Several medications are approved to treat coronavirus disease 2019 (COVID-19) in Korea including nirmatrelvir/ritonavir, remdesivir, and regdanvimab. There is potential drug-drug interaction between antiepileptic drugs (AEDs) and the medications used to treat COVID-19. Several AEDs such as phenytoin, carbamazepine, phenobarbital, and primidone are strong cytochrome P450 inducers and can inhibit the drugs used for COVID-19. Particularly, these drugs are contraindicated with nirmatrelvir/ritonavir (Paxlovid®). There is a weaker drug-drug interaction between the AEDs and remdesivir. No significant interaction has been reported between the AEDs and molnupiravir. Pharmacokinetic interactions of the AEDs are important in effective management of COVID-19 in patients with epilepsy.

Background: and PurposeGait problems are a primary complaint in patients with multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD). The 12-item Multiple Sclerosis Walking Scale (MSWS-12) is a patient-reported measure assessing the impact of MS on the walking ability. We aimed to adapt and validate the Korean version of the MSWS-12 for the Korean population with MS and NMOSD. Methods: Thirty-four MS and 35 NMOSD patients were recruited. The MSWS-12 questionnaire was translated into the Korean language and evaluated for its validity and reliability in these patients. Results: The MS and NMOSD patients had mean ages of 35.9 and 42.1 years, respectively, median disease durations of 5.6 and 7.2 years, median Expanded Disability Status Scale (EDSS) scores of 2.75 (range, 0–6.5) and 3.5 (range, 0–7.5), and median baseline MSWS-12 total scores of 25 [interquartile range (IQR), 2.60–53.65] and 25 (IQR, 7.29–50.00). The baseline MSWS-12 total score in the patients with MS showed strong correlations with scores for the EDSS, timed 25-foot walk (T25FW), Multiple Sclerosis Impact Scale-29 (MSIS-29) physical dimension, and 36-item Short-Form Health Survey (SF-36) physical component summary (PCS), with Spearman's correlation coefficients (ρ) of 0.922, 0.756, 0.933, and −0.874, respectively. In patients with NMOSD, the baseline MSWS-12 total score showed strong correlations with scores for the EDSS, MSIS-29 physical dimension, and SF-36 PCS (ρ=0.769, 0.910, and −0.852, respectively), and moderate correlations with scores for the T25FW and Fatigue Severity Scale-9 (ρ=0.597 and 0.630, respectively). Conclusions The Korean version of the MSWS-12 appears to be a valid and reliable scale that can be used for Korean patients with MS. The MSWS-12 can also be applied to patients with NMOSD.

BACKGROUND: AND PURPOSE: To compare the characteristics of neuropathic pain in neuromyelitis optica spectrum disorder (NMOSD) and multiple sclerosis (MS). METHODS: From 2016 to 2018, 500 patients with NMOSD and MS from 6 referral hospitals in Korea underwent pain investigation. After the patients with current pain were matched for sex ratio and disease duration as confounding factors, PainDETECT questionnaires were assessed in 99 NMOSD and 58 MS patients to investigate neuropathic pain. The short form of the Brief Pain Inventory from 74 patients with neuropathic pain component was also analysed. RESULTS: According to the PainDETECT questionnaire, mechanical allodynia (p=0.014) and thermal hyperalgesia (p=0.011) were more severe in NMOSD patients than in MS patients. Strong involvements (score >3) of the pain in domains of tingling/prickling sensation (p=0.024), mechanical allodynia (p=0.027), sudden pain attacks (p=0.018), and thermal hyperalgesia (p=0.002) were significantly more frequent in NMOSD compared to MS patients. Among the patients experiencing pain with a neuropathic component, total pain-related interference (p=0.045) scores were significantly higher in NMOSD patients than in MS patients. In daily life, pain interfered with normal work (p=0.045) and relationships with other people (p=0.039) more often in NMOSD patients than in MS patients. Although pain medication was prescribed more frequently in NMOSD patients, the percentage of patients experiencing medication-related pain relief was lower in those patients. CONCLUSIONS The severity of neuropathic pain and the pain-related interference in daily life were greater in NMOSD patients than in MS patients. Individualized analgesic management should be considered based on a comprehensive understanding of neuropathic pain in these patients.

