Neutrophil-to-lymphocyte ratio is an independent predictor for neurological disability in patients with idiopathic transverse myelitis.

INTRODUCTION: The neutrophil-to-lymphocyte ratio (NLR) has been found to be useful in the prognostication of immune-mediated neurological disorders because it roughly reflects the systemic innate immune response compared to the adaptive immune response. However, studies on the validity of NLR in demyelinating disorders of the central nervous system have shown conflicting results. Therefore, we aimed to investigate NLR in the idiopathic transverse myelitis (ITM) cohort. METHODS: We retrospectively analyzed the cohort data of patients with ITM between January 2006 and February 2020. The medical data of all patients with myelitis were reviewed to exclude patients with disease-associated myelopathy according to predefined exclusion criteria. The relationship between the natural log-transformed NLR (lnNLR) and the clinical, paraclinical, and imaging data was evaluated. Factors associated with neurological disability were analyzed using a linear mixed-effects model. Predictive factors for moderate-to-severe neurological disability (Expanded Disability Status Scale [EDSS] score ≥ 4) were investigated. RESULTS: A total of 124 participants were included in the analysis. The lnNLR correlated with EDSS and lesion length. Linear mixed-effects analysis showed that age, lesion length, and lnNLR were independently associated with neurological disabilities. Multivariable logistic regression revealed that lnNLR (odds ratio [OR] = 4.266, 95% confidence interval [CI] = 1.220-14.912, p = 0.023) and lesion length (OR = 1.848, 95% CI = 1.249-2.734, p = 0.002) were independent predictive factors of the worst neurological disability. CONCLUSION: NLR may be used as an independent prognostic factor for predicting poor neurological outcomes in patients with ITM.

Corticosteroid-induced bradycardia in multiple sclerosis and maturity-onset diabetes of the young due to hepatocyte nuclear factor 4-alpha mutation: A case report.

BACKGROUND: Intravenous steroid pulse therapy is the treatment of choice for acute exacerbation of multiple sclerosis (MS). Although steroid administration is generally well-tolerated, cases of cardiac arrhythmia have been reported. Herein, we describe a young woman who developed marked sinus bradycardia and T-wave abnormalities after corticosteroid administration. We also present plausible explanations for the abnormalities observed in this patient. CASE SUMMARY: An 18-year-old woman experienced vertiginous dizziness and binocular diplopia 1 wk prior to admission. Neurological examination revealed left internuclear ophthalmoplegia with left peripheral-type facial palsy. The initial laboratory results were consistent with those of type 2 diabetes. Brain magnetic resonance imaging revealed multifocal, non-enhancing, symptomatic lesions and multiple enhancing lesions. She was diagnosed with MS and maturity-onset diabetes of the young. Intravenous methylprednisolone was administered. On day 5 after methylprednisolone infusion, marked bradycardia with T-wave abnormalities were observed. Genetic evaluation to elucidate the underlying conditions revealed a hepatocyte nuclear factor 4-alpha (HNF4A) gene mutation. Steroid treatment was discontinued under suspicion of corticosteroid-induced bradycardia. Her electrocardiogram changes returned to normal without complications two days after steroid discontinuation. CONCLUSION: Corticosteroid-induced bradycardia may have a significant clinical impact, especially in patients with comorbidities, such as HNF4A mutations.

Safety and efficacy of clonazepam in patients with hemifacial spasm: A double-blind, randomized, placebo-controlled trial.

INTRODUCTION: Hemifacial spasm (HFS) is an involuntary intermittent twitching of the facial muscles. Medical and surgical treatments can be considered for HFS. Among medical treatments, clonazepam is a benzodiazepine used to treat epilepsy, psychiatric symptoms, and movement disorders. This study aimed to investigate the efficacy and safety of clonazepam for the treatment of HFS. METHODS: This randomized double-blind placebo-controlled trial prospectively enrolled patients with HFS aged 20-79 years. The patients were randomly assigned in a 1:1 ratio to receive either clonazepam (0.5 mg twice daily) or a placebo for 4 weeks. All participants underwent clinical assessment and laboratory tests at baseline and visit 2. The primary endpoint was the clinical global impression-improvement (CGI-I) score at visit 2. RESULTS: A total of 34 patients with HFS assessed for eligibility were enrolled between April 2015 and November 2016. Among them, two patients were withdrawn before randomization. Thus, the intention-to-treat analysis included 32 patients with HFS. The median CGI-I scores at visit 2 did not differ significantly between the clonazepam (3; range 1-6) and placebo (3.5; range 3-5) groups. In the safety analysis, only mild or no serious adverse events were observed. CONCLUSION: The results of this study demonstrated the safety of clonazepam in patients with HFS. However, clonazepam did not show a statistically significant effect on HFS. Further studies are needed to provide evidence of the clinical benefits in patients with HFS.

