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.

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.

To compare CSF adenosine deaminase levels and CSF-PCR for tuberculous meningitis.

This study was planned to compare the adenosine deaminase (ADA) levels and polymerase chain reaction (PCR) in cerebrospinal fluid (CSF) as a rapid method to diagnose tuberculosis meningitis (TBM). Fifty-four adult patients with suspected TBM and 37 controls were included in this study. The median ADA level was 21U/L of most likely TBM, 14U/L of unconfirmed TBM and 5U/L of controls. PCR for Mycobacterium tuberculosis was positive in 12 out of 27 most likely TBM cases, 5 out of 27 unconfirmed TBM cases and 3 out of 37 controls. Using a cut off level of >10U/L, CSF-ADA had a sensitivity of 92.5% and specificity of 97% for the diagnosis of TBM. PCR for M. tuberculosis had a sensitivity of 44.5% and specificity 92% in the most likely TBM cases. This study shows that CSF-ADA is a more sensitive indicator than PCR for the diagnosis of M. tuberculosis.

Hyperhomocysteinemia as a risk factor for ischemic stroke: an Indian scenario.

BACKGROUND: Hyperhomocysteinemia has been proposed as an important risk factor for ischemic stroke worldwide, but data available from the Indian subcontinent is scarce. AIM: To study homocysteine levels in patients with ischemic stroke and compare it with age- and sex-matched controls. SETTINGS AND DESIGN: Case-control prospective study. MATERIALS AND METHODS: Fifty-seven patients with ischemic stroke and 30 controls were recruited for the study. They were subdivided into two subgroups (< 40 years and> 40 years of age) and plasma fasting total homocysteine (tHcy) levels were measured. STATISTICAL ANALYSIS USED: Student's 't' test and chi-square test. RESULTS: The tHcy were significantly high in patients with stroke, compared to controls (9.91 +/- 2.25 vs 8.00 +/- 2.74 micromol/l; P vs 8.45 +/- 2.72 micromol/l; P = 0.01) and female patients compared to controls (9.08 +/- 1.81 vs 6.79 +/- 2.60 micromol/l; P = 0.04). The tHcy levels were significantly high in patients with hypertension compared to normotensive patients (10.96 vs 9.49 micromol/l; P = 0.01) and smokers compared to nonsmokers (11.17 vs 9.33 micromol/l; P = 0.01). CONCLUSIONS: Hyperhomo-cysteinemia emerged as an important independent risk factor for ischemic stroke. A strong positive correlation was also observed between hypertension, smoking, and high-tHcy levels in the present study.

Acute onset paraneoplastic cerebellar degeneration in a patient with small cell lung cancer.

A patient with small cell lung cancer presented with a rare presentation of an acute onset pancerebellar dysfunction. His clinical condition markedly improved following the surgical removal of the tumor and chemo- and radiotherapy.

Visual loss with papilledema in Guillain-Barre syndrome.

Papilledema and raised intracranial pressure have been reported in association with Guillain-Barre syndrome. Papilledema is usually asympotomatic or associated with mild visual field defects, without any visual loss. The cerebrospinal fluid protein is usually reported to be high. A case of a 35 year old lady is reported, who presented with headache, diplopia and progressive visual loss in both eyes and limb weakness with hyporeflexia. Optic fundus examination showed bilateral papilledema. She had features of pseudotumor cerebri. Nerve conduction studies were suggestive of polyradiculopathy. The unusual things in this case, were the profound visual loss normal cerebrospinal fluid profiles and the presentation of papilledema before the limb weakness.

Albendazole therapy for solitary persistent cysticercus granuloma.

Use of Albendazole therapy for the treatment of patients having persisting intracranial solitary cysticercus granuloma is controversial. Most of the times these patients are treated empirically with variety of drugs for variable period. Some authors advocate biopsy before definitive treatment. 25 patients having radiologicaly persistent solitary cysticercus granuloma (>6 months) were given 15 days course of oral albendazole (15 mg/kg body wt). Cranial CT scan was repeated one month after the completion of albendazole therapy. It was evaluated for complete resolution, partial response (> 50% decrease in size of lesion) or no change as compared to previous scan. 12 patients (48%) showed complete resolution, 4 patients (16%) showed a partial response, while 9 patients (36%) did not show any change on follow up. Albendazole therapy may be useful for patients having persistent cysticercus granuloma.

Non-compressive myelopathy: clinical and radiological study.

