Hyperglycaemic chorea-ballism or unmasking of Huntington’s chorea in a patient with diabetes

Abstract

Chorea-ballism is a neurological syndrome characterised by violent involuntary movements of one or both extremities. In the last decades, several patients with these involuntary movements were reported in association with hyperglycaemia. Here, we present a unique case of possible Huntington’s disease, which could have been unmasked by the hyperglycaemic insult to the basal ganglia in a 64-year-old man who presented with chorea-ballism.

Background

Hyperglycaemia is most commonly a complication of poorly controlled diabetes mellitus (DM), but rarely it presents as an acute neurological syndrome with chorea and ballistic movements. This type of presentation usually raises suspicion for stroke and prompts further workup. Huntington’s chorea can be unmasked by hyperglycaemia. Here, we will discuss a case of possible Huntington’s disease (HD), which manifested secondary to the hyperglycaemic insult to the basal ganglia in a patient with poorly controlled diabetes.

Case presentation

A 64-year-old man with a strong family history of HD in the father, grandfather, daughter and granddaughter came for evaluation and management of abnormal movements in all the four extremities. Four weeks prior to this presentation, he experienced non-specific headaches that were followed a week later by a gradual onset of sudden, non-rhythmic and involuntary movements in the arms and the legs, which resolved spontaneously. Initially, the patient neglected these involuntary movements until they reappeared and started increasing in frequency. These movements involved both the upper and lower limbs, including the eyelids. The patient and family denied similar problems in the past. He has been diagnosed with diabetes 20 years ago and was not compliant with medications and was inconsistent in following with primary care provider. The patient developed complications secondary to DM that include peripheral neuropathy, retinopathy and chronic kidney disease.

On examination, he was alert and oriented to time, place and person. He was able to follow commands, but the speech was incomprehensible. Cranial nerves examination was unremarkable. Muscle bulk and strength preserved throughout with a normal motor tone in both the upper and lower extremities. Sensations were intact throughout with normal deep tendon reflexes in all the extremities. Choreiform dyskinesias was noted in both the upper and lower extremities (video 1).

Video 1.

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DOI: 10.1136/bcr-2019-232726.video01

Investigations

Routine labs, including complete blood count, serum ammonia levels, urine analysis and urine drug screen, were unremarkable. Other lab data are shown in table 1.

Table 1.

Laboratory data on admission and at the time of discharge

Tests	On admission	At discharge
Fasting blood glucose level (ref: 74–109 mg/dL)	247	205
Haemoglobin A1C (ref: 4%–6%)	16.4%	–
Anion gap (ref: 0–20 mmol/L)	32	16
BUN (ref: 08–23 mg/dL)	75	46
Creatinine (ref: 0.70–1.20 mg/dL)	4.99	4.04
Serum beta hydroxybutyrate (ref: 0–0.29 mmol/L)	4.89	–
Osmolality (ref: 270–310 mOsm/kg)	319	–

BUN, blood urea nitrogen; Ref, reference.

Based on the above laboratory results, the patient was diagnosed with diabetes ketoacidosis (DKA) and managed with intravenous fluids and insulin. CT scan of the head showed a bilateral hyperdense signal in the globus pallidus with the sparing of the internal capsule. MRI of the brain showed an increased T1 signal intensity in the putamen, bilaterally, and a decreased T2 signal intensity of the bilateral putamen and the caudate lobes (figure 1). While the characteristic findings on the imaging may vary to some degree, the pattern of basal ganglia involvement with the sparing of the internal capsule, along with the sudden onset of abnormal movements in the setting of markedly elevated blood glucose levels, aided us to consider the diagnosis of hyperglycaemia-induced chorea-ballism.

Figure 1.

(A) Axial CT of the head at the level of caudate nucleus shows a hyperdense signal in the globus pallidus with sparring of internal capsule bilaterally (white arrows). (B) Axial MRI of the brain T1 sequence shows putaminal hyperintensity (red arrows) and (C) caudate and putaminal hypointensity on T2 sequence bilaterally (green arrows).

Differential diagnosis

The conditions causing T1 hyperintensity in basal ganglia are limited, and the aetiologies could be from the deposition of blood products, metals and calcification as shown in box 1.¹ Physiological calcification, which is the most common cause, is usually seen in the elderly.¹ However, if seen in young patients, suspicion of alternate diagnoses like Cockayne syndrome, and metabolic causes must be considered. Metals like copper and manganese deposition, as seen in Wilson’s disease and total parenteral nutrition, have a predilection for deposition in basal ganglia (due to higher concentration of these metals in this structure).¹ These different aetiologies are distinguished by their clinical symptoms. Other differentials to consider include calcification, which can be idiopathic or secondary to metabolic causes (hyperparathyroidism, pseudohyperparathyroidism) and infections (toxoplasmosis, cytomegalovirus). As described in our case, hyperglycaemia-induced chorea-ballism can cause T1 hyperintensity of basal ganglia and could be secondary to either haemorrhagic process or astrocytosis.¹ So, it is important to consider the differentials mentioned above when approaching a patient with T1 hyperintensity on brain MRI.

Box 1. Differential diagnosis for T1-weighted hyperintense lesion in basal ganglia on MRI scan.

• Haemorrhagic infarct.

• Carbon monoxide poisoning.

• Hypoxic ischaemic encephalopathy.

• Hepatocerebral degeneration.

• Wilson’s disease.

