Evolution of MRI abnormalities in paediatric acute disseminated encephalomyelitis

Objective

Acute disseminating encephalomyelitis (ADEM) is an inflammatory demyelinating disease affecting the central nervous system and mainly occurs in young children. Children who initially presented with ADEM can be diagnosed with multiple sclerosis (MS) in case new non-encephalopathic clinical symptoms occur with new lesions on MRI at least three months after onset of ADEM. We aim to study the timing of MRI abnormalities related to the evolution of clinical symptoms in our Dutch paediatric ADEM cohort.

急性播散性脑脊髓炎合并抗接触蛋白关联蛋白2抗体自身免疫性脑炎1例报告

目的 探讨急性播散性脑脊髓炎(ADEM)合并抗接触蛋白关联蛋白2(Caspr 2)抗体自身免疫性脑炎的临床特征.方法 回顾分析1例ADEM合并抗Caspr2抗体自身免疫性脑炎患儿的临床资料.结果 患儿,女性,7岁10月龄,因发热伴精神差入院,病程中相继出现癫痫发作、嗜睡、昏迷、认知功能损害、精神性格改变、失眠、神经性疼...     

Acute urinary retention in a child with acute disseminated encephalomyelitis

Acute disseminated encephalomyelitis (ADEM) is an immune-mediated inflammatory demyelinating encephalomyelitis with often monosymptomatic abrupt onset, followed by multifocal neurologic symptomatology depending on lesion-site. Diagnosis is made on the basis of characteristic magnetic resonance imaging (MRI) signal alterations. ADEM is sensitive to steroid therapy, immunoglobulins and plasmapheresis, presents usually a monophasic course and disappears completely after 2 or 3 weeks. Resolution of MRI lesions appears usually within 6 months of presentation. We report on a 14-year-old male, admitted to our Emergency Unit because of fever and acute urinary retention with a normal neurological examination. Urinary tract ultrasonography and mictional cystography were normal; electrophysiology showed a mild involvement of the peripheral nervous system and brain and spine MRI revealed disseminated areas of increased signal on T2-weighted sequences suggestive of ADEM. Steroid therapy brought about clinical recovery in a few days. Resolution of lesions on MRI after 4 months and absence of relapses during four-year clinical follow-up confirmed definitive diagnosis. Our case is interesting because, to our knowledge, this is the first literature report with acute urinary retention as predominant symptom in monosymptomatic forms. Another peculiar feature is the absence of associated neurologic symptomatology despite MRI evidence of important brain and spine alterations.     

Calcineurin-inhibitor-induced pain syndrome after a second allogeneic bone marrow transplantation for a child with aplastic anemia

Abstract:  We report a 10-yr-old boy who developed CIPS after a second allogeneic BMT for severe aplastic anemia. He received the second BMT from the same HLA-matched sibling donor 16 months after the first BMT due to secondary graft failure. The preparative regimen for the second BMT consisted of fludarabine, cyclophosphamide, and anti-thymocyte globulin. Prophylaxis for acute GVHD was tacrolimus and oral PSL. Engraftment was achieved on day 15. On day 19, he suddenly complained of intermittent pain in the bilateral lower limbs. Electric shock-like pain continued for a few minutes in succession. This intractable pain was not ameliorated by various analgesic drugs including pentazocine. MRI demonstrated bone marrow edema with high T2 signal intensity in the femur. He was diagnosed as CIPS based on his symptoms and MRI findings. The trough concentration of tacrolimus (10.1 ng/mL) at the onset of CIPS was within the therapeutic range. Bouts of severe pain naturally resolved after day 43 without the discontinuation of tacrolimus. CIPS is a rare complication in HSCT. This is the first non-malignant, and the first pediatric, case who developed CIPS after HSCT.     

Lung transplantation in children following bone marrow transplantation: A multi‐center experience

Allogenic BMT has been successfully performed as a treatment for hematologic diseases with an expected long‐term survival. This survival is truncated by respiratory complications including airway obstruction especially BO. Chronic GVHD has been reported to precede almost all cases reported. LTx has become a therapeutic life‐saving option for patients with end‐stage lung disease that maybe offered for the treatment of GVHD. We report a multi‐center experience of pediatric LTx following BMT in 11 patients age‐ and gender‐matched with 11 controls who received LTx for end‐stage lung disease secondary to CF. Overall death was 36.4% over a follow‐up period of 19 months (range 3–36 months) for the cases and 27.3% for the control group followed for 17 months (range 8–32 months). Median FEV₁ one yr post‐transplant for the cases was 78% predicted compared with 67.3% predicted for the controls. The median for episodes of infection was comparable at a median of one episode per patient through the entire follow‐up period among both groups. Acute rejection episodes were significantly higher in the control group with a median of one episode per patient in the control group compared to none within the cases. Our data suggest that LTx may be a valuable therapeutic option for children with end‐stage lung disease post‐BMT with comparable survival outcome to that after LTx in children for other indications such as CF. Hospital stay was significantly longer in our case group. Infection rate was comparable between groups albeit type of infection varied. Significantly and of interest is that acute rejection episodes were non‐existent in these cases.     