Fifty seven patients (42 males and 15 females) with non-compressive myelopathy were studied from 1997 to 1999. Acute transverse myelitis (ATM) was the commonest (31) followed by Vit B12 deficiency myelopathy (8), primary progressive multiple sclerosis (5), hereditary spastic paraplegia (3), tropical spastic paraplegia (2), subacute necrotising myelitis (1), radiation myelitis (1), syphilitic myelitis (1) and herpes zoster myelitis (1). 4 cases remained unclassified. In the ATM group, mean age was 30.35 years, antecedent event was observed in 41.9% case, 25 cases had symmetrical involvement and most of the cases had severe deficit at onset. CSF study carried out in 23 patients of ATM revealed rise in proteins (mean 147.95mg%, range 20-1200 mg/dL) and pleocytosis (mean 20.78/cumm, range 0-200 mm3). Oligoclonal band (OCB) was present in 28% of cases of ATM. The most common abnormality detected was a multisegment hyperintense lesion on T2W images, that occupied the central area on cross section. In 6 patients hyperintense signal was eccentric in location. MRI was normal in 4 cases of ATM. Thus ATM is the leading cause of non-compressive myelopathy. Clinical features combined with MRI findings are helpful in defining the cause of ATM.

Neurofibromatosis 2 : unusual presentation with review of literature.

A case of central neurofibromatosis with various associated neurological abnormalities is reported. Apart from symptoms of eighth nerve involvement the patient had a hypotonic, hyporeflexic quadriparesis. Radiology revealed scoliosis, an intramedullary spinal tumour, bilateral acoustic neurinoma, tectal glioma and hydrocephalus. In view of the rapid progression of the disease process a palliative shunt procedure was carried out without any definitive surgery. The various ravages of nervous system in NF2 are discussed along with a brief review of literature.

Comparison of cellular responses in single- and multiple-lesion neurocysticercosis.

Leucocytes from 14 cases of neurocysticercosis who had multiple lesions showed a significantly lower level of chemotaxis than those from healthy controls [with mean (S.D.) movements of 49.86 (15.0) and 89.1 (12.9) microns, respectively; P < 0.05). In contrast, the leucocytes from 14 cases with single lesions had similar chemotactic responses to the controls. Although the level of lymphoproliferation stimulated with phytohaemagglutinin, a measure of T-lymphocyte function, was also considerably less using cells from the multiple-lesion cases than when cells from the single-lesion cases were used, the difference was not statistically significant [0.644 (0.248) of control values v. 0.463 (0.317); P < 0.1]. Flow cytometry indicated that the total numbers of CD4 cells and CD4/CD8 ratios in all blood samples were normal. It therefore appears that, among neurocysticercosis patients, only those with multiple lesions have defective neutrophils and may also have dysfunctional lymphocytes.

Cerebellar degeneration following neuroleptic malignant syndrome.

A 55-year-old woman with a history of bipolar affective disorder developed hyperpyrexia, rigidity and depressed consciousness (neuroleptic malignant syndrome) after commencing neuroleptic therapy. On regaining consciousness, she was mute and had signs suggesting pancerebellar involvement. Hyperpyrexia, which is a cardinal feature of neuroleptic malignant syndrome, may have caused cerebellar damage. Neuroleptic malignant syndrome needs both early recognition and prompt treatment to obviate devastating complications.

Non-invasive detection of Chlamydia trachomatis genital infections in asymptomatic males and females by enzyme immunoassay (Chlamydiazyme).

First voided urine, urethral and cervical swabs were collected from 300 asymptomatic inmates made up of 200 males and 100 females from prisons in Fiji. The enzyme immunoassay for detection of chlamydial antigen test was performed on the sediment of the urine samples. The prevalence of chlamydial urethritis in the study population of men as determined by culture of urethral swabs was 15%. Compared with the urethral cultures for chlamydia the urine EIA had a sensitivity of 86.6% and a specificity of 98.2%. In women the incidence of urogenital chlamydia infection was 18%. Using the results of the cervical swabs as a reference standard the urine EIA in the females showed a sensitivity of 61.1% with a specificity of 97.6%. Culturing urine sediments from both men and women showed low results (30.0% for men and 22.2% for women). The rapid enzyme immunoassay testing of male FVU sediment appears to be a reliable, non-traumatic and rapid method of diagnosing Chlamydia infection. The judicious use of this non-invasive method may help in detecting and treating men, thus reducing the rapid spread of the pathogen in the community.