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.

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.

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.

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.

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.

An elusive diagnosis: Scedosporium apiospermum infection after near-drowning.

A 51-year-old male was admitted in our institute following an episode of near-drowning. He later developed ventriculitis and cerebral ring-enhancing lesions. He died following a subarachnoid hemorrhage due to rupture of a mycotic aneurysm involving the right fetal posterior cerebral artery. Scedosporium apiospermum was isolated from the cerebrospinal fluid. Central nervous system invasion by S apiospermum may present insidiously in near-drowning patients and, therefore, requires a high index of suspicion. In cases with the characteristic cerebral ring-enhancing lesions and concomitant ventriculitis, treatment should be instituted while awaiting fungal culture. With this article we intend to alert neurologists, intensivists, and physicians to this near fatal infection, as early identification and prompt treatment with voriconazole may be life saving.

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.

Acquired anterior Basal encephalocele in idiopathic hypertrophic pachymeningitis.

This report describes a 49-year-old woman diagnosed as idiopathic hypertrophic pachymeningitis (IHCPM) with imaging evidence of diffuse dural sinus thrombosis. Over the years, secondary to the raised intracranial pressure, she had developed an anterior basal encephalocele through the defects in the cribriform plate of the ethmoid bone. The relation between elevated intracranial pressure and encephalocele is discussed.

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.

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.

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.

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.

Immunocytochemical method for early laboratory diagnosis of tuberculous meningitis.

A simple immunocytochemical method was standardized for the direct demonstration of mycobacterial antigen in cerebrospinal fluid (CSF) specimens of patients with tuberculous meningitis (TBM). CSF-cytospin smears were prepared from 22 patients with a clinical diagnosis of TBM and also from an equal number of patients with nontuberculous neurological diseases (disease control). Immunocytological demonstration of mycobacterial antigens in the cytoplasm of monocytoid cells was attempted, by using rabbit immunoglobulin G to Mycobacterium tuberculosis as the primary antibody. Of the 22 CSF-cytospin smears from TBM patients, 16 showed positive immunostaining, while all of the CSF-cytospin smears from the disease control showed negative immunostaining for mycobacterial antigen. The technical aspects of this immunocytological method for the demonstration of mycobacterial antigens are simple, rapid, and reproducible, as well as specific, and therefore can be applied for the early diagnosis of TBM, particularly in patients in whom bacteriological methods did not demonstrate the presence of M. tuberculosis in the CSF.

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.