Establishment of a registry of clinical data and bioresources for rare nervous system diseases.

Rare diseases are predominantly genetic or inherited, and patients with these conditions frequently exhibit neurological symptoms. Diagnosing and treating many rare diseases is a complex challenge, and their low prevalence complicates the performance of research, which in turn hinders the advancement of therapeutic options. One strategy to address this issue is the creation of national or international registries for rare diseases, which can help researchers monitor and investigate their natural progression. In the Republic of Korea, we established a registry across 5 centers that focuses on 3 rare diseases, all of which are characterized by gait disturbances resulting from motor system dysfunction. The registry will collect clinical information and human bioresources from patients with amyotrophic lateral sclerosis, spinocerebellar ataxia, and hereditary spastic paraplegia. These resources will be stored at ICreaT and the National Biobank of Korea. Once the registry is complete, the data will be made publicly available for further research. Through this registry, our research team is dedicated to identifying genetic variants that are specific to Korean patients, uncovering biomarkers that show a strong correlation with clinical symptoms, and leveraging this information for early diagnosis and the development of treatments.

Serial Nerve Conduction Studies in Guillain-Barré Syndrome: Its Usefulness and Precise Timing.

PURPOSE: Nerve conduction study (NCS) is essential for subclassifying Guillain-Barré syndrome (GBS). It is well known that the GBS subclassification can change through serial NCSs. However, the usefulness of serial NCSs is debatable, especially in patients with early stage GBS. METHODS: Follow-up NCS data within 3 weeks (early followed NCS, EFN) and within 3 to 10 weeks (late-followed NCS, LFN) were collected from 60 patients with GBS who underwent their first NCS (FN) within 10 days after symptom onset. Each NCS was classified into five subtypes (normal, demyelinating, axonal, inexcitable, and equivocal), according to Hadden's and Rajabally's criteria. We analyzed the frequency of significant changes in classification (SCCs) comprising electrodiagnostic aggravation and subtype shifts between demyelinating and axonal types according to follow-up timing. RESULTS: Between FN and EFN, 33.3% of patients with Hadden's criteria and 18.3% with Rajabally's criteria showed SCCs. Between FN and LFN, 23.3% of patients with Hadden's criteria and 21.7% with Rajabally's criteria showed SCCs, of which 71.4% (Hadden's criteria) and 46.2% (Rajabally's criteria) already showed SCCs from the EFN. The conditions of delayed SCCs between EFN and LFN were very early FN, mild symptoms at the FN, or persistent electrophysiological deterioration 3 weeks after symptom onset. CONCLUSIONS: A substantial proportion of patients with GBS showed significant changes in neurophysiological classification at the early stage. Serial NCS may be helpful for precise neurophysiological classification. This study suggests that follow-up NCSs should be performed within 3 weeks of symptom onset in patients with GBS in whom FN was performed within 10 days of symptom onset.

Early rituximab treatment reduces long-term disability in aquaporin-4 antibody-positive neuromyelitis optica spectrum.

BACKGROUND: Neuromyelitis optica spectrum disorder (NMOSD) causes relapsing inflammatory attacks in the central nervous system, leading to disability. As rituximab, a B-lymphocyte-depleting monoclonal antibody, is an effective in preventing NMOSD relapses, we hypothesised that earlier initiation of rituximab can also reduce long-term disability of patients with NMOSD. METHODS: This multicentre retrospective study involving 19 South Korean referral centres included patients with NMOSD with aquaporin-4 antibodies receiving rituximab treatment. Factors associated with the long-term Expanded Disability Status Scale (EDSS) were assessed using multivariable regression analysis. RESULTS: In total, 145 patients with rituximab treatment (mean age of onset, 39.5 years; 88.3% female; 98.6% on immunosuppressants/oral steroids before rituximab treatment; mean disease duration of 121 months) were included. Multivariable analysis revealed that the EDSS at the last follow-up was associated with time to rituximab initiation (interval from first symptom onset to initiation of rituximab treatment). EDSS at the last follow-up was also associated with maximum EDSS before rituximab treatment. In subgroup analysis, the time to initiation of rituximab was associated with EDSS at last follow-up in patients aged less than 50 years, female and those with a maximum EDSS score ≥6 before rituximab treatment. CONCLUSIONS: Earlier initiation of rituximab treatment may prevent long-term disability worsening in patients with NMOSD, especially among those with early to middle-age onset, female sex and severe attacks.

