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Biomedical subjects

G Zanette

Publications and source records attributed to G Zanette.

At least 19 recordsLinked to original sources

Hyperexcitable cortical responses in progressive myoclonic epilepsy: a TMS study.

OBJECTIVE: Transcranial magnetic stimulation (TMS) has allowed investigators to study intracortical inhibition and facilitation and sensorimotor integration in motor disorders and epilepsy. The authors used TMS to elucidate the pathophysiology of reflex myoclonus with giant somatosensory evoked potentials (SEP). METHODS: The authors studied four patients with progressive myoclonic epilepsy. All patients had giant SEP elicited by mixed and digital nerve stimulation. They studied the response to paired-pulse TMS at interstimulus intervals (ISI) ranging from 1 to 15 ms and the conditioning effect of digital electrical stimulation at ISI ranging from 10 to 100 ms on the motor evoked potential amplitude to TMS. RESULTS: Digital stimulation markedly facilitated conditioned motor evoked potentials at ISI ranging from 25 to 40 ms in all patients. This pattern was significantly different from the inhibition observed in controls (n = 12) at the same ISI. In the patients, paired-pulse TMS showed a decrease in intracortical inhibition in the motor cortex in comparison with controls. CONCLUSIONS: These findings suggest cortical and subcortical components of abnormal sensorimotor integration in addition to hyperexcitability of the sensory and motor cortex in our myoclonic patients.

Adolescent↗

Decrease in motor cortical excitability in human subjects after sleep deprivation.

The effect of sleep deprivation on human motor cortical excitability was investigated by evaluating the changes in motor evoked potentials from the thenar eminence muscles of the right hand in seven subjects. Motor threshold, motor evoked potential amplitude, silent period, intracortical inhibition, intracortical facilitation and F wave were studied. Recordings were performed every 6 h during the day-time (from 09.00 to 21.00 h) and every 3 h during the night-time (from 21.00 to 09.00 h). Significant increases in motor threshold, intracortical inhibition and silent period were noted in the recordings during the night associated with a return to baseline values in the morning. No significant changes were observed in any of the other parameters. Enhancement of intracortical motor inhibition is suggested to explain the effect of sleep deprivation.

Adult↗

Intravenous clomipramine decreases excitability of human motor cortex. A study with paired magnetic stimulation.

Several recent reports suggest the possibility of monitoring pharmacological effects on brain excitability through transcranial magnetic stimulation (TMS). In these studies, paired magnetic stimulation has been used in normal subjects and on patients who were taking different antiepileptic drugs. The aim of our study was to investigate motor area excitability on depressed patients after intravenous administration of a single dose of clomipramine, a tricyclic antidepressant. Motor cortex excitability was studied by single and paired transcranial magnetic stimulation (TMS) before and after 4, 8 and 24 h from intravenous administration of 25 mg of clomipramine. Cortical excitability was measured using different TMS parameters: motor threshold (MT), motor evoked potential (MEP) amplitude, duration of cortical silent period (CSP), intracortical inhibition (ICI) and intracortical facilitation (ICF). Spinal excitability and peripheral nerve conduction was measured by F response and M wave. A temporary but significant increase of motor threshold and intracortical inhibition and a decrease of intracortical facilitation were observed 4 h following drug administration. MEP amplitude, cortical silent period, F response and M wave were not significantly affected by drug injection. Our findings suggest that a single intravenous dose of clomipramine can exert a significant but transitory suppression of motor cortex excitability in depressed patients. TMS represents a useful research tool in assessing the effects of motor cortical excitability of neuropsychiatric drugs used in psychiatric disease.

Adult↗

Cutaneomotor integration in human hand motor areas: somatotopic effect and interaction of afferents.

