Resting-state functional connectivity predicts motor cortex stimulation-dependent pain relief in fibromyalgia syndrome patients.

MRI-based resting-state functional connectivity (rsFC) has been shown to predict response to pharmacological and non-pharmacological treatments for chronic pain, but not yet for motor cortex transcranial magnetic stimulation (M1-rTMS). Twenty-seven fibromyalgia syndrome (FMS) patients participated in this double-blind, crossover, and sham-controlled study. Ten daily treatments of 10 Hz M1-rTMS were given over 2 weeks. Before treatment series, patients underwent resting-state fMRI and clinical pain evaluation. Significant pain reduction occurred following active, but not sham, M1-rTMS. The following rsFC patterns predicted reductions in clinical pain intensity after the active treatment: weaker rsFC of the default-mode network with the middle frontal gyrus (r = 0.76, p < 0.001), the executive control network with the rostro-medial prefrontal cortex (r = 0.80, p < 0.001), the thalamus with the middle frontal gyrus (r = 0.82, p < 0.001), and the pregenual anterior cingulate cortex with the inferior parietal lobule (r = 0.79, p < 0.001); and stronger rsFC of the anterior insula with the angular gyrus (r = - 0.81, p < 0.001). The above regions process the attentional and emotional aspects of pain intensity; serve as components of the resting-state networks; are modulated by rTMS; and are altered in FMS. Therefore, we suggest that in FMS, the weaker pre-existing interplay between pain-related brain regions and networks, the larger the pain relief resulting from M1-rTMS.

Conditioned pain modulation is more efficient in patients with painful diabetic polyneuropathy than those with nonpainful diabetic polyneuropathy.

ABSTRACT: Endogenous pain modulation, as tested by the conditioned pain modulation (CPM) protocol, is typically less efficient in patients with chronic pain compared with healthy controls. We aimed to assess whether CPM is less efficient in patients with painful diabetic polyneuropathy (DPN) compared with those with nonpainful DPN. Characterization of the differences in central pain processing between these 2 groups might provide a central nervous system explanation to the presence or absence of pain in diabetic neuropathy in addition to the peripheral one. Two hundred seventy-one patients with DPN underwent CPM testing and clinical assessment, including quantitative sensory testing. Two modalities of the test stimuli (heat and pressure) conditioned to cold noxious water were assessed and compared between patients with painful and nonpainful DPN. No significant difference was found between the groups for pressure pain CPM; however, patients with painful DPN demonstrated unexpectedly more efficient CPMHEAT (-7.4 ± 1.0 vs -2.3 ± 1.6; P = 0.008). Efficient CPMHEAT was associated with higher clinical pain experienced in the 24 hours before testing (r = -0.15; P = 0.029) and greater loss of mechanical sensation (r = -0.135; P = 0.042). Moreover, patients who had mechanical hypoesthesia demonstrated more efficient CPMHEAT (P = 0.005). More efficient CPM among patients with painful DPN might result from not only central changes in pain modulation but also from altered sensory messages coming from tested affected body sites. This calls for the use of intact sites for proper assessment of pain modulation in patients with neuropathy.

Focused Ultrasound Thalamotomy in Tremor Dominant Parkinson's Disease: Long-Term Results.

BACKGROUND: MRI-guided focused ultrasound (FUS) has established short-term efficacy in tremor relief. OBJECTIVE: We report our long-term experience of treating tremor with unilateral FUS unilateral VIM-thalamotomy in tremor dominant Parkinson's disease (TDPD) patients. METHODS: We report outcome of FUS thalamotomy in TDPD patients with 1-5 years of follow-up. OUTCOMES: tremor reduction assessed with Clinical Rating Scale for Tremor (CRST) and Unified Parkinson's Disease Rating Scale (UPDRS part III) overall and in the treated hemibody and safety. RESULTS: Twenty-six TDPD patients completed 1-5 years of follow-up (median follow-up 36 months, range 12-60 months). Median age was 60 years (range 46-79), with median disease duration of 6 years (range 2-16). Immediately, treatment resulted in 100%improvement in tremor in the treated arm in 23 patients and 90%improvement in 3 patients. In 15 patients with leg tremor, 2 patients with chin tremor and 1 patient with head tremor, tremor was significantly improved. Up to 5 years, median CRST score, median UPDRS score, overall and in treated hemibody, decreased significantly as compared with baseline (p < 0.0001). In 2 patients tremor returned completely and in 8 patients there was partial return of tremor. Adverse events were mild and resolved within 3 months. At baseline 4 patients were not receiving any medication vs. 3 at last follow-up and 15 were not taking levodopa vs.9 at last follow-up. CONCLUSION: Unilateral FUS VIM-thalamotomy in TDPD patients was effective and safe and provided long-term tremor relief in most patients. FUS thalamotomy for tremor may delay initiation of levodopa treatment.