Efficacy and Safety of Pregabalin for Muscle Cramps in Liver Cirrhosis: A Double-Blind Randomized Controlled Trial.

BACKGROUND: Muscle cramp is possibly related to peripheral nerve hyperexcitability (PNH), and one of the most debilitating symptoms frequently encountered in patients with liver cirrhosis. We investigated whether pregabalin, a gamma-aminobutyric acid analogue, can suppress neuronal excitability and reduce muscle cramps in cirrhotic patients. METHODS: We conducted a randomized, double-blind, placebo-controlled trial in which study participants with cirrhosis from a single tertiary center were enrolled. Primary endpoint was the relative change in cramp frequency from the run-in to standard dose treatment phase (4 weeks per each). Secondary endpoints included the responder rate, and the changes in cramp frequency during sleep, pain intensity, health-related quality of life (Liver Disease Quality of Life Instrument, Short Form-36) and electrophysiological measures of PNH. RESULTS: This study was terminated early because of insufficient accrual. 80% (n = 56) of the target number of participants (n = 70) were randomized to pregabalin (n = 29) or placebo (n = 27). Median baseline frequency of muscle cramps (interquartile range) was 5.8 (3.5-10) per week in the pregabalin group and 6.5 (4.0-10) in the placebo group (P = 0.970). The primary analysis showed a significant reduction in cramp frequency with pregabalin compared to placebo (-36% vs. 4.5% for the percentage change, P = 0.010). Secondary outcomes did not differ significantly between the two groups. Adverse effects with pregabalin were mainly dizziness and lethargy. CONCLUSION: With multiple problems emerging from premature termination in mind, the results suggested an acceptable safety profile and favorable effect of pregabalin in reducing muscle cramps compared to placebo in cirrhotic patients. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01271660.

Changing patterns of multiple sclerosis in Korea: Toward a more baseline MRI lesions and intrathecal humoral immune responses.

BACKGROUND: The environmental risks of multiple sclerosis (MS), including adolescent obesity and vitamin D deficiency, are increasing in Korea. We aimed to determine whether the patterns and/or severity of MS in Korea can change according to the year of birth or disease onset. METHODS: Two hundred and sixty-six patients with adult-onset MS, including 164 with an available baseline magnetic resonance imaging (MRI), were retrospectively included from 17 nationwide referral hospitals in Korea. The demographics, MRI T2 lesion burden at disease onset, cerebrospinal fluid markers, and prognosis were assessed. RESULTS: The birth year, time from disease onset to first MRI, and female sex were associated with a higher number of baseline MRI T2 lesions. The birth year was also associated with the presence of oligoclonal band in the cerebrospinal fluid and high immunoglobin G index. An increased female/male ratio was observed among those with a more recent year of birth and/or disease onset. CONCLUSIONS: In Korea, the disease pattern of adult-onset MS may be changing toward a more baseline T2 MRI lesions, intrathecal humoral immune responses, and also higher female ratio.

Takotsubo cardiomyopathy in amyotrophic lateral sclerosis.

OBJECTIVE: To investigate the frequency, features, and prognosis of takotsubo cardiomyopathy (TTC) in patients with amyotrophic lateral sclerosis (ALS). METHODS: We reviewed detailed clinical, laboratory, and cardiovascular data from 64 ALS patients (38 men and 26 women) who underwent echocardiographic evaluation for various reasons at a single referral center between January 2011 and December 2015. RESULTS: TTC was diagnosed in 9 ALS patients (4 men and 5 women). Mean age was 61.3years (range 55-71years), and median disease duration was 51.5months (range 18-134months). All patients were bulbar or cervical onset, and were at advanced stages of ALS when TTC was diagnosed. Acute exacerbation of dyspnea was an invariable presentation, and chest discomfort mimicking acute coronary syndrome was present in 2 patients. Six patients had significant hypotension requiring intravenous fluid challenge and inotropic support. Three patients showed altered mentality, and 2 of them suffered cardiopulmonary arrest. CONCLUSIONS: TTC should be suspected in ALS patients presenting with acute exacerbation of dyspnea and chest discomfort, particularly at advanced stages of the disease. This study highlights the need for proper evaluation and management of cardiac dysfunction in ALS.

