Early life oxytocin treatment improves thermo-sensory reactivity and maternal behavior in neonates lacking the autism-associated gene Magel2.

Atypical responses to sensory stimuli are considered as a core aspect and early life marker of autism spectrum disorders (ASD). Although recent findings performed in mouse ASD genetic models report sensory deficits, these were explored exclusively during juvenile or adult period. Whether sensory dysfunctions might be present at the early life stage and rescued by therapeutic strategy are fairly uninvestigated. Here we found that under cool environment neonatal mice lacking the autism-associated gene Magel2 present pup calls hypo-reactivity and are retrieved with delay by their wild-type dam. This neonatal atypical sensory reactivity to cool stimuli was not associated with autonomic thermoregulatory alteration but with a deficit of the oxytocinergic system. Indeed, we show in control neonates that pharmacogenetic inactivation of hypothalamic oxytocin neurons mimicked atypical thermosensory reactivity found in Magel2 mutants. Furthermore, pharmacological intranasal administration of oxytocin to Magel2 neonates was able to rescue both the atypical thermosensory response and the maternal pup retrieval. This preclinical study establishes for the first-time early life impairments in thermosensory integration and suggest a therapeutic potential benefit of intranasal oxytocin treatment on neonatal atypical sensory reactivity for autism.

Cerebral mechanisms of hypnotic hypoesthesia. An ERP investigation on the expectancy stage of perception.

The present study aims at identifying reliable markers of neural preparatory processes during hypnosis. To this goal, we recorded the electroencephalographic activity of 23 volunteers regardless of their hypnotizability score. Somatosensory evoked potentials (SEPs) were elicited while participants received non-painful electrical stimuli on the left median nerve in the conditions of relaxation and hypnosis with suggestions of reduced sensation. SEPs analysis was focused on the pre-stimulus activity and revealed two main components: the prefrontal negativity (pN) and the somatosensory negativity (sN) over the frontal and parietal areas of the scalp, respectively. Results showed reduced amplitudes for both components under hypnosis, mostly for the pN, suggesting a change of top-down control of parietal and prefrontal areas. Furthermore, the sLORETA source imaging showed a deactivation of the lateral and anterior portions of the prefrontal cortex (PFC) during the hypnotic state. The present study highlights the downregulation of the PFC as a core aspect of the adopted hypnotic task and confirms the ability of hypnosis to modulate the activity of frontal executive functions. Further, since the majority of participants fell into the medium range of hypnotizability, the present findings could reflect the hypnosis effects in most of the population.

Manipulation-induced hypoalgesia in musculoskeletal pain populations: a systematic critical review and meta-analysis.

Background: Manipulation-induced hypoalgesia (MIH) represents reduced pain sensitivity following joint manipulation, and has been documented in various populations. It is unknown, however, whether MIH following high-velocity low-amplitude spinal manipulative therapy is a specific and clinically relevant treatment effect. Methods: This systematic critical review with meta-analysis investigated changes in quantitative sensory testing measures following high-velocity low-amplitude spinal manipulative therapy in musculoskeletal pain populations, in randomised controlled trials. Our objectives were to compare changes in quantitative sensory testing outcomes after spinal manipulative therapy vs. sham, control and active interventions, to estimate the magnitude of change over time, and to determine whether changes are systemic or not. Results: Fifteen studies were included. Thirteen measured pressure pain threshold, and four of these were sham-controlled. Change in pressure pain threshold after spinal manipulative therapy compared to sham revealed no significant difference. Pressure pain threshold increased significantly over time after spinal manipulative therapy (0.32 kg/cm2, CI 0.22-0.42), which occurred systemically. There were too few studies comparing to other interventions or for other types of quantitative sensory testing to make robust conclusions about these. Conclusions: We found that systemic MIH (for pressure pain threshold) does occur in musculoskeletal pain populations, though there was low quality evidence of no significant difference compared to sham manipulation. Future research should focus on the clinical relevance of MIH, and different types of quantitative sensory tests. Trial registration: Prospectively registered with PROSPERO (registration CRD42016041963).

Electrical stimulation for evoking offset analgesia: A human volunteer methodological study.

