Neural implants and recovery of function: human work.
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Biomedical subjects
Publications and source records attributed to E Hitchcock.
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Open Stereotactic Surgery [OSS] may be defined as the use of precise stereotactic techniques to facilitate conventional neurosurgical procedures. The field has expanded in recent years particularly in the areas of imaging, instrumentation and co-ordinate transfer. The factors influencing the developments are explored.
Conventional methods of in situ hybridization are not only complex, laborious and lengthy, tending to produce poor cellular resolution but are also inherently hazardous. We report a new method that overcomes many of these difficulties. Denovo attachment of a non-isotopic ligand, viz. 5-bromo-2'-deoxyuridine (BrdU) to oligonucleotide probes guaranteed the production of labelled probes of 100% specific activity that gave consistent, reproducible results, within hours, in a rapid in situ hybridization (ISH) technique. The method is demonstrated by localization of insulin-like growth factor II (IGF-II) mRNA in human intracranial tumours and foetal brain. Five of 10 meningiomas expressed IGF-II mRNA to an extent of 1% of their tumour cells and two of three pituitary adenomas exhibited a less than 0.2% IGF-II mRNA-positive cell population. IGF-II may be important in the progression and/or maintenance of these tumours. Foetal brain showed no hybridization. The method's simplicity, rapidity and reliability commends its use in a variety of research and diagnostic applications and the BrdU-labelled probes can be used in any hybridization technique.
Electrical stimulation of a point in the visual pathway can evoke a visual sensation which is called a phosphene. The phosphenes elicited by intracerebral stimulation were investigated in twenty-three subjects. One hundred and seven phosphenes were reported and all of them appeared in the visual field contralateral to the side of stimulation. The exception was a single case where a diffuse flashing sensation appeared in the whole visual field. Thirteen patients reported white phosphenes and nine patients reported coloured phosphenes. In the medial area (10-15 mm from the midline) of the occipital lobe, stimuli above the calcarine fissure resulted in phosphenes in the lower quadrant of the visual field. In the lateral area (16-32 mm from the midline), however, stimuli above the level of the calcarine fissure tended to produce phosphenes in the upper quadrant. These findings appear to conflict with traditional concept of the physiological anatomy of the visual pathway in man. The possible mechanism of this phenomenon produced by intracerebral stimulation is discussed in relation to the phosphenes produced by cortical stimulation.
The influence of various factors upon the survival of human foetal neurones has been examined. The viability of several brain structures was assessed using ethidium bromide and acridine orange fluorescence in both 'intact' and mechanically dispersed tissue. Striatum was least vulnerable to dissociation while cortex, mesencephalon, pons, cerebellum and cord were more vulnerable to a greater or lesser extent. Material can be preserved in vitro with greater viability in the undissociated rather than dissociated state. The effects of other factors including foetal age upon viability are discussed.
A rapid and versatile method has been developed for estimating proliferating/labelling indices (enumerated S-phase cells) of brain tumours. Fragments of fresh, surgically excised tumour specimens are labelled in vitro with 10 microM bromodeoxyuridine (BrdU) at 37 degrees for 1 hour in MEM + 10% FCS, washed in PBS, blotted dry and then imprinted on glass slides leaving a mirror image monolayer of cells of the impressed surface. The incorporated BrdU is then detected indirectly by immunoperoxidase staining after fixation. No fewer than 1000 cells are counted under high power and the PI is expressed as the % of BrdU positive cells to the total number counted. The PI of the various tumours analysed ranged 2.54-13.08% for gliomas, 5.29-7.60% for metastases, 0-0.83% for benign meningiomas. Thirty one cases have been studied. Results, obtainable within a few hours of tumour biopsy/resection, correlate favourably with published flow-cytometry proliferating indices for the tumours analysed and thus validate the method as a comparable alternative to in vivo BrdU labelling.
Dystonia musculorum deformans (DMD) is an idiopathic movement disorder which usually involves pediatric age group and progresses to the generalized type. On the contrary in adult-onset DMD, dystonia is usually confined to an upper extremity and its clinical course is benign. The authors report seven patients with adult-onset DMD whose initial symptom was confined to the neck. Diagnosis of idiopathic spasmodic torticollis had been made in all of them. Average ages at the onsets of torticollis and extranuchal dystonia were 49 +/- 13 and 54 +/- 9 years (mean +/- SD) respectively. The duration between these onsets was 2-3 years in five patients and 10-17 years in two younger patients. Two patients finally developed generalized dystonia and one patient became hemidystonic type. These findings suggest that some patients diagnosed as idiopathic spasmodic torticollis are in an early stage of DMD and that this particular type progresses more likely to the generalized form than other types of adult-onset DMD.