The aim of this study was to elucidate sensorimotor integration in human hand motor areas, its time course, somatotopy and the interaction of sensory fields arising from two different fingers. We studied the influence of different intensities of electrical digital stimulation of two different fingers on motor-evoked potentials elicited in hand muscles by transcranial magnetic stimulation (TMS). Single conditioning electrical stimuli were applied to the right second (D2) and fifth fingers (D5) individually and also to both fingers (D2+D5) simultaneously in six normal volunteers. Magnetic tests, adjusted to produce a response in the abductor digiti minimi muscle of the right hand, were delivered using a circular and a focal coil. The digital stimuli were delivered to the finger at the sensory threshold (ST), at 3 and 5 times the ST, and over the pain threshold at interstimulus intervals (ISIs) ranging from 10 to 100 ms. In order to define the anatomical level of the sensorimotor interactions, the effect of the digital stimulation on TMS was compared to the effect on transcranial electrical stimulation. When the peripheral stimulation was delivered at the ST a small inhibitory effect was found only when stimulating both fingers. At 3 times the ST we detected a topographic distribution of motor-evoked potential inhibition, which partially disappeared at higher intensity (5 times the ST); two types of convergence effects took place at different ISIs. When conditioning stimuli were painful, somatotopy and convergence were lost. Sensorimotor integration shows somatotopy and interaction of afferents at different sites. The intensity of the conditioning stimulus plays an important role in topography and sensory convergence. The importance of these mechanisms in physiology and physiopathology is discussed.

Afferent Pathways↗

Contribution of motor cortex in generation of evoked spikes in patients with benign rolandic epilepsy.

OBJECTIVES: Among the different kinds of rolandic epilepsy there is a form of benign epilepsy with centrotemporal spikes (BECT) presenting the peculiar characteristic of evoking rolandic paroxysmal activity, characterized by a spike followed by a slow wave, using electrical stimulation of the fingers. METHODS: We evaluated 7 patients suffering from BECT presenting evoked scalp activity by electrical stimulation of the fingers of the hand. Electrical stimulation was performed using a pair of ring electrodes applied to the thumb. The motor evoked potentials (MEPs) were elicited in hand muscles by transcranial magnetic stimulation (TMS) and were conditioned by the same electrical digital stimulation producing the evoked spikes at interstimulus intervals ranging from 10 to 200 ms. RESULTS: Digital stimulation in epileptic patients produced an increase in MEP amplitude substantially above the normal ranges. MEP facilitation showed a time course overlapping the ascending phase and peak of the evoked spike, whereas no significant MEP changes were found during the early positive peak and the descending phase of the spike, or during the following slow wave. CONCLUSIONS: Several considerations support the hypothesis that the short-lasting M1 facilitation is related to the spread of an abnormal hypersynchronous discharge of the S1 neurones to functionally related motor areas via cortico-cortical connections.

Age of Onset↗

Cardiovascular mortality in non-insulin-dependent diabetes mellitus. A controlled study among 683 diabetics and 683 age- and sex-matched normal subjects.

Although non-insulin-dependent diabetes mellitus (NIDDM) is considered a major cause of death, the role of some independent risk factors in diabetic patients is under debate. In fact the prognosis of NIDDM diabetes varies considerably in relation to the individual risk pattern, and the different studies are not directly comparable because of differences in size, age and geography of the samples, and type of statistical analysis. The aim of the study is to identify the independent predictors of mortality in a cohort of subjects with NIDDM, and to verify whether the relative risk (RR) of cardiovascular mortality is different in comparison to that of coeval non-diabetic subjects from a general population. The study includes 683 patients with NIDDM from the Northern Italian town of Pordenone, followed up for 6 years and age- and sex-matched to 683 non-diabetic subjects from a Northern Italian general population. When the two cohorts were compared, NIDDM turned out to be a strong risk factor for cardiovascular mortality (RR: 2.67). Age, coronary artery disease (RR: 1.78), arterial hypertension (RR: 1.39), macro- (RR: 2.97) and microalbuminuria (RR: 2.01) were independent predictors of cardiovascular mortality in the diabetics. In conclusion, survival of diabetic patients is worse than that of non-diabetic coeval subjects. Only few items are able to predict cardiovascular mortality in the diabetics, namely age, hypertension, CAD, macro- and microalbuminuria.

Adult↗

Early and late intracortical inhibition in juvenile myoclonic epilepsy.

PURPOSE: We investigated 15 patients with juvenile myoclonic epilepsy (JME) by subjecting them to single and paired transcranial magnetic stimulation to test the hypothesis that motor cortical inhibition may be abnormal in this form of benign epilepsy. METHODS: Different conditioning paradigms of paired transcranial magnetic stimulation were used with interstimulus intervals (ISIs) of varying lengths (1 to 400 milliseconds) to investigate changes in balance between excitatory and inhibitory intracortical circuits. RESULTS: Motor evoked potential (MEP) inhibition at ISIs of 1 to 4 milliseconds was significantly lower in JME patients than in age-matched healthy controls (p < 0.001), whereas no significant differences in MEP inhibition were noted at long ISIs (100 to 150 milliseconds). This pattern was observed in both hemispheres in seven of seven patients studied bilaterally and was present in both treated and untreated patients. There were no group differences between JME patients and controls in intracortical facilitation, motor threshold, MEP amplitude, and cortical silent period. CONCLUSIONS: We documented a different pattern of MEP inhibition in JME patients, suggesting impaired functioning of inhibitory interneuronal circuits, which may account for the hyperexcitability of the motor system in this form of epilepsy.

