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Occult infarct with acute hemorrhagic stroke in juvenile diabetic ketoacidosis
Brain & Development 30 (2008) 91–93 www.elsevier.com/locate/braindev
Case report
Occult infarct with acute hemorrhagic stroke in juvenile diabetic ketoacidosis Jainn-Jim Lin
a,c
, Kuang-Lin Lin
a,*
, Huei-Shyong Wang a, Alex Mun-Ching Wong b, Shao-Hsuan Hsia c
a
b
Division of Pediatric Neurology, Department of Pediatrics, Chang Gung Children’s Hospital and Chang Gung Memorial Hospital, Chang Gung University College of Medicine, 5 Fu-Shin Street, Kwei-Shan, Taoyuan 333, Taiwan Division of Neuroradiology, Chang Gung Children’s Hospital and Chang Gung Memorial Hospital, Chang Gung University College of Medicine, 5 Fu-Shin Street, Kwei-Shan, Taoyuan 333, Taiwan c Division of Pediatric Critical and Emergency Medicine, Chang Gung Children’s Hospital and Chang Gung Memorial Hospital, Chang Gung University College of Medicine, 5 Fu-Shin Street, Kwei-Shan, Taoyuan 333, Taiwan Received 6 February 2007; received in revised form 11 May 2007; accepted 6 June 2007
Abstract Diabetes ketoacidosis (DKA) is one of the common complications of type I insulin-dependent diabetes mellitus. Neurological deterioration during an episode of DKA is usually assumed to be caused by cerebral edema and cerebral vascular accidents. However, hemorrhagic stroke is a very rare complication of juvenile DKA. We describe a girl who had newly diagnosed insulin-dependent diabetes mellitus with juvenile DKA developed intracerebral hemorrhage. 2007 Elsevier B.V. All rights reserved. Keywords: Pediatric hemorrhagic stroke; Juvenile diabetic ketoacidosis
1. Introduction
2. Case report
Type 1 diabetes mellitus is an autoimmune disease that affects thousands of children around the world. Diabetic ketoacidosis (DKA) is a well-recognized complication of type I insulin-dependent diabetes mellitus in children and adolescents. Several neurologic deficiencies associate with DKA include cerebral edema with increased intracranial pressure resulting in coma; partial and generalized seizures; and cerebrovascular occlusive disease resulting in motor and/or sensory dysfunction. Hemorrhagic stroke is a rare presentation of juvenile DKA. Here, we report a girl who had developed intracerebral hemorrhage secondary to juvenile DKA.
A 5-year-old girl who had previously been healthy, presented with fever up to 38 C and had been vomiting about 3–5 times a day for 2 days. No epigastric pain, polydipsia or secondary nocturnal enuresis was noted. The physician was informed that the girl had lost 7 kg of body weight. She was sent to a local hospital for immediate care. The initial assessment revealed the signs of tachypnea with Kussmaul’s respiration, tachycardia and moderate dehydration with an estimated fluid deficit of 10%. The laboratory data results showed severe degree of hyperglycemia (plasma glucose level: 414 mg/ dL) and acidosis (pH 7.293, bicarbonate level 4.6 mmol/L). The results of urinalysis revealed ketonuria and glucosuria. This girl with the diagnosis of DKA was then transferred to our pediatric intensive care unit.
*
Corresponding author. Tel.: +886 3 3281200x8200; fax: +886 3 3288957. E-mail address: [email protected] (K.-L. Lin). 0387-7604/$ - see front matter 2007 Elsevier B.V. All rights reserved. doi:10.1016/j.braindev.2007.06.001
92
J.-J. Lin et al. / Brain & Development 30 (2008) 91–93
After admission, we immediately initiated appropriate fluid resuscitation and insulin treatment with the use of the ‘‘two bags system’’. Furthermore, empiric antibiotics with cefazolin and gentamycin were prescribed. Fever subsided after admission. Her DKA was resolved 2 days after the admission at a point which a diabetic diet was introduced along with subcutaneous insulin therapy. At the ward, the blood sugar was thoroughly controlled within the range between 200 and 250 mg/dL. The systolic blood pressure ranged from 93 to 118 mmHg. On day 7 of admission, physical and neurologic examinations showed right central facial palsy and right hemiplegia with a positive Babinski sign on the right side. Magnetic resonance imaging (MRI) and magnetic resonance angiography (MRA) of the brain performed on day 11, showed a 2.1 · 2.4 · 2.1 cm resolving hematoma in the left thalamus (Fig. 1). Brain MRA confirmed no traces of the associated vascular anomaly. There was no history of trauma. The platelet counts (295,000/lL), coagulation profile and prothrombotic studies (prothrombin time 15 s, activated partial thromboplastin time 45 s, D-dimer 725 ng/mL, fibrinogen 233 mg/dL, protein C 108%, protein S 119.8%) were normal. Homocysteine level was 5.0 lmol/L and the results of echocardiography showed no specific findings and no associated congenital heart disease was evident. Blood culture yielded negative findings. Intensive rehabilitation therapy and supportive treatment were started, and the insulin treatment was contin-
ued. A period of 8 weeks after the commencement of the above-mentioned therapy, she could walk stably with normal upper limbs movement. A year after the incidence of stroke, the patient did not develop motor deficit but only presented very mild learning difficulties.
