Role of inflammatory and hemostatic biomarkers in Alzheimer's and vascular dementia - A pilot study from a tertiary center in Northern India.

INTRODUCTION: A reliable plasma biomarker in differentiating between Alzheimer's disease (AD) and Vascular dementia (VaD) is the need of the hour, in most memory clinics. Even though there is no disease modifying treatment, it is important to know the type of dementia for both symptomatic treatment and prognostication. METHODS: Neuropsychological assessment, MRI brain, FDG-PET brain and CSF biomarkers of AD (Aß42 and total tau) were used for establishing the diagnosis of Mild Cognitive Impairment (MCI), AD or VaD. RESULTS: 68 diagnosed patients of AD/MCI/VaD were included. FDG PET brain, plasma fibrinogen, d dimer, IL6 and CRP were done in all 68 patients while 48 patients underwent CSF biomarker analysis. Sixteen patients had MCI, of which 11 were MCI-AD and 5 were MCI-VaSC. There were 41 patients with AD (Mild AD-9, Mod AD-23, Severe AD-9) and 11 patients with VaD. Alzheimer group (MCI-AD and AD) and Vascular group (MCI VaSC & VaD) consisted of 52 and 16 patients respectively. Alzheimer and Vascular groups did not exhibit significant difference in IL6 and CRP levels. Plasma fibrinogen levels were significantly higher in VaD and vascular group as compared to Alzheimer group. But MCI-VaSC was not significantly different from MCI-AD. Plasma d dimer levels were significantly higher in all vascular subgroups compared to Alzheimer subgroups except between MCI-VaSC and MCI-AD. CONCLUSION: Hemostatic biomarkers were higher in Vascular group compared to Alzheimer group whereas there was no difference in inflammatory biomarkers. But the sensitivity and specificity of fibrinogen and d-dimer were not high enough for routine clinical use. Further studies in a larger sample are required to confirm these results.

Clinical and radiological predictors of outcome in tubercular meningitis: A prospective study of 209 patients.

OBJECTIVES: The predictors of poor outcome in tuberculous meningitis (TBM) remain to be delineated. We determined role of various clinical, radiological and cerebrospinal fluid (CSF) parameters in prediction of outcome in TBM. PATIENTS AND METHODS: Current study was a prospective observational study including 209 patients of TBM. All patients underwent detailed evaluation including Gadolinium enhanced Magnetic resonance imaging (GdMRI) of brain as well as tests to detect evidence of tuberculosis elsewhere in body. They also underwent GdMRI at three and nine month follow up. All patients received treatment as per standard guidelines. RESULTS: Mean age was 30.4±13.8years. 139 (66.5%) patients had definite TBM while 70 (34.5%) had highly probable TBM. 53 (25.4%) patients died. On univariate analysis, longer duration of illness, altered sensorium, stage III TBM, hydrocephalus and exudates correlated with poor outcome. On multivariate analysis presence of hydrocephalus (p=0.003; OR=3.2; 95% CI=1.5-6.7) and stage III TBM (p<0.0001; OR=8.7; 95% CI=3.7-20.2) correlated with higher risk of mortality. In addition, there was significant positive association between presence of hydrocephalus (p=0.05; OR=2.2; 95% CI=0.97-5.1), stage III TBM (p<0.0001; OR=28; 95% CI=4.9-158) and presence of altered sensorium (p=0.05; OR=22; 95% CI=0.99-4.8) with either death or survival with severe disability. CONCLUSIONS: It is possible to prognosticate TBM using a combination of clinical and radiological. The duration of illness (65.9±92days) before diagnosis of TBM continues to be unacceptably long and this stresses on need to educate primary care physicians about TBM. Future studies where intensity and duration of treatment is guided by these cues may help in sorting out some of the most difficult questions in TBM, namely duration of antitubercular therapy as well as dose and duration of steroid therapy etc.

Cytokines do play a role in pathogenesis of tuberculous meningitis: A prospective study from a tertiary care center in India.

