Anti-basal ganglia antibodies: a possible diagnostic utility in idiopathic movement disorders?

BACKGROUND: The spectrum of post-streptococcal brain disorders includes chorea, tics, and dystonia. The proposed mediators of disease are anti-basal ganglia (neuronal) antibodies (ABGA). AIM: To evaluate ABGA as a potential diagnostic marker in a cohort of UK post-streptococcal movement disorders. METHODS: Forty UK children presenting with movement disorders associated with streptococcal infection were recruited. ABGA was measured using ELISA and Western immunoblotting. To determine ABGA specificity and sensitivity, children with neurological diseases (n = 100), children with uncomplicated streptococcal infection (n = 40), and children with autoimmune disease (n = 50) were enrolled as controls. RESULTS: The mean ELISA result was increased in the post-streptococcal movement disorder group compared to all controls and derived a sensitivity of 82.4% and specificity of 79%. The Western immunoblotting method to detect ABGA derived a sensitivity and specificity of 92.5% and 94.7% respectively. There was common binding to basal ganglia antigens of 40, 45, and 60 kDa. Immunofluorescence localised the antibody binding to basal ganglia neurones. CONCLUSION: ABGA appears to be a potentially useful diagnostic marker in post-streptococcal neurological disorders. Western immunoblotting appears to be the preferred method due to good sensitivity and specificity and the ability to test several samples at once.     

Childhood infections in the tropical north of Australia

Abstract : In the tropical north of Australia there are high rates of infections in Aboriginal children living in remote communities. In addition to the burden of respiratory infections, diarrhoeal disease and skin sepsis, there are high rates of acute rheumatic fever, outbreaks of poststreptococcal glomerulonephritis and gonococcal conjunctivitis, endemic trachoma and various intestinal parasites. A number of infections generally restricted to the tropics are also present and can cause disease in both indigenous and non-indigenous children. These include melioidosis, Murray Valley encephalitis and dengue on the east coast. With global warming, these infections may become more common and more widespread within Australia and the potential for establishment of introduced infections such as Japanese encephalitis and malaria may increase.     

Typhoid glomerulonephritis.

15 patients with typhoid glomerulonephritis were studied and compared with a group of children with poststreptococcal nephritis. Useful criteria distinguishing the two diseases are given. The diseases may present in a similar manner and therefore it is important to remember typhoid as a cause of glomerulonephritis in endemic areas or in patients travelling from endemic areas.     

Acute poststreptococcal glomerulonephritis: an update

PURPOSE OF REVIEW: Acute poststreptococcal glomerulonephritis, the most common form of acute glomerulonephritis in children, continues to be a major concern worldwide. This review summarizes the recent advances in the pathogenesis, host susceptibility factors, diverse clinical presentations, and treatment of the condition. RECENT FINDINGS: Several recent advances have been made in identifying streptococcal antigens that may play a pathogenic role in acute poststreptococcal glomerulonephritis. Nephritis-associated streptococcal plasmin receptor and streptococcal pyrogenic exotoxin B are currently considered major putative nephritogens. Host susceptibility factors including HLA-DRB1*03011 have been found at a higher frequency in acute poststreptococcal glomerulonephritis patients than in healthy controls. Reversible posterior leukoencephalopathy and autoimmune hemolytic anemia are newly reported clinical associations with the disease. Studies from developing countries question whether the outcome is always benign. Treatment remains mostly conservative; however, controversy exists over the use of aggressive therapy with poor prognostic factors. SUMMARY: Severe group A streptococcal disease including acute poststreptococcal glomerulonephritis remains a cause of morbidity and mortality in developing countries and among impoverished populations. Various reports on the diverse clinical manifestations that can be associated with the condition will aid physicians in prompt diagnosis and intervention, while studies focusing on better understanding of immunopathogenesis may facilitate vaccine development and prevention.     