3. Discussion DKA is one of the common complications of type I insulin-dependent diabetes mellitus in children and adolescents. Optimal management of juvenile DKA requires judicious correction of dehydration and metabolic abnormalities, and administration of insulin is also essential. Several neurologic deficiencies have been associated with DKA, including cerebral edema with increased intracranial pressure resulting in coma; partial and generalized seizures; and cerebrovascular occlusive disease resulting in motor and/or sensory dysfunction [1]. Neurological deterioration during an episode of DKA is usually assumed to be caused by cerebral edema. Early signs and symptoms of cerebral edema include headache, confusion, drowsiness or unexplained changes in heart rate, blood pressure and respiratory pattern. Therefore, patients should have their neurological status closely monitored for at least 48 h after the surfacing of the above mentioned symptoms. Intracerebral arterial or sinus venous thrombosis may also cause acute neurological deterioration in children with DKA [2]. Carl et al. reported the increased von
Fig. 1. MRI of the brain shows a resolving hematoma in the left thalamus. (a) Axial T1 weighted image (TR/TE = 450/12 ms) shows central hyperintensity and peripheral hypointensity in the hematoma. (b) On axial T2 weight image (TR/TE = 3600/90 ms), the hematoma shows central hypointensity and peripheral hyperintensity.
J.-J. Lin et al. / Brain & Development 30 (2008) 91–93
Willebrand factor (vWF) and the decreased levels of protein C activity and free protein S during DKA and its treatment. This supported the idea that DKA and its treatment could put the patients in a prothrombotic state and activate the vascular endothelium, which in turn predispose the patients to vascular thrombosis [3]. This condition is thought to be a risk factor for small and lacunar infarcts. Otherwise, central venous thrombosis can arise as an isolated entity or in association with an underlying systemic condition such as dehydration, sepsis, malignancy, or trauma. However, intracerebral hemorrhages are less frequent in pediatric diabetic patients. As far as we are aware, the association between juvenile DKA and intracerebral hemorrhage is unknown. Large hematoma associated with cerebral edema was reported in an 11 year-old girl who had a brain computed tomography (CT) imaging test on day 4. It was then suggested that the pathophysiology of the lesions might have been due to a hypotensive episode resulting in watershed infarcts with subsequent softening and secondary hemorrhage [1]. Another report described multiple cerebral edema associated cerebral hematomas in 3 children. The characteristic findings on CT and MRI of the brain included hemorrhagic infarctions of the thalami, basal ganglia and lentiform nuclei [4,5]. In a case-control study of 41 patients with a hemorrhagic infarct, Beghi and colleagues reported that 31% of diabetics had hemorrhagic conversion of the infarcts compared to 18% of stroke patients without a history of diabetes [6]. In addition, hyperglycemia and acidosis could enhance endothelial damage with subsequent extravasation of red blood cells through the leaky vessels [7]. Although the exact mechanism by which DKA induces cerebral bleeding has not been clear, the combination of hyperglycemia, acidosis and hemorrhagic transformation of cerebral infarcts secondary to hypotension, cerebral edema or venous thrombosis could be the possible mechanism. Although prothrombotic study of this particular case was within normal limits, dehydration secondary to DKA might contribute to the development of venous thrombosis. The hemorrhagic event might be secondary to cerebral infarct induced by venous thrombosis. The initial presentation of pediatric stroke can be subtle, with nonspecific changes in behavior, new-onset seizures or altered level of consciousness. Asymptomatic or silent infarcts are believed to occur more frequently in diabetes subjects [8]. Patients suspected of having central nervous system (CNS) complications should be treated
93
in a pediatric intensive care unit. Furthermore, intensive and prompt neurological imaging studies (Brain CT or MRI, or both) are also critical to look for evidence of cerebral edema or other intracranial pathologies. Although the patient revealed no apparent neurologic symptoms during the first 7 days after the occurrence of a DKA episode, the initial presentation of ischemic stroke could be subtle. During this silent period, hyperglycemia status induced secondary hemorrhagic transformation of cerebral infarcts. In summary, several key clinical issues should be emphasized. Firstly, DKA is a serious condition which could result in coma or even death if it is not treated appropriately. Precise replacement of insulin, fluids, glucose and electrolytes is essential. Secondly, although neurological deterioration in children with DKA is more likely to be due to cerebral edema, clinicians must consider the possibility of the presence of hemorrhage stroke in the differential diagnosis due to the prothrombotic tendency in these children. Finally, a high index of suspicion and early recognition of CNS complications in DKA is required for prompt initiation of therapy and the ensuing optimization of treatment outcomes.
