Vitamin E Deficiency and Associated Neurological Deficits in Children with Protein-energy Malnutrition

Vitamin E Deficiency and Associated Neurological Deficits in Children with Protein-energy Malnutrition by V. Kalra,* J. Grover,** G. K. Ahuja,*** S. Rathi,* and D. S. Khurana* * Department of Pediatrics, All India Institute of Medical Sciences, New Delhi, India ** Department of Pharmacology, All India Institute of Medical Sciences, New Delhi, India *** Department of Neurology, All India Institute of Medical Science, New Delhi, India Summary Vitamin E is important in maintaining normal neurological structure and function. In this study, 100 children with protein-energy malnutrition (PEM) were studied and compared to a suitably agematched control group. Posterior column deficits, cerebellar deficits, and problems with fine motor coordination were present to a significant degree in the PEM subjects. The presence of neurological signs was correlated with various parameters of vitamin E deficiency, including low serum atocopherol levels and a low tocopherol/total Iipid ratio which was present in 92 per cent of subjects. There was good concordance between vitamin E levels and vitamin E to serum Upid ratio in assessing vitamin E deficiency. We conclude that vitamin E deficiency is prevalent, to a hitherto unsuspected degree, in children with PEM and that these malnourished children have significant neurological deficits attributable to low vitamin E levels. This observation is of clinical significance as the neurological deficits are potentially reversible with vitamin E supplementation. Introduction Since the discovery of vitamin E,1 its physiologic role has been controversial. There is evidence to suggest that it may have a role in maintaining normal neurological structure and function.2"3 Multiple disease states like abetalipoproteinaemia, chronic fat malabsorption, cystic fibrosis, and primary isolated vitamin E deficiency all reveal neurological deficits in vitamin E deficient subjects. Studies indicate the potential reversibility and preventability of the neurological symptoms with appropriate and timely treatment.5'7 The therapeutic implication justifies investigation of the role of vitamin E as an important factor in human malnutrition. Patients and Methods Between June 1990 and December 1993, 130 children of either sex between the ages of 3 and 8 years with moderate protein-energy malnutrition (PEM) were Acknowledgements The authors are grateful to the Indian Council of Medical Research (ICMR), New Delhi for funding the research project on vitamin E deficiency in protein-energy malnutrition, Dr K. R. Sundaram, Professor, Biostatistics Unit, All India Institute of Medical Sciences helped in statistical analysis of the data. All the patients who cooperated in the study are duly acknowledged. Correspondence: V. Kalra, Additional Professor of Pediatrics, All India Institute of Medical Sciences, New Delhi-110029, India. Fax 0091 II 6862663. Journal of Tropical Pediatrics Vol. 44 October 1998 identified on the basis of weight-for-age criteria using the norms of the Indian Academy of Pediatrics. Children up to 80 per cent of the reference weight for age (50th percentile of the Harvard standard) were considered normal. Those between 50 and 70 per cent of the reference were enrolled into the study. Patients were recruited from the pediatrics out-patient clinics and rural health centres of the All India Institute of Medical Sciences, New Delhi, India. Children with acute severe illness, neurological illnesses, and neurodevelopmental and mental retardation were excluded. Sixty healthy age-matched subjects with similar exclusion criteria were selected as control subjects. Controls were recruited from the immunization clinics at both centres. From amongst the total of 190 subjects, 40 had to be excluded owing to either unwillingness to participate, non-compliance, or follow-up dropout. This left 100 PEM subjects and 50 controls. A clinical examination was performed and anthropometric data collected on a predesigned form. All the children were examined by two clinicians independently and only those positive findings on which there was interobserver agreement were recorded as positive. Features suggestive of malnutrition and associated vitamin deficiencies were recorded. A detailed neurological examination was performed on all subjects and controls. Serum a-tocopherol was measured by the modified spectrophotometric technique of Hashim and Schuttinger.9 Total Iipid levels were measured using standard kits and the ratio of serum a-iocopherol to total Iipid was calculated as it is thought to provide a better © Oxford University Press 1998 291 V. KALRAETAL. TABLE 1 Abnormal neurological signs in control and PEM subjects Abnormal neurological signs Normal control (n = 50) PEM group ( n = 100) p value 1(2) 2(4) 0 0 2(4) 3(6) 1(2) 1(2) 3(6) 1(2) 0 38 (38) 23 (23) 32 (32) 10(10) 28 (28) 43 (43) 17(17) 18(18) 26 (26) 20 (20) 27 (27) <0.00l <0.0l <0.001 <0.05 <0.0l <0.00l <0.05 <0.05 <0.0l <0.0l <0.00l Vibration sense Joint position Dysdiadokinesia Intention tremor Ataxia Tandem walking Two-point discrimination Synkinetic movements Finger agnosia L-R discrimination Hyporeflexia Figures in parentheses are percentages. approximation of vitamin E status. A ratio of less than 0.6 is reported to suggest vitamin E deficiency.10 Electroneurophysiological data included visual evoked responses and brainstem auditory evoked potentials. Results Birthweight and gestational age were similar among PEM subjects and controls. Ten per cent of patients in the PEM group had a history of perinatal illnesses or insults, compared to 4 per cent of controls. Presenting symptoms in the PEM group included upper respiratory infections (72 per cent), diarrhoea (22 per cent), malabsorption (2 per cent), skin rash (13 per cent), and urinary complaints 7 per cent. On examination, muscle wasting was seen in the majority (80 per cent); other findings included anaemia (64 per cent), clinical vitamin A deficiency (11 per cent), hair and skin changes (9 per cent), pedal oedema (6 per cent), stomatitis and cheilosis (8 per cent), rickets (2 per cent), multiple vitamin deficiencies including vitamins D, B, and A (6 per cent). A detailed neurologic examination of the PEM subjects revealed multiple subtle deficits pertaining to the posterior columns, cerebellum, and co-ordination. A comparison of the signs between PEM subjects and controls is shown in Table I. Absent tandem walking, diminished vibration sense, diminished joint/position sense, dysdiadokinesia, ataxia, and hyporeflexia were all found to be present to a statistically significant degree ( p < 0 . 0 l ) in the PEM group compared to controls. Finger agnosia, impaired left-right discrimination, and synkinetic movements were also present to a significant degree in the PEM subjects. The distribution of abnormal neurological signs was similar between different age groups. Mean serum or-tocopherol level in PEM subjects was 0.26 ± 0.11 mg/dl, compared to (...truncated)