Clinical manifestations and analytical reports for MDPHP acute intoxication cases.

MDPHP is a synthetic cathinone (SC) belonging to α-pyrrolidinophenone derivatives. It is a central nervous system stimulant and may induce hallucinations, paranoia, tachycardia, hypertension, chest pain, and rhabdomyolysis. In literature, a few cases of intoxication have been reported. In the present study, 17 cases of MDPHP intake were described including the analytical findings and clinical manifestations. MDPHP was quantified by liquid chromatography-tandem mass spectrometry in blood (range 1.26-73.30 ng/mL) and urine (range 19.31-8769.64 ng/mL) samples. In three cases the presence of α-PHP was observed. In one case, MDPHP was the only detected substance. Concomitant use of MDPHP with other substances, particularly psychostimulants, was common and it was difficult to describe the peculiar clinical characteristics of this SC. Most of the symptoms overlapped those expected, some of them were unusual and all of them particularly severe thus inducing the research of NPS in laboratory tests. We demonstrated the presence of psychiatric, neurological, and respiratory symptoms, as well as the possible presence of rhabdomyolysis and cardiotoxicity associated with the use of MDPHP. ED admissions were also more frequent in patients with addiction problems. In some cases, MDPHP intake required intensive supportive care. A multidisciplinary approach, including specialist consultation, is recommended for patients showing challenging features. Moreover, we demonstrated that the adoption of advanced analytical techniques, i.e., liquid chromatography-tandem mass spectrometry, is necessary to detect these molecules. Further studies are needed to understand MDPHP intake patterns and associated symptoms. It is essential to raise awareness in addiction treatment centers and among potential users, especially young people, and chemsex addicted.

Acupuncture-Induced Changes in Nociception, Measured by Pain-Related Evoked Potentials: A Pilot Mechanistic Study.

Objective: The nociceptive system has been implicated in acupuncture analgesia, although acupuncture's precise mechanism of action remains unknown. Electric pain-related evoked potentials (PREPs) have emerged as an effective and reliable electrophysiologic method for evaluation of the human nociceptive system by electric stimulation of nociceptive Aδ and C fibers. This pilot mechanistic study aims to assess the feasibility of using advanced PREP techniques together with electroacupuncture and to use PREPs to characterize acupuncture's effect on nociception. Methods: Seven healthy volunteers underwent a previously designed electroacupuncture protocol using acupoints in the legs bilaterally, which has been demonstrated to induce systemic analgesia. Advanced PREP techniques involving tripolar stimulating electrode, varying interstimulus interval, and incorporating a cognitive task during PREPs were used. PREPs were assessed before electroacupuncture, during electroacupuncture, and 30 min after electroacupuncture. Subjective pain perception in response to the PREP-related electric pain stimuli delivered to the nondominant hand was assessed on the visual analog scale (VAS) at baseline, during electroacupuncture, and 30 min postelectroacupuncture. Results: Reliable PREP N1, P1, and N2 waves were obtained from all subjects at the following average latencies: N1 = 131.5 msec, P1 = 189.4 msec, and N2 = 231.1 msec. Electroacupuncture caused a significant reduction in PREP N1P1 wave amplitudes from 25.6 to 15.4 µV (p = 0.006) and electric pain perception on the VAS-from 2.86 to 2.14 (p = 0.008), compared to baseline. These effects were sustained at 30 min postacupuncture with N1P1 wave amplitude 17.2 µV (p = 0.030) and VAS 2.28 (p = 0.030), compared to baseline. Conclusions: Electroacupuncture causes significant changes in objective nociception, measured by PREP N1P1 wave amplitudes, and in subjective nociception, measured by the VAS, and these effects are sustained for 30 min after electroacupuncture. Planned future studies will involve chronic pain populations and will aim to assess acupuncture's longer term analgesic effects.

Local and Systemic Analgesic Effects of Nerve-Specific Acupuncture in Healthy Adults, Measured by Quantitative Sensory Testing.

