Determinants of Suboptimal Outcome Following Thymectomy in Myasthenia Gravis.

BACKGROUND: Response to thymectomy in myasthenia gravis (MG) is influenced by various patient-, disease-, and therapy-related factors. METHODS: Retrospective analysis of 128 patients with MG who underwent maximal thymectomy over 15 years was done to identify the determinants of suboptimal clinical outcome. RESULTS: Among the 128 patients, 62 (48.4%) were females with a mean age of 38.97 (12.29) years. Thymomatous MG occurred in 66 (51.6%). Overall improvement from preoperative status was noted in 88 (68.8%) patients after mean follow-up of 51.68 (33.21) months. The presence of thymoma was the major predictor of suboptimal clinical outcome (P = 0.001), whereas age, gender, preoperative disease severity, and seropositive status did not attain significance. Patients with better outcome had received higher steroid dose preoperatively (P = 0.035). CONCLUSIONS: Suboptimal response after thymectomy occurred in one-third of MG patients, more commonly with thymomatous MG. Relationship of preoperative steroid therapy to remission merits evaluation.

Baroreflex device therapy in the treatment of hypertension.

Despite therapy with multiple optimally dosed medications, hypertension remains poorly controlled in a sizeable number of people worldwide. This has spurred interest in exploring other pharmacologic and nonpharmacologic options for treatment. The carotid baroreceptors are important in regulating blood pressure in chronic hypertension by centrally mediated sympathoinhibitory effects and other effects. This has led to renewed interest in treating hypertension by electrically stimulating the carotid baroreceptors. Although this concept was first studied several decades ago, modern technology and better understanding of physiology have finally allowed the development of a feasible treatment option. Ongoing trials are finding significant and sustained reductions in blood pressure, a good safety profile, and tolerable side-effects. These promising results indicate that this modality has the potential to become a useful tool in future treatment of hypertension.

Acute subdural effusion in vasculitis.

We report a 29-year-old man with a unique presentation of vasculitis as acute unilateral subdural effusion and meningoencephalitis. Magnetic resonance imaging showed a brainstem lesion that spread to the thalamus over time. There were no systemic features of vasculitis other than a positive pathergy test. Histopathological examination from the pathergy site showed neutrophilic infiltrate and leucocytoclastic vasculitis. The condition was steroid responsive and he remained in remission at two years' follow-up. The anatomy of the brainstem lesion, absence of other inflammatory and infective conditions on evaluation suggests a vasculitic pathology either as primary central nervous system angiitis or as neurological presentation of systemic vasculitis like Behetaet's disease although the international diagnostic criteria for Behetaet's were not fulfilled.

Differential formation of octadecadienoic acid and octadecatrienoic acid products in control and injured/infected potato tubers.

Lipoxygenases in plants have been implicated in the activation of defense responses against injury/infection. Pathogen-derived polyunsaturated fatty acids, such as arachidonic acid, eicosapentaenoic acid and their metabolites have been shown to elicit defense responses against pathogen infection in plants. However, not much is known about the role of host-derived fatty acids and their metabolites in plant defense responses. In this study, isolation and characterisation of endogenous lipoxygenase metabolites formed in potato tubers in response to injury/infection was undertaken. While 9-hydroperoxyoctadecadienoic acid (9-HPODE), derived from octadecdienoic acid (linoleic acid) is the major lipoxygenase product formed in control potato tubers, 9-hydroperoxyoctadecatrienoic acid (9-HPOTrE), derived from octadecatrienoic acid (alpha-linolenic acid) is the major lipoxygenase product formed in potato tubers in response to injury or infection with Rhizoctonia bataticola. As a result, the relative ratio of 9-HPODE to 9-HPOTrE showed a shift from 4:1 in control to 1:2 and 1:4.5 in injured and infected potato tubers respectively. From this study, it is proposed that lipoxygenase metabolites of octadecadienoic acid may be involved in physiological responses under control conditions, while octadecatrienoic acid metabolites are mediating the defense responses. This forms the first report on the differential formation of endogenous lipoxygenase products in potato tubers under control and stress conditions.

