Involvement of central nervous system in patients with diabetes mellitus detected by evoked potentials

Somatosensory (SSEPs) and brainstem auditory evoked potentials (BAEPs) were recorded for 44 patients with diabetes mellitus (age, 63.0 +/- 9.3 years, mean +/- SD) and 20 age-matched healthy controls (age, 67.3 +/- 9.1 years) to elucidate the involvement of the central nervous system (CNS) in diabetes mellitus. Furthermore, relationships between SSEP or BAEP and clinical variables such as autonomic nervous function, peripheral nerve conduction velocity, duration of diabetes, metabolic control (fasting blood sugar level, HbA1 and HbA1c levels) and therapeutic method, were studied. The central conduction time (CCT), which represents the peak latency between N13 and N20, in patients with diabetes mellitus was significantly longer than that of the healthy controls (p less than 0.005). Likewise, diabetic patients showed significant prolongation of interpeak latency between waves I and V (I-V IPL) compared to the healthy controls (p less than 0.005). Significant correlations between CCT and motor conduction velocity of median nerve (p less than 0.05) were observed although the correlation between CCT and sensory nerve conduction velocity was not found to be significant (p less than 0.1). Furthermore, I-V IPL was significantly correlated with the duration of illness (p less than 0.05). There were no significant correlations between CCT or I-V IPL and autonomic nervous dysfunction as determined by orthostatic hypotension and the coefficient variation of the R-R interval or metabolic control or therapeutic method. From the present results, it would appear that there is CNS involvement even in diabetic patients not manifesting overt CNS signs and symptoms and that it is correlated somewhat with impairment of the peripheral nervous system and duration of illness.     

Electrophysiological comparison between patients with Binswanger's encephalopathy and Alzheimer's disease

Short-latency somatosensory (SSEPs), brainstem auditory evoked potentials (BAEPs) and event-related potentials (ERPs) were studied in 7 patients with Binswanger's encephalopathy, 12 patients with Alzheimer's disease and 17 normal subjects. Patients with Binswanger's encephalopathy showed significantly prolonged central conduction time (CCT) and P300 latency, and prolonged tendency of I-V IPL compared to those of normal subjects. In particular, CCT showed significant prolongation compared to that of patients with Alzheimer's disease. In patients with Alzheimer's disease, I-V IPL and P300 latency were significantly prolonged compared to those of normals although there was no significant difference in CCT between Alzheimer's disease and normal subjects. These results indicate some difference between Binswanger's encephalopathy and Alzheimer's disease from the electrophysiological aspects although both of these entities are characterized by progressive mental deterioration.     

Changes in body temperature produced by prostaglandins and pyrogens in the chicken.

Bacterial pyrogen from S. abortus equi (SAE) was injected into the wing veins of chickens. Following injection of 0.05-0.5 mug SAE, body temperatures did not change significantly, whereas 2.0 or 10 mug of pyrogen caused falls in body temperature of 0.56 +/- 0.10degrees C and 1.1 +/- 0.21degrees C (mean +/- SE, n=5). The temperature falls were accompanied by a flushing of the comb and an increase in respiratory rate and were not antagonized by 1.0 g of acetylsalicylic acid (ASA) given orally. The injection of SAE (0.1 mug in 1 mul) into the anterior hypothalamus produced fevers averaging 1.24 +/- 0.07 degrees C (n=9) which were antagonized by oral ASA. Injections of SAE at other brainstem loci produced no temperatur changes. Seven chickens were also injected with 0.1 mug PGE in 1.0 mul into the anterior hypothalamus, and they developed fevers averaging 0.90 +/- 0.16 degrees C. The results support the concept that prostaglandins may be involved in fever in chickens but suggest that the action of pyrogen injected intravenously may be different from that following its injection directly into the hypothalamus.     

