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Home , Korsakoff syndrome, Marasmus, Vitamin E deficiency

Ann Natl Acad Med Sci (India), 47(1&2): 1-12, 2011

Malnutrition in Asia and Neurological Consequences

Jagjit S. Chopra*, Sudesh S. Prabhakar* and Pratibha D. Singhi** Departments of Neurology* and Peadiatric Medicine**, Post Graduate Institute of Medical Education and Research, Chandigarh-160012

ABSTRACT Prevalence of is a global phenomenon but the greatest contribution towards it is from the developing countries. Malnutrition impairs physical growth, cognitive functions of brain, physiological functions, immune response changes. Twenty Seven percent of children under 5 years are malnourished in the developing countries. India contributes to approximately 5.6 million child deaths annually with almost one billion children dying worldwide from the consequences of malnutrition. Malnutrition produces lasting effect on developing brain during the “Brain growth spurt’’ phase which corresponds to the period from 30 weeks of gestation to two-year of post natal age. In the peripheral nervous system the growth of axons, migration of Schwann cells and onset of myelination starts at 14 to 20 weeks of gestation. Malnutrition causes muscle wasting, hypotonia and impaired deep tendon reflexes from 30-40% of malnourished children. Deficiency of micronutrients in malnourished can cause myelopathy, peripheral neuropathy, dementia, infantile seizures, infantile tremor syndrome, night blindness, optic neuropathy and spinocerebellar degeneration. Keywords : Malnutrition, prevalence, , peripheral nervous system.

Correspondence : Dr Jagjit S. Chopra, H.No. 1153, Sector 33-C, Chandigarh- 160020 Malnutrition in Asia and Neurological Consequences 2

Introduction According to WHO by 2015 According to United Nations malnutrition will decrease by 17.6%. statistics about 25% of Indian population Globally 113.4 million children younger particularly children <14 years are then 5 yrs are affected. Malnutrition undernourished. Nervous System decreases educational achievement, disease due to dietary deprivation labour productivity and economic appears under circumstances as diverse growth. Under nutrition during as famine, extreme , intestinal pregnancy linked with low birth weight malabsorption due to disorders such and low brain weight. as sprue, chronic and National survey 2004-05 in India administration of metabolic antagonists (1) showed that out of 1.1 billion such as INH, nervosa and population 38% are poor and 40% fads, especially among adolescents. new born are under weight. Northern Protein Calorie Malnutrition or Protein region which is bread-bowl of India Energy Malnutrition (PEM) in children almost 80% infants are anaemic, every produced by failure of lactation/ 2nd child is stunted, every 3rd child of inadequate food intake is due to poverty. educated mother is malnourished and Epidemiology 60% children anaemic (2). Malnutrition is a predominant In India, according to Economic problem of the tropics due to poverty, Survey 2008-2009, 5.6 million children over population, illiteracy and die annually due to malnutrition (3). Forty socioeconomic disparity. According to percent of worlds’ malnourished children UNICEF, Asia pacific is home to 50% are from India. State wise, Madhya of slum population worldwide, with 30% Pradesh has highest malnourished children <5 yrs being underweight. Fifty children, i.e. 60.3% and with Jharkhand percent of world’s malnourished resides being 2nd with 59.2%. The prevalence of collectively in India, Bangladesh and severe PEM in India is 5 million. Countr- Pakistan. To anextent of 54% deaths in ywise data are illustrated on the startup children in developing countries are due of children (Fig.1), acute to PEM. 300, 000 children <5 yrs die per malnutrition (Fig. 2) and malnutrition year in developing countries (WHO). underweight and stunting inchildren (Fig. 3).

