Paroxysmal Extreme Pain Disorder (PEPD): clinical and genetic investigation

Objectifs 1) Caractériser une famille avec PEPD aux plans clinique, généalogique et génétique. 2) Identifier la cause génétique de la maladie dans cette famille, et en démontrer la pathogénicité. Introduction Le "Paroxysmal Extreme Pain Disorder " (PEPD) est une maladie génétique de transmission autosomique dominante caractérisée par des douleurs paroxystiques rectales, oculaires, maxillaires ou dans les membres inférieurs, qui peuvent être accompagnées d'un érythème. Les épisodes sont déclenchés par le contact cutané, les traumatismes mineurs et l'exposition au chaud. Leur intensité est telle qu'elle en est invalidante. PEPD est causé par des mutations du gène SCN9A, qui code pour la sous-unité alpha du canal sodique Nav1.7. Ce canal est distribué dans des cellules nerveuses périphériques appelées "nocicepteurs" qui sont impliquées dans la transmission du signal lié à la douleur. Méthode et Résultats Résultats Cliniques La partie clinique s'est déroulée à l'aide d'interviews structurées par visite directe, entretiens téléphoniques ou par correspondance. L'anamnèse, les données généalogiques et l'examen clinique ont été étudiés de façon extensive et tabulée. Résultats Génétiques Suite à l'identification de la mutation, un génotypage a été effectué à l'aide de techniques standards, afin de démontrer la co-ségrégation de la mutation avec la maladie. En outre, un groupe contrôle de 92 sujets suisses sans maladie connue ont été génotypés pour exclure la possibilité d'un polymorphisme rare. Grâce aux techniques de PCR et de séquençage, nous avons pu démontrer la présence d'une nouvelle mutation hétérozygote dans l'exon 27 du gène SCN9A, ce dernier étant impliqué dans plusieurs maladies dont PEPD. Cette mutation est codante, et conduit à un changement d'acide aminé dans le canal sodique Nav1.7 (mutation p.L1612P). Conclusions L'étude démontre la présence d'une nouvelle mutation du gène SCN9A permettant d'expliquer les symptômes décrits dans la famille investiguée. En effet, le groupe contrôle et tous les individus non symptomatiques de la famille n'ont pas la mutation, ce qui soutient fortement sa pathogénicité. En outre, il s'agit d'une mutation codante non-synonyme, localisée à proximité d'autres mutations causales précédemment étudiées au plan électrophysiologique.

Sedation and analgesia for colonoscopy: patient tolerance, pain, and cardiorespiratory parameters.

BACKGROUND: Colonoscopy is generally performed with the patient sedated and receiving analgesics. However, the benefit of the most often used combination of intravenous midazolam and pethidine on patient tolerance and pain and its cardiorespiratory risk have not been fully defined. METHODS: In this double-blind prospective study, 150 outpatients undergoing routine colonoscopy were randomly assigned to receive either (1) low-dose midazolam (35 micrograms/kg) and pethidine (700 micrograms/kg in 48 patients, 500 micrograms/kg in 102 patients), (2) midazolam and placebo pethidine, or (3) pethidine and placebo midazolam. RESULTS: Tolerance (visual analog scale, 0 to 100 points: 0 = excellent; 100 = unbearable) did not improve significantly more in group 1 compared with group 2 (7 points; 95% confidence interval [-2-17]) and group 3 (2 points; 95% confidence interval [-7-12]). Similarly, pain was not significantly improved in group 1 as compared with the other groups. Male gender (p < 0.001) and shorter duration of the procedure (p = 0.004), but not amnesia, were associated with better patient tolerance and less pain. Patient satisfaction was similar in all groups. Oxygen desaturation and hypotension occurred in 33% and 11%, respectively, with a similar frequency in all three groups. CONCLUSIONS: In this study, the combination of low-dose midazolam and pethidine does not improve patient tolerance and lessen pain during colonoscopy as compared with either drug given alone. When applying low-dose midazolam, oxygen desaturation and hypotension do not occur more often after combined use of both drugs. For the individual patient, sedation and analgesia should be based on the endoscopist's clinical judgement.

Consensus interdisciplinaire CHUV-HUG sur la prise en charge des douleurs du dos. Son application lausannoise dans la filière du dos [Inter-hospital CHUV-HUG medical consensus of back pain management. Its application in care pathways within CHUV of Lausanne].

Back pain is a considerable economical burden in industrialised countries. Its management varies widely across countries, including Switzerland. Thus, the University Hospital and University of Lausanne (CHUV) recently improved intern processes of back pain care. In an already existing collaborative context, the two university hospitals in French-speaking Switzerland (CHUV, University Hospital of Geneva), felt the need of a medical consensus, based on a common concept. This inter-hospital consensus produced three decisional algorithms that bear on recent concepts of back pain found in literature. Eventually, a fast track was created at CHUV, to which extern physicians will have an organised and rapid access. This fast track aims to reduce chronic back pain conditions and provides specialised education for general practitioners-in-training.

