Acute reversible cognitive dysfunction due to vitamin B12 deficiency: A case report with rare magnetic resonance imaging findings

Abstract

Vitamin B12 deficiency can manifest with hematological and neurological abnormalities, though intracranial involvement is less common than spinal cord or peripheral nerve manifestations. We report the case of a man in his 70s who developed acute cognitive decline over 4 days, accompanied with left lower limb weakness and visual disturbances. Neurological examination revealed reduced verbal output, dysarthria, significant cognitive impairment (Mini-Mental State Examination score, 7/30), and left lower limb weakness (Medical Research Council grade, 4/5). Laboratory tests showed pancytopenia (white blood cell count, 2.7 × 10⁹/L; red blood cell count, 1.34 × 10¹²/L; hemoglobin level, 6.3 g/dL; platelet count, 55 × 10⁹/L), with macrocytic anemia (mean corpuscular volume, 134 fL; mean corpuscular hemoglobin, 47 pg) and markedly low serum vitamin B12 levels (<83 pg/mL). Brain magnetic resonance imaging demonstrated distinctive bilateral periventricular hyperintensities on T2‑weighted and diffusion‑weighted imaging, suggestive of cytotoxic edema, a finding often associated with metabolic disturbances. A diagnosis of acute metabolic encephalopathy due to vitamin B12 deficiency was established. Following vitamin B12 supplementation, the patient’s symptoms resolved completely (Mini-Mental State Examination score: 24/30, Montreal Cognitive Assessment score, 23/30, adjusted for educational level). This case illustrates that vitamin B12 deficiency can present with acute cognitive dysfunction and may manifest on magnetic resonance imaging as symmetrical periventricular brain cytotoxic edema. Early recognition and treatment are crucial for achieving both clinical and radiographic recovery.

Background

Vitamin B12 is an essential water-soluble vitamin derived mainly from dietary animal protein. ¹ It plays a critical role in DNA synthesis, hematopoiesis, and myelin formation within the nervous system. ² Consequently, vitamin B12 deficiency can lead to a spectrum of severe hematological and neurological manifestations.^2,3 Although well‑documented, intracranial involvement is comparatively uncommon, and findings of restricted diffusion on magnetic resonance imaging (MRI) are particularly rare. This report describes the case of an adult patient with acute cognitive dysfunction secondary to vitamin B12 deficiency, whose MRI presented with distinctive bilateral periventricular hyperintensities on both T2-weighted imaging (T2WI) and diffusion-weighted imaging (DWI) sequences—an unusual neuroimaging presentation of vitamin B12 deficiency encephalopathy. We document the patient’s clinical and radiological improvement following vitamin B12 replacement therapy. This report has been prepared in accordance with the Case Report (CARE) guidelines. ⁴

Case presentation

A male patient in his 70s was admitted to Chongqing Medical University Affiliated Banan Hospital in October 2024, presenting with a 4-days history of rapidly progressive cognitive decline and behavioral abnormalities. The symptoms initially manifested as impaired executive function (evidenced by his inability to continue playing poker), reduced verbal output, and worsening functional status that culminated in urinary incontinence. The patient’s family reported frequent collisions with objects in his path (e.g. door frames), suggesting possible visual disturbance from nutritional optic neuropathy, a previously reported complication of vitamin B12 deficiency. ⁵

Relevant medical history included a finding of mild macrocytic anemia 3 months ago, with hemoglobin (Hb) level of 110 g/L, mean corpuscular volume (MCV) of 132.7 fL, and mean corpuscular hemoglobin (MCH) level of 44.5 pg, which was not further evaluated at that time. One month before admission, he underwent an outpatient gastroscopy for poor appetite. The pathological findings indicated moderate chronic inflammation with atrophy (++) and intestinal metaplasia (+) in the gastric body and fundus, consistent with autoimmune gastritis; the antrum was spared, and Helicobacter pylori test was negative. The patient had no alcohol abuse or restrictive dietary practices.

