Corticospinal tract degeneration in ALS unmasked in T1‐weighted images using texture analysis

The purpose of this study was to investigate whether textures computed from T1‐weighted (T1W) images of the corticospinal tract (CST) in amyotrophic lateral sclerosis (ALS) are associated with degenerative changes evaluated by diffusion tensor imaging (DTI). Nineteen patients with ALS and 14 controls were prospectively recruited and underwent T1W and diffusion‐weighted magnetic resonance imaging. Three‐dimensional texture maps were computed from T1W images and correlated with the DTI metrics within the CST. Significantly correlated textures were selected and compared within the CST for group differences between patients and controls using voxel‐wise analysis. Textures were correlated with the patients' clinical upper motor neuron (UMN) signs and their diagnostic accuracy was evaluated. Voxel‐wise analysis of textures and their diagnostic performance were then assessed in an independent cohort with 26 patients and 13 controls. Results showed that textures autocorrelation, energy, and inverse difference normalized significantly correlated with DTI metrics (p < .05) and these textures were selected for further analyses. The textures demonstrated significant voxel‐wise differences between patients and controls in the centrum semiovale and the posterior limb of the internal capsule bilaterally (p < .05). Autocorrelation and energy significantly correlated with UMN burden in patients (p < .05) and classified patients and controls with 97% accuracy (100% sensitivity, 92.9% specificity). In the independent cohort, the selected textures demonstrated similar regional differences between patients and controls and classified participants with 94.9% accuracy. These results provide evidence that T1‐based textures are associated with degenerative changes in the CST.     

Transcranial sonography in patients with myotonic dystrophy type 1

Introduction: In this study we analyzed transcranial sonography (TCS) in patients with myotonic dystrophy type 1 (DM1). Methods: This cross‐sectional study included 66 DM1 patients and 55 matched healthy controls (HCs). Echogenicity of the brainstem raphe (BR) and substantia nigra (SN) and third ventricle width (DTV) were assessed by TCS. Results: BR hypoechogenicity was more common in DM1 patients than in HCs (37.7% vs. 7.8%, P < 0.01). Patients with depression or fatigue were more likely to have BR hypoechogenicity (80.0% vs. 29.4%, P < 0.01 and 51.9% vs. 24.2%, P < 0.05, respectively). Both hypoechogenicity and hyperechogenicity of SN were more frequent in DM1 patients than in controls (26.2% vs. 10.9% and 13.1% vs. 1.8%, respectively, P < 0.01). DTV was increased in DM1 patients compared with HCs (6.0 ± 1.4 vs. 4.9 ± 0.9 mm, P < 0.01). Conclusion: TCS can offer new insight into structural changes of several cerebral areas in patients with DM1. Muscle Nerve 50:278–282, 2014     

The corticospinal tract profile in amyotrophic lateral sclerosis

This work evaluates the potential in diagnostic application of a new advanced neuroimaging method, which delineates the profile of tissue properties along the corticospinal tract (CST) in amyotrophic lateral sclerosis (ALS), by means of diffusion tensor imaging (DTI). Twenty‐four ALS patients and twenty‐four demographically matched healthy subjects were enrolled in this study. The Automated Fiber Quantification (AFQ), a tool for the automatic reconstruction of white matter tract profiles, based on a deterministic tractography algorithm to automatically identify the CST and quantify its diffusion properties, was used. At a group level, the highest non‐overlapping DTI‐related differences were detected in the cerebral peduncle, posterior limb of the internal capsule, and primary motor cortex. Fractional anisotropy (FA) decrease and mean diffusivity (MD) and radial diffusivity (RD) increases were detected when comparing ALS patients to controls. The machine learning approach used to assess the clinical utility of this DTI tool revealed that, by combining all DTI metrics measured along tract between the cerebral peduncle and the corona radiata, a mean 5‐fold cross validation accuracy of 80% was reached in discriminating ALS from controls. Our study provides a useful new neuroimaging tool to characterize ALS‐related neurodegenerative processes by means of CST profile. We demonstrated that specific microstructural changes in the upper part of the brainstem might be considered as a valid biomarker. With further validations this method has the potential to be considered a promising step toward the diagnostic utility of DTI measures in ALS. Hum Brain Mapp 38:727–739, 2017. © 2016 Wiley Periodicals, Inc.     