Clinical Effects of Repetitive Transcranial Magnetic Stimulation of the Motor Cortex Are Associated With Changes in Resting-State Functional Connectivity in Patients With Fibromyalgia Syndrome.

In this double-blinded, sham-controlled, counterbalanced, and crossover study, we investigated the potential neuroplasticity underlying pain relief and daily function improvements following repetitive transcranial magnetic stimulation of the motor cortex (M1-rTMS) in fibromyalgia syndrome (FMS) patients. Specifically, we used magnetic resonance imaging (MRI) to examine changes in brain structural and resting-state functional connectivity (rsFC) that correlated with improvements in FMS symptomology following M1-rTMS. Twenty-seven women with FMS underwent real and sham treatment series, each consisting of 10 daily treatments of 10Hz M1-rTMS over 2 weeks, with a washout period in between. Before and after each series, participants underwent anatomical and resting-state functional MRI scans and questionnaire assessments of FMS-related clinical pain and functional and psychological burdens. The expected reductions in FMS-related symptomology following M1-rTMS occurred with the real treatment only and correlated with rsFC changes in brain areas associated with pain processing and modulation. Specifically, between the ventromedial prefrontal cortex and the M1 (t = -5.54, corrected P = .002), the amygdala and the posterior insula (t = 5.81, corrected P = .044), and the anterior and posterior insula (t = 6.01, corrected P = .029). Neither treatment significantly changed brain structure. Therefore, we provide the first evidence of an association between the acute clinical effects of M1-rTMS in FMS and functional alterations of brain areas that have a significant role in the experience of chronic pain. Structural changes could potentially occur over a more extended treatment period. PERSPECTIVE: We show that the neurophysiological mechanism of the improvement in fibromyalgia symptoms following active, but not sham, rTMS applied to M1 involves changes in resting-state functional connectivity in sensory, affective and cognitive pain processing brain areas, thus substantiating the essence of fibromyalgia syndrome as a treatable brain-based disorder.

Head- and neck-related symptoms post-motor vehicle collision (MVC): Separate entities or two-sides of the same coin?

BACKGROUND AND AIM: Although post-motor vehicle collision (MVC) pain and symptoms are largely convergent among those with mild traumatic brain injury (mTBI) and whiplash associated disorder (WAD), and patients oftentimes report initial neck and head complaints, the clinical picture of mTBI and WAD has been primarily studied as separate conditions which may result in an incomplete clinical picture. As such, this study was conducted to explore the role of pain and post-traumatic psychological features in explaining both head and neck-related symptom variability in a cohort of post-collision patients. This is with the goal of disentangling if contributory factors are uniquely related to each diagnosis, or are shared between the two. METHODS: Patients recruited in the very early acute phase (<72 h) returned for clinical and psychological assessment at 6 months post-accident. In order to determine which factors were unique and which ones were overlapping the same potential contributors: mean head pain, mean neck pain, female gender, number of post-collision painful body areas, PTSD, and depression were included in the regression models for both neck disability index (NDI) and Rivermead post-concussion symptoms questionnaire (RPQ). RESULTS: Of 223 recruited participants, 70 returned for a follow-up visit (age range 18-64, mean(SD) 37.6 (11.9), 29F). This cohort primarily met the criteria for mTBI, but also fulfilled the criteria for whiplash, reinforcing the duality of injury presentation. Correlations existed between the NDI and RPQ scores (Spearman's ρ=0.66, p<0.001), however overlap was only partial. Regression analysis showed that after the removal of area-of-injury pain neck related disability (r = 0.80, p <0.001) was explained solely by number of painful body areas (ß=0.52, p <0.001). In contrast, post-concussion syndrome symptoms (r = 0.86, p<0.001) are influenced by clinical pain, painful body areas (ß=0.31, p = 0.0026), female gender (ß=0.19, p = 0.0053), and psychological factors of depression (ß=0.31, p = 0.0028) and PTSD symptoms (ß=0.36, p = 0.0013). CONCLUSIONS: It seems that while mechanisms of neck- and head-related symptoms in post-collision patients do share a common explanatory feature, of residual body pain, they are not entirely overlapping. In that psychological factors influence post-concussion syndrome symptoms, but not post-whiplash neck disability.

