Seizure threshold manipulation in electroconvulsive therapy via repetitive transcranial magnetic stimulation. A novel way of augmentation?

INTRODUCTION: A high seizure threshold (ST) is an impeding factor in certain patients, potentially preventing a successful electroconvulsive therapy (ECT) treatment. Several pharmacological and non-pharmacological methods have been put forward to augment ECT in such patients, however, to this date, only a handful of case reports existed about the potential role of repetitive transcranial magnetic stimulation (rTMS), as an augmentation method. OBJECTIVES: and Methods: In this randomized, double-blinded, sham controlled study, we set out to test the hypothesis of whether the application of high frequency transcranial magnetic stimulation (HF rTMS) lowers the seizure threshold for electroconvulsive therapy and whether it has an effect on other aspects of ECT treatment, such as seizure duration (SD), efficacy and safety. RESULTS: 46 patients treated for a major depressive episode, indicated for ECT, were recruited to this study. A significantly lower seizure threshold was observed in the experimental group during ECT titration, on average a decrease by 34.55%, from 34.23 mC to 22.4 mC, p < 0.001 (Wilcox test). We had not observed a significant effect of TMS stimulation before ECT on seizure duration or clinical outcome. Another potentially important observation of this study is that 4 patients in the experimental group developed transient symptoms of hypomania/mania, all of which were stabilized after the combined stimulation protocol was halted spontaneously within a week, without the need to administer mood stabilizers. CONCLUSION: It is likely that HF rTMS stimulation prior to ECT is a novel and simple way of reducing the ST, which is useful in certain groups of patients undergoing this important treatment modality.

Paediatric onset of multiple sclerosis: Analysis of chemokine and cytokine levels in the context of the early clinical course.

BACKGROUND: Inflammatory activity in children with paediatric onset multiple sclerosis (POMS) is higher than that in adults with MS. Chemokine/cytokine profiling in children may provide new insights into the disease pathogenesis and clinical course. The levels of chemokines/cytokines and their roles in POMS remain largely unknown. OBJECTIVE: To identify the possible utility of chemokines/cytokines in children with POMS, we analysed their levels at the time of disease diagnosis and in the context of subsequent clinical relapse. METHODS: CC and CXC motif ligand chemokines (CCL2, CXCL8, CXCL10, and CXCL13), interleukin (IL)-4, IL-17A, interferon gamma and B cell-activating factor in the blood and cerebrospinal fluid (CSF) of 34 POMS patients and 20 age-related controls were measured using Luminex multiplex bead and enzyme-linked immunosorbent assay techniques. Nonparametric tests were used for statistical analyses. RESULTS: The CSF levels of CXCL8 (p = 0.002), CXCL10 (p = 0.001), and CXCL13 (p<0.0001) were higher in POMS than in controls; CXCL10 and CXCL13 correlated with pleocytosis and oligoclonal bands. A subsequent clinical relapse occurred in 17/34 of the children; the median time from the diagnosis of POMS was 6 months (range, 2-64 months). The follow-up period of patients who did not experience a clinical relapse was significantly longer than the time to first relapse (p = 0.003). The initial CCL2 level was lower in relapsing than in non-relapsing patients (p = 0.063) and correlated negatively with the CSF/serum albumin ratio and positively with the time to relapse (p<0.04). CONCLUSIONS: Elevated CSF levels of CXL10 and CXCL13 in children with POMS at the time of disease diagnosis reflect inflammatory activity and suggest the involvement of adaptive immunity; elevated CXCL8 levels further indicate the involvement of innate immunity. An initial low CSF level of CCL2 may be associated with an unfavourable early MS course.

Accelerated atherosclerosis, hyperlipoproteinemia and insulin resistance in long-term survivors of Hodgkin lymphoma during childhood and adolescence.

