Sa Yoon Kang

Comparison between Clinical Disabilities and Electrophysiological Values in Charcot-Marie-Tooth 1A Patients with PMP22 Duplication

Background and Purpose Charcot-Marie-Tooth disease (CMT) type 1A (CMT1A) is the demyelinating form of CMT that is significantly associated with PMP22 duplication. Some studies have found that the disease-related disabilities of these patients are correlated with their compound muscle action potentials (CMAPs), while others have suggested that they are related to the nerve conduction velocities. In the present study, we investigated the correlations between the disease-related disabilities and the electrophysiological values in a large cohort of Korean CMT1A patients. Methods We analyzed 167 CMT1A patients of Korean origin with PMP22 duplication using clinical and electrophysiological assessments, including the CMT neuropathy score and the functional disability scale. Results Clinical motor disabilities were significantly correlated with the CMAPs but not the motor nerve conduction velocities (MNCVs). Moreover, the observed sensory impairments matched the corresponding reductions in the sensory nerve action potentials (SNAPs) but not with slowing of the sensory nerve conduction velocities (SNCVs). In addition, CMAPs were strongly correlated with the disease duration but not with the age at onset. The terminal latency index did not differ between CMT1A patients and healthy controls. Conclusions In CMT1A patients, disease-related disabilities such as muscle wasting and sensory impairment were strongly correlated with CMAPs and SNAPs but not with the MNCVs or SNCVs. Therefore, we suggest that the clinical disabilities of CMT patients are determined by the extent of axonal dysfunction.

Effects of lacunar infarctions on cognitive impairment in patients with cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy.

Background and Purpose Cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an inherited microangiopathy caused by mutations in the Notch3 gene. Although previous studies have shown an association between lacunar infarction and cognitive impairment, the relationship between MRI parameters and cognition remains unclear. In this study we investigated the influence of MRI parameters on cognitive impairment in CADASIL. Methods We applied a prospective protocol to 40 patients. MRI analysis included the normalized volume of white-matter hyperintensities (nWMHs), number of lacunes, and number of cerebral microbleeds. Cognition was assessed with the aid of psychometric tests [Mini-Mental State Examination (MMSE), Alzheimers Disease Assessment Scale-cognition (ADAS-cog), Trail-Making Test, and Stroop interference (Stroop IF)]. Results A multivariate regression analysis revealed that the total number of lacunes influenced the performance in the MMSE, ADAS-cog, and Stroop IF, while nWMHs had a strong univariate association with ADAS-cog and Stroop IF scores. However, this association disappeared in the multivariate analysis. Conclusions These findings demonstrate that the number of lacunes is the main predictive factor of cognitive impairment in CADASIL.

Expression of Erythropoietin in the Spinal Cord of Lewis Rats with Experimental Autoimmune Encephalomyelitis

Background and Purpose Erythropoietin (Epo), originally recognized for its central role in erythropoiesis, has been shown to improve the outcomes in patients with various neurological disorders. The aim of this study was to elucidate the Epo expression pattern in the spinal cords of Lewis rats with experimental autoimmune encephalomyelitis (EAE) and to assess the systemic effect of Epo during the course of EAE. Methods We used an EAE model induced in Lewis rats by immunization with myelin basic protein. Immunized rats were given recombinant human Epo (rhEpo) intraperitoneally at a dose of 5,000 U/kg for 7 consecutive days, either starting on day 3 post-immunization (five rats) or on the day of clinical symptom onset (score ≥1, five rats). After immunization, the rats were observed daily for clinical signs of EAE. Epo expression was investigated by Western blot analysis and immunohistochemistry. Results Western blot analysis showed that, Epo expression was significantly elevated relative to control in the rat spinal cord during the peak stage of EAE (p<0.05), and then decreased thereafter. Immunohistochemistry demonstrated that Epo was expressed in some neurons and glial cells. Epo immunoreactivity was detected in ED1-positive macrophages and astrocytes in EAE lesions. Furthermore, we found that the intraperitoneal administration of rhEpo reduced both the disease severity and duration of paralysis in EAE rats, and reduced macrophage activity and increased Epo activity. Conclusions Based on these findings, we postulate that Epo expression begins to increase at the start of EAE and that rhEpo administration leads to functional recovery from EAE paralysis.

The Impacts of Influenza Infection and Vaccination on Exacerbation of Myasthenia Gravis

Background and Purpose Upper respiratory infection (URI), including influenza, may exacerbate the symptoms of myasthenia gravis (MG), which is an autoimmune disease that causes muscle weakness. There is also concern that the influenza vaccine may trigger or worsen autoimmune diseases. The objective of this study was to determine the impacts of influenza infection and vaccination on symptom severity in MG patients. Methods Patients diagnosed with MG were enrolled from 10 university-affiliated hospitals between March and August 2015. Subjects completed a questionnaire at the first routine follow-up visit after enrolling in the study. The patient history was obtained to determine whether a URI had been experienced during the previous winter, if an influenza vaccination had been administered before the previous winter, and whether their MG symptoms were exacerbated during or following either a URI or vaccination. Influenza-like illness (ILI) was defined and differentiated from the common cold as a fever of ≥38℃ accompanied by a cough and/or a sore throat. Results Of the 258 enrolled patients [aged 54.1±15.2 years (mean±SD), 112 men, and 185 with generalized MG], 133 (51.6%) had received an influenza vaccination and 121 (46.9%) had experienced a common cold (96 patients) or ILI (25 patients) during the analysis period. MG symptoms were aggravated in 10 (40%) patients after ILI, whereas only 2 (1.5%) experienced aggravation following influenza vaccination. The rate of symptom aggravation was significantly higher in patients experiencing an ILI (10/25, 40%) than in those with the common cold (15/96, 15.6%, p=0.006). Conclusions The results of this study suggest that the potential risk of aggravating autoimmune disease is higher for ILI than for influenza vaccination, which further suggests that influenza vaccination can be offered to patients with MG.