Kang Min Park

A randomized open-label observational study to compare the efficacy and tolerability between topiramate and valproate in juvenile myoclonic epilepsy

Juvenile myoclonic epilepsy (JME) is managed with valproate in most patients; however, valproate is an antiepileptic drug that has relatively severe adverse effects, especially in women. We performed a prospective, open-label, randomized observational study for comparison of efficacy and tolerability between topiramate and valproate in patients with JME. The inclusion criteria were patients with newly diagnosed JME or previously diagnosed JME with a history of a poor response or adverse effects to other antiepileptic drugs. The primary endpoint of this study was percentage of patients who were free of myoclonic seizures for 24 weeks in the two groups. The frequency and severity of adverse effects were also assessed. Sixteen patients were randomized to topiramate and 17 to valproate. In the topiramate arm, 11 of 16 patients (68.9%) completed 24-week maintenance therapy and seven of the 11 (64%) were seizure-free. In the valproate arm, 16 of 17 patients (94.1%) completed 24-week follow-up and nine of 16 (56%) were seizure-free. The difference (64% topiramate versus 56% valproate) did not reach statistical significance in this study group (p = 0.08, Fishers exact test). However, the severity of adverse effects was significantly different. Only 1 of 10 adverse effects from topiramate was ranked moderate-to-severe (10%), in comparison with severe rankings for 10 of 17 adverse effects from valproate (59%) (p = 0.018, Fishers exact test). In summary, the efficacy of topiramate and valproate was not different, but the severity of adverse effects was favourable for topiramate. Our findings suggest that valproate may be replaced with topiramate, especially for the patients with JME who do not tolerate valproate.

Pre-existing structural abnormalities of the limbic system in transient global amnesia

This study aimed to investigate the clinical and radiological findings in patients with transient global amnesia and to evaluate structural abnormalities using voxel-based morphometry. The subjects were diagnosed with transient global amnesia. For the voxel-based morphometry analyses, Statistical Parametric Mapping, running on the MATLAB platform (MathWorks, Natick, MA, USA), was employed to analyze the structural differences between patients with transient global amnesia and control subjects. Eighty patients met the inclusion criteria. Twenty-three patients (29%) were men, and 57 patients (71%) were women. There were significantly more women among the transient global amnesia patients compared with the general Korean population. MRI revealed hippocampal cavities in 41 patients (51%), and the incidence of such cavities was significantly different from that of the control subjects (24%). There were no differences in the clinical factors between the patients with and without hippocampal cavities. Diffusion-weighted imaging was performed in 54 patients, and 13 patients (24%) exhibited high signal intensity in the hippocampus. There were also no differences in the clinical factors between the patients with and without high signal intensities in the hippocampus on diffusion-weighted imaging. Twenty-six patients underwent three-dimensional volumetric T1-weighted imaging that produced results suitable for voxel-based morphometry, and these patients presented with gray matter volume reductions in the hippocampus, cingulum, and cerebellum. There were significant structural differences in the limbic structures between patients with transient global amnesia and the control subjects that might have contributed to vulnerability of the memory pathways of the patients with transient global amnesia.

Initial response to antiepileptic drugs in patients with newly diagnosed epilepsy

This study aimed to identify factors predicting the response to antiepileptic drugs in patients with newly diagnosed epilepsy. We prospectively studied 176 patients with newly diagnosed epilepsy. Patients were included if they had a history of two or more clinically definite unprovoked seizures, or had a definite epileptic focus on MRI or epileptiform discharges on electroencephalography if they had suffered only one seizure. The primary endpoint was seizure freedom during the initial 6 months of antiepileptic drug treatment. The secondary endpoint was the time to the first seizure during the maintenance period of antiepileptic drug treatment. A total of 100 patients were included, and seizure freedom for 6 months was achieved in 73 patients. The response to antiepileptic drugs was significantly lower in patients with early age at seizure onset (⩽ 16 versus >16 years old, odds ratio=4; 95% confidence interval [CI] 1.5-12.9; relative risk=1.4; 95% CI 1.1-1.8). In addition, the time to the first seizure during the maintenance period was significantly earlier in patients with age at seizure onset ⩽ 16 years compared with those with age at seizure onset >16 years on the Kaplan-Meier survival analysis (p=0.011). Early age at seizure onset is an important factor influencing the response to antiepileptic drugs in patients with newly diagnosed epilepsy.

