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Functional neurological disorders have rarely been described in patients recovering from Covid-19 or after vaccination but they are probably under diagnosed.Six patients referred for rehabilitation of persistent symptoms and/or sequelae of Coronavirus disease 2019 (COVID-19) were diagnosed with functional neurological disorders. A literature review was conducted to identify reported cases of functional neurological disorders after Covid-19 infection or vaccination.In the current case series, patients diagnosed with functional neurological disorders presented high variability of clinical symptoms including hemiplegia, lower limb unilateral or bilateral paralysis, myoclonus, dystonia, tremor and sensory impairment. Four patients were young females with mild Covid-19 infection without hospital admission. Their neurological symptoms developed over the course of 4 weeks after the beginning of Covid-19 symptoms or vaccine administration with normal ancillary exams. One patient presented overlapping functional neurological symptoms and mild impairment of the left common peroneal nerve after prolonged ICU stay. In addition, all patients in our case series reported other non-motor symptoms such as fatigue, cognitive impairment and diffuse pain or dysesthesia, which are compatible with post Covid-19 condition.It is important that clinicians recognize functional neurological symptoms and consider it as a differential diagnosis in patients with neurological complications of Covid-19 infection and vaccination.

Purpose This prospective, observational cohort study investigated the effects of multidisciplinary rehabilitation of post Covid-19 sequelae and persistent symptoms and their impact on patients' functioning and quality of life. Methods From 58 patients referred for neurorehabilitation, 43 were eligible for and participated in the present study. Before and after 8 weeks of rehabilitation, patients underwent physical, neuropsychological and respiratory evaluations and assessment of functional independence, impact of fatigue and quality of life. Results Forty of 43 individuals (52 ± 11.4 years, 24 male) completed the rehabilitation program. Fatigue (87.5%), dyspnea and/or shortness of breath (62.5%), and cognitive impairment (37.5%) were reported by both previously hospitalized and home-confined patients. Neurological sequelae (35.5%) were present only in hospitalized patients. After 8 weeks of rehabilitation, patients reported significant improvements in motor functional independence, upper and lower limb functionality, impact of fatigue on daily activities, respiratory muscle strength, cognitive performance, and quality of life. Conclusions Post Covid-19 patients present with heterogeneous neurological, physical, and respiratory impairments requiring a multidisciplinary rehabilitation approach to reduce disability and improve functionality and quality of life. A comprehensive assessment of clinical profiles and responses to rehabilitation may facilitate the identification of rehabilitation candidates and help to design effective rehabilitation interventions.Implication for rehabilitationPost Covid-19 patients present multiple, heterogeneous neurological, physical and respiratory impairments that are observed in both previously hospitalized and home-confined patients.Eight weeks of multidisciplinary rehabilitation may significantly reduce disability and improve functionality and quality of life.A comprehensive assessment of their clinical profile and response to rehabilitation may facilitate the identification of rehabilitation candidates and help to design more effective rehabilitation interventions.

IntroductionThe prefrontal cortex (PFC) plays a crucial role in cognition, particularly in executive functions. Cortical reactivity measured with Transcranial Magnetic Stimulation combined with Electroencephalography (TMS-EEG) is altered in pathological conditions, and it may also be a marker of cognitive status in middle-aged adults. In this study, we investigated the associations between cognitive measures and TMS evoked EEG reactivity and explored whether the effects of this relationship were related to neurofilament light chain levels (NfL), a marker of neuroaxonal damage.MethodsFifty two healthy middle-aged adults (41–65 years) from the Barcelona Brain Health Initiative cohort underwent TMS-EEG, a comprehensive neuropsychological assessment, and a blood test for NfL levels. Global and Local Mean-Field Power (GMFP/LMFP), two measures of cortical reactivity, were quantified after left prefrontal cortex (L-PFC) stimulation, and cognition was set as the outcome of the regression analysis. The left inferior parietal lobe (L-IPL) was used as a control stimulation condition.ResultsLocal reactivity was significantly associated with working memory and reasoning only after L-PFC stimulation. No associations were found between NfL and cognition. These specific associations were independent of the status of neuroaxonal damage indexed by the NfL biomarker and remained after adjusting for age, biological sex, and education.ConclusionOur results demonstrate that TMS evoked EEG reactivity at the L-PFC, but not the L-IPL, is related to the cognitive status of middle-aged individuals and independent of NfL levels, and may become a valuable biomarker of frontal lobe-associated cognitive function.