Considerable progress has been made in treatments for multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD) over the last several decades. However, the present treatments do not show satisfactory efficacy or safety in a considerable proportion of patients, who experience relapse or disability progression despite receiving treatment and suffer from side effects, which can be severe. Improvements in the understanding of the pathophysiologies of MS and NMOSD have led to numerous therapeutic approaches being proposed and developed. Monoclonal antibodies (mAbs) are receiving increasing attention because of their specificity of action and likelihood of high efficacy with fewer side effects.Many mAbs have been evaluated, and some have been approved for MS or NMOSD treatment. This article reviews the use of mAbs for treating MS and NMOSD, including summarizing their mechanisms of action, efficacy, and safety profiles.

Background: and Purpose: Iron retained by activated microglia and macrophages in multiple sclerosis (MS) lesions may serve as a marker of innate immune system activation. Among several magnetic resonance imaging (MRI) methods, there has been recent interest in using quantitative susceptibility mapping (QSM) as a potential tool for assessing iron levels in the human brain. This study examined QSM findings in MS and neuromyelitis optica spectrum disorder (NMOSD) lesions obtained with 3-T MRI to assess imaging characteristics related to paramagnetic rims around brain lesions in MS and NMOSD. Methods: This study included 32 MS and 21 seropositive NMOSD patients. MRI images were obtained using two 3-T MRI devices (Ingenia, Philips Healthcare; and Magnetom Verio, Siemens Healthineers) during routine diagnosis and treatment procedures. Multi and single echo gradient echo magnitude and phase images were obtained for QSM reconstruction.QSM images were used to characterize the detected lesions, and the findings were compared between MS and NMOSD. Results: Totals of 71 and 35 MRI scans were performed during the study period in MS and NMOSD patients, respectively. In QSM images, paramagnetic rims were found in 26 (81.2%) MS patients and 1 (4.8%) NMOSD patient. Eight of the 22 MS patients and only 1 of the 10 NMOSD patients who underwent follow-up MRI showed new paramagnetic rims. The paramagnetic rim lesions appeared after enhancement or in new T2-weighted lesions without enhancement. Conclusions Paramagnetic rims might be a characteristic MRI finding for MS, and therefore they have potential as an imaging marker for differentially diagnosing MS from NMOSD using 3-T MRI.

BACKGROUND AND PURPOSE: This study assessed the long-term outcomes of disease-modifying therapies (DMTs) in Korean multiple sclerosis (MS) patients treated in real-world clinical settings in Korea. METHODS: We retrospectively evaluated the medical records of 160 patients with an initial diagnosis of clinically isolated syndrome or relapsing-remitting MS who were treated for at least 2 years. A status of 3 for no evidence of disease activity (NEDA3) was defined as no relapse, disability progression, or active lesions in annual magnetic resonance imaging (MRI) evaluations. RESULTS: Patients who were initially treated with interferon β (n=152), glatiramer acetate (n=6), or teriflunomide (n=2) were included. The mean disease duration was 8.2 years. Compared to pretreatment, annualized relapse rates were significantly reduced after treatment [from 1.0±0.8 to 0.2±0.4 (mean±standard deviation), p < 0.001]. At the follow-up, 79 patients (49%) had changed their treatment regimen due to lack of efficacy (33%), side effects (14%), or other reasons (2%). Disability progression was observed in 18% of the patients over a mean treatment duration of 5.7 years. After 2 years, NEDA3 was observed in 38% of the patients. Loss of NEDA3 at 2 years was associated with long-term disability progression [odds ratio (OR)=17.975, p=0.003]. Poor response to first-line treatment was independently associated with a delay in treatment from disease onset (OR=1.238, p=0.049) and 10 or more brain lesions in the initial MRI (OR=3.648, p=0.047). CONCLUSIONS: This study has provided real-world evidence that DMTs are effective in reducing disease activity and disability progression in Korean MS patients.
Brain ; Diagnosis ; Follow-Up Studies ; Glatiramer Acetate ; Humans ; Interferons ; Korea ; Magnetic Resonance Imaging ; Medical Records ; Multiple Sclerosis* ; Recurrence ; Retrospective Studies