Adult↗

Parkinson's disease and lower limb somatosensory evoked potentials: apomorphine-induced relief of the akinetic-rigid syndrome and vertex P37-N50 potentials.

We evaluated brainstem P30, vertex-central P37-N50 and contralateral frontal N37 somatosensory evoked potentials (SEPs) from the tibial nerve in 14 patients affected by Parkinson's disease (PD) with akinetic-rigid syndrome. In seven patients SEPs were recorded after administration of apomorphine. The cortical P37-N50 complex was either absent (five patients, eight tested sides) or significantly smaller in patients as compared to the control group (n = 18). There was a relationship between abnormalities of early vertex potentials and degree of motor impairment. Administration of apomorphine was followed by an increase in amplitude of P37-N50 response, which was maximal after 15-30 min and then progressively returned to basal values in parallel with clinical improvement. Amplitude of brainstem P30 and frontal N37 responses was within normal values and did not vary following drug administration. These results suggest that the P37-N50 complex arises from independent cortical generators, probably located in the pre-rolandic cortex, which may be selectively affected by basal ganglia dysfunction. Amplitude decrease of the P37-50 complex may reflect an abnormal processing of somatosensory inputs within the pre-central cortex due to defective modulation exerted by basal ganglia circuitry on cortical excitability. SEP potentiation following apomorphine, besides indicating that this dysfunction is partly reversible, might suggest objective method to measure therapeutic efficacy.

Aged↗

Phantom endometriosis of the sciatic nerve.

OBJECTIVE: To assess the efficacy and diagnostic value of GnRH agonist (GnRH-a) therapy in cases of hidden sciatic nerve endometriosis. DESIGN: Case report. SETTING: Academic tertiary referral center for endometriosis treatment. PATIENT(S): Three patients with cyclic, catamenial sciatica associated with pelvic endometriosis who had electromyographic evidence of sciatic nerve damage but negative computed tomography and magnetic resonance imaging findings. INTERVENTION(S): Monthly administration of the GnRH-a leuprolide acetate plus daily transdermal E2 (25 microg). MAIN OUTCOME MEASURE(S): Relief of pain symptoms and improvement in motor function. RESULT(S): All three patients had clear decreases in pain and partial amelioration of claudication. CONCLUSION(S): Endometriosis of the sciatic nerve may be hard to diagnose with the use of current imaging techniques but may be proved by clinical response to GnRH analogue treatment and may be more frequent than previously thought.

Administration, Cutaneous↗

Clinical and electrophysiological assessment of inferior alveolar nerve function after lateral nerve transposition.

Inferior alveolar nerve (IAN) transposition surgery may cause some degree of sensory impairment. Accurate and reproducible tests are mandatory to assess IAN conduction capacity following nerve transposition. In this study subjective (heat, pain and tactile-discriminative tests) and objective (electrophysiological) assessments were performed in 10 patients receiving IAN transposition (bilaterally in 8 cases) in order to evaluate any impairment of the involved nerves one year post-operatively. All patients reported a tingling, well-tolerated sensation in the areas supplied by the mental nerve with no anaesthesia or burning paresthesia. Tactile discrimination was affected the most (all but 1 patient). No action potential was recorded in 4 patients' sides (23.5%); 12 sides showed a decreased nerve conduction velocity (NCV) (70.5%) and 1 side normal NCV values (6%). There was no significant difference in NCV decrease between partial and total transposition sides, if examined separately. Nerve conduction findings were related 2-point discrimination scores, but not to changes in pain and heat sensitivity. These findings show that lateral nerve transposition, though resulting in a high percentage of minor IAN injuries, as determined by electrophysiological testing, provides a viable surgical procedure to allow implant placement in the posterior mandible without causing severe sensory complaints. Considering ethical and forensic implications, patients should be fully informed that a certain degree of nerve injury might be expected to occur from the procedure. Electrophysiological evaluation is a reliable way to assess the degree of IAN dysfunction, especially if combined with a clinical examination. Intraoperative monitoring of IAN conduction might help identify the pathogenetic mechanisms of nerve injury and the surgical steps that are most likely to harm nerve integrity.