Pain is a complex experience involving both nociceptive and affective–cognitive mechanisms. The present study evaluated whether modulation of pain perception, employing a conditioned pain modulation (CPM) paradigm, is paralleled by changes in contact heat-evoked potentials (CHEPs), a brain response to nociceptive stimuli. Participants were 25 healthy, pain-free, college students (12 males, 13 females, mean age 19.24 ± 0.97 years). Twenty computer-controlled heat stimuli were delivered to the non-dominant forearm and CHEPs were recorded at Cz using a 32-channel EEG system. After each stimulus, participants rated the intensity of the heat pain using the 0–100 numerical rating scale. The latency and amplitude of N2, P2 components as well as single-sweep spectral analysis of individual CHEPs were measured offline. For CPM, participants had to submerge their dominant foot into a neutral (32 °C) or noxious (0 °C) water bath. CHEPs and heat pain ratings were recorded in 3 different conditions: without CPM, after neutral CPM (32 °C) and after noxious CPM (0 °C). The noxious CPM induced a facilitatory pain response (p = 0.001) with an increase in heat pain following noxious CPM compared to neutral CPM (p = 0.001) and no CPM (p = 0.001). Changes in CHEPs did not differ between conditions when measured as N2–P2 peak-to-peak amplitude (p = 0.33) but the CPM significantly suppressed the CHEPs-related delta power (p = 0.03). Changes in heat pain in the noxious CPM were predicted by trait catastrophizing variables (p = 0.04). The current study revealed that pain facilitatory CPM is related to suppression of CHEPs delta power which could be related to dissociation between brain responses to noxious heat and pain perception.

BACKGROUND: Coronavirus disease 2019 (COVID-19) patients present long-lasting physical and neuropsychological impairment, which may require rehabilitation. OBJECTIVES: The current cross-sectional study characterizes postCOVID-19 sequelae and persistent symptoms in patients in an outpatient rehabilitation program. METHODS: Thirty patients [16 post-ICU and 14 non-ICU; median age = 54(43.8-62) years; 19 men] presenting sequelae and/or persistent symptoms (>3 months after acute COVID-19) were selected of 41 patients referred for neurorehabilitation. Patients underwent physical, neuropsychological and respiratory evaluation and assessment of impact of fatigue and quality of life. RESULTS: The main reasons for referral to rehabilitation were: fatigue (86.6%), dyspnea (66.7%), subjective cognitive impairment (46.7%) and neurological sequelae (33.3%). Post-ICU patient presented sequelae of critical illness myopathy and polyneuropathy, stroke and encephalopathy and lower forced vital capacity compared to non-ICU patients. Cognitive impairment was found in 63.3% of patients, with a similar profile in both sub-groups. Increased physical fatigue, anxiety and depression and low quality of life were prevalent irrespective of acute COVID-19 severity. CONCLUSIONS: The variability of post COVID-19 physical and neuropsychological impairment requires a complex screening process both in ICU and non-ICU patients. The high impact of persistent symptoms on daily life activities and quality of life, regardless of acute infection severity, indicate need for rehabilitation.

Background Outlet constipation is a major problem in spinal cord injury (SCI) patients. We aimed to study the efficacy of external anal sphincter (EAS) infiltration with type-A botulinum toxin (BTX-A) in motor incomplete SCI patients with outlet constipation. Methods Double blind, randomized, placebo controlled, comparative study in 16 motor incomplete SCI subjects. Patients were randomly assigned toreceive100 UI of BTX-A (n = 9) or physiologic serum infiltration (n = 7) in the EAS under electromyographic guidance. Outcome measures included a questionnaire for clinical bowel function evaluation, colonic transit time and anorectal manometry. All assessments were done at baseline, 1 and 3 months after treatment. Results Fourteen patients completed the study. In the BTX-A group we observed an improvement of subjective perception of bowel function (p = 0.01), constipation (p = 0.02) and neurogenic bowel dysfunction score (p = 0.02). The anorectal manometry revealed are duction of EAS voluntary contraction pressure (p = 0.01). No changes were observed in the placebo group. No significant side effects were observed in none of the groups. Conclusion BTX-A infiltration of the EAS is a safe technique that in motor incomplete SCI, decreases the EAS contraction and the anal canal pressure during straining, and improves outlet constipation symptoms. Future studies in larger populations are needed.

Background: Patients infected with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), responsible for the coronavirus disease 2019 (COVID-19), exhibit a wide spectrum of disease behaviour. Since DNA methylation has been implicated in the regulation of viral infections and the immune system, we performed an epigenome-wide association study (EWAS) to identify candidate loci regulated by this epigenetic mark that could be involved in the onset of COVID-19 in patients without comorbidities. Methods: Peripheral blood samples were obtained from 407 confirmed COVID-19 patients 61 years of age and without comorbidities, 194 (47.7%) of whom had mild symptomatology that did not involve hospitalization and 213 (52.3%) had a severe clinical course that required respiratory support. The set of cases was divided into discovery (n = 207) and validation (n = 200) cohorts, balanced for age and sex of individuals. We analysed the DNA methylation status of 850,000 CpG sites in these patients. Findings: The DNA methylation status of 44 CpG sites was associated with the clinical severity of COVID-19. Of these loci, 23 (52.3%) were located in 20 annotated coding genes. These genes, such as the inflammasome component Absent in Melanoma 2 (AIM2) and the Major Histocompatibility Complex, class I C (HLA-C) candidates, were mainly involved in the response of interferon to viral infection. We used the EWAS-identified sites to establish a DNA methylation signature (EPICOVID) that is associated with the severity of the disease. Interpretation: We identified DNA methylation sites as epigenetic susceptibility loci for respiratory failure in COVID-19 patients. These candidate biomarkers, combined with other clinical, cellular and genetic factors, could be useful in the clinical stratification and management of patients infected with the SARS-CoV-2., The Unstoppable campaign of the Josep Carreras Leukaemia Foundation, the Cellex Foundation and the CERCA Programme/Generalitat de Catalunya.

