The variability of atlas-based targets in relation to surrounding major fibre tracts in thalamic deep brain stimulation

Background

In essential tremor (ET), the main target for deep brain stimulation (DBS) is the thalamic ventralis intermedius nucleus (Vim). This target cannot be identified on conventional magnetic resonance imaging (MRI). Therefore, targeting depends on probabilistic coordinates derived from stereotactic atlases. The goal of our study was to investigate the variability of atlas-based Vim targets in relation to surrounding major fibre tracts.

Methods

With the MRI and computed tomography (CT) scan data of ten patients who underwent DBS, we planned atlas based Vim targets in both hemispheres. We also performed deterministic fibre-tracking with diffusion tensor imaging (DTI) of the dentato-rubro-thalamic tract (DRTT), pyramidal tract (PT) and lemniscus medialis (LM) in all 20 hemispheres. Subsequently, we measured the distance from the atlas-based Vim target to each tract along the medial/lateral (x-coordinate), anterior/posterior (y-coordinate) and superior/inferior axis (z-coordinate).

Results

Seventeen out of 20 DRTTs could be depicted with our standardised DTI/fibre-tracking parameters. The PT and the LM could be displayed in all 20 hemispheres. The atlas-based Vim target was found inside the DRTT in 11 (concerning the x-coordinate) and 10 hemispheres (concerning the z-coordinate). Regarding the anterior/posterior direction, the target was posterior to the DRTT in 11 cases. In 19 hemispheres the Vim target was located medial and superior to the PT and in 17 hemispheres posterior to it. Concerning the LM, the Vim target was found inside the LM in 16 (regarding the x-coordinate) and in 14 cases (regarding the z-coordinate). In eight cases it was located inside and in 12 cases anterior to the LM concerning the y-coordinate.

Conclusions

We found a considerable variability of the location of atlas-based target points of the ventralis intermedius nucleus in relation to neighbouring major fibre tracts in individual patients. These results suggest that individualised targeting to structures not directly visible on conventional MRI is necessary.

     

Neonatal blue light phototherapy increases café-au-lait macules in preschool children

Neonatal blue light phototherapy (NBLP) is an effective treatment for hyperbilirubinaemia. Concerning the influence on melanocytic nevi, conflicting studies have been published. To assess the role of NBLP according to the incidence of melanocytic nevi in preschool children, a cohort of 104 5- to 6-year-old children were included. The case group consisted of 52 NBLP-exposed children, while the control group (n?=?52) never had NBLP and was matched regarding age, gender, gestational age and skin phototype. Six dizygotic twins were included with one twin having received NBLP, respectively. The following parameters were recorded: nevi count, presence of freckles, café-au-lait macules, skin phototype and previous history of sun exposure. There was no significant association between nevi count and exposure to NBLP (median nevi count 17.0 compared to 18.5 in controls). No significant difference was also found in the dizygotic twin pairs with a median nevi count of 10.0 (with NBLP) compared to 14.5 (without NBLP). However, a significantly higher prevalence of café-au-lait macules was found in children with NBLP (mean count 0.5) than in children without NBLP (mean count 0.2; p?=?0.001). Significant predictors for the number of melanocytic nevi included skin phototype, sun exposure and vacations in the South. Conclusion: In this study, NBLP had no significant influence on the development of melanocytic nevi, but on café-au-lait macules which was a new finding. Differences with comparable studies regarding age, differentiation between nevi and other pigmented lesions as well as dose and type of NBLP need to be taken into account for further investigations.     

Vaspin – a link of obesity and psoriasis?

Psoriasis is an inflammatory skin disease often associated with obesity. The anti-inflammatory adipokine vaspin, a suggested serine proteinase inhibitor of the serpin family, is discussed as a new link between inflammation and obesity. Here, we demonstrate that - different from healthy controls - vaspin serum levels in patients with psoriasis were body mass index independent. Moreover, we could identify keratinocytes as the major source of vaspin in skin. Vaspin expression in lesional psoriatic skin was reduced compared with uninvolved skin as shown by immunohistochemistry and RT-PCR. In aggregate, we report on the cellular source of vaspin in skin and its expression in psoriasis.     