Action Potentials↗

Pharmacokinetic and pharmacodynamic effects of high-dose continuous intravenous verapamil infusion: clinical experience in the intensive care unit.

OBJECTIVE: Our study aimed at evaluating the pharmacokinetic, cardiovascular, and metabolic effects of high-dose verapamil continuous intravenous infusion in cancer patients. DESIGN: Prospective clinical and pharmacokinetic study. SETTING: Intensive care unit of a Cancer Research Institute. PATIENTS: Nine patients (age range 31 to 57 yrs) with progressive cancer disease and without cardiovascular, renal, or hepatic dysfunctions. INTERVENTIONS: After a loading dose (0.15 mg/kg followed by 12 hrs of continuous intravenous infusion at 0.20 mg/kg/hr), the infusion rate of verapamil was increased every 24 hrs (0.25, 0.30, 0.35, and 0.40 mg/kg/hr). The highest rate was maintained for 48 hrs. Doxorubicin was given from the 60 th to the 108 th hr. Hydrochlorothiazide (25 mg/day) and potassium (36 mmol/day) were given orally. Altogether, 17 courses were completed. MEASUREMENTS AND MAIN RESULTS: Steady state concentration (C(SS) and systemic clearance of verapamil and nor-verapamil (active metabolite) for each infusion rate were calculated. Mean arterial pressure (MAP), central venous pressure (CVP), heart rate (HR), PR, QT and QTc intervals, and left ventricular ejection fraction (LVEF) were measured, as well as daily body weight, blood glucose and potassium. C(SS) of verapamil and nor-verapamil increased more than proportionally to the infusion rate (p<.001). Systemic clearance of verapamil decreased over the range of the infusion rate (p<.005). MAP and HR decreased at the 12th hr (p<.001) and then plateaued. CVP increased (p<.01). The relationship between MAP, HR, CVP, and verapamil plasma concentrations was significant (r2 = .25, .14, and .35, respectively; p<.0001). LVEF did not change. Six patients (11 courses) developed junctional rhythm. Three patients (six courses) showed a PR interval increase (p<.05). Patients with junctional rhythm had higher Css of verapamil (p<.009). Overall, QT and QTc intervals increased (p<.01). A linear relationship was observed between verapamil plasma concentrations and QT intervals (r2 = .09, p<.01). Cardiovascular side effects did not determine treatment withdrawal in any patient. Body weight, blood glucose, and potassium did not show significant changes. CONCLUSIONS: Our data suggest a capacity-limited clearance of high-dose verapamil. In the absence of heart disease, following a step by step increase of the dosage, the high plasma verapamil concentrations (617 to 2970 ng/mL) produce frequent but well tolerated hemodynamic and electrocardiogram changes.

Adult↗

Cortical excitability in patients after loading doses of lamotrigine: a study with magnetic brain stimulation.

PURPOSE: Transcranial magnetic stimulation (TMS) of the brain allows the pharmacologic effects of anti-convulsant drugs (AEDs) on the excitability of motor corticospinal pathways to be evaluated in patients with epilepsy and normal subjects. However, no study has yet documented the changes in motor excitability in patients treated with lamotrigine (LTG). We aimed to study the effects of loading doses of LTG on TMS recordings in patients with epilepsy at the beginning of their treatment. METHODS: We investigated single-pulse TMS in six patients with complex partial seizures. The TMS recordings were performed in five sessions before and during 5 weeks of treatment. Motor threshold, motor-evoked potential (MEP) amplitude, cortical silent period, and peripheral conduction velocity were used as parameters of evaluation. LTG was started with a dosage of 25 mg/day until a daily maintenance dosage of 200 mg/day was reached. RESULTS: The motor threshold activation of thenar muscles was significantly increased by LTG after 2 weeks of treatment and was increased in a parallel way to the loading dose of the drug at week 3 and 5 of treatment. The MEP size recorded from the thenar muscles did not show significant changes at high- or low-intensity stimulation. The cortical silent period remained unchanged at low- and high-intensity stimulation. The absolute latency of MEPs after cortical and cervical stimulation was unchanged, as was the central motor conduction time. CONCLUSIONS: Our study documents that loading doses of LTG, administered as monotherapy, progressively increases patients' motor thresholds over short periods.

