R Grover

Apolipoprotein E Gene Polymorphism in Indian Patients with Alzheimer’s Disease and Vascular Dementia

The association of apolipoprotein E (ApoE) gene polymorphism with Alzheimer’s disease (AD) has been reported in several populations including one from a rural community in North India. However, the association of ApoE polymorphism with vascular dementia (VaD) is yet to be established in this population. In a case-control study involving 54 cases of dementia (29 AD and 25 VaD) and 76 age-matched healthy controls, the frequency of Ε4 allele was significantly higher among cases of AD and VaD compared with controls (p < 0.001). The Ε3Ε3 (p < 0.05) and Ε2Ε3 (p < 0.001) genotypes were found to be protective. The odds of developing AD or VaD were 4.4 and 3.7 times higher, respectively, in the presence of even a single Ε4 allele. Our results suggest that the increased risk of developing AD or VaD is similar among Asian Indians with ApoE Ε4 compared with the Caucasian population.

Prevalence of peripheral neuropathy in patients with newly diagnosed rheumatoid arthritis

Abstract Objective To look for the frequency and pattern of neuropathy in Indian patients with rheumatoid arthritis (RA). Patients and Methods One hundred newly diagnosed patients with RA (ACR 1987 revised criteria) visiting our hospital, over a period of 3 years were screened. Diabetics, outstation patients, chronic alcoholics, those with any known cause for peripheral neuropathy and patients having an overlap with the other rheumatological illness were excluded. Clinical assessment included detailed history and examination with special reference to extra-articular features and neuropathy with relevant clinical parameters like tender joint count, swollen joint count, etc. Routine laboratory investigations and autoantibodies (RF, ANA, anti-CCP) were obtained on all patients. All the patients with or without clinical manifestations of neuropathy underwent nerve conduction studies. Autonomic function studies were performed in selected patients. Results Subjects included 66 patients (M 13:F 53) with mean age of 42 (±13.42) years and median disease duration of 36 months (IQR-13.5, 60). Sensory symptoms were present in 9 patients (13.6%). None had motor symptoms. On neurological examination, 16 patients had sensory (24.2%) and 6 (9.09%) had motor abnormalities. Nerve conduction studies showed abnormality in 25 patients (37.87%). Evidence of entrapment neuropathy was found in 6 patients (9.09%; 5 patients with median nerve involvement [unilateral, 3 and bilateral, 2] and 1 patient with unilateral ulnar nerve involvement), 3 patients had only sensory neuropathy, 5 had mixed sensory motor and 3 had only motor neuropathy. Eight patients (12.12%) had only small fibre neuropathy as detected by sympathetic skin response and quantitative sensory testing. Conclusion This study shows high prevalence of subclinical neuropathy in Indian patients with RA. This may be an important contributor to disability.

DAS 28 for defining remission in rheumatoid arthritis in Indian patients

Abstract Objective To establish DAS 28 and DAS 28-3 scores that best define remission in Indian patients with rheumatoid arthritis (RA). Patients and Methods All patients diagnosed with RA visiting AIIMS, New Delhi over a period of 3 months were recruited. Clinical assessment included 28 joint counts for swelling and tenderness, duration of early morning stiffness, patient global assessment of disease activity, fatigue, joint pains and ESR. DAS 28 and DAS 28-3 scores were calculated and receiver operating characteristics curve analysis was performed to define cutoff values utilizing ‘ACR 5/6’ and ‘ACR 4/5’ remission criteria. Results Subjects included 207 patients (M: 44; F: 163) with mean age of 47.4 ± 12.6 years, median disease duration of 8 [4.12–14] years.‘ACR 5/6’ and ‘ACR 4/5’ criteria for remission were satisfied by 34 (16.42%) and 44 patients (21.25%) patients, respectively. DAS 28 score of 2.94 (sensitivity 84.4%, specificity 85.3%) and DAS 28-3 score of 3.02 (sensitivity 82.1%, specificity 82.4) best defined the ‘ACR 5/6’ remission. Corresponding values using ‘ACR 4/5’ remission were 3.04 (sensitivity 85.9%, specificity 84.1%) for DAS 28 and 3.05 (sensitivity 82.2%, specificity 81.8%) for DAS 28-3. Conclusions A cutoff value