De novo hepatocellular carcinoma post‐multivisceral transplantation in a child

De novo hepatocellular carcinoma (HCC) post‐transplantation in patients without viral hepatitis is extremely rare, with only three reported adult cases in the English literature. Here, we present a case of de novo HCC that developed in a 7‐year‐old female, who at 8 months of age received a liver, small bowel, spleen, and pancreas transplantation 6.5 years ago for gastroschisis and total parenteral nutrition (TPN)‐related cirrhosis. The post‐transplant course was complicated by Epstein‐Barr virus (EBV) infection, post‐transplant lymphoproliferative disease, and subsequent development of multifocal EBV‐associated post‐transplant smooth muscle tumors (EBV‐PTSMT) in the small bowel 1 year and 10 months after transplantation, respectively. This was managed by reducing immunosuppression with rituximab and EBV‐specific cytotoxic T‐cell therapy. She was noted to have a new lesion in her transplanted liver graft 6.5 years post‐transplantation that was diagnosed as HCC. The HCC was resected, and the patient remained clinically stable for 7 months. At that time, recurrence of the HCC was discovered on MRI. She passed away 6 months after. To the best of our knowledge, this is the first reported occurrence of de novo HCC post‐transplantation in the pediatric population that is unrelated to viral hepatitis in either recipient or donor.     

Fulminant form of acute disseminated encephalomyelitis in a child treated with mild hypothermia

We describe the case of a 3‐year‐old boy diagnosed with the fulminant form of acute disseminated encephalomyelitis (ADEM). He developed general fatigue, fever, drowsiness and difficulty in walking. He had extensive multiple high‐intensity lesions in the white matter of the cerebrum and cerebellum, which are typical findings of ADEM. He became comatose and developed decerebrate rigidity with severe brain edema despite high‐dose methylprednisolone therapy, and then was subjected to mild hypothermia therapy, and given i.v. immunoglobulin. The patient recovered remarkably with the sequela of only mild action tremor. The patient was considered to have acute hemorrhagic leukoencephalitis (AHLE), an extremely severe form of ADEM, in terms of the rapidly deteriorating clinical course and neuroimaging features. It was speculated that AHLE and ADEM might be a continuous disease spectrum. It is considered that the severe brain edema associated with ADEM or AHLE is a suitable indication for mild hypothermia therapy.     

Acute disseminated encephalomyelitis associated with herpes virus infection: a case report

Acute disseminated encephalomyelitis (ADEM) is a demyelinating disease of the central nervous system, also called post-infectious encephalitis; it is triggered by an autoimmune mechanism and follows an infection or a vaccination after a free interval of 2 to 30 days. We report a case of ADEM in a 4-year-old girl, who was diagnosed based on the data from a brain MRI, which revealed multiple demyelinization foci in the periventricular white matter, the semi-oval centers, and the thalamic regions, both bilaterally and symmetrically. The clinical course was characterized by complete recovery 10 days after steroid therapy. In the literature, more than the half of the patients treated for ADEM had a good prognosis, with recovery and no sequelae. Clinical improvement is generally noted in the hours or days following the initiation of treatment. However, in the most severe cases of ADEM, the most frequent neurological sequelae consist in focal deficiencies of the limbs and ataxia or visual disorders. Cognitive and behavioral disorders are noted in 6 to 50% of pediatric patients.     

Treatment of adrenoleukodystrophy with bone marrow transplantation

Three children with adrenoleukodystrophy (ALD) underwent allogeneic bone marrow transplantation (BMT) between 1992 and 1993. The first boy had attention deficits, marked neuropsychological deficits and widespread demyelination in the frontal lobes on MRI before transplantation. Four years later he has mentally deteriorated and the demyelination on MRI has progressed. The second boy had no symptoms but had white matter lesions on MRI when diagnosed. He was regularly followed with MRI and neuropsychological investigations until BMT 18 months later. A progress of the lesions was noted on the initial MRI investigations, and 4 months before BMT a worsening of deficits in attention and kinaesthetic praxis could be observed. He rapidly deteriorated after the transplantation and died 18 months later. Both PCR and in situ hybridization confirmed the presence of donor cells in the brain. The third boy had no symptoms but white matter lesions on MRI when diagnosed. The neuropsychological tests remained normal but a slight progress was observed on MRI just before transplantation. This boy is still healthy 3.5 years after BMT. BMT as treatment for ALD has to be considered very early, even in a child without symptoms but signs of demyelination on MRI, if a suitable donor is available.     

