Fabrizio Monti

Sexual dysfunction in multiple sclerosis: a MRI, neurophysiological and urodynamic study

We studied 31 patients with relapsing-remitting (RR) multiple sclerosis (MS) in which we performed an urodynamic study, the pudendal cortical evoked potentials, the tibial cortical evoked potentials and the cranial and cervical spinal cord magnetic resonance imaging (MRI). We calculated the T(1) and T(2) lesion load (LL) and brain parenchymal fraction (BPF) of whole brain, frontal lobes, pons and cervical spinal cord. We also estimated the cross-sectional area at C(2) level. Spearmans rank correlation analysis showed a relationship between symptoms of sexual dysfunction and age (r=0.73, p<0.0001), cognitive performances (r=-0.63, p<0.0001), level of independence (r=-0.63, p<0.0001), disability (r=0.56, p<0.001), symptoms of anxiety (r=0.55, p<0.001) and depression (r=0.50, p<0.005), disease duration (r=0.42, p<0.02) and parenchymal atrophy in the pons (r=-0.38, p=0.031). Sexual dysfunction was not correlated with any other MRI measure, urodynamic patterns or cortical evoked potentials. In multiple regression analysis, sexual dysfunction was predicted only by T(1) lesion load of the pons. In conclusion, we confirmed previous correlations of sexual dysfunction with various clinical variables and demonstrated an association between sexual dysfunction and destructive lesions in the pons, as detected by MRI, in patients with relapsing-remitting multiple sclerosis.

Double-Blind, Placebo-Controlled, Randomized, Crossover Trial of High-Dose Methylprednisolone in Patients with Chronic Progressive Form of Multiple Sclerosis

A double-blind, placebo-controlled, randomized crossover trial of high-dose methylprednisolone (MP) was performed in 35 patients with a primarily chronic progressive form of multiple sclerosis as defined clinically according to Posers criteria. At time 0 of every course of treatment (1 g MP administered i.v. daily for 5 days followed by oral prednisone tapering over 4 days, or placebo) and at 10, 30 and 90 days thereafter, each patient underwent psychometric tests and was clinically tested according to Kurtzkes Expanded Disability Status Scale (EDSS). The disability pattern of most patients who were treated with placebo either worsened or did not change. A statistically significant improvement (p < 0.001) of EDSS in MP-treated patients was recorded. The improvement mainly concerned the pyramidal, cerebellar and sensitive disorders; it was already evident at the first clinical follow-up and lasted for 3 months from the beginning of the treatment. No frequent and/or important side effects were detected throughout the trial.

Effect of Transcranial Magnetic Stimulation (TMS) on Parietal and Premotor Cortex during Planning of Reaching Movements

Background Cerebral activation during planning of reaching movements occurs both in the superior parietal lobule (SPL) and premotor cortex (PM), and their activation seems to take place in parallel. Methodology The activation of the SPL and PM has been investigated using transcranial magnetic stimulation (TMS) during planning of reaching movements under visual guidance. Principal Findings A facilitory effect was found when TMS was delivered on the parietal cortex at about half of the time from sight of the target to hand movement, independently of target location in space. Furthermore, at the same stimulation time, a similar facilitory effect was found in PM, which is probably related to movement preparation. Conclusions This data contributes to the understanding of cortical dynamics in the parieto-frontal network, and suggests that it is possible to interfere with the planning of reaching movements at different cortical points within a particular time window. Since similar effects may be produced at similar times on both the SPL and PM, parallel processing of visuomotor information is likely to take place in these regions.

Motor excitability evaluation in developmental stuttering: a transcranial magnetic stimulation study.

