Fish oil has beneficial effects on behavior impairment and oxidative stress in rats subjected to a hepatic encephalopathy model.

Hepatic encephalopathy (HE) is a severe neuropsychiatric complication of liver failure, in which there is injury to brain cells, particularly neurons and glia. Brain cells and their function are greatly influenced by omega-3 polyunsaturated fatty acids, essential components of cell membrane phospholipids in the brain that are crucial to normal function. This study assessed the effect of chronic fish oil (FO) supplementation (rich in omega-3 polyunsaturated fatty acids) on behavior and oxidative stress of Wistar rats subjected to HE due to a liver failure caused by thioacetamide (TAA) intoxication. The FO supplementation started in an early phase of brain development, that is, at the 21st day of life, and extended to the 122th day of life. The results indicated that cognitive function, specifically spatial memory, was markedly affected in the group that received TAA. Most notably, the ill effects caused by TAA administration were counteracted by FO supplementation. In addition to behavioral improvements, FO also promoted reduction in levels of thiobarbituric acid-reactive substances and superoxide dismutase activity in hippocampus and cerebral cortex. In summary, FO protected against spatial memory deficits and oxidative stress caused by HE in rats subjected to liver lesion due to TAA intoxication. Further studies are necessary to understand the mechanism underlying FO behaviors in rats subjected to encephalopathy.

Neurophysiological aspects of chronic motor cortex stimulation.

Chronic motor cortex stimulation is a treatment option for neuropathic drug-resistant pain and possibly associated movement disorders. Preliminary studies suggest the possibility to treat symptoms of Parkinson disease in selected patients. Recently, MCS has been suggested to enhance motor recovery in patients with poststroke hemiparesis. One or more electrodes are placed extradurally over the motor cortex through a burr hole or a small craniotomy, and then connected to a totally implantable neurostimulator. The accurate positioning of the stimulating electrodes over the motor cortex is the key point of the surgical procedure. Motor cortex identification results from the integration of anatomical, neuroradiological, functional, and neurophysiological data, taking into account the huge population variability. Intraoperative neurophysiological mapping of the motor cortex is of paramount importance, in spite of very sophisticated neuroradiological mathematical reconstructions of the motor area. We discuss and compare the different techniques that are utilized by different authors. Moreover, clinical neurophysiology is also helpful in evaluating the results of this neuromodulation procedure and in hypothesizing the mechanisms that are put in play by MCS.

Spinal cord stimulation and early experimental cerebral spasm: the "functional monitoring" and the "preventing effect".

BACKGROUND: Clinical and experimental data on cerebral blood flow (CBF) changes during spinal cord stimulation (SCS) were published since 1986. The aims of the present work are: 1. To find an experimental model of reliable, simple and in vivo monitoring of "early" basilar artery spasm after subarachnoid haemorrhage (SAH) and 2. To investigate the effects of cervical spinal cord stimulation (CSCS) on it. Vasospasm due to SAH is both "acute" and "recurrent". Early spasm occurs within minutes of the SAH. its duration is approximately 1 hour. The need of different morphological and haemodynamic methods to evaluate experimental early spasm is reported. To overcome intracranial surgical manipulations and biological effects of contrast and fixation media we designed a model that allows "in vivo" functional monitoring of basilar blood flow far away from the spasm without direct surgical and chemical interference. Subsequently we investigated the effects of CSCS on the new model of "functional monitoring" of the "early" cerebral vasospasm. METHOD: 29 adult Burgundy rabbits were studied. Group 1: under homeostatic monitoring, "on-line" carotid blood flow (carotid BF) changes produced by SAH in cisterna magna of 12 (plus 5 sham treated) animals were studied from the common carotid artery after external carotid artery occlusion before, during SAH and up to the end of the experiments. All the animals underwent digital subtraction cerebral panangiography (CPA) after SAH obtaining a significant increase of carotid BF only when basilar vasospasm was shown by CPA. Carotid BF increase during basilar vasospasm was defined "functional monitoring" of early spasm. Group 2: Twelve animals wearing a cervical epidural electrode underwent carotid BF "functional monitoring" of early basilar spasm before and during CSCS. FINDINGS: Carotid BF changes during CSCS occurred in 10 animals. No carotid BF changes (i.e. no basilar vasospasm) occurred after SAH up to the end of the experiments in all the stimulated animals. INTERPRETATION: CSCS is able to prevent "early spasm" due to SAH in all the animals studied with the new model of "functional monitoring" described, independently from the occurence and the sign for stimulation-induced carotid BF variations. The role and the limits of reversible functional sympathectomy in mediating the effect of CSCS on early vasospam are discussed.

