Consultant’s corner: the “breakthrough” seizure

Seizures are a common cause of emergency department visits. This article provides an algorithm for evaluation and management of the patient with a known seizure disorder who presents with a breakthrough event. If the seizure represents a significant deviation from the usual pattern or the patient has an established pattern of episodes of status epilepticus, early involvement of the consultant neurologist is warranted. Otherwise, the first step is to search for provocative influences such as fever, intercurrent illness, or non-compliance with prescribed anti-epileptic drugs. Measurement of drug levels will guide the next rational phase of management. The overwhelming majority of patients can be managed following this logical framework.     

“Marden-Walker Syndrome”: Neuropathologic Findings in Two Siblings

Neuropathologic examination of two siblings with phenotypic features consistent with Marden-Walker syndrome revealed central nervous system abnormalities which include reduction in the number of spinal anterior horn cells. The occurrence of these changes in a sibling pair provides strong evidence for a genetic etiology. The relationship between the neuropathologic changes and other phenotypic manifestations in this syndrome and in the closely related syndrome of Pena-Shokeir are discussed.     

Long-term survival in childhood acute leukemia: “Late” relapses

The “late” relapse patterns of childhood acute leukemia were studied in 83 children in their first continuous complete remission for more than three years prior to randomization for stopping therapy (40 patients) or continuing therapy (43 patients) for a total of six years. Twenty of 83 (22.9%) have relapsed: Ten in the bone marrow, one in the central nervous system, and nine in the testes. The testes relapse rate of 41.1% (7/17) in males discontinuing therapy at three years was much higher than that of 8.7% (2/23) in males continuing therapy. This difference is significant at P = 0.01 (Wilcoxon test).     

Plasma phenylalanine: Tyrosine ratios during high-dose methotrexate-citrovorum “rescue”

We have measured phenylalanine and tyrosine in the plasma of patients with osteogenic sarcoma undergoing chemotherapy with high-dose methotrexate (HDMTX) citrovorum factor rescue (CFR). During 14 treatments in six different patients, the phenylalanine to tyrosine ratio (PHE/TYR) at 21 to 38 hours was elevated over pretreatment levels. The observed increase in plasma phenylalanine is attributed to inhibition by MTX of the phenylalanine hydroxylase system of the liver, which is not folate-dependent and thus is not corrected by administration of CF. A post-infusion increase in PHE/TYR of 571% after 22 hours in one patient and of 410% after 30 hours in another were associated with marked MTX toxicity. The greatest increase in PHE/TYR seen in a patient who did not experience toxicity was was 249% in 21 hours. Thus, in this group of patients, there appears to be a correlation between evidence of clinical MTX toxicity and the magnitude of the percentage increase in PHE/TYR in the plasma, which indicates inhibition of a liver enzyme and thus reflects the intracellular concentration of MTX.     

James Ewing (1866–1943): “the chief”

“It is a growing conviction that to know cancer in man, one must study the disease most carefully in the human subject. Personally, I do not look for any startling advances or sensational discoveries, since it is much more likely that a steady reduction in the mortality from cancer will come chiefly from a large number of separate factors, of which the most significant appear to be increased control of the conditions leading to cancer, more general recognition of the preliminary stages of the disease, early diagnosis, and treatment of the established disease. From the consideration of these various functions of the modern cancer research hospital, I think that it must be evident that such an institution not only can justify its existence, but fills a very urgent need without which, progress of cancer research would be handicapped, and much relief that might early be extended to cancer victims would be unavailable. Nor is there any doubt that the function of supporting such an institution is properly exercised by the State, which support should be continuous and liberal”—James Ewing [2]. © 1993 Wiley-Liss, Inc.