The effect of TEE on treatment change in patients with acute ischemic stroke.

BACKGROUND AND PURPOSE: Ischemic stroke is a widespread disease carrying high morbidity and mortality. Transesophageal echocardiography (TEE) is considered an important tool in the work-up of patients with acute ischemic stroke (AIS) and transient ischemic attack (TIA) patients; its utility is limited by a semi-invasive nature. The purpose of this study was to evaluate the probability of treatment change due to TEE findings (yield) in the work-up of AIS and TIA patients. METHODS: Retrospective data on patients with AIS or TIA who underwent TEE examination between 2000-2013 were collected from the institutional registry. RESULTS: The average age of 1284 patients who were included in the study was 57±10.4, 66% of patients were male. The most frequent TEE findings included aortic plaques in 54% and patent foramen ovale (PFO) in 15%. TEE findings led to treatment change in 135 (10.5%) patients; anticoagulant treatment was initiated in 110 of them (81%). Most common etiology for switch to anticoagulation was aortic plaques (71 patients); PFO was second most common reason (26 patients). Significant TEE findings (thrombus, endocarditis, tumor) were found in 1.9% of patients, they were more common in young patients (<55; 56% of the patients). CONCLUSIONS: The beginning of anticoagulation treatment in patients with thick and complicated plaques was found frequently in our study. Significant TEE findings, were infrequent, constituted an absolute indication for treatment change and were more common in younger patients.

Explaining very early acute mild traumatic brain injury after motor vehicle collision pain variability: additive value of pain sensitivity questionnaire.

INTRODUCTION AND OBJECTIVES: Chronic pain is a common postcollision consequence. Wherein, a clearer understanding of acute pain can help stem the acute-to-chronic pain transition. However, the variability of acute pain is only partially explained by psychophysical pain characteristics as measured by quantitative sensory testing. The Pain Sensitivity Questionnaire (PSQ) may reflect inherent psychocognitive representations of patient's sensitivity and thus may reveal less-explored pain dimensions. In the vein of the biopsychosocial approach, this study aimed to explore whether PSQ holds additive value in explaining head and neck pain reports in very early acute-stage mild traumatic brain injury (mTBI) after collision, above the use of psychophysical assessment. METHODS: Study cohort (n = 130) consisted of mTBI patients (age range 19-66, 57 F) after accident with area-of-injury pain of at least 20 on the day of testing (mean pain 58.4 ± 21.6, range 20-100 Numerical Pain Scale) who underwent clinical, psychophysical, and pain-related psychological assessment within 72-hour after injury. RESULTS: Pain Sensitivity Questionnaire scores were significantly correlated with acute clinical, psychophysical, and pain-related psychological measures. Regression model (R 2 = 0.241, P < 0.001) showed that, together, age, sex, high PSQ, enhanced temporal summation, and less-efficient conditioned pain modulation explained head and neck pain variance. This model demonstrated that the strongest contribution to degree of postinjury pain was independently explained by PSQ (ß = 0.32) and then pressure pain threshold-conditioned pain modulation (ß = -0.25). CONCLUSION: Appraisal of cognitive daily-pain representations, by way of memory and imagination, provides an additional important dispositional facet to explain the variability in the acute mTBI postcollision clinical pain experience, above assessing nociceptive responsiveness to experimentally induced pain.