Mesangiolytic Poststreptococcal Glomerulonephritis

We describe two children with poststreptococcal glomerulonephritis associated with prolonged oligoanuria (12, 13 days). Kidney biopsies at 10 and 6 days, respectively, revealed acute glomerulonephritis with prominent mesangiolysis. Both patients recovered uneventfully. It is proposed that damage to the mesangium accounts for the clinical course.     

病毒性脑炎患儿脑脊液中VEGF VCAM-1变化及其意义

目的：病毒性脑炎（VE）是脑实质广泛受损的病变，具有较高的病死率和后遗症发生率。VE发病机制的一个重要部分即是血管内皮细胞的损伤。该研究通过测定VE患儿脑脊液中血管内皮细胞生长因子（VEGF）及血管细胞粘附分子-1（VCAM-1）水平的变化，探讨VEGF，VCAM-1在VE发病机制中的作用，以及其对VE病情严重性及预后评估的临床意义。方法：应用双抗体夹心ELISA法检测65例VE患儿不同时期脑脊液中VEGF和VCAM-1的水平。结果：VEGF，VCAM-1水平在VE急性期与恢复期明显高于对照组；急性期与恢复期相比，其差异具有统计学意义。VE重度组患儿脑脊液中VEGF，VCAM-1水平与轻度组相比不具有统计学差异。VE各组脑脊液中VEGF与VCAM-1水平均具有明显相关性。VE患儿脑脊液中蛋白含量越大，脑脊液中VEGF，VCAM-1水平越高，尤以蛋白含量在0.4 g/L～1.0 g/L明显，与蛋白含量＜0.4 g/L相比，差异具有统计学意义。VE患儿脑脊液中细胞数越多，脑脊液中VEGF，VCAM-1水平越高，但却不具有明显相关性。VE组患儿抽搐次数、EEG改变与脑脊液中VEGF，VCAM-1水平之间无统计学上的差异。但头MRI改变严重者，脑脊液中VEGF，VCAM-1水平增高明显，且差异有显著性。结论：VEGF，VCAM-1可能参与VE的发病机制，对VE的病情严重性评估及预后判断有一定意义。     

Poststreptococcal reactive arthritis: clinical course and outcome in 15 patients

Patients with Group A beta-hemolytic streptococcal infection and articular disease, who do not fulfill the modified Jones criteria for diagnosis of acute rheumatic fever (ARF), have been classified as having poststreptococcal reactive arthritis (PSRA). We reviewed the clinical characteristics, laboratory findings and outcome of 15 patients with PSRA. None of these patients had clinical evidence of carditis. The pattern of joint involvement was variable and included arthritis in five patients and arthralgia in the remaining ten patients. Nine patients were treated with salicylates for one to 16 weeks; the others recovered spontaneously. Usually, the patients with arthralgia responded promptly to salicylates, while the response was poor in patients with arthritis. One patient with monoarthritis developed carditis nine months after his first arthritis attack. Another patient presenting with monoarthritis later had two additional episodes of poststreptococcal reactive arthralgia. It seems there is a wide spectrum of poststreptococcal rheumatic diseases, and patients with PSRA are also at risk for cardiac disease; therefore, prophylactic antibiotic therapy should be considered in these patients.     

Acute glomerulonephritis

Acute glomerulonephritis (AGN) manifests with abrupt onset of hematuria, facial edema, hypertension and impairment of renal function. The commonest form of AGN in developing countries is that following a beta hemolytic streptococcal infection where the glomerular injury is mediated by deposition of immune complexes. In the usual patient with moderately severe poststreptococcal AGN (PSAGN) the above-mentioned features are present However, gross or microscopic hematuria may be the only abnormality. A similar picture may occasionally be produced by a variety of infections (when GN is referred to as post-infectious and the mechanism of glomerular damage and the renal histology are similar to that in PSAGN), primary renal glomerular disorders (eg. membranoproliferative GN, IgA nephropathy), collagen vascular diseases (systemic lupus erythematosus), systemic vasculitis (Henoch Schonlein purpura) and hereditary nephritis and some nonglomerular conditions. PSAGN may also present with one or more of its complications such as profound volume expansion with heart failure and hypertensive encephalopathy. PSAGN resolves rapidly and has an excellent prognosis. Patients with severe renal involvement and life threatening complications need expert supportive management. AGN with associated systemic features or very pronounced azotemia, nonstreptococcal AGN and unresolving GN need prompt, appropriate evaluation that often includes a renal biopsy. If extensive crescentic changes are found (crescentic GN), aggressive immunosuppression will be necessary.     

