KCNJ3 is a novel candidate gene for autosomal dominant pure hereditary spastic paraplegia identified using whole genome sequencing.

Hereditary spastic paraplegia (HSP) is a group of familial diseases characterized by progressive corticospinal tract degeneration. Clinically, patients present with lower-limb spasticity and weakness. To date, more than 80 genetic HSP types have been identified. Despite advances in molecular genetics, novel HSP gene discoveries are ongoing, with a low genetic diagnostic yield. In this study, we aimed to determine pathogenic variants in a family with HSP, which was not diagnosed through conventional genetic testing. We clinically characterized a large family and conducted whole genome sequencing (WGS) analysis of four affected and three unaffected individuals in the family to identify the genetic cause of HSP. This family had autosomal dominant pure (uncomplicated) late childhood-onset HSP. The patients' symptoms accelerated between the ages of 20 and 30. Brain magnetic resonance images typically showed white matter changes, a thin corpus callosum, and cerebellar atrophy. We identified a heterozygous missense variant, KCNJ3 c.1297T>G (p.Leu433Val), through WGS and family genetic analysis, confirmed by Sanger sequencing. We suggest that the identification of KCNJ3 c.1297T>G (p.Leu433Val) constitutes the discovery of a potential novel gene responsible for HSP in this family. This is the first study to report the possible role of a KCNJ3 variant in HSP pathogenesis. Our findings further expand the phenotypic and genotypic spectrum of HSP.

Herpes simplex encephalitis initially presenting without fever or cerebrospinal fluid pleocytosis and with typical neuroimaging findings: a case report.

Herpes simplex encephalitis (HSE) is a common viral encephalitis that can be fatal if not adequately treated. Fever, cerebrospinal fluid (CSF) pleocytosis, and typical neuroimaging findings are commonly observed in HSE cases. We encountered a patient with HSE who did not exhibit these classic clinical features. A 63-year-old male presented with his first-ever seizure. Fever did not develop until the fourth day of admission, and neither neuroimaging nor CSF analysis revealed abnormalities. Under suspicion of autoimmune encephalitis, methylprednisolone was administered. Subsequently, when the patient developed fever, a follow-up neuroimaging study was performed and revealed abnormalities consistent with HSE. The patient was promptly treated with acyclovir, which led to a full recovery. Diagnosing HSE in patients who present without fever or CSF pleocytosis and with typical neuroimaging findings poses a challenge. Therefore, prior to initiating immunosuppressive treatment, it is crucial to closely observe patients and to conduct follow-up tests, including neuroimaging and CSF analysis.

A Survey of Perspectives on Telemedicine for Patients With Parkinson's Disease.

OBJECTIVE: Parkinson's disease (PD) patients often find it difficult to visit hospitals because of motor symptoms, distance to the hospital, or the absence of caregivers. Telemedicine is one way to solve this problem. METHODS: We surveyed 554 PD patients from eight university hospitals in Korea. The questionnaire consisted of the clinical characteristics of the participants, possible teleconferencing. METHODS: , and preferences for telemedicine. RESULTS: A total of 385 patients (70%) expressed interest in receiving telemedicine. Among them, 174 preferred telemedicine whereas 211 preferred in-person visits. The longer the duration of disease, and the longer the time required to visit the hospital, the more patients were interested in receiving telemedicine. CONCLUSION: This is the first study on PD patients' preferences regarding telemedicine in Korea. Although the majority of patients with PD have a positive view of telemedicine, their interest in receiving telemedicine depends on their different circumstances.

Patient with Epilepsy Showing Psychiatric Symptoms after Remission of Seizures and Normalization of Electroencephalography: The Phenomenon of Forced Normalization?

Psychiatric disorders are commonly observed in patients with epilepsy. Among them, the phenomenon known as forced normalization is scarce. Herein, we report the case of a 41-year-old patient who showed long-term first-onset psychiatric symptoms after seizure remission and normalization of electroencephalography. After changing the antiepileptic drug regimen and psychiatric treatment, the patient's symptoms regressed. However, the exact pathological mechanisms remain to be elucidated. Changing the regimen of antiepileptic drugs and long-term psychiatric treatment may help control this phenomenon.

A Role of ß2-Adrenoreceptor Agonists Related to the Development of Parkinson's Disease.

