Keywords

Chorea, hemichorea-hemiballismus, hyperglycemia

Introduction

Chorea is characterized by irregular, purposeless, unpredictable, brief and jerky involuntary, movements, while ballismus is marked by large amplitude flinging, incessant movements that occur on one side of body.1 Hemichorea-hemiballismus (HC-HB) is a rare complication of nonketotic hyperglycemia (NKH) and only 53 case reports of this particular condition were published between 1985 and 2001.2 Most of the cases were over 60 years of age and represented type 2 diabetes and NKH.

Hemi-ballismus associated with NKH was first noted by Bedwell in 1960. These patients are usually older females and this suggested that increased dopaminergic activity in postmenopausal period can cause hyperkinetic movement disorder.3 The underlying pathophysiology leading to basal ganglia dysfunction is multifactorial.

Diabetic HC-HB can be caused by wide variety of degenerative, metabolic or vascular lesions affecting the basal ganglia. These include metabolic diseases like Wilson’s disease, thyrotoxicosis, ischemic or hemorrhagic stroke, infections, drugs, toxins, epilepsy and neoplasms as well as systemic process including systemic lupus erythematosus and Sydenham’s chorea.1 Here, we present a case with diabetes manifesting as hyperglycemia-induced involuntary movements.

Case Report

An 82-year-old female was brought to the medical OPD with a history of sudden onset of paroxysm of involuntary movements, initially involving the right hand followed by left leg and subsequently entire left side of the body, increasing during activity and decreasing during sleep, of 5-7 days duration. There was no history of fever, headache and/or any neurological illness. She did not receive any medication. The patient was nonsmoker and nonalcoholic. Clinical examination revealed normal memory and normal physical examination. Blood pressure was 110/70 mmHg. An initial clinical diagnosis of HC-HB was made.

The clinical symptom of spontaneous hemichorea was considered secondary to a poststreptococcal neurological disease (Sydenham’s chorea) but it was not associated with other clinical features of rheumatic fever (carditis, arthritis, erythema, rheumatic nodule and neuropsychological features (dysarthria and emotional disorder). Also, the choreiform movements are rather more continuous in Sydenham’s chorea than paroxysmal as observed in the present case. Serumantistreptolysin ‘O’ titer was <200 IU. The possibility of continuous focal seizure (epilepsia partialis continua) causing unilateral movement and involvement of the central nervous system (the contralateral basal ganglion, the thalamus and subcortical areas) was also considered and so, electroencephalography (EEG) and CT were scheduled.

Ischemic and hemorrhagic strokes are a common cause of chorea in most elderly patients and these etiologies were excluded in our patient based on the neuroimaging studies. Other differential diagnoses (systemic lupus erythematosus, Wilson’s disease, thyroid disease, basal ganglia, calcification) were also ruled out. Antinuclear antibodies were negative and serum ceruloplasmin and thyroxin levels were within normal range. Kayser- Fleischer ring was absent on a slit lamp examination. CT contrast head revealed a hyperdense enhancing area in left lentiform nucleus, suggestive of probable extrapyramidal neurodegenerative disorder (Fig. 1). EEG was normal even during the ictal recording excluding the possibility of epilepsy. Table 1 describes the laboratory investigations undertaken. Her lipid profile was abnormal. A diagnosis of diabetes was made and patient was started on rapid analog insulin 10 units IV stat after 50 units in drip infusion. At the end of 24 hours, blood sugar was 165 mg/dL and involuntary movements had completely abolished. The patient remained asymptomatic during her hospital stay and was discharged home on a combination of insulin 30:70 subcutaneously. Insulin C-peptide levels within normal limit excluded type 1 diabetes mellitus. So, a diagnosis of type 2 diabetes mellitus was made.

Discussion

Hyperglycemia-induced HC-HB is an uncommon movement disorder probably related to vascular insult of the basal ganglia in patients with poorly-controlled diabetes. When these movements are confined to one side of the body i.e., HC-HB, lesions in the contralateral subthalamic nucleus and pallidosubthalamic pathways are usually present.1,2 Recognition of the association of these neurological abnormalities and NKH is important because the correction of underlying hyperglycemia will lead to rapid improvement. Many hypotheses have been proposed for the development of NKH-induced HC-HB, such as loss of γ-aminobutyric acid (GABA) activity, disinhibition of dopaminergic neurons, local vascular insult and brain edema,4 but all are poorly understood. In ketoacidosis, ketones are used as energy source and GABA can be produced. As a result, HC-HB and partial seizure activity rarely occurs but in NKH, brain metabolizes GABA into succinic acid via the succinic acid semialdehyde pathway thus rapidly decreasing GABA.5 During NKH, the activity of Kreb’s cycle and glucose utilization are decreased in the brain, so cerebral metabolism shifts to anaerobic metabolism, which causes the brain to utilize GABA synthesized from acetoacetate, which is thus rapidly depleted causing cellular dysfunction.3 Recent imaging analysis revealed reduced cerebral glucose metabolism on positron emission tomography (PET) scans with concomitant hyperperfusion in affected basal ganglia seen on single photon emission computed tomography (SPECT).5 In some cases, as also in our case, the basal ganglia in diabetic HC-HB were hyperdense without mass effect on CT scans and hyperintense on T1- weighted magnetic resonance imaging (MRI), but these imaging features completely reverse after therapy.2 This evidence supports the idea that basal ganglia, generally weak in hyperglycemia stress, might induce involuntary movements and neurotransmitting functional disorder. Chorea should be considered potentially reversiblewhen associated with NKH as rapid detection and early correction of hyperglycemia could lead to complete recovery of these involuntary movements in some cases.3 The prognosis of HC-HB as a complication of NKH is excellent.

Conclusion

NKH is an unusual cause of chorea ballismus. HC-HB is a rare manifestation of primary diabetes. So, HC-HB in our case may be due to long-standing hyperglycemic stress leading to neurodegenerative changes in basal ganglia causing striatum dysfunction. On reviewing the literature,6 and in our case, after insulin therapy for 12-48 hours, all the involuntary movements had been almost abolished after removal of hyperglycemia stress. So, every patient who presents with abnormal body movements should be screened for diabetes.

References

1. Block H, Scozzafava J, Ahmed SN, et al. Uncontrollable movements in patient with diabetes mellitus. CMAJ 2006;175(8):871.
2. Oh SH, Lee KY, Im JH, et al. Chorea associated with nonketotic hyperglycemia and hyperintensity basal ganglia lesion on T1-weighted brain MRI study: a meta-analysisof 53 cases including four present cases. J Neurol Sci 2002;200(1-2):57-62.
3. Lin JJ, Chang MK. Hemiballismus-hemichorea and nonketotic hyperglycaemia. J Neurol Neurosurg Psychiatry 1994;57(6):748-50.
4. Higa M, Kaneko Y, Inokuchi T. Two cases of hyperglycemic chorea in diabetic patients. Diabet Med 2004;21(2):196-8.
5. Hsu JL, Wang HC, Hsu WC. Hyperglycemia-induced unilateral basal ganglion lesion with and without hemichorea. A PET study. J Neurol 2004;251(12):1486-90.
6. Hamide A, Kumarsamy R, Srimannarayana J, et al. Chorea due to nonketotic hyperglycemia. Neurol India 2002;50(2):213-4.