Peripheral third cranial nerve enhancement in multiple sclerosis

Cranial nerve III dysfunction in multiple sclerosis (MS) is uncommon. Seven cases of isolated cranial nerve III paresis associated with MS have been reported in the English-language literature. MR imaging was obtained in five cases demonstrating lesions within the midbrain. We present the detailed clinical and MR imaging findings of a young woman with MS and an isolated, painful pupil involving complete left cranial nerve III palsy. Initial MR imaging showed isolated enhancement of the cisternal portion of the cranial nerve III, suggesting that peripheral nervous system involvement may develop as part of the disease process in some patients with MS.     

Local complications after cosmetic breast implant surgery in Finland

Concerns regarding potential health effects of silicone breast implants have recently shifted from long-term illnesses to postoperative local complications. In this study, occurrence of local complications and treatment procedures were evaluated in a population of 685 Finnish women who received cosmetic silicone breast implants between 1968 and 2002. Patient records were abstracted, and additional information was gathered using a structured questionnaire that was mailed to 470 of the women in the cohort. Overall, 36% of the women had 1 or more diagnoses of postoperative complications in their medical records. The most common complication was capsular contracture, occurring in 17.7% of women and 15.4% of implantations. Other complications were more rare. The majority of women (74%) needed no postoperative treatment. However, 22% of women required 1 or more surgical procedures after the primary implantation. Most of the women were satisfied with the implantation, but only 40% considered the preoperative information on possible risks related to implantation as sufficient. With respect to the occurrence of local complications following cosmetic breast implantation, the findings of this study are consistent with previous studies. Frequencies of complications were remarkably similar in medical records and self-reports.     

Role of core needle biopsy in the treatment of radial scar

Invasive tumor or ductal carcinoma in situ occur in radial sclerosing lesions in one third of the cases therefore, surgical excision is mandatory. Forty-five patients with radial scar morphology were examined. Ultrasound guided fine-needle aspiration biopsy (FNAB) and core biopsy (CB) were performed in all cases. The postoperative pathological findings were compared to the results of preoperative biopsies. Sensitivity of preoperative percutaneous biopsies (FNAB and CB) was 17.6% and 70.6%, false-negative rate was 82.4% with FNAB and 29.4% with CB. The negative predictive value was 48.1% and 84.8% respectively. Had we done preoperative cytology only, we would have had to perform a two-step procedure (sentinel lymph node biopsy) in 7 patients (15.6%), while with preoperative core biopsy it has decreased to 2 patients (4.4%). Preoperative CB in small radial stellate lesions is recommended to achieve accurate diagnosis in order to avoid a two-step surgical procedures.     

Pathological amygdala activation during working memory performance: Evidence for a pathophysiological trait marker in bipolar affective disorder

Recent evidence suggests that deficits of working memory may be a promising neurocognitive endophenotype of bipolar affective disorder. However, little is known about the neurobiological correlates of these deficits. The aim of this study was to determine possible pathophysiological trait markers of bipolar disorder in neural circuits involved in working memory. Functional magnetic resonance imaging was performed in 18 euthymic bipolar patients and 18 matched healthy volunteers using two circuit‐specific experimental tasks established by prior systematic neuroimaging studies of working memory. Both euthymic bipolar patients and healthy controls showed working memory‐related brain activations that were highly consistent with findings from previous comparable neuroimaging studies in healthy subjects. While these patterns of brain activation were completely preserved in the bipolar patients, only the patients exhibited activation of the right amygdala during the articulatory rehearsal task. In the same task, functional activation in right frontal and intraparietal cortex and in the right cerebellum was significantly enhanced in the patients. These findings indicate that the right amygdala is pathologically activated in euthymic bipolar patients during performance of a circuit‐specific working memory task (articulatory rehearsal). This pathophysiological abnormality appears to be a trait marker in bipolar disorders that can be observed even in the euthymic state and that seems to be largely independent of task performance and medication. Hum Brain Mapp, 2010. © 2009 Wiley‐Liss, Inc.     

