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CASE IN POINT in Patients With Poorly Controlled Type 2 Diabetes Mellitus

Pressley Chakales, MD; Ariel Park; Austin Amos, MS; Esther Baldinger, MD; Igor Sirotkin, MD; and Alfred Frontera, MD Swift identification of hemiballismus as a complication of poorly controlled type 2 diabetes mellitus may help facilitate optimal care through glycemic control and prevent debilitating loss of patients' function and autonomy, prolonged hospital stays, and overuse of resources.

Austin Amos and Ariel emiballismus is an acquired hyperki- numerous case reports have described pa- Park are Medical Students, netic character- tients with DM with acute and subacute Pressley Chakales was a ized by unilateral, involuntary, often onset of hemiballistic and hemichorei- Medical Student at the time H the article was written; large-amplitude limb movements. Ballis- form movements while in a hyperglyce- Esther Baldinger and movements are now considered to be mic state or after its resolution. Reported Alfred Frontera are on the choreiform spectrum.1 Movements cases have been limited to small numbers Associate Professors of ; and Igor Sirotkin usually involve both the arm and leg, and of patients with only a few larger-scale re- 7,9 is an Assistant Professor of in half of cases, facial movements such as views of more than 20 patients. Most re- Neurology; all at the tongue clucking and grimacing are seen.2,3 ported cases involve geriatric patients and University of Central Florida College of Medicine in Presentations of hemiballismus vary in more commonly, females of Eastern Asian Orlando. Igor Sirotkin is an severity from intermittent to nearly con- descent with an average age of onset of Assistant Professor of tinuous movements, which, in some cases, 71 years.4,10 Patients typically present with Radiology at the may lead to exhaustion, injury, or disability. glucose levels from 500 to 1,000 mg/dL University of Southern Florida in Tampa. Esther Some patients are unable to ambulate or and hemoglobin A1c (HbA1c) levels almost Baldinger and Alfred feed themselves with the affected limb. double the normal values. Interestingly, Frontera are Neurologists neuroimaging findings in these patients and Igor Sirotkin is a BACKGROUND have consistently shown hyperintense sig- Neuroradiologist, all at Bay Pines VA Healthcare System The 2 most common causes of nal in the contralateral on in Florida. hemichorea-hemiballismus are stroke and T1-weighted magnetic resonance images Correspondence: , with an incidence of 4% (MRIs). Noncontrast computed tomogra- Pressley Chakales 1,3,4 ([email protected]) and unknown incidence, respectively. phy (CT) shows well-defined unilateral in- Other causes include HIV, traumatic brain creased density in the contralateral basal injury, , vasculitis, mass effect, ganglia without mass effect.1,9,11 multiple sclerosis, and adverse drug reac- This report aims to illustrate and enhance tions.4-7 Acute or subacute hemiballismus is the understanding of hemiballismus associ- classically attributed to a lesion in subtha- ated with hyperglycemia. One patient pre- lamic nucleus (STN), but this is true only sented to the US Department of Veterans in a minority of cases. Hemiballismus can Affairs (VA) Bay Pines VA Healthcare System be caused by any abnormality in various (BPVAHCS) in Florida, which motivated us subnuclei of the basal ganglia, including the to search for other similar cases. We reviewed classic location in the STN, , and the charts of 2 other patients who presented globus pallidus.4 Evidence shows the le- to BPVAHCS over the past 10 years. The sions typically involve a functional network first case presented with severe hypergly- connected to the posterolateral .8 cemia and abnormal movements that were Although not commonly recognized, not clearly diagnosed as hemiballismus. MRI hyperglycemia in patients with type 2 findings were characteristic and assisted in diabetes mellitus (T2DM) is the sec- making the diagnosis. The second case was ond most common cause of hemichorea- misdiagnosed as hemiballismus secondary to hemiballismus.3 Over the past 90 years, ischemic stroke. The third case was initially

282 • FEDERAL PRACTITIONER • JUNE 2020 mdedge.com/fedprac FIGURE 1 Noncontrast Axial T1-Weighted Magnetic Resonance Imaging of Case 1 Head A B C

Contiguous axial slices demonstrate the varying levels of basal ganglia involvement. Arrows indicate increased signal in the right basal ganglia putamen (A), globus pallidus (B), and caudate (C).

