Management of hemichorea hemiballismus syndrome in an acute palliative care setting.

Hemichorea hemiballismus (HCHB) is a rare and debilitating presentation of hyperglycemia and subcortical stroke. Early identification, proper assessment and management of HCHB can lead to complete symptom relief. We describe a case of HCHB presenting to a palliative care setting. A 63-year-old diabetic and hypertensive lady, with history of ovarian cancer presented to Palliative Medicine outpatient clinic with two days history of right HCHB. Blood investigations and brain imaging showed high blood sugar levels and lacunar subcortical stroke. Blood sugar levels were controlled with human insulin and Aspirin. Clopidogrel and Atorvastatin were prescribed for the management of lacunar stroke. HCHB reduced markedly post-treatment, leading to significant reduction in morbidity and improvement in quality of life. The symptoms completely resolved within one week of starting the treatment and the patient was kept on regular home and outpatient follow up for further monitoring. Acute palliative care (APC) approach deals with the management of comorbidities and their complications along with supportive care. Prompt assessment and management of such complications lead to better patient outcomes.

INTRODUCTION

Hemiballismus is characterized by high amplitude, violent, flinging and flailing movements confined to one side of body and hemichorea is characterized by involuntary random-appearing irregular movements that are rapid and non-patterned confined to one side of body. The common causes of hemichorea hemiballismus syndrome (HCHB) are hemorrhagic or ischemic stroke, neoplasm, systemic lupus erythematosus, hyperglycemic hyperosmolar non-ketotic (HHNK) state, Wilson's disease, and thyrotoxicosis.[1] Cases described in the literature are mostly in elderly, females and people of Asian descent, which may imply a causal genetic predisposition.[2] Female predilection is suggested to be related to postmenopausal estrogen-induced alterations of gamma aminobutyric acid (GABA) or dopamine receptors.[3] HCHB is commonly described in patients with HHNK due to longstanding uncontrolled diabetes. These cases illustrate the need to be aware of hyperglycemia as a cause of hemichorea.

Hyperglycemia alters cerebral auto regulation, causing decreased perfusion, activation of anaerobic metabolism and depletion of GABA, which is a major inhibitory neurotransmitter in the basal ganglia.[45] In HHNK, rapid depletion of GABA and acetate causes decrease in acetylcholine synthesis.[56] Hyperglycemia causes hyper viscosity, which leads to damage to the blood brain barrier leading to temporary ischemia of susceptible striatal neurons.[6] Hemichorea occurs due to the synergistic effects of uncontrolled hyperglycemia and vascular insufficiency that causes transient dysfunction of the striatum.[7] Histopathologically, patients with hemichorea show selective neuronal loss, gliosis and reactive astrocytes, without evidence of hemorrhage or infarction at the striatal areas.[7]

APC model of palliative care includes management of symptoms with appropriate clinically indicated interventions, which decreases mortality, ICU admissions, achieves better symptom control, and family and patient satisfaction.[8] APC deals with managing comorbidities along with the supportive care. Uncontrolled blood sugars and vascular events are not uncommon and it is pertinent that palliative care physicians are able to identify and manage these complications.

We report a unique case of HCHB syndrome secondary to hyperglycemia and stroke presenting in an acute palliative care setting.

CASE REPORT

A 63-year-old lady, a known diabetic and hypertensive on treatment for the past 10 years, with the history of adenocarcinoma of ovary post-disease modifying treatment, was referred to the Department of Palliative Medicine for best supportive care. She was seen at home by our home care team with history of continuous non-rhythmic involuntary movements in the right arm and leg that was present for one day. The patient reported that the involuntary movement initially started in her right leg then progressed to also involve the right arm, increasing to an extent that it prevented her from performing her routine activities of daily living [Figure 1]. However, these involuntary movements resolved during sleep. There was no history of anxiety, depression, psychotic symptoms such as hallucinations, delusions or any other previously diagnosed psychiatric disorder. There was no history of use of any psychotropic drugs or substance. However, no formal psychiatric assessment was done for the patient. There was no history of any preceding trauma or stroke. She was on tablet Dicyclomine hydrochloride 20 mg + Paracetamol 500 mg thrice a day, tablet Pantoprazole 40 mg once a day, tablet Atenolol 25 mg twice a day, tablet Glimepiride 1 mg once a day and tablet Metformin 500 mg twice day. A spot blood glucose analysis was 391 mg/dl. She was advised to meet the local family physician for control of blood sugar and report to the Palliative Medicine outpatient clinic the next day. She was administered insulin by the family physician and blood sugar was normalized but the involuntary movements persisted.