INTRODUCTION Developmental stuttering (DS) is viewed as a motor speech-specific disorder, although several lines of research suggest that DS is a symptom of a broader motor disorder. We investigated corticospinal excitability in adult DS and normal speakers. METHODS Transcranial magnetic stimulation (TMS) was administered over left/right hand representation of the motor cortex while recording motor evoked potentials (MEPs) from the contralateral first dorsal interosseous (FDI) muscle. Resting, active motor thresholds, silent period threshold and duration were measured. A stimulus-response curve at resting was also obtained to evaluate MEP amplitudes. RESULTS Lower corticospinal responses in the left hemisphere of DS were found, as indicated by a reduction of peak-to-peak MEP amplitudes compared to normal speakers. CONCLUSIONS This provides further evidence that DS may be a general motor deficit that also involves motor non-speech-related structures. Moreover, our results confirm that DS may be related to left hemisphere hypoactivation and/or lower left hemisphere dominance. The present data and protocol may be useful for diagnosis of subtypes of DS that may benefit from pharmacological treatment by targeting the general level of cortical excitability.

Parieto-occipital cortex and planning of reaching movements: a transcranial magnetic stimulation study.

A large amount of evidence supports a role for the parietal and frontal cortex in the planning of reaching movements. Nevertheless, neither the timing of involvement of these areas nor if and how their activity can be influenced by external stimuli has been clarified. The parieto-occipital cortex has been investigated by applying transcranial magnetic stimulation (TMS) at 25% (Time 1), 50% (Time 2) and 75% (Time 3) of the reaction time from a go signal to hand movement. No local effect was found with Time 1, since pulses were administered before subjects opened their eyes. Reduction of reaction time was observed at Time 2 when stimuli were applied over the anterior occipital lobe, parieto-occipital cortex and posterior parietal cortex. The effect on the posterior parietal cortex reverted when Time 3 was used. The present data confirm the existence, in humans, of a dorso-medial set of areas involved in on-line planning of reaching movements. Moreover, they provide novel evidence on the time course of this involvement. Finally, present data show that it is possible to interact with the flow of activity along this stream by appropriately delivering TMS pulses.

Investigating the efficacy of paroxetine in developmental stuttering.

Objectives:Paroxetine has been reported to be useful for management of stuttering symptoms, but only a few reports have examined its effects. We have investigated the efficacy of paroxetine in a randomized, placebo-controlled study. Methods:Five stuttering subjects received paroxetine at 20 mg once daily at night for 12 weeks, and 5 received placebo. The percentages of stuttered words and stuttering-associated movements during speech were measured at baseline and after 6 and 12 weeks of treatment. Moreover, left primary motor cortex excitability was measured using transcranial magnetic stimulation. Specifically, resting and active motor thresholds and the cortical silent period (CSP) were obtained at the same periods in both groups. Results:Paroxetine did not affect the percentage of stuttered words between groups. Stuttering-associated movements, however, during speech in facial muscular districts were significantly reduced in subjects treated with paroxetine. Finally, paroxetine administration shortened the CSP with no effect on motor thresholds. Conclusion:Paroxetine may be useful in qualitative management of stuttering symptoms and may act on the stuttering brain by diminution of intracortical inhibition, as revealed by the shortening of the CSP after paroxetine administration.

Transcranial magnetic stimulation and preparation of visually-guided reaching movements

To better define the neural networks related to preparation of reaching, we applied transcranial magnetic stimulation (TMS) to the lateral parietal and frontal cortex. TMS did not evoke effects closely related to preparation of reaching, suggesting that neural networks already identified by our group are not larger than previously thought. We also replicated previous TMS/EEG data by applying TMS to the parietal cortex: new analyses were performed to better support reliability of already reported findings (Zanon et al., 2010; Brain Topography 22, 307–317). We showed the existence of neural circuits ranging from posterior to frontal regions of the brain after the stimulation of parietal cortex, supporting the idea of strong connections among these areas and suggesting their possible temporal dynamic. Connection with ventral stream was confirmed. The present work helps to define those areas which are involved in preparation of natural reaching in humans. They correspond to parieto-occipital, parietal and premotor medial regions of the left hemisphere, i.e., the contralateral one with respect to the moving hand, as suggested by previous studies. Behavioral data support the existence of a discrete stream involved in reaching. Besides the serial flow of activation from posterior to anterior direction, a parallel elaboration of information among parietal and premotor areas seems also to exist. Present cortico-cortical interactions (TMS/EEG experiment) show propagation of activity to frontal, temporal, parietal and more posterior regions, exhibiting distributed communication among various areas in the brain. The neural system highlighted by TMS/EEG experiments is wider with respect to the one disclosed by the TMS behavioral approach. Further studies are needed to unravel this paucity of overlap. Moreover, the understanding of these mechanisms is crucial for the comprehension of response inhibition and changes in prepared actions, which are common behaviors in everyday life.

