Clinical and laboratory findings in scrub typhus associated Guillain-Barré syndrome in South Korea.

BACKGROUND AND AIMS: Scrub typhus is an endemic disease in the fall season that occurs in a limited number of places known as the Tsutsugamushi Triangle. Peripheral neuropathy is a common complication of scrub typhus. Herein, we encountered several patients with ascending paralysis after scrub typhus infection, who were diagnosed with Guillain-Barré syndrome (GBS). We aimed to investigate the clinical and laboratory characteristics of patients who developed GBS after scrub typhus. METHODS: Patients were retrospectively recruited from six nationwide tertiary centers in South Korea from January 2017 to December 2021. Patients who had been clinically diagnosed with GBS and confirmed to have scrub typhus via laboratory examination and/or the presence of an eschar before the onset of acute limb paralysis were included. The GBS-associated clinical and electrophysiological characteristics, outcomes, and scrub typhus-associated features were collected. RESULTS: Of the seven enrolled patients, six were female and one was male. The median time from scrub typhus infection to the onset of limb weakness was 6 (range: 2-14) days. All patients had eschar on their bodies. Four patients (57.1%) were admitted to the intensive care unit and received artificial ventilation for respiratory distress. At 6 months, the median GBS disability score was 2 (range, 1-4) points. INTERPRETATION: Patients with scrub typhus-associated GBS have a severe clinical presentation and require intensive treatment with additional immunotherapies. Therefore, GBS should be included in the differential diagnosis when peripheral neuropathies develop during scrub typhus treatment. Notably, scrub typhus is associated to GBS.

Contrast-enhanced MRI findings of patients with acute Bell palsy within 7 days of symptom onset: A retrospective study.

The brain magnetic resonance imaging (MRI) findings seen in patients with Bell palsy are abnormal contrast enhancement of affected facial nerves. Previous studies were conducted on a few patients, mainly those who had experienced palsy for several weeks. This study investigated the diagnostic usefulness of MRI by examining MRI findings of acute Bell palsy (within 7 days of symptom onset) in a large cohort. Among the patients with Bell palsy (idiopathic unilateral facial palsy) who visited the hospital, 123 patients who underwent contrast-enhanced MRI of the internal auditory canal within 7 days of symptom onset were reviewed retrospectively. MRI examination results were investigated along with the patient's clinical symptoms and electrodiagnostic test results. Based on the MRI results, the frequency of abnormal contrast enhancement and contrast-enhanced areas were investigated. Of the 123 patients, 13 (11%) had normal brain MRI results, and 110 (89%) had abnormal findings. The frequency of abnormal contrast enhancement was not significantly associated with test timing (P = .56). Of the 110 patients with abnormal findings, 65 (59%) showed contrast enhancement in the labyrinthine segment and 36 (33%) in both the labyrinthine segment and geniculate ganglion. Most patients with Bell palsy who are in the acute phase showed abnormal contrast enhancement in their facial nerves, and similar findings were even observed in the examination conducted on the day of symptom onset. Brain MRI helps in the diagnosis of acute Bell palsy.

Clinical pitfalls and serological diagnostics of MuSK myasthenia gravis.

