Multimodal evoked potentials to assess the evolution of multiple sclerosis: a longitudinal study.

BACKGROUND: Evoked potentials are used in the functional assessment of sensory and motor pathways. Their usefulness in monitoring the evolution of multiple sclerosis has not been fully clarified. OBJECTIVE: The aim of this longitudinal study was to examine the usefulness of multimodal evoked potential in predicting paraclinical outcomes of disease severity and as a prognostic marker in multiple sclerosis. METHODS: Eighty four patients with clinically definite multiple sclerosis underwent Expanded Disability Status Scale (EDSS) and functional system scoring at study entry and after a mean (standard deviation) follow-up of 30.5 (11.7) months. Sensory and motor evoked potentials were obtained in all patients at study entry and at follow-up in 64 of them, and quantified according to a conventional score. RESULTS: Cross-sectionally, the severity of each evoked potential score significantly correlated with the corresponding functional system (0.32 < R < 0.60, p < 0.01, for all but follow-up visual evoked potential) and with EDSS (0.34 < R < 0.61; p < 0.001 for all but brain stem evoked potential). EDSS significantly correlated with global evoked potential score severity (baseline R = 0.60, follow-up R = 0.46, p < 0.001). Using longitudinal analysis, only changes in somatosensory evoked potential scores were significantly correlated with changes of sensory functional system (R = 0.34, p = 0.006). However, patients with multiple sclerosis with disability progression at follow-up had more severe baseline evoked potential scores than patients who remained stable. Patients with severe baseline global evoked potential score (higher than the median value) had a risk of 72.5% to progress on disability at follow-up, whereas patients with multiple sclerosis with lower scores had a risk of only 36.3%. CONCLUSIONS: These results suggest that evoked potential is a good marker of the severity of nervous damage in multiple sclerosis and may have a predictive value regarding the evolution of disability.

Acute- and insidious-onset myelopathy of undetermined aetiology: contribution of paraclinical tests to the diagnosis of multiple sclerosis.

Brain magnetic resonance imaging (MRI), multimodality evoked potentials (EPs) and cerebrospinal fluid examination were performed in 42 patients with myelopathy of undetermined aetiology in order to detect abnormalities usually related to multiple sclerosis (MS). Patients were divided into three groups: insidious-onset myelopathy with only motor signs (group A; 11 patients), with both motor and sensory signs (group B; 18 patients) and acute-onset myelopathy (group C; 13 patients). Multiple brain MRI lesions were found in 18 patients (2 of group A, 13 of group B and 3 of group C). Another 7 patients had a single white-matter lesion. Visual EPs were abnormal in 21 and brain-stem auditory EPs in 12 patients. Paraclinical tests supported the diagnosis of MS in 25 patients (60%) by showing subclinical brain abnormalities. Oligoclonal bands were found in 16 of these 25 patients. The findings strongly suggest a diagnosis of MS in the patients of group B.

Correlation between multimodal evoked potentials and magnetic resonance imaging in multiple sclerosis.

Sixty multiple sclerosis (MS) patients (33 definite, 13 probale and 14 suspected were investigated by computed tomography (CT), magnetic resonance imaging (MRI), multimodality evoked potentials (EPs) and cerebrospinal fluid (CSF) electrophoresis. MRI abnormalities were found in 50 cases, while at least one abnormal evoked potential was detected in each of 52 cases. Brain-stem auditory evoked potentials were more sensitive than MRI for the detection of brain-stem involvement. All the patients with oligoclonal bands had abnormal MRI and none of the patients with normal MRI had oligoclonal bands in the CSF. The number and the extent of MRI lesions were significantly correlated with the duration of disease and with the degree of disability. Our observations stress the importance of the combined use of MRI and EPs in detecting silent CNS lesions in MS patients.

Homocystinuria with transverse sinus thrombosis.

A case of cerebral venous thrombosis caused by undiagnosed homocystinuria is reported. The pitfalls regarding the diagnosis of a potentially medically treatable condition are discussed. Cerebral venous thrombosis in children has a variable type of onset and a multiplicity of causes. This type of pathology, although not frequent, is more common than previously thought. Among the different etiologies, undiagnosed homocystinuria is not routinely considered. We report a case of venous thrombosis of the left transverse cerebral sinus in a girl with drug-resistant partial epilepsy and homocystinuria. This diagnosis was considered and confirmed after the appearance of acute cerebral symptoms caused by venous thrombosis.

