Universidade Federal de São Paulo (UNIFESP) Movement Disorders Unit Department of Neurology and NeurosurgeryUniversidade de São Paulo Faculdade de Medicina Psychiatry InstituteUniversidade Estadual Paulista Faculdade de Medicina de Botucatu Department of MedicineUNIFESP, Movement Disorders Unit Department of Neurology and NeurosurgerySciEL

CHANG, Claudia V.

FELICIO, Andre C.

FERRAZ, Henrique B.

GODEIRO-JUNIOR, Clecio

OKOSHI, Marina P.

Biblioteca Digital da Produção Intelectual da Universidade de São Paulo (BDPI/USP)

Arq Neuropsiquiatr 2008;66(2-A):249-250
 249
HemicHorea-Hemiballism as tHe first  
presentation of type 2 diabetes mellitus
Andre C. Felicio1, Claudia V. Chang2, Clecio Godeiro-Junior1, Marina P. Okoshi3, Henrique B. Ferraz1
Hemicoreia-Hemibalismo como primeira manifestação de diabetes mellitus tipo 2
1 Department of Neurology and Neurosurgery, Movement Disorders Unit,  Universidade Federal de São Paulo, São Paulo SP, Brazil (UNIFESP); 2Neuroen-
docrinology Division, Psychiatry Institute, Faculdade de Medicina da Universidade de São Paulo, São Paulo SP, Brazil (USP); 3Department of Medicine, 
Faculdade de Medicina de Botucatu, Universidade Estadual Paulista, Botucatu SP, Brazil (UNESP).
Received 11 September 2007, received in final form 5 December 2007. Accepted 7 February 2008.
Dr. Andre C. Felicio – Disciplina Neurologia - Rua Pedro de Toledo 650 - 04039-002 São Paulo SP - Brasil. E-mail: cf.andre@gmail.com
Hemichorea-hemiballism (HCHB) can be the solely 
presentation of a wide range of non-neurological clinical 
pictures, such as metabolic or hydro-electrolyte derange-
ments. HCHB as the first presentation of type 2 diabetes 
mellitus has been rarely described1-3. 
The case depicted herein reinforces this association 
highlighting that especially in elder patients with new-
ly diagnosed HCHB, non-ketotic hyperglycemia should 
promptly be recognized. 
case
A 70-year-old white man presented with one month history 
of involuntary movements of the left upper and lower limbs. He 
also noticed polyuria and polydipsia for the last 2 months and 
lost 10 kg within this period. His past medical history included 
controlled hypertension and a heart attack three years before. 
He used to take on a regular basis and at the time of presenta-
tion to our emergency department captopril 50 mg per day, hy-
drochlorothiazide 25 mg per day, propranolol 120 mg per day, 
aspirin 200 mg per day, and digoxin 0.25 mg per day. He used to 
be a heavy drinker (stopped 15 years ago) and smoker (stopped 3 
years ago). There was no history of diabetes mellitus, other dis-
eases or exposure to neuroleptic medication. No family history 
of movement disorders was obtained. 
On admission, he was fully alerted and oriented. He had 
HCHB involving his left upper and lower limb with normal mus-
cle strength, but mild hypotonia. The movements were almost 
continuous during wakefulness, and disappeared during sleep. 
Fasting blood glucose was obtained (560 mg/dL) and type 2 dia-
betes mellitus was diagnosed. Glycosylated hemoglobin A1c was 
6.6%. No ketones were detected in urinalysis and urine pH was 
normal. Corrected sodium concentration was 140 mmol/L, and 
estimated serum osmolality was 332 mOsm/L. Other routine 
blood tests including calcium, potassium, magnesium, and phos-
phate concentrations, and thyroid and parathyroid hormone 
tests were normal as well liver and kidney functional status. A 
brain computer tomography (CT) showed a slight hyperdense 
lesion on the right putamen. T1-weighted brain magnetic reso-
nance imaging (MRI) showed a right hyperintense lesion on pu-
tamen with iso-signal intensity on T2-weighted and Flair images. 
With the administration of haloperidol (10 mg per day) and 
glycemia control (10 IU bed time NPH insulin) and 6 mg per day 
glimepiride his movement disorder decreased in severity and 
completely disappeared 15 days after the first medical appoint-
ment. A nine-month re-scan with MRI showed a normal putamen 
without the previously seen hyperintense lesion (Figure). 
The patient signed an informed consent to allow his data 
publication.
discussion
The underlying mechanisms of brain alterations in pa-
tients with non-ketotic hyperglycemia-induced HCHB are 
not known yet, but they have been attributed to base gan-
glia cerebral blood flow reduction, petechial hemorrhage, 
depletion of both GABA and acetylcholine, or metabolic 
acidosis4. Interestingly, among neuronal subtypes, striatal 
medium spiny neurones are highly vulnerable to energy 
depletion and this might explain the predilection for le-
sions situated in the striatum4. In a recent case report 
Figure. MRI scan showing a hyperintense lesion in the right putamen 
on T1-weighted image (left). A nine-month re-scan (right) shows com-
plete disappearance of the putaminal lesion, even after contrast gad-
olinium enhancement. Arrow corresponds to the right putamen. A la-
cunar infarct is also seen on the left thalamic-internal capsular region.
