Prism adaptation in patients with unilateral lesion of the parietal or cerebellar cortex: A pilot study on two single cases using a concurrent exposure procedure.

Neuroimaging studies showed that prism adaptation (PA), a widely used tool for the rehabilitation of neglect, involves a wide network of brain regions including the parietal cortex and the cerebellum. In particular, the parietal cortex has been suggested to mediate the initial stage of PA through conscious compensatory mechanisms as a reaction to the deviation induced by PA. The cerebellum, on the other side, intervenes in sensory errors prediction to update internal models in later stages. It has been suggested that two mechanisms may underlie PA effects: recalibration, a strategic cognitive process occurring in the initial stages of PA, and realignment, a fully automatic reorganization of spatial maps emerging later and more slowly in time. The parietal lobe has been proposed to be involved mainly in the recalibration whereas the realignment would be carried over by the cerebellum. Previous studies have investigated the effects of a lesion involving either the cerebellum or the parietal lobe in PA taking into account both realignment and recalibration processes. Conversely, no studies have compared the performance of a patient with a cerebellar lesion to that of a patient with a parietal lesion. In the present study, we used a recently developed technique for digital PA to test for differences in visuomotor learning after a single session of PA in a patient with parietal and a patient with cerebellar lesions, respectively. The PA procedure, in this case, includes a digital pointing task based on a concurrent exposure technique, which allows patients to fully see their arm during the pointing task. This procedure has been shown to be as effective as the terminal exposure condition in neglect rehabilitation albeit different processes take place during concurrent exposure condition compared to the most used terminal exposure (allowing to see only the final part of the movement). Patients' performances were compared to that of a control group. A single session of PA was administered to 1) a patient (BC) with left parieto-occipital lesion involving superior parietal lobe (SPL) and inferior parietal lobe (IPL), 2) a patient (TGM) with a stroke in the territory sub-served by the superior cerebellar artery (SCA) , and 3) 14 healthy controls (HC). The task included three conditions: before wearing prismatic goggles (pre-exposure), while wearing prisms (exposure) and after removing the goggles (post-exposure). Mean deviations were calculated for the following phases: pre-exposure, early-exposure, late-exposure, post-exposure. The presence of after-effect was calculated as the difference between pre-exposure and post-exposure conditions. For each of these conditions, patients' performance was compared to that of the control group by using a modified Crawford t-test. We found that the patient with the parietal lesion had a significantly different performance in the late-exposure and in the post-exposure compared to both HC and the patient with the cerebellar lesion. Conversely, no differences were observed between TGM and HC across all the conditions. Our results show an increase in the magnitude of the adaptation during the late stage of PA in the patient with the parietal lesion whereas no differences in the performance between the cerebellar patient and the controls were found. These results confirm previous studies suggesting that the parietal cortex is an important node of a wider network involved in PA effect. Furthermore, results concerning the cerebellar patient suggest that visuomotor learning is not affected by lesions of the SCA territory when a concurrent exposure is used as, in such case, it less relies on sensory errors prediction to update internal models. Results are discussed considering the novelty of the applied PA technique.

A questionnaire to collect unintended effects of transcranial magnetic stimulation: A consensus based approach.

Transcranial magnetic stimulation (TMS) has been widely used in both clinical and research practice. However, TMS might induce unintended sensations and undesired effects as well as serious adverse effects. To date, no shared forms are available to report such unintended effects. This study aimed at developing a questionnaire enabling reporting of TMS unintended effects. A Delphi procedure was applied which allowed consensus among TMS experts. A steering committee nominated a number of experts to be involved in the Delphi procedure. Three rounds were conducted before reaching a consensus. Afterwards, the questionnaire was publicized on the International Federation of Clinical Neurophysiology website to collect further suggestions by the wider scientific community. A last Delphi round was then conducted to obtain consensus on the suggestions collected during the publicization and integrate them in the questionnaire. The procedure resulted in a questionnaire, that is the TMSens_Q, applicable in clinical and research settings. Routine use of the structured TMS questionnaire and standard reporting of unintended TMS effects will help to monitor the safety of TMS, particularly when applying new protocols. It will also improve the quality of data collection as well as the interpretation of experimental findings.