Disseminated intravascular coagulation and severe peripheral neuropathy complicating ketoacidosis in a newly diagnosed diabetic child.

Disseminated intravascular coagulation is a very rare complication of diabetic ketoacidosis. Central nervous system palsy but not peripheral neuropathy has been reported in these patients. On the other hand, signs of peripheral neuropathy may also be present at the onset of diabetes, but they are usually reversible within a few days after correction of the metabolic derangement. We describe an unusual case of mononeuritis multiplex syndrome still present after 2 months of follow-up in a child with diabetic ketoacidosis complicated by disseminated intravascular coagulation at the onset of insulin-dependent diabetes. These neurological impairments may be consistent with functional neural lesions due to vasa nervorum thrombosis and prolonged ischaemia.

Evoked potentials in monitoring multiple sclerosis.

The usefulness of evoked potentials (EPs) in the diagnosis of multiple sclerosis is limited by its relatively low sensitivity to subclinical lesions. However, they are still a good tool to assess the integrity of afferent and efferent pathways and to quantify the severity of white matter involvement. Transversal and longitudinal studies have demonstrated good correlation between EP abnormalities and disability, suggesting that multimodal evoked potentials could be useful in monitoring the disease evolution in single patients and as surrogate end points in clinical trials.

Measuring evoked responses in multiple sclerosis.

Evoked potentials (EPs) have been widely utilised in Multiple Sclerosis (MS) patients to demonstrate the involvement of sensory and motor pathways. Their diagnostic value is based on the ability to reveal clinically silent lesions and to objectivate the central nervous system damage in patients who complain frequently of vague and indefinite disturbances which frequently occurs in the early phases of the disease. The advent of magnetic resonance imaging (MRI) techniques has greatly reduced the clinical utilisation of EPs, which is not fully justifiable, as the information provided by EPs are quite different from those provided by MRI. The abnormalities of evoked responses reflect the global damage of the evoked nervous pathway and are significantly correlated with the clinical findings, while the vast majority of MRI lesions are not associated to symptoms and signs. Transversal and longitudinal studies have demonstrated that EP changes in MS are more strictly related to disability than MRI lesion burden. On the contrary, MRI is more sensitive than EPs in revealing the disease activity. Evoked responses modifications observed in MS are not disease-specific; moreover longitudinal studies showed latency and morphology changes of evoked responses not always related to clinical changes. Such a dissociation can be explained both by technical factors and by subclinical disease activity. To reduce the negative impact of technical aspects, only reproducible parameters of the evoked responses should be used to monitor disease evolution and therapeutic interventions.

Presence of carpal tunnel syndrome in diabetics: effect of age, sex, diabetes duration and polyneuropathy.

Common thought is that diabetic neuropathy is a predisposing factor to entrapment syndromes. Carpal tunnel syndrome (CTS) is the most frequent entrapment neuropathy; females and old people are most frequently affected (Comi et al., 1978). Prevalence of CTS in diabetics and associated risk factors were studied in 401 patients (208 males and 193 females) with insulin-dependent and non-insulin-dependent diabetes using electrophysiological techniques. Median nerve sensory and motor conduction velocity, ulnar and peroneal nerve motor conduction velocity and sural nerve sensory conduction velocity were investigated in all patients. Diagnostic criteria for CTS were the presence of delayed median nerve sensory conduction velocity in the palm-wrist tract and of increased distal motor latency. Polyneuropathy was defined by slowing-down of conduction velocity in two or more nerves. Forty-five patients (11.2%), 36 females and 9 males, showed CTS. One-hundred-sixty-eight patients (41.8%), 74 females and 94 males, were suffering from peripheral neuropathy. The strongest risk factors for CTS, in order of importance, were: female sex, older age and presence of neuropathy. Polyneuropathy but not CTS was related to duration of diabetes.

Neurophysiological and cognitive markers of disease evolution in multiple sclerosis.

