Summary:Purpose: This pilot study prospectively evaluated the efficacy of long-term deep brain stimulation (DBS) in medial temporal lobe (MTL) structures in patients with MTL epilepsy.Methods: Twelve consecutive patients with refractory MTL epilepsy were included in this study. The protocol included invasive video-EEG monitoring for ictal-onset localization and evaluation for subsequent stimulation of the ictal-onset zone. Side effects and changes in seizure frequency were carefully monitored.Results: Ten of 12 patients underwent long-term MTL DBS. Two of 12 patients underwent selective amygdalohippocampectomy. After mean follow-up of 31 months (range, 12-52 months), one of 10 stimulated patients are seizure free (>1 year), one of 10 patients had a >90% reduction in seizure frequency; five of 10 patients had a seizure-frequency reduction of ≥50%; two of 10 patients had a seizure-frequency reduction of 30-49%; and one of 10 patients was a nonresponder. None of the patients reported side effects. In one patient, MRI showed asymptomatic intracranial hemorrhages along the trajectory of the DBS electrodes. None of the patients showed changes in clinical neurological testing. Patients who underwent selective amygdalohippocampectomy are seizure-free (>1 year), AEDs are unchanged, and no side effects have occurred.Conclusions: This open pilot study demonstrates the potential efficacy of long-term DBS in MTL structures that should now be further confirmed by multicenter randomized controlled trials.
Primary central nervous system lymphomas (PCNSLs) have recently received considerable clinical attention due to their increasing incidence. To clarify the histogenetic origin of these intriguing neoplasms, PCNSLs from 10 HIV-negative patients were analyzed for immunoglobulin (Ig) gene rearrangements. All tumors exhibited clonal IgH gene rearrangements. Of the 10 cases, 5 used the V4-34 gene segment, and all of these lymphomas shared an amino acid exchange from glycine to aspartate due to a mutation in the first codon of the complementarity-determining region 1. No preferential usage of D(H), J(H), V(kappa), J(kappa), V(lambda), or J(lambda) gene segments was observed. All potentially functional rearrangements exhibited somatic mutations. The pattern of somatic mutations indicated selection of the tumor cells (or their precursors) for expression of a functional antibody. Mean mutation frequencies of 13. 2% and 8.3% were detected for the heavy and light chains, respectively, thereby exceeding other lymphoma entities. Cloning experiments of three tumors showed ongoing mutation in at least one case. These data suggest that PCNSLs are derived from highly mutated germinal-center B cells. The frequent usage of the V4-34 gene and the presence of a shared replacement mutation may indicate that the tumor precursors recognized a shared (super) antigen.
The investigated CBSDA has a high sensitivity and an acceptable specificity for triggering VNS. Despite the moderate effects on seizure frequency, combined open- and closed-loop VNS may provide valuable improvements in seizure severity and QOL in refractory epilepsy patients.
A fundamental question about human memory is which brain structures are involved, and when, in transforming experiences into memories. This experiment sought to identify neural correlates of memory formation with the use of intracerebral electrodes implanted in the brains of patients with temporal lobe epilepsy. Event-related potentials (ERPs) were recorded directly from the medial temporal lobe (MTL) as the patients studied single words. ERPs elicited by words subsequently recalled in a memory test were contrasted with ERPs elicited by unrecalled words. Memory formation was associated with distinct but interrelated ERP differences within the rhinal cortex and the hippocampus, which arose after about 300 and 500 milliseconds, respectively. These findings suggest that declarative memory formation is dissociable into subprocesses and sequentially organized within the MTL.
Criteria for the non-invasive diagnosis of lymphocytic hypophysitis (LyHy) and the results of the first prospective trial of high dose methylprednisolone pulse therapy (HDMPT) in nine patients are presented. In three patients, the diagnosis was established histologically, and in the others by clinical and endocrinological assessment, MRI, CSF examination, and measurement of thyroglobulin autoantibody concentration. After HDMPT, adenopituitary function improved in four of the nine patients and diabetes insipidus ceased or improved in all four concerned patients. The MRI findings improved in seven patients. LyHy has to be considered in the diVerential diagnosis of sellar lesions. The presumptive non-invasive diagnosis of LyHy seems possible in a high proportion of patients. HDMPT may result in the improvement of clinical, endocrinological, and MRI findings. (J Neurol Neurosurg Psychiatry 1999;67:398-402) Keywords: lymphocytic hypophysitis; high dose methylprednisolone pulse therapy Lymphocytic hypophysitis (LyHy) is a rare chronic inflammatory disease with little known natural history, 1-7 usually diagnosed unexpectedly at surgery for presumptive pituitary adenoma.1 5 8 9 Experience in the treatment of LyHy is scarce. Non-invasive diagnostic criteria and results of standardised HDMPT are presented. Patients and methodsAll patients with LyHy (mean age 41 years, seven women) diagnosed at our institution are reported on. Adenohypophyseal function was dynamically assessed as described by Thorner et al. 13 Neurohypophyseal function was assessed as described by Reeves and Andreoli.14 Evaluation of the sellar region by MRI was carried out as described by Elster. 15 In the six patients not operated on, CSF was evaluated by white cell count, cytology, global protein content, and neurotropic virus serology (herpes simplex, varicella zoster, mumps). The thyroglobulin autoantibody concentration was measured in four patients. In three patients, LyHy was diagnosed histologically. In the others, diVerential diagnosis was considered for tuberculosis, sarcoidosis, and syphilis by clinical, laboratory (tuberculin test, angiotensin I converting enzyme measurement, treponema pallidum haemaglutination test), and chest radiograhy evaluation.The high dose short lasting methylprednisolone administration aimed at minimising the side eVects of chronic corticosteroid therapy and at diVerentiating therapeutic eVects from longterm natural course of LyHy. HDMPT consisted of 120 mg methylprednisolone daily for 2 weeks, followed by a dose reduction to 80, 60, 40, and 20 mg daily for 1 week each. Each patient received one course of HDMPT.Results were assessed by endocrinology and MRI as presented above, at 3, 6, and 12 month intervals thereafter. The average follow up amounted to 29 (19-38) months.Literature research was done using the Medline program and the key word hypophysitis. ResultsThe patient's details and courses of disease are listed in the table.Two of the three patients operated on were only biopsied because the intraoperat...
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