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.

Shear-wave elastography evaluation of thenar muscle in carpal tunnel syndrome.

PURPOSE: We aim to evaluate the shear wave velocity (SWV) of the thenar muscle as an adjunct diagnostic tool for carpal tunnel syndrome (CTS). METHODS: Ninety-two wrists with CTS and 30 control wrists without CTS underwent ultrasonographic evaluation of thenar muscle and median nerve including shear-wave elastography. Cross sectional area (CSA) of medial nerve and SWV of thenar muscle and median nerve were evaluated. CTS patients were assessed for Boston CTS, Padua CTS, modified Hirani grading scores, and nerve conduction study (NCS). SWVs, CSA, and NCS parameters were compared between two groups. RESULTS: The SWVs of thenar muscle and median nerve (p < 0.001, respectively), and CSA of median nerve (p < 0.001) were more significantly greater in patients with CTS than in controls. The SWV of median nerve was moderately correlated with CSA of median nerve (r = 0.35, p < 0.001) and modified Hirani CTS score (r = 0.35, p < 0.001). The SWV of thenar muscle was inversely correlated with modified Hirani CTS score (r = -0.21, p = 0.04). CONCLUSION: The SWV of thenar muscle and median nerve of CTS were significantly increased compared to that of control, and significantly negatively correlated with NCS parameters (modified Hirani CTS score). SWVs may be used as an adjunct diagnostic tool for CTS.

Glymphatic system dysfunction in obstructive sleep apnea evidenced by DTI-ALPS.

OBJECTIVES: This study aimed to evaluate the glymphatic system function in patients with obstructive sleep apnea (OSA) compared to healthy controls using diffusion tensor imaging (DTI) with the perivascular space (DTI-ALPS) method. Our hypothesis is that patients with OSA may have glymphatic system dysfunction, which is correlated with OSA severity. METHODS: We enrolled 24 patients with OSA and 24 healthy controls. All participants underwent DTI magnetic resonance imaging (MRI) using the same 3T MRI scanner, and we calculated the DTI-ALPS index from the DTI. We evaluated the differences in the DTI-ALPS index between patients with OSA and healthy controls. In addition, we conducted a correlation analysis between the DTI-ALPS index and clinical characteristics. RESULTS: The DTI-ALPS index was significantly different between the groups. The DTI-ALPS in patients with OSA was significantly lower than in healthy controls (1.30450 vs. 1.61600, p = 0.0006). Furthermore, the DTI-ALPS index was significantly negatively correlated with the apnea-hypopnea index in sleep stage N (r = -0.427, p = 0.042) and oxygen desaturation index during sleep N (r = -0.497, p = 0.036). CONCLUSION: We successfully demonstrated glymphatic system dysfunction in patients with OSA. In addition, glymphatic system dysfunction is well correlated with OSA severity, especially during sleep stage N. Thus, these findings can explain the effects of OSA on increased risk of developing dementia and highlight the importance of OSA treatment.

Alterations in the structural covariance network of the hypothalamus in patients with narcolepsy.

PURPOSE: The hypothalamus plays a pivotal role in the pathogenesis of narcolepsy. This study aimed to evaluate the differences in the structural covariance network of thehypothalamus based on volume differences between patients with narcolepsy and healthy controls. METHODS: We retrospectively enrolled 15 patients with narcolepsy and 19 healthy controls.All subjects underwent three-dimensional T1-weighted imaging using a 3-T magnetic resonance imaging scanner. Hypothalamic subunits were segmented, and the volumes of individual hypothalamic subunits were obtained using the FreeSurfer program. Subsequently, we conducted a structural covariance network analysis of the subunit volumes with graph theory using the BRAPH program in patients with narcolepsy and in healthy controls. RESULTS: There were no significant differences in the volumes of the entire right and left hypothalamus nor in the hypothalamic subunit between patients with narcolepsy and healthy controls. However, we found significant differences in the structural covariance network in the hypothalamus between these groups. The characteristic path length was significantly lower in patients with narcolepsy than in healthy controls (1.698 vs. 2.831, p = 0.001). However, other network measures did not differ between patients with narcolepsy and healthy controls. CONCLUSION: We found that the structural covariance network of the hypothalamus, as assessed from the subunit volumes of hypothalamic regions using a graph theoretical analysis, is different in patients with narcolepsy compared to healthy controls. These findings may contribute to the understanding of the pathogenesis of narcolepsy.

