Somatosensory evoked potentials and blood lactate levels.

We compared, in 20 subjects, the effects of high blood lactate levels on amplitude and latency of P1, N1, P2 and N2 components of lower limb somatosensory evoked potential (SEP), an useful, noninvasive tool for assessing the transmission of the afferent volley from periphery up to the cortex. SEPs were recorded from CPz located over the somatosensory vertex and referenced to FPz with a clavicle ground. Measurements were carried out before, at the end as well as 10 and 20 min after the conclusion of a maximal exercise carried out on a mechanically braked cycloergometer. After the exercise, P2-N2 amplitudes as well as latency of P1 and N1 components showed small but significant reductions. On the contrary, latency of N2 component exhibited a significant increase after the exercise's conclusion. These results suggest that blood lactate appears to have a protective effect against fatigue, at least at level of primary somatosensory cortex, although at the expense of efficiency of adjacent areas.

Relationship of high blood lactate levels with latency of visual-evoked potentials.

We studied, in healthy adult subjects, the association of high blood lactate levels, induced with an exhaustive exercise (12 subjects) or an intravenous infusion (four subjects) of a lactate solution (3 mg/kg in 1 min), with amplitude and latency of visual-evoked potentials. Amplitude of N75, P100, and N145 components did not show significant changes, whereas latency of P100 was reduced at exercise's end and that of N145 increased 10 min after the conclusion. Therefore, an increase of blood lactate induced by an exhaustive exercise or an intravenous infusion appears to induce an improvement in the conduction time between eye and striate cortex, while it seems to evoke a worsening of intracortical communication between striate and extrastriate areas.

Effects of repetitive transcranial magnetic stimulation in performing eye-hand integration tasks: four preliminary studies with children showing low-functioning autism.

This report, based on four studies with children with low-functioning autism, aimed at evaluating the effects of repetitive transcranial magnetic stimulation delivered on the left and right premotor cortices on eye-hand integration tasks; defining the long-lasting effects of high-frequency repetitive transcranial magnetic stimulation; and investigating the real efficacy of high-frequency repetitive transcranial magnetic stimulation by comparing three kinds of treatments (high-frequency repetitive transcranial magnetic stimulation, a traditional eye-hand integration training, and both treatments combined). Results showed a significant increase in eye-hand performances only when high-frequency repetitive transcranial magnetic stimulation was delivered on the left premotor cortex; a persistent improvement up to 1 h after the end of the stimulation; better outcomes in the treatment combining high-frequency repetitive transcranial magnetic stimulation and eye-hand integration training. Based on these preliminary findings, further evaluations on the usefulness of high-frequency repetitive transcranial magnetic stimulation in rehabilitation of children with autism are strongly recommended.

Changes in cortical excitability and blood lactate after a fatiguing hand-grip exercise.

Excitability of primary hand motor cortex (PHMC), evaluated with transcranial magnetic stimulation by using the "1 mV resting motor threshold" method, and capillary blood lactate were measured at the end, as well as 5 and 10 min after a fatiguing hand-grip exercise. The relation between blood lactate and the amplitudes of motor-evoked potentials showed a significant direct proportionality. Blood lactate seems to exert a protective role on PHMC against fatigue reduction during extremely intensive isometric exercises.

Attentional processes during submaximal exercises.

Blood levels of lactate and glucose were measured in 15 healthy male athletes with the purpose of evaluating possible correlation between their blood values and intensity and selectivity of attention, after a 30-min steady-state test performed at 60 and 80% of maximal oxygen consumption (VO2max). On the basis of the results, we conclude that, during aerobic exercise, a worsening of attentional capabilities does not occur unless there is an increase of blood lactate above 4 mmol/l.

Brainstem excitability is not influenced by blood lactate levels.

The influence of blood lactate on brainstem excitability was tested by using the blink reflex (BR) recovery cycle on 18 sprinters. Blood lactate was measured before maximal cycling, at the end, as well as 5 and 10 min after the exhaustion. Blood lactate was associated with a decrement of R2 whereas only small changes were observed after an intravenous infusion of lactate. It seems, therefore, that lactate influences BR mainly by acting at the cortical level.

