Neurological and pathophysiological analyses of patients with absent auditory brainstem evoked response

Seventeen patients with no auditory brainstem evoked response (ABR) who suffered from various neurological disorders were reported. We evaluated the possibilities of co-existent brainstem lesions in addition to the peripheral impairment in the auditory pathway, by assessing neurological findings and other laboratory examinations, including cranial CT and electrically elicited blink reflex. Patients who showed cranial nerve symptoms other than that of the acoustic nerve or abnormal postural reflexes were suspected to have brainstem dysfunction. It was difficult, however, to exclude the influence from the dysfunction in the more central level CNS. Definite brainstem atrophy was revealed radiologically only in one case who was at the end stage of the degenerative disease. Blink reflex was studied in eleven cases, four of whom revealed abnormal responses, also suggesting brainstem dysfunction. All the five cases, consistent with these abnormal laboratory findings, had shown severe delay in motor development. Other five patients who showed rather good auditory behavior were considered to have 'desynchronization' response to ABR in the auditory pathway at the peripheral level. Many pathophysiological conditions may be involved in the phenomenon of absent ABR, which should be carefully evaluated from the viewpoints of clinical neurology.     

Five patients with a recently described novel leukoencephalopathy with brainstem and spinal cord involvement and elevated lactate

Recently, a novel leukoencephalopathy syndrome was described in eight patients with a distinct pattern of MRI abnormalities. Here we describe the clinical, laboratory, and MRI findings in five new, unrelated patients. The clinical picture was homogeneous with onset in childhood, a slowly progressive course, variable mental deficits, signs of pyramidal and cerebellar dysfunction and sometimes dorsal column dysfunction. In two patients, a minor head trauma was followed by neurological deterioration and fever. No underlying metabolic defect was found. In two patients serum lactate was elevated, but no evidence of a mitochondrial defect was found. MRI showed variably extensive, diffuse, or spotty cerebral white matter abnormalities and a selective involvement of particular brainstem tracts. The tracts involved included the pyramidal tracts, sensory tracts, superior and inferior cerebellar peduncles, and intraparenchymal trajectories of the trigeminal nerve. In four patients spinal MRI was performed and revealed involvement of tracts over the entire length depicted. Single voxel proton MRS in three patients revealed increased lactate within the abnormal white matter. The uniform and highly characteristic MRI findings, in combination with the similarities in clinical and MRS findings, provide evidence for a distinct nosological entity.     

Autosomal dominant diffuse leukoencephalopathy with neuroaxonal spheroids

OBJECTIVE: To provide clinical, MRI, and histopathologic findings in a rare white matter disorder with autosomal dominant inheritance, so-called hereditary diffuse leukoencephalopathy with spheroids (HDLS). BACKGROUND: Progressive leukoencephalopathies often constitute a diagnostic dilemma in both children and adults. In some cases, histopathologic examination of brain tissue is required for a classifying diagnosis. METHODS: Clinical history, MRI, and autopsy findings were reviewed in three patients with HDLS: a father, his daughter, and an unrelated patient. RESULTS: Clinical history consisted of an adult-onset neurologic deterioration with signs of frontal lobe dysfunction, epilepsy, spasticity, ataxia, and mild extrapyramidal disturbances. MRI findings included cerebral atrophy and patchy white matter changes, most pronounced in the frontal and frontoparietal area with extension through the posterior limb of the internal capsule into the pyramidal tracts of the brainstem. Autopsy in two patients revealed a leukoencephalopathy with frontoparietal and frontal preponderance and numerous neuroaxonal spheroids in the abnormal white matter. The pyramidal tracts were affected throughout the brainstem. CONCLUSION: Similar clinical and histopathologic findings have been reported in members of a Swedish pedigree. The homogeneity of the findings strongly suggests that HDLS is a distinct disease entity. In the absence of a biochemical or genetic marker, a definitive diagnosis requires histopathologic confirmation in one of the affected family members. Neuroaxonal spheroids.     

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.     

