Somatosensory Impairment and Chronic Pain Following Stroke: An Observational Study.

BACKGROUND: Chronic pain and somatosensory impairment are common following a stroke. It is possible that an interaction exists between pain and somatosensory impairment and that a change in one may influence the other. We therefore investigated the presence of chronic pain and self-reported altered somatosensory ability in individuals with stroke, aiming to determine if chronic pain is more common in stroke survivors with somatosensory impairment than in those without. METHODS: Stroke survivors were invited to complete an online survey that included demographics, details of the stroke, presence of chronic pain, and any perceived changes in body sensations post-stroke. RESULTS: Survivors of stroke (n = 489) completed the survey with 308 indicating that they experienced chronic pain and 368 reporting perceived changes in somatosensory function. Individuals with strokes who reported altered somatosensory ability were more likely to experience chronic pain than those who did not (OR = 1.697; 95% CI 1.585, 2.446). Further, this difference was observed for all categories of sensory function that were surveyed (detection of light touch, body position, discrimination of surfaces and temperature, and haptic object recognition). CONCLUSIONS: The results point to a new characteristic of chronic pain in strokes, regardless of nature or region of the pain experienced, and raises the potential of somatosensory impairment being a rehabilitation target to improve pain-related outcomes for stroke survivors.

Effect of Graded Sensorimotor Retraining on Pain Intensity in Patients With Chronic Low Back Pain: A Randomized Clinical Trial.

Importance: The effects of altered neural processing, defined as altering neural networks responsible for perceptions of pain and function, on chronic pain remains unclear. Objective: To estimate the effect of a graded sensorimotor retraining intervention (RESOLVE) on pain intensity in people with chronic low back pain. Design, Setting, and Participants: This parallel, 2-group, randomized clinical trial recruited participants with chronic (>3 months) nonspecific low back pain from primary care and community settings. A total of 276 adults were randomized (in a 1:1 ratio) to the intervention or sham procedure and attention control groups delivered by clinicians at a medical research institute in Sydney, Australia. The first participant was randomized on December 10, 2015, and the last was randomized on July 25, 2019. Follow-up was completed on February 3, 2020. Interventions: Participants randomized to the intervention group (n = 138) were asked to participate in 12 weekly clinical sessions and home training designed to educate them about and assist them with movement and physical activity while experiencing lower back pain. Participants randomized to the control group (n = 138) were asked to participate in 12 weekly clinical sessions and home training that required similar time as the intervention but did not focus on education, movement, and physical activity. The control group included sham laser and shortwave diathermy applied to the back and sham noninvasive brain stimulation. Main Outcomes and Measures: The primary outcome was pain intensity at 18 weeks, measured on an 11-point numerical rating scale (range, 0 [no pain] to 10 [worst pain imaginable]) for which the between-group minimum clinically important difference is 1.0 point. Results: Among 276 randomized patients (mean [SD] age, 46 [14.3] years; 138 [50%] women), 261 (95%) completed follow-up at 18 weeks. The mean pain intensity was 5.6 at baseline and 3.1 at 18 weeks in the intervention group and 5.8 at baseline and 4.0 at 18 weeks in the control group, with an estimated between-group mean difference at 18 weeks of -1.0 point ([95% CI, -1.5 to -0.4]; P = .001), favoring the intervention group. Conclusions and Relevance: In this randomized clinical trial conducted at a single center among patients with chronic low back pain, graded sensorimotor retraining, compared with a sham procedure and attention control, significantly improved pain intensity at 18 weeks. The improvements in pain intensity were small, and further research is needed to understand the generalizability of the findings. Trial Registration: ANZCTR Identifier: ACTRN12615000610538.

Eliapixant is a selective P2X3 receptor antagonist for the treatment of disorders associated with hypersensitive nerve fibers.

ATP-dependent P2X3 receptors play a crucial role in the sensitization of nerve fibers and pathological pain pathways. They are also involved in pathways triggering cough and may contribute to the pathophysiology of endometriosis and overactive bladder. However, despite the strong therapeutic rationale for targeting P2X3 receptors, preliminary antagonists have been hampered by off-target effects, including severe taste disturbances associated with blocking the P2X2/3 receptor heterotrimer. Here we present a P2X3 receptor antagonist, eliapixant (BAY 1817080), which is both highly potent and selective for P2X3 over other P2X subtypes in vitro, including P2X2/3. We show that eliapixant reduces inflammatory pain in relevant animal models. We also provide the first in vivo experimental evidence that P2X3 antagonism reduces neurogenic inflammation, a phenomenon hypothesised to contribute to several diseases, including endometriosis. To test whether eliapixant could help treat endometriosis, we confirmed P2X3 expression on nerve fibers innervating human endometriotic lesions. We then demonstrate that eliapixant reduces vaginal hyperalgesia in an animal model of endometriosis-associated dyspareunia, even beyond treatment cessation. Our findings indicate that P2X3 antagonism could alleviate pain, including non-menstrual pelvic pain, and modify the underlying disease pathophysiology in women with endometriosis. Eliapixant is currently under clinical development for the treatment of disorders associated with hypersensitive nerve fibers.