Acute disseminated encephalomyelitis (ADEM) after pertussis infection

Acute disseminated encephalomyelitis (ADEM) is an immune-mediated demyelinating disorder of the central nervous system which is usually precipitated by a viral infection or vaccination. A 3-month-old boy is reported who developed ADEM a week after full recovery from pertussis. MRI detected a high-intensity lesion extending from the pons to the mesencephalon, compatible with ADEM. Following the administration of intravenous immunoglobulins, the patient's clinical symptoms improved. This case report demonstrates that pertussis is capable of inducing an immune-mediated demyelinating disorder of the central nervous system.     

Evolución clínica de la forma hiperaguda de la encefalomielitis aguda desmielinizante

IntroductionAcute disseminated encephalomyelitis (ADEM) is an inflammatory disease that damages the white matter of the central nervous system. Its clinical course is monophasic and multifocal. The outcome is usually favourable. We report our experience in the management of the hyperacute form of ADEM.Patients and methodsA retrospective chart review was performed on five patients admitted in coma with a diagnosis of ADEM in the Paediatric Intensive Care Unit (PICU). We describe their epidemiological, clinical, microbiological, magnetic resonance imaging features and their treatment and outcomes.ResultsThe mean age was 5.2 years and all were male. None of them fulfilled radiologic criteria for acute haemorrhagic leukoencephalitis. At admission all patients were in a coma, and all were on controlled mechanical ventilation support. Before their admission all patients had fever. In all cases the time between the first neurological symptom and coma was ≤ 24 hours. The cerebrospinal fluid examination was abnormal in three patients, and in one case, oligoclonal bands were detected. The first brain magnetic resonance imaging (MRI) showed white matter and basal ganglia lesions in all patients, and in three cases the spinal medulla was affected by demyelination. All patients were treated with a course of high-dose methylprednisolone. Four patients were also treated with high-dose immunoglobulins, and one of them received plasmapheresis. Two patients died, and one patient had severe sequelae at discharge from the PICU. At discharge the lesions in the white matter were still present in the MRI. After nine months the three survivors had a Glasgow Outcome Scale score of five and no one relapsed.ConclusionsThere is a hyperacute clinical form of ADEM which has a high mortality rate. In the short term, the clinical improvement of hyperacute ADEM is not accompanied by a decrease of severity of the brain MRI.     

Bone marrow transplantation in cartilage-hair hypoplasia: Correction of the immunodeficiency but not of the chondrodysplasia

Abstract We diagnosed cartilagehair hypoplasia (CHH) in a female child with prenatal-onset short stature, metaphyseal chondrodysplasia, and severe combined immunodeficiency leading to recurrent, severe respiratory tract infections. The patient required several hospital admissions during her 1st year of life and failed to thrive in spite of antimicrobial therapy and hypercaloric nutrition. Bone marrow transplantation (BMT) from an HLA-identical sister was performed at age 16 months after conditioning with busulphan and cyclophosphamide, using 9×10⁸ nucleated bone marrow cells/kg body weight. Graft-versus-host disase prophylaxis consisted of cyclosporine and methotrexate. The post-transplantation period was uneventful. She developed full and sustained chimerism as demonstrated by DNA analysis of granulocytes and mononucleated cells on days 44, 69 and 455 post BMT. Cellular immunity was completely reconstituted at 4 months, humoral immunity at 15 months post BMT. The patient is alive and well 24 months post BMT without medication, but the radiological osseous changes persist, and longitudinal growth remains markedly below the 10th percentile for CHH standards; her height at age 3 years 4 months is 66 cm.Conslusions In this patient with unusually severe CHH, bone-marrow transplantation has fully corected the immune deficiency but has had no influence on the course of the chondrodysplasia.     