Impact of human myelin on the maturation and function of human monocyte-derived dendritic cells

Macrophages and dendritic cells (DC) play an important role in the immunopathology of multiple sclerosis. We analyzed the impact of human myelin on monocyte-derived DC and describe their immunostimulatory capacity. Cells were grown on myelin and stimulated with LPS or a defined maturation cocktail. DC activation was analyzed by the expression of cell surface markers and the secretion of cytokines and chemokines. The immunostimulatory capacity of DC was assessed by allogeneic mixed-leukocyte reactions via proliferation. Additionally, their ability to bias T cells towards Th1, Th17 or Treg differentiation was investigated. We found that phagocytosis of myelin impaired the activation of DC, displayed by an impaired ability to stimulate allogeneic T cells, an increased production of TGF-β1 and a diminished upregulation of CCR7 but did not affect the differentiation into T helper cell subsets. We hypothesize that myelin influences DC activation and plays a pivotal role in balancing immunity and tolerance.     

Gain and loss of extracellular molecules in sporadic inclusion body myositis and polymyositis--a proteomics-based study

Sporadic inclusion body myositis (sIBM) contains non-necrotic myofibers that are surrounded and/or invaded by inflammatory cells. In this study we aimed to identify selective molecules that are present at this site. Myofibers of four biopsies of sIBM that were surrounded and/or invaded by inflammatory cells were microdissected, pooled and profiled by proteomic studies using mass spectrometry. Normal skeletal muscle tissue served as control. Based on the table of proteins that were detected in sIBM only, we selected nine extracellular matrix molecules and validated the results performing immunofluorescence. Seven out of nine proteins that were detected in sIBM by mass spectrometry showed different immunohistochemical results in myositis and normal controls. Of these, the small leucine-rich repeat proteins proline arginine-rich end leucine-rich repeat protein (PRELP) and biglycan were deposited precisely at myofibers surrounded and/or invaded by inflammatory cells both in sIBM and polymyositis. The basement membrane (BM) molecules merosin, perlecan, nidogen-2 and collagen IV were variably destroyed or increased at these sites. P component, which ensheathed all myofibers in normal controls, was absent from invaded myofibers. Similar to BM remodeling, the specific deposition of PRELP and biglycan may represent a mechanism to defend against immune attack. Loss of P component may affect the anchorage of the myofiber in the endomysium.     

An EAACI position paper on the investigation of perioperative immediate hypersensitivity reactions

Perioperative immediate hypersensitivity reactions are rare. Subsequent allergy investigation is complicated by multiple simultaneous drug exposures, the use of drugs with potent effects and the many differential diagnoses to hypersensitivity in the perioperative setting. The approach to the investigation of these complex reactions is not standardized, and it is becoming increasingly apparent that collaboration between experts in the field of allergy/immunology/dermatology and anaesthesiology is needed to provide the best possible care for these patients. The EAACI task force behind this position paper has therefore combined the expertise of allergists, immunologists and anaesthesiologists. The aims of this position paper were to provide recommendations for the investigation of immediate‐type perioperative hypersensitivity reactions and to provide practical information that can assist clinicians in planning and carrying out investigations.     

Food allergy to the carbohydrate galactose-alpha-1,3-galactose (alpha-gal): four case reports and a review

Until recently, food allergies to mammalian meats have been considered to be very rare. The observation that patients not previously exposed to the monoclonal chimeric antibody cetuximab suffered from severe anaphylaxis upon first exposure, led to the identification of galactosealpha- 1,3-galactose as a new relevant carbohydrate allergen. These patients later often suffered from anaphylactic reactions to red meat. Epidemiological data indicated that bites by the tick Amblyomma americanum in the USA, later also by Ixodes species in other continents, resulted in sensitisation to alpha-gal. On the other hand, in African patients with parasitic disorders, a high prevalence of anti-alpha-gal IgE, without clinical relevance, has been reported. In our four cases, one patient with a late onset of meat allergy had a history of a tick bite. The other three patients had symptoms from childhood or at a juvenile age. This indicates that in some patients, other ways of sensitisation may also take place. However, in patients without atopy, tick bite-induced IgE to alpha-gal may be more relevant. Diagnosis is based on a history of delayed onset of anaphylaxis. Skin tests with commercially available meat test solutions are often equivocal or negative; skin tests with raw meat and particularly pork kidney are more sensitive. Determination of specific IgE to alpha-gal is commercially available. The highest sensitivity is observed with skin and basophil activation tests with cetuximab which is, however, limited by its high costs.     

