Bedwell firstly described HC-HB in the year 1960 as an unusual movement disorder induced by poorly controlled diabetes. NKH induced HC-HB were sporadically reported in cases with east Asian origin, which suggested hyperglycemia as a rare cause (only 1%) of chorea with a possible genetic disposition [1, 6].
Although the precise mechanism of NKH induced HC-HB remained controversial, the mainstream theory holds that hyperglycemia causes the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) to be consumed as an alternative energy source in the affected parenchyma [1, 7]. Consequently, reduction of GABA signaling in the thalamus could lead to increased excitatory thalamocortical drive and secondary involuntary movements on the contralateral side [7].
The cause-and-effect relationship of NKH induced HC-HB between hyperglycemia state and imaging patterns has not yet been fully proved. The T1-hyper-intensity was initially thought to be due to focal hemorrhage, demyelination, or calcification after ‘‘ischemic events’’, but currently attributed to presence of gemistocytes (special reactive astrocytes) that could accumulate manganese (causing T1 shortening effect) after chronic ischemia [1–4, 6].
The glioma-like appearance in the first case, as an unexpected discovery, was mainly ascribed to the obvious enhancement on T1WI after injection of paramagnetic contrast agent. We assumed that the abnormal contrast enhancement may be due to high-glucose-induced inflammatory responses and increased blood-brain barrier permeabilities under hyperglycemia conditions [3, 7]. It should also be noted that DWI revealed no evidence of cytotoxic edema or active cell proliferation (presented as restricted diffusion in patients with acute cerebral infarction or high-grade glioma) in the corresponding area.
MRS is a non-invasive method used for identifying specific metabolic markers of seizure-induced neuronal damage, which has not been systematically reported in patients with NKH induced HC-HB [8]. Excessive activation of various molecular pathways could lead to loss of balance between anaerobic glycolysis and oxidative metabolism (which produces large quantities of Lac) in such cases [2]. Thus, in-situ Lac level as illustrated by MRS could be applied in assessing possible “ischemic damage” of NKH induced HC-HB [3, 8]. Besides, the quantitative parameter Cho/NAA ratio of MRS is widely used in the differentiation of brain tumors and non-tumor diseases. In the vast majority of gliomas (especially glioblastoma), Cho peak markedly increased (suggesting increased cell membrane synthesis) and NAA peak markedly decreased (suggesting neuronal damage). By contrast, a relatively low Cho/NAA ratio (<1) suggested the diagnosis of a metabolic/reversible disease as revealed by our case.
In conclusion, a combination of long-term uncontrolled hyperglycemia, unilateral involuntary movements and contralateral basal ganglia abnormalities may suggest the diagnosis of NKH induced HC-HB. In addition to the classic T1-hyper-intensity characteristic, this report emphasizes the reversible focal neurological disorder may exhibit a unique appearance mimicking glioma. Slightly elevated Cho/NAA ratio with marked increased Lac peak on MRS may help to exclude neoplastic diseases.