Deep brain stimulation of the ventral intermediate nucleus in patients with essential tremor: stimulation below intercommissural line is more efficient but equally effective as stimulation above

Background

The posterior subthalamic area (PSA), ventral to the intercommissural line (ICL) and the ventral intermediate nucleus (VIM), has been suggested as a promising target for deep brain stimulation (DBS) in patients suffering from essential tremor (ET). In this study the clinical benefit of VIM and PSA DBS on postural tremor suppression was systematically evaluated in a two step approach with a 3D ultrasound kinematic analysis tool.

Methods

We defined the exact position of 40 VIM-DBS-electrodes from 21 ET patients. In a first experiment with a subgroup of electrodes we subsequently activated a thalamic and a contact below ICL (sub-ICL) with equal parameter settings for within subject comparison. In a second step, we divided all electrodes into two groups, i.e. one group with activated thalamic and the other group with activated contacts below ICL and performed a group comparison under patients' individual stimulation parameters. Here, the corrected amplitude required for tremor suppression was analyzed separately for both groups.

Results

Within subject comparison with equal parameter settings revealed a significant improvement of sub-ICL compared to thalamic stimulation. In contrast, group comparison under patients' individual stimulation did not show any significant difference in tremor suppression between VIM and PSA DBS. Although higher corrected stimulation amplitude was needed in the thalamic group this difference was not significant.

Conclusion

The data suggest that sub-ICL stimulation may be more efficient compared to thalamic stimulation but equally effective when patients' individual stimulation parameters are used.     

True bipolar and integrated bipolar sensing and detection by implantable defibrillators

Introduction: Sensing and detection can be performed in true bipolar or integrated bipolar configuration by implantable defibrillators. New Medtronic generators (Medtronic Inc., Minneapolis, MN, USA) can be configured so that the sensing function of the device can be either true bipolar or integrated bipolar. We compared the sinus rhythm R‐wave amplitude and detection time of induced ventricular fibrillation (VF) at implant (acute phase), and sinus rhythm R‐wave amplitude 3 months or more after the implant (chronic phase) in these two configurations. Methods: Twenty‐eight patients were studied in the acute phase, and a subgroup of 15 patients was tested in the chronic phase. The generators were Medtronic model numbers D224VRC, D224TRK, D224DRG, D284VRC, D284TRK, and D284DRG. The leads were Medtronic 6947 or 6935. Sensing was evaluated by recording the electrogram and measuring the R‐wave peak‐to‐peak amplitude in the two configurations. Detection was evaluated by measuring the detection time in the two configurations in two consecutive inductions. The detection time was measured on programmer paper from the marker of the T shock to the marker of VF. Results: The acute‐phase values were: R wave in true bipolar configuration 13.9 ± 7.1 mV, R wave in integrated bipolar configuration 13.6 ± 6.9 mV (p = 0.38),VF detection time in true bipolar configuration 3.12 ± 0.39 seconds, and VF detection time in integrated bipolar configuration 3.17 ± 0.39 seconds (p = 0.52). Conclusions: Sensing and detection at implant were not significantly different between the true bipolar and the integrated bipolar configurations for the tested leads and generators. (PACE 2011; 34:1561–1568)     

Unique case of primary malignant fibrous histiocytoma of the right ventricle with moderator band involvement

Malignant primary tumors of the heart are very rare and in most cases are located in the left side of the heart, but involvement of the moderator band of the right heart has not yet been described in the literature. We report the case of a 22-year-old woman who presented after an episode of transient sudden loss of consciousness. The transthoracic echocardiography (TTE) and transesophageal echocardiography evaluations showed an echogenic mass that originated in the right ventricle and protruded into the tricuspid valve during systole. While operating on the patient, we found a sessile tumor that originated exclusively from the moderator band of the right ventricle. The tumor was completely resected through the tricuspid valve. An immunohistochemistry examination of the tumor confirmed the diagnosis of a malignant fibrous histiocytoma (MFH) (undifferentiated pleomorphic sarcoma). To our knowledge, this case is the first of moderator band involvement among the 50 cases of primary MFH of the heart that have been reported in the literature. After a year and a half, TTE, computed tomography (CT), and positron emission tomography CT (PET-CT) showed the absence of cardiac tumor, a normal tricuspid function, and no metastasis. The completeness of the surgical resection and the absence of local recurrence >1 year after surgery are encouraging signs for the patient's outcome.     

