Motor nervous pathway function is impaired after treatment of childhood acute lymphoblastic leukemia: a study with motor evoked potentials.

BACKGROUND: The objective was to evaluate whether motor nervous pathways are affected when patients are treated for childhood acute lymphoblastic leukemia (ALL). PROCEDURE: Thirty-two children with ALL were studied at the end of treatment by means of motor evoked potentials (MEPs) elicited by magnetic stimulation (MS) transcranially and peripherally and underwent a detailed neurological examination. Thirty-two healthy children matched with them for age, sex, and height served as a control group. RESULTS: The latencies of the MEPs were significantly prolonged along the entire motor nervous pathway in the patients with ALL compared with the healthy controls, indicating demyelination in the thick motor fibres. The MEP amplitudes of the distal extremities elicited by stimulation at the brachial plexus and LV spinal level were significantly lowered in the patients treated for ALL, also indicating anatomical or functional loss of descending motor fibres and/or muscle fibres. The MEP amplitudes elicited by cortical MS showed wider variation and no clear abnormalities were found. Neurological signs and symptoms were common after treatment: 41% of the patients had depressed deep tendon reflexes, 31% had fine motor difficulties and 63% gross motor difficulties, and 34% had dysdiadochokinesia. The conduction delay within the peripheral nerve was related to the post-therapeutic interval after administration of vincristine and the lesions within the CNS to the number of injections of intrathecal methotrexate. CONCLUSIONS: The present results show adverse effects of the ALL treatment on the entire motor nervous pathways. In our experience, the measurement of MEPs by MS provides an objective, painless, and practical tool for assessing the treatment-related neurotoxicity in both the CNS and the peripheral nerves. These disturbances in the motor nervous pathways at the end of treatment raise the question of the long-term effects of ALL treatment on the motor nerve tracts, and have led us to employ MEPs to study these effects in long-term survivors of ALL.

Bone marrow changes on MRI in children with acute lymphoblastic leukaemia 5 years after treatment.

T1-weighted magnetic resonance imaging (MRI) of the lower extremities was performed 5 years after the cessation of therapy on 25 children treated for acute lymphoblastic leukaemia (ALL). Signal intensity pathologies considered to be related with the leukaemia itself or the treatment of ALL were found in nine of 25 children (36%). Two of these children had findings of osteonecrosis, five had a patchy signal pattern, one had diffuse inhomogeneity of the bone marrow signal intensity in complete remission and one had diffusely decreased signal intensity preceding the diagnosis of relapse. MRI unexpectedly revealed many bone marrow pathologies in symptomless children successfully treated for ALL. Especially, osteonecrosis might cause significant disability, and the aetiology, clinical course and prognosis of this complication are not well known. The intensive dexamethasone medication included in the treatment protocols may be responsible for the development of osteonecrosis. However, the prognosis of osteonecrosis in the long run requires further studies.

Nerve lesions after therapy for childhood acute lymphoblastic leukemia.

BACKGROUND: The objective of the current study was to use somatosensory evoked potentials (SEP) to detect signs of nerve lesions in the peripheral nerve and in the central nervous system (CNS) after 3 years of treatment for childhood acute lymphoblastic leukemia (ALL). METHODS: The somatosensory potentials evoked by stimulation of the median nerve and posterior tibial nerve were recorded in 31 children with ALL after 3 years of therapy. All patients were examined clinically. The 14 standard risk patients had been treated with chemotherapy according to the Nordic regimen, and the 17 intermediate risk or high risk patients had been treated with chemotherapy and cranial irradiation according to the ALL BFM-83 protocol. RESULTS: A decrease in amplitudes was observed at the brachial plexus and spinal cord (C7) in the median SEP, and at the knee, spinal cord (Th12), and cortex in the tibial SEP, indicating axonal injury within the entire CNS in the patients with ALL compared with healthy age-, gender-, and height-matched controls. Prolongation of the SEP latencies was found within the spinal cord, indicating demyelination. These SEP changes had persisted for 2 years since the last injection/infusion of vincristine or methotrexate, which are the principal neurotoxic drugs used in chemotherapy for ALL. Clinical signs of nerve injury such as depressed deep tendon reflexes and gross or fine motor difficulties were found in approximately 33% of the patients and dysdiadochokinesia in 50%. CONCLUSIONS: Treatment of ALL in children principally with vincristine and methotrexate causes long-standing axonal injury throughout the nervous system and demyelination within the spinal cord. These changes are associated with clinical neurologic findings.

A longitudinal magnetic resonance imaging study of the brain in survivors in childhood acute lymphoblastic leukemia.

BACKGROUND: The objective of this study was to evaluate changes in magnetic resonance imaging (MRI) of the brain in children with acute lymphoblastic leukemia (ALL) during the first 5 years after the cessation of therapy and to correlate MRI abnormalities with neuropsychologic outcome. METHODS: Thirty-two children with ALL were studied at the end of treatment and 5 years later by brain MRI and the results were compared with the neuropsychologic findings. Fifteen patients had received chemotherapy alone and 17 had received chemotherapy plus cranial radiation. RESULTS: MRI of the brain was abnormal in 6 of 30 patients at the end of treatment and in 8 of 32 patients 5 years later. White matter changes (WMC) were found in 3 patients at the end of treatment and in 4 patients 5 years later. Two patients had developed new mild changes, whereas in one case WMC had normalized during the follow-up. Two patients had old hemorrhages or calcifications at each examination, with some improvement after follow-up, although one case revealed a new calcification or hemorrhage. Signs of cortical atrophy were observed in five patients at both evaluations. The patients with abnormal MRI findings did not differ significantly in their performance in the neuropsychologic tests from the patients with normal MRI findings, but the two patients with persistent WMC had a depression of verbal functions. CONCLUSIONS: Abnormalities in brain MRI were infrequent at the end of treatment for childhood ALL and 5 years later. They did not appear to correlate significantly with neuropsychologic outcome. Brain MRI is not very informative as a routine follow-up method during the first 5 years after treatment.

