Abstract: It has been claimed that verb processing (as opposed to noun processing) is subserved by specific neural circuits in the left prefrontal cortex. In this study, we took advantage of the unusual grammatical characteristics of clitic pronouns in Italian (e.g., lo and la in portalo and portala 'bring it [masculine]/[feminine]', respectively)-the fact that clitics have both nominal and verbal characteristics, to explore the neural correlates of verb and clitic processing. We used repetitive transcranial magnetic stimulation (rTMS) to suppress the excitability of the left prefrontal cortex and to assess its role in producing verb+det+noun and verb+clitic phrases. Results showed an interference effect for both kinds of phrases when stimulation was applied to the left but not to the right prefrontal cortex. However, the interference effect was significantly greater for the verb+clitic than for the verb+det+noun phrases. These findings support the view that clitics increase the morphosyntactic complexity of verbs.
Abstract: Dopaminergic drugs and deep brain stimulation restore cortical inhibition in Parkinson disease (PD) patients. High-frequency rTMS was also found to increase cortical inhibition in PD but its therapeutic effect is still controversial. Here we hypothesize that, if dopaminergic drugs reverse to normal cortical excitability in M1, the effect of high-frequency (hf)-rTMS in PD patients could depend on whether they are in a medicated or unmedicated state. The present study aims to explore the lasting effects of sub-threshold hf rTMS trains over M1 on cortical inhibition in patients with "on" and without "off" L-DOPA treatment. Fourteen PD patients were examined twice while "on" and "off" medication. In both conditions, a paired-pulse paradigm was used to evaluate short intracortical inhibition (SICI) and long intracortical inhibition (LICI) that were evaluated before and after hf rTMS trains applied on the motor cortex. The results were compared with those obtained from normal controls. In baseline condition, SICI and LICI were significantly reduced in "off" compared to "on" patients and controls. hf-rTMS over the motor cortex significantly increased SICI and LICI in "off" medication PD patients. Magnetic stimulation proved to be ineffective when the same patients were in "on" state. The results showed that hf-rTMS affected intracortical inhibition (ICI) only in unmedicated patients. By restoring cortical inhibitory circuits dopaminergic drugs, normalize the excitability changes in M1 subsequent to motor rTMS. Whether patients are in a medicated or an unmedicated state would therefore appear to be critical for rTMS effects in PD patients. If a positive correlation exists between increased cortical inhibition and clinical improvement, hf-rTMS during the "off" state could be regarded as a potential add-on treatment to reduce the need of L-dopa and thus delay the adverse effects of its chronic use.
Abstract: Hemicrania continua (HC) is an uncommon and under-recognized primary headache disorder characterized by a strictly unilateral continuous headache of moderate intensity with possible exacerbations and associated with ipsilateral autonomic features. HC has generally a prompt and enduring response to indomethacin although 25% to 50% of treated patients develop gastrointestinal side effects. These cases pose a difficult management challenge as no other drug is consistently effective in HC. Recently 2 HC patients responsive to topiramate treatment have been reported. Here we describe 2 more patients effectively treated with topiramate. Neither reported any side effects and one had persisting response for 6 months after drug withdrawal.
Abstract: Prominent or isolated weakness of cervical extensor muscles is a relatively rare clinical sign. Commonly, this is known as "dropped-head syndrome". This abnormal flexion of the head may occur in a variety of neuromuscular diseases and in a few non-neurological disorders as well. The case we describe concerns a 61-year-old woman with dropped-head syndrome as the unique complaint of myasthenia gravis.
Abstract: Clinical observations and data from animal experiments point to a physiological facilitatory influence of the deep cerebellar structures on the motor system through the cerebello-thalamo-cortical pathways. The aim of the present study was to explore the long-term effects of low-frequency (1 Hz) repetitive transcranial magnetic stimulation (rTMS) over the cerebellum on short intracortical inhibition (SICI) and facilitation (ICF) of the motor cortex in normal subjects. Eight healthy subjects (mean age 26.9 +/- 3.1) underwent 1 Hz frequency rTMS delivered on the right cerebellar hemisphere. Before and after cerebellar rTMS, SICI and ICF were assessed in the motor cortex contralateral to the stimulated cerebellar hemisphere by means of a paired pulse paradigm with a conditioning subthreshold stimulus set to 80% of the motor threshold (MT) followed by a testing stimulus at 120% of MT intensity. Five different interstimulus intervals (ISIs) were used to assess SICI (2 and 4 ms) and ICF (7, 10 and 15 ms). Amplitude of the responses was expressed as the percentage of motor evoked potential (MEP) to test stimulus alone. Results showed a significant decrease of ICF at 10 ms ISI that persisted up to 20 min after cerebellar rTMS. This was the only significant modulatory effect of cerebellar stimulation on intracortical motor excitability A suppressive effect of the low-frequency TMS on Purkinje cells could be supposed, even if, the lack of effects on other facilitatory ISIs, stands for more complex modulatory effects of rTMS over cerebellum. The study is a further demonstration that rTMS over the cerebellum induces a long-lasting modulatory effect on the excitability of the interconnected motor area.