Diffusion tensor imaging patterns differ in bulbar and limb onset amyotrophic lateral sclerosis

Background

Amyotrophic lateral sclerosis (ALS) is characterized by pronounced clinical heterogeneity in terms of onset and disease progression. Widespread changes in white matter fibres could be observed by diffusion tensor imaging (DTI), which detects alterations in the degree (diffusivity, ADC) and directedness (fractional anisotropy, FA) of proton movement. The aim of the current study was to determine whether different ALS onset types were reflected in different DTI brain patterns.

Methods

Seventeen patients with a diagnosis of ALS (6 bulbar, 11 limb onset) and seventeen age-matched controls received 1.5T DTI, where FA and ADC were analyzed using statistical parametric mapping.

Results

In ALS patients, an increased diffusivity in the white matter was found below the precentral gyrus and along the corticospinal tract (CST) right into the internal capsule. The FA was decreased in the posterior limb of internal capsule and in the subcortical white matter in the precentral gyrus. In bulbar onset increased diffusivity was found in the CST, whilst in limb onset, frontal subcortical areas displayed an increased diffusivity.

Conclusion

DTI changes can be regarded as prominent features in ALS. Herein we were able to demonstrate discriminating brain DTI patterns due to bulbar or limb onset.     

Distal Predominance of Electrodiagnostic Abnormalities in Early‐Stage Amyotrophic Lateral Sclerosis

Introduction: In this study we compared the electrodiagnostic (EDX) yield of limb muscles in revealing lower motor neuron (LMN) dysfunction by electromyography (EMG) in early‐stage amyotrophic lateral sclerosis (ALS). Methods: This investigation was undertaken as a retrospective review at a single center. Results: Our study included 122 consecutive patients with possible ALS, as defined by revised El Escorial criteria. Distal limb muscles showed more frequent EMG abnormalities than proximal muscles. EDX yield was found to be higher in the limb where weakness began and when clinical signs of LMN dysfunction were evident. Adoption of the Awaji criteria significantly increased the yield of EMG‐positive segments in the cervical (P < 0.0005) and lumbosacral (P < 0.0001) regions, and upgraded 19 patients into the probable category and 1 patient into the definite category. Discussion: EMG abnormalities are predominant in the distal limb in early‐stage ALS. A redefinition of an EDX‐positive cervical or lumbosacral segment, with an emphasis on distal limb muscles, may result in an earlier ALS diagnosis. Muscle Nerve 58 : 389–395, 2018     

Motor outcome of deep intracerebral haemorrhage in diffusion tensor imaging: comparison of data from different locations along the corticospinal tract

Abstract

Objectives:

Although diffusion tensor imaging (DTI) is widely studied to assess the motor outcome after ischaemic stroke, there is paucity of data regarding outcomes of intracerebral haemorrhage (ICH). The aim of this study was to determine the DTI data from different locations along the corticospinal tract (CST) and association to motor outcome.

Methods:

We prospectively recruited patients with deep ICH admitted to our hospital from November 2010 to July 2012.Diffusion tensor imaging was performed within 14?days after the onset of ICH. Fractional anisotropy (FA) was measured along the CST at corona radiata, perihaematomal oedema, cerebral peduncle and pons. Corticospinal tract integrity was classified into three types by diffusion tensor tractography (DTT): type A with preserved CST, type B with partially interrupted CST and type C with completely interrupted CST. Motor outcome was assessed by Motricity index (MI) at admission, after 1 and 3?months.

Results:

Forty-eight patients were enrolled with a mean age of 62?years. The median time interval from onset of ICH to DTI study was 7?days. The patients in type C had significantly worse MI at admission (P?<?0.001), after 1?month (P?<?0.001) and after 3?months (P?<?0.001) as compared to those with type A and type B. Lower rFA at the corona radiata was significantly correlated with poorer motor outcome at admission, after 1?month and after 3?months.

