Abnormalities of cognitive functions in IDDM revealed by P300 event-related potential analysis. Comparison with short-latency evoked potentials and psychometric tests.

The possible influence of diabetes on the higher mnestic and cognitive functions has been investigated. The P300 wave latency, an endogenous electrophysiological event, was explored and compared with the multimodal short-latency evoked potential (EP) recordings (visual [VEP], brainstem auditory [BAEP], and median and tibial nerve somatosensory EPs [mSEP and tSEP, respectively]) and psychometric test measures in 16 insulin-dependent diabetic (IDDM) patients, in 16 age- and (IDDM) sex-matched nondiabetic subjects, and in a large normal reference population. The age of subjects, the duration of IDDM, and the metabolic control of patients were taken into account. P300 values were significantly increased in IDDM versus matched control subjects (P less than 0.001), and 3 patients showed values above the reference value range. Abnormal VEP recordings were present in 1 of 16 patients, BAEP in 3 of 16, mSEP in 7 of 16, and tSEP in 6 of 16. Digit-span backward test results were significantly (P less than 0.02) modified in the diabetic cohort. There was no tendency for anomalies of P300, short-latency EPs, and psychometric test values to be contemporarily present, except in 1 patient. Electrophysiological or psychometric abnormalities were not clearly correlated with the duration of IDDM or the degree of short-term metabolic control. These findings give evidence that 1) higher cognitive functions may be affected in diabetes as documented by P300 analysis and short-term memory tests, 2) endogenous electrophysiological analysis highlights neuropsychological changes not detectable by psychometric tests, 3) an alteration of evoked potentials was present in half of the IDDM subjects studied, and 4) anomalies of the CNS are patchily distributed in diabetes.

Early detection of neurological involvement in IDDM and NIDDM. Multimodal evoked potentials versus metabolic control.

Clarification of the extent and mechanisms of damage to the central nervous system in diabetes is a frontier of current neurological research. Our aim was to obtain ample electrophysiological documentation of possible neurological abnormalities in both insulin-dependent (IDDM) and non-insulin-dependent (NIDDM) diabetic patients with a short duration of disease and without overt complications, taking into account metabolic control. Group 1 comprised 11 IDDM patients, and group 2 included 14 NIDDM patients treated with diet alone; the duration of disease was less than 4 yr, and no concomitant clinical complications were present. Age- and sex-matched normal subjects formed groups 3 and 4. Pattern visual evoked potentials (VEP), brain stem auditory evoked potentials (BAEP), and somatosensory evoked potentials (SEP; after the stimulation of both median and tibial nerves) were recorded in all subjects, and metabolic control was evaluated in terms of glycemia and glycosylated hemoglobin. In group 1, significant abnormalities were found in the latency values of VEP, median SEP, and tibial SEP compared with control subjects. Similar latency abnormalities were shown in group 2 for VEP, median SEP, and tibial SEP values and for wave I latency of BAEP. Glycosylated hemoglobin values were correlated with BAEP and SEP abnormalities in many patients in both groups. Furthermore, in group 2, glycemic values correlated with SEP abnormalities. We therefore conclude that neurophysiological abnormalities are present at different levels in IDDM and NIDDM patients only a few years after clinical diagnosis and before the appearance of overt complications, and these abnormalities seem to be correlated with metabolic control status.

Effects of spontaneous chronic hypoglycemia on central and peripheral nervous system in insulinoma patients before and after surgery: a neurophysiological follow-up.

