Brain structural and psychometric alterations in chronic low back pain.

PURPOSE: Chronic low back pain (CLBP) is one of the most important pain disorders with increasing social and economic implications. Given that CLBP is a multidimensional process associated with comorbidities such as anxiety and depression, treatment of chronic low back pain is still a challenge. Advancement of in vivo brain imaging technologies has revealed increasing insights into the etiology and pathogenesis of chronic pain; however, the exact mechanisms of chronification of LBP remain still unclear. The purpose of the present study was to analyse the neurostructural alterations in CLBP and to evaluate the role of comorbidities and their neurostructural underpinnings. METHODS: In the present study we investigated a well-characterized group of 14 patients with CLBP and 14 healthy controls applying structural MRI and psychometric measures. Using an improved algorithm for brain normalization (DARTEL) we performed a voxel-based morphometry (VBM) approach. Correlation analyses were performed to evaluate the role of anxiety and depression in neurostructural alterations observed in CLBP. RESULTS: The psychometric measures revealed significantly higher scores on depression and anxiety in the patient population. VBM analysis showed significant decreases in grey matter density in areas associated with pain processing and modulation, i.e. the dorsolateral prefrontal cortex, the thalamus and the middle cingulate cortex. With respect to anxiety and depression scores, we did not observe any correlations to the structural data. CONCLUSIONS: In the present study we found compelling evidence for alterations of grey matter architecture in CLBP in brain regions playing a major role in pain modulation and control. Our results fit the hypothesis of a "brain signature" in chronic pain conditions. The results of the psychometric assessment underline the importance of an interdisciplinary therapeutic approach including orthopedic, neurological and psychological evaluation and treatment.

Horizontal gaze palsy with progressive scoliosis: three novel ROBO3 mutations and descriptions of the phenotypes of four patients.

PURPOSE: Clinical and molecular characterization of patients with horizontal gaze palsy with progressive scoliosis (HGPPS) to extend existing knowledge of the phenotype caused by mutations in the Roundabout homolog of Drosophila 3 (ROBO3) gene. METHODS: Four patients (aged 6 months to 13 years), two of them siblings, with features of horizontal gaze palsy and their parents were examined clinically and by molecular testing of the ROBO3 gene. The three families were unrelated, but parents in each family were consanguineous. RESULTS: We identified three novel homozygous ROBO3 mutations in four patients with typical ophthalmologic signs of HGPPS. We found an exonic insertion/deletion mutation (c.913delAinsTGC; p.Ile305CysfsX13), a 31 bp deletion including the donor splice site of exon 17 and adjacent exonic and intronic sequences (c.2769_2779del11, 2779+1_+20del20), and a missense mutation located next to a splice donor site (c.3319A>C) resulting in skipping of exon 22, as shown by cDNA analysis. CONCLUSIONS: We describe three novel mutations in the ROBO3 gene and the detailed clinical phenotype of HGPPS. One patient displayed marked convergence upon attempting smooth pursuits to both sides. In one patient, the typical ophthalmologic phenotype, the neuroradiologic findings, and molecular testing led to the diagnosis even before scoliosis developed. In addition to the typical magnetic resonance imaging brain signs of HGPPS, this patient had marked hypoplasia of the frontal lobes and corpus callosum. In summary, diagnosis of HGPPS may be established by ophthalmologic and molecular investigation early in life, allowing ongoing orthopedic surveillance from an early stage.

Human knee joint anatomy revisited: morphometry in the light of sex-specific total knee arthroplasty.

This study investigates differences in the anatomy of male and female knee joints to contribute to the current debate on sex-specific total knee implants. Morphometric data were obtained from 60 human cadaver knees, and sex differences were calculated. All data were corrected for height, and male and female specimens presenting with an identical length of the femur were analyzed as matched pairs. Male linear knee joint dimensions were significantly larger when compared with females. When corrected for differences in height, medial-lateral dimensions of male knees were significantly larger than female; however, matched paired analysis did not prove these differences to be consistent. Although implant design should focus interindividual variations in knee joint anatomy, our data do not support the concept of a female-specific implant design.

Tuberculous spondylitis and paravertebral abscess formation after kyphoplasty: a case report.

STUDY DESIGN: Case report. OBJECTIVE: To report a patient with spinal tuberculosis (TB) and paravertebral abscess formation after kyphoplasty of L1. The literature is reviewed, and diagnostic options are discussed. SUMMARY OF BACKGROUND DATA: Kyphoplasty is a well-established procedure in the treatment of osteoporotic compression fractures and metastatic tumors of the vertebrae. Although complication rates are low, there is evidence for an increased risk of serious local infections after kyphoplasty in patients with any history of systemic infection. Spinal TB accounts for 2% of all TB cases with a trend toward an increased incidence in parallel with the growing number of immunocompromised patients. To our knowledge, only 1 article had reported a patient suffering from Pott disease after vertebroplasty. METHODS: A 70-year-old patient with compression fracture of L1 underwent percutaneous kyphoplasty using polymethyl methacrylate. RESULTS: Two weeks after kyphoplasty, the patient was readmitted with backache and signs of acute infection. Magnetic resonance imaging confirmed the diagnosis of spondylitis with paravertebral abscess formation. A tissue specimen obtained by computed tomography-guided percutaneous biopsy did not yield any pathogen. As broad-spectrum antibiotic therapy failed, combined surgery consisting of posterior instrumentation of Th11-L3 and anterior debridement, corporectomy of L1, and interposition of a titanium mesh cage filled with autologous rib graft was performed. Histologic examination of resected tissue and PCR and culture results confirmed diagnosis of spinal TB. Despite adequate antibiotic treatment and local surgical interventions, the patient died from septic multiple organ failure. CONCLUSION: Indication for kyphoplasty in patients with any history of local or systemic infection should be scrutinized rigorously. Symptoms of spinal TB are often nonspecific, and the clinician should be aware of this entity. Active investigation including microbiological and histologic examination is of utmost importance to avoid any delay in correct diagnosis and specific treatment.