Discussion:

Clinical motor outcome of ICH within 2?weeks can be identified with a statistically significant decrease in rFA at the corona radiata.     

Combined MR spectroscopic imaging and diffusion tensor MRI visualizes corticospinal tract degeneration in amyotrophic lateral sclerosis

Abstract. Motor neuron damage and cortical spinal tract (CST) degeneration are pathological features of amyotrophic lateral sclerosis (ALS). We combined whole-brain diffusion tensor imaging (DTI) and three-dimensional magnetic resonance spectroscopic imaging (MRSI) to study the CST at different locations. Eight ALS patients were compared with normal controls. Fractional anisotropy (FA) and mean diffusivity (MD), and the ratio of N-acetyl-aspartate (NAA) to creatine (Cr) were measured at various locations in the CST, including the subcortical white matter (SWM), centrum semiovale (CS), periventricular white matter (PV), posterior limb of the internal capsule (PIC) and cerebral peduncle (CP). Patients showed significantly lower FA than controls in the CST, including the SWM, CS, PV and PIC. Although there was a trend towards elevated MD in ALS patients, this did not reach statistical significance. NAA/Cr ratios were also decreased in ALS patients compared with normal controls, with significant differences in the SWM and PV but not in PIC. Combined whole-brain DTI and MRSI can detect axonal degeneration in ALS. Measurements of FA obtained in the SWM, CS, PV and PIC, and NAA/Cr ratios in the SWM and PV yield the most robust results.     

Quantification of upper motor neuron loss in amyotrophic lateral sclerosis.

OBJECTIVE: To quantitatively estimate upper motor neuron (UMN) loss in ALS. METHODS: We used the recently developed triple stimulation technique (TST) to study corticospinal conduction to 86 abductor digiti minimi muscles of 48 ALS patients. This method employs a collision technique to estimate the proportion of motor units activated by a transcranial magnetic stimulus. At the same time, it yields an estimate of lower motor neuron (LMN) integrity. RESULTS: The TST disclosed and quantified central conduction failures attributable to UMN loss in 38 sides of 24 patients (subclinical in 15 sides), whereas conventional motor evoked potentials detected abnormalities in only 18 sides of 12 patients (subclinical in two sides). The increased sensitivity of the TST to detect UMN dysfunction was particularly observed in early cases. Increased central motor conduction times (CMCT) occurred exclusively in sides with conduction failure. In sides with clinical UMN syndromes, the TST response size (but not the CMCT) correlated with the muscle weakness. In sides with clinical LMN syndromes, the size of the peripherally evoked compound muscle action potentials correlated with the muscle weakness. CONCLUSION: The TST is a sensitive method to detect UMN dysfunction in ALS. It allows a quantitative estimate of the UMN loss, which is related to the functional deficit. Therefore, the TST has a considerable impact on diagnostic certainty in many patients. It will be suited to follow the disease progression and therapeutic trials.     

Brain white matter diffusion tensor metrics from clinical 1.5T MRI distinguish between ALS phenotypes

Patients with amyotrophic lateral sclerosis (ALS) can present with varying degrees of upper motor neuron (UMN) and lower motor neuron dysfunction. Previous diffusion tensor imaging (DTI) studies, in which ALS patients were not separated by the degree of UMN dysfunction, have resulted in conflicting or inconclusive results. We hypothesized that (1) categorizing ALS patients by their clinical phenotype can reveal differences in DTI abnormalities along the corticospinal tract (CST), and (2) data obtained from routine clinical DTI scans can provide this type of information. Clinical DTI scans were obtained at 1.5T in 87 ALS patients (categorized into four subgroups based on clinical phenotype) and in 12 neurologic controls. Fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity values from the CST were compared between ALS subgroups and controls. Significantly reduced FA and elevated MD values were observed in ALS patients compared to controls at the subcortical motor cortex level. Significant differences in AD values were not only seen between control and ALS patients but also between the ALS subgroups, suggesting divergent pathologies in these ALS patients. Classifying ALS patients by phenotype reveals differences in CST abnormalities between subgroups and may provide novel insights into disease mechanisms. The close similarity of our results from routine clinical scans with published research studies suggests wider accessibility to useful DTI metrics.     

