[Show abstract][Hide abstract] ABSTRACT: Background and Purpose
The receptor for advanced glycation end products (RAGE) may contribute to the development of diabetic neuropathy. To assess its relevance in humans, this study examined the expression of RAGE in the skin biopsy samples of patients with diabetes mellitus, and investigated its correlation with intraepidermal nerve-fiber density (IENFD) and clinical measures of neuropathy severity.
Forty-four patients who either had type 2 diabetes or were prediabetes underwent clinical evaluation and a 3-mm skin punch biopsy. The clinical severity of their neuropathy was assessed using the Michigan Diabetic Neuropathy Score. IENFD was measured along with immunohistochemical staining for RAGE in 29 skin biopsy samples. The expression of RAGE was also quantified by real-time reverse-transcription PCR in the remaining 15 patients.
RAGE was localized mostly in the dermal and subcutaneous vascular endothelia. The staining was more intense in patients with a lower IENFD (p=0.004). The quantity of RAGE mRNA was significantly higher in patients with severe neuropathy than in those with no or mild neuropathy (p=0.003). The up-regulation of RAGE was related to dyslipidemia and diabetic nephropathy. There was a trend toward decreased sural nerve action-potential amplitude and slowed peroneal motor-nerve conduction with increasing RAGE expression.
The findings of this study demonstrate up-regulation of RAGE in skin biopsy samples from patients with diabetic neuropathy, supporting a pathogenic role of RAGE in the development of diabetic neuropathy.
[Show abstract][Hide abstract] ABSTRACT: Neuromyelitis optica (NMO) is an inflammatory demyelinating disorder of the central nervous system with a relapsing and remitting course. We aimed to identify factors associated with the time to next attack, including the effect of the natural disease course and the diverse treatment regimens, by applying a longitudinal statistical analysis to the individual attacks of each patient.
In total, 184 acute attacks among 58 patients with either NMO or NMO spectrum disorder with anti-aquaporin-4 antibody were assessed retrospectively. Patient demographics, clinical characteristics at each attack, and type of treatment during inter-attack periods were assessed. The dependent variable was defined as the time from each attack to the next attack (inter-attack interval). An exponential accelerated failure time model with shared gamma frailty was adapted for statistical analysis.
A multivariable analysis revealed that the time from each attack to the next attack in NMO increased independently by 1.31 times (95% confidence interval (CI), 1.02-1.67; p = 0.035) with each additional cumulative attack experienced, by 5.34 times (95% CI, 1.57-18.13; p = 0.007) with combined azathioprine treatment and continued oral prednisolone, and by 4.26 times (95% CI, 1.09-16.61; p = 0.037) with rituximab treatment.
The time to next attack in NMO can increase naturally in the later stages of the disease as the number of cumulative attacks increases. Nevertheless, both combined azathioprine treatment with continued oral prednisolone and rituximab treatment were also associated with a longer time to next attack, independently of the natural disease course of NMO.
PLoS ONE 12/2013; 8(12):e82325. DOI:10.1371/journal.pone.0082325 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that leads to progressive weakness of the respiratory and limb muscles. Consequently, most patients with ALS exhibit progressive hypoventilation, which worsens during sleep. The aim of this study was to evaluate the relationship between nocturnal hypoxia and cognitive dysfunction and to assess the pattern of nocturnal hypoxia in patients with ALS.
Twenty-five patients with definite or probable ALS underwent neuropsychologic testing, nocturnal pulse oximetry, and capnography. Patients were grouped according to the presence of nocturnal hypoxia (SpO2<95% for ≥10% of the night) and their clinical characteristics and cognitive function were compared.
Compared to patients without nocturnal hypoxia, those with nocturnal hypoxia (n = 10, 40%) had poor memory retention (p = 0.039) and retrieval efficiency (p = 0.045). A cluster-of-desaturation pattern was identified in 7 patients (70%) in the Hypoxia Group.
These results suggest that nocturnal hypoxia can be related to cognitive dysfunction in ALS. In addition, a considerable number of patients with ALS may be exposed to repeated episodes of deoxygenation-reoxygenation (a cluster-of-desaturation pattern) during sleep, which could be associated with the generation of reactive oxygen species. Further studies are required to define the exact causal relationships between these phenomena, the exact manifestations of nocturnal cluster-of-desaturation patterns, and the effect of clusters of desaturation on ALS progression.
PLoS ONE 09/2013; 8(9):e75324. DOI:10.1371/journal.pone.0075324 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Mutations in mitofusin-2 (MFN2) are the most common cause of axonal Charcot-Marie-Tooth (CMT) neuropathy. Herein, we report a novel double mutation in cis (c.[474+4A>G; 668T>A]) in a Korean family with late-onset autosomal dominant mild axonal CMT. Transcriptional analysis demonstrated aberrant splicing with exon 5 skipping and premature termination of translation before the missense mutation in exon 7. Interestingly, the aberrant splicing was incomplete, with some of the primary transcripts being spliced correctly and expressing the downstream missense mutation. The pathogenic relevance of the missense mutation would not be appreciated without the leaky aberrant splicing and the insensitivity of MFN2 to haploinsufficiency.
[Show abstract][Hide abstract] ABSTRACT: Livedoid vasculitis is a chronic dermatological problem with an unclear etiology. Clinical findings are petechiae with painful ulcers in both lower extremities, which heal to become hyperpigmented and porcelain-white satellite lesions. There are only a few reported cases of livedoid vasculitis presenting in combination with peripheral neuropathy.
We report the first case of a Korean patient presenting with mononeuritis multiplex combined with livedoid vasculitis, which was confirmed by electrophysiological and pathological studies.
Our report supports the possible vaso-occlusive etiology of livedoid vasculitis in multifocal ischemic neuropathy.