Enhanced motor cortex facilitation in patients with vascular cognitive impairment-no dementia.

Data on Transcranial Magnetic Stimulation (TMS) derived measures of cortical excitability and intracortical circuits in age-related white matter changes are scarce. We aimed to assess early changes of motor cortex excitability in nondemented elderly patients with subcortical ischemic vascular disease (SVD). Ten SVD elderly and ten age-matched controls underwent paired-pulse TMS for the analysis of intracortical inhibition (ICI) and facilitation (ICF). All subjects performed neuropsychological assessment and brain magnetic resonance imaging. SVD patients showed abnormal executive control function. No statistically significant differences were found for resting motor threshold, cortical silent period between SVD patients and controls or between the two hemispheres, in patients. A significant enhancement of mean ICF was observed in SVD patients. This study provides the first evidence of functional changes in intracortical excitatory neuronal circuits in patients with SVD and clinical features of vascular cognitive impairment-no dementia. Further studies are required to evaluate whether the observed change of ICF might predict cognitive and/or motor impairment in a population at risk for subcortical vascular dementia.

Spinal cord excitability is not influenced by elevated blood lactate levels.

The aim of the present study was to examine the association of high blood lactate levels, induced with a maximal cycling or with an intravenous infusion, with spinal cord excitability. The study was carried out on 17 male athletes; all the subjects performed a maximal cycling test on a mechanically braked cycloergometer, while 6 of them were submitted to the intravenous infusion of a lactate solution (3 mg/kg in 1 min). Before the exercise or the injection, also at the end as well as 5 and 10 min after the conclusion, venous blood lactate was measured and excitability of the spinal α-motoneurons was evaluated by using the H reflex technique. In both experimental conditions, it has been observed that an exhaustive exercise is associated with a strong increase of blood lactate (but not of blood glucose) and with a significant reduction of spinal excitability. Since a similar augment of blood lactate induced by an intravenous infusion, in subjects not performing any exercise, is not associated with significant changes of spinal excitability, it can be concluded that the increase of blood lactate levels during a maximal exercise is not per se capable of modifying the excitability of spinal α-motoneurons.

Motor cortex hyperexcitability in subcortical ischemic vascular dementia.

To study whether in subcortical ischemic vascular dementia (SIVD) the changes of motor cortex excitability are due to the dementing process or to the cerebrovascular lesions, we examined 20 SIVD patients, 20 patients with subcortical ischemic disease without dementia (SIDWD) and 20 control subjects who underwent transcranial magnetic stimulation (TMS). Motor threshold (MT), amplitudes of motor evoked potentials (MEPs) and silent period (SP) were considered. MT in SIVD patients (32.7 ± 2.6%) was significantly lower (p<0.001) than in SIDWD patients (47.9 ± 3.4%) and in controls (49.1 ± 4.2%). MEP amplitude was larger in SIVD patients (6.8 ± 1.7 mV) than in the other groups (5.7 ± 1.9 mV and 5.2 ± 1.8 mV, p<0.02). Motor cortex excitability is enhanced in SIVD. Our data, taken together with previous results in Alzheimer disease (AD), indicate that motor cortex hyperexcitability is a common finding in different dementing illnesses.

Gender differences in changes of motor cortex excitability during elevated blood lactate levels.

Gender differences in cortical excitability have been detected by using transcranial magnetic stimulation (TMS). The present study was carried out to compare the effects of high blood lactate levels, induced by performing a maximal exhausting exercise, on the excitability of the primary motor cortex in young male and female athletes. The study was carried out on 21 young males and 20 females from the Middle Distance Track Team of our university. Before the exercise, at the end, as well as 5 and 10 min after the conclusion, venous blood lactate and glucose were measured and excitability of the motor cortex was evaluated by using TMS. We observed a similar enhancement of excitability of primary motor cortex, concomitantly with an increase of blood lactate, in both young male and female athletes. However, the improvement was significantly higher (p < 0.05) in women (37.4% +/- 3.97) than in men (42.0% +/- 6.43), suggesting a greater sensitiveness of female cerebral cortex to blood lactate.