Hypocomplementemic and normocomplementemic acute nephritis in children: a comparison with respect to etiology,clinical manifestations,and glomerular morphology

Of 182 patients with acute glomerulonephritis, 20 had normal C3 levels at onset. Normocomplementemic and hypocomplementemic patients were similar with respect to incidence and site of preceding streptococcal infection, elevation of ASO titer, distribution by age, sex, race, season, and year,\and glomerular morphology by light and electron microscopy. They differed in that the normocomplementemic patients tended to have normal serum C5 levels and, for reasons not clear, reduced serum albumin and elevated cholesterol levels. The consistent absence by immunofluorescence of IgG in the glomeruli of five hypocomplementemic patients and its presence in five normocomplementemic patients was considered a chance observation. The data suggest that in each group the nephritis was poststreptococcal and that the mechanism producing poststreptococcal glomerulonephritis is capable of acting independently of that activating circulating C3.     

Concurrent Poststreptococcal Acute Glomerulonephritis and Schonlein-Henoch Purpura

A 5-year-old Japanese boy developed concurrent poststreptococcal acute glomerulonephritk (PSAGN) and Schonlein-Henoch purpura (SHP). An elevated titer of ASK on admission confiied the preceding streptococcal infection. Arthritis of the left knee and petechiae on admission were regarded as features of SHP. The presence of SHP was further confiied by the pathological fmding of leukocytoclastic vasculitk in the skin. PSACN was strongly suspected due to the sndings of microscopic hematuria and hypocomplementemia in the acute phase. The concwrence of SHP and PSAGN suggests similar underlying pathophys iological processes as poststreptococcal sequelae. At the height of the illness, peripheral blood lymphocyte subset analysis showed a marked increase in the suppressor inducer T subset and a reciprocal decrease in the helper T subset. lhis alteration in T lymphocyte subsets was regarded as indicative of the immunological derangement in this patient.     

Relapsing acute encephalopathy: A complication of diphtheria-tetanus-poliomyelitis immunization in a young boy

Abstract Neurological complications of immunizations are rare. We report the case of relapsing acute encephalitis in a boy after two subsequent diphtheria-tetanus-poliomyelitis vaccinations. First the clinical signs were those of acute disseminated encephalitis. During the second episode, the boy experienced optic neuritis. Recovery was complete after both events. Because of the close temporal relationship of both these demyelinating episodes with the immunizations, we favour a cause and effect relationship.Conclusion The observation of a 7-year-old boy who developed relapsing acute encephalitis after two diphtheria-tetanus-poliomyelitis vaccinations and a similar case in the literature suggests that this neurological manifestation may occur as a very rare complication of diphtheria-tetanus-poliomyelitis vaccination.     