Background aims: Spinal cord injury (SCI) represents a devastating condition leading to severe disability related to motor, sensory and autonomic dysfunction. Stem cell transplantation is considered a potential emerging therapy to stimulate neuroplastic and neuroregenerative processes after SCI. In this clinical trial, the authors investigated the safety and clinical recovery effects of intrathecal infusion of expanded Wharton jelly mesenchymal stromal cells (WJ-MSCs) in chronic complete SCI patients. Methods: The authors designed a randomized, double-blind, crossover, placebo-controlled, phase 1/2a clinical trial (NCT03003364). Participants were 10 patients (7 males, 3 females, age range, 25-47 years) with chronic complete SCI (American Spinal Injury Association A) at dorsal level (T3-11). Patients were randomly assigned to receive a single dose of intrathecal ex vivo-expanded WJ-MSCs (10 x 10(6) cells) from human umbilical cord or placebo and were then switched to the other arm at 6 months. Clinical evaluation (American Spinal Injury Association impairment scale motor and sensory score, spasticity, neuropathic pain, electrical perception and pain thresholds), lower limb motor evoked potentials (MEPs) and sensory evoked potentials (SEPs), Spinal Cord Independence Measure and World Health Organization Quality of Life Brief Version were assessed at baseline, 1 month, 3 months and 6 months after each intervention. Urodynamic studies and urinary-specific quality of life (Qualiveen questionnaire) as well as anorectal manometry, functional assessment of bowel dysfunction (Rome III diagnostic questionnaire) and severity of fecal incontinence (Wexner score) were conducted at baseline and at 6 months after each intervention. Results: Intrathecal transplantation of WJ-MSCs was considered safe, with no significant side effects. Following MSC infusion, the authors found significant improvement in pinprick sensation in the dermatomes below the level of injury compared with placebo. Other clinically relevant effects, such as an increase in bladder maximum capacity and compliance and a decrease in bladder neurogenic hyperactivity and external sphincter dyssynergy, were observed only at the individual level. No changes in motor function, spasticity, MEPs, SEPs, bowel function, quality of life or independence measures were observed. Conclusions: Intrathecal transplantation of human umbilical cord-derived WJ-MSCs is a safe intervention. A single intrathecal infusion of WJ-MSCs in patients with chronic complete SCI induced sensory improvement in the segments adjacent to the injury site. (C) 2020 International Society for Cell & Gene Therapy. Published by Elsevier Inc. All rights reserved.

Objective Multiple and specific types of childhood adverse events are risk factors for chronic pain conditions. Although both can covary, no study has evaluated one aspect while controlling for the other. Therefore, the current study examined whether more adverse events would be a risk factor for common chronic pain conditions and pain medication use in young adults after controlling for different adversity types such as physical, emotional, and sexual traumatic events or vice versa. Methods This cross-sectional study recruited 3,073 undergraduates (72% female, mean age = 18.8 years, SD = 1.4 years) who completed the survey for current health status and early life traumatic events. Results More adverse events were associated with a 1.2-1.3-fold increase in the odds of any chronic pain, chronic back pain, headache, and dysmenorrhea with adjusting for adversity types, but they were not associated with the risk of comorbid pain conditions and use of pain medications. In contrast, specific adversity types were unrelated to chronic pain conditions when controlling for the number of adverse events. Conclusions Cumulative childhood adverse events may be a more relevant risk factor for chronic pain conditions than the experience of a specific type of adverse event. Clinicians and researchers need to evaluate cumulative childhood adversity when assessing its link to chronic pain.

Changes in EEG activity have been related to clinical and experimental pain. Expectation of a negative outcome can lead to pain enhancement (nocebo hyperalgesia) and can alter the response to therapeutic interventions. The present study characterizes EEG alteration related to pain facilitation by nocebo. Thirty healthy subjects were randomly assigned to the nocebo or control group. Five-minute EEG was recorded under: resting state, tonic innocuous heat and tonic noxious heat before and after the application of a sham inert cream to the non-dominant volar forearm combined with cognitive manipulation. The intensity and unpleasantness of heat-induced pain increased after cognitive manipulation in the nocebo group compared to control and was associated with enhanced low alpha (8–10 Hz) activity. However, changes in alpha activity were predicted by catastrophizing but not by pain intensity or unpleasantness, which suggest that low alpha power might reflect brain activity related to negative cognitive–affective responses to pain.