Elevated blood lactate is associated with increased motor cortex excitability.

No information has yet been provided about the influence of blood lactate levels on the excitability of the cerebral cortex, in particular, of the motor cortex. The aim of the present study was to examine the effects of high blood lactate levels, induced with a maximal cycling or with an intravenous infusion, on motor cortex excitability. The study was carried out on 17 male athletes; all the subjects performed a maximal cycling test on a mechanically braked cycloergometer, whereas 6 of them were submitted to the intravenous infusion of a lactate solution (3 mg/kg in 1 min). Before the exercise or the injection, at the end, as well as 5 and 10 min after the conclusion, venous blood lactate was measured and excitability of the motor cortex was evaluated by using the transcranial magnetic stimulation. In both of these experimental conditions, it was observed that an increase of blood lactate is associated with a decrease of motor threshold, that is, an enhancement of motor cortex excitability. We conclude by hypothesizing that in the motor cortex the lactate could have a protective role against fatigue.

Changes of blood lactate levels after repetitive transcranial magnetic stimulation.

The objective was to study whether repetitive transcranial magnetic stimulation (rTMS) of the motor cortex could induce modification of peripheral blood lactate values. Nineteen young healthy volunteers were included; during the study, all subjects were at rest, sitting on a comfortable armchair. The muscular activation was evaluated by continuous electromyographic record. TMS was performed by using a circular coil at the vertex. Resting motor threshold (rMT) was defined as the lowest TMS intensity able to induce motor responses of an amplitude >50 microV in the relaxed contralateral target muscle in approximately 50% of 20 consecutive stimuli. Venous blood lactate values were measured before, immediately after and 10 min after a single session of low frequencies (1Hz for 15 min) rTMS (LF rTMS) or high frequency (20 Hz for 15 min) rTMS (HF rTMS). As expected, LF rTMS induced a decrease of motor cortex excitability, whereas HF rTMS evoked an increase of motor cortex excitability. However, in the present investigation we observed that both conditions are associated to a significant increase of blood lactate. Since in our experimental conditions we can exclude a muscular production of lactate, the significant increment of peripheral blood lactate values, observed 10 min after the end of the rTMS session, is probably due to the crossing by brain-produced lactate of the blood-brain barrier.

Effects of either LT4 monotherapy or LT4/LT3 combined therapy in patients totally thyroidectomized for thyroid cancer.

After total thyroidectomy all thyroid cancer patients require lifelong treatment with thyroid hormones; the treatment of choice is synthetic levothyroxine (LT4). The question of whether these patients might benefit from the combined LT4 and liothyronine (LT3) treatment has been addressed with conflicting conclusions. The aim of the present study was to compare the effects of combined low LT4/LT3 molar ratio therapy versus LT4 monotherapy on various target organs and tissues in patients thyroidectomized for thyroid cancer. Urine collection (24 hour), a fasting blood sample for laboratory examinations, thyroid function clinical score, and cardiovascular, neurological, and neuropsychological evaluations were obtained. Clinical parameters and peripheral markers of thyroid function were measured during the two different treatment regimens in 20 patients. Mean serum aspartate aminotransferase, alanine aminotransferase, sex hormone binding globulin, and osteocalcin values were significantly higher during the combined treatment. No significant differences in the clinical score, the systolic and diastolic performance, and the neurological and neuropsychological evaluations were observed between the two treatment regimens. Moreover, no alteration due to subclinical hyperthyroidism or to the fluctuations in serum T3 concentrations during the combined therapy was observed. In conclusion, we found no evidence that combined therapy with a low LT4/LT3 molar ratio resulted in improved well-being and cognitive function or in increased thyroid hormone action on peripheral tissues in respect to LT4 monotherapy. Until future large, blind, randomized, and controlled trials prove otherwise, LT4 should remain the standard treatment for thyroid cancer patients.

Repetitive transcranial magnetic stimulation in schizophrenic patients reporting auditory hallucinations.

