inner ear diseases. In this article, the authors report nine infants and children who had an absent or difficult to detect ABR at the first examination with subsequent normalization of ABR. Repeated otological examinations were always normal in these patients. The final diagnoses were delayed development, Waardenburg syndrome with congenital heart disease and epilepsy, healthy infant, infantile convulsion, mental retardation with history of low birth weight, in each case, and chromosomal aberration in four patients. The reason for normalization of ABR in our patients is not clear and is yet to be ascertained. However, the authors believe that neurological maturation rather than an improved primary peripheral disorder is responsible for the noted normalization of the ABR, because of the high incidence of neurological abnormalities in these patients.     

Electrophysiological studies in siblings of De Sanctis-Cacchione syndrome

Multi-modality evoked potentials in two cases, who were siblings, of De Sanctis-Cacchione syndrome were reported. The case 1, who was elder sister of the case 2, was a 25-year-old female. And the case 2 was a 23-year-old female. They have the history of consanguinity. They were first noted to have skin erythema on exposure to sunlight, and a diagnosis of xeroderma pigmentosum was made. At the childhood neurological manifestation, such as mental retardation, deafness and muscular weakness developed gradually. The case 2, who was a elder sister, was operated on for squamous cell carcinoma of the eyelid at the age of 20 and 21 years old. Motor conduction velocity obtained from lower limbs were severely reduced and that from upper limbs were moderately delayed. Sensory conduction velocity of median nerve were severely diminished. Auditory brainstem responses (ABR) of the case 1 showed the prolongation in interpeak latency of I-V. ABR of the case 2 could not be obtained. N19 and N13 of short-latency somatosensory evoked potentials (SSEP) to median nerve stimulation with case 2 could not be obtained too. N13-N19 latency of case 1 was remarkably prolonged compared to the normal subjects. Central motor conduction time (CMCT) was studied in case 2 by using the magnetic stimulator. CMCT of case 2 was within the upper limit of normal control. Interpeak latency of I-V in ABR represents the brainstem dysfunction in auditory pathway, and interpeak latency of N13-N19 in SSEP was recognized as central conduction time from medial lemniscus to primary sensory area of cortex. So the prolongation of these interpeak latency in this cases may mean the dysfunction in the central nervous system.(ABSTRACT TRUNCATED AT 250 WORDS)     

Auditory brain-stem response in zitter rats with genetic spongiform encephalopathy.

Zitter rats with genetic spongiform encephalopathy and hypomyelination developed an abnormal auditory brain-stem response (ABR) before the appearance of spongy lesions in the central nervous system (CNS). The ABR abnormalities were characterized by a dual peak of wave I, with a longer latency than in normal rats, and decreased or absent waves III and IV. Hypomyelination in both peripheral and central nerves may have been responsible for these abnormalities. The slow negative wave became wide and obscure with aging. These changes accompanied age-dependent progression of spongy changes in the CNS. These findings suggest that at least two mechanisms, one involving hypomyelination and the other causing spongy lesions, are responsible for the brain-stem auditory pathway dysfunction in zitter rats.     

Spectral analysis of heart rate variability in the dysfunction of the brainstem

The heart rate variability, modulated by autonomic nervous system, has been reported to decrease in depression of the central nervous system, especially of the brainstem. To assess the brainstem dysfunction, we analyzed R-R interval values (the intervals between R waves of ECG) in 9 children (7 in comatose children and 2 in central apnea) by spectral analysis using an autoregressive model. The findings of spectral analysis were compared with those of auditory brainstem response (ABR). In comatose children with the brainstem dysfunction, the reduction of the total power was apparent before the appearance of ABR abnormality. In central apnea due to the dysfunction of respiratory center in brainstem, only the respiratory component decreased without the reduction of the total power or ABR abnormality. Spectral analysis of the heart rate variability is a useful means for assessment of the brainstem function.     

Auditory brainstem evoked responses in autistic children

Auditory brainstem evoked responses (ABRs) were studied in 16 autistic children. Three children had severe delays in wave I latency, indicating defective functioning of the peripheral auditory pathway. The remaining subjects also had delayed wave I latency but only for right ear stimulation at the lowest stimulus intensity. Eight autistic children (and no control subjects) had ABR transmission time values 3 SDs beyond the normal mean, suggesting auditory processing defects peripheral to or within the brainstem auditory pathway. These findings (1) may have no causal relationship to the child's autistic handicaps, (2) may represent distortions in auditory input that impair the learning of language, and (3) may reflect an earlier state in which abnormal input directly caused maldevelopment of forebrain systems necessary for language and cognitive function.     

