GENERAL DISCUSSION AND CONCLUSION

Degeneration of the Purkinje cells in patients with epilepsy was described by Spielmeyer (1920), who divided the changes into several stages, ending in loss of Purkinje cells. Pei f fer (1963) found a loss of Purkinje cells in 59 of 285 patients with grand ma1 epilepsy. The incidence of neuropathological changes was highest in those patients with frequent convulsions. In epilepsy induced in cats by stereotactic injection of alumina cream into the brain, an extensive loss of Purkinje cells was found in those animals with generalized convulsions but not in those with >>psychomotorcc seizures only (Gastaut et al. 1959). Loss of Purkinje cells and proliferation of glial cells were prominent in children who died in status epilepticus (Zimmerman 1938) and in kittens subjected to febrile convulsions (Lennox et al. 1954). The age at which frequent seizures occur may thus be a factor, but it has not been studied systematically. As to the cause of loss of Purkinje cells, Skielmeyer and his school held that patients with epilepsy had a functional vascular insufficiency with spasms of the arteries involving mainly the cerebellum and Ammon’s horn, and that the resultant hypoxia caused the pathology (Sbielmeyer 1927, 1929, 1930, 1933, Liebers 1928, Dreszer & Schotr 1939, Scholz & ]o>vascular spasma theory of epilepsy is contradicted by the fact that the cerebral circulation during seizures is greatly increased (Gibbs et al. 1934, Penfield et al. 1939, Plum et al. 1968), though not enough to compensate for the increased demand for oxygen and production of C 0 2 and metabolites (Meyer & Gotoh 1965). Zimmerman (1938, 1959) thought that asphyxia and obstructed venous return from the head during convulsions were additional factors causing hypoxia. I t has been shown experimentally that there is an increased cerebral metabolism during convulsions (Beresford et al. 1969, and his references). DPH has been widely used since it was introduced by Merritt & Putnam in 1938. The toxic signs of ataxia and nystagmus generally disappear when the dose is lowered or the drug withdrawn, and instances of poisoning with excessive doses without permanent sequelae have been reported (Robinson 1940, Aring & Rosenbaum 1941, Cattan et al. 1947, Nauth-Misir 1948, Price & Frank 1950, H ~ y r u k & Vinten-Johansen 1952, Putnam & Rothenberg 1953, Grosz 1956, Floyd 1961). Until 1954 there were no reports of cases of ataxia persisting after withdrawal of the drug (Livingston 1954, 1957, Utterback 1958, Utterback et al. 1958, Hofmann 1958, Roger & Soulayrol 1959, Viukari 1962, Haberland 1962, Kokenge et al. 1965, Hogelmeier & Wenre l 1969).