P1-14-07 Detection of upper motor neuron impairment masked by lower motor neuron impairment using central motor conduction time in ALS patients

Aim: The aim of this study was to evaluate the corticospinal tract (CST) diffusion profile in pure lower motor neuron disease (pLMND) patients who at baseline did not show any clinical or electrophysiological involvement of upper motor neurons (UMN), and in amyotrophic lateral sclerosis (ALS) patients. Materials and Methods: Fifteen ALS patients with delayed central motor conduction time (CMCT) and 14 pLMND patients with normal CMCT were enrolled together with 15 healthy controls. Fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) maps were obtained. The tract profile of CST was reconstructed with the automated fiber quantification tool and its diffusion properties were quantified voxel-by-voxel and then compared pairwise between groups. Moreover, a random forest (RF) classifier was trained to evaluate the ability of CST diffusion metrics in distinguishing pairwise the groups from the controls. Results: ALS patients presented wide microstructural abnormalities in the entire CST as assessed by FA decrease and RD increase while pLMND patients showed focal FA decrease and a larger AD increase in the cerebral peduncle and posterior limb of the internal capsule in comparison with controls. RF revealed that diffusion tensor imaging (DTI) metrics accurately distinguished ALS patients and pLMND patients from controls (96.67 and 95.71% accuracy, respectively). Conclusions: Our study demonstrates that the CST was impaired in both ALS and pLMND patients, thus suggesting that DTI metrics are a reliable tool in detecting subtle changes of UMN in pLMND patients, also in the absence of clinical and CMCT abnormalities.

Download Full-text

Central motor conduction time reveals upper motor neuron involvement masked by lower motor neuron impairment in a significant portion of patients with amyotrophic lateral sclerosis

Clinical Neurophysiology ◽

10.1016/j.clinph.2020.05.021 ◽

2020 ◽

Vol 131 (8) ◽

pp. 1896-1901

Author(s):

Ryo Tokimura ◽

Takenobu Murakami ◽

Yoshikazu Ugawa

Keyword(s):

Amyotrophic Lateral Sclerosis ◽

Motor Neuron ◽

Lower Motor Neuron ◽

Conduction Time ◽

Central Motor Conduction Time ◽

Lateral Sclerosis

Download Full-text

Role of MAPT in Pure Motor Neuron Disease: Report of a Recurrent Mutation in Italian Patients

Neurodegenerative Diseases ◽

10.1159/000497820 ◽

2018 ◽

Vol 18 (5-6) ◽

pp. 310-314 ◽

Cited By ~ 5

Author(s):

Paola Origone ◽

Alessandro Geroldi ◽

Merit Lamp ◽

Francesca Sanguineri ◽

Claudia Caponnetto ◽

...

Keyword(s):

Motor Neuron ◽

Motor Neuron Disease ◽

Lower Motor Neuron ◽

Multiple Gene ◽

C9orf72 Expansion ◽

Mapt Gene ◽

Als Patients ◽

Lateral Sclerosis ◽

Pure Motor

The aim of our study was to evaluate the role of mutations in the MAPT gene in patients with pure amyotrophic lateral sclerosis (ALS). A cohort of 120 ALS patients, both sporadic and familial, without cognitive impairment was analyzed by next-generation sequencing with a multiple-gene panel comprising 23 genes, including MAPT, known to be associated with ALS and frontotemporal dementia. The presence of the C9orf72 expansion was also investigated. Twelve patients had mutations in the SOD1, TARDBP, MATR3, and FUS genes, while 10 patients carried the C9orf72 expansion. One female patient was found to carry the D348G mutation in MAPT, previously reported in an Italian family with lower motor neuron disease. Our patient presented both upper and lower motor neuron signs, early development of dyspnea, resting and kinetic tremor, and a slow disease course (> 11 years). The present case further broadens the clinical phenotype associated with MAPT mutations and suggests that, although rarely, MAPT mutations can cause ALS and, therefore, should be analyzed in ALS patients, especially in those with early breathing difficulties and long-lasting disease.

Download Full-text

Heterogeneity of central motor conduction time to upper and lower limbs in patients with motor neuron disease and spasmodic paraplegia

Electroencephalography and Clinical Neurophysiology ◽

10.1016/0013-4694(93)91165-w ◽

1993 ◽

Vol 87 (2) ◽

pp. S70

Author(s):

R. Mercelis ◽

J.J. Martin

Keyword(s):

Motor Neuron ◽

Motor Neuron Disease ◽

Lower Limbs ◽

Conduction Time ◽

Central Motor Conduction Time

Download Full-text

S150. Detection of upper motor neuron impairment in ALS with central motor conduction time

Clinical Neurophysiology ◽

10.1016/j.clinph.2018.04.510 ◽

2018 ◽

Vol 129 ◽

pp. e197-e198

Author(s):

Takenobu Murakami ◽

Ryo Tokimura ◽

Setsu Nakatani-Enomoto ◽

Hiroyuki Enomoto ◽

Yoshikazu Ugawa

Keyword(s):

Motor Neuron ◽

Conduction Time ◽

Central Motor Conduction Time

Download Full-text

A Novel Variant in Superoxide Dismutase 1 Gene (p.V119M) in Als Patients with Pure Lower Motor Neuron Presentation

Genes ◽

10.3390/genes12101544 ◽

2021 ◽

Vol 12 (10) ◽

pp. 1544

Author(s):

Claudia Ricci ◽

Fabio Giannini ◽

Giulia Riolo ◽

Silvia Bocci ◽

Stefania Casali ◽

...

Keyword(s):

Superoxide Dismutase ◽

Motor Neuron ◽

Motor Neurons ◽

Lower Limbs ◽

Lower Motor Neuron ◽

Superoxide Dismutase 1 ◽

Sporadic Als ◽

Novel Variant ◽

History Of ◽

Als Patients

Amyotrophic lateral sclerosis (ALS) is a progressive and fatal disorder characterized by degeneration of motor neurons in the cerebral cortex, brain stem, and spinal cord. Most cases of ALS appear sporadically, but 5–10% of patients have a family history of disease. Mutations in the superoxide dismutase 1 gene (SOD1) have been found in 12–23% of familial cases and in 1–2% of sporadic cases. Currently, more than 180 different SOD1 gene variants have been identified in ALS patients. Here, we describe two apparently sporadic ALS patients carrying the same SOD1 c.355G>A variant, leading to the p.V119M substitution, not previously described. Both the patients showed pure lower motor neuron phenotype. The former presented with the flail leg syndrome, a rare ALS variant, characterized by progressive distal onset weakness and atrophy of lower limbs, slow progression and better survival than typical ALS. The latter exhibited rapidly progressive weakness of upper and lower limbs, neither upper motor neuron nor bulbar involvement, and shorter survival than typical ALS. We provide an accurate description of the phenotype, and a bioinformatics analysis of the p.V119M variant on protein structure. This study may increase the knowledge about genotype-phenotype correlations in ALS and improve the approach to ALS patients.

Download Full-text