Figure 1

Clinical image sequence demonstrating involuntary movements in the right upper and lower limb

Initial Assessment

During Palliative Medicine OPD visit the following day, she had significant upper and lower extremity involuntary flailing, irregular and non-patterned movements on right half of body impairing her gait. Higher mental functions and cranial nerve examinations were unremarkable. Motor examination showed increased tone in right upper and lower limb with demonstrable cogwheel rigidity in right wrist. No sensory deficits were noted. However, non-purposeful, jerky, rhythmic, involuntary movements were noted in right upper and lower limb. All deep tendon reflexes and plantar reflex were normal. Meningeal and cerebellar signs were absent. General examination and other system examinations were unremarkable. Review of ongoing medications was not suggestive of any possible drug-induced involuntary movements.

Initial laboratory workup [Table 1] revealed no metabolic abnormalities. Her clinical condition was initially ascribed to hyperglycemia, stroke, intracranial metastasis, etc., Magnetic resonance imaging of the brain was performed; T1-weighted image showed a significant area of hyper-intensity involving the left lentiform nucleus and small-scattered areas of hyper-intensity bilaterally [Figure 2].

Table 1

Link to the video of this case

Figure 2

MRI Brain T1 weighed images (sagittal): Area of hyper-intensity noted at the left lentiform nucleus (red arrow)

Management and follow up

Adequate blood sugar control was attained with long-acting human insulin along with strict blood sugar monitoring. Lacunar stroke was managed with Aspirin and Clopidogrel (loading and maintenance doses) and Atorvastatin. Small dose of Clonazepam was initiated to control involuntary movements. After two days, the involuntary movements significantly reduced and she was able to perform activities of daily living. At the end of one week, she had complete resolution of the involuntary movements of her extremities, had well-controlled blood sugar levels. The clinical improvement of her condition was possible due to prompt and adequate management of hyperglycemia and lacunar stroke. At present, she is at home and attending palliative care outpatient clinic on a regular interval.

DISCUSSION

We describe a case of HCHB syndrome as a complication of hyperglycemia and subcortical lacunar stroke in a patient of advanced ovarian cancer. Common differential diagnoses of this case are neoplastic disorders (metastases to brain), ischemic or hemorrhagic stroke, trauma, drug toxicity (dopamine agonist or phenytoin) and Huntington's disease. Our patient had no other clinical manifestations or family history to suggest Huntington's disease, no recent traumatic head injuries and was not on any anti-psychotic or anti-seizure medications. The specific laboratory and imaging reports suggested hyperglycemia and subcortical lacunar stroke as cause of HCHB.

Most patients with HCHB syndrome can be managed medically. HCHB occurs due to severe hyperglycemia and symptomatic improvement occurs with restoration of blood sugar levels.[9] HCHB is resolves partially or completely with control of raised blood sugar levels but radiological resolution takes 6 months after control of hyperglycemia.[10] Case reports in the literature suggest that hyperkinesias resolve considerably with control of hyperglycemia, which suggests that HCHB related to hyperglycemia is reversible and has good prognosis.[11] There are case reports that the HCHB can occur a few weeks after normalization of blood sugar levels which suggests a late response to rise in blood sugar levels.[12]

Post-stroke HCHB is uncommon. It may occur due to lacunar infarcts affecting fronto-temporo-parietal cortex and subcortical white matter. There is no evidence of one specific area involvement causing HCHB. Pure hemiballismus can be associated with isolated subthalamic lesions.[13] In a study on post-stroke HCHB, it was found to be associated with lesions in caudate, putamen, subthalamus, globus pallidus and cerebral cortex, and the proposed theories were involvement of cortical-basal ganglia pathways along with presence of small infarct in basal ganglia.[14]

MRI in patients with HCHB in HHNK shows T1-weighted hyperintensities in striatum and globus pallidus, with restricted diffusion on diffusion-weighted imaging.[15] An abnormal signal may extend into the globus pallidus and up to the medial part of the cerebral peduncle in the midbrain along the striatonigral pathway.[16] Magnetic resonance spectroscopy shows low N-acetyl aspartate to creatinine ratio and high choline-to-creatinine ratio and associated lactate peak.[17] Positron emission tomography has shown reduced glucose metabolism in the basal ganglia.

We have presented this case as an uncommon complication of comorbid conditions in an acute palliative medicine setting and managed appropriately with complete resolution of symptoms. This suggests that scope of palliative medicine not only includes supportive management for the primary life-limiting condition but also early identification and management of the comorbidities and related complications. Hence, awareness about such conditions and complications is essential among the palliative medicine physicians for a comprehensive patient management.

CONCLUSIONS

Although hemichorea is rarely caused by a dysfunction of glucose metabolism, we advise simple investigations like checking blood glucose whenever patients with these symptoms

Early identification and prompt intervention improves both mortality and morbidity associated with these complications

Impeccable assessment and management of readily reversible complications is an essential component of acute palliative care services.