Assessment of serum nitrite as biomarker of disease activity in ankylosing spondylitis

Abstract Background The assessment of disease activity in patients with ankylosing spondylitis (AS) continues to be a challenging issue. The currently available markers like C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) show poor correlation with clinical disease activity. There is a need for good biomarkers to assess disease activity. We explored serum nitrite, a stable end product of metabolism of NO, which is known to rise in inflammation, as a potential biomarker of disease activity in AS. Objectives To compare the levels of serum nitrite between patients with AS and healthy controls and to correlate levels of serum nitrite with disease activity in four assessment in ankylosing spondylitis (ASAS) domains. Methods Fifty patients satisfying modified New York criteria for AS were recruited for the study. Patients were assessed in the following ASAS domains: physical function (BASFI), pain (VAS, 0–100), patient global assessment (VAS, 0–100) and inflammation (mean of the two morning stiffness related BASDAI scores). Eighty-seven healthy controls were also included for comparison. Blood samples (12 hours fasting) were obtained and stored for serum nitrite level estimation, which was done by Dings method. The median levels of serum nitrite were compared between the two groups. Correlation of serum nitrite levels was sought with individual domains of disease activity. Results The median serum nitrite levels in patients with AS were markedly elevated as compared to those in controls (39 μmol/L [IQR 27–50] vs. 4.75 μmol/L [2.53–12], P = 0.001 (Mann-Whitney U test). There was only one patient whose serum nitrite level overlapped with that of controls. Clinical assessment of disease activity (individual ASAS domains-physical function (BASFI), pain, patient global assessment and inflammation (mean of the two morning stiffness) did not show a good correlation with serum nitrite levels. Conclusions Serum nitrite level was increased eight folds in patients with AS when compared with controls. Thus its measurement holds promise in differentiating between inflammatory and mechanical low back pain. However, there was no variation across a range of levels of disease activity making it unsuitable as a biomarker to monitor disease activity in AS.

Efficacy of oral pilocarpine in patients with Sjøgren's syndrome

Abstract Introduction A number of drugs have been tried for the relief of sicca symptoms in Sjogrens syndrome (SS) without much benefit. Lately, oral pilocarpine, a muscarinic cholinergic agent, has been reported to be useful. Objective To document the effect of oral pilocarpine on sicca symptoms in patients with SS. Patients and Methods The study group comprised 41 patients (4 men and 37 women) diagnosed as SS (primary or secondary) according to European criteria. Patients were recruited from the rheumatology clinic, cornea clinic, and medicine OPD of AIIMS between April 2003 and March 2005. Study subjects received oral pilocarpine, 5 mg thrice a day for a total duration of 12 weeks. Assessment included measurement of salivary flow, Schirmers test, Rose Bengal staining of cornea and slit lamp examination at 0, 6, and 12 weeks. Measurement of salivary flow and Schirmers test was performed twice at every visit, pre-dose and post-dose. All the patients underwent subjective self-assessment of sicca symptoms on visual analogue scale (VAS). Statistical analysis was carried out using paired t-test and repeated measure analysis of variance. Results The mean age was 52.61 ±9.14 years. Mean duration of dry eye and dry mouth symptoms were 52.02 and 42.51 months, respectively. Treatment with pilocarpine was associated with a significant decrease in the VAS score for dry mouth and dry eye symptoms. Statistically significant increase in salivary flow rate was noticed after the first dose of pilocarpine and was maintained for 12 weeks. Rose Bengal score showed a significant improvement even though Schirmers test result did not show improvement. The most common side effect was sweating. No serious side effect was noticed. Conclusions Treatment of sicca symptoms of SS with oral pilocarpine was found to be safe and efficacious.