Spinal cord stimulation in patients with refractory anginal pain and normal coronary arteries.

BACKGROUND: Spinal cord stimulation (SCS) has been shown to be effective in patients with refractory angina and coronary artery disease. No previous study assessed the clinical effects of SCS in patients with refractory angina who present angiographically normal coronary arteries. METHODS: SCS was performed in 7 patients (4 men, 3 women, mean age 59.3 +/- 11 years) with refractory angina and normal coronary arteries. Clinical status was assessed 1 month after SCS device implantation and at a mean follow-up of 11 months (range 2-17 months) by: 1) an estimate of the number of anginal attacks and nitrate consumption in the 2 weeks prior to implantation and to follow-up visits; 2) a score of quality of life by a visual analogic scale; 3) a five-item questionnaire assessing effort angina and satisfaction with treatment; 4) treadmill exercise testing. RESULTS: At the last follow-up the number of anginal episodes (p < 0.001) and nitrate consumption (p < 0.004) were both reduced by SCS. Visual analogic scale score improved from 2.1 +/- 0.98 to 9.0 +/- 0.9 (p < 0.001) at 1 month and to 6.4 +/- 2.3 (p < 0.01) at the last follow-up. Questionnaire analysis showed that mild (p = 0.006) and moderate (p = 0.000) physical activity, as well as patient satisfaction with anginal status (p = 0.000) and with current treatment (p = 0.000) all improved by SCS. Finally, time to 1 mm ST segment depression, time to angina, and exercise duration were all prolonged by SCS. CONCLUSIONS: Our data point out that SCS may considerably improve anginal symptoms and exercise tolerance in a significant number of patients with refractory angina and normal coronary arteries and therefore it should be considered as a valuable treatment option in this group of patients.

Spinal cord stimulation and cerebral blood flow in stroke: personal experience.

Spinal cord stimulation (SCS) can increase cerebral blood flow (CBF) and improve stroke patients. In order to better understand the haemodynamic changes underlining the clinical improvement, we have studied with transcranial Doppler (TCD), SPECT and NIRS 18 patients harbouring a stroke. SPECT Group: An increase of regional CBF during SCS was measured far from the stroke areas in 9 patients, further decrease in CBF was found in 2, no changes in 1. TCD Group: An increase of CBF velocities during SCS was found in 4 patients, no changes in 6, a decrease in 1. NIRS Group: Data consistent with and increase in CBF were obtained during SCS in the only patient undergone such a study. In 6 patients studied with different techniques, data obtained fitted only in 2 patients. In 3 patients no changes in TCD faced with changes in SPECT. In one case an improvement in TCD was evident in the left while an improvement of SPECT was shown in the right site. SCS is a valid therapeutic tool in stroke patient even if, as matter of fact, parallelism between clinical and haemodynamic changes during SCS is not demonstrated in our patients, rising the question on the role of ischemic penumbra in mediating clinical improvement.

Direct demonstration of the effect of lorazepam on the excitability of the human motor cortex.

OBJECTIVES: The present study explored the effects of lorazepam, a benzodiazepine with agonist action at the GABA(A) receptor, on human motor cortex excitability as tested using transcranial magnetic stimulation. METHODS: We recorded directly the descending volley evoked by single and paired transcranial magnetic stimulation from the spinal cord of a conscious subject with a cervical epidural electrode before and after a single oral dose of lorazepam. We evaluated the effects of lorazepam on the descending volleys evoked by a single magnetic stimulation and paired cortical stimulation using the intracortical inhibition paradigm (subthreshold conditioning stimulus) and the short latency intracortical facilitation paradigm (suprathreshold conditioning stimulus). RESULTS: Using a single magnetic stimulus lorazepam decreased the amplitude of the later I waves in the descending volley; this was accompanied by a decrease in the amplitude of the evoked EMG response. Using the intracortical inhibition paradigm lorazepam increased the amount of corticocortical inhibition, particularly at 4 and 5 ms interstimulus intervals. There was no effect on the amount of facilitation observed in the short latency intracortical facilitation paradigm. CONCLUSIONS: The present findings provide direct evidence that lorazepam increases the excitability of inhibitory circuits in the human motor cortex.

Spinal cord stimulation in the treatment of paraplegic pain.

