Visuospatial learning is fostered in migraine: evidence by a neuropsychological study.

BACKGROUND: Cognitive profile in migraine patients still remains undefined. Contradictory evidence has been provided, with impairments in different cognitive domains, normal cognition, or even better performance compared to healthy controls (HC). The latter is of particular interest considering the evidence of glutamatergic upregulation in migraine, particularly in the visual cortex, and the role of the glutamatergic system in synaptic plasticity and learning. The aim of our study is to compare cognitive performance for visuospatial memory and learning (supraspan modality) between migraineurs without aura (MwoA) and HC. METHODS: Twenty-one subjects suffering from MwoA and 21 HC were enrolled. Migraineurs during the interictal phase and HC underwent visuospatial memory test (Corsi test) and verbal memory test (Buschke Selective Reminding Test) in supraspan modality, Trial Making Test A (TMTA) and B (TMTB) as test exploring attention, and TMTB-TMTA as test of executive functioning. Depression was assessed with the Beck Depression Inventory Short Form (BDI-SF). Migraine characteristics (i.e., disease duration and frequency expressed as attacks per month) were collected. RESULTS: Subjects with MwoA showed better performance than HC in test exploring both short (p = 0.002) and long-term (p = 0.001) visuospatial memory. No significant difference between groups was found in verbal memory, attention, executive functioning, and depression (BDI-SF). No significant association emerged between cognitive performance and migraine characteristics. DISCUSSION: Subjects with MwoA had significant better performance in visuospatial memory and learning than HC. Occipito-parietal hyperexcitability (in particular in the visual cortex), which is a hallmark of the migraine brain, would probably explain these results. These data need to be confirmed in larger samples of migraineurs.

Anodal tDCS of the swallowing motor cortex for treatment of dysphagia in multiple sclerosis: a pilot open-label study.

Swallowing difficulties are a common symptom of multiple sclerosis (MS). The early detection and treatment of dysphagia is critical to prevent complications, including poor nutrition, dehydration, and lung infections. Recently, transcranial direct current stimulation (tDCS) has been proven to be effective in ameliorating swallowing problems in stroke patients. In this pilot study, we aimed to assess safety and efficacy of transcranial direct current stimulation (tDCS) in the treatment of dysphagia in MS patients. We screened 30 patients by using the 10-item DYsphagia in MUltiple Sclerosis (DYMUS) questionnaire, and patients at risk for dysphagia underwent a clinical and fiberoptic endoscopic evaluation of swallowing (FEES). Six patients who presented with mild to moderate dysphagia underwent the experimental procedures. These consisted of 5 sessions of anodal tDCS applied in consecutive days over the right swallowing motor cortex. Patients were followed-up at 1 week, 1 month and 3 months after treatment, and changes in the Dysphagia Outcome and Severity Scale (DOSS) score between baseline and post-tDCS were assessed. Our results showed that in all patients, the tDCS treatment determined a mild but significant clinical benefit (one-point improvement in the DOSS score) lasting up to 1 month. In conclusion, our preliminary results show that anodal tDCS has therapeutic potential in the treatment of swallowing problems in patients suffering with MS. However, future double-blind, randomized, and sham-controlled studies are needed to confirm the present findings.

The importance of the reproducibility of oropharyngeal swallowing in amyotrophic lateral sclerosis. An electrophysiological study.

OBJECTIVE: To investigate electrophysiologically the reproducibility of oropharyngeal swallowing in patients with ALS. METHODS: We enrolled 26 ALS patients, both with and without clinical signs of dysphagia, and 30 age-matched controls. The reproducibility of the electrophysiological signals related to the oral phase (electromyographic activity of the submental/suprahyoid muscles) and the pharyngeal phase (laryngeal-pharyngeal mechanogram) of swallowing across repeated swallows was assessed. To do this we computed two similarity indexes (SI) by using previously described mathematical algorithms. RESULTS: The reproducibility of oropharyngeal swallowing was significantly reduced both in patients with and in those without clinical signs of dysphagia, with more marked alterations being detected in the dysphagic group. The SI of both phases of swallowing, oral and pharyngeal, correlated significantly with dysphagia severity and disease severity. CONCLUSIONS: In ALS different pathophysiological mechanisms can alter the stereotyped motor behaviors underlying normal swallowing, thus reducing the reproducibility of the swallowing act. A decrease in swallowing reproducibility could be a preclinical sign of dysphagia and, beyond a certain threshold, a pathological hallmark of oropharyngeal dysphagia. SIGNIFICANCE: Electrophysiological assessment is a simple and useful tool for the early detection of swallowing abnormalities, and for the management of overt dysphagia in ALS.

Efficacy and safety of topiramate in migraine prophylaxis: an open controlled randomized study comparing Sincronil and topamax formulations.

