Relationship of nuclear magnetic resonance examinations to clinical data,cerebrospinal fluid findings and visual evoked potentials in multiple sclerosis

We examined 150 patients with a 0.5 Tesla MR system. Fourteen patients were excluded from the study, because, in addition to the clinical signs of multiple sclerosis, they showed other abnormalities (spinal canal narrowing, embolic disease, Vitamin B12 deficiency, etc.). The results of the 136 examinations were related to the duration of disease, index of impairment on Kurtkze's disability scale, the clinical course, and the CSF and VEP results. The MR studies were evaluated in a semiquantitative manner. Patients with a long duration of disease demonstrated more changes than did cases with a short course. We found more periventricular confluences and more white matter plaques in the centrum semiovale. In addition, more lesions were seen in patients with a severe course of disease. All patients with negative CSF results (n = 13) showed positive MR examinations, and vice versa, patients with positive CSF findings showed negative MR results (n = 5). First results of a follow-up study demonstrate that most abnormalities in MR are not related to the clinical course or therapeutical procedure.     

Entwicklung eines Meßinstrumentes zur Bestimmung der Aufmerksamkeit bei Patienten mit cerebralen Läsionen und Funktionsstörungen

Zusammenfassung 58 aufmerksamkeitsgestörte Patienten mit verschiedenen neurologisch-internistischen Grundleiden und 12 Patienten ohne Aufmerksamkeitsstörung wurden untersucht. Ziel der Untersuchung war es, ein standardisiertes Untersuchungsinstrument zur Messung klinisch faßbarer Aufmerksamkeitsstörungen zu erstellen. Es wurde eine additive, 4stufige Skala der Stimulierbarkeit (Guttman-Skala) aus mehreren heterogenen Reizen entwickelt. Auf der anderen Seite wurde eine 4stufige, additive Skala der Reaktivität aus einem Katalog definierter Reaktionen aufgebaut. Mit diesen beiden Skalen wurden Stimulierbarkeit und Reaktivität aufmerksamkeitsgestörter Patienten gemessen. Stimulierbarkeit und Reaktivität der Patienten verhalten sich proportional zueinander. Die Transformation von Stimulierbarkeit in Reaktivität leistet ein internes System, das der gesuchten Aufmerksamkeitsdimension zugeordnet wird.

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Development of a method of measuring the attention of patients with cerebral lesions

Summary 58 patients with various underlying neurological diseases, who had an impairment of attention, were examined. 12 patients without clinically evident disorders of attention were examined as a control group. The aim of the study was the development of a standardized procedure for the assessment of impaired attention. An additive, 4 step scale of the susceptibility to stimulation (Guttman scale) was constructed out of several, heterogeneous stimuli. In addition, an additive 4 step scale of reactivity was constructed out of a catalogue of defined reactions. The two scales permitted the assessment of reactivity and susceptibility to stimulation, the degree of which could be demonstrated as being proportional to one another. The transformation of susceptibility to stimulation into reactivity is thought to be performed by an internal system which is attributed to attention.

     

Early experience with intravenous immunoglobulin treatment in Wegener's granulomatosis with ocular involvement

Background: Pooled intravenous gammaglobulin (IVIg) was reported to be effective in the treatment of Wegener's granulomatosis (WG). No reports have been made on the effects of this new treatment on ocular manifestations of WG. Method: IVIg treatment was given to two patients suffering from WG with ocular involvement after several other treatment regimes had failed. Results: Although the systemic disease was under control, the ocular symptoms of both patients worsened during and after IVIg treatment. In one case an adverse effect consisting of retinal vasculitis was noted on two occasions. Conclusion: Although beneficial effects of IVIg treatment on WG have been previously described, the two cases with ocular involvement presented here did not reveal any positive response. Paradoxical and unpredictable reactions cannot be ruled out. Thus, patients treated with IVIg should be closely surveyed by an ophthalmologist.     

The measurement of change in endogenous affective disorders

Summary Psychopathological syndromes, as originally revealed by clinical observation, can also be detected by multivariate statistical analyses of symptom ratings. Changes in the course of psychiatric syndromes may be rated simply by improvement scales or by consecutive quantifications of symptoms and their comparison in chronological order. For the latter approach, which is less liable to bias, clinical ratings of psychopathology by staff members, self-ratings by the patients, analyses of patients' overt behavior (including video and speech records), or objective measurements of psychological and/or physiological variables can be used. Advantages and limitations of these different methods are discussed and illustrated by examples from ongoing clinical research in affective disorders. Generally, the combined use of different rating procedures is recommended. Self-ratings are economical, but they may represent aspects of psychopathology other than clinical ratings. In endogenous depression, mood scales are valid (supplementary) tools for the quantification of long-term as well as short-term changes, including diurnal variations. In severe conditions of mania, however, clinical rating has been—until now—the only valid basis for quantifying the degree of psychopathology and its changes with time. Precise evaluation of changes in psychopathology is essential in longitudinal investigations of endogenous affective disorders, since psychopathology up to now seems to have been the most sensitive and the most specific indicator of the hypothetical underlying abnormalities of cerebral functioning.Paper presented at a symposium on The Measurement of Change in Psychopathology at the VI World Congress of Psychiatry, Honolulu, USA, August 1977     