Auditory hallucinations are experienced by 60-80% of person with schizophrenia and can often cause significant distress behavioural dyscontrol. The application of rTMS in the left temporoparietal cortex could modulate the neuronal activation and reduce the occurrence of auditory disperceptions. Sixteen schizophrenic patients (treated with atypical antipsycothic drugs) reporting auditory hallucinations were included in the study. Low frequency rTMS (1 Hz) was performed at the 90% of resting motor threshold (MT), during 4 sessions in four consecutive days for 15 minutes each application. Eight patients received active stimulation, while eight patients received sham stimulation. Scale for the assessment of positive symptoms (SAPS), scale for the assessment of negative symptoms (SANS) and a scale to asses the severity of the auditory hallucinations (SAH) were administered at the beginning and at regular intervals during the follow-up. The present study confirms the reduction in auditory hallucinations by means of rTMS. The main finding was the long-term reduction in auditory hallucinations in the active group, with a return to the baseline in the sham group. The negative symptomatology improved only in the later sessions and lasted during the follow-up. The improvements in auditory hallucinations and positive symptomatology increased and lasted during the follow-up till the end-point. These data suggest that this approach may lead to an alternative somatic intervention for auditory hallucination in patients with schizophrenia.

Helicobacter pylori and Alzheimer's disease: a possible link.

BACKGROUND: Although serological findings indicate the presence of a relationship between Helicobacter pylori (HP) and vascular disease, no data have been reported about a possible association of HP with dementia. The aim of the present study was to determine whether chronic HP infection might play a role in Alzheimer's disease (AD). METHODS: Plasma homocysteine level, serum folate and vitamin B(12) concentrations, plasma pyridoxal phosphate level, IgG and IgA antibodies to HP, and C-reactive protein (CRP) were determined in 30 AD patients, 30 patients affected by vascular dementia (VaD), and 30 control subjects. All patients and control subjects were matched for age, educational level, and nutritional and socioeconomic status. None of the subjects had a history of chronic gastritis, peptic ulcer, gastric cancer, or major abdominal surgery. RESULTS: HP-IgG level was significantly increased in VaD patients as compared to controls and AD patients, while AD patients had HP-IgG levels higher than those of normal controls. HP-IgA levels were equally increased in both VaD and AD patients. CRP was higher in AD patients than in VaD patients and controls, although CRP levels in VaD patients were also significantly increased. CONCLUSIONS: The present study found an association between HP infection and AD. The question remains as to whether this association is due to the ubiquity of HP, or whether it contributes to the neuroinflammatory process in AD. The relationship between HP and AD, if confirmed by additional studies with a greater number of patients, may have important clinical and therapeutic implications.

Homocysteine, vitamin B12 and folate in vascular dementia and in Alzheimer disease.

The association between elevated plasma levels of homocysteine (Hcy) and nutritional status has been shown in Alzheimer disease (AD) patients and also in vascular dementia (VaD). Moreover, a previous study provided evidence that the relation between a high Hcy level and low vitamin B12 and folate levels in AD patients is due to biochemical damage, rather than a nutritional deficit. The purpose of this study was to investigate the relationship between plasma Hcy levels and vitamins involved in its metabolism in AD and VaD. Twenty-two VaD patients, 22 AD patients and 24 healthy subjects were studied for Hcy, vitamin B12, vitamin B6 and folate. All patients and control subjects were comparable for age, educational level, nutritional and socioeconomic status. None of them showed macrocytic anemia or impaired renal function. Hcy was significantly increased in VaD patients (26.0 +/- 6.58 micromol/l) as compared to controls (10.7 +/- 3.0 micromol/l) and AD patients (22.3 +/- 4.51 micromol/l; p<0.001); however, AD patients also showed increased levels of Hcy. Folates were significantly reduced in both VaD (10.8 +/- 2.81 nmol/l) and AD (10.0 +/- 2.72 nmol/l; p<0.001) patients, while vitamin B12 showed significantly reduced levels only in AD patients (392.1 +/- 65.32 pmol/l; p=0.02). Vitamin B6 was not significantly different in the three groups. Increased levels of Hcy associated with low vitamin B12 plasma levels were found only in AD patients. This observation led us to consider that vitamin B12 metabolism does not represent the direct consequence of the nutritional status and suggests that neuronal damage results in a functional vitamin B12 deficiency, as emphasized by recent reports. New therapeutic strategies are necessary, considering that available pharmaceutical forms of vitamin B12 are not utilized by neurons in oxidative stress conditions.

