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Facial onset sensory motor neuronopathy (FOSMN) syndrome is a rare sporadic entity which has only recently been described ( Vucic et al., 2006 ). It is presumed to be neurodegenerative; its etiology however, remains unknown. Despite initial facial sensory symptoms, FOSMN syndrome has been linked to amyotrophic lateral sclerosis (ALS), a link which has recently been underpinned by a description of a D90A superoxide dismutase-1 (SOD-1) mutation in a case of FOSMN syndrome ( Dalla Bella et al., 2014 ). We describe another case of a presumed FOSMN syndrome in a 70-year-old man. At the age of 56, the patient experienced facial and bulbar motor symptoms, though without prominent trigeminal sensory symptoms. He developed slow progressive mild dysarthria, dysphagia, and hoarseness, showing pronounced facial weakness, fasciculation, and myokymia, wasted furrowed tongue, but no upper or lower limb weakness or fasciculation or no upper motor neuron signs. Electrodiagnostic findings revealed an abnormal blink reflex, masseter reflex, masseteric silent period, and trigeminal SEPs. Nerve conduction studies showed a sensory-motor polyneuropathy predominantly demyelinating. A chronic neuropathy with predominant remyelination and regeneration, though without cellular infiltration or amyloid deposition, could be observed in a sural nerve biopsy. A pathologic trinucleotide CAG repeat expansion in the androgen receptor gene (spinal and bulbar muscular atrophy, Kennedy’s disease) and a dynactin mutation were excluded by means of Sanger sequencing. Additionally, next-generation sequencing targeted to 242 neurodegeneration associated genes revealed a homozygous variant in the CYP2U1 gene (c.992A>G, p.N331S) and a heterozygous variant in the SYNE1 gene (c.6268G>C, p.E2090Q). These variants have yet to be described in genetic databases. No mutations could be detected among 26 screened ALS-related genes. Mutations in CYP2U1 can cause autosomal recessive inherited spastic paraplegia type 56 (SPG 56). Mutations in SYNE1 can cause either autosomal dominant Emery-Dreifuss muscular dystrophy-4 (EDMD4) or autosomal recessive spinocerebellar ataxia type 8 (SCAR8). The relationship between the CYP2U1 and SYNE1 variants and FOSMN syndrome established here requires further investigation. The genetic data presented showed no link between FOSMN syndrome and ALS, instead pointing towards evidence of an oligogenic basis for FOSMN syndrome. [ABSTRACT FROM AUTHOR]

Introduction Diffusion tensor imaging (DTI)-based metrics are increasingly used for analyzing ALS-associated whitematter alteration patterns and were included inthe Neuroimaging Society in Amyotrophic Lateral Sclerosis (NiSALS) concept ( Turner et al., 2011 ). The objective of this multicenter study was to assess structural connectivity in ALS at a large sample size to address the challenges of DTI data analysis from multiple study sites. Methods Four-hundred and ninety DTI data sets from patients with ALS ( N = 268) and controls ( N = 222) were collected from 8 study centers (Dublin, Ireland; Edinborough, UK; Jena, Germany; Miami, US; Milan, Italy; Oxford, UK; Rostock, Germany, Ulm, Germany). Data were obtained by different MRI-systems and by use of different DTI-protocols. In a first step, comparability of data with the aim of pooling was tested by a statistical analysis of fractional anisotropy (FA) in controls’ data. All analyses were performed by use of the Tensor Imaging and Fiber Tracking (TIFT) software. Statistical comparisons in terms of average FA-values ( Müller et al., 2013 ) were performed for the controls’ groups of the different centers. In a consecutive step, the calculated 3D correction matrices were then applied to the corresponding ALS patient subgroups of the different centers. Results Data collection and data quality control resulted in 442 DTI data sets (253 ALS patients and 189 controls) useful for this study, i.e. 48 data sets had to be excluded. All data samples of all centers showed a characteristic pattern (FA decrease along the corticospinal tracts) for comparison at the group level. Inter-center pooling of data showed ALS affectations in the CST (“horseshoe” configuration) as well as affectations in regions that have recently been reported to be relevant in ALS (frontocortical whitematter regions, hippocampal regions, as well as midbrain and brainstem) ( Kassubek et al., 2014 ). Conclusion This large scale multicenter NiSALS study investigated solutions to challenges in the process of pooling MRI data recorded at various study centers in ALS. This approach is of utmost importance in order to establish MRI-based techniques as read-outs both fornatural history assessment and for potential upcoming disease-modifying multicenter studies in ALS ( Roßkopf et al., in press ). [ABSTRACT FROM AUTHOR]