The role of BDNF methylation and Val66Met in amygdala reactivity during emotion processing

Epigenetic alterations of the brain‐derived neurotrophic factor (BDNF) gene have been associated with psychiatric disorders in humans and with differences in amygdala BDNF mRNA levels in rodents. This human study aimed to investigate the relationship between the functional BDNF‐Val⁶⁶Met polymorphism, its surrounding DNA methylation in BDNF exon IX, amygdala reactivity to emotional faces, and personality traits. Healthy controls (HC, n = 189) underwent functional MRI during an emotional face‐matching task. Harm avoidance, novelty seeking and reward dependence were measured using the Tridimensional Personality Questionnaire (TPQ). Individual BDNF methylation profiles were ascertained and associated with several BDNF single nucleotide polymorphisms surrounding the BDNF‐Val⁶⁶Met, amygdala reactivity, novelty seeking and harm avoidance. Higher BDNF methylation was associated with higher amygdala reactivity (x = 34, y = 0, z = ?26, t₍₁₆₆₎ = 3.00, TFCE = 42.39, p_(FWE) = .045), whereby the BDNF‐Val⁶⁶Met genotype per se did not show any significant association with brain function. Furthermore, novelty seeking was negatively associated with BDNF methylation (r = ?.19, p = .015) and amygdala reactivity (r = ?.17, p = .028), while harm avoidance showed a trend for a positive association with BDNF methylation (r = .14, p = .066). The study provides first insights into the relationship among BDNF methylation, BDNF genotype, amygdala reactivity and personality traits in humans, highlighting the multidimensional relations among genetics, epigenetics, and neuronal functions. The present study suggests a possible involvement of epigenetic BDNF modifications in psychiatric disorders and related brain functions, whereby high BDNF methylation might reduce BDNF mRNA expression and upregulate amygdala reactivity.     

Serum chromogranin A concentration and intradialytic hypotension in chronic haemodialysis patients

Aim The aim of this study was to investigate the influence of haemodialysis on plasma chromogranin A (CgA) concentration and to assess the relationship between CgA, blood pressure, occurrence of intradialytic hypotension episodes and residual renal function, respectively. Methods The study included 38 chronic haemodialysis patients (24 M, 14 F; mean age 56.2 ± 13.6 years). Plasma CgA and blood pressure were measured before and after a mid-week dialysis. Control group included 10 age- and sex-matched healthy subjects. Results Plasma CgA levels were on average 50-fold higher in HD patients than in the controls (699 ± 138 vs. 14 ± 6 U/L). In HD patients plasma CgA corrected for ultrafiltration rates significantly increased (to 836 ± 214 U/L, P < 0.001) at the end of dialysis procedure. In patients with (n = 8) and without frequent symptomatic intradialytic hypotension episodes predialysis values of CgA were similar (701 ± 169 vs. 698 ± 132 U/L) but post-dialysis were significantly lower in the former group (746 ± 312 vs. 860 ± 177 U/L; P = 0.03) despite a similar rate of ultrafiltration (2675 ± 1009 and 2583 ± 1311 ml, respectively). Accordingly, in patients with intradialytic hypotension an increase of plasma CgA during dialysis was also much lower than in patients without hypotension (45 ± 81 vs. 163 ± 144 U/L; P = 0.001). Conclusions CgA undergoes marked accumulation in renal failure. The increase of plasma CgA during dialysis is impaired in subjects with intradialytic hypotension episodes, which confirms the role of autonomic dysfunction in the pathogenesis of this complication.     

The chondrocyte channelome: A narrative review

Chondrocytes are the main cells in the extracellular matrix (ECM) of articular cartilage and possess a highly differentiated phenotype that is the hallmark of the unique physiological functions of this specialised load-bearing connective tissue. The plasma membrane of articular chondrocytes contains a rich and diverse complement of membrane proteins, known as the membranome, which defines the cell surface phenotype of the cells. The membranome is a key target of pharmacological agents and is important for chondrocyte function. It includes channels, transporters, enzymes, receptors, and anchors for intracellular, cytoskeletal and ECM proteins and other macromolecular complexes. The chondrocyte channelome is a sub-compartment of the membranome and includes a complete set of ion channels and porins expressed in these cells. Many of these are multi-functional proteins with “moonlighting” roles, serving as channels, receptors and signalling components of larger molecular assemblies. The aim of this review is to summarise our current knowledge of the fundamental aspects of the chondrocyte channelome, discuss its relevance to cartilage biology and highlight its possible role in the pathogenesis of osteoarthritis (OA). Excessive and inappropriate mechanical loads, an inflammatory micro-environment, alternative splicing of channel components or accumulation of basic calcium phosphate crystals can result in an altered chondrocyte channelome impairing its function. Alterations in Ca²⁺ signalling may lead to defective synthesis of ECM macromolecules and aggravated catabolic responses in chondrocytes, which is an important and relatively unexplored aspect of the complex and poorly understood mechanism of OA development.