A novel association of ocular neuromyotonia with brainstem demyelination: two case reports.

Ocular neuromyotonia (ONM) is a rare disorder of ocular mal-alignment in which painless, transient spontaneous or gaze-induced abnormal deviation of the eye manifests as episodic diplopia. With only a few cases reported in the literature, ONM mostly follows months to years after cranial irradiation for sellar or suprasellar lesions. Here we present two patients with this rare ocular condition, secondary to brainstem demyelination, the association of which is hitherto unreported in the literature. Both patients were 15-year-old girls who presented to us with episodic forced-eye deviation with diplopia. Examination during these attacks revealed ONM involving the superior rectus and medial rectus in the first and second patient, respectively. There was clinical evidence of intrinsic brainstem involvement with downbeat nystagmus and skew deviation in one patient without any other cerebellar or long tract signs. MRI showed evidence of demyelination involving the brainstem in both, with CSF showing positive immunological markers and with positive aquaporin-4 antibody in one patient. Both patients responded remarkably to immunomodulatory therapy and are asymptomatic at follow-up. That ONM can occur with brainstem demyelination has not been reported in the literature. This association may help in explaining the pathophysiology of ONM as secondary to segmental demyelination.

Neurogenic orthostatic hypotension: chasing "the fall".

Orthostatic hypotension (OH) is a frequently encountered problem affecting nearly 30% of the population aged more than 60 years. It can result from neurological and non-neurological derangements which compromise the perfusion of the brain in an erect posture. Neurogenic OH is a manifestation of autonomic failure. It is an important cause of recurrent falls in the elderly, syncopal events and also has been shown to be associated with increased long term mortality from vascular and non-vascular causes. This review will discuss the pathophysiology, aetiology, clinical features and management of neurogenic OH and its differentiation from OH caused by non-neurological causes at each step. A clinician should primarily look for any reversible causes in a patient with neurogenic OH and should not forget that treatment is aimed at restoring the functioning capability of the patient rather than normotension. Co-existent supine hypertension in some patients should be taken into account while treating them.

Disseminated necrotizing leukoencephalopathy following low-dose oral methotrexate.

Leukoencephalopathy is a recognized complication with intrathecal or intravenous methotrexate (MTX). We report a 59-year-old lady who developed MTX leukoencephalopathy with long-term low-dose oral MTX. She developed posterior leukoencephalopathy (PLE) that initially was reversible on discontinuation of oral MTX. Four months later, she developed disseminated necrotizing leukoencephalopathy (DNL), and was left with devastating neurological deficits. The sequential conventional magnetic resonance imaging (MRI), diffusion weighted imaging (DWI), MR perfusion (MRP) and MR spectroscopic (MRS) changes are highlighted in this report. MRP and MRS showed more wide spread abnormalities than DWI. Stereotactic biopsy from the lesion revealed demyelination with macrophagic infiltration, pericapillary lymphomononuclear aggregation, fibrinoid changes in the capillaries and neovascularization. Of the two cases of PLE with oral MTX reported in literature, one reversed clinically and radiologically with the discontinuation of MTX. To the best of our knowledge, this is the first reported case of DNL following oral MTX in the world literature.

Carotid artery stenting: results and long-term follow-up.

BACKGROUND AND PURPOSE: The role of carotid artery stenting (CAS) as an alternative to carotid endarterectomy in the treatment of for symptomatic carotid artery stenosis is investigated. MATERIALS AND METHODS: Forty-seven patients underwent CAS over 10-year period. Forty-nine vessels were treated. Stenosis quantification was done using North American symptomatic carotid endarterectomy trial method. The mean follow-up period by clinical and Duplex examination ranged is 5.6 years. RESULTS: The technical success rate was 100%. There were four deaths (8.1%) and two (4.1%) minor strokes within thirty days of procedure. There was no major strokes. All patients with minor stroke achieved complete recovery at 1-month follow up. Two deaths occurred probably due to hyperperfusion syndrome (HS) and two due to cardiac arrest. CONCLUSION: CAS is an effective treatment modality of symptomatic carotid artery disease but should be carefully done in high-risk groups having severe medical ailments and those having severe bilateral stenosis of the carotid arteries.

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.

Serum tumor necrosis factor-alpha in Guillain-Barré syndrome and its relation to plasma exchange.