diagnosed as conversion disorder until move- Case 2 ments worsened and the correct diagnosis of A white male aged 71 years with a history hyperglycemia-induced hemichorea hemibal- of T2DM, hypertension, and hyperlipid- lismus was confirmed by the pathognomonic emia was admitted due to increased jerky neuroimaging findings. movements in the left upper extremity. On admission, his vital signs were within nor- CASE PRESENTATIONS mal limits and his physical examination dem- Case 1 onstrated choreoathetoid movements with A 65-year-old male with a history of un- ballistic components of his left upper extrem- controlled T2DM presented with repetitive ity. His laboratory results showed a glucose

twitching and kicking movements that in- level of 528 mg/dL with a HbA1c of 16.3%. volved his left upper and lower extremities An initial CT obtained in the emergency de- for 3 weeks. The patient reported that he did partment (ED) demonstrated a well-defined not take his medications or follow the rec- hyperdensity in the striatal (caudate and len-

ommended diabetes diet. His HbA1c on ad- tiform nucleus) region (Figure 2). There was mission was 12.2% with a serum glucose of no associated edema/mass effect that would 254 mg/dL. The MRI showed a hyperintense be typical for an intracranial hemorrhage. T1 signal within the right basal ganglia in- An MRI obtained 1 week later showed cluding the right caudate with sparing of the hyperintense TI signal corresponding to the internal capsule (Figure 1). There was no as- basal ganglia (Figure 3). In addition, there sociated mass effect or restricted diffusion. It was a questionable lacunar infarct in the was compatible with a diagnosis of hypergly- right internal capsule. Due to lack of aware- cemia-induced hemichorea-hemiballismus. ness regarding hyperglycemic associated The patient was advised to resume taking basal ganglia changes, the patient’s move- glipizide 10 mg daily, metformin 1,000 mg ment disorder was presumed to be ischemic by mouth twice daily, and to begin 10 units in etiology. The patient was prescribed oral of 70/30 insulin aspart 15 minutes before 100 mg 3 times daily for the meals twice daily, and to follow a low car- hemiballismus in conjunction with treat- bohydrate diet, with reduce dietary intake ment of his T2DM. The only follow-up oc- of sugar. At his 1-month follow-up visit, the curred 5 weeks later, which showed no patient reported an improvement in his in- improvement of uncontrollable movements. voluntary movements. At the 5-month Imaging at that time (not available) indi-

follow-up, the patient’s HbA1c level was cated the persistence of the abnormal signal 10.4% and his hyperkinetic movements had in the right basal ganglia. This patient died completely resolved. later that year without further follow-up.

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FIGURE 2 Noncontrast Axial Computed FIGURE 3 Noncontrast Axial T1-Weighted Tomography Image of Case 2 Head Magnetic Resonance Image of Case 2 Head

Arrow shows a well-defined region of increased Arrow shows a well-defined region of increased signal in the attenuation in the right basal ganglia (putamen, right basal ganglia. globus pallidus, and caudate head).

Case 3 ceding the onset of his symptoms. A 78-year-old white male with a history of On admission a MRI showed a uni- syncope, transient ischemic attacks (TIAs), lateral right-sided T1 hyperintensity and poorly controlled T2DM presented with in the basal ganglia, no acute a 1-month history of progressively worsen- (Figure 4). In retrospect, subtle increased ing involuntary, left-sided movements that T1 signal can be seen on the earlier MRI began in his left shoulder and advanced to in- (Figure 5). In view of the patient’s left-sided volve his arm, hand, and leg, and the left side symptoms, DM, and MRI findings, a diag- of his face with grimacing and clucking of his nosis of hyperglycemia-induced hemicho- tongue. Three weeks earlier, the patient had rea-hemiballismus was made as the etiology been discharged from the ED with a diag- of the patient’s symptoms. nosis of conversion disorder particularly be- The patient was prescribed numerous cause he experienced decreased movements medications to control his hyperkinesia in- when given a dose of Vitamin D. It was over- cluding (and in combination): benztropine, looked that administration of , , diphenhydramine, had occurred a few hours before, and because , risperidone, , the sounds made by his tongue were not felt and valproic acid, which did not control his to be consistent with a known movement movements. Ultimately, his hyperglycemic disorder. A MRI of the brain was read as hemiballismus improved with tight glycemic normal. control and oral 12.5 mg twice The patient returned 3 weeks later (the daily. This patient underwent a protracted original presentation) due to his inability to course of treatment with 17 days of inpatient perform activities of daily living because of medical admission, 3 weeks inpatient reha- his worsening involuntary movements. On bilitation, and subsequent transfer to an as-

admission, his HbA1c was 11.1% and his glu- sisted living facility. cose was 167 mg/dL. On chart review, it was

revealed that the patient’s HbA1c had been DISCUSSION > 9% for the past 3 years with an increase The 3 cases presented in this report con- from 10.1% to 11.1% in the 3 months pre- tribute to the evidence that severe

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FIGURE 4 Noncontrast T1-Weighted Magnetic Resonance Image of Case 3 Head A B

A, axial image, arrow shows a well-defined region of increased signal in the right basal ganglia. B, sagittal image, arrow shows increased signal in the right basal ganglia.

FIGURE 5 Noncontrast Axial and Sagittal T1-Weighted Magnetic Resonance Imaging of Case 3 Head A B

Arrows show the subtle increased signal in the right basal ganglia can be seen about 1 month earlier in both axial (A) and sagittal (B) images.