A case of hypocalcemia-related epilepsia partialis continua

Epilepsia partialis continua (EPC) is a syndrome clinically defined as continuous spontaneous jerking confined to one part of the body, sometimes aggravated by action or sensory stimuli, occurring over hours, days or even years. In adults the more frequent recognized cause of EPC is an acute cerebrovascular disease. Acute severe hypocalcemia is a highly epileptogenic ionic disturbance, abnormally increasing neuronal excitability. In this short communication we describe the first probable case of acute hypocalcemia-related EPC. Eight months after a left parietal lobe cardioembolic stroke, a 74-year-old woman experienced a generalized tonic-clonic seizure for the first time in her life, at the beginning of a Clostridium difficile enterocolitis. Four days later, while the abdominal symptoms were clinically improving, continuous semi-rhythmic jerks of right face, shoulder and arm began suddenly. Despite several appropriated antiepileptic treatments those involuntary movements did not cease. On routine biochemical examination we noted a total calcium serum level of 1.2 mmol/L (normal range 2.1-2.8 mmol/L), not previously known. After intravenous calcium gluconate supplementation, the jerks started to fade, disappearing completely as a total calcium serum level of 1.9 mmol/L was reached. Two separated CT brain scans did not reveal new cerebral lesions. Neurophysiological studies did not show any cortical activity related to jerks. Taken together, the treatment refractoriness and the clinical improvement after ionic imbalance correction point towards a highly possible role of hypocalcemia in sustaining the activity of a previously silent epileptogenic focus.

Involvement of ipsilateral parieto-occipital cortex in the planning of reaching movements: evidence by TMS.

Involvement of the ipsilateral hemisphere during planning of reaching movements is still matter of debate. While it has been demonstrated that the contralateral hemisphere is dominant in visuo-motor integration, involvement of the ipsilateral hemisphere has also been proposed. Furthermore, a dominant role for left posterior parietal cortex has been shown in this process, independently of the hand and visual field involved. In this study, the possible involvement of ipsilateral parieto-occipital cortex in planning of reaching movements was investigated by transcranial magnetic stimulation (TMS). TMS was applied on four points of the parietal and occipital cortex at 50% (Time 1), 75% (Time 2) and 90% (Time 3) of reaction time from a go-signal to hand movement. The only effect observed was an increase in reaction time when a region around the parieto-occipital junction was stimulated at Time 2. These results provide further support to the hypothesis that, in the posterior parietal cortex, planning of reaching movements also relies on the ipsilateral hemisphere, in addition to the contralateral or dominant one.

Linear and non-linear parameterization of EEG during monitoring of carotid endarterectomy

In this paper, new quantitative linear (HLF ratio: high frequency/low frequency spectral power ratio) and non-linear parameters (ZC: zero crossing and FD: fractal dimension) which can assist the physician in real-time decision whether a shunt is required or not during intra-operative EEG monitoring of carotid endarterectomy are presented. The results obtained with the new parameters are compared with those achieved by other indexes proposed in the literature. The HLF ratio and ZC parameters yielded the best results with a 100% of correct identification of both shunt and no-shunt situations. The ZC can be also easily implemented in the real-time monitoring of EEG.