Corticospinal fibers with different origins impair in amyotrophic lateral sclerosis: A neurite orientation dispersion and density imaging study

Aims

To investigate microstructural impairments of corticospinal tracts (CSTs) with different origins in amyotrophic lateral sclerosis (ALS) using neurite orientation dispersion and density imaging (NODDI).

Methods

Diffusion-weighted imaging data acquired from 39 patients with ALS and 50 controls were used to estimate NODDI and diffusion tensor imaging (DTI) models. Fine maps of CST subfibers originating from the primary motor area (M1), premotor cortex, primary sensory area, and supplementary motor area (SMA) were segmented. NODDI metrics (neurite density index [NDI] and orientation dispersion index [ODI]) and DTI metrics (fractional anisotropy [FA] and mean/axial/radial diffusivity [MD/AD/RD]) were computed.

Results

The patients with ALS showed microstructural impairments (reflected by NDI, ODI, and FA reductions and MD, AD, and RD increases) in CST subfibers, especially in M1 fibers, which correlated with disease severity. Compared with other diffusion metrics, NDI yielded a higher effect size and detected the greatest extent of CST subfibers damage. Logistic regression analyses based on NDI in M1 subfiber yielded the best diagnostic performance compared with other subfibers and the whole CST.

Conclusions

Microstructural impairment of CST subfibers (especially those originating from M1) is the key feature of ALS. The combination of NODDI and CST subfibers analysis may improve diagnosing performance for ALS.     

White matter alterations of the corticospinal tract in adults born very preterm and/or with very low birth weight

White matter (WM) injury, either visible on conventional magnetic resonance images (MRI) or measurable by diffusion tensor imaging (DTI), is frequent in preterm born individuals and often affects the corticospinal tract (CST). The relation between visible and invisible white mater alterations in the reconstructed CST of preterm subjects has so far been studied in infants, children and up to adolescence. Therefore, we probabilistically tracked the CST in 53 term‐born and 56 very preterm and/or low birth weight (VP/VLBW, < 32 weeks of gestation and/or birth weight < 1,500 g) adults (mean age 26 years) and compared their DTI parameters (axial, radial, mean diffusivity—AD, RD, MD, fractional anisotropy—FA) in the whole CST and slice‐wise along the CST. Additionally, we used the automatic, tract‐based‐spatial‐statistics (TBSS) as an alternative to tractography. We compared control and VP/VLBW and subgroups with and without CST WM lesions visible on conventional MRI. Compared to controls, VP/VLBW subjects had significantly higher diffusivity (AD, RD, MD) in the whole CST, slice‐wise along the CST, and in multiple regions along the TBSS skeleton. VP/VLBW subjects also had significantly lower (TBSS) and higher (tractography) FA in regions along the CST, but no different mean FA in the tracked CST as a whole. Diffusion changes were weaker, but remained significant for both, tractography and TBSS, when excluding subjects with visible CST lesions. Chronic CST injury persists in VP/VLBW adults even in the absence of visible WM lesions, indicating long‐term structural WM changes induced by premature birth. Hum Brain Mapp 37:289–299, 2016. © 2015 Wiley Periodicals, Inc.     

White matter pathology in ALS and lower motor neuron ALS variants: a diffusion tensor imaging study using tract-based spatial statistics