Treatment of chronically unreduced complex dislocations of the elbow.

Chronic dislocation of the elbow is an exceedingly disabling condition associated with severe instability, limitation of elbow function and significant pain. Due to the potentially conflicting goals of restoring elbow stability and regaining a satisfactory arc of motion, successful treatment is a challenge for the experienced trauma surgeon. We report our treatment strategy in three patients suffering from chronically unreduced fracture-dislocations of the elbow. The treatment protocol consists of in situ neurolysis of the ulnar nerve, distraction and reduction of the joint using unilateral hinged external fixation and repair of the osseous stabilizers. A stable elbow was achieved in all patients, without the need of reconstruction of the collateral ligaments. At final follow-up, the average extension/flexion arc of motion was 107 degrees (range, from 100 degrees to 110 degrees ). The average MEPI score at follow-up was 93, and the average DASH score was 19. This is a promising treatment protocol for the treatment of chronically unreduced complex elbow dislocations to restore elbow stability and regain an excellent functional outcome.

Spondylolisthesis caused by extreme pedicle elongation in osteogenesis imperfecta.

Although osteogenesis imperfecta is a well-known skeletal disorder, reports of spondylolisthesis in osteogenesis imperfecta are rare. Only very few cases of spondylolisthesis caused by elongation of lumbar pedicles have been described in the literature. Here we report three patients suffering from osteogenesis imperfecta showing a severe form of hyperlordosis caused by lumbar pedicle elongation and consecutive spondylolisthesis. Radiographs in the course of childhood and adolescence show a rapid progression of pedicle elongation and hyperlordosis with increased mechanical loads. The treatment strategy consists of physiotherapy, medical treatment with bisphosphonates, and orthopedic surgery and is preferably conservative. In the three patients reported here, one patient was treated with laminectomy and postero-lateral fusion, whereas in the other two patients surgery is currently not considered as necessary.

No evidence for association between NOTCH4 and schizophrenia in a large family-based and case-control association analysis.

OBJECTIVES: An analysis of 80 British parent-offspring trios by Wei and Hemmings in 2000 revealed thre1e out of five markers within the NOTCH4 locus to be strongly associated with schizophrenia. In our present study, we have examined NOTCH4 markers in large samples of German and Palestinian-Arab origin. METHODS: Our study population comprised a German case-control sample (n=512 schizophrenia patients and n=232 controls) and two independent parent-offspring trio samples of German (n=159 trios) and Palestinian-Arab (n=208 trios) descent. We examined a total of ten single nucleotide polymorphisms within the NOTCH4 locus and the adjacent loci, spanning a region of approximately 100 kb. RESULTS: Neither single marker nor haplotype analyses showed association with schizophrenia. In addition, analyses of the German case-control and trio samples revealed no significant association between NOTCH4 polymorphisms and early-onset schizophrenia. CONCLUSIONS: Our results suggest that NOTCH4 is unlikely to play a major role in the genetic predisposition to schizophrenia in the German or the Palestinian-Arab population.

Monoamine related functional gene variants and relationships to monoamine metabolite concentrations in CSF of healthy volunteers.

BACKGROUND: Concentrations of monoamine metabolites in human cerebrospinal fluid (CSF) have been used extensively as indirect estimates of monoamine turnover in the brain. CSF monoamine metabolite concentrations are partly determined by genetic influences. METHODS: We investigated possible relationships between DNA polymorphisms in the serotonin 2C receptor (HTR2C), the serotonin 3A receptor (HTR3A), the dopamine D4 receptor (DRD4), and the dopamine beta-hydroxylase (DBH) genes and CSF concentrations of 5-hydroxyindolacetic acid (5-HIAA), homovanillic acid (HVA), and 3-methoxy-4-hydroxyphenylglycol (MHPG) in healthy volunteers (n = 90). RESULTS: The HTR3A 178 C/T variant was associated with 5-HIAA levels (p = 0.02). The DBH-1021 heterozygote genotype was associated with 5-HIAA (p = 0.0005) and HVA (p = 0.009) concentrations. Neither the HTR2C Cys23Ser variant, nor the DRD4 -521 C/T variant were significantly associated with any of the monoamine metabolites. CONCLUSIONS: The present results suggest that the HTR3A and DBH genes may participate in the regulation of dopamine and serotonin turnover rates in the central nervous system.