The Endogenous Analgesia Signature in the Resting Brain of Healthy Adults and Migraineurs.

Altered pain modulation and resting state functional connectivity (rsFC) were found to be related to migraine pathology and clinical manifestation. We examined how pain modulation psychophysical measures are related to resting-state networks and rsFC between bottom-up and top-down pain modulation areas. Thirty-two episodic migraineurs and 23 age-matched healthy individuals underwent temporal summation of pain (TSOP) and conditioned pain modulation (CPM) tests, followed by a resting-state imaging scan. No differences in temporal summation of pain and CPM were found between groups. However, in healthy individuals, more efficient CPM was correlated with 1) stronger rsFCs of the posterior cingulate cortex, with the ventromedial prefrontal cortex and with the pregenual anterior cingulate cortex; 2) weaker rsFC of the anterior insula with the angular gyrus. Conversely, in migraineurs, the association between CPM and rsFC was altered. Our results suggest that the functional connectivity within the default mode network (DMN) components and the functional coupling between the DMN and pain inhibitory brain areas is linked with pain inhibition efficiency. In migraineurs, this interplay is changed, yet enables normal pain inhibition. Our findings shed light on potential functional adaptation of the DMN and its role in pain inhibition in health and migraine. PERSPECTIVE: This article establishes evidence for the relationship between the resting-state brain and individual responses in psychophysical pain modulation tests, in both migraine and healthy individuals. The results emphasize the significant role of the default mode network in maintaining pain inhibition efficiency in health and in the presence of chronic pain.

Magnetic resonance-guided focused ultrasound thalamotomy for essential tremor: a 5-year single-center experience.

OBJECTIVE: The authors report their experience in treating patients suffering from medication-resistant essential tremor (ET) with MR-guided focused ultrasound (MRgFUS) thalamotomy over a 5-year period. METHODS: Forty-four ET patients treated with unilateral MRgFUS ventral intermediate nucleus (VIM) thalamotomy were assessed using the Clinical Rating Scale for Tremor (CRST) score and the Quality of Life in Essential Tremor Questionnaire (QUEST) over a 5-year span. RESULTS: Tremor was significantly improved immediately following MRgFUS in all patients and ceased completely in 24 patients. CRST scores in the treated hand at baseline (median 19; range 7-32, 44 patients) improved by a median of 16 at 1 month (44 patients; p < 0.0001), 17 at 6 months (31 patients; p < 0.0001), 15 at 1 year (24 patients; p < 0.0001), 18 at 2 years (15 patients; p < 0.0001), 19 at 3 years, (10 patients; p < 0.0001), 21 at 4 years (6 patients; p < 0.01), and 23 at 5 years (2 patients, significance not tested). Return of tremor that impacted activities of daily living was reported in 5 patients (11%). QUEST scores showed significant improvement, with median change of 35 points (p < 0.0001; 44 patients) at 1 month, 33 (p < 0.0001; 31 patients) at 6 months, 27 (p < 0.0001; 24 patients) at 1 year, 26 (p < 0.001; 15 patients) at 2 years, 25 (p < 0.001; 10 patients) at 3 years, 33 (p < 0.001; 6 patients) at 4 years, and 28 (significance not tested, 2 patients) at 5 years. Adverse events after the procedure were reversible in all but 5 patients (11%). CONCLUSIONS: MRgFUS thalamotomy for ET is an effective and safe procedure that provides long-term tremor relief and improvement in quality of life even in patients with medication-resistant disabling tremor. Additional studies with a larger group of patients is needed to substantiate these favorable results.

Individualization of Migraine Prevention: A Randomized Controlled Trial of Psychophysical-based Prediction of Duloxetine Efficacy.

