Jung-Ick Byun

Anti‐LGI1 Encephalitis is Associated with Unique HLA Subtypes

Autoimmune encephalitis (AE), represented by anti–leucine‐rich glioma‐inactivated 1 (anti‐LGI1) and anti–N‐methyl‐D‐aspartate receptor (anti‐NMDAR) encephalitis, has increasing clinical significance based on recent discoveries of neuronal autoantibodies. However, its immunopathogenesis is not fully understood. Here, we investigated whether AE is associated with the human leukocyte antigen (HLA) subtypes.

Orthostatic intolerance symptoms are associated with depression and diminished quality of life in patients with postural tachycardia syndrome

BackgroundPatients with postural tachycardia syndrome often appear depressive and report diminished quality of life (QOL). In the current study, we first evaluated if the maximal heart rate (HR) increment after standing is associated with the clinical symptoms in patients with excessive orthostatic tachycardia (OT). Next, we investigated the correlations among the symptoms of orthostatic intolerance (OI), depression, and health-related QOL in these patients. Finally we assessed if patients with minimal OI symptoms suffer from depression or diminished QOL.MethodsWe performed a comprehensive questionnaire-based assessment of symptoms in 107 patients with excessive OT with a ≥ 30 beats/min heart rate increment (or ≥ 40 beats/min in individuals aged between 12 and 19) within 10 min after standing up. An existing orthostatic intolerance questionnaire (OIQ), the Beck depression inventory-II (BDI-II), and the 36 Item Short-Form Health Survey were completed prior to any treatment. Correlation analyses among the items of the questionnaires and other parameters were performed. Additionally, patients with minimal OI symptoms were analysed separately.ResultsThe maximal orthostatic HR increment was not associated with the clinical symptoms. The OI symptoms were significantly correlated with depression and diminished QOL. The BDI-II score demonstrated a positive linear relationship with total OIQ score (r = 0.516), and both physical and mental component summary scales of SF-36 showed a negative linear relationship with total OIQ score (r = -0.542 and r = -0.440, respectively; all p <0.001). Some OI symptoms were more strongly associated with depression, and others were more strongly related to QOL. Chest discomfort and concentration difficulties were the most influential OI symptoms for depression, while nausea and concentration difficulties were the most influential symptoms for physical and mental QOL, respectively. Dizziness and headache were the two most common complaints in patients with mild to moderate OI symptoms. In addition, subjects with minimal OI symptoms also had considerable deterioration in QOL.ConclusionThe OI symptoms, but not the maximal HR increment, are significantly correlated with depression and diminished QOL in patients with excessive OT. Therefore, pervasive history taking is important when encountering patients with excessive OT.

New feasible treatment for refractory autoimmune encephalitis: Low-dose interleukin-2

Low-dose interleukin-2 (IL-2) restores the balance of regulatory and effector T cells. We aimed to determine the feasibility of low-dose IL-2 as a treatment for refractory autoimmune encephalitis (AE). Ten patients who had received low-dose IL-2 were retrospectively identified. We observed an improvement in the modified Rankin Scale scores of six patients at the last follow-up compared with the scores at the initiation of low-dose IL-2 (p=0.014). One patient experienced treatment-related grade 3 neutropenia. Overall, low-dose IL-2 is a feasible and relatively safe treatment for AE patients who are refractory to the first- and second-line immunotherapies.

HLA-B*40:02 and DRB1*04:03 are risk factors for oxcarbazepine-induced maculopapular eruption.

Oxcarbazepine (OXC) is a widely used antiepileptic drug for the treatment of partial seizures that was developed through structural variation of carbamazepine. Although OXC has a lower risk of cutaneous adverse drug reactions (cADRs) than carbamazepine, cADRs ranging from maculopapular eruption (MPE) to the more severe Stevens‐Johnson syndrome and toxic epidermal necrolysis still limit the use of OXC in some patients. A few human leukocyte antigen (HLA)–related genetic risk factors for carbamazepine‐induced cADRs have been identified. However, the HLA‐related genetic risk factors associated with OXC‐induced cADRs are unknown.

Frequent rhabdomyolysis in anti-NMDA receptor encephalitis

The aim of this study was to analyze the clinical presentation and provocation factors of rhabdomyolysis in anti-NMDAR encephalitis. Among the 16 patients with anti-NMDAR encephalitis in our institutional cohort, nine patients had elevated CK enzyme levels and clinical evidence of rhabdomyolysis. Rhabdomyolysis was more frequent after immunotherapy. The use of dopamine receptor blocker (DRB) increased the risk of rhabdomyolysis. None of the patients without rhabdomyolysis received DRBs. Rhabdomyolysis is a frequent complication in anti-NMDAR encephalitis and more common after immunotherapy and the use of DRBs increases the risk. Therefore, DRBs should be administered carefully in patients with anti-NMDAR encephalitis.

