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Objective Correlate serial T2 relaxometry (T2R) values with long term seizure outcome in patients with solitary cerebral cysticercosis (SCC) in order to establish its usefulness as a prognostic marker in these patients. Methods Patients with new-onset seizures due to SCC were imaged serially using a pre-determined MRI protocol at enrolment and after 3, 6, 12 and 24 months. T2 relaxometry was performed using a dual echo sequence with maps generated manually from the measured image intensities at the level of the lesion. Patients were randomised to receive albendazole plus antiepileptic drugs, or only antiepileptic treatment (“controls”). At each visit, as well as four years after study initiation, patients were reviewed for seizure recurrence. Clinical and radiological outcomes were assessed by physicians blinded to treatment received. Results Of 123 patients recruited, 77 had at least four MRIs and > 12 month follow-up, and were included for analysis. Baseline clinical and demographic parameters as well as antiepileptic treatment were similar between albendazole and control groups. T2 values from the lesion were higher than normal parenchyma initially, and fell to approach normal over six months. Controls had higher T2 values from the lesion centre and wall at six months than those who received albendazole. However no difference was seen in T2 values from perilesional parenchyma between treatment and control groups, indicating lack of modulation of the development of perilesional gliosis by albendazole therapy. Patients with seizures persisting > 6 months after enrolment had higher perilesional T2 values than those who were seizure-free. A rise in perilesional T2 value at 12 months is probably due to gliosis. A later stage of degeneration was associated with a reduced likelihood of seizure relapse. Significance T2 relaxometry at three and six months after seizure onset can identify patients likely to have seizures beyond six months after onset. Persistently abnormal T2 values in patients with poorer outcomes reflect the development of perilesional gliosis.

IntroductionMadras motor neuron disease (MMND), MMND variant (MMNDV) and Familial MMND (FMMND) have a unique geographic distribution predominantly reported from Southern India. The characteristic features are onset in young, weakness and wasting of limbs, multiple lower cranial nerve palsies and sensorineural hearing loss. There is a considerable overlap in the phenotype of MMND with Brown–Vialetto–Van Laere syndrome (BVVL) Boltshauser syndrome, Nathalie syndrome and Fazio–Londe syndrome. Recently a number of BVVL cases and families have been described with mutations in two riboflavin transporter genes SLC52A2 and SLC52A3 (solute carrier family 52, riboflavin transporter, member 2 and 3 respectively).Methods and resultsWe describe six families and four sporadic MMND cases that have been clinically characterized in detail with history, examination, imaging and electrophysiological investigations. We sequenced the SLC52A1, SLC52A2 and SLC52A3 in affected probands and sporadic individuals from the MMND series as well as the C9ORF72 expansion. No genetic defects were identified and the C9ORF72 repeats were all less than 10.ConclusionsThese data suggest that MMND is a distinct clinical subgroup of childhood onset MND patients where the known genetic defects are so far negative. The clinico-genetic features of MMND in comparison with the BVVL group of childhood motor neuron diseases suggest that these diseases are likely to share a common defective biological pathway that may be a combination of genetic and environmental factors.

A six year old boy presented with classical features of Duchenne Muscular Dystrophy (DMD) and was confirmed by absent dystrophin staining on muscle biopsy. In the paternal line there were 5 affected individuals across two generations with classical DMD. There was no family history of the illness in the maternal line. Molecular genetics analysis by PCR of the exons showed a deletion in exon 45 in two affected individuals. Microsatellite analysis showed that though the deletion was observed in the same locus in exon 45 it is a new independent mutation.

Madras motor neuron disease (MMND) and Madras motor neuron disease variant (MMNDV) have an unique geographic distribution with concentration of majority of cases in the southern states of India. They have the characteristic features of onset in young, weakness and wasting of the limbs, multiple cranial nerve palsies particularly involving the 7th, 9th to 12th and sensorineural hearing impairment. In addition, all patients with MMNDV have bilateral optic atrophy. During the past 32 years, a total of 104 patients were diagnosed to have MMND and among these 25 patients with the familial form were further evaluated. In this report, we describe the clinical features of these 25 patients diagnosed to have familial Madras motor neuron disease (FMMND) or familial Madras motor neuron disease variant (FMMNDV), belonging to 15 families hailing from southern India. There were 10 patients diagnosed to have FMMND and 15 with FMMNDV. There were 14 males and 11 females with mean age at onset of 13.0 ± 6.2 years and mean duration of illness of 73.6 ± 74.0 months. Notably, the occurrence of MMNDV in the familial group (15 of 25 patients) was significantly more as compared to occurrence in the group with sporadic MMND (SMMND) [12 of 79 patients] ( p = 0.0002).

