PTPN11 mutation manifesting as LEOPARD syndrome associated with hypertrophic plexi and neuropathic pain.

BACKGROUND: LEOPARD syndrome (LS) belongs to the family of neuro-cardio-facio-cutaneous syndromes, which include Neurofibromatosis-1 (NF1), Noonan syndrome, Costello Syndrome, cardio-facio-cutaneous syndrome, Noonan-like syndrome with loose anagen hair and Legius syndrome. These conditions are caused by mutations in genes encoding proteins involved in the RAS-MAPK cellular pathway. Clinical heterogeneity and phenotype overlaps across those different syndromes is already recognized. CASE PRESENTATION: We hereby report a heterozygous de novo mutation in the PTPN11 gene (c.1403C > T) manifesting with a clinical picture of LS during childhood, and later development of neuropathic pain with hypertrophic plexi, which are typically observed in NF1 but have not been reported in LS. CONCLUSION: LS caused by PTPN11 mutations may be associated with hypertrophic roots and plexi. Consequently, clinicians should be aware of the possible development of neuropathic pain and consider specific diagnostic work-up and management.

Expert clinical reasoning and pain assessment in mechanically ventilated patients: A descriptive study.

BACKGROUND: Pain assessment in mechanically ventilated patients is challenging, because nurses need to decode pain behaviour, interpret pain scores, and make appropriate decisions. This clinical reasoning process is inherent to advanced nursing practice, but is poorly understood. A better understanding of this process could contribute to improved pain assessment and management. OBJECTIVE: This study aimed to describe the indicators that influence expert nurses' clinical reasoning when assessing pain in critically ill nonverbal patients. METHODS: This descriptive observational study was conducted in the adult intensive care unit (ICU) of a tertiary referral hospital in Western Switzerland. A purposive sample of expert nurses, caring for nonverbal ventilated patients who received sedation and analgesia, were invited to participate in the study. Data were collected in "real life" using recorded think-aloud combined with direct non-participant observation and brief interviews. Data were analysed using deductive and inductive content analyses using a theoretical framework related to clinical reasoning and pain. RESULTS: Seven expert nurses with an average of 7.85 (±3.1) years of critical care experience participated in the study. The patients had respiratory distress (n=2), cardiac arrest (n=2), sub-arachnoid bleeding (n=1), and multi-trauma (n=2). A total of 1344 quotes in five categories were identified. Patients' physiological stability was the principal indicator for making decision in relation to pain management. Results also showed that it is a permanent challenge for nurses to discriminate situations requiring sedation from situations requiring analgesia. Expert nurses mainly used working knowledge and patterns to anticipate and prevent pain. CONCLUSIONS: Patient's clinical condition is important for making decision about pain in critically ill nonverbal patients. The concept of pain cannot be assessed in isolation and its assessment should take the patient's clinical stability and sedation into account. Further research is warranted to confirm these results.

Gonalgies: que faire en médecine de premier recours [Knee pain in ambulatory practice].

Knee pain is a frequent complaint in ambulatory practice. Because of its complexity, the knee is prone to trauma, arthritis and the impact of aging. Septic arthritis is an emergency and has to be suspected when important knee pain is associated with fever, an alteration of the general condition, or in a particular social context. In most cases the clinical examination can identify the type of pathology. Conservative treatment is beneficial in most cases and physiotherapy a major component of the prognosis.

Neuropathic Pain Phenotype Does Not Involve the NLRP3 Inflammasome and Its End Product Interleukin-1β in the Mice Spared Nerve Injury Model.

The NACHT, LRR and PYD domains-containing protein 3 (NLRP3) inflammasome is one of the main sources of interleukin-1β (IL-1β) and is involved in several inflammatory-related pathologies. To date, its relationship with pain has not been studied in depth. The aim of our study was to elucidate the role of NLRP3 inflammasome and IL-1β production on neuropathic pain. Results showed that basal pain sensitivity is unaltered in NLRP3-/- mice as well as responses to formalin test. Spared nerve injury (SNI) surgery induced the development of mechanical allodynia and thermal hyperalgesia in a similar way in both genotypes and did not modify mRNA levels of the NLRP3 inflammasome components in the spinal cord. Intrathecal lipopolysaccharide (LPS) injection increases apoptosis-associated speck like protein (ASC), caspase-1 and IL-1β expression in both wildtype and NLRP3-/- mice. Those data suggest that NLRP3 is not involved in neuropathic pain and also that other sources of IL-1β are implicated in neuroinflammatory responses induced by LPS.