BACKGROUND: Though animal studies have suggested a role for proinflammatory cytokines in pathogenesis their exact role in pathogenesis of human meningeal tuberculosis continues to be controversial with different studies yielding contradictory results. AIM AND OBJECTIVES: To study the levels of proinflammatory cytokines in serum and cerebrospinal fluid (CSF) of patients with tubercular meningitis (TBM) and to determine whether these correlate with disease severity. PATIENTS AND METHODS: Present study included 146 patients with TBM (90- Definite TBM; 56- Probable TBM), diagnosed according to criteria laid by Ahuja et al. which were modified to include CSF nucleic acid based tests. Serum (n=146) and CSF (n=140) levels of various proinflammatory cytokines (IL-1ß, IL-2, IL-6, TNF-α and IFNγ) were compared between TBM patients and healthy volunteers (n=99). These levels were correlated with various clinical, radiological and CSF parameters of TBM patients. RESULTS: Proinflammatory cytokines include cytokines which promote systemic inflammation. In current study, the serum and CSF levels of various cytokines (IL-2, IL-4, IL-6, IL-1ß, IFN-γ and TNF-α) were significantly elevated in TBM patients compared to controls. A significant correlation was found between a) Higher stage of TBM and various cytokines (except for serum IL-6 and CSF IFN-γ); b) High CSF TNF-α, IL-4 and IL-1ß with severity of hydrocephalus; c) High CSF IL1ß and IFN-γ with presence of exudates on MRI; d) Serum and CSF levels of all cytokines with poor outcome as determined by death or as defined by S and E ADL (Schwab and England activities of daily living) score or by GOS (Glasgow outcome scale) (except for interferon gamma); and e) Serum and CSF IL-4 and IL1ß with presence of infarcts on MRI brain. CONCLUSION: Proinflammatory cytokines play an important role in the pathogenesis of TBM and contribute significantly towards severity of disease.

Cavernous sinus syndrome: A prospective study of 73 cases at a tertiary care centre in Northern India.

OBJECTIVES: To study the clinical and etiological profile of patients with cavernous sinus syndrome (CSS) and identify factors which could determine the etiology and influence the outcome of these patients. PATIENTS AND METHODS: This prospective observational study included 73 consecutive patients satisfying the criteria of CSS (i.e. involvement of any 2 of the 3rd, 4th, 5th and 6th cranial nerves or any one of them with radiological evidence of cavernous sinus involvement). All these patients were subjected to detailed haematological, biochemical and radiological investigations and diagnosed and treated as per guidelines. The clinical and investigational data was recorded and analysed meticulously. RESULTS: A definitive etiological diagnosis of CSS could be achieved in 86% of patients. Tumours, fungal infections and Tolosa Hunt syndrome (THS) were most common causes. On univariate analysis, diabetes, severe vision loss (visual acuity of <3/60 in at least one eye), and presence of nasal discharge showed a significantly positive association with a fungal CSS. Evidence of paranasal sinusitis, bone erosion and ICA (internal carotid artery) involvement on Gadolinium enhanced MRI (magnetic resonance imaging) of brain were significantly associated with a fungal CSS (p=0.0001), whereas involvement of orbital apex had a negative association with a neoplastic etiology (p=0.014). On multiple logistic regression, orbital apex involvement on MRI was associated with diagnosis of THS (p=0.019, OR: 18.7; 95% CI: 1.6-217.4) while MRI evidence of paranasal sinusitis (p=0.014, OR: 45; 95% CI: 2.1-94.3) and bone erosion ((p=0.019, OR: 12.5; 95% CI: 1.5-103) correlated with diagnosis of fungal CSS. 65.2% of patients (fungal CSS- 70%) had a good prognosis at six months follow up. CONCLUSION: Most patients with CSS can be diagnosed accurately and managed properly with good outcomes.

Emergence of Balamuthia mandrillaris meningoencephalitis in India.

We report two cases of fatal chronic meningoencephalitis caused by Balamuthia mandrillaris in immunocompetent men. Diagnosis of amoebic meningoencephalitis was made ante-mortem in one case and postmortem in another by histopathological examination and confirmed by demonstration of B. mandrillaris deoxyribonucleic acid (DNA) by polymerase chain reaction (PCR).

Tubercular osteomyelitis of the clavicle: a report of four cases.

We report the clinicoradiological features of tuberculosis in the clavicle in 4 patients. The patients' ages ranged from 9 months to 29 years. All patients were managed with antitubercular drug therapy for one year and one underwent surgical debridement and curettage as well. Clinicians should be aware of the varied presentation (pain, non-healing ulcer, abscess, multifocal osteoarticular tuberculosis) of this condition. With the worldwide resurgence of tuberculosis, clinicians should maintain a high index of suspicion. The diagnosis of osteoarticular tuberculosis is usually made on clinico-radiological features.