Acupuncture for patients recovering from lacunar infarction: A protocol for systematic review and meta-analysis.

BACKGROUND: Lacunar infarction (LI) is the mild type in the classification of ischemic stroke, mostly occurs in the middle-aged and elderly, with mild hemiplegia and partial sensory disorder as the main manifestations. In the treatment of LI, acupuncture is often regarded as dominant therapy in the convalescence period. However, acupuncture for treatment of LI in the recovery period lacks high-quality reports and evidence-based medical evidence. Thus, we aim to evaluate the curative effect and safety of acupuncture for LI objectively. METHODS: Pubmed, Cochrane Library, Web of Science, EBSCO, Springer, China National Knowledge Infrastructure, Chinese Scientific and Technical Journals Database (VIP), Wan-fang Database, Chinese Biomedical Literature Database, Chinese Science Citation Database, and other electronic databases will be retrieved from the inception to May, 2021. Randomized controlled trials related to this subject will be searched. The inclusion criteria are established and a detailed literature search strategy is designed through discussion. Article retrieval, screening, excluding repetitive studies, assessment of quality, and data processing will be conducted by 2 reviewers independently using EndNote (X9) and Review Manager (5.3.5). The outcome measures include primary outcome measures (total effective rate, National Institute of Health Stroke Scale score, and Fugl-Meyer Assessment score), secondary outcome measures (blood pressure, plasma glucose, and blood lipid), and safety outcome measures. We will perform a meta-analysis, descriptive analysis, and subgroup analysis based on data conditions. RESULTS: The study of total effective rate, National Institute of Health Stroke Scale score, Fugl-Meyer Assessment score, blood pressure, plasma glucose, blood lipid, and adverse effects will provide evidenced outcome for high-quality synthesis and descriptive analysis. CONCLUSION: This systematic review will kindly provide evidence of whether acupuncture is an effective and safe intervention for LI in the recovery period. INPLASY REGISTRATION NUMBER: INPLASY202150060 (DOI:10.37766/inplasy2021.5.0060).

Severe Unilateral Proprioceptive Loss in Medullary- Rostral Spinal Cord Infarction. A Posterior Spinal Artery Syndrome.

We draw attention to a unique presentation, severe unilateral loss of limb proprioception, in patients with medullary and rostral spinal cord infarction. Two patients developed acute severe proprioceptive loss in the limbs ipsilateral to infarcts that involved the caudal medulla and rostral spinal cord. They also had symptoms and signs often found in lateral medullary infarction. The proprioceptive loss is attributable to injury to the gracile and cuneate nuclei and/or their projections to the medial lemniscus. The infarct territory is supplied by the posterior spinal branches of the vertebral artery near its penetration into the posterior fossa. The presence of severe ipsilateral proprioceptive loss in a patient with features of lateral medullary infarction indicates involvement of the rostral spinal cord.

Nociplastic pain: towards an understanding of prevalent pain conditions.

Nociplastic pain is the semantic term suggested by the international community of pain researchers to describe a third category of pain that is mechanistically distinct from nociceptive pain, which is caused by ongoing inflammation and damage of tissues, and neuropathic pain, which is caused by nerve damage. The mechanisms that underlie this type of pain are not entirely understood, but it is thought that augmented CNS pain and sensory processing and altered pain modulation play prominent roles. The symptoms observed in nociplastic pain include multifocal pain that is more widespread or intense, or both, than would be expected given the amount of identifiable tissue or nerve damage, as well as other CNS-derived symptoms, such as fatigue, sleep, memory, and mood problems. This type of pain can occur in isolation, as often occurs in conditions such as fibromyalgia or tension-type headache, or as part of a mixed-pain state in combination with ongoing nociceptive or neuropathic pain, as might occur in chronic low back pain. It is important to recognise this type of pain, since it will respond to different therapies than nociceptive pain, with a decreased responsiveness to peripherally directed therapies such as anti-inflammatory drugs and opioids, surgery, or injections.

Acute Dizziness, Vertigo, and Unsteadiness.