STUDY DESIGN: Cross-sectional study. BACKGROUND: Sleep disturbances are frequently reported by individuals with spinal cord injury (SCI) and are associated both with poor quality of life and reduced ability to participate in rehabilitation and daily life activities. OBJECTIVES: This study investigated sleep quality based on self-reports and actigraphy in individuals with SCI as compared to able-bodied. We also explored the relationship between sleep quality, physical activity, and neuropathic pain. SETTING: Institute Guttmann, Neurorehabilitation Hospital, Badalona, Barcelona, Spain. METHODS: Fourteen SCI patients (12 males, 43.10 ± 10.59 y.o.) and 10 healthy individuals (7 males, mean age 46.21 ± 12.58 y.o.) were enrolled in the study. Participants wore wrist actigraphs for 7 consecutive days to characterize their sleep–wake cycle, rest-activity circadian rhythm and physical activity. Sleep quality, chronotype, daytime sleepiness, neuropathic pain severity and interference were assessed based on questionnaires. RESULTS: SCI individuals reported poorer sleep quality compared to healthy individuals. Actigraphy-based sleep measurements revealed that patients woke up later, spent more time in bed and slept longer compared to the healthy controls but did not differ significantly in the estimated sleep efficacy and number of awakenings from the able-bodied controls. In individuals with SCI greater physical activity predicted higher sleep efficacy and less awakening episodes as well as shorter sleep latency and lower sleep disturbance. CONCLUSIONS: The actigraphy-based sleep estimates indicate that patients with SCI spent more time in bed and slept longer but their sleep efficacy was similar to able-bodied controls. Maintaining regular physical activity could improve pain control and sleep quality.

Maladaptive plasticity in the sensorimotor system, following neurological lesions or diseases, plays a central role in the generation and maintenance of neuropathic pain. Repetitive magnetic stimulation of the central and peripheral nervous system has gained relevance as noninvasive approach for neuromodulation and pain relief. Systematic reviews that evaluate the effectiveness and specificity of different protocols of repetitive magnetic stimulation to control neuropathic pain in clinical populations have the potential to improve the therapeutic applicability of this technique.Studies whose primary goal was to evaluate the effectiveness of repetitive magnetic stimulation for the treatment of various types of neuropathic pain published in PubMed until August 2015 have been included in this systematic review.A total of 39 articles fulfilling the inclusion criteria were analyzed of which 37 studies investigated pain modulation using repetitive magnetic stimulation over the motor or non-motor cortices and two studies evaluated pain modulation using repetitive peripheral magnetic stimulation protocols.Repetitive transcranial magnetic stimulation of the primary motor cortex using high frequency stimulation protocols can effectively reduce neuropathic pain, particularly in individuals with pain related to non-cerebral lesions. The application of multiple sessions can lead to long-lasting pain modulation and cumulative effects. Implications for Rehabilitation Maladaptive plasticity plays a central role in sensitization of nociceptive pathways, generation and maintainance of neuropathic pain; Most neuropathic pain conditions are refractory to pharmacological therapies; Repetitive magnetic stimulation of the central and peripheral nervous system has gained relevance as noninvasive approach for neuromodulation and pain relief.

Introduction Changes in spinal reflexes can result from alterations in the spinal cord and descending pathways. We studied whether H-reflex excitability and its recovery depend on the level and/or severity of spinal cord injury (SCI). Methods The soleus Hmax and Mmax responses and the H-reflex recovery curve (HRC) at interstimulus intervals (ISIs) ranging from 50 to 1,000 ms were recorded in 38 SCI individuals and 18 healthy subjects. Results Amplitude of Mmax correlated with level and severity of lesion (smaller amplitude correlated with more severe SCI or with more caudal lesion). Hmax/Mmax correlated only with age in the SCI group. HRC was increased significantly in complete SCI at ISIs 200 ms with respect to healthy subjects. Conclusions The changes in spinal reflexes as measured by the H-reflex and its recovery curve after SCI depend on the severity, but not on the level of the lesion. Muscle Nerve 52: 616–622, 2015