Our earlier studies have shown that cerebrospinal fluid (CSF) of patients with amyotrophic lateral sclerosis (ALS), when intrathecally injected into the neonatal rats, produces an aberrant phosphorylation of neurofilaments (NF) in the ventral horn neurons and reactive astrogliosis in the spinal cord. We wanted to investigate the effect of cyclophosphamide in the spinal cords of neonatal rats exposed to ALS-CSF. A single dose (5 μg in 5 μl saline) of cyclophosphamide was injected, 24 h after the administration of CSF samples from ALS and non-ALS neurological patients into the spinal subarachnoid space of 3-day-old rat pups. Rats were sacrificed after a period of 24 h, and stained with antibodies against the phosphorylated NF (SMI-31 antibody) and glial fibrillary acidic protein (GFAP). Cyclophosphamide treatment resulted in a 50% decrease in the number of SMI-31 stained neuronal soma in ventral horns of spinal cords of ALS-CSF exposed rats. This was accompanied by a decrease in the number of GFAP immunoreactive astrocytes. Furthermore, lactate dehydrogenase (LDH) activity was also decreased significantly, following cyclophosphamide treatment. These results suggest that cyclophosphamide could exert a neuroprotective effect against the neurotoxic action of factor(s) present in the ALS-CSF.

Based on the evidence that autoimmunity may play a role in the pathogenesis of amyotrophic lateral sclerosis (ALS), a variety of immunomodulating agents have been used in the treatment. In an uncontrolled trial we treated 44 patients of ALS with intravenous cyclophosphamide (IVCP) at a total dose of 1.5 g/m2 given over a period of 8 to 10 days. The patients were evaluated using neurological score which included bulbar, motor and daily activity scores before and following treatment. Twenty three patients showed a significant improvement (P=

We report a young adult man who presented with chronic raised intracranial tension features and unusually progressive bilateral visual and hearing impairment of 18 months duration. MR imaging showed extensive dural involvement and contiguous orbital and spinal disease. Cerebrospinal fluid demonstrated persistent high lymphocytic pleocytosis. Dural biopsy obtained from posterior cervical approach with C1 arch excision and meningeal biopsy revealed features of classical of Rosai-Dorfman disease. Histiocytes were strongly positive for CD-68 and S-100 proteins. The illness relentlessly progressed with patient developing total deafness and near total blindness at last follow-up.

Background Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is a distinctive autosomal recessive disorder with mitochondrial alterations due to mutations TYMP gene encoding thymidine phosphorylase. Materials and methods Study of clinical and biochemical characteristics of a family with MNGIE. Results Index case was a 32 year old man presenting with recurrent vomiting, early satiety and progressive weight loss. He had ptosis, restricted eye movements, generalized muscle wasting, and absent tendon reflexes. Lactate levels were elevated in venous blood and CSF lactate. MRI brain showed diffuse leucoencephalopathy. Barium swallow showed near total obstruction at mid portion of vertical limb of duodenum with ileus. Esophageal manometry suggested myopathy. Muscle biopsy revealed moderate numbers of ragged blue and ragged red fibers as well as cytochrome c oxidase deficient fibers. An elder brother had similar symptoms and expired after a surgical procedure and a 28 year old brother has similar illness. The father had asymptomatic bilateral ptosis with mild ophthalmoparesis. The paternal grandfather and paternal aunt also had bilateral ptosis. Clinical diagnosis of MNGIE was confirmed in the two living brothers by demonstrating severe defects of thymidine phosphorylase activity in buffy coat, elevated thymidine and deoxyuridine in plasma, and a homozygous TYMP c.893 G > A mutation. Conclusions This family with biochemically and genetically confirmed mitochondrial neurogastrointestinal encephalopathy syndrome uncharacteristically included heterozygous TYMP mutation carriers manifesting extra-ocular weakness. It is important to identify MNGIE patients early because therapeutic options are emerging.