OBJECTIVE: This study aims to assess whether acupuncture analgesia's effects are local or systemic and whether there is a dose response for these effects. METHODS: Twenty-eight healthy volunteers aged 18-45 were randomized to two doses of acupuncture using points closely associated with peripheral nerves in the legs. The lower-dose group involved acupoints overlying the deep peroneal nerve (DP), and the higher-dose involved acupoints overlying the deep peroneal and posterior tibial nerves (DPTN). Baseline and acupuncture quantitative sensory testing (QST) assessments were obtained locally in the calf and great toe and systemically in the hand. Results were analyzed using factorial repeated-measures analysis of variance for each of the QST variables-cold detection threshold (CDT), vibration detection threshold (VDT), heat pain threshold (HP0.5), and heat pain perception of 5/10 (HP5.0). Location (leg/hand) and time (baseline/acupuncture) were within-subject factors. Intervention (DP/DPTN) was a between-subject factor. RESULTS: CDT was increased in the calf (P < 0.001) and in the hand (P < 0.001). VDT was increased in the toe (P < 0.001) but not in the hand. HP0.5 was increased in the calf (P < 0.001) and in the hand (P < 0.001). HP5.0 was increased in the calf (P = 0.002) and in the hand (P < 0.001), with the local effect being significantly greater than the systemic (P = 0.004). In all of the above QST modalities, there was no difference between the low-dose (DP) and high-dose (DPTN) acupuncture groups. CONCLUSIONS: Acupuncture caused comparable local and systemic analgesic effects in cold detection and heat pain perception and only local effects in vibration perception. There was no clear acupuncture dose response to these effects.

Local effects of acupuncture on the median and ulnar nerves in patients with carpal tunnel syndrome: a pilot mechanistic study protocol.

BACKGROUND: While acupuncture's mechanism of action is not fully understood, there is consensus that the nervous system plays a key role in processing its effects. This research is based on the structural theory of acupuncture, which aims to correlate the location of acupuncture points to peripheral nerves, spinal segments, and spinal plexuses. This mechanistic study explores the close anatomical association between the Pericardium meridian/median nerve and the Heart meridian/ulnar nerve in an attempt to produce electrophysiologic data measuring acupuncture's direct, nerve-specific effect on the underlying nerves. Specifically, the purpose of this research is to use nerve conduction studies (NCSs) and quantitative sensory testing (QST) to assess for any local, nerve-specific effect of three acupuncture modalities on two anatomically distinct nerves in the forearm - the median and ulnar nerves - in subjects with carpal tunnel syndrome (CTS). The choice of CTS as an injured nerve model allows for comparisons between the response in an injured nerve (median) to that of a healthy one (ulnar). METHODS: Subjects with mild to moderate CTS will be randomized to three intervention groups: manual acupuncture and low- and high-frequency electroacupuncture. Each subject will receive two treatments, 1 week apart, to points in the forearm, which overlay the median nerve (Pericardium meridian) or the ulnar nerve (Heart meridian). Acupuncture will be administered in random order to minimize learning effects in sensory testing. During Week 1, baseline NCS and QST (vibration and cold detection thresholds) will be obtained in both nerve territories, followed by acupuncture and post-acupuncture NCS and QST measurements in both nerve territories. During Week 2, repeat baseline QST and NCS measurements will be obtained, followed by acupuncture to points overlying the nerve not treated in Week 1, followed by post-acupuncture NCS and QST measurements in both nerve distributions. DISCUSSION: This works aims to capture and characterize the local effects of acupuncture on an underlying nerve and compare them to those on a neighboring nerve. Quantifying acupuncture's effects using physiologic parameters and discrete values could standardize treatment regimens and help assess their therapeutic effect. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03036657 . Registered on 30 January 2017. Retrospectively registered.

The Case for Local Needling in Successful Randomized Controlled Trials of Peripheral Neuropathy: A Follow-Up Systematic Review.

