The c-Jun N-terminal kinase 1 (JNK1) in spinal astrocytes is required for the maintenance of bilateral mechanical allodynia under a persistent inflammatory pain condition.

Peripheral inflammation induces persistent central sensitization characterized by mechanical allodynia and heat hyperalgesia that are mediated by distinct mechanisms. Compared to well-demonstrated mechanisms of heat hyperalgesia, mechanisms underlying the development of mechanical allodynia and contralateral pain are incompletely known. In this study, we investigated the distinct role of spinal JNK in heat hyperalgesia, mechanical allodynia, and contralateral pain in an inflammatory pain model. Intraplantar injection of complete Freund's adjuvant (CFA) induced bilateral mechanical allodynia but unilateral heat hyperalgesia. CFA also induced a bilateral activation (phosphorylation) of JNK in the spinal cord, and the phospho JNK1 (pJNK1) levels were much higher than that of pJNK2. Notably, both pJNK and JNK1 were expressed in GFAP-positive astrocytes. Intrathecal infusion of a selective peptide inhibitor of JNK, D-JNKI-1, starting before inflammation via an osmotic pump, reduced CFA-induced mechanical allodynia in the maintenance phase but had no effect on CFA-induced heat hyperalgesia. A bolus intrathecal injection of D-JNKI-1 or SP600126, a small molecule inhibitor of JNK also reversed mechanical allodynia bilaterally. In contrast, peripheral (intraplantar) administration of D-JNKI-1 reduced the induction of CFA-induced heat hyperalgesia but did not change mechanical allodynia. Finally, CFA-induced bilateral mechanical allodynia was attenuated in mice lacking JNK1 but not JNK2. Taken together, our data suggest that spinal JNK, in particular JNK1 plays an important role in the maintenance of persistent inflammatory pain. Our findings also reveal a unique role of JNK1 and astrocyte network in regulating tactile allodynia and contralateral pain.

Severe neurologic manifestations from cervical spine instability in spondylo-megaepiphyseal-metaphyseal dysplasia.

Spondylo-megaepiphyseal-metaphyseal dysplasia (SMMD; OMIM 613330) is a dysostosis/dysplasia caused by recessive mutations in the homeobox-containing gene, NKX3-2 (formerly known as BAPX1). Because of the rarity of the condition, its diagnostic features and natural course are not well known. We describe clinical and radiographic findings in six patients (five of which with homozygous mutations in the NKX3-2 gene) and highlight the unusual and severe changes in the cervical spine and the neurologic complications. In individuals with SMMD, the trunk and the neck are short, while the limbs, fingers and toes are disproportionately long. Radiographs show a severe ossification delay of the vertebral bodies with sagittal and coronal clefts, missing ossification of the pubic bones, large round "balloon-like" epiphyses of the long bones, and presence of multiple pseudoepiphyses at all metacarpals and phalanges. Reduced or absent ossification of the cervical vertebrae leads to cervical instability with anterior or posterior kinking of the cervical spine (swan neck-like deformity, kyknodysostosis). As a result of the cervical spine instability or deformation, five of six patients in our series suffered cervical cord injury that manifested clinically as limb spasticity. Although the number of individuals observed is small, the high incidence of cervical spine deformation in SMMD is unique among skeletal dysplasias. Early diagnosis of SMMD by recognition of the radiographic pattern might prevent of the neurologic complications via prophylactic cervical spine stabilization. © 2012 Wiley Periodicals, Inc.

False negative apraclonidine test in two patients with Horner syndrome

BACKGROUND: Because of denervation supersensitivity, a miotic pupil in a sympathetically-denervated eye dilates in response to a dilute or weak alpha-1-agonist drug. A reversal of anisocoria after topical apraclonidine is considered as a positive test result that diagnoses a unilateral Horner syndrome. HISTORY AND SIGNS: Two women aged 34 and 46 years with a cocaine-confirmed oculosympathetic defect (Horner syndrome) were tested with 1 % topical apraclonidine on separate days. THERAPY AND OUTCOME: In one patient, her miotic Horner pupil dilated marginally but not enough to reverse the baseline anisocoria. Additionally, the upper lid on the same side retracted. There was no discernable effect of apraclonidine on the normal, contralateral eye. In the second patient, there was no pupillary response to apraclonidine but there was resolution of her ptosis. CONCLUSIONS: Neither patient demonstrated a reversal of anisocoria, the current criterion for diagnosing a Horner syndrome using apraclonidine. Thus, these two patients with an established oculosympathetic defect were said to have a "negative test" for Horner syndrome. Yet both women showed subtle pupil and/or lid changes in response to apraclonidine that were consistent with sympathetic denervation supersensitivity. Reversal of anisocoria following topical apraclonidine does not occur in all patients with a unilateral oculosympathetic defect and more specific parameters for defining a positive test result might optimize apraclonidine's utility as a diagnostic test for Horner syndrome

