- Anti-ganglioside complex antibody profiles in a recurrent complicated case of GQ1b-seronegative miller fisher syndrome and Bickerstaff brainstem encephalitis: a case report. [Journal Article]
- BNBMC Neurol 2018 May 23; 18(1):72
- CONCLUSIONS: This study reports novel phenomena about the GSC-Abs profiles and its relationship with clinical features in a case with recurrent GBS spectrum disorder, showing different phenotypes in different episodes. Further studies are required to reveal the significance of the GSC-Abs profiles in recurrent GBS spectrum disorder.
- Understanding Refugees' Health. [Journal Article]
- SNSemin Neurol 2018; 38(2):152-162
- According to the United Nations Refugee Agency (UNHCR), 65.6 million people have been forcibly displaced worldwide. Several factors have a major influence on asylum seekers' health; so, their health ...
According to the United Nations Refugee Agency (UNHCR), 65.6 million people have been forcibly displaced worldwide. Several factors have a major influence on asylum seekers' health; so, their health profile is markedly different from that of the population in the country of asylum. The aim of this study is to review the major issues physicians need to be aware of when treating asylum seekers, with a special focus on the neurological problems of asylum seekers and refugees. The major impact factors on refugees' health are linked to experiences and exposure (1) in the country of origin, (2) in refugee camps and en route to Europe, and (3) in the process of immigration into the host country and living in European asylum centers. Refugees' health is also affected by psychological problems and by infectious diseases. Additionally, chronic diseases resulting in polymorbidity, cancer, and neurological diseases are easy to overlook and demand special attention. Neurological injuries/diseases may be traumatic (e.g., spinal cord injuries), posttraumatic (e.g., chronic pain syndromes), the result of cerebral infections, or the consequences of starvation (e.g., epilepsy, ataxia, and paraesthesia). The main challenges for physicians are lack of awareness of the asylum seekers' specific health care problems, language and intercultural communication problems, as well as access and integration of asylum seekers into the health care system. The health issues of asylum seekers are manifold and challenging to physicians. Awareness of these conditions is mandatory to ensure good clinical practice for this patient population, which has a huge burden in chronic, infectious, mental, and neurological diseases.
- A de novo KCNA1 Mutation in a Patient with Tetany and Hypomagnesemia. [Journal Article]
- NNephron 2018 May 23; :1-8
- Mutations in the KCNA1 gene encoding the voltage-gated potassium (K+) channel Kv1.1 have been linked to rare neurological syndromes, episodic ataxia type 1 (EA1) and myokymia. In 2009, a KCNA1 mutati...
Mutations in the KCNA1 gene encoding the voltage-gated potassium (K+) channel Kv1.1 have been linked to rare neurological syndromes, episodic ataxia type 1 (EA1) and myokymia. In 2009, a KCNA1 mutation was identified in a large family with autosomal dominant hypomagnesemia. Despite efforts in establishing a genotype-phenotype correlation for the wide variety of symptoms in EA1, little is known on the serum magnesium (Mg2+) levels in these patients. In the present study, we describe a new de novo KCNA1 mutation in a Polish patient with tetany and hypomagnesemia. Electrophysiological and biochemical analyses were performed to determine the pathogenicity of the mutation. A female patient presented with low serum Mg2+ levels, renal Mg2+ wasting, muscle cramps, and tetanic episodes. Whole exome sequencing identified a p.Leu328Val mutation in KCNA1 encoding the Kv1.1 K+ channel. Electrophysiological examinations demonstrated that the p.Leu328Val mutation caused a dominant-negative loss of function of the encoded Kv1.1 channel. Cell surface biotinylation showed normal plasma membrane expression. Taken together, this is the second report linking KCNA1 with hypomagnesemia, thereby emphasizing the need for further evaluation of the clinical phenotypes observed in patients carrying KCNA1 mutations.
- Peripheral blood gene expression reveals an inflammatory transcriptomic signature in Friedreich's ataxia patients. [Journal Article]
- HMHum Mol Genet 2018 May 22
- Transcriptional changes in Friedreich's ataxia (FRDA), a rare and debilitating recessive Mendelian neurodegenerative disorder, have been studied in affected but inaccessible tissues - such as dorsal ...
Transcriptional changes in Friedreich's ataxia (FRDA), a rare and debilitating recessive Mendelian neurodegenerative disorder, have been studied in affected but inaccessible tissues - such as dorsal root ganglia, sensory neurons, and cerebellum - in animal models or small patient series. However, transcriptional changes induced by FRDA in peripheral blood, a readily accessible tissue, have not been characterized in a large sample. We used differential expression, association with disability stage, network analysis, and enrichment analysis to characterize the peripheral blood transcriptome and identify genes that were differentially expressed in FRDA patients (n = 418) compared to both heterozygous expansion carriers (n = 228) and controls (n = 93, 739 individuals in total), or were associated with disease progression, resulting in a disease signature for FRDA. We identified a transcriptional signature strongly enriched for an inflammatory innate immune response. Future studies should seek to further characterize the role of peripheral inflammation in FRDA pathology and determine its relevance to overall disease progression.