La radiochirurgie dans le traitement de la douleur [Radiosurgery in Pain Treatment]

Le traitement de radiochirurgie par Gamma Knife (GK) est utilisé de plus en plus souvent comme une alternative à la microchirurgie conventionnelle pour le traitement des pathologies neurochirurgicales intracrâniennes. Il s'agit d'irradier en dose unique et à haute énergie, en condition stéréotaxique et à l'aide d'une imagerie multimodale (imagerie par résonance magnétique [IRM], tomodensitométrie et éventuellement artériographie). Le GK a été inventé par le neurochirurgien suédois Lars Leksell, qui a réalisé le premier ciblage du nerf trijumeau en 1951, sur la base d'une radiographie standard. Depuis, les progrès de l'informatique et de la robotique ont permis d'améliorer la technique de radiochirurgie qui s'effectue actuellement soit par accélérateur linéaire de particules monté sur un bras robotisé (Novalis®, Cyberknife®), soit par collimation de près de 192 sources fixes (GK). La principale indication radiochirurgicale dans le traitement de la douleur est la névralgie du nerf trijumeau. Les autres indications, plus rares, sont la névralgie du nerf glossopharyngien, l'algie vasculaire de la face, ainsi qu'un traitement de la douleur d'origine cancéreuse par hypophysiolyse. Gamma Knife surgery (GKS) is widely used as an alternative to open microsurgical procedures as noninvasive treatment of many intracranial conditions. It consists of delivering a single dose of high energy in stereotactic conditions, and with the help of a multimodal imaging (e.g., magnetic resonance imaging [MRI], computer tomography, and eventually angiography). The Gamma Knife (GK) was invented by the Swedish neurosurgeon Lars Leksell who was the first to treat a trigeminal neuralgia sufferer in 1951 using an orthogonal X-ray tube. Since then, the progresses made both in the field of informatics and robotics have allowed to improve the radiosurgical technique, which is currently performed either by a linear accelerator of particles mounted on a robotized arm (Novalis®, Cyberknife®), or by collimation of 192 fixed Co-60 sources (GK). The main indication of GKS in the treatment of pain is trigeminal neuralgia. The other indications, less frequent, are: glossopharyngeal neuralgia, cluster headache, and hypophysiolyse for cancer pain.

Significance of an isolated new right bundle branch block in a patient with chest pain.

Chest pain is a common presenting symptom in emergency departments, and a typical manifestation of acute myocardial infarction (AMI). Recognition of ECG changes in AMI is essential for timely diagnosis and treatment. Right bundle branch block (RBBB) may be an isolated sign of AMI, and was previously considered as a criterion for fibrinolytic therapy. Since the most recent European Society of Cardiology and American Heart Association guidelines in 2013, RBBB alone is no longer considered a diagnostic criterion of AMI, even if it occurs in the context of acute chest pain, as RBBB does not usually interfere with the interpretation of ST-segment alteration. Our case illustrates an acute septal myocardial infarction with an isolated RBBB, and thus the importance of recognising this pattern in order to permit timely diagnosis and treatment.

Transcriptional regulator PRDM12 is essential for human pain perception.

Pain perception has evolved as a warning mechanism to alert organisms to tissue damage and dangerous environments. In humans, however, undesirable, excessive or chronic pain is a common and major societal burden for which available medical treatments are currently suboptimal. New therapeutic options have recently been derived from studies of individuals with congenital insensitivity to pain (CIP). Here we identified 10 different homozygous mutations in PRDM12 (encoding PRDI-BF1 and RIZ homology domain-containing protein 12) in subjects with CIP from 11 families. Prdm proteins are a family of epigenetic regulators that control neural specification and neurogenesis. We determined that Prdm12 is expressed in nociceptors and their progenitors and participates in the development of sensory neurons in Xenopus embryos. Moreover, CIP-associated mutants abrogate the histone-modifying potential associated with wild-type Prdm12. Prdm12 emerges as a key factor in the orchestration of sensory neurogenesis and may hold promise as a target for new pain therapeutics.

Energetics and mechanics of walking in patients with chronic low back pain and healthy matched controls.