BACKGROUND: Offset analgesia (OA) is a disproportionally large decrease in the pain perception in response to a small decrease in the stimulation intensity. Traditionally, heat stimulation has been used to evoke OA. The aim of this study was to investigate whether OA could be evoked by electrical stimulation. METHODS: Healthy volunteers (N = 24) underwent two OA-experimental sessions consisting of heat stimuli intensities of 48-49-48 °C (traditional OA-paradigm) and electrical stimuli at 150%-180%-150% of the electrical pain perception (EPP) threshold. The three stimuli were delivered for 5 s (STIM1), 5 s (STIM2) and 20 s (STIM3), respectively. The sessions were randomized to the dominant or nondominant volar forearm. Two control sessions were performed with 30 s constantly heat (48 °C) and electrical stimuli (150% of the EPP) (CONTROL-STIM). In all sessions, the pain intensities were constantly rated on a Visual Analog Scale (VAS, 0-10). RESULTS: Significantly reduced STIM3 VAS ratings as compared to the CONTROL-STIM were reported for heat (1.81 ± 0.54; p < 0.001) and electrical (2.12 ± 0.42; p < 0.001) stimuli. The degrees of OA produced by heat and electrical stimuli were similar. A significantly positive correlation was found between thermal and electrical OA-effects (r = 0.48, p < 0.02). CONCLUSIONS: These findings demonstrate that electrical stimulation can elicit significant OA in humans indicating that the peripheral receptors can be bypassed and still evoke OA. Application of the electrical OA model may be of interest for further basic and clinical investigations as a potential new biomarker for central pain inhibition and provide the option to back-translate the technology to animals to understand the underlying neurobiology. SIGNIFICANCE: Electrical stimulation can elicit offset analgesia in humans, indicating that this perceptual modification can be obtained even bypassing peripheral receptors.

Surveillance of the armed forces as a sentinel system for detecting adverse effects of dietary supplements in the general population.

OBJECTIVE: Half the US population takes dietary supplements, but surveillance systems available to regulatory and public health authorities to determine whether specific dietary supplements present a risk are inadequate and numerous severe injuries and deaths have occurred from their consumption. Uniformed military personnel regularly use dietary supplements and are more likely to use potentially dangerous supplements than civilians. Recently, the supplement 1,3-dimethylamylamine (DMAA) was marketed for physical performance-enhancement and weight loss. However, after over 100 reports of illness attributed to DMAA, including six deaths, the Food and Drug Administration issued a warning to cease its sale. DESIGN: When DMAA was legal (2010-2011), we conducted, using convenience samples, supplement surveys of service members and determined prevalence of use and self-reported symptoms of DMAA use. SUBJECTS: We surveyed 4374 armed forces personnel using a standardized dietary supplement survey administered by local health-care professionals. RESULTS: Overall, 11 % of survey respondents used dietary supplements labelled as containing DMAA at least once/week. Regular users were over two times more likely to report tachycardia (P<0·0001), tremors (P<0·0001) and dizziness (P=0·0004), and over three times more likely to report numbness/tingling (P<0·0001) than non-users. CONCLUSIONS: Military services could readily monitor adverse events associated with dietary supplements using electronic surveys and medical records. Since armed forces personnel are much more likely than civilians to use potentially dangerous dietary supplements like DMAA, near real-time surveillance of them using electronic surveys and medical records would provide early warning to regulatory agencies and the medical and public health communities when high-risk dietary supplements are introduced.

Cheiro-Oral Syndrome.

Cheiro-Oral Syndrome (COS) is a very rare neurological syndrome associated with varied etiology. We report a 53-year-old man presented with left sided perioral and ipsilateral hand/fingers burning sensation for a one-month duration. On examination, he had hypesthesia over left perioral and distal palmar aspect of all five fingers. MRI revealed subacute infarct in the posterior limb of right internal capsule adjacent to and minimally involving thalamus. He was diagnosed as CheiroOral Syndrome as a result of ischemic stroke and managed.

Minimally symptomatic hypocalcaemia unmasking celiac disease.