Arq Neuropsiquiatr 2008;66(2-A)
250
Hemichorea-hemiballism as the: diabetes mellitus
Felicio et al. 
study, it was suggested that petechial hemorrhage sec-
ondary to erythrocyte diapedesis due to hyperglycemia-
induced blood-brain barrier dysfunction might also have 
a role in the syndrome5. 
Typically, the neuroimaging abnormalities seen in 
patients with HCHB last several months to years disap-
pearing much later than the movement disorder. The 
characteristic features are high signal intensity lesions 
on T1-weighed brain MRI, and these alterations are not 
yet fully understood. There is, however, hyperglycemia-
induced HCHB without MRI abnormalities2, and therefore 
these unique imaging alterations should not be taken as 
a clear-cut surrogate marker for putaminal dysfunction 
associated to an hyperglycemic insult. 
Elder female diabetic patients from East Asian origin 
are more prone to develop HCHB, but whether this is re-
lated to a particular genetic predisposition is still a matter 
of debate. Recently, it was suggested that the presence of 
acanthocytes in circulating peripheral blood might render 
diabetic patients prone to develop HCHB6. In our case we 
did not search for acanthocytes on the peripheral blood 
since a good relief of symptoms was obtained with gly-
cemia control and the use of neuroleptics. 
The prognosis of non-ketotic hyperglycemia-induced 
HCHB is favorable and depends on the prompt identifi-
cation of undiagnosed diabetes or the compensation of 
previously diagnosed patients. Additionally, typical neu-
roleptics and sometimes benzodiazepines are useful in 
the management of the choreic movements. Topiramate7, 
levetiracetan8 and tetrabenazine9 have also been tried in 
selected cases with favorable outcomes. 
We recently reported three other cases (2 men, 1 
woman) of new onset HCHB in elder patients attributed 
to non-ketotic hyperglycemia3. One of these patients, 
similarly to this case, was unaware of having type 2 diabe-
tes mellitus. The mean time for their movement disorder 
to fully recover was approximately 12 days and they all 
took haloperidol in a long-term basis without side effects. 
Two of the patients had concurrent infection (pneumonia 
and meningitis) suggesting that this might play as a trig-
ger factor for HCHB in predisposed patients. The charac-
teristic T1-weigthed hyperintense lesions in the striatum 
were found in all patients especially contralateral to the 
affected limb. Cupidi and coworkers also described a dia-
betic patient mild uremia that developed an acute but 
reversible form of parkinsonism, emphasizing that acute 
extrapyramidal syndromes may occur in diabetic patients 
with concurrent decompensated metabolic diseases and 
that this clinical syndrome is likely independent from ra-
cial and/or genetic variables10.
In conclusion, this case report underscores the non-
ketotic hyperglycemia-induced HCHB syndrome as an 
unusual presentation of type 2 diabetes mellitus, high-
lighting that its recognition and stringent glycemia control 
associated to the use of neuroleptics hasten the patient 
recovery. Moreover HCHB syndrome should be regularly 
included in the differential diagnosis of acute movement 
disorders, especially in the elder population.
references
	 1.	 Ifergane	G,	Masalha	R,	Herishanu	YO.	Transient	hemichorea/hemi-
ballismus	associated	with	new	onset	hyperglycemia.	Can	J	Neurol	Sci	
2001;28:365-368.
	 2.	 Branca	D,	Gervasio	O,	Le	Piane	E,	et	al.	Chorea	induced	by	non-ketot-
ic	hyperglycaemia:	a	case	report.	Neurol	Sci	2005;26:275-277.
	 3.	 Chang	CV,	Felicio	AC,	Godeiro-Junior	CO,	et	al.	Chorea-ballism	as	a	
manifestation	of	decompensated	type	2	diabetes	mellitus.	Am	J	Med	
Sci	2007;333:175-177.
	 4.	 Oh	S-H,	Lee	K-Y,	Im	J-H,	et	al.	Chorea	associated	with	non-ketotic	hy-
perglycemia	and	hyperintensity	basal	ganglia	lesion	on	T1-weighted	
brain	MRI	study:a	meta-analysis	of	53	cases	including	four	present	cas-
es.	J	Neurol	Sci	2002;200:57-62.	
	 5.	 Mestre	TA,	Ferreira	JJ,	Pimentel	J.	Putaminal	petechial	haemorrhage	
as	the	cause	of	non-ketotic	hyperglycaemic	chorea:	a	neuropathologi-
cal case correlated with MRI findings. J Neurol Neurosurg Psychiatry 
2007;78:549-550.
	 6.	 Pisani	A,	Diomedi	M,	Rum	A,	et	al.	Acanthocytosis	as	a	predisposing	
factor	for	non-ketotic	hyperglycemia	induced	chorea-ballism.	J	Neurol	
Neurosurg	Psychiatry	2005;76:1717-1719.
	 7.	 Driver-Dunckley	E,	Evidente	VG.	Hemichorea-hemiballismus	may	re-
spond	to	topiramate.	Clin	Neuropharmacol	2005;28:142-144.
	 8.	 Zesiewicz	TA,	Pathak	A,	Sullivan	KL,	Shamayev	M,	Hauser	RA.	Treat-
ment	of	chorea	with	levetiracetam.	Eur	J	Clin	Pharmacol	2006;62:87
	 9.	 Sitburana	O,	Ondo	WG.	Tetrabenazine	for	hyperglycemic-induced	
hemichorea-hemiballismus.	Mov	Disord	2006;21:2023-2025.
10.	 Cupidi	C,	Piccoli	F,	La	Bella	V.	Acute	reversible	parkinsonism	in	a	dia-
betic-uremic	patient.	Clin	Neurol	Neurosurg	2006;108:601-603.


