Rapid improvements in sequencing and array-based platforms are resulting in a flood of diverse genome-wide data, including data from exome and whole-genome sequencing, epigenetic surveys, expression profiling of coding and noncoding RNAs, single nucleotide polymorphism (SNP) and copy number profiling, and functional assays. Analysis of these large, diverse data sets holds the promise of a more comprehensive understanding of the genome and its relation to human disease. Experienced and knowledgeable human review is an essential component of this process, complementing computational approaches. This calls for efficient and intuitive visualization tools able to scale to very large data sets and to flexibly integrate multiple data types, including clinical data. However, the sheer volume and scope of data pose a significant challenge to the development of such tools.

Integrative Genomics Viewer

L'incidence annuelle du syndrome de Guillain-Barre est de 1,5/100000 habitants La mortalite actuelle est estimee a environ 5 % d'apres des essais therapeutiques recents, bien conduits Dix pour cent des malades gardent des sequelles motrices tres invalidantes un an apres le debut des premiers signes neurologiques La prise en charge de ces malades necessite des equipes entrainees, multidisciplinaires, pouvant pratiquer l'ensemble des therapeutiques specifiques La corticotherapie per os'ou par voie intraveineuse est inefficace Les echanges plasmatiques sont le premier traitement dont l'efficacite a ete demontree par rapport a un groupe controle Les indications sont maintenant mieux connues Les formes benignes (marche possible) beneficient de 2 echanges plasmatiques; 2 echanges supplementaires sont realises en cas d'aggravation Dans les formes intermediaires (marche impossible) et les formes severes (recours a la ventilation mecanique), 4 echanges plasmatiques sont conseilles Il n'est pas utile d'augmenter leur nombre dans les formes severes ou en cas d'absence d'amelioration De fortes doses d'immunoglobulines donnees par voie intraveineuse (lq IV) [0,4 g/kg/j pendant 5 jours] sont aussi efficaces que les echanges plasmatiques dans les formes intermediaires et severes Dans ces formes, le choix entre Ig IV et echanges plasmatiques depend des contre-indications respectives de ces traitements et de leur faisabilite Les travaux en cours ont comme objectif de mieux preciser les indications respectives des echanges plasmatiques et des lq IV dans des formes de gravite differente, leur morbidite comparee, la dose optimale des lq IV

[Guillain-Barré syndrome].

https://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(06)68175-0.pdf

Guillain-Barré syndrome

Amyotrophic lateral sclerosis (ALS) is an idiopathic, fatal neurodegenerative disease of the human motor system. In this Seminar, we summarise current concepts about the origin of the disease, what predisposes patients to develop the disorder, and discuss why all cases of ALS are not the same. In the 150 years since Charcot originally described ALS, painfully slow progress has been made towards answering these questions. We focus on what is known about ALS and where research is heading-from the small steps of extending longevity, improving therapies, undertaking clinical trials, and compiling population registries to the overarching goals of establishing the measures that guard against onset and finding the triggers for this neurodegenerative disorder.

SeminarAmyotrophic lateral sclerosis

Background: Components of the innate immune complement system have been implicated in the pathogenesis of amyotrophic lateral sclerosis (ALS); however, a comprehensive examination of complement expression in this disease has not been performed. This study therefore aimed to determine the expression of complement components (C1qB, C4, factor B, C3/C3b, C5 and CD88) and regulators (CD55 and CD59a) in the lumbar spinal cord of hSOD1 G93A mice during defined disease stages. Methods: hSOD1 G93A and wild-type mice were examined at four different ages of disease progression. mRNA and protein expression of complement components and regulators were examined using quantitative PCR, western blotting and ELISA. Localisation of complement components within lumbar spinal cord was investigated using immunohistochemistry. Statistical differences between hSOD1 G93A and wild-type mice were analysed using a two-tailed t-test at each stage of disease progression. Results: We found several early complement factors increased as disease progressed, whilst complement regulators decreased; suggesting overall increased complement activation through the classical or alternative pathways in hSOD1 G93A mice. CD88 was also increased during disease progression, with immunolocalisation demonstrating expression on motor neurons and increasing expression on microglia surrounding the regions of motor neuron death. Conclusions: These results indicate that local complement activation and increased expression of CD88 may contribute to motor neuron death and ALS pathology in the hSOD1 G93A mouse. Hence, reducing complement-induced