Treatment of Propriospinal Myoclonus at Sleep Onset

Dear Editor, Propriospinal myoclonus (PSM) is characterized by jerks arising in axial muscles that spread to more caudal and rostral segments along propriospinal pathways. PSM at sleep onset is a subtype of PSM that occurs during the sleep–awake transition and causes severe sleep-onset insomnia.1 Previous case reports have focused on the etiology and mechanism of PSM, but have not evaluated treatment responses objectively. Moreover, most treatments have only employed clonazepam.1 We present a patient with PSM at sleep onset who improved after treatment with clonazepam and add-on levetiracetam. The improvement was confirmed by serial video polysomnography (VPSG).

Clinical characterization of unknown/cryptogenic status epilepticus suspected as encephalitis: A multicenter cohort study

Autoimmune and unknown/cryptogenic encephalitis have been increasingly noted in the inflammatory etiology of new-onset status epilepticus (SE). We aimed to investigate clinical characteristics and the potential role of immunotherapy in encephalitis-related adult SE through our multicenter prospective SE registry. Among the 274 patients with SE, 35 (12.8%) patients demonstrated an inflammatory etiology and 19 out of 35 (54.3%) patients demonstrated unknown/cryptogenic cause. Patients with autoimmune and unknown/cryptogenic encephalitis shared similar clinical features. In unknown/cryptogenic encephalitis, the proportion of favorable outcomes (mRS 0-3) showed a different propensity at 3-6months after discharge between patients receiving active immunotherapy and not receiving any immunotherapy, although it was not statistically significant (at admission 28.6% vs 20%, p=0.603; at discharge 57.1% vs 60%, p=0.570; at 3-6months after discharge 90% vs 60%, p=0.214 in patients treated with active immunotherapy or without immunotherapy, respectively). Extensive autoantibody screening should be carried out and empirical immunotherapy may be potentially helpful even in patients without antibodies, although longer term and multi-national studies may be necessary to make a stronger recommendation.

Safety and Efficacy of Gamma-Aminobutyric Acid from Fermented Rice Germ in Patients with Insomnia Symptoms: A Randomized, Double-Blind Trial

Background and Purpose This study aimed to determine the subjective and objective improvements in sleep quality after treatment with gamma-aminobutyric acid (GABA; 300 mg daily) extracted from unpolished rice germ. Methods This study was a prospective, randomized, double-blind, and placebo-controlled trial. In total, 40 patients who complained of insomnia symptoms were enrolled and randomly assigned to the GABA treatment group (n=30) or the placebo group (n=10). Polysomnography was performed, and sleep questionnaires were administered before treatment and after 4 weeks of treatment. Results After 4 weeks of treatment the sleep latency had decreased [13.4±15.7 min at pretreatment vs. 5.7±6.2 min at posttreatment (mean±SD), p=0.001] and the sleep efficacy had increased (79.4±12.9% vs. 86.1±10.5%, p=0.018) only in the GABA treatment group. Adverse events occurred in four subjects (10%). Conclusions This study shows that treatment with unpolished-rice-germ-derived GABA improved not only the subjective sleep quality but also the objective sleep efficacy without severe adverse events.

Increased adverse events associated with antiepileptic drugs in anti-leucine-rich glioma-inactivated protein 1 encephalitis

Anti–leucine‐rich glioma‐inactivated protein 1 (LGI1) encephalitis is a rare autoimmune condition presenting mainly as altered mental state, cognitive dysfunction, and seizure. Antiepileptic drugs (AEDs) are usually initiated to control seizures despite their limited efficacy; however, accumulating clinical experience suggests a high incidence of adverse reactions to AEDs in anti‐LGI1 encephalitis. We reviewed the medical records of patients who were diagnosed with anti‐LGI1 encephalitis to analyze the adverse effects of AEDs in these patients. Among the 20 patients who were treated with AEDs, 10 (50%) changed their AEDs due to adverse cutaneous drug reaction. Eight of them presented with maculopapular eruption, one with drug rash with eosinophilia and systemic symptoms syndrome, and one with eczema. Causative agents mostly consisted of aromatic AEDs. Oxcarbazepine was discontinued in two additional patients due to hyponatremia. Six patients (30%) discontinued their dose of levetiracetam because of psychiatric manifestations including irritability/aggressive behavior (four patients), insomnia (one patient), and depressive mood (one patient). Clinicians should consider adverse cutaneous drug reaction, psychiatric adverse events, and hyponatremia when selecting AEDs for the treatment of anti‐LGI1 encephalitis.

Clinical manifestations and treatment outcomes of parvovirus B19 encephalitis in immunocompetent adults

Parvovirus B19 (PVB19) has rarely been identified as a cause of encephalitis in immunocompetent adults, in whom clinical information regarding PVB19 encephalitis has remained unclear. Herein, we report the clinical presentations, laboratory and imaging findings, and treatment outcomes of five immunocompetent adults with PVB19 encephalitis. Although none of the patients showed any distinctive features of PVB19 infection, they showed various clinical manifestations, including one instance of brainstem involvement. Additionally, immunotherapy can be considered an effective approach, especially in immunocompetent adults with PVB19 encephalitis who are resistant to the initial management.