Abstract: BACKGROUND: Migraine is a highly prevalent and disabling disease which is substantially underdiagnosed in primary care. Recently, the ID Migraine, a self-administered questionnaire, consisting of only 3 items, was shown to be a valid and reliable screening instrument for migraine in primary care in the United States. OBJECTIVE: The aim of the present study was to validate an Italian version of the "ID Migraine" questionnaire. METHODS: Two hundred and twenty-two consecutive headache patients referring to 8 headache centers in Sicily (Italy) completed an Italian version of the ID Migraine. The responses to the questionnaire were compared with the diagnosis of headache made by a headache specialist blind to the result of the questionnaire. Sensitivity, specificity, positive and negative predictive values for migraine were calculated. RESULTS: The statistical analysis of 222 patients examined showed a very good performance of the ID Migraine with high sensitivity: 0.95 (95% CI, 0.91 to 0.98), specificity: 0.72 (95% CI, 0.62 to 0.82), and positive predictive value: 0.88 (95% CI, 0.82 to 0.93). ID Migraine showed also a very good accuracy level: 0.87 (95% CI, 0.83 to 0.92). CONCLUSION: This validation study showed "ID Migraine" as a valid tool for migraine screening also in Italian patients referring to headache centers. If confirmed in a primary care setting, these results establish the "ID Migraine" as a valid screening instrument for migraine in Italian population.
Abstract: The aim of this study was to investigate the role of the cerebellum in a temporal-discrimination task without movement production in healthy subjects. Ten healthy subjects underwent a time-perception task with somatosensory stimuli. Two pairs of electrical stimuli: the first considered the reference pair (rp) with a standard interval of 400 ms and the second, the test pair (tp), with variable intervals ranging from 300 to 500 ms, were applied by surface electrodes on the right forearm. Subjects were instructed to compare time intervals of rp and tp and to estimate whether the tp interval was shorter than, equal to, or longer than that of rp. The task was performed in baseline and after 1 Hz rTMS over the right and left cerebellar hemisphere. The right cerebellar rTMS worsened temporal discrimination of cutaneous somatosensory electrical stimuli on the ipsilateral hand. rTMS of the left cerebellar hemisphere did not determine significant changes in the subjects' performance with respect to the baseline. These findings suggest that the cerebellum plays a role in merely perceptive aspects of temporal information processing.
Abstract: OBJECTIVE: We previously observed a relative contralateral neglect by right parietal single-pulse TMS given 150 ms after visual stimulus presentation. Here we investigated the effects of parietal paired TMS in normal subjects performing a visuospatial task. METHODS: Thirteen right-handed healthy subjects underwent a line-length judgement task during single-pulse and paired (1, 3, 5, 10 ms ISIs) TMS, delivered on the right parietal cortex 150 ms after visual stimulus. RESULTS: Single pulse TMS over the right parietal cortex induced a significant rightward bias compared to the baseline condition. At 1 and 3 ms ISIs, paired-pulse TMS did not show any effect in comparison with single pulse TMS. More importantly, 5 ms ISI was able to restore baseline levels, thus inducing a significant improvement of the performance compared to single-pulse TMS and 1-3 ms ISIs. CONCLUSIONS: Paired TMS seems able to modulate activity of the right posterior parietal cortex in healthy subjects performing a cognitive visuospatial task.
Abstract: Cerebrospinal fluid (CSF) volume depletion syndrome is due to leakage of cerebrospinal fluid through lesions of the dural sac at the level of the cranial base or of the spine. When past medical history is negative for recent trauma or surgery, the term spontaneous intracranial hypotension (SIH) is used. SIH is characterized clinically by orthostatic headache, neck pain, nausea, emesis, horizontal diplopia, tinnitus, plugged ear, hearing difficulties, blurring of vision, facial numbness, and upper limb radicular symptoms. In SIH, brain and cervical MR scans show a diffuse pachymeningeal gadolinium enhancement that ends at the site of CSF leakage. The application of epidural blood patches has been proposed as an effective therapy for SIH. Here we describe a case of SIH with very unusual headache features; the patient reported a paradoxical pattern of postural headache provoked by clinostatic position. The CSF leakage was identified at the convexity of the skull and headache disappeared following treatment with fluid, analgesics and steroids.
Abstract: Electrical stimulation of the cerebellar cortex by implanted electrodes has been shown to ameliorate refractory epilepsy. We investigated the potential therapeutic role of high-frequency cerebellar rTMS in patients affected by refractory epilepsy due to single or multiple foci. Six patients, three with single and three with multiple epileptic foci, underwent 20 rTMS sessions. Each session was given daily, excluding weekends, and consisted of two trains of 50 stimuli (5 Hz frequency and 90% motor threshold intensity), separated by 50s interval. rTMS was delivered through a focal coil (2 cm below and lateral to the inion) bilaterally in patients with multiple foci (two trains for hemisphere: 100 stimuli each side) and contralaterally to the epileptic focus in the others. Seizure frequency was monitored four weeks before stimulation (pre-rTMS), during the four-week treatment (rTMS) and four weeks after the treatment (post-rTMS). The rTMS over the cerebellar cortex was associated with a significant decrease of rTMS versus pre-rTMS seizure frequency both in patients with single and multiple epileptic foci. However, during the post-rTMS period seizure frequency was back to the pre-rTMS frequency. Although the results are still preliminary, they encourage further studies on larger series of patients. In particular, this rTMS approach, as compared with others, might be more useful in patients with multiple epileptic foci.
