Ornella Daniele

1 Hz repetitive transcranial magnetic stimulation of the unaffected hemisphere ameliorates contralesional visuospatial neglect in humans

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.

rTMS of the prefrontal cortex in the treatment of chronic migraine: a pilot study.

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.

Modulatory effects of low‐ and high‐frequency repetitive transcranial magnetic stimulation on visual cortex of healthy subjects undergoing light deprivation

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.

Low-frequency transcranial magnetic stimulation in patients with cortical dysplasia - a preliminary study.

Sirs: Because of the increasing attention to the potential therapeutic role of repetitive transcranial magnetic stimulation (rTMS) in intractable epilepsy [2, 4], the aim of this study was to find out whether patients with medically refractory epilepsy due to cortical dysplasia could benefit from low-frequency rTMS. 1 Hz rTMS have been able to decrease motor cortex excitability [1]. Lower stimulation frequencies (0,33 and 0.5 Hz) have been successfully employed in the treatment of seizures in humans and experimental animals [2–4]. In this open pilot study we investigated the effect of 0.5 Hz rTMS in four patients (1 M, 3 F mean age 29.5 ± 2.6, range 27–33 years) with very frequent partial and secondary generalized seizures due to a single frontal focus (2 patients: 1a, 2a) or to multiple foci (2 patients: 1b, 2b) of cortical dysplasia evidenced by ictal video-EEG monitoring and MRI. Patients gave their informed consent to participate in the study, which was approved by the local ethics committee. rTMS was performed biweekly for four consecutive weeks by means of a Cadwell high frequency magnetic stimulator with monophasic stimulus configuration (pulse width 200 μs). Each session consisted of 100 pulses at 0.5 Hz frequency delivered at 90 % of motor threshold through a water-cooled eightshaped coil positioned tangential to the scalp with the handle pointing backwards parallel to the midline. Locations for TM stimulation were determined according to 10–20 EEG coordinate system: over the EEG site of focal epileptic activity in patients with single focus and at Cz point (vertex) in patients with multifocal epilepsy. The average stimulus intensity (expressed as % of maximum stimulator output) was 65 ± 3.7 %. Patients tolerated rTMS treatment well and no adverse events were observed. They recorded every definite seizure or any seizure-like event from one month before to one month after the treatment. Patients were on antiepileptic polytherapy with each drug in its therapeutic range (the most effective combination of lamotrigine and sodium valproate in patients with single epileptic focus, and of phenobarbital, carbamazepine and clobazam in patients with multifocal epilepsy). During the study period medication was kept constant. The number of seizures during the month before stimulation (time I) was compared with that of the month during stimulation (time II) and after stimulation (time III). rTMS markedly reduced number and severity of seizures in patients with a single dysplasic focus. The improvement was predominantly in the disappearance of secondary generalization and was still persistent one month after the end of the treatment. The overall number of seizures at times I, II and III was respectively 19,13, and 12 for patient 1a and 19, 11 and 13 for patient 2a (see Fig. 1 A). By contrast, no changes in seizure frequency and severity were observed in patients with multiple foci (the overall number of seizures at times I, II and III was 33, 43, and 27 respectively for patient 1b and 39, 33 and 47 for patient 2b). Our results suggest that a longlasting depression of a cortical dysplasic area may improve intractable epilepsy. Focal phenomena of synaptic plasticity induced by lowfrequency rTMS at the site of stimulation might reduce hyperactivity of the affected hemisphere that would be part of the underlying physiology of the seizure. On such a basis the distance of epileptic foci from the site of stimulation (at the vertex) could explain the inefficacy of the treatment in patients with multifocal epilepsy. In this case it would have been more reasonable to use a non-focal round coil at the vertex to cause a widespread cortical stimulation, but the overheating with the long rTMS trains employed limited its use. On the other hand the effect observed in patients with single focus suggests the opportunity of serial administration of rTMS over each of the dysplasic foci in multifocal epilepsy. These data are preliminary and need to be confirmed by controlled studies with longer follow-up, in larger series of patients.