Study of Japanese encephalitis and other viral encephalitis in Nepali children

BACKGROUND: A hospital-based prospective cross-sectional study was conducted in children aged 1 month-14 years to identify the proportion of viral encephalitis due to Japanese encephalitis (JE) and compare the clinico-laboratory profile and outcome of JE with that of other viral encephalitis (non-JE). METHODS: All probable cases of viral encephalitis on clinical and laboratory evaluation were confirmed as JE on anti-JE IgM in cerebrospinal fluid (CSF) and/or serum. Patients not having anti-JE IgM in CSF and/or serum were diagnosed as having non-JE. RESULTS: Of 94 cases, 58 were JE and 36 non-JE. Although practice of rearing pigs at home was associated with JE (P = 0.0001), significantly higher serum creatinine, protein, aspartate aminotransferase and CSF protein levels were observed in non-JE. Longer duration of fever was associated with complete recovery in JE whereas shorter duration of fever was associated with recovery in non-JE. Risk of neurological sequelae (P = 0.01), especially hemiparesis (P = 0.03) was significantly more in JE. Sequelae were observed at 6 weeks follow up in 18.8% of JE and 13.9% of non-JE. CONCLUSION: JE was the most common cause of viral encephalitis in eastern Nepal and should be suspected in encephalitic patients having pig rearing at home and neurological sequelae. Although duration of hospitalization and complication were higher in JE, final outcome was similar to non-JE. Longer duration of fever in JE and shorter duration of fever in non-JE correlated with recovery, while altered sensorium and focal neurological deficit were independent predictors of sequelae at 6 weeks only in JE and not in non-JE.     

Polyarteritis nodosa associated with streptococcus.

Twelve children are described with an essentially benign vasculitic illness in association with streptococcal infection. They demonstrated characteristic clinical features of nodular cutaneous polyarteritis with fever. Laboratory findings showed an acute phase response associated with raised antistreptolysin and antihyaluronidase titres in all patients and a positive throat culture for beta haemolytic streptococcus in three patients. Ten required corticosteroids. Two patients had systemic involvement with abnormal arteriography; both had appreciably raised white cell counts (> 40 x 10(9)/l). They may represent a subset of poststreptococcal vasculitis, requiring cytotoxic treatment for effective disease control.     

Emerging viral infections in Australia

Emerging viruses include known viruses that have increased in incidence or geographic range (such as enteroviruses and Japanese encephalitis virus), new viruses associated with known diseases (Australian bat lyssavirus) and new viruses associated with previously unrecognized diseases (Hendra and Nipah viruses). Some may have a predilection for children (Japanese encephalitis, influenza viruses and enterovirus 71) and vigilance is essential to ensure early recognition of these agents.     

Anti-N-methyl D-aspartate receptor encephalitis mimics viral encephalitis

We describe the clinical courses of 3 children with a psychochoreiform encephalitis associated with anti-N-methyl D-aspartate receptor autoantibodies. These cases, including the most severely medically complicated survivor to date, illustrate the challenges of diagnosis, supportive care, and immune-modulating therapy. Clinical and laboratory features are similar to those of viral encephalitis, and the condition is often reversible with appropriate diagnosis and treatment.     

Acute poststreptococcal glomerulonephritis: a manifestation of immune reconstitution inflammatory syndrome

Immune reconstitution inflammatory syndrome (IRIS) is a well-described complication of initiation of highly active antiretroviral therapy in HIV-infected patients. As the immune system recovers, an inappropriate inflammatory response often occurs that causes significant disease. It is most commonly seen in patients na?ve to therapy with CD4+ T-lymphocyte counts <100 cells/cmm and usually presents as a flare of mycobacterial, cytomegalovirus, or herpes zoster infections. Less commonly, this syndrome occurs in response to noninfectious triggers and results in autoimmune or malignant disease. Here we present the first case of acute poststreptococcal glomerulonephritis associated with varicella zoster virus and IRIS in an adolescent with perinatally acquired HIV and hepatitis C virus infections. Our patient was not na?ve to therapy but was starting a new regimen of therapy because of virologic failure and had a relatively high CD4+ T-lymphocyte count. This case report indicates that IRIS remains a concern after initiation of a new highly active antiretroviral therapy regimen in HIV-infected patients with high viral loads, even in the presence of CD4+ T-lymphocyte counts >100 cells/cmm. It may present as infectious, malignant, or autoimmune conditions including poststreptococcal glomerulonephritis.     