The current study examined pain and neurogenic inflammation responses to topical capsaicin during the interictal period (between headache) and their relationship with plasma oxytocin in individuals with migraine.Individuals with migraine can experience generalized (extracephalic) hyperalgesia, which can persist even between headache attacks. Elevated levels of plasma and cerebrospinal fluid oxytocin have been observed during migraine attacks, oxytocin levels being positively associated with the intensity of migraine symptoms. However, whether oxytocin plays a role in the mechanisms of generalized pain sensitization and neurogenic inflammation during the interictal period has not been studied yet. Understanding migraineurs' interictal pain phenotype and endogenous oxytocin might help identify individuals who would benefit from intranasal oxytocin treatment.Thirty-two subjects with migraine and 26 healthy controls underwent pain testing. The current study compared capsaicin-induced pain, central sensitization (areas of secondary mechanical allodynia and hyperalgesia), and neurogenic inflammation (capsaicin-induced flare) responses on the nondominant volar forearm between migraineurs and healthy controls. Additionally, we studied plasma oxytocin levels and their relationship to migraine symptoms, experimental pain and affect.The results indicated a significant group effect (P = .019): Migraineurs reported greater capsaicin-induced pain unpleasantness (M = 1.2, SD = 1.4) on a 0-10 scale and showed larger areas of flare (LnM = 2.8, SD = 0.4) than healthy controls (M = 0.5, SD = 0.8; LnM = 2.6, SD = 0.4; ps .032). In a subgroup analysis, enhanced capsaicin-induced pain unpleasantness was found in the chronic (P = .007), but not the episodic (Ps .200), migraineurs. The oxytocin levels were elevated in migraineurs and accounted for 18% of the group difference in capsaicin-induced pain unpleasantness. Within migraineurs, interictal oxytocin levels were negatively associated with psychological distress (Ps .030). However, during the interictal period, pain sensitivity in extracephalic regions and plasma oxytocin levels were unrelated to migraine symptom parameters (Ps .074). Lastly, the results found no group difference in areas of secondary mechanical allodynia and hyperalgesia (Ps.298).The current study revealed that individuals with migraine exhibit enhanced extracephalic capsaicin-induced pain unpleasantness and flare responses during interictal periods. In addition, migraineurs, especially those with chronic migraine, had slightly elevated interictal oxytocin levels compared to controls, which was associated with their affective component of experimental pain. Therefore, treatment targeting affective pain during the interictal period may help to reduce generalized pain in migraine. Furthermore, endogenous increases in oxytocin may be a compensatory mechanism that may help decrease affective distress in migraineurs. The therapeutic effects of intranasal oxytocin may benefit migraineurs by reducing their affective distress.

Objective: Repetitive application of peripheral electrical stimuli paired with transcranial magnetic stimulation (rTMS) of M1 cortex at low frequency, known as paired associative stimulation (PAS), is an effective method to induce motor cortex plasticity in humans. Here we investigated the effects of repetitive peripheral magnetic stimulation (rPMS) combined with low frequency rTMS ('magnetic-PAS') on intracortical and corticospinal excitability and whether those changes were widespread or circumscribed to the cortical area controlling the stimulated muscle.& para;& para;Methods: Eleven healthy subjects underwent three 10 min stimulation sessions: 10 Hz rPMS alone, applied in trains of 5 stimuli every 10 s (60 trains) on the extensor carpi radialis (ECR) muscle; rTMS alone at an intensity 120% of ECR threshold, applied over motor cortex of ECR and at a frequency of 0.1 Hz (60 stimuli) and magnetic PAS, i.e., paired rPMS and rTMS. We recorded motor evoked potentials (MEPs) from ECR and first dorsal interosseous (FDI) muscles. We measured resting motor threshold, motor evoked potentials (MEP) amplitude at 120% of RMT, short intracortical inhibition (SICI) at interstimulus interval (ISI) of 2 ms and intracortical facilitation (ICF) at an ISI of 15 ms before and immediately after each intervention.& para;& para;Results: Magnetic-PAS but not rTMS or rPMS applied separately, increased MEP amplitude and reduced short intracortical inhibition in ECR but not in FDI muscle.& para;& para;Conclusion: Magnetic-PAS can increase corticospinal excitability and reduce intracortical inhibition. The effects may be specific for the area of cortical representation of the stimulated muscle.& para;& para;Significance: Application of magnetic-PAS might be relevant for motor rehabilitation. (C) 2017 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Background : Repetitive magnetic stimulation (rMS) modulates thermal somatosensory function at both low (0.2–1.0 Hz) and high (5.0–20.0 Hz) frequencies within the conditioned dermatome. However the effects of 1 Hz and 20 Hz cervical (C6-C7) rMS on thermosensory thresholds and contact heat evoked potentials (CHEPs) tested within local and remote spinal dermatomes are not known. Methods : Thirty healthy subjects participated in the study. Warm and cold detection threshold, heat and cold pain thresholds, and Cz/Fz CHEPs were evaluated within the C6, T10 and extrasegmental V3 control dermatome, before and after random assignment of subjects to sham, 1 or 20 Hz C6-C7 rMS. Results : Following both 1 and 20 Hz cervical rMS, warm detection threshold increased within the local C6 dermatome. Furthermore 1 Hz cervical rMS increased warm detection threshold within the remote T10 dermatome, but not within the V3-trigeminal control area. Cervical rMS failed to modulate cold detection threshold, heat and cold pain threshold or Cz/Fz CHEP amplitude from the dermatomal test sites. Conclusion : Both 1 and 20 Hz cervical rMS modulated warm detection threshold within the locally conditioned C6 dermatome. The concomitant increase in warm detection threshold within the T10 dermatome following 1 Hz rMS provides evidence for remote neuromodulation of thermosensory function via intraspinal control mechanisms.