BACKGROUND: To correlate the serum tumor necrosis factor-alpha (TNFalpha) concentrations before, during and following plasma exchange in patients with Guillain-Barré syndrome (GBS). In this prospective study, 21 GBS patients were selected. Patients in clinical stages III to V were subjected to plasma exchange. The control group included equal numbers of age-matched patients with other neurological diseases and healthy voluntary blood donors. A sandwich ELISA method was applied to estimate serum TNFalpha concentrations in test and control groups. REVIEW SUMMARY: Twelve GBS patients had elevated serum TNFalpha levels that ranged between 74 and 182 pg/mL. All 12 GBS patients showed a steady decrease in the TNFalpha concentration following plasma exchange and also showed a positive correlation with neurological recovery. CONCLUSIONS: We conclude that serum TNFalpha concentrations are elevated in 57.1% of GBS patients and TNFalpha level decreases following plasma exchange.

Significance of serum antibody to GD1b ganglioside in patients with Guillain-Barré syndrome.

BACKGROUND & OBJECTIVES: The precise etiological factors in Guillain-Barré syndrome (GBS) are still unknown. However, humoral and cellular immune factors may have a role in the pathogenesis of GBS. The present study was undertaken to evaluate the clinical significance of circulating serum IgG antibody to GD1b ganglioside in patients with GBS. METHODS: Serial samples of serum were collected from 18 patients with GBS undergoing plasma exchange (PE) during their hospital stay. Serum IgG antibody titers to GD1b, before, during as well as following PE were measured by an indirect enzyme-linked immunosorbent assay (ELISA). RESULTS: In 10 of 18 patients with GBS the antibody to GD1b was present in high titers (1:640-1:5120) prior to PE and the antibody titers in these 10 patients decreased following PE. At the time of completion of the study, the anti GD1b antibody titers declined in relation to clinical recovery in 7 of 10 patients with GBS. INTERPRETATION & CONCLUSION: The findings of the present study show that antibody to GD1b gangliosides may be one of the immunological factors in the pathogenesis of GBS and PE decreases the anti GD1b antibody titers in these patients.

Circulating tumour necrosis factor alpha & soluble TNF receptors in patients with Guillain-Barre syndrome.

BACKGROUND & OBJECTIVES: Tumour necrosis factor-alpha (TNF-alpha) is regarded as one of the immune factors that can induce demyelination of peripheral nerves in patients with Guillian-Barre syndrome (GBS). This present study was undertaken to find out the role of TNF-alpha and soluble TNF receptors in the pathogenesis of GBS; and to study the effect of intravenous immunoglobulin (ivIg) therapy on the serum TNF-alpha and soluble TNF receptors in patients with GBS. METHODS: Thirty six patients with GBS in progressive stages of motor weakness were included in this study. The serum TNF-alpha and soluble TNF receptors (TNF-RI, TNF-RII) were measured in the serum samples of these patients before and after ivIg therapy by a sandwich ELISA. RESULTS: Of the 36 patients with GBS, 26 (72.2%) showed elevated serum TNF-alpha levels prior to ivIg therapy. Following a complete course of ivIg therapy there was a progressive decrease in the serum TNF-alpha concentrations in these 26 patients. On the other hand, the soluble TNF receptors, particularly TNF-RII showed an increase in the serum of GBS patients following ivIg therapy. INTERPRETATION & CONCLUSION: The results indicate that ivIg reduces the serum TNF-alpha concentrations in the GBS patients having elevated levels prior to ivIg therapy. Elevated serum levels of soluble TNF receptors following ivIg therapy may play a protective role by inhibiting the demyelinating effect of TNF-alpha in the peripheral nerves of patients with GBS.

Detection of Campylobacter jejuni/C.coli infection in patients with Guillain-Barré syndrome by serology and culture.

Serum samples from 43 cases of Guillain-Barré Syndrome (GBS), 32 non-GBS neurology patients, and 35 healthy persons from a medical institute in Kerala, India, were tested for antibody levels against a Campylobacter jejuni strain Penner serotype 0:19 by agglutination and ELISA. Twenty-six percent of samples from GBS cases showed high antibody levels in all assays. Of 8 stool samples of new GBS cases examined by culture, 38% were positive for C. jejuni/C. col1. The results suggest that at least a quarter of GBS cases studied were associated with Campylobacter infection.

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.