Pain assessment in PICU and NICU: Have we got it right?

Pain assessment in critically ill infants and nonverbal children remains a challenge for health professionals. Despite the numerous pain observational measures that have been developed or adapted for infants and children with impaired communication, pain prevalence in paediatric and neonatal intensive care unit remains too high. As pain assessment has been recognised as a pre-requisite for appropriate pain management, much effort was put in the validation or the adaptation of pain measures with little emphasis on implementation of these instruments into practice. Only a few studies demonstrated the benefit of using standardised protocols for the management of pain to guide practice with variable effects. When standardised protocols are undeniably useful in practice, they do not replace health professionals' clinical reasoning necessary to care for individuals. The diversity of the PICU population makes that pain scores need to be interpreted within its clinical context. This session will present pain assessment as a complex transaction that describes structured clinical reasoning from expert nurses that goes beyond the "silver" standard of hetero-evaluation of pain in non-communicative children. Besides pain scores, several patients and nurses factors play a major role in making decisions about analgesia and/or sedation. Patient's clinical instability, change in patient's clinical status, source for observed agitated behaviour, patient's known reactions to analgesia and sedation and anticipation of risks are factors that should be taken into account when implementing pain assessment and management guidelines in PICU and NICU.

Heerfordt syndrome with unilateral facial nerve palsy: a rare presentation of sarcoidosis.

BACKGROUND: Heerfordt syndrome is rare and is characterized by fever, uveitis, parotid gland enlargement, and facial nerve palsy. We hereby present a case of Heerfordt syndrome with unilateral facial nerve palsy as a presentation of sarcoidosis. HISTORY AND SIGNS: A 29-year-old male patient from Sri Lanka presented with eye redness OU, blurred vision OD, fever, headache, night sweat, fatigue, and weight loss (5 kg over 1 month). Examination revealed mild anterior uveitis OU, mild vitritis OD, fundus whitish lesions OU, left otalgia, taste disorders, bilateral parotid gland enlargement, and left facial nerve palsy. Work-up for infection or tumour was negative. Chest computed tomography and transbronchial lymph node biopsy set the diagnosis of sarcoidosis. THERAPY AND OUTCOME: The patient recovered completely within 2 months under therapy with prednisone and azathioprine. One year after onset of treatment, no recurrence was noted. CONCLUSIONS: Heerfordt syndrome is a rare manifestation of neurosarcoidosis and has to be included in the differential diagnosis of facial nerve palsy.

Epaule douloureuse: prise en charge ambulatoire [Shoulder pain in ambulatory practice].

Scapulalgias or omalgias are a frequent complaint, with more than half of them being linked to an injury of the rotators cuff. As they often become chronic, omalgias result in higher rates of absenteeism and significant health care costs. Scapulalgias have three main causes: posttraumatic, intrinsic of the joint, or extrinsic. The extrinsic omalgias, either of neurologic, cardiovascular, pulmonary, or abdominal etiology, require swift identification, as their treatment is often an emergency. Most of the scapulalgias can be treated conservatively. Main factors of poor prognosis are old age, women gender and associated cervicalgias.

La fonction de Moi auxiliaire dans la prise en charge des douloureux chroniques [The role of the auxiliary ego in the care of the chronic pain patient]

La prise en charge des patients souffrant de douleurs chroniques, à l'interface entre corps et psyché, nécessite une approche globale et souvent un réseau de soins coordonnés, contenant et stable. La psychiatrie de liaison a naturellement trouvé sa place dans ce réseau de soins spécifiques auprès des différents soignants impliqués. Les réflexions issues de cette expérience ont pour objectif de mieux comprendre le rôle thérapeutique des soignants et font émerger la notion de Moi auxiliaire comme élément clé dans le traitement de ces patients. Dans cet article, nous reprendrons les fondements historiques et conceptuels de la fonction de Moi auxiliaire pour nous intéresser à ses différentes applications dans ces prises en charge : consultation médicale, psychothérapie individuelle ou de groupe, colloque interdisciplinaire. The management of the patient suffering from chronic pain, situated on the interface between body and psyche, necessitates a global approach and often a coordinated, stable and containing network of care. Liaison psychiatry has become part of this network, together with various health care professionals from somatic disciplines. Based on these experiences, this article aims to better understand the therapeutic role of those who take care of the chronic pain patient by identifying the auxiliary ego as a key element of care. The historical development and conceptual framework of the auxiliary ego are utilized to highlight its roles in the different aspects of care of these patients:in the medical consultation, individual psychotherapy, group psychotherapy and in the interdisciplinary meetings.