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??Objective??To describe the clinical features and neurologic outcome of acute disseminated encephalomyelitis??ADEM?? in children.Methods??A study on medical record and follow-up information of prospective efficacy was conducted in 68 children with ADEM. Results????1??The age of patients at onset ranged from 1 to 15.3 years?? with a median of 6.5 years??with the inpatients numbers increasing year by year. ??2??An infectious event preceded the onset of illness in 57.4% of patients?? and a vaccination event in 4.4% of patients?? while the others were cryptogenic. ??3??Clinical classification?? 42??61.8%??cases had presentations of the brain?? 18??26.4%??of the brain and spinal cord?? 8??11.8%??of the spinal cord?? the most common presenting symptoms were fever?? palsy?? seizures??changes in mental status ??extrapyramidal syndrome??consciousness impairment?? cognitive handicap?? sphincter muscle disturbance and ataxia and some patients appeared linguistic functional disturbance and cranial palsy. ??4??Increased IgG index and/or oligoclonal band positive were present in the cerebrospinal fluid of 77.2% of cases.??5?? prognosis?? ??near-future curative effect of corticosteroid treatment?? 55.9% of cases showed initiation effective in 3 days?? 26.5% in 7 days?? 17.6% after 1 week?? 48.5% of cases improved in 1 week?? and 11.2% improved spontaneously ??while one case died. ??prospective efficacy ?? 48 cases whose course was longer than one year and 20 cases less than one year course. At the end of follow-up?? 38 cases recovered?? 9 cases had disability??whose course longer than one year???? relapse was seen in 7 cases?? 8 cases were in follow-up??5 cases lost follow-up. Conclusion??ADEM in childhood often occur at the age of 3 to 12 years. The presenting symptoms are various and complicated?? the states of the illness vary from slight to severe and the course varies from short to long. Neuroimaging??especially brain MRI?? is extremely important in early diagnosis of ADEM when a patient presenting a polysymptomatic encephalopathy. Most children with ADEM present a good outcome in long-term follow-up?? some patients with severe condition recover after 6 months?? and a few have disability of nervous system.     

Acute disseminated encephalomyelitis associated with Mycoplasma pneumoniae infection

An 8 year old girl with acute disseminated encephalomyelitis (ADEM) is described. Elevated serum antibody titers suggested recent Mycoplasma pneumoniae infection. T2-weighted image of magnetic resonance imaging (MRI) disclosed multiple lesions of high signal intensity in bilateral basal ganglia and thalami as well as in the white matter. Postcontrast T1-weighted image revealed an enhanced lesion in the deep white matter. She showed rapid clinical improvement in response to corticosteroid therapy. The lesions had disappeared completely on MRI performed 10 weeks after the onset. ADEM is believed to be a demyelinating disorder of probable autoimmune etiology. MRI findings in this case may support the hypothesis that the primary pathological event is vascular injury and demyelination occurs only as a secondary phenomenon.     

Successful allogeneic unrelated bone marrow transplantation using reduced-intensity conditioning for the treatment of X-linked adrenoleukodystrophy in a one-yr-old boy

Abstract:  The childhood cerebral form of X-linked ALD is a demyelinating disorder of the central nervous system, which rapidly leads to total disability and death. Allogeneic stem cell transplantation benefits patients who show early evidence of the demyelination. We report here a one-yr-old boy with ALD who received HLA-matched unrelated BMT in an early stage of the disease after careful planning and observation since his birth. BMT was performed when MRI began to show slight signal intensity changes in the white matter of the brain. Pretransplant conditioning consisted of fludarabine, l -PAM and TBI (2 Gy). GVHD prophylaxis consisted of cyclosporine A and short-course methotrexate. The patient showed an uneventful BMT course with fast and stable engraftment. Following BMT, the plasma levels of VLCFA decreased gradually and MRI changes improved. The patient did not have any evidence of further neurological deterioration 22 months following the transplant. Although this is still a short follow-up, it has been shown that BMT should be considered when a child has a biochemical diagnosis and MRI findings of ALD without any neurological signs. RIST should be considered as a pretransplant conditioning for ALD.     

Improvement of native pulmonary alveolar proteinosis after contralateral single living‐donor lobar lung transplantation: A case report

PAP is a rare disease characterized by the accumulation of surfactant materials in the alveolar spaces due to the imbalance of surfactant homeostasis (production and clearance). We herein report a case of an 8‐year‐old girl who developed PAP after BMT from her mother for the treatment of DBA. The anemia was improved by BMT; however, respiratory dysfunction due to graft‐versus‐host disease gradually progressed. She eventually underwent right single LDLLT from her mother when she was 14 years old. A pathological examination of the excised lung confirmed the finding of diffuse bronchiolitis obliterans and unexpectedly revealed widespread alveolar proteinosis. Interestingly, the GGO of her native left lung on chest X‐ray was improved after LDLLT. We present the very unique clinical course of this patient and discuss the mechanisms underlying the development of PAP after BMT and its improvement after LDLLT from the same donor.     