Early enucleation does not alter the gross morphology of identified projection neurons in the chicken optic tectum

Auditory information ascends through the brainstem to the cerebral cortices in two parallel pathways, known as the classical and the non-classical ascending auditory pathways. The importance of the non-classical auditory pathway for hearing in humans is unknown but its subcortical connection to limbic structures may be important in tinnitus. In this study we show evidence that non-classical pathways are involved in loudness perception in young individuals but not in adults. We used the fact that some neurons in the non-classical auditory pathways receive somatosensory input and we determined the effect on loudness perception of monaural sounds from electrical stimulation of the median nerve at the wrist. Stimulation of the somatosensory system had the greatest effect on loudness perception in the youngest children that we studied (7-8 years) and the effect was minimal for individuals above 20 years of age. The effect was an increase in loudness in 20 of the 40 individuals we studied and a decrease in 4 individuals; 16 experienced no noticeable change in loudness during somatosensory stimulation.     

Precortical filtering and selective attention: an evoked potential analysis

Attention-related changes in the human auditory brainstem response and the short-latency somatosensory evoked potential (SLSEP) were demonstrated in separate experiments. In Experiment 1, ABRs were recorded during conditions in which subjects awaited the presentation of either auditory or somatosensory target stimuli. In Experiment 2, median nerve SLSEPs were recorded in a similar task context. Analyses of ABR and SLSEP component amplitudes and latencies revealed that the auditory nerve (wave II) and rostral brainstem (wave V) components of the ABR, and the cervical component (N12) of the SLSEP, were facilitated when attention was directed toward stimuli that were presented in the same sensory modality and receptive field as the EP-eliciting stimuli. These results suggest that central mechanisms can modulate the transmission of auditory and somatosensory information at an early, precortical stage and that these mechanisms play a role in auditory and somatosensory selective attention.     

A thalamic component of the cervical evoked potential in man

Somatosensory evoked potentials (SEPs) were recorded simultaneously from scalp and neck locations following median nerve stimulation. By subtracting the latency of the major negative peak of the cervical SEP (N13) from that of the primary cortical response (N20), the central somatosensory conduction time was calculated (5.9 ms). On the descending slope of the cervical SEP was superimposed a positive potential of probable thalamic origin (P17). By subtracting the latency of N13 from that of P17 and P17 from that of N20 respectively, the transit time for the afferent volley both within the brainstem (3.9 ms) and the thalamo-cortical radiation (2.0 ms) was obtained.     

Influence of body temperature on bacterial growth rates in experimental pneumococcal meningitis in rabbits.

We examined the role of fever as a host defense in experimental pneumococcal meningitis in rabbits. Twelve hours after intracisternal inoculation of an encapsulated type 3 Streptococcus pneumoniae strain, body temperature was manipulated by using two different anesthetic drugs: pentobarbital, which did not affect temperature, and urethane, which mitigated the febrile response to infection. Growth rates of pneumococci in cerebrospinal fluid were dramatically influenced by modification of the febrile response. Rabbits whose fever was not suppressed had mean bacterial doubling times of 2.76 +/- 1.43 h. Animals with a blunted febrile response had a significantly faster mean bacterial growth rate (doubling time = 1.10 +/- 0.27 h; P less than 0.02). When the antipyretic effect of urethane was counteracted by raising the ambient temperature, animals also showed a marked reduction in pneumococcal growth rates. In vitro, the pneumococci grew well at 37 degrees C in Trypticase soy broth (doubling time = 0.61 +/- 0.05 h) and in pooled rabbit cerebrospinal fluid (doubling time = 0.85 +/- 0.07 h). However, at 41 degrees C neither medium supported growth. Thus, body temperature appears to be a critical determinant of pneumococcal growth rates in experimental meningitis, and fever could be a host defense in this disease.     

Cross-Modal Selective Attention Effects on Retinal, Myogenic, Brainstem, and Cerebral Evoked Potentials

Short latency evoked potentials were recorded during a cross-modal selective attention task to evaluate recent proposals that sensory transmission in the peripheral auditory and visual pathways can be modified selectively by centrifugal mechanisms in humans. Twenty young adult subjects attended in turn to either left-ear tones or right-field flashes presented in a randomized sequence, in order to detect infrequent, lower-intensity targets. Attention-related enhancement of longer-latency components, including the visual P105 and the auditory N1/Nd waves and T-complex, showed that subjects were able to adopt a selective sensory set toward either modality. Neither the auditory evoked brainstem potentials nor the early visual components (electroretinogram, occipito-temporal N40, P50, N70 waves) were significantly affected by attention. Measures of retinal B-waves were significantly reduced in amplitude when attention was directed to the flashes, but concurrent recordings of eyelid electromyographic activity and the electro-oculogram indicated that this effect may have resulted from contamination of the retinal recordings by blink microreflex activity. A trend toward greater positivity in the 15-50 ms latency range for auditory evoked potentials to attended tones was observed. These results provide further evidence that the earliest levels of sensory transmission are unaffected by cross-modal selective attention, but that longer latency exogenous and endogenous potentials are enhanced to stimuli in the attended modality.     

