Infantile Tremor Syndrome (ITS) is a clinical state characterized by tremors, anemia, pigmentary skin disease, regression of mental development, and hypotonia of muscles [1]. Studies suggest that the most probable etiology of ITS is nutritional deficiencies [1]. Despite predominance of neurological symptoms, very few studies have documented neuroanatomical and/or neurophysiologic changes in ITS [2]. Reduced brain substance has been documented in children with ITS [3]. In contrast several studies in children with Protein Energy Malnutrition (PEM) have documented cerebral atrophy [4,5] and its reversibility after treatment [5].

A 10-month-old exclusively breastfed female child was admitted with the complaints of abnormal rhythmic jerky movements of both hands, feet, tongue and head nodding for 6 days prior to admission. Movements were suggestive of coarse resting tremors. Child was having moderate wasting and normal height for age. Head circumference was below –2 SD for age and sex. Developmentally, child was able to sit without support, had a palmar grip, and was able to tell monosyllables before the onset of disease (DQ 92±5). At admission, she was not able to sit without support and only cooing was present (DQ 44±5). Blood investigations suggested predominantly microcytic hypochromic anemia with normal serum levels of albumin and Vitamin B12. MRI brain suggested mild diffuse cerebral atrophy (Fig.1a and 1b). Nutritional rehabilitation was continued at home after 5 days of admission. Follow-up of the patient was done after 17 months when she had normal development for her age (DQ 84±5). Anthropometrically she had normal weight for age, and length. Head circumference was still below -2 SD. MRI scan of brain showed improvement in cerebral atrophy with no sulcal prominence or ventricular enlargement (Fig.1c and 1d).

Fig 1-3. Flair and T2W sequence of MRI brain in axial plane showing: mild cerebral atrophic changes (1A & 1B), moderate atrophic changes appearing as prominent sylvian fissure and CSF spaces in frontal region (2A & 2B), significant atrophic changes appearing as prominent sylvian fissure and CSF spaces in temporo-fronto-parietal region (3A & 3B). On follow up with same sequences of brain in axial plane is within normal limits (1C, 1D, 2C, 2D, 3C & 3D).

An 8-month-old exclusively breastfed female child admitted with abnormal rhythmic movements of tongue and upper extremities and tremulous cry, along with loose motions for two days. She was having normal weight for height and mild stunting with head circumference <-2SD. She had normal development before illness (DQ 90±5) with regression of milestones during tremors (DQ 74±5). Child was mostly remaining in a flexed posture with fisting of the palms. Tremors used to increase on crying but disappeared on sleep. She stayed in hospital for 11 days and was treated with oral rehydration solution, Zinc sulfate, Vitamin B12 and Folic acid. Propranolol was given to control tremors. Blood investigations suggested normocytic hypochromic anemia with normal serum levels of albumin and Vitamin B12. MRI brain was suggestive of mild diffuse cerebral atrophy (Fig. 2a and 2b), which showed reversal of atrophy on follow up after 15 months (Fig. 2 c and 2d) with normal development (DQ 100±5).

A 13-month-old female with inadequate complementary feeding was admitted with complaints of not able to sit for about 6 weeks, cough for 4 days and abnormal cry, head nodding and rhythmic movements in extremities for one day. Severe pallor was present along with knuckle hyper-pigmentation. Child was having severe wasting, mild stunting and head circumference <-1SD (DQ 25±5). Blood investigations showed moderate polychromasia, mild anisopoikilocytosis, mainly normocytes, tear drop cells, target cells with normal serum albumin and sub-normal serum vitamin B12 levels. MRI brain suggested diffuse cerebral atrophy with prominent CSF spaces including sulci and sylvian fissures of both hemispheres and enlarged lateral ventricles (Fig. 3a and 3b).On follow-up, child was again admitted at the age of 20 months. Anthropometrically she had normal weight for height with mild stunting and mid arm circumference 14 cm. Head circumference was <-1SD with normal development (DQ 78±5). MRI brain showed reversal of atrophy and it revealed minimal residual prominence of sylvian fissures (Fig. 3c and 3d).

We demonstrated reversibility of cerebral atrophy by MRI brain in cases of ITS, after nutritional rehabilitation. All three cases had various grades of cerebral atrophy on MRI during acute tremor phase of ITS. Bajpai, et.al. [3] observed a reduced brain substance with normal sized skull in majority of cases of ITS on Pneumoencephalo-graphy [3]. Other cross-sectional studies [2,6] have done CT/ MRI scan during tremor phase of ITS and demonstrated cerebral atrophy, but none of these studies did follow-up neuroimaging. Ozer EA, et al. [7] described two cases of tremors in infantile cobalamin deficiency and cerebral atrophy on CT scan [7]. However, cobalamin deficiency is not constantly present in all patients of ITS, as shown in our series in which only one child had sub-normal vitamin B12 levels.