Cerebral Cavernous Malformation (CCM)-like Vessel Lesion in the Aged ANKS1A-deficient Brain

In this study, we show that ANKS1A is specifically expressed in the brain endothelial cells of adult mice. ANKS1A deficiency in adult mice does not affect the differentiation, growth, or patterning of the cerebrovascular system; however, its absence significantly impacts the cerebrovascular system of the aged brain. In aged ANKS1A knock-out (KO) brains, vessel lesions exhibiting cerebral cavernous malformations (CCMs) are observed.In addition, CCM-like lesions show localized peripheral blood leakage into the brain. The CCM-like lesions reveal immune cells infiltrating the parenchyma. The CCM-like lesions also contain significantly fewer astrocyte endfeets and tight junctions, indicating that the integrity of the BBB has been partially compromised. CCM-like lesions display increased fibronectin expression in blood vessels, which is also confirmed in cultured endothelial cells deficient for ANKS1A. Therefore, we hypothesize that ANKS1A may play a role in maintaining or stabilizing healthy blood vessels in the brain during aging.

Central Nervous System Infection-Related Isolated Hippocampal Atrophy as Another Subtype of Medial Temporal Lobe Epilepsy with Hippocampal Atrophy:A Comparison to Conventional Medial Temporal Lobe Epilepsy with Hippocampal Atrophy

Background@#and Purpose: Hippocampal atrophy (HA) resulting from a central nervous system (CNS) infection might be a relevant lesion responsible for the clinical characteristics of medial temporal lobe epilepsy. @*Methods@#The clinical characteristics of 54 patients with CNS infection-related medial temporal lobe epilepsy (MTLE) with isolated HA (CNS infection group) and 155 patients with conventional MTLE with HA (conventional group) were compared retrospectively. CNS infection alone and bilateral involvement of the HA were analyzed as prognostic factors, in addition to the detailed clinical characteristics, such as limbic aura and the presence and proportion of each type of automatism, between the two groups, and both medical and surgical prognoses were separately considered. A logistic regression analysis was performed. @*Results@#A statistical analysis including all clinical factors, including CNS infection with bilateral HA, did not reveal significant differences between the two groups. An analysis comparing the prognosis of the two groups based on good or poor prognosis among patients who received medical treatment and good or poor outcomes among patients who received surgical treatment did not produce significant differences. @*Conclusions@#In addition to bilateral HA, CNS infection alone was not a poor prognostic factor for the CNS infection-related epilepsy with HA group compared with the conventional MTLE with HA group. Based on these negative results, HA is a plausible and relevant lesion with similar clinical characteristics to HA in patients with conventional MTLE. Therefore, CNS infection-related MTLE with isolated HA might represent another subtype of MTLE with HA with a different etiology.

Outcomes of Augmented Surgery Performed after Simplified Prism Adaptation Testing in Patients with Intermittent Exotropia

PURPOSE@#We explored whether the deviation angle in patients with intermittent exotropia was greater when the prism adaptation test was used rather than the prism cover test.@*METHODS@#From January 2013 to December 2017, we performed the prism cover and adaptation tests on patients with intermittent exotropia. If the deviation angle increased by more than 5 PD after the prism adaptation test, surgery was performed. The outcomes of patients followed-up for more than 1 year after surgery were analyzed retrospectively.@*RESULTS@#In total, 76 of 100 patients (76.0%) exhibited deviation angle increases of over 5 PD, the mean increase was 9.8 ± 6.3 prism diopters (PD) for near vision and 3.6 ± 3.5 PD for distance vision. Satisfactory motor alignment was achieved in 57 patients; 42 were undercorrected and 1 was overcorrected. The success rate was 62.5% in the non-responder group (n = 24, patients in whom the deviation angle did not increase after prism adaptation) and 68.9% in the full augmentation group (n = 45, in whom the deviation angle was increased). In the partial augmentation group (n = 31), where the surgical target was a 50% increase in the deviation angle, the success rate was lower than in the other groups.@*CONCLUSIONS@#The preoperative prism adaptation test can be used to determine the angle of deviation and improves the surgical outcomes of patients with intermittent exotropia.