Transient Ischemic Attacks Preceding Acute Lacunar Infarction.

BACKGROUND: It has been reported that some patients with lacunar infarction have transient ischemic attacks (TIAs) before stroke. This study was aimed at evaluating the factors and prognostic value related to TIAs preceding acute lacunar stroke. METHODS: A total of 1,424 patients were admitted to the hospital for first-ever ischemic stroke. Of which 314 patients with acute lacunar infarction were enrolled for this study. The patients were divided into 2 groups based on the occurrence of TIAs before stroke. RESULTS: Fifty-eight patients (18.5%) had a history of preceding TIAs. The interval between TIA and stroke was less than 24 h in most patients (87.9%). Diabetes mellitus was more often found in patients with TIAs than in those without TIAs (48.3 vs. 28.9%, p = 0.004). Initial National Institute of Health Stroke Scale scores showed no significant difference between the 2 groups (median 2 vs. 3, p = 0.067). However, patients with preceding TIAs had a more favorable outcome (modified Rankin scale 0-1) than those without TIA at 3 months after stroke (79.6 vs. 63.2%, p = 0.021). CONCLUSION: Lacunar TIA may occur due to small perforating microatheromatous arteries caused by diabetes. This study suggests that ischemic tolerance may play a role in patients with preceding TIAs before lacunar infarct, allowing better recovery from a subsequent ischemic stroke.

Split-hand phenomenon in amyotrophic lateral sclerosis: A motor unit number index study.

INTRODUCTION: The split-hand phenomenon refers to preferential wasting of the thenar muscles with relative sparing of the hypothenar muscles in amyotrophic lateral sclerosis (ALS). METHODS: We compared the split-hand index (SI) calculated from the compound muscle action potential (CMAP; SICMAP ) with that calculated from the motor unit number index (MUNIX; SIMUNIX ). We performed MUNIX on the abductor policis brevis (APB), first dorsal interosseous (FDI), and abductor digiti minimi (ADM) muscles of 39 ALS patients and 40 age-matched, healthy controls. SI is derived by multiplying the CMAP (or MUNIX) recorded over the APB and FDI and dividing by the CMAP (or MUNIX) recorded over the ADM. RESULTS: Receiver-operating characteristic curve analysis revealed good diagnostic accuracy for both indices, but better performance of SIMUNIX than SICMAP . CONCLUSION: SIMUNIX and SICMAP were useful in differentiating ALS patients from healthy controls. SIMUNIX appears to be a better electrophysiological marker than SICMAP for the split-hand sign of ALS. Muscle Nerve 53: 885-888, 2016.

Paroxysmal alternating nystagmus.

Paroxysmal reversal of spontaneous nystagmus has rarely been described. Herein, we report recurrent bouts of vertigo and oscillopsia in association with reversed spontaneous nystagmus in a patient with prior surgical resection of the cerebellar vermis due to medulloblastoma and subsequent labyrinthine damage. The symptoms almost completely resolved with carbamazepine. The episodes may be ascribed to paroxysmal reversal of the vestibular asymmetry due to intermittent decompensation by the deficient cerebellum.

A case of pigmentary orthochromatic leukodystrophy with findings of proton MR spectroscopy and serial brain MRIs.

Despite a few case reports over the last 60 years, little progress has been made in defining the phenotype, genotype and pathophysiological mechanisms involved in pigmentary orthochromatic leukodystrophy (POLD). Furthermore, there is currently no data available regarding MRI in patients in the relatively early stages of POLD. Here, we present a 37 year old male patient with brain biopsy-proven POLD who had brain MRIs three times during the first year of his clinical course and proton MR spectroscopy (MRS) throughout his diagnostic evaluation. This patient with POLD was clinically characterized by seizures, rapidly progressive frontally predominant dementia and gait disturbance. The brain MRIs taken serially over the first year revealed progressive development of frontal-predominant white matter changes in the periventricular areas during the earlier periods, which later spread into the deep white matter. His MRS was helpful in the diagnostic approach because the results enabled demyelinating changes to be distinguished from other disease processes such as ischemia, gliosis or tumors. The MRS findings also reflected the disease dynamics because metabolic derangement was observed, even in the white matter that appeared normal. The findings presented here provide insight into the dynamics of POLD.