Objective Paralytic poliomyelitis (pPM) is clinically suspected in individuals experiencing a non-progressive syndrome of flaccid paralysis and atrophy as a sequel of an acute infection. Despite normal sensory perception, patients with pPM complain of pain more than matched siblings. Here, we studied the characteristics of evoked pain in a cohort of pPM patients using contact heat evoked potentials and psychophysical tests. Methods Fifteen patients with pPM and 15 controls were studied. Inclusion criteria were unilateral or asymmetric involvement of lower extremities. Mechanical, warm and heat pain perception thresholds and evoked pain were measured in both thighs. Contact heat evoked potentials were recorded from the vertex. Results Mechanical and heat pain thresholds were significantly lower in the affected than in the less-affected leg or in the legs of controls. Evoked pain ratings were significantly higher in the affected leg than in either the less-affected leg or in controls. Evoked potentials were significantly higher in the affected than in the less-affected leg. Conclusion Patients with pPM have mechanical and thermal hyperalgesia, which suggests abnormalities in processing of somatosensory inputs in these patients. Significance This phenomenon should be taken into account in the routine clinical evaluation and management of pPM patients.

Recent studies report high incidence of restless legs syndrome (RLS) in patients with spinal cord injury (SCI), who may also present pain and sensory disturbances. In the present manuscript, we examine and discuss diagnostic and treatment challenges of comorbid RLS and neuropathic pain (NP) in SCI. We evaluated seven men with a mean age of 55.6 (s.d.=14.0) years, with chronic complete or incomplete SCI at the thoracic or lumbar level, for complaints of sensory disturbances in the legs, which initially were attributed to drug-resistant NP. Because overlapped RLS was suspected, clinical evaluation of NP and RLS, serum ferritin and iron level assessment, and video polysomnographic (VPSG) studies were conducted. Pramipexole (0.18 mg q.d.−1) was added to treat RLS, and a follow-up was performed at 2 months. We found that in six subjects the RLS was comorbid with NP and in one subject the symptoms of RLS were misdiagnosed as NP. VPSG revealed periodic limb movements (PLMs) in all patients, including PLMs of the legs, arms or both. Serum ferritin was

The contribution of endogenous pain modulation dysfunction to clinical and sensory measures of neuropathic pain (NP) has not been fully explored. Habituation, temporal summation, and heterotopic noxious conditioning stimulus-induced modulation of tonic heat pain intensity were examined in healthy noninjured subjects (n = 10), and above the level of spinal cord injury (SCI) in individuals without (SCI-noNP, n = 10) and with NP (SCI-NP, n = 10). Thermoalgesic thresholds, Cz/AFz contact heat evoked potentials (CHEPs), and phasic or tonic (30 seconds) heat pain intensity were assessed within the C6 dermatome. Although habituation to tonic heat pain intensity (0-10) was reported by the noninjured (10 s: 3.5 ± 0.3 vs 30 s: 2.2 ± 0.5 numerical rating scale; P = 0.003), loss of habituation was identified in both the SCI-noNP (3.8 ± 0.3 vs 3.6 ± 0.5) and SCI-NP group (4.2 ± 0.4 vs 4.9 ± 0.8). Significant temporal summation of tonic heat pain intensity was not observed in the 3 groups. Inhibition of tonic heat pain intensity induced by heterotopic noxious conditioning stimulus was identified in the noninjured (-29.7% ± 9.7%) and SCI-noNP groups (-19.6% ± 7.0%), but not in subjects with SCI-NP (+1.1% ± 8.0%; P < 0.05). Additionally, the mean conditioned pain modulation response correlated positively with Cz/AFz CHEP amplitude (ρ = 0.8; P = 0.015) and evoked heat pain intensity (ρ = 0.8; P = 0.007) in the SCI-NP group. Stepwise regression analysis revealed that the mean conditioned pain modulation (R = 0.72) correlated with pain severity and pressing spontaneous pain in the SCI-NP group. Comprehensive assessment of sensory dysfunction above the level of injury with tonic thermal test and conditioning stimuli revealed less-efficient endogenous pain modulation in subjects with SCI-NP.

Changes in spinal reflexes can result from alterations in the spinal cord and descending pathways. We studied whether H-reflex excitability and its recovery depend on the level and/or severity of spinal cord injury (SCI).The soleus Hmax and Mmax responses and the H-reflex recovery curve (HRC) at interstimulus intervals (ISIs) ranging from 50 to 1,000 ms were recorded in 38 SCI individuals and 18 healthy subjects.Amplitude of Mmax correlated with level and severity of lesion (smaller amplitude correlated with more severe SCI or with more caudal lesion). Hmax/Mmax correlated only with age in the SCI group. HRC was increased significantly in complete SCI at ISIs500 ms and in incomplete SCI at ISIs200 ms with respect to healthy subjects.The changes in spinal reflexes as measured by the H-reflex and its recovery curve after SCI depend on the severity, but not on the level of the lesion.

