Striatal Atrophy and Hypometabolism in Drug‐Resistant Non‐Ketotic Hyperglycemic Chorea‐Ballism

Non-ketotic hyperglycemic chorea-ballism (NKHCB) is a rare movement disorder associated with poorly controlled type-2 diabetes,1 in the majority of cases characterized by: unilateral hemicorea-hemiballism, contralateral striatum hyperintensity on T1-weighted magnetic resonance imaging (MRI), and clinical and radiological improvement after blood glucose correction.2 Herein, we present a case of NKHCB with following evidence of striatal atrophy. A 56-year-old woman presented to the emergency department of another hospital because of sudden onset of involuntary movements of the left limbs attenuated during rest. She had a recent history of type-2 diabetes mellitus treated with poor glycemic control. A computed tomography scan showed striatal hyperdensity. Routine laboratory findings were normal, despite a fasting blood glucose level of 167 mg/dL and glycate hemoglobin level of 130 mmol/mol (14%). MRI scan showed striatal T1-weighted hyperintensity with a corresponding hyperintensity in T2-weighted (Fig. 1A and B) and fluid attenuated inversion recovery (FLAIR) scans. The patient was diagnosed with NKHCB. Glucose control was optimized and anti-choreic therapy was started with haloperidol 5 mg/day and tetrabenazine 25 mg/day with a slight clinical benefit. The patient arrived at our attention 4 months after symptom onset for diagnostic re-evaluation. The motor impairment persisted and involuntary movements worsened insidiously. The neurological examination showed choreoatetosic and ballic movements of the left body side. Involuntary movements increased with distraction maneuvers and resolved during rest at bed. Blood fasting glucose was 126 mg/dL and glycated hemoglobin was 62 mmol/mol (7.8%). MRI scan showed the resolution of the striatal alteration, but highlighted atrophic evolution (Fig. 1C and D). A fluorodeoxyglucose positron emission tomography scan showed an intense hypometabolism consistent with morphological MRI atrophy findings (Fig. 1E and F). Haloperidol was discontinued and clinical improvement was obtained with tetrabenazine 25 mg thrice/day, piracetam 3 g/day and topiramate 25 mg twice/day. The comparison of MRI volumes at the two timepoints showed, on the right side, a decrease in caudate head and putamen volumes and an increase in the lateral ventricle volume. The two main pathophysiological mechanisms proposed for NKHCB are related to metabolic dysfunction and to microvascular damage.3, 4 Our findings may be explained by irreversible metabolic or vascular damage. The microvascular hypothesis might explain the prevalent unilateral clinical onset. The prognostic implication of our observation is related to the high variability in outcomes.1 Extended lesions at MRI were associated with prolonged involuntary movements.5 Our findings of focal atrophy strengthen these results, suggesting a role of the pathological disease severity, in-vivo assessed by MRI, to determine the persistence of the disorder. We hypothesize that a mild disorder, solved with anti-chorea treatment, might be associated with a lower degree of atrophy, unrecognized without a volumetric analysis. In conclusion, our case of NKHCB showed focal striatal atrophy and hypometabolism after radiological resolution in a 4-month follow-up, associated with poor response to glucose-control and anti-chorea treatment. To date, for the first time we documented nuclear volume changes with a quantitative approach demonstrating irreversible pathological changes in NKHCB, explaining drug-resistant cases. (1) Research project: A. Conception, B. Organization, C. Execution. (2) Statistical Analysis: A. Design, B. Execution, C: Review and Critique. (3) Manuscript: A. Writing of the first draft, B. Review and Critique. P.G.S.: 1A, 1B, 1C, 2A, 2B, 3A F.A.: 1A, 1B, 2C, 3B N.A.: 1C, 3B M.A.V.: 1A, 1B, 1C, 2C, 3B M.F.: 1A, 1B, 2C, 3B This study has been approved by the Ethics Committee of IRCCS San Raffaele Hospital and has been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments. The patient provided written informed consent to be anonymously included in this report. We confirm that we have read the Journal's position on issues involved in ethical publication and affirm that this work is consistent with those guidelines. No funding was received for this work and the authors have no conflicts of interest to report. P.G. Scamarcia, N. Anzalone, and M.A. Volontè have nothing to disclose. F. Agosta is Section Editor of NeuroImage: Clinical; has received speaker honoraria from Philips, Novartis and Biogen Idec; and receives or has received research supports from the Italian Ministry of Health, AriSLA (Fondazione Italiana di Ricerca per la SLA), and the European Research Council. M. Filippi is Editor-in-Chief of the Journal of Neurology; received compensation for consulting services and/or speaking activities from Bayer, Biogen Idec, Merck-Serono, Novartis, Roche, Sanofi Genzyme, Takeda, and Teva Pharmaceutical Industries; and receives research support from Biogen Idec, Merck-Serono, Novartis, Roche, Teva Pharmaceutical Industries, Italian Ministry of Health, Fondazione Italiana Sclerosi Multipla, and ARiSLA (Fondazione Italiana di Ricerca per la SLA).