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Fig. 1 : Under Weight Children

Millions are malnourished in 5 years are malnourished, 35.2% are Bangladesh(48%), 11.7% are wasted, undernourished and 32.6% population 57.5% are stunted, 60.0% are low weight is below poverty line. and height, 70% women are anaemic, Nepal one of the poorest country of 20% goiter and 9% have in this the world has highest (49%) malnutrition country (4). in south Asia, its 50%population is In Pakistan 40% children under stunted, 40% anaemic and 40% with

Fig. 2 : Acute Malnutrition

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Fig. 3 : Malnutrition, Under-weight, Stunting (UNICEF, UN) . Twenty eight percent of malnutrition, 50% children below of its population survive on one US 5 years, 60% children (6 months to 7 dollar a day. In Myanmar 33% young years), 35-45% under 5 years and 13% children suffer from chronic malnutrition are malnourished, respectively. and 82% eat damaged rice. In Sri Lanka Effects on Developing Nervous System 22% children are underweight, 18% are stunted and 15% suffer from acute Human brain growth spurt begins malnutrition. In Jaffna area 24% suffer at 13th week gestation and continue till from acute malnutrition (5). 4th year after birth (6). The neuronal In Afghanistan a child dies every 3 multiplication ends at birth and seconds, 50% live below poverty line, glial multiplication ends little later. 54% under 5 years are stunted and 72% Myelination starts during second half under 5 years are anaemic. In Cambodia of growth spurt period (7). Cellular 40% population live below poverty proliferation, migration, myelination line, 90% are poor in rural areas, 33% and synaptogenesis occur in early phase population is malnourished and it is of development. White matter is more highest in South Asia, 45% under 5 years vulnerable to PEM than grey matter. are stunted. If nutritional deficiency occurs during Laos, North Korea, Vietnam and growth spurt, it can cause irreversible Mangolia, there is also very high level

4 5 Jagjit S. Chopra et al. damage to CNS, muscle and peripheral with delayed peripheral and central nerves are less affected. Complete conduction on SEP. BAER is prolonged recovery occurs if adequate nutrition in 40% Kwashiorkar children (10). is started early and recovery is partial Nutritional deficiency if nutritional correction is delayed (8). Classification based on deficient nutrients Lamination of cord tracts identifiable by 14th week and adult 1. Protein and/or calories pattern is reached by 30th week. In Primary PEM: - peripheral nervous system myelination - Kwashiokar starts by 14-20th week of gestation Secondary PEM: - Marasmus- and continues till 4th postnatal year. Protein calorie malnutrition results in lack lustre scholastic performance, 2. Specific Deficiency inadequate perception, maladjustment at home and school (9). Further the Primary : B1, B2, B3, B6, children show attention deficit, easy B12, Folate, C distractibility, low IQ, impaired Vitamin A, D, E, K, and and cognition. Abstract abilities are mixed worst hit. Beneficial effects are noted Conditional: (dependency states) following protein supplementation (9). Malnutrition also impairs physical Minerals: Calcium, Iron, growth, cognitive and physiological Magnesium, Zinc, Iodine, Copper, function and impairs immune response. Selenium, etc. PEM and Nervous System Protein deficiency Functional deficit were noted in Kwashiorkor : This type of malnutrition nerve and muscle due to reduced protein is usually seen in the age group of 2-3 synthesis, reduced oxygen uptake, years with , hair changes, stunted functional impairment of mitochondria, growth and hypoalbuminemia. instability of ribosomes and enhanced Marasmus is seen usually between IGF 1 and 2 binding. 6-18 months with growth retardation, EEG showed nonspecific slowing decrease protein calories which can be

5 Malnutrition in Asia and Neurological Consequences 6 mild, moderate or severe. Two disorders that appear most In PEM muscle wasting is seen in clearly related to deficiency all cases with hypotonia, hyporeflexia are nutritional polyneuropathy and the and delayed motor milestone in 15-45% Wernicke-. cases. Occasionally proximal muscle Nutritional polyneuropathy: weakness is noted. Electrophysiology Nutritional polyneuropathy is the most study done showed evidence of sensory common of all nutritional disorders motor polyneuropathy. Severity of of nervous system. Clinically, it is myelin and axonal loss parallels with symmetrical, mixed sensorimotor severity of PEM (11-12). neuropathy affecting lower limbs much and nervous system: more than upper limbs. Signs and A number of factors in the B group symptoms of dysfunction of autonomic of are of clinical importance nervous system are sometimes with regards to neurological disease. encountered as well, including vocal Although each is considered separately cord paralysis with hoarseness, below, in many instances deficiencies dysphagia, pupillary abnormalities, and of these and other vitamins occur in hypotension. Hyperhydrosis of hand and combination and may lead to complex feet is common. clinical distribution. Electrophysiological studies Thiamine (Vitamin B1): Thiamine reveal findings suggestive of axonal pyrophosphate serves as a coenzyme in polyneuropathy (11). Pathologically oxidative decarboxylation and cofactor in the primary change is segmental trans-ketolation. Deficiency of thiamine demyelination with axonal degeneration, in animals results in accumulation of affecting distal portion of the peripheral lactic acid and reduction in oxygen uptake nerves. In long standing cases, retrograde and depression of trans-ketolase activity changes may be found within the spinal especially in brainstem (13). Thiamine cord. deficiency studied in developed countries Restoration of a well balanced diet in chronic alcoholics easily transposed with supplemental of thiamine is the to those in nutritionally depleted non keystone of therapy. Thiamine is given alcoholics. parenterally initially at 50-100mg/day then orally for several days. Symptomatic