Brain networks in migraine with and without aura: An exploratory arterial spin labeling MRI study.

OBJECTIVES: The aim of this exploratory study was to investigate the underlying pathomechanisms of migraine with aura (MA) and migraine without aura (MO) in the interictal phase using a connectivity analysis. METHODS: We prospectively enrolled patients who were newly diagnosed with migraine. All patients underwent brain MRI, including diffusion tensor imaging and arterial spin labeling perfusion MRI. We analyzed the differences between patients with MA and those with MO in structural connectivity based on diffusion tensor imaging and functional connectivity based on arterial spin labeling perfusion MRI using a graph theoretical analysis. RESULTS: We enrolled 58 patients with migraine (11 patients with MA and 47 patients with MO). There were no differences between patients with MA and those with MO in the network measures of global structural connectivity. However, differences in global functional connectivity were found between the two groups. The assortative coefficient was lower in patients with MA than in those with MO (-0.050 vs. -0.012, p = .017). There were no differences in local structural and functional connectivity between patients with MA and those with MO. CONCLUSION: We found differences in global functional connectivity between patients with MO and those with MA. The study of MA and MO using a connectivity analysis may shed light on migraine pathophysiology. We suggest it is worthwhile to investigate if changes in functional connectivity may serve as novel biomarkers in MA. In this regard, ASL MRI appears to be valuable in the context of network analysis, but further studies are needed to confirm our findings.

Glymphatic system dysfunction in patients with juvenile myoclonic epilepsy.

OBJECTIVE: The glymphatic system is a glial cell-dependent waste clearance pathway in the brain that is essential for the maintenance of brain homeostasis. In this study, we evaluated glymphatic system function in patients with juvenile myoclonic epilepsy (JME) compared with healthy controls. METHODS: Patients with JME and healthy controls were retrospectively enrolled in this study. All the participants underwent brain diffusion tensor imaging (DTI). The "DTI-analysis along the perivascular space (ALPS)"-index was calculated to evaluate the glymphatic system function of the participants. The ALPS-indices of the patients with JME were compared with those of the healthy controls. In addition, the correlations between ALPS-index and the clinical characteristics of the patients with JME were analyzed to validate changes in glymphatic system function. RESULTS: A total of 39 patients with JME and 38 healthy controls were enrolled in this study. The mean ALPS- index of the patients with JME was significantly lower than that of the healthy controls (1.541 vs. 1.653, p = 0.041). ALPS-index was negatively correlated with age in patients with JME (r = -0.375, p = 0.018). However, ALPS-index was not correlated with age at onset, duration of epilepsy, or anti-seizure medication load in patients with JME. CONCLUSION: This study is the first in which the ALPS method was used to demonstrate that patients with JME have significant glymphatic system dysfunction. The results also show that glymphatic system index is negatively correlated with age in patients with JME, a finding which demonstrates that the glymphatic system function of patients with JME gradually declines with age. The ALPS-index might be a potential biomarker for monitoring glymphatic system function in patients with epilepsy.

Identifying juvenile myoclonic epilepsy via diffusion tensor imaging using machine learning analysis.

The aim of this study was to evaluate the feasibility of using a machine learning approach based on diffusion tensor imaging (DTI) to identify patients with juvenile myoclonic epilepsy. We analyzed the usefulness of combining conventional DTI measures and structural connectomic profiles. This retrospective study was conducted at a tertiary hospital. We enrolled 55 patients with juvenile myoclonic epilepsy. All of the subjects underwent DTI from January 2017 to March 2020. We also enrolled 58 healthy subjects as a normal control group. We extracted conventional DTI measures and structural connectomic DTI profiles. We employed the support vector machines (SVM) algorithm to classify patients with juvenile myoclonic epilepsy and healthy subjects based on the conventional DTI measures and structural connectomic profiles. The SVM classifier based on conventional DTI measures had an accuracy of 68.1% and an area under the curve (AUC) of 0.682. Another SVM classifier based on the structural connectomic profiles demonstrated an accuracy of 72.7% and an AUC of 0.727. The SVM classifier based on combining the conventional DTI measures and structural connectomic profiles had an accuracy of 81.8% and an AUC of 0.818. DTI using machine learning is useful for classifying patients with juvenile myoclonic epilepsy and healthy subjects. Combining both the conventional DTI measures and structural connectomic profiles results in a better classification performance than using conventional DTI measures or the structural connectomic profiles alone to identify juvenile myoclonic epilepsy.