To investigate the effects of spontaneous chronic hypoglycemia on the peripheral and central nervous system, a multimodal neurophysiological evaluation [median somatosensory (mSEP), brain stem auditory (BAEP), and visual (VEP) evoked potentials recordings] was performed in seven insulinoma patients before and 3 and 6 months after surgical removal of tumor. Before surgery, mSEP findings showed abnormal reduction in peripheral wrist-Erb conduction velocity in three patients as well as a pathological increase in Erb-N13, N13-N20, and Erb-N20 conduction times in five cases. BAEP and VEP recordings gave pathological results in two patients. Moreover, during hypoglycemia, the III-V and I-V interpeak latencies of BAEPs were significantly prolonged (P < 0.01 and P < 0.005, respectively) compared to recordings in euglycemia. After 6 months, a mSEP recovery, even if partial was noted in four patients, BAEPs were normalized in one case, and VEPs were unmodified. Compared to presurgery data, these recordings showed a significant (P < 0.05), but incomplete, shortening of BAEPs (III-V and I-V interpeak latencies) and mSEPs (Erb-N13 and Erb-N20 conduction times). Our findings demonstrate that multiple and selective neurophysiological abnormalities are present in insulinoma patients, confirm that hypoglycemia impairs suddenly brain stem function, and show that after tumor removal, long recovery times for improvement of some neurophysiological anomalies are requested.

Pain, anxiety, and contingent negative variation: a clinical and pharmacological study.

Contingent negative variation (CNV) behavior was studied in 16 volunteers who were suffering from spontaneous recurrent pain syndromes (idiopathic trigeminal neuralgia, classic migraine). The subjects were divided into two groups, "more anxious" and "less anxious," based on psychometric tests (MMPI and STAI X2). The CNV recordings were carried out, respectively, in basal resting state, during an episode of pain, while under anxiolytic treatment, and lastly, during an episode of pain while under anxiolytic therapy. CNV voltage decrease and frequent appearance of postimperative negative variation (PINV) were observed when pain was present during the recording session. These phenomena were more marked when the pain was accompanied by a greater degree of anxiety. Finally, our results suggest that this slow evoked potential is sensitive to various degrees of anxiety and to pain perception in man, making it useful in the investigation of pain as a complex sensation.

Effect of islet transplantation on neuroelectrophysiological abnormalities in diabetic inbred Lewis rats: comparison of primary versus secondary prevention.

BACKGROUND: Neuroelectrophysiological abnormalities in diabetes indicate nervous function failure. Restoration of euglycemia by islet transplantation may prevent or reverse these abnormalities. METHODS: Pancreatic islets were transplanted in inbred Lewis rats after 15 days (Ta12, primary prevention) or 8 months (Tb12, secondary prevention) from streptozotocin-induced diabetes. Transplanted and control (normal and diabetic) rats were followed for a total period of 12 months. Metabolic parameters, somato-sensory, brain-stem auditory, and visual evoked potentials were determined at the beginning and at the end of the study and before transplantation for secondary prevention. RESULTS: The metabolic parameters in transplanted animals were similar to those of normal animals. Ta12 and normal group somato-sensory conduction velocities did not vary and were always significantly higher than those of diabetic animals. By contrast, Tb12 group conduction velocities showed only a partial improvement, values lying between those of diabetic and normal rats. Brain-stem auditory (waves I, II, and III) latencies in Ta12 group were similar to those of normal rats and significantly lower than those of diabetic animals (wave I: P<0.01; waves II and III: P<0.05). Tb12 group wave I and II latency values remained altered (P<0.005 and P<0.01 versus normal values respectively). Visual evoked potentials-P1 wave latencies in transplanted rats were always higher than those of normal and diabetic animals. CONCLUSIONS: After primary prevention, central and peripheral neurological alterations were abolished. After secondary prevention, transplantation beneficial effects were partial, occurring mainly at peripheral level. These results highlight the importance of early transplantation to prevent hyperglycemia-dependent neuroelectrophysiological alterations.

A simple method for estimating conduction velocity of the spinothalamic tract in healthy humans.

OBJECTIVES: The object of this study was to establish a method for estimating the conduction velocity (CV) of the spinothalamic tract (STT) in relation to clinical application. METHODS: The CV of the STT was estimated by an indirect method based on that reported by Kakigi and Shibasaki in 1991 (Kakigi R, Shibasaki H. Electroenceph clin Neurophysiol 80 (1991) 39). Laser-evoked potentials (LEP) were measured in 8 subjects following hand (LEPH) and foot (LEPF) laser stimulation. The conduction times recorded at the scalp (P340, P400 and N150 potentials) were considered as the summation of peripheral and central components. The peripheral conduction times were calculated by measuring the latency of the electrical cutaneous silent period (from the same stimulus site of LEPs), corrected for F- and M-wave latency values. RESULTS: The CV of the STT ranged between 8.3 and 11.01 m/s and its mean value was found to be approximately 9.87+/-1.24 m/s. The CV of the STT obtained by the N150 latencies overlapped that obtained by the P340/P400 latencies. CONCLUSIONS: Our data suggest that our method appears appropriate and useful for practical clinical purposes, furnishing an additional tool for investigating the physiological function of small-fiber pathways.