Neuromyelitis optica and neuromyelitis optica spectrum disorder: Natural history and long-term outcome, an Indian experience.

BACKGROUND: Neuromyelitis optica (NMO) has evolved from devic's classical description to a broader disease spectrum, from monophasic illness to a polyphasic illness with multiple recurrences, disease confined to optic nerve and spinal cord to now brain stem, cerebrum and even endocrinopathy due to hypothalamic involvement. OBJECTIVES: To report, the epidemiological characteristics, clinical presentations, recurrence rate, treatment and response to therapy in 26 patients with NMO and NMO spectrum disorder among the Indian population. METHODS: We performed observational, retrospective analysis of our prospectively maintained data base of patients with NMO, longitudinally extensive transverse myelitis during the period of January 2003-December 2012 who satisfied the national multiple sclerosis society (NMSS) task force criteria for diagnosis of NMO and NMO spectrum disorder. RESULTS: There were 26 patients (female: male, 21:5), the mean age of onset of symptom was 27 years (range 9-58, standard deviation = 12). Twenty-one patients (80%) fulfilled NMSS criteria for NMO while rest 5 patients (20%) were considered as NMO spectrum disorder. Seven patients (27%) had a monophasic illness, 19 patients (73%) had a polyphasic illness with recurrences. The Median recurrence rate was 4/patient in the polyphasic group. 13 (50%) patient were tested for aquaporin 4 antibody, 8 (61%) were positive while 5 patients (39%) were negative. All patients received intravenous methyl prednisolone, 9 patients (35%) required further treatment for acute illness in view of unresponsiveness to steroids. Thirteen patients (50%) received disease-modifying agents for recurrences. Mean duration of follow-up was 5 years. All patients had a good outcome (modified Rankin scale, <3) except one who had poor visual recovery. CONCLUSION: Neuromyelitis optica/NMO spectrum disorder is demyelinating disorder with female predominance, polyphasic course, myelitis being most common event although brain stem involvement is not uncommon with NMO antibody positivity in 60% patients, confirms the literature data.

A newer approach for the laboratory diagnosis of tuberculous meningitis.

In this prospective study, a simple method was standardized for measuring circulating mycobacterial antigen in the cerebrospinal fluid (CSF) for the laboratory diagnosis of tuberculous meningitis (TBM). The heat-inactivated CSF specimens from tuberculous and non-tuberculous patients were subjected to sodium dodecyl sulfate (SDS) - polyacrylamide gel electrophoresis (PAGE) (SDS-PAGE) and they were subsequently transferred onto nitrocellulose membrane (NCM) Using a rabbit polyvalent antibody to M tuberculosis, a heat stable 82 kDa mycobacterial antigen was demonstrated in the CSFs of patients with TBM. This antigen was conspicuous by its absence in the CSFs of non-tuberculous subjects. Due to inactivation of CSF specimens, there is a minimal risk of handling of infectious material in the laboratory. Besides, this newer approach is simple, inexpensive and can be readily applied in any routine clinical laboratory and it is particularly suited to developing countries.

A comparative evaluation of dot immunobinding assay (Dot-Iba) and polymerase chain reaction (PCR) for the laboratory diagnosis of tuberculous meningitis.

The results of a Dot immunobinding assay (Dot Iba) for the detection of mycobacterial antigen in the cerebrospinal fluid (CSF) of 45 patients with tuberculous meningitis (TBM) were compared with the results of a polymerase chain reaction (PCR) for the detection of Mycobacterium tuberculosis. In eight patients with culture proven TBM, Dot-Iba gave positive results, while PCR yielded positive results only in six patients. The overall sensitivities of Dot-Iba and PCR in 37 patients with culture negative (probable) TBM were 75.67% and 40.5% respectively. Dot-Iba, in contrast to PCR is a rapid and relatively easier method. More importantly, Dot-Iba is suitable for the routine application for the laboratory diagnosis of TBM and therefore best suited to laboratories in the developing world.