Vestibular symptoms, including dizziness, vertigo, and unsteadiness, are common presentations in the emergency department. Most cases have benign causes, such as vestibular apparatus dysfunction or orthostatic hypotension. However, dizziness can signal a more sinister condition, such as an acute cerebrovascular event or high-risk cardiac arrhythmia. A contemporary approach to clinical evaluation that emphasizes symptom duration and triggers along with a focused oculomotor and neurologic examination can differentiate peripheral causes from more serious central causes of vertigo. Patients with high-risk features should get brain MRI as the diagnostic investigation of choice.

Aging-induced microbleeds of the mouse thalamus compared to sensorimotor and memory defects.

The aim of this study is to investigate the relationship between aging and brain vasculature health. Three groups of mice, 3, 17-18, and 24 months, comparable to young adult, middle age, and old human were studied. Prussian blue histology and fast imaging with steady precession T2∗-weighted magnetic resonance imaging were used to quantify structural changes in the brain across age groups. The novel object recognition test was used to assess behavioral changes associated with anatomical changes. This study is the first to show that the thalamus is the most vulnerable brain region in the mouse model for aging-induced vascular damage. Magnetic resonance imaging data document the timeline of accumulation of thalamic damage. Histological data reveal that the majority of vascular damage accumulates in the ventroposterior nucleus and mediodorsal thalamic nucleus. Functional studies indicate that aging-induced vascular damage in the thalamus is associated with memory and sensorimotor deficits. This study points to the possibility that aging-associated vascular disease is a factor in irreversible brain damage as early as middle age.

Intra-arterial Stem Cell Therapy Diminishes Inflammasome Activation After Ischemic Stroke: a Possible Role of Acid Sensing Ion Channel 1a.

Studies from our lab demonstrated that 1 × 105 intra-arterial mesenchymal stem cells (IA MSCs) at 6 h following ischemic stroke are efficacious owing to its maximum homing due to elevated stromal derived factor 1 (SDF1) in the tissue. Further, IA MSCs could abate the infarct progression, improve functional outcome, and decrease expression of calcineurin by modifying neuronal Ca2+ channels following ischemic stroke. Since stroke pathology also encompasses acidosis that worsens the condition; hence, the role of acid sensing ion channels (ASICs) in this context could not be overlooked. ASIC1a being the major contributor towards acidosis triggers Ca2+ ions overload which progressively contributes towards exacerbation of neuronal injury following ischemic insult. Inflammasome involvement in ischemic stroke is well reported as activated ASIC1a increases the expression of inflammasome in a pH-dependent manner to trigger inflammatory cascade. Hence, the current study aimed to identify if IA MSCs can decrease the production of inflammasome by attenuating ASIC1a expression to render neuroprotection. Ovariectomized Sprague Dawley (SD) rats exposed to middle cerebral artery occlusion (MCAo) for 90 min were treated with phosphate-buffered saline (PBS) or 1 × 105 MSCs IA at 6 h to check for the expression of ASIC1a and inflammasome in different groups. Inhibition studies were carried out to explore the underlying mechanism. Our results demonstrate that IA MSCs improves functional outcome and oxidative stress parameters, and decreases the expression of ASIC1a and inflammasomes in the cortical brain region after ischemic stroke. This study offers a preliminary evidence of the role of IA MSCs in regulating inflammasome by modulating ASIC1a.

Cheiro-Oral syndrome.

The Cheiro-Oral (COS) Syndrome is a rare neurologic condition characterized by sensory disturbances involving the peri-oral area and the upper extremity, typically isolated to the hand or fingers. The thalamus contralateral to the symptomatic side is the brain region most commonly involved. Most cases are caused by ischemic or hemorrhagic strokes, although other structural lesions have been implicated. These include tumors, subdural hematomas, aneurysms, and infections. The unusual and seemingly unrelated nature of the symptoms may contribute to misdiagnosis and incomplete workup for potentially serious conditions. We are unable to identify a report of this condition in the emergency medicine literature despite the emergency department being the likely point of presentation for patients with COS. In this report, we describe two patients with COS who presented to our emergency department and review the features of COS as described in published case reports.

Submaximal Force Steadiness and Accuracy in Patients With Chronic Ankle Instability.