Liver transplantation in an adolescent with acute liver failure from acute lymphoblastic leukemia

The most common identifiable causes of acute liver failure in pediatric patients are infection, drug toxicity, metabolic disease, and autoimmune processes. In many cases, the etiology of acute liver failure cannot be determined. Acute leukemia is an extremely rare cause of acute liver failure, and liver transplantation has traditionally been contraindicated in this setting. We report a case of acute liver failure in a previously healthy 15‐yr‐old male from pre‐B‐cell acute lymphoblastic leukemia. He underwent liver transplantation before the diagnosis was established, and has subsequently received chemotherapy for pre‐B‐cell acute lymphoblastic leukemia. He is currently alive 31 months post‐transplantation. The published literature describing acute lymphoblastic leukemia as a cause of acute liver failure is reviewed.     

Hypocellular acute myeloid leukemia treated with bone marrow transplantation

Hypocellular acute myeloid leukemia (AML) mainly occurs in elderly patients, and is extremely rare in childhood. There is still no established treatment for hypocellular AML. We report the case of an 11‐year‐old boy with hypocellular AML who was treated successfully with allogenic bone marrow transplantation (allo‐BMT). He presented with fever, pallor and pancytopenia. Bone marrow aspiration and biopsy confirmed a diagnosis of hypocellular AML. Although low‐dose cytarabine induced reduction of blasts, it did not lead to complete remission. He subsequently received myeloablative conditioning and allo‐BMT. Graft‐versus‐host disease (GVHD) prophylaxis included short‐course methotrexate and cyclosporine. Neutrophil engraftment (>5 × 10⁸/L) and platelet recovery (>10 × 10¹⁰/L) were achieved on days 13 and 27, respectively. He developed acute GVHD of the skin (grade 2), which responded well to treatment with prednisolone. He has remained in complete remission for 5 years since allo‐BMT. We consider allo‐BMT to be feasible for children with hypocellular AML.     

Post‐streptococcal acute glomerulonephritis associated with pneumococcal infection

Streptococcus pyogenes is the most common cause of post‐infectious glomerulonephritis. Described herein is the case of a 5‐year‐old girl with febrile post‐streptococcal acute glomerulonephritis (PSAGN) associated with pneumococcal bacteremia. The chief complaints were fever and macrohematuria without respiratory symptoms. Urinalysis indicated a protein level of 3+. Serological data showed elevated anti‐streptolysin O (ASO) and hypocomplementemia. Blood culture was positive for S. pneumoniae. Her acute renal failure was mild and improved over several days. Although PSAGN was confirmed by elevated ASO and transient hypocomplementemia, the clinical course was consistent with those of several reported cases of AGN associated with pneumococcal infection. To our knowledge, there have been few reports on the relationship between pneumococcal infection and the incidence of PSAGN. We suggest the hypothesis that pneumococcal infection itself could exaggerate the complement reaction leading to PSAGN. It is important to consider PSAGN associated with a microbial infection such as S. pneumoniae when faced with a febrile patient with AGN.     

Post‐varicella thrombocytopenic purpura

Aims: The aim of the study was to characterize the clinical course of post‐varicella idiopathic thrombocytopenic purpura (ITP) and to asses the risk of acquiring ITP after varicella infection. Methods: A retrospective study of all children diagnosed with ITP in a tertiary medical centre during 1998–2008. Findings were compared with the Intercontinental Childhood ITP Study Group database. The risk of acquiring ITP after a varicella infection was assessed. Results: Ten children were diagnosed with post‐varicella ITP. The incidence of post‐varicella ITP was 1.9% amongst children diagnosed with ITP and 1.1% amongst children hospitalized for varicella. ITP was diagnosed, on average, 8.5 days after the onset of the varicella rash. The female‐to‐male ratio was 1:1.5. The average minimal platelet count was 9.5 × 10⁹ platelets/L. Post‐varicella ITP had an acute course in 80% of cases and a chronic course in the remaining 20%. Bleeding episodes occurred in three patients. During the follow‐up period, 11 patients with previously diagnosed ITP developed varicella. The infection had no apparent affect on the platelet count of the children with acute ITP, but caused a relapse in 71% of the patients with chronic ITP. Conclusions: Post‐varicella ITP has similar clinical features and course to non‐varicella associated ITP. The calculated risk of ITP as a complication of varicella infections is approximately 1:25 000.