BACKGROUND: We aimed to evaluate the diagnostic accuracy of enzyme-linked immunosorbent assay (ELISA) for anti-muscle specific tyrosine kinase (MuSK) antibody (Ab) in a large cohort of anti-acetylcholine receptor (AChR) Ab-negative generalized myasthenia gravis (MG), and also to investigate clinical contexts for the diagnosis of MuSK MG. METHODS: A retrospective study of 160 patients with a clinical suspicion of AChR Ab-negative generalized MG was performed. The serum samples were tested for anti-clustered AChR Ab by cell-based assay (CBA), anti-MuSK Ab by ELISA, CBA and/or radioimmunoprecipitation assay (RIPA). Clinical data were compared between anti-MuSK Ab-positive MG and double seronegative (AChR and MuSK) MG groups. RESULTS: After excluding non-MG and clustered AChR Ab-positive patients, we identified 89 patients as a cohort of AChR Ab-negative generalized MG. Anti-MuSK Ab was positive by ELISA in 22 (24.7%) patients. While CBA identified five additional anti-MuSK Ab-positive patients, the results of ELISA were mostly consistent with CBA and RIPA with Cohen's kappa of 0.80 and 0.90, respectively (p < 0.001). The most frequent differential diagnosis was motor neuron disease particularly of bulbar onset which showed remarkably overlapping clinical and electrophysiological features with MuSK MG at presentation. CONCLUSION: While confirming the highest sensitivity of CBA for detecting anti-MuSK Ab, our results highlight the clinical pitfalls in making a diagnosis of MuSK MG and may support a diagnostic utility of MuSK-ELISA in clinical practice.

Magnetic resonance imaging findings of delayed facial palsy after dental procedures suggest viral reactivation as pathogenesis: a retrospective study.

PURPOSE: We hypothesize that delayed facial paralysis following dental procedures is also associated with viral reactivation. In this study, the brain magnetic resonance imaging (MRI) findings of patients were analyzed to identify the pathogenesis of facial nerve palsy after dental treatment. MATERIALS AND METHODS: We retrospectively reviewed the medical records of patients with unilateral facial nerve palsy and identified those diagnosed with delayed facial nerve palsy within 30 days of dental treatment. We assessed the clinical characteristics, electrodiagnostic findings, and imaging findings of these patients and looked for MRI findings that support a viral hypothesis for facial palsy. RESULTS: Among 924 patients with facial palsy, 11 (1.2%) had delayed facial paralysis following dental procedures. Patients developed facial palsy at an average of 3.2 days (1-11 days) after undergoing a dental procedure. The internal auditory canal MRI revealed abnormal enhancement of affected facial nerve in nine patients. The intensity and pattern of the enhancement were similar to those of Bell's palsy. CONCLUSIONS: Facial palsy can develop within the days following dental procedures, and the MRI results suggest that delayed facial palsy after dental treatment is related to viral reactivation-like Bell's palsy.

Usefulness of ultrasound assessment of median nerve mobility in carpal tunnel syndrome.

BACKGROUND: Carpal tunnel syndrome (CTS) is the most common peripheral compression neuropathy of the upper extremity. Recently, dynamic ultrasound (US) imaging has shown differences in median nerve mobility between the affected and unaffected sides in CTS. PURPOSE: The present study was performed to compare the median nerve mobility between patients with CTS and healthy individuals, and to correlate median nerve mobility with the severity of CTS. MATERIAL AND METHODS: A total of 101 patients (128 wrists) with CTS and 43 healthy individuals (70 wrists) were evaluated. Electrodiagnostic studies were initially conducted to determine the neurophysiological grading scale (NGS). The cross-sectional area (CSA) of the median nerve and the grade of median nerve mobility were measured using US. RESULTS: The mean grade of median nerve mobility in the CTS group (1.9) was significantly lower than that in the control group (2.6; P < 0.001). There were significant negative correlations between the grade of median nerve mobility and distal motor latency of the median nerve (r = -0.218, P = 0.015), NGS (r = -0.207, P = 0.020) and CSA of the median nerve (r = -0.196, P = 0.028). CONCLUSION: The grade of median nerve mobility was negatively correlated with the severity of CTS. US assessment of median nerve mobility may be useful in diagnosing and determining the severity of CTS.

A multicenter prospective observational study on the safety and efficacy of tacrolimus in patients with myasthenia gravis.