Conceptual framework for strengthening exercises to prevent hamstring strains

High-speed running accounts for the majority of hamstring strains in many sports. The terminal swing phase is believed to be the most hazardous as the hamstrings are undergoing an active lengthening contraction in a long muscle length position. Prevention-based strength training mainly focuses on eccentric exercises. However, it appears crucial to integrate other parameters than the contraction type. Therefore, the aim of this study is to present a conceptual framework based on six key parameters (contraction type, load, range of motion, angular velocity, uni-/bilateral exercises, kinetic chain) for the hamstring's strength exercise for strain prevention. Based on the biomechanical parameters of sprinting, it is proposed to use high-load eccentric contractions. The movement should be performed at a slow to moderate angular velocity and focused at the knee joint, while the hip is kept in a large flexion position in order to reach a greater elongation stress of the hamstrings than in the terminal swing phase. In this way, we believe that, during sprinting, athletes would be better trained to brake the knee extension effectively in the whole range of motion without overstretch of the hamstrings. Finally, based on its functional application, unilateral open kinetic chain should be preferred.

Toxoplasma gondii: flat-mounting of retina as a new tool for the observation of ocular infection in mice.

Ocular toxoplasmosis is the principal cause of posterior uveitis and a leading cause of blindness. Animal models are required to improve our understanding of the pathogenesis of this disease. The method currently used for the detection of retinal cysts in animals involves the observation, under a microscope, of all the sections from infected eyes. However, this method is time-consuming and lacks sensitivity. We have developed a rapid, sensitive method for observing retinal cysts in mice infected with Toxoplasma gondii. This method involves combining the flat-mounting of retina - a compromise between macroscopic observation and global analysis of this tissue - and the use of an avirulent recombinant strain of T. gondii expressing the Escherichia coli beta-galactosidase gene, visually detectable at the submacroscopic level. Single cyst unilateral infection was found in six out of 17 mice killed within 28 days of infection, whereas a bilateral infection was found in only one mouse. There was no correlation between brain cysts number and ocular infection.

Ligamentous and tendinous anatomy of the intermetacarpal and common carpometacarpal joints: evaluation with MR imaging and MR arthrography.

PURPOSE: The purpose of this work was to demonstrate the normal ligamentous and tendinous anatomy of the intermetacarpal (IMC) and common carpometacarpal (CCMC) joints with MRI and MR arthrography. METHOD: MR images of 22 wrists derived from fresh human cadavers were obtained before and after arthrography. The MR imaging features of the ligaments and tendons about the CCMC and IMC joints and the joints themselves were analyzed in a randomized fashion and correlated with those seen on anatomic sections. RESULTS: Six CCMC ligaments were visualized. The dorsal and palmar CCMC ligaments and the pisometacarpal ligament were best visualized in the sagittal plane. The radial and ulnar CCMC collateral ligaments and the capito-third metacarpal ligament were best visualized in the coronal plane. Three main IMC ligaments were observed: a dorsal and a palmar ligament and an interosseous ligament complex. All three ligaments were best visualized in the axial plane. Four tendinous insertions to the metacarpal bases were evident. CONCLUSION: The anatomy of the ligaments and tendinous insertions about the second to fifth IMC and the CCMC joints is well demonstrated by MR imaging and MR arthrography. MR arthrography does not significantly improve the visualization of these complex structures.

EFNS guidelines on cognitive rehabilitation: report of an EFNS task force.