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. METHODS: 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. RESULTS: 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). CONCLUSION: In conclusion, in this study Topamax (reference product) and Sincronil (generic formulation) have proven therapeutically equivalent and both products were well tolerated.

Neglect-like effects induced by tDCS modulation of posterior parietal cortices in healthy subjects.

BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) over right posterior parietal cortex was shown to induce interference on visuospatial perception in healthy subjects. Transcranial direct current stimulation (tDCS) is another noninvasive brain stimulation technique that works modulating cortical activity. It is applied through easy to use, noncostly, and portable devices. OBJECTIVE/HYPOTHESIS: The aim of the current study was to investigate if the novel approach of "dual" stimulation over parietal cortices compared with the unilateral (right) cathodal one is able to induce greater and/or longer-lasting neglect-like effects in normal subjects performing a computerized visuospatial task. METHODS: Eleven healthy subjects underwent a computerized visuospatial task requiring judgments about the symmetry of prebisected lines in baseline condition, during and after tDCS. Right cathodal and left anodal tDCS were simultaneously applied over homologue posterior parietal cortices in the "dual" approach, whereas right cathodal tDCS was used in the traditional unihemisphere stimulation. RESULTS: A significant rightward bias in symmetry judgments as compared with baseline and sham conditions was observed in both the stimulation approaches. With "dual" tDCS compared with cathodal stimulation the effect was stronger and appeared earlier, but no longer-lasting after effects were found. CONCLUSIONS: We speculate that the resulting modulation of interhemispheric inhibition mediated the additional rightward bias in task performance for "dual" hemisphere compared with unihemisphere tDCS. If "dual" tDCS may better reproduce mechanisms underlying real lesions, it could provide a more suitable model for rehabilitation of negligent patients.

A painful tic convulsif due to double neurovascular impingement.

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.

Visuospatial attention lateralization in volleyball players and in rowers.

In the present study, differences in visuospatial attention lateralization were evaluated in athletes engaged in open-compared to closed-skill sports and sedentary nonathletes. 23 volleyball players (open skill; Italian national level and regional level), 10 rowers (closed skill, Italian national level), and 23 sedentary participants responded to a computerized line-length judgment task. Five lines, differing in the length of their right and left segments, were randomly presented; the respondent made a forced-choice decision about the respective length of the two segments. Volleyball players responded significantly faster; those at the higher competitive level were also more accurate, making a statistically significantly lower number of leftward errors as compared with rowers and controls. If such responses are due to training rather than self-selection of ability, then the results may suggest the possibility of changing the distribution of visuospatial attention by training in open-skill sports.

Does habituation depend on cortical inhibition? Results of an rTMS study in healthy subjects.

Habituation, i.e. the decremental response to repeated sensorial stimulation, is studied in humans through evoked potential stimulation. Mechanisms underlying habituation are not yet cleared, even if inhibitory circuits are supposed to play an important role. Light deprivation (LD) increases visual cortical excitability likely through down-regulation of GABA circuits. We previously found that high-frequency repetitive transcranial magnetic stimulation (hf-rTMS) can revert these facilitatory effects likely restoring the activity of inhibitory circuits. Here, we studied the effects of LD and rTMS on habituation of visual evoked potentials (VEPs). The hypothesis was that if the inhibitory circuits have a role in habituation, then LD that downregulates GABA circuits, should impair habituation that in turn should be restored by hf-rTMS. Fifteen healthy subjects underwent VEPs recording in baseline (without LD), in LD alone (without rTMS), in LD and 1 Hz rTMS and in LD and 10 Hz rTMS. Habituation observed in baseline (without LD) was significantly impaired after LD; 10 Hz but not 1 Hz rTMS was able to restore normal habituation phenomena. VEPs habituation is impaired by LD but it could be restored if hf-rTMS is given during LD. As LD acts reducing GABA circuits activity and hf-rTMS likely upregulates such circuits, these data give support to the hypothesis that cortical inhibition can play a relevant role in mechanisms underlying habituation.

A case of post-traumatic complex auditory hallucinosis treated with rTMS.

Previous studies of auditory hallucinations in schizophrenia found that the hallucinations were reduced by the application of transcranial magnetic stimulation (rTMS). Here we describe a case of traumatic brain injury associated with continuous music hallucinations. An MRI scan showed a structural lesion of the right temporal pole and a PET scan indicated a hyperactive area of the posterior right temporal lobe. We hypothesized that rTMS applied to the right temporal area would reduce this activity and the corresponding hallucinations. The patient's music hallucinations were significantly reduced by rTMS treatment. A PET scan following treatment also indicated that rTMS treatment reduced brain activity in the right temporal lobe. This case provides initial evidence that rTMS may be a successful treatment of syndromes associated with hyperactive brain areas.

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.