Acid-sensing channels in human bladder: expression, function and alterations during bladder pain syndrome.

Purpose: To examine the possible role of H+-activated acid-sensing ion channels (ASICs) in pain perception we characterized their expression in bladder dome biopsies of Bladder Pain Syndrome (BPS) patients and controls, in cultured human urothelium and in urothelial TEU-2 cells.Materials and Methods: Cold cut biopsies from the bladder dome were obtained in 8 asymptomatic controls and 28 patients with symptoms of BPS. ASIC expression was analyzed by QPCR and immunofluorescence. The channel function was measured by electrophysiology.Results: ASIC1a, ASIC2a and ASIC3 mRNAs were detected in human bladder. Similar amounts of ASIC1a and -3 were detected in detrusor smooth muscle, whereas in urothelium ASIC3 levels were higher than -1a. ASIC2a mRNA levels were lower than either -1a or -3 in both layers. ASIC currents were measured in TEU-2 cells and in primary cultures of human urothelium, and ASIC expression was confirmed by QPCR. Differentiation of TEU-2 cells caused an up-regulation of ASIC2a and ASIC3, and a down-regulation of ASIC1a mRNAs. BPS patients showed an up-regulation of ASIC2a and -3 mRNA, whereas ASIC1a remained unchanged. In contrast, the mRNA levels of TRPV1 were down-regulated during BPS. All differences were statistically significant (p<0.05)Conclusions: Several different ASIC subunits are expressed in human bladder and TEU-2 cells, where their levels are regulated during urothelial differentiation. An up-regulation of ASIC2a and -3 in BPS suggests their involvement in increased pain and hyperalgesia. A down-regulation of TRPV1 mRNA levels might indicate a different regulatory mechanism, controlling its expression in human bladder.

The use of 3D planning in facial surgery: Preliminary observations.

Three-dimensional (3D) planning is becoming a more commonly used tool in maxillofacial surgery. At first used only virtually, 3D planning now also enables the creation of useful intraoperative aids such as cutting guides, which decrease the operative difficulty. In our center, we have used 3D planning in various domains of facial surgery and have investigated the advantages of this technique. We have also addressed the difficulties associated with its use. 3D planning increases the accuracy of reconstructive surgery, decreases operating time, whilst maintaining excellent esthetic results. However, its use is restricted to osseous reconstruction at this stage and once planning has been undertaken, it cannot be reversed or altered intraoperatively. Despite the attractive nature of this new tool, its uses and practicalities must be further evaluated. In particular, cost-effectiveness, hospital stay, and patient perceived benefits must be assessed.

Decreased Probability of Initial Pain Cessation in Classic Trigeminal Neuralgia Treated With Gamma Knife Surgery in Case of Previous Microvascular Decompression: A Prospective Series of 45 Patients With >1 Year of Follow-up.

BACKGROUND: Microvascular decompression (MVD) is the reference technique for pharmacoresistant trigeminal neuralgia (TN). OBJECTIVE: To establish whether the safety and efficacy of Gamma Knife surgery for recurrent TN are influenced by prior MVD. METHODS: Between July 1992 and November 2010, 54 of 737 patients (45 of 497 with >1 year of follow-up) had a history of MVD (approximately half also with previous ablative procedure) and were operated on with Gamma Knife surgery for TN in the Timone University Hospital. A single 4-mm isocenter was positioned in the cisternal portion of the trigeminal nerve at a median distance of 7.6 mm (range, 3.9-11.9 mm) anterior to the emergence of the nerve. A median maximum dose of 85 Gy (range, 70-90 Gy) was delivered. RESULTS: The median follow-up time was 39.5 months (range, 14.1-144.6 months). Thirty-five patients (77.8%) were initially pain free in a median time of 14 days (range, 0-180 days), much lower compared with our global population of classic TN (P = .01). Their actuarial probabilities of remaining pain-free without medication at 3, 5, 7, and 10 years were 66.5%, 59.1%, 59.1%, and 44.3%. The hypoesthesia actuarial rate at 1 year was 9.1% and remained stable until 12 years (median, 8 months). CONCLUSION: Patients with previous MVD showed a significantly lower probability of initial pain cessation compared with our global population with classic TN (P = .01). The toxicity was low (only 9.1% hypoesthesia); furthermore, no patient reported bothersome hypoesthesia. However, the probability of maintaining pain relief without medication was 44.3% at 10 years, similar to our global series of classic TN (P = .85). ABBREVIATIONS: BNI, Barrow Neurological InstituteCI, confidence intervalCTN, classic trigeminal neuralgiaGKS, Gamma Knife surgeryHR, hazard ratioMVD, microvascular decompressionTN, trigeminal neuralgia.