Utility of serological markers in predicting the early occurrence of complications and surgery in pediatric Crohn's disease patients

BACKGROUND AND OBJECTIVES: Many Crohn's disease (CD) patients develop complications (fistulae and abscesses), and require surgery, often repeatedly and at variable instances. Identifying serological markers that determine their early or repeated manifestation can enable implementing more aggressive preventive strategies. Our objective was to study the ability of serological markers for predicting development of early (first) and recurrent complications or requirement for surgery. METHODS: Serum anti-Saccharomyces cervisiae (ASCA) (IgA & IgG) and perinuclear antineutrophil cytoplasmic antibodies (pANCA) were assayed close to diagnosis in a pediatric cohort of CD patients identified between 1996 and 1998. At diagnosis and follow-up, information was acquired on demographic and clinical features of disease. Relation between ASCA and clinical events was studied using adjusted Cox-proportional hazards modeling. The relative rates of recurrent clinical events according to the marker measures were compared. RESULTS: The mean age (SD) at diagnosis was 11.2 (3.4) yr. Among 139 patients, 35 (25.9%) and 31 (22.3%) acquired one or more CD related surgery or complication, respectively. Time to occurrence of the first complication was lower among patients ASCA+ (IgA or IgG) (hazards ratio (HR) = 2.33; 95% confidence interval (CI) = 0.99-5.50) and among those with higher ASCA-IgA titers (HR = 1.20; 95% CI = 1.08-1.34). The rates of recurrent complications were higher among those positive or with higher ASCA titers. ASCA did not predict time to undergoing surgery independent of complications, and was unrelated to the occurrence of recurrent surgeries. CONCLUSIONS: Our study shows that serum ASCA measured close to diagnosis can determine the occurrence of early complications in pediatric CD. Preventive treatment targeted toward these susceptible patients could potentially modify the disease course.     

Clinically active Crohn's disease in the presence of a low C-reactive protein

OBJECTIVE: Clinical interest in C-reactive protein (CRP) -- a component of the innate immune system -- has focused mainly on its worth as an indicator of disease activity. There has been a resurgence of interest in CRP in the Crohn's disease (CD) literature because several trials of new treatments for active CD have been characterized by both a large proportion of patients with low CRP (<10 mg/l) at entry to the trials and by a negative therapeutic outcome. It is therefore of interest to study the clinical characteristics of patients who are thought to have at the same time both active CD and a low CRP. MATERIAL AND METHODS: Patients were prospectively recruited as part of the Brisbane IBD clinical and research programme. Subjects were included in the low CRP group only if there were complete datasets for CRP on all occasions of active CD, and CRP was < 10 mg/l. Active disease was defined as CD activity index (CDAI)>200. The low CRP group was compared with patients in the raised CRP group for a range of clinical variables as well as the major NOD2 variants. RESULTS: There were data sets for 223 CD patients, with a mean disease duration of 12 years. Of these, 22 patients fulfilled the criteria for low CRP. The low CRP group (group 1) showed significant differences for disease site (p<0.01) and for BMI (p=0.006) compared to the raised CRP group (group 2). Specifically, group 1 had a predominance of pure ileal disease (95% versus 53%) and lack of pure colonic disease (0% versus 24%) compared to group 2, and their BMI was significantly lower (20.3 kg/m(2) versus 25.0 kg/m(2)). Groups 1 and 2 did not differ with respect to Vienna behaviour at diagnosis, smoking, appendicectomy, extra-intestinal manifestations of CD, or NOD2 SNP variants. There was a trend for low CRP patients with previous ileal resection to evolve to a stricturing phenotype. Fat wrapping was noted in 11/13 (85%) of low CRP patients undergoing ileal resections. CONCLUSIONS: Patients with CD and a persistently low CRP in the face of active disease were characterized by an almost exclusive ileal disease distribution and a low BMI, compared to those with a raised CRP. These patients had a similar frequency and distribution of NOD2/CARD15 variants. Stricturing (v inflammatory or penetrating) behaviour may explain some low CRP. Despite the abnormally low BMI, fat wrapping was noted in the majority of low CRP patients undergoing ileal resection.     

The A3243G tRNALeu(UUR) MELAS mutation causes amino acid misincorporation and a combined respiratory chain assembly defect partially suppressed by overexpression of EFTu and EFG2

The majority of patients with MELAS (mitochondrial encephalomyophathy, lactic acidosis, stroke-like episodes) carry a heteroplasmic A3243G mutation in the mitochondrial tRNA(Leu(UUR)). The mutation prevents modification of the wobble U base, impairing translation at UUA and UUG codons; however, whether this results in amino acid misincorporation in the mitochondrial translation products remains controversial. We tested this hypothesis in homoplasmic mutant myoblasts isolated from a MELAS patient and investigated whether overexpression of the mitochondrial translation elongation factors could suppress the translation defect. Blue-Native gel electrophoretic analysis demonstrated an almost complete lack of assembly of respiratory chain complexes I, IV and V in MELAS myoblasts. This phenotype could be partially suppressed by overexpression of EFTu or EFG2 but not EFTs or EFG1. Despite the severity of the assembly defect, overall mitochondrial protein synthesis was only moderately affected, but some anomalously migrating translation products were present. Pulse-chase labeling showed reduced stability of all mitochondrial translation products consistent with the assembly defect. Labeling patterns of the translation products were similar with [(3)H]-leucine or [(3)H]-phenylalanine, showing that loss of the wobble U modification did not permit decoding of UUY codons; however, endoproteinase fingerprint analysis showed clear evidence of amino acid misincorporation in three polypeptides: CO III, CO II and ATP6. Taken together, these data demonstrate that the A3243G mutation produces both loss- and gain-of-function phenotypes, explaining the apparent discrepancy between the severity of the translation and respiratory chain assembly defects, and suggest a function for EFG2 in quality control of translation elongation.