Clinical and Imaging Characteristics of Arteriopathy Subtypes in Children with Arterial Ischemic Stroke: Results of the VIPS Study.

BACKGROUND AND PURPOSE: Childhood arteriopathies are rare but heterogenous, and difficult to diagnose and classify, especially by nonexperts. We quantified clinical and imaging characteristics associated with childhood arteriopathy subtypes to facilitate their diagnosis and classification in research and clinical settings. MATERIALS AND METHODS: The Vascular Effects of Infection in Pediatric Stroke (VIPS) study prospectively enrolled 355 children with arterial ischemic stroke (2010-2014). A central team of experts reviewed all data to diagnose childhood arteriopathy and classify subtypes, including arterial dissection and focal cerebral arteriopathy-inflammatory type, which includes transient cerebral arteriopathy, Moyamoya disease, and diffuse/multifocal vasculitis. Only children whose stroke etiology could be conclusively diagnosed were included in these analyses. We constructed logistic regression models to identify characteristics associated with each arteriopathy subtype. RESULTS: Among 127 children with definite arteriopathy, the arteriopathy subtype could not be classified in 18 (14%). Moyamoya disease (n = 34) occurred mostly in children younger than 8 years of age; focal cerebral arteriopathy-inflammatory type (n = 25), in children 8-15 years of age; and dissection (n = 26), at all ages. Vertigo at stroke presentation was common in dissection. Dissection affected the cervical arteries, while Moyamoya disease involved the supraclinoid internal carotid arteries. A banded appearance of the M1 segment of the middle cerebral artery was pathognomonic of focal cerebral arteriopathy-inflammatory type but was present in <25% of patients with focal cerebral arteriopathy-inflammatory type; a small lenticulostriate distribution infarct was a more common predictor of focal cerebral arteriopathy-inflammatory type, present in 76%. It remained difficult to distinguish focal cerebral arteriopathy-inflammatory type from intracranial dissection of the anterior circulation. We observed only secondary forms of diffuse/multifocal vasculitis, mostly due to meningitis. CONCLUSIONS: Childhood arteriopathy subtypes have some typical features that aid diagnosis. Better imaging methods, including vessel wall imaging, are needed for improved classification of focal cerebral arteriopathy of childhood.

Presumed pre- or perinatal arterial ischemic stroke: risk factors and outcomes.

A subgroup of children with arterial ischemic stroke in the pre- or perinatal period present with delayed diagnosis. We identified 22 children who met the following criteria: (1) normal neonatal neurological history, (2) hemiparesis and/or seizures first recognized after two months of age, and (3) computed tomography or magnetic resonance imaging showing remote cerebral infarct. Laboratory evaluations included protein C, protein S, antithrombin, activated protein C resistance screen (APCR), Factor V Leiden (FVL), prothrombin gene defect, methylene tetrahydrofolate reductase variant (MTHFR), anticardiolipin antibody (ACLA), and lupus anticoagulant. Not all children received all tests. Age at last visit ranged from 8 months to 16.5 years (median 4 years). Twelve were boys. Fourteen had left hemisphere infarcts. Median age at presentation was 6 months. Eighteen had gestational complications. Fourteen children had at least transient coagulation abnormalities (ACLA = 11, ACLA + APCR = 1, APCR = 2 with FVL + MTHFR = 1); six of these children had family histories suggestive of thrombosis. Cardiac echocardiogram was unremarkable in the 15 tested. Outcomes included persistent hemiparesis in 22; speech, behavior, or learning problems in 12; and persistent seizures in five, with no evidence of further stroke in any patient. The persistence and importance of coagulation abnormalities in this group need further study.

Neurologic outcome in survivors of childhood arterial ischemic stroke and sinovenous thrombosis.

Ischemic stroke during infancy and childhood has the potential for life-long morbidity. Information on the neurologic outcome of children who survive ischemic stroke is lacking. Children surviving ischemic stroke between January 1, 1995 and July 1, 1999 were prospectively followed. Neurologic deficit severity was based on the Pediatric Stroke Outcome Measure (PSOM) developed in this study and parental response to two recovery questions. Predictor variables for poor outcome were tested. One-hundred twenty-three children with arterial ischemic stroke and 38 with sinovenous thrombosis were followed for a mean of 2.1 years (range, 0.8 to 6.6 years). The primary outcome based on PSOM assessment was: normal, 37%; mild deficit, 20%; moderate deficit, 26%; and severe deficit, 16%. The secondary outcome was full recovery in 45% of patients, based on parental response. The primary and secondary outcome measures were moderately correlated (P < .001; K = 0.5). In bivariate analysis, arterial stroke type, male gender, age of at least 28 days, presence of associated neurologic disorders, and need for rehabilitation therapy after stroke were predictors of poor outcome (P < .05). Multivariate analysis showed that only arterial ischemic stroke, associated neurologic disorders, and presence of rehabilitation therapy were independent predictors of poor outcome (P < .02). Poor outcome in children after ischemic stroke is therefore frequent and more likely in the presence of arterial stroke, rehabilitation therapy, and associated neurologic disorders, which justifies clinical trials of treatment strategies in childhood ischemic stroke.