Long-term survivors of Hodgkin lymphoma during childhood or adolescence (HL survivors) are at high risk of developing treatment-related late cardiovascular sequelae. In our study we evaluated the presence of modifiable cardiovascular risk factors (hypertension, hyperlipoproteinemia, hyperinsulinemia, obesity), endothelial and inflammatory markers (E-selectin, PAI-1, hs-CRP) and atherosclerotic changes in the common carotid arteries. Assessment was performed in 80 young adult Hodgkin lymphoma long-term survivors at more than 10 years after the potentially cardiovascular toxic anticancer treatment (median age at evaluation 34.7 years; range 24.1-40.9 years). The HL survivors were compared with 83 age- and gender-matched healthy volunteers. The HL survivors showed unfavorable lipid profiles compared to those of healthy controls: triglycerides (p=0.01), total cholesterol (p=0.0004), low density lipoprotein cholesterol (p=0.005). In HL survivors, we found a higher prevalence of hypertension (p=0.004) and insulin resistance - HOMA-IR (p=0.0002). Ultrasonographic examination of both common carotid arteries revealed a higher prevalence of atherosclerotic plaques (p=0.0009) and higher carotid intima-media thickness (p<0.0001) in HL survivors. Markers of oxidative stress (advanced oxidation protein products, oxidized low-density lipoprotein), inflammation (hs-CRP) and endothelial dysfunction (E-selectin, PAI-1) were also higher in HL survivors (p<0.0001, p=0.0002, p=0.0031, p=0.0087, p=0.004, respectively). Adult survivors of Hodgkin lymphoma during childhood and adolescence need closer follow-up with screening of metabolic syndrome components, unfavorable lifestyle factors and early management of these risk factors.

Analysis of expression profiles of genes involved in F(o)F(1)-ATP synthase biogenesis during perinatal development in rat liver and skeletal muscle.

During the process of intra-uterine mammalian fetal development, the oxygen supply in growing fetus is low. A rapid switch from glycolysis-based metabolism to oxidative phosphorylation (OXPHOS) must proceed during early postnatal adaptation to extra-uterine conditions. Mitochondrial biogenesis and mammalian mitochondrial F(o)F(1)-ATP synthase assembly (complex V, EC 3.6.3.14, ATPase) are complex processes regulated by multiple transcription regulators and assembly factors. Using RNA expression analysis of rat liver and skeletal tissue (Rattus norvegicus, Berkenhout, 1769), we describe the expression profiles of 20 genes involved in mitochondrial maturation and ATP synthase biogenesis in detail between the 16th and 22nd day of gestation and the first 4 days of life. We observed that the most important expression shift occurred in the liver between the 20th and 22nd day of gestation, indicating that the fetus prepares for birth about two days before parturition. The detailed mechanism regulating the perinatal adaptation process is not yet known. Deeper insights in perinatal physiological development will help to assess mitochondrial dysfunction in the broader context of cell metabolism in preterm newborns or neonates with poor adaptation to extra-uterine life.

Perirenal metastases from lung cancer: CT diagnosis.

Three patients with primary lung cancer had perirenal metastases detected with CT. In two cases a symptomatic perirenal mass was the first evidence of metastatic spread and CT-guided biopsy of the perirenal lesion confirmed the diagnosis of metastatic lung cancer. The perirenal space is an unusual but potentially significant site of metastasis from lung cancer as well as other tumors such as malignant melanoma. It is suggested that connections between perirenal and intrathoracic lymphatics are the most probable mechanism of this pattern of spread by lung cancers.

Modern methodologies of differentiating thyroid masses.

The rational treatment of thyroid diseases requires an understanding of the thyroid function and an accurate evaluation of its functional (endocrine), as well as it morphological alteration. There are several different imaging techniques which are available and are in use in the evaluation of thyroid diseases. In this article we present a protocol for the use of diagnostic imaging to evaluate a focal thyroid mass, a diffusely enlarged gland, regional, and distant metastatic disease. The current diagnostic applications of radionuclide scanning, ultrasound, computed tomography, and magnetic resonance imaging (MRI) will be discussed.

Choroidal hematoma and effusion: evaluation with MR imaging.

To evaluate the usefulness of magnetic resonance (MR) imagining in the evaluation of choroidal pathologic conditions, the authors studied 15 patients with either choroidal hematoma or choroidal effusion with a 1.5-T MR imager. These two lesions were reliably distinguished from each other on the basis of MR findings. Choroidal hematomas appeared as lenticular-shaped masses in the wall of the eyeball, and signal intensity depended on the age of the hematoma. Choroidal effusions appeared as crescentic or ring-shaped areas of increased signal on both T1- and T2-weighted images in an anatomic distribution corresponding to the choroidal and suprachoroidal spaces.

Direct sagittal CT in the evaluation of temporal bone disease.