On admission, general physical examination was notable for pallor and pale conjunctivae as signs of anemia; no other systemic abnormalities were detected. Bedside fundoscopic examination revealed no obvious optic disc pallor or edema. In contrast, neurological examination revealed markedly reduced verbal output with dysarthria, and severe cognitive impairment, evidenced by a Mini-Mental State Examination (MMSE) ⁶ score of 7/30 and an inability to complete the Montreal Cognitive Assessment (MoCA). ⁷ The patient demonstrated left lower extremity weakness (Medical Research Council (MRC) ⁸ grade 4/5). Although deep tendon reflexes were normoactive, a left Babinski sign was present, while both superficial and deep sensations (including joint position sense and vibration sense) remained intact throughout.

Diagnostic investigations were then pursued to identify the cause. Laboratory investigations revealed pancytopenia (white blood cell (WBC) count, 2.7 × 10⁹/L; red blood cell (RBC) count, 1.34 × 10¹²/L, Hb level, 6.3 g/dL; platelet count, 55 × 10⁹/L) with marked macrocytosis (MCV, 134 fL; MCH level, 47 pg). Serum studies demonstrated severe vitamin B12 deficiency (<83 pg/mL) with significantly elevated homocysteine (160.06 μmol/L), while folate levels were within the normal range (15.1 ng/mL). The pepsinogen I/II ratio was markedly reduced (3.3 ng/mL and 3.4 ng/mL, respectively), consistent with autoimmune gastritis. Neuroimaging and neurophysiological studies were pivotal in demonstrating the extent of nervous system involvement. Brain MRI revealed multiple T2WI/DWI hyperintense lesions (Figure 1(a) to (d)) within the bilateral frontal lobes, periventricular white matter, and centrum semiovale, with corresponding reduced apparent diffusion coefficient (ADC) values, consistent with cytotoxic edema. ⁹ Magnetic resonance angiography showed no significant intracranial stenosis. Furthermore, spinal cord MRI revealed no pathological abnormalities. Objective neurophysiological evidence of central nervous system impairment was obtained. Prolonged P100 latencies were observed on visual evoked potentials (right, 147 ms; left, 143 ms; normal, ≤118 ms). This objective finding confirmed the clinically suspected visual pathway dysfunction, correlating with the patient’s family-reported history of colliding with objects. Event-related potentials revealed significant delays in both P300 (442 ms, normal ≤365 ms) and N400 (511 ms, normal ≤420 ms) components. Concurrent electroencephalography demonstrated diffuse background slowing (5–7 Hz) with preserved symmetry. Cerebrospinal fluid analysis was normal, with absent oligoclonal bands and negative aquaporin-4 immunoglobulin G. Investigations to exclude alternative diagnoses, including a comprehensive metabolic panel, inflammatory markers (erythrocyte sedimentation rate, C-reactive protein), autoimmune serologies (anti-neutrophil cytoplasmic antibodies, cardiolipin antibodies), thrombophilia workup, and malignancy screening, yielded no significant abnormalities.

Figure 1.

Serial brain MRI changes during treatment and follow-up. (a to d) Admission MRI. DWI sequences demonstrate symmetrical periventricular hyperintensities (red arrows), indicative of cytotoxic edema. (e to h) Follow-up MRI at discharge (day 20 of treatment). Post-contrast T1-weighted images show perilesional enhancement (red arrows). (I to l) Follow-up MRI at 3 months. Images reveal the evolution of some previous lesions into small foci of encephalomalacia or cystic change, consistent with gliosis (red arrows). MRI: magnetic resonance imaging; DWI: diffusion-weighted imaging.