OBJECTIVE: Finding an effective preventive agent for the individual migraineur is often long and frustrating. An individual-specific, efficacy-predicting tool would be invaluable in directing, shortening, and improving this process. As the serotonin-norepinephrine reuptake inhibitor duloxetine is a pain modulator, we hypothesized that pronociceptivity will directly predict drug efficacy, so that the more pronociceptive the patient is, the more efficacious the drug. Therefore, we used psychophysical pain measures to predict duloxetine efficacy in migraine prevention. METHODS: Fifty-five migraineurs participated: 27 received duloxetine and 28 nonactive placebo. Responses to painful stimuli, conditioned pain modulation, and temporal summation of pain were measured before treatment. Treatment outcome measures included changes in attack frequency, migraine days, pain levels, and a reported self-estimate of migraine improvement at weeks 4 and 5. To examine treatment effects, the outcome measures were compared with pretreatment levels. Treatment by the psychophysical-predictor effect on treatment outcome was examined in separate regression models. RESULTS: Duloxetine was more efficacious than placebo in migraine prevention, as indicated by the patient's estimation of migraine improvement (duloxetine: 52.3±30.4%; placebo: 26.0±27.3%; P=0.001). Further, this measure, in the duloxetine group, was predicted by higher pretreatment pain ratings for tonic heat pain (P=0.012); greater pain sensitivity at baseline predicted greater percent of migraine improvement in duloxetine (r=0.47; P=0.013), but not in placebo (r=-0.36; P=0.060). DISCUSSION: Our results suggest how personalized medicine can be applied to designing appropriate migraine prevention treatment. Psychophysical testing can reveal and characterize pronociceptive migraineurs, who seem to be more likely than non-pronociceptive ones to benefit from migraine prevention with serotonin-norepinephrine reuptake inhibitors.

Motor corticospinal excitability: a novel facet of pain modulation?

INTRODUCTION: Increase in excitability of the primary motor cortex (M1) is associated with pain inhibition by analgesics, which is, in turn, associated with the psychophysical antinociceptive pain modulation profile. However, the relationship between neurophysiological M1 excitability and psychophysical pain modulation has not yet been explored. OBJECTIVES: We aim to study these relationships in healthy subjects. METHODS: Forty-one young healthy subjects (22 women) underwent a wide battery of psychophysical testing that included conditioned pain modulation (CPM) and pain temporal summation, and a transcranial magnetic stimulation neurophysiological assessment of the motor corticospinal excitability, including resting motor threshold, motor-evoked potentials (MEPs), and cortical silent period. RESULTS: Increased motor corticospinal excitability in 2 parameters was associated with more efficient CPM: (1) higher MEP amplitude (r = -0.574; P _Bonferroni = 0.02) and (2) longer MEP duration (r = -0.543; P _Bonferroni = 0.02). The latter also correlated with the lower temporal summation magnitude (r = -0.421; P = 0.007); however, on multiplicity adjustment, significance was lost. CONCLUSIONS: Increased corticospinal excitability of the primary motor cortex is associated with more efficient inhibitory pain modulation as assessed by CPM, in healthy subjects. Motor-evoked potential amplitude and duration may be considered as an additional, objective and easy to measure parameter to allow for better individual assessment of pain modulation profile.

Do patients with interictal migraine modulate pain differently from healthy controls? A psychophysical and brain imaging study.

Studies in interictal migraine show either normal or impaired pain modulation, at the psychophysical level. To date, pain modulation in migraineurs has yet to be explored concurrent with imaging methods. We aimed to investigate brain activity associated with endogenous analgesia by functional magnetic resonance imaging in attack-free migraineurs. Thirty-nine episodic migraineurs and 35 controls participated. Endogenous analgesia efficiency was assessed by the conditioned pain modulation (CPM) paradigm during functional magnetic resonance imaging. Conditioned pain modulation included 4 stimulation sequences of either test stimulus (noxious contact heat at forearm) given stand alone (Ts_alone) or concomitant to contralateral foot immersion in cold water (Ts_conditioned). The psychophysical CPM (Ts_conditioned minus Ts_alone; 0-10 numerical rating scale) and related brain activity were examined. No group differences were found in the psychophysical CPM (controls: -0.52 ± 0.80; migraineurs: -0.20 ± 0.88; repeated-measures analysis of variance: P = 0.110) or related brain activity (family wise error [P < 0.05] correction at the voxel level). Within groups, controls showed a significant CPM effect (Ts_alone: 6.15 ± 2.03 vs Ts_conditioned: 5.63 ± 1.97; P < 0.001), whereas migraineurs did not (Ts_alone: 5.60 ± 1.92 vs Ts_conditioned: 5.39 ± 2.30; P = 0.153); yet, both groups showed significant CPM-related decreased deactivation in prefrontal areas including the superior frontal gyrus and parietal regions including precuneus. The change in brain activity seems related to task demands rather than to pain reduction. The lack of group difference between migraineurs and controls in CPM and its related brain activity may result from (1) the specific CPM methodology used in this study, since migraineurs are reported to show various pain modulation efficiency for different test paradigms and/or (2) pathophysiological diversity of patients with migraine.

