Respiratory Muscle Training Improves Functional Outcomes and Reduces Fatigue in Patients with Myasthenia Gravis: A Single-Center Hospital-Based Prospective Study.

BACKGROUND: Myasthenia gravis (MG) is an immune-mediated disorder characterized by muscle fatigue and fluctuating weakness. Impairment in respiratory strength and endurance has been described in patients with generalized MG. We tested the hypothesis that respiratory muscle training (RMT) can improve functional outcomes and reduce fatigue in patients with MG. METHODS: Eighteen patients with mild to moderate MG participated in this study. The training group underwent home-based RMT three times a week for 12 weeks. Sixteen patients with MG without RMT were enrolled as a disease control group. Lung function, autonomic testing, Multidimensional Fatigue Symptom Inventory-Short Form (MFSI-SF), and functional outcome measurement by using quantitative myasthenia gravis (QMG) score and myasthenia gravis composite (MGC) scale were measured before and after the 12-week RMT. RESULTS: The 12-week RMT significantly increased forced vital capacity (FVC) from 77.9 ± 12.6% to 83.8 ± 17.7% (p = 0.03), forced expiratory volume in one second (FEV1) from 75.2 ± 18.3% to 83.3 ± 19.0% (p = 0.03), forced expiratory volume in one second (FEV1) from 75.2 ± 18.3% to 83.3 ± 19.0% (p = 0.03), forced expiratory volume in one second (FEV1) from 75.2 ± 18.3% to 83.3 ± 19.0% (p = 0.03), forced expiratory volume in one second (FEV1) from 75.2 ± 18.3% to 83.3 ± 19.0% (p = 0.03), forced expiratory volume in one second (FEV1) from 75.2 ± 18.3% to 83.3 ± 19.0% (p = 0.03), forced expiratory volume in one second (FEV1) from 75.2 ± 18.3% to 83.3 ± 19.0% (. CONCLUSION: The home-based RMT is an effective pulmonary function training for MG patients. The RMT can not only improve short-term outcomes but also reduce fatigue in patients with mild to moderate generalized MG.

Characterization of Fibrinogen as a Key Modulator in Patients with Wilson's Diseases with Functional Proteomic Tools.

Wilson's disease (WD) is an autosomal recessive disorder of copper metabolism caused by defects in the ATPase gene (ATP7B). The various clinical features result from the massive accumulation of copper in the liver, cornea and basal ganglia. Although WD can be effectively treated with proper medicine, this disease is difficult to clearly diagnose due to its indefinite symptoms. In the current study, we achieved a positive correlation between clinical symptoms and the enzymatic activity of ceruloplasmin in WD patients. Furthermore, proteome profiles of plasma as well as network analysis demonstrated that fibrinogen is a critical indicator which is significantly unregulated in WD subjects in comparison to healthy donors and closely linked to pathogenesis of WD. Here, we applied 2DE-immunoblots and immunohistochemistry to verify the protein level and localization in situ. The enhanced expression of fibrinogen in the plasma of WD subjects with respect to that of healthy controls and patients with distinct disorders was also confirmed by utilizing clinical samples. As expected, application of high dose of copper induced expression of fibrinogen, while knockdown of ceruloplasmin also resulted in upregulation of fibrinogen as well as elimination of superoxide dismutase (SOD), leading to increased oxidative stress in cells. In summary, the liver injury or oxidative stress induced by the progression of WD may account for the obvious increase of fibrinogen, which in turn triggers inflammatory responses and interferes coagulation cascades; this finding sheds light on the early detection and diagnosis of WD.

Effects of Homocysteine on white matter diffusion parameters in Alzheimer's disease.