References [1] Atluru VL. Spontaneous intracerebral hematomas in juvenile diabetic ketoacidosis. Pediatr Neurol 1986;2:167–9. [2] Keane S, Gallagher A, Ackroyd S, McShane MA, Edge JA. Cerebral venous thrombosis during diabetic ketoacidosis. Arch Dis Child 2002;86:204–5. [3] Carl GF, Hoffman WH, Passmore GG, Truemper EJ, Lightsey AL, Cornwell PE, et al. Diabetic ketoacidosis promotes a prothrombotic state. Endocr Res 2003;29:73–82. [4] Rogers B, Sills I, Cohen M, Seidel FG. Diabetic ketoacidosis. Neurologic collapse during treatment followed by severe developmental morbidity. Clin Pediatr 1990;29:451–6. [5] Kanter RK, Oliphant M, Zimmerman JJ, Stuart MJ. Arterial thrombosis causing cerebral edema in association with diabetic ketoacidosis. Crit Care Med 1987;15:175–6. [6] Beghi E, Bogliun G, Cavaletti G, Sanguineti I, Tagliabue M, Agostoni F, et al. Hemorrhagic infarction: risk factors, clinical and tomographic features, and outcome. A case-control study. Acta Neurol Scand 1989;80:226–31. [7] Broderick JP, Hagen T, Brott T, Tomsick T. Hyperglycemia and hemorrhagic transformation of cerebral infarcts. Stroke 1995;26:484–7. [8] Jorgensen HS, Nakayama H, Raaschou HO, Gam J, Olsen TS. Silent infarction in acute stroke patients. Prevalence, localization, risk factors, and clinical significance: the copenhagen stroke study. Stroke 1994;25:97–104.
Case report
Occult infarct with acute hemorrhagic stroke in juvenile diabetic ketoacidosis Jainn-Jim Lin
a,c
, Kuang-Lin Lin
a,*
, Huei-Shyong Wang a, Alex Mun-Ching Wong b, Shao-Hsuan Hsia c
a
b
Division of Pediatric Neurology, Department of Pediatrics, Chang Gung Children’s Hospital and Chang Gung Memorial Hospital, Chang Gung University College of Medicine, 5 Fu-Shin Street, Kwei-Shan, Taoyuan 333, Taiwan Division of Neuroradiology, Chang Gung Children’s Hospital and Chang Gung Memorial Hospital, Chang Gung University College of Medicine, 5 Fu-Shin Street, Kwei-Shan, Taoyuan 333, Taiwan c Division of Pediatric Critical and Emergency Medicine, Chang Gung Children’s Hospital and Chang Gung Memorial Hospital, Chang Gung University College of Medicine, 5 Fu-Shin Street, Kwei-Shan, Taoyuan 333, Taiwan Received 6 February 2007; received in revised form 11 May 2007; accepted 6 June 2007
Abstract Diabetes ketoacidosis (DKA) is one of the common complications of type I insulin-dependent diabetes mellitus. Neurological deterioration during an episode of DKA is usually assumed to be caused by cerebral edema and cerebral vascular accidents. However, hemorrhagic stroke is a very rare complication of juvenile DKA. We describe a girl who had newly diagnosed insulin-dependent diabetes mellitus with juvenile DKA developed intracerebral hemorrhage. 2007 Elsevier B.V. All rights reserved. Keywords: Pediatric hemorrhagic stroke; Juvenile diabetic ketoacidosis
1. Introduction
2. Case report
Type 1 diabetes mellitus is an autoimmune disease that affects thousands of children around the world. Diabetic ketoacidosis (DKA) is a well-recognized complication of type I insulin-dependent diabetes mellitus in children and adolescents. Several neurologic deficiencies associate with DKA include cerebral edema with increased intracranial pressure resulting in coma; partial and generalized seizures; and cerebrovascular occlusive disease resulting in motor and/or sensory dysfunction. Hemorrhagic stroke is a rare presentation of juvenile DKA. Here, we report a girl who had developed intracerebral hemorrhage secondary to juvenile DKA.