The usefulness of terminal latency index of median nerve and f-wave difference between median and ulnar nerves in assessing the severity of carpal tunnel syndrome.

Summary: The calculated electrophysiological parameters, such as terminal latency index (TLI), residual latency, modified F ratio, and F-wave inversion, have been investigated as a diagnostic tool for detection of early stage of carpal tunnel syndrome (CTS) in the literature. However, the correlation of these calculated electrophysiological parameters with the clinical severity of CTS has not been reported. The aim of this study was to determine the correlation of the calculated electrophysiological parameters and clinical severity in patients with CTS. A retrospective study was performed with 212 hands of 106 CTS patients. The CTS hands were classified as asymptomatic, mild, moderate, and severe according to the clinical severity. The distal motor latency and distal motor conduction velocity of median nerve, minimal F-wave latency of median and ulnar nerves, and sensory nerve conduction velocity in the finger–wrist and palm–wrist segment of median nerve (SNCV f-w and SNCV p-w) were obtained in a conventional nerve conduction study. The TLI, residual latency, and modified F ratio of the median nerve and the difference of minimal F-wave latencies between the median and ulnar nerves (F-diff M-U) were calculated. The distal motor latency, residual latency, and F-diff M-U were significantly increased according to the clinical severity of CTS. The motor conduction velocity, SNCV p-w, SNCV f-w, TLI, and modified F ratio were significantly decreased according to the clinical severity of CTS. In analyses of variance and Kruskal–Wallis test, we used the Scheffe test as a post-hoc comparison analysis. The TLI, F-diff M-U, and SNCV f-w showed a significant difference among all groups of each CTS severity. The sensitivity, specificity, and cut-off value of TLI, F-diff M-U, and SNCV f-w between asymptomatic and mild, mild and moderate, and moderate and severe CTS groups were calculated by using receiver operating characteristic curve analysis. The cut-off values of TLI, F-diff M-U, and SNCV f-w between the asymptomatic and mild CTS groups were, respectively, 0.33 millisecond, 0.3 millisecond, and 40 cm/second. The cut-off values of TLI, F-diff M-U, and SNCV f-w between mild and moderate were, respectively, 0.27 millisecond, 2.3 milliseconds, and 34.8 cm/second. The cut-off values of TLI, F-diff M-U, and SNCV f-w between moderate and severe CTS groups were, respectively, 0.20 millisecond, 4.2 milliseconds, and 26.4 cm/second. We found that calculated electrophysiological parameters of conventional nerve conduction study could be a good indicator to determine the severity of CTS.

Prolonged Corrected QT Interval in Patients with Myotonic Dystrophy Type 1.

Background and Purpose Sudden cardiac death is one of the leading causes of death in patients with myotonic dystrophy type 1 (DM1). It has been proposed that a prolonged QT interval is associated with sudden cardiac death in several neurological diseases, including multiple system atrophy, idiopathic Parkinsons disease, and diabetic autonomic neuropathy. However, analyses of the corrected QT (QTc) interval in DM1 patients are rare in the literature. The purposes of this study were to determine the association between the QT interval and DM1, and the affecting factors. Methods Thirty-nine patients diagnosed with DM1 through genetic testing were enrolled. The QTc interval (calculated using Bazetts formula: QTc=QT/√RR) was compared between these patients and 39 normal healthy controls. The clinical and laboratory factors affecting QTc interval in the patient group were investigated. Results The QTc interval was significantly longer in the DM1 group (411.2±44.7 msec, mean±SD) than in the normal control group (355.6±20.6 msec). Intragroup analysis revealed that a prolonged QTc interval in DM1 patients was associated with being female and older, having a longer disease duration, and exhibiting abnormal electrocardiography findings. Conclusions The higher incidence of sudden cardiac death in the DM1 population is associated with the observed prolonged QTc interval in those patients.

Clinical Significance of Fluid-Attenuated Inversion Recovery Vascular Hyperintensities in Borderzone Infarcts.