Functional Role of Cerebellar Gamma Frequency in Motor Sequences Learning: a tACS Study.

Although the role of the cerebellum in motor sequences learning is widely established, the specific function of its gamma oscillatory activity still remains unclear. In the present study, gamma (50 Hz)-or delta (1 Hz)-transcranial alternating current stimulation (tACS) was applied to the right cerebellar cortex while participants performed an implicit serial reaction time task (SRTT) with their right hand. The task required the execution of motor sequences simultaneously with the presentation of a series of visual stimuli. The same sequence was repeated across multiple task blocks (from blocks 2 to 5 and from blocks 7 to 8), whereas in other blocks, new/pseudorandom sequences were reproduced (blocks 1 and 6). Task performance was examined before and during tACS. To test possible after-effects of cerebellar tACS on the contralateral primary motor cortex (M1), corticospinal excitability was assessed by examining the amplitude of motor potentials (MEP) evoked by single-pulse transcranial magnetic stimulation (TMS). Compared with delta stimulation, gamma-tACS applied during the SRTT impaired participants' performance in blocks where the same motor sequence was repeated but not in blocks where the new pseudorandom sequences were presented. Noteworthy, the later assessed corticospinal excitability was not affected. These results suggest that cerebellar gamma oscillations mediate the implicit acquisition of motor sequences but do not affect task execution itself. Overall, this study provides evidence of a specific role of cerebellar gamma oscillatory activity in implicit motor learning.

Effects of low-gamma tACS on primary motor cortex in implicit motor learning.

In the primary motor cortex (M1), rhythmic activity in the gamma frequency band has been found during movement planning, onset and execution. Although the role of high-gamma oscillatory activity in M1 is well established, the contribution of low-gamma activity is still unexplored. In this study, transcranial alternating current stimulation (tACS) was used with the aim to specifically modulate low-gamma frequency band in M1, during an implicit motor learning task. A 40 Hz-tACS was applied over the left M1 while participants performed a serial reaction time task (SRTT) using their right hand. The task required the repetitive execution of sequential movements in response to sequences of visual stimuli. Sequential blocks were interleaved by a random block, which served as interference to sequence learning. Sham and 1 Hz tACS were used as control. Task performance was examined before, during and after tACS (pre-, online- and post-phase, respectively). Furthermore, cortical reactivity of M1 was assessed in the pre- and post-tACS phases, by measuring motor-evoked potentials (MEPs) elicited by single-pulse transcranial magnetic stimulation (TMS). Compared to sham and pre-tACS, the 40 Hz stimulation applied during SRTT slowed down response times in blocks that required retrieving previously learned sequences, after performing the random block. In addition, M1 cortical reactivity was selectively inhibited following 40 Hz-tACS, as quantified by reduced MEP amplitude. These results show that low-gamma tACS delivered over M1 during motor learning enhanced susceptibility to interference generated by the random sequence (i.e., proactive interference effect). Importantly, only low-gamma stimulation produced long-lasting effects on M1 cortical reactivity.

Nutritional strategies for psoriasis: current scientific evidence in clinical trials.

OBJECTIVE: Several nutritional strategies for the management of psoriasis are promising. Even if recent data support that nutrition may play a pivotal role in prevention and co-treatment and despite patient's concerns regarding the best nutritional habits, the consensus regarding the nutritional strategies to be adopted lacks in clinical settings. In this manuscript, the effects of several nutritional strategies for psoriasis patients such as hypocaloric diet, vitamin D, fish oil, selenium, and zinc supplementation were systematically reviewed. Randomized controlled trials (RCTs) on beneficial botanical oral supplements were also included in the analysis. MATERIALS AND METHODS: For each topic, a search was conducted in MEDLINE electronic databases for articles published in English between January 1, 1990 and September 2018. Two independent reviewers assessed and extracted the data. Only controlled clinical trials were selected. RESULTS: The evidence regarding the current nutritional strategies for psoriasis patients were summarized and translated into a global, comprehensible recommendation. CONCLUSIONS: Weight loss combined with a healthy lifestyle was shown to be very beneficial for patients with moderate to severe disease with a significant reduction of the Psoriasis Area and Severity Index (PASI) score. Currently, oral vitamin D supplementation for prevention or treatment of psoriasis in adults with normal vitamin D levels is not recommended; however, psoriasis patients with a deficit in plasma vitamin D levels are advised to complement with oral supplements to prevent psoriasis-related comorbidities. Instead of zinc, selenium, and omega 3 supplements have been proven beneficial for psoriasis patients. Among botanical species, Dunaliella bardawil (D. bardawil), Tripterygium wilfordii (T. wilfordii), Azadirachta indica (A. indica), Curcuma longa (C. longa), and HESA-A are the most beneficial. In conclusion, a close cooperation between nutritionists and dermatologists may be useful for the management of psoriasis.

