Despite advances in the diagnosis and management of rare diseases (RDs), there remains a tendency to overlook adult RD patients. In addition to the considerable number of adult-onset RDs, advances in the diagnosis and management of pediatric RDs have led to an increase in the survival of these patients into adulthood. Adult RDs exhibit distinct features from pediatric counterparts, necessitating careful consideration during medical assessments. Given the extended life expectancy of adult RD patients, precise diagnosis and management strategies can significantly enhance patient outcomes. This review aims to provide an in-depth exploration of the characteristics unique to adult RDs. Special emphasis will be placed on the importance of cascade screening and prenatal genetic testing in the context of adult RDs, highlighting the need for a comprehensive understanding of these aspects in clinical practice.

Gene therapy is a potential therapeutic strategy for treating hereditary movement disorders, including hereditary ataxia, dystonia, Huntington's disease, and Parkinson's disease. Genome editing is a type of genetic engineering in which DNA is inserted, deleted or replaced in the genome using modified nucleases. Recently, clustered regularly interspaced short palindromic repeat/CRISPR associated protein 9 (CRISPR/Cas9) has been used as an essential tool in biotechnology. Cas9 is an RNA-guided DNA endonuclease enzyme that was originally associated with the adaptive immune system of Streptococcus pyogenes and is now being utilized as a genome editing tool to induce double strand breaks in DNA. CRISPR/Cas9 has advantages in terms of clinical applicability over other genome editing technologies such as zinc-finger nucleases and transcription activator-like effector nucleases because of easy in vivo delivery. Here, we review and discuss the applicability of CRISPR/Cas9 to preclinical studies or gene therapy in hereditary movement disorders.
Biotechnology ; Deoxyribonuclease I ; DNA ; Dystonia ; Genetic Engineering ; Genetic Therapy ; Genome ; Huntington Disease ; Immune System ; Movement Disorders* ; Parkinson Disease ; Spinocerebellar Degenerations ; Streptococcus pyogenes

BACKGROUND: Neurological deterioration following acute lacunar infarction is not uncommon. Its association with poor clinical outcome is well-known, but little is known about what causes it. This study aimed to elucidate whether 3 stigmas of cerebral microangiopathy, a pathogenesis of lacunar infarction, are associated with neurological deterioration in patients with acute lacunar infarction. METHODS: Patients with acute lacunar infarction who were admitted within 24 hours of onset were identified using a prospective stroke registry. Patients who presented neurological deterioration within 7 days of hospitalization (progressive lacune group) were matched to 4 controls (non-progressive lacune group) for 'onset to arrival time'. Three stigmas of cerebral microangiopathy (leukoaraiosis, cerebral microbleeds, and silent lacunes) were measured using initial brain MRI, and their associations with neurological deterioration were analyzed. RESULTS: During 45 months, a total of 23 patients were identified and matched to 80 controls. Simple comparison of 2 groups showed that those 3 stigmas of cerebral microangiopathy were not significantly associated with neurological deterioration. Hyperlipidemia (p=0.18), history of transient ischemic attack or stroke (p=0.01), initial NIH stroke scale (p=0.07), white blood cell counts (p=0.16), and lesion volume (p=0.03) were possibly different (p's<0.2) between 2 groups. Multivariable logistic regression analysis did not reveal any significant association of those 3 stigmas with neurological deterioration, too (all p values>0.5). CONCLUSIONS: This study did not find a relationship between cerebral microangiopathy and neurological deterioration following acute lacunar infarction. The possibility of inadequate power should be noted.
Brain ; Cerebral Small Vessel Diseases ; Hospitalization ; Humans ; Hyperlipidemias ; Ischemic Attack, Transient ; Leukocyte Count ; Logistic Models ; Prospective Studies ; Stroke ; Stroke, Lacunar

BACKGROUND AND PURPOSE: Herpes simplex encephalitis (HSE) is the most common type of sporadic encephalitis worldwide, and it remains fatal even when optimal antiviral therapy is applied. There is only a weak consensus on the clinical outcomes and prognostic factors in patients with HSE. This study examined whether the radiological and electrophysiological findings have a prognostic value in patients with HSE. METHODS: We retrospectively analyzed patients who were diagnosed with HSE by applying the polymerase chain reaction to cerebrospinal fluid and who received intravenous acyclovir at our hospital from 2000 to 2014. We evaluated the clinical outcomes at 6 months after onset and their correlations with initial and clinical findings, including the volume of lesions on MRI, the severity of EEG findings, and the presence of epileptic seizures at the initial presentation. RESULTS: Twenty-nine patients were enrolled (18 men and 11 women). Univariate analysis revealed that the presence of severe EEG abnormality and epileptic seizures at the initial presentation were significant correlated with a poor clinical outcome at 6 months (p=0.005 and p=0.009, respectively). In multivariate analysis, the presence of severe EEG abnormality was the only independent predictor of a poor outcome at 6 months (p=0.006). CONCLUSIONS: In cases of HSE, the initial EEG severity and seizure presentation may be useful predictive factors for the outcome at 6 months after acyclovir treatment.
Acyclovir ; Cerebrospinal Fluid ; Consensus ; Electroencephalography* ; Encephalitis ; Encephalitis, Herpes Simplex* ; Epilepsy ; Herpes Simplex* ; Humans ; Magnetic Resonance Imaging* ; Male ; Multivariate Analysis ; Polymerase Chain Reaction ; Retrospective Studies ; Seizures ; Simplexvirus

Background: and Purpose Focal cortical dysplasia (FCD) is one of the most common causes of drug-resistant epilepsy, and necessitates a multimodal evaluation to ensure optimal surgical treatment. This study aimed to determine the supportive value of the morphometric analysis program (MAP) in detecting FCD using data from a single institution in Korea. Methods: To develop a standard reference for the MAP, normal-looking MRIs by two scanners that are frequently used in this center were chosen. Patients with drug-resistant epilepsy and FCD after surgery were candidates for the analysis. The three-dimensional T1-weighted MRI scans of the patients were analyzed as test cases using the MAP. Results: The MRI scans of 87 patients were included in the analysis. The radiologist detected abnormal findings correlated with FCD (RAD positive [RAD(+)]) in 34 cases (39.1%), while the MAP could detect FCD in 25.3% of cases. A combination of the MAP (MAP[+] cases) with interpretations by the radiologist increased the detection to 42.5% (37 cases). The lesion detection rate was not different according to the type of reference scanners except in one case. MAP(+)/RAD(-) presented in three cases, all of which had FCD type IIa. The detection rate was slightly higher using the same kind of scanner as a reference, but not significantly (35.0% vs. 22.4% p=0.26). Conclusions The results of postprocessing in the MAP for detecting FCD did not depend on the type of reference scanner, and the MAP was the strongest in detecting FCD IIa. We suggested that the MAP could be widely utilized without developing institutional standards and could become an effective tool for detecting FCD lesions.