Both evoked potentials and cognitive tests may provide useful information which cannot be derived from the clinical observation. For this reason, there have been some attempts to use EPs in monitoring the natural history of the disease and in assessing the efficacy of therapeutic trials. However, no conclusion can be derived from the few available data. Although MRI is more sensitive than EPs in revealing new lesions in brain, cerebellum and brainstem, EPs are more sensitive in revealing optic nerve and spinal cord lesions. Moreover, the poor relationship between brain MRI abnormalities and disability has raised the possibility that cognitive evaluation may be an additional sensitive marker of brain involvement over time. Since the gold standard for the assessment of disease activity is uncertain, it is therefore advisable that frequent MRI, EPs and cognitive assessment may integrate clinical outcomes measured by conventional scales, both in the study of the natural disease course and in monitoring clinical trials.

Clinical, neurophysiological, and magnetic resonance imaging correlations in multiple sclerosis.

Magnetic resonance imaging (MRI) has a pivotal role in diagnosis of multiple sclerosis and is being increasingly used as a paraclinical measure to assess treatment efficacy in clinical trials. However, the correlations between clinical and MRI findings in patients with multiple sclerosis are weak and, therefore, newer MR techniques are being developed to increase both MRI sensitivity for detecting disease activity and its pathological specificity for better assessing disease evolution. Evoked potentials (EPs) can be used to confirm the diagnosis of multiple sclerosis and their abnormalities are correlated with symptoms and signs referable to involvement of the corresponding nervous pathways. However, their use is limited when assessing disease progression and monitoring clinical trials in multiple sclerosis. Both magnetic resonance imaging (MRI) and evoked potentials (EPs) provide information which cannot be obtained by clinical evaluation, especially for assessing disease activity. Nevertheless, both these paraclinical techniques cannot substitute for clinical measures of disability when assessing disease progression and monitoring phase III clinical trials in multiple sclerosis.

Visual evoked potentials in diabetic teen-agers: influence of metabolic control and relationship with peripheral neuropathy.

85 type 1 diabetics aged between 8 and 20 years (mean: 15.06) performed Pattern Reversal Visual Evoked Potentials (PRVEP). In addition all of them were investigated for peripheral neuropathy and 63 subjects for retinopathy. Our study disclosed a subclinical involvement of optic nerve pathways in about 1/4 of diabetic teen-agers. P100 mean latency was delayed in diabetics for both 30' (112.8 +/- 7.7 msec versus 109.1 +/- 4.8 msec) and 15' check size (119.1 +/- 10.5 msec versus 112.8 +/- 5.2 msec). The N75-N140 interpeak latency was also significantly delayed and the mean N75-P100 amplitude was significantly reduced in diabetics. No correlation was found between PRVEPs latency and age, HbA1, and insulin requirement. The mean P100 latency significantly increased with the duration of diabetes. A negative correlation was found at the 30' check size between P100 latency and motor and sensory conduction velocity in all the examined nerves. 10 out of 63 patients, who had been examined with fluorangiography, showed abnormalities; only 2 of these 10 subjects had abnormal PRVEP. The association of prolonged P100 latency, prolonged N75-N140 interpeak latency and reduced N75-P100 amplitude can be considered consequent to a desincronisation of the impulses travelling along the optic pathways.

Brain stem magnetic resonance imaging and evoked potential studies of symptomatic multiple sclerosis patients.

In this study we evaluated the sensitivity of neuroradiological and neurophysiological tests for detecting brain stem (BS) lesions in multiple sclerosis patients, since the recent introduction of the gradient motion rephasing technique has markedly increased the image quality of magnetic resonance imaging (MRI). From 50 MS patients (33 women and 17 men; mean age 35.9 +/- 8.3 years; mean duration of the disease 7.2 +/- 4.1 years) with clinical signs of BS involvement, brain MRI, BS auditory evoked potentials (BAEPs), and left and right median somatosensory evoked potentials (mSEPs) were obtained. BS MRI lesions were detected in 41 patients (82%); in 14 cases they were located in the medulla oblongata, in 55 in the pons, and in 24 in the midbrain. Single lesions were present in 20 patients, while two or more BS lesions were demonstrated in 21 patients; 30 patients had at least one lesion located close to the inner or the outer cerebrospinal fluid border. BAEPs were abnormal in 19 of the 50 patients (38%), and BS components of mSEPs were abnormal in 15 of 46 (33%). With combined use of these neurophysiological techniques, BS abnormalities were revealed in 24 patients (48%). Only 1 patient had neurophysiological BS abnormalities and normal MRI. Moreover, there was a good correlation (74%) between the clinical and MRI BS findings in the 23 patients with signs referable to focal neurological BS lesions. The concordances considering clinical and evoked potential reports were positive, but less marked.(ABSTRACT TRUNCATED AT 250 WORDS)