INTRODUCTION: Several clinical studies using tacrolimus revealed reasonable therapeutic mechanisms and efficacy in patients with myasthenia gravis (MG). However, long-period studies in a large number of patients with MG are limited; therefore, the aim of this study was to investigate the therapeutic efficacies and safety of tacrolimus in patients with MG during a 12-month follow-up period. METHODS: Tacrolimus was administered to 150 patients with MG who were recruited based on the inclusion criteria. Fifteen medical centers in Korea participated in this study. The efficacy of tacrolimus was assessed using MG composite scales (MGCS) and the prednisolone-sparing effect. And the adverse drug reactions (ADRs) of tacrolimus were monitored in each patient from the beginning of tacrolimus treatment to the end of the follow-up period. RESULTS: After starting tacrolimus, the 32 patients were affected by ADRs, and consequentially 134 patients of the enrolled patients were followed up for 12months. They showed that the mean prednisolone dosage significantly decreased (6.1±7.6mg/day), compared to that in the baseline (11.3±9.5mg/day), and MGCS significantly improved after 12months of tacrolimus treatment, compared to that at the baseline. CONCLUSIONS: Our study showed that tacrolimus would be an effective immunosuppressant as an initial therapeutic agent in patients with MG; in addition, it showed tolerable safety profiles during the 12-month follow-up evaluation.

Efficacy of mastoid oscillation and the Gufoni maneuver for treating apogeotropic horizontal benign positional vertigo: a randomized controlled study.

To determine the immediate and short-term efficacies of mastoid oscillation vs. Gufoni maneuver in treating the apogeotropic type of horizontal canal benign paroxysmal positional vertigo (HC-BPPV), we designed a randomized, prospective, sham-controlled study. In eight dizziness clinics in Korea, 209 consecutive patients with apogeotropic HC-BPPV were enrolled. The patients were randomly assigned to receive a single application of Gufoni (n = 70), mastoid oscillation (n = 67), or sham maneuver (n = 72). Immediate and second-day responses were determined based on the results within 1 h after a single trial of each maneuver and the following day, respectively. Second-day response was assessed in patients who were non-responders on the first day. The short-term response was determined based on the cumulative response for 2 days. Successful treatment was defined as a resolution of positional nystagmus or as a transition into geotropic horizontal nystagmus (not requires vertigo symptom resolution). The immediate responses of the Gufoni maneuver (33/70, 47.1%) and mastoid oscillation (32/67, 47.8%) were better than the sham maneuver (14/72, 19.4%) (p = 0.00). The second-day results did not differ among the three groups (p = 0.76). The short-term responses showed better efficacies with the Gufoni maneuver (51/70, 76.1%) and mastoid oscillation (46/67, 71.9%) than with the sham maneuver (38/72, 53.5%) (p = 0.02). Therapeutic efficacies did not differ between the Gufoni and mastoid oscillation groups in terms of both immediate and short-term outcomes (p = 0.94, 0.57). Both the Gufoni maneuver and mastoid oscillation are valid methods for treating apogeotropic HC-BPPV, with a success rate of approximately 70% for a single maneuver during the short-term follow-up. TRIAL REGISTRATION: clinicaltrials.gov identifier number: NCT02046980.

Physiological factors influencing median nerve mobility in normal subjects.

INTRODUCTION: The purpose of this study was to assess the mobility of the median nerve in the axial plane in normal healthy subjects and to evaluate physiological factors associated with lesser degrees of mobility. METHODS: Our study included 80 healthy volunteers between 20 and 60 years of age. For all subjects, mobility of the median nerve was assessed with ultrasound at the carpal tunnel. RESULTS: With wrist and finger flexion, the median nerve moved in all 160 wrists; in 78, the nerve dove deep to the flexor tendons (full), and in 82 it made a partial turn, but did drop below the tendons (partial). Among all demographic factors and sonographic measurements, only height was significantly related to partial mobility. CONCLUSIONS: Full or partial mobility of the median nerve with wrist flexion is an attribute of normal subjects; partial mobility is common, particularly in taller individuals. Muscle Nerve 54: 883-886, 2016.

Evaluation of extensor digitorum brevis thickness in healthy subjects: A comparative analysis of nerve conduction studies and ultrasound scans.

