Clinical Features of Multicenter Autoimmune Glial Fibrillary Acidic Protein Astrocytosis / 罕见病研究

  Objective  To investigate the clinical features of autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy.  Methods  We collected and analyzed the clinical and laboratory data and obtained the clinical characteristics of diagnosis and treatment from fifteen patients with positive GFAP antibody tested by cerebrospinal fluid and diagnosed autoimmune GFAP astrocytopathy by the multi-centers.  Results  The mean age of the first onset of autoimmune GFAP astrocytopathy was 39.73 years old (range 4-65 years), with no significant gender difference. In terms of clinical manifestations, we found the whole brain symptoms including abnormal mental behavior, disturbance of consciousness, epileptic attack accounting for more than 50, , meningitis accounting for 66.7%, myelitis (53.3%), limb tremor (53.3%), vision loss (33.3%); systemic symptoms including fever(100%) and fatigue(86.7%). 46.7% of patients were initially diagnosed with tuberculous meningoencephalitis and were treated with diagnostic antituberculous therapy. The MRI showed 46.7% of patients showed brain linear perivascular radial gadolinium enhancement in the white matter perpendicular to the ventricle.  Conclusions  Autoimmune GFAP astrocytopathy are acute or subacute dieases and the main clinical features include encephalitis, meningitis, myelitis and optic neuritis. They are likely to be misdiagnosed as tuberculous meningoencephalitis and can manifest progressive loss of consciousness in early phase, which is even life threatening.

Critical Cerebrospinal Fluid Adenosine Deaminase Activity In Tubercular Meningitis

Background:Tuberculosis of the central nervous system accounts for ~5% of extrapulmonary cases in the United States. It is seen most often in young children but also develops in adults, especially those infected with HIV. If unrecognized, tuberculous meningitis is uniformly fatal. This disease responds to chemotherapy.Cerebrospinal fluid (CSF) evaluation is the single most important aspect of laboratory diagnosis of meningitis. Basic studies of CSF that should be performed in meningitis include measurement of pressure, cell count and differential count, estimation of glucose and protein levels, Gram's stain and culture.Objectives:To evaluate the diagnostic significance of CSF adenosine deaminase (ADA) activity in tuberculous meningitis.Material & Methods:70 Tubercular Meningitis patients who were admitted in Department of Medicine, Victoria hospital were included. The study was approved by the Ethical Committee of Bangalore Medical College and Research Institute, Bangalore. Patients were selected after fulfilling the following inclusion and exclusion criteria.Results:The mean age of the 70 patients studied was 39.82+16.48 years. The youngest patient was 18 years old and oldestpatient was 70 years.The mean value of ADA activity in tubercular meningitis was 18.07±8.03IU/L. Cut-off value of ADA in our study was 10 IU/. The result was statistically significant with a p value<0.001. Conclusion: The test for ADA in CSF is simple and can be carried out in a central laboratory with a rapid diagnosis, thus reducing unwarranted or harmful therapy for patients.Elevated CSF-ADA level helpsin differentiating tubercular from non-tubercular meningitis.

Levels of vitamin D in tuberculosis and comparison of vitamin D level in severe variant of tuberculosis like tubercular meningitis, miliary tuberculosis, disseminated tuberculosis with non severe variant of tuberculosis like pulmonary tuberculosis, tubercular lymphadenitis etc in paediatric age group

