Chorea Hyperglycemia Basal Ganglia (CHBG) Syndrome: A Case Report

Abstract

Chorea, characterized by sudden, involuntary movements of the face and limbs, arises from various causes, including neurodegenerative diseases, metabolic disorders, and structural brain changes, notably in the basal ganglia. Acute lesions in the basal ganglia due to ischemia or vascular pathology can also precipitate chorea. Hyperglycemia-induced basal ganglia changes, termed chorea hyperglycemia basal ganglia, predominantly affect elderly females with type 2 diabetes. We report a 62-year-old female with poorly managed diabetes presenting with involuntary jerking movements, initially in the right leg, progressing to the right arm, face, and lips over three days. Her history included hyperlipidemia and hypertension, and lab results showed significant hyperglycemia (601 mg/dL) [fasting <140 mg/dl], hyponatremia, renal impairment, and a high Hemoglobin A1C (HbA1c) (10.4) [<6 %]. Imaging revealed left putamen hypodensity on Computed Tomography (CT) and confirmed microhemorrhage on magnetic resonance imaging (MRI). Diagnosed with Hyperosmolar Hyperglycemic State (HHS) and hemichorea, she was treated with intravenous (IV) insulin and fluids, leading to symptom resolution within two days. This case highlights the link between non-ketotic hyperglycemia and chorea, involving hyperviscosity-induced GABAergic neuron dysfunction in the putamen. Diagnosis relies on choreiform movements, elevated blood glucose, and striatal hyperintensity on T1 MRI. Effective management includes treating underlying HHS with hydration and glycemic control, occasionally supplemented with anti-chorea medications. Recognizing diabetic striatopathy is crucial for prompt treatment and symptom resolution, emphasizing the need for early diagnosis and intervention in patients with uncontrolled diabetes presenting with new-onset chorea.

1. Introduction

Chorea, a neurologic disorder, is a movement dysfunction that causes sudden, arrhythmic, involuntary movements involving the face and limbs. The etiology of chorea consists of various neurodegenerative diseases, autoimmune conditions, metabolic derangements, and structural changes within distinct regions of the brain.1 The basal ganglia, specifically the striatum, appears to be the structure most commonly indicated by choreiform movement dysfunctions.2 Other sites of injury within the basal ganglia that are often involved are the putamen and subthalamic nucleus.5 The most common cause of chorea is due to genetic disorders such as Huntington’s, Wilson’s, and benign hereditary chorea, with prevalences of 0.01 %, 0.003 %, and 0.0002 % respectively.3,4

Acute structural lesions to the basal ganglia can be attributed to ischemia and vascular pathology.6 Upon suspicion of chorea, neuroimaging of the basal ganglia typically reveals hyperintensity compared to surrounding gray matter, potentially indicative of various pathological processes such as petechial hemorrhage, myelinolysis, and calcification. 7 There is ongoing discourse regarding non-ketotic hyperglycemia as the sole systemic condition precipitating choreiform movements; this condition is consistent with striatal hyperintensity detected on neuroimaging, a phenomenon designated as chorea hyperglycemia basal ganglia.8 This condition predominantly affects elderly females, particularly within the Asian demographic.13 Hyperglycemic chorea commonly arises amidst inadequate glycemic regulation, such as settings of hyperglycemic hyperosmolar states, and may be overlooked as an infrequent complication of type 2 diabetes.15,22 Studies have shown that choreiform movements can be reversed with proper hyperglycemic control, which emphasizes the importance of early recognition in improving prognosis. Here, we present a case of new onset choreiform movement in an uncontrolled type 2 diabetic patient. A comprehensive review of patient history, presentation, and clinical workup led to the discovery of underlying basal ganglia pathology with diabetic etiology.

2. Case presentation

A 62-year-old female presented to the emergency department (ED) with complaints of involuntary jerking movements. The symptoms initially manifested in her right leg and progressed to involve the right arm, face, and lips over a three-day period. She was alert and oriented and denied chest pain, dyspnea, or any pain. She denied any history of trauma, falls, seizures, or focal neurological deficits. Her medical history included Type 2 diabetes mellitus without any known microvascular complications on presentation like neuropathy, retinopathy or nephropathy, hyperlipidemia, and hypertension. Family history includes Type 2 diabetes mellitus and hypertension. The patient’s diabetes had been inadequately managed despite the implementation of insulin therapy within the last five years. Further, she had undergone gastric banding in 2010 but had it removed. On arrival, her vital signs were Heart Rate: 72 bpm, Respiratory Rate: 16 breaths/min, Blood Pressure: 118/76 mmHg, Temperature: 98.4 °F (36.9 °C), SpO2: 97 %, the initial laboratory investigations were remarkable for hyperglycemia (blood sugar 601 mg/dL (fasting <140 mg/dL), hyponatremia (sodium 119 mmol/L corrected for glucose ~131 mmol/L) [136–146 mmol/L], normal anion gap (12 mEq/L [8–16 mEq/L]), renal impairment (GFR 40 mL/min [90–120 mL/min/1.73 m²]), creatinine 1.46 mg/dL [0.7–1.3 mg/dL], BUN 39 mg/dL [6–24 mg/dL], and HbA1c 10.4 %. While a neurology workup was needed, we suspected a concurrent diagnosis of Hyperosmolar Hyperglycemic State (HHS).