Psychophysic-psychological dichotomy in very early acute mTBI pain: A prospective study.

OBJECTIVE: To characterize the pain-related somatosensory and psychological presentation of very early acute patients with a mild traumatic brain injury (mTBI). METHODS: Patients with an mTBI participated in a prospective observational study undergoing clinical, psychophysic, and psychological assessment within 72 hours after the accident. Healthy controls underwent similar protocol. RESULTS: One hundred acute patients with an mTBI (age 36 ± 12.5 [SD] years, range 19-67 years, 42 women) and 80 healthy controls (age 43 ± 14.3 years, range 24-74 years, 40 women) participated. Patients with an mTBI demonstrated a pronociceptive psychophysic response in most tests such as less efficient pressure-pain threshold-conditioned pain modulation (0.19 ±0.19±.09 vs. 0.91±.10 kg, p < 0.001) and lower temperature needed to elicit a Pain50 response (44.72 ± 0.26°C vs 46.41 ± 0.30°C, p < 0.001). Their psychophysic findings correlated with clinical pain measures, e.g., Pain50 temperature and mean head (r = -0.21, p = 0.045) and neck (r = -0.26, p = 0.011) pain. The pain-catastrophizing magnification subscale was the only psychological variable to show a difference from the controls, while no significant correlations were found between any psychological measures and the clinical or psychophysic pain measures. CONCLUSIONS: There appears to be a dichotomy between somatosensory and psychological findings in the very early acute post-mTBI stage; while the first is altered and is associated with the clinical picture, the second is unchanged. In the context of the ongoing debate on the pathophysiologic nature of the post-mTBI syndrome, our findings support its "physical" basis, free of mental influence, at least in the short time window after the injury.

Efficacy of Parenteral Amantadine Therapy in the Treatment of Multiple System Atrophy With Predominant Parkinsonism.

OBJECTIVE: The aim of this study was to assess clinical response to a high-dose intravenous (IV) amantadine given for 5 consecutive days in patients with multiple system atrophy parkinsonism (MSA-P). METHODS: Subjects with a diagnosis of MSA-P treated with IV amantadine were included. Patients' disease severity before and after therapy was evaluated using the Unified Multiple System Atrophy Rating Scale (UMSARS). RESULTS: Fourteen subjects (8 females) were included. In 10 subjects (71.4%), clinical improvement was noted. The UMSARS score after treatment decreased by 2 points (median [interquartile range, 0-3]) when compared with UMSARS score at baseline (P = 0.0020). Upon examining the walking parameter, a trend of improvement was shown (P = 0.0625) (range, 0-1 points). Neither specific demographic parameters nor occurrence of adverse effects was found to be a predictive factor for improvement. Adverse events were mild and transient except for one patient who experienced acute psychosis prompting treatment cessation, upon which psychosis resolved. CONCLUSIONS: Our preliminary data show that IV amantadine may be a safe and effective therapy in MSA-P. A double-blind placebo-controlled trial is needed to establish the true benefit of amantadine therapy.

Can a single pulse transcranial magnetic stimulation targeted to the motor cortex interrupt pain processing?