Background: Several studies have suggested the potential protective role of ß2-adrenoreceptor agonist (ß2AR-agonist) on the development of Parkinson's disease (PD). However, those could not reflect a different epidemiologic background in eastern countries. We explored ß2AR-agonist's effect on PD development by controlling for smoking. Materials and Methods: We used the Korean national sample cohort data (from 2002 to 2013) containing 1,025,340 participants (2.2% of the whole population). The subjects over 60 years were included. PD was defined based on the ICD-10 code, which should be diagnosed by neurologists. Atypical Parkinsonisms or ataxic disorders were excluded. We made Set 1 (from 2003 to 2007) and Set 2 (from 2003 to 2008) based on the exposure period for the sensitivity analysis. We observed whether PD had developed during the follow-up periods in each subset. Results: The PD (Set 1, n = 742; Set 2, n = 699) and non-PD group (Set 1, n = 57,645; Set 2, n = 66,586) were collected. Old age, Medicaid, and asthma were risk factors, whereas smoking was a significant protective factor for PD development. The proportion of ß2AR-agonist use was significantly higher in the PD group than in the non-PD group (Set 1, 3.6% vs. 2.4%; Set 2, 4.1% vs. 2.6%). ß2AR-agonist use still was a risk factor in developing PD from the multiple logistic regression analysis. Conclusions: ß2-AR-agonist looked like a risk factor rather than a protective factor for PD development. Well-controlled studies reflecting various epidemiologic backgrounds are required to confirm the role of ß2AR-agonist.

Characteristic MR Imaging Features and Serial Changes in Adult-Onset Alexander Disease: A Case Report.

Adult-onset Alexander Disease (AOAD) is a rare genetically determined leukoencephalopathy that presents with ataxia, spastic paraparesis, or brain stem signs including speech abnormalities, swallowing difficulties, and frequent vomiting. The diagnosis of AOAD is frequently proposed based on the findings on MRI. We demonstrate two cases (37-year-old female and 61-year-old female) with characteristic imaging findings and changes in follow-up MRI in patients with AOAD, which were confirmed via glial fibrillary acidic protein (GFAP) mutation analysis. On MRI, the typical tadpole-like brainstem atrophy and periventricular white matter abnormalities were noted. The presumptive diagnoses were made based on the typical MRI appearances and, subsequently, confirmed via GFAP mutation analysis. Follow-up MRI demonstrated the progression of atrophy in the medulla and upper cervical spinal cord. Our report could help raise awareness of characteristic MRI findings of AOAD, thus helping clinicians use GFAP analysis for AOAD diagnosis confirmation.

Diffusion tensor tractography of the corticobulbar tract in a dysphagic patient with progressive supranuclear palsy: A case report.

RATIONALE: This paper reports the changes over time in the corticobulbar tract (CBT) analyzed using diffusion tensor tractography (DTT) in a dysphagic patient with progressive supranuclear palsy (PSP). PATIENT CONCERNS: A 53-year-old man initially presented with dysarthria, gait disturbance, and bradykinesia, and approximately 1-year later, downward gaze paralysis appeared. Initially, there was no dysphagia; however, approximately 2 years after visiting the hospital, symptoms of dysphagia, including difficulty swallowing pills, aspiration, and oral movement impairments appeared. The symptoms gradually progressed, and finally, mouth opening was severely damaged to the extent that it was difficult to orally feed. INTERVENTIONS: We performed diffusion tensor imaging 3 times; at 3-month, 20-month, and 41-month from onset. OUTCOMES: On 3-month DTT, the left CBT was well reconstructed, whereas the right CBT showed partial tearing. In the 20-month DTT, both CBTs became thinner compared to the 3-month DTT. On 41-month DTT, both CBTs became much thinner than after 3-month and 20-month DTT. LESSONS: We observed the degree of CBT injury over time in a dysphagic patient with PSP. These results suggest that the analysis of CBT using DTT is helpful in predicting the degree of dysphagia and prognosis in patients with PSP.

Long Short-Term Memory-Based Deep Learning Models for Screening Parkinson's Disease Using Sequential Diagnostic Codes.