BACKGROUND: The clinical features of Alzheimer's disease (AD) are related to brain network degeneration, and hyperhomocysteinemia is related to greater white matter hyperintensities. We investigated the changes in four diffusion tensor imaging parameters in the white matter of patients with early stage AD, examined their associations with homocysteine level, and tested the clinical significance of the diffusion tensor imaging parameters and homocysteine level in correlation analysis with cognitive test scores. METHODS: We enrolled 132 patients with AD and analyzed white matter (WM) macrostructural changes using diffusion tensor neuroimaging parameters including fractional anisotropy (FA), mean diffusion (MD), axial diffusivity (axial-D) and radial diffusivity (RD). Two neuroimaging post-processing analyses were performed to provide complementary data. First, we calculated 11 major bundle microstructural integrities using a WM parcellation algorithm, and correlated them with serum homocysteine levels to explore whether the fiber bundles were affected by homocysteine. Second, we used tract-based spatial statistics to explore the anatomical regions associated with homocysteine levels. Changes in cognitive test scores caused by homocysteine served as the major outcome factor. RESULTS: The results suggested that homocysteine levels did not have a direct impact on cross-sectional cognitive test scores, but that they were inversely correlated with renal function, B12 and folate levels. Topographies showing independent correlations with homocysteine in FA and MD were more diffusely located compared to the posterior brain regions in axial-D and RD. In the association bundle analysis, homocysteine levels were significantly correlated with the four diffusion parameters even after correcting for confounders, however no association between homocysteine and WM to predict cognitive outcomes was established. CONCLUSIONS: In our patients with AD, homocysteine levels were associated with renal dysfunction and decreased levels of vitamin B12 and folate, all of which require clinical attention as they may have been associated with impaired WM microstructural integrity and modulated cognitive performance in cross-sectional observations.

Non-cephalosporin-susceptible, glucose non-fermentative Gram-negative bacilli meningitis in post-neurosurgical adults: clinical characteristics and therapeutic outcome.

OBJECTIVE: The clinical and laboratory characteristics of non-cephalosporin-susceptible (non-CS) glucose non-fermentative Gram-negative (G(-)) infections in adults with postneurosurgical meningitis are rarely examined solely in the literature. METHODS: The data of 28 post-neurosurgical adults meningitis with glucose non-fermentative G(-) infections, collected during a study period of 5 years (2006-2010), were reviewed. The clinical and laboratory data between the non-cephalosporin-susceptible groups and the cephalosporin-susceptible groups were compared. RESULTS: A total of 30 G(-) strains were collected from the 28 enrolled cases. Among the implicated glucose non-fermentative G(-) strains, 18 strains, belonging to 17 cases, were non-CS. Among the 18 non-cephalosporin-susceptible strains, Acinetobacter spp. (39%, 7/18) was the most common, followed by Pseudomonas spp. (22%, 4/18), Stenotrophomonas maltophilia (22%, 4/18) and Elizabethkingia meningoseptica (11%, 2/18). With a comparative analysis, there were no significant difference between the non-cephalosporin-susceptible and cephalosporin-susceptible glucose non-fermentative G(-) groups. The clinical and laboratory data were also of no statistical significance between the fatal (n=4) and non-fatal (n=13) non-cephalosporin-susceptible groups. CONCLUSION: Sixty percent (18/30) of implicated glucose non-fermentative G(-) strains of post-NS meningitis in adults are non-cephalosporin-susceptible. Among the non-cephalosporin-susceptible glucose non-fermentative G(-) strains, Acinetobacter spp., Pseudomonas spp., S. maltophilia and E. meningoseptica are the commonly implicated pathogens, and their emergence in this specific group of meningitis has caused a therapeutic dilemma. The clinical manifestations of non-cephalosporin-susceptible glucose non-fermentative G(-) meningitis were not unique; therefore, only bacterial culture and antimicrobial susceptibility test are the methods for identification confirmation.

Clinical characteristics of Stenotrophomonas maltophilia meningitis in adults: a high incidence in patients with a postneurosurgical state, long hospital staying and antibiotic use.

