Beniamina Mercante

Paired neurophysiological and clinical study of the brainstem at different stages of Parkinson’s Disease

OBJECTIVE To study brainstem function in Parkinsons Disease (PD) at different stages, through a battery of vestibular-evoked myogenic potentials (VEMPs) and compare the results with scores on clinical scales assessing the presence of symptoms linked to brainstem involvement. METHODS Cervical, masseter and ocular VEMPs were recorded in patients with early PD (n=14, disease duration 1.42±0.7years), advanced PD (n=19, disease duration 7.26±2.9years) and in 27 age-matched controls. In PD, the following clinical scales were administered: Mini-BESTest, REM sleep Behavior Disorder Screening Questionnaire (RBD-SQ), PD Sleep Scale, Epworth Sleepiness Scale and Geriatric Depression Scale. RESULTS Rate of VEMPs alterations was higher (p<0.001) in PD than controls, but similar within PD groups. However, early and advanced PD showed a different pattern of abnormalities (p=0.02), being latency delay prevalent in the former and absence in the latter. VEMP impairment correlated directly with RBD-SQ scores in both PD cohorts and inversely with Mini-BESTest scores in advanced PD. CONCLUSIONS VEMPs displayed progressive severity of alterations at different stages of PD, with remarkable correlations with presence of postural instability and RBD. SIGNIFICANCE The combined use of VEMPs may provide interesting insights into the pathophysiological mechanisms of PD at the earliest and prodromal stage of the disease.

Ultrasound and laser as stand-alone therapies for myofascial trigger points: a randomized, double-blind, placebo-controlled study.

BACKGROUND AND PURPOSE Ultrasound (US) and low-level laser therapy (LLLT) are commonly employed for myofascial trigger points (MTP) despite lack of evidence for usage as stand-alone treatments. The aim of the study was to determine, on MTP of the upper trapezius muscle (uTM), the effects of US and LLLT per se, as delivered in accordance with the procedures reported by surveys about their usage among physiotherapists. METHODS Design was set as a double-blind, randomized, placebo-controlled study. Sixty participants with at least one active MTP in uTM (28 women and 32 men; mean age 24.5 ± 1.44 years) were recruited and randomly assigned to one out of five groups: active US (n = 12), placebo US (n = 12), active LLLT (n = 11), placebo LLLT (n = 11) and no therapy (control, n = 14). The participants and outcome assessor were blinded to the group assignment and therapy delivered. Three outcome measures were assessed at baseline, after a 2-week treatment and 12 weeks after the end of the intervention (follow-up): pressure pain threshold, subjective pain on a numerical rating scale and muscle extensibility performing a cervical lateral flexion. All subjects assigned to the intervention groups were treated five times weekly for overall 10 treatments given. Two-way ANOVA was used to compare differences before and after intervention and among groups at each time-point. RESULTS After the 2-week intervention, all groups showed pressure pain threshold, numerical rating scale and cervical lateral flexion significant improvements (p < 0.05), which were confirmed at the follow-up. When performing multiple comparisons, controls scored significantly less than both the active therapies and placebos, whereas no differences were detected between active therapies and placebos. CONCLUSIONS Ultrasound and LLLT provided significant improvements in pain and muscle extensibility, which were superior to no therapy but not to placebos, thus raising concerns about the suitability, both economically and ethically, of administering such common physical modalities as stand-alone treatments in active MTP of the uTM.

Acute restraint stress prevents nicotine-induced mesolimbic dopaminergic activation via a corticosterone-mediated mechanism: A microdialysis study in the rat

BACKGROUND Stress affects the responsiveness to nicotine (NIC), by increasing drug use, facilitating relapse and reinstating NIC self administration even after prolonged abstinence. In turn, high corticosterone (CORT) blood levels induced by stress may alter the neurobiological properties of NIC by acting on the dopamine (DA) mesolimbic system. METHODS In this study, we evaluated the effect of exposure to acute restraint stress on NIC-induced stimulation of the mesolimbic DA system of the rat, by studying extracellular DA levels in the nucleus accumbens shell (NAccs) with microdialysis. RESULTS NIC intravenous administration (130 μg/kg) increased DA levels in the NAccs in control rats but not in subjects exposed to stress; this latter phenomenon was prevented by blockade of CORT effects with the inhibitor of corticosterone synthesis metirapone (100 mg/kg) or the glucorticoid receptor antagonist mifepristone (150 μmol/kg). CONCLUSIONS These observations show that exposure to acute stress inhibits the stimulatory response of the mesolimbic DA system to NIC and suggest that this effect is mediated by circulating CORT acting on its receptors. These results may bear relevance in explaining the role played by stressful stimuli in NIC-seeking and taking behavior.