Background Although the spasticity syndrome is an important sensorimotor disorder, the impact of grade of lower limb muscle hypertonia, spasm and clonus activity on voluntary muscle function, gait and daily activities has not been systematically analysed during subacute and chronic spinal cord injury (SCI). Objective To determine the prevalence of spasticity signs and symptoms during SCI, and to assess their impact on motor function and activities. Methods A descriptive transverse study of sixty-six subjects with SCI was performed by assessing injury characteristics, spasticity (modified Ashworth scale, Penn scale, SCATS scale) and motor function (lower limb manual muscle scores, WISCI II, spinal cord injury spasticity evaluation tool). Results Most subjects with the spasticity syndrome presented lower limb hypertonia and spasms during both subacute and chronic SCI, interfering with daily life activities. Subjects with incomplete SCI and hypertonia revealed a loss of voluntary flexor muscle activity, while extensors spasms contributed strongly to loss of gait function. The Penn spasms scale no correlated with muscle function or gait. Conclusions Specific diagnosis of spasm activity during subacute SCI, and its impact on lower limb voluntary muscle activity, gait function and daily activities, is required to develop a more effective neurorehabilitation treatment strategy.

Spasticity is an important sensorimotor disorder that affects between 65-78% of people with spinal cord injury (SCI). Although the standard diagnosis of spasticity relies on the standard measurement of hypertonia and stretch hyperreflexia, these symptoms are often described by patients as beneficial and may only play a limited role in motor dysfunction. In contrast related spasticity signs, such as involuntary muscle contractions (spasms) and cutaneous long-latency hyperreflexia, may be more problematic for residual motor function and general daily activities. As such there is a real need to characterize the impact of the symptoms of spasticity on neurological, functional, and daily activity during SCI rehabilitation. In this lecture the diagnostic utility of cutaneous hyperreflexia during both active and passive movement, as a possible hallmark of SCI spasticity will be discussed, in addition to its tractability to novel pharmacological and sensory neurorehabilitative strategies designed to modulate this specific sign of motor dysfunction.

Objective. To determine the temporal relationship between pain-related coping strategies and psychosocial factors with non-evoked neuropathic pain (NP) intensity and unpleasantness in patients during the subacute phase of spinal cord injury (SCI). Design. Exploratory longitudinal study of NP from 2 to 12 months. Setting. Hospital Nacional de Paraplejicos, Toledo, Spain. Subjects. A maximum of 26 patients with early symptoms of NP after SCI with a neurological level above the Th10 spinal level. Outcome Measures. Multidimensional Pain Inventory-Spinal Cord Injury Version, Coping Strategies Questionnaire, General 7-day pain intensity and unpleasantness rated with a visual analog scale, Spearman correlation analysis. Results. Pain-related coping strategies and psychosocial factors remained stable from 2 to 12 months after SCI. Initially pain intensity and unpleasantness were rated independently, but at 6 months were intercorrelated along with “pain severity,” “life interference,” and “catastrophizing.” “Coping self-statements” and “solicitous responses from others” were frequently adopted, compared with “ignoring pain sensations” and “catastrophising.” Perception of “pain severity” correlated with “support,” “solicitous responses from others,” “distracting responses from others,” and “life control” at 6 months, while pain intensity and unpleasantness were related to “coping self-statements,” “catastrophizing,” “distancing from pain,” and “praying.” Conclusions. Pilot longitudinal data suggest that pain-related coping strategies are adopted early after subacute SCI, and correlate with both pain intensity and unpleasantness. Future longitudinal studies of SCI with sufficient sample size will be instrumental to determine the causal relationship between psychosocial factors and coping strategies on pain.

Case report of a 42-year-old woman with non-evoked pain diagnosed with a cavernous C7-Th6 spinal haemangioma.To assess the effect of intramedullary haemorrhage (IH) on nociception and neuropathic pain (NP) at and below an incomplete spinal cord injury (SCI).Sensorimotor Function Group, Hospital Nacional de Parapléjicos de Toledo (HNPT).T2*-susceptibility weighted image (SWI) magnetic resonance imaging (MRI) of spinal haemosiderin and a complete pain history were performed 8 months following initial dysaesthesia complaint. Thermal pain thresholds were assessed with short 1 s stimuli, while evidence for central sensitization was obtained with psychophysical electronic Visual Analogue Scale rating of tonic 10 s 3 °C and 48 °C stimuli, applied at and below the IH. Control data were obtained from 10 healthy volunteers recruited from the HNPT.Non-evoked pain was present within the Th6 dermatome and lower legs. T2*-SWI MRI imaging detected extensive haemosiderin-rich IH (C7-Th5/6 spinal level). Cold allodynia was detected below the IH (left L5 dermatome) with short thermal stimuli. Tonic thermal stimuli applied to the Th6, Th10 and C7 dermatomes revealed widespread heat and cold allodynia.NP was diagnosed following IH, corroborated by an increase in below-level cold pain threshold with at- and below-level cold and heat allodynia. Psychophysical evidence for at- and below-level SCI central sensitization was obtained with tonic thermal stimuli. Early detection of IH could lead to better management of specific NP symptoms, an appreciation of the role of haemorrhage as an aggravating SCI physical factor, and the identification of specific spinal pathophysiological pain mechanisms.