- Behçet's Syndrome and Nervous System Involvement. [Review]
- CNCurr Neurol Neurosci Rep 2018 May 23; 18(7):35
- Although Behçet's syndrome (BS) is classified as a rare disease in European countries and the USA, its neurologic involvement "neuro-Behçet's syndrome (NBS)" is commonly included in the differential ...
Although Behçet's syndrome (BS) is classified as a rare disease in European countries and the USA, its neurologic involvement "neuro-Behçet's syndrome (NBS)" is commonly included in the differential diagnosis of many inflammatory and vascular central nervous system (CNS) disorders. Clinical and neuroimaging findings support two major forms of NBS: parenchymal NBS (p-NBS) and an extra-parenchymal form that presents with cerebral venous sinus thrombosis (CVST). The present review summarizes recent findings on the etiopathogenesis and clinico-radiological features of this disorder as well as its treatment options.
- Inhibition of ATR acutely sensitizes acute myeloid leukemia cells to nucleoside analogs that target ribonucleotide reductase. [Journal Article]
- BABlood Adv 2018 May 22; 2(10):1157-1169
- The ataxia telangiectasia and Rad3-related (ATR) protein kinase promotes cancer cell survival by signaling stalled replication forks generated by replication stress, a common feature of many cancers ...
The ataxia telangiectasia and Rad3-related (ATR) protein kinase promotes cancer cell survival by signaling stalled replication forks generated by replication stress, a common feature of many cancers including acute myeloid leukemia (AML). Here we show that the antileukemic activity of the chemotherapeutic nucleoside analogs hydroxyurea and gemcitabine was significantly potentiated by ATR inhibition via a mechanism involving ribonucleotide reductase (RNR) abrogation and inhibition of replication fork progression. When administered in combination with gemcitabine, an inhibitor of the M1 RNR subunit, the ATR inhibitor VX-970, eradicated disseminated leukemia in an orthotopic mouse model, eliciting long-term survival and effective cure. These data identify a synergistic interaction between ATR inhibition and RNR loss that will inform the deployment of small molecule inhibitors for the treatment of AML and other hematologic malignancies.
- Lumbosacral transitional vertebrae in cats and its relationship to lumbosacral vertebral canal stenosis. [Journal Article]
- JFJ Feline Med Surg 2018 May 01; :1098612X18774449
- Objectives Although a clear relationship has been demonstrated between the presence of lumbosacral transitional vertebrae and the development of lumbosacral stenosis in dogs, this relationship has no...
Objectives Although a clear relationship has been demonstrated between the presence of lumbosacral transitional vertebrae and the development of lumbosacral stenosis in dogs, this relationship has not been evaluated in cats. The aim of this study was to investigate the relationship between the presence of lumbosacral transitional vertebrae and lumbosacral stenosis in cats. Methods The medical records and diagnostic imaging studies of 13 cats diagnosed with lumbosacral stenosis were retrospectively reviewed for lumbosacral abnormalities and compared with findings of 405 cats that underwent CT for reasons unrelated to spinal disease. Results Clinical signs associated with lumbosacral stenosis included lumbosacral pain, low tail carriage, difficulty jumping, and urinary or faecal incontinence. Neurological signs included proprioceptive deficits, ambulatory paraparesis, pelvic limb ataxia, reduced spinal reflexes and reduced perianal reflex. Duration of clinical signs ranged from 1 day to 10 months (mean 3 months). Of the 13 cats with lumbosacral stenosis, seven (53.8%) were diagnosed with lumbosacral transitional vertebrae. In the control population of 405 cats, 24 (5.9%) were diagnosed with lumbosacral transitional vertebrae. Results indicated that lumbosacral transitional vertebrae were significantly ( P <0.0001) more prevalent in cats with lumbosacral stenosis compared with the control feline population (odds ratio 18.52, 95% confidence interval 6.1-62.1). Development of clinical signs of lumbosacral stenosis in cats with lumbosacral transitional vertebrae (mean 10.8 years) was not significantly different from that of cats without lumbosacral transitional vertebrae (mean 12.7 years). Likewise, there was no significant influence of breed ( P >0.99) or sex ( P = 0.29) on the occurrence of lumbosacral transitional vertebrae. Conclusions and relevance Despite lumbosacral stenosis being a rare spinal condition in cats, lumbosacral transitional vertebrae can be considered a risk factor for its development.