BACKGROUND AND PURPOSE: It is challenging to detect Parkinson's disease (PD) in its early stages, which has prompted researchers to develop techniques based on machine learning methods for detecting PD. However, previous studies did not fully incorporate the slow progression of PD over a long period of time nor consider that its symptoms occur in a time-sequential manner. Contributing to the literature on PD, which has relied heavily on cross-sectional data, this study aimed to develop a method for detecting PD early that can process time-series information using the long short-term memory (LSTM) algorithm. METHODS: We sampled 926 patients with PD and 9,260 subjects without PD using medical-claims data. The LSTM algorithm was tested using diagnostic histories, which contained the diagnostic codes and their respective time information. We compared the prediction power of the 12-month diagnostic codes under two different settings over the 4 years prior to the first PD diagnosis. RESULTS: The model that was trained using the most-recent 12-month diagnostic codes had the best performance, with an accuracy of 94.25%, a sensitivity of 82.91%, and a specificity of 95.26%. The other three models (12-month codes from 2, 3, and 4 years prior) were found to have comparable performances, with accuracies of 92.27%, 91.86%, and 91.81%, respectively. The areas under the curve from our data settings ranged from 0.839 to 0.923. CONCLUSIONS: We explored the possibility that PD specialists could benefit from our proposed machine learning method as an early detection method for PD.

Aphasic Status Epilepticus Associated with Alzheimer's Disease: Clinical and Electrographic Characteristics.

In aphasic status epilepticus (ASE), aphasia is the sole manifestation of seizure in patients with this disorder. Alzheimer's disease (AD) is one of neurological disorders causing ASE. Herein, we report two cases of ASE associated with AD, and discuss their clinical characteristics. Patient 1 presented Broca's aphasia, and patient 2 presented global aphasia during the ictal period. Both patients exhibited atypical ictal electroencephalographic (EEG) patterns, which improved after antiepileptic drug administration. ASE was the presenting symptom of AD in patient 1. ASE can develop at any stage of AD. Alterations in clinical symptoms and EEG patterns after treatment with antiepileptic drug are the key to diagnosis. Prompt diagnosis and treatment are critical for preventing further consciousness dysfunction.

Semiautomated Algorithm for the Diagnosis of Multiple System Atrophy With Predominant Parkinsonism.

OBJECTIVE: Putaminal iron deposition is an important feature that helps differentiate multiple system atrophy with predominant parkinsonism (MSA-p) from Parkinson's disease (PD). Most previous studies used visual inspection or quantitative methods with manual manipulation to perform this differentiation. We investigated the value of a new semiautomated diagnostic algorithm using 3T-MR susceptibility-weighted imaging for MSA-p. METHODS: This study included 26 MSA-p, 68 PD, and 41 normal control (NC) subjects. The algorithm was developed in 2 steps: 1) determine the image containing the remarkable putaminal margin and 2) calculate the phase-shift values, which reflect the iron concentration. The next step was to identify the best differentiating conditions among several combinations. The highest phaseshift value of each subject was used to assess the most effective diagnostic set. RESULTS: The raw phase-shift values were present along the lateral margin of the putamen in each group. It demonstrates an anterior- to-posterior gradient that was identified most frequently in MSA-p. The average of anterior 5 phase shift values were used for normalization. The highest area under the receiver operating characteristic curve (0.874, 80.8% sensitivity, and 86.7% specificity) of MSA-p versus PD was obtained under the combination of 3 or 4 vertical pixels and one dominant side when the normalization methods were applied. In the subanalysis for the MSA-p patients with a longer disease duration, the performance of the algorithm improved. CONCLUSION: This algorithm detected the putaminal lateral margin well, provided insight into the iron distribution of the putaminal rim of MSA-p, and demonstrated good performance in differentiating MSA-p from PD.

Anti-N-Methyl-D-Aspartate Receptor Encephalitis after BNT162b2 COVID-19 Vaccination.

After the coronavirus disease 2019 (COVID-19) pandemic emerged, the development of vaccines was accelerated. Neurologic complications of COVID-19 vaccination had been reported, which included encephalitis. In this study, we report a very rare case of a female with anti-N-methyl-D-aspartate receptor encephalitis associated with ovarian teratoma that would be triggered by BNT162b2 m-RNA COVID-19 vaccination.

