Wilson's disease: evoked potentials and computed tomography

Summary Multi-modality evoked potentials and computed cranial tomography (CT) were performed in ten patients with Wilson's disease to determine if any of these studies would correlate reliably with neurologic status. While all four patients with CT abnormality had neurologic signs, two additional patients with neurologic findings had normal scans. Evoked responses were normal in nine patients. The remaining patient displayed abnormal visual, brainstem, and somatosensory evoked potentials, and follow-up studies after clinical deterioration revealed worsening of the brainstem and visual evoked potentials. This patient died unexpectedly from a subdural hematoma, and postmortem examination confirmed the radiographic findings of cortical atrophy of the cerebrum and cerebellum and bilateral cystic degeneration of the basal ganglia. However, localized demyelination in the visual, auditory, and sensory pathways was not present. We conclude that the clinical neurologic status of patients with Wilson's disease cannot be reliably predicted by either CT or multi-modality evoked potentials.     

Correlation of electrophysiologic findings in neural muscular atrophy

In a collective of 22 patients (18 adults, 4 children) with the clinical diagnosis of peroneal muscular atrophy the correlation of various neurophysiological parameters was examined. These included electromyography, motor and sensory nerve conduction velocity, visual (VEP), acoustic (AEP) and somatosensory (SEP) evoked potentials and conventional EEG. In all cases we found a high correlation between the findings of nerve conduction velocities and somatosensory evoked responses. Acoustic evoked potentials were examined in 18 cases and showed 10 pathological findings; visual evoked responses were also examined in 18 cases and produced 5 pathological findings. If nerve conduction velocity measurements are possible, SEP examinations are superfluous as they do not provide additional information. On the other hand, VEP and AEP testing is warrented in all cases to document the impairment of central nervous pathways.     

Evoked potentials in multiple system atrophy (MSA)

OBJECTIVES: To study the involvement of pyramidal tracts and sensory pathways in multiple system atrophy (MSA). MATERIALS AND METHODS: Evoked potential studies were performed in 45 MSA patients suffering from either MSA of cerebellar type (MSA-C) or MSA of parkinsonian type (MSA-P). RESULTS: Motor evoked potentials were normal in all MSA patients, whereas visual and somatosensory evoked potential abnormalities were found in about 40% of the MSA patients with no significant difference between the cerebellar (MSA-C) and parkinsonian (MSA-P) subgroup. Abnormal latencies of wave III in brainstem auditory evoked potentials were significantly more frequent in MSA-C. CONCLUSIONS: Abnormalities of somatosensory, visual and auditory evoked potentials are frequent findings in MSA, whereas abnormal motor evoked potentials are not a characteristic feature of the disease.     

Clinical, multimodal electrophysiological study of a family with progressive cerebellar ataxia and late deafness and an autosomal recessive inheritance]

We described the clinical, electrophysiological (electromyography, sensory and motor nerve conduction study, somatosensory evoked potentials, brainstem auditory evoked potentials, visual evoked potentials) and neuroradiological (brain magnetic resonance) data in 3 siblings (2 males and 1 female, age range: 54-48 years) affected by autosomal recessive late onset cerebellar ataxia. The 3 patients showed at the electrophysiological examination: mild peripheral neuropathy, involvement of somatosensory pathways both on central and peripheral side. A mild cerebellar atrophy, most evident in the female more severely disabled, was found by magnetic resonance.     

Evoked potentials and contingent negative variation during treatment of multiple sclerosis with spinal cord stimulation.

Cervical somatosensory evoked potentials, brainstem evoked potentials, visual evoked potentials, and the cerebral contingent negative variation were recorded in patients with definite multiple sclerosis before, during, and after spinal cord stimulation. Improvements were seen in the cervical somatosensory and brainstem evoked potentials but neither the visual evoked potential nor the contingent negative variation changed in association with spinal cord stimulation. The results indicate that spinal cord stimulation acts at spinal and brainstem levels and that the clinical improvements seen in patients are caused by an action at these levels rather than by any cerebral arousal or motivational effect. The evoked potentials were not useful in predicting which patients were likely to respond to stimulation.     