Twenty-five patients suffering from intractable pain due to a chronic spinal cord lesion underwent a percutaneous test of spinal cord stimulation. At the end of the test period, 40.9% of the patients reported a mean of 65% pain relief and these patients were selected for ongoing stimulation. At a mean follow-up time of 37.2 months the success rate, based on the number of patients with more than 50% pain relief, had fallen to 18.2%. Pain relief rates were analyzed in relation to quality of pain, neurological status, level and extent of the lesion, and electrode level to identify prognostic factors that could improve the clinical usefulness of spinal cord stimulation. Patients experiencing painful spasms or a constrictive type of pain and with incomplete thoracic lesions were found to be the best candidates for spinal cord stimulation.

Increase of cerebral blood flow and improvement of brain motor control following spinal cord stimulation in ischemic spastic hemiparesis.

A 64-year-old man had an ischemic stroke in the left parietotemporal cortical-subcortical areas. He developed a severe right spastic hemiparesis and dysphasia. An angiographic study showed left internal carotid artery occlusion and right internal carotid artery stenosis. A right internal endoarteriectomy was performed without any clinical improvement. After 1 year the patient was a candidate for cervical spinal cord stimulation (SCS) for the treatment of his spastic hemiparesis. An epidural electrode (Medtronic Sigma 3483) was positioned at the cervical level, mediodorsal to the cord. Clinical and neurophysiological studies (surface polyelectromyography, PEMG, for evaluation of brain motor control) were performed before and after 7 days of SCS (0.2 ms, 80 c/s, intensity for paresthesiae, continuous mode). A transcranial Doppler (TCD) study of both middle cerebral arteries (MCA) at rest and during SCS was performed on two occasions. SCS was followed by improvement of voluntary movement, decrease of spasticity and better endurance. The clinical findings were confirmed by the PEMG recordings. TCD examination showed an increase of flow velocities on both the right MCA (+43%) and the left MCA (+130%) during SCS. Such a TCD pattern, suggesting an increase of cerebral blood flow (CBF) during SCS, was reproducible. This case confirms efficacy of SCS in the treatment of ischemic hemiparesis and the increase of CBF following cervical SCS in man. The marked increase of CBF, particularly evident on the ischemic side, may play a role in mediating the improvement of motor control in our patient together with a possible arousal of the so-called 'sleeping neurons' of the penumbra zone.

Spinal cord stimulation and cerebral blood flow: an experimental study.

Spinal cord stimulation (SCS) affects peripheral, coronary and cerebral blood flow (CBF) in humans. In 1986 Meglio et al. [Appl Neurophysiol 1986;49:139-146] advocated a functional reversible sympathectomy as one of the mechanisms of SCS in man. An experimental animal model was developed to study SCS effects on CBF and to investigate the possible mechanisms. Twenty-one white New Zealand rabbits were anesthetized with Fluothane; spontaneous ventilation was permitted. A steady hemodynamic and metabolic state was maintained. A small cervical laminectomy was performed and an electrode (Medtronic Sigma 3483) was placed in the epidural space over the posterior spinal cord. Both common carotid arteries were exposed and external carotid arteries were ligated. In 3 animals, the cervical symapthetic trunk (CST) was exposed and wrapped with bipolar hook-stimulating electrodes. SCS was performed for 20 min with electrical square waves of 210 microseconds duration, 80 cycles/s, at 2/3 motor threshold intensity. CST stimulation was delivered for 1 min with the following parameters: 10 V, 10 cycles/s, 0.5 ms duration. CBF velocities of both internal carotid arteries were measured by using a CW Doppler (in all the animals) and electromagnetic flowmeter (in 2 animals), at rest, during sympathetic trunk stimulation, during SCS, during simultaneous SCS and CST stimulation. During SCS, an increase of CBF was detected in 11 rabbits (52.4%); a decrease was observed in two cases (9.5%). No change was detected in the remaining 8 animals (38%). CST stimulation induced a decrease of CBF in all animals. Electromagnetic flowmetry confirmed velocitometric findings in the 2 cases studied.(ABSTRACT TRUNCATED AT 250 WORDS)

Spinal cord stimulation in low back and leg pain.

We have reviewed our experience with spinal cord stimulation (SCS) in patients with low back and leg pain. 33 patients complaining of leg and low back pain underwent percutaneous tests of SCS. 28 patients had failed back surgery syndromes, 1 patient had pain related to an L1 vertebral body fracture, another from Tarlow cysts and the remaining 3 patients had lumbosacral spondyloarthrosis and osteoporosis without radiological signs of root compression. 28 patients showed mono- or pluriradicular deficits. At the end of the test period (5-65 days), 21 patients (63.6%) reported more than 50% of pain relief (mean analgesia 75%) and were submitted to chronic stimulation. The mean follow-up was 45.5 months. At maximum available follow-up, 40% of the patients (13 out of the 33 initial patients) were successfully using the stimulator (mean analgesia 66.6%).