Intravenous immunoglobulin reduces serum tumor necrosis factor alpha in patients with Guillain-Barre syndrome.

BACKGROUND: Tumor necrosis factor a TNF-alpha has a possible role in the pathogenesis of the Guillain-Barre syndrome (GBS). AIMS: To study the effect of intravenous immunoglobulin (IVIg) on serum TNF-alpha concentrations in patients with GBS. MATERIAL AND METHODS: The effect of IVIg on TNF-alpha was evaluated in 36 patients with GBS. Serum TNF-alpha concentration was measured by enzyme-linked immunosorbent assay (ELISA). The sera of 22 (61%) patients with GBS showed elevated concentrations of TNF-alpha (35-182 pg/ml) and these sera were individually incubated in vitro with IVIg (0.25 mg/ml) at 37 degrees C for 24 hours. RESULTS: The serum TNF-alpha concentrations in the 22 GBS patients with elevated levels showed a steady decline (60.34-19.78 pg/ml) following incubation with IVIg. These 22 patients also received IVIg therapy, and serum TNF-alpha concentrations showed a significant decline (65.5-9.75 pg/ml) at the end of the therapy. At the time of discharge from the hospital, there was a positive correlation between neurological recovery and decline in TNF-alpha concentrations in these 22 GBS patients. CONCLUSIONS: The results of this study indicate that elevated levels of TNF-alpha occur in a proportion of patients with GBS and in these patients elevated serum TNF-alpha levels decline with IVIg therapy.

Nitroimidazoles, Part XXIII--activity of satranidazole series against anaerobic infections.

A large number of nitroimidazoles have been examined for in vitro activity against three anaerobes - Bacteroides fragilis (Bf), a strain of Bf resistant to metronidazole (16a) and Clostridium perfringens and many found to be active. Among these may be mentioned 1-methyl-5-nitroimidazoles carrying N - bound hetetocycles at position 2, such as satranidazole 1a, 1b, 1c, 1k, 1n and 1v which are at least twice as active as metronidazole (16a), ornidazole (16b) and tinidazole (16c). Even more active are 5-nitroimidazolyl benzimidazole 5d, -thiazolidinone 6b and thiadiazolidine dioxide 8a. Many other types of compounds derived from 1-methyl-2-amino-5-nitroimidazole are feebly active. Among 5-nitroimidazoles with a carbon substituent at position 2, 16a, 16b and 16c are equiactive while dimetridazole 14f is more active than 16a against Bf. Some 2-vinyl derivatives are very potent, with 18f and 18i being outstanding. Activity better than that of metronidazole is seen for nitroimidazooxazepines, e.g. 29d. 5-Nitroimidazoles are more active against anaerobes than 4-nitro isomers. Antianaerobic and antiamoebic activities generally run parallel in these classes of compounds. The study has led to the elaboration of the antianaerobic profile of satranidazole 1a.

Spinal muscular atrophy--a clinicopathologic analysis.

In this retrospective study the clinical features in 16 children with spinal muscular atrophy (SMA) were reviewed and classified into three stages. The muscle biopsy specimen were routinely processed with liquid-nitrogen-isopentane and 8 micron thick frozen-sections were studied for histochemical changes. The clinical features in Type III SMA resembled with limb-girdle muscular dystrophy and the muscle biopsy was useful in distinguishing these two entities. It is being evaluated that prenatal diagnosis of SMA is possible with DNA technology developed recently in our country.

Inflammatory myopathies--a clinicopathologic study.

In this study, clinical, histopathological and immunological profiles were analysed in ten patients with inflammatory myopathies. Polymyositis and dermatomyositis were more common than other forms of inflammatory myopathies. The pathogenetic mechanisms and distinguishing histopathological and immunological profiles between polymyositis and dermatomyositis have been highlighted.

Mitochondrial myopathies--a clinicopathological study.

Mitochondrial myopathies are heterogeneous group of clinical disorders that can affect multiple systems besides skeletal muscles. The mitochondrial abnormalities in the skeletal muscles are morphologically identified by the presence of characteristic Ragged-red fibers (RRF) in the cryostat sections of the muscle stained with modified Gomori's trichrome stain. In this retrospective study, clinical and histopathological features in six patients with mitochondrial myopathies have been analysed. The utility of histochemical methods in confirming the diagnosis of mitochondrial myopathy has been emphasised.

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.

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.