Background: Tuberculosis is deadliest disease killing nearly 2 million people every year. Before the etiologic cause of TB was determined by Koch, cod liver oil and sunlight, both sources of vitamin D, were used in treatment of tuberculosis. After discovery of antibiotics, anti-infectious value of vitamin D was ignored until increasing cost of antibiotics and rise in resistance led to the need to search for alternative and antibiotic-independent therapeutic strategies. This study shed light on vitamin D, which is very safe and inexpensive by adding vitamin D to antibiotic treatment, immune system can be boosted to help body to clear TB, rather than relying on antibiotics.Methods: A prospective, observational, comparative study in which 62 TB patients were taken and vitamin D level were estimated.Results: The results of study show that out of total 62 patients, 31 (50.00%) had deficient(<20ng/ml) vitaminD,23(37.10%) had insufficient(20-30ng/ml) vitamin D, 8(12.90%) had sufficient (>30ng/ml) vitamin D level. Out of 62 patients, 10(62.13%) had severe variety of TB and 52(83.87%) had' nonsevere TB. Among the 52 patients, 24(46.2%) had deficient vitamin D, 20(38.5%) had insufficient vitamin D and 8(15.4%) had sufficient vitamin D. Among the 10 patients with severe TB, 7(70.00%) had deficient vitamin D, 3(30.00%) had insufficient vitamin D and none had sufficient vitamin D level.Conclusions: Majority of children with tuberculosis demonstrated low serum levels of vitamin D (deficient and insufficient levels) suggest that vitamin D deficiency is' risk factor of tuberculosis and very low levels of vitamin D were noted in severe variant of TB then non severe suggest that in severe form of tuberculosis vitamin D levels were less compared to nonsevere variant.

Landouzy Sepsis (Atypical ARDS like Features) and Paradoxical Reaction of Tubercular Meningitis Complications, in a Case of Disseminated Extrapulmonary Tuberculosis

Introduction: Chronic Obstructive Pulmonary Disease(COPD) is a major health problem globally. Spirometry is theGold standard for the diagnosis of COPD and it also gradesit’s severity. 6MWT is a simple reproducible test to assess thepatient’s functional capacity. It is of help in management andprediction of prognosis. Objective: This study was done to findcorrelation between 6MWT results with patient’s clinical andspirometric parameters. The study also assessed if 6 minutewalk distance (6MWD) can be an alternative to spirometry inpredicting severity of COPD in resource poor setup.Material and methods: This was a hospital based crosssectional study. 60 consecutive confirmed patients of COPD(by GOLD guidelines) were included in the study afterapplying inclusion and exclusion criteria. Severity wasassessed by pre and post-bronchodilator spirometry test. Thiswas followed by 6MWT as per ATS guidelines. 6MWD wasrecorded and % predicted 6MWD was also calculated. Resultsof 6MWT were correlated with spirometric and clinicalparameters of the patients.Results: 6MWD had statistically significant (p <.05) positivecorrelation with following parameters: Height, FEV1, %predicted FEV1, FVC, FEV1/FVC and PEFR. Correlationwith age, weight and BMI was not significant. % 6MWDsignificantly correlated with Height, FEV1, % predictedFEV1, FVC and PEFR. Distances in meters walked bydifferent severity groups were as follows: Mild: 410 + 15;Moderate: 367.66 + 57.71; Severe: 364.60 + 62.91 and Verysevere: 281.21 + 55.99. On one way analysis of variance(ANOVA) these differences were found significant (p <.01)Conclusion: In this study 6MWD and percent 6MWD hadsignificant positive correlation with patients’ parameters(Height, FEV1, %FEV1, FVC and PEFR). The severity ofCOPD may be assessed with 6MWT.

Clinical study of meningitis in children and role of adenosine deaminase in differentiating tubercular from non-tubercular meningitis

Background: In diseases where cell mediated immunity plays an important role like in tuberculosis, CSF (Cerebrospinal fluid) adenosine deaminase (ADA) activity is increased. Hence, this testing is done especially among children with suspected tubercular meningitis. The objective of this was to study role of Adenosine Deaminase in differentiating tubercular from non-tubercular meningitis.Methods: This was a hospital based cross sectional study was carried out among 50 children of proven meningitis for a period of two years. CSF ADA levels were done for all cases. They were divided into tubercular meningitis and non-tubercular meningitis group and compared.Results: Incidence of tuberculous meningitis (TBM) was found high in the age group 5-8 years. Male:female ratio was 2.3:1. Fever was present in all cases followed by vomiting and neck rigidity. CSF AFB was positive in 3 cases (6%). Neuroimaging was done in all cases in which 3 patients had basal exudate in which 2 patients had TBM and 1 patient was Non-TBM. 3 patients had hydrocephalus in MRI in which 2 had TBM diagnosed and 1 had non-TBM. As per ADA levels, 10 were diagnosed as TBM out of which 8 patients had ADA level ?10 IU/L and 2 had ADA level <10 IU/L which was missed by ADA and later confirmed by other modalities.Conclusions: It was concluded that if ADA level in CSF is ?10IU/l the diagnosis of TBM should be considered.