A 5-year-old girl who had previously been healthy, presented with fever up to 38 C and had been vomiting about 3–5 times a day for 2 days. No epigastric pain, polydipsia or secondary nocturnal enuresis was noted. The physician was informed that the girl had lost 7 kg of body weight. She was sent to a local hospital for immediate care. The initial assessment revealed the signs of tachypnea with Kussmaul’s respiration, tachycardia and moderate dehydration with an estimated fluid deficit of 10%. The laboratory data results showed severe degree of hyperglycemia (plasma glucose level: 414 mg/ dL) and acidosis (pH 7.293, bicarbonate level 4.6 mmol/L). The results of urinalysis revealed ketonuria and glucosuria. This girl with the diagnosis of DKA was then transferred to our pediatric intensive care unit.
*
Corresponding author. Tel.: +886 3 3281200x8200; fax: +886 3 3288957. E-mail address: [email protected] (K.-L. Lin). 0387-7604/$ - see front matter 2007 Elsevier B.V. All rights reserved. doi:10.1016/j.braindev.2007.06.001
92
J.-J. Lin et al. / Brain & Development 30 (2008) 91–93
After admission, we immediately initiated appropriate fluid resuscitation and insulin treatment with the use of the ‘‘two bags system’’. Furthermore, empiric antibiotics with cefazolin and gentamycin were prescribed. Fever subsided after admission. Her DKA was resolved 2 days after the admission at a point which a diabetic diet was introduced along with subcutaneous insulin therapy. At the ward, the blood sugar was thoroughly controlled within the range between 200 and 250 mg/dL. The systolic blood pressure ranged from 93 to 118 mmHg. On day 7 of admission, physical and neurologic examinations showed right central facial palsy and right hemiplegia with a positive Babinski sign on the right side. Magnetic resonance imaging (MRI) and magnetic resonance angiography (MRA) of the brain performed on day 11, showed a 2.1 · 2.4 · 2.1 cm resolving hematoma in the left thalamus (Fig. 1). Brain MRA confirmed no traces of the associated vascular anomaly. There was no history of trauma. The platelet counts (295,000/lL), coagulation profile and prothrombotic studies (prothrombin time 15 s, activated partial thromboplastin time 45 s, D-dimer 725 ng/mL, fibrinogen 233 mg/dL, protein C 108%, protein S 119.8%) were normal. Homocysteine level was 5.0 lmol/L and the results of echocardiography showed no specific findings and no associated congenital heart disease was evident. Blood culture yielded negative findings. Intensive rehabilitation therapy and supportive treatment were started, and the insulin treatment was contin-
ued. A period of 8 weeks after the commencement of the above-mentioned therapy, she could walk stably with normal upper limbs movement. A year after the incidence of stroke, the patient did not develop motor deficit but only presented very mild learning difficulties.
3. Discussion DKA is one of the common complications of type I insulin-dependent diabetes mellitus in children and adolescents. Optimal management of juvenile DKA requires judicious correction of dehydration and metabolic abnormalities, and administration of insulin is also essential. Several neurologic deficiencies have been associated with DKA, including cerebral edema with increased intracranial pressure resulting in coma; partial and generalized seizures; and cerebrovascular occlusive disease resulting in motor and/or sensory dysfunction [1]. Neurological deterioration during an episode of DKA is usually assumed to be caused by cerebral edema. Early signs and symptoms of cerebral edema include headache, confusion, drowsiness or unexplained changes in heart rate, blood pressure and respiratory pattern. Therefore, patients should have their neurological status closely monitored for at least 48 h after the surfacing of the above mentioned symptoms. Intracerebral arterial or sinus venous thrombosis may also cause acute neurological deterioration in children with DKA [2]. Carl et al. reported the increased von
Fig. 1. MRI of the brain shows a resolving hematoma in the left thalamus. (a) Axial T1 weighted image (TR/TE = 450/12 ms) shows central hyperintensity and peripheral hypointensity in the hematoma. (b) On axial T2 weight image (TR/TE = 3600/90 ms), the hematoma shows central hypointensity and peripheral hyperintensity.
