Pediatr Nephrol (1996) 10:634-636 9 IPNA 1996 Pediatric Nephrology Brief report Cerebral vaseulitis in Henoeh-Sehiinlein purpura: a ease report with sequential magnetic resonance imaging Tae-Sun Ha 1 and Sang-Hoon Cha 2 I Department of Pediatrics, Chungbuk National University College of Medicine, Cheongju, Chungbuk, Korea 2 Department of Diagnostic Radiology, Chungbuk National University College of Medicine, Cheongju, Chungbuk, Korea Received May 25, 1995; received in revised form December 20, 1995; accepted December 22, 1995 Abstract. Neurological complications are rare during the course of Henoch-Schrnlein purpura (HSP). We report a 5-year-old girl with HSP who presented with seizures. Sequential magnetic resonance imaging and electroencephalography showed bilateral multifocal cerebral lesions initially, which gradually and completely resolved with clinical improvement. These lesions were compatible with the radiological pattern of the non-hemorrhagic vasculitic involvement of cerebral parenchyma. Key words: Henoch-Sch6nlein purpura - Cerebral vasculitis - Seizure - Magnetic resonance imaging Introduction Although Henoch-Sch6nlein purpura (HSP) may involve various organs, as a systemic vasculitis [1], there are only a few reports of central nervous system (CNS) complications [2-8] and the diagnosis of vasculitic involvement of the CNS is difficult. Hypertensive or uremic encephalopathy, metabolic abnormalities, electrolyte abnormalities, or cerebral vasculitis were suggested as the possible causes of the neurological manifestations [3, 7, 9, 10]. Magnetic resonance imaging (MRI) of the brain is the modality of choice for the evaluation of the CNS disease, and yet only one 10year-old boy who presented with visual loss has been documented and followed with MRI [7]. We report a CNS complication in a 5-year-old girl with HSP evaluated with MRI after several seizures of sudden onset during the course of the disease. Correspondence to: T-S Ha, Department of Pediatrics, College of Medicine, Chungbuk National University Hospital, Gaesin-dong 62, Heungduk-gu, Cheongju-si, 361-240 Chungbuk, Korea Case report A 5-year-old girl was transferred to our hospital from a local orthopedic clinic with a multiple purpuric rash and pain on her face and both legs and arms which had developed following a mild upper respiratory tract infection, 4 days prior to transfer. She complained of migrating arthralgia and tenderness over the wrists, the elbows, the ankles, and the back with mild periumbilical pain. There was no history of travel, recent immunization, or drug ingestion prior to the illness. The past and family medical history were unremarkable. On admission, she looked acutely ill with a blood pressure of 110/ 70 mmHg. Except for a limp and mild periumbilical tenderness, positive physical findings were limited to a multiple tender nonconfluent purpuric rash of variable size over the face, legs, and arms with intermittent central ischemic lesions and edema. Initial laboratory studies revealed a hematocrit of 37.8% with a reticulocyte count of 3.0%, platelet count of 387,000, and white blood cell count of 10,100/mm 3 with a normal differential count. Coagulation parameters were normal. Biochemical investigations revealed: blood urea nitrogen 9 mg/dl, creatinine 0.6 mg/dl, uric acid 4.4 mg/dl, calcium 10.1 mg/dl, phosphorus 4.8 mg/dl, protein 7.4 g/dl, albumin 4.0 g/dl, and cholesterol 176 mg/dl. The erythrocyte sedimentation rate was 34 mm/h and the C-reactive protein level was increased, but no anti-streptolysin 0 antibodies were detected. No anti-nuclear antibodies were detected and complement levels and immunoglobulin levels were normal. Urinalysis and 24-h urine protein excretion were within normal limits. Chest X-ray and an electrocardiogram were normal. Urine culture was negative. From the 3rd day of admission, a 2 mg/kg daily divided dose of prednisolone was prescribed for abdominal pain. On the 8th day of hospitalization, she developed sudden tonic and jerky movements of the left arm with eyeball deviation without cyanosis, which responded well to intravenous valium injections. The number of insults was four and each was of less than 10 min duration. Her