PURPOSE: Walking in patients with chronic low back pain (cLBP) is characterized by motor control adaptations as a protective strategy against further injury or pain. The purpose of this study was to compare the preferred walking speed, the biomechanical and the energetic parameters of walking at different speeds between patients with cLBP and healthy men individually matched for age, body mass and height. METHODS: Energy cost of walking was assessed with a breath-by-breath gas analyser; mechanical and spatiotemporal parameters of walking were computed using two inertial sensors equipped with a triaxial accelerometer and gyroscope and compared in 13 men with cLBP and 13 control men (CTR) during treadmill walking at standard (0.83, 1.11, 1.38, 1.67 m s(-1)) and preferred (PWS) speeds. Low back pain intensity (visual analogue scale, cLBP only) and perceived exertion (Borg scale) were assessed at each walking speed. RESULTS: PWS was slower in cLBP [1.17 (SD = 0.13) m s(-1)] than in CTR group [1.33 (SD = 0.11) m s(-1); P = 0.002]. No significant difference was observed between groups in mechanical work (P ≥ 0.44), spatiotemporal parameters (P ≥ 0.16) and energy cost of walking (P ≥ 0.36). At the end of the treadmill protocol, perceived exertion was significantly higher in cLBP [11.7 (SD = 2.4)] than in CTR group [9.9 (SD = 1.1); P = 0.01]. Pain intensity did not significantly increase over time (P = 0.21). CONCLUSIONS: These results do not support the hypothesis of a less efficient walking pattern in patients with cLBP and imply that high walking speeds are well tolerated by patients with moderately disabling cLBP.

EEG reactivity to pain in comatose patients: Importance of the stimulus type.

INTRODUCTION: Electroencephalogram (EEG) background reactivity is a potentially interesting outcome predictor in comatose patients, especially after cardiac arrest, but recent studies report only fair interrater reliability. Furthermore, there are no definite guidelines for its testing. We therefore investigated the EEG effect of standardized noxious stimuli in comatose patients not reactive to auditory stimuli. METHODS: In this prospective study we applied a protocol using three different painful stimuli (bilateral nipple pinching, pinprick at the nose base, finger-nail compression on each side), grouped in three distinct clusters with an alternated sequence, during EEG recordings in comatose patients. We only analyzed recordings showing any reactivity to pain. Fisher and χ2 tests were used as needed to assess contingency tables. RESULTS: Of 42 studies, 12 did not show any background reactivity, 2 presented SIRPIDs, and 2 had massive artefacts; we thus analyzed 26 EEGs recorded in 17 patients (4 women, 24%). Nipple pinching more frequently induced a change in EEG background activity (p<0.001), with a sensitivity of 97.4% for reactivity. Neither the order of the stimuli in the cluster (p=0.723), nor the cluster order (p=0.901) influenced the results. CONCLUSION: In this pilot study, bilateral, synchronous nipple pinching seems to be the most efficient method to test nociceptive EEG reactivity in comatose patients. This approach may enhance interrater reliability, but deserves confirmation in larger cohorts.

Mieux comprendre le syndrome douloureux fémoro-patellaire... pour mieux le traiter [Patellofemoral pain syndrome: understand better in order to treat better].

Le syndrome douloureux fémoro-patellaire (SDFP) est l'une des causes les plus fréquentes de douleur antérieure du genou chez l'adolescent et l'adulte. De par son étiologie complexe, multifactorielle et encore mal comprise, sa prise en charge est un important challenge pour le praticien. Le diagnostic se fait principalement sur l'anamnèse et l'examen clinique du genou mais aussi de l'ensemble du membre inférieur, pouvant parfois nécessiter la réalisation d'une imagerie. Le traitement est dans la grande majorité des cas conservateur, principalement axé sur la rééducation avec de la physiothérapie ciblée et personnalisée. Le traitement chirurgical est réservé aux cas présentant une anomalie structurelle causale. Patellofemoral pain syndrome (PFPS) is one of the most frequent cause of anterior knee pain in adolescents and adults. Due to its complex etiology, which is multifactorial and still poorly understood, its management is a major challenge for the practitioner. The diagnosis is made primarily on the history and clinical examination of the knee, but also of the entire lower limb, which may sometimes require the completion of imaging. The treatment is mostly conservative, focussing on rehabilitation with targeted and personalized therapy. Surgical treatment is reserved for cases with a causal structural lesion.