Giovanna Alagona

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

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

Ipsilateral Motor Responses to Focal Transcranial Magnetic Stimulation in Healthy Subjects and Acute-Stroke Patients

Background and Purpose— Prevalence and characteristics of ipsilateral upper limb motor-evoked potentials (MEPs) elicited by focal transcranial magnetic stimulation (TMS) were compared in healthy subjects and patients with acute stroke. Methods— Sixteen healthy subjects and 25 patients with acute stroke underwent focal TMS at maximum stimulator output over motor and premotor cortices. If present, MEPs evoked in muscles ipsilateral to TMS were analyzed for latency, amplitude, shape, and center of gravity (ie, preferential coil location to elicit them). In stroke patients, possible relationships between early ipsilateral responses and functional outcome at 6 months were sought. Results— With relaxed or slightly contracting target muscle, maximal TMS over the motor cortex failed to elicit ipsilateral MEPs in the first dorsal interosseous (FDI) or biceps of any of 16 normal subjects. In 5 of 8 healthy subjects tested, ipsilateral MEPs with latencies longer than contralateral MEPs were evoked in FDI muscle (in biceps, 6 of 8 subjects) during strong (>50% maximum) contraction of the target muscle. In 15 of 25 stroke patients, ipsilateral MEPs in the unaffected relaxed FDI (in biceps, 6 of 25 stroke patients) were evoked by stimulation of premotor areas of the affected hemisphere. Their latencies were shorter than those that MEPs evoked in the same muscle by stimulation of the motor cortex of the contralateral unaffected hemisphere. Such responses were never obtained in normal subjects and were mostly observed in patients with subcortical infarcts. Patients harboring these responses had slightly better bimanual dexterity after 6 months. Conclusions— Ipsilateral MEPs obtained in healthy individuals and stroke patients have different characteristics and probably different origins. In the former, they are probably conveyed via corticoreticulospinal or corticopropriospinal pathways, whereas in the latter, early ipsilateral MEPs could originate in hyperexcitable premotor areas.

Repetitive transcranial magnetic stimulation in schizophrenic patients reporting auditory hallucinations

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

Transcranial magnetic stimulation in Alzheimer disease: motor cortex excitability and cognitive severity

To study the possible changes of cortical excitability in the Alzheimer disease (AD) by transcranial magnetic stimulation (TMS) and to evaluate their eventual correlation with its stage twenty-one AD patients and 18 normal controls underwent TMS. Motor threshold, amplitudes of motor evoked potentials (MEPs), central motor conduction time (CMCT) and silent period (SP) were considered. The motor threshold in AD patients was lower than in normal subjects with a significant correlation between the stage of cognitive severity. The amplitude of MEPs was increased and the SP duration was reduced in AD patients. No significant differences were obtained for CMCT. These findings could suggest a correlation between increased motor cortical excitability and cognitive severity. Moreover, the increased cortical excitability could represent a key to understand the mechanism of AD and may have implication for novel treatment strategies.

Transcranial magnetic stimulation after pure motor stroke

OBJECTIVES The objective of this study was to assess the sensitivity of motor-evoked potentials (MEPs) elicited by transcranial magnetic stimulation (TMS) in demonstrating the possible subclinical impairment of the corticospinal pathway after recovery, in patients with a clinical history of pure motor stroke (PMS) due to a single lacunar infarct detectable by magnetic resonance imaging (MRI). METHODS MEPs were recorded from the first dorsal interosseous muscle of 20 healthy subjects and 40 patients, 6 months or more after PMS onset. Patients were evaluated clinically by means of the NIH stroke scale, the Medical Research Council (MRC) scale and the Barthel Index. The patients with full hand strength recovery and the normal controls were also tested by means of the 9-hole peg test. RESULTS Motor threshold (MT), MEP amplitude and central motor conduction time (CMCT) of the affected side were significantly different from those of the normal side and of the control subjects. MT, MEP amplitude and CMCT obtained after stimulation of the affected hemisphere were significantly correlated with the MRC scale values of the affected hand. Eighty-six percent of patients with persistent hand strength deficit showed MEP abnormalities. In 21 patients with complete clinical recovery, a significant increase in MT and decrease in MEP amplitude on the affected side were observed. CONCLUSIONS After PMS, neurophysiological changes may persist despite complete clinical recovery. TMS represents a sensitive tool that enables to demonstrate objectively the clinical and subclinical impairment of the corticospinal pathway.

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

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

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

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

Elevated blood lactate is associated with increased motor cortex excitability.

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

Reduced excitability of the motor cortex in untreated patients with de novo idiopathic “grand mal” seizures

OBJECTIVES Transcranial magnetic stimulation (TMS) was used to investigate motor cortex excitability, intracortical excitatory, and inhibitory pathways in 18 patients having experienced a first “grand mal” seizure within 48 hours of the electrophysiological test. All had normal brain MRI, and were free of any treatment, drug, or alcohol misuse. Results were compared with those of 35 age matched normal volunteers. METHODS The following parameters of responses to TMS were measured: motor thresholds at rest and with voluntary contraction, amplitudes of responses, cortical silent periods, and responses to paired pulse stimulation with interstimulus intervals of 1 to 20 ms. RESULTS In patients, there were significantly increased motor thresholds with normal amplitudes of motor evoked potentials (MEPs), suggesting decreased cortical excitability. Cortical silent periods were not significantly different from those of normal subjects. Paired TMS with short interstimulus intervals (1–5 ms) induced normal inhibition of test MEPs, suggesting preserved function of GABAergic intracortical inhibitory interneurons. On the contrary, the subsequent period of MEP facilitation found in normal subjects (ISIs of 6–20 ms) was markedly reduced in patients. This suggests the existence of abnormally prolonged intracortical inhibition or deficient intracortical excitation. In nine patients retested 2 to 4 weeks after the initial seizure, these abnormalities persisted, although to a lesser extent. CONCLUSION The present findings together with abnormally high motor thresholds could represent protective mechanisms against the spread or recurrence of seizures.

Impairment of neuromuscular transmission in a subgroup of migraine patients

Neuronal voltage-dependent P/Q Ca2+ channels are genetically abnormal in many cases of familial hemiplegic migraine and possibly associated with the more common forms of migraine with and without aura. Besides the brain, these channels are found in motor nerve endings where they control stimulation-induced acetylcholine release. Using single fiber EMG recordings we were able to demonstrate subclinical abnormalities of neuromuscular transmission in a subgroup of patients suffering from migraine with aura. This could be related to genetic abnormalities of P/Q Ca2+ channels in certain patients suffering from migraine with aura, which needs to be explored by proper genetic analyses.