of amyotrophic lateral sclerosis

Objective: To evaluate the area of the midbrain and pons on mid-sagittal MRI in patients with progressive supranuclear palsy (PSP), Parkinson disease (PD), and multiple-system atrophy of the Parkinson type (MSA-P), compare these appearances and values with those of normal control subjects, and establish diagnostic MRI criteria for the diagnosis of PSP. Methods: The authors prospectively studied MRI of 21 patients with PSP, 23 patients with PD, 25 patients with MSA-P, and 31 age-matched normal control subjects. The areas of the midbrain tegmentum and the pons were measured on mid-sagittal MRI using the display tools of a workstation. The ratio of the area of the midbrain to the area of the pons was also evaluated in all subjects. Results: The average midbrain area of the patients with PSP (56.0 mm 2 ) was significantly smaller than that of the patients with PD (103.0 mm 2 ) and MSA-P (97.2 mm 2 ) and that of the age-matched control group (117.7 mm 2 ). The values of the area of the midbrain showed no overlap between patients with PSP and patients with PD or normal control subjects. However, patients with MSA-P showed some overlap of the values of individual areas with values from patients with PSP. The ratio of the area of the midbrain to the area of pons in the patients with PSP (0.124) was significantly smaller than that in those with PD (0.208) and MSA-P (0.266) and in normal control subjects (0.237). Use of the ratio allowed differentiation between the PSP group and the MSA-P group. Conclusion: The area of the midbrain on mid-sagittal MRI can differentiate PSP from PD, MSA-P, and normal aging.

New and reliable MRI diagnosis for progressive supranuclear palsy

A new quantitative motor unit potential (MUP) analysis method, called multi-MUP analysis, is described. Multi-MUP analysis is a type of decomposition analysis of the EMG signal. At each site 6 different MUPs may be recorded during an epoch of 4.8 sec. Calculation time is about 3 sec. A study of 20–30 MUPs including editing takes 4–8 min. Compared to many earlier MUP analysis methods it is faster and more user friendly, therefore it can be used in daily routine EMG analysis. The accuracy and reliability of the method are good. The differences from methods based on manual analysis, spike triggered averaging, template matching and decomposition are discussed. The main advantages of multi-MUP analysis are: (1) quick acquisition of many MUPs; (2) simultaneous collection of several MUPs at one recording site; (3) possibility to analyze not only low threshold MUPs; (4) less bias in the selection of MUPs; and (5) the reproducibility of the results that allow the same reference values to be used in different laboratories. So far we have successfully used this method for 2 years on more than 2000 patients.

Multi-MUP EMG analysis--a two year experience in daily clinical work.

The ability of MUP parameters to discriminate between normal and neurogenic MUPs in concentric EMG: analysis of the MUP “thickness” and the proposal of “size index”

Previous studies suggest that in amyotrophic lateral sclerosis (ALS) the abductor pollicis brevis (APB) and first dorsal interosseous (FDI) are more severely involved than abductor digiti minimi (ADM). To elucidate the pattern, frequency, extent, and specificity of such dissociated muscle atrophy in ALS, compound muscle action potentials recorded from APB, FDI, and ADM were analyzed in 77 ALS patients, 171 normal controls, and 196 disease controls. Compared with normal controls, ALS patients had a reduced APB/ADM amplitude ratio (P < 0.001) and FDI/ADM ratio (P < 0.001), whereas patients with other anterior horn diseases showed similar APB/ADM and FDI/ADM ratios to normal values. Decreased APB/ADM ratio was found in 41% of ALS patients, 5% of normal controls, and 4% of disease controls. Prominent muscle atrophy in APB and FDI, with relatively preserved ADM, appears to be specific to ALS. Dissociated hand muscle atrophy presumably reflects part of the pathophysiology and supports the diagnosis of ALS.

http://zielinskifam.com/lit/neuro/als/hand-atrophy-emg.pdf

Dissociated small hand muscle atrophy in amyotrophic lateral sclerosis: frequency, extent, and specificity

A method for quantifying shape variability, the jiggle, or motor unit potentials (MUPs) recorded with conventional EMG electrodes is presented Amplitude variability at each point of time of the MUP was analyzed Two new parameters are proposed: the normalized value of the consecutive amplitude differences (CAD), and the cross-correlational coefficient of the consecutive discharges (CCC) Simulations showed that increased jitter of the constituent single fiber potentials increases the jiggle as expressed by an increase in CAD and decrease in CCC values Even when the jitter value of each component was fixed, increased temporal dispersion increased the jiggle whereas an increased number of fibers decreased the jiggle This new method has been applied in normal subjects, patients with chronic neurogenic diseases and patients with ALS Jiggle was significantly increased in the ALS group, in agreement with visual observations We believe that this method for quantifying jiggle will increase the information obtainable from routine EMG investigations

Masahiro Sonoo

Papers

New and reliable MRI diagnosis for progressive supranuclear palsy

Multi-MUP EMG analysis--a two year experience in daily clinical work.

The ability of MUP parameters to discriminate between normal and neurogenic MUPs in concentric EMG: analysis of the MUP “thickness” and the proposal of “size index”

Dissociated small hand muscle atrophy in amyotrophic lateral sclerosis: frequency, extent, and specificity

Assessment of variability in the shape of the motor unit action potential, the “jiggle,” at consecutive discharges