Iatrogenic meningitis after lumbar puncture-a preventable health hazard.

Iatrogenic meningitis (IM) is a rare complication of diagnostic and therapeutic lumbar puncture (LP). This study includes cases of IM managed in the Departments of Neurology, of two referral hospitals, in India between January 1984 and April 2002. The diagnosis of IM was made when symptoms of meningitis occurred 24 h to 21 days after LP. All the procedures were performed in the peripheral hospitals before they were referred to the two centres. There were 17(63%) women and 10(37%) men. The age range was 19-50 years with a mean age of 31. The precipitating event was spinal anaesthesia for pelvic and intra-abdominal surgeries (Caesarean section 11 cases, hysterectomy three cases, herniorraphy two cases, appendicectomy two cases, anal fissurectomy one case, varicocelectomy one case and hydrocelectomy one case) laminectomy in two and diagnostic myelogram in four patients. The cerebrospinal fluid (CSF) culture was positive in six (22%) patients. The organisms were Pseudomonas aeruginosa in one case, Staphylococcus aureus in three cases, Acinetobacter spp. in one case and Mycobacterium tuberculosis in one case. In five individuals, mycotic aneurysms with subarachnoid haemorrhage due to invasive aspergillosis was documented at autopsy. The mean follow-up was 10.6 months (range 1-18). Seventeen (63%) patients received conventional antibiotics alone, while 10 patients received antibiotics and anti-tuberculous drugs when the meningitis became chronic. The mortality was 36%. The poor prognostic factors were women who underwent Caesarean section (P < 0.04) presence of hemiplegia (P < 0.04) and altered mental status (P < 0.0004). This study shows high morbidity and mortality of IM after LP. Simple aseptic precautions under- taken before the procedure can prevent IM. The urgent need for increasing the awareness among medical personnel in peripheral hospitals of developing countries cannot be over emphasized.

Significance of circulating immune complexes in myasthenia gravis.

In this study, circulating immune complexes (CICs) were isolated and characterized in the sera of myasthenia gravis (MG) patients with thymoma and MG patients without any thymic lesions. High titres of antistriational antibodies in the CICs were demonstrated by an indirect immunofluorescence (IF) method in 60 per cent (15/25) MG patients with thymoma. The CICs showed a steady decrease in these 15 patients during the post thymectomy period. Antistriational antibodies in the CICs of MG patients without thymic lesions were not detected by IF method. The results of this study emphasised the usefulness of estimation of CICs in the overall management of MG patients with thymoma.

Detection of heat stable mycobacterial antigen in cerebrospinal fluid by Dot-Immunobinding assay.

BACKGROUND: Isolation of Mycobacterium tuberculosis in cerebrospinal fluid (CSF) specimen in patients with tuberculous meningitis (TBM) is infrequent and carries low sensitivity. Thus development of an alternative laboratory diagnostic test is essential for the early diagnosis and treatment of TBM. OBJECTIVE: A simple, rapid Dot immunobinding assay (Dot-Iba), for the laboratory diagnosis of TBM is devised. This method minimizes the risk of handling infectious material in the laboratory. METHOD: The Dot-Iba was standardized with heat-inactivated M tuberculosis antigen (PPD). The heat-inactivated CSF from TBM and non-TBM patients was similarly assayed and it can detect antigen upto 1ng/ml in CSF. RESULT: A positive result was obtained in all the five culture positive patients with TBM and in 20/25 probable TBM. A negative result was obtained in 38/40 CSF from disease control group. The overall sensitivity and specificity of Dot-Iba was 83.3% and 95% respectively. CONCLUSION: Dot-Iba can be used as an adjunct for the laboratory diagnosis of TBM, particularly in culture negative TBM patients and also in those clinical situations where no laboratory tests are available to distinguish between TBM and partially treated pyogenic meningitis.