Disorders of language, spatial perception, attention, memory, calculation and praxis are a frequent consequence of acquired brain damage [in particular, stroke and traumatic brain injury (TBI)] and a major determinant of disability. The rehabilitation of aphasia and, more recently, of other cognitive disorders is an important area of neurological rehabilitation. We report here a review of the available evidence about effectiveness of cognitive rehabilitation. Given the limited number and generally low quality of randomized clinical trials (RCTs) in this area of therapeutic intervention, the Task Force considered, besides the available Cochrane reviews, evidence of lower classes which was critically analysed until a consensus was reached. In particular, we considered evidence from small group or single cases studies including an appropriate statistical evaluation of effect sizes. The general conclusion is that there is evidence to award a grade A, B or C recommendation to some forms of cognitive rehabilitation in patients with neuropsychological deficits in the post-acute stage after a focal brain lesion (stroke, TBI). These include aphasia therapy, rehabilitation of unilateral spatial neglect (ULN), attentional training in the post-acute stage after TBI, the use of electronic memory aids in memory disorders, and the treatment of apraxia with compensatory strategies. There is clearly a need for adequately designed studies in this area, which should take into account specific problems such as patient heterogeneity and treatment standardization.

Evaluation of the caloric test by combining 3 response parameters.

The slow-phase velocity of nystagmus is one of the most sensitive parameters of vestibular function and is currently the standard for evaluating the caloric test. However, the assessment of this parameter requires recording the response by using nystagmography. The aim of this study was to evaluate whether frequency and duration of the caloric nystagmus, as measured by using a clinical test with Frenzel glasses, could predict the result of the recorded test. The retrospective analysis of 222 caloric test results recorded by means of electronystagmography has shown a good association between the 3 parameters for unilateral weakness. The asymmetry observed in the velocity can be predicted by a combination of frequency and duration. On the other hand, no relationship was observed between the parameters for directional preponderance. These results indicate that a clinical caloric test with frequency and duration as parameters can be used to predict the unilateral weakness, which would be obtained by use of nystagmography. We propose an evaluation of the caloric test on the basis of diagrams combining the 3 response parameters.

Induction of the acyl-coenzyme A synthetase gene by fibrates and fatty acids is mediated by a peroxisome proliferator response element in the C promoter.

The long-chain acyl-coenzyme A synthetase (ACS) gene gives rise to three transcripts containing different first exons preceded by specific regulatory regions A, B, and C. Exon-specific oligonucleotide hybridization indicated that only A-ACS mRNA is expressed in rat liver. Fibrate administration induced liver C-ACS strongly and A-ACS mRNA to a lesser extent. B-ACS mRNA remained undetectable. In primary rat hepatocytes and Fa-32 hepatoma cells C-ACS mRNA increased after treatment with fenofibric acid, alpha-bromopalmitate, tetradecylthioacetic acid, or alpha-linolenic acid. Nuclear run-on experiments indicated that fenofibric acid and alpha-bromopalmitate act at the transcriptional level. Transient transfections showed a 3.4-, 2.3-, and 2.2-fold induction of C-ACS promoter activity after fenofibric acid, alpha-bromopalmitate, and tetradecylthioacetic acid, respectively. Unilateral deletion and site-directed mutagenesis identified a peroxisome proliferator activator receptor (PPAR)-responsive element (PPRE) mediating the responsiveness to fibrates and fatty acids. This ACS PPRE contains three imperfect half sites spaced by 1 and 3 oligonucleotides and binds PPAR.retinoid X receptor heterodimers in gel retardation assays. In conclusion, the regulation of C-ACS mRNA expression by fibrates and fatty acids is mediated by PPAR.retinoid X receptor heterodimers interacting through a PPRE in the C-ACS promoters. PPAR therefore occupies a key position in the transcriptional control of a pivotal enzyme controlling the channeling of fatty acids into various metabolic pathways.

Efficacy of the Semont maneuver in benign paroxysmal positional vertigo.