Antipyretic effect of indomethacin in malignant lymphoma

Fifteen patients with lymphoid malignancies and tumour-related fever (greater than 38.0 degrees C) were given 50 mg indomethacin (IM) orally. This resulted in a reduction of body temperature in all cases (mean +/- SD 3.4 +/- 2.0 degrees C). In one patient with untreated Hodgkin's disease, temperature fell from 40.6 degrees C to 30.6 degrees C within 12 hours without any cardiovascular or respiratory distress. The lytic effect of IM on fever was more pronounced and more rapid in the 15 patients with lymphoma than in a group of 10 patients with acute myocardial infarction. IM therapy has a clear value in relieving tumour-associated fever in patients with malignant lymphoma. There may be a qualitative difference between the IM response of tumour-related fever and fever related to non-malignant diseases.     

Elevated body temperature restricts growth of Haemophilus influenzae type b during experimental meningitis.

Elevation of the environmental temperature appeared to counteract the temperature-depressing effects of urethane anesthetic and allowed rabbits intracisternally infected with Haemophilus influenzae type b to mimic the development of a fever following infection. Elevated core body temperature (greater than 39 degrees C) was associated with an inhibition of the growth of H. influenzae in cerebrospinal fluid (CSF) during the first 12 h postinfection, whereas bacterial growth was essentially unrestricted in rabbits with reduced (approximately 37 degrees C) body temperature. Bacterial densities 24 h postinfection were different, hyperthermic animals having log 6.0 +/- 0.4 CFU/ml of CSF and hypothermic rabbits having log 8.2 +/- 0.8 CFU/ml of CSF (P less than 0.05, Wilcoxon rank sum test). However, the growth of this bacterium in vitro, in either pooled rabbit CSF or brain heart infusion broth, was not inhibited at 39 degrees C. These results suggest that elevated body temperature associated with the development of fever during meningitis may be associated with restriction of the growth of H. influenzae in vivo but that this effect is apparently not due to an innate inability of the bacterium to grow at elevated temperatures.     

Fever alters characteristics of sleep in rats

This study examined the effects of a fungal infection on body temperature (Tb) and sleep states. Tb and sleep were recorded in male rats for 24 hr after a saline injection and 48 hr after a subcutaneous injection of live brewer's yeast, at ambient temperatures (Ta's) of 20 degrees and 30 degrees C. Peak fevers of 1.6-3.1 degrees C occurred within 6-10 hr at both Ta's. The rats remained febrile for the next 12-24 hr. For the first 24 hr postyeast, amounts of SWS increased by 19 +/- 3% at 20 degrees C and 12 +/- 2% at 30 degrees C. Specifically, SWS was significantly increased from hr 5-8 (lights-on) and 13-24 (lights-off) at 20 degrees, and from hr 5-8 and 17-24 at 30 degrees C. Ta did not affect the changes in Tb or the changes in SWS after either saline or yeast. Duration of REMS varied with Ta after saline. After yeast, REMS increased by 21 +/- 12% at 20 degrees and decreased by 28 +/- 6% at 30 degrees C, with the net result that REMS at the two Ta's was equal during the fever. Furthermore, while the rats were febrile the normal diurnal variation in REMS was eliminated. Sleep and Tb returned to control values during the second fever day. These results suggest that an activated immune system both increases SWS and overrides the diurnal and thermoregulatory modulations of REMS.     

