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Introduction Recently defined consensus criteria for the diagnosis of neuromyelitis optica spectrum disorders (NMOSD) allow establishing the diagnosis in patients without elevated AQP4-Ab and optic nerve involvement. According to the new extended definition, NMOSD is closely associated with extensive spinal cord inflammation occurring in the course of systemic autoimmune diseases as sarcoidosis or lupus erythematodes. NMOSD occurring in the course of hematological disease have not yet been reported in the literature. Case report A 38 year old male subsequently developed thrombocytopenia, hemolytic anemia and agranulocytosis over a 23 month period. Three months after an episode of agranulocytosis, he noticed ascending sensory disturbances and progressive weakness of his legs. Within two days, symptoms worsened to give almost complete paraplegia and loss of sensation below a midthoracic level. MRI revealed signal hyperintensity and edema in T2-weighted sequences reaching from the 2nd cervical to the 9th thoracic vertebral body. Two years later, he developed a second episode with lesions in the spinal cord and periventricular areas of brain stem and thalamus. Conclusion The relapsing time course and the topographical pattern of central nervous system lesions restricted to axial brain structures and the spinal cord fulfill the criteria that have recently been defined for AQP4-Ab-negative NMO-spectrum disease. Systematic studies on the association of hematological autoimmune phenomena and spinal cord disease are needed to clarify whether this coincidence is just a casual phenomenon or whether it points to a yet undiscovered but perhaps therapeutically interesting link of immunological mechanisms affecting both organ systems. [ABSTRACT FROM AUTHOR]

The combination of bilateral lytic lesions in the bones of the lower and upper extremities and presenile dementia is characteristic of polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy, also known as Nasu-Hakola disease. The clinical course of this rare and fatal disorder is characterized by pathologic fractures of these often painful lesions, rapid progression of dementia, and death in the fifth decade of life. The radiographic changes may be confused with cystic angiomatosis, focal metastasizing hemangioendothelioma, or Langerhans' cell histiocytosis. We report five patients to illustrate the clinical presentation, radiographic images, psychiatric abnormalities, and new genetic findings. Three of the patients were siblings. A biopsy is not needed to confirm the diagnosis of polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy because of the unique combination of radiographic and neurologic features. [ABSTRACT FROM AUTHOR]

The pathomorphological correlate of Kennedy's disease (KD) is a degeneration of spinal and bulbar α‐motor neurons. The disease is caused by a CAG repeat expansion in the first exon of the X‐chromosomal androgene receptor gene. Contrary to the common belief that cognitive disorders in motor neuron diseases (MND) are either rare or only mild, there is now an increasing number of case reports on dementia in amyotrophic lateral sclerosis (ALS). In ALS, dementia of the frontal lobe type (frontotemporal dementia, FTD) seems to be the characteristic pattern. However, in KD cognitive dysfunction has not been studied systematically. Here we present a case with clinical characteristics of FTD in a patient with genetically confirmed KD. It remains speculative whether there is an association between KD and FTD comparable to a genetic linkage between ALS and FTD, which has been proposed in recent years. However, we suggest that cognitive dysfunction may be more common in KD than reported until today. [ABSTRACT FROM AUTHOR]

Rotaviruses are important pathogens associated with diarrhoeal diseases in almost all species of mammals. In the present study, a nested reverse transcriptase-polymerase chain reaction (RT-PCR) for the detection of group A rotaviruses was developed, which is based on a target region in gene segment 6. Rotavirus strains of human, bovine, porcine, canine, feline, equine, and ovine origin were examined. Furthermore several faecal specimens, in which rotavirus had already been detected using other methods than PCR, were included in the study. A nested RT-PCR product was formed with all strains and faecal samples tested. The detection limit for virus-containing cell culture supernatant was 3 × 10–2 [50% tissue culture infective dose (TCID50 )] by RT-PCR and 3 × 10–3 TCID50 by nested amplification. In order to examine the influence of the sample matrix on sensitivity, a rotavirus-negative faecal specimen was spiked with virus-containing cell culture suspension of the porcine rotavirus OSU. The detection limit of the present PCR procedure was approximately 1.6 × 102 TCID50 per g faeces and could be increased by one order of magnitude using nested PCR. The present method for detection and identification of group A rotaviruses represents a powerful diagnostic tool and was shown to be applicable to rotaviruses of different origin, including human sources. [ABSTRACT FROM AUTHOR]

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]

Objective In-vivo assessment of ALS-associated white matter alteration patterns by diffusion tensor imaging (DTI)-based metrics have been included in the NiSALS neuroimaging concept (Turner et al., LancetNeurol 2011). The objective of this multicenter study was to assess structural connectivity in ALS at a large sample-size. Methods Four-hundred-and-seven DTI data sets from patients with ALS ( N = 239) and controls ( N = 168) were collected from 8 international centers with different scanner systems and different DTI-protocols. Comparability of data with the aim of pooling was tested and differences were regressed out. Results Beyond patterns of alterations in the corticospinal tracts, whole brain-based statistical analysis, after pooling of data sets from all centers, additionally captured significant white matter tract changes in the frontal lobe, brainstem and hippocampal regions, in keeping with the DTI-based correlates of post mortem neuropathological ALS-stages 1–4 (Kassubek et al., Brain 2014). Conclusion This study using an unprecedented number of subjects has detected more wide spread changes than typical single-site studies.The observed pattern of fiber tract pathology has the potential to serve as a biomarker of disease and progression and as a read-out for future clinical trials. Key message By this multi-centre approach, it was possible to non-invasively confirm the pathoanatomy of ALS in vivo . [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]