Abstract: This case-report shows that high frequency repetitive Transcranial Magnetic Stimulation (hf-rTMS), applied to the left prefrontal cortex, may improve the linguistic skills in Primary Progressive Aphasia (PPA). The patient's performance was evaluated on a battery of language production and memory span tasks, before and after two hf-rTMS treatments and one SHAM treatment. We observed a significant and lasting improvement of the patient's performance on verb production following the application of hf-rTMS versus Baseline and SHAM conditions. This finding suggests that hf-rTMS may directly strengthen the neural connections within an area of metabolic dysfunction and encourages the use of rTMS as an alternative therapeutic tool for neurodegenerative forms of aphasia.
Abstract: Hemispatial neglect refers to the defective ability of patients to explore or act upon the side of space contralateral to the lesion and to attend to stimuli presented in that portion of space. Evidence from animal models suggests that many of the behavioural sequelae associated with visual neglect may result not solely from the size of the lesion, but also from a pathological state of increased inhibition exerted on the damaged hemisphere by the contralesional hemisphere. On the basis of these potential mechanisms underlying neglect, in this review we discuss therapeutic approaches, focusing particularly on recent research using transcranial magnetic stimulation (TMS). This technique, besides representing an ideal tool to investigate visuo-spatial attentive mechanisms in humans, has shown promising beneficial effects that might have an impact on clinical practice.
Abstract: OBJECTIVE: To evaluate the efficacy of levetiracetam as prophylactic treatment for migraine with aura with high frequency of attacks. BACKGROUND: Migraine with aura with high frequency of attacks could represent a very demanding therapeutic problem. Efficacy of the antiepileptic drug, lamotrigine, has been reported in this form of migraine. Levetiracetam is a new antiepileptic drug with an excellent tolerability profile. Mechanisms of action of this drug remain largely unknown, but recently, it has been shown to exert inhibitory effects on neuronal-type calcium channels. METHODS: We performed a small open-label trial treating 16 patients affected by migraine with aura with high frequency of attacks. After a 1-month run-in period, patients were treated with levetiracetam at a dosage of 1000 mg/d for 6 months. RESULTS: The number of attacks per month was significantly reduced during the first month (compared with run-in; P < 0.001), and it was reduced further during the second (second month vs first month; P < 0.001) and the third months (third month vs second month; P < 0.001) of the treatment. This improvement persisted unchanged for the remaining 3 months of treatment. In 7 (44%) of the 16 patients, the attacks were completely abolished after 3 months of treatment. Severity of headache and duration of headache and aura were also significantly reduced at the third and sixth months of treatment (P < 0.001). Levetiracetam was well tolerated (6 patients complained of slight dizziness, nervousness, and somnolence). CONCLUSIONS: Levetiracetam seems to be a safe and effective treatment for migraine with aura. Controlled trials are needed to confirm the observed results.
Abstract: The aim of the present study was to explore further the effects of light deprivation (LD) on visual cortex excitability. Healthy subjects reporting reliable induction of phosphenes by occipital transcranial magnetic stimulation (TMS) underwent 60 min of complete LD. Phosphene threshold (PT) was measured before (T0), after 45 min (T1) and 60 min (T2) of LD, and then every 10 min after light re-exposure until recovery to T0 values. Repetitive TMS (rTMS) (at 1 or 10 Hz) was applied in separate sessions during the last 15 min of LD. PTs significantly decreased after 45 min of LD. rTMS differentially modified the effects of 60 min LD on PTs depending on stimulation frequency. One hertz rTMS did not change the decreasing of PT values as observed in baseline condition, but significantly prolonged the time to recover T0 PT values after light re-exposure. By contrast, 10 Hz rTMS significantly increased PT and the time to recover T0 PT values after light re-exposure was shortened. The results of this study show that the modulatory effects of different rTMS frequencies on visual cortex critically depend on the pre-existing excitability state of inhibitory and facilitatory circuits, and provide novel insights into the neurophysiological changes that take place in the visual cortex following functional visual deafferentation.