OBJECTIVES: (1) To evaluate the relationship between the thickness and compound muscle action potential (CMAP) of the extensor digitorum brevis (EDB) muscle; (2) to obtain reference values for distal lower extremity muscle thickness as a possible measure of peripheral neuropathy; and (3) to evaluate various factors associated with unexplained EDB atrophy. METHODS: We measured the thickness of EDB, abductor hallucis brevis (AHB) and tibialis anterior (TA) muscles in 80 healthy volunteers with ultrasound and assessed EDB CMAP with fibular nerve stimulation. Two foot muscle-associated lifestyle factors were assessed and sociodemographic information was collected. RESULTS: A significant correlation was observed between the amplitude of the fibular nerve CMAP and EDB thickness. The thickness of each of the three muscles was greater in men compared to women. EDB thickness decreased significantly with age although the thicknesses of the AHB and TA muscles were not correlated with age. CONCLUSIONS: EDB thickness was closely associated with fibular nerve CMAP but with less variation and differed among groups by age and sex; it was not associated with lifestyle factors. SIGNIFICANCE: The ability to obtain this measure painlessly with ultrasound and its low variation recommend it as a potentially useful complementary measure of distal neuromuscular function.

Does delayed facial involvement implicate a pattern of "descending reversible paralysis" in Fisher syndrome?

OBJECTIVE: Delayed facial palsy (DFP) has often been described during the recovery stage of Fisher syndrome (FS), but the implications of DFP in FS pathophysiology have not been reported previously. The aim of this study was to identify the incidence and clinical course of DFP in FS, and to determine its clinical/pathophysiological implications in FS. METHODS: About 71 FS patients were enrolled from seven university-based hospitals in Korea. DFP was defined with respect to new development of unilateral or bilateral facial palsies with delayed onset after either the nadir or improvement of initial neurological signs of FS. RESULTS: Eleven of the 71 patients (16%) satisfied the definition of DFP. No other cranial palsies developed as a delayed pattern. With the exception of two patients with bulbar involvement, DFP developed after a latent period of upper-cranial neuropathies. Comparison of FS patients without and with DFP revealed no significant clinical, serological, or electrophysiological differences. All except one patient with DFP exhibited a good outcome within 1 month of follow-up. CONCLUSION: DFP was identified as a common and specific phenomenon in FS. Nearly all cases of DFP were developed in a descending manner and were associated with a good outcome, while other cranial neuropathies developed or followed as a sequential pattern. These findings suggest the involvement of so-called "descending reversible paralysis" in the pathophysiology of FS.

Long-term therapy with clevudine for chronic hepatitis B can be associated with myopathy characterized by depletion of mitochondrial DNA.

UNLABELLED: Clevudine (Revovir), a pyrimidine nucleoside analogue, is a recently introduced antiviral drug. Clinical trials have demonstrated potent, sustained antiviral activity against hepatitis B virus without specific adverse events. The lack of cytotoxicity and absence of an effect on mitochondrial function have been considered the reasons for the fewer adverse events. However, it came to our attention that several hepatitis B patients developed myopathy during clevudine therapy. Our study was aimed to analyze the clinical and pathological features of patients with clevudine-induced myopathy with some consideration of its pathogenetic mechanism. Seven hepatitis B patients who developed severe skeletal myopathy during clevudine therapy were examined in this study. The demographic data, clinical features, pathological findings, and molecular studies of these patients were analyzed with speculation about the underlying pathogenic mechanisms. All seven patients were treated with clevudine for more than 8 months (8-13 months). In all, the main symptom was slowly progressive proximal muscular weakness over several months. A markedly elevated creatine kinase level and myopathic patterns on electromyography were found. Muscle biopsies revealed severe myonecrosis associated with numerous ragged red fibers, cytochrome c oxidase-negative fibers, and predominant type II fiber atrophy. Molecular studies using quantitative polymerase chain reaction showed a depletion of the mitochondrial DNA in the patients' skeletal muscle. CONCLUSION: To the best of our knowledge, this is the first report of myopathy associated with clevudine therapy. This study has clearly shown that long-term clevudine therapy can induce the depletion of mitochondrial DNA and lead to mitochondrial myopathy associated with myonecrosis. Careful clinical and laboratory attention should be paid to patients on long-term clevudine therapy for this skeletal muscle dysfunction.