Cerebral hemodynamics during spinal cord stimulation.

An increase of cerebral blood flow (CBF) during spinal cord stimulation (SCS) has been shown in man using the 133Xenon inhalation technique. We report the effects of SCS on cerebral hemodynamics studied with transcranial Doppler sonography (TCD). Twenty-six patients with epidural electrodes implanted at the cervical level (11 patients) and at the thoracic level (15 patients) were investigated with recordings of CBF velocity in the middle cerebral arteries before and during SCS. Sixty-three and two-thirds percent of patients with cervical stimulation and 29.4% of patients with thoracic stimulation showed a decrease of cerebral vascular resistance simultaneously with an increase of the velocity of CBF.

Spinal cord stimulation and cerebral haemodynamics.

An increase of regional cerebral blood flow (rCBF) has been shown to occur in man during spinal cord stimulation (SCS) by Hosobuchi (1986) and by Meglio et al. (1988) using the 133-Xenon wash-out technique. In this paper we report the effects of SCS on CBF as measured by two different techniques: 8 patients were studied with the 133-Xe method and 28 with the transcranial doppler sonography (TCD), in two cases both studies were performed. The aim of our study was to: 1-verify the effect of SCS on CBF, 2-compare observations made by two different methods, and 3-evaluate a possible correlation between the stimulated spinal segmental level and the modification of CBF. The results of our study confirm that SCS interacts with the mechanisms of regulation of CBF. The stimulation of different spinal cord levels in the same patient can produce different effects and such effects are reproducible. An increase of CBF is more likely to occur with the stimulation of the cervical spinal cord. In patients studied by both methods the sign of CBF changes induced by SCS was the same. Finally, in two patients the effect of SCS on CO2 autoregulation was studied with TCD. The results of such a study, although preliminary, suggest that CO2 and SCS have a competitive effect upon the mechanisms of regulation of CBF.

Spinal cord stimulation in management of chronic pain. A 9-year experience.

Between 1978 and 1986, 109 patients with chronic pain underwent spinal cord stimulation (SCS) at the authors' institute as part of their pain treatment program. The results of SCS in these patients at the end of the test period and at the latest follow-up examination are analyzed in relation to the etiology of their pain. In 40 patients pain was associated with an obstructive peripheral vasculopathy, in 10 with a previous herpes zoster infection, in 15 with an incomplete traumatic spinal cord lesion, in nine with root and/or nerve damage, in 11 with cancer, and in 19 with previous back surgery. The etiology of the pain in five patients was uncertain. This experience supports the conclusion that the best indications for SCS are vasculopathic pain and post-herpetic neuralgia. No clinical usefulness was found for SCS in cancer pain or in central deafferentation types of pain.

Spinal cord stimulation (SCS) in deafferentation pain.

Spinal cord stimulation is considered to be ineffective in relieving deafferentation pain. We have retrospectively analyzed the results obtained in a series of 41 patients. Sixteen suffered from pain associated with an incomplete traumatic spinal lesion, 15 from a posttherapeutic neuralgia, and 10 from pain due to root and/or nerve damage. At the end of the test period, 43.7% of the patients with paraplegic pain, (40% of those with peripheral deafferentation pain and 66.6% of the ones with postherapeutic neuralgia), reported satisfactory pain relief and were connected to a chronic stimulation system. At mean follow-up (15 months), only 20% of the patients of the first two groups reported sufficient pain relief. In the postherapeutic group the figure of responders was unchanged. The mean analgesia achieved was 70%. From this analysis we conclude that the results achieved in the postherapeutic pain patients, although positive in only 66% of them, are remarkably stable with time. Therefore, we recommend a percutaneous test trial of SCS in every case of postherapeutic pain resistant to medical treatment.

Spinal cord stimulation (SCS) in spastic hemiparesis.

Thirteen patients with post-stroke spastic hemiparesis underwent a percutaneous test trial of spinal cord stimulation (SCS) in order to modify their motor disturbances. Clinical evaluation based on Albert's motor scale and neurophysiological evaluation consisting of surface EMG during voluntary, involuntary, and reflex motor activity were performed before and during SCS. At the end of the test period, eight patients showed a significant improvement in their motor performance. The EMG analysis confirmed the clinical data. SCS was followed by a reduction or disappearance of synergic coactivation with better agonist-antagonist coordination, a decrease of clonus both in duration and spreading, and better endurance. The effect on motor control did not increase with time after the first month of SCS, but was long lasting (mean follow-up: 2 years). There was a correlation between sensory deficit and motor outcome suggesting that the enhancement of sensory input put into play by SCS and the consequent development of new sensory-motor integration might be responsible for the improvement in motor performance.