Abstract: We previously showed paradoxical facilitatory effects of low-frequency repetitive transcranial magnetic stimulation (rTMS) on striate and extrastriate cortex of patients suffering migraine with aura. In this study we evaluated the effects of 1 Hz rTMS on the excitability of inhibitory and facilitatory circuits of motor cortex to explore whether the abnormal pattern of excitability extends beyond the sensory cortex also involving motor areas in migraine with aura. Nine patients affected by migraine with aura and eight healthy controls entered into the study. The hot spot for activation of the right abductor pollicis brevis (APB) was checked by means of a figure-of-eight coil and motor threshold (MT) recorded on this point. Nine hundred magnetic stimuli at 1 Hz frequency and 90% MT intensity were delivered at the hot spot. Before and after rTMS, intracortical inhibitory and facilitatory circuit excitability was assessed by means of a paired pulse paradigm (conditioning stimulus 80% MT and test stimulus 120% MT) with two different interstimulus intervals: 2 ms (inhibitory) and 10 ms (facilitatory). Amplitude of the responses was expressed as the percentage of motor evoked potential (MEP) to test stimulus alone. Results showed that in basal condition migraineurs present significantly reduced levels of intracortical inhibition (ICI) compared to controls. More importantly, opposite results were obtained in migraineurs with respect to controls when 1 Hz rTMS was applied. Specifically, whereas intracortical facilitation (ICF) significantly decreased in controls, it significantly increased in migraineurs. ICI levels were not significantly affected by low-frequency stimulation. Our results showed that motor as well as sensory cortex of migraine patients present an abnormal modulation of cortical excitability, where a relevant role is likely played by the inefficiency of inhibitory circuits.
Abstract: The aim of the study was to explore excitability of a motor and a non-motor (visual) area in patients affected by Friedreich ataxia and to correlate neurophysiological data with clinical parameters. Seven patients (3M/4F) and ten healthy controls (5M/5F) participated in the study. The hot-spot for activation of right abductor pollicis brevis was checked by means of a figure-of-eight coil and the motor threshold (MT) on this point was recorded. The phosphene threshold (PT) was measured by means of a focal coil over the occipital cortex as the lower intensity of magnetic stimulation able to induce the perception of phosphenes. The patients showed a significantly higher mean PT (p<.03) and MT values (p<.001) than controls. In all but one patient unable to perceive phosphenes (42% vs. 50% of controls), TMS at 100% intensity did not elicit motor response at rest. The difference in percentage of patients (57.1%) and controls (100%) with motor responses was nearly significant. The size of GAA1 expansion showed significant correlations with PT and MT values. The results of our study showed that FA patients had reduced cortical activation, involving both the motor and the visual cortex. The cortical involvement in these patients seems to be mainly genetically determined. The study provides the first evidence of cortical dysfunction in patients with genetically defined Friedreich ataxia.
Abstract: Migraine is a highly prevalent and disabling disease that is substantially undiagnosed in primary care. Recently, the ID Migraine, a self-administered questionnaire, was shown to be a valid and reliable screener for migraine in primary care in the USA. To validate an Italian version of the ID Migraine, we planned a multicentric study, evaluating at least 220 patients affected by various form of headache. The responses to the questionnaire were compared with the diagnosis of headache made by a headache specialist blind to the result of the questionnaire. Sensitivity, specificity, and positive and negative predictive values for migraine were calculated. The statistical analysis on 140 patients now examined showed a very good performance of the ID Migraine with high sensitivity: 0.94 (95% CI: 0.89-0.95), specificity: 0.70 (95% CI: 0.54-0.86) and positive predictive value: 0.89 (0.82-0.95). If confirmed, these results would establish ID Migraine as a valid screening instrument for migraine in Italian headache patients and warrant further investigation in primary care to assess the validity of this ID screener in Italian population.
Abstract: The continuous care of headache patients, from headache centres to general practice, is a managerial problem that is still unsolved in Italy. In fact, if on the one hand patients do not usually go to headache centres because of poor information, on the other hand, if they do, they do not find their general practitioner (GP) sufficiently prepared to continue the management. In Sicily we have formed a dense network of headache centres that we will try to link on the Internet to deal with the problem of poor patients information and poor specialist consultation. We also have faced the problem of the continuous care, trying to overcome "the difficulties of communication between specialists, GPs and patients" and "the difficulties of GPs in diagnostic work", by simple instruments like the Italian version of ID-Migraine, a simple three-item questionnaire.
Abstract: A recent fMRI study showed that dorsolateral prefrontal cortex (DLPFC) exerts an inhibitory control on pain pathways in humans. We investigated whether high-frequency rTMS over left DLPFC could ameliorate chronic migraine. Treatment consisted of 12 rTMS sessions, delivered in alternate days over left DLPFC. Sham rTMS was used as placebo. Eleven patients were randomly assigned to the rTMS (n=6) or to the placebo (n=5) treatment. Measures of attack frequency, headache index, number of abortive medications (outcome measures) were recorded in the month before, during and in the month after treatment. Subjects treated by rTMS showed a significant reduction of the outcome measures during and in the month after the treatment as compared to the month before treatment. No significant differences in the outcome measures were observed in the placebo group. High-frequency rTMS over left DLPFC was able to ameliorate chronic migraine. This is in agreement with the suggested role of DLPFC in pain control.
Abstract: The aim of the study was to investigate whether low-frequency repetitive transcranial magnetic stimulation (rTMS) over the unaffected hemisphere can ameliorate visuospatial neglect. We treated three right brain damaged patients with left neglect. 900 pulses (1 Hz frequency) were given over left posterior parietal cortex every other day for 2 weeks. Patients performed a computerized task requiring length judgement of prebisected lines, tachistoscopically presented for 150 ms. With respect to rTMS the task was given 15 days before, at the beginning, at the end and 15 days after. At these times patients performed also line bisection and clock drawing tasks. rTMS induced a significant improvement of visuo-spatial performance that remained quite unchanged 15 days after. Patients performance at Time 3 and 4 improved also as concerns line bisection and clock drawing tasks.
