This thesis has been written in two parts which are
(i) a systematic clinical analysis of giddiness as it presented in a neurological practice
(ii) histochemical measurements of the oxidative enzyme activity of certain brain stem and cerebellar neurons.
The concept which connects these two parts arose from the observation that giddiness tended to occur more rapidly and frequently than other symptoms which might have been expected when the territory of supply of the vertebro-basilar arterial system became ischaemic. In particular cochlear symptoms occurred less readily and less often in these circumstances. There was reason to believe that the giddiness arose from vestibular nuclear disturbance in the brain stem, and that this disturbance could not be determined purely by vascular factors. It seemed possible that there was something unusual about the metabolism of part or all of the vestibular nuclei, and this possibility was investigated by enzyme histochemistry.
THE WORK ON GIDDINESS
The study of giddiness began with an attempt to define "giddiness" in a way adequate to take in all partly or wholly hallucinatory experiences of disturbed equilibrium of the body, and particularly of the head, in space. This involved assessing the use of the word "giddiness" by 250 consecutive neurological patients. The definition decided on was then used to collect a series of 318 consecutive patients suffering from such giddiness, and these patients were analysed as to clinical features and cause of their symptom. Certain aspects of giddiness were considered in some detail. These included (a) paroxysmal positional giddiness, (b) giddiness occurring in vertebro-basilar arterial insufficiency (c) recurrent episodes of non-positional giddiness, and (d) the possible role of neck proprioceptive disturbance in giddiness.
The main findings from this clinical study of giddiness were
(a) how frequently giddiness occurred only on change in head position, or on placing the head into a particular critical position.
(b) the wide variety of peripheral and central pathologies associated with such paroxysmal positional giddiness.
(c) the frequency of ischaemia (in vertebro-basilar arterial insufficiency or in basilar artery migraine) as a cause of giddiness.
(d) how often no conventional diganosis could be made to explain giddiness, and the possibility that altered neck proprioceptive activity might be related to the mechanism of some of this undiagnosed giddiness.
THE HISTOCHEMICAL WORK
The histochemical studies attempted to measure the activities of five enzymes involved in glucose and oxygen metabolism in neurons of the medial and lateral vestibular nuclei, the dorsal cochlear nucleus, the abducens nucleus and the Purkinje cell layer of the cerebellum of three rabbit and three human rains. In addition the activities of the same enzymes were measured in the molecular and granular layers of the cerebellum in all six brains, and in ventral cochlear neurons in two human brains.
Before these measurements could be carried out it was necessary to develop chromatographic methods to assess the purity of tetrazolium salts, the reagents used to demonstrate the enzyme activity. Some aspects of tetrazolium chemistry were studied and it appeared that both mono- and di-tetrazolium salts may reduce to formazans through an intermediate stage. Because of this two stage reduction, definitive formazan production may not be in direct linear proportion to the strength of reducing conditions, so that it is necessary to calibrate reactions involving tetrazolium reduction in order to obtain reliable quantitative histochemical data.
The principles and details of the methods developed for measuring enzyme activity in situ in individual perikarya are described. It was argued that vulnerability of a perikarya to partial ischaemia would depend on its total amount of aerobic and anaerobic oxidative enzyme activity, and would be inversely related to its concentration of anaerobic enzymes. If this view were accepted the data of the study would suggest that lateral vestibular neurons should be more susceptible to ischaemia than neurons in the cochlear nuclei, a finding in keeping with clinical experience that giddiness occurs sooner than cochlear symptoms in brain stem ischaemia. The data also would help explain the well known selective ischaemic vulnerability of the Purkinje cells in the cerebellum.
In 1922 C. and 0. Vogt introduced a concept of pathoclysis - a local differential tissue sensitivity determined by the physical and chemical properties of the tissue itself - to explain selective vulnerability to ischaemia in situations in brain where vascular factors could not account for this phenomenon. For long time the physio-chemical factors underlying pathoclysis have been in doubt, but the present study has provided data which could explain, at least in part, how pathoclysis may come about in two different situations in the nervous system.