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• We describe 10 patients with a previously unreported, to our knowledge, association of multiple sclerosis and unusual vitamin B 12 deficiency. The clinical features and the age at presentation were typical of multiple sclerosis, with eight cases occurring before age 40 years, which is a rare age for vitamin B 12 deficiency. Nine patients had hematologic abnormalities, but only two were anemic. All six patients examined had low erythrocyte cobalamin levels. Only two patients had pernicious anemia; in the remaining patients the vitamin B 12 deficiency was unexplained. A vitamin B 12 binding and/or transport is suspected. The nature of the association of multiple sclerosis and vitamin B 12 deficiency is unclear but is likely to be more than coincidental. Further studies of vitamin B 12 metabolism, binding, and transport in multiple sclerosis are indicated, as these cases may offer a clue to the understanding of a still mysterious neurologic disorder.

• Subacute combined degeneration of the spinal cord due to vitamin B 12 deficiency invariably has been associated with a low serum vitamin B 12 level. We describe a young man who presented with a unique syndrome of subacute combined degeneration associated with high serum vitamin B 12 level, low red blood cell vitamin B 12 level, and an abnormal plasma vitamin B 12 -binding protein. Uptake of cobalamin by his leukocytes in vitro was inhibited by his own but not by normal control plasma. Intensive hydroxocobalamin (vitamin B 12 ) treatment was associated with clinical and electrophysiologic recovery accompanied by normalization of mean corpuscular volume, red blood cell vitamin B 12 level, plasma homocysteine, and urinary methylmalonic acid. The subacute combined degeneration was probably precipitated by treatment with folic acid as the significance of his high serum vitamin B 12 level was not apparent when he first presented with megaloblastic anemia 3 years earlier. To our knowledge, this is the first example of neurologic disease associated with high serum vitamin B 12 level and provides further evidence that sometimes a serum vitamin B 12 level may not be a reliable guide to vitamin B 12 deficiency.

We have previously described 10 patients with multiple sclerosis (MS) and unusual vitamin B12 deficiency. We have therefore studied vitamin B12 metabolism in 29 consecutive cases of MS, 17 neurological controls, and 31 normal subjects. Patients with MS had significantly lower serum vitamin B12 levels and significantly higher unsaturated R-binder capacities than neurological and normal controls, and they were significantly macrocytic compared with normal controls. Nine patients with MS had serum vitamin B12 levels less than 147 pmol/L and, in the absence of anemia, this subgroup was significantly macrocytic and had significantly lower red blood cell folate levels than neurological and normal controls. Nine patients with MS had raised plasma unsaturated R-binder capacities, including three patients with very high values. There is a significant association between MS and disturbed vitamin B12 metabolism. Vitamin B12 deficiency should always be looked for in patients with MS. The cause of the vitamin B12 disorder and the nature of the overlap with MS deserve further investigation. Coexisting vitamin B12 deficiency might aggravate MS or impair recovery from MS.

To the Editor. —May we comment on the controversy between Hauser 1 and Hart and Easton 2 on the subject of seizure recurrence after a first unprovoked seizure and the implications for treatment, as much of the debate centers on our own study? 3 In his figure, Hauser 1 compares our 3 high (71%) recurrence rate after a single seizure with the moderate (55%) and low (27%) three-year recurrence rates in the studies by himself and his colleagues at Rochester, Minn, 4 and Minneapolis, 5 respectively. There are many possible explanations for the variation in these three (and other 2 ) studies, but two factors appear most important to us. First, in both the Rochester and Minneapolis studies, approximately two thirds of the patients were actually treated with anticonvulsants, whereas none of our patients were so treated. This is very likely to have reduced the overall recurrence rate in the American studies. It

• Hughlings Jackson (1835-1911), who was born in Yorkshire (England), was the most famous graduate of the York Medical School, which closed in 1862. In York, he received his earliest neurological influences under Laycock. Jackson's most outstanding contributions were in the field of epilepsy. His were the definitive studies of unilateral convulsions that led Charcot to introduce the term Jacksonian epilepsy . His radically new view of epilepsy in terms of discharging lesions was the first neuronal theory and the foundation stone of our modern understanding of the disorder. His theories were based on detailed clinical observation and were later confirmed by the experimental studies of Fritsch and Hitzig, and by his colleague David Ferrier. He was more concerned with the nature than with the classification of epilepsy, and he linked his concepts of the disease to his hierarchical views of nervous system function. His writings on epilepsy over 40 years are on a par with the Hippocratic writings on the Sacred Disease.