Centrifugal regulation of task-relevant somatosensory signals to trigger a voluntary movement

Many previous papers have reported the modulation of somatosensory evoked potentials (SEPs) during voluntary movement, but the locus and mechanism underlying the movement-induced centrifugal modulation of the SEPs elicited by a task-relevant somatosensory stimulus still remain unclear. We investigated the centrifugal modulation of the SEPs elicited by a task-relevant somatosensory stimulus which triggers a voluntary movement in a forewarned reaction time task. A pair of warning (S1: auditory) and imperative stimuli (S2: somatosensory) was presented with a 1 s interstimulus interval. Subjects were instructed to respond by moving the hand ipsilateral or contralateral to the somatosensory stimulation which elicits the SEPs. In four experiments, the locus and selectivity of the SEPs’ modulation, the contribution of cutaneous afferents and the effect of contraction magnitude were examined, respectively. A control condition where subjects had no task to perform was compared to several task conditions. The amplitude of the frontal N30, parietal P30, and central P25 was decreased and that of the long latency P80 and N140 was increased when the somatosensory stimuli triggered a voluntary movement of the stimulated finger compared to the control condition. The N60 decreased with the movement of any finger. These results were considered to be caused by the centrifugal influence of neuronal activity which occurs before a somatosensory imperative stimulus. The present findings did not support the hypothesis that the inhibition of afferent inputs by descending motor commands can occur at subcortical levels. A higher contraction magnitude produced a further attenuation of the amplitude of the frontal N30, while it decreased the enhancement of the P80. Moreover, the modulation of neuronal responses seems to result mainly from the modulation of cutaneous afferents, especially from the moved body parts. In conclusion, the short- and long-latency somatosensory neuronal activities evoked by task-relevant ascending afferents from the moved body parts are regulated differently by motor-related neuronal activities before those afferent inputs. The latter activities may be associated with sensory gain regulation related to directing attention to body parts involved in the action.     

Facioscapulohumeral muscular dystrophy. Multimodal evoked potentials and electroretinogram

BACKGROUND: Clinical or subclinical abnormalities of the central nervous system (CNS) have been reported in a range of primary muscle diseases, including the muscular dystrophies. PURPOSE: To ascertain by neurophysiologic techniques evidence of CNS dysfunction in a relatively large, homogeneous group of patients with facioscapulohumeral muscular dystrophy (FSHD). METHODS: Standard evoked potential (EP) and electroretinogram techniques were used to study the visual, auditory and somatosensory pathways in 20 patients with FSHD. RESULTS: Abnormal values were recorded in 70% (14/20) of patients, specifically of visual pathways (4/20), brainstem auditory pathways (4/20), median (5/20) and tibial nerve (2/20) somatosensory pathways, and of the retina (2/18). Abnormal results did not correlate with clinical parameters of patient age, disease duration and degree of weakness. CONCLUSIONS: Any process that caused CNS conduction delays was tentatively associated with FSHD. Sensorineural hearing deficit and vascular retinopathy were rare causes of abnormal EPs. Peripheral conduction delay of the arms was ascribed to mechanical factors secondary to shoulder girdle weakness. Progress in genetics and molecular pathogenesis of FSHD may shed further insight into the association between the myodystrophic process and nervous system abnormalities.     

Comparative study of evoked potentials in multiple sclerosis and neuro-Beh?et's syndrome

We studied somatosensory evoked potentials (SEPs) and brainstem auditory evoked potentials (BAEPs) in Japanese patients with multiple sclerosis (MS) and those with neuro-Behcet's disease (NB). Abnormal cortical P37 of posterior tibial nerve SEPs or cervical N13 of median nerve SEPs were more frequently found in the MS patients than in the NB patients. On the other hand, prolongation of the central conduction time of median nerve SEPs or abnormal BAEPs were more common in NB than in MS. The present data showed that lesions were mainly present in the spinal cord in MS and in the brainstem in NB. SEPs and BAEPs were considered of great value for detecting the involvement of the central nervous system in MS and NB and distinguishing between these diseases.     

Nerve conduction study, electromyography and somatosensory evoked potentials in non-Friedreich early onset cerebellar ataxia. A comparative study with Friedreich's ataxia and late onset cerebellar ataxia.