A CT head revealed hypodensity in the left putamen, concerning a microhemorrhage, prompting evaluation with MRI. An MRI confirmed a microhemorrhage in the left putamen, consistent with the diagnosis of hemichorea. Thus, she was diagnosed with HHS and cerebral microhemorrhage. Initial management of her condition included rapid glycemic control with IV insulin with aggressive IV fluid resuscitation, and once sugars were stabilized below 200 mg/dL, she was started on a basalbolus insulin regimen. After euglycemia was achieved, the patient’s hemichorea was clinically resolved. Neurology and neurosurgical consultation supported the diagnosis of HHS-induced hemichorea and recommended conservative management. The patient’s symptoms were completely resolved by day 2 of hospitalization, and she was discharged with outpatient follow-up with neurology and strict continuation of glycemic control measures.

3. Discussion

Hyperosmolar hyperglycemic state (HHS) is a severe manifestation of uncontrolled diabetes mellitus characterized by profound dehydration, hyperosmolality, and altered mental status. Neurological manifestations such as seizures, focal deficits, and movement disorders, including hemichoreahemiballismus, have been reported in the literature, 1,8 but incidence of hemichorea in the context of HHS is not well-documented in large-scale epidemiological studies, but some case series and reviews provide insight into its occurrence. For instance, a study by Misra et al. reported that out of 17 patients with HHS, three presented with hemichoreahemiballismus syndrome, which responded to the correction of hyperosmolarity.9 Another study by Ryan et al. identified seven cases of hyperglycemic chorea/ballism over 15 years at a tertiary medical center, comprising about 1 % of all chorea cases during that period.10 Ryan et al. also found that hyperglycemic chorea primarily developed in later life, with a median age of 80 years among the cases studied. The association between non-ketotic hyperglycemia and chorea was first described in 1960 by Bedwell, but the exact pathophysiological mechanisms underlying hemichorea-hemiballismus in hyperglycemic states remain incompletely understood. 11 One of the leading theories is that severe hyperglycemia in uncontrolled diabetes can lead to a hyper viscosity-induced GABAergic neuron dysfunction in the putamen, resulting in dysregulated movement control.12–14 Putaminal hemorrhage is another known cause of new onset hemichorea.8 Here we present a unique case with a triad of HHS, hemichorea-hemiballismus, and evidence of microhemorrhage of the left putamen on MRI. The Diagnosis of HHS-induced hemichorea-hemiballismus, also known as diabetic striatopathy, 15 is primarily clinical, based on the characteristic choreiform movements in the absence of structural brain lesions, an elevated blood glucose in the setting of uncontrolled diabetes, and striatal hyperintensity on T1 MRI.16 The prevalence of diabetic striatopathy is 1 in 100,000 (0.001 %)17 however, this number may be underestimated due to the rarity of the condition. One meta-analysis found the average serum glucose in patients with diabetic striatopathy to be 414 mg/dL17, consistent with the high value of 601 mg/dL found in our patient. The T1 hyperintensity in the setting of diabetic striatopathy has historically been attributed to calcification,18 petechial hemorrhage,19 myelin destruction,20 and infarction with astrocytosis.18,21 In our case, the CT head showed a hypodensity in the left putamen and a putaminal hyperintensity on T1 MRI favoring microhemorrhage. The exact cause for the hyperdensity on CT and hyperintensity on MRI seen in HHS-induced hemichorea-hemiballismus continues to be an area of discussion and pathological analysis can elucidate further on this topic.

The management of HHS-induced hemichoreahemiballismus mainly consists of hydration and tight glycemic control to correct the underlying metabolic derangements.22 The addition of antichorea medication can also be indicated when strict glycemic control alone does not lead to a resolution of symptoms.17 The most used single anti-chorea agents in the context of HHS-induced hemichoreahemiballismus are haloperidol, tetrabenazine, risperidone, and clonazepam respectively.17 HHS-induced hemichorea-hemiballismus is known to have an excellent prognosis.8,23 Our patient showed complete resolution of her symptoms and returned to her baseline with glycemic control under a sliding scale regimen. Diabetic striatopathy should be considered in the differential diagnosis for a patient with new onset choreiform movements and a history of uncontrolled diabetes. Prompt imaging and strict glycemic control should be the first line of treatment before resorting to antichorea agents.