[Show abstract][Hide abstract] ABSTRACT: Neurophysiological studies in migraine have reported conflicting findings of either cortical hyper- or hypoexcitability. In migraine with aura (MwA) patients, we recently documented an inhibitory response to suprathreshold, high-frequency repetitive transcranial magnetic stimulation (hf-rTMS) trains applied to the primary motor cortex, which is in contrast with the facilitatory response observed in the healthy subjects. The aim of the present study was to support the hypothesis that in migraine, because of a condition of basal increased cortical responsivity, inhibitory homeostatic like mechanisms of cortical excitability could be induced by high magnitude stimulation. For this purpose, the hf-rTMS trains were preconditioned by transcranial direct current stimulation (tDCS), a noninvasive brain stimulation technique able to modulate the cortical excitability state.
Twenty-two MwA patients and 20 patients with migraine without aura (MwoA) underwent trains of 5-Hz repetitive transcranial magnetic stimulation at an intensity of 130% of the resting motor threshold, both at baseline and after conditioning by 15 minutes of cathodal or anodal tDCS. Motor cortical responses to the hf-rTMS trains were compared with those of 14 healthy subjects.
We observed abnormal inhibitory responses to the hf-rTMS trains given at baseline in both MwA and MwoA patients as compared with the healthy subjects (P < .00001).The main result of the study was that cathodal tDCS, which reduces the cortical excitability level, but not anodal tDCS, which increases it, restored the normal facilitatory response to the hf-rTMS trains in both MwA and MwoA.
The present findings strengthen the notion that, in migraine with and without aura, the threshold for inducing inhibitory mechanisms of cortical excitability might be lower in the interictal period. This could represent a protective mechanism counteracting cortical hyperresponsivity. Our results could be helpful to explain some conflicting neurophysiological findings in migraine and to get insight into the mechanisms underlying recurrence of the migraine attacks.
Headache The Journal of Head and Face Pain 04/2014; 54(4):663-74. DOI:10.1111/head.12249 · 2.71 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The primary brain dysfunctions leading to the onset of a migraine attack remain largely unknown. Other important open questions concern the mechanisms of initiation, continuation, and termination of migraine pain, and the changes in brain function underlying migraine transformation. Brief trains of high-frequency repetitive transcranial magnetic stimulation (rTMS), when applied to the primary motor cortex at suprathreshold intensity (⩾ 120% of resting motor threshold, RMT), elicit in healthy subjects a progressive, glutamate-dependent facilitation of the Motor Evoked Potentials (MEP). Conversely, in conditions of increased cortical excitability, the rTMS trains induce inhibitory MEP responses likely mediated by cortical homeostatic mechanisms. We enrolled 66 migraine without aura (MwoA) patients, 48 migraine with aura (MwA) patients, 14 patients affected by chronic migraine (CM), and 20 healthy controls. We assessed motor cortical response to 5-Hz rTMS trains of 10 stimuli given at 120% RMT. Patients with episodic migraine (EM) were studied in different phases of the migraine cycle, i.e. interictal, preictal, ictal and postictal state. Results showed a facilitatory MEP response during the trains in patients evaluated in the preictal phase, whilst inhibitory responses were observed during and after a migraine attack, as well as in CM patients. In the interictal phase, different responses were observed depending on attack frequency: facilitation in patients with low and inhibition with those with high attack recurrence. Our findings suggest that changes in cortical excitability and fluctuations in the threshold for inhibitory metaplasticity underlie the migraine attack recurrence, and could be involved in the process of migraine transformation.
[Show abstract][Hide abstract] ABSTRACT: Objective
To evaluate the effects of transcranial direct current stimulation (tDCS) on esophageal peristalsis in patients with gastroesophageal reflux disease (GERD).
Patients with GERD preliminary diagnosis were included in a randomized double-blind sham-controlled study. Esophageal manometry was performed before and during transcranial direct current stimulation (tDCS) of the right precentral cortex. Half of patients were randomly assigned to anodal, half to sham stimulation. Distal waves amplitude and pathological waves percentage were measured, after swallowing water boli, for ten subsequent times. Last, a 24 h pH-bilimetry was done to diagnose non-erosive reflux disease (NERD) or functional heartburn (FH). The values obtained before and during anodal or sham tDCS were compared.