Platelet function and thrombin activity in patients with recent cerebral transient ischemic attacks.

Platelet function and thrombin activity were investigated in 12 hospitalized patients (7 men and 5 women, mean age 53 years) who had had transient cerebral ischemic attacks in the previous 2-12 weeks. Each patient was given an extensive clinical and instrumental evaluation, including Doppler sonography of the cervical and lower limb vessels, cerebral angiography, and head computed tomography scan, after which relevant atherosclerotic disease was excluded. The controls consisted of 12 subjects hospitalized for nonvascular neurologic problems and matched for age, sex, and risk factors to the transient ischemic attack patients. Collagen-induced platelet thromboxane B2 production, plasma beta-thromboglobulin, and fibrinopeptide A were significantly higher in the patients than the controls. Platelet aggregability by collagen was the same in the 2 groups. Platelet hyperfunction and enhanced thrombin activity are present in patients some weeks after the acute episode, suggesting that the hemostatic system has a primary pathogenetic role.

Evaluation of central nervous conduction by visual evoked potentials in insulin-dependent diabetic children. Metabolic and clinical correlations.

Peripheral neuropathy is a well-known complication of diabetes, but few data are available on central lesions. Visual evoked potentials (VEPs) seem a reliable and feasible technique for detecting a conduction delay in the central nervous system. Seventy-one insulin-dependent type 1 diabetic children (mean age 15 +/- 3 years) and 33 controls were investigated for central neuropathy. We used a pattern of reversal stimulation with television display of a checker board pattern (15 min and 30 min check size). The latencies of the positive peak (P100 wave) were significantly lengthened in 17 patients (27%) but no correlation was found between VEPs and age, duration of diabetes, insulin requirement and HbA1 level. A negative correlation was found between VEPs and peripheral nervous conduction velocity. VEPs measurement seems a simple and reliable technique for detecting early alterations in CNS function in diabetics. Our data suggest that central and peripheral nervous alterations progress simultaneously.

Comparison between magnetic resonance imaging and other techniques in 39 multiple sclerosis patients.

Till now there are no specific laboratory tests to confirm the diagnosis of Multiple Sclerosis (MS). For this reason the diagnosis of MS is based on the clinical evidence of central nervous system white matter disease with temporal and spatial dissemination of the lesions. Recent advances in neurophysiology and imaging techniques can provide more objective criteria towards more accurate and earlier diagnosis, detecting clinically unsuspected lesions. We evaluated 39 MS patients (23 definite, 7 probable, 9 possible) by Magnetic Resonance Imaging (MRI), CT scan, Evoked Potentials (EPs) testing and Cerebrospinal Fluid analysis. MRI was abnormal in 34 cases (87%) and CT scan in 14 (36%); EPs were also abnormal in 34 cases. 30 patients had both EPs and MRI alterated and 4 patients had alterated only one of the two investigations. The frequency of EPs alterations was: VEP 74%, Median SEP 44%, Tibial SEP 59% and BAEP 54%. The BAEP was more sensitive than MRI in detecting brainstem involvement. On the other hand MRI was more sensitive than SEPs in detecting somatosensory pathways involvement. The combined use of the two techniques allowed a reclassification of 10 out of 16 possible or probable MS cases.

Effects of long-lasting antiepileptic therapy on brainstem auditory evoked potentials.