12,13 persistent hyperglycemia can result in move- setting of elevated HbA1c, as in Case 3. ment disorders that mimic those seen after Notably, all 3 cases in this series had marked

basal ganglia strokes. As with Case 2, past elevation in their HbA1c levels, which sug- literature describes many cases of acute hy- gests that a more chronic hyperglycemic perglycemic episodes with glucose ranging state or multiple shorter periods of hypergly- from 500 to 1,000 mg/mL presenting with cemia may be necessary to produce the de- hemiballismus.1,3 However, there are many scribed hyperkinetic movements. cases that describe hemiballismus occurring Case reports describe the pathognomonic after glycemic correction, persisting despite T1 hyperintensity of the basal ganglia that glycemic correction, and presenting without is identified in all 3 cases presented here. an acute hyperglycemic episode, but in the While the exact etiology remains unclear, the

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hyperintensity is hypothesized to be related in deteriorating symptoms, prolonged hospi- to metabolic derangements caused by hy- tal stays, and unnecessary health care costs. perviscosity of the blood in the small end arteries feeding the basal ganglia.3,11 These CONCLUSIONS abnormalities in turn interrupt the signal- While hemiballismus due to severe persis- ing cascade with abnormal firing rates or fir- tent hyperglycemia is rare, the goal of this ing patterns, leading to reduced inhibition report is to highlight its occurrence in pa- of the motor and ultimately pres- tients with T2DM. Further research can help ent as hemiballismus.1,3,7 While most cases develop a standardized, effective treatment presented with unilateral hyperkinesis and strategy for these patients. Currently, lower- associated contralateral basal ganglia abnor- ing and maintaining appropriate glucose and

malities, there are reports of both unilateral HbA1c levels is the most effective treatment and bilateral movements associated with bi- approach. Potential areas of research include lateral basal ganglia hyperintensities on im- alternative medical and surgical treatment in- aging.9 The predilection for unilateral brain terventions for patients while glycemic con- lesions may be explained by the varying de- trol is being achieved or for those who fail to gree of small vessel disease in different areas benefit from glycemic control alone. Some of the brain leading to perfusion deficits success has been demonstrated with the worsened by hyper viscosity. Further research use of antidopaminergic medications such into this is required to elucidate the exact as atypical and tetrabenazine pathophysiologic mechanism. and these medications should be considered The course of disease for patients ranges when tight, sustained glycemic control alone from resolution within hours of tight gly- is not successful in treating this disorder in cemic control to persistent movements for the acute stages. Hopefully, with increasing > 3 months with a gradual improvement in awareness and recognition of hemiballismus severity.12,13 Treatments center on the im- related to hyperglycemia, more large-scale portance of tight glycemic control to pro- clinical trials can be conducted that will re- tect against the protracted course described sult in an effective treatment strategy for this in Case 3. Swift recognition of this rare devastating disorder. condition is critical because improved gly- cemic control decreases the severity and Acknowledgments We thank Mahlon DeLong, MD, for his comments on the duration of this disease. The significant manuscript. disability associated with Case 3 highlights the need for prompt recognition and early, Author disclosures The authors report no actual or potential conflicts of interest aggressive glycemic management to pre- with regard to this article. vent the progression of hemiballismus. In addition to glycemic control, various CNS Disclaimer medications such as typical and atypical The opinions expressed herein are those of the authors and do antipsychotics and tetrabenazine are first- not necessarily reflect those of Federal Practitioner, Frontline Medical Communications Inc., the US Government, or any line therapy with chemodenervation and of its agencies. This article may discuss unlabeled or inves- surgical lesioning in cases unresponsive to tigational use of certain drugs. Please review the complete prescribing information for specific drugs or drug combina- medication therapy. tions—including indications, contraindications, warnings, and When unrecognized, hyperglycemic hemi- adverse effects—before administering pharmacologic therapy ballismus is associated with significant mor- to patients. bidity and mortality. The patients presented References in this report were subject to either delayed 1. Hawley JS, Weiner WJ. Hemiballismus: current con- diagnosis or misdiagnosis as stroke or psy- cepts and review. Relat Disord. 2012;18(2):125‐129. doi:10.1016/j.parkreldis.2011.08.015 chiatric disorder. The rarity of the disorder, 2. Gasca-Salas C, Lang AE. Paroxysmal Hemiballism/ lack of evidence delineating pathogenesis and Hemichorea Resulting from Transient Ischemic At- causality, low level of awareness, and vary- tacks. Mov Disord Clin Pract. 2015;3(3):303‐305. doi:10.1002/mdc3.12268 ing presentations of patients all contribute to 3. Garcia-Grimshaw MA, Jimenez-Ruiz A, Ornelas-Velazquez the challenge of recognizing, diagnosing, and A, Luna-Armenta A, Gutierrez-Manjarrez FA. New-onset diabetes presenting as monoballism secondary to a treating hemiballismus due to hyperglyce- mixed hyperglycemic crisis. Cureus. 2018;10(6):e2882. mia. This challenge can subsequently result doi:10.7759/cureus.2882

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