Sixty-eight patients were enrolled in the study. Distal waves mean amplitude increased significantly only during anodal tDCS in NERD (p = 0.00002) and FH subgroups (p = 0.008) while percentage of pathological waves strongly decreased only in NERDs (p = 0.002).
Transcranial stimulation can influence cortical control of esophageal motility and improve pathological motor pattern in NERD and FH but not in erosive reflux disease (ERD) patients.
Pathophysiological processes in GERD are not only due to peripheral damage but to central neural control involvement as well. In ERD patients dysfunctions of the cortico-esophageal circuit seem to be more severe and may affect central nervous system physiology.
[Show abstract][Hide abstract] ABSTRACT: Aim:
Topiramate is a small molecule widely used for the treatment of epilepsy, migraine, bipolar disorders and alcoholism, and its availability as a generic formulation could significantly reduce the National Health Service expenditure. A generic formulation, available in Italy under the trademark Sincronil, recently showed superimposable blood levels, after oral administration to healthy volunteers, with the reference formulation. In the present study we report the results of an open label, parallel group, randomized, controlled study performed to evaluate the efficacy, tolerability and impact on disability of two different formulations of topiramate (Sincronil and Topamax) in patients with migraine without aura.
Sixty patients aged between 18 and 65 years, suffering from migraine without aura with an attack frequency of 3-15 attacks/month were enrolled and received, after a titration phase lasting 20 days, randomly either Sincronil or Topamax at the dose of 25 mg twice daily for 3 months.
Fifteen out of the 30 patients who were administered Sincronil reported an improvement in the clinical condition, with a decrease in the frequency of attacks at the 3rd month of treatment higher than 50% with respect to the run-in period, 9 reported their clinical condition as being substantially unchanged and 6 reported that they had suspended the treatment within the first 4 weeks of therapy due to side effects. Among the 24 patients who continued treatment up to the 3rd month, the frequency of attacks during the 3rd month of treatment was significantly decreased from 7 ± 3.6 to 3.7 ± 3.7 (P<0.0001), migraine severity was reduced from 2.5 ± 0.5 to 1.7 ± 0.7 (P<0.0005) and the MIDAS score was reduced from 14.3 ± 4.9 to 8.6 ± 5.5 (P<0.0001). Sixteen out of the 30 patients who were administered Topamax reported an improvement in the clinical condition with a reduction in the attack frequency at the 3rd month of treatment higher than 50% with respect to the run-in period, 10 reported a substantially unchanged clinical condition and 4 stopped the treatment within the first weeks due to side effects. Among the 26 patients who continued treatment up to the 3rd month, headache frequency during the 3rd month of treatment was significantly reduced, from 7.3 ± 2.6 to 3.5 ± 2.7 (P<0.0001), migraine severity decreased from 2.4 ± 0.6 to 1.6 ± 0.8 (P<0.0005) and the MIDAS score from 14.1 ± 4.2 to 6.8 ± 4.8 (P<0.0001).
In conclusion, in this study Topamax (reference product) and Sincronil (generic formulation) have proven therapeutically equivalent and both products were well tolerated.
[Show abstract][Hide abstract] ABSTRACT: Experimental studies emphasize the importance of homeostatic plasticity as a mean of stabilizing the properties of neural circuits. In the present work we combined two techniques able to produce short-term (5-Hz repetitive transcranial magnetic stimulation, rTMS) and long-term (transcranial direct current stimulation, tDCS) effects on corticospinal excitability to evaluate whether and how the effects of 5-Hz rTMS can be tuned by tDCS preconditioning. Twelve healthy subjects participated in the study. Brief trains of 5-Hz rTMS were applied to the primary motor cortex at an intensity of 120% of the resting motor threshold, with recording of the electromyograph traces evoked by each stimulus of the train from the contralateral abductor pollicis brevis muscle. This interventional protocol was preconditioned by 15 min of anodal or cathodal tDCS delivered at 1.5 mA intensity. Our results showed that motor-evoked potentials (MEPs) increased significantly in size during trains of 5-Hz rTMS in the absence of tDCS preconditioning. After facilitatory preconditioning with anodal tDCS, 5-Hz rTMS failed to produce progressive MEP facilitation. Conversely, when 5-Hz rTMS was preceded by inhibitory cathodal tDCS, MEP facilitation was not abolished. These findings may give insight into the mechanisms of homeostatic plasticity in the human cerebral cortex, suggesting also more suitable applications of tDCS in a clinical setting.