Cerebellar magnetic stimulation decreases levodopa-induced dyskinesias in Parkinson disease.

BACKGROUND: The neural mechanisms and the circuitry involved in levodopa-induced dyskinesia (LID) are still partially obscure. LID can be considered the consequence of an abnormal pattern or code of activity that originates and is conveyed from the basal ganglia to the thalamus and the cortical motor areas. However, not only striatothalamocortical motor circuits but also other interconnected pathways could be implicated in its pathogenesis. METHODS: In a series of experiments, we applied repetitive transcranial magnetic stimulation (rTMS) over the lateral cerebellum in a group of patients with advanced Parkinson disease, to investigate whether modulation of cerebellothalamocortical circuits by means of rTMS may result in a modification of a dyskinetic state induced by levodopa ingestion. RESULTS: We found that a single session of cerebellar continuous theta burst stimulation (cTBS) was capable of transiently reducing LID. In the same patients, we observed that cerebellar cTBS changed the profile of activation of intracortical circuits in the contralateral primary motor cortex. Cerebellar cTBS reduced short intracortical inhibition and increased long intracortical inhibition, inducing a cortical reorganization that is associated with a reduction of LID. Furthermore, in another experiment, we observed that a 2-week course of bilateral cerebellar cTBS induced persistent clinical beneficial effects, reducing peak-dose LID for up to 4 weeks after the end of the daily stimulation period. CONCLUSIONS: Our study demonstrates that cerebellar continuous theta burst stimulation has an antidyskinetic effect in Parkinson disease patients with levodopa-induced dyskinesia, possibly due to modulation of cerebellothalamocortical pathways.

[The support of the ultrasonography of the shoulder in the diagnosis of polymyalgia rheumatica with normal erythrocyte sedimentation rate]. / L'ausilio dell'ecografia della spalla nella diagnosi della polimialgia reumatica con velocità di eritrosedimentazione normale.

Polymyalgia rheumatica (PMR) is a chronic inflammatory syndrome that affects the elderly population and whose diagnosis is mainly based on clinical criteria taking little advantage of the latest innovatory methods of diagnostic imaging, for instance ultrasonography. Although it is generally characterised by increasing of inflammation values as well as pain and stiffness on the shoulder and pelvic girdles, there is a significant percentage of patients with PMR whose erythrocyte sedimentation rate (ESR) is normal; in this case to make a diagnosis is difficult. The purpose of our study is to demonstrate how useful ultrasound investigations on the shoulders joints could be in order to make a diagnosis of PMR, especially for those patients with atypical normal ESR. Our case control study included 23 patients with atypical PMR and 88 patients with standard symptomatic PMR; both groups underwent shoulder ultrasound scans before receiving steroid therapy. As it has been previously shown, the ultrasound method is able to detect distinctive aspects in the joints and tissues of the patients with PMR; so that we could find that 90% of the patients with PMR of both groups suffered from bilateral subdeltoid bursitis. This disorder is seldom found in healthy people and consequently its presence could be considered a useful diagnostic test/check for/of PMR independently from ESR values.

[Therapy of rheumatic polymyalgia: the pathophysiologic management]. / Trattamento della polimialgia reumatica: l'approccio fisiopatologico.

