Correlation of Tc-99 m ethyl cysteinate dimer single-photon emission computed tomography and clinical presentations in patients with low cobalamin status

Abstract

BackgroundCobalamin (Cbl) deficiency has been associated with various neuropsychiatric symptoms of different severities. While some studies dedicated in structural neuroimaging credibly address negative impact of low Cbl status, functional imaging reports are limited. We herein retrospectively review the correlation of Tc-99 m ethyl cysteinate dimer single-photon emission computed tomography (Tc-99 m-ECD SPECT) and clinical presentations among patients with low serum cobalamin (Cbl) status (<250 pg/ml).MethodsTwelve symptomatic patients with low serum Cbl status were enrolled. Clinical presentations, Tc-99 m-ECD SPECT, and neuropsychological tests were reviewed.ResultsDysexecutive syndrome (67 %), forgetfulness (50 %), attention deficits (42 %), and sleep disorders (33 %) constituted the major clinical presentations. All patients (100 %) had temporal hypoperfusion on the Tc-99 m-ECD SPECT. Five patients (42 %) had hypoperfusion restricted within temporal regions and deep nuclei; seven patients (58 %) had additional frontal hypoperfusion. In patients with hypoperfusion restricted within temporal regions and deep nuclei, psychiatric symptoms with spared cognition were their main presentations. Among patients with additional frontal hypoperfusion, six of seven patients (86 %) showed impaired cognitive performances (two of them were diagnosed as having dementia). Among ten patients who finished neuropsychological tests, abstract thinking (70 %) was the most commonly affected, followed by verbal fluency (60 %), short-term memory (50 %), and attention (50 %). Anxiety and sleep problems were the major clinically remarkable psychiatric features (33 % both). Four Tc-99 m-ECD SPECT follow-up studies were available; the degree and extent of signal reversal correlated with cognitive changes after Cbl replacement therapy.ConclusionsOur TC-99 m-ECD SPECT observations provide pivotal information of neurobiological changes within basal ganglia and fronto-temporal regions in conjunction with disease severity among patients with Cbl deficiency. Hypoperfusion within thalamus/basal ganglia and temporal regions may be seen in the earlier state of Cbl deficiency, when psychiatric symptoms predominate. Hypoperfusion beyond thalamus/basal ganglia and involving frontal regions appears when cognitive problems, mostly dysexecutive syndrome, are manifested. Symmetric hypofrontality of SPECT in the context of dysexcutive syndrome serves as a distinguishing feature of non-amnestic mild cognitive impairment attributed to Cbl deficiency. Concordant with TC-99 m-ECD SPECT findings, the psychiatric symptoms and dysexcutive syndrome undergird impaired limbic and dorsolateral prefrontal circuits originating from basal ganglia respectively.

Neurological presentations and therapeutic responses to cobalamin deficiency

“…Both studies reported benefits in verbal fluency, suggesting that frontalsubcortical circuit dysfunction is one of the main pathogenesis related to Cbl deficiency [14]. This hypothesis is also supported by a functional imaging study, in which hypoperfusion within frontal regions and basal ganglia were associated with dysexecutive syndrome in patients with Cbl deficiency [7]. Additionally, we also found therapeutic benefits in short-term memory, in which both frontal and temporal lobes are regarded as pivotal neural substrates.…”

“…Aside from sub-acute combined degeneration and polyneuropathies, the best known neurological presentations, the association between Cbl deficiency and cognitive impairment has been gaining attention recently. Although the negative impact of Cbl deficiency on cognition has been reported in several studies [4][5][6][7][8], the causality is unclear. One of the major issues is that the reported therapeutic responses after Cbl supplement therapy differ.…”

Vitamin B12 deficiency: Cognitive impairment and neuroimaging correlates

“…For example, we associated impaired fronto-subcortical circuits with cognitive decline on the basis that the morphometric parameters aiming on the frontal regions showed divergent correlations with multiple cognitive domains [2]. Consistently, two SPECT studies supported the critical role of the frontal regions in cognitive prognosis and/ or performance [3,8]. Specifically, although the temporal regions were associated with variable psychiatric symptoms or the state of delirium, intact function of the frontal regions appeared to govern the orchestration of global cognitive process.…”

“…In patients with cognitive impairment due to a low vitamin B12 status, we previously reported that a hastening ageing process through impaired myelin integrity and subsequent volume reduction as seen in structural imaging findings may be the pathogenesis [2]. In addition, the derangement of neurotransmitters, neuronal dysfunction, and damage of vessels and myelin secondary to the accumulation of homocysteine and methylmalonic acid may contribute to the mechanisms related to our functional imaging observations [3]. Consistent with a previous study [10], we also demonstrated a dissociative involvement between neurological and hematological systems in our previous cohort study [2].…”

“…As neuronal dysfunction would be expected to coexist or even predate overt structural changes in neurodegenerative diseases, we also conducted another study using Tc-99m ethyl cysteinate dimer single-photon emission computed tomography (Tc-99m-ECD SPECT) as the functional neuroimaging tool to investigate its clinical relevance [3]. We enrolled 12 symptomatic patients with low serum vitamin B12 status (< 250 pg/ml), and investigated associations between Tc-99m-ECD SPECT and clinical presentations as well as performance on neuropsychological tests.…”