Abstract: Functional magnetic resonance imaging studies showed that perception of illusory contours is associated with extrastriate cortex activation prevailing on the right side. 1 Hz repetitive transcranial magnetic stimulation (rTMS) is able to induce lasting inhibition of cortical activity. The objective of the study was to investigate the role of extrastriate cortex in illusory contour perception inducing 1 Hz rTMS interference in healthy subjects. Eight healthy subjects underwent 1 Hz rTMS (600 pulses) through a figure-of-eight coil over right and left occipital cortex (O1 and O2 of 10/20 EEG system); sham magnetic stimulation on the same sites and right motor cortex rTMS (in three subjects) were given as control. Subjects performed a computerized task requiring perception of illusory and real contours of Kanizsa squares in baseline and after rTMS. After stimulus presentation the subject made a forced-choice decision about the regularity or irregularity of stimulus contour, by hitting as fast as possible one of two keys on the computer keyboard. Reaction times (RT) were measured. Right occipital stimulation significantly increased RT for illusory contour perception (vs. baseline, P < 0.05). No significant RT changes were observed in the other experimental conditions with respect to the baseline condition. It is concluded that 1Hz rTMS of right extrastriate cortex can disrupt perception of illusory contours and the effect appears to be side-specific, being evident only after right occipital stimulation. This study supports the critical role of right extrastriate cortex in illusory contour perception.
Abstract: We report the case of a patient who, following a right thalamic haemorrhage, developed thalamic syndrome characterised by burning pain and hyperalgesia in the left side of the body. Three years later, following a further (contralateral ischaemic) stroke, she reported the complete disappearance of the pain and hyperalgesia. To our knowledge, this is the first described case of disappearance of thalamic syndrome following a second stroke, different in nature from and contralateral to the first. Various hypotheses, based on the nervous tracts and nuclei involved in pain processing, may be advanced to explain this occurrence.
Abstract: We recently reported a paradoxical facilitatory effect of 1 Hz repetitive TMS (rTMS) on the primary visual cortex in migraine possibly due to the failure of inhibitory circuits, unable to be upregulated by low frequency rTMS. To investigate if inhibitory circuit dysfunction extends beyond striate cortex in migraine with aura, we studied the effects of 1 Hz rTMS over the right extrastriate cortex on perception of illusory contours in these patients. Low-frequency rTMS enhanced activity of extrastriate cortex in migraineurs, speeding up reaction times on illusory contour perception. This finding supports the view of a failure of inhibitory circuits also involving the extrastriate cortex in migraine with aura.
Abstract: Recently some authors have challenged the conventional association of directional motor neglect with damage of frontal structures, showing that pure sensory perceptual neglect (classically associated with parietal lesion) can follow damage of right frontal cortex. The aim of the present study was to assess the type of defect in visuo-spatial attention consequent upon a virtual frontal or parietal lesion induced by transcranial magnetic stimulation in normal subjects. To this purpose eleven subjects performed a visuo-spatial task requiring judgement about the length of the two segments of asymmetrically bisected horizontal lines, presented for 50 ms on a computer monitor. After each visual stimulus, subjects made a binary forced choice decision according to two different response conditions: A and B. In condition A, they had to name (right or left) the longer segment and in B the shorter segment of the line. The task was given in baseline condition and during repetitive transcranial magnetic stimulation. Trains of 10 stimuli at 25 Hz of frequency were applied over right frontal premotor and right posterior parietal areas, synchronously with visual stimuli. Parietal and frontal magnetic stimulation gave rise to significant perceptual bias as compared to baseline performance (i.e. subjects made opposite errors in the two response conditions). No significant response bias (i.e. the tendency to name the same side of the line in the two response conditions) was induced by magnetic stimulation on parietal and frontal sites. The present study highlights both the relevant contribution of frontal cortex in the determinism of neglect and the predominant role of sensory perceptual factors in parietal and frontal neglect.
Abstract: OBJECTIVE: To investigate the efficacy of two different high doses of intravenous methylprednisolone (IVMP) during Multiple Sclerosis (MS) relapses. BACKGROUND: Transcranial Magnetic Stimulation (TMS) is the most sensitive neurophysiological ascertainment to quantify motor disability, to follow the recovery from an MS relapse, and to detect the response to treatment. DESIGN AND METHOD: Twenty-four clinically definite relapsing - remitting MS patients presenting a relapse were randomly assigned to a treatment for 5 days with IVMP 1 or 2 g/day. The response to treatment of each patient was evaluated through Expanded Disability Status Scale (EDSS), Medical Research Council (MRC) score, and TMS by means of motor evoked potential (MEP) parameters. RESULTS: Motor threshold (MT), central motor conduction time (CMCT) and MRC showed a higher improvement with the highest dose of IVMP. Silent period and EDSS improved with both treatments. CONCLUSION: The dose of 2 g/day of IVMP is more effective in MS relapse.