INTRODUCTION: Celiac disease is an autoimmune disease of the small intestine which occurs in genetically predisposed people of all ages. A large clinical spectrum of manifestations accompanies the onset of the disease with diarrhoea, flatulence and weight loss being the most common. However, findings like osteoporosis, iron deficiency, anaemia and hypocalcaemia could also insinuate the existence of the disease. CASE PRESENTATION: We report the case of a 55-year-old man with numbness and tingling of the upper extremities due to hypocalcaemia that proved to be an uncommon case of celiac disease. CONCLUSION: A non-negligible number of adult patients with celiac disease can present with only minor and subclinical manifestations of the disease. As such, hypocalcaemia may be the sole manifestation of celiac disease. A high index of suspicion is needed for prompt diagnosis.

Manual Therapy and Exercise for a Patient With Neck-Tongue Syndrome: A Case Report.

STUDY DESIGN: Case report. BACKGROUND: Neck-tongue syndrome (NTS) is defined as neck and/or head pain accompanied by ipsilateral dysesthesia of the tongue with sudden rotation of the head. Proposed causes include compression or irritation of the C2 nerve root as it courses behind the atlantoaxial joint or hypertrophy of the inferior oblique muscle. The primary purpose of this case report was to describe the conservative physical therapy treatment of a patient with uncomplicated NTS. CASE DESCRIPTION: The patient was a 13-year-old girl who reported insidious onset of sharp pain in the neck, numbness/tingling of the ipsilateral tongue/face, and tinnitus with cervical rotation. Symptoms occurred several times a week for approximately 10 seconds. Examination revealed impaired function, increased forward head posture, decreased cervical range of motion, and positive neurodynamic assessment. The patient's treatment included manual therapy and exercise for postural stabilization. OUTCOMES: Following 8 visits, pain of the neck and tongue numbness had resolved. Score on the Patient-Specific Functional Scale (PSFS), cervical range of motion, and posture had also improved. At the 22-month follow-up, infrequent, momentary symptoms in the neck and dysesthesia of the tongue were reported. The PSFS remained the same. Objective measures were normal. DISCUSSION: This case report describes the physical therapy management of an individual with NTS. The management strategy followed a protocol similar to that used for cervicogenic headaches, due to the involvement of the upper cervical spine with both NTS and cervicogenic headache and the lack of evidence for the treatment of NTS. Level of Evidence Therapy, level 4.

Efficacy of neuromuscular electrostimulation intervention to improve physical function in haemodialysis patients.

BACKGROUND: Haemodialysis (HD) patients are characterised by muscle wasting, decreased physical function and poor quality of life. The objective was to analyse the effect of an intradialysis NMES training programme in muscular strength, functional capacity and quality of life in our HD patients. MATERIAL: HD patients were assigned to NMES (ESG) or control group (CG) in a 12-week single-centre prospective study. Transversal quadriceps muscular area, maximum length quadriceps strength (MLQS), handgrip, sit-to-stand-to-sit 10 test (STS10), "6-min walking test" (6MWT); EuroQol-5D health-related quality of life (EQ-5D) questionnaire, subjective global assessment (SGA) and NMES symptoms questionnaires (SQ) were completed. RESULTS: Thirty-eight patients (54 % men). Mean age 69.7 years. 32.1 months on HD, 23 ESG and 15 in CG. In contrast with CG, ESG significantly (*p < 0.05) improved MLQS* (10.2 6.7 vs. 13.1 8.1 kg), STS10* (41 18.7 vs. 37.2 23.9 s), 6MWT* (12 %, 280.5 vs. 312.4 m) and EQ-5D score* (52.7 vs. 65.5) at the end of the study. However, lower SQ score* (8.5 vs. 5.8 sympt./patient) in ESG was observed, mainly due to muscular pain* (2.2 vs. 1.2), cramps* (1.6 vs. 1.2), numbness* (1.7 vs. 1.1) or stinging* (1.5 vs. 1.1). In ESG, 44 and 72 % referred better wellness sensation and physical condition in SGA, respectively. CONCLUSIONS: Intradialytic NMES of both quadriceps improved muscular strength, functional capacity and quality of life in our HD patients. With the obtained results, NMES constitutes a novel therapeutic alternative to improve the deteriorated physical condition and quality of life of these patients.