Recurrent Altered Mental State Associated with Nonhepatic Hyperammonemia Presented in an Elderly Female Patient: Probable Late-Onset Urea Cycle Disorder.

Altered mentality associated with hyperammonemia is usually diagnosed in patients with liver disease. Nonhepatic hyperammonemia may be present in critically ill patients or may be caused by high protein diets or certain drugs. Urea cycle disorders (UCDs) rarely present with altered mentality with hyperammonemia in adult patients. An 82-year-old female visited our hospital with complaints of abnormal behavior and confusion. Routine blood tests revealed elevated serum ammonia. Her mentality and serum ammonia level normalized after lactulose enema and she was discharged thereafter. However, she was later re-admitted because of recurrent altered mentality. Amino acid analysis revealed that serum levels of ornithine and glutamine increased significantly, whereas the levels of alanine and glutamic acid increased slightly, and the levels of arginine, lysine, and citrulline were normal, which were probably caused by reduced activity of the mitochondrial ornithine carrier-1. Although our patient was not diagnosed genetically, this case illustrates the under-recognized fact that UCD can occur in a senile age. Clinical suspicion of UCDs in patients with hyperammonemia is critical for early diagnosis and to prevent the significant neurologic sequelae.

Three Cases of Aphasic Status Epilepticus: Clinical and Electrographic Characteristics.

Aphasic status epilepticus (ASE) is unusual and has clinical characteristics similar to those of other disorders. Herein, we report 3 cases of ASE. A left-handed man (patient 1) showed continuous aphasia after the administration of flumazenil. He had underlying alcoholic liver cirrhosis and traumatic brain lesions in the right hemisphere. Electroencephalography (EEG) revealed periodic epileptiform discharges in the right frontotemporal area, which were intervened by rhythmic activity with spatiotemporal evolutions. A right-handed woman (patient 2) showed recurrent aphasia. Blood tests revealed a high blood glucose level (546 mg/dL) and high serum osmolality (309 mMol/L). Her EEG showed rhythmic activity in the left frontotemporal area with spatiotemporal evolutions on a normal background rhythm. She became seizure-free after the administration of an antiepileptic drug and strict glucose regulation. A right-handed woman (patient 3) developed subacute aphasia a week before hospital admission. She had a gradual decline of cognition 1 year before. Her EEG showed intermittent quasi-rhythmic fast activity in the frontotemporal area bilaterally, with fluctuating frequency and amplitude. The patient became seizure-free after the administration of an antiepileptic drug. Brain single-photon emission tomography performed after seizure control showed decreased perfusion in the left frontotemporal area. After discharge, her cognitive function gradually declined to a severe state of dementia. ASE can be caused by diverse etiologies; it is usually caused by cerebral lesions and less frequently by non-lesional etiologies or degenerative disorders. Adequate treatment of underlying disorders and seizures is critical for curing the symptoms of ASE.

Clinical Characteristics and Treatment Outcomes of De Novo Nonconvulsive Status Epilepticus: A Retrospective Study.

BACKGROUND AND PURPOSE: Nonconvulsive status epilepticus (NCSE) is challenging to diagnose. This study aimed to describe and classify the clinical features and electroencephalography (EEG) findings of patients with de novo NCSE and to correlate them with clinical outcomes. METHODS: We retrospectively reviewed the medical and EEG records of patients admitted to our institution with altered mentation and EEG abnormalities from January 1, 2013 to December 31, 2018. We evaluated premorbid modified Rankin Scale (mRS) scores, underlying disorders, precipitating factors, clinical manifestations, laboratory tests, and outcomes after a 3-month follow-up. Patients who met the Salzburg Consensus Criteria for NCSE were categorized into good-outcome and poor-outcome groups. A good outcome was defined as 1) clinical and electrographic seizures ceasing after treatment, and 2) an mRS score of ≤2 or remaining unchanged during the 3-month follow-up. A poor outcome was defined as 1) death, 2) seizures continuing despite treatment, or 3) a follow-up mRS score of ≥3 in a patient with a premorbid mRS score of ≤2, or a follow-up mRS score that increased in a patient with a premorbid mRS score of ≥3. RESULTS: The 48 included patients comprised 37 categorized into the good-outcome group and 11 into the poor-outcome group. The presence of acute metabolic disturbances was significantly correlated with poor outcome (p=0.036), while the other analyzed variables were not significantly correlated with outcomes. CONCLUSIONS: Acute metabolic disturbances in NCSE are associated with poor outcomes. Adequate treatment of underlying reversible disorders alongside controlling seizures is critical for patients with NCSE.