Diagnosis, treatment, and follow-up

The patient showed no cerebrovascular risk factors, with no evidence of atherosclerosis or atrial fibrillation. Based on the 2023 McDonald criteria for multiple sclerosis and the 2015 International Panel Diagnosis criteria for neuromyelitis optica spectrum disorders,^10,11 both diagnoses were considered unlikely given the acute presentation, absence of typical imaging features, and negative cerebrospinal fluid findings. Subcutaneous vitamin B12 (1000 µg daily) was initiation and nutritional support was provided, with concurrent gastric mucosal protection using teprenone and Wei Fu Chun Pian (a Chinese herbal patent medicine). A follow-up laboratory assessment performed 3 days later showed a rise in his vitamin B12 level but identified subnormal folate levels, likely secondary to poor dietary intake, prompting the addition of folic acid supplementation. Serial laboratory monitoring demonstrated gradual normalization of pancytopenia, with MCV and MCH level trending toward normal within 1 month. The patient’s cognitive function improved progressively. By hospital day 20, at discharge, he had shown significant clinical improvement. A follow-up contrast-enhanced MRI at this time revealed enhancing lesions in the perilesional brain regions (Figure 1(e) to (h)). Following this improvement, the treatment was transitioned to a maintenance phase with weekly intramuscular vitamin B12 injections (1 mg) for 1 month. The regimen was subsequently tapered to monthly injections. At the 3-months follow-up, the patient’s clinical symptoms had resolved completely, and cognitive assessment confirmed full functional recovery (MMSE score, 24/30; MoCA score, 23/30; adjusted for educational level). A repeat MRI suggested the evolution of some prior lesions into small foci of encephalomalacia or cystic change, consistent with gliosis (Figure 1(i) to (l)). The maintenance B12 injections were thereafter discontinued. Sustained clinical recovery without recurrence was confirmed at the 6-months follow-up.

Discussion

Cytotoxic edema on brain MRI is most frequently associated with acute cerebral infarction; however, it may also occur in metabolic disorders and other conditions. ⁹ In acute metabolic encephalopathies, imaging often reveals bilaterally symmetrical abnormalities that may be reversible. ¹² Our patient presented with acute cognitive dysfunction, and MRI showed symmetrical periventricular cytotoxic edema. Laboratory investigation identified severe vitamin B12 deficiency, with other metabolic, toxic, and infectious etiologies ruled out using appropriate testing; complete symptomatic recovery followed replacement therapy, strongly supporting this deficiency as the cause of the encephalopathy.

Vitamin B12 deficiency can cause a variety of hematological, psychiatric, and neurological symptoms. The neurological symptoms may include subacute combined degeneration of the spinal cord, acute or chronic cognitive dysfunction, visual impairment, and sensory-motor polyneuropathy.^3,13,14 The underlying neurotoxicity is attributed to the accumulation of homocysteine and methylmalonic acid. Elevated homocysteine acts as a glutamate receptor agonist, particularly at N-methyl-D-aspartate receptor sites, inducing excitotoxicity, calcium influx, oxidative stress, and neuronal apoptosis.^15,16 Methylmalonic acid impairs mitochondrial function, further promoting oxidative damage and neuronal injury. ¹⁷ These processes collectively contribute to demyelination, axonal degeneration, neuronal loss, and reduced brain volume.^15–17

In vitamin deficiency states, spinal cord lesions often exhibit distinctive imaging features, ¹⁸ whereas brain involvement can vary from focal to extensive periventricular white matter lesions.^3,19,20 In previous reports, intracranial abnormalities caused by vitamin B12 deficiency have almost always been characterized by high T2 signal, while high DWI signals have been rarely reported. Few studies have reported high DWI signal in the splenium of the corpus callosum ²⁰ and symmetrical cortical/subcortical involvement in the cingulate and insular regions. ²¹ In this case, gadolinium enhancement on T1-weighted images suggests blood–brain barrier disruption and local inflammation, indicating an acute disease phase. Although the patient’s clinical symptoms had resolved, the presence of necrotic foci implied irreversible structural damage, underscoring the critical importance of early diagnosis and intervention to mitigate long-term neurological deficits,^3,22 even when the immediate clinical outcome appears favorable.

Serial MMSEs in our patient demonstrated rapid cognitive recovery, with scores increasing from 7/30 to 24/30 following vitamin B12 therapy, which paralleled the reversible DWI changes. Consistent with previous studies, ²³ our patient showed cognitive improvement after B12 therapy; however, the tight temporal and imaging correlation we observed contrasts with their finding of no association between MRI abnormalities and cognitive function in B12 deficiency encephalopathy. Our patient demonstrated acute, severe encephalopathy secondary to vitamin B12 malabsorption, with reversible cytotoxic edema on DWI that closely mirrored clinical recovery. This suggests that in acute metabolic derangement, DWI changes serve as a dynamic marker of disease activity.

Conclusion

This case illustrates that vitamin B12 deficiency can present with acute neurological manifestations and distinctive MRI findings, including symmetrical paraventricular T2/DWI abnormalities. It serves as a reminder that early diagnosis and replacement therapy are critical for achieving favorable neurological outcomes.