Early complications in type 1 diabetes: central nervous system alterations preceded kidney abnormalities.

Abnormalities of the central nervous system (CNS), as discerned by neuroelectrophysiological studies, and an impaired, charge-related, differential filtration of protein at kidney level as evaluated by selective protein clearance, have recently been shown in diabetes of short duration and without any apparent complication. In order to explore the time of appearance and possible correlations, CNS and kidney abnormalities have been evaluated in parallel both in short-term and long-standing type 1 diabetic subjects. Two groups of patients were studied: Group 1 (no. 15), with no previously known clinical sign of complications and less than 5 years from diagnosis; Group 2 (no. 15) with more than 10 years of disease and with or without clinical signs of diabetic complications. Twenty age and sex comparable normal subjects were included in the study (Group 3). Short-latency multimodal evoked potentials (visual-VEP, brainstem auditory-BAEP, median and tibial somatosensory m- and t-SEP) and charge and/or size selective protein clearances (albumin, anionic immunoglobulins, neutral/cationic immunoglobulins) were evaluated. In Group 1, 27% of patients showed neurophysiological abnormalities (P < 0.05 vs. Group 3) while one showed proteinuria. In Group 2, 60% of patients showed electrophysiological changes (P < 0.0001 vs. Group 3) while 67% showed abnormal charge or size selective proteinuria (P < 0.0001 vs. controls) with a significant association between the abnormalities of CNS and of charge selective proteinuria (P < 0.05). Thus, CNS abnormalities may be detected even in patients with diabetes of short duration and are later associated with subclinical kidney abnormalities. These findings stress the value of the multimodal evoked potential evaluation as a sensitive and early diagnostic approach to the study of diabetic complications.

Role of advanced glycation end-products (AGE) in late diabetic complications.

To evaluate accumulation of advanced glycation end-products (AGE) in diabetes and its possible correlation with late diabetic complications, AGE levels were measured by spectrofluorimetry in eye lens and sciatic nerve proteins and isolated tail tendon collagen of rats with experimental diabetes of 3- and 6-month duration. The values obtained were compared to those from age-matched control rats and correlated with cataract presence and somatosensory evoked potential (SEP) alterations. Diabetic animals had increased AGE levels in all tissues at both times; cataract developed in 29% of diabetic rats at 3 months and in 57% at 6 months; SEP conduction velocity was reduced in diabetic animals both at 3 (54.5 +/- 1.8 S.E.M. m/s vs. 73.9 +/- 1.0, P < 0.0001) and 6 months (59.5 +/- 1.4 vs. 71.5 +/- 1.6, P < 0.0001) from diabetes induction. No eye lens AGE level differences were observed when cataract presence was considered. Interestingly, in diabetic rats, increased sciatic nerve AGE levels were associated with reduced SEP. These data show that: (1) AGE levels are increased as early as 3 months from development of hyperglycemia; (2) other factors, in addition to an enhanced rate of fluorescent AGE formation, might play important roles in the pathogenesis of diabetic cataract; (3) increased peripheral nerve AGE levels are associated with SEP alterations.

Electrophysiological study in patients with chronic hepatic insufficiency.

Twenty patients affected by chronic hepatic insufficiency were studied by means of combined EEG, VEP and BAEP recordings. Subjects were classified, according to Parsons-Smith criteria, in grade 0 (without any clinical sign) and grade I (with minimal mental disturbances). In group 0 patients an elevated incidence of VEP alterations (40%) was observed, while EEG and BAEP recordings were less frequently (10%) abnormal. In group I patients a high degree of EEG (60%), VEP (70%) and BAEP (70%) abnormalities was found. Mean latency and interpeak interval values in group I patients were significantly prolonged if compared with the grade 0 and control groups. No correlations were found between electrophysiological data and blood biochemical parameters examined (ammoniemia, aminoacidemic pattern).

