Vitamin B12 deficiency as a treatable cause of severe brain atrophy
←
→
Page content transcription
If your browser does not render page correctly, please read the page content below
Neurology Asia 2021; 26(1) : 187 – 191
Vitamin B12 deficiency as a treatable cause of
severe brain atrophy
1
Hamit OZYUREK, 2Meltem CEYHAN, 3Hulya INCE, 3Omer Faruk AYDIN
Pediatric Neurology Unit, Ankara City Hospital, Ministry of Health; 2Department of Radiology,
1
Faculty of Medicine, Ondokuz Mayis University; 3Pediatric Neurology Unit, Faculty of Medicine,
Ondokuz Mayis University, Ankara, Turkey
Abstract
We report here two infants with vitamin B12 deficiency who presented with delay in motor and
mental development. Neuroimaging studies in our cases revealed diffuse severe cerebral atrophy.
Follow-up MRI after vitamin B12 treatment showed significant regression of the brain atrophy. Early
diagnosis and treatment in infantile vitamin B12 deficiency are important to prevent the irreversible
neurological damage.
Keywords: Vitamin B12 deficiency, cerebral atrophy, magnetic resonance imaging, psychomotor
development
INTRODUCTION delayed when compared to his peers. He had head
control when 4 months old but never able to sit
Infantile vitamin B12 (vit B12) deficiency is a rare
on his own.
clinical entity that results in hematological and
On admission he was apathetic and hypotonic.
neurological symptoms. Etiologic factors, clinical
His body temperature was 36.5°C, pulse rate
presentation, and radiological findings in infantile
was 134/min, breath rate was 42/min, and
vit B12 deficiency are different from adult form.
blood pressure was 85/50 mmHg. Both his
In contrast to mild neuropsychiatric symptoms
weight (8.6 kg) and height (75 cm) were at 75th
in adolescents and adults; in infancy, irritability,
percentile. Head circumference was 46cm (10-25th
apathy, progressive lethargy, developmental
percentile). He had crackles and rhonchi on distal
delay or regression, hypotonia, sensory deficits,
zones of lungs and liver palpated 3cm below the
involuntary movements, seizures and coma are
costal margin. He had head control, but was not
frequently observed as neurological symptoms.
able to sit without support. Deep tendon reflexes
These symptoms may be seen in some infants
were normoactive.
even without hematological findings. Instead of
Chest radiograph showed right paracardiac
subacute combined degeneration of the cord that
infiltration. The MRI of brain revealed atrophy
is detected in adults, cerebral atrophy and white
of frontal, frontotemporal, and anterior parietal
matter lesions are seen in infants. 1-3
regions on both hemispheres, and dilatation
Here we report two infants with vit B12
of lateral ventricles with mild retardation in
deficiency showing severe diffuse cerebral
myelination in the periventricular white matter
atrophy which was improved after vit B12
(Figure 1a). Blood screening tests revealed
supplementation.
mild pancytopenia (WBC:3x109/L, Hb:9.6g/dL,
Htc:29.1%, PLT:147x109/L, MCV:87.8fL). Iron
CASE REPORTS
status was normal. There were hypersegmentated
neutrophils, and anisocytosis in the peripheral
Patient 1 blood smear. Further investigation for the etiology
A 12-month-old boy suffering from respiratory of pancytopenia revealed a low serum level of vit
tract infection and dyspnea was referred to our B12 (15 ng/dL N:3-14) and high urine level of
The family history was noninformative. The methylmalonate. The serum level of homocysteine
parents reported that the baby was developmentally could not be measured on admission. The serum
Address correspondence to: Hamit Ozyurek, MD, Ministry Of Health, Ankara City Hospital, Pediatric Neurology Unit, Universiteler Mah. Bilkent cad. No:1,
Cankaya/Ankara/Turkey. Tel: +903125526000, E-mail: hozyurekibu@hotmail.com
Date of Submission: 21 October 2020; Date of Acceptance: 30 November 2020
187Neurology Asia March 2021 level of vit B12 of his mother was also low (
Figure 1. a. T-weighted image showed diffuse severe cortical atrophy at the age of 12 months and b. 8 months
later, there was complete regression of cortical atrophy.
DISCUSSION malabsorption are two main causes of maternal vit
B12 deficiency. Dietary source of vitamin B12 are
The clinical and laboratory findings and nutritional mostly from animal products including meat, eggs,
history of both infants and their mothers revealed fish, and milk. Nutritional deficiency can occur if
vit B12 deficiency. The most common cause of vit only small amount of animal product is consumed.
B12 deficiency in infants is maternal deficiency Pernicious anemia is the most common cause
as seen in our cases. Nutritional deficiency and of malabsorption resulting in maternal vit B12
Figure 2. a. T-weighted image revealed severe cortical atrophy. b. Follow-up image performed 12 months later
was normal.