Interpretation of polyamine levels found in the tissues and red blood cells of tumour patients has been plagued by the wide variations seen in the concentrations when estimated in groups of either tumour or control patients. To ascertain whether the patient's age or sex were contributing factors, red blood cell polyamine concentrations of 117 control patients were examined by high-performance liquid chromatography. Concentrations of spermidine were consistently higher than those of spermine. Also, regression analysis showed that spermidine and spermine levels tended to change with age and sex, though these trends were statistically non-significant.
Posterior third ventricular masses are uncommon and posterior intraventricular masses are rare. Intraventricular and paraventricular lesions are difficult to differentiate in this region and present particular problems of diagnosis and treatment. Uncertain radiology and frequently confusing histology make treatment planning difficult. The first requirement of histological confirmation of the speculative pathology is best achieved by stereotactic biopsy rather than craniotomy exposure and biopsy, the mortality and morbidity for each being compared. The problem of CSF pathway obstruction can be dealt with by aspiration of the mass or CSF diversion; solid tumours frequently require a definitive shunting procedure while other lesions may not.
Red blood cell (RBC) polyamines, spermine and spermidine have been assayed from 103 patients with confirmed intracranial tumours and 87 controls. For spermine the test had a specificity of 97% and a sensitivity of 30% in preoperative patients, increasing to 40% in glioma patients. Tumour recurrence in postoperative patients gave a sensitivity of 48% increasing to 60% in glioma groups. For initial tumour presentation, therefore, this test is suggestive, though not unequivocal, of tumour presence. Its major role probably lies in monitoring the progress of the patient and its major importance in the detection of tumour recurrence.
Red blood cell polyamine levels have been determined in patients with various histologically confirmed brain tumours. Increased spermine and spermidine levels were found in most patients with perifocal oedema demonstrated by CT; no correlation was found to other CT variables, nor to tumour localization. Polyamine levels increased during the clinical course coincident with tumour activity and decreased in response to surgery and radiotherapy. The response to chemotherapy involved a change in the relationship between spermine and spermidine levels. Our results underline the significance of regular polyamine level estimation during the management of patients with brain tumours.
We describe the design of a programmable neurosurgical stimulator with impedance monitoring facilities. The computer is used both to control a stimulator and for the storage of various parameters employed in the process. The stimulator is designed to minimize tissue damage by injecting net zero charge; its output is a current, independent of load resistance. By measuring electrode voltage, the load impedance can be calculated. Software is provided in order to log patient data, and trajectory details with reference to coordinates calculated from other imaging systems such as CAT scanners.
Red blood cell polyamine levels were followed in 13 patients treated with stereotactic radiosurgery for various types of brain tumours. In the most malignant tumours radiosurgery resulted in a decrease in spermine and an increase in spermidine levels. This discrepancy between variations in polyamine levels was not found after conventional radiotherapy. The results may indicate a change in tumour polyamine activity induced by high energy radiotherapy.
Conventional neuropathological stains, immunocytochemistry and cell culture can be performed on small tissue fragments obtained by stereotactic biopsy. A simple processing technique is described with particular attention to immunocytochemistry. The results of this technique are described for 34 specimens obtained from patients with low- and high-grade gliomas, lymphomas, pineal tumour and benign processes. The application of immunocytochemical techniques is of value in achieving a definitive diagnosis in the small tissue fragments obtained by stereotactic biopsy.
A system of stereotactic radiosurgery using a linear accelerator is described and the experience with a variety of neurosurgical lesions including gliomas, acoustic neurinomas and arteriovenous malformations is recorded. The system is simple, inexpensive and effective and can be used with any CT scanner and linear accelerator.
Symptomatic and functional assessments have been made on a number of patients with a variety of involuntary movement disorders. Difficulties of assessment and their relevance to outcome are discussed. Almost all groups showed a substantial symptomatic improvement but functional improvement was less pronounced.
Fifty meningiomas of four major histological types have been examined by immunocytochemical methods applied to formalin fixed paraffin embedded material and using readily available commercial antisera. The expression of GFAP, S100, NSE, vimentin, cytokeratin, fibronectin and desmoplakin was investigated. The majority of tumours contained NSE (86%) and S100 (78%), and all irrespective of histological type, contained vimentin and fibronectin. The epithelial marker cytokeratin was found in 56% of cases, but showed only focal expression. The relevance of these findings to histogenesis and metabolism is discussed and it is suggested that intermediate filament typing provides valuable information on meningiomas structure and function. The possible role of NSE and S100 in meningeal neoplasm is discussed.
An anti-epithelial membrane antigen monoclonal (Clone E29) was used as part of a panel of antisera in the investigation of primary CNS and metastatic tumours. In contrast to others, definite and often strongly positive cross-reactivity has been demonstrated on glial cells. The material consisted of fourteen astrocytomas, two ependymomas, six cerebral metastases and two cases of gliosis.