Angiographically occult brainstem vascular malformation: a longitudinal comparison of magnetic resonance imaging (MRI) and multimodal evoked potential (EP) recordings.

Over a period of several years, a patient with angiographically occult vascular malformation (AOVM) involving the brainstem was longitudinally studied by means of serial Magnetic Resonance Imaging (MRI) and multimodal Evoked Potential (EP) recordings (visual-VEP, brainstem auditory-BAEP, somatosensory--SEP--by stimulating median and peroneal nerves). MRI did contribute to an accurate definition of AOVM features. In particular, it was able to follow over time the AOVM size, and to discriminate between recent and old bleedings. Multimodal EP recordings displayed different pathological BAEP and peroneal SEP values, which documented a transient segmental brainstem involvement (related to the presence of hemorrhage), along with persistent and probably irreversible signs of diffuse brainstem dysfunction. Thus, MRI and EP assessment is useful in monitoring the clinical course of brainstem occult vascular malformations.

Crural amyotrophy associated with a parietal lesion: a case report.

The authors have observed a 33-year-old woman with a 3-year history of a clinical syndrome characterised by atrophy of the musculature of the left foot and leg with impaired motor function, associated with a paracentral cortical oligodendroglioma located in the right parietal region. Clinical, neuroradiological (MRI), electrophysiological (electromyography: EMG; motor evoked potential: MEP; median and tibial somatosensory evoked potential: m-SEP and t-SEP), and neuropsychological studies were performed every year for three years. Neurological examination showed an abnormal gait along with foot drop, pes cavus and pyramidal involvement. MEP and t-SEP recordings were abnormal on the left side, while EMG and neuropsychological tests gave normal results, which were unmodified over time. Our observations suggest that the crural amyotrophy observed in this case may be defined as of "parietal" or "central" origin, a clinical feature which more frequently affects the hand. A review of the literature is presented.

Pattern visual evoked potentials and brainstem auditory evoked responses in uremic patients.

With the improvement of dialysis therapy and subsequent increase in the average lifespan of uremic patients more interest has been directed towards neurological complications induced by chronic renal failure. Twelve uremic patients were selected on the basis of negative neurological and psychiatric examinations. Electroencephalogram, pattern visual evoked potentials (VEPs) and brainstem auditory evoked responses (BAERs) were recorded in all patients. Pathological latency increases of VEPs in six patients and of BAERs in three patients had been observed. These findings have been related by the authors to the action of toxic substances or to the presence of minimal demyelinating lesions of CNS. Since these pathological findings were observed in patients who were normal at the clinical examination, it has been suggested that the evoked potentials recording might be a sensitive index of initial early lesions of the CNS in uremic patients (Acta neurol. belg., 1982, 82, 72-79).

Electrophysiological (BAEPs) changes in subacute sclerosing panencephalitis.

Over a period of time, the authors have studied a case of subacute sclerosing panencephalitis (SSPE), by means of brainstem auditory evoked potentials (BAEPs). The observed abnormalities of the conduction time along the early auditory pathways appeared to be related to the clinical picture; in fact, during periods of transitory clinical improvement these abnormalities were less evident. In addition, the encountered electrophysiological alterations consisted of a marked pathologic increase in the III-V interpeak latencies. The authors suggest that the BAEPs findings in their case could have been influenced by either unfavourable endogenous conditions (edema, electrolyte changes, etc.) or CNS segmental lesions due to focal viral distribution.

Pattern visual evoked potentials in pseudotumor cerebri. A longitudinal study.