Delayed blood-brain barrier disruption after shallow-water diving demonstrated by magnetic resonance imaging.

A 22-year-old diver presented to our emergency room complaining of headaches and left side numbness three days after diving to a depth of 6 metres for 25 minutes. On examination, he had left-sided hypaesthesia, and a post-contrast FLAIR brain MRI sequence revealed significant diffuse meningeal enhancement, indicating blood-brain-barrier (BBB) disruption. The patient was treated with hyperbaric oxygen; the initial four sessions resulted in only partial symptom improvement correlating with partial improvement in the MRI findings. Ten additional hyperbaric treatments resulted in complete resolution of the symptoms and normalization of MRI findings. The main aim of this case report is to present a probable, atypical, delayed-onset case of shallow-water decompression sickness culminating in significant BBB damage, which was demonstrated by special MRI techniques.

Lumbar disc herniation and cauda equina syndrome following spinal manipulative therapy: a review of six court decisions in Canada.

The purpose of this review is to expand practitioners' knowledge on areas of liability when treating low back pain patients. Six cases where chiropractors in Canada were sued for allegedly causing or aggravating lumbar disc herniation after spinal manipulative therapy were retrieved using the CANLII search database. The case series involves 4 men and 2 women with an average age of 37.3 years (range, 31-48 years). Trial courts' decisions were rendered between 2000 and 2011. This study highlights the following conclusions from Canadian courts: 1) informed consent is an ongoing process that cannot be entirely delegated to office personnel; 2) when the patient's history reveals risk factors for lumbar disc herniation the chiropractor has the duty to rule out disc pathology as an etiology for the symptoms presented by the patients before beginning anything but conservative palliative treatment; 3) lumbar disc herniation may be triggered by spinal manipulative therapy on vertebral segments distant from the involved herniated disc such as the thoracic spine.

Reduced upper limb sensation impairs mental chronometry for motor imagery after stroke: clinical and electrophysiological findings.

BACKGROUND: Motor imagery (MI) is increasingly recognized as a treatment option after stroke, but not all stroke patients are able to perform MI. OBJECTIVE: To examine if severe somatosensory deficits would affect MI ability. METHODS: The Box and Block Test (BBT) was used to evaluate mental chronometry as 1 component of MI. Two groups of stroke patients and an age-matched healthy control group (CG) were studied. Patient group 1 (n = 10, PG1) had a severe somatosensory impairment on the affected side and PG2 (n = 10) had pure motor strokes. All subjects first performed the BBT in a mental and in a real version. The time needed to move 15 blocks from 1 side of the box to the other was measured. To compare the groups independently of their performance level, a (real performance--MI)/(real performance) ratio was calculated. Corticospinal excitability was measured by transcranial magnetic stimulation at rest and while the subjects performed an imagined pinch grip. RESULTS: The CG performed the BBT faster than both patient groups, and PG1 was slower than PG2. MI ability was impaired in PG1 but only for the affected hand. Transcranial magnetic stimulation data showed an abnormally low MI-induced corticospinal excitability increase for the affected hand in PG1, but not in PG2. CONCLUSIONS: Severe somatosensory deficits impaired mental chronometry. A controlled study is necessary to clarify if these patients benefit at all from MI as an additional treatment.

[Subacute inflammatory demyelinating polyradiculopathy associated with Epstein-Barr viral infection: a clinical case].

The clinical case of treatment a patient for subacute inflammatory demyelinating polyradiculopathy associated with Epstein-Barr viral infection is presented. It is showed that the period of rehabilitation after the indicated disease lasts long enough. It requires the differentiated approach in acute and recovery treatment period with using of different rehabilitation measures.

Profiling of patients presenting with posttraumatic neuropathy of the trigeminal nerve.

