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.

Cystic hygroma in a female suckling pig: a case report.

BACKGROUND: Cystic hygromas (lymphangiomas) are rarely reported in various animal species, humans included. A hygroma is a benign congenital malformation of the lymphatic drainage system, presenting itself as a mass consisting of multiple cysts of various sizes with a watery content. CASE PRESENTATION: This report describes clinical, ultrasonographic, and post-mortem findings of a cystic hygroma in a suckling pig. The mass was characterized by a few thin-walled cysts, containing clear yellow serous fluid. Histologically, the central cavity was lined by a single layer of squamous cells, supported by a thick fibrous stroma. On immunohistochemistry, scattered lining cells were weakly positive for Factor-VIII, suggesting their possible endothelial origin. CONCLUSIONS: This case report contributes to raising awareness on this condition in pigs allowing early identification in life so that appropriate care can be provided. The case report attributes to science on hygromas in general, as better understanding of pathologic features, the aetiology and appropriate treatment are needed.

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 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.

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.

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.

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.

p53 mutations in skin and internal tumors of xeroderma pigmentosum patients belonging to the complementation group C.

Fifty-eight skin biopsies and three primary internal tumors from patients affected by the rare hereditary disease xeroderma pigmentosum (XP) were studied by an improved PCR-single strand conformation polymorphism analysis to detect the mutations of the tumor suppressor gene p53. The results from cutaneous XP tumors, including 27 squamous cell carcinomas and 6 basal cell carcinomas, show a very high level (86%) of p53 mutations. The analysis of mutations found in XP skin cancers according to the complementation group of the patients shows that tandem CC-->TT transitions are a characteristic of XP-C patients with a frequency much higher in their skin tumors (85%) compared with tumors in XP patients who do not belong to group C (33%). In all XP-C biopsies, mutations were due to replication of unrepaired DNA lesions on the nontranscribed strand of the p53 gene, substantiating the preferential repair in vivo of the transcribed strand of this gene in human tissues. For the first time, we were able to analyze three primary internal tumors (a neuroendocrine tumor of the thyroid, a gastric adenocarcinoma, and a glioma of the brain) of young XP children. All of them contained one mutation on the p53 gene, which were different from the ones found in the XP skin tumors and could have resulted from unrepaired lesions caused by oxidative damage.

Antepartum and early postpartum predictors of type 2 diabetes development in women with gestational diabetes mellitus.

OBJECTIVES: This study aimed at identifying ante-partum and early post-partum (one year) clinical and metabolic characteristics capable of predicting the future development of type 2 diabetes in pregnant women of Mediterranea area affected by gestational diabetes mellitus (GDM). MATERIAL AND METHODS: Seventy GDM patients were evaluated: mean age during pregnancy, plasma glucose levels under OGTT (100 gr. glucose), fasting, 1-h post-prandial plasma glucose levels, HbA(1c) at the third trimester, gestational week of GDM diagnosis, insulin therapy, and weight gain were all taken into consideration. Some maternal risk factors such as pre-pregnancy BMI, and maternal and fetal outcome of index pregnancy were also assessed. One year after delivery in the same patients, BMI, fasting and 1-h post-prandial plasma glucose, plasma glucose and insulinemia under OGTT (75 gr. glucose) were measured. We focused our attention on women who presented type 2 diabetes 5 years after pregnancy or IGT and those who, one year after pregnancy, were normal. RESULTS: Five years after pregnancy 49 women were normal, 5 had developed type 1 diabetes and were not considered, 6 had developed IGT, and 10 type 2 diabetes. Analysis of variables during pregnancy showed that those variables predicting type 2 diabetes were pre-pregnancy BMI, gestational week of diagnosis, need for insulin therapy, obesity, and plasma glucose at 60' OGTT. Analysis of variables evaluated one year after pregnancy showed that BMI, fasting and post-prandial plasma glucose, plasma glucose at each point of the OGTT, and plasma insulin at 30' OGTT were predictive of the development of type 2 diabetes. Furthermore, age, post-partum fasting plasma glucose, and plasma glucose under OGTT post-partum were predictive of the development of IGT. Our data show for the first time that, also in a Caucasian Mediterranean population, markers of the future development of diabetes do exist, as reported in literature. They also stress the importance of correct identification of GDM patients, in order to screen those at greater risk of developing diabetes, for whom it is imperative to set up prevention programs.