Hemispheric cerebellar rTMS to treat drug-resistant epilepsy: case reports.

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.

High-Frequency Transcranial Magnetic Stimulation on Motor Cortex of Patients Affected by Migraine With Aura: A Way to Restore Normal Cortical Excitability?

We showed reduced motor intracortical inhibition (ICI) and paradoxical increase of intracortical facilitation (ICF) to 1 Hz repetitive transcranial magnetic stimulation (rTMS) in patients affected by migraine with aura (MA). In conditions of enhanced excitability due to a reduced inhibition, high-frequency rTMS was found to potentiate intracortical inhibition. Here we explored the conditioning effects of high-frequency priming stimulation of motor cortex with the aim of normalizing excitability reverting paradoxical facilitation by 1 Hz rTMS in MA. Nine patients with MA and nine healthy controls underwent a paired-pulse TMS paradigm to evaluate motor intracortical excitability (ICI and ICF) before and after the following rTMS conditions: 1 Hz alone or preceded by a real or sham conditioning high-frequency (10 Hz) rTMS. Sham was used to control for rTMS specificity. In baseline, ICI was significantly lower in migraineurs with respect to controls. One hertz stimulation reduced motor evoked potential amplitude and ICF in healthy controls, while it caused a significant paradoxical ICF increase in migraineurs. High-frequency rTMS conditioning normalized excitability in migraine, increasing short ICI and so reversing the paradoxical effects of 1 Hz rTMS. These findings raise the possibility that the interictal reduced intracortical inhibition in migraine could be normalized by high-frequency rTMS. This would open perspectives for new treatment strategies in migraine prevention.

Motor intracortical inhibition in PD: L-DOPA modulation of high-frequency rTMS effects

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.

Gabapentin in the treatment of hemifacial spasm.

Objectives– To evaluate the efficacy of gabapentin in the treatment of hemifacial spasm. Material and methods– Twenty‐three patients with hemifacial spasm not suitable for surgery or therapy with botulinum toxin were treated with gabapentin. The main efficacy parameter was the percentage of spasm reduction. Results– A clinically significant reduction of spasms was obtained by 16 patients. Conclusion– Gabapentin was effective and safe in reducing hemifacial spasm in 16 out 23 (69.6%) patients.

Dropped head as an unusual presenting sign of myasthenia gravis.

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.

Auditory event-related potentials in subcortical vascular cognitive impairment and in Alzheimer's disease

Summary.Background: Few studies exist on ERPs and patients with subcortical vascular cognitive impairment (SVCI). This latter is a quite homogeneous subtype of vascular dementia whose cognitive profile is quite different from that of Alzheimer disease (AD).Aims: The present study aims at comparing the ERPs profile both in patients with SVCI and in patients with AD.Subjects and methods: ERPs and psychometric tests were collected from 39 healthy elderly controls, 51 patients with SVCI and 43 patients with AD. Subjects mentally count high pitched target tones that were randomly intermixed with low pitched frequent tones. We measured ERPs latencies (N1, P2, N2 and P3), and interpeak latencies (N1–P3, N1–P2, N1–N2).Results: Grand averaged potentials in SVCI showed a significant increase of P3 latency. AD patients showed a prolongation of N1, P2, N2, P3 latencies. As far as interpeak latencies are concerned, SVCI patients showed a significant prolongation of N1–P3, AD patients had a significant increase of N1–N2, and N1–P3 intervals. When all patients were considered as a single group, correlation of neuropsychological tests scores showed a significant negative relationship between P300 latency and, respectively, Mini Mental Status Examination, auditive and visual span forward. In both groups, ERPs latency sensitivity, was low, whilst specificity values were quite high.Conclusions: Our finding suggest that these two dementing diseases have different electrophysiologic features that may be related to their specific underlying pathogenetic mechanism; in particular, we hypothesise that, differently from AD, P300 latency prolongation characterizes the early stage of SVCI. So, this ERPs approach could be helpful to detect early alterations of the attentional/working-memory functions in patients with subcortical ischaemic vascular disease.