Fabry disease: immunocytochemical characterization of neuronal involvement.

Fabry disease is an X-linked glycosphingolipid storage disease caused by deficiency of alpha-galactosidase. Storage of globotriaosylceramide, also known as ceramide trihexoside, is maximal in blood vessels but also occurs in neurons. We performed neuropathological histochemical studies on the brains and spinal cords of 2 patients with confirmed Fabry disease. Luxol fast blue-positive deposits were found in blood vessels throughout the central and peripheral nervous system and within selected neurons in spinal cord and ganglia, brainstem, amygdala, hypothalamus, and entorhinal cortex. Regions adjacent to involved neuronal groups, including nucleus basalis, striatum, globus pallidus, and thalamus, were spared. Electron microscopy showed lamellar cytoplasmic neuronal inclusion bodies. Using a monoclonal antibody reactive with ceramide trihexoside, we found more extensive neuronal deposition than evident by Luxol-fast blue staining and new areas of neuronal storage in the spinal cord and cerebral cortex. Blood vessels throughout the nervous system were strongly immunoreactive. The highly selective pattern of neuronal involvement we found suggests that glycosphingolipid exposure, uptake, or catabolism varies greatly with respect to neuronal morphology and distribution. The degree of toxicity to neurons and the clinical significance of this neuronal storage remains to be defined.

Low dose ciclosporin from the early postoperative period yields potent immunosuppression after renal transplantation.

This study sought to determine if low doses of ciclosporin (CS) designed to give fasting serum levels of 50-100 ng/ml achieve effective immunosuppression when used from the early postoperative period after renal transplantation. Ninety-four primary renal transplant recipients were studied. Group 1 patients were treated with CS 100 ng/ml and prednisone (0.15 mg/kg/day). Group 2 patients received CS 50 ng/ml, prednisone (0.15 mg/kg/day) and azathioprine (1 mg/kg/day). These patients were compared to a control group of 26 patients (group 3) maintained on only prednisone and azathioprine. CS-treated patients suffered significantly fewer rejection episodes than control subjects (rejection episodes per patient in first year: group 1: 0.3 +/- SD 0.6; group 2: 0.7 +/- SD 0.7; group 3: 1.3 +/- SD 1.1, p less than 0.005). In addition, a greater number of CS-treated patients were completely free of rejection episodes during the first year posttransplant (group 1: 63%; group 2: 64%; group 3: 19%, p less than 0.005). Patient and graft survival were similar in all groups after 1 year (group 1: 92 and 92% respectively; group 2: 95 and 87% respectively; group 3: 96 and 85% respectively). These data suggest that the dose of CS required for effective immunosuppression in vivo is lower than has been previously thought.

Percutaneous needle biopsy of the transplanted kidney: technique and complications.

Over 11 1/2 years, 420 percutaneous needle biopsies were obtained from the transplanted kidneys of 205 patients at one institution. The procedure was performed by one nephrologist and 55 nephrology trainees. No limit was placed on the number of biopsies performed on one kidney, and the highest number was seven. The complications were macroscopic hematuria in 28 biopsies, prolonged hematuria (greater than 24 hours) in eight, transient anuria in five, and prolonged anuria requiring surgical intervention in one. Perinephric hematoma occurred in three patients; retroperitoneal hematoma led to compression of the iliac vein in one. None of these complications led to loss of the transplant. It is suggested that the freedom from serious complication is related to the safety of the technique and the precautions applied to preparation of the patient. These are described in detail.

Wegener's granulomatosis and the respiratory system.

Wegener's granulomatosis is a disease characterized by necrotizing vasculitis of the upper and lower respiratory tracts, necrotizing glomerulonephritis, and varying degrees of disseminated small vessel vasculitis. Patients can present to an otolaryngologist head and neck surgeon with ear, nose, throat, lung, orbit, salivary gland, or cutaneous lesions. The disease is variable in its presentation and progression. Tissue biopsies may be non-diagnostic even in the presence of active disease. Although the disease was rapidly fatal as recently at 1970, it can now be effectively treated. This paper reviews the diagnosis and management of Wegener's granulomatosis at a major university hospital between 1965 and 1979. during this period there was a significant evolution of treatment methods.

The arthropathy of maintenance intermittent peritoneal dialysis.