Widely varying TNF-alpha levels in patients with myasthenia gravis.

Animal studies have indicated an important role of tumor necrosis factor-alpha (TNF-alpha) in the pathogenesis of myasthenia gravis (MG), and trials of monoclonal antibodies that block TNF-alpha have shown clinical improvement. However, before a TNF-alpha blocking agent is proposed for treatment of MG, whether serum TNF-alpha level correlates with the patient's condition should be confirmed. Therefore, we evaluated the relationship between the serum TNF-alpha level and clinical factors, including the quantitative MG score and the anti-acetylcholine receptor antibody level, in 33 MG patients. TNF-alpha levels ranged from 0.44 to 3.63 pg/mL and did not correlate with clinical factors. Overall, we found that serum TNF-alpha levels varied greatly among MG patients.

Bilateral basal ganglia and unilateral cortical involvement in a diabetic uremic patient.

We report a 57-year-old woman with uremic encephalopathy who presented with dysarthria, dysphagia, hypophonia, and drowsiness. The patient's radiologic findings were rather unusual in that magnetic resonance imaging (MRI) showed abnormal findings involving the basal ganglia bilaterally and frontal cortex unilaterally. After intensified hemodialysis, her symptoms and follow-up brain MRI showed marked improvement. We postulated that the underlying mechanism of uremic encephalopathy based on diffusion-weighted imaging and apparent diffusion coefficient maps.

Residual dizziness after successful repositioning treatment in patients with benign paroxysmal positional vertigo.

BACKGROUND AND PURPOSE: Benign paroxysmal positional vertigo (BPPV) is the most common form of vertigo. Although the repositioning maneuver dramatically improves the vertigo, some patients complain of residual dizziness. We evaluated the incidence and characteristics of persistent dizziness after successful particle repositioning and the clinical factors associated with the residual dizziness. METHODS: We performed a prospective investigation in 49 consecutive patients with confirmed BPPV. The patients were treated with a repositioning maneuver appropriate for the type of BPPV. Success was defined by the resolution of nystagmus and positional vertigo. All patients were followed up until complete resolution of all dizziness, for a maximum of 3 months. We collected data on the characteristics and duration of any residual dizziness and analyzed the clinical factors associated with the residual dizziness. RESULTS: Of the 49 patients, 11 were men and 38 were women aged 60.4+/-13.0 years (mean +/-SD), and 30 (61%) of them complained of residual dizziness after successful repositioning treatment. There were two types of residual dizziness: continuous lightheadedness and short-lasting unsteadiness occurring during head movement, standing, or walking. The dizziness lasted for 16.4+/-17.6 days (range=2-80 days, median=10 days). A longer duration of BPPV before treatment was significantly associated with residual dizziness (p=0.04). CONCLUSIONS: Residual dizziness after successful repositioning was observed in two-thirds of the patients with BPPV and disappeared within 3 months without specific treatment in all cases. The results indicate that early successful repositioning can reduce the incidence of residual dizziness.

Can aspirin resistance be clinically predicted in stroke patients?

