Hemichorea as initial presentation of newly diagnosed diabetes and acute lacunar stroke

Introduction

Hemichorea is one of the spectra of the choreiform disorder characterized by brief, random, non-purposeful, and often involuntary contractions on one side of the body. This type of abnormal involuntary movement is uncommon, but there are increasing reports of acquired systemic disorders that trigger hemichorea. Unlike generalized chorea, which can be caused by various inherited or acquired causes that affect the basal ganglia, hemichorea usually has a vascular origin or is caused by metabolic disturbances like hyperglycemia. ¹

This case highlighted a patient who presented with hemichorea as the initial presentation of newly diagnosed diabetes mellitus and an incidental finding of an acute lacunar stroke. A condition now referred to in the medical literature as non-ketotic hyperglycemia hemichorea (NHH), also known as diabetic striatopathy or chorea, hyperglycemia, basal ganglia (C-H-BG) syndrome. Extensive literature revealed that there might be overlapping pathophysiology where the synergistic effects of uncontrolled hyperglycemia and vascular insufficiency cause an incomplete transient dysfunction of the striatum, leading to hemichorea in these patients. ² Recognizing this disease entity is pertinent for early diagnosis and prompt treatment while avoiding unnecessary investigations and achieving an excellent clinical outcome.

Case report

A 62 years old Indian female was admitted for the complaint of abnormal right upper limb movement of four days duration. It started with the right arm tingling, pulling, and numbness sensation four weeks ago. Then, four days before her presentation to the hospital, she started having worsening “dancing” movements of her right arm and hand. It could occur with intentional activities and also at rest. She also felt that the grip on her right hand was weaker. She is right-handed; hence this affected her work.

She was not on any regular medication and was not known to have any chronic conditions before this presentation. She denied any alcohol history, use of traditional medicines, and drug abuse in the past. There was no recent trauma or injury to her neck or limbs. Incidentally, she was found to have hyperglycemia in her admission laboratory. On further questioning, she had polydipsia and polyuria for a few weeks. Her appetite was good, and she had gained some weight recently. However, she noticed that she had generalized lethargy for the past weeks. Occasionally, her urine was frothy. Her family history does not include any inherited neurological disorder.

On examination, she was afebrile, with stable vitals of blood pressure 129/70 mmHg and heart rate 80 beats per minute. She had a slightly high body mass index of 26.2. She appeared alert and calm. There were prominent right upper limb chorea-athetoid movements, mainly affecting the distal part of the limb. The power of right arm elbow flexion and extension and right wrist flexion and extension were full, but right-hand finger grip was diminished at 4 out of 5. Left upper limb power and lower limbs power were full. Sensation and proprioception were intact. The deep reflexes were 2 + over bilateral biceps, triceps, supinators, and knees. The plantar reflexes were downgoing bilaterally. Her gait was steady. The cranial nerves were intact, and no fasciculation of the tongue, muscles, or muscle wasting was detected. The cerebellar examination was normal. Other systemic examinations were unremarkable.

At the time of her admission, her glucose level was 27.7 mmol/L, with a normal anion gap and serum ketones level (ketones 0.1 mmol/L). Her glycosylated hemoglobin A1c was 14.2%, and her urine albumin creatinine ratio was below the lower detection limit. Hemoglobin level was 15.1 G/DL, with hematocrit at 45.3%. Computed tomography of the brain showed asymmetrical hyper-density of the left basal ganglia (Figure 1). Subsequently, the Magnetic resonance imaging (MRI) brain showed T1weighted hyperintensity of the left lentiform nucleus (Figure 2), with associated decreased T2weighted signal and mild restricted diffusion. In addition, a small acute infarct was seen in the left centrum semiovale with chronic microvascular ischemic changes (Figure 3).OPEN IN VIEWER

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Figure 2.

Magnetic resonance imaging of the brain showing T1-weighted hyperintensity of the left lentiform nucleus.

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Figure 3.

Magnetic resonance imaging of the brain showing decreased T2-weighted signal and mild restricted diffusion, and a small acute infarct is seen in the left centrum semiovale with chronic microvascular ischemic changes.

The lipid profile showed dyslipidemia with a total cholesterol level of 5.99 mmol/L, triglyceride 2.18 mmol/L, and LDL 3.79 mmol/L. Further tests were sent to rule out possible causes of chorea, even though Wilson’s disease and autoimmune causes were deemed less likely given the lack of concurrent symptoms and signs. Her serum ceruloplasmin and autoimmune screen (anti-nuclear antibody, extractable nuclear antigen antibodies) returned normal. In addition, vitamin B12 and folate levels were replete.