The modulatory role of the primary motor cortex (M1), reflected by an inhibitory effect of M1-stimulation on clinical pain, motivated us to deepen our understanding of M1's role in pain modulation. We used Transcranial Magnetic Stimulation (TMS)-induced virtual lesion (VL) to interrupt with M1 activity during noxious heat pain. We hypothesized that TMS-VL will effect experimental pain ratings. Three VL protocols were applied consisting of single-pulse TMS to transiently interfere with right M1 activity: (1) VLM1- TMS applied to 11 subjects, 20 msec before the individual's first pain-related M1 peak activation, as determined by source analysis (sLORETA), (2) VL-50 (N = 16; TMS applied 50 ms prior to noxious stimulus onset), and (3) VL+150 (N = 16; TMS applied 150 ms after noxious stimulus onset). Each protocol included 3 conditions ('pain-alone', ' TMS-VL', and 'SHAM-VL'), each consisted of 30 noxious heat stimuli. Pain ratings were compared, in each protocol, for TMS-VL vs. SHAM-VL and vs. pain-alone conditions. Repeated measures analysis of variance, corrected for multiple comparisons revealed no significant differences in the pain ratings between the different conditions within each protocol. Therefore, our results from this exploratory study suggest that a single pulse TMS-induced VL that is targeted to M1 failed to interrupt experimental pain processing in the specific three stimulation timing examined here.

Assessment of Responsiveness to Everyday Non-Noxious Stimuli in Pain-Free Migraineurs With Versus Without Aura.

Migraineurs with aura (MWA) express higher interictal response to non-noxious and noxious experimental sensory stimuli compared with migraineurs without aura (MWoA), but whether these differences also prevail in response to everyday non-noxious stimuli is not yet explored. This is a cross-sectional study testing 53 female migraineurs (30 MWA; 23 MWoA) who underwent a wide battery of noxious psychophysical testing at a pain-free phase, and completed a Sensory Responsiveness Questionnaire and pain-related psychological questionnaires. The MWA group showed higher questionnaire-based sensory over-responsiveness (P = .030), higher magnitude of pain temporal summation (P = .031) as well as higher monthly attack frequency (P = .027) compared with the MWoA group. Overall, 45% of migraineurs described abnormal sensory (hyper- or hypo-) responsiveness; its incidence was higher among MWA (19 of 30, 63%) versus MWoA (6 of 23, 27%, P = .012), with an odds ratio of 3.58 for MWA. Sensory responsiveness scores were positively correlated with attack frequency (r = .361, P = .008) and temporal summation magnitude (r = .390, P = .004), both regardless of migraine type. MWA express higher everyday sensory responsiveness than MWoA, in line with higher response to experimental noxious stimuli. Abnormal scores of sensory responsiveness characterize people with sensory modulation dysfunction, suggesting possible underlying mechanisms overlap, and possibly high incidence of both clinical entities. PERSPECTIVE: This article presents findings distinguishing MWA, showing enhanced pain amplification, monthly attack frequency, and over-responsiveness to everyday sensations, compared with MWoA. Further, migraine is characterized by a high incidence of abnormal responsiveness to everyday sensation, specifically sensory over-responsiveness, that was also found related to pain.

Remote kinematic training for patients with chronic neck pain: a randomised controlled trial.

PURPOSE: To evaluate short- and intermediate-term effects of kinematic training (KT) using virtual reality (VR) or laser in patients with chronic neck pain. METHODS: A randomised controlled trial with three arms (laser, VR, control) to post-intervention (N = 90), and two arms (laser or VR) continuing to 3 months follow-up. Home training intervention was provided during 4 weeks to VR and laser groups while control group waited. OUTCOME MEASURES: Primary outcome measures included neck disability index (NDI), global perceived effect (GPE), and cervical motion velocity (mean and peak). Secondary outcome measures included pain intensity (VAS), health status (EQ5D), kinesiophobia (TSK), range, smoothness, and accuracy of neck motion as measured by the neck VR system. Measures were taken at baseline, immediately post-training, and 3 months later. RESULTS: Ninety patients with neck pain were randomised to the trial, of which 76 completed 1 month follow-up, and 56 the 3 months follow-up. Significant improvements were demonstrated in NDI and velocity with good effect sizes in intervention groups compared to control. No within-group changes were presented in the control group, compared to global improvements in intervention groups. Velocity significantly improved at both time points in both groups. NDI, VAS, EQ5D, TSK and accuracy significantly improved at both time points in VR and in laser at 3 months evaluation in all but TSK. GPE scores showed 74-84% of participants perceived improvement and/or were satisfied. Significant advantages to the VR group compared to laser were found in velocity, pain intensity, health status and accuracy at both time points. CONCLUSION: The results support home kinematic training using VR or laser for improving disability, neck pain and kinematics in the short and intermediate term with an advantage to the VR group. The results provide directions for future research, use and development. TRIAL REGISTRATION: ACTRN12615000231549.