CONTEXT: Patients with chronic ankle instability (CAI) have demonstrated sensorimotor impairments. Submaximal force steadiness and accuracy measure sensory, motor, and visual function via a feedback mechanism, which helps researchers and clinicians comprehend the sensorimotor deficits associated with CAI. OBJECTIVE: To determine if participants with CAI experienced deficits in hip and ankle submaximal force steadiness and accuracy compared with healthy control participants. DESIGN: Case-control study. SETTING: Research laboratory. PATIENTS OR OTHER PARTICIPANTS: Twenty-one patients with CAI and 21 uninjured individuals. MAIN OUTCOME MEASURE(S): Maximal voluntary isometric contraction (MVIC) and force steadiness and accuracy (10% and 30% of MVIC) of the ankle evertors and invertors and hip abductors were assessed using the central 10 seconds (20%-87% of the total time) of the 3 trials. RESULTS: Relative to the control group, the CAI group demonstrated less accuracy of the invertors (P < .001). Across all motions, the CAI group showed less steadiness (P < .001) and less accuracy (P < .01) than the control group at 10% of MVIC. For MVIC, the CAI group displayed less force output in hip abduction than the uninjured group (P < .0001). CONCLUSIONS: Patients with CAI were unable to control ongoing fine force (10% and 30% of MVIC) through a feedback mechanism during an active test. These findings suggested that deficits in sensorimotor control predisposed patients with CAI to injury positions because they had difficulty integrating the peripheral information and correcting their movements in relation to visual information.

Occurrence and remission of loss of sensitivity of inferior alveolar nerve in mandibular fractures

ABSTRACT Purpose: to evaluate the occurrence of loss of sensitivity of the inferior alveolar nerve, and to monitor the remission of this change in patients with mandibular fractures subjected to surgical treatment. Methods: patients with mandibular fractures, surgically treated within one year, were prospectively evaluated. Data regarding etiology, fracture location, type and displacement, and surgical access, were obtained. The tactile and thermal tests were applied at eighteen points in the mental region, within a period of six months. Statistical tests were applied to compare the categories of variables and the period of observation (p ≤ 0.050). Results: during the study, 37 patients were included. There were 24 bilateral and 13 unilateral fractures. Sensory changes occurred in 56.8% of the patients in the preoperative period, in 83.8% of the patients, in the postoperative period, and 35.1% of the patients presented complete remission during the final period of the study. Conclusion: sensory changes occurred in about half of the patients, due to the fracture, increasing greatly in the postoperative period, with complete remission in about one third of the cases. The fracture type, degree of displacement and surgical access type influenced the occurrence of sensory alterations.

Diving medical officers as hospitalists: a case of arterial gas embolism following a routine GI procedure.

Arterial gas embolism is a well-described and frequently seen injury encountered in both civilian and military diving operations. It is becoming increasingly reported and potentially increasingly more common in the hospital environment as a complication of more frequent gastroenterology procedures. We present a case of a 49-year-old, active-duty female who developed significant left-sided neurological deficits manifesting as diffuse left-sided weakness, subjective confusion, and severe headache following esophagogastroduodenoscopy. With increased clinical suspicion for arterial gas embolism, the patient was evaluated by the hyperbaric medicine team at our facility and subsequently treated to near-resolution of symptoms by multiple hyperbaric oxygen treatments. This case highlights the importance of considering this rare complication during or following common invasive procedures. Furthermore, the unique training and experience of physicians with expertise in diving medicine and their ability to recognize these types of injury in the hospital setting highlights the importance of continued training in these fields within Military Medicine in addition to civilian Undersea and Hyperbaric Medicine fellowships.

Impairment of intermediate somatosensory function in corticobasal syndrome.

Corticobasal syndrome (CBS) is characterized by unilateral atrophy of the brain. New diagnostic criteria for CBS include intermediate somatosensory dysfunction. Here, we aimed to carefully examine intermediate somatosensory function to identify tests which can assess impairment in CBS patients. Using voxel-based morphometry (VBM), we also aimed to show the anatomical bases of these impairments. Subjects included 14 patients diagnosed with CBS and 14 patients with Parkinson's disease (PD). Patients were evaluated using intermediate somatosensory tests and neuropsychological assessments. VBM was used to analyze differences in gray matter volumes between CBS and PD patients. In the PD group, no tests showed a significant difference between the dominant-side onset and the non-dominant-side onset. In the CBS group, all tests showed worse scores on the affected side. For detecting intermediate somatosensory dysfunction in CBS, two tests are recommended: tactile object naming and 2-point discrimination. VBM analysis showed that the volume of the left post- and pre-central gyrus, and both sides of the supplementary motor area were significantly decreased in the CBS group compared to the PD group. Although CBS remains untreatable, early and correct diagnosis is possible by performing close examination of intermediate somatosensory function.

More Than Smell-COVID-19 Is Associated With Severe Impairment of Smell, Taste, and Chemesthesis.