Hemicoreia-hemibalismo como primeira manifestação de diabetes mellitus tipo 2

Universidade Federal de São Paulo (UNIFESP) Movement Disorders Unit Department of Neurology and NeurosurgeryUniversidade de São Paulo Faculdade de Medicina Psychiatry InstituteUniversidade Estadual Paulista Faculdade de Medicina de Botucatu Department of MedicineUniversidade Estadual Paulista Faculdade de Medicina de Botucatu Department of Medicin

Felicio, Andre C.

Chang, Claudia V.

Godeiro-Junior, Clecio

Okoshi, Marina Politi [UNESP]

Ferraz, Henrique B.

Repositório Institucional UNESP

Arquivos de Neuro-Psiquiatria

Andre C. Felicio

Claudia V. Chang

Clecio Godeiro-Junior

Marina P. Okoshi

Henrique B. Ferraz

Directory of Open Access Journals

Hemichorea-hemiballism as the first presentation of type 2 diabetes mellitus Hemicoreia-hemibalismo como primeira manifestação de diabetes mellitus tipo 2

Felício, André Carvalho [UNIFESP]

Godeiro-Junior, Clecio [UNIFESP]

Okoshi, Marina P.

Ferraz, Henrique B. [UNIFESP]

Repositório Institucional UNIFESP

Arq Neuropsiquiatr 2008;66(2-A):249-250 249HemicHorea-Hemiballism as tHe first  presentation of type 2 diabetes mellitusAndre C. Felicio1, Claudia V. Chang2, Clecio Godeiro-Junior1, Marina P. Okoshi3, Henrique B. Ferraz1Hemicoreia-Hemibalismo como primeira manifestação de diabetes mellitus tipo 21 Department of Neurology and Neurosurgery, Movement Disorders Unit,  Universidade Federal de São Paulo, São Paulo SP, Brazil (UNIFESP); 2Neuroen-docrinology Division, Psychiatry Institute, Faculdade de Medicina da Universidade de São Paulo, São Paulo SP, Brazil (USP); 3Department of Medicine, Faculdade de Medicina de Botucatu, Universidade Estadual Paulista, Botucatu SP, Brazil (UNESP).Received 11 September 2007, received in final form 5 December 2007. Accepted 7 February 2008.Dr. Andre C. Felicio – Disciplina Neurologia - Rua Pedro de Toledo 650 - 04039-002 São Paulo SP - Brasil. E-mail: cf.andre@gmail.comHemichorea-hemiballism (HCHB) can be the solely presentation of a wide range of non-neurological clinical pictures, such as metabolic or hydro-electrolyte derange-ments. HCHB as the first presentation of type 2 diabetes mellitus has been rarely described1-3. The case depicted herein reinforces this association highlighting that especially in elder patients with new-ly diagnosed HCHB, non-ketotic hyperglycemia should promptly be recognized. caseA 70-year-old white man presented with one month history of involuntary movements of the left upper and lower limbs. He also noticed polyuria and polydipsia for the last 2 months and lost 10 kg within this period. His past medical history included controlled hypertension and a heart attack three years before. He used to take on a regular basis and at the time of presenta-tion to our emergency department captopril 50 mg per day, hy-drochlorothiazide 25 mg per day, propranolol 120 mg per day, aspirin 200 mg per day, and digoxin 0.25 mg per day. He used to be a heavy drinker (stopped 15 years ago) and smoker (stopped 3 years ago). There was no history of diabetes mellitus, other dis-eases or exposure to neuroleptic medication. No family history of movement disorders was obtained. On admission, he was fully alerted and oriented. He had HCHB involving his left upper and lower limb with normal mus-cle strength, but mild hypotonia. The movements were almost continuous during wakefulness, and disappeared during sleep. Fasting blood glucose was obtained (560 mg/dL) and type 2 dia-betes mellitus was