Electrophysiological findings in 14 patients with non-Friedreich early onset cerebellar ataxia are reported. Nerve conduction studies showed reduction of sensory action potential amplitudes in 7 cases associated in 3 with a decrease of sensory conduction velocities. Six subjects also exhibited a chronic neurogenic pattern to standard needle electromyography. Motor conduction velocities were normal in all cases; only two cases showed an increase in distal motor latencies. Short-latency somatosensory evoked potentials following median nerve stimulation revealed a prolonged central conduction time (N13-N20 interpeak latency) in 7 cases, compatible with supraspinal damage of the somatosensory pathways. These electrophysiological data are compared with those obtained in two reference groups of patients, respectively affected by Friedreich's ataxia and olivo-ponto-cerebellar atrophy.     

Interleukin-1β-Induced Fever Does not Alter the Ability of 5- to 6-Day-Old Rat Pups to Autoresuscitate from Hypoxia-Induced Apnoea

Experiments were carried out to determine if endogenous pyrogen-induced fever impairs protective responses of newborn rats to hypoxia. Twenty-seven 5- to 6-day-old conscious rat pups received a subcutaneous injection of 0.20 microg of recombinant rat interleukin-1beta (rrIL-1beta) per kilogram of body weight to induce fever, or an equal volume of vehicle. They were then either exposed to a single period of hypoxia produced by breathing an anoxic gas mixture (97 % N(2)-3 % CO(2)) and their time to last gasp was determined, or they were exposed repeatedly to hypoxia and their ability to autoresuscitate from primary apnoea was determined. Core temperature increased significantly following administration of rrIL-1beta but did not change following administration of vehicle (i.e. vehicle, 0.0 +/- 0.1 degrees C; rrIL-1beta, 0.7 +/- 0.3 degrees C; P < 0.001) before exposure to hypoxia. IL-1beta-induced fever did not alter the time to last gasp when the pups were exposed to a single period of hypoxia or the number of successful autoresuscitations upon repeated exposure to hypoxia. Thus, our data do not support the hypothesis that endogenous pyrogen-induced fever impairs the protective responses in newborns that may prevent death during hypoxia as may occur during single or repeated episodes of prolonged sleep apnoea.     

Effects of elbow flexion on radial nerve motor conduction velocity

The position of the elbow while conducting motor studies of the radial nerve is generally extended (15) or slightly flexed (10), but little is known about the effects of elbow flexion on the radial motor conduction velocity. We attempted to measure the effects of the elbow position on the radial motor conduction velocity, as well as directly measure the change in the length of the nerve at different elbow positions in the cadaver. In addition, we established normal values for the radial F-wave with the recording electrode on the extensor indicis proprius muscle. Radial motor nerve conduction was studied in 25 normal subjects to evaluate the effect of 3 different elbow positions (0 degree, 45 degrees, and 90 degrees) on motor conduction velocity (MCV) across the elbow. Direct (in situ) radial nerve measurements were performed on four cadaver specimens to compare changes in nerve length during elbow flexion. Normal values for radial F-wave latencies recording from the extensor indicis proprius muscle were also determined in 23 subjects. The radial MCV decreased significantly as the elbow flexed from 0 degree to 90 degrees. The normal range of values for radial motor nerve conduction at 0 degree of elbow flexion was 71.7 +/- 4.7 m/s, 68.9 +/- 4.9 at 45 degrees of elbow flexion, and 62.0 +/- 6.4 m/s at 90 degrees elbow flexion. Actual (in situ) radial nerve measurements were also found to decrease in length as the elbow flexed. The minimal radial F-wave latency was 19.8 +/- 3.7 milliseconds. For routine determination of motor nerve conduction velocity across the elbow, we recommend that the elbow be fully extended, as the distance measurement most accurately reflects the maximum anatomic length of the nerve. We also feel that the radial nerve F-wave latency is readily obtainable from the extensor indicis proprius muscle.     

Intracerebroventricular taurine in rabbits: effects of normal body temperature, endotoxin fever and hyperthermia produced by PGE1 and amphetamine.