A diagnosis of NHH was made due to newly diagnosed uncontrolled diabetes and acute asymptomatic left centrum semiovale infarction due to small vessel disease. She was initiated on subcutaneous insulin basal-bolus regime (insulin glargine and insulin aspart) and oral glucose-lowering drug (metformin). The treatment was titrated according to inpatient glycemic monitoring. In addition, atorvastatin and aspirin with omeprazole were started for secondary stroke prevention. Her symptoms improved inpatient after her glucose level was controlled. She was subsequently followed up at a specialist outpatient clinic after three months, and her symptoms had resolved during the review. MRI brain was not repeated, given the resolution of her symptoms.

Discussions

The basal ganglia are responsible for regulating movement through direct and indirect pathways. They are involved in a highly complex positive and negative feedback system with the endpoint in the thalamus, and when this structure is uninhibited, they facilitate movements. Hypoxia-ischemia can injure the basal ganglia through hypo-perfusion of subcortical vascular watershed areas and altering the striatal neurotransmitter systems. Understanding this means we can correlate the clinical findings with vascular and radiological areas of involvement.

Hemichorea associated with non-ketotic hyperglycemia was first reported in 1960 by Bedwell SF. ³ The patients usually have longstanding and poorly controlled diabetes and present with unilateral hemichorea combined with striatal abnormalities on neuroimaging. Rapid remission of symptoms typically occurs after treating hyperglycemia. It is less often described as the presenting sign of new-onset diabetes mellitus. The involuntary movements' severity can vary from mild to severe and appear to occur in acute or subacute onset. ⁴ The Asian population has a higher risk, and there is an increased incidence in elderly with an average age of 70 years and female patients.^4,5

Although the exact mechanism of the syndrome is unclear, there are various postulations regarding the pathophysiology of hyperglycemia resulting in hemichorea. Based on a meta-analysis of 53 cases and the literature series, the metabolic disorder due to hyperglycemia plays a prominent role. In the hyperglycaemic stage, the brain tissue obtains energy by anaerobic metabolism, and the tricarboxylic acid (Krebs) cycle becomes inactivated. As a result, the brain tissues obtain alternative energy sources by metabolizing gamma-aminobutyric acid (GABA) to succinic acid. But in contrast to ketosis patients, non-ketosis patients deplete GABA rapidly as it is not resynthesized. This also leads to reduced acetylcholine synthesis by acetate depletion and relatively decreased cholinergic activity compared to dopaminergic activity. The combination of metabolic acidosis, energy depletion, and decreased GABA and acetylcholine levels may cause dysfunction in the basal ganglia, resulting in chorea.^5,6

Another popular theory is the ischaemic or vascular injury mechanism. Although nonspecific, most NHH patients have unilateral hyperdense T1-weighted (T1W) signals in the basal ganglia contralateral to the symptomatic side.^4,5 MRI is the modality of choice for neuroimaging to rule out other causes of hemichorea-hemiballismus, such as stroke, neurodegenerative disorders, neoplasm, etc. In NHH, it characteristically shows T1-weighted hyperintensities in the striatum and globus pallidus, demonstrating variable signal changes in T2-weighted and FLAIR images. But the follow-up MRI studies often show the disappearance of hyperintense basal ganglia lesions.^5,7,8 Broderick et al. d also reported that the hemorrhagic infarction is due to diapedesis of erythrocytes from ischemic capillary endothelium without vessels rupture, which contribute to the hyperintensity changes in MRI in hemichorea hyperglycemic patients. ⁹

Knowing the underlying pathophysiology helps us to understand how these two conditions of diabetes and stroke can coexist and lead to this clinical presentation. Poorly controlled diabetic patients risk decrease in cerebral blood flow and resultant cerebrovascular ischemia. ¹⁰ As this condition recovers rapidly with control of the hyperglycemia, it is pertinent to recognize this disease entity and screen for hyperglycemia, even in patients without prior history of diabetes, when they present with an involuntary movement disorder.

Overall the diagnosis of NHH carries a good prognosis. The general treatment measures include improving control of blood glucose and the use of neuroleptic drugs such as dopamine antagonists and benzodiazepines. This is a very treatable condition with an excellent outcome, as described in the literature and illustrated in our case. Though generally benign, this condition can lead to caudate atrophy and persistent movement disorder if not recognized and appropriately treated. ¹¹ Hence, physicians need to be aware of this condition and consider it in appropriate clinical settings.

Conclusions

Non-ketotic hyperglycemia hemichorea warrants recognition as a potential presentation of uncontrolled diabetes. Though this condition is uncommon, with rising prevalence of diabetes mellitus and atherosclerotic disease, we might encounter more of such unusual presentation as the first sign of unknown diabetes mellitus or after months of poor glycemic control in known diabetic patients. Recognizing this disease entity allows timely neuroimaging and active blood glucose control, thus avoiding misdiagnosis and delay in treatment.