Estimation of the size of the iatrogenic Creutzfeldt-Jakob disease outbreak associated with cadaveric dura mater grafts in Korea / 한국역학회지

OBJECTIVES: This study estimated the overall incidence of iatrogenic Creutzfeldt-Jakob disease (iCJD) based on dura graft cases in Korea using a mathematical model. METHODS: We estimated the number of annual dura grafts performed between 1980 and 1995 by applying the proportion of dura grafts recorded by the Health Insurance Review Agency claim dataset in Korea to the number of nationwide neurosurgery cases. The distribution of the incubation period was assumed to fall under a Weibull distribution with density function or a log-logistic distribution with density function. RESULTS: The total number of neurosurgery procedures performed from 1980 to 1995 was estimated to be 263,945, and among those operations, 37% used dura graft products. Between the years of 1980 and 2020, our model predicted that the total number of iCJD cases would be between 14.9 and 33.2 (95% confidence interval [CI], 13.4 to 50.9). Notably, we estimated that the cumulative number of iCJD cases caused by dura grafts between 1980 and 2011 was approximately 13.3 to 27.3 (95% CI, 12.2 to 40.6). CONCLUSIONS: Based on our model, we postulate that the incidence of iCJD will sharply decline from 2012 to 2020. However, additional new cases are still expected, which necessitates a strong national surveillance system.

Brain-Region Specific Apoptosis Triggered by Eph/ephrin Signaling

Eph receptors and their ligands, ephrins, are abundantly expressed in neuroepithelial cells of the early embryonic brain. Overstimulation of Eph signaling in vivo increases apoptotic cell death of neuroepithelial cells, whereas null mutation of the Eph gene leads to the development of a larger brain during embryogenesis. Thus, it appears that Eph-ephrin signaling plays a role in regulating apoptotic cell death of neuroepithelial cells, thereby influencing brain size during embryonic development. Interestingly, Eph-ephrin signaling is bi-directional, with forward signaling from ephrin- to Eph-expressing cells and reverse signaling from Eph- to ephrin-expressing cells. However, it is not clear whether this forward or reverse signaling plays a role in regulating the size of the neuroepithelial cell population during early brain development. Also, Eph receptors and their corresponding ligands are mutually exclusive in their expression domains, and they encounter each other only at interfaces between their expression domains. This expression pattern may be a critical mechanism for preventing overstimulation of Eph-ephrin signaling. Nevertheless, Eph receptors are co-expressed with their corresponding ligands in certain brain regions. Recently, two studies demonstrated that brain region-specific apoptosis may be triggered by the overlapping expression of Eph and ephrin, a theme that will be explored in this mini-review.

Ectopic Expression of Ephrin-A5 Under the EphA8 Promoter at the Anterior Region of the Superior Colliculus

EphA/ephrin-A mediated signaling has emerged as a key mechanism regulating axon guidance and topographic mapping, particularly in the well-characterized visual system from the retina to the superior colliculus (SC). In this study, EphA8 bacterial artificial chromosome (BAC) was manipulated to contain a floxed eGFP and human ephrin-A5 expression cassette using homologous recombination method. In the mice containing the recombinant BAC, it was shown that GFP is expressed in an anterior>posterior gradient in the SC. Furthermore, when these mice were crossed with the transgenic mice expressing Cre under the EphA8 promoter, it was evident that a GFP expression cassette was eliminated, and that human ephrin-A5 was ectopically expressed in the anterior region of the SC. This transgenic model would be useful to analyze the role of ephrin-A5 in the SC during the retinocollicular topography formation.

Thrombosis of the Superior Sagittal Sinus in Behcet's Disease With Vascular and Enteric Involvements

We report superior sagittal sinus thrombosis as a central nervous system presentation of Behcet's disease in a patient with peripheral vascular and enteric involvement. The main symptoms were headache and horizontal diplopia due to intracranial hypertension. T1-weighted MRI with gadolinium enhancement revealed a similar pattern of the "empty delta sign" that is usually seen on brain CT. A magnetic resonance venogram revealed filling defects resulting from the thrombosis. These features are helpful for the noninvasive diagnosis of sagittal sinus thrombosis.

Ictal Focus on the Bialateral Claustrum in a Case of Insular Seizure Manifesting as Status Epilepticus

Insular lobe seizure (ILS) is very rare and ictal focus has not been documented by neuroimaging studies. Clinical characteristics consist of clearly preserved consciousness, visceral sensation, somatomotor symptoms, and dysphonic or dysarthric speech. We report a 34-year-old female with ILS, manifesting as first onset status epilepticus. SISCOM and SPM analysis through brain MRI and 18F FDG PET-CT reveals ictal focus on the bilateral claustrum, which has a close relationship with insula anatomically. This is the first case report in Korea.

Two Cases of Generalized Nonconvulsive Status Epilepticus with Eyelid Myoclonia with Absence

Eyelid myoclonia with absence is a distinct syndrome of idiopathic generalized epilepsy, characterized by the triad of eyelid myoclonia associated with brief absences, generalized discharges of 3-6 Hz polyspike and slow waves, which are mainly precipitated by eye closure or photosensitivity. We experienced two women with eyelid myoclonia with absence, who typically showed fixation off sensitivity and catatmenial exacerbation. Carabamazepine monotherapy aggravated the seizure frequency and resulted in nonconvulsive status epilepticus. These cases have not previously been reported in Korea.