The aim of this work was to investigate white-matter microstructural changes within and outside the corticospinal tract in classical amyotrophic lateral sclerosis (ALS) and in lower motor neuron (LMN) ALS variants by means of diffusion tensor imaging (DTI). We investigated 22 ALS patients and 21 age-matched controls utilizing a whole-brain approach with a 1.5-T scanner for DTI. The patient group was comprised of 15 classical ALS- and seven LMN ALS-variant patients (progressive muscular atrophy, flail arm and flail leg syndrome). Disease severity was measured by the revised version of the functional rating scale. White matter fractional anisotropy (FA) was assessed using tract-based spatial statistics (TBSS) and a region of interest (ROI) approach. We found significant FA reductions in motor and extra-motor cerebral fiber tracts in classical ALS and in the LMN ALS-variant patients compared to controls. The voxel-based TBSS results were confirmed by the ROI findings. The white matter damage correlated with the disease severity in the patient group and was found in a similar distribution, but to a lesser extent, among the LMN ALS-variant subgroup. ALS and LMN ALS variants are multisystem degenerations. DTI shows the potential to determine an earlier diagnosis, particularly in LMN ALS variants. The statistically identical findings of white matter lesions in classical ALS and LMN variants as ascertained by DTI further underline that these variants should be regarded as part of the ALS spectrum.     

Brain sonography insight into the midbrain in myotonic dystrophy type 2

Introduction: The aim of this study was to analyze transcranial sonography (TCS) findings in genetically confirmed myotonic dystrophy type 2 (DM2) patients. Methods: Forty DM2 patients and 38 gender‐ and age‐matched healthy controls (HCs) underwent TCS through the pre‐auricular acoustic bone window. Results: Substantia nigra hyperechogenicity was found in 20% of DM2 patients compared with 3% of HCs. Brainstem raphe (BR) hypoechogenicity was more common in DM2 patients compared with HCs (56% vs. 10%, P < 0.01), and it was more common in patients with fatigue and excessive daytime sleepiness (P < 0.05). Diameter of the third ventricle was increased in DM2 patients compared with HCs (5.8 ± 1.7 vs. 5.1 ± 1.0 mm, P < 0.05). Conclusions: Finding BR hypoechogenicity might have clinical implication because of the potential response to serotonin‐reuptake inhibitors. TCS revealed alterations in brain structures previously not seen in MRI studies. Muscle Nerve 53 : 700–704, 2016     

Cerebrospinal fluid and serum antibodies against neurofilaments in patients with amyotrophic lateral sclerosis

Background: The aim of the study was to assess autoimmune involvement in amyotrophic lateral sclerosis (ALS). Methods: We measured IgG antibodies against light (NFL) and medium (NFM) subunits of neurofilaments using ELISA in paired cerebrospinal fluid (CSF) and serum samples from 38 ALS patients and 20 controls. Results: Serum levels of anti‐NFL were higher in ALS patients than in controls (P < 0.005). Serum anti‐NFL antibodies and intrathecal anti‐NFM antibodies were related to patient disability (serum anti‐NFL: P < 0.05; intrathecal anti‐NFM: P < 0.05). Anti‐NFL levels were significantly correlated with anti‐NFM levels in ALS (P < 0.001) and the control group (P < 0.0001) in the CSF, but not in serum. Anti‐NFL and anti‐NFM antibodies significantly correlated between serum and CSF in the ALS group (anti‐NFL: P < 0.0001; anti‐NFM: P < 0.001) and in the control group (anti‐NFL: P < 0.05; anti‐NFM: P < 0.05). Conclusions: Autoimmune humoral response to neurocytoskeletal proteins is associated with ALS.     

Distributed corpus callosum involvement in amyotrophic lateral sclerosis: a deterministic tractography study using q-ball imaging

Diffusion tensor imaging (DTI) has become a useful tool for investigating early white matter (WM) abnormalities in motor neuron disease. Furthermore, fiber tracking packages that apply multi-tensorial algorithms, such as q-ball imaging (QBI), have been proposed as alternative approaches to overcome DTI limitations in depicting fiber tracts with different orientations within the same voxel. We explored motor and extra-motor WM tract abnormalities in phenotypically heterogeneous amyotrophic lateral sclerosis (ALS) cases aiming to establish a consistent QBI-based WM signature of disease. We performed a whole-brain, QBI tract-based spatial statistics analysis with deterministic tractography of genu, body and splenium of corpus callosum (CC) and corticospinal tracts (CST) in 20 ALS patients (12 classical and 8 lower motor neuron variants) compared to 20 healthy controls. Mean tract length, fiber volume and density, and generalized fractional anisotropy were extracted and related to clinical indices of pyramidal impairment (upper motor neuron score), disease disability (ALS functional rating scale-revised) and progression. ALS patients showed significantly decreased fiber density and volume, and increased tract length in all regions of CC and left CST (p < 0.05, corrected). In CC body, pyramidal impairment was inversely correlated to fiber density (p = 0.01), while in CC splenium, clinical disability (p = 0.01) and progression (p = 0.02) were inversely correlated to tract length. Our findings further suggest that QBI tractography might represent a promising approach for investigating structural alterations in neurodegenerative diseases and confirm that callosal involvement is a consistent feature of most ALS variants, significantly related to both pyramidal dysfunction and disease disability.     