Effect of spinal cord stimulation on motor performances in hemiplegics.

Spinal cord stimulation (SCS) was performed in 11 patients with stabilized spastic hemiparesis due to cerebrovascular ischaemic accident in order to improve their motor performances. The patients were studied before and after 5-7 days of stimulation of the cervical cord according to the following protocol: (1) clinical evaluation based on assessment of the neurological status and on Albert's motor scale and (2) neurophysiological evaluation of reflex voluntary and involuntary motor activity, obtained by means of surface electromyography. Improvement in motor performance following SCS occurred in 7 of the 11 patients. The effect appeared to be particularly evident during specific voluntary movements and gait. Analysis of the electromyography recordings showed that SCS mainly broke down pathological patterns of voluntary movement and reduced agonist-antagonist coactivation and clonus. A relationship between motor outcome and status of the sensory function was noticed as well. We conclude that SCS may play a role in the motor rehabilitation of post-stroke patients with spastic hemiparesis, provided that a careful selection be made before surgery.

Spinal cord stimulation (SCS) in the treatment of postherpetic pain.

SCS is considered to be of poor value in treating postherpetic pain. We have retrospectively analyzed the results obtained in 10 patients suffering from postherpetic neuralgia. An epidural electrode was implanted, aiming the tip in a position where stimulation could produce paraesthesiae over the painful area. At the end of the test period 6 out of 10 patients reporting a mean analgesia of 52.5% underwent a permanent implant. At mean follow-up (15 months) all the 6 patients were still reporting a satisfactory pain relief (74% of mean analgesia). These figures remained unchanged at the next follow-ups (max 46 months). The result of SCS in our patients, although positive in only 60% of them, are remarkably stable with time. We therefore recommend a percutaneous test trial of SCS in every case of postherpetic neuralgia resistent to medical treatment.

Spinal cord stimulation improves motor performances in hemiplegics: clinical and neurophysiological study.

We studied the effects of spinal cord stimulation (SCS) on motor performances in patients with spastic hemiparesis due to cerebrovascular ischemic accident. 11 patients were evaluated before and after 7 days of SCS by means of the Albert's motor scale and a surface polyelectromyography. SCS significantly improved motor performances in 63% of the patients. It reduced agonist-antagonist coactivation and clonus. Such an effect was particularly evident during voluntary movements and gait.

Spinal cord stimulation affects the central mechanisms of regulation of heart rate.

The effect of spinal cord stimulation (SCS) on heart rate (HR) was studied in 25 patients without cardiological symptoms, who were undergoing SCS for various reasons. HR at rest significantly decreased during SCS. Physiological and pharmacological maneuvers of sympathetic and parasympathetic activation or blockade before and during SCS indicate that SCS interferes with the central mechanisms of regulation of HR mainly by inducing a functional sympathectomy, and that such an effect is mediated by an action on spinal cord ascending fibers.

Epidural recordings of electrical events produced in the spinal cord by segmental, ascending and descending volleys.

Epidural electrodes implanted for a percutaneous trial of therapeutic spinal cord stimulation were used to record electrical events evoked by the stimulation of peripheral nerves or of the spinal cord itself. The data collected in patients with no neurological deficit were analyzed in order (1) to check the consistency between epidural and surface recordings, (2) to get information on the genesis of such potentials, and (3) to demonstrate the feasibility of complex neurophysiological studies by means of epidural electrodes. Spinal cord potentials evoked by segmental volleys were recorded at cervical levels with the recording electrodes anterior, lateral and posterior to the spinal cord. The refractory period of the evoked potentials has been studied as well. Responses to stimulation of the tibial nerve were obtained at T11-12 vertebral level with posterior epidural electrodes. Segmental cervical potentials were characterized by a P10, N11, N13/P13 followed by a slow positivity/negativity. A response of similar waveform, but with different peak latencies, was recorded at segmental levels following tibial nerve stimulation. Such a response showed an increasing number of spikes while ascending along the spinal cord. Maximum conduction velocities in the cord were between 65 and 85 m/s. Our epidural recordings are similar to those obtained from the skin, but with a greater amplitude and waveform resolution. Furthermore, the use of epidural electrodes made it feasible to perform complex examinations of sensory function (i.e., the study of orthodromic and antidromic conduction along the dorsal cord and of the influence of a single dorsal cord volley on the segmental cervical potential). Finally, the genesis of the potentials recorded is discussed.