Clinicophysiological study of multimodality evoked potentials and computed tomographic findings in persistent vegetative state

The auditory brainstem response (ABR), short latency somatosensory evoked potential (SSEP) and visual evoked potential (VEP) of patients in the persistent vegetative state (PVS) are reported, and the correlations between the electrophysiological findings and the CT scan findings with the three clinical grades of the PVS (transitional, incomplete and complete vegetative syndromes) are discussed. Twenty two patients in a vegetative state caused by subarachnoid hemorrhage (3), hypertensive intracerebral hemorrhage (5), cerebral infarction (6), head injury (3), cerebral anoxia (4) and brain tumor (1). Each evoked response was evaluated for the presence or absence of abnormalities and assigned a grade ranked I to III. Briefly an evoked response was assigned a grade I, II, III if it satisfied the respective criteria of normal, moderately abnormal and severely abnormal or absent electrical activity. On the other hand CT scan findings in the PVS were evaluated for abnormal low density areas, ventricular dilatation and enlargement of the sulci and cisterns indicative of atrophy of the brain parenchyma. SSEP and VEP were better correlated with the clinical grade than ABR, and upper brainstem atrophy and abnormal low density area in CT scan findings were more valuable as an index to expresses the clinical features than ventricular dilatation. On the basis of these results, it is concluded that studies of ABR, SSEP and VEP associated with CT scan findings in the PVS could be a useful diagnostic aid to evaluate the lesions of these patients.     

Phenotypic patterns of MELAS/LS overlap syndrome associated with m.13513G>A mutation,and neuropathological findings in one autopsy case

The 13513G>A mutation in the ND5 gene of mitochondrial DNA (mtDNA) is usually associated with mitochondrial encephalomyopathy with lactate acidosis and stroke‐like episodes (MELAS), or Leigh syndrome (LS). In this study, we describe three young Chinese patients with MELAS/LS overlap syndrome who carried the m.13513G>A mutation. Clinical and MRI features were characteristic of both MELAS and LS. Interestingly, the clinical presentation of this overlap syndrome could be variable depending on the degree of relative contribution of MELAS and LS, that is, MELAS as the initial presenting syndrome, LS as the predominant syndrome, or both MELAS and LS appearing at the same time. The final brain MRI showed findings characteristic of both MELAS and LS, with asymmetrical lesions in the cortex and subcortical white matter of the occipital, temporal, and frontal lobes (MELAS), and bilateral and symmetrical lesions in the basal ganglia and brainstem (LS). Brain autopsy in one case revealed infarct‐like lesions in the cerebral cortex, basal ganglia and brainstem, providing further insight into the distribution of the pathological lesions in MELAS/LS overlap syndrome. This is the first report of the brain pathological changes in a patient with m.13513G>A mutation. The spatial distribution of infarct‐like lesions in the brain could explain the symptoms in MELAS/LS overlap syndrome.     

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.

     

Comparison of MRI and electrophysiological studies for detecting brainstem lesions in traumatic brain injury

The yield of magnetic resonance imaging (MRI) and electrophysiological studies in detecting brainstem lesions was assessed in 35 patients suffering from traumatic brain injury (Glasgow Coma Scale, 3-10). As an inclusion criterion, all patients had brainstem trauma as revealed by early MRI or electrophysiological studies. Of the 35 cases, 7 (20%) had brainstem lesions detected by MRI only, whereas in 10 patients (29%), electrophysiological examination disclosed impairment of brainstem function with normal MRI. In 18 (51%) subjects, both diagnostic techniques revealed brainstem lesions. The midbrain was the most common location of lesions. Masseter reflex recording had the highest yield (93%) of abnormal findings. No mismatch with respect to site and side of abnormality occurred between MRI and electrophysiological studies. Outcome analysis indicated an unfavorable course for the vast majority (83%) of patients, regardless of the diagnostic means disclosing traumatic brainstem injury. Therefore, both techniques are effective in disclosing traumatic brainstem injury, with diagnostic overlap in about 50% of cases. In contrast to MRI, electrophysiological investigation is easily performed and repeated at low cost in the setting of an intensive care unit, where such patients are typically hospitalized after trauma. In addition to electrophysiological assessment of brainstem function, MRI is recommended in each case having normal electrophysiological findings when brainstem injury is suspected.     