Upper motor neuron involvement in amyotrophic lateral sclerosis evaluated by triple stimulation technique and diffusion tensor MRI

The objective of this study was to evaluate the diagnostic value of triple stimulation technique (TST) and diffusion tensor imaging (DTI) tractography as markers of upper motor neuron (UMN) degeneration in amyotrophic lateral sclerosis (ALS). Fourteen ALS patients fulfilling the El Escorial criteria and 30 control subjects participated in the study. TST amplitude and area ratio were used as an estimate of the degree of central motor conduction failure. DTI fractional anisotropy was used as a quantitative measure of the structural integrity of the corticospinal tract and the posterior limb of the internal capsule. Mean TST amplitude and area ratio were lower in patients than controls, while there were no differences in mean fractional anisotropy of the corticospinal tract or the posterior limb of the internal capsule. TST was abnormal in 7/13 patients (sensitivity 54 %) and DTI was abnormal in 3/12 (sensitivity 25 %). Combining TST and DTI disclosed abnormalities in 8/11 patients (sensitivity 73 %). TST confirmed UMN degeneration in one of every 2.25 patient in the diagnostic categories lower than ‘probable’ ALS. Using results from TST as a criterion for UMN degeneration, four patients in diagnostic categories lower than ‘probable’ ALS and without clinical signs of UMN degeneration in the cervical region increased in diagnostic category. Our findings indicate that TST has a significant diagnostic value as an early objective marker of UMN degeneration in ALS, while the value of DTI analysis seems limited.     

Stratifying disease stages with different progression rates determined by electrophysiological tests in patients with amyotrophic lateral sclerosis

By determining the usefulness of motor unit number estimate (MUNE) and compound muscle action potential (CMAP) amplitude in patients with amyotrophic lateral sclerosis (ALS), we tried to find an effective way to stratify the disease stages. In all, 112 consecutive ALS patients were enrolled, among whom 73 were elicited in a longitudinal study. MUNE by the standard incremental technique, the average CMAP amplitude, total Medical Research Council (MRC) score, ALS‐functional rating score (ALS‐FRS), Appel ALS rating scale (AARS), and forced vital capacity (FVC) were performed at baseline and months 3, 6, and 12 after study entry. We found MUNE correlated with CMAP amplitude (P < 0.01) as well as MRC score (P < 0.01) in regionally concordant distal muscles. Both MUNE and CMAP amplitude correlated significantly with ALS‐FRS (P < 0.05) and AARS (P < 0.01). A MUNE decrease was observed at months 3, 6, and 12 compared with baseline, and the rate of change at month 3 was 50.47%. The decrease in MUNE over the first 3 months was significantly greater than other measurements. We arbitrarily divided the patients into three stages: (1) rapid progression: the rate of change of MUNE and CMAP amplitude during the first 3 months exceeded 50%; (2) moderate progression: the rate of change of MUNE was greater than 50% but CMAP amplitude was less than 50%; (3) slow progression: the rate of change of both MUNE and CMAP amplitude were less than 50%. Comparing the rate of ALS‐FRS descent per year using one‐way ANOVA showed a significant difference among the three groups (P < 0.01). Muscle Nerve 39: 304–309, 2009     

The ε4 genotype of apolipoprotein E and white matter integrity in Alzheimer's disease