OBJECTIVES: To assess the efficacy of the Semont maneuver in the treatment of benign paroxysmal positional vertigo (BPPV) of the posterior semicircular canal and to evaluate the possible effect of various factors on the efficacy of this maneuver. DESIGN AND SETTING: Retrospective study in an outpatient clinic. PATIENTS: Two hundred seventy-eight patients presenting with symptomatic, unilateral BPPV of the posterior semicircular canal, exclusively treated with the Semont maneuver. INTERVENTIONS: During the first consultation, each patient was treated with a Semont maneuver. When BPPV persisted, this maneuver was repeated during follow-up visits, performed at weekly intervals. MAIN OUTCOME MEASURES: Patients were considered cured when vertigo disappeared within 30 days (allowing up to 4 maneuvers). RESULTS: More than 90% of patients were cured after a maximum of 4 maneuvers, and 83.5% were cured after only 2 maneuvers. The efficacy of the maneuver decreased each time it was repeated (from 62.6% at the first maneuver to 18.2% at the fourth). The duration of symptoms before initial consultation and the etiology of BPPV had a significant effect on the maneuver's efficacy (P<.001 and P =.002, respectively), whereas age (P =.12), sex (P =.06), and affected side (P =.20) had no effect. CONCLUSIONS: The Semont maneuver demonstrated a 90.3% cure rate after a maximum of 4 sessions. Patients consulting late (>6 months after the beginning of symptoms) or having traumatic BPPV had lower recovery rates than patients without these factors (74.7% vs 96.5%).

Prenatal detection of congenital renal malformations by fetal ultrasonographic examination: an analysis of 709,030 births in 12 European countries.

The study was performed to evaluate the prevalence of prenatal ultrasound diagnoses for renal anomalies in 20 registries of 12 European countries, and to compare the different prenatal scanning policies. Standardized data were acquired from 709,030 livebirths, stillbirths, and induced abortions during the study period of 2.5 years and transmitted for central analysis. At least one renal malformation was diagnosed in 1130 infants and fetuses. Prenatal diagnosis (PD) was given in 81.8% of all cases, 29% of these pregnancies were terminated. The highest detection rate was reported for unilateral multicystic dysplastic kidneys with 97% (102/105). An early diagnosis was documented for exstrophy of bladder at a mean gestational age of 18.5 weeks. Dilatations of the upper urinary tract were seen late in pregnancy at 28.3 weeks. Terminations of pregnancies (TOP) were performed in 67% (58/86) of the detected bilateral renal agenesis/dysgenesis, but only 4% of the unilateral multicystic dysplastic renal malformations (4/102). In about 1/3 of the cases, renal malformations are within the category of associated malformations, which include multiple non-syndromal malformations, chromosomal aberrations, and non-chromosomal syndromes. Renal malformations were detected in 2/3 of the associated category by the first prenatal ultrasound scan. Detection rates vary in the different countries of the European community due to diverse policies, ethical, and religious background. Countries with no routine ultrasound show the lowest rates in detection, and termination of pregnancy. Prenatally detected renal malformations should result in a careful examination for further anomalies. Prenatal ultrasound fulfills the needs of screening examinations and is a good tool in detecting lethal and severe renal malformations.

Primärer Hyperaldosteronismus bei Katzen [Primary hyperaldosteronism in cats].

Primary hyperaldosteronism is a clinical syndrome characterized by an elevated aldosterone secretion by the adrenals. The present case series describes 7 cats with primary hyperaldosteronism, which were presented between 2002 and 2011. Common clinical symptoms were weakness, anorexia, cervical ventroflexion and blindness. All cats showed hypokalemia. In 6 cats, blood pressure was determined: 5 cats showed hypertension, of which 4 animals exhibited retinal detachment and blindness. In the ultrasonographic examination, unilateral adrenomegaly was present in 6 cats whereas one animal showed normal adrenals. In 4 cats, the serum aldosterone concentration was above the reference range. Five cats underwent unilateral adrenalectomy, which was accomplished uneventfully and returned the electrolytes back to normal. Histopathological examination of the adrenals revealed 2 carcinomas and 4 adenomas; one cat with ultrasonographic normal adrenals exhibited bilateral nodular hyperplasia.

