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Doi:10.3402/jchimp.v5.27825

JOURNAL OF COMMUNITY HOSPITAL
NTERNAL MEDICINE PERSPECTIVES
Non-ketotic hyperglycemia unmasks hemichorea Abhijeet Danve, MDSupriya Kulkarni, MD1 and Girja Bhoite, MD2 1Department of Internal Medicine, Metropolitan Hospital, New York Medical College, New York, NY, USA; 2Department of Internal Medicine, Medstar Washington Hospital Center, Washington, DC, USA Background: Chorea can be caused by a variety of diseases, including neurodegenerative disorders, vascularevents, toxic-metabolic states, and immunologic and infectious diseases. We describe a patient who presentedwith hemichorea as the initial manifestation of Diabetes Mellitus (DM) and responded partially to theglycemic control.
Case report: A 63-year-old, healthy Hispanic man with no prior history of medical illness presented withsubacute onset, gradually progressive hemichorea of 6 weeks' duration. On evaluation, he was found to havenon-ketotic hyperglycemia with high serum glucose (328 mg/dL), elevated hemoglobin A1C (9.9%), andabsent ketones. Magnetic Resonance Imaging of the brain demonstrated hyper intense signals in bilateralbasal ganglia on T1W images. He was diagnosed to have DM. Despite optimal glycemic control with insulin,the patient continued to have hemichorea at 3 months follow-up and required haloperidol for control of theinvoluntary movements.
Significance: Involuntary movements, particularly hemichorea, can be a manifestation and rarely be apresenting sign of DM.
Keywords: chorea; diabetes mellitus; hemichorea; non-ketotic hyperglycemia; movement disorders *Correspondence to: Abhijeet Danve, 11322 Franklin Plaza Apt 915, Omaha, NE 68154, USA, Email:[email protected] Received: 9 March 2015; Revised: 1 June 2015; Accepted: 4 June 2015; Published: 1 September 2015 which can be caused by a variety of diseases, prompting him to come to our hospital. He did not have including neurodegenerative disorders, vascular abnormal behavior, headache, and weakness on any side events, toxic-metabolic states, and immunologic and or sensory disturbances. Patient was never treated with infectious diseases. Manifestation of hemichorea (HC) antipsychotic, antiemetic, or herbal medications. Family as the initial presentation of non-ketotic hyperglycemia history was unremarkable. He was a reformed smoker and (NKH) is rare in patients with diabetes mellitus (DM).
We describe HC as presenting sign of diabetes in a On examination, he was alert, awake, and oriented.
Hispanic patient.
Blood pressure was 148/60 mmHg, and heart rate was64/min. Cranial nerve examination was normal. Motor examination revealed normal strength, but hypotonia, A 63-year-old, right-handed Hispanic man was brought hyporeflexia, and rapid, jerky, continuous non-stereotyped to the emergency room with the complaint of abnormal involuntary choreiform movements involving right upper movements of right arm and right leg for about 6 weeks.
and lower extremities. Plantar reflex was flexor bilaterally.
The patient initially developed intermittent twitches in The sensations were intact. He could not walk without the right shoulder and arm as noticed by his daughter, support due to abnormal movements in right leg and which the patient was unaware of. Two weeks later, he was briefly admitted to an outside hospital for dizziness, dehy- Complete blood count, liver, and renal function tests dration, and high serum glucose levels up to 1,100 mg/dL.
were normal. His serum glucose was 328 mg/dL, HbA1C He was diagnosed to have DM and was started on sub- level 9.9%, and serum ketones were negative. Urine cutaneous insulin regimen. After 6 days of discharge from toxicology, serum alcohol, as well as TSH and HIV were the hospital, he experienced worsening of involuntary unremarkable. CT brain (Fig. 1a) revealed a 1 1.7 cm movements which now involved whole right upper ex- area of subtle increased density in left lentiform nucleus with tremity and progressed in 2 weeks to right leg and foot.
surrounding decreased attenuation. Magnetic resonance Journal of Community Hospital Internal Medicine Perspectives 2015. # 2015 Abhijeet Danve et al. This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License permitting all non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
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Fig. 1. (a) Non-contrast CT scan showing ill-defined hyperdensity in left putamen. (b) Axial T1-W without contrast showinghyperintensities in bilateral putamen and caudate. (c) Axial T2-W without contrast showing corresponding hypointensities inputamen and caudate. (d) Axial T1-W with contrast showing no enhancement of abnormal signals after gadolinium.
imaging (MRI) brain with gadolinium contrast showed Despite adequate glycemic control using insulin, he con- non-enhancing hyper intense lesions in bilateral lentiform tinued to have HC and responded partially to haloperidol.
and caudate nuclei on T1W images and old stable infarcts At 3-month follow-up, the patient had persistent but mild (Figs. 1b
d).