A Study on Pattern of Neurological Complications in Human Immunodeficiency Virus Infected Patients Attending a Tertiary Care Center in South Tamil Nadu, India

background: Highly active antiretroviral therapy and adequate chemoprophylaxis for opportunistic infections for humanimmunodeficiency virus (HIV) infected patients have led to increasing survival in people living with HIV/AIDS. The nervous systemis among the most frequent and serious targets of HIV infection. 40–70% of all persons infected with HIV develop symptomaticneurological disorders. This study was undertaken to study the diverse clinical presentations of neurologic abnormalities in HIVpatients admitted in a tertiary care center in South Tamil Nadu.Materials and Methods: A prospective study was conducted for 2 years in HIV-infected patients who were admitted at a tertiarycare hospital were subjected to thorough neurological evaluation and those with symptoms referring to neurological illnesswere enrolled, and clinical signs and symptoms were noted. CD4 counts of all the cases were performed by FACS counter,and neuroimaging study was performed on necessary cases.Results: A total of 71 cases with 74.6% males and 25.4% females were enrolled. Mean age for males 34.6 years; for females31.1 years. Headache was the most common symptom (67.3%) followed by altered sensorium (40.8%). Central nervous system(CNS) tuberculosis (TB) is the most common disease in patients presenting with neurological abnormalities (42.25%). Thereis a significant correlation between the levels of CD4 counts and the type of neurological manifestations.Conclusions: Incidence of neurological illness in HIV infection was 41.7%. Opportunistic infections are the leading cause ofneurological disorders in our population. Meningitis was the most common neurological presentation (57.7%). TB is the singlemost common organism affecting CNS (42.2%).

A study on clinical profile of neurological manifestations among HIV infected patients attending a tertiary care hospital of south India

Background: Current statistics show that 36.9 million (31.1-43.9 million) people were living with HIV globally at the end of 2017. 15-73% of people with HIV may develop neurological disorders with sometimes as a presenting illness. The aim of present study is to document the various neurological manifestations and presentations with relation to CD4 counts among the HIV/AIDS cases attending a tertiary care hospital of south India.Methods: A prospective study was conducted for two years at a tertiary care hospital among confirmed cases of HIV and the neurological manifestations were diagnosed and clinical signs and symptoms were noted. CD4 counts of all the cases were performed by FACS counter and Neuroimaging study was performed on necessary cases.Results: Total of 125 cases with 69.6% males and 30.4% females were enrolled. Mean age of cases was 35.14±3.8years. 86.4% were positive for HIV-1 type. Headache was the most common ailment (78.4%). Meningeal enhancement observed in 24.5% followed in order by ring enhancing lesion (18.37%), cerebral atrophy and infarction (12.24%). Tubercular meningitis was the commonest type (33.6%). In 12 cases of cryptococcal meningitis the CD4 counts were <100 cells/mm3.Conclusions: To conclude in present study, secondary neurological manifestations were more common than primary manifestations in present study. Tubercular meningitis being the most common and CD4 counts <100cells/mm3 were associated with cryptococcal meningitis. Cases with CD4 counts less than 100cells/mm3 had poor prognosis.