diagnosed. Glycosylated hemoglobin A1c was 6.6%. No ketones were detected in urinalysis and urine pH was normal. Corrected sodium concentration was 140 mmol/L, and estimated serum osmolality was 332 mOsm/L. Other routine blood tests including calcium, potassium, magnesium, and phos-phate concentrations, and thyroid and parathyroid hormone tests were normal as well liver and kidney functional status. A brain computer tomography (CT) showed a slight hyperdense lesion on the right putamen. T1-weighted brain magnetic reso-nance imaging (MRI) showed a right hyperintense lesion on pu-tamen with iso-signal intensity on T2-weighted and Flair images. With the administration of haloperidol (10 mg per day) and glycemia control (10 IU bed time NPH insulin) and 6 mg per day glimepiride his movement disorder decreased in severity and completely disappeared 15 days after the first medical appoint-ment. A nine-month re-scan with MRI showed a normal putamen without the previously seen hyperintense lesion (Figure). The patient signed an informed consent to allow his data publication.discussionThe underlying mechanisms of brain alterations in pa-tients with non-ketotic hyperglycemia-induced HCHB are not known yet, but they have been attributed to base gan-glia cerebral blood flow reduction, petechial hemorrhage, depletion of both GABA and acetylcholine, or metabolic acidosis4. Interestingly, among neuronal subtypes, striatal medium spiny neurones are highly vulnerable to energy depletion and this might explain the predilection for le-sions situated in the striatum4. In a recent case report Figure. MRI scan showing a hyperintense lesion in the right putamen on T1-weighted image (left). A nine-month re-scan (right) shows com-plete disappearance of the putaminal lesion, even after contrast gad-olinium enhancement. Arrow corresponds to the right putamen. A la-cunar infarct is also seen on the left thalamic-internal capsular region.Arq Neuropsiquiatr 2008;66(2-A)250Hemichorea-hemiballism as the: diabetes mellitusFelicio et al. study, it was suggested that petechial hemorrhage sec-ondary to erythrocyte diapedesis due to hyperglycemia-induced blood-brain barrier dysfunction might also have a role in the syndrome5. Typically, the neuroimaging abnormalities seen in patients with HCHB last several months to years disap-pearing much later than the movement disorder. The characteristic features are high signal intensity lesions on T1-weighed brain MRI, and these alterations are not yet fully understood. There is, however, hyperglycemia-induced HCHB without MRI abnormalities2, and therefore these unique imaging alterations should not be taken as a clear-cut surrogate marker for putaminal dysfunction associated to an hyperglycemic insult. Elder female diabetic patients from East Asian origin are more prone to develop HCHB, but whether this is re-lated to a particular genetic predisposition is still a matter of debate. Recently, it was suggested that the presence of acanthocytes in circulating peripheral blood might render diabetic patients prone to develop HCHB6. In our case we did not search for acanthocytes on the peripheral blood since a good relief of symptoms was obtained with gly-cemia control and the use of neuroleptics. The prognosis of non-ketotic hyperglycemia-induced HCHB is favorable and depends on the prompt identifi-cation of undiagnosed diabetes or the compensation of previously diagnosed patients. Additionally, typical neu-roleptics and sometimes benzodiazepines are useful in the