(page number not for citation purpose) Neurotransmitter dysfunction mainly hyperactivity of Polyphagia, polydipsia, weight loss, fatigue, and weak- dopaminergic neurons is thought to be a prominent cause.
ness are common presenting symptoms in patients In NKH, brain metabolism shifts to anaerobic pathway with DM. Chorea is a rare manifestation of NKH in and brain utilizes GABA as energy source. Unlike in dia- DM and was described first in 1960 (1). It has rarely been betic ketoacidosis, GABA is not resynthesized and rapid described as the presenting sign of new onset diabetes depletion of GABA leads to decreased acetyl choline syn- (2, 3). Hemichorea has been more commonly described thesis. Reduced GABA, acetyl choline, decreased energy, to be associated with NKH than generalized chorea. In a and regional metabolic failure may cause basal ganglia meta-analysis of 53 patients by Oh et al., mean age was dysfunction leading to chorea (4).
71 years and male: female ratio was 1:1.8 (4). In a study HC in NKH presents with characteristic though not of 35 patients, 86% were Asians suggesting genetic specific neuroimaging findings. Majority have hyperin- predisposition (5). Patients typically present with sub- tense signals in contralateral putamen on T1-weighted acute onset, gradually progressive involuntary move- images. In few case series, patients also had hyperinten- ments over days to weeks associated with high glucose sities in contralateral caudate (19). Patients can also levels, absent ketones, and high serum osmolality. How- have bilateral basal ganglia hyperintense signals on T1W ever, chorea starting few days after the hyperglycemic images. In the meta-analysis of 53 cases by Oh et al., all crisis and even after adequate sugar control has been patients had hyperintense signals in contralateral puta- reported (6). The movement disorder in NKH range men on T1W images and six (11%) patients had bilateral from mild choreoathetoid movements to hemiballism basal ganglia lesions (4). Usually, there is hypointensity or with violent flinging movements. Associated features no significant alternation in T2-weighted images and on such as personality changes, seizures, painful sensory symp- contrast MRI lesions are mostly non-enhancing. Another toms, and weakness have been described as well (7, 8).
characteristic finding is the resolution of abnormal signals Usually, movements resolve within 24
48 h of aggres- in follow-up imaging although it may be seen well ahead sive sugar control (9, 10). However, prolonged HC and of clinical improvement (4). We suggest that detailed neuro- relapse after the initial response has also been described imaging should be performed including DWI and SWI to exclude infarction, hidden ischemia (perfusion deficit), Ahlskog et al. reported five female patients who and hemorrhagic processes, which may affect treatment developed chorea concurrently or shortly after hypergly- strategies. CT scan may be normal or may show hyper- cemic episode and all patients continued to have persistent density in contralateral basal ganglia. SPECT studies chorea despite sugar control for 6 months to 5 years of in patients show hypoperfusion in the corresponding follow-up (6). Patients with HC with incomplete recovery areas (16). PET scan in three patients with chorea and from glycemic control may respond well to the conven- NKH showed markedly reduced rates of cerebral glucose tional neuroleptics, such as haloperidol, perphenazine, metabolism in the corresponding lesions on T1-weighted and chlorpromazine. Also, risperidone and an anticon- images on MRI suggesting evidence of regional metabolic vulsant such as topiramate may be useful (11
13). The failure (13).
prognosis of chorea associated with NKH has been reported As DM is a widely prevalent disease and hemichorea as good (10).
due to NKH is amenable to rapid sugar control, it is Exact pathogenesis of chorea in NKH is unclear.
important for physicians to be aware of this condition and Striatum may be directly susceptible to alterations of consider it in appropriate clinical settings. Why chorea blood glucose because even patients with hypoglycemia persists in some patients of NKH despite optimal glycemic can develop choreoathetoid movements (14). Ischemia control is not entirely clear though neuronal loss from secondary to hyperviscosity or neural injury due to ischemia and putaminal microhemorrhage are possible hyperglycemia could be the possible cause for abnormal causes. Please see appendix for common questions on this movements (15). Another theory is putaminal petechial hemorrhage causing dyskinesia (16). Broderick et al.
reported two cases of DM and chorea where hemorrhagic infarction was caused by diapedesis from damaged but Involuntary movements, particularly hemichorea, can be a not ruptured capillaries (17). Biopsy and autopsy studies manifestation and rarely be a presenting sign of DM.
have showed striatal neuronal loss and astrocytosis (18).
Usually, hemichorea is associated with NKH. Char- It is also possible that chorea in NKH is due to a acteristic MRI feature is hyperintensity at contralateral functional abnormality rather than structural disease.
putamen on T1W images. Hemichorea usually, but not Putamen may have inhibitory influence on globus pal- always, responds to glycemic control. Exact pathogenesis lidus and lesions of putamen cause uninhibited activity is unclear; direct affection of striatum by altered glucose of globus pallidus leading to choreiform movements.
levels is possible.
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Authors' contributions T1-weighted MR image hyperintensities. Intern Med 2005; 44:1280
5.
All the listed authors have participated actively in the study, 9. Wintermark M, Fischbein NJ, Mukherjee P, Yuh EL, Dillon have met the requirements for the authorship, and have read WP. Unilateral putaminal CT, MR, and diffusion abnormalities and approved the submitted manuscript.
secondary to nonketotic hyperglycemia in the setting ofacute neurologic symptoms mimicking stroke. AJNR Am JNeuroradiol 2004; 25: 975.
