seizure in patients with systemic lupus erythematosus ( sle ) is considered to be one of the major manifestations of the disease .
the prevalence of seizure has been documented as about 10 to 20% in the patients with sle ( 1 , 2 ) .
this neuropsychiatric event is likely to be primary to the sle or secondary due to other concomitant conditions , including infection , hypertension , hyperlipidemia , metabolic derangement and the toxic effects of therapy ( 3 , 4 ) .
hyperglycemic hyperosmolar syndrome ( hhs ) is a metabolic emergency , and it commonly occurs in elderly , disabled people with type 2 diabetes .
the report of sament and schwartz in 1957 is widely credited as the original description of hhs .
the proposed criteria for hhs are a plasma glucose concentration > 33.3 mm / l , a serum carbon dioxide concentration > 15 mm / l , no or mild ketonuria , absent to mild ketonemia , a serum osmolarity > 320 mm / kg and mental change ( 5 ) . however , hhs without other metabolic derangement and that occurs in a patient with lupus nephritis without diabetes and who received short term steroid therapy is a very rare complication .
a 51-yr - old female was referred to our outpatient clinic for the evaluation of generalized edema on november 17 , 2009 .
two years previously , she had been diagnosed with idiopathic thrombocytopenic purpura ( itp ) .
she had taken no medicine . except for the itp , she had no history of systemic disease like diabetes or hypertension . on admission ,
her blood pressure was 140/80 mmhg with a pulse rate of 76 beats / min .
the chest radiography revealed cardiomegaly ( the ct ratio was 0.54 ) and bilateral pleural effusions .
both kidneys showed diffusely increased parenchymal echogenicity with partially obliteration of the corticomedullary differentiation and a normal range of size ( the right kidney was 10.3 cm by 4.5 cm in size , and the left kidney was 9.5 cm by 4.5 cm in size ) .
the laboratory findings showed nephrotic syndrome with generalized edema ; the 24 hr urine protein was 5.3 g/24 hr , the total cholesterol was 7 mm / l ( normal : < 5.2 mm / l ) and the serum albumin was 22
the fasting blood glucose and hemoglobin a1c ( hba1c ) were 5.4 mm / l and 0.05 hb fraction , respectively .
the blood urea nitrogen and serum creatinine were 20.6 mm / l ( normal : 2.6 - 7.3 mm / l ) and 0.23 mm / l ( normal : 0.05 - 0.11
in addition , the patient had a positive antinuclear antibody titer at 1:1,600 ( normal : negative ) , positive antibodies against double - stranded dna at 400 iu / ml ( normal : < 100 iu / ml ) and she was negative for antiphospholipid antibodies .
she was diagnosed with systemic lupus erythematosus by the american college of rheumatology criteria ( 6 ) . at diagnosis ,
a renal biopsy was performed . that showed diffuse global glomerulonephritis with active lesion and iv - g(a ) by the isn / rps classification ( 7 ) .
immunosuppressions consisting of high - dose steroid ( methylprednisolone 750 mg for 3 days followed by prednisolone 60 mg ) , cyclophosphamide pulses ( 500 mg at the 6th and 36th day of admission ) , as well as plasma exchange were all started .
in addition , she had oliguria that was refractory to diuretics , and this led us to start hemodialysis .
while maintaining a stable clinical course , a generalized myoclonic seizure occurred at the 47th day of admission . at that time , her body temperature was 36.1. the laboratory and neurology studies showed hyperglycemic hyperosmolar syndrome with a blood glucose level of > 44.4 mm / l , the serum osmolarity was 382 mm / kg ( normal : 275 - 300 mm / kg ) and the hemoglobin a1c was 0.082 hb fraction .
the serum ph was 7.348 and the bicarbonate was 26.2 mm / l ( normal : 21 - 28
the c - reactive protein was normal at 3.9 mg / l ( normal : 0.1 - 4.7 mg / l ) .
g / l ) , respectively . at shortly before seizure , the sledai score was 12 .
the seizure stopped after the blood sugar and serum osmolarity declined below the upper normal limit mentioned above .
the patient became asymptomatic and she was discharged 10 weeks after admission under maintenance therapy with prednisolone 10 mg , insulin glargine 12 unit and nateglinide 270 mg .
on follow - up 1 , 2 , and 3 month after discharge , the hba1c was 0.051 , 0.049 , and 0.06 hb fraction , respectively .