Subacute sclerosing panencephalitis : experience of a tertiary referral centre in Thiruvanthapuram, Kerala.

A retrospective review of 32 patients with subacute sclerosing panencephalitis (SSPE) referred during 1984-1992 to SCTIMST, Thiruvananthapuram was conducted. It was observed that SSPE was more in the rural poor people. No ethnic or geographic clustering of cases could be defined the rough this referral group of patients. A reliable history of measles occurred before the age of 2 years in the majority. Moreover, SSPE occurred at an younger age in those with a history of measles. The clinical features differed little from that reported in the literature. SSPE appeared to occur less frequently in Kerala compared to that reported from Bihar. However, only population-based studies can answer the question of geographic variation in the incidence of SSPEin India.

Satoyoshi syndrome.

Satoyoshi syndrome (Komuragaeri disease) is a rare disorder of presumed autoimmune etiology, characterized by painful muscle spasms, alopecia, diarrhea, endocrinopathy with amenorrhoea and secondary skeletal abnormalities. Most of the previous reports are of the Japanese people. We report the first case from India.

Fulminant cerebral infarction in a patient with nephrotic syndrome.

Fulminant cerebral infarction secondary to arterial thrombosis in adults with nephrotic syndrome is rare. We report a 42 year old male with fulminant right anterior cerebral and middle cerebral artery infarction. Minimal change disease of the kidney was documented by renal biopsy. The possible pathogenesis is discussed and pertinent literature reviewed.

Serological diagnosis of human brucellosis: analysis of seven cases with neurological and cardiological manifestations.

Serum Tube Agglutination (STA) test was used as routine test to detect antibrucellar antibodies in diagnosis of brucella infection in sera (n = 75) and CSF (n = 14) from 78 patients with neurological (n = 60) and cardiological (n = 15) complaints in whom brucellosis was suspected, over a period of two and a half years from January, 1997 to July 1999. Seven (neurological-six and cardiac-one) serum samples (9.33%) were positive by STA, while none of the CSFs were positive. STA titres ranged from 1:10 to 1:1280. We report the findings of these seven cases with neurological and cardiac manifestations in whom STA were found positive. Treatment was accomplished in two cases (neurological-one and cardiac-one), while remaining five cases either were treated empirically with antitubercular treatment or lost for follow up. However these reported cases should alert clinicians to investigate for Brucella infection in cases of pyrexia of unknown origin and this condition in cases of chronic meningitis with unproven aetiology.

Toxoplasma gondii IgM antibody prevalence study in patients suffering from neurological disorders.

One hundred and twenty seven patients belonging to Neurosurgery (49), Neuromedicine (48), Cardiac medicine (30) wards and Blood donors (30) as healthy controls were investigated for the prevalence of Toxoplasmosis by means of detecting specific IgM antibody against Toxoplasma gondii (T. gondii) employing Enzyme Immuno Assay (EIA). The detection rate of specific IgM antibody against T.gondii was found to be 32.7% (16/49) among Neurosurgery patients, 20.8% (10/48) among Neuromedical patients and 20% (6/30) among Cardiac medical patients. None of the voluntary blood donors tested was found to have T. gondii IgM antibody. Maximum prevalence rate was found among female patients undergoing Neurosurgery (42.3%) followed by Neuromedical patients (40%). There is an increasing rate of prevalence of Toxoplasmosis from the lower age group upto thirty years and a declining prevalence rate among the higher age groups. The present study revealed high prevalence rate of Toxoplasmosis in Neurosurgery patients (32.7%) and in particular among female (35.2%) than male (17.8%) patients.

Multipoint incremental motor unit number estimation versus amyotrophic lateral sclerosis functional rating scale and the medical research council sum score as an outcome measure in amyotrophic lateral sclerosis.