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.     

Utility of multimodal evoked potentials study in neurofibromatosis type 1 of childhood

A group of 21 children affected by neurofibromatosis type 1 has been investigated with the aim of studying multimodal (visual, brainstem auditory, and somatosensory) evoked potentials and their correlations with neurologic, electroencephalographic, and cranial magnetic resonance imaging. In the present series, cranial magnetic resonance imaging and evoked potentials were the most frequently abnormal instrumental tests. In approximately two thirds of the cases at least one of the evoked potentials (particularly visual and auditory evoked potentials) was compromised, always without clinical signs of related sensory (visual, auditory, and somatosensory) pathway pathology and sometimes in the absence of magnetic resonance imaging signs of central nervous system involvement. This study indicates that in patients with neurofibromatosis type 1, multimodal evoked potentials are useful and should be part of the diagnostic protocol of encephalic lesions together with magnetic resonance imaging. The use of both methods could aid in early detection of central nervous system dysfunction in both the initial evaluation of disease and its follow-up.     

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.     

Familial paroxysmal exercise-induced dyskinesia and benign epilepsy: a clinical and neurophysiological study of an uncommon disorder

We report a family with 6 members affected by a long-lasting paroxysmal exertion-induced dyskinesia. Fasting and stress were precipitating factors. All the patients of this family had also epileptic seizures mainly of generalised type with a favourable outcome. All patients were submitted to a neurophysiological study which included somatosensory evoked potentials by median nerve stimulation (MN-SEPs), somatosensory evoked potentials by posterior tibial nerve stimulation (PTN-SEPs), brainstem auditory evoked potentials (BAEPs), visual evoked potentials (VEPs), motor evoked potentials (MEPs) by magnetic transcranial cortical stimulation (TCS) and electromyography (EMG). The neurophysiological findings suggest a hyperexcitability at the muscular and brain membrane levels, probably due to an ion channel disorder. Received: 2 February 2000 / Accepted in revised form: 16 June 2000     

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.     

Neurophysiological (evoked auditory and somatosensory potentials) and neuroradiological (cranial CT) study in patients with olivopontocerebellar atrophy

Thirteen patients affected by either dominant or recessive and/or sporadic olivopontocerebellar atrophy were studied. All patients were subjected to auditory evoked potential recordings including early and long latency components, CT scans, vestibular and EMG-ENG examinations. In nine patients somatosensory evoked potentials were also recorded. Clear-cut abnormalities in brainstem auditory evoked potentials were observed in only two patients while a slight reduction of the IV-V/I amplitude ratio was found in seven cases. N85 was increased in two patients. The main feature of somatosensory evoked potentials abnormalities was a delayed N20 in association with prolonged N13-N20 central conduction time (five patients). For all patients the CT scan varying degrees of cerebellar and brainstem atrophy. There was no clear correlation between the abnormalities revealed by neurophysiological and neuroradiological investigations and the severity and duration of the illness. It is noteworthy that auditory and/or somatosensory evoked potential changes were found in all dominant olivopontocerebellar atrophy patients.     

F response and somatosensory and brainstem auditory evoked potential studies in HMSN type I and II.

To evaluate conduction along the proximal and distal segments of motor and sensory long limb nerves, as well as along the very short acoustic nerve, F response and somatosensory and brainstem auditory evoked potential were studied in a series of patients with hereditary motor and sensory neuropathy (HMSN) types I and II. A diffuse and comparable slowing of conduction in proximal and distal nerve segments, as well as along the acoustic nerve, seems to favour a primary myelin defect in HMSN I. F response and motor conduction velocity showed a similar derangement in both proximal and distal motor segments. Latencies of somatosensory evoked potentials were symmetrically prolonged and correlated with motor nerve impairment. Central conduction times were normal. Studies of brainstem auditory evoked potentials showed a high incidence of acoustic nerve involvement, the most evident abnormality being a statistically significant increase in the latency of the I wave. Our data seem to support the presence of primary myelinopathic damage in HMSN I.     

