LETTER
TO
THE
EDITOR
Spontaneous Intracerebral Hemorrhage in a Pediatric Patient With Nephrotic Syndrome To the Editor: An 8-year-old girl was admitted to our department with a sudden onset of headache, unconsciousness, and fever. Five months ago, she was diagnosed with nephrotic syndrome (NS) and treated with oral prednisone (2 mg/ kg/d) and dipyridamole (3 mg/kg/d). Her blood pressure was within the normal fluctuation range during therapy. She had no history of stroke. On admission, her blood pressure was 172/120 mm Hg, heart rate was 136 beats per minute, axillary temperature was 39.2°C, and oxygen saturation was 97%. Physical examination showed the presence of typical Cushing’s appearance and obvious pitting edema. The pupils were equal and round but poorly reactive to light. Muscle tension was reduced in all 4 limbs. No pathologic reflexes were elicited. Laboratory studies revealed massive proteinuria (24-hour urine protein 150.8 mg/kg/d), hypoalbuminemia (serum albumin 22.2 g/L), hyperlipidemia (total cholesterol 10.3 mmol/L), and thrombocytopenia (platelet 879109/L). Other chemistries were C-reactive protein (CRP) 41 mg/L, blood urea nitrogen 5.87 mmol/L, creatinine 41 lmol/L, and uric acid 264 lmol/L. Estimated glomerular filtration rate derived from Schwartz’s equation was 131.5 mL/min/ 1.73 m2. Findings from a cranial computed tomographic (CT) scan demonstrated a hyperintense lesion measuring 192 cm within the left occipital lobe and a strand-like hematoma located in the right subdural space (Figure). The patient was diagnosed as having NS in combination with spontaneous intracerebral hemorrhage
(SICH). To minimize the damage from increased intracranial pressure (ICP) and reduce the risk of ventilatorassociated pneumonia, her head was elevated 30 degrees; a 20% mannitol solution was given at 1.5 g/kg intravenously over 30 minutes, and then followed by bolus doses of 0.5 g/kg if needed. During the first 2 days, we lowered her blood pressure to around 110/ 70 mm Hg with intravenous infusion of sodium nitroprusside (2 lg/kg/min). Ibuprofen (10 mg/kg) and physical cooling were also given to keep the axillary temperature below 38.5°C. On day 3, because the patient’s consciousness recovered from coma gradually and her axillary temperature and blood pressure were back to normal levels completely, we stopped intravenous antihypertensive therapy and started NS treatment with a corticosteroid. One month later, the hematoma disappeared on CT and the patient was discharged home with no neurological deficit. This young girl may have at least 4 risk factors for the presence of SICH, including hypoalbuminemia, elevated CRP level, antiplatelet therapy, and hypertension. First, hypoalbuminemia directly affects red cell deformability and possible endothelial function. In the Cox proportional hazards model conducted by Seliger and colleagues,1 a 1-g/dL decrement in serum albmin was associated with a 43% higher risk of stroke among patients with end-stage renal disease. Second, CRP, a nonspecific marker of inflammation, is described as a fundamental biomarker for endothelial dysfunction in patients with chronic kidney disease (CKD), and increases markedly over the 48- to 72-hour period
FIGURE. Cranial computed tomographic scan demonstrated a hyperintense lesion measuring 192 cm within the left occipital lobe and a strand-like hematoma located in the right subdural space (arrows).
doi: 10.1111/jch.12247
236
The Journal of Clinical Hypertension
Vol 16 | No 3 | March 2014
Letter to the Editor
following SICH.2 Third, in our patient, antiplatelet effects of dipyridamole prodominated on initial presentation but were outweighed by platelet dysfunction during the later clinical phases of NS, possibly contributing to SICH. Fourth, hypertension is by far the most important and prevalent risk factor for SICH. Conversely, hypertension may occur within the first few hours after SICH, even if these patients have normal blood pressure at their usual time.3 In the present case, blood pressure was within the normal fluctuation range during treatment for NS but significantly increased after SICH. In addition, SICH in our patient was located in the left occipital lobe and the right subdural space, instead of in the typical areas of hypertension-related hemorrhages such as in the basal ganglia and thalamus. Therefore, her hypertension was not a trigger but a compensatory symptom of SICH. Early recognition and diagnosis of SICH are essential. The classic clinical symptoms include headache, vomiting, hypertension, unconsciousness, fever, and neurological deficit; however, clinical symptoms alone are insufficient to reliably identify the exact positions of hematoma and differentiate SICH from other stroke subtypes. Thus, cranial CT is necessary to confirm the diagnosis. The beneficial and inexpensive medical approaches for SICH include minimizing the damages from both increased ICP and secondary hypertension and avoiding the antiplatelet therapy. Surgical indications for the removal of SICH remian controversial, particularly in patients with CKD. In a clinical report from Japan, neck-clipping surgery was performed in 11 adults with CKD, of whom 10 died.4 Taking into account that emergency surgical evacuation of hematoma did not improve the SICH outcome, operation was not undertaken in our patient. The prognosis for CKD patients with large SICH is poor. CKD is a strong, independent predictor of SICH mortality, and some hemorrhages may continue to grow
and expand over several hours after the first onset. According to data from multiple countries, the cumulative probability of death 1 year after SICH in CKD patients is twice that of non-CKD patients. A sudden increased ICP, hypertension, local tissue distortion and shear forces, and disruption of the normal cerebral anatomy can lead to a multifocal bleeding process and early hematoma growth.