Cytokine balance in infants undergoing cardiac operation

BACKGROUND: The control of the systemic inflammatory response taking place during cardiac operations depends on adequate antiinflammatory reaction. In this prospective study we tested the hypothesis that cytokine balance during pediatric cardiac surgical procedures would be influenced by the patients' preoperative clinical condition, defined as hypoxemia or heart failure. METHODS: Twenty infants (median age, 8 months) with hypoxemia owing to intracardiac right-to-left shunt (group 1, n = 10) or with heart failure because of intracardiac left-to-right shunt (group 2, n = 10), scheduled for elective primary corrective operation, were enrolled. Plasma levels of the proinflammatory cytokine interleukin (IL) 6, the natural antiinflammatory cytokine IL-10, and the markers of the acute-phase response, C-reactive protein and procalcitonin, were sequentially measured before, during, and after cardiac operation up to the 10th postoperative day. The ratio of IL-10 to IL-6 levels served as a marker for the individual's antiinflammatory cytokine balance. RESULTS: Group 1 showed higher preoperative IL-6 (p < 0.001), lower IL-10 levels (p < 0.02), and lower ratio of IL-10 to IL-6 levels (p < 0.001) than group 2. Preoperative C-reactive protein and procalcitonin were not detectable. In group 1, preoperative IL-6 levels inversely correlated with preoperative oxygen saturation (Spearman correlation coefficient, -0.74, p < 0.02). During cardiopulmonary bypass, IL-6 levels were higher, whereas IL-10 and ratio of IL-10 to IL-6 levels were lower in group 1 than in group 2. In all patients, postoperative IL-6 levels were positively correlated with duration of inotropic support and serum creatinine value and inversely correlated with oxygenation index and diuresis. CONCLUSIONS: Infants with hypoxemia show a preoperative inflammatory state with low antiinflammatory cytokine balance in contrast to those with heart failure. This in turn is associated with lower perioperative antiinflammatory cytokine balance and might contribute to postoperative morbidity.     

Impaired phase synchronization of motor‐evoked potentials reflects the degree of motor dysfunction in the lesioned human brain

The functional corticospinal integrity (CSI) can be indexed by motor‐evoked potentials (MEP) following transcranial magnetic stimulation of the motor cortex. Glial brain tumors in motor‐eloquent areas are frequently disturbing CSI resulting in different degrees of motor dysfunction. However, this is unreliably mirrored by MEP characteristics. In 59 consecutive patients with diffuse glial tumors and 21 healthy controls (CTRL), we investigated the conventional MEP features, that is, resting motor threshold (RMT), amplitudes and latencies. In addition, frequency‐domain MEP features were analyzed to estimate the event‐related spectral perturbation (ERSP), and the induced phase synchronization by intertrial coherence (ITC). The clinical motor status was captured including the Medical Research Council Scale (MRCS), the Grooved Pegboard Test (GPT), and the intake of antiepileptic drugs (AED). Motor function was classified according to MRCS and GPT as no motor deficit (NMD), fine motor deficits (FMD) and gross motor deficits (GMD). CSI was assessed by diffusion‐tensor imaging (DTI). Motor competent subjects (CTRL and NMD) had similar ERSP and ITC values. The presence of a motor deficit (FMD and GMD) was associated with an impairment of high‐frequency ITC (150–300 Hz). GMD and damage to the CSI demonstrated an additional reduction of high‐frequency ERSP (150–300 Hz). GABAergic AED increased ERSP but not ITC. Notably, groups were indistinguishable based on conventional MEP features. Estimating MEP phase synchronization provides information about the corticospinal transmission after transcranial magnetic stimulation and reflects the degree of motor impairment that is not captured by conventional measures.