Preservation of brainstem neurophysiological function in hydranencephaly

The preservation of central neurophysiological function was assessed in a 32-year-old woman with hydranencephaly using brainstem auditory evoked responses (BAER), auditory middle latency responses (MLR), cortical auditory evoked responses (CER), strobe electroretinograms (ERG), strobe-flash visual evoked responses (VER) and median and tibial nerve somatosensory evoked responses (SER). The BAER to the right ear stimulation revealed wave peaks I through VII with normal thresholds, morphology and latencies, while the BAER in the left ear was abnormal. The auditory MLR and CER were absent. Grossly normal strobe ERGs were acquired bilaterally with peak waves at 20 and 50 ms. Strobe VERs were poorly defined and abnormal bilaterally. Left and right median nerve SER revealed significant conduction defects in the large fiber sensory system caudal to the thalamus, above the lower pontine level. Bilateral tibial nerve stimulation revealed normal knee popliteal fossa potentials, but distinct conduction defects in the large fiber sensory system rostral to the lower spinal cord. Brainstem electrophysiological measures revealed functional auditory afferent tracts and nuclei, in the absence of cortical influence, suggesting intact unilateral auditory function, which would support clinical observations of behavioral auditory responses in hydranencephaly.     

Importance of evoked potentials in the evolutive prognosis of coma during cerebral anoxia in adults]

Ten cases of postanoxic coma have been studied. A clinical neurological examination with study of brainstem reflexes and the EEG recording were made on the first day (J1), the third day (J3) and the tenth day (J10) after the start of the coma. A recording of the visual evoked potentials, the brainstem evoked potentials and the somatosensory potentials combined was made at the same time. A clinical examination is carried out one month after the coma when the patient survives. According to the initial clinical examination, we distinguished 3 groups of subjects. The results show that in group III the visual evoked potentials such as EEG have a slightly significant prognostic value; frequently the near outcome lead to death whereas EEG activity persists and the visual evoked potentials disappear later. On the other hand, the association of brainstem evoked potentials and somatosensory potentials clearly has a higher prognostic value in this group. The disappearance of the shortest brainstem responses and the cortical somatosensory responses is clearly an unfavourable prognosis. This disappearance associated with the end EEG activity is the absolute proof of brain death. On the other hand, the persistence of these responses is of a better prognosis at least on the survival level, but their degradation during evolution is unfavourable.     

Characteristic evoked potentials in childhood-onset dentatorubral-pallidoluysian atrophy

To determine the characteristics of multimodal evoked potentials (MEPs) in childhood-onset dentatorubral-pallidoluysian atrophy (DRPLA) we studied three DRPLA patients with progressive myoclonus epilepsy. Brainstem auditory evoked potentials showed reduced or absent brainstem components as well as delayed latencies. In addition, short latency somatosensory evoked potentials (S-SEPs) had prolonged central conduction time and reduced amplitude of cortical components. Two patients with symptom onset in the first decade of life had extremely enlarged flash visual evoked potentials with shortened latency even in the absence of giant SEPs. Therefore, children with progressive myoclonus epilepsy and the above MEP findings are likely candidates for childhood-onset DRPLA and should undergo DNA analysis for DRPLA.     