Abstract: Recent studies showed hyperexcitability of the occipital cortex in subjects affected by migraine with aura. It has been shown that 1 Hz repetitive transcranial magnetic stimulation (rTMS) reduces excitability of visual cortex in normal subjects. The aim of the study was to investigate the effects of low frequency (1 Hz) rTMS on visual cortical excitability by measuring changes in phosphene threshold (PT) in subjects with migraine with aura. Thirteen patients with migraine with aura and 15 healthy controls were examined. Using a standardized transcranial magnetic stimulation protocol of the occipital cortex, we assessed the PT (the lowest magnetic stimulation intensity at which subjects just perceived phosphenes) before and after a 1-Hz rTMS train delivered at PT intensity for 15 min. The difference in the proportion of subjects reporting phosphenes in migrainer and control groups was significant (migrainers: 100% vs controls 47%; P<0.05), and 1 Hz rTMS over the occipital cortex led to a significantly increased visual cortex excitability expressed as a decrease in PT in subjects affected by migraine with aura. Conversely, after a 1-Hz TMS train normal subjects showed increased PT values, which suggests a decreased visual cortex excitability. Our findings confirm that the visual cortex is hyperexcitable in migrainers and suggest a failure of inhibitory circuits, which are unable to be upregulated by low frequency rTMS.
Abstract: We studied the changes of duration of subsequent silent periods (SPs) during repetitive magnetic stimulation (rTMS) trains of ten stimuli delivered at low (1 Hz) and high (7 Hz) frequencies. The effects at different intensities of stimulation (motor threshold, MT, 115% and 130% above the MT) were also evaluated. rTMS was performed in eight healthy subjects with a figure-of-eight coil placed over the hand motor area. The SP was recorded from abductor pollicis brevis (APB) muscle during a voluntary contraction of 30% of maximum effort. rTMS at 1-Hz frequency progressively decreased the duration of SP, whereas an alternating pattern of smaller and larger values was observed during trains at 7-Hz frequency and higher stimulus intensity. The findings show that rTMS changes the duration of cortical SPs; the effect is probably due to the modulation of intracortical inhibitory interneurons depending on the frequency and intensity of stimulation.
Abstract: To verify the role of interhemispheric influences on manifestations of neglect, the authors investigated the effects of a transient repetitive transcranial magnetic stimulation (rTMS)-induced disruption of the unaffected hemisphere on contralesional visuospatial neglect in two left- and five right-brain-damaged patients. Parietal rTMS of the unaffected hemisphere during the execution of a computerized task of bisected line's length judgment transiently decreased the magnitude of neglect as expressed in the number of errors.
Abstract: In a recent study we showed that repetitive transcranial magnetic stimulation (rTMS) with train duration of 400 ms over right frontal and right posterior parietal cortices gives rise to transitory contralateral visuo-spatial neglect in normal subjects. In the present experiment we investigated whether using single-pulse TMS it is possible to obtain information about the timing of cortical activity related to spatial cognition. Nine healthy subjects performed in baseline condition and during TMS a tachistoscopic task, requiring a forced-choice estimation of the length of the two segments of prebisected horizontal lines. Single-pulse TMS was triggered at various time intervals (150 ms, 225 ms, 300 ms) after visual stimulus onset with a focal coil over P6 and F4 (according to 10/20 EEG system). Relative transitory rightward bias was observed only when parietal TMS was delivered 150 ms after visual stimulus presentation. Frontal stimulation induced no effect on visuo-spatial perception with the time intervals explored.
Abstract: The aim of the study was to assess if the observation of single or more complex muscle movements activates the premotor cortex in man. We stimulated by transcranial magnetic stimulation the right and left motor cortex recording from the abductor pollicis brevis of eight normal subjects, during observation of different movements performed by the examiner: (1) single movements: thumb abduction, arm elevation; (2) motor sequences: finger opposing movements performed in an ordinate sequence: 1-2, 1-3, 1-4, 1-5, 1-2ellipsis, and in a non-consecutive non-repetitive order: 1-3, 1-5, 1-4, 1-2, 1-5, 1-2ellipsis We found an increased excitability of the right cortex during observation of isolated muscle movement regardless of which muscle is moved. At the stimulation of the left cortex, MEPs were significantly increased during observation of complex muscular synergies.
Abstract: We applied repetitive transcranial magnetic stimulation (rTMS) in order to induce interference on visuo-spatial perception in 11 healthy subjects. Subjects performed a visuo-spatial task requiring judgements about the symmetry of prebisected lines. Visual stimuli consisted of symmetrically or asymmetrically transected lines, tachystoscopically presented for 50 ms on a computer-monitor. Performance was examined in basal condition and during rTMS trains of 10 stimuli at 25 Hz, delivered through a focal coil over right or left posterior parietal cortex (P5 and P6 sites) and triggered synchronously with visual stimulus. Randomly intermixed sham rTMS trains were employed to control for non-specific effects. Right parietal rTMS induced a significant rightward bias in symmetry judgements as compared with basal and sham rTMS conditions. No differences emerged between other conditions.