Background and Purpose— Fluid-attenuated inversion recovery vascular hyperintensities (FVHs) are seen in some cases with cerebral hemodynamic impairment and collateral flow. Because the worst outcomes of patients with borderzone infarcts were mainly correlated with impaired hemodynamics, the presence of FVH might provide another clue for predicting the prognosis of patients with borderzone infarcts. Methods— We reviewed 1377 consecutive patients with ischemic stroke. Cortical borderzone (CBZ) and internal borderzone infarcts were selected based on diffusion-weighted imaging. FVHs were defined as tubular- or serpentine-shaped hyperintensities in the subarachnoid space. We investigated the clinical significance of FVHs in borderzone-infarcted patients. Results— Among 87 patients with borderzone infarcts, the presence of FVH was observed in 30 (34.5%). We identified 62 patients with CBZ infarcts and 25 patients with internal borderzone infarcts. In the cases with CBZ infarcts, the initial National Institutes of Health Stroke Scale scores and the portions of nonfavorable outcome at 3 months in the FVH(+) group were significantly higher than in the FVH(−) group (P<0.05 and P<0.001, respectively). Unlike the cases with CBZ infarcts, there were no significant differences of these clinical features between the FVH(+) group and the FVH(−) group in the patients with internal borderzone infarcts. Conclusions— The findings of FVH are associated with relatively severe clinical presentation and nonfavorable prognosis in patients with CBZ infarcts, but not in patients with internal borderzone infarcts. The presence of FVH may help to identify CBZ-infarcted patients who require close observation and hemodynamic control.

Searching the Footprints of Pioneers on Neurology: A Bibliometric Analysis

Background: We identify the most cited articles that have influenced the clinical practices of neurologists. Methods: We first analyzed the top 100 cited articles published in 50 neurology journals with high impact factors. We collected all of the original articles on clinical neurology published in all 554 medical journals. The Institute for Scientific Information Web of Science search tools were used to identify the top 100 cited articles in the database of Journal Citation Reports since 1950, which were then manually reviewed to discover their contents. Results: In the first part of analysis, the top 100 cited articles were all published in 17 journals, with 26 articles published in Neurology. The most frequent topic subject of neurodegeneration appeared in 40 articles. The second part of the analysis revealed that the top 100 cited articles were also all published in 17 journals, with 30 articles published in New England Journal of Medicine. In contrast to the first part of the analysis, stroke was the most frequent topic subject (in 38 articles). Conclusions: Our bibliometric analysis has yielded 2 detailed lists of the top 100 cited articles that were listed separately using different methods. This approach can provide information about the trends and academic achievements in the field of clinical neurology.

Modification of electrophysiological activity pattern after anterior thalamic deep brain stimulation for intractable epilepsy: report of 3 cases.

OBJECTIVE Thalamic stimulation can provoke electroencephalography (EEG) synchronization or desynchronization, which can help to reduce the occurrence of seizures in intractable epilepsy, though the underlying mechanism is not fully understood. Therefore, the authors investigated changes in EEG electrical activity to better understand the seizure-reducing effects of deep brain stimulation (DBS) in patients with intractable epilepsy. METHODS Electrical activation patterns in the epileptogenic brains of 3 patients were analyzed using classical low-resolution electromagnetic tomography analysis recursively applied (CLARA). Electrical activity recorded during thalamic stimulation was compared with that recorded during the preoperative and postoperative off-stimulation states in patients who underwent anterior thalamic nucleus DBS for intractable epilepsy. RESULTS Interictal EEG was fully synchronized to the β frequency in the postoperative on-stimulation period. The CLARA showed that electrical activity during preoperative and postoperative off-stimulation states was localized in cortical and subcortical areas, including the insular, middle frontal, mesial temporal, and precentral areas. No electrical activity was localized in deep nucleus structures. However, with CLARA, electrical activity in the postoperative on-stimulation period was localized in the anterior cingulate area, basal ganglia, and midbrain. CONCLUSIONS Anterior thalamic stimulation could spread electrical current to the underlying neuronal networks that connect with the thalamus, which functions as a cortical pacemaker. Consequently, the thalamus could modify electrical activity within these neuronal networks and influence cortical EEG activity by inducing neuronal synchronization between the thalamus and cortical structures.