Among 61 patients undergoing maintenance peritoneal dialysis for an average of 20 months, 13 (21%) had a history of attacks of acute arthritis and 19 (31%) were found to have tender and often swollen joints. Deposits of calcium pyrophosphate dihydrate crystals in articular cartilage were identified in four patients and inflammation probably induced by hydroxyapatite crystals was noted in one. Periarticular calcification was observed in 12 patients and subperiosteal resorption of the phalanges in 20. The average calcium X phosphorus product was significantly higher (P < 0.025) in patients with a history of attacks of acute arthritis or with inflamed joints (58 +/- 12) than in those without (50 +/- 12). In the 19 patients whose treatment was changed to continuous ambulatory peritoneal dialysis there was a significant decrease (P < 0.025) in the calcium X phosphorus product but not in the proportion of patients with attacks of acute arthritis or with inflamed joints. The results indicate that articular complications are frequent among patients undergoing maintenance peritoneal dialysis and may be more common than with long-term hemodialysis.

A controlled trial evaluating intensive plasma exchange in renal transplant recipients.

Sixty patients have been entered into a controlled trial evaluating the use of intensive plasma exchange (IPE) in renal transplant recipients. During the first three months post-transplant, patients receive either conventional anti-rejection therapy alone (control group) or conventional anti-rejection therapy and IPE (IPE group) for all rejection episodes. Twenty percent of the grafts in the control group versus 10% in the IPE group have been lost to rejection (p = NS). The actual three month patient and graft survival in the control group (97% and 70%), respectively, is similar to the IPE group (94% and 80%), as is the one year actuarial graft and patient survival in the two groups. No statistically significant benefit of IPE has yet been demonstrated but the trend is encouraging and the complication rate sufficiently low so as to justify continuing the study.

Erythroleukemia in a renal transplant recipient.

A 53-year-old male developed acute erythroleukemia three years after renal transplantation. He had received three years of immunosuppressive therapy with azathioprine. A preleukemia phase associated with chromosome abnormalities was recognized. Azathioprine has been associated with chromosome abnormalities. The chronic stimulation of an abnormal erythroid clone by transplantation may have hastened the development of erythroleukemia.

Influence of exchange volume and dialysate flow rate on solute clearance in peritoneal dialysis.

To find the ideal dialysate flow rate and exchange volume for use in long-term peritoneal dialysis, 10 patients were studied over a period of 1.5 yr. Exchange volumes of 1 or 2 liters and dialysate flow rates of 1, 2, 3, 4, and 6 liters/hr were tested. Dextrose concentration remained constant at 1.5 g/100 ml. Peritoneal clearances for BUN, creatinine, and uric acid were calculated at 2, 5, 10, 15, and 20 hr during dialysis making a total of 120 clearances for each patient. All patients used a reverse osmosis automatic machine. The clearance of all three solutes tended to be higher with exchange volumes of 2 liters than they did with 1 liter; this trend was significant for BUN (P less than 0.025) and uric acid (P less than 0.025) but not for creatinine. There was a significant rise in clearance with increasing flow rates per hour for all solutes as shown in the following table. (Formula: see text), Since patients could not tolerate a flow rate of 6 liters/hr, we conclude that flow rate of 4 liters/hr with a 2-liter exchange will give maximum efficiency.

Visceral calcification and the CaXP product.

The authors studied the presence of visceral calcification as evidenced by the visceral uptake of bone-seeking radionuclides during the course of a bone scan among 22 patients with terminal renal failure maintained on dialysis, nine patients with hypercalcemia secondary to malignancy, and nine patients with primary hyperparathyroidism. Uptake by the lungs or stomach was observed in 11 renal failure patients (50%) and in four of those with malignancy and hypercalcemia (44%). None of the patients with primary hyperparathyroidism had evidence of visceral calcification. The serum CaXP product was significantly higher among those with visceral calcification than those without. The results of this study indicate that a CaXP product of 60 represents the saturation product of calcium phosphate in serum above which spontaneous precipitation of this salt may occur in such viscera as stomach and lungs.

Pregnancy in renal transplant recipients: report of two successful pregnancies in a patient with impaired renal function.

Pregnancy in renal transplant recipients is common and, in spite of several potential problems, overall maternal and fetal outcome has been good in patients with transplants that are functioning well. The presence of renal impairment or hypertension, or both, usually leads to complications, especially in the mother. A patient is described who had a baseline creatinine clearance of about 35 mL/min-1.73 m2 and two successful pregnancies. Renal function deteriorated in the 3rd trimester of the first pregnancy but was reversible; permanent loss of function occurred in the 3rd trimester of the second pregnancy. The potential fetal and maternal risks and details of management of pregnant transplant recipients are reviewed.