Evaluation of hearing and auditory nerve function by combining ABR, DPOAE and eABR tests into a single recording session

In this article, we describe an efficient method for testing both auditory receptor and auditory nerve function in a single recording session. Auditory receptor function is tested in response to pure tone, tone burst and click acoustic stimuli (i.e. distortion products of otoacoustic emissions, DPOAE; and auditory-evoked brainstem responses, ABR). The function of the auditory neurons and nerve is measured in response to direct electric current stimulation (i.e. electrically evoked auditory brainstem responses, eABR). All measurements were obtained from anesthetized laboratory rats during single recording sessions using hardware and software stimulation and analysis programs developed by Intelligent Hearing Systems, Miami, FL.     

COMPARISON OF REFLEX MODIFICATION PROCEDURES AND AUDITORY BRAINSTEM RESPONSE IN HIGH-RISK NEONATES

This study compared the results of reflex modification (RM)--an objective technique for assessing brainstem sensorineural processing--with those of auditory brainstem response (ABR) for a group of high-risk infants at comparable postconceptional ages. For the RM procedure, an eyeblink-eliciting tap to the glabella was presented either alone or accompanied by a brief 90dB SPL tone. 37 high-risk infants were tested with both RM and ABR at a mean postconceptional age of 37.3 weeks. Seven had an increased brainstem conduction time ('failed ABR') and eight did not exhibit significant reflex augmentation ('failed RM'), seven of whom also failed the ABR. These data provide evidence that sensory stimuli which affect the neural mechanisms responsible for the organization of the startle response and auditory processing share essential neural components.     

Isolated cranial nerve palsies in multiple sclerosis

During a 10 year period 24 patients with definite multiplesclerosis with isolated cranial nerve palsies were studied (third andfourth nerve: one patient each, sixth nerve: 12 patients, seventhnerve: three patients, eighth nerve: seven patients), in whom cranialnerve palsies were the presenting sign in 14 and the only clinical signof an exacerbation in 10 patients. MRI was carried out in 20 patientsand substantiated corresponding brainstem lesions in seven patients(third nerve: one patient, sixth nerve: four patients, eighth nerve:two patients). Additional abnormal findings of electro-oculography, ormasseter reflex, or blink reflex, or combinations of these were foundin 20 patients and interpreted in favour of a brainstem lesion at thelevel of the respective cranial nerve. In 11 of 14 patients withisolated cranial nerve palsies as the presenting sign of multiplesclerosis, dissemination in space was documented by MRI, and in theremaining three by evoked potentials. In patients with multiplesclerosis with isolated cranial nerve palsies, MRI is the mostsensitive method of documenting dissemination in space andelectrophysiological testing the most sensitive at disclosing brainstem lesions.

     

Neurophysiologic study of olivopontocerebellar atrophy with or without glutamate dehydrogenase deficiency

By neurophysiologic investigations, we evaluated 20 patients with olivopontocerebellar atrophy (OPCA), comprising 8 with glutamate dehydrogenase (GDH) deficiency and 12 with normal GDH activity. We found sensorimotor, predominantly sensory axonal neuropathy distally in the legs, and peripheral auditory nerve dysfunction (prolonged wave I but normal interpeak latencies in brainstem auditory evoked response) in GDH-deficient patients. These findings seem distinctive enough to serve as the electrophysiologic marker for diagnosis and monitoring of treatment and progression of the disease. The pattern-reversal visual and median nerve somatosensory evoked responses did not differ among the patients and controls.     

Early dietary treatments with Lorenzo's oil and docosahexaenoic acid for neurological development in a case with Zellweger syndrome

We treated a girl with Zellweger syndrome using a special infant formula supplemented with middle chain triglyceride (MCT) milk, docosahexaenoic acid (DHA), Lorenzo's oil, and Lunaria oil, which is rich in nervonic acid (C24:1). We examined the fatty acid contents of the plasma and red blood cell (RBC) membrane. Neurological development was evaluated using Denver developmental screening test and auditory brainstem response (ABR). Her delayed neurological development, liver dysfunction, and cholestasis were all improved 2 weeks after starting the dietary treatment. DHA level in RBC membranes was increased and very long chain fatty acid (VLCFA,C26:0) levels were decreased. Our findings suggest that the dietary treatment with combination of MCT milk, DHA, Lorenzo's oil, and Lunaria oil in the patients with Zellweger syndrome bring some benefits for neurological development.