Objectives: This work follows-up on a systematic review, published in 2017, of acupuncture for the treatment of mono- and polyneuropathy and associated symptoms. Previously reviewed trials of acupuncture for neuropathy primarily used acupuncture points in close proximity to underlying nerves. Further exploration of point selection for the treatment of each neuropathic condition is needed to assess the anatomical relationships between acupuncture points and peripheral nerves with respect to the treatment of neuropathy. Methods: The 13 randomized controlled trials included in the original review studied acupuncture for neuropathy caused by diabetes, Bell's palsy, carpal tunnel syndrome (CTS), human immunodeficiency virus (HIV), and idiopathic causes. The present review reexamines all acupuncture points used, focusing on specific neuropathic condition treated. Anatomical diagrams are presented to highlight acupuncture points underlying the nerves' anatomical relationships. Each selected acupuncture point is reviewed in detail, including its Traditional Chinese Medicine theory-based function, the point's indications for use, and the peripheral nerve most closely associated with it. Results: In Bell's palsy, the majority of selected acupuncture points were associated with the ipsilateral facial nerve. In CTS, the majority of the selected acupuncture points were closely associated with the median nerve and its branches. In polyneuropathy caused by diabetes, HIV, or idiopathic causes, most selected acupuncture points were in close proximity to peripheral nerves. Conclusions: All reviewed trials of acupuncture for neuropathy and neuropathic pain use acupuncture points that are closely associated with the peripheral nerves treated. Local needling is crucial for successful treatment of peripheral neuropathy.

Introducing a Standardized Acupuncture Protocol for Peripheral Neuropathy: A Case Series.

Background: Peripheral neuropathy (PN) is defined as damage to the peripheral nervous system caused by a primary lesion or dysfunction. Multiple recent trials have suggested that acupuncture is beneficial for treating neuropathic pain. One challenge in acupuncture research is the lack of standardization of point selection, number of needles used, needle-retention time, needling depth, amount of needle manipulation, and use of moxibustion and electroacupuncture (EA). Objectives: This article presents a standardized acupuncture protocol for the treatment of PN that incorporates structural acupuncture principles based on proximity to peripheral nerves and on traditional approaches to the treatment of neuropathic pain. Materials and Methods: Ten consecutive patients diagnosed with large- or small-fiber neuropathy of various etiologies were treated with a standardized protocol, based on anatomical correlations of peripheral nerves and acupuncture points. Manual acupuncture was applied to left LR 4, LU 5; bilateral LI 11, KI 27, ST 36, GB 34, SP 6, SP 9, LI 4, TE 5, and BaFeng (except for the space between the first and second digits of the toes; LR 3 was used for that space). EA was applied to bilateral KI 3-1 and bilateral ST 41-LR 3. Patients underwent at least six acupuncture sessions, although the total number of sessions varied. Outcomes were measured using a visual analogue scale (VAS) and clinical signs and symptoms. Results: All 10 patients indicated improvement on the VAS and in clinical presentation. Conclusions: This standardized protocol appears to be effective for the treatment of neuropathy of various causes, including large- and small-fiber involvement. Further studies with larger sample sizes and randomized comparisons against sham acupuncture and other acupuncture regimens will be helpful to determine if this protocol could be established as a guideline for approaching peripheral neuropathy.

Acupuncture for the Treatment of Peripheral Neuropathy: A Systematic Review and Meta-Analysis.

OBJECTIVES: Neuropathy and its associated pain pose great therapeutic challenges. While there has been a recent surge in acupuncture use and research, little remains known about its effects on nerve function. This review aims to assess the efficacy of acupuncture in the treatment of neuropathy of various etiologies. METHODS: The Medline, AMED, Cochrane, Scopus, CINAHL, and clintrials.gov databases were systematically searched from inception to July 2015. Randomized controlled trials (RCTs) assessing acupuncture's efficacy for poly- and mononeuropathy were reviewed. Parallel and crossover RCTs focused on acupuncture's efficacy were reviewed and screened for eligibility. The Scale for Assessing Scientific Quality of Investigations in Complementary and Alternative Medicine was used to assess RCT quality. RCTs with score of >9 and active control treatments such as sham acupuncture or medical therapy were included. RESULTS: Fifteen studies were included: 13 original RCTs, a long-term follow-up, and a re-analysis of a prior RCT. The selected RCTs studied acupuncture for neuropathy caused by diabetes, Bell's palsy, carpal tunnel syndrome, human immunodeficiency virus (HIV), and idiopathic conditions. Acupuncture regimens, control conditions, and outcome measures differed among studies, and various methodological issues were identified. Still, the majority of RCTs showed benefit for acupuncture over control in the treatment of diabetic neuropathy, Bell's palsy, and carpal tunnel syndrome. Acupuncture is probably effective in the treatment of HIV-related neuropathy, and there is insufficient evidence for its benefits in idiopathic neuropathy. Acupuncture appears to improve nerve conduction study parameters in both sensory and motor nerves. Meta-analyses were conducted on all diabetic neuropathy and Bell's palsy individual subject data (six RCTs; a total of 680 subjects) using a summary estimate random effects model, which showed combined odds ratio of 4.23 (95% confidence interval 2.3-7.8; p < 0.001) favoring acupuncture over control for neuropathic symptoms. CONCLUSIONS: Acupuncture is beneficial in some peripheral neuropathies, but more rigorously designed studies using sham-acupuncture control are needed to characterize its effect and optimal use better.