Abstract: Median and tibial somatosensory evoked potentials (SEPs) were performed on 12 patients at three and twelve weeks after a first acute stroke, the relationship with motor and functional outcome as measured by British Medical Scale and Barthel Index was searched. Results indicated that the amplitude abnormalities of cortical potentials performed about three weeks after stroke are a good indicator of a poor motor and functional impairment after three months. Moreover changes in amplitude appeared more frequent and permanent than the latency abnormalities.
Abstract: OBJECTIVE: Focal transcranial magnetic stimulation (TMS) was used to study the motor maps of upper limb muscles in 7 adult patients with a history of paralytic poliomyelitis. The aim of the study was to verify the potential for long-term cortical reorganization of a selective peripheral motor neuron lesion suffered early in life. METHODS: Patient selection was based on the prevalent involvement of proximal muscles in only one of the upper limbs. Motor evoked potentials (MEPs) were recorded from deltoid and abductor pollicis brevis (APB) muscles. Each muscle map was characterized by area (no. of excitable positions), volume (the sum of MEP amplitudes at all scalp positions), maximal amplitude (the highest MEP recorded). RESULTS: In the patients, the mean area, volume and maximal amplitude were significantly greater in affected vs. contralateral deltoid (P<0.05) and vs. controls (P<0.01). No significant differences were found in APB map parameters. The APB/deltoid ratio for area was lower in the affected compared with the unaffected side and controls (P = 0.06). Cortical reorganization was not significantly correlated with motor performance. CONCLUSION: These findings are consistent with a rearrangement in human motor pathways targeting muscles affected by a lower motor neuron lesion.
Abstract: Ten patients with myotonic muscular dystrophy (MD) were examined by auditory event-related potentials (P300 ERPs), spirometric and blood gas analyses: arterial oxygen tension (PaO2), arterial carbon dioxide tension (PaCO2) and arterial oxygen saturation (SaO2). The aim of the study was to analyse the frequency of ERP abnormalities in this disease and to determine whether the neurophysiological evidence of cognitive impairment might be related to the ventilatory function abnormalities frequently described in MD. The mean P300 latency was significantly altered in MD patients compared with controls; P300 latencies did not correlate with spirometric parameters, blood gas values or with age, age at onset, duration or clinical status of the disease. This study provides neurophysiological evidence of cognitive impairment in MD patients. The cognitive deficits are not related to alveolar hypoventilation and appear to be a non progressive feature of the disease.
Abstract: We performed clinical, radiological (MRI) and neurophysiological (NCV, SEPs, and BAEPs) investigations in 36 unselected patients affected by Systemic Lupus Erythematosus (SLE). Fifteen patients (42%) presented clear neurological events and were considered as definite neuropsychiatric lupus (NPLE); 21 (58%) presented minor subjective complaints or no neurological problems referable to SLE and were considered as no-NPLE. Twenty-three patients (64%) showed neurophysiological abnormalities: 21 (58%) presented central abnormal neurophysiological measurements (including SEP and BAEP values), while 17 (47%) has slowed peripheral nerve conduction. Twenty-six out of 36 patients executed brain MRI examination. High intensity spots (HIS) in deep or subcortical white matter were the most common abnormalities and were present in 19 of the 26 patients (73%). We found that the incidence of neurophysiological and radiological abnormalities did not significantly differ in neurologically symptomatic and asymptomatic patients. Central nervous system impairment evidenced by abnormal N13-20 interpeak intervals (p = 0.05) and HIS (p = 0.01) findings was significantly associated with the presence of cutaneous vasculitis; while peripheral nerve involvement was significantly more frequent in patients with renal failure (p = 0.006).
Abstract: A neurophysiological (SEP, VEP) follow-up study was carried out in 30 diabetic patients with type I diabetes mellitus of ten or more years duration. This in order to investigate whether one year of improved glucoregulation may influence the progression of central damage. In our series, patients showed a significant decrement of HbA1C levels (p < 0.05) in the one-year follow-up. In the same period the frequency of SEP and VEP abnormalities varied from 10/30 (33%) to 16/30 (53%) and from 8/30 (26%) to 5/30 (16%) respectively. This finding would suggest that prevailing glycaemic control would be a major determinant for the outcome of VEP measurements. SEP alterations, in contrast, tend to progress in a 12 months period despite a considerable improvement in glycaemic control. However, by dividing patients in two groups according mean one year HbA1C less than 8% and more than 8%, the latter group only showed a significant increasing of absolute latencies of each median and tibial SEP components. Our results suggest that VEP abnormalities are still reversible in diabetic patients with improved metabolic control. The acquired abnormalities of somatosensory pathways persist longer, but a strict glycaemic control may influence and retard the progression of central conduction involvement.
