Movement disorders: A complication of chronic Hyperglycemia? A case report

Case Report

Movement disorders: A complication of chronichyperglycemia? A case report

R. Ben Othman a,*, A. Ben Mahmoud b, A. Mankai a, N. Trabelsi a,F. Hentati b, F. Ben Mami a

aDepartment (C) of Diabetology, Nutrition and Metabolic Diseases, The National Institute of Nutrition,

Avenue Jbel Lakhdhar, 1007 Tunis, TunisiabDepartment of Neurology, National Institute Mongi Ben Hmida of Neurology, Tunis, Tunisia

a r t i c l e i n f o

Article history:

Received 29 March 2013

Accepted 9 October 2013

Available online xxx

Keywords:

Diabetes mellitus

Chorea

Dyskinesia

Hyperglycemia

Nonketotic hyperglycemia

a b s t r a c t

Introduction: The association of chorea with a specific lesion on brain imaging is described

as an atypical manifestation of chronic hyperglycemia.

Case report: Patient of 77 years, hospitalized for bilateral choreic movements predominant

on the right with dystonic movements, appeared a month ago.

At admission: Hyperglycemia at 2.4 g/L, without ketosis, a type 2 diabetes (HbA1c 17.3%) on

oral antidiabetic agents. CT scan shows hyperdensity of putamen and lenticular nucleus

that eliminates an ischemic attack. Evolution after glycemic reequilibration and treatment

by haloperidol is favorable, with regression of chorea.

Discussion: This is a rare syndrome, affecting more elderly, presenting a diabetes poorly

controlled. There is hyperglycemia without ketosis and moderate hyperosmolarity. The

symptomsusually regress after glycemic control andneuroleptic treatment (recurrence in 13%

of cases). The appearance of this syndrome seems to be related to the achievement of the

control system GABAergic of the basal ganglia leading to an excitation of the cerebral cortex,

causing involuntary movements. The etiopathogenic hypotheses advanced are multiple:

impairedstriatalneurotransmissionassociatedwithmetabolicdisturbancesofhyperglycemia,

dysfunctionof thehematoencephalicbarrier andabnormalitiesof the cerebralvascularization.

Conclusion: Chorea secondary to nonketotic hyperglycemia is a rare complication and little

known of type 2 diabetes. Transitional neuroleptic treatment and glycemic control make

the symptoms regress in most cases with the disappearance of the lesion imaging.

Copyright ª 2013, Indraprastha Medical Corporation Ltd. All rights reserved.

1. Introduction

The uncontrolled diabetes can be responsible for different

neurological symptoms such as epileptic seizures and disor-

ders of consciousness. Transient chorea or ballism provoked

by an episode of nonketotic hyperglycemia has been reported

by numerous authors over the past couple of decades.1,2 In

this case, the choreiform movements have resolved within

days after normalization of blood glucose. In the vast majority

of cases, the chorea/ballism triggered by hyperglycemia has

* Corresponding author. Tel.: þ216 97291139.E-mail address: benothmanr@gmail.com (R. Ben Othman).

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been unilateral. Several recent reports have documented

characteristic brain imaging findings consisting of high den-

sity on computed tomography (CT) scans. We describe a case

of chorea developing subacutely during an episode of revers-

ible nonketotic hyperglycemia.

2. Observation

A patient, aged 77 years, followed for type II diabetes on oral

antidiabetic agents for three months and for hypertension

since two years, presents to the emergency for abnormal

movements of the upper limbs, the head and neck. These

movements are type of flexion-extension and rotation. They

are abrupt, irregular and of large amplitude, exaggerating to

emotion and disappearing during sleep.

There is no remarkable family history or a prior history of

dopamine antagonist or estrogen medication use and no his-

tory of rheumatic fever/Sydenham’s chorea.

At admission, the patient was conscious, afebrile and well

oriented in time and space. Neurological examination objec-

tify chorea in both upper limbs, the head and neck predomi-

nant at right without oral or lingual abnormal movements. In

addition, the review found hypotonia in all four limbs.

The remainder of the examination shows no motor or

sensory deficit, nor parkinsonism nor cerebellar nor cranial

disorder. A specialized neuropsychological examination did

not show significant cognitive disorders (mini-mental

state ¼ 28/30) except an alteration of executive functions

(frontal score ¼ 8/18). In addition, a psychomotor instability

was noted as well as irritability.

A cerebral CT scan was performed in emergency, which

objectified a spontaneous hyperdensity of putamen and

lenticular nuclei (Fig. 1a et b). Our patient did not benefit of

brain MRI. Urinalysis was strongly positive for glucose and

negative for ketones. The following laboratory data were

notable: fasting blood glucose 13.2 mmol/l (240 mg/dl), glyco-

sylated hemoglobin A1c 17.3%, creatinine 140 mmol/l, clear-

ance 37 ml/min.