6 7 Jagjit S. Chopra et al. treatment with amitryptaline, pregabalin Bilateral sixth nerve palsies are and carbamazepine is required. Recovery most common but any pattern of is variable depending upon chronocity. restricted ocular motility may be Wernicke-Korsakoff Syndrome: found. Diplopia is charectasticelly Traditionally looked on as two distinct experienced. entities, they are best regarded as 3. – typically encountered representing simply two aspects of the in both the horizontal and vertical same disease, seperable chronologically planes. into acute (Wernicke’s encephalopathy) 4. Ataxia- has both trunkal and gait and chronic (Korsakoff’s syndrome) ataxic with occasionally trunkal phase (14). Thus the typical mental titubation. changes of Korsakoff’s syndrome may be present from the early stages The clinical course is dramatically of acute Wernicke’s encephalopathy. altered by administration of thiamine Furthermore examination of patients (14-15). Within hour of the parenteral with classic Korsakoff’s psychosis thiamine 50 mg, the ophthalmoplegia reveals residual features of Wernicke’s improves and ocular palsies generally such as nystagmus and trunkal ataxia. disappear with in few days but nystagmus may persist. Trunkul ataxia recovers Wernicke Encephlopahty: Wernicke’s slowly. Patients are maintained on 50- disease is an acute or subacutely evolving 100 mg of thiamine three times a day disorder. Appearing on a background for several weeks. The disease can be of chronic or severe undernutrition fatal in 10-20 % cases. The pathology frequently preceded by some additional is mainly seen involving brain stem metabolic stress like trauma or . and hypothalamus. Lesions are seen in Characteristic clinical features of this mamillary bodies, disorder include the following of in the periaquaductal 1. Abnormal mental status which gray matter and mesencephalon and include apathetic, restlessness in the superior cerebellar vermis. and drowsiness to hallucination, The characterstic lesion is subtotal agitation and confusion. tissue necrosis and hemorrhage in few involving , axons and myelin to 2. Ophthalmoplegia - is the hallmark. variable degrees.

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Korsakoff’s syndrome: This is a cerebellar features are noted. Niacin chronic from of Wernicke -Korsakoff deficiency can cause polyneuropathy syndrome and is characterized primarily which has mixed sensory motor by an amnesic dementia. The core of the involvement. Although it is widely defect appears to be an impairment of the held that the above features are due ability to acquire new information. The to niacin deficiency, the neurological patient tends to confabulate. The outlook changes are remarkably resistant to for patients with established syndrome high dose of niacin even parentally. is discouraging. However, thiamine Associated deficiency of other vitamins administration 50 mg three to four like thiamine, vit B12 and pyridoxine times a day is advised and in few cases may be important. though initial improvement may not be seen but over a period of months few Pyridoxine (): Neurological show remarkably complete functional disorder reflecting both pyridoxine recovery. The neuropathological deficiency and excess has been changes are identical to Wernicke’s recognized. During infancy pyridoxine encephlophathy with only note worthy deficiency results in seizure, excessive change being chronic form of glial irritability, tremulousness and poor reaction. psychomotor development. Niacin: Deficiency of niacin causes Deficiency of dietary pyridoxine seen predominantly in India causes a mixed distal symmetric and South Africa. In its fully developed polyneuropathy. The lack of pyridoxal clinical form, pellagra comprises a phosphate as a coenzyme is responsible host of symptoms referable to the for neuropathy. Although the minimum gastrointestinal tract (diarrhoea, daily requirement is only 2 mg, 50 mg anorexia, nausea and vomiting), skin or more may be required for successful and nervous system. Both central and therapy of deficiency state daily for one peripheral nervous systems may be week then once a week for 4 weeks and affected. then monthly. Central nervous system involvement Vitamin B12: Poor dietary intake of vitamin B12 as in malnutrition, extreme includes irritability to frank dementia. vegetarian, fish tapeworm infestation in Occasionally extra pyramidal or addition to various other causes may lead