management of the choreic movements. Topiramate7, levetiracetan8 and tetrabenazine9 have also been tried in selected cases with favorable outcomes. We recently reported three other cases (2 men, 1 woman) of new onset HCHB in elder patients attributed to non-ketotic hyperglycemia3. One of these patients, similarly to this case, was unaware of having type 2 diabe-tes mellitus. The mean time for their movement disorder to fully recover was approximately 12 days and they all took haloperidol in a long-term basis without side effects. Two of the patients had concurrent infection (pneumonia and meningitis) suggesting that this might play as a trig-ger factor for HCHB in predisposed patients. The charac-teristic T1-weigthed hyperintense lesions in the striatum were found in all patients especially contralateral to the affected limb. Cupidi and coworkers also described a dia-betic patient mild uremia that developed an acute but reversible form of parkinsonism, emphasizing that acute extrapyramidal syndromes may occur in diabetic patients with concurrent decompensated metabolic diseases and that this clinical syndrome is likely independent from ra-cial and/or genetic variables10.In conclusion, this case report underscores the non-ketotic hyperglycemia-induced HCHB syndrome as an unusual presentation of type 2 diabetes mellitus, high-lighting that its recognition and stringent glycemia control associated to the use of neuroleptics hasten the patient recovery. Moreover HCHB syndrome should be regularly included in the differential diagnosis of acute movement disorders, especially in the elder population.references	 1.	 Ifergane	G,	Masalha	R,	Herishanu	YO.	Transient	hemichorea/hemi-ballismus	associated	with	new	onset	hyperglycemia.	Can	J	Neurol	Sci	2001;28:365-368.	 2.	 Branca	D,	Gervasio	O,	Le	Piane	E,	et	al.	Chorea	induced	by	non-ketot-ic	hyperglycaemia:	a	case	report.	Neurol	Sci	2005;26:275-277.	 3.	 Chang	CV,	Felicio	AC,	Godeiro-Junior	CO,	et	al.	Chorea-ballism	as	a	manifestation	of	decompensated	type	2	diabetes	mellitus.	Am	J	Med	Sci	2007;333:175-177.	 4.	 Oh	S-H,	Lee	K-Y,	Im	J-H,	et	al.	Chorea	associated	with	non-ketotic	hy-perglycemia	and	hyperintensity	basal	ganglia	lesion	on	T1-weighted	brain	MRI	study:a	meta-analysis	of	53	cases	including	four	present	cas-es.	J	Neurol	Sci	2002;200:57-62.		 5.	 Mestre	TA,	Ferreira	JJ,	Pimentel	J.	Putaminal	petechial	haemorrhage	as	the	cause	of	non-ketotic	hyperglycaemic	chorea:	a	neuropathologi-cal case correlated with MRI findings. J Neurol Neurosurg Psychiatry 2007;78:549-550.	 6.	 Pisani	A,	Diomedi	M,	Rum	A,	et	al.	Acanthocytosis	as	a	predisposing	factor	for	non-ketotic	hyperglycemia	induced	chorea-ballism.	J	Neurol	Neurosurg	Psychiatry	2005;76:1717-1719.	 7.	 Driver-Dunckley	E,	Evidente	VG.	Hemichorea-hemiballismus	may	re-spond	to	topiramate.	Clin	Neuropharmacol	2005;28:142-144.	 8.	 Zesiewicz	TA,	Pathak	A,	Sullivan	KL,	Shamayev	M,	Hauser	RA.	Treat-ment	of	chorea	with	levetiracetam.	Eur	J	Clin	Pharmacol	2006;62:87	 9.	 Sitburana	O,	Ondo	WG.	Tetrabenazine	for	hyperglycemic-induced	hemichorea-hemiballismus.	Mov	Disord	2006;21:2023-2025.10.	 Cupidi	C,	Piccoli	F,	La	Bella	V.	Acute	reversible	parkinsonism	in	a	dia-betic-uremic	patient.	Clin	Neurol	Neurosurg	2006;108:601-603.

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Hemichorea-hemiballism as the first presentation of type 2 diabetes mellitus

Hemicoreia-hemibalismo como primeira manifestação de diabetes mellitus tipo 2

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