The neurophysiological balance in Chiari type 1 malformation (CM1), tethered cord and related syndromes

The Chiari malformation (CM) is a syndrome embodied in heterogeneous groups of malformations, spanning from the more benign and known, the CM1, to more complex syndromes such as the rare association with the tethered cord, as spinal lipomas, and the CM2, associated to open spina bifida. The clinical picture may be well expressed and detected at birth or even during intrauterine life, as for CM2, but in the other cases they may run a rather subtle clinical course. The diagnosis of these syndromes is driven by clinical examination and MRI, and it usually requires a multidisciplinary approach in order to plan the therapeutic strategies, such as surgery. Among the diagnostic investigations, the imaging techniques represent the most useful, for their capabilities to detect subclinical lesions, such as syringomyielia and lipoma; the urological investigation is useful to evaluate the urogenital dysfunctions. The neurophysiological investigations represent a non invasive diagnostic procedure to investigate the peripheral nerve, the spinal cord, the brainstem functionalities and more higher brain functions; the nerve conduction studies and the cranial reflexes, the brainstem (BAEP) and the somatosensory (SEPs) evoked potentials (EPs), alone or in combination, can be used for the diagnosis, follow-up and intraoperative monitoring. The most useful diagnostic tools in CM1 are likely represented by the brainstem auditory evoked potentials (BAEPs) and the blink-reflex (BR), while the usefulness of SEPs is still doubtful and debated; in CM2 and tethered cord the neurophysiological techniques can be combined in different ways in order to make a functional balance and to answer specific questions. BAEPs and BR can be useful to investigate the brain stem functionality and SEP to evaluate whether the ascending sensory pathway to the cortex can be hampered at some level; the visual EPs are particularly useful to evaluate the integrity of posterior visual pathway and visual cortex in the case of associated hydrocephalus. In the tethered cord, both nerve conduction study and somatosensory evoked potentials (SEPs) are useful to evaluate motor and sensory dysfunction of the lombosacral roots and nerves and spinal cord for their capability to detect subclinical impairment of conduction along the sensory and motor pathway. Finally, last but not the least, the neurophysiological techniques are remarkably useful during surgery; the intraoperative monitoring (IOM) by means of electromyography and direct nerve stimulation and recordings are able to detect early nerve damage, minimize nerve lesions and optimise the surgical techniques. In the operated children with incomplete removal of lipoma and/or persistent tethering, the recordings of SEP and BAEP are useful to demonstrate a conduction deterioration along the ascending sensory pathway due to increasing tethering of the spinal cord due to somatic growth.     

The neurophysiological balance in Chiari type 1 malformation (CM1), tethered cord and related syndromes

The Chiari malformation (CM) is a syndrome embodied in heterogeneous groups of malformations, spanning from the more benign and known, the CM1, to more complex syndromes such as the rare association with the tethered cord, as spinal lipomas, and the CM2, associated to open spina bifida. The clinical picture may be well expressed and detected at birth or even during intrauterine life, as for CM2, but in the other cases they may run a rather subtle clinical course. The diagnosis of these syndromes is driven by clinical examination and MRI, and it usually requires a multidisciplinary approach in order to plan the therapeutic strategies, such as surgery. Among the diagnostic investigations, the imaging techniques represent the most useful, for their capabilities to detect subclinical lesions, such as syringomyielia and lipoma; the urological investigation is useful to evaluate the urogenital dysfunctions. The neurophysiological investigations represent a non invasive diagnostic procedure to investigate the peripheral nerve, the spinal cord, the brainstem functionalities and more higher brain functions; the nerve conduction studies and the cranial reflexes, the brainstem (BAEP) and the somatosensory (SEPs) evoked potentials (EPs), alone or in combination, can be used for the diagnosis, follow-up and intraoperative monitoring. The most useful diagnostic tools in CM1 are likely represented by the brainstem auditory evoked potentials (BAEPs) and the blink-reflex (BR), while the usefulness of SEPs is still doubtful and debated; in CM2 and tetherd cord the neurophysiological techniques can be combined in different ways in order to make a functional balance and to answer specific questions. BAEPs and BR can be useful to investigate the brain stem functionality and SEP to evaluate whether the ascending sensory pathway to the cortex can be hampered at some level; the visual EPs are particularly useful to evaluate the integrity of posterior visual pathway and visual cortex in the case of associated hydrocephalus. In the tethered cord, both nerve conduction study and somatosensory evoked potentials (SEPs) are useful to evaluate motor and sensory dysfunction of the lombosacral roots and nerves and spinal cord for their capability to detect subclinical impairment of conduction along the sensory and motor pathway. Finally, last but not the least, the neurophysiological techniques are remarkably useful during surgery; the intraoperative monitoring (IOM) by means of electromyography and direct nerve stimulation and recordings are able to detect early nerve damage, minimize nerve lesions and optimise the surgical techniques. In the operated children with incomplete removal of lipoma and/or persistent tethering, the recordings of SEP and BAEP are useful to demonstrate a conduction deterioration along the ascending sensory pathway due to increasing tethering of the spinal cord due to somatic growth.     