Existence and Significance of Internal Border Zone Infarcts with Accessory Lesions Located in the Anteromedial Temporal Lobe.

OBJECTIVES: To examine the existence and significance of internal border zone (IBZ) infarcts with accessory lesions in the anteromedial temporal lobe (ATL). MATERIALS AND METHODS: IBZ infarcts located at the corona radiata were selected based on diffusion-weighted imaging of 2535 consecutive patients with ischemic stroke and the presence of lesions in the ATL was identified. The Mann-Whitney U test, Student t-test, Pearson χ2 test, or Fisher exact test was used to analyze differences between the IBZ infarct groups with and without accessory lesions in the ATL. RESULTS: Thirty-six of 2535 patients (1.4%) had IBZ infarcts. The IBZ group with accessory lesions in the ATL (17 cases, 47.2%) showed a higher portion of occluded middle cerebral arteries than the IBZ group without accessory lesions in the ATL (p = 0.02). The initial National Institutes of Health Stroke Scale score (odds ratio, 2.03; 95% confidence interval, 1.04-3.99;   = 0.039) and progression after admission (odds ratio, 25.43; 95% confidence interval, 2.47-261.99; p = 0.007) were independently associated with poor prognosis in patients with IBZ infarcts. There were no differences in the progression rate and clinical outcomes, regardless of the presence of lesions in the ATL. CONCLUSIONS: Our study suggests the existence of a distinct type of IBZ infarct characterized by accessory lesions in the ATL, which is associated with different arterial features but has a similar clinical course to IBZ infarcts without accessory lesions in the ATL.

Quantitative gait and postural analyses in patients with diabetic polyneuropathy.

BACKGROUND: Although gait disturbances are relatively common symptoms in diabetic polyneuropathy (DPN), few studies have quantitatively analyzed gait and posture in DPN patients. This study aimed to analyze gait and posture quantitatively in DPN patients and to determine the association between clinical and electrophysiological parameters and gait and posture parameters. METHODS: Sixty-four DPN patients were enrolled in this study. DPN was clinically assessed using the Toronto clinical neuropathy score (TCNS). All participants underwent nerve conduction study (NCS), three-dimensional motion analysis, and static posturography. We evaluate the correlation of gait and posture parameters with electrophysiological and clinical parameters. RESULTS: Foot height, step length, and stride length among gait parameters were inversely correlated with the TCNS. Anteroposterior range during eyes-closed and mediolateral distance and range during eyes-open and eyes-closed were inversely correlated with the sensory nerve action potential amplitude in the sural nerve. Mediolateral distance during eyes-open and eyes-closed was correlated with the compound muscle action potential amplitude in the peroneal nerve. CONCLUSIONS: Gait parameters are associated with clinical parameters, and postural parameters are associated with electrophysiological parameters, particularly sensory NCS. Gait and postural analysis can be a useful tool for assessing the neurological status in DPN patients.

Comparison of MOG and AQP4 antibody seroprevalence in Korean adults with inflammatory demyelinating CNS diseases.

We aimed to compare seroprevalence of anti-myelin oligodendrocyte glycoprotein (MOG) and anti-aquaporin-4 (AQP4) antibodies in Korean adults with inflammatory demyelinating diseases (IDDs) of the central nervous system (CNS), based on a multicenter nationwide database. Sera were analyzed using a live cell-based assay for MOG and AQP4 antibodies. Of 586 Korean adults with IDDs of the CNS, 36 (6.1%) and 185 (31.6%) tested positive for MOG and AQP4 antibodies, respectively. No participant showed double positivity. Seroprevalence of MOG antibodies was about five times lower than that of AQP4 antibodies in a large cohort of Korean adults with IDDs of the CNS.

Comparison of the Diagnostic Performance of Strain Elastography and Shear Wave Elastography for the Diagnosis of Carpal Tunnel Syndrome.