Cerebral Toxocara canis larval infection presenting as delayed encephalopathy and nonconvulsive status epilepticus: a case report.

Adult cerebral Toxocara canis larval infections are rare. Humans are infected by contacting soil that contains infectious eggs or by eating undercooked meat. We encountered a patient with cerebral T. canis infection who showed recurrent altered mentality with nonconvulsive status epilepticus (NCSE). A 71-year-old male was admitted with complaints of drowsy mentality and abnormal behavior. Magnetic resonance imaging revealed non-enhanced multiple gliosis and calcified lesions. Electroencephalography revealed NCSE, which was cured with valproate. However, he was readmitted because of recurrence of symptoms. On cerebrospinal fluid examination, T. canis antibodies were observed. Subsequently, he was treated with albendazole and corticosteroids. Although corticosteroid improved his symptoms, the therapy could not be continued because the patient developed septic shock. This is the first report of cerebral T. canis larval infection presenting as delayed encephalopathy and NCSE. In patients with unexplainable progressive encephalopathy, particularly when gliosis or calcified lesions are observed on neuroimaging, cerebral T. canis larval infection should be considered and treated promptly.

Bilateral Subthalamic Nucleus Deep Brain Stimulation under General Anesthesia: Literature Review and Single Center Experience.

Bilateral subthalamic nucleus (STN) Deep brain stimulation (DBS) is a well-established treatment in patients with Parkinson's disease (PD). Traditionally, STN DBS for PD is performed by using microelectrode recording (MER) and/or intraoperative macrostimulation under local anesthesia (LA). However, many patients cannot tolerate the long operation time under LA without medication. In addition, it cannot be even be performed on PD patients with poor physical and neurological condition. Recently, it has been reported that STN DBS under general anesthesia (GA) can be successfully performed due to the feasible MER under GA, as well as the technical advancement in direct targeting and intraoperative imaging. The authors reviewed the previously published literature on STN DBS under GA using intraoperative imaging and MER, focused on discussing the technique, clinical outcome, and the complication, as well as introducing our single-center experience. Based on the reports of previously published studies and ours, GA did not interfere with the MER signal from STN. STN DBS under GA without intraoperative stimulation shows similar or better clinical outcome without any additional complication compared to STN DBS under LA. Long-term follow-up with a large number of the patients would be necessary to validate the safety and efficacy of STN DBS under GA.

Patient selected goals and satisfaction after bilateral subthalamic nucleus deep brain stimulation in Parkinson's disease.

Assessing patient goals is crucial in understanding patient centered outcomes and satisfaction. However, patient goals may change throughout treatment. Our objective is to identify the changes in patient-selected goals of Parkinson's disease (PD) patients undergoing bilateral subthalamic nucleus deep brain stimulation (STN-DBS) and examine the relationship among patient-selected goal achievement, standard DBS outcome measures, and overall patient satisfaction. Seventy-five patients undergoing bilateral STN-DBS listed three patient-selected goals before surgery. After six months, patients were asked to restate the three goals and to rate the degree of goal achievement and the overall satisfaction of surgery. The three most frequently selected goals were "dyskinesia", "gait disorder", and "medication off duration". After six months, 80.0% of patients could not accurately recall their pre-DBS goals. "Dyskinesia" was the most consistently selected goal, more patients selected "tremor" and "less medication" at post-DBS compared to pre-DBS, and less patients selected "gait disorder" at post-DBS compared to pre-DBS. 74.7% of patients reported overall satisfaction by stating they were "very much" or "much better after surgery". Patient satisfaction significantly correlated with goal achievement (r = 0.640; p < 0.001). Interestingly, change in UPDRS motor scores did not correlate with patient satisfaction (r = 0.100; p = 0.395). Although recalled goals do not accurately represent the pre-surgical goals, the achievement score for recalled goals significantly correlated with patient satisfaction. Patient goals change due to many reasons. Therefore, follow-up patient counseling to discuss goals and outcomes is important in improving patient satisfaction after STN-DBS.