Conflict of interest and funding 10. Branca D, Gervasio O, Le Piane E, Russo C, Aguglia U. Chorea induced by non-ketotic hyperglycaemia: a case report. Neurol Abhijeet Danve, Supriya Kulkarni and Girija Bhoite have Sci 2005; 26: 275
7.
no conflict of interest.
11. Saleh MM, Zacks ES, Katz JS. Delayed recovery of diabetic chorea following correction of hyperglycemia. J Neurol 2002; 249: 1323
4.
12. Driver-Dunckley E, Evidente VG. Hemichorea-hemiballismus may respond to topiramate. Clin Neuropharmacol 2005; 28: 1. Bedwell SF. Some observations on hemiballismus. Neurology 1960; 10: 619
22.
13. Hsu JL, Wang HC, Hsu WC. Hyperglycemia-induced unilateral 2. Lin JJ, Chang MK. Hemiballism-hemichorea and NKH.
basal ganglia lesions with and without hemichorea: a PET study.
J Neurol Neurosurg Psychiatry 1994; 57(6): 748
50.
J Neurol 2004; 251: 1486
90.
3. Verma R, Praharaj HN. Hemichorea-hemiballism as the pre- 14. Newman RP, Kinkel WR. Paroxysmal choreioathetosis due to senting manifestation of diabetes mellitus. BMJ Case Rep 2013; hypoglycemia. Arch Neurol 1984; 41(3): 341
2.
15. Altafullah I, Pascual-Leone A, Duvall K, Anderson DC, 4. Oh SH, Lee KY, Im JH, Lee MS. Chorea associated with NKH and hyperintensity basal ganglia lesion on T1-weighted brain Taylor S. Putaminal hemorrhage accompanied by hemichorea- MRI study; a meta-analysis of 53 cases including 4 present hemiballism. Stroke 1990; 21(7): 1093
4.
cases. J Neurol Sci 2002; 200(1
2): 57
62.
16. Chang MH, Chiang HT, Lai PH, Sy CG, Lee SS, Lo YY.
5. Lin JJ, Lin GY, Shih C, Shen WC. Presentation of Striatal Putaminal petechial hemorrhage as cause of chorea: a neuroi- hyperintensity on T1- weighted MRI in patients with HC-HB maging study. J Neurol Neurosurg Psychiatry 1997; 63(3): caused by NKH: report of seven new cases and review of literature. J Neurol 2001; 248(9): 750
5.
17. Broderick JP, Hagen T, Brott T, Tomsick T. Hyperglycemia and 6. Ahlskog JE, Nishino H, Evidente VG, Tulloch JW, Forbes GS, hemorrhagic transformation of cerebral infarcts. Stroke 1995; Caviness JN, et al. Persistent chorea triggered by hyperglycemic crisis in diabetics. Mov Disord 2001; 16(5): 890
8.
18. Nagai C, Kato T, Yamamoto K, Sasaki H. Hyperintense 7. Sarah MK, Raymond P, Sashank P, Howard IH. Clinical Putamen on T1weighted MR images in case of chorea with reasoning: a 52 year old woman with subacute hemichorea.
hyperglycemia. AJNR 1994; 16: 124
6.
Neurology 2008; 71(20): 59
62.
19. Lai PH, Tien RD, Chang MH, Teng MM, Yang CF, Pan HB, 8. Ohmori H, Hirashima K, Ishihara D, Maeda Y, Hirano T, et al. Chorea- Ballismus with NKH in primary diabetes mellitus.
Uyama E, et al. Two cases of hemiballism-hemichorea with Am J Neuroradiol 1996; 17(6): 1057
4.
(page number not for citation purpose) Multiple choice questions 1. Chorea can be a manifestation of which of the following conditions?A. Non-ketotic hyperglycemia in diabetesB. Diabetic ketoacidosisC. HypoglycemiaD. A and CCorrect answer: DBoth hypoglycemia and non-ketotic hyperglycemia can trigger chorea.
2. Hemichorea due to non-ketotic hyperglycemia is common in which of the following races?A. AsianB. WhiteC. HispanicD. BlackCorrect answer: AMajority of reported cases have been Asian women.
3. What is the typical brain MRI finding in patients with diabetic hemichorea?A. Hypointensity on T1W images in contralateral caudate nucleusB. Hyperintensity on T1 W images in contralateral putamenC. Hypointensity on T1W images in ipsilateral putamenD. Hyperintensity on T2W images in contraletral globus pallidusCorrect answer: BMajority have hyperintense signals in contralateral putamen on T1-weighted images.
4. Which of the following is the treatment of choice in patients with diabetic hemichorea?A. HaloperidolB. OxcarbazepineC. TopiramateD. Adequate glycemic controlCorrect answer: DMajority of patients respond within 24
48 h with adequate glycemic control.
5. Which of the following has been implicated in the pathogenesis of diabetic hemichorea?A. Ischemia secondary to hyperviscosity or neural injuryB. Putaminal hemorrhageC. Uninhibited activity of globus pallidusD. Depletion of GABAE. All of the aboveCorrect answer: EAll of the above mechanisms have been reported to contribute to development of diabetic hemichorea.
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