189Neurology Asia March 2021
deficiency. Malabsorption due to achlorhydria, more frequent than cortical atrophy.11 In addition,
ileal damage, and gastric bypass surgery are coexistence of cortical atrophy and myelination
also rare causes of maternal vit B12 deficiency. disorder was reported in some cases.10
If infants are exclusively breast-fed by mothers In the literature, there are limited reports of
with vit B12 deficient, neurological manifestations long-term MRI follow-up of infantile vitamin B12
usually appear between 2 and 12 months of age.4,5 deficiency. Korenke et al. reported a 4-month-
The mothers of our cases were not vegetarian, but old girl with vitamin B12 deficiency showing
animal product consumptions were very low in global cerebral atrophy on first MRI. When the
their diet due to the low socioeconomic status. We second MRI was performed at the age of 7 years,
usually make a consultation with internal medicine moderate enlargement of the ventricles with a
department to exclude other causes of maternal reduction of myelin was detected.1 Kocaoglu et
vit B12 deficiency. The vit B12 supplementation al. reported clinical and radiological follow-up
is simultaneously prescribed to the mother in our of 12 -month-old infant with vit B12 deficiency.
clinical practice. At the diagnosis, cranial MRI revealed severe
We observed coarse tremors on the 3th day cerebral atrophy with enlargement of cortical
of vit B12 treatment lasting 8 days in Patient sulci and subarachnoid spaces. They performed
2. Following therapy with vit B12, involuntary cranial MRI three months after the initiation
movements consisting of tremor and myoclonus of therapy. Recovery of cerebral atrophy and
involving hand, feet, face, tongue and pharynx normal subarachnoid space were detected.12 In
appear in some infants. The prevalence rate our cases, reversal of diffuse cortical atrophy
of involuntary movements was reported as were seen approximately 8 and 12 months after
between 12-33%. The movement disorders first neuroimaging, respectively. Although rapid
disappear within a few weeks.6,7 Although the clinical and radiological improvements are
mechanisms underlying the movement disorder achieved by supplementation of vit B12, infants
are not clear, it is hypothesized that sudden often suffer long-term neurological dysfunctions
availability of vit B12 produced a temporary consisting of low IQ, psychomotor and linguistic
imbalance of cobalamin and folate pathways, delay. It appears that the duration of deficiency and
with local deficiencies and excesses of metabolic severity of symptoms rather than serum vit B12
intermediates that lead to tremors and myoclonus. level affect the long-term prognosis. By reviewing
Denervation supersensitivity, hyperglycinemia, 26 reported cases of cobalamin deficiency, Von
cerebral thromboembolism, toxic effect of the Schenck et al. observed that patients diagnosed
cyanide moiety in cyanocobalamin are other at the mean age of 10 months were associated
explanations for mechanism of involuntary with a normal outcome while patients diagnosed
movement secondary to vit B 12 therapy.8,9 We at the mean age of 13 months showed permanent
use hydroxocobalamin instead of cyanocobalamin neurological abnormalities.3 However, Korenke
to treat the infants with diagnosis of vit B12 et al. did not report any correlation between the
deficiency in Turkey. Therefore the pathogenesis diagnosis age and long-term prognosis when
of involuntary movements seen in our cases is not they reviewed the 30 infants reported in the
due to toxic effect of cyanide moiety mentioned literature with vit B12 deficiency due to maternal
above. pernicious anemia and vegan diet.1 Additionally,
Neuroimaging findings in infantile vit the initial improvement after the treatment may
B12 deficiency are different from adult form. not result in favorable outcome in the long term.
Diffuse or focal cortical atrophy, thinning of The neurological recovery was slow in our cases
corpus callosum, structural abnormalities and even though the diagnosis of Patient 2 was made
retardation in myelination are the most frequent at 9 month of age. We thought that the delay in
neuroradiological findings in infantile vit B12 improvement of developmental milestones in
deficiency.2,3,7,10,11 Acipayam et al. evaluated our patient after vit B12 supplementation was
neuroradiological findings of 21 infants with vit consistent with the brain atrophy being more
B12 deficiency. Cerebral atrophy was observed in diffuse and severe than cases reported in the
almost all patients. Ten infants had diffuse cortical literature.
atrophy, one had frontoparietal atrophy, two The neurotoxicity mechanism of vit B12
had frontotemporal atrophy and two had corpus deficiency is not well understood. Several theories
callosum thinning.7 In another study consisting have been proposed to explain the mechanisms
of 15 infants with nutritional vit B12 deficiency, by which vit B12 deficiency results in delayed
thinning of the corpus callosum was detected myelination or demyelination of nerves. Firstly,
190cobalamin is necessary in the breakdown of caused by subclinical maternal pernicious anemia:
methylmalonyl CoA to succininyl CoA in case report and review of the literature. Eur J Pediatr
fatty acid metabolism. Due to inappropriate 2004;163:196-201.
