Hemichorea-Hemiballism as a Delayed Manifestation of Hyperglycemia: A Case Report

Abstract

Hemichorea is characterized by involuntary, continuous, non-patterned movements on one side of the body. While it is most commonly caused by strokes, it can also be caused by metabolic derangements such as hyperglycemia. We present two patients who developed hemichorea in the setting of hyperglycemia. Our first patient had a history of uncontrolled diabetes mellitus and developed chorea 2 weeks following a hyperglycemic event. The second patient developed chorea while being on steroids for hip pain and was later diagnosed to have underlying diabetes mellitus. MRI showed hyperintensity in the contralateral lentiform nucleus in both cases. The chorea did not improve despite the correction of the hyperglycemia. Both patients were started on Tetrabenazine with significant improvement. Hyperglycemia-induced hemichorea might be underdiagnosed given the prevalence of diabetes mellitus in the population. Chorea can even be the presenting symptom of diabetes mellitus and in some cases is a delayed manifestation of hyperglycemia.

Introduction

Hemichorea is characterized by involuntary, continuous, non-patterned movements on one side of the body. It is most commonly caused by strokes, metabolic abnormalities such as hyperglycemia, infections, or focal inflammatory lesions. ¹ Predisposing factors for hyperglycemia-related hemichorea include advanced age, female gender, uncontrolled diabetes, and Asian descent. ² The prevalence of hyperglycemia-related chorea has been estimated to be about one in 100 000 but it is thought that this might be an underestimation because of a lack of awareness or misdiagnosis.^3,4 There have also been reports of hemichorea being the first manifestation of diabetes mellitus. ⁵ In some cases, the chorea manifested a few weeks after the hyperglycemia was treated, suggesting a delayed reaction to the hyperglycemia. ⁶ Hyperdensity and hyperintensity on CT scan and MRI respectively are typically seen in the contralateral striatum and contribute to the diagnosis. Here we present two patients who developed hemichorea in the setting of hyperglycemia. The first patient developed chorea as a delayed reaction to the hyperglycemia. The second patient developed chorea while taking steroids for hip pain but then was diagnosed to have underlying diabetes mellitus. Both patients had persistent chorea despite improvement in blood glucose but demonstrated significant improvement with Tetrabenazine.

Case Series

Case 1

The patient was a 68-year-old woman with a history of hypertension and uncontrolled diabetes mellitus (last HbA1c of 14%) who presented to the Emergency Department in early March 2021 with complaints of nausea and vomiting for a day. She denied any abdominal pain or any other symptoms at that time. Her vitals were normal. Her blood glucose was 431 mg/dL, sodium was 126 mEq/L, creatinine 1.5 mg/dL, anion gap was 7, calculated serum osmolality was 282 mOsm/kg and alkaline phosphatase was 148 U/L. Her WBC was 13.3 k/cmm, urine ketones were absent and urine glucose was >500 mg/dL. The rest of the complete metabolic panel and CBC were normal. She underwent a CT abdomen with contrast which showed cholelithiasis and her CT chest with contrast was normal. She was treated with IV fluids and was discharged home. She returned two weeks later with complaints of involuntary movements of the right upper and lower extremity. The movements had gradually worsened to become more violent over the past day. She denied any urge or suppressibility. On the physical examination, she was noted to have continuous choreiform movements of the right arm and leg. These movements worsened with distraction. There was no evidence of bradykinesia and her tone was normal. The rest of her neurological exam was within normal limits. Her repeat blood glucose was 167 mg/dL with a WBC of 14.6 k/cmm. The rest of the labs were normal. CT head showed hyperdensity in the left basal ganglia. MRI brain with and without contrast showed a hyperintense T1 signal in the left lentiform nucleus with slight enhancement (Figure 1). She was asked to monitor her blood glucose closely and ensure it was well controlled.

Figure 1:

MRI T1-weighted images show hyperintensity in the left lentiform nucleus and slight enhancement on post-contrast images.

She returned after a month with complaints that the movements were significantly impacting her life and affecting her balance. CT head was repeated and was unchanged. She was admitted to the inpatient service and Tetrabenazine was started in the hospital at a dose of 12.5 mg twice daily and titrated to 12.5 mg thrice daily. She had a remarkable improvement in her movements within 3 days (VIDEO 1).

Case 2

The patient was an 83-year-old right-handed man with a history of hypertension and hyperlipidemia, who presented for his 6-monthly follow-up for his essential tremor with complaints of new-onset involuntary movements of his right arm and right leg. He had received cortisone shots to his hip as well as oral steroids for his hip pain. After a few weeks of oral steroid therapy, he developed involuntary movements of the right side which resulted in falls. He went to an outside hospital where his blood glucose was reportedly in the 700s mg/dL. He was admitted for 2 weeks with subsequent improvement in glucose control. He was also diagnosed to have underlying diabetes mellitus (HbA1c was 8.6%). In the clinic, he was noted to have choreiform movements of the right arm and leg (VIDEO 2). He needed to use a walker because the chorea made him unsteady. The choreiform movements worsened with distraction. He did not exhibit any bradykinesia and his tone was normal. He had a mild postural tremor in his hands due to his underlying essential tremor. The rest of the neurological exam was normal. He was started on Tetrabenazine 12.5 mg thrice daily. MRI brain with and without contrast was ordered which showed hyperintense T1 signal in the left lentiform and caudate nuclei. On subsequent follow-up, his brother noted that his chorea was improved as long as he remained compliant with the regimen.