Motor cortex excitability in Alzheimer's disease and in subcortical ischemic vascular dementia.

Twenty Alzheimer's disease (AD) patients, 20 subcortical ischemic vascular dementia (SIVD) patients and 20 neurologically and cognitively normal subjects underwent transcranial magnetic stimulation to study motor cortex excitability changes. Motor threshold (MT), amplitude of motor evoked potentials, silent period and the H/M ratio (amplitude of maximal Hoffman reflex vs. that of maximal motor response) were considered. MT was lower in SIVD patients when compared with AD patients (P = 0.003) and the control group (P < 0.001) and lower in AD patients when compared with the control group (P < 0.001). The increment of motor cortex excitability in AD and SIVD did not lead us to distinguish clearly the two types of dementia. It is likely that the electrophysiological similarity between AD and SIVD could represent another common mechanism shared from these forms of dementia.

Post-stroke reorganization of hand motor area: a 1-year prospective follow-up with focal transcranial magnetic stimulation.

OBJECTIVE: Focal transcranial magnetic stimulation was used to test prospectively corticospinal excitability changes and reorganization of first dorsal interosseous (FDI) motor cortical representation in 31 patients who experienced a first ischemic stroke in the middle cerebral artery territory. All had severe hand palsy at onset. METHODS: Patients were assessed clinically with the Medical Research Council, Rankin, the National Institutes of Health stroke scales and Barthel Index at days 1, 8, 30, 90, 180 and 360 after stroke. The following parameters of FDI motor evoked potential (MEPS) to focal transcranial magnetic stimulation were measured at the same delays: motor threshold, MEP amplitude, excitable cortical area, hot spot and center of gravity of FDI motor maps on affected and unaffected hemispheres. Correlations were sought between clinical and electrophysiological parameters. RESULTS: In patients whose affected motor cortex remained excitable at day 1, motor thresholds were not significantly different between sides and were similar to those of controls. Persistence of MEP on the affected side at day 1 was a strong predictor of good recovery. If present at day 1, MEPs recorded in affected FDI were significantly smaller than of the opposite side or in normals and progressively recovered up to day 360. In these patients, area of excitable cortex remained stable throughout the entire study. At day 1, amplitudes of MEPs obtained in unaffected FDI were significantly larger than later. Between days 1 and 360, we observed a significant displacement of center of gravity of motor maps towards more frontal regions on the affected side while no change was noted on the unaffected side. CONCLUSIONS: Our data confirm the early prognosis value of transcranial magnetic stimulation in stroke. They indicate that the brain insult induces a transient hyperexcitability of the unaffected motor cortex. The evolution of FDI motor maps along the course of recovery mostly reflect corticospinal excitability changes but might also reveal some degree of brain plasticity. Most modifications observed occurred within 3 months of stroke onset.

Motor cortex excitability in Alzheimer disease: one year follow-up study.

Seventeen patients affected by Alzheimer disease (AD) underwent two transcranial magnetic stimulation (TMS) studies separated by an interval of 12 months, in order to monitor possible changes in motor cortex excitability. After the first examination, all patients were treated with cholinesterase inhibitor drugs. Motor threshold (MT), amplitude of motor evoked potentials and central motor conduction time were considered. After one year, the mean MT values showed a decrease significantly correlated with the severity of cognitive involvement, evaluated by means of the Mini Mental State Examination (MMSE). The difference in MT between the two recording sessions showed no significant correlation with the difference in MMSE score. One year of treatment with cholinesterase inhibitor drugs did not stop the progressive increase in motor cortex excitability. Serial analysis of TMS might represent a method to monitor the rate of change in motor cortex excitability in patients with AD.