Chronic Intermittent Ethanol Regulates Hippocampal GABA(A) Receptor Delta Subunit Gene Expression

Chronic ethanol consumption causes structural and functional reorganization in the hippocampus and induces alterations in the gene expression of gamma-aminobutyric acid type A receptors (GABAARs). Distinct forced intermittent exposure models have been used previously to investigate changes in GABAAR expression, with contrasting results. Here, we used repeated cycles of a Chronic Intermittent Ethanol paradigm to examine the relationship between voluntary, dependence-associated ethanol consumption, and GABAAR gene expression in mouse hippocampus. Adult male C57BL/6J mice were exposed to four 16-h ethanol vapor (or air) cycles in inhalation chambers alternated with limited-access two-bottle choice between ethanol (15%) and water consumption. The mice exposed to ethanol vapor showed significant increases in ethanol consumption compared to their air-matched controls. GABAAR alpha4 and delta subunit gene expression were measured by qRT-PCR at different stages. There were significant changes in GABAAR delta subunit transcript levels at different time points in ethanol-vapor exposed mice, while the alpha4 subunit levels remained unchanged. Correlated concurrent blood ethanol concentrations suggested that GABAAR delta subunit mRNA levels fluctuate depending on ethanol intoxication, dependence, and withdrawal state. Using a vapor-based Chronic Intermittent Ethanol procedure with combined two-bottle choice consumption, we corroborated previous evidences showing that discontinuous ethanol exposure affects GABAAR delta subunit expression but we did not observe changes in alpha4 subunit. These findings indicate that hippocampal GABAAR delta subunit expression changes transiently over the course of a Chronic Intermittent Ethanol paradigm associated with voluntary intake, in response to ethanol-mediated disturbance of GABAergic neurotransmission.

Auricular Neuromodulation: The Emerging Concept beyond the Stimulation of Vagus and Trigeminal Nerves

Neuromodulation, thanks to intrinsic and extrinsic brain feedback loops, seems to be the best way to exploit brain plasticity for therapeutic purposes. In the past years, there has been tremendous advances in the field of non-pharmacological modulation of brain activity. This review of different neurostimulation techniques will focus on sites and mechanisms of both transcutaneous vagus and trigeminal nerve stimulation. These methods are scientifically validated non-invasive bottom-up brain modulation techniques, easily implemented from the outer ear. In the light of this, auricles could transpire to be the most affordable target for non-invasive manipulation of central nervous system functions.

Trigeminal nerve stimulation induces Fos immunoreactivity in selected brain regions, increases hippocampal cell proliferation and reduces seizure severity in rats

Sites and mechanisms by which trigeminal nerve stimulation (TNS) exerts beneficial effects on symptoms of drug-resistant epilepsy and depression are still unknown. Effects of short-term TNS on brain regions involved in the physiopathology of these disorders were investigated in this study. Forty male rats were assigned to three groups: TNS (undergoing electrical stimulation of the left infraorbitary nerve via surgically implanted cuff electrodes); Sham (undergoing surgical procedure but without a stimulation); Naïve rats. The effects of TNS (3-hour session; 30-s ON, 5-min OFF; 30Hz; 500μs; 2mA) were evaluated on: (i) behavioral pattern of pentylenetetrazole (PTZ)-induced seizures as measured by the Racine scale; (ii) c-Fos-like immunoreactivity in discrete brain areas; (iii) hippocampal cell proliferation by bromodeoxyuridine (BrdU)-like immunoreactivity. In comparison with Sham groups, TNS significantly decreased the duration of PTZ-induced seizures (p<0.05) and promoted a faster recovery (p<0.001) by reducing the most severe seizure types. In the TNS group the number of c-Fos-labeled cells was significantly increased (p<0.001) in the trigeminal nuclear complex, nucleus of the solitary tract, locus coeruleus, dorsal raphe nucleus, hippocampus, amygdala, endopiriform nucleus, entorhinal cortex and sensorimotor cortex. In the TNS group the number of BrdU-positive cells in the dentate gyrus was significantly greater with respect to both Naïve and Sham groups. Data show that acute TNS effectively counteracted PTZ-induced seizures and boosted hippocampal cell proliferation in rats. TNS increased c-Fos-like immunoreactivity in brainstem and forebrain structures which play a pivotal role in the physiopathology of epilepsy and depression.