Prominent fatigue in spinal muscular atrophy and spinal and bulbar muscular atrophy: Evidence of activity-dependent conduction block

ObjectivesTo clarify whether patients with spinal muscular atrophy (SMA) or spinal and bulbar muscular atrophy (SBMA) suffer disabling muscle fatigue, and whether activity-dependent conduction block (ADCB) contributes to their fatigue. ADCB is usually caused by reduced safety factor for impulse transmission in demyelinating diseases, whereas markedly increased axonal branching associated with collateral sprouting may reduce the safety factor in chronic lower motor neuron disorders.MethodsWe assessed the fatigue severity scale (FSS) in 22 patients with SMA/SBMA, and in 100 disease controls (multiple sclerosis, myasthenia gravis, chronic inflammatory demyelinating polyneuropathy (CIDP), and axonal neuropathy). We then performed stimulated-single fibre electromyography (s-SFEMG) in the extensor digitorum communis (EDC) muscle of 21 SMA/SBMA patients, 6 CIDP patients, and 10 normal subjects.ResultsThe FSS score was the highest in SMA/SBMA patients [4.9 ± 1.1 (mean ± SD)], with 81% of them complaining of disabling fatigue, compared with normal controls (3.5 ± 1.0), whereas patients with multiple sclerosis (4.3 ± 1.6), myasthenia gravis (4.0 ± 1.6) or CIDP (4.3 ± 1.4) also showed higher FSS score. When 2000 stimuli were delivered at 20 Hz in s-SFEMG, conduction block of single motor axons developed in 46% of patients with SMA/SBMA, and 40% of CIDP patients, but in none of the normal controls.ConclusionSMA/SBMA patients frequently suffer from disabling fatigue presumably caused by ADCB induced by voluntary activity.SignificanceADCB could be the mechanism for muscle fatigue in chronic lower motor neuron diseases.     

Patterns of sensory nerve conduction abnormalities in Fisher syndrome: More predominant involvement of group Ia afferents than skin afferents

ObjectiveTo elucidate the features of sensory nerve involvement in Fisher syndrome (FS), this study extensively investigated sensory electrophysiology.MethodsIn 47 consecutive FS patients, results of sensory nerve conduction studies in the median, ulnar and sural nerves, soleus H-reflexes, and median or tibial somatosensory-evoked potentials (SEP) were reviewed. Because of the large effects of age on amplitude of sensory nerve action potentials (SNAP), we strictly defined reduction of SNAP amplitudes by using a nomogram which age and amplitude obtained from 87normal subjects.ResultsIn routine nerve conduction studies, SNAP amplitude was reduced only in 32% of the patients, and conduction velocity was decreased in 2%. In contrast, soleus H-reflexes were frequently absent or reduced (67%). SEPs were abnormal only in 17%.ConclusionsIn FS, absent soleus H-reflexes are the most frequent electrophysiologic abnormalities, whereas SNAPs amplitudes are rarely affected. The pattern is characterized by predominant involvement of group Ia afferents with relatively preserved cutaneous afferents without evidence suggestive of demyelination.SignificanceThe major targets of immune attack by anti-GQ1b antibodies in FS appear to be group Ia neurons in the dorsal root ganglia, and this is presumably responsible for ataxia and areflexia in FS.     

Successful radiofrequency catheter ablation of common atrial flutter at the bottom of a coronary sinus diverticulum

We describe a patient who underwent radiofrequency (RF) catheter ablation of cavo-tricuspid isthmus-dependent atrial flutter (AFL). Extensive ablation at the isthmus failed to terminate the AFL. A coronary sinus (CS) diverticulum arising from the proximal portion of the middle cardiac vein was found near the isthmus. An RF energy application at the bottom of the CS diverticulum resulted in completion of a bidirectional block line at the isthmus, as well as AFL termination.     