1 , 2 . the patient remained asymptomatic under maintenance therapy with deflazacort 12 mg and without insulin or medication for blood sugar control .
in patients with lupus nephritis , the causes of seizure are a multiplicity of different factors , such as cns involvement of sle , infections , hypertension and metabolic derangement .
a large prospective study reported that infection was the most common cause of neurologic episodes and primary involvement of sle was the secondary cause ( 8) . the presence of seizure increases the risk of death in patients with sle by approximately 2-fold ( 2 , 9 ) . when seizure is noted in patients with lupus nephritis , identifying the cause and proper treatment are important to improve survival .
most studies have revealed that reversible posterior leukoencephalopathy syndrome and cerebral vascular accident are other important causes of seizure in patients with lupus nephritis .
by contrast , the neurologic episodes by purely metabolic derangement without infection or cns lupus are very rare , and especially hhs was a seldom cause of seizure ( 8) .
steroid is associated with the risk of hyperglycemia in patients with or without diabetes ( 10 , 11 ) .
this inhibit insulin signalling in skeletal muscle and liver , resulting in reduced glucose uptake and glycogen systhesis , increased breakdown of skeletal muscle mass , increased hepatic glucose production . in additions ,
steroid increase whole body lipolysis , resulting in increased nonesterified fatty acids ( nefa ) and triglyceride ( tg ) . augmented levels of nfea and tg may enhance the accumulation of intracellular lipids , which impair glucose metabolisms and induce hepatic steatosis , dyslpidemia .
steroid most likely exert inhibitory effects in the beta - cell after exposure , resulting decreased beta - cell insulin production ( 12 - 14 ) .
as an acute complication of diabetes , the overall mortality of hhs is in the range of 10%-50% . however , when therapy is promptly instituted , the mortality rate can be reduced .
treatment is targeted towards 1 ) correcting the intravascular volume and electrolyte derangements ; 2 ) decreasing the hyperglycemia and hyperosmolarity by insulin ; and 3 ) identifying and managing the comorbidities triggering the hhs ( 5 , 16 ) .
althought hyperglycemia due to steroid therapy is a common , but acute complication of diabetes , hhs as a first manifestation is a very rare event .
our case showed that seizure developed due to hhs despite of the short - term steroid therapy .
we should consider hhs as a cause of seizure in patient with lupus nephritis and who are treated with steroid . in conclusion
, our case highlights the importance of regular blood glucose testing during or before high - dose steroid therapy .
 a 51-yr - old female was referred to our outpatient clinic for the evaluation of generalized edema . 
 she had been diagnosed with idiopathic thrombocytopenic purpura ( itp ) . 
 she had taken no medicine . except for the itp , she had no history of systemic disease . 
 she was diagnosed with systemic lupus erythematosus . 
 immunosuppressions consisting of high - dose steroid were started . when preparing the patient for discharge , a generalized myoclonic seizure occurred at the 47th day of admission . 
 at that time , the laboratory and neurology studies showed hyperglycemic hyperosmolar syndrome . 
 brain mri and eeg showed brain atrophy without other lesion . 
 the seizure stopped after the blood sugar and serum osmolarity declined below the upper normal limit . 
 the patient became asymptomatic and she was discharged 10 weeks after admission under maintenance therapy with prednisolone , insulin glargine and nateglinide . 
 the patient remained asymptomatic under maintenance therapy with deflazacort and without insulin or medication for blood sugar control . 
INTRODUCTION
CASE DESCRIPTION
DISCUSSION