Osteonecrosis in children treated for acute lymphoblastic leukemia: a magnetic resonance imaging study after treatment.

The purpose of the study was to find out the prevalence of osteonecrosis in children with acute lymphoblastic leukemia (ALL) in complete bone marrow remission at the end of the treatment. Twenty-eight children with ALL underwent MRI of the upper and/or lower extremities. Bone marrow signal intensity was analyzed on T1-weighted images, where circumscribed lesions with a rim of low signal intensity were considered typical of osteonecrosis. Osteonecrosis was found in 9 of the 28 children (32%, 95% CI 16% to 52%). Five of them were asymptomatic. They had been treated with high risk and intermediate risk protocols, both of which include a delayed intensification phase with dexamethasone. None of the patients with standard risk ALL were found to have developed osteonecrosis. Osteonecroses occurred unexpectedly in symptomless patients and in patients with mild transient symptoms treated with high risk and intermediate risk protocols. Our study suggests that the intensification phase of the treatment protocols with intensive dexamethasone medication might be responsible for the development of osteonecrosis.

Abdominal ultrasound findings during and after treatment of childhood acute lymphoblastic leukemia.

BACKGROUND: The treatment of acute leukemia in childhood has been increasingly successful. Concurrently, severe leukemia-related gastrointestinal complications have become more common. METHODS: We evaluated the findings of the abdominal ultrasound (US) examinations of 52 children with acute lymphoblastic leukemia (ALL) who had severe clinical symptoms indicating infection or abdominal complication during chemotherapy treatment or after the cessation of such treatment and assessed the impact of these findings on patients' subsequent treatment and survival. RESULTS: Our study presents ten cases of typhlitis with a prevalence of 9%, all of which were rapidly diagnosed by US and had a favourable outcome. We also found focal intra-abdominal parenchymal lesions in six children, five of them due to fungal infection and one due to leukemic infiltration. Several other intra-abdominal pathologies significant for the patients' treatment are also reported. DISCUSSION: We believe that abdominal US is a useful, rapid, safe, and accurate imaging method for children with ALL suspected to suffer from leukemia- or chemotherapy-related gastrointestinal complications. More invasive imaging methods are seldom needed. CONCLUSIONS: According to our results, abdominal US gives the necessary information in most of the cases and provides prompt diagnosis, which may prevent possible fatal complications.

Brain perfusion after treatment of childhood acute lymphoblastic leukemia.

UNLABELLED: Children with acute lymphoblastic leukemia (ALL) have impairment in their neuropsychological functioning and morphological changes in their brain after cranial irradiation and chemotherapy. The aim of this study was to identify possible brain perfusion defects caused by different types of treatment and their association with abnormalities in cerebral MRI and neuropsychological and clinical neurological findings. METHODS: Twenty-five consecutive children with ALL at the cessation of chemotherapy or after 1 yr were included. All of the children were given intravenous and intrathecal methotrexate for central nervous system therapy, 13 of them received cranial radiation therapy. Brain SPECT, cerebral MRI, clinical neurological and neuropsychological evaluations were performed. RESULTS: Eleven of the 25 patients (44%) had brain perfusion defects in SPECT, eight of whom were treated with chemotherapy alone, and three received cranial irradiation. Two patients had small bilateral white matter changes on MRI; their brain SPECT scans were abnormal, although the findings were not related. Impairment of neuropsychological functioning was found in 86% of the patients tested. No significant difference between the patients with abnormal and normal SPECT were found. Those patients with abnormal SPECT were younger than those with normal SPECT and had received more frequent intravenous methotrexate infusions. CONCLUSION: Brain SPECT detected perfusion defects that had occurred after treatment for childhood ALL. These defects may be related to frequent administration of a combination of intravenous and intrathecal methotrexate and/or young age.

Abdominal sonographic findings at primary diagnosis of acute lymphoblastic leukemia in children: a comparison with different clinical risk factors.

We evaluated the presence of abdominal organomegaly and lymphadenopathy with ultrasound in 92 children with acute lymphoblastic leukemia (ALL) prior to chemotherapy, and compared these findings with the different immunophenotypes, age groups, and white blood cell (WBC) counts as well as the survival of the patients and the clinical findings of organomegaly. All the patients (n = 13) with a WBC higher than 50/microL showed intra-abdominal pathology compared with the patients with a low WBC, of whom 37% (n = 18) had normal scans. The children with a high WBC count also had hepatomegaly (P = 0.003) and splenomegaly (P = 0.06) significantly more often, and showed high echogenicity of the kidneys (P = 0.001). Lymphadenopathy was found significantly more often in children with T-cell leukemia (P = 0.005). The younger age groups (0 to 2 and 2 to 5 years of age) had hepatomegaly significantly more often (P = 0.02), and the youngest age group (0 to 2 years) showed increased echogenicity of the kidneys more often (P = 0.04). Ultrasound showed hepatomegaly in 14 patients and splenomegaly in 23 patients who were assessed clinically as normal. According to our results, abdominal ultrasound is a useful tool for evaluating abdominal organomegaly and the extramedullary leukemic burden and can give information that is not available in clinical examination. There was no statistical association between the primary ultrasonographic findings and the patients' later survival.