levoleucovorin and Paraplegia

Topics: Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Catheterization, Central Venous; Central Venous Catheters; Colorectal Neoplasms; Epidural Space; Fatal Outcome; Fluorouracil; Humans; Iatrogenic Disease; Leucovorin; Male; Middle Aged; Neoplasm Metastasis; Organoplatinum Compounds; Paraplegia; Spinal Cord; Spinal Cord Diseases

Cerebral folate deficiency is characterized by low cerebrospinal fluid (CSF) concentrations of 5-methyltetrahydrofolate and a broad spectrum of clinical signs and symptoms. A patient with progressive spasticity, gait disturbance, speech difficulties, initially diagnosed as a recessive spastic paraplegia recovered on folinic acid (15-30 mg/day) and her 5-methyltetrahydrofolate in CSF normalized. This report demonstrates the importance of CSF investigation in the diagnosis of cerebral folate deficiency and efficiency of folinic acid (5-formyltetrahydrofolate) supplementation.

Topics: Brain Diseases; Child; Child, Preschool; Dietary Supplements; Dose-Response Relationship, Drug; Female; Folic Acid Deficiency; Gait; Humans; Leucovorin; Life Style; Movement Disorders; Paraplegia; Pregnancy; Speech Disorders; Tetrahydrofolates

Normal brain development and function depend on the active transport of folates across the blood-brain barrier. The folate receptor-1 (FR 1) protein is localized at the basolateral surface of the choroid plexus, which is characterized by a high binding affinity for circulating 5-methyltetrahydrofolate (5-MTHF).. We report on the clinical and metabolic findings among five children with normal neurodevelopmental progress during the first four to six months followed by the acquisition of a neurological condition which includes marked irritability, decelerating head growth, psychomotor retardation, cerebellar ataxia, dyskinesias (choreoathetosis, ballism), pyramidal signs in the lower limbs and occasional seizures. After the age of six years the two oldest patients also manifested a central visual disorder. Known disorders have been ruled out by extensive investigations. Cerebrospinal fluid (CSF) analysis included determination of biogenic monoamines, pterins and 5-MTHF.. Despite normal folate levels in serum and red blood cells with normal homocysteine, analysis of CSF revealed a decline towards very low values for 5-methyltetrahydrofolate (5-MTHF), which suggested disturbed transport of folates across the blood-brain barrier. Genetic analysis of the FR 1 gene revealed normal coding sequences. Oral treatment with doses of the stable compound folinic acid (0.5-1 mg/kg/day Leucovorin(R)) resulted in clinical amelioration and normalization of 5-MTHF values in CSF.. Our findings identified a new condition manifesting after the age of 6 months which was accompanied by low 5-MTHF in cerebrospinal fluid and responded to oral supplements with folinic acid. However, the cause of disturbed folate transfer across the blood-brain barrier remains unknown.

Topics: Blood-Brain Barrier; Brain Diseases, Metabolic, Inborn; Carrier Proteins; Child; Child, Preschool; DNA-Binding Proteins; Erythrocytes; Female; Folate Receptor 1; Folate Receptors, GPI-Anchored; Humans; Infant; Intellectual Disability; Leucovorin; Male; Membrane Proteins; Membrane Transport Proteins; Movement Disorders; Neurologic Examination; Paraplegia; Psychomotor Disorders; Receptors, Cell Surface; Replication Protein C; Spinocerebellar Degenerations; Tetrahydrofolates; Transcription Factors

Vincristine is an anti-neoplastic agent for intravenous use. Inadvertent intrathecal administration of vincristine tends to follow a predictable clinical sequence of a progressive ascending radiculomyeloencephalopathy, usually fatal in outcome. We report a case of a 10-year-old girl who suffered an inadvertent intrathecal vincristine administration. We have outlined the management strategy used and her consequent neurological progress. She has survived but with a significant neurological deficit. Her outcome is, however, less severe than in previous literature reports; this may in part be attributable to early aggressive neurological management. This case also serves to highlight the tragic consequences of human error when handling chemotherapeutic agents of this nature.

Topics: Antidotes; Caffeine; Child; Female; Humans; Leucovorin; Medication Errors; Paralysis; Paraplegia; Pyridoxine; Vincristine