OBJECTIVES: To compare the diagnostic performance between strain elastography and shear wave elastography (SWE) for the diagnosis of carpal tunnel syndrome (CTS). METHODS: Between July 2018 and June 2019, 66 consecutive patients with 95 imaged wrists underwent wrist ultrasound, including grayscale ultrasound, strain elastography, and SWE, because of the suspicion of CTS. During wrist ultrasound, the cross-sectional area (CSA), strain ratio, elasticity, and shear wave velocity of each median nerve were measured at the proximal carpal bone level (scaphoid to pisiform). The variables were compared between the normal and CTS groups by using the independent t test, and subgroup analyses were performed using one-way analysis of variance. Receiver operating characteristic (ROC) curves were used to evaluate the diagnostic performance of each variable. RESULTS: CSA, elasticity, and shear wave velocity showed significant intergroup differences (P < 0.001, P < 0.001, and P = 0.002, respectively). However, the strain ratio showed no statistically significant intergroup difference (P = 0.639). In the subgroup analyses, elasticity showed significantly higher values in the severe group than in the mild and moderate groups (P < 0.001 and P = 0.001, respectively). Other parameters showed no significant differences among the different subgroups. The areas under the ROC curve were 0.823 for CSA, 0.772 for elasticity, and 0.779 for shear wave velocity. The differences in the areas under the ROC curve among CSA, elasticity, and shear wave velocity were not statistically significant (all P > 0.05). CONCLUSIONS: SWE has a good diagnostic value in CTS. In particular, elasticity can discriminate the severe group from the other groups.

Characteristics of Perfusion Computed Tomography Imaging in Patients with Seizures Mimicking Acute Stroke.

INTRODUCTION: Seizures as acute stroke mimics are a diagnostic challenge. OBJECTIVE: The aim of the study was to characterize the perfusion patterns on perfusion computed tomography (PCT) in patients with seizures masquerading as acute stroke. METHODS: We conducted a study on patients with acute seizures as stroke mimics. The inclusion criteria for this study were patients (1) initially presenting with stroke-like symptoms but finally diagnosed to have seizures and (2) with PCT performed within 72 h of seizures. The PCT of seizure patients (n = 27) was compared with that of revascularized stroke patients (n = 20) as the control group. RESULTS: Among the 27 patients with seizures as stroke mimics, 70.4% (n = 19) showed characteristic PCT findings compared with the revascularized stroke patients, which were as follows: (1) multi-territorial cortical hyperperfusion {(73.7% [14/19] vs. 0% [0/20], p = 0.002), sensitivity of 73.7%, negative predictive value (NPV) of 80%}, (2) involvement of the ipsilateral thalamus {(57.9% [11/19] vs. 0% [0/20], p = 0.007), sensitivity of 57.9%, NPV of 71.4%}, and (3) reduced perfusion time {(84.2% [16/19] vs. 0% [0/20], p = 0.001), sensitivity of 84.2%, NPV of 87%}. These 3 findings had 100% specificity and positive predictive value in predicting patients with acute seizures in comparison with reperfused stroke patients. Older age was strongly associated with abnormal perfusion changes (p = 0.038), with a mean age of 66.8 ± 14.5 years versus 49.2 ± 27.4 years (in seizure patients with normal perfusion scan). CONCLUSIONS: PCT is a reliable tool to differentiate acute seizures from acute stroke in the emergency setting.

Development of a predictive scale for cardioembolic stroke using extracted thrombi and angiographic findings.

We analyzed the histopathological findings of the clots obtained from patients with acute ischemic stroke by mechanical thrombectomy. We then developed a clinical scoring system for predicting pathogenic causes in patients with undetermined ischemic stroke using these histopathological and the angiographic findings during endovascular treatment. Only cases with the occlusion of the intracranial internal carotid artery or the proximal part of the middle cerebral artery were included in this study. Histopathologic findings of clots were compared and analyzed using the Trial of Org 10,172 in Acute Stroke Treatment (TOAST; large artery atherosclerosis, cardioembolic, and undetermined groups) and angiographic occlusion type (AOT; branching-site occlusion and truncal-type occlusion groups) classification systems. Fifty-two patients had enough clots extracted by mechanical thrombectomy for full histopathologic examination. There was no significant within-group difference in the fraction of components in the thrombi for either the TOAST or AOT system; however, the platelet distribution patterns were different. The large artery atherosclerotic group and truncal-type occlusion group had mostly peripheral patterns, whereas the cardioembolic group, undetermined group and branching-site occlusion group had mostly clustering patterns (p = 0.02 in TOAST classification; p = 0.007 in AOT classification). Patients with scores of 3 or 4 on our new scale had a sensitivity of 93.5% and a specificity of 100% for cardioembolic stroke. The BOCS2 scale, developed using a combination of the TOAST and AOT classification systems, may be helpful as an adjunctive diagnostic tool for identifying cases caused by cardiogenic embolism in patients with undetermined ischemic stroke.