Discussion:

Hyperglycemia-induced hemichorea was first described by Bedwell in 1960. It has been described more commonly in Asian women but there have been more reports in the Western population as well recently.^2,7 Despite this growing body of evidence, a retrospective study performed at the Mayo Clinic in Minnesota, USA showed that patients were still misdiagnosed. ⁴ The estimated prevalence is about 1 in 100 000. The ratio of females:males is 1.8:1 and the incidence increases with age. In most cases, it occurs in patients with a long-standing history of poorly controlled diabetes. In a recent study, it was shown that one-sixth of cases with hyperglycemia-induced hemichorea had newly diagnosed diabetes suggesting that chorea might also be the first manifestation of diabetes mellitus. ⁷ It can also manifest weeks after the hyperglycemic event which can result in the cause being missed. ⁶ Our first patient developed chorea in the setting of uncontrolled diabetes mellitus. In this patient, the chorea was a delayed manifestation of hyperglycemia. The second patient had underlying diabetes and his hyperglycemia was exacerbated by the steroids he was taking for his hip pain. Both patients showed characteristic findings on brain imaging. Both patients were treated with Tetrabenazine with significant improvement in their symptoms.

It has been hypothesized that hyperglycemia impairs the cerebral autoregulatory mechanisms of the central nervous system. This can result in hypoperfusion and activation of anaerobic metabolism. ⁸ Gamma-aminobutyric acid (GABA) and acetate are alternative sources of energy in anaerobic states which results in depletion of GABA and acetylcholine and subsequently hyperkinetic movements. ⁸ Hyperviscosity, induced by hyperglycemia, resulting in ischemia of vulnerable striatal neurons has also been presented as a likely cause.

The chorea is mostly unilateral but can be bilateral in 10% of cases. The onset can vary from insidious to abrupt while it could be mild to severe in intensity. The chorea, similar to most movement disorders, will worsen with stress and excitement and will disappear in sleep. The chorea can substantially affect the patient’s ability to carry out their daily activities and might also increase the risk of falls.

The classical imaging findings reported are hyperdensity in the contralateral basal ganglia on CT scan and corresponding hyperintensity on MRI T1-weighted images. T2-weighted images may show variable signal characteristics ranging from hypointense to hyperintense. The most common patterns of striatal anomalies are isolated putamen involvement, followed by combined caudate nucleus-putamen involvement and the globus pallidus in a minority of cases. ⁹ Lesions are unilateral in the vast majority of cases, but bilateral involvement has been reported even in patients who have not yet manifested symptoms. Interestingly, lesions in the ipsilateral basal ganglia have also been reported. The lesions may persist for months to 6 years after onset. Advanced imaging techniques such as MR Spectroscopy showed a low N-acetylaspartate to creatine ratio, high choline to creatine ratio, and lactate peak. These findings indicated neuronal damage, gliosis, and acute or chronic ischemic changes, respectively. ¹⁰ SPECT studies have shown a significant reduction in blood flow in the basal ganglia contralateral to the hemichorea. ¹¹ PET scans have shown a reduction in glucose metabolism in the contralateral basal ganglia. ¹² The above findings indicate that the changes observed are possibly a consequence of a metabolic derangement rather than a pure vascular pathology.

Adequate control of blood glucose is the mainstay of management. In many cases, the chorea resolves over weeks and might be associated with a resolution of the imaging findings. In some cases, like our patients, the hemichorea might persist despite the improvement of hyperglycemia. Persistent chorea can be treated with neuroleptics, benzodiazepines, or vesicular monoamine transporter type 2 (VMAT2) inhibitors as demonstrated in our case. There have also been some reports documenting the effectiveness of pallidotomy, ventrolateral thalamotomy, transcranial magnetic stimulation, and globus pallidus internus deep brain stimulation for persistent chorea. ⁷ The symptoms might recur due to discontinuation of anti-chorea medications or recurrent hyperglycemia. ⁷

In conclusion, hemichorea-hemiballism is a potential complication of hyperglycemia. It is important to be cognizant that the hyperglycemia may have improved by the time the patient seeks medical attention for the hemichorea. Hemichorea is an uncommon manifestation of hyperglycemia but is typically associated with a good prognosis when appropriately treated.

Supplemental Material

Video 1. Case 1 demonstrating chorea before and after treatment

Video 2. Case 2 demonstrating chorea before and after treatment

ORCID iD

Vikram Shivkumar https://orcid.org/0000-0003-1658-7881