blood pressure was 90/50 mmHg prior to the seizure, and at the time of seizure serum metabolic and electrolyte findings were all within normal limits. Immediate MRI of her head demonstrated bilateral, multiple lesions in both cortical and subcortical regions of variable size, which were interpreted as multifocal vasculitic manifestations of cerebral ischemia and/or infarction. There was no evidence of bleeding in or around the cerebral lesions (Fig. l a, b). An electroencephalogram (EEG) showed continuous, mild-to-moderateamplitude, delta slowings in all leads. Neuro-ophthamological evaluation was impossible due to the patient's lack of co-operatrion. She was started on intravenous methylprednisolone (1.5 mg/kg per day in three divided doses for 1 week) then changed to oral prednisolone. A skin biopsy was performed on the 9th day of hospitalization and revealed leukocytoclastic vasculitis. There was no recurrence of 635 Fig. 2. Follow-up MRI repeated 5 months later (0.5 T) shows complete resolution of the previous cerebral lesions except for that located in the periventricular white matter of the left frontal lobe Fig. 1. Initial brain magnetic resonance imaging (MRI) performed immediately after the onset of the first seizure, a Spin echo T2weighted axial images (0.5 T) demonstrate multiple, variable-sized and wedge-shaped, high signal intensity areas (arrows) in both cortical and subcortical areas of the occipital and the frontal lobes, suggesting the multifocal vasculitic nature of the disease associated with tissue ischemia, b Ti-weighted axial scans look normal. The parenchymal hemorrhage, if any, would present the abnormal signal intensity in either TI or T2-weighted images seizures and the girl remained in a relatively good condition other than mild abdominal pain and microscopic hematuria. During the following hospital days, the prednisolone was tapered. The follow-up MRI scans (2 weeks and 6 weeks after the initial MRI, respectively) demonstrated sequential improvement of the cerebral lesions. The last MRI scan (Fig. 2) performed 5 months after the onset demonstrated complete resolution of the cerebral lesions, except for a fixed left periventricular sequela. The EEG normalized and the microscopic hematuria also disappeared without any medication. Discussion Neurological involvement in HSP has been reported rarely [ 2 - 8 ] . Although the possible contribution of hypertensive or uremic encephalopathy, metabolic abnormalities, corticosteroid therapy, electrolyte abnormalities, or cerebral vasculitis has been suggested, the precise etiology of the neurological manifestations in each patient has not been identified [3, 7, 9, 10]. Our patient developed acute focal seizures when her blood pressure and serum chemistry and electrolytes were normal. Therefore, we could rule out the possibility of uremic or hypertensive encephalopathy. Moreover, brain MRI demonstrated multifocal non-hemorrhagic vasculitic involvement of the CNS. Hence we diagnosed cerebral vasculitis with HSP. MRI is much more sensitive than other imaging methods for CNS lesions, including vasculitis [7, 11], and can identify the lesions as having a high signal intensity ("being bright"). As it is non-invasive atraumatic, and without known specific complications, it appears to be the best diagnostic tool available for the detection of cerebral vasculitis. Glucocorticoids in the treatment of vasculitis act by inhibiting inflammation, but would enhance platelet activation, thrombus formation, and vasoconstriction [12]. Therefore, the effect of different doses, schedules, and mode of administration of steroids on the course of the cerebral vasculitis in this patient is not known. However, we suggest that oral steroid therapy is not as effective in the prevention and treatment of cerebral vasculitis in HSP as intravenous methylprednisolone. In conclusion, although cerebral vasculitis is rare in HSP, the possibility of neurological involvement should be considered in future cases with neurological manifestations and should be investigated with MRI. References 1. Allen DM, Diamond LK, Howell DA (1960) Anaphylactoid purpura in children (Henoch-Sch6nlein purpura). Am J Dis Child 99:833-854 