BackgroundIn this multicenter study, we investigated a possible association between the APOE ε4 allele and white matter (WM) integrity in Alzheimer's disease (AD) using diffusion tensor imaging (DTI).MethodsWe analyzed fractional anisotropy (FA) and mean diffusivity (MD) as indices of WM integrity in 70 AD patients (35 APOE ε4 carriers, 35 noncarriers) and 56 healthy control (HC) subjects (28 APOE ε4 carriers, 28 noncarriers). APOE ε4 carriers and noncarriers were matched for age and gender within each diagnostic group.ResultsWe found significant effects of diagnosis (P_corrected < .05 [FWE]; i.e., smaller FA values and larger MD values in AD patients compared with HCs) and significant effects (P < .001) of APOE ε4 carrier status on MD in HCs but not in AD subjects.ConclusionsThe results indicate that APOE ε4 has a moderate effect on WM integrity in HCs, but no effect on WM integrity in manifest AD.     

Brain plasticity in the motor network is correlated with disease progression in amyotrophic lateral sclerosis

Objective: To test the influence of functional cerebral reorganization in amyotrophic lateral sclerosis (ALS) on disease progression. Methods: Nineteen predominantly right‐handed ALS patients and 21 controls underwent clinical evaluation, functional Magnetic Resonance Imaging (fMRI), and diffusion tensor imaging. Patients were clinically re‐evaluated 1 year later and followed until death. For fMRI, subjects executed and imagined a simple hand‐motor task. Between‐group comparisons were performed, and correlations were searched with motor deficit arm Medical Research Council (MRC) score, disease progression ALS Functional Rating Scale (ALSFRS), and survival time. Results: By the MRC score, the hand strength was lowered by 12% in the ALS group predominating on the right side in accordance with an abnormal fractional anisotropy (FA) limited to the left corticospinal tract (37.3% reduction vs. controls P < 0.01). Compared to controls, patients displayed overactivations in the controlateral parietal (P < 0.004) and somatosensory (P < 0.004) cortex and in the ipsilateral parietal (P < 0.01) and somatosensory (P < 0.01) cortex to right‐hand movement. Movement imagination gave similar results while no difference occurred with left‐hand tasks. Stepwise regression analysis corrected for multiple comparisons showed that controlateral parietal activity was inversely correlated with disease progression (R² = 0.43, P = 0.001) and ipsilateral somatosensory activations with the severity of the right‐arm deficit (R² = 0.48, P = 0.001). Conclusions: Cortical Blood Oxygen Level Dependent (BOLD) signal changes occur in the brain of ALS patients during a simple hand‐motor task when the motor deficit is still moderate. It is correlated with the rate of disease progression suggesting that brain functional rearrangement in ALS may have prognostic implications. Hum Brain Mapp 34:2391–2401, 2013. © 2012 Wiley Periodicals, Inc.     

Autonomic system and amyotrophic lateral sclerosis

Introduction: The aim of this study is to characterize autonomic impairment in motor neuron disease. Methods: Neurological evaluations and autonomic testing were analyzed retrospectively in 132 patients: 86 classic amyotrophic lateral sclerosis (ALS), 36 lower motor neuron (LMN), and 10 upper motor neuron (UMN) predominant disease. Results: One‐third of patients were symptomatic; urinary urgency and constipation were the most frequent symptoms. Increased Composite Autonomic Severity Score (CASS) was present in 75% with mild impairment (CASS 1–3) in 85% and moderate (CASS 4–7) in 15%. The frequencies of testing abnormalities were: sudomotor 46%, cardiovagal 50%, and adrenergic 14%. The UMN group had significantly higher median CASS scores than the classic ALS (P = 0.021) and LMN group (P = 0.018). Conclusions: We found predominantly mild autonomic impairment in ALS patients, with mostly cardiovagal and sudomotor involvement. Moderate autonomic failure occurred in 1 of 7 patients, especially those with an UMN presentation. Patients with selective corticospinal tract involvement may have more impairment of autonomic pathways. Muscle Nerve 51 :676–679, 2015