Polyneuropathy in Acute Lymphoblastic Leukemia Long-Term Survivors: Clinical and Electrophysiological Characteristics With the Impact of Radiotherapy

Abstract

Introduction: Acute lymphoblastic leukemia (ALL) is the most common childhood cancer with one of the highest survival rates. Long-term complications that occur after intensive oncological treatment often impair normal daily functioning. However, existing data on peripheral nervous system condition in ALL survivors remain conflicting.Materials and Methods: The study group consisted of 215 ALL survivors. Patients were treated with New York (NY, n = 45), previous modified Berlin–Frankfurt–Münster (pBFM, n = 64), and BFM95 (n = 106) protocols. Time elapsed between the end of the treatment and the control examination varied from 0.3 to 20.9 years. The analyzed patients underwent a neurophysiological analysis with electroneurography (ENG) of motor (median and peroneal) and sensory (median and sural) nerves as well as electromyography (EMG) of tibialis anterior, vastus lateralis, and interosseous I muscles. To estimate the influence of radiotherapy on recorded neurophysiological responses, a joint analysis of NY, and pBFM groups was performed.Results: Clinical symptoms of polyneuropathy were noted among 102 (47.4%) children during the ALL therapy and in 111 (51.6%) during follow-up. At the time of treatment, polyneuropathy was diagnosed in 57.8% participants from NY group, 35.9%—pBFM and 50.0%—BFM95 (p = 0.145). A significantly higher incidence of polyneuropathy was observed during a follow-up in the NY group (68.9%; p < 0.001 vs. pBFM, p = 0.002 vs. BFM95). The most frequent abnormality within all the protocols was demyelination (NY: 44.4%, pBFM: 59.4%, BFM95: 41.5%), in contrast to the least frequently registered isolated axonal changes. The negative influence of oncological treatment on neurophysiological parameters in ALL survivors was observed. Complex disorders of motor nerves, sensory nerves, and motor unit potentials were registered. Motor-sensory neuropathy was the most frequently found pathology in all analyzed protocols. The harmful effect of radiotherapy was also observed in EMG results.Conclusions: Detailed neurophysiological analysis in long-term childhood ALL survivors has shown generalized abnormalities in registered parameters. To our knowledge, the current study is the largest and one of the most comprehensive ones among those examining disturbances in ENG and EMG in this group of patients. Moreover, we are the first ones to demonstrate the negative influence of radiotherapy on peripheral nerve conduction parameters.

Acute Lymphoblastic Leukemia Masquerading as Guillain-Barré Syndrome

“…These neurological complications are the result of the infiltrative process of ALL to both the central and peripheral system causing signs of intracranial hypertension such as headache and papilledema, cranial nerves palsies, and nerve root compressions 1. Moreover, the neurological complication in ALL could be secondary to chemotherapy agents, especially the commonly used microtubule-targeting drug (vincristine) in ALL treatment, which has known associated neurotoxicity producing sensory deficit 2. Symmetrical polyradiculopathy in ALL patients has been described.…”

“…The neurological deficits associated with ALL can be due to either the spread of the malignancy to the nervous system or as a consequence of commonly used chemotherapeutic drugs. 1,2 Of these neurological side effects, polyneuropathies have commonly been described. However, these cases have generally reported children with history of ALL and were treated, only later developing ascending lower limb paralysis and areflexia likely secondary to neurotoxicity of the chemotherapeutic agents received.…”

“…Neurological involvement in patients diagnosed with acute lymphoblastic leukemia (ALL) is not uncommon. The neurological deficits associated with ALL can be due to either the spread of the malignancy to the nervous system or as a consequence of commonly used chemotherapeutic drugs 1,2. Of these neurological side effects, polyneuropathies have commonly been described.…”

Neurological complications following pediatric allogeneic hematopoietic stem cell transplantation: Risk factors and outcome

“…Our study included symptomatic patients; a future research direction could be screening of all transplanted children for presymptomatic changes, both by imaging and cognitive tests, as described above for leukemic patients (20), and by newer neuro-electrophysiological tools like evoked potentials, as already done by Kroczka et al (44)(45)(46) in leukemic patients (with emphasis on irradiated patients (45). With these modern tools, the group of patients presenting NCs would likely be larger.…”

Long-Term Effects of Pediatric Acute Lymphoblastic Leukemia Chemotherapy: Can Recent Findings Inform Old Strategies?

“…Clinical neuropathy symptoms were noted in 51.6% of patients during the follow-up, with demyelination as the most frequent abnormality. Follow-up was carried at a range of 0.3 to 20.9 years following treatment completion (48). Accordingly, there is increasing evidence supporting the persistence of chemotherapyneurotoxic consequences in pediatric ALL survivors in the long term.…”