Electrophysiological findings in neurofibromatosis type 1

Neurofibromatosis type 1 (NF1) is a common, autosomal dominant neurocutaneous disorder in which any organ system, including the skin, skeleton and nervous system can be affected. In this study, we compared the electrophysiological and magnetic resonance imaging (MRI) findings in patients with NF1. Thirty-nine adolescent and adult patients (23 women and 16 men) diagnosed with NF1 with a mean age of 25.8±10 years (10-56) were included in this study. We collected data in the form of the results of neurological examinations, multimodal evoked potentials (EPs; brainstem auditory evoked potentials, BAEPs; somatosensory evoked potentials, SEPs; and visual evoked potentials, VEPs), cerebral/orbital/spinal MRIs, and electroneuromyography (ENMG). Twenty (51.3%) patients showed abnormal VEPs, 14 (35.9%) showed abnormal SEPs, and six (15.4%) showed abnormal BAEPs. All evoked potentials were abnormal in four (10.3%) cases. These electrophysiological findings occurred primarily in the absence of any clinical sign related to the affected system. MRI revealed pathologic findings in 26 of 39 patients, and these were not always correlated with visual, auditory, or somatosensory pathway abnormalities. ENMG showed polyneuropathy in two of 33 patients who underwent ENMG. Our study showed that MRI and electrophysiological abnormalities may be found in most patients with NF1, even in the absence of associated clinical symptoms or signs. Electrophysiological testing is helpful for monitoring the subclinical involvement of the central and peripheral nervous systems in patients with NF1.     

Correlations between clinical and magnetic resonance imaging findings in multiple sclerosis

40 patients with multiple sclerosis were investigated by magnetic resonance imaging (MRI) and computer tomography (CT). Additionally, cerebrospinal fluid (CSF) findings and evoked potentials (EPs; visual, brainstem) were evaluated. MRI findings were abnormal in 85% of the patients, whilst CT scan showed pathological changes in only 23%. The sensitivity for detecting lesions was significantly higher for MRI than CT. 86% of 23 patients with a duration of disease of more than 1 year had pathological MRI findings, and MRI was abnormal in 82% of 17 patients with a duration of symptoms up to 1 year. All patients with abnormal MRI had at least one other pathological laboratory finding. CT revealed only large lesions, and in patients with abnormal CT MRI visualized lesions more extensively. Additionally, brainstem lesions could be verified in 6 patients and spinal cord lesions in 3 cases. CSF was abnormal in 86%, and positive MRI findings occurred in 26 of 31 patients with abnormal CSF. Abnormalities of EPs were found in 76%, and MRI was positive in 24 of 33 patients with abnormal EPs.     

A study of clinical, MRI and multimodality evoked potentials in neurologic Wilson disease

The aims of this study were evaluate motor, somatosensory, visual and auditory brainstem evoked potential (MEP, SEP, VEP, ABER) changes in Wilson disease (WD) and correlate these with magnetic resonance imaging (MRI) and clinical findings.
Neurologic WD diagnosed on the basis of clinical, ceruloplasmin and Kayser–Fleischer ring were evaluated including pedigree charting, hepatic, renal, hematologic and osteoarticular manifestations. Blood counts, serum chemistry, MRI, MEP to tibialis anterior, tibial SEP, VEP and ABER were performed. Evoked potential (EP) changes were correlated with clinical and MRI findings.
Eighteen WD patients were recruited from 17 families whose mean age was 16 years. Movement disorders were present in 14, cognitive decline in 12 and pyramidal signs in 12 patients. MRI revealed involvement of basal ganglia in 80%, thalamus in 40%, brain stem in 46.7% and subcortical white matter in 53.3%. MEP was abnormal in 35.7%, SEP in 30.8%, VEP in 57% and ABER in 61.5% patients; the latter three EP changes were subclinical. Frequency and number of EP abnormalities were higher with increasing severity of illness.
SEP, VEP and ABER reveals subclinical abnormality and MEP helps in documenting both clinical and subclinical abnormalities. Number of EP abnormalities increases with increasing clinical severity of WD.     

CNS involvement in Japanese patients with chronic inflammatory demyelinating polyradiculoneuropathy

Thirteen consecutive Japanese patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) were studied by MRI, evoked potentials, and EEG. We found 3 of these patients exhibited symptoms of CNS disorders. Of these 3, 2 with abnormal MRI and visual evoked potentials, and one with abnormal brainstem auditory evoked potentials were detected. Another case without clinical CNS signs showed abnormal EEG findings. The subclinical CNS abnormalities found in the Japanese patients were considered to be less frequent than in cases from Western countries reported previously.     