抗N-甲基-D-天冬氨酸受体脑炎相关细胞因子的研究进展

抗N-甲基-D-天冬氨酸受体(N-methyl-D-aspartate receptor,NMDAR)脑炎为一类中枢神经系统自身免疫炎症性疾病，目前对其免疫机制知之甚少。脑脊液中除抗NMDAR抗体检测外，缺乏与疾病相关标志物，导致部分患者延误诊治。为此，近年针对细胞因子的研究不断增加，旨在评价其是否可作为新型生物标志物对疾病进行评估并协助诊治。现有研究表明部分细胞因子与抗NMDAR脑炎疾病进程可能相关，故该文就抗NMDAR脑炎相关细胞因子研究进展进行综述。     

Herpes simplex virus encephalitis during childhood: importance of brain biopsy diagnosis

Twelve consecutive pediatric patients 1 day to 11 years of age with suspected herpes simplex virus (HSV) encephalitis underwent brain biopsy. Five were proved to have HSV encephalitis; seven had subdural empyema, malignant glioma, enteroviral encephalitis, (one each), and presumed viral encephalitis, non-HSV (four). Neither epidemiologic, clinical, nor noninvasive laboratory tests were able to help differentiate the two groups of patients. The EEG was more sensitive than the CT scan in demonstrating focal lesions in early HSV encephalitis. In patients with HSV encephalitis, the mean time from hospital admission to appropriate antiviral chemotherapy was 3 days, and the outcome of HSV encephalitis was uniformly poor. In patients with febrile encephalitis-like syndromes with CSF pleocytosis, focal neurologic signs, or other localizing test results (EEG, CT), anticipatory antiviral chemotherapy and brain biopsy are the only hope to prevent the poor outcome associated with HSV encephalitis, to exclude other treatable conditions, and to avoid multiple types of unnecessary empiric therapies.     

Thrombocytopenia during the course of acute poststreptococcal glomerulonephritis

A four-year old boy was admitted to the hospital due to acute thrombocytopenic purpura. Three days later he developed edema, hematuria and hypertension. The diagnosis of acute poststreptococcal glomerulonephritis was based upon the evidence of previous sore throat, hypocomplementemia and increased antistreptolysin O titer. Renal biopsy was contraindicated due to throbocytopenia. An extensive work-up was done to exclude mebranoproliferative glomerulonephritis and systemic diseases such as hemolytic uremic syndrome or systemic lupus erythematosus. The clinical outcome of the nephritis and thrombocytopenia was excellent in respect to both conditions. To the best of our knowledge concurrent occurrence of acute thrombocytopenic purpura and poststreptococcal glomerulonephritis is very rare; there are only four similar cases reported in the literature. A careful work-up and follow-up are mandatory to exclude systemic disease.     

Pathology of Chronic Herpes Infection Associated with Seizure Disorder: A Report of Two Cases with Tissue Detection of Herpes Simplex Virus 1 by the Polymerase Chain Reaction

Although uncommon, the association of chronic encephalitis with epilepsy is well recognized. While a viral etiology has been suspected based on the morphology, to date no virus has been successfully cultured from the brain in patients with Rasmussen's encephalitis. We describe the pathologic findings and report the detection of herpes simplex virus 1 (HSV1) in the brain in two patients who presented primarily with intractable seizures. In the first patient, an intrauterine infection was suspected as the underlying basis for the seizure disorder and the extensive cerebral calcification and gliosis. The second patient (with presumed HSV1 encephalitis at age 7 months) underwent a temporal lobectomy for medically refractory seizures at the age of 3 years and pathologic examination revealed a chronic encephalitis. While immunohistochemical, ultrastructural, and culture studies were negative for viral pathogens, molecular analysis by the polymerase chain reaction (PCR) revealed HSV1 DNA sequences in both cases. Thus our cases represent two examples of chronic encephalitis associated with a seizure disorder, where a definitive viral etiology was documented by PCR.