A Potential Biomarker in Amyotrophic Lateral Sclerosis: Can Assessment of Brain Iron Deposition with SWI and Corticospinal Tract Degeneration with DTI Help?

BACKGROUND AND PURPOSE: Iron-mediated oxidative stress plays a pivotal role in the pathogenesis of amyotrophic lateral sclerosis. This study aimed to assess iron deposition qualitatively and quantitatively by using SWI and microstructural changes in the corticospinal tract by using DTI in patients with amyotrophic lateral sclerosis. MATERIALS AND METHODS: Seventeen patients with amyotrophic lateral sclerosis and 15 age- and sex-matched controls underwent brain MR imaging with SWI and DTI. SWI was analyzed for both signal-intensity scoring and quantitative estimation of iron deposition in the anterior and posterior banks of the motor and sensory cortices and deep gray nuclei. The diffusion measurements along the corticospinal tract at the level of pons and medulla were obtained by ROI analysis. RESULTS: Patients with amyotrophic lateral sclerosis showed reduced signal-intensity grades in the posterior bank of the motor cortex bilaterally. Quantitative analysis confirmed significantly higher iron content in the posterior bank of the motor cortex in patients with amyotrophic lateral sclerosis. In contrast, no significant differences were noted for the anterior bank of the motor cortex, anterior and posterior banks of the sensory cortex, and deep nuclei. Receiver operating characteristic comparison showed a cutoff of 35µg Fe/g of tissue with an area under the curve of 0.78 (P = .008) for the posterior bank of the motor cortex in discriminating patients with amyotrophic lateral sclerosis from controls. Fractional anisotropy was lower in the pyramidal tracts of patients with amyotrophic lateral sclerosis at the pons and medulla on either side, along with higher directionally averaged mean diffusivity values. The combination of SWI and DTI revealed an area under the curve of 0.784 for differentiating patients with amyotrophic lateral sclerosis from controls. CONCLUSIONS: Measurements of motor cortex iron deposition and diffusion tensor parameters of the corticospinal tract may be useful biomarkers for the diagnosis of clinically suspected amyotrophic lateral sclerosis.

Increasing trend of extreme rain events over India in a warming environment.

Against a backdrop of rising global surface temperature, the stability of the Indian monsoon rainfall over the past century has been a puzzle. By using a daily rainfall data set, we show (i) significant rising trends in the frequency and the magnitude of extreme rain events and (ii) a significant decreasing trend in the frequency of moderate events over central India during the monsoon seasons from 1951 to 2000. The seasonal mean rainfall does not show a significant trend, because the contribution from increasing heavy events is offset by decreasing moderate events. A substantial increase in hazards related to heavy rain is expected over central India in the future.

Investigation of pathways for the low-pH conformational transition in influenza hemagglutinin.

Targeted molecular dynamics simulations were used to study the conformational transition of influenza hemagglutinin (HA) from the native conformation to putative fusogenic or postfusion conformations populated at low pH. Three pathways for this conformational change were considered. Complete dissociation of the globular domains of HA was observed in one pathway, whereas smaller rearrangements were observed in the other two. The fusion peptides became exposed and moved toward the target membrane, although occasional movement toward the viral membrane was also observed. The effective energy profiles along the paths show multiple barriers. The final low-pH structures, which are consistent with available experimental data, are comparable in effective energy to native HA. As a control, the uncleaved precursor HA0 was also forced along the same pathway. In this case both the final energy and the energy barrier were much higher than in the cleaved protein. This study suggests that 1) as proposed, the native conformation is the global minimum energy conformation for the uncleaved precursor but a metastable state for cleaved HA; 2) the spring-loaded conformational change is energetically plausible in full-length HA; and 3) complete globular domain dissociation is not necessary for extension of the coiled coil and fusion peptide exposure, but the model with complete dissociation has lower energy.

Tropical spastic paraparesis in Kerala.

Tropical Spastic Paraparesis (TSP) is an uncommon myeloneuropathy with an insular geographic distribution. In 1985, Human T-lymphotropic virus type I (HTLV-1) was reported to be a possible etiological factor. We did an epidemiological, clinical and virological study of 25 cases of TSP. They were predominantly young adult men, whose duration of illness ranged from 6 months to 15 years. Difficulty in walking, stiffness of legs and paraesthesia of legs were the main symptoms. None had tuberculosis, syphilis, malnutrition or lathyrism. Pyramidal signs of the lower limbs, upper limbs, posterior column involvement and spinothalamic tract dysfunction were the common signs. Laboratory findings and cerebrospinal fluid analysis were normal in most. Myelograms or MRI were normal in all. Only 1 case repeatedly tested positive for HTLV-1 antibodies. None of his relatives had clinical or virological evidence of TSP or HTLV-1 infection. Based on our study, we could not link HTLV-I infection to TSP in Indian cases. Virological testing for HTLV-I infection by polymerase chain reaction may be a better tool to reveal such an association. Our cases were similar to seronegative spinal spastic paraplegia. A related new retrovirus or an altered immune response to HTLV-1 due to environmental or dietary factors are possibilities which require further exploration.