INTRODUCTION: Monitoring the disease progression in amyotrophic lateral sclerosis (ALS) is a challenge due to different rates of progression between patients. Besides clinical methods to monitor disease progression, such as the ALS functional rating scale (ALSFRS) and the medical research council (MRC) sum score, quantitative methods like motor unit number estimation (MUNE) are of interest. OBJECTIVE: The objective of the present study is to evaluate the rate of progression in ALS using multipoint incremental MUNE and to compare MUNE, ALSFRS and MRC sum score at baseline and at 6 months for progression of the disease. MATERIALS AND METHODS: Multipoint incremental MUNE using median nerve, ALS-FRS and MRC sum score was carried out in 29 ALS patients at baseline and then at 6 months. RESULTS: Of the 29 ALS patients studied, the mean MUNE at baseline was 21.80 (standard deviation [SD]: 19.46, range 4-73), 15.9 in the spinal onset group (SD: 14.60) and 30.16 (SD: 22.89) in the bulbar onset group. Spinal onset patients had 74.02% of baseline MUNE value while bulbar onset patients had only 24.74% baseline value MUNE at 6 months follow-up (Unpaired t-test, P = 0.001). ALSFRS and MRC sum score showed statistically significant decline (P < 0.001) at 6 months follow-up. MUNE had the highest sensitivity for progression of the disease when compared to the ALS FRS and MRC sum score. CONCLUSION: Multipoint incremental MUNE is a valuable tool for outcome measure in ALS and other diseases characterized by motor unit loss. The rate of decline of multipoint incremental MUNE is more sensitive than that of MRC sum score and ALSFRS-R, when expressed as the percentage change from baseline.

Guillain-Barre syndrome with acute lymphoblastic leukemia.

Guillain-Barre syndrome (GBS) is rarely reported in children with acute lymphoblastic leukemia and may be difficult to differentiate from vincristine induced neuropathy. We report two children with acute lymphoblastic leukemia on induction chemotherapy who developed GBS. The diagnostic issues and potential pathogenic mechanisms underlying GBS in pediatric patients with ALL are discussed.

Congenital myasthenic syndromes: Natural history and long-term prognosis.

INTRODUCTION: Congenital myasthenia syndrome (CMS) is a rare, heterogeneous group of genetically determined, disorder of neuromuscular transmission. They have a varied presentation and progression and very few studies have addressed the natural history. Aim of the present study is to describe the clinical profile and natural history of patients with CMS. MATERIALS AND METHODS: Study includes patients with CMS who attended comprehensive-neuromuscular-clinic (CNMC) during the period January, 2000-2008 with a minimum follow-up of 2 years, with inclusion criteria: (1) Onset in infancy or childhood with fluctuating ocular, bulbar, respiratory or limb muscle weakness (2) Acetylcholine receptor antibody negative (3) normal computed tomography (CT) thymus (4) Abnormal repetitive nerve stimulation (RNS) testing (5) Exclusion of other autoimmune disorders. RESULTS: Out of 314 patients with myasthenia who attended the CNMC during study period, 15 (4.8%) were with CMS (8 boys, 7 girls). Patients were divided as infantile and childhood onset. The mean age of onset and diagnosis in infantile and childhood onset groups were 5.5 months/3.1 years and 3.6 years/6.5 years respectively. Eleven patients had ptosis and 4 had generalized presentation. Most common site of decremental response was over facial nerve in 12 (75%) patients. All patients showed good response to treatment with acetyl cholinesterase inhibitor with stable course on follow-up without exacerbations. Mean dose for neostigmine was 28 mg/day and for pyridostigmine was 153 mg/day. CONCLUSION: Ptosis is most common symptom at onset in CMS, emphasing importance of RNS of the facial nerve, in the absence of molecular diagnosis of CMS. Our CMS cohort had relatively stable course without intermittent exacerbations with fair response to acetyl cholinesterase inhibitor.