Internal carotid artery dissection among younger and older patients with acute ischemic stroke.

Purpose/Aim of the study: Carotid artery dissection (CAD) is a known causative factor in the etiology of acute ischemic stroke in young patients. However, the significance of CAD in older patients with acute ischemic stroke is unclear with only a few prior clinical studies. In order to isolate the influence of CAD as an independent factor, we performed multivariate analyses of common covariables in acute ischemic stroke patients in northern Israel. MATERIALS AND METHODS: Three hundred and forty-seven consecutive patients who suffered from acute ischemic stroke had initial CT angiography (CTA) ordered from the emergency room. We reviewed the CTAs for radiologic signs of CAD, and recorded patients' demographic and clinical data from the hospital's computerized information system. RESULTS: Eighteen of the 347 patients (5.19%) had CTA evidence of CAD, with no statistically significant differences based on age, gender or ethnicity. A statistically significant inverse association between hypertension and a lower rate of CAD was found before and after stepwise logistic regression, while hyperlipidemia showed a trend toward a similar inverse association that was borderline for statistical significance. CONCLUSIONS: Our study shows that CAD is an independent and significant causative factor for acute ischemic stroke. Therefore, diagnostic imaging is indicated to rule out CAD not only in young patients, but rather in all patients with acute ischemic stroke. The inverse correlation between common vascular risk factors (i.e. hypertension and hyperlipidemia) and CAD points to CAD as an independent nonatherosclerotic causative factor in the etiology of acute ischemic stroke.

Bi-phasic activation of the primary motor cortex by pain and its relation to pain-evoked potentials - an exploratory study.

The primary motor cortex (M1) is a known target for brain stimulation aimed at pain alleviation in chronic pain patients, yet the mechanisms through which analgesia occurs, and the exact pain-motor interrelations are not fully understood. We used noxious contact heat evoked potentials (CHEPs) and cortical source analysis to further explore the relevance of M1 in pain processing. Twenty-four healthy young females received brief noxious heat stimuli to their left non-dominant volar forearm, simultaneously with CHEPs recordings. Thereafter, the pain-evoked activity of M1 and a control area in the occipital cortex (OC) was analyzed and estimated using sLORETA (standardized low-resolution brain electromagnetic tomography). This analysis revealed two phases of M1 pain-evoked activation (phase 1: the peak at 261.5±25.7ms; phase 2: the peak at 381.3±28.3ms). Canonical correlations revealed that M1, but not the OC, was the main factor contributing to the relation with the CHEPs components. In detail, the activity magnitude of M1 first and second phases was related to the N2 and P2 amplitude, respectively. The latency of the second phase was associated with both N2 and P2 latencies. In relation to pain, the latency of M1's first activity phase was positively correlated with pain ratings, suggesting pain interference to synchronized activity in M1. Our results confirm the established relevance of the primary motor cortex to pain processing.

The Effect of External and Internal Focus of Attention on Gait Variability in Older Adults.

Internal focus of attention on a movement or focusing on an external target are both strategies that can affect motor performance. The authors explored whether manipulating subjects' focus of attention while walking would alter gait variability, a measure reflecting consistency of gait and associated with the risk of falling in older adults. Twenty community-living older adults participated in the study and were tested while focusing their attention on (a) gait consistency (internal focus) or (b) metronome beats (external focus). In both conditions gait variability increased (i.e., worsened p < .05) or did not change. No benefit was found in instructing subjects to focus on gait consistency or metronome beats. Such instructions may actually have distracted and interfered with the execution of gait.