8 9 Jagjit S. Chopra et al. to serious disease involving both central have long been recognized in patients and peripheral nervous systems. with subacute combined degeneration The most widely recognized of spinal cord. Reversible depression resulting from and cognitive decline have frequently is subacute been reported in individuals with folate combined degeneration of the spinal deficiency cord. Clinically presents as tingling Vitamin A (Retinol): A deficiency of paresthesias of the feet subsequently vitamin A is remarkably common in associated with weakness and stiffness many parts of the world, such as southeast of the legs and a spastic gait. It is an Asia, Africa and the Middle-East where important cause for upgoing planters and extreme poverty and nutritional depletion sluggish or absent ankle reflex. It can are endemic (18). Hypovitaminosis A present as pure axonal polyneuropathy leads most importantly to a variety of (16) or pure myelopathy. Occasionally ophthalmic disorders, grouped under the primary optic atrophy may be seen. rubric xeropthalmia. Early manifestation A variety of mental changes may also include night blindness, followed by be seen ranging from depression to conjunctival xerosis, Bitot’s spots, paranoid states and most important corneal xerosis and keratomalacia. progressive dementia. and growth retardation On MRI, an increased T2 –weighted is noted. Hypovitaminosis A can cause signal, decreased T2-weighted signal and intracranial hypertension similar to contrast enhancement of the posterior A. and lateral columns of the spinal cord should be may be found in the cervical cord (17). treated urgently. 200, 000 IU of retinol Electrophysiological studies done to palmitate orally on two successive days confirm polyneuropathy show mixed which will reverse the clinical features. demyelization and axonal neuropathy. Vitamin D: Deficiency of vitamin Treatment should be early and D causes rickets in children and aggressive. 1,000 mg of cynocobalamin in adults. Both rickets intramuscularly daily for 1 week and and osteomalacia are frequently reported then once a week for 4 weeks, followed in India. A deficiency in vitamin D has by monthly injection. been held responsible, in part for the Folic Acid: Reduced serum folate levels

9 Malnutrition in Asia and Neurological Consequences 10 weakness, fatiguability and muscular in deficient patients. atrophy due to hyperparathyrodisim Variable improvement in the clinical and renal tubular acidosis. Muscle and electrophysiological parameter were weakness and tetany is seen secondary seen after the administration of oral to hypocalcaemia. Minor myopathic or preferably paraterally (50-100 mg features may be noted histologically. weekly) for several months to years, but Vitamin E: There has been growing may not necessarily reverse the clinical awareness of the role of aquired vitamin symptomatology (22). E deficiency in neurological dysfunction Other Vitamins (19, 20). A deficiency of vitamin E results in a remarkable constellation Pantothenic acid deficiency is a rare of abnormalities referable to both case of predominant sensory neuropathy. central and peripheral nervous system Deficiency of biotin can cause dementia, (21). Features of both spinocerebellar seizures and ataxia. degeneration and polyneuropathy had Trace element deficiency causes been noted. In few cases seizures have various neurological dysfunctions as been recorded. A lack of has shown in the Table 1. been demonstrated in peripheral nerves

Table 1 : Neurological and other manifestation of trace element Element Deficient Clinical Features Iron Anaemia, poor brain development Zinc Microcephaly, psychological disturbance, encephalopathy, congenital malformation Copper Anaemia, growth failure, mental deterioration Cobalt Features similar to vitamin B12 deficiency Selenium Myopathy Iodine Cretinism, developmental delay, deaf mutism Magnesium Myopathy