Aim To describe the evolution of imaging characteristics of solitary cerebral cysticercal lesions (SCCL) on serial MRI, and to study the effect of treatment with albendazole. Design Randomised controlled prospective trial. Methods and material 123 patients with new-onset seizures and SCCL on contrast MRI were randomised to treatment with albendazole and followed with up to five serial MRIs. Results 81 patients (M — 41, F — 40) with mean age of 19.6 ± 11.7 years and 4 or 5 serial MRI were included in the analysis. Analysis was performed on 356 MRI's. Scolex was seen in 61.9% of patients in postcontrast T1 sequence in the first MRI study, and there was a significant drop in visibility from the next scan onwards. Cyst contents were initially T1-hypointense and T2-hyperintense with inversion on FLAIR in 30.8% and later scans showed T2-hypointensity. Cyst wall characteristics changed significantly from initially T2-hypointensity to later hyperintense rim. Initial scan revealed perilesional oedema in 98.5%, which is resolved by the second scan. Around 17.5% showed subtle perilesional T2-hyperintensity in follow-up scans. Enhancement pattern changed significantly from ring to disc, and later to non-enhancement. Initially, 69.7% lesions were in colloid-vesicular stage. Lesions moved through subsequent stages of cyst degeneration: time needed for this process is described. Imaging characteristics, both on the first and on subsequent scans, did not differ between albendazole and control groups. Conclusions Evolution of SCCL follows a predictable sequence corresponding to morphologic stages described earlier, taking over a year to complete. Contrast enhancement decreases as degeneration progresses, but some calcific lesions continue to enhance. Albendazole therapy may hasten resolution of inflammation around the lesion but affects neither the morphology of the cysticercus nor the process of degeneration and subsequent healing.

No trials to date have focused on long-term seizure outcome in solitary cerebral cysticercal lesion (SCCL), which is believed to produce a relatively benign form of epilepsy. This is a prospective randomized controlled study to evaluate the effect of Albendazole on long-term seizure outcome in patients with MRI-confirmed solitary cerebral cysticercal lesion (SCCL). One hundred and twenty-three patients with new-onset seizures and SCCL on contrast MRI were randomized to treatment with albendazole and followed for up to five years with serial MRI and clinical evaluation. At final analysis 103 patients (M-54, F-49) with a mean age of 18.6+/-10.7 years and follow-up period more than 12 months were included. The mean follow-up duration was 31.4+/-14.8 months (12-64). At one month follow-up more patients receiving albendazole were seizure-free (62% versus 49% for controls). Subsequently there was no significant difference in overall seizure outcome between the two groups. There was no correlation between seizure semiology, albendazole therapy and long-term seizure outcome. Baseline MRI showed active lesions in all; 23% remained active at 12 months with no difference between the albendazole and control groups. Patients whose lesions resolved at 12 months showed better seizure outcome. Reduction in mean cyst area was greater in the albendazole group as compared to the controls and the difference at six months was significant (p0.05). At three months follow-up perilesional edema also resolved faster in albendazole group (p0.05). Thus, albendazole did not alter the long-term seizure outcome in patients with SCCL and epilepsy. However, albendazole hastened resolution of SCCL on MRI, but interestingly 23% of lesions were still active 12 months after treatment.

Amyotrophic Lateral Sclerosis is a progressive disease causing degeneration of upper and lower motor neurons with an average survival of 2 to 3 years. We retrospectively analyzed 1,153 patients of classical sporadic ALS seen over 30 years for the clinical manifestations and survival pattern. There were 855 (74.2%) men and 298 (25.8%) women with a M:F ratio of 3:1. The mean age of onset was 46.2+/-14.1 years (18-85) and the mean duration of illness at evaluation was 17.7+/-20.7 months (0.5-180). Mean age of onset for bulbar onset group was 52.8+/-11.6 and for limb onset was 43.7+/-14.1 (p