Complex regional pain syndrome—management options

Abstract The natural history of Complex Regional Pain Syndrome (CRPS) is not well understood and the progression varies between different patients. The pathogenesis of this disorder is not well understood and a single mechanism can barely account for all the changes that are seen. In the absence of any pathognomonic sign or investigation, the diagnosis is suggested by the presence of constellation of symptoms, signs and laboratory findings. It is often under-diagnosed and undertreated resulting in significant morbidity and impaired quality of life. The crux of management lies in formulating a multidisciplinary planned approach based on the principles of chronic pain management, rehabilitation and psychotherapy with physiotherapy playing a very important role. Corticosteroids might be useful in a select group of patients in the early stages. Long-term use is not recommended as it has a questionable risk-benefit ratio. A number of new drugs are being tried that include thalidomide, calcium channel blockers, free radical scavengers, oral sympatholytic drugs, and clonidine. Encouraging results have been seen with bisphosphonates. Lenalinomide and neurotropin are other newer agents undergoing evaluation for efficacy in CRPS. Owing to lack of proper understanding of the pathogenesis and lack of animal models, current treatment for CRPS is essentially symptomatic and suboptimal. This paper attempts to review the role of various therapeutic modalities in the management of CRPS with emphasis on the emerging therapies.

A comparative evaluation of MRI, radionucleide bone scan and plain radiographs in Indian patients with spondyloarthropathy

Abstract Background Spondyloarthropaties (SpA) are a diverse group of disorders characterized by inflammatory low backache, genetic predisposition and a variety of articular and extraarticular manifestations. Evidence of sacroiliitis in plain radiographs forms the cornerstone for establishing the diagnosis. However, it may take many years for the sacroiliitis to become visible. With the availability of biologics that have the potential to modify the course of SpAs, there is a need for early diagnosis of these disorders. Magnetic resonance imaging (MRI) and nuclear scintigraphy (radionuclide bone scan) appear promising in this context with their ability to pick up structural damage and inflammation before their presence is detected in plain radiographs. Objectives To assess the role of MRI and bone scan in patients with early SpA. Methods This was a cross sectional study done at a tertiary care rheumatology center of the armed forces. Patients satisfying the European Spondyloarthropathy Study Group (ESSG) criteria for Spodyloarthropathy and disease duration of less than 8 years were included. All patients underwent conventional radiography, MRI imaging and nuclear scintigraphy of the sacroiliac (SI) joints. The primary outcome assessed was the positivity rate for sacroiliitis of each of the three modalities in this group of patients. The sensitivity of each modality in contributing to the diagnosis over and above that of plain radiographs was assessed. Results Forty-four patients (predominantly young men, n = 39) with a median disease duration of 5 years were included in the study. Most patients had ankylosing spondylitis ( n = 21, 47.7%) closely followed by undifferentiated spondyloarthropathy ( n = 14, 31.8%), reactive arthritis ( n = 5, 11.1%) and psoriatic arthropathy ( n = 4, 9.2%). Evidence of sacroiliitis was seen in 59% (26/44) patients in plain radiographs, in 73% (34/44) with bone Scan and in 77% (34/44) with MRI. There was significant discordance among the three imaging modalities, documented in 49 of the 132 observations (37%). Amongst patients with a disease duration n = 14), none of the patients had evidence of sacroiliitis on plain radiographs. However 10 (71.5%) patients each had evidence of sacroiliitis on MRI and bone scan, with 8 (57.1%) patients having both MRI and bone scan findings suggestive of sacroiliitis. Plain radiographs, MRI and bone scan, when used in combination, are able to detect sacroiliitis in almost all patients with SpA. Conclusions MRI had the maximum sensitivity (78%) for detecting sacroiliitis closely followed by bone scan (73%). Their utility was most apparent in patients with disease duration lesser than 2 years where plain radiographs have the least sensitivity in detecting sacroiliitis. They were also very useful in the subgroup of patients with uSpA where the radiographs were universally negative. MRI and bone scan individually picked up evidence of sacroiliitis in most of the patients with USpA and in combination picked up all the cases suggesting their usefulness in this group. However, there was a significant discordance rate amongst the three modalities and bone scan seems to lack specificity. MRI may be the preferred modality in patients with USpA and in those with early disease, given the poor specificity of bone scan.