Recent anecdotal and scientific reports have provided evidence of a link between COVID-19 and chemosensory impairments, such as anosmia. However, these reports have downplayed or failed to distinguish potential effects on taste, ignored chemesthesis, and generally lacked quantitative measurements. Here, we report the development, implementation, and initial results of a multilingual, international questionnaire to assess self-reported quantity and quality of perception in 3 distinct chemosensory modalities (smell, taste, and chemesthesis) before and during COVID-19. In the first 11 days after questionnaire launch, 4039 participants (2913 women, 1118 men, and 8 others, aged 19-79) reported a COVID-19 diagnosis either via laboratory tests or clinical assessment. Importantly, smell, taste, and chemesthetic function were each significantly reduced compared to their status before the disease. Difference scores (maximum possible change ±100) revealed a mean reduction of smell (-79.7 ± 28.7, mean ± standard deviation), taste (-69.0 ± 32.6), and chemesthetic (-37.3 ± 36.2) function during COVID-19. Qualitative changes in olfactory ability (parosmia and phantosmia) were relatively rare and correlated with smell loss. Importantly, perceived nasal obstruction did not account for smell loss. Furthermore, chemosensory impairments were similar between participants in the laboratory test and clinical assessment groups. These results show that COVID-19-associated chemosensory impairment is not limited to smell but also affects taste and chemesthesis. The multimodal impact of COVID-19 and the lack of perceived nasal obstruction suggest that severe acute respiratory syndrome coronavirus strain 2 (SARS-CoV-2) infection may disrupt sensory-neural mechanisms.

Is Recovery of Somatosensory Impairment Conditional for Upper-Limb Motor Recovery Early After Stroke?

Background. Spontaneous recovery early after stroke is most evident during a time-sensitive window of heightened neuroplasticity, known as spontaneous neurobiological recovery. It is unknown whether poststroke upper-limb motor and somatosensory impairment both reflect spontaneous neurobiological recovery or if somatosensory impairment and/or recovery influences motor recovery. Methods. Motor (Fugl-Meyer upper-extremity [FM-UE]) and somatosensory impairments (Erasmus modification of the Nottingham Sensory Assessment [EmNSA-UE]) were measured in 215 patients within 3 weeks and at 5, 12, and 26 weeks after a first-ever ischemic stroke. The longitudinal association between FM-UE and EmNSA-UE was examined in patients with motor and somatosensory impairments (FM-UE ≤ 60 and EmNSA-UE ≤ 37) at baseline. Results. A total of 94 patients were included in the longitudinal analysis. EmNSA-UE increased significantly up to 12 weeks poststroke. The longitudinal association between motor and somatosensory impairment disappeared when correcting for progress of time and was not significantly different for patients with severe baseline somatosensory impairment. Patients with a FM-UE score ≥18 at 26 weeks (n = 55) showed a significant positive association between motor and somatosensory impairments, irrespective of progress of time. Conclusions. Progress of time, as a reflection of spontaneous neurobiological recovery, is an important factor that drives recovery of upper-limb motor as well as somatosensory impairments in the first 12 weeks poststroke. Severe somatosensory impairment at baseline does not directly compromise motor recovery. The study rather suggests that spontaneous recovery of somatosensory impairment is a prerequisite for full motor recovery of the upper paretic limb.

Subjective postural vertical in Parkinson's disease with lateral trunk flexion.

BACKGROUND: Patients with Parkinson's disease (PD) and associated lateral trunk flexion (LTF) cannot accurately perceive their own verticality. OBJECTIVE: We measured the subjective postural vertical in coronal plane (SPVc) angle on patients' ipsilateral and contralateral sides and combined to clarify the effects of SPVc on LTF. We also investigated effects of the SPVc angle on LTF severity. METHODS: Thirty-nine patients (aged 74.1 ± 7.6 years) were divided between those with mild LTF (LTF angle < 10°, n = 34) and those with moderate to severe LTF (LTF angle ≥ 10°, n = 5) for comparison of the LTF angle, SPVc angle on both sides, inter-measurement variation in the SPVc angle, and the LTF to SPVc angle ratio (SPVc ratio). RESULTS: We found significant positive correlation between LTF and the SPVc angle on the combined (r = .54, P = .001), ipsilateral (r = .51, P = .002), and contralateral (r = .50, P = .002) sides. We found significant negative correlation between the LTF angle and the SPVc ratio on the combined SPVc (r = -.82, P = .001), ipsilateral (r = -.69, P = .001), and contralateral (r = -.75, P = .001) sides and between the LTF and ipsilateral side coefficient of variation (r = -.34, P = .038). SPVc angles on ipsilateral and contralateral sides were significantly greater in cases of moderate to severe LTF than in cases of mild LTF (P < .01). CONCLUSIONS: Subjective postural vertical in coronal plane assessment may be useful for assessing patients with PD and associated LTF.