European Journal of Neuroscience 01/2012; 35(1):119-24. DOI:10.1111/j.1460-9568.2011.07939.x · 3.18 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Here we present the case of a 50-year-old man suffering from "painful tic convulsif", on the left side of the face, i.e., left trigeminal neuralgia associated with ipsilateral hemifacial spasm. An angio-MRI scan showed a neurovascular confliction of left superior cerebellar artery with the ipsilateral V cranial nerve and of the left inferior cerebellar artery with the ipsilateral VII cranial nerve. Neurophysiological evaluation through esteroceptive blink reflex showed the involvement of left facial nerve. An initial carbamazepine treatment (800 mg/daily) was completely ineffective, so the patient was shifted to lamotrigine 50 b.i.d. that was able to reduce attacks from 4 to 6 times per day to 1 to 2 per week. Considering the good response to the drug, the neurosurgeon decided to delay surgical treatment.
The Journal of Headache and Pain 08/2011; 12(6):653-6. DOI:10.1007/s10194-011-0370-0 · 2.80 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: High cerebrospinal fluid (CSF) and plasma levels of homocysteine (HC) have been reported in certain neurodegenerative disorders, such as Alzheimer's, Parkinson's diseases and, recently, amyotrophic lateral sclerosis (ALS).
To assay the CSF and plasma levels of HC in ALS patients and controls, and to evaluate the relationship between HC levels and clinical variables of the disease.
Cerebrospinal fluid from sixty-nine (M/F 1.87) and plasma from sixty-five ALS patients (M/F 1.83) were taken and stored at -80 degrees C until use. Controls (CSF = 55; plasma = 67) were patients admitted to our hospital for neurological disorders with no known relationship to HC changes. CSF and plasma from ALS patients and controls were obtained as a necessary step of the diagnostic workup. HC levels in CSF and plasma were assayed using a high performance liquid chromatograph (HPLC) and a fluorimeter detector.
The median level of total HC in the CSF of ALS patients was 0.46( )microM, significantly higher than that of the controls (0.24 microM, +91.6%, P < 0.001). A similar trend was observed when HC was assayed in plasma (ALS, 12.4 microM vs. controls, 7.26 microM, +70.8%, P < 0.001). The CSF and plasma HC levels showed no relationship with the disease progression, age at onset, and the site of onset.
Homocysteine is a biochemical marker in ALS, and it might be related to the pathophysiology of the disease.
European Journal of Neurology 07/2009; 17(1):84-9. DOI:10.1111/j.1468-1331.2009.02752.x · 4.06 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder leading to progressive motor neuron cell death. Etiopathogenesis is still imperfectly known and much effort have been undertaken to find a biological marker that could help in the early diagnosis and in the monitoring of disease progression. Cerebrospinal fluid (CSF) concentrations of tau, an axonal microtubule-associated protein, have been measured in ALS with levels found increased in some studies and unchanged in others.
Total CSF tau level was assayed in a population of ALS patients (n = 57) and controls (n = 110) using a specific ELISA method.
No significant differences in the median CSF tau levels between ALS cases and controls were found [ALS: 126 pg/ml (78-222); controls: 112 pg/ml (71-188), P = ns]. In the ALS group, the bulbar-onset patients showed increased CSF tau levels as compared with the spinal-onset cases. These differences might be related to the higher age of the bulbar-onset patients. Further, no correlations were found between CSF tau concentrations and the rate of progression of the disease.
These results do not support the hypothesis that total CSF tau protein is a reliable biological marker for ALS.
European Journal of Neurology 02/2009; 16(2):257-61. DOI:10.1111/j.1468-1331.2008.02405.x · 4.06 Impact Factor