AIMS: To describe the cause, clinical signs, and symptoms of patients presenting to a tertiary care center with iatrogenic lesions to the mandibular branches of the trigeminal nerve. METHODS: Pain history, pain scores using the visual analog scale, and mechanosensory testing results were recorded from 93 patients with iatrogenic lingual nerve injuries (LNI) and 90 patients with iatrogenic inferior alveolar nerve injuries (IANI). Results were analyzed using the SPSS statistical software. Chi-square tests were applied for nonparametric testing of frequencies, where P ⋜ .05 indicated statistical significance. Appropriate correlations were also carried out between certain data sets. RESULTS: Significantly more females were referred than males (P < .05). Overall, third molar surgery (TMS) caused 73% of LNI, followed by local anesthesia (LA) (17%). More diverse procedures caused IANI, including TMS (60%), LA (19%), implants (18%), and endodontics (8%). Approximately 70% of patients presented with neuropathic pain coincident with anesthesia and÷or paresthesia. Neuropathy was demonstrable in all patients with varying degrees of loss of mechanosensory function, paresthesia, dysesthesia, allodynia, and hyperalgesia. Functionally, IANI and LNI patients mostly had problems with speech and eating, where speech was affected amongst significantly more patients with LNI (P < .001). Sleep, brushing teeth, and drinking were significantly more problematic for IANI patients (P < .05, P < .001, and P < .0001, respectively). CONCLUSION: Neuropathic pain, as well as anesthesia, frequently occurs following iatrogenic trigeminal nerve injury similar to other posttraumatic sensory nerve injuries. This must be acknowledged by clinicians as a relatively common problem and informed consent appropriately formulated for patients at risk of trigeminal nerve injuries in relation to dentistry requires revision.

Trigeminal nerve injuries in relation to the local anaesthesia in mandibular injections.

OBJECTIVE: This study reports the signs and symptoms that are the features of trigeminal nerve injuries caused by local anaesthesia (LA). METHODS: Thirty-three patients with nerve injury following LA were assessed. All data were analysed using the SPSS statistical programme and Microsoft Excel. RESULTS: Lingual nerve injury (LNI; n = 16) and inferior alveolar nerve injury (IANI; n = 17) patients were studied. LNI were more likely to be permanent. Neuropathy was demonstrable in all patients with varying degrees of paraesthesia, dysaesthesia (in the form of burning pain) allodynia and hyperalgesia. All injuries were unilateral. A significantly greater proportion of LNI patients (75%) had received multiple injections, in comparison to IANI patients (41%) (p <0.05). Fifty percent of patients with LNI reported pain on injection. The presenting signs and symptoms of both LNI and IANI included pain. These symptoms of neuropathy were constant in 88% of the IANI group and in 44% of LNI patients. Functional difficulties were different between the LNI and IANI groups, a key difference being the presence of severely altered taste perception in nine patients with LA-induced LNI. CONCLUSIONS: Chronic pain is often a symptom after local anaesthetic-induced nerve injury. Patients in the study population with lingual nerve injury were significantly more likely to have received multiple injections compared to those with IANI.

Efficacy of keishibukuryogan, a traditional Japanese herbal medicine, in treating cold sensation and numbness after stroke: clinical improvement and skin temperature normalization in 22 stroke patients.

Cold sensation and numbness have been reported as post-stroke sensory sequelae attributable to distal axonopathy, which is caused by chronic ischemia of diseased limbs resulting from dysfunction of vasomotor regulatory systems. Keishibukuryogan is a traditional herbal medicine used to treat symptoms of peripheral ischemia such as cold extremities. This study investigated clinical improvement and skin temperature in peripheral ischemia patients to determine the efficacy of keishibukuryogan in alleviating post-stroke cold sensation and numbness. Twenty-two stroke patients with cold sensation and/or numbness were enrolled in this study. Subjective cold sensation and numbness, evaluated using the visual analogue scale, were found in 21 and 31 limbs, respectively. The skin temperature of diseased and healthy limbs was recorded. We observed all patients for 4 weeks and 17 patients for 8 weeks after administration of keishibukuryogan. The skin temperature of diseased limbs was significantly higher than baseline at 4 weeks and 8 weeks, whereas that of healthy limbs did not change significantly. Cold sensation and numbness were significantly improved at 4 weeks and 8 weeks compared to baseline. Keishibukuryogan administration resulted in warming of diseased limbs and improved cold sensation and numbness, probably by increasing peripheral blood flow.