INTRODUCTION
Diabetic ketoacidosis (DKA) is a life- threatening acutecomplication of type 1 diabetes mellitus (T1DM). Infection,trauma, myocardial infarction, surgery are some of theconditions which lead to an increase in insulin requirementsand thus to DKA (1). During the treatment of DKA, [tbl:8]thepatient’s neurolog[/tbl]ical status may show impairment withsymptoms of confusion, lethargy, stupor, or even coma.Cerebral edema is the commonest cause of morbidity andmortality during the first day of treatment for DKA in pediatricpatients (2). Although cerebral edema is the commonestcause of abnormal neurology in a child with DKA, otherpossibilities such as hemorrhage, thrombosis, and/orintracranial infection should also be considered.
CASE REPORTS
An 8-year-old girl with T1DM was admitted to the hospitalwith fever, lethargy, anorexia, and vomiting. She wasdiagnosed three years ago and had been on insulin therapy(four daily injections) since. According to the history obtainedfrom her family, she had experienced nausea, vomiting, fever,lethargy, and headache for the last 24 hours. There was nohistory of previous neurological disease. On physicalexamination, her temperature was 38.1°C, pulse rate was 112beats/min, and respiratory rate was 30/min. She hadKussmaul respiration and was mildly dehydrated. Her historyrevealed no BCG vaccination. On neurological examination,lethargy and irritability were observed. There were no signs ofmeningeal irritation.
Laboratory Findings
[tbl:8]On initial[/tbl] laboratory examination, the patient’s hemoglobinlevel was 15.5 g/dL. C-reactive protein (CRP) level was 5mg/dL. Leukocyte count was 36 100/µL and differential countshowed a shift to the left with toxic granulations in neutrophils.Blood glucose level was 444 mg/dL. Metabolic acidosis waspresent with a pH of 7.19. The other biochemical values wereas follows: blood urea nitrogen level: 16 mg/dL, serumcreatinine: 0.86 mg/dL, sodium: 124 mmol/L, potassium: 3.6mmol/L, chloride: 102 mmol/L, serum osmolarity: 312mOsm/kg. Hemoglobin A1c was 8.1%. The patient’s urinewas strongly positive for sugar and ketones.
Management and Course
DKA treatment was started with intravenous fluids andinsulin infusion. In view of the presence of fever, elevated CRPand elevated white blood cell count with neutrophilia,antibiotics were also started. Plasma glucose was monitoredregularly. During the course of treatment, bradycardiadeveloped and the lethargic state progressed to stupor.Cranial computed tomography (CT) scan displayed cerebraledema. Lumbar puncture was not performed because ofcerebral edema. Antiedema therapy was started with mannitoland dexamethasone. After 24 hours of treatment withintravenous insulin, blood glucose level decreased to 186mg/dL. On the second day of treatment, diabetes insipidusoccurred, and thus, desmopressin was added to the therapy.With treatment, the metabolic parameters became normal,but the neurological status was not improved. Magneticresonance imaging (MRI) was performed in order to detectany central nervous system (CNS) infection and revealedstructures which were consistent with tuberculoma, such as isseen in tuberculous meningitis (Figure 1). After the resolutionof the cerebral edema on repeat MRI, a lumbar puncture wasperformed. In the cerebrospinal fluid (CSF) examination,glucose level was 129 mg/dL, protein: 44 mg/dL, andleukocyte count was 3 (2 lymphocytes, 1 polymorphonuclearleukocyte). CSF staining demonstrated acid- fast bacilli,implying a diagnosis of tuberculosis (Figure 2). The patientwas started on antituberculosis treatment (rifampicin,isoniazid, pyrazinamide, ethambutol).
DISCUSSION
DKA is a life-threatening acute complication of T1DM and ifnot diagnosed promptly and treated appropriately, may lead tofurther serious complications. DKA is commonly precipitated byinadequate insulin treatment or by an acute episode of infection.Infections were reported to be responsible for development ofDKA in 32% of the cases. The infections which contribute toDKA include bacteria (49%), viruses (49%), and tuberculosis(2%) (3). Intracranial infections (meningitis/encephalitis) may beassociated with DKA. DKA with tuberculous meningitis, herpessimplex type 2 encephalitis and group B streptococcalmeningitis have been reported (4,5,6).Cerebral edema is the most common cause of acuteneurological deterioration in DKA. However, in about 20% ofacute neurological episodes, other causes such as localizededema due to infection, hemorrhage or thromboses aredetected by CT scan or on postmortem examination (7,8).Infection is also the most common precipitating factor for DKAand the symptoms of DKA such as fever, headache,confusion, irritability are typical findings in intracranialinfections as well. Therefore, patients with fever, headache,confusion, aphasia, personality change, cloudingconsciousness and even coma should be further evaluated forintracranial infections (9).The diagnosis of tuberculous meningitis is difficult in itsearly stages. Nonspecific symptoms seen in the early stage ofthis condition such as fever, headache, irritability, drowsinessare also common in cerebral edema occurring in DKApatients. Therefore, in a type 1 diabetic patient, the symptomsof DKA could easily mask those of a concomitant stage Ituberculous meningitis, as in our patient. Our patientpresented in a state of moderate ketoacidosis with fever,Kussmaul respiration and symptoms of dehydration.Although metabolic control and blood glucose regulation wereachieved through proper fluid replacement and insulintherapy, the neurological condition of the patient deteriorated,which was suggestive of brain edema or CNS infection.Suspicion for presence of CNS infection also increased due tocontinuation of high fever, leukocytosis and high CRP levelsdespite the improved hydration. The CT scan showedenlarged ventricles and tuberculomas, indicating tuberculousmeningitis. Tuberculous meningitis is an infection that is caused by the hematogenous dissemination of tuberculosisbacilli from a primary focus. In diabetic patients with poormanagement, immune resistance of the organism is low,which facilitates development and rapid dissemination ofinfections like tuberculosis. Therefore, particularly in countrieswith a relatively high incidence of tuberculosis, routinefollow-up of diabetic patients should involve PPD tests andpulmonary radiographs.4In conclusion, when the neurological condition of thepatients with DKA deteriorates despite improved metabolicparameters, presence of concomitant CNS infections shouldbe seriously considered.