OBJECTIVES: Aspirin resistance is one of several possible explanations for limited efficacy or treatment failure of aspirin. However, the predictors of aspirin resistance are not well known. We therefore conducted a study of laboratory-defined aspirin resistance in Korean patients with ischemic stroke and considered a wide range of factors as possible predictors. PATIENTS AND METHODS: A total of 88 patients taking aspirin daily for the secondary prevention of stroke were included. Platelet function was assessed using the Rapid Platelet Function Assay-Aspirin (RPFA-ASA) system and the level of urinary thromboxane B2 (TX-B2). The result of the RPFA-ASA system was expressed as an aspirin reaction unit (ARU). We analyzed a wide range of factors including demographic data, stroke risk factors, and laboratory findings to identify the clinical predictors of aspirin resistance. RESULTS: Eleven (12%) patients were identified as aspirin resistant by the ARU criteria. Univariate analysis showed that an older age, lower LDL cholesterol levels, and concurrent use of angiotensin converting enzyme inhibitors or receptor blockers were related to aspirin resistance by ARU criteria. Aspirin resistance by urinary TX-B2 criteria was observed in 18 (25%) patients and associated with an older age, metabolic syndrome, diabetes, cigarette smoking, and the use of angiotensin-converting enzyme inhibitors or receptor blockers. In multivariate analysis, this association lost significance by ARU criteria, and only lower fibrinogen levels were associated with increased risk by TX-B2 criteria. In addition, the stroke subtypes and the degree of atherosclerosis were not associated with aspirin resistance. The correlation between the two criteria was poor (r=-0.115, p=0.34). CONCLUSION: Despite the comprehensive analysis of this study, we failed to identify independent predictors for laboratory-defined aspirin resistance. Additionally, little overlap was found between the two criteria with which to assess aspirin resistance.

Clinical MRI cutoff points for predicting lacunar stroke may not exist: need for a grading rather than a dichotomizing system.

BACKGROUND: Lacunar stroke has been defined as an infarct <15 mm in diameter in the presence of symptoms of lacunar syndromes. We investigated a new approach in predicting whether a deep infarct is caused by small arterial occlusion. METHODS: A total of 319 consecutive patients with acute symptomatic infarcts within the striatocapsular territory underwent diffusion-weighted imaging (DWI) and diagnostic workups, including vascular and cardiological studies. Predictors for nonlacunar mechanisms were evaluated by logistic regression analysis, with the size of infarct (1-mm increase) and stroke syndrome (traditional vs. atypical lacunar syndrome vs. cortical syndrome) graded rather than dichotomized. RESULTS: Amongst the 171 patients who did not meet the established criteria for lacunar stroke, that is, deep infarct of >or=15 mm or presenting symptoms of nontraditional lacunar syndrome, a documented etiology could not be determined in 97 (56.7%) patients. In contrast, amongst the 148 patients who met the criteria, 27 (18.2%) had nonlacunar mechanisms. Logistic regression analysis identified the variables that predicted nonlacunar stroke mechanisms with statistical significance as nontraditional lacunar syndromes (OR 2.19 for atypical lacunar syndrome, and OR 6.72 for cortical syndrome), infarct size on DWI (OR 1.05 per 1-mm increase), and unilateral multiple deep infarcts on DWI (OR 2.22, p < 0.05 in all cases). Receiver operating characteristic curves showed that discrimination power of the model derived from logistic regression analysis (grading system) was better than that of the previously established dichotomizing criterion in predicting nonlacunar mechanisms (p = 0.004). CONCLUSIONS: A clinically significant proportion of clinical MRI lacunae are associated with underlying nonlacunar mechanisms. Decisions regarding the extent of diagnostic procedures in patients with subcortical infarcts can be guided by the point value in terms of the stroke syndrome and infarct patterns, as well as the size of infarct.

Neuropsychological findings of extrapontine myelinolysis without central pontine myelinolysis.

Central pontine myelinolysis (CPM) and extrapontine myelinolysis (EPM) are well recognized syndromes related to the rapid correction of hyponatremia, which are reported to show brain stem signs and various movement disorders. Cognitive dysfunction and neuropsychological findings, however, have seldom been reported. Cognitive manifestations in osmotic myelinolysis may have been underestimated due to the prominent brain stem symptoms and movement disorders. We report a case of EPM without CPM and describe the neuropsychological findings of EPM. The absence of CPM in this case made it possible to test neuropsychological function in the acute stage. Neuropsychological testing showed severe impairment of attention, verbal and visual memory, visuospatial function, and frontal/executive function. Language and language-related functions were normal except naming.