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Nutritional Recovery Syndrome 5. Commission General- Essential During recovery of PEM mainly Services- UN World Food kwashiorkor following nutritional Programme (2007). supplementation, the child develop 6. Dobbing J and Smart JL (1974). coarse tremors, myoclonus, bradykinesia, Vulnerability of developing brain rigidity, trunkal ataxia and up gaze palsy and behaviour. Br Med Bull 30:164- which are self limiting. 168. Deficiency Disorder of Unknown 7. Wiggins, RC, Miller SL, Benjamins Origin JA, Krigman MR and Morell P Infantile tremor syndrome (1976). Myelin synthesis during postnatal nutritional deprivation This is seen in north, central and and subsequent rehabilitation. north east India usually during Feb Brain Research Rev 107:257-273. to July. This syndrome is exclusively of breast fed children between 6 to 8. Da-Silva AT, Costa FBR, Costa 24 months in poor socioeconomic JA, Teodiosio JE, Cabral F, et al . population.Abrupt onset tremors and (1987). Sciatic Nerve Conduction trunkal dystonia along with mental and velocity of malnourished rats fed physical retardation, pallor, hair and the human “basic regional diet of skin pigmentation are noted. This is self the northeast of Brazil”. Braz J Med limiting entity. Biol Res 20 :383-392. 9. Gopinath G, Roy S and Karmarkar References MG (1983). Effects of undernutrition 1. Economic Survey of India (2004- and later rehabilitation on post natal 05). growth of skeletal muscle and nerve 2. National Family Health Survey of in rat. Indian J Med Res 77:702- India-3 (2005-2006). 712. 3. Economic Survey of India ( 2008- 10. Galler JR and Kanis K (1987). 2009). Animal models of malnutrition applied to brain research . In:Basic 4. World Bank Development Indicators and Clinical Aspects of Nutrition (2003).

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and Brain Development: Rappin D, with Kwashiorkar. Neuropediatrics Haber B Drujan B and Alan R (eds), 17:178-182. New York : Liss 57-73. 16. Mc Leod JG (1984). The Peripheral 11. Chopra JS, Bakshi V, Rana SV, Neuropathy of vitamin B 12 Mehta J and Dhand UK (1986). deficiency. J Neurol Sci 66: 117- Effects of protein calorie 121. malnutrition on peripheral nerves. 17. Locatelli ER, Laureno R and A clinical, electrophysiological and Ballard P(1999). MRI in vitamin histopathological study. Brain 109: B12 deficiency myelopathy. Can J 307-323. Neurol Sci 26:60-63. 12. Chopra JS (1991). Neurological 18. Goodman DS (1984). Vitamin A consequences of protein and protein and retinoids in health and disease. calorie malnutrition. Critical N Engl J Med 310:1023-1025. Reviews in Neurobiology. Nelson JS(Ed). Boca Raton: CRC Press 19. Muller DPR, Lloyd JK and Wolff OH USA 6 (2) 99-118. (1983). Vitamin E and neurological function. Lancet 1:225-226. 13. Nelson M, Naismith DJ, Burley V, Gatenby S and Geddes N (1990). 20. Satya- Murti S, Howard L and Nutrient intakes, vitamin-mineral Krohel G (1986). The spectrum of supplementation and intelligence in neurologic disorder from vitamin E British school children.Br Nutrition deficiency.Neurology 36: 917-919. 64:13-22. 21. Weder B, Meieberg O and Wildi 14. Victor M, Adams RD and Collins E (1984). Neurologic disorder of GH (1971). The Wernicke’s in acquired Korsakoff Syndrome. In:FA Davis, intestinal malabsorption. Neurology Philadephia: McCombe PA. 34:156-157. 15. Bertel PR, Robinson E, Conradie JM 22. Perlmutter DH, Gross P and Jones and Prinsloo JG (1986). Brainstem HR (1987). Intramuscular vitamin auditory evoked potentials in E repletion in children with chronic severely malnourished children cholestasis. Am J Dis Child 141:170- 173.

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