Cellular localization of angiotensin type 1 receptor and angiotensinogen mRNAs in the subfornical organ of the rat brain

The cellular localization of angiotensin type 1 receptor (AT 1) and angiotensinogen mRNA expression in the subfornical organ (SFO) of the rat brain has been studied by means of non-radioactive in situ hybridization combined with immunocytochemistry for glial fibrillary acidic protein (GFAP) and Neutral red staining. The AT 1 receptor mRNA expression is shown to be within putative nerve cells without any association with the glial fibrillary acidic protein (GFAP)-immunoreactive (IR) cells. In contrast the angiotensinogen cRNA expression is associated predominantly with GFAP-IR cells. The results demonstrate that a neuronal AT 1 receptor mediates the actions of circulating angiotensin II on the SFO and that the angiotensinogen mRNA is predominantly expressed in the SFO astroglial cells.     

Perioperative ultrasound-guided wire marking of calcific deposits in calcifying tendinitis of the rotator cuff

The identification of a calcific deposit in the rotator cuff can often cause difficulties. A new technique is described to identify the calcific deposit perioperatively with a ultrasound-guided wire. The technique allows a safe direct marking of calcific deposits making the procedure faster especially in difficult cases.     

Homeostatic bioenergetic network regulation - a novel concept to avoid pharmacoresistance in epilepsy

INTRODUCTION: Despite epilepsy being one of the most prevalent neurological disorders, one third of all patients with epilepsy cannot adequately be treated with available antiepileptic drugs. One of the significant causes for the failure of conventional pharmacotherapeutic treatment is the development of pharmacoresistance in many forms of epilepsy. The problem of pharmacoresistance has called for the development of new conceptual strategies that improve future drug development efforts. AREAS COVERED: A thorough review of the recent literature on pharmacoresistance in epilepsy was completed and select examples were chosen to highlight the mechanisms of pharmacoresistance in epilepsy and to demonstrate how those mechanistic findings might lead to improved treatment of pharmacoresistant epilepsy. The reader will gain a thorough understanding of pharmacoresistance in epilepsy and an appreciation of the limitations of conventional drug development strategies. EXPERT OPINION: Conventional drug development efforts aim to achieve specificity of symptom control by enhancing the selectivity of drugs acting on specific downstream targets; this conceptual strategy bears the undue risk of development of pharmacoresistance. Modulation of homeostatic bioenergetic network regulation is a novel conceptual strategy to affect whole neuronal networks synergistically by mobilizing multiple endogenous biochemical and receptor-dependent molecular pathways. In our expert opinion we conclude that homeostatic bioenergetic network regulation might thus be used as an innovative strategy for the control of pharmacoresistant seizures. Recent focal adenosine augmentation strategies support the feasibility of this strategy.     

Engineered adenosine-releasing cells for epilepsy therapy: Human mesenchymal stem cells and human embryonic stem cells

Adenosine is a modulator of neuronal activity with anticonvulsant and neuroprotective properties. Conversely, focal deficiency in adenosine contributes to ictogenesis. Thus, focal reconstitution of adenosine within an epileptogenic brain region constitutes a rational therapeutic approach, whereas systemic augmentation of adenosine is precluded by side effects. To meet the therapeutic goal of focal adenosine augmentation, genetic disruption of the adenosine metabolizing enzyme, adenosine kinase (ADK) in rodent cells was used as a molecular strategy to induce adenosine release from cellular brain implants, which demonstrated antiepileptic and neuroprotective properties. Currently, the second generation of adenosine-releasing cells is under development based on the rationale to use human stem cell-derived brain implants to avoid xenotransplantation. To effectively engineer human stem cells to release adenosine, a lentiviral vector was constructed to express inhibitory micro-RNA directed against ADK. Lentiviral knockdown of ADK induced therapeutic adenosine release in human mesenchymal stem cells, which reduced acute injury and seizures, as well as chronic seizures, when grafted into the mouse hippocampus. The therapeutic potential of this approach suggests the feasibility to engineer autologous adenosine-releasing stem cells derived from a patient. Human embryonic stem cells (hESCs) have a high proliferative capacity and can be subjected to specific cellular differentiation pathways. hESCs, differentiated in vitro into neuroepithelial cells and grafted into the mouse brain, displayed intrahippocampal location and neuronal morphology. Using the same lentiviral micro-RNA vector, we demonstrated knockdown of ADK in hESCs. New developments and therapeutic challenges in using human mesenchymal stem cells and hESCs for epilepsy therapy will be critically evaluated.