CONCLUSIONS Fortunately, our patient recovered well following the above-mentioned comprehensive treatments. A high level of total cholesterol may provide a protective factor for SICH in our patient, because the data based on 750 autopsied men indicated that mean serum cholesterol was lower in patients whose deaths were caused by SICH.5 Peng Hu, PhD, MD; Xue Qi Zhao, MD; Bo Hu, MD; Ling Lu, MD; Fang Deng, PhD, MD; Li Ping Yuan, PhD, MD From the Department of Pediatrics, the First Affiliated Hospital of Anhui Medical University, Hefei, China References 1. Seliger SL, Gillen DL, Tirschwell D, et al. Risk factors for incident stroke among patients with end-stage renal disease. J Am Soc Nephrol. 2003;14:2623–2631. 2. Di Napoli M, Godoy DA, Campi V, et al. C-reactive protein in intracerebral hemorrhage: time course, tissue localization, and prognosis. Neurology. 2012;79:690–699. 3. Wang K, Li H, Liu W, et al. Seasonal variation in spontaneous intracerebral hemorrhage frequency in Chengdu, China, is independent of conventional risk factors. J Clin Neurosci. 2013;20:565–569. 4. Murakami M, Hamasaki T, Kimura S, et al. Clinical features and management of intracranial hemorrhage in patients undergoing maintenance dialysis therapy. Neurol Med Chir (Tokyo). 2004;44: 225–232. 5. Konishi M, Iso H, Komachi Y, et al. Associations of serum total cholesterol, different types of stroke, and stenosis distribution of cerebral arteries. The Akita Pathology Study. Stroke 1993;24:954–964.
The Journal of Clinical Hypertension
Vol 16 | No 3 | March 2014
237
TO
THE
EDITOR
Spontaneous Intracerebral Hemorrhage in a Pediatric Patient With Nephrotic Syndrome To the Editor: An 8-year-old girl was admitted to our department with a sudden onset of headache, unconsciousness, and fever. Five months ago, she was diagnosed with nephrotic syndrome (NS) and treated with oral prednisone (2 mg/ kg/d) and dipyridamole (3 mg/kg/d). Her blood pressure was within the normal fluctuation range during therapy. She had no history of stroke. On admission, her blood pressure was 172/120 mm Hg, heart rate was 136 beats per minute, axillary temperature was 39.2°C, and oxygen saturation was 97%. Physical examination showed the presence of typical Cushing’s appearance and obvious pitting edema. The pupils were equal and round but poorly reactive to light. Muscle tension was reduced in all 4 limbs. No pathologic reflexes were elicited. Laboratory studies revealed massive proteinuria (24-hour urine protein 150.8 mg/kg/d), hypoalbuminemia (serum albumin 22.2 g/L), hyperlipidemia (total cholesterol 10.3 mmol/L), and thrombocytopenia (platelet 879109/L). Other chemistries were C-reactive protein (CRP) 41 mg/L, blood urea nitrogen 5.87 mmol/L, creatinine 41 lmol/L, and uric acid 264 lmol/L. Estimated glomerular filtration rate derived from Schwartz’s equation was 131.5 mL/min/ 1.73 m2. Findings from a cranial computed tomographic (CT) scan demonstrated a hyperintense lesion measuring 192 cm within the left occipital lobe and a strand-like hematoma located in the right subdural space (Figure). The patient was diagnosed as having NS in combination with spontaneous intracerebral hemorrhage
(SICH). To minimize the damage from increased intracranial pressure (ICP) and reduce the risk of ventilatorassociated pneumonia, her head was elevated 30 degrees; a 20% mannitol solution was given at 1.5 g/kg intravenously over 30 minutes, and then followed by bolus doses of 0.5 g/kg if needed. During the first 2 days, we lowered her blood pressure to around 110/ 70 mm Hg with intravenous infusion of sodium nitroprusside (2 lg/kg/min). Ibuprofen (10 mg/kg) and physical cooling were also given to keep the axillary temperature below 38.5°C. On day 3, because the patient’s consciousness recovered from coma gradually and her axillary temperature and blood pressure were back to normal levels completely, we stopped intravenous antihypertensive therapy and started NS treatment with a corticosteroid. One month later, the hematoma disappeared on CT and the patient was discharged home with no neurological deficit. This young girl may have at least 4 risk factors for the presence of SICH, including hypoalbuminemia, elevated CRP level, antiplatelet therapy, and hypertension. First, hypoalbuminemia directly affects red cell deformability and possible endothelial function. In the Cox proportional hazards model conducted by Seliger and colleagues,1 a 1-g/dL decrement in serum albmin was associated with a 43% higher risk of stroke among patients with end-stage renal disease. Second, CRP, a nonspecific marker of inflammation, is described as a fundamental biomarker for endothelial dysfunction in patients with chronic kidney disease (CKD), and increases markedly over the 48- to 72-hour period
FIGURE. Cranial computed tomographic scan demonstrated a hyperintense lesion measuring 192 cm within the left occipital lobe and a strand-like hematoma located in the right subdural space (arrows).