Postaxial polydactyly.

We present a case of postaxial polydactyly with well formed six digits on left hand and seven digits on right hand. Both conditions are rare and combination of these two conditions even rarer. The patient also had supernumerary sixth right toe and cleft lip. Very few cases of postaxial polydactyly are reported previously.

Do cytokines have any role in Wilson's disease?

The aim of this study was to determine the serum cytokine levels in patients with Wilson's disease (WD) and correlate with phenotype, therapeutic status and laboratory data. In this cross-sectional study, the serum levels of cytokines were estimated in 34 patients (M : F, 23 : 11; drug-naive, 11) with WD (mean age: 13.8 +/- 8.6 and 19.6 +/- 9.03 years) and compared with 30 controls. The following serum cytokines were analysed using enzyme-linked immunosorbent assay: (i) tumour necrosis factor (TNF)-alpha, (ii) interferon (IFN)-gamma, (iii) interleukin (IL)-2, (iv) IL-6 and (v) IL-4. Serum TNF-alpha (P < 0.001), IFN-gamma (P = 0.005) and IL-6 (P < 0.001) were detectable in WD compared with controls. However, serum level elevation of IL-4 (P = 0.49) and IL-2 (P = 0.11), although detectable compared with controls, was statistically insignificant. The disease severity and therapeutic status did not affect the cytokines. Presence of anaemia, leucopenia, thrombocytopenia, pancytopenia and hepatic dysfunction did not influence cytokine levels. There was a significant negative correlation between IL-6 and ceruloplasmin (P = 0.04) and anti-inflammatory cytokines (IL-4) and copper level (P = 0.01). Serum cytokines, both proinflammatory and anti-inflammatory subtypes, were elevated significantly in patients with WD. Further studies would establish their role in its pathogenesis.

Role of MR imaging in the evaluation of etiology of status epilepticus.

PURPOSE: MRI helps in detecting the etiology of epilepsy, which may assist in better management. However its role in emergency situations like status epilepticus (SE) is still not clear. We analyzed the MRI findings in various subtypes of SE and tried to find out if etiological diagnosis improves by doing MRI over and above that provided by clinical evaluation, CT scan and CSF and other laboratory data. METHOD: This prospective study involved 34 patients (M:F:: 23:11, mean age: 25.8+/-17.2 years; range=1-60 years) of SE. Patients were chosen irrespective of type of SE, etiology of SE, duration of SE, or treatment received. MRI was performed using standard parameters and sequences. Details of clinical, laboratory, EEG, and CT/MRI scan data were recorded. RESULTS: While 23 patients had received some treatment prior to admission, the rest did not receive any treatment. Eight patients had past history of seizures and 3 of them had history of SE. EEG revealed background slowing (22) and epileptiform discharges (15). CT scan (n=32) observations were: normal (25), inconclusive (2), diagnostic (3). MRI improved the diagnosis in 32.4% (11/34) patients over and above that provided by clinical examination, EEG, other laboratory investigations and CT scan. Seizures could be controlled with recommended treatment in 29 patients, while in 5 (Generalized Convulsive SE: 3, Epilepsia Partialis Continua: 2), it remained uncontrolled. At discharge, all but eight scored '0' on modified Rankin Scale. CONCLUSIONS: MRI is an important diagnostic tool even in emergency situation like SE. Detection of proper etiology assists in appropriate treatment and hence improves the outcome of SE.

Outbreak of poliomyelitis in Gizan, Saudi Arabia: cocirculation of wild type 1 polioviruses from three separate origins.

In 1989, a localized outbreak of 10 cases of poliomyelitis occurred in Saudi Arabia. Wild poliovirus type 1 was isolated from 5 patients. To determine the patterns of poliovirus circulation, partial nucleotide sequences of the poliovirus isolates were compared. These isolates were remarkably diverse. Two isolates were closely related to each other and to viruses isolated during the 1988 epidemic in Oman. Two other isolates were very similar to viruses found in Egypt. The fifth isolate was distantly related to the latter pair. The molecular data suggest that the 10 cases represented three separate outbreaks. The virologic findings underscore the potential for Saudi Arabia, which receives millions of guest workers and their families each year from countries in which polio is endemic, to be exposed to frequent importations of wild polioviruses. To restrict the circulation of imported polioviruses, Saudi Arabia must maintain high population immunity to poliovirus in all geopolitical divisions.