Prise en charge des fentes labio-maxillo-palatines au CHUV = [Children born with a cleft: treatment at the CHUV in Lausanne]

A cleft can be labial, labial-maxillary, unilateral or bilateral labial-maxillary-palatal, or isolated palatal. A multidisciplinary team includes several specialists who will handle the diverse problems of children born with a cleft. This team will follow the child through each developmental stage and assemble an optimal treatment plan, thus reducing the onus on the family. Depending on the type of cleft and the age of the child, feeding, speech, ORL, dental, orthodontic, esthetic and possibly also psychological problems will be taken care of. This is why cleft treatment starts at the time it is diagnosed, before or after birth, and ends when the child is fully grown. It requires a complete interdisciplinary team and the collaboration with obstetricians and geneticians.

BCOR analysis in patients with OFCD and Lenz microphthalmia syndromes, mental retardation with ocular anomalies, and cardiac laterality defects.

Oculofaciocardiodental (OFCD) and Lenz microphthalmia syndromes form part of a spectrum of X-linked microphthalmia disorders characterized by ocular, dental, cardiac and skeletal anomalies and mental retardation. The two syndromes are allelic, caused by mutations in the BCL-6 corepressor gene (BCOR). To extend the series of phenotypes associated with pathogenic mutations in BCOR, we sequenced the BCOR gene in patients with (1) OFCD syndrome, (2) putative X-linked ('Lenz') microphthalmia syndrome, (3) isolated ocular defects and (4) laterality phenotypes. We present a new cohort of females with OFCD syndrome and null mutations in BCOR, supporting the hypothesis that BCOR is the sole molecular cause of this syndrome. We identify for the first time mosaic BCOR mutations in two females with OFCD syndrome and one apparently asymptomatic female. We present a female diagnosed with isolated ocular defects and identify minor features of OFCD syndrome, suggesting that OFCD syndrome may be mild and underdiagnosed. We have sequenced a cohort of males diagnosed with putative X-linked microphthalmia and found a mutation, p.P85L, in a single case, suggesting that BCOR mutations are not a major cause of X-linked microphthalmia in males. The absence of BCOR mutations in a panel of patients with non-specific laterality defects suggests that mutations in BCOR are not a major cause of isolated heart and laterality defects. Phenotypic analysis of OFCD and Lenz microphthalmia syndromes shows that in addition to the standard diagnostic criteria of congenital cataract, microphthalmia and radiculomegaly, patients should be examined for skeletal defects, particularly radioulnar synostosis, and cardiac/laterality defects.

Outcome of long-axis percutaneous sacroplasty for the treatment of sacral insufficiency fractures.

Our aim was to assess the clinical outcome of patients who were subjected to long-axis sacroplasty for the treatment of sacral insufficiency fractures. Nineteen patients with unilateral (n = 3) or bilateral (n = 16) sacral fractures were involved. Under local anaesthesia, each patient was subjected to CT-guided sacroplasty using the long-axis approach through a single entry point. An average of 6 ml of polymethylmethacrylate (PMMA) was delivered along the path of each sacral fracture. For each individual patient, the Visual Analogue pain Scale (VAS) before sacroplasty and at 1, 4, 24 and 48 weeks after the procedure was obtained. Furthermore, the use of analgesics (narcotic/non-narcotic) along with the evolution of post-interventional patient mobility before and after sacroplasty was also recorded. The mean pre-procedure VAS was 8 +/- 1.9 (range, 2 to 10). This rapidly and significantly (P < 0.001) declined in the first week after the procedure (mean 4 +/- 1.4; range, 1 to 7) followed by a gradual and significant (P < 0.001) decrease along the rest of the follow-up period at 4 weeks (mean 3 +/- 1.1; range, 1 to 5), 24 weeks (mean 2.2 +/- 1.1; range, 1 to 5) and 48 weeks (mean 1.6 +/- 1.1; range, 1 to 5). Eleven (58%) patients were under narcotic analgesia before sacroplasty, whereas 8 (42%) patients were using non-narcotics. Corresponding values after the procedure were 2/19 (10%; narcotic, one of them was on reserve) and 10/19 (53%; non-narcotic). The remaining 7 (37%) patients did not address post-procedure analgesic use. The evolution of post-interventional mobility was favourable in the study group as they revealed a significant improvement in their mobility point scale (P < 0.001). Long-axis percutaneous sacroplasty is a suitable, minimally invasive treatment option for patients who present with sacral insufficiency fractures. More studies with larger patient numbers are needed to explore any unrecognised limitations of this therapeutic approach.