The prognosis of "benign" intracranial hypertension (Pseudotumor cerebri) is generally favorable. In fact, the resolution of the clinical picture is related to the disappearance of the increased intracranial pressure. However, sometimes an irreversible visual loss can occur. The authors studied, over a period of time, seven subjects suffering from pseudotumor cerebri utilizing pattern visual evoked potentials (VEPs). Five patients showed normal VEPs latencies that remained such in the successive controls. Two patients displayed pathological P100 VEPs latencies. Such findings tended towards a progressive transient improvement following decompressive lumbar puncture. The authors suggest that the VEPs alterations in these patients could be due to the association of general (increased CSF pressure) and local (malformations, scleral canalis constrictions) ocular factors. In these circumstances, the pattern VEPs recordings could be coupled with traditional methods of evaluation of visual pathway damage capable of provoking an irreversible compromission of the visual function.

[Syringomyelia. Clinical and neurophysiologic correlations (SEP) as a function of surgical treatment]. / La siringomielia. Correlati clinici e neurofisiologici (PES) in funzione del trattamento chirurgico.

The authors have studied the somatosensory evoked potential (SEP) behavior following stimulation of upper and lower limbs in two subjects affected by syringomyelia. The patients were evaluated electrophysiologically before and after decompressive surgical treatment. The findings indicate a positive correlation between the SEP recordings and the role of CSF pressure in the central nervous system.

Subacute necrotizing encephalomyelopathy (Leigh's disease): clinical correlations with computerized tomography in the diagnosis of the juvenile and adult forms.

A computerized tomography (CT) scan was performed on 6 surviving patients with a suspected diagnosis of subacute necrotizing encephalomyelopathy of the juvenile and adult forms. Bilateral low density areas were observed in the putamina in all cases. This CT pattern conformed with the characteristic pathological changes of the disease. Once the possibility of Wilson's disease or an earlier episode of acute cerebral hypoxia, syndromes which both display a similar appearance in CT, is excluded, a diagnosis of subacute necrotizing encephalomyelopathy may be considered in cases showing bilateral low density areas in the basal ganglia, especially in the putamina, and with a consistent clinical history.

Brainstem auditory evoked potentials in toxic, metabolic and anoxic coma.

The aim of this study was to evaluate the efficacy of brainstem auditory evoked responses as a prognostic tool in conditions of coma which interfere with cerebral metabolism. Thirteen patients in coma resulting from different systemic disorders (barbiturate intoxication, cardiac arrest, chronic hepatic insufficiency) were included in the study. Brainstem auditory evoked potentials were recorded and patients were graded according to the results. When used in conjunction with other clinical parameters (Glasgow Coma Scale), brainstem auditory evoked potentials provided a more reliable prognostic tool than the traditional EEG exam alone. A good correlation was found between electrophysiological data and clinical outcome not only in barbiturate (toxic) coma, but also in hepatic (metabolic) coma. Of particular significance was the disappearance of the components which follow wave III (grade 2), leading to a fatal outcome in all three patients in hepatic coma.

Pattern visual evoked potentials and flash electroretinogram in clinically definite multiple sclerosis.

The authors have studied, by means of pattern visual evoked potential (VEP) and flash electroretinogram (ERG) recordings, a group of 15 patients affected by definite multiple sclerosis. All of the subjects examined presented a clinical history indicating involvement of the visual pathways; VEPs were altered in a high percentage of eyes examined (93.3%), while a lower percentage of abnormal ERGs was seen (20% of eyes examined). The only type of ERG alteration found consisted of a pathologic b wave voltage increase, observed mainly with red flash stimuli. This finding could be attributed to an involvement of centrifugal optic nerve fibers having inhibitory functions on retinal cells.

[Longitudinal study of evoked responses (VEP, BAEP, SSEP) in multiple sclerosis]. / Studio longitudinale delle risposte evocate (PEV, BAEP, PES) nella sclerosi multipla.

The Authors have examined 20 subjects affected by "possible" multiple sclerosis by means of a multimodal (VEP, BAEP, SEP) electrophysiologically evaluation longitudinally conducted during a time period of 1 year. The electrophysiological data obtained are related to the clinical picture, the disease's evolution, and to the adopted pharmacological therapy, in order to attempt a more precise diagnostic and prognostic assessment of these patients.