Action Potentials↗

Modulation of ipsilateral motor cortex in man during unimanual finger movements of different complexities.

To understand the role of the ipsilateral motor cortex in the control of unimanual movements, we evaluated changes in cortical motor evoked potentials (MEP) from the left abductor pollici brevis (APB) to transcranial magnetic stimulation (TMS) of the right hemisphere in nine normal subjects during execution of right finger movements of different complexities. The motor tasks were (a) repetitive opposition movement (thumb tapping the 3rd finger); (b) isolated finger movements in a 'usual' sequence (thumb tapping fingers 2, 3, 4 and 5) and (c) in an 'unusual' sequence (thumb tapping fingers 3, 5, 2 and 4). Subjects were trained before the study up to disappearance of EMG synkinetic activity in the left APB. As compared to the rest condition, MEP amplitude was enhanced in all subjects during paradigm (b) and even more during (c), but remained unchanged during paradigm (a). The MEP increase disappeared in four out of the nine subjects undergoing overtraining. No significant modifications in MEP amplitude were found in the left proximal muscle (biceps, five subjects). The H reflex induced by left median nerve stimulation at the elbow (four subjects) and MEPs from the left APB to transcranial electrical stimulation (three subjects) were not significantly affected by any of the motor paradigms, indicating that the motor cortex was the site of change. These results provide evidence of an increased excitability of cortical motor outputs targeting the unmoving hand muscles during contralateral sequential finger movements which disappears with overtraining. We conclude that during motor learning there is an interhemispheric transfer of information, possibly in order to inhibit the opposite hemisphere from interfering when a fine unimanual movement is required.

Adult↗

Transcranial magnetic stimulation selectively impairs interhemispheric transfer of visuo-motor information in humans.

We investigated the cerebral cortical route by which visual information reaches motor cortex when visual signals are used for manual responses. Subjects responded unimanually to photic stimuli delivered to the hemifield ipsilateral or contralateral to the moving hand. On some trials, trans-cranial magnetic stimulation (TMS) was applied unilaterally over the occiput, with the aim of stimulating extrastriate visual areas and thereby modifying transmission of visual input. In association with the side of a visual stimulus and a motor response, TMS could change inter- or intra-hemispheric transmission needed to convey visual information to motor areas. Reaction time differences following TMS suggested that TMS exerted an inhibitory effect only when visuo-motor information had to be transferred interhemispherically. This result reinforces evidence for an extrastriate pathway of interhemispheric transfer of visuomotor information.

Acoustic Stimulation↗

Scalp topography and source analysis of interictal spontaneous spikes and evoked spikes by digital stimulation in benign rolandic epilepsy.

OBJECTIVES: We report the analysis of scalp topography and dipole modeling of the rolandic spikes in 6 patients suffering of benign rolandic epilepsy of childhood with extremely high amplitude SEP by tapping stimulation of the finger of the hand. METHODS: EEG and BESA analysis were performed for both rolandic spontaneous interictal spikes and high amplitude scalp activity evoked by tapping and electrical stimulation of the first finger of the right hand. RESULTS: The evoked responses showed a morphology characterized by a rapid phase (spike) followed by a slow phase (slow wave). The spike presented an early small positive component followed by a main negative component. Similar morphology, dipole configuration and source localization were observed for both rolandic spikes and evoked high amplitude scalp responses. Dipole localization showed an overlap of spatial coordinates between rolandic and evoked spikes. CONCLUSIONS: These findings suggest that the extremely high amplitude SEPs could be evoked spikes which probably had the same cortical generators of the spontaneous rolandic spikes.

Brain Mapping↗

Spike topography and functional magnetic resonance imaging (fMRI) in benign rolandic epilepsy with spikes evoked by tapping stimulation.

We performed a spike topography study and a functional magnetic resonance imaging (fMRI) in a female patient with benign rolandic epilepsy presenting single high-amplitude evoked spikes in response to somatosensory peripheral stimulation. The stimulus was delivered to the first finger of the right hand using a tendon hammer, which evoked a single spike followed by a slow wave, showing the maximal amplitude over the left central regions. fMRI showed that the contralateral sensory cortices (S1 and S2) and the motor cortex (M I) were activated during tapping stimulation. In 3 normal subjects, tapping stimulation produced no fMRI activation. This fMRI study documents a highly focal activation of sensorimotor areas related to subclinical evoked spikes in benign rolandic epilepsy.

Acoustic Stimulation↗