Prevalence of migraine in patients with celiac disease and inflammatory bowel disease.

OBJECTIVE: To assess the prevalence of headache in clinic and support group patients with celiac disease and inflammatory bowel disease (IBD) compared with a sample of healthy controls. BACKGROUND: European studies have demonstrated increased prevalence of headache of patients with celiac disease compared with controls. METHODS: Subjects took a self-administered survey containing clinical, demographic, and dietary data, as well as questions about headache type and frequency. The ID-Migraine screening tool and the Headache Impact Test (HIT-6) were also used. RESULTS: Five hundred and two subjects who met exclusion criteria were analyzed - 188 with celiac disease, 111 with IBD, 25 with gluten sensitivity (GS), and 178 controls (C). Chronic headaches were reported by 30% of celiac disease, 56% of GS, 23% of IBD, and 14% of control subjects (P<.0001). On multivariate logistic regression, celiac disease (odds ratio [OR] 3.79, 95% confidence interval [CI] 1.78-8.10), GS (OR 9.53, 95%CI 3.24-28.09), and IBD (OR 2.66, 95%CI 1.08-6.54) subjects all had significantly higher prevalence of migraine headaches compared with controls. Female sex (P=.01), depression, and anxiety (P=.0059) were independent predictors of migraine headaches, whereas age >65 was protective (P=.0345). Seventy-two percent of celiac disease subjects graded their migraine as severe in impact, compared with 30% of IBD, 60% of GS, and 50% of C subjects (P=.0919). There was no correlation between years on gluten-free diet and migraine severity. CONCLUSIONS: Migraine was more prevalent in celiac disease and IBD subjects than in controls. Future studies should include screening migraine patients for celiac disease and assessing the effects of gluten-free diet on migraines in celiac disease.

Reward-seeking behavior in human narcolepsy.

STUDY OBJECTIVES: The hypocretin system enhances signaling in the mesolimbic pathways regulating reward processing and addiction. Because individuals with narcolepsy with cataplexy have low hypocretin levels, we hypothesized that they may be less prone to risk- and reward-seeking behaviors, including substance abuse. DESIGN: Endpoints were performance on an array of psychometric tests (including the Eysenck Impulsiveness Scale, the Zuckerman Sensation Seeking Scale, the Gormally Binge Eating Scale, and the Beck Depression and Anxiety Inventory) and on the Balloon Analogue Risk Task (BART). SETTING: Tertiary narcolepsy referral centers in Leiden (The Netherlands) and Boston (USA). PATIENTS: Subjects with narcolepsy with cataplexy (n = 30), narcolepsy without cataplexy (n = 15), and controls (n = 32) matched for age, sex, and smoking behavior. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: There was no difference in risk-taking behavior between narcolepsy with or without cataplexy and the control group, as measured using the BART and the array of questionnaires. However, subjects in the narcolepsy with cataplexy group had significantly higher scores on the Eysenck Impulsiveness Scale (p < 0.05), with 10.0% categorized as impulsive, compared to 6.7% of the narcolepsy without cataplexy group and none of the controls. Narcoleptics with cataplexy also scored significantly higher than controls on the Binge Eating Scale (p < 0.05), with moderate or severe binge eating in 23%. On the depression and anxiety scales, all narcolepsy patients, especially those with cataplexy, scored significantly higher than controls. CONCLUSIONS: We found that narcoleptics with or without cataplexy generally have normal risk-taking behavior, but narcoleptics with cataplexy were more impulsive and more prone to binge eating than patients without cataplexy and controls. Our findings shed new light on the relation between sleepiness and impulsiveness. Furthermore, rates of depression and anxiety were higher in all narcoleptic subjects. However, using the current methods, no evidence could be found to support the hypothesis that hypocretin deficiency would affect reward-processing in humans.