In the nervous system,
cobalamine deficiency results in defective myelin synthesis,
leading to several neurological dysfunctions that may affect both the central (brain,
spinal cord and optic nerve) and the peripheral nervous system.
Peripheral nerve abnormalities and optic nerve involvement are usually too subtle to be recognized by current ultrasound,
CT and MRI,
while nerve conduction studies are the preferred diagnostic tools in these cases.
Nevertheless,
neuroimaging is of choice for the remaining CNS manifestations,
including subacute combined degeneration,
decrease in total brain volume and periventricular white matter lesions.
- Subacute combined degeneration
Subacute combined degeneration is one of the most frequent clinical manifestations of vitamin B12 deficiency.
Clinically,
the first abnormality is usually sensory impairment,
most often presenting as distal and symmetrical paraesthesias at lower limbs frequently associated with ataxia.
Almost all patients have loss of vibratory sensation,
often associated with diminished proprioception and cutaneous sensation and Romberg sign.
Corticospinal tract involvement is common in the more advanced cases,
with abnormal reflexes,
motor impairment and,
ultimately,
spastic paraparesis.
The involvement of the dorsal and dorsolateral columns of the the spinal cord is responsible for these clinical manifestations.
It typically commences in the cervical and upper thoracic cord,
but can extend to involve other levels.
The most consistent MRI finding is a symmetrical abnormally increased T2 signal intensity in the posterior and lateral columns of the cervical and thoracic spinal cord Fig. 1 .
Involvement of anterior columns has occasionally been reported.
In acute and severe cases,
the spinal cord might also present as swollen.
T2-hyperintensity of spinal cord columns has been related to demyelination.
However,
it has also been reported that these areas can appear hyperintense on diffusion weighted imaging (DWI) and show restricted diffusion on apparent diffusion coefficient (ADC) maps,
consistent with the co-existence of intramyelin edema.
Sometimes,
enhancement is noted after the administration of gadolinium,
due to the disruption of the blood-brain barrier.
Fig. 1: A 57-year-old woman with subacute history of gait instability and sensory impairment in lower limbs, associated to low levels of vitamin B12. Sagital (A) and axial (B) T2-weighted imaging shows a symmetrical hyperintensity in the posterior area of the cervical spinal cord (levels C3 to C6).
Follow-up MRI findings correlate with clinical outcome after treatment with vitamin B12 supplementation.
The abnormal MR signals on the spinal cord might either disappear on follow-up after months Fig. 2,
or sometimes,
it might persist,
especially in cases diagnosed and treated at an advanced stage.
Fig. 2: Follow-up MRI in the previous patient, 1 year after vitamin B12 replacement therapy, shows complete resolution of the hyperintense area in the cervical spinal cord.
Brain involvement might consist in a reduction in the total brain volume or/and extensive areas of a high signal intensity in the periventricular white matter.
These findings may be reversible after correction of B12 levels.
Reduction in total brain volume
Low serum vitamin B12 concentrations have been correlated negatively with cognitive functioning in healthy elderly subjects.
There is a linear correlation between serum cobalamin concentration and cognitive function,
both in healthy elderly people and in patients with Alzheimer’s disease.
Symptoms described include slow mentation,
memory impairment,
attention deficits and dementia.
In regard to neuroimaging,
different studies support that poor vitamin B12 status is a risk factor for brain atrophy which in turn may contribute to cognitive impairment.
The reduction in the brain volumen seems to be diffuse,
not demonstrating any specific pattern Fig. 3 .
On the basis of repeated MRI scans,
brain atrophy associated with cognitive decline appears to be a slow process; brain atrophy rates among adults aged 70 years or more ranged from 0.7% to 1.1% per year.
Fig. 3: A 65-year-old man without vascular risk factors, with long history of vitamin B12 deficiency and gait instability. Axial T2-weighted fluid-attenuated inversion recovery sequences (FLAIR), with fat supression, show a diffuse reduction of brain volume, with no specific pattern.
Diffuse cerebral atrophy has also been described in infants with vitamin B12 deficiency or with errors of vitamin B12 metabolism.
In some studies,
this diffuse loss of brain volumen has been demonstrated to be reversible if treated.
Furthermore,
in patients with Alzheimer’s disease (AD) some studies have demonstrated that B-vitamin treatment reduces,
by as much as seven fold,
the cerebral atrophy in those gray matter regions specifically vulnerable to the AD process,
including the medial temporal lobe.
White matter lesions
Leukoencephalopathy have been described in individuals with very low serum B12 levels.
White matter abnormalities usually involves the periventricular area and show a centrifugal and rostrocaudal expansion Fig. 4 Fig. 5.
Fig. 4: A 60-year-old woman with vitamin B12 deficiency and no history of vascular risk factors. Axial T2-weighted fluid-attenuated inversion recovery sequences (FLAIR) show non-specific patchy hyperintensities in the periventricular and subcortical white matter, predominantly in the frontal and parietal lobes.
Fig. 5: A 62-year-old man with history of vitamin B12 deficiency and gait disturbances. Axial T2-weighted fluid-attenuated inversion recovery sequences (FLAIR) show non-specific hyperintensities in the periventricular whitte matter with a posterior predominance.
Vitamin B12 status has been associated with the severity of white-matter lesions,
especially the periventricular ones,
in some studies.
The partial reversal of white matter lesions has been documented with cobalamin treatment,
emphasizing the importance of early detection and treatment of vitamin B12 deficiency Fig. 6.
Fig. 6: Follow-up MRI in the previous patient, 2 years after vitamin B12 replacement therapy, shows partial resolution of the prior white matter changes.
Brain MRI interpretation of white matter disease in an adult without risk factors deserves further investigation,
including the determination of cobalamine levels.