BACKGROUND AND PURPOSE: Patients treated with interferon-beta (IFN-β) can develop neutralizing antibodies (NAbs) against IFN-β that can negatively affect the therapeutic response. This study assessed the prevalence of NAbs and the impact of NAb positivity on the therapeutic response to IFN-β in Korean patients with multiple sclerosis (MS). METHODS: This was a multicenter study involving 150 MS patients from 9 Korean medical centers who were treated with IFN-β for at least 6 months. Sera that had not been influenced by acute treatment were assessed for NAbs using a luciferase reporter gene assay. To evaluate the association between persistent positivity for NAbs and disease activity, NAbs were tested at 2 different time points in 75 of the 150 patients. Disease activity was defined as the presence of clinical exacerbations and/or active MRI lesions during a 1-year follow-up after NAb positivity was confirmed. RESULTS: NAbs were found in 39 of the 150 (26%) MS patients: 30 of the 85 (35%) who were treated with subcutaneous IFN-β-1b, 9 of the 60 (15%) who were treated with subcutaneous IFN-β-1a, and 0 of the 5 (0%) who were treated with intramuscular IFN-β-1a. Thirty of the 39 patients exhibiting NAb positivity were tested at different time points, and 20 of them exhibited persistent NAb positivity. Disease activity was observed more frequently in patients with persistent NAb positivity than in those with transient positivity or persistent negativity [16/20 (80%) vs. 4/55 (7%), respectively; p < 0.001]. When disease activity was compared between patients with persistent and transient NAb positivity, the difference was unchanged and remained statistically significant [16/20 (80%) vs. 2/10 (20%), p=0.004]. CONCLUSIONS: These results further support that persistent NAb positivity is associated with disease activity in MS patients treated with IFN-β.
Antibodies, Neutralizing* ; Follow-Up Studies ; Genes, Reporter ; Humans ; Interferon-beta* ; Luciferases ; Magnetic Resonance Imaging ; Multiple Sclerosis* ; Prevalence

BACKGROUND AND PURPOSE: Brain lesions involving the cerebral cortex are rarely described in patients with neuromyelitis optica spectrum disorder (NMOSD), in contrast to multiple sclerosis. We investigated cerebral cortex involvement using conventional brain magnetic resonance imaging (MRI) in anti-aquaporin-4 (AQP4)-antibody-positive NMOSD patients. METHODS: The study enrolled 215 NMOSD patients who were seropositive for the anti-AQP4 antibody from 5 referral hospitals, and retrospectively analyzed their demographic, clinical, and MRI findings. Abnormal cerebral cortex lesions on brain MRI were identified by a neuroradiologist and two neurologists using consensus. RESULTS: Most of the 215 enrolled patients (87%) were female. The median age at onset was 22.5 years (range: 15-36 years) and the mean follow-up duration was 123 months. Brain lesions were found in 143 of 194 patients (74%) in whom MRI was performed during follow-up. Brain lesions involving the cerebral cortex were identified in 6 of these 194 patients (3.1%). Five of the patients were female, and the six patients together had a median age of 29 years (range: 15-36 years) at the time of lesion presentation. Three of them showed leptomeningeal enhancement in the lesions. At presentation of the cortex-involving lesions, five of these patients were not being treated at the time of presentation, while the sixth was being treated with interferon-beta. CONCLUSIONS: Although rare, cortical involvement occurs in NMOSD and is commonly combined with leptomeningeal enhancement. We speculate that this occurs only in patients who are not treated appropriately with immunosuppressant drugs.
Brain ; Cerebral Cortex* ; Consensus ; Female ; Follow-Up Studies ; Humans ; Interferon-beta ; Magnetic Resonance Imaging ; Multiple Sclerosis ; Neuromyelitis Optica* ; Referral and Consultation ; Retrospective Studies

Classical multiple sclerosis (MS) treatments using first-line injectable drugs, although widely applied, remain a major concern in terms of therapeutic adherence and efficacy. New oral drugs recently approved for MS treatment represent significant advances in therapy. The oral route of administration clearly promotes patient satisfaction and increases therapeutic compliance. However, these drugs may also have safety and tolerability issues, and a thorough analysis of the risks and benefits is required. Three oral drugs have been approved by regulatory agencies for MS treatment: fingolimod, teriflunomide, and dimethyl fumarate. This article reviews the mechanisms of action, safety, and efficacy of these drugs and two other drugs that have yielded positive results in phase III trials: cladribine and laquinimod.
Cladribine ; Compliance ; Dimethyl Fumarate ; Fingolimod Hydrochloride ; Multiple Sclerosis* ; Patient Satisfaction ; Risk Assessment