Madras motor neuron disease (MMND), MMND variant (MMNDV) and Familial MMND (FMMND) have a unique geographic distribution predominantly reported from Southern India. The characteristic features are onset in young, weakness and wasting of limbs, multiple lower cranial nerve palsies and sensorineural hearing loss. We describe the clinical features and survival pattern in 116 patients with Sporadic MMND, MMND variant and FMMND. A retrospective review of patients' medical records for clinical manifestations, electromyography, imaging, audiological and histopathology findings was performed. Over 36 years (1971 to 2007) 116 patients (men: 59; women: 57) particularly hailing from Southern India were seen. Mean age of onset was 15.8+/-7.9 years. Predominant initial manifestations were impaired hearing with wasting and weakness of distal limb muscles and pyramidal dysfunction. All patients had clinical and/or audiological evidence of hearing impairment. Patients with MMNDV in addition had optic atrophy. The overall mean survival duration was 334.9+/-27.9 months. Thus, Madras motor neuron disease is clinically a distinct entity with features of amyotrophic lateral sclerosis but with young age of onset and presence of auditory neuropathy. Studies to look for environmental and genetic basis of this intriguing disease are necessary to find the causation of this rare disorder.

Our earlier studies have shown that cerebrospinal fluid (CSF) of amyotrophic lateral sclerosis (ALS) patients causes death of motor neurons, both in in-vitro as well as in-vivo. There was an aberrant phosphorylation of neurofilaments in cultured spinal cord neurons of chick and rats following exposure to CSF of ALS patients (ALS-CSF). Other features of neurodegeneration, such as swollen neuronal soma and beading of neurites were also observed. In neonatal rat pups exposed to ALS-CSF, we observed phosphorylated neurofilaments in the soma of spinal motor neurons in addition to the increased lactate dehydrogenase activity and reactive astrogliosis. The present study examines the effect of ALS-CSF on the expression of glial glutamate transporter (GLT-1) in embryonic rat spinal cord cultures as well as in spinal astrocytes of neonatal rats. Immunostaining suggested a decrease in the expression of GLT-1 by astrocytes both in culture and in-vivo following exposure to ALS-CSF. Quantification of Western blots confirmed the decreased expression of GLT-1. Our results provide evidence that toxic factor(s) present in ALS-CSF depletes GLT-1 expression. This could lead to an increased level of glutamate in the synaptic pool causing excitotoxicity to motor neurons, possibly by triggering the 'glutamate-mediated toxicity-pathway'.

Several lines of evidence in the literature purport the contribution of glutamate mediated excitotoxicity in the etiology of amyotrophic lateral sclerosis (ALS) but the cellular mechanisms responsible for selective loss of motor neurons are still obscure. Elevation of intracellular Ca(2+) is considered as the early event in glutamate mediated cell injury. We have studied the changes in [Ca(2+)](i) and cytotoxicity in motor neurons and other spinal neurons in culture upon exposure to cerebrospinal fluid (CSF) from ALS patients. CSFs from 20 ALS patients and 20 disease control patients were examined. Eighteen out of twenty (90%) ALS-CSF samples induced a transient but pronounced elevation of [Ca(2+)](i) in neurons, whereas only 1/20 (5%) sample from disease control patients induced a marginal elevation of [Ca(2+)](i). Strikingly the [Ca(2+)](i) rise was 2-3-fold higher and longer lasting in motor neurons in comparison to the other spinal neurons. Exposure of cells to ALS-CSF drastically decreased the survival rate of motor neurons to 32.26+/-2.06% whereas a moderate decrease was observed in case of other spinal neurons (67.90+/-2.04%). In cultures treated with disease control CSF, a small decrease was observed in the survival rate with 80.14+/-2.00% and 90.07+/-1.37% survival of motor neuron and other spinal neurons respectively. The AMPA/kainate receptor antagonist NBQX rendered significant protection against the ALS-CSF induced Ca(2+) influx and neurotoxicity while the NMDA receptor antagonist APV showed a mild effect. Our data demonstrate that the exposure of spinal cord neurons to ALS-CSF differentially elevates [Ca(2+)](i) and neurotoxicity in motor neurons by activation of glutamate receptors, the AMPA/kainate receptor playing the major role.

Monomelic amyotrophy (MMA) is a benign lower motor neuron disorder in the young with male preponderance. It is characterized by insidious onset and progressive weakness and wasting of a distal extremity over a few years followed by spontaneous arrest. The exact pathogenesis is unknown. It is predominantly a sporadic disorder but rarely familial forms have been documented. In this report, we describe the phenotype of a 21-year-old man and his mother who were diagnosed to have MMA. The index case presented with left upper limb weakness and wasting of 3 years duration while his mother had right upper limb amyotrophy and weakness of 34 years. A total of 190 patients were diagnosed to have MMA in our institute over the last 27 years and this is the first case of familial MMA.