Incidence of tacrolimus-induced gingival overgrowth in the absence of calcium channel blockers: a short-term study

AIM: The aim of this study was to determine the incidence and severity of gingival overgrowth (GO) induced by tacrolimus (Tcr) compared with ciclosporin A (CiA) in the absence of calcium channel blockers (CCB) in renal transplant recipients. METHODS: Forty patients (20 Tcr and 20 CiA) were evaluated before and 30 and 90 days after kidney transplantation. Demographic (age, gender) and periodontal parameters were recorded for all patients. Patients taking CCB at any time during the study were excluded from the investigation. RESULTS: The mean GO score was significantly lower (p=0.014) in the Tcr group (6.4%) compared with the CiA group (17.9%) after 90 days of immunosuppressive therapy. At 90 days post-transplant, clinically significant GO was observed in four patients of the CiA group and in two of the Tcr group. This difference was not statistically significant (0.66). CONCLUSION: No significant difference in the incidence of clinically significant GO was observed between the CiA and Tcr groups up to 90 days of immunosuppressive therapy.     

Role of Thrombin in Soluble Thrombomodulin-Induced Suppression of Peripheral HMGB1-Mediated Allodynia in Mice

High mobility group box 1 (HMGB1), a nuclear protein, once released into the extracellular space under pathological conditions, plays a pronociceptive role in redox-dependent distinct active forms, all-thiol HMGB1 (at-HMGB1) and disulfide HMGB1 (ds-HMGB1), that accelerate nociception through the receptor for advanced glycation endproducts (RAGE) and Toll-like receptor 4 (TLR4), respectively. Thrombomodulin (TM), an endothelial membrane protein, and soluble TM, known as TMα, promote thrombin-mediated activation of protein C and also sequester HMGB1, which might facilitate thrombin degradation of HMGB1. The present study aimed at clarifying the role of thrombin in TMα-induced suppression of peripheral HMGB1-dependent allodynia in mice. Thrombin-induced degradation of at-HMGB1 and ds-HMGB1 was accelerated by TMα in vitro. Intraplantar (i.pl.) injection of bovine thymus-derived HMGB1 in an unknown redox state, at-HMGB1, ds-HMGB1 or lipopolysaccharide (LPS), known to cause HMGB1 secretion, produced long-lasting mechanical allodynia in mice, as assessed by von Frey test. TMα, when preadministered i.pl., prevented the allodynia caused by bovine thymus-derived HMGB1, at-HMGB1, ds-HMGB1 or LPS, in a dose-dependent manner. The TMα-induced suppression of the allodynia following i.pl. at-HMGB1, ds-HMGB1 or LPS was abolished by systemic preadministration of argatroban, a thrombin-inhibiting agent, and accelerated by i.pl. co-administered thrombin. Our data clearly indicate that TMα is capable of promoting the thrombin-induced degradation of both at-HMGB1 and ds-HMGB1, and suppresses the allodynia caused by either HMGB1 in a thrombin-dependent manner. Considering the emerging role of HMGB1 in distinct pathological pain models, the present study suggests the therapeutic usefulness of TMα for treatment of intractable and/or persistent pain.     

Fibrosing Cholestatic Hepatitis Developing within One Month after Living Donor Liver Transplantation for Chronic Hepatitis C-related Cirrhosis: A Case Report

Fibrosing cholestatic hepatitis (FCH) is a life-threatening consequence of hepatitis C virus (HCV) infection occurring in a small minority of liver transplantation (LT) recipients. We herein report a case of early-onset FCH after living donor LT in a 47-year-old woman with HCV-related cirrhosis. The patient underwent balloon-occluded retrograde transvenous obliteration of a splenorenal shunt to treat an impaired portal flow on the sixth postoperative day (POD 6) and a bypass operation for hepatic artery thrombosis on POD 12. Thereafter, the serum bilirubin levels increased gradually; however, computed tomography revealed no evidence of biliary stricture. The serum HCV-RNA level on POD 27 was >7.8 log IU/mL. Histopathology of a needle graft biopsy performed on POD 28 revealed FCH with extensive portal fibrosis accompanied by mild inflammation, hepatocyte ballooning, and ductular proliferation with cholestasis. The patient received combination therapy with pegylated interferon, ribavirin, and double-filtration plasmapheresis for the treatment of early-onset FCH. Both the recipient and the donor carried the major genotype single nucleotide polymorphism (TT) at rs8099917 near the interleukin-28B gene. Furthermore, the HCV genotype was treatment-sensitive 2a. Nonetheless, the recipient died of hepatic failure on POD 211. Thus far, few cases of FCH occurring within 1 month after LT have been reported. In addition, the early onset of FCH may be an adverse prognostic factor.