Polymyalgia rheumatica (PMR) is an inflammatory syndrome affecting older people whose prevalence has increased in recent years. The suppression of the hypothalamic-pituitary-adrenal axis (HPA) and ageing may contribute to the pathogenesis of PMR. Chronic stress (i.e. interpersonal, chronic infections etc.) in elderly people may represent a risk factor for the development of PMR. In fact, elderly represent per se a condition of endocrine senescence including adrenal hypofunction, in addition chronic stress represents a further harmful stimulus to seriously compromise endogenous glucocorticoid production. Synovitis and vasculitis characterize the majority of the patients. Serum cytokine and steroidal hormone patterns suggest that patients with PMR have an intensive inflammatory reaction. As a matter of fact, glucocorticoids represent the most useful temporary "replacement" treatment during the active phase of PMR. The use of modified-release glucocorticoids that might induce higher levels during the night (circadian rhythms as in physiological conditions), will represent another important approach to optimize PMR treatment and reduce the side effects. Combination therapy between glucocorticoids and inhibitors of pro-inflammatory cytokines should be tested in large studies and early cases of PMR.

The time course of idiom processing.

Recent neuropsychological and neurophysiological studies have suggested that the neural correlates of idiom processing are predominantly located in the left Brodmann's area (BA) 22 and, to some extent, in the prefrontal cortex. The present study explores the temporal dynamics of left prefrontal and temporal cortex in idiom processing by using repetitive transcranial magnetic stimulation (rTMS) in normal subjects. Forty-five opaque highly familiar idioms and 45 literal sentences were used. Forty-three subjects completed 5 blocks of 18 trials (9 idioms, 9 literal sentences) corresponding to 4 stimulation conditions (left prefrontal, left temporal, vertex, no-stimulation baseline). Each subject was assigned to one of three groups, which differed in the timing of stimulation delivery. A selective impairment in accuracy for idioms was found when rTMS was applied to the prefrontal and temporal cortex 80ms after picture presentation, confirming the role of these regions in this task. Moreover, rTMS to the prefrontal cortex, but not to the temporal cortex, continued to affect the performance with idiomatic sentences at the later time of 120ms. The results seem to suggest that the prefrontal region is involved in both the retrieval of the figurative meaning from semantic memory and the monitoring of the response by inhibiting alternative interpretations when a picture-matching task is used.

High prevalence of secondary hyperparathyroidism due to hypovitaminosis D in hospitalized elderly with and without hip fracture.

OBJECTIVES: To determine and compare the prevalence of secondary hyperparathyroidism (HPTH) in a population of community-dwelling and institutionalized older adults hospitalized with and without hip fracture, and to evaluate factors correlated with secondary HPTH in this population. METHODS: Circulating concentrations of serum intact PTH, 25-hydroxyvitamin D [25(OH)D] total serum calcium and albumin were measured in 160 subjects with an osteoporotic fracture of the proximal femur and in 160 matched controls hospitalized for a disease unrelated to bone status. Patients with secondary causes of bone loss and taking medications affecting bone metabolism were excluded. Age, sex, place of residence and the ability to perform basic activities of daily living (BADL) two weeks before hospital admission were recorded at baseline. RESULTS: Patients were comparable with regard to the baseline demographic, biochemical and functional characteristics. The overall prevalence of secondary hyperparathyroidism was 51.2%, without significant differences between hip fractured patients and controls (50.6 vs 51.9%, p=0.911). In bivariate analysis only the age and functional status (BADL) demonstrated a significant relationship with secondary HPTH, while sex and place of residence were not significant. These results were also confirmed in multivariate analysis. Particularly, the risk of secondary HPTH increased with age and with the number of functions lost in BADL: patients fully dependent showed a 3 times as high risk (odd ratio 3.07, 95% confidence interval 1.73 to 5.46, p=0.000) compared to patients independent in BADL, and subject aged >88 yr had a twice as high risk of developing secondary HPTH compared to younger ones (odd ratio 2.28, 95% confidence interval 1.20 to 4.32, p=0.012). CONCLUSION: These results show that secondary HPTH due to hypovitaminosis D is a frequent disorder in hospitalized elderly, strongly correlated with the functional status, irrespective of sex and place of residence.

rTMS of supplementary motor area modulates therapy-induced dyskinesias in Parkinson disease.