A Case of Voltage Gated Potassium Channel Antibodies-associated Nonparaneoplastic Limbic Encephalitis

Limbic encephalitis has been reported usually as an autoimmune complication related to onconeuronal antigen of underlying cancer with poor prognosis. Antibodies reactive with neuronal voltage-gated potassium channels (VGKCs) are recently recognized as a pathogenic cause in nonparaneoplastic limbic encephalitis, which is responsive to immunotherapy. We report a patient who had subacute encephalopathy with clinical and radiographic evidences of limbic encephalitis. The patient was seropositive for VGKC antibodies and resulted in a good prognosis with steroids. This has not yet been reported in Korea.

Over-expression of EphrinA2 in the Anterior Region of the Developing Mouse Midbrain and Diencephalon / 대한해부학회지

The Eph family is thought to exert its function through the complementary expression of receptors and ligands. The dorsal mesencephalon appears to be segmented into two broad regions demarcated by the mutually exclusive expression of EphA receptors and ephrinA ligands. In this study, we analyzed transgenic embryos expressing ephrinA2 in the anterior region of the developing midbrain where the EphA8 receptor is expressed. First, 1% of transgenic embryos showed cephalic neural tube closure defects. Second, it was confirmed that mis-expression of ephrin-A2 in the anterior mesencephalon induced an increase in the EphA8 tyrosine kinase activity. Accordingly, an increased MAPK activity was also detected in the anterior mesencephalon of E14.5 transgenic embryo. Third, cell adhesion assay revealed that mis-expression of ephrinA2 promoted cell attachment to fibronectin. Taken together, these findings suggest that co-expression of EphA receptors and ephrinA ligands significantly alter cell behaviors including cell adhesion.

Imaging Evidence of Basal Ganglia Pathology in Hemi choreoballistic Movement of the Patient with Nonketotic Hyperglycemia: Case Report with Serial Follow Up of Neuroimages

The mechanism of chorea underlying nonketotic hyperglycemia was controversial. Serial follow up of brain MRI, 99mTc-ECD SPECT, and 18F-FDG PET in conjunction with clinical observation was done to clarify the pathologic localization. From the functional neuroimages, according to the clinical improvement, the relevant pathology was localized on the lentiform nucleus, mainly on the putamen. In caudate, the mismatch between glucose metabolism and blood flow was observed during and after choreoballistic movement which suggested an important cue to understand the pathogenesis of chorea.

A Case of Eosinophilic Meningitis Associated with Idiopathic Hypereosinophilic Syndrome

Idiopathic hypereosinophilic syndrome (IHES) is a rare disease characterized by peripheral blood eosinophilia and eosinophilic infiltration of multiple organs, including the nervous system. The neurologic manifestations in hypereosinophilic syndrome are variable, but eosinophilic meningitis as a manifestation has not been well documented in IHES. We report a case of eosinophilic meningitis associated with IHES, which showed a good response to steroid treatment.

A Case of Orgasmic Aura Associated with Temporal Lobe Epilepsy from the Nondominant Hemisphere

We experienced a patient with an orgasmic aura originating from the right mesial temporal structure. A 36-year-old right-handed woman suffered from a specific sensation of sexual arousal and orgasm-like euphoria lasting 1~2 minutes for several years. Video EEG monitoring ascertained those sensations as epileptic in nature arising from the right mesial temporal area through a foramen ovale electrode. The findings of 99mTc-ECD-SPECT and 18F-FDG PET were concordant with those of the brain MRI which was pathologically consistent with hippocampal sclerosis.

18F-FDG PET and 99mTc-ECD SPECT between Ictal and Interictal Phase in a Patient with Status Epilepticus Arising from the Occipital Lobe

A 35-year-old woman suffered from elementary visual symptom that was confirmed as nonconvulsive simple partial status epilepticus arising from the right occipital lobe. 99mTc-ECD SPECT and 18F-FDG PET were done during the ictal and interictal phase, respectively, which were documented by EEG. Subtraction images of SPECT and PET were overlayed on the MRI by SISCOM to compare the area of metabolic change with that of perfusion change. There was no definite mismatch between the hypermetabolic area and the hyperperfusion area during nonconvulsive status epilepticus.