The brainstem auditory evoked potentials of 84 epileptic patients in chronic monotherapy with carbamazepine (n = 36), phenobarbital (n = 19), Na-valproate (n = 20) or progabide (n = 9) were studied. The mean values of I-III and I-V interpeak latencies (IPLs) were respectively 2.16 +/- 0.11 and 4.03 +/- 0.17 in the control group, 2.31 +/- 0.09 and 4.17 +/- 0.16 in the valproic group, 2.30 +/- 0.17 and 4.19 +/- 0.20 in the carbamazepine group, 2.17 +/- 0.16 and 4.10 +/- 0.18 in the phenobarbital group and 2.16 +/- 0.11 and 4.12 +/- 0.17 in the progabide group. The prolongation of I-III and I-V IPLs was statistically significant only for the valproic acid and carbamazepine groups. Neither duration of the epilepsy and treatment and frequency of seizures nor the serum drug levels were correlated with I-V IPL values.

Prognostic value of the nervous system involvement in HIV patients.

About 30-40% of AIDS patients present CNS and/or PNS involvement, due to direct action of HIV virus or opportunistic infections. Nervous system involvement in the HIV correlated syndromes is not a rare occurrence; nevertheless no studies about prognosis of AIDS related syndromes have been published yet. We tested 38 HIV positive patients for the assessment of neurological complications by means of clinical and instrumental evaluations: multimodal evoked potentials, EMG/ENG studies, nerve and muscle biopsy. At the baseline evaluation, 26/38 patients had neurological complications: 14 of CNS, 9 of PNS, 3 of both CNS and PNS. At follow-up, 16/37 patients had developed AIDS and 10/16 patients with AIDS died. Of these 16 patients, 14 had clinical and neurophysiological alterations at the baseline evaluation. Our results suggest that the presence of clinical and/or neurophysiological nervous system involvement in patients with HIV-related syndromes constitutes a negative prognostic factor for developing AIDS.

Neurophysiologic studies and cognitive function in congenital hypothyroid children.

Minor neurologic and intellectual impairments have been described in some congenital hypothyroid (CH) children in spite of early detection by neonatal screening. The aim of our study was to assess cognitive functions as well as neurophysiologic parameters in hypothyroid children and to compare children detected by neonatal screening (group A) versus hypothyroid patients clinically diagnosed before the beginning of the screening program (group B). Group A consisted of 15 children (13 girls, mean age at the beginning of treatment 33 d). Group B consisted of 11 patients (7 girls, mean age at the start of treatment 10.1 mo). Twenty age-matched healthy children were studied as a control group for neurophysiologic tests. Neurophysiologic tests (Auditory P 300, long latency somatosensory evoked potentials (LL-SEP) were performed along with IQ evaluation. Abnormalities of neurophysiologic tests were detected in 82% of clinically diagnosed hypothyroid children. Surprisingly, 47% of the children detected by neonatal screening, having normal mental development index, showed at least one abnormal neurophysiologic test. LL-SEP latencies were found significantly increased in both groups of CH patients compared with controls. Our data are suggestive for a prenatal or perinatal CNS damage in some children with congenital hypothyroidism, despite early treatment.

Cognitive function and neurophysiological evaluation in early-treated hypothyroid children.

In this study, we assessed cognitive function and neurophysiological development in congenitally hypothyroid (CH) children. We performed a cross-sectional study at the outpatient Pediatric Clinic and Department of Neurophysiology at San Raffaele Hospital, Milan. The study enrolled 25 CH patients (6.00-10.83 years of age) detected by neonatal screening, and 34 healthy control children (4-11 years of age). Patients and controls had comparable scores at neuropsychological tests (WISC-R), and at auditory P300 tests. In contrast, we found significantly longer LLSEP latencies in CH patients (p < 0.03). CH patients treated 30 days after birth showed lower scores at neuropsychological tests, but not at neurophysiological tests, compared to patients who started the replacement therapy earlier. Patients with more severe fetal hypothyroidism (T4 levels at diagnosis < or = 2 micrograms/dl) had lower neuropsychological scores, and similar neurophysiological results, compared with patients with moderate fetal hypothyroidism. The severity of fetal hypothyroidism and early treatment influence the mental outcome of CH patients. Neurophysiological results show that central nervous system damage occurs in some patients despite early treatment.