doi: 10.1111/jch.12247
236
The Journal of Clinical Hypertension
Vol 16 | No 3 | March 2014
Letter to the Editor
following SICH.2 Third, in our patient, antiplatelet effects of dipyridamole prodominated on initial presentation but were outweighed by platelet dysfunction during the later clinical phases of NS, possibly contributing to SICH. Fourth, hypertension is by far the most important and prevalent risk factor for SICH. Conversely, hypertension may occur within the first few hours after SICH, even if these patients have normal blood pressure at their usual time.3 In the present case, blood pressure was within the normal fluctuation range during treatment for NS but significantly increased after SICH. In addition, SICH in our patient was located in the left occipital lobe and the right subdural space, instead of in the typical areas of hypertension-related hemorrhages such as in the basal ganglia and thalamus. Therefore, her hypertension was not a trigger but a compensatory symptom of SICH. Early recognition and diagnosis of SICH are essential. The classic clinical symptoms include headache, vomiting, hypertension, unconsciousness, fever, and neurological deficit; however, clinical symptoms alone are insufficient to reliably identify the exact positions of hematoma and differentiate SICH from other stroke subtypes. Thus, cranial CT is necessary to confirm the diagnosis. The beneficial and inexpensive medical approaches for SICH include minimizing the damages from both increased ICP and secondary hypertension and avoiding the antiplatelet therapy. Surgical indications for the removal of SICH remian controversial, particularly in patients with CKD. In a clinical report from Japan, neck-clipping surgery was performed in 11 adults with CKD, of whom 10 died.4 Taking into account that emergency surgical evacuation of hematoma did not improve the SICH outcome, operation was not undertaken in our patient. The prognosis for CKD patients with large SICH is poor. CKD is a strong, independent predictor of SICH mortality, and some hemorrhages may continue to grow
and expand over several hours after the first onset. According to data from multiple countries, the cumulative probability of death 1 year after SICH in CKD patients is twice that of non-CKD patients. A sudden increased ICP, hypertension, local tissue distortion and shear forces, and disruption of the normal cerebral anatomy can lead to a multifocal bleeding process and early hematoma growth.
CONCLUSIONS Fortunately, our patient recovered well following the above-mentioned comprehensive treatments. A high level of total cholesterol may provide a protective factor for SICH in our patient, because the data based on 750 autopsied men indicated that mean serum cholesterol was lower in patients whose deaths were caused by SICH.5 Peng Hu, PhD, MD; Xue Qi Zhao, MD; Bo Hu, MD; Ling Lu, MD; Fang Deng, PhD, MD; Li Ping Yuan, PhD, MD From the Department of Pediatrics, the First Affiliated Hospital of Anhui Medical University, Hefei, China References 1. Seliger SL, Gillen DL, Tirschwell D, et al. Risk factors for incident stroke among patients with end-stage renal disease. J Am Soc Nephrol. 2003;14:2623–2631. 2. Di Napoli M, Godoy DA, Campi V, et al. C-reactive protein in intracerebral hemorrhage: time course, tissue localization, and prognosis. Neurology. 2012;79:690–699. 3. Wang K, Li H, Liu W, et al. Seasonal variation in spontaneous intracerebral hemorrhage frequency in Chengdu, China, is independent of conventional risk factors. J Clin Neurosci. 2013;20:565–569. 4. Murakami M, Hamasaki T, Kimura S, et al. Clinical features and management of intracranial hemorrhage in patients undergoing maintenance dialysis therapy. Neurol Med Chir (Tokyo). 2004;44: 225–232. 5. Konishi M, Iso H, Komachi Y, et al. Associations of serum total cholesterol, different types of stroke, and stenosis distribution of cerebral arteries. The Akita Pathology Study. Stroke 1993;24:954–964.
The Journal of Clinical Hypertension
Vol 16 | No 3 | March 2014
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