The neural mechanisms and circuitry involved in levodopa-induced dyskinesia are unclear. Using repetitive transcranial magnetic stimulation (rTMS) over the supplementary motor area (SMA) in a group of patients with advanced Parkinson disease, the authors investigated whether modulation of SMA excitability may result in a modification of a dyskinetic state induced by continuous apomorphine infusion. rTMS at 1 Hz was observed to markedly reduce drug-induced dyskinesias, whereas 5-Hz rTMS induced a slight but not significant increase.

IFN-gamma low production capacity in type 1 diabetes mellitus patients at onset of disease.

In type 1 diabetes mellitus (T1DM), cytokines can be directly cytotoxic to beta-cells, and/or play an indirect role influencing some cells of the immune system. Since several factors could impair cytokine serum levels, the purpose of our study was to longitudinally evaluate intracellular cytokines, in T1DM patients, and in subject at risk, by flow cytometry analysis. At T1DM onset we observed significantly lower percentage of peripheral CD4 + and CD8 + cells producing IFN-gamma in patients compared to controls and subjects at risk. The 15-month follow-up patients showed significantly lower percentage of CD4 + and CD8 + cells producing IFN-gamma compared to the other groups. At 8-year follow-up no significant differences were observed among the groups in the percentage of cells producing cytokines. We could have considered "exhausted cells" or these T cell subsets may be migrated from peripheral blood to pancreas. On the other hand, our results are in agreement with those reported in literature: in animal model the absence of IFN-gamma production makes beta-cells highly susceptible to viral infection and subsequent attack by natural killer cells, which lead to hyperglycaemia and diabetes mellitus.

High-frequency rTMS improves time perception in Parkinson disease.

Patients with Parkinson disease (PD) are impaired in time processing. The authors investigated the effects of high-frequency (5 Hz) repetitive transcranial magnetic stimulation (rTMS) in patients with PD performing a time reproduction task. The authors found significant improvement in time processing induced by rTMS when trains were applied over the right dorsolateral prefrontal cortex (DLPFC) but not over the supplementary motor area, suggesting that the circuit involving the basal ganglia and the DLPFC might constitute the neural network subserving time perception.

Overestimation of numerical distances in the left side of space.

Normal subjects presented with a middle number and two left- and right-sided outer numbers overestimate the numerical distance between the middle number and that positioned at its left side. Repetitive transcranial magnetic stimulation (rTMS) of the right posterior parietal cortex specifically counteracts this bias, suggesting that the mental representation of space defined by numbers is shifted toward the left side depending on a greater activity of the right hemisphere.

Increased visual cortical excitability in ecstasy users: a transcranial magnetic stimulation study.

OBJECTIVES: To test the presence of abnormalities of visual cortical excitability in people using ecstasy as a recreational drug. METHODS: Ecstasy users and control subjects underwent single pulse transcranial magnetic stimulation (TMS) of the occipital cortex. The phosphene threshold was analysed and compared in the two groups. RESULTS: Phosphene thresholds were significantly lower in ecstasy users compared with control subjects, and were correlated negatively with frequency of ecstasy use. Frequency of use was positively correlated with the presence of visual hallucinations. The phosphene threshold of subjects with hallucinations was significantly lower than that of subjects without hallucinations. CONCLUSIONS: The use of ecstasy as a recreational drug is associated with an increased excitability of the visual cortex, possibly linked with massive serotonin release, followed by serotonin depletion, in this cortical area.

Influence of the supplementary motor area on primary motor cortex excitability during movements triggered by neutral or emotionally unpleasant visual cues.

