source: https://doi.org/10.7892/boris.117570 | downloaded: 17.4.2021

Pediatr Radio! (1997) 27: 155-158© Springer-Verlag 1997

Karl-Olof Lovblad Retardation of myelinationGianpaoloo Ramelli due to dietary vitamin B12 deficiency:Luca Remonda

Christoph Ozdoba l MRI findings

cranialOzdoba gGerhard Schroth

Received: 19 February 1996Accepted: 26 March 1996

Abstract Vitamin B 12 deficiency isknown to be associated with signs ofdemyelination, usually in the spinalcord. Lack of vitamin B 12 in the ma-ternal diet during pregnancy hasbeen shown to cause severe retarda-tion of myelination in the nervoussystem. We report the case of a 14 1 /2-month-old child of strictly vegetar-ian parents who presented with se-vere psychomotor retardation. Thisseverely hypotonic child had anemiadue to insufficient maternal intakeof vitamin B 12 with associated meg-aloblastic anemia. MRI of the brainrevealed severe brain atrophy withsigns of retarded myelination, the

frontal and temporal lobes beingmost severely affected. It was con-cluded that this myelination retar-dation was due to insufficient intakeof vitamin B 12 and vitamin B 12 ther-apy was instituted. The patient re-sponded well with improvement ofclinical and imaging abnormalities.We stress the importance of MRI inthe diagnosis and follow-up of pa-tients with suspected diseases ofmyelination.

K.-O. Lovblad (®) - L. RemondaC. Ozdoba • G. SchrothDepartment of Neuroradiology, IDR,Inselspital, University of Bern,Freiburgstrasse, CH-3010 Bern,Switzerland

G. RamelliDepartment of Pediatrics, Inselspital,University of Bern, Switzerland

A. C. NirkkoDepartment of Neurology, Inselspital,University of Bern, Switzerland

Introduction

Neurologic disease due to a lack of vitamin B 12 is a clin-ical entity known since the turn of the century [1]. Defi-ciency of vitamin B 12 affects particularly hematopoietic,epithelial and nervous tissues but the exact role of B 12 inthe metabolism of the nervous system remains unclear.Long-term deficiency of the vitamin cobalamin cancause demyelination of the spinal cord and brain [2-5]but the mechanism of demyelination is also not fully un-derstood [6]. Neurologic symptoms as a sign of dietarydeficiency in infancy have rarely been reported [7, 8],and indeed shortage of B 12 in the diet is today an un-usual cause for deficiency. Other causes are a lack of in-trinsic factor, the presence of antibodies to B 12 andintrinsic factor, malabsorption syndromes, ileal diseaseand inborn errors in metabolism. In previously pub-lished series, the administration of vitamin B 12 has beenshown to lead to restoration of neurologic function inmany cases. Early diagnosis, therefore is of value.

Case report

This girl was born into a family of vegetarians whose intake of milkand dairy products had been minimal. She was born naturally afteran uneventful pregnancy and had a weight at birth of 3300 g. Atfirst postnatal development was normal, but at 6 months of ageshe presented with lack of progress and would only fixate light forshort periods at 14.5 months. She was therefore seen by a pediatricneurologist. On examination she was in poor condition, weighingonly 7300 g (below the 3rd percentile). Her skin was markedlypale and the sclera slightly yellow. Neurologic examination re-vealed generalized hypotonia, few spontaneous movements, a fewinvoluntary movements of the extremities and continuous rollingmovements of the tongue. The reflexes were very marked and apositive Babinski's sign was noted on the right side. There wasalso a positive foot grip reflex on the right. Analysis showed a meg-aloblastic anemia with hemoglobin (Hb) of 6.0,1.56 x 10 12 erythro-cytes, mean corpuscular Hb (MCHb) 39, hematocrit 0.17, MCvolume 111, MCHb concentration 35; 2.9 x 10 9 leukocytes with89.5 % lymphocytes and 43 x 10 9 thrombocytes. Blood electrolytesand blood gases were normal. Vitamin B 12 was low with a level of92 pmol/l (normal value 180-750) but the B 12 binding capacitywas within normal limits at 1061 pg/ml. Levels of folic acid

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(17 nmol/l) and ferritin (48 µg/1) were normal. The electroencepha-logram showed generalized slowing of the basal activity compati-ble with diffuse encephalopathy. Auditory evoked brainstempotentials showed normal bilateral cochlear function.

It was decided to initiate therapy with vitamin B 12 , consisting of1000 ng every 2nd day with additional iron, folic acid, trace ele-ments and vitamins. The patient responded well and at 20 monthscan sit alone, crawl, walk with help and speak simple words. Mus-cular strength is almost normal. Reflexes are normal and Babin-ski's sign is no longer present. Laboratory test values havecompletely returned to normal.

Materials and methods

MRI of the brain and spine was performed on a 1.5-T MagnetomVision system (Siemens Medical Systems, Erlangen, Germany) us-ing head and surface coils. Sagittal and axial Ti-weighted, as wellas axial and coronal T2-weighted sequences of the brain were ac-quired.