Evoked potentials in patients with non-neurological Wilson's disease

Summary In Wilson's disease neurological manifestations result from the damage in the basal ganglia, even if a widespread degeneration of the brain occurs. The few studies performed using evoked potentials with the aim of identifying subclinical dysfunction in the three major sensory pathways have never shown abnormalities in patients without neurological manifestations. To verify this observation we studied 12 patients suffering from Wilson's disease in a pre-neurological stage by using pattern visual evoked potentials (VEPs), somatosensory evoked potentials (SEPs) to median nerve stimulation and brainstem auditory evoked potentials (BAEPs). Four of these patients had not yet been treated with penicillamine or trientine (triethylenetetramine dihydrochloride), while the remaining 8 patients were on treatment for at least 1 year. In 3 patients of this second group and in 1 patient of the first group we observed a significant (3 SD over the mean) increase in P100 wave latency, while SEPs and BAEPs were found to be abnormal in only 1 patient, respectively.     

Brain volume analyses and somatosensory evoked potentials in multiple system atrophy

We investigated a progression of brain atrophy and somatosensory system dysfunction in multiple system atrophy (MSA). Subjects were 21 MSA patients [12 MSA-C (cerebellar type) and 9 MSA-P (parkinsonism type)]. The relative volumes of cerebrum, brainstem and cerebellum to the intracranial volume were obtained from three-dimensional computed tomography (3D-CT) of the brain. The median nerve somatosensory evoked potentials (SEPs) were recorded, and the latencies and amplitudes of N9, N11, P13/14, N20 and P25 components were measured. We studied correlations between brain volumes, SEP and clinical features. The brainstem and cerebellar atrophies were aggravated with progression of the disease. The central sensory conduction time (CSCT) was progressively prolonged in parallel with the disease duration irrespective of the actual age of the patients. In MSA patients, the volume reductions of cerebellum and brainstem could be one of structural markers of disease progression, and the sensory pathway is progressively involved with the progression of disease processes.     

Sleep disordered breathing in spinal muscular atrophy

Sleep disordered breathing is a common but under-diagnosed complication causing sleep disturbance and daytime symptoms in children with spinal muscular atrophy. Non-invasive (positive pressure) ventilation is an established treatment of respiratory failure; its role in treatment of sleep disordered breathing though remains controversial. Aim of this study was to verify the hypothesis that nocturnal non-invasive ventilation has beneficial impact on breathing during sleep, sleep quality and daytime complaints in children with spinal muscular atrophy. Twelve children with spinal muscular atrophy type I or II (7.8±1.9 years) underwent polysomnography and were asked to fill out a symptom questionnaire. Seven patients (six with spinal muscular atrophy I and one with spinal muscular atrophy II) had sleep disordered breathing and received non-invasive ventilation during sleep. Five less severely affected patients (one with spinal muscular atrophy I and four with spinal muscular atrophy II) had no sleep disordered breathing and served as reference group. Patients were restudied after 6–12 months. In patients with sleep disordered breathing both sleep architecture and disease related symptoms were significantly worse than in the reference-group. Non-invasive ventilation during sleep completely eliminated disordered breathing, normalized sleep architecture and improved symptoms (P<0.05 for all). In children with spinal muscular atrophy sleep disordered breathing may cause relevant impairment of sleep and well-being. Both can be highly improved by nocturnal non-invasive ventilation.