- Acrylamide acute neurotoxicity in adult zebrafish. [Journal Article]
- SRSci Rep 2018 May 21; 8(1):7918
- Acute exposure to acrylamide (ACR), a type-2 alkene, may lead to a ataxia, skeletal muscles weakness and numbness of the extremities in human and laboratory animals. In the present manuscript, ACR ac...
Acute exposure to acrylamide (ACR), a type-2 alkene, may lead to a ataxia, skeletal muscles weakness and numbness of the extremities in human and laboratory animals. In the present manuscript, ACR acute neurotoxicity has been characterized in adult zebrafish, a vertebrate model increasingly used in human neuropharmacology and toxicology research. At behavioral level, ACR-treated animals exhibited "depression-like" phenotype comorbid with anxiety behavior. At transcriptional level, ACR induced down-regulation of regeneration-associated genes and up-regulation of oligodendrocytes and reactive astrocytes markers, altering also the expression of genes involved in the presynaptic vesicle cycling. ACR induced also significant changes in zebrafish brain proteome and formed adducts with selected cysteine residues of specific proteins, some of them essential for the presynaptic function. Finally, the metabolomics analysis shows a depletion in the monoamine neurotransmitters, consistent with the comorbid depression and anxiety disorder, in the brain of the exposed fish.
- TLR-activated repression of Fe-S cluster biogenesis drives a metabolic shift and alters histone and tubulin acetylation. [Journal Article]
- BABlood Adv 2018 May 22; 2(10):1146-1156
- Given the essential roles of iron-sulfur (Fe-S) cofactors in mediating electron transfer in the mitochondrial respiratory chain and supporting heme biosynthesis, mitochondrial dysfunction is a common...
Given the essential roles of iron-sulfur (Fe-S) cofactors in mediating electron transfer in the mitochondrial respiratory chain and supporting heme biosynthesis, mitochondrial dysfunction is a common feature in a growing list of human Fe-S cluster biogenesis disorders, including Friedreich ataxia and GLRX5-related sideroblastic anemia. Here, our studies showed that restriction of Fe-S cluster biogenesis not only compromised mitochondrial oxidative metabolism but also resulted in decreased overall histone acetylation and increased H3K9me3 levels in the nucleus and increased acetylation of α-tubulin in the cytosol by decreasing the lipoylation of the pyruvate dehydrogenase complex, decreasing levels of succinate dehydrogenase and the histone acetyltransferase ELP3, and increasing levels of the tubulin acetyltransferase MEC17. Previous studies have shown that the metabolic shift in Toll-like receptor (TLR)-activated myeloid cells involves rapid activation of glycolysis and subsequent mitochondrial respiratory failure due to nitric oxide (NO)-mediated damage to Fe-S proteins. Our studies indicated that TLR activation also actively suppresses many components of the Fe-S cluster biogenesis machinery, which exacerbates NO-mediated damage to Fe-S proteins by interfering with cluster recovery. These results reveal new regulatory pathways and novel roles of the Fe-S cluster biogenesis machinery in modifying the epigenome and acetylome and provide new insights into the etiology of Fe-S cluster biogenesis disorders.
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- Mouse models of nesprin-related diseases. [Review]
- BSBiochem Soc Trans 2018 May 21
- Nesprins (nuclear envelope spectrin repeat proteins) are a family of multi-isomeric scaffolding proteins. Nesprins form the LInker of Nucleoskeleton-and-Cytoskeleton (LINC) complex with SUN (Sad1p/UN...
Nesprins (nuclear envelope spectrin repeat proteins) are a family of multi-isomeric scaffolding proteins. Nesprins form the LInker of Nucleoskeleton-and-Cytoskeleton (LINC) complex with SUN (Sad1p/UNC84) domain-containing proteins at the nuclear envelope, in association with lamin A/C and emerin, linking the nucleoskeleton to the cytoskeleton. The LINC complex serves as both a physical linker between the nuclear lamina and the cytoskeleton and a mechanosensor. The LINC complex has a broad range of functions and is involved in maintaining nuclear architecture, nuclear positioning and migration, and also modulating gene expression. Over 80 disease-related variants have been identified in SYNE-1/2 (nesprin-1/2) genes, which result in muscular or central nervous system disorders including autosomal dominant Emery-Dreifuss muscular dystrophy, dilated cardiomyopathy and autosomal recessive cerebellar ataxia type 1. To date, 17 different nesprin mouse lines have been established to mimic these nesprin-related human diseases, which have provided valuable insights into the roles of nesprin and its scaffold LINC complex in a tissue-specific manner. In this review, we summarise the existing nesprin mouse models, compare their phenotypes and discuss the potential mechanisms underlying nesprin-associated diseases.