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.

Limbic encephalitis: Clinical spectrum and long-term outcome from a developing country perspective.

INTRODUCTION: Limbic encephalitis (LE) is characterized by rapidly progressive short-term memory loss, psychiatric symptoms and seizures. We describe the clinical spectrum, underlying etiology and long-term follow-up of patients with LE from India. MATERIALS AND METHODS: This prospective study included patients during the period of January 2009 and December 2011 with the clinical features consistent with LE with one or more of the following: (1) Magnetic resonance imaging (MRI) evidence of temporal lobe involvement; (2) cerebrospinal fluid inflammatory abnormalities, or (3) detection of antineuronal antibodies. Patients with metastasis, infection, metabolic and nutritional deficits, stroke, were excluded. RESULTS: There were 16 patients (9 females), mean age of presentation was 36.6 years (range 15-69 years). The mean duration of symptoms before presentation was 11 months (range 5 days-2 years). The most common symptom at presentation was short-term memory impairment in 7 patients followed by seizures in 5 and behavioral changes in three. Nine patients had seizures, 11 had change in behavior, language involvement in eight, cerebellar features in 3 and autonomic dysfunction in two. Four patients had associated malignancy, 3 of four presented with neurological symptoms and on investigations found to be have malignancy. Antineuronal antibody testing was done in 6 of 12 non paraneoplastic and two paraneoplastic patients, one positive for N-methyl-D-aspartate and one for anti-Hu antibody. MRI brain showed typical fluid attenuated inversion recovery or T2 bilateral temporal lobe hyperintensities in 50% of patients. At a mean follow-up of 21 months (3-36 months), 10 patients improved, 4 patients remained same and two patients expired. CONCLUSION: Early recognition of LE is important based upon clinical, MRI data in the absence of antineuronal surface antibody screen in developing nations. Early institution of immunotherapy will help in improvement in outcome of these patients in long-term.

Subacute sclerosing panencephalitis: A clinical appraisal.

INTRODUCTION: Subacute sclerosing panencephalitis (SSPE) is a rare chronic, progressive encephalitis affecting primarily children and young adults, caused by a persistent infection of immune resistant measles virus. The aim of the present study is to describe the clinical profile and natural history of patients with SSPE. METHODS: We collected data of patients with SSPE during 2004-2010 who fulfilled Dyken's criteria. We analyzed demographical, clinical, electrophysiological, and imaging features. RESULTS: Study included 34 patients, 26 (76.5%) males with age of onset from 3 to 31 years. Twenty one patients were below 15 years of age formed childhood SSPE and 13 above 15 years of age constituted adult onset group. 85.3% had low-socioeconomic status. Eleven received measles vaccination and seven were unvaccinated. 59.9% patients had measles history. Most common presenting symptom was scholastic backwardness (52.5%) followed by seizures (23.5%). Three patients each had cortical blindness, macular degeneration, decreased visual acuity, and optic atrophy. Electroencephalographic (EEG) showed long interval periodic complexes and cerebrospinal fluid anti-measles antibody was positive in all. Magnetic resonance imaging was done in 70.5% with was abnormal in 52.5%. Mean incubation period of SSPE after measles was 9.6 years. The follow-up duration was 1-10 years, (average of 2 years). Only one patient died from available data of follow-up, 9 were stable and 10 deteriorated in the form of progression of staging. CONCLUSION: SSPE is common in low-socioeconomic status. The profile of adult onset did not differ from childhood onset SSPE, except for a longer interval between measles infection and presence of the ophthalmic symptom as presenting feature in adult onset group.

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.