Results

MRI revealed marked brain atrophy with widening ofboth the inner and outer CSF-containing spaces, espe-cially at the level of the frontal and temporal lobes(Figs. 1, 2). There were also signs of retardation of myeli-nation, which was equal to that of a normal 4-month-oldchild. This retardation was most marked at the level ofthe temporal and frontal lobes (Fig. 3) where myelina-tion was almost absent. There was also retardation inthe brainstem, cerebellum, internal capsule and the pos-terior parts of the hemispheres. In addition, the corpuscallosum was small for the age of the child (Fig. 1). Fol-low-up MRI 5 months later showed significant regres-sion of the brain atrophy (Fig. 4), with only a fewcerebral sulci in the frontal lobes being still too promi-nent (Figs. 5, 6). Definite signs of progressive myelina-tion were visible and there was further development ofthe corpus callosum (Fig.4).

Discussion

This young child of vegetarian parents presented withsevere psychomotor retardation, retarded myelinationand marked atrophy of the central nervous system dueto a dietary lack of vitamin B 12 with megaloblastic ane-mia. Neurologic diseases caused by cobalamin defi-ciency were first described at the turn of the century. In1900 Russell et al. reported the classic findings in sub-acute combined degeneration of the spinal cord [1]. La-ter, Adams and Kubik presented a review of cases alsoinvolving the brain in adults [4].

Vitamin B 12 plays an important part in the metabo-lism of the nervous system, even though its exact rolein normal and pathologic conditions is not fully under-

stood. In infants, the damage is thought to occur in thefirst 6 months of life, when myelination of the brain isvery active. In children the main causes of pathologicmyelination associated with vitamin B 12 deficiency areinsufficient oral intake or an inborn error of metabo-lism. A syndrome consisting of megaloblastic anemiawith mucous membrane pallor and hyperpigmentationof the skin associated with neurologic signs such as de-velopmental regression with involuntary movements ofthe head, trunk and extremities has been reported to oc-cur in infants breast-fed by mothers with B 12 deficiency.It was first described in infants in southern India andcorresponds to the disease reported in this case. Patientsresponded favorably to the oral administration of vita-min B 12 .

Until now isolated case reports on MRI of the ner-vous system in vitamin B 12 deficiency have centered onsubacute combined degeneration or funicular spinal dis-ease [9-13]. Most reports were in adults and MRIshowed high signal changes on T2-weighted sequencesin the posterior columns of the spinal cord. Theselesions consist of demyelination with damage to themyelin sheaths initially and subsequent axonal degener-ation. Extensive lesions in the brain itself have onlybeen found in a few cases showing small perivascular ar-eas of demyelination within the white matter. The histo-logic findings are identical to those of the spinal cordlesions. These lesions have been seen in the white matteron MRI of the brain and spine in the few previously re-ported cases. One report concerned three cases present-ing with demyelination of the nervous system due tosequential inborn errors of the methyl-transfer pathwayassociated with white matter changes on MRI [14].Upon treatment all three patients showed imaging find-ings consistent with improvement, which was also pre-sent clinically; one of the patients even presentedcomplete reversal of MRI signs. The improvementupon treatment is thought to be due to improved myeli-nation confirmed by follow-up MRI, which showed lessbrain atrophy and signs of progression of myelination.In a series of 11 infants, cranial MRI in two showed clearretardation of myelination. Follow-up MRI in one ofthese patients showed normalization of the imagingfindings but the neurologic exam was still abnormal, es-pecially speech [15]. It is unclear to what extent treat-ment may be beneficial when the lack of vitamin B 12

has been prolonged during a very critical period for thematuration of oligodendrocytes. Our patient presentedwith a progression of development of 9-10 months in aperiod of 6 months. MRI is a non-ionizing imagingmethod with known multiplanar imaging abilities thathas proven to be a sensitive tool in the assessment ofmyelination in children; it allows both safe diagnosisand monitoring of the disease.

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Fig.1 Sagittal Ti-weighted MR image displaying the markedlythin but structurally normal corpus callosum in addition to theprominent frontal cerebrospinal fluid containing spaces

Fig.2 Axial T1-weighted image of the brain showing markedbrain atrophy, most prominent in the frontal and temporal lobes(AFanterior frontal)

Fig. 3 Coronal T2-weighted section showing markedly wide cere-bral sulci and ventricles. There is also significant brain substanceloss in the frontal and temporal lobes

Fig.4 Sagittal TI-weighted MRI control scan 5 months after ther-apy showing regression of the brain atrophy. The corpus callosumis also substantially more developed

Fig.5 Axial T1-weighted image of the brain displaying almost nor-malized cerebral sulci, only a few frontal sulci being too wide forthe age of the patient (AF anterior frontal)Fig.6 Coronal T2-weighted section displaying the less marked lossof cerebral volume

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