UV lesions located on the leading strand inhibit DNA replication but do not inhibit SV40 T-antigen helicase activity.

DNA replication in eucaryotic cells involves a variety of proteins which synthesize the leading and lagging strands in an asymmetric coordinated manner. To analyse the effect of this asymmetry on the translesion synthesis of UV-induced lesions, we have incubated SV40 origin-containing plasmids with a unique site-specific cis, syn-cyclobutane dimer or a pyrimidine-pyrimidone (6-4) photoproduct on either the leading or lagging strand template with DNA replication-competent extracts made from human HeLa cells. Two dimensional agarose gel electrophoresis analyses revealed a strong blockage of fork progression only when the UV lesion is located on the leading strand template. Because DNA helicases are responsible for unwinding duplex DNA ahead of the fork and are then the first component to encounter any potential lesion, we tested the effect of these single photoproducts on the unwinding activity of the SV40 T antigen, the major helicase in our in vitro replication assay. We showed that the activity of the SV40 T-antigen helicase is not inhibited by UV-induced DNA lesions in double-stranded DNA substrate.

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.

1 Hz rTMS enhances extrastriate cortex activity in migraine: evidence of a reduced inhibition?

We recently reported a paradoxical facilitatory effect of 1 Hz repetitive TMS (rTMS) on the primary visual cortex in migraine possibly due to the failure of inhibitory circuits, unable to be upregulated by low frequency rTMS. To investigate if inhibitory circuit dysfunction extends beyond striate cortex in migraine with aura, we studied the effects of 1 Hz rTMS over the right extrastriate cortex on perception of illusory contours in these patients. Low-frequency rTMS enhanced activity of extrastriate cortex in migraineurs, speeding up reaction times on illusory contour perception. This finding supports the view of a failure of inhibitory circuits also involving the extrastriate cortex in migraine with aura.

Molecular analysis of glioma and skin-tumour alterations in a xeroderma-pigmentosum child.

Xeroderma pigmentosum (XP) is a rare hereditary disease characterized by a very high frequency of skin tumours due to a defect in the nucleotide-excision-repair process. Some of these patients have also been reported to develop internal tumours with higher frequency than the normal population. Reported here are the clinical features and molecular analysis of an XP patient who developed multiple skin cancers as well as a thalamic glioma. Complementation analysis with recombinant retrovirus, cloning efficiency and unscheduled DNA synthesis after UV-C indicate that the patient belongs to the C group. Characterization of the p53 mutations in the 2 tumours of the patient leads to speculation on the aetiological agents involved in tumour initiation. The skin tumour is clearly induced by the presence of unrepaired UVB-induced DNA damage on the non-transcribed strand of the p53 gene, while the glioma may be induced by unrepaired DNA lesions produced by free radicals.

Illusory contours and specific regions of human extrastriate cortex: evidence from rTMS.

Functional magnetic resonance imaging studies showed that perception of illusory contours is associated with extrastriate cortex activation prevailing on the right side. 1 Hz repetitive transcranial magnetic stimulation (rTMS) is able to induce lasting inhibition of cortical activity. The objective of the study was to investigate the role of extrastriate cortex in illusory contour perception inducing 1 Hz rTMS interference in healthy subjects. Eight healthy subjects underwent 1 Hz rTMS (600 pulses) through a figure-of-eight coil over right and left occipital cortex (O1 and O2 of 10/20 EEG system); sham magnetic stimulation on the same sites and right motor cortex rTMS (in three subjects) were given as control. Subjects performed a computerized task requiring perception of illusory and real contours of Kanizsa squares in baseline and after rTMS. After stimulus presentation the subject made a forced-choice decision about the regularity or irregularity of stimulus contour, by hitting as fast as possible one of two keys on the computer keyboard. Reaction times (RT) were measured. Right occipital stimulation significantly increased RT for illusory contour perception (vs. baseline, P < 0.05). No significant RT changes were observed in the other experimental conditions with respect to the baseline condition. It is concluded that 1Hz rTMS of right extrastriate cortex can disrupt perception of illusory contours and the effect appears to be side-specific, being evident only after right occipital stimulation. This study supports the critical role of right extrastriate cortex in illusory contour perception.