The human temporal bone is an extremely complex structure. Direct axial and coronal CT sections are quite satisfactory for imaging the anatomy of the temporal bone; however, many relationships of the normal and pathologic anatomic detail of the temporal bone are better seen with direct sagittal CT sections. The sagittal projection is of interest to surgeons, as it has the advantage of following the plane of surgical approach. This article describes the advantages of using direct sagittal sections for studying various diseases of the temporal bone. The CT sections were obtained with the aid of a new head holder added to our GE CT 9800 scanner. The direct sagittal projection was found to be extremely useful for evaluating diseases involving the vertical segment of the facial nerve canal, vestibular aqueduct, tegmen tympani, sigmoid sinus plate, sinodural angle, carotid canal, jugular fossa, external auditory canal, middle ear cavity, infra- and supralabyrinthine air cells, and temporomandibular joint.

Orbital space-occupying lesions: role of computed tomography and magnetic resonance imaging. An analysis of 145 cases.

CT and MRI of the orbit have significantly enhanced the diagnosis of orbital lesions. Because of these techniques, disorders of the globe, structures within the bony orbit, surrounding structures of the eye, and optic pathways can now be diagnosed with much more certainty than before.

Malignant uveal melanoma and simulating lesions: MR imaging evaluation.

Twenty-one patients with intraocular disease were studied by magnetic resonance (MR) imaging and computed tomography (CT). In 13 cases, malignant uveal melanoma was considered the likely diagnosis. Both imaging methods were accurate in determining the location and size of uveal melanomas. MR imaging was superior for the assessment of possible associated retinal detachment, for assessment of vitreous change, and for differentiating uveal melanoma from choroidal hemangioma and choroidal detachment. A case of retinal gliosis could not be differentiated from uveal melanoma by either technique. Uveal melanomas appeared as hyperintense lesions on T1-weighted images and as hypointense lesions on T2-weighted images. High signal intensity of the vitreous was observed in patients with vitritis and in those who were thought to have protein leaking into the vitreous as a result of impairment of the retinal-blood barrier.

Magnetic resonance imaging in the diagnosis of nonsquamous tumors of the head and neck.

Nonsquamous cell tumors of the head and neck can be reliably evaluated by MRI. In certain pathologic entities, it appears that MRI can provide more information than CT scan.

Chronic otomastoiditis: a conceptual understanding of CT findings.

Inflammation of the middle ear cleft is a disease of great interest from both clinical and radiologic points of view. The attic floor (tympanic diaphragm), the tympanic isthmus, and the aditus ad antrum play important roles in inflammatory processes of the middle ear cleft. The anatomy of the temporal bone at this level was examined by studying microdissections of 250 fresh temporal bones and reviewing over 1,000 high-resolution computed tomography (CT) scans of the temporal bones. The pertinent anatomy is described, and the role of the tympanic diaphragm and isthmus in determining the degree to which middle ear disease may progress is stressed. The appearances on CT scans of chronic otomastoiditis, tympanosclerosis, cholesterol granuloma, attic retraction pocket, and acquired cholesteatoma are reviewed and illustrated.

CT in the evaluation of the orbit and the bony interorbital distance.

The distance between the orbits and their individual dimensions are important in the diagnosis of craniofacial anomalies. Most observers rely on standard radiographs for measuring the bony interorbital distance. Tomography of the skull base and orbital computed tomography (CT) can also be used. This article describes the normal range of the bony interorbital distance and other useful orbital linear and angular measurements as determined from a series of CT scans of the orbits in 400 adults who had CT for other purposes. The normal interorbital distance measured at the posterior border of the frontal processes of the maxilla on nonrotated scans, in the plane of the optic nerve, ranges from 2.29 to 3.21 cm (average, 2.67 cm) in men and 2.29 to 3.20 cm (average, 2.56 cm) in women. The widest interorbital distance lies behind the posterior poles of the globes. This ranges from 3.16 to 4.10 cm (average, 3.37 cm) in men and 2.93 to 3.67 cm (average, 3.20 cm) in women.

Regional cerebral blood flow assessment prior to balloon detachment in the treatment of intracranial giant aneurysms.

Three patients with giant aneurysms (2 internal carotid and 1 anterior communicating) were treated by internal carotid occlusion with a detachable balloon. 133Xe regional cerebral blood flow (rCBF) was performed on each patient on admission. Due to low CBF, one patient received a superficial temporal artery--middle cerebral artery (STA-MCA) bypass. The rCBF was repeated when the balloon was inflated in the internal carotid prior to detachment of the balloon. All three patients were discharged within one week with no neurologic deficit. The rCBF assessment appears useful to decide which patient will tolerate acute balloon occlusion of the internal carotid and to help select patients who will need an extra-cranial-intracranial (EC-IC) bypass to avoid ischemic complication.