The patient was put on insulin and small doses of halo-

peridol (3 mg/day in three divided doses). A significant

reduction in abnormal movements was noted, these dis-

appeared within four days, which motivated progressive

stopping of haloperidol .The patient was admitted in dia-

betology for initiation of insulin 6UI at morning due to

contraindication for the use of oral antidiabetic .The patient is

still asymptomatic after six months. Control brain CT scan

was not performed.

3. Discussions

Chorea and ballism are hyperkinetic movement disorders

which are characterized by the occurrence of uncontrollable,

sudden, irregular, high amplitude and short duration move-

ments of all or a part of the body.3,4 Chorea and/or ballismhave

been reported for thefirst time, as a complication ofnonketotic

hyperglycemia by Bedwell in 1960.5 These abnormal move-

mentsare rarely revealingofdiabetes.2 The symptomatology is

made from hemichorea and/or hemiballismus in most cases

correlated to unilateral scannographic images.6 For our case

thedamage is bilateral predominantly to the right in relation to

imagery and in accordancewith somesimilar cases reported in

the literature where the lesion is bilateral.7

Physiopathology subtending the development of these

movements during hyperglycemia without ketosis is still un-

clear.3 Several hypotheses have been evoked.

Brain structures implicated in the genesis of chorea are

represented by the basal ganglia, mainly the subthalamic

nucleus, theway pallido-subthalamic, striatum and to a lesser

degree the cerebral cortex and the thalamus.8 These cores are

susceptible to ATP and cellular energy depletion which prob-

ably explain the predilection of lesions at their level.8

Indeed, during hyperglycemia, there is an alteration of the

bloodebrain barrier (BBB) leading to, on one hand, the reduc-

tion of regional cerebral blood flow and on the other hand, the

passage of the cerebral metabolism to anaerobic, resulting in

an inhibition of the tricarboxylic acid cycle (Krebs).9,10

Fig. 1 e (a and b) A CT scan showing a spontaneous hyperdensity in the putamen and the lenticular nucleus.

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Please cite this article in press as: Ben Othman R, et al., Movement disorders: A complication of chronic hyperglycemia? A casereport, Apollo Medicine (2014), http://dx.doi.org/10.1016/j.apme.2013.10.006

Thebrain thenuses thegamma-aminobutyricacid (GABA) as

an alternative source of energy. In patients without ketosis,9e12

the amount of GABA and acetate is rapidly depleted.11,13

Because of this deficiency of acetate, acetylcholine synthesis

may also be decreased. The depletion of these two principal

neurotransmitters (GABAandacetylcholine) in thebasalganglia,

in combinationwith loss of energy andmetabolic acidosis is the

cause of the appearance of movement disorders.11,13,14

Hyperglycemia has also a role in the extravasation of red

blood cells that is the cause of hemorrhagic suffusions found

in cerebral imaging of the majority of these patients.8

Other indirect factorshavebeen incriminated in thegenesis

of chorea, in fact most cases of chorea during nonketotic hy-

perglycemia have been reported in elderly patients with hy-

pertension associated with diabetes.14,15 Indeed, these two

vascular risk factors are often responsible for cerebral vascular

lesions especially lacunar mainly at the basal ganglia.16 These

lesions are usually not visible on standard neuroimagery, but

responsible for clinical manifestations such as chorea.14,17

Finally, the acanthocytosis as a predictor of the onset of

chorea during diabetes has been reported.12 Several hypotheses

have suggested that erythrocyte membrane proteins can un-

dergo, secondary to a particular metabolic state (diabetes),

functional and morphological changes, with acanthocytes for-

mation.18 So hyperviscosity induced by hyperglycemia may

cause a transientmalfunction in striatal neurons inpredisposed

individuals. This hypothesis is in agreement with the concept

that hyperglycemia worsens the evolution of stroke. For our

patient, the search for acanthocytes came back negative.

Chorea in the context of hyperglycemia without ketosis is

generally good prognosis. Most patients improve when

normalization of blood glucose, sometimes without the use of

neuroleptics or with very low doses.10,14 Radiological abnor-

malities may persist longer and disappear for days or weeks

after normalization of glycemia.12

Neuroleptics is the treatment of choice. Benzodiazepines

can also be used.

4. Conclusion

Chorea during uncontrolled diabetes is an unusual compli-

cation, however it remains favorable prognosis in most cases,

which makes necessary the knowledge of this association

since therapeutic implications arising.

Conflicts of interest

All authors have none to declare.

r e f e r e n c e s

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Please cite this article in press as: Ben Othman R, et al., Movement disorders: A complication of chronic hyperglycemia? A casereport, Apollo Medicine (2014), http://dx.doi.org/10.1016/j.apme.2013.10.006

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