OBJECTIVE: Stenotrophomonas (S.) maltophilia is an uncommon pathogen of adult bacterial meningitis (ABM). METHODS: The clinical characteristics of six S. maltophilia ABM cases, collected during a study period of nine years (2001-2009) were included. In the related literature, 13 S. maltophilia ABM cases were reported, and their clinical data were also collected. RESULTS: The 19 S. maltophilia ABM cases included 11 men and 8 women, aged 28-70 years. Of these 19 cases, 89.5% (17/19) had underlying neurosurgical (NS) conditions as the preceding event. Before the development of S. maltophilia ABM, 52.6% (10/19) of them had long stays in hospital and 63.2% (12/19) had undergone antibiotic treatment. Among the implicated S. maltophilia cases, three strains were found to have a resistance to sulfamethoxazole-trimethoprim (SMZ-TMP). Two of our five cases had resistant strains to levofloxacin. Among the antibiotics chosen for treatment, SMZ-TMP was the most common followed by quinolone (ciprofloxacin, levofloxacin, moxifloxacin). The therapeutic results showed 2 cases expired while the other 17 cases survived. CONCLUSIONS: S. maltophilia ABM usually develops in patients with a preceding neurosurgical condition, a long hospital stay and antibiotic use. SMZ-TMP and quinolones, especially the ciprofloxacin, are the major antibiotic used. This study also shows the emergence of clinical S. maltophilia strains which are not susceptible to SMZ-TMP and quinolones and this development may pose a more serious threat in the near future because treatment options may become depleted and limited despite the mortality rate of this specific group of ABM not being high at this time.

Clinical significance of serological biomarkers and neuropsychological performances in patients with temporal lobe epilepsy.

BACKGROUND: Temporal lobe epilepsy (TLE) is a common form of focal epilepsy. Serum biomarkers to predict cognitive performance in TLE patients without psychiatric comorbidities and the link with gray matter (GM) atrophy have not been fully explored. METHODS: Thirty-four patients with TLE and 34 sex - and age-matched controls were enrolled for standardized cognitive tests, neuroimaging studies as well as measurements of serum levels of heat shock protein 70 (HSP70), S100ß protein (S100ßP), neuronal specific enolase (NSE), plasma nuclear and mitochondrial DNA levels. RESULTS: Compared with the controls, the patients with TLE had poorer cognitive performances and higher HSP70 and S100ßP levels (p < 0.01). The patients with higher frequencies of seizures had higher levels of HSP70, NSE and S100ßP (p < 0.01). Serum HSP70 level correlated positively with duration of epilepsy (σ = 0.413, p < 0.01), and inversely with memory scores in the late registration (σ = -0.276, p = 0.01) and early recall score (σ = -0.304, p = 0.007). Compared with the controls, gray matter atrophy in the hippocampal and parahippocampal areas, putamen, thalamus and supplementary motor areas were found in the patient group. The HSP70 levels showed an inverse correlation with hippocampal volume (R square = 0.22, p = 0.007) after controlling for the effect of age. CONCLUSIONS: Our results suggest that serum biomarkers were predictive of higher frequencies of seizures in the TLE group. HSP70 may be considered to be a stress biomarker in patients with TLE in that it correlated inversely with memory scores and hippocampal volume. In addition, the symmetric extratemporal atrophic patterns may be related to damage of neuronal networks and epileptogenesis in TLE.

Spinal epidural abscess in adults caused by Staphylococcus aureus: clinical characteristics and prognostic factors.