2. Lewis IC, Philpott MG (1956) Neurologic complications in the Sch6nlein-Henoch syndrome. Arch Dis Child 31: 369-370 3. Aita JA (1973) Neurological manifestations of Henoch-Sch6nlein purpura. Nebr Med J 58:37 4. Ryder HG, Marcus J (1976) Henoch-Sch6nlein purpura. A case report. South Afr Med J 50:2005-2006 5. Ritter FJ, Seay AR, Lahey ME (1983) Peripheral mononeuropathy complicating anaphylactoid purpura. J Pediatr 103:77-78 6. Belman AL, Leicher CR, Moshe SL, Mezey AP (1985) Neurologic manifestations of Schoenlein-Henoch purpura: report of three cases and reviews of the literature. Pediatrics 75:687-692 636 7. Elinson P, Foster KW, Kaufman DB (1990) Magnetic resonance imaging of central neivous system vasculitis. A case report of Henoch-Schrnlein purpura. Acta Paediatr Scand 79:710-713 8. Ostergaard JR, Storm K (1991) Neurologic manifestations of Schrnlein-Henoch purpura. Acta Pediatr Scand 80:339-343 9. Gifford RW, Westbrook E (1974) Hypertensive encephalopathy: mechanisms, clinical features, and treatment. Prog Cardiovasc Dis 17:115-124 10. Moore PM, Cupps TR (1983) Neurological complications of vasculitis. Ann Neurol 14: 155-167 11. Miller DH, Ormerod IE, Gibson A, Du Boulay EP, Rudge P, McDonald WI (1987) MR brain scanning in patients with vasculit• differentiation from multiple sclerosis. Neuroradiology 29:226-231 12. Conn DL, Tompkins RB, Nichols WL (1988) Glucocorticoids in the management of vasculitis - a double edged sword? J Rheumatol 15:1181-1183 Literature abstract Kidney Int (1996) 49: 1413-1421 Growth promoting effects of growth hormone and IGF-I are additive in experimental uremia Gfibor T. Kovdcs, Jun Oh, J6zsef Kovdcs, Burkhard T'dnshoff,Ernst B. Hunziker, Jiirgen Zapf, and Otto Mehls Exogenous growth hormone (GH) stimulates the endogenous production of IGF-I and improves growth in uremia. We investigated whether exogenous IGF-I is also able to improve uremic growth failure in rats and whether the growth promoting effects of GH and IGF-I are additive. In female 150 g uremic (subtotal nephrectomy, NX) SpragueDawley rats, both rhGH in doses from 2 • 1.25 to 2 • 10 IU/kg bid s.c. and rhlGF-I in doses from 2 • 0.5 to 2 • 4.0 mg/kg bid s.c. caused a dose-dependent increase in weight gain and length gain. However, endogenous production of GH was suppressed by both agents. Peptide hormone treatment did not affect cumulative food intake, but significantly increased food efficiency ratio (weight gain/food intake). Concomitant s.c. treatment with maximally effective doses of rhGH ( 12 x 5 IU/kg bid) and of rhlGF-I (2 • 2 mg/kg bid) resulted in additive growth promoting effects in NX and pair-ed control (CO) animals during the observation period of 12 days. Cumulative length gain was 3.2• cm in solvent-treated NX-animals, 4.1 • cm with rhGH (+28% above solvent), 4.2-t-0.6 cm with rhlGF-I (+31%) and 4.9 • 0.5 cm with both peptides (+52%). The food efficiency ratio was 0.16+0.05 in solvent NX, 0.33+0.04 with rhGH (+106% above solvent), 0.23___0.02 with rhlGF-I (+44%), and 0.38 ___0.02 with both peptides (+138%). Histomorphometric analysis and measurements of length gain by fluorescence microscopy in the upper tibial metaphysis confirmed the growth promoting effects of both peptide hormones. The serum concentrations of IGF binding protein (BP)-4 (Western ligand blotting analysis) and of IGFBP-2 (immunoblot) were increased in uremic animals whereas IGFBP-3 was unchanged. Treatment with IGF-I and/or rhGH increased serum concentration of IGF-I but did not change the IGFBP pattern, rhlGF-I lowered blood glucose levels within one to two hours after injection. The effect was most pronounced during the first treatment day and declined thereafter. Concomitant treatment with rhGH attenuated the glucose lowering effect of rhlGF-I (glucose serum concentration at day one: 120 • 11 mg% in solvent NX, 50+21 mg% with rhlGF-I, 8 0 • mg% with both peptides). It is concluded that: (i) IGF-I is able to stimulate growth in NX animals but suppresses endogenous GH production in the long run; (ii) the concomitant treatment with IGF-I and GH has additive effects on gorwth; and (iii) concomitant treatment with rhGH prevents hypoglycemia that is noted with rhlGF-I alone.