• Total parenteral nutrition.

• Idiopathic calcification.

• Hyperglycaemia-induced chorea.

Outcome and follow-up

1. The patient made an uneventful recovery from DKA with intravenous fluids and insulin administration. However, the patient continued to have low amplitude and mild bilateral lower extremity movements at the time of discharge.

2. On follow-up at 4 weeks, the patient continued to experience bilateral lower extremity dyskinesias (video 2). Given the patients strong family history of HD, and the lack of motor symptoms before the hyperglycaemic episode, we hypothesised that the hyperglycaemic insult to the basal ganglia could have unmasked the motor manifestations of HD.

Video 2.

Download video file ^{(4.8MB, mp4)}

DOI: 10.1136/bcr-2019-232726.video02

Discussion

Hyperglycaemia-induced chorea-ballism is a rare complication of diabetes. It is characterised by an irregular, non-rhythmic and involuntary movements of one or both extremities. These abnormal movements are usually unilateral but sometimes can be bilateral. A study from the Mayo Clinic analysed 596 cases with chorea-ballism and found that only 7 patients (5 women) had chorea preceded by a hyperglycaemic episode. Out of the seven patients, six had unilateral involvement.² Another study identified 25 patients with chorea-ballism at admission and found to be in a hyperglycaemic state. Of these, only two patients had bilateral involvement.³

The pathophysiology of this acute syndrome is unclear. It is thought that hyperglycaemia might result in higher utilisation of gamma-aminobutyric acid (GABA) as an alternative energy source resulting in the depletion of GABA, a major inhibitory neurotransmitter in the brain and the basal ganglia circuitry. This reduction in GABA can lead to the disinhibition of the thalamus resulting in abnormal movements.⁴ Other mechanisms have been suggested, acute basal ganglia dysfunction in the setting of hyperosmolar state,⁵ hyperviscosity,⁶ petechial haemorrhage,⁷ inflammation⁸ and cerebrovascular insufficiency.⁹

HD is an autosomal dominant neurodegenerative disorder characterised by choreiform movements, behavioural problems and cognitive decline. It is due to cytosine–adenine–guanine (CAG) trinucleotide repeat expansion in the huntingtin (HTT) gene on chromosome 4p. Studies have shown that HD is associated with insulin disturbance and DM.¹⁰ It is also reported that hyperglycaemic chorea-ballism or acute exacerbation of Huntington’s chorea occurs in patients with diabetes.¹¹ Transgenic models of HD have demonstrated that the accumulation of intracellular inclusions in the beta cells, as well as altered expression of insulin gene transcription regulators, can lead to reduced levels of pancreatic insulin.¹² CAG repeats, which are responsible for HD, can also affect the pancreas, which also expresses the HTT gene like other tissues in the body and cause a decrease in insulin and glucagon release.¹³

A significant family history of HD (presence of the disease in father, grandfather, daughter and granddaughter) and the lack of motor symptoms prior to the current presentation suggests that the patient either has a ‘CAG contraction’, making him asymptomatic or is probably in the presymptomatic phase of the disease. Given the autosomal dominant inheritance and the evidence of the disease in both parent and offspring, our patient is likely an obligate carrier.

The most commonly affected region of the brain in HD is the striatum of basal ganglia. The characteristic imaging findings include caudate and putamen atrophy. Lateral ventricular enlargement (frontal horns) has also been noticed along with the atrophy of the frontal lobes.¹⁴ The most common MRI finding in patients with hyperglycaemia-induced chorea-ballism is T1 putamen hyperintensity, which sometimes can be mistaken for basal ganglia haemorrhage.¹⁵ Our patient had increased T1 signal within the basal ganglia bilaterally along with T2 and Fluid-attenuated inversion recovery (FLAIR) hypointensity. This pattern was also reported previously with hyperglycaemia-induced chorea-ballism.² The condition is typically easily treatable by correcting the hyperglycaemia and neuroleptics for the abnormal movements as needed. Most of the patients with this condition have a favourable prognosis.

Hyperglycaemic insult affects the same portion of the brain, the basal ganglia, as seen in HD. Hence, we hypothesise that the hyperglycaemic insult to the basal ganglia might have unmasked the motor manifestations of the HD in our patient, and the genetic defect made it more likely to involve the bilateral basal ganglia. On review of literature, we found one other case report in which a type 1 diabetic female with DKA had hyperglycaemia-induced chorea-ballism. DKA resolved with administration of fluids and insulin. However, the patient continued to experience choreatic movements in the upper extremities and was later diagnosed with HD.¹¹

The limitation of this case report is that the patient was not a genetically proven case of HD. Due to financial reasons, the patient declined to get genetic testing. However, the family history of genetically proven HD in the patient’s offspring and granddaughter, along with clinically documented HD in his father and grandfather, makes him an obligate carrier of the genetic defect. Hence, the genetic testing is deferred, as it is an adjunct to our suspicion, and we obliged to the patient’s discretion. We hypothesise that the hyperglycaemic insult could have unmasked the motor manifestations of HD in this patient.

Learning points.

• Chorea-ballism can be seen with elevated blood glucose levels.

• Huntington’s disease (HD) is associated with insulin disturbance and diabetes mellitus.

• The chorea of HD could be exacerbated by hyperglycaemia in a patient with poorly controlled diabetes.

• In this case, we hypothesise that the hyperglycaemic episode could have unmasked the symptom of his underlying disease mutation.