Cerebellar white matter changes in patients with newly diagnosed partial epilepsy of unknown etiology

OBJECTIVE We hypothesize that pre-existing susceptible structures in the brain may be associated with the development of newly diagnosed partial epilepsy of unknown etiology. METHODS Twenty-two patients with newly diagnosed partial epilepsy of unknown etiology and 36 healthy controls were enrolled in this study. In addition, we included 24 patients with chronic partial epilepsy of unknown etiology as a disease control group. We analyzed whole-brain T1-weighted MRIs using FreeSurfer 5.1. The volumes of the hippocampus, amygdala, thalamus, caudate, putamen, pallidum, brainstem, cerebellar gray and white matter, as well as cerebral gray and white matter were compared between the groups. We also analyzed the changes in brain volumes associated with the chronicity of epilepsy in the patients with chronic epilepsy compared to newly diagnosed epilepsy. RESULTS The volume of cerebellar white matter in patients with newly diagnosed epilepsy was significantly smaller than that which was observed in the healthy controls (p=0.0001). This finding was also observed in patients with chronic epilepsy (p<0.0001). Cerebral white matter volume was negatively correlated with the duration of epilepsy (r=-0.4, p=0.04). CONCLUSION These findings support our hypothesis that cerebellar white matter changes may constitute a pre-existing susceptible structure in the brain that is associated with the development of partial epilepsy of unknown etiology. In addition, cerebral white matter was the structure that was the most vulnerable to the progression of epilepsy.

Response to antiepileptic drugs in partial epilepsy with structural lesions on MRI.

OBJECTIVE Although partial epilepsy with structural lesions on MRI (lesional epilepsy) is less favorably responsive to antiepileptics than those without structural lesions on MRI, the response to antiepileptics in lesional epilepsy is a heterogeneous condition. There is growing evidence that the extent of epileptic network beyond the visible lesion on MRI may be related with the response to antiepileptics. The aims of this study are to clarify whether (1) the epilepsy network beyond the visible lesion on MRI, or (2) duration of lesional epilepsy on MRI are related with the response to antiepileptics or not. METHODS The inclusion criteria for this study were (1) having structural lesions on MRI, (2) taking antiepileptics for at least 1 year, and (3) age ≥13 years old. The definition for drug-resistance epilepsy was a failure of adequate trials of two tolerated, appropriately chosen and used antiepileptics to achieve sustained seizure freedom. The duration was defined as the interval between the start of antiepileptics and the last follow-up. We defined the lesion-plus group as the structural lesions on MRI that has wider spread of epileptic network beyond the visible lesions on MRI, such as hippocampal sclerosis and malformation of cortical development. Lesion-restriction group was defined as the epileptic network being believed to be limited on the structural lesions. RESULTS We found 234 patients with lesional epilepsy, who met the inclusion criteria. Of these 234 patients, 115 patients were male (49%) and 119 patients were female (51%). The median age was 22 years old (range 13-78 years old) and the median duration was 131 months (range 12-516 months). Forty percent (90/234 patients) were intractable to antiepileptics. Of the structural lesions on MRI, hippocampal sclerosis was most frequent (N=90). Other structural lesions were malformation of cortical development (N=38), cerebromalatic lesions related with trauma (N=34), tumor (N=19), cystic lesion (N=15), cerebral infarction (N=11), vascular malformation (N=10), and other miscellaneous lesion (N=24). Lesion-plus group had significantly higher drug-resistance epilepsy than cystic lesions on MRI (60/128 vs. 2/15, p=0.013 by Fishers exact test). There was a tendency of having more drug-resistance epilepsy in the lesion-plus group than the lesion-restriction group (56/121 vs. 30/89, p=0.09 by Chi-square test). The median duration in drug-resistance epilepsy was significantly longer than that of medically controlled epilepsy (178 months (range 23-516 months) vs 102 months (range 12-479 months), p<0.0001 by Mann-Whitney test). In addition, duration was only the significant variable associated with drug-resistance epilepsy in lesional epilepsy by multiple logistic regression analysis (p=0.02 for overall model fit). CONCLUSION In lesional epilepsy, hippocampal sclerosis and malformation of cortical development are more intractable to antiepileptics, reflecting wider epileptic network beyond the visible lesion. In addition, the response to antiepileptics may be expected to decrease when the duration is prolonged.