Abstract: Somatosensory evoked potentials (SEPs) and brainstem auditory evoked potentials (BAEPs) were recorded in 10 patients with myotonic dystrophy and in 20 sex and age-matched healthy controls. In all patients a brain MRI examination was also performed. In our results, the significantly longer absolute peak latencies of the SEPs and the abnormal increasing of the later components of the BAEPs suggest an involvement of the afferent sensory and central auditory pathways. Brain MRI showed white matter hyperintense lesions (WMHL) in eight patients (80%). No correlations were found between individual abnormal electrophysiological parameters or severity of WMHL and age, age at onset, disease duration or muscular impairment. The total number (SEP + BAEP) of electrophysiological abnormalities significantly correlated with muscular impairment (p < 0.05) and MRI changes (p < 0.005), suggesting a strict pathogenetic linkage between muscular and nervous system alterations in this disease.
Abstract: Nerve conduction velocities (NCVs), somatosensory (SEPs) and auditory evoked potentials (BAEPs) were recorded in 9 patients with facio-scapulo-humeral dystrophy (FSHD) and in 20 age-matched controls. In FSHD patients a significant increase of the nerve distal sensory latencies and of the absolute SEP latencies revealed a subclinical involvement of the afferent sensory pathways, as well as the abnormal slowing of the later components of the BAEPs, pointed to a central auditory dysfunction. Moreover all patients underwent brain MRI that showed the presence of white matter hyperintense lesions in 4 of them (44%). No correlations were found between individual or total number of SEP and BAEP abnormal electrophysiological parameters and severity of WMHL, age, age at onset, duration of the disease or muscular impairment. These findings make the interpretation and pathophysiology of the nervous damage in FSHD rather uncertain. More studies are required to better define the aspects of neurogenic involvement in this type of muscular dystrophy.
Abstract: To further define motor nervous system alterations in myotonic dystrophy (MD), motor potentials to transcranial and cervical magnetic stimulation (MEPs) were recorded from the right abductor pollicis brevis muscle in 10 patients with MD and in 10 healthy controls. Cortical and cervical latencies, central motor conduction time (CMCT), stimulus threshold intensity and cortical MEP amplitudes expressed both as absolute values and as %M were analysed. MEP cervical latency, absolute or relative amplitude and excitability threshold did not significantly differ in patients and controls. The mean cortical motor latency and CMCT were significantly prolonged in MD patients with respect to normal subjects. Moreover, CMCTs were found to be significantly related to stimulus threshold intensity (P = 0.03) and only marginally related to absolute cortical amplitude (P = 0.06). These findings are indicative of a central motor delay, also related to decreased excitability of motor neurons, in patients with MD. No correlations were found between individual neurophysiological parameters and age, duration of disease and clinical impairment. Our results suggest that magnetic stimulation studies can detect subclinical dysfunctions of the central motor system in MD patients, as one of the multisystemic manifestations of the disease, rather independent of the primitive muscle damage.
Abstract: To evaluate central nervous system involvement in diabetes, somatosensory (SEPs) and visual (VEPs) evoked potentials were investigated in a group of 35 patients and 20 sex, age-matched controls. In order to avoid methodological biases due to different type and duration of disease, we studied an omogeneous group of young insulin-dependent diabetics with ten or more year duration of disease. In our results VEP and SEP parameters were found abnormal in 10 (28%) patients, all of whom presenting clear signs of peripheral neuropathy. In diabetic patients median and tibial SEPs showed significant increase in absolute latency mean values of several components except interpeak intervals, as well as mean P 100 latencies were significantly increased in both eyes at 15' check size stimulation pattern. VEP and SEP components were not generally significantly associated with the indices of peripheral function. In contrast, in diabetics significant correlations were found between P 100 latencies and median SEP parameters including interpeak intervals. No major associations related VEP and SEP latencies to duration of diabetes and prevailing glycaemic control. In conclusion the central nervous system involvement in young insulin-dependent diabetics, even though diffusely present, seems unequivocally concomitant to peripheral conduction impairment.
Abstract: Beta-N-oxalylamino-L-alanine (BOAA), a non-protein amino acid present in the seeds of Lathyrus Sativus (LS), is one of several neuroactive glutamate analogs reported to stimulate excitatory receptors and, in high concentrations, cause neuronal degeneration. In the present study, the in vivo acute effects of synthetic BOAA and LS seed extract were investigated on rat cerebellar cyclic GMP following intraperitoneal (10-100 mg/kg) or oral (100 mg/kg) administration of subconvulsive doses of toxin. Furthermore, the BOAA content in LS seeds and in the cerebellum of injected rats was determined by high performance liquid chromatograph analysis. A dose- and time-dependent increase of cerebellar cyclic guanosine monophosphate (cGMP) level was observed after intraperitoneal administration of synthetic BOAA or LS extract. The neurotoxin evoked a maximum stimulation 90 min after injection within the dose range of 50-75 mg/kg, elevating cGMP from basal levels of 5.3 +/- 0.5 pmol/mg protein to 15 +/- 1.3 pmol/mg protein. Similarly, the oral intake of LS-extracted neurotoxin resulted in the elevation of cGMP content. Kynurenic acid (300 mg/kg i.p.), a non specific excitatory amino acid antagonist, was effective in blocking LS BOAA-elicited cGMP enhancement. The data suggest that in the cerebellum acute administration of low concentrations of BOAA exert in vivo activation of glutamate receptors involved in the regulation of cGMP level.
