Recognition and Treatment of Intracranial Manifestations of Leukemia

Abstract

One of the prime objectives in the therapy of acute childhood leukemia is to maintain the patient symptom-free and capable of enjoying normal activity. The development of neurologic complications poses a serious threat to this aim.Leukemia involving the central nervous system may be manifested by symptoms and signs of meningeal irritation and increased intracranial pressure, seizures, and/or cranial nerve palsies. Not infrequently patients who have had no symptoms or signs of central nervous system involvement during life may at necropsy be found to have widespread infiltrative lesions involving the meninges and brain.Since orally administered antimetabolites apparently do not penetrate the blood-cerebrospinal fluid barrier in sufficient concentrations to prevent or control such complications, therapy in the past has included steroids and irradiation to the skull. The beneficial effects of these modes of therapy may be quite short in duration. 1 Recently, Burchenal and co-workers 2 described a dramatic beneficial effect in five patients after the intrathecal administration of amethopterin. The present report will describe four children, one of whom pre¬ sented with acute hydrocephalus, who re¬ sponded quite well to this therapy.* Editorial Note : The occurrence of intracranial complications in acute childhood leukemia has become increasingly important as more and more prolonged hématologie remissions are achieved with current methods of therapy. While the presentation of the cases tends to bring out the importance of this fact, the experience of the author is not entirely typical of that gained by the study of a larger series. Specifically, it might be well to stress that in many instances neurologic symptoms occur, sometimes repeatedly, while not only the peripheral blood but study of the bone marrow indicates a prolonged complete hématologie remission. It is also worth pointing out that by intrathecal therapy freedom from neurologic symptoms can often be maintained for longer periods than the results of this article would indicate.As the natural history of leukemia has been modified by induced remissions, it has become clear that increased intracranial pressure due to the leukemic process may be present for long periods of time without frank clinical manifestations, and only systematic examination of the eyegrounds and periodic checks on the pressure and composition of the spinal fluid will alert the clinician. The author's experi¬ ence in one other respect is not typical of that in other clinics. We have usually found a significant elevation of the protein and a decrease in sugar initially and then a reversal of these changes under therapy. As it is now possible to maintain life up to several years, the study and treatment of the intracranial manifestations of leukemia luive become important, and it wotdd be desirable to have a dosage schedule for intra¬ thecal therapy and to have the role of supplementary radiation more definitely estab¬ lished.Four children with acute lymphocytic leukemia were studied in who...

Intracranial Complications of Leukaemia Treated with Intrathecal Amethopterin

“…That these remissions are temporary was noted by Whiteside et al (1958) who found the effect to last for only four to six weeks in the four children they treated for presumed intracranial leukaemic infiltration. Nevertheless, one of the four patients reported by Cramblett (1959), and eight of the 23 patients reported by Murphy (1959) had a remission of intracranial complications of up to eight months. The last author considered that the best results were obtained in the patient with headache, increased intracranial pressure, papilloedema, vomiting, separation of the cranial sutures and a pleiocytosis of the cerebrospinal fluid; all the signs shown by the first child reported here who also survived for eight months after treatment of the first intracranial complications.…”

“…levels were 30 to 100 times higher than those found after a massive single oral dose. Treatment of these neurological complications of leukaemia with intrathecal amethopterin have been published in the American literature (Whiteside et al, 1958;Cramblett, 1959;Murphy, 1959). In the first child reported here the response to intrathecal therapy was quite dramatic.…”

Intracranial leukaemia and the cerebrospinal fluid.

“…Non-metastatic neurological syndromes have also been reported (Currie et al, 1970). Clinically, leukaemic involvement of the central nervous system may be manifest as signs of meningeal irritation, increased intracranial pressure, seizures, or cranial nerve palsies (Cramblett, 1959).…”

Leukaemic Meningitis

“…It was present in only 20% of the 334 cases studied by Schwab and Weiss (1935). Since the use of more effective chemotherapy, cases of children receiving such treatment who have developed signs of intracranial involvement are being reported (Poncher, Waisman, Richmond, Horak and Limarzi, 1952;Sansone, 1954;Sullivan, 1957;Meneely, 1958;Whiteside, Philips, Dargeon and Burchenal, 1958;Cramblett, 1959;Murphy, 1959). Hamilton and Elion (1954) showed that the concentration of labelled 6-mercaptopurine in cerebral tissue was only one-tenth of that found in blood and that an even greater differential existed between its concentration in blood and cerebrospinal fluid.…”