Tratamiento de meningitis tuberculosa en paciente HIV negativo, posible reacción paradojal / Possible paradoxical reaction to treatment of tubercular meningitis in an HIV negative patient

La respuesta paradojal al tratamiento tuberculoso es la aparición de manifestaciones clínico-radiológicas nuevas, o el empeoramiento de las previas, luego de una mejoría inicial con el tratamiento específico. Se puede observar en 6-30% de los casos de tuberculosis meníngea. Es una reacción inmunológica exagerada y debe tenerse presente ya que su tratamiento se basa en el uso de inmunomoduladores y no en el cambio de las drogas antituberculosas. Presentamos el caso de una paciente adulta HIV negativa con meningitis tuberculosa que, luego de una adecuada respuesta inicial al tratamiento, intercurre a las 10 semanas con una reacción paradojal tratada satisfactoriamente con corticoides.

The paradoxical response to tuberculosis treatment consists in the appearance of new clinical or radiologic manifestations or worsening of previous injuries after an initial improvement with anti-tuberculosis therapy. It can be observed in 6 to 30 percent of the cases of tubercular meningitis. It is the consequence of an exaggerated immune reaction that should be considered since the treatment is based on the use of immunomodulators and not in the change of anti-tuberculous drugs. We present the case of an HIV negative adult with tuberculous meningitis with a good initial response to specific therapy who showed, 10 weeks later, a paradoxical reaction to treatment that responded successfully to corticosteroids.

Pharmaceutical Care for One Patient with Bone Tuberculosis Complicated with Tubercular Meningitis / 中国药师

Objective:To explore the approaches and ideas for the pharmaceutical care performed by clinical pharmacists for the patients with bone tuberculosis and tubercular meningitis. Methods:Pharmacists participated in the clinical consultation for one patient with bone tuberculosis and tubercular meningitis. The methods and effect of clinical pharmacists were analyzed comprehensively in re-spect of the adjustment of anti-tuberculosis treatment scheme according to the disease condition, attention pald to the adverse reactions of anti-tuberculosis drugs, medical education for the patient and so on. Results: During the treatment, clinical pharmacists did have some actions to assist doctors in rational drug use, and the suggestions of clinical pharmacists in the consultation obtalned clinical rec-ognition, which significantly improved the effect of the medication. Conclusion:Clinical pharmacists can perform individual pharma-ceutical care for patients and help clinicians optimize drug therapy, which can improve the safety and efficacy of medication.

Electroimmunotransferblot assay for the detection of mycobacterial antigens in the cerebrospinal fluid for diagnosis of tubercular meningitis.

Background: The diagnosis of tubercular meningitis (TBM) is often delayed as it presents initially with non-specific signs and symptoms leading to delay in appropriate therapy. Conventional modes of diagnosis are time-taking and immunodiagnosis has its own pitfalls. Antigen detection assays have been found to be quite promising in this aspect. Aim: In the present study, attempts were made to evaluate the ElectroImmunoTransferBlot (EITB) test for detection of Mycobacterium tuberculosis antigens in CSF. Methods: A total of 46 CSF specimens were collected from 26 clinically suspected cases of TBM and 20 non-TBM cases. The mycobacterial antigens were concentrated by immunoprecipitation and separated based on their molecular weight by SDS-PAGE which were further transferred and immobilized onto a matrix and detected by EITB. Results: In TBM CSF specimens distinct bands of molecular weight 12kDa, 30-32kDa, 71kDa, 86kDa, 96kDa, 110kDa and 120kDa were seen in addition to 50kDa Immunoglobulin (Ig) heavy chain, 25kDa Ig light chain and an indistinct human albumin band at 69kDa. The control group CSF specimens also showed the Ig and albumin bands but showed no cross-reactive antigens. The following proteins 12kDa (7.7%), 30-32kDa (23%), 71kDa (19.2%), 86kDa (77%), 96kDa (57.5), 110kDa (23%) and 120kDa (15.4%) were identified as reactive bands. The results were compared to the reverse passive latex agglutination test. Conclusion: The likelihood of diagnosing TBM as evidenced by detecting at least a single mycobacterium specific band was 88.4% by our protocol for antigen detection in CSF. The specificity of EITB for diagnosing TBM was found to be 100% when the 86kDa antigen was excluded from the analysis. However, the method of diagnosis is labour/reagent intensive and needs substantial validation.