The stronger anatomo-functional connections of the supplementary motor area (SMA), as compared with premotor area (PM), with regions of the limbic system, suggest that SMA could play a role in the control of movements triggered by visual stimuli with emotional content. We addressed this issue by analysing the modifications of the excitability of the primary motor area (M1) in a group of seven healthy subjects, studied with transcranial magnetic stimulation (TMS), after conditioning TMS of SMA, during emotional and non-emotional visually cued movements. Conditioning TMS of the PM or of contralateral primary motor cortex (cM1) were tested as control conditions. Single-pulse TMS over the left M1 was randomly intermingled with paired TMS, in which a conditioning stimulation of the left SMA, left PM or right M1 preceded test stimulation over the left M1. The subjects carried out movements in response to computerised visual cues (neutral pictures and pictures with negative emotional content). The amplitudes of motor-evoked potentials (MEPs) recorded from the right first dorsal interosseous muscle after paired TMS were measured and compared with those obtained after single-pulse TMS of the left M1 under the various experimental conditions. Conditioning TMS of the SMA in the paired-pulse paradigm selectively enhanced MEP amplitudes in the visual-emotional triggered movement condition, compared with single-pulse TMS of M1 alone or with paired TMS during presentation of neutral visual cues. On the other hand, conditioning TMS of the PM or cM1 did not differentially influence MEP amplitudes under visual-emotional triggered movement conditions. This pattern of effects was related to the intensity of the conditioning TMS over the SMA, being most evident with intensities ranging from 110% to 80% of motor threshold. These results suggest that the SMA in humans could interface the limbic and the motor systems in the transformation of emotional experiences into motor actions.

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.

Is it necessary to screen for celiac disease in postmenopausal osteoporotic women?

Decreased bone mass is a frequent finding in celiac patients, and subclinical celiac disease (CD) appears to be unusually overrepresented among patients with idiopathic osteoporosis. Since silent CD may be more common than previously believed, it has been suggested that all osteoporotic patients should be checked for occult CD. The aim of this study was to explore the prevalence of CD in a well-defined population of postmenopausal osteoporotic women. We evaluated 127 consecutive postmenopausal patients (mean age: 68 years; range: 50-82 years) with verified osteoporosis. The observed prevalence of CD in this group was compared to that observed in a group of 747 women recruited for a population-based study. The screening algorithm used to diagnose CD was based on a 3-level screening using type IgA and IgG antigliadin antibodies (AGA) in all the patients (1st level) followed by antiendomysial antibodies (EmA) and total IgA (2nd level) of samples testing positive, and intestinal biopsy of positive cases (3rd level). At the end of the serological screening, only 1 of 127 osteoporotic women was eligible for jejunal biopsy showing a characteristic celiac flat mucosa (prevalence 7.9 x 1,000; 95% CI 0.2-43.1). In addition, CD was diagnosed in 6 of 747 women of the population-based study (prevalence: 8.0 x 1,000; 95% CI 3.3-18.3). There was no significant difference between the two groups. Therefore, our study showed that the prevalence of CD in postmenopausal osteoporotic women was lower than that reported in previous studies and similar to that of the general population. In conclusion, although the relatively small size of the group tested does not allow us to be conclusive, the results suggest that a case finding policy in postmenopausal osteoporosis would have a high cost/benefit ratio except for patients not responding to conventional therapies, or presenting borderline laboratory results.

Modulation of spinal cord excitability by subthreshold repetitive transcranial magnetic stimulation of the primary motor cortex in humans.

Repetitive transcranial magnetic stimulation (rTMS) allows the modulation of intra-cortical excitability and may therefore affect the descending control of spinal excitability. We applied rTMS at subthreshold intensity and 1 Hz frequency for 10 min to the left primary motor cortex representation of the flexor carpi radialis muscle (FCR) in 10 subjects and assessed the H and M responses to median nerve stimulation before and after the rTMS. Following rTMS, H wave thresholds significantly reduced by approximately 20%. Maximal H but not M wave amplitude significantly increased over the baseline, so that H/M amplitude ratio was increased by 41%. Sham stimulation did not induce any noticeable change in M or H waves. Slow rTMS might facilitate monosynaptic spinal cord reflexes by inhibiting the cortico-spinal projections modulating spinal excitability.

rTMS of the unaffected hemisphere transiently reduces contralesional visuospatial hemineglect.

To verify the role of interhemispheric influences on manifestations of neglect, the authors investigated the effects of a transient repetitive transcranial magnetic stimulation (rTMS)-induced disruption of the unaffected hemisphere on contralesional visuospatial neglect in two left- and five right-brain-damaged patients. Parietal rTMS of the unaffected hemisphere during the execution of a computerized task of bisected line's length judgment transiently decreased the magnitude of neglect as expressed in the number of errors.