Effects of cerebellar TMS on motor cortex of patients with focal dystonia: a preliminary report.

Recent evidence suggests a role for cerebellum in pathophysiology of dystonia. Here we explored, the cerebellar modulation of motor cortex in patients with focal upper limb dystonia. Eight patients and eight controls underwent a transcranial magnetic stimulation protocol to study the cerebellar-brain-inhibition (CBI): a conditioning cerebellar stimulus (CCS) was followed 5 ms after by the contralateral motor cortex stimulation (test stimulus: TS). We explored the effects of CBI on MEP amplitude, short intracortical inhibition (SICI) and intracortical facilitation (ICF) measures. At baseline no differences in TS-MEP amplitude, SICI or ICF were found between patients and controls. Cerebellar-conditioning significantly reduced TS-MEP amplitude, increased ICF, and decreased SICI in control subjects. In contrast, no changes in these neurophysiological measures were observed in the motor cortex of patients, regardless of which side was tested. If further confirmed, these findings suggest a reduced cerebellar modulation of motor cortex excitability in patients with focal dystonia.

Genetic background of IL-10(-/-) mice alters host-pathogen interactions with Campylobacter jejuni and influences disease phenotype.

We hypothesized that particular genetic backgrounds enhance rates of colonization, increase severity of enteritis, and allow for extraintestinal spread when inbred IL-10(-/-) mice are infected with pathogenic C. jejuni. Campylobacter jejuni stably colonized C57BL/6 and NOD mice, while congenic strains lacking IL-10 developed typhlocolitis following colonization that mimicked human campylobacteriosis. However, IL-10 deficiency alone was not necessary for the presence of C. jejuni in extraintestinal sites. C3H/HeJ tlr4(-/-) mice that specifically express the Cdcs1 allele showed colonization and limited extraintestinal spread without enteritis implicating this interval in the clinical presentation of C. jejuni infection. Furthermore, when the IL-10 gene is inactivated as in C3Bir tlr4(-/-) IL-10(-/-) mice, enteritis and intensive extraintestinal spread were observed, suggesting that clinical presentations of C. jejuni infection are controlled by a complex interplay of factors. These data demonstrate that lack of IL-10 had a greater effect on C. jejuni induced colitis than other immune elements such as TLR4 (C3H/HeJ, C3Bir IL-10(-/-)), MHC H-2g7, diabetogenic genes, and CTLA-4 (NOD) and that host genetic background is in part responsible for disease phenotype. C3Bir IL-10(-/-) mice where Cdcs1 impairs gut barrier function provide a new murine model of C. jejuni and can serve as surrogates for immunocompromised patients with extraintestinal spread.

When nominal features are marked on verbs: a transcranial magnetic stimulation study.

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.

Role of the cerebellum in time perception: a TMS study in normal subjects.

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.

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.

C57BL/6 and congenic interleukin-10-deficient mice can serve as models of Campylobacter jejuni colonization and enteritis.

Campylobacter jejuni is a globally distributed cause of human food-borne enteritis and has been linked to chronic joint and neurological diseases. We hypothesized that C. jejuni 11168 colonizes the gastrointestinal tract of both C57BL/6 mice and congenic C57BL/6 interleukin-10-deficient (IL-10(-/-)) mice and that C57BL/6 IL-10(-/-) mice experience C. jejuni 11168-mediated clinical signs and pathology. Individually housed mice were challenged orally with C. jejuni 11168, and the course of infection was monitored by clinical examination, bacterial culture, C. jejuni-specific PCR, gross pathology, histopathology, immunohistochemistry, and anti-C. jejuni-specific serology. Ceca of C. jejuni 11168-infected mice were colonized at high rates: ceca of 50/50 wild-type mice and 168/170 IL-10(-/-) mice were colonized. In a range from 2 to 35 days after infection with C. jejuni 11168, C57BL/6 IL-10(-/-) mice developed severe typhlocolitis best evaluated at the ileocecocolic junction. Rates of colonization and enteritis did not differ between male and female mice. A dose-response experiment showed that as little as 10(6) CFU produced significant disease and pathological lesions similar to responses seen in humans. Immunohistochemical staining demonstrated C. jejuni antigens within gastrointestinal tissues of infected mice. Significant anti-C. jejuni plasma immunoglobulin levels developed by day 28 after infection in both wild-type and IL-10-deficient animals; antibodies were predominantly T-helper-cell 1 (Th1)-associated subtypes. These results indicate that the colonization of the mouse gastrointestinal tract by C. jejuni 11168 is necessary but not sufficient for the development of enteritis and that C57BL/6 IL-10(-/-) mice can serve as models for the study of C. jejuni enteritis in humans.

Hypo-excitability of cortical areas in patients affected by Friedreich ataxia: a TMS study.

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.