It is an honor to be asked to deliver the Silversides Lecture. Dr. Silversides’ clear understanding of the need for the collaboration of the basic and clinical sciences is a measure of the good sense for which he is admired. For a clinician, the greatest challenge to his clinical judgment lies in formulation of strategies to deal with vexing and serious conditions. Often we are called upon to treat conditions for which no satisfactory pathophysiologic mechanism has been elucidated. It is said that the clinician must frequently “get on top of the problem before he gets to the bottom of it.” In the spirit of all clinicians who seek better clinical approaches to poorly understood disease, I will devote this discussion to the diagnosis and treatment of pseudotumor cerebri.

Neurologists have had a long tradition of commitment and excellence in education. Whether we see our major role in clinical practice or clinical investigation, whether we are based in the community or in a university, virtually all of us have a role as teachers, a role in which we take great pride.

Normal CSF-MBP levels as determined by a RIA were <6.2 ng/ml CSF (mean 3.9). Eighty percent of patients with acute optic neuritis have CSF-MBP levels greater than 6.2 ng/ml (mean 7.6 ng/ml CSF). Five of 7 patients with acute internuclear ophthalmoplegia due to an initial exacerbation of demyelination have CSF-MBP levels above 6.2 ng/ml (mean 6.8 ng/ml). Fifty percent of MS patients with chronic progressive disease have CSF-MBP levels above 6.2 ng/ml (mean 6.7 ng/ml). MS patients experiencing monosymptomatic exacerbations show elevated CSF-MBP levels in 75% of cases (mean 8.2 ng/ml). MS patients experiencing polysymptomatic exacerbations show significantly higher levels of CSF-MBP (mean 22.3 ng/ml) than the patients with monosymptomatic exacerbations. Ninety-five percent of MS patients experiencing polysymptomatic exacerbations have elevated levels of CSF-MBP.

Myelin basic protein (MBP) is an antigenic component of circulating immune complexes (CIC) in patients with multiple sclerosis (MS). Immune complexes were isolated from the sera by adsorption to Raji cells and then acid eluted. Final identification of MBP from Raji eluates was done by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) followed by MBP radioimmunoassay (RIA) of gel eluates and by an immunoblot technique.

We describe nine patients with plexopathies or proximal mononeuropathies due to mass lesions. In four, computed tomography (CT) was the only radiological technique to show the cause of the neuropathy. In five patients, CT either unequivocally confirmed the presence of an abnormality or was superior to other imaging techniques in showing its full anatomical extent. CT scanning is a valuable aid in the assessment of lesions of the peripheral nervous system, particularly plexopathies and mononeuropathies caused by retroperitoneal, pelvic or superior pulmonary sulcus tumors.

The lumbar spines of one hundred patients with suspected lumbar disc herniations were analysed with computed tomography. The results are compared with the patients’ surgical diagnosis and with myelography. CT scanning is with few exceptions the diagnostic procedure of choice in investigating lumbar disc disease.

Normal values for the amplitudes of digital sensory nerve action potentials were obtained from 190 control subjects, using an orthodromic surface-recording technique. Lower limits were calculated, taking into account laterality, age and sex; the ratios of amplitudes between different digits were also estimated. The results in control subjects were compared with those of 20 cases of trauma involving root avulsion or extraspinal injury, 38 patients with intraspinal disease, 6 patients with extraspinal disorder and 9 cases of neuralgic amyotrophy. The variability of the dermatomes is discussed and it is concluded that digital sensory potential amplitudes offer a useful method of determining the site of a nerve lesion, provided certain limitations are recognized.

The pattern electroretinogram (PERG) is probably generated by the ganglion cell layer of the retina whose axons constitute the conductive fibres of the optic nerves. A study was undertaken of the PERG in a group of patients with clinically definite multiple sclerosis who had suffered optic nerve demyelination to assess the value of recording the PERG as a method for electrophysiological determination of optic nerve dysfunction. Pattern visual evoked potentials (PVEP) were simultaneously recorded, each eye being stimulated separately, and four different check sizes were used. Although individual patients showed PERG abnormalities the results as a group showed no significant difference from the normal population so far as latency or amplitude of the PERG was concerned. Thus we conclude that the PERG, while an interesting measurement, does not satisfactorily reflect optic nerve dysfunction. Further, our results indicate that it is not such a useful measure as the pattern visual evoked response for detecting optic nerve disease.

We report multimodal evoked response studies in eleven children with ataxia telangiectasia. The ABRs were normal in all but one patient despite the severity of the disorder. The SERs were abnormal in all of the patients, the waveforms being either absent or of delayed latency, the abnormalities were more marked in the older patients. Abnormal motor and sensory nerve conduction studies were also found in all but the younger few patients. Most notably, the VERs were abnormal in all but 2, the older patients had delayed VERs and most had small amplitude responses. The electrophysiological profile of ataxia telangiectasia patients on the multimodal evoked responses differs from that found in certain other degenerative ataxias studied and may have some diagnostic utility.

Two paragangliomas resected from the cauda equina had similar morphology, both containing cells having dense core secretory granules with no associated sustentacular or supporting cells. The cells were arranged in characteristic lobules that were surrounded by basement membrane and separated by a fibrovascular stroma. This tumor, although rarely found elsewhere in the central nervous system, does occur in the region of the filum terminale, and causes a clinical syndrome typical of tumors in that area.

A patient with long standing sustained unilateral headache (“background vascular”) and occasional multiple jabs received prompt and lasting relief from indomethacin. The effectiveness of the drug was tested in a placebo controlled double-blind trial. Indomethacin may be of value in some types of sustained headache.