Experimental pain can be modulated by nocebo manipulations through Pavlovian conditioning and expectancy. Neurogenic inflammation plays an important role in pain hypersensitivity and locally-exaggerated immune reactions yet its susceptibility to conditioning remains under investigated. This pilot study used a 4-day within-subject differential conditioning paradigm to investigate conditioning of capsaicin-induced neurogenic inflammation in healthy participants. On days 1–3, capsaicin solution (US) was applied to one forearm using colored filter paper as conditioned stimulus (CS+) while a neutral control solution associated with another color (CS−) was applied to the contralateral forearm. To test conditioning on day 4, the CS+ and CS− colors were applied as before using only control solution. CS applications were randomized between arms over days. Pain intensity and unpleasantness were assessed every 5 minutes for 35 minutes following CS application. Flare, a measure of neurogenic inflammation, was evaluated daily on both forearms pre- and post-application using a Laser Doppler Imager. Daily within-session flare changes were calculated for each forearm and were used to compute difference scores between forearms. Although 10 of 11 participants developed contingency awareness (expectancy), we found no conditioning of pain intensity, pain unpleasantness, or flare using a within-subject repeated measures design ( ps > . 05 ). This might be related to the USs (capsaicin-induced pain) gradually increasing and persistent effects suggesting that nocebo may not occur for pain-producing stimuli with gradual onsets.

The aim of the study was to evaluate the diagnostic methods and therapeutical results in patients with extrahepatic cholangiocarcinoma admitted between 2000 and 2003 and to assess the efficacy of various imaging methods.We included 124 consecutive patients with suspected cholangiocarcinoma who underwent endoscopic retrograde cholangiopancreatography (ERCP) between 2000 and 2003. Every patient underwent an ultrasound (US) examination before ERCP. ERCP was considered as the "gold standard" for diagnosis. The therapy applied consisted of endoscopic stenting, US guided biliary drainage or surgery. The sensitivity, specificity and accuracy were calculated for every tumour localisation and also globally for all tumours.The sensitivity, specificity and accuracy of US were 85.9 %, 76.9 %, and 84.4 % for hilar localization, 59.1 %, 50 % and 57.1 % for the mid bile duct (CBD) and 33.3 %, 42.8 % and 36.8 % for the distal CBD tumours. The global performances for US in diagnosing extrahepatic cholangiocarcinoma were 73.5 %, 61.5 % and 70.9 %. In 73 cases (74.5%) an endoscopic stent was placed. In 11 cases (11.2%) we performed an US guided biliary drainage and in 14 cases (14.2%) surgery was recommended.Ultrasonography proved to be a reliable method for the diagnosis of cholangiocarcinoma in spite of its low accuracy for distal localization. The combination of the two investigations (US and ERCP) was very efficient in the management of these patients. Endoscopic stenting for hilar localization is a good therapeutical option.

The aim of this study was to evaluate the effect of the PGE1 analogue, Misoprostol, on gallbladder fasting volume and meal-stimulated emptying. Prostaglandins' effects on the gallbladder were studied principally regarding mucus production during lithogenesis. In the few in vitro and in vivo studies, contradictory results concerning their influence upon gallbladder motility were obtained.13 healthy subjects, 8 females, 5 males, aged 23.4 years (ranges 22-25).Gallbladder volumes were assessed by ultrasound, after measuring the three diameters of the gallbladder in two perpendicular planes, using a conventional 2D equipment and a 3D equipment, after the 3D-reconstruction of the gallbladder. The volumes were calculated by means of the ellipsoid formula. Gallbladder emptying variables (residual volume, ejection fraction, area under emptying curve) were assessed during 90 minutes after a test meal (14 g fat, 425 kcal). Gallbladder emptying was evaluated in each subject on three different days: without prior Misoprostol administration, after 200 mg Misoprostol, and after 400 mg Misoprostol. Misoprostol was given orally as a single dose, 60 minutes before the meal. The two-tailed Student's t test for paired observations was used to compare the results.Misoprostol induced a significant decrease of the gallbladder fasting volume: from 12.8 +/- 4.4 (SD) ml (controls) to 9.1 +/- 3.6 ml (200 mg Misoprostol) and 5.4 +/- 2.6 ml (400 mg Misoprostol). Gallbladder meal-stimulated emptying was not influenced by Misoprostol.Our results indicated that, in healthy subjects, misoprostol induced a dose-dependent gallbladder emptying in the fasting state, but did not influence gallbladder postprandial emptying. Pre-prandial Misoprostol administration might be useful to treat gallbladder stasis in patients with chronic constipation, thus preventing gallstone formation.