OBJECTIVE: Spinal epidural abscess (SEA) is a devastating infectious disease, which may result in neurologic sequelae. Staphylococcus (S.) aureus is a common pathogen of SEA. Here, we analyzed the clinical characteristics and laboratory data of adult patients with S. aureus SEA and compared the clinical characteristics of methicillin-sensitive S. aureus (MSSA) and methicillin-resistant S. aureus (MRSA) infections. METHODS: Between 2003 and 2008, we collected data regarding 29 adult cases of S. aureus SEA and analyzed the clinical presentations, magnetic resonance (MR) imaging features, therapeutic outcome, and prognostic factors. Antibiotic susceptibility test results of 11 implicated MRSA strains were also further analyzed. RESULTS: We identified 17 MSSA strains and 12 MRSA strains. Lumbar and lumbosacral spine segments were the most commonly involved segments. All 29 patients had back pain. Other findings included sensory abnormalities (25), motor weakness (21), fever (16), bladder dysfunction (16), and altered consciousness (3). Disease onset at admission was acute in 6 cases and chronic in 23. The stages of disease severity were early stage in 9 and late stage in 20. After therapy, 21 patients had a good prognosis and 8 had a poor prognosis. Significant prognostic factors included older age (>70years), presence of diabetes mellitus, adrenal insufficiency, and MRSA infection. The prognosis alone was clinically different between patients with MSSA and MRSA infections. CONCLUSIONS: Patients with localized back pain, particularly those with a fever and compromised immune system, should undergo MR imaging to ensure an early diagnosis and management.

Diagnosis and management of adult bacterial meningitis.

The early use of appropriate antibiotic therapy is one of the important and explicit steps in the management of potentially fatal adult acute bacterial meningitis (ABM). Changing epidemiology of ABM, especially with regards to the change of the relative frequency of causative pathogens, has been noted in a serial of studies in Taiwan. This change may influence the choice of initial empiric antibiotic treatment. In this review, the authors will discuss the epidemiologic trend, diagnosis and management of ABM in Taiwan. For a better understanding, the clinical and laboratory data of 204 adult ABM cases diagnosed at Chang Gung Memorial Hospital-Kaohsiung, collected over a period of 8 years (1999-2006), were included for analysis. This review may help first-line, primary-care neurologists have a better view on handling this critical central nervous system infection.

Damage of white matter tract correlated with neuropsychological deficits in carbon monoxide intoxication after hyperbaric oxygen therapy.

Carbon monoxide (CO) intoxication can result in cognitive deficits and demyelinating changes of the white matter (WM), for which hyperbaric-oxygen (HBO) treatment is considered effective in reducing neuropsychiatric symptoms. This study aimed to analyze cognitive functions and WM diffusion properties in CO intoxication after standard HBO treatment. Seventeen CO intoxicated patients were evaluated 4-6 months after HBO treatment. They also underwent diffusion tensor imaging (DTI) and cognitive assessment, and the results were compared with those from 34 age-matched controls. DTI was transformed into fractional anisotropy (FA) and mean diffusivity (MD) and assessed at every voxel level with tract-based spatial statistics across the brain. Correlation between reduced FA and increased MD with neuropsychological deficits were performed. Cognitive results showed that impairment in executive function, as well as verbal and visual memories, were most prominent. There were extensive areas of increased MD and decreased FA. Correlation analyses showed that memory retrieval, judgment, and verbal generation tasks were related to FA of the frontotemporal WM. MD showed weaker correlation with cognitive deficits. These data suggest that neurologic deficits and WM changes are detectable 4-6 months after HBO therapy. The correlation of WM diffusion with cognitive deficits also suggests that reduced connectivity between different cortical regions is a pathophysiologic mechanism.

Klebsiella meningitis in adults: clinical features, prognostic factors and therapeutic outcomes.

Sixty adult Klebsiella meningitis patients have been identified at Kaohsiung Chang Gung Memorial Hospital in a period of 13 years. Most cases were associated with debilitating diseases, and devastating metastatic septic abscesses are common in diabetic patients with K. pneumoniae meningitis. Although the mortality rate has been significantly reduced in recent years, there has been an increase in nosocomial infections and the emergence of multi-antibiotic resistant strains. Significant prognostic factors include appropriate antibiotic therapy, the presence of septic shock, disseminated intravascular coagulation, and high cerebrospinal fluid protein levels and white blood cell counts. Initial empiric therapy with a third generation cephalosporin should be considered for community-acquired meningitis while antibiotics such as carbapenems should be considered as initial empiric therapy for patients with postneurosurgical meningitis. Early diagnosis and the use of appropriate antibiotics are of crucial importance.