In vivo Mapping of the Cis-acting Element Responsible for Spatial Regulation of the EphA8 Gene Expression in Mesencephalon / 대한해부학회지

This study was aimed to map the 1 kb cis-acting DNA of ephA8 gene, which regulates the spatial and temporal expression in the anterior mesencephalon. It was demonstrated that the 1 kb ephA8 enhancer DNA was sufficient to drive the lacZ expression to the anterior mesencephalon under the human beta-globin minimal promoter. It was also found that a 180 bp within the 1 kb enhancer DNA was highly conserved between human and mouse, and that this 180 bp DNA was capable of inducing the lacZ expression in the anterior mesencephalon under the ephA8 or human beta-globin basal promoter. Further analysis using 5'-55 bp deleted or 3'-55 bp deleted mutant DNA revealed that the 55 bp portion present at the 3'-end of 180 bp DNA was critical for the regulation of ephA8 gene expression in the anterior mesencephalon. Taken together, these results indicate that 180 bp ephA8 enhancer DNA contains cisacting elements for the regulation of ephA8 gene expression in the anterior mesencephalon.

A Case of Pure Autonomic Seizure Presenting as Sinus Tachycardia

Tachycardia rarely consists of an ictal symptomatology associated with autonomic symptoms such as sialorrhea, even if it commonly precedes or combines with a limbic aura of complex partial seizure. A 14-year-old boy with recurrent palpitation, chest discomfort, and sialorrhea suffered from a pure autonomic seizure presenting as sinus tachycardia with a neural origin, which had been misdiagnosed as paroxysmal supraventricular tachycardia without improvement by cardiac medication. The right mesial temporal origin was revealed by video CCTV-EEG with the profile of the heart rate during ictus.

A Case of Probable Creutzfeldt-Jakob Disease with Coexistence of the Features of Hashimoto Encephalopathy

Hashimoto encephalopathy shares common clinical features with Creutzfeldt-Jakob disease and must be regarded as a differential diagnosis because of its good prognosis. We report a case of Hashimoto encephalopathy, which had not been recognized before the diagnosis of Creutzfeldt-Jakob disease. The electroclinical findings were compatible with probable Creutzfeldt-Jakob disease and coexistence of Hashimoto thyroiditis was supported by high titers of anti-thyroid microsomal antibody and cytopathologic findings. Hashimoto encephalopathy was not improved, which was most likely due to the coexistence of Creutzfeldt-Jakob disease.

Ictal Nystagmus by Epileptic Activation of Cortical Smooth Pursuit System: Electrophysiological and Neuroimaging Study

BACKGROUND: Epileptic nystagmus is rare. There is no report in Korea about epileptic nystagmus by the activation of cortical smooth pursuit area. We studied a 29-year-male patient with nonconvulsive simple partial status epilepticus presenting as pure ictal nystagmus. METHODS: The EEG including electrooculogram and electronystagmogram during ictus was done. Brain MRI including (99m)Tc-ECD SPECT and 18F-FDG PET were also done during ictus and repeated after complete relief from symptom. Subtraction images obtained from each of SPECT and PET were coregistrated onto MRI. Humphrey visual field test was done for documentation of visual field defect. RESULTS: EEG was compatible with nonconvulsive status epilepticus arising from right mesial occipital area with 9-10 Hz frequency. Compensatory left beating nystagmus with midline crossing feature was noted and characteristic ipsiversive linear slow phase was presented in electronystagmogram. Brain neuroimages from MRI, (99m)Tc-ECD SPECT, and 18F-FDG PET revealed that the right parietotemporooccipital area was relevant area, but the right frontal eye field area was spared, which was much clear in SISCOM image. CONCLUSIONS: Clinical feature and electronystagmogram in this case showed typical epileptic nystagmus by activation of cortical smooth pursuit regions in which the relevant regions was posterior parietotemporooccipital area. The sparing of the frontal eye field area in this case suggested clearly that the epileptic nystagmus by the activation of cortical smooth pursuit regions could occur without involvement of frontal eye field area.

Chorea Following Acute Carbon Monoxide Poisoning

The clinical cases of 6 patients suffering with chorea after acute carbon monoxide (CO) poisoning were reviewed. There were 2 men and 4 women, and the age at onset ranged from 11 to 60 (mean 33.0) years. All the patients except one were associated with mild delayed CO encephalopathy. The latency period between CO poisoning and the onset of chorea was 10 to 30 (mean 21.7) days. The duration of chorea after CO poisoning was 14 to 90 (mean 39.8) days. The brain CT findings were bilateral low- density lesions in the basal ganglia and/or in the white matter of the cerebral cortex, and there was no correlation between the lesion sites on the imagings and the development of chorea. Neuroleptic agents alleviated the chorea and the patients did not relapse after neuroleptic agents were halted.