J.-J. Lin et al. / Brain & Development 30 (2008) 91–93
Willebrand factor (vWF) and the decreased levels of protein C activity and free protein S during DKA and its treatment. This supported the idea that DKA and its treatment could put the patients in a prothrombotic state and activate the vascular endothelium, which in turn predispose the patients to vascular thrombosis [3]. This condition is thought to be a risk factor for small and lacunar infarcts. Otherwise, central venous thrombosis can arise as an isolated entity or in association with an underlying systemic condition such as dehydration, sepsis, malignancy, or trauma. However, intracerebral hemorrhages are less frequent in pediatric diabetic patients. As far as we are aware, the association between juvenile DKA and intracerebral hemorrhage is unknown. Large hematoma associated with cerebral edema was reported in an 11 year-old girl who had a brain computed tomography (CT) imaging test on day 4. It was then suggested that the pathophysiology of the lesions might have been due to a hypotensive episode resulting in watershed infarcts with subsequent softening and secondary hemorrhage [1]. Another report described multiple cerebral edema associated cerebral hematomas in 3 children. The characteristic findings on CT and MRI of the brain included hemorrhagic infarctions of the thalami, basal ganglia and lentiform nuclei [4,5]. In a case-control study of 41 patients with a hemorrhagic infarct, Beghi and colleagues reported that 31% of diabetics had hemorrhagic conversion of the infarcts compared to 18% of stroke patients without a history of diabetes [6]. In addition, hyperglycemia and acidosis could enhance endothelial damage with subsequent extravasation of red blood cells through the leaky vessels [7]. Although the exact mechanism by which DKA induces cerebral bleeding has not been clear, the combination of hyperglycemia, acidosis and hemorrhagic transformation of cerebral infarcts secondary to hypotension, cerebral edema or venous thrombosis could be the possible mechanism. Although prothrombotic study of this particular case was within normal limits, dehydration secondary to DKA might contribute to the development of venous thrombosis. The hemorrhagic event might be secondary to cerebral infarct induced by venous thrombosis. The initial presentation of pediatric stroke can be subtle, with nonspecific changes in behavior, new-onset seizures or altered level of consciousness. Asymptomatic or silent infarcts are believed to occur more frequently in diabetes subjects [8]. Patients suspected of having central nervous system (CNS) complications should be treated
93
in a pediatric intensive care unit. Furthermore, intensive and prompt neurological imaging studies (Brain CT or MRI, or both) are also critical to look for evidence of cerebral edema or other intracranial pathologies. Although the patient revealed no apparent neurologic symptoms during the first 7 days after the occurrence of a DKA episode, the initial presentation of ischemic stroke could be subtle. During this silent period, hyperglycemia status induced secondary hemorrhagic transformation of cerebral infarcts. In summary, several key clinical issues should be emphasized. Firstly, DKA is a serious condition which could result in coma or even death if it is not treated appropriately. Precise replacement of insulin, fluids, glucose and electrolytes is essential. Secondly, although neurological deterioration in children with DKA is more likely to be due to cerebral edema, clinicians must consider the possibility of the presence of hemorrhage stroke in the differential diagnosis due to the prothrombotic tendency in these children. Finally, a high index of suspicion and early recognition of CNS complications in DKA is required for prompt initiation of therapy and the ensuing optimization of treatment outcomes.
References [1] Atluru VL. Spontaneous intracerebral hematomas in juvenile diabetic ketoacidosis. Pediatr Neurol 1986;2:167–9. [2] Keane S, Gallagher A, Ackroyd S, McShane MA, Edge JA. Cerebral venous thrombosis during diabetic ketoacidosis. Arch Dis Child 2002;86:204–5. [3] Carl GF, Hoffman WH, Passmore GG, Truemper EJ, Lightsey AL, Cornwell PE, et al. Diabetic ketoacidosis promotes a prothrombotic state. Endocr Res 2003;29:73–82. [4] Rogers B, Sills I, Cohen M, Seidel FG. Diabetic ketoacidosis. Neurologic collapse during treatment followed by severe developmental morbidity. Clin Pediatr 1990;29:451–6. [5] Kanter RK, Oliphant M, Zimmerman JJ, Stuart MJ. Arterial thrombosis causing cerebral edema in association with diabetic ketoacidosis. Crit Care Med 1987;15:175–6. [6] Beghi E, Bogliun G, Cavaletti G, Sanguineti I, Tagliabue M, Agostoni F, et al. Hemorrhagic infarction: risk factors, clinical and tomographic features, and outcome. A case-control study. Acta Neurol Scand 1989;80:226–31. [7] Broderick JP, Hagen T, Brott T, Tomsick T. Hyperglycemia and hemorrhagic transformation of cerebral infarcts. Stroke 1995;26:484–7. [8] Jorgensen HS, Nakayama H, Raaschou HO, Gam J, Olsen TS. Silent infarction in acute stroke patients. Prevalence, localization, risk factors, and clinical significance: the copenhagen stroke study. Stroke 1994;25:97–104.