Clinical and magnetic resonance imaging features of elderly onset dentatorubral–pallidoluysian atrophy

Dentatorubral–pallidoluysian atrophy (DRPLA) is an autosomal dominant spinocerebellar ataxia caused by CAG triplet expansion in atrophin 1 and is frequently associated with cerebral white matter lesions. To elucidate the clinical features of elderly onset DRPLA and the key radiological findings for differentiating DRPLA from physiological white matter lesions in healthy elderly subjects, we reviewed the clinical and magnetic resonance imaging (MRI) features of ten patients with elderly onset genetically confirmed DRPLA (> 60 years) and compared their MRI findings with those of age- and sex-matched ten healthy subjects with asymptomatic cerebral white matter lesions. The initial symptom was cerebellar ataxia in all DRPLA patients, and five of them did not have any symptoms other than ataxia at the time of MRI examination. Atrophy of the brainstem, superior cerebellar peduncle, and cerebellum was detected in all DRPLA patients and none of the healthy subjects. Abnormal signals in the brainstem (inferior olive, pons, and midbrain), thalamus, and cerebellar white matter were frequently observed in elderly onset DRPLA patients but not in healthy subjects. In conclusion, elderly onset DRPLA presents as cerebellar ataxia alone in the early stage of disease. Atrophy of the brainstem, superior cerebellar peduncle, and cerebellum and abnormal signals in the brainstem, cerebellum, and thalamus are key findings for differentiating elderly onset DRPLA from asymptomatic cerebral white matter lesions in healthy subjects.     

Evaluation of patients with multiple sclerosis by evoked potentials and magnetic resonance imaging: a comparative study

We compared the diagnostic usefulness of evoked potential (EP) studies and magnetic resonance imaging (MRI) in the evaluation of 27 patients with definite or probable multiple sclerosis (MS). MRI scans demonstrated multiple lesions in 21 patients whereas EP studies showed multiple abnormalities in 14 patients (4 of whom had only somatosensory EP abnormalities). Eighteen patients had similar MRI and EP results (e.g., normal or multiple abnormalities), 8 had multiple abnormalities shown by MRI but normal or single-modality abnormal EPs, and 1 had multiple abnormal EPs but a normal MRI scan. There was no significant difference in the sensitivity of the two techniques in detecting multiple lesions in the patients with definite MS, whereas among those with probable MS, MRI had a significantly higher yield. Seventeen patients showed clinical evidence of posterior fossa involvement, 6 patients had abnormal brainstem auditory evoked potentials (BAEPs), and 4 patients had areas of increased signal intensity revealed by MRI of the brainstem. There was no clinical evidence of brainstem involvement in 2 patients with BAEP abnormalities, 2 with an abnormal posterior fossa shown by MRI, and one patient with abnormalities shown by both BAEP and MRI. We conclude that MRI is more sensitive in detecting multiple lesions than are multimodality EP studies, but that BAEP assessment may be slightly more sensitive than MRI in detecting brainstem lesions.     

Efferent and afferent evoked potentials in patients with adrenomyeloneuropathy

Objective

This paper investigates efferent and afferent conductions of the central nervous system by various evoked potentials in patients with adrenomyeloneuropathy (AMN).

Patients and methods

Ten pure AMN patients without cerebral involvement were studied. Motor evoked potentials (MEPs), somatosensory evoked potentials (SEPs), auditory brainstem response (ABR), and pattern reversal full-field visual evoked potentials (VEPs) were recorded. For MEP recording, single-pulse or double-pulse magnetic brainstem stimulation (BST) was also performed.

Results

Abnormal MEP was observed in all ten patients, abnormal SEP in all ten, abnormal ABR in nine, and abnormal VEP in only one. Brainstem latency was measured in three of the seven patients with central motor conduction time (CMCT) prolongation. The cortical–brainstem conduction time was severely prolonged along the normal or mildly delayed brainstem–cervical conduction time in those three patients.

Conclusions

The pattern of normal VEP and abnormal MEP, SEP, ABR is a clinically useful electrophysiological feature for the diagnosis. BST techniques are helpful to detect, functionally, intracranial corticospinal tract involvement, probably demyelination, in pure AMN patients.     