2. Casella EB, Valente M, de Navarro JM, Kok F.
conversion, the levels of methylmalonyl Vitamin B12 deficiency in infancy as a cause of
CoA and its precursor propionyl CoA are developmental regression. Brain Dev 2005;27:592-4.
increased and may lead to odd chain fatty acid 3. von Schenck U, Bender-Götze C, Koletzko B.
synthesis. Abnormal fatty acids disturb the Persistence of neurological damage induced by
myelin integrity by impairing the synthesis of dietary vitamin B12 deficiency in infancy. Arch Dis
ethanolamine, phospholipids, and sphingomyelin. Child 1997;77:137-9.
4. Dror DK, Allen LH. Effect of vitamin B12 deficiency
Cobalamin is also a cofactor in the conversion
on neurodevelopment in infants: current knowledge
of homocysteine to methionine. Methionine and possible mechanism. Nut Rev 2008;66:250-5.
is converted to S-adenosylmethionine (SAM), 5. Graham SM, Arvela OM, Wise GA. Long-term
which is converted to S-adenosylhomocysteine neurologic consequences of nutritional vitamin B12
(SAH). Vit B12 deficiency results in elevation deficiency in infants. J Pediatr 1992;121:710-14.
of SAH and homocysteine levels, and depression 6. Ozer EA, Turker M, Bakiler AR, Yaprak I, Ozturk
of SAM levels. SAM gives its methyl group for C. Involuntary movements in infantile cobalamin
deficiency appearing after treatment. Pediatr Neurol
the conversion of phosphotidylethanolamine 2001;25:81-3.
to phosphatidylcholine. These lipids make 7. Acipayam C, Gunes H, Gungor O, Ipek S, Sarisik N,
up about 14% and 11% of central nervous Demir NS. Cerebral atrophy in 21 hypotonic infants
system myelin, respectively. So, vit B12 with severe vitamin B12 deficiency. J Paediatr Child
deficiency may lead to inefficient conversion of Health 2020;56:751-6.
phosphotidylethanolamine to phosphatidylcholine 8. Zanus C, Alberini E, Costa P, Colonna F, Zennaro F,
that may impair myelination or result in Carrozzi M. Involuntary movements after correction
of vitamin B12 deficiency: a video-case report.
demyelination.4 Epileptic Disord 2012;14:174-80.
Imbalance of neurotrophic and neurotoxic 9. De Souza A. Moloi MW. Involuntary movements due
cytokines, and accumulation of lactate in to vitamin B12 deficiency. Neurol Res 2014;36:1121-
brain cells were mentioned as novel theories 8.
of neurotoxicity of vit B12 deficiency. Some 10. Lövblad KO, Ramelli G, Remondo L, Nirkko AC,
cytokines like tumor necrosis factor-α (TNF-α) Ozdoba C, Schroth G. Retardation of myelination
due to dietary vitamin B12 deficiency: cranial MRI
act as neurotoxins in CNS diseases that are
findings. Pediatr Radiol 1997;27:155-8.
characterized by demyelination, and others such as 11. Taskesen M, Yaramis A, Pirinccioglu AG, Ekici F.
epidermal growth factor are neurotrophic. Higher Cranial magnetic resonance imaging findings of
serum and cerebrospinal fluid concentration of nutrional vitamin B12 deficiency in 15 hypotonic
TNF-α and lower concentrations of EGF are infants. Eur J Paediatr Neurol 2012;16:266-70.
found in adult patients with vit B12 deficiency. 12. Kocaoglu C, Akin F, Caksen H, Boke SB, Arslan S,
This imbalance of cytokines is corrected by vit Aygun S. Cerebral atrophy in a vitamin B12-deficient
infants of a vegetarian mother. J Health Popul Nutr
B12 treatment.4 2014;32:367-71.
In conclusion, infantile vit B12 deficiency
is a treatable cause of neurological disorders.
Radiologic and clinic findings may be reversible
with early diagnosis and adequate supplementation
therapy in infants with infantile vit B12 deficiency.
However mild or moderate neurological squeals
may rarely persists long-term, even when infantile
vit B12 deficiency is diagnosed early.
DISCLOSURE
Financial support: None
Conflict of interest: None
REFERENCES
1. Korenke GC, Hunneman DH, Eber S, Hanefeld F.
Severe encephalopathy with epilepsy in an infant
191You can also read