1. Intracerebroventricular (I.C.V.) injections of taurine into rabbits resting at an ambient temperature (Ta) of 10 degrees or 23 degrees C caused hypothermia but at 30 degrees C ambient temperature, rectal temperature was unchanged. 2. An I.C.V. bolus of 0=5 mg taurine immediately followed by a slow infusion of taurine (0-01--0-2 mg/min) into rabbits at 23 degrees C ambient temperature caused sedation and peripheral vasodilation and blocked the febrile response to Salmonella typhosa endotoxin (1 microng/kg i.v.). Sustained fevers, characteristic of fevers caused by central administration of pyrogens, developed after taurine infusions were stopped. Control infusions of taurine at the same rates in the same rabbits when they were afebrile had little effect on rectal temperature. 3. An I.C.V. injection of 0-5 mg taurine reduced the hyperthermia caused by prostaglandin E1 (PGE1; 2 microng) given I.C.V. A dose of 5-0 mg not only blocked PGE1 hyperthermia but also caused marked hypothermia. 4. Bilateral injections of taurine into the preoptic/anterior hypothalamic region, at sites where injections of Salmonella typhosa endotoxin caused long-lasting fevers, had no effect on rectal temperature. Similar injections into the reticular substance of the medulla oblongata, in the region believed to be concerned with a secondary temperature control function, were also without effect on body temperature. 5. Taurine (0-5 and 5-0 mg, I.C.V.) had no consistent effect on hyperthermia induced by amphetamine (2 mg/kg, I.V.) 6. We conclude that the hypothermic effect of taurine is not due to an action on the central neurone pool or pools concerned with the integrative control of thermoregulatory effectors. This amino acid appears to inhibit neuronal activity in efferent pathways which control peripheral vasomotor tone and heat production and to depress the level of arousal. Taurine delays the onset and extends the duration of endotoxin-induced fever, perhaps by two separate action: by inhibiting activity in central thermoregulatory pathways and by promoting accumulation of endogenous pyrogen in the brain.     

Tolerance and withdrawal in goldfish exposed to ethanol

Acute ethanol exposure decreases regulated body temperature. Tolerance and dependence develop with continued exposure. Removal of ethanol following chronic exposure produces withdrawal. There is little information on the time course for the development of tolerance and disagreement about the presence of a rebound effect on body temperature during withdrawal. For tolerance, we monitored the selected temperature [T(sel)] of goldfish [Carassius auratus] for 8 h while they were exposed to one of three doses of ethanol. During the period from 90 to 150 min post-exposure, T(sel) was: control: 24.1+/-0.07 degrees C; 0.4% ethanol: 21.9+/-0.09 degrees C; 0.8% ethanol: 21.3+/-0.05 degrees C; 1.1% ethanol: 18.4+/-0.10 degrees C. The difference between control and experimental T(sel) decreased by the following amounts for the final 1.5 h in the gradient: 0.4% ethanol: 2.60+/-0.12 degrees C; 0.8% ethanol: 1.58+/-0.09 degrees C; 1.1% ethanol: 4.08+/-0.12 degrees C. At all 3 doses, tolerance proceeded in a stepwise manner rather than continuously. Temperature regulation during withdrawal was evaluated by maintaining the goldfish in 0.8% ethanol for three days and subsequently monitoring T(sel) in an ethanol-free temperature gradient for 36 h. During withdrawal there was no evidence for an effect on T(sel); experimental and control values were nearly identical.     

Evidence of state dependent learning of brightness discrimination in hypothermic mice

Shock-elicited escape behavior of C57Bl mice in a brightness discrimination task was examined to investigate the effects of hypothermia on acquisition and reversal. Neither acquisition nor reversal was impaired by 7 degrees C or 13 degrees C decreases in central body temperature when body temperature remained at those levels throughout testing. However, body temperature changes from acquisition to reversal were accompanied by memory deficits during reversal if acquisition occurred at body temperature decreased by 13 degrees and reversal occurred at normal body temperature or body temperature decreased by 7 degrees and reversal at body temperature decreased by 13 degrees. This finding suggests the occurrence of a state dependent discrimination response: an instance of asymmetrical dissociation. In addition, during acquisition, latency of the escape response was longer in hypothermic animals than in controls, and should be interpreted as a performance deficit, rather than failure or delayed rate of learning. Depressed intertrial activity also was observed in hypothermic animals.