The clinical and pathological features of siblings with infantile neuroaxonal dystrophy--early neurological, radiological, neuroelectrophysiological and neuropathological characteristics]

The clinical and pathological features of siblings with infantile neuroaxonal dystrophy were reported. Early clinical symptoms were marked hypotonia in legs, mental regression and poor vision. Laboratory data were normal except for the mild elevation of GOT and LDH in serum and cerebrospinal fluid. MRI showed progressive atrophy of cerebellar vermis and brainstem. EEG showed a progressive increase in the amount and amplitude of the fast activities over the age of 3 years. Auditory brainstem response (ABR) showed progressive worsening with no response by 2 years and 6 months. Somatosensory evoked potentials (SEP) showed no cortical response by 4 years. Nerve conduction velocity (NCV) of both motor and sensory nerves was within normal limits. Pathologically, spheroid bodies were found in the axons of central and peripheral nerves, remarkably in brainstem and dorsal column. MRI, ABR and SEP findings were clinically useful, suggestive of the degeneration of brainstem.     

Vigabatrin‐associated reversible MRI signal changes in patients with infantile spasms

Purpose: To evaluate the magnetic resonance imaging (MRI) of pediatric patients with infantile spasms (IS) treated with vigabatrin (VGB) in order to investigate whether VGB affects the brain. Methods: One hundred seven pediatric patients diagnosed with IS and treated with (n = 95) ≥120 mg/kg/day VGB or without (n = 12) VGB were included. MRI and diffusion‐weighted imaging (DWI) were retrospectively analyzed. Results: Of the patients who had MRI scans during, but not before, VGB treatment (n = 81), 25 (30.9%) exhibited abnormal MRI signal intensity and/or restricted DWI in the deep gray nuclei and brainstem. Follow‐up scans (performed in 15 of the 25 patients) revealed that these changes were reversible upon withdrawal of the medication. Analysis of patients undergoing scans before, during, and after VGB treatment (n = 14) revealed that four patients had abnormal MRI signal during treatment with VBG, two of whom reversed with cessation of VGB, one reversed without cessation of VGB, and another had persistent abnormal signal while being weaned from the VGB. Patients who had not received VGB treatment (n = 12) displayed normal imaging. Younger infants (≤12 months) and those with cryptogenic IS were more likely to develop abnormal signal changes on MRI during VGB treatment. Discussion: In pediatric patients, VGB induces reversible MRI signal changes and reversible diffusion restriction in the globi pallidi, thalami, brainstem, and dentate nuclei. The risk for this phenomenon was greater in younger infants and patients with cryptogenic IS.     

Abnormal findings of dichotic listening test in patients with childhood adrenoleukodystrophy

Ten Japanese boys with childhood-onset adrenoleukoqdystrophy (ALD) were evaluated with dichotic listening test (DLT). Six cases showed abnormal findings especially of laterality index (L.I.) calculated from the score of each ear. Some of them showed no abnormal findings with other auditory examinations containing auditory brainstem responses (ABR). One patient showed abnormal L.I. of DLT at an early stage. The abnormality of laterality index was similar to the so-called "strong left-ear suppression" in patients who underwent callosotomy. Although all of these six patients had a high signal lesion at the splenium of the corpus callosum in a T3-weighted MRI sequence, it was difficult to evaluate the width of demyelinated area. DLT could detect the early damage of connecting fibers mediating inter-hemispheric transfer of auditory information, and might be a useful method for evaluating the cerebral function of auditory processing in patients with childhood ALD.     

Auditory brainstem response and extratympanic recorded electrocochleography in patients with multiple and severe handicaps

Nine patients ranged between 5 months and 35 years (means 14 years) of age with multiple and severe disabilities were comparatively studied, on extra-tympanic recorded compound action potential (AP) of electrocochleography and auditory brainstem response (ABR). Both ABR and AP were obvious in 3 patients with clear auditory behavioral responses. The ABR was not recorded to high intensity click stimuli in six patients without visible auditory behavioral responses. Four of the 6 cases showed undetectable AP and the 2 rest of the 6 cases showed abnormal but discernible AP. In two cases with history of the anoxic encephalopathy, AP was recorded but ABR was not detected in one case, and in the other, neither AP nor ABR was recorded. At least two different levels of lesions could be differentiated in cases without detectable ABR by using extra-tympanic recorded electrocochleography in these kinds of severely handicapped patients.