Like hair and eye color or ethnic differences in average height, which are genetically determined characteristics, human behavior has shown to be affected by the genetic background. In the field of genetics, human behavior is included within the phenotype study. Since a congenital anomaly syndrome is naturally caused by a genetic variant, the study of the patients' clinical manifestations sheds light on the genotype-phenotype correlation. Some syndromes cause distinct characteristic behavior such as self-biting in patients with Lesch-Nyhan syndrome or sudden laughter in patients with Angelman syndrome. Behavioral problems observed in Williams and Prader-Willi syndromes may provide characteristic detection of patients with those syndromes, which is now under study. Likewise, the innate behavioral characteristics of non-specific intellectual disabilities and autism spectrum disorders may be caused by specific genes. Understanding the genetic basis of the affected individual's behavior facilitates the administration of appropriate personalized treatment, rehabilitation, and education to those who need special support.

View full abstract

Understanding the pathophysiology of developmental and behavioral disturbances is highly crucial in providing therapeutic opportunities within the field of developmental neurology. Nevertheless, systematic functional assessments of the brain in childhood neurodevelopmental disorders remain difficult. Diffusion tensor imaging (DTI), based on a high field magnetic resonance imaging (MRI), is an imaging technique capable of providing in-vivo information on brain maturation in a non-invasive manner. Clinical applications of DTI have successfully detected brain developmental abnormalities in individuals with not only genetically-related but also experience-dependent alterations of behavior. DTI appears to be a promising tool in elucidating developmental pathophysiology of the brain in neurodevelopmental disorders.

View full abstract

Autistic spectrum disorder (ASD) is a disease concept that encompasses several conditions that were previously diagnosed under different disease names, such as autistic disorder, pervasive developmental disorder, and Asperger's syndrome. Its manifestations include a range of symptoms of varying degrees. Other developmental disorders may overlap within the same individual. During childhood, support is provided to patients with ASD, mainly with medical and educational/developmental interventions that focus on having family members devise and practice lifestyle and relationship-building ideas that consider the child's special characteristics. Medication and psychotherapies may also be utilized in some cases. Many types of difficulties in daily living may emerge during different stages of the patient's life. Since patients are also known to experience psychiatric complications, physicians must provide treatment based on overall longitudinal and cross-sectional understanding of individual clinical cases. There also is a call to provide assistance by constantly and actively collaborating with individuals who are engaged in welfare and education.

View full abstract

A total of 61 patients, who were diagnosed with idiopathic orbital inflammation and could be followed up for at least four months, were investigated for clinical characteristics, treatments, and outcomes. Idiopathic orbital inflammation was diagnosed based on clinical symptoms and MRI findings, and subsequently classified into the following patterns: extraocular myositis, dacryoadenitis, optic perineuritis, intraorbital diffuse inflammation, tenonitis/scleritis and orbital apex inflammation. These patterns frequently overlapped, with tenonitis/scleritis and optic perineuritis often occurring together with other patterns. While the overall prevalence of idiopathic orbital inflammation was higher in patients in their 50s and 60s, extraocular myositis was more common in patients in their 20s, 50s, and 60s, and orbital apex inflammation was more common in patients in their 60s and 70s. With an overall recurrence rate of 55.7%, the disease recurred more often in patients in their 20s to 40s. Additionally, the disease tended to recur more frequently and be intractable in patients in their 20s and 30s with extraocular myositis and those with tenonitis/scleritis and optic perineuritis. While steroids were used as the first-line treatment, immunosuppressants were used in 52.9% of patients with recurrence. In addition, 61.8% of patients with recurrence received maintenance therapy, while 11.8% of these patients had a poor response and still suffered relapses.

View full abstract

We report the case of a patient who presented with optic neuritis while being treated with adalimumab (ADA) for ulcerative colitis (UC). A 42-year-old woman had been diagnosed with UC 13 years before, and had been receiving ADA therapy since February 2015. She presented with right eye pain in April 2015, and was referred to us when her symptoms did not improve. The best corrected visual acuity was 0.6 and the critical flicker frequency (CFF) was 12.3 Hz in the right eye. Additionally, she also had a paracentral scotoma in the right eye. Magnetic resonance imaging (MRI) showed increased signal intensity in the right optic nerve and fundus angiography showed hyperfluorescence in the right optic nerve head. We investigated the possibility of multiple sclerosis or neuromyelitis optica; however, testing of the cerebrospinal fluid and autoantibody tests yielded normal results. The patient was diagnosed with right optic neuritis due to ADA therapy. Following the discontinuation of ADA and steroid pulse therapies, visual acuity in the right eye improved to 1.5, CFF improved to 33.3 Hz, and the paracentral scotoma disappeared. Since optic neuritis can be caused by anti-TNF-α therapy, to ensure an accurate diagnosis, it is necessary to obtain a detailed medical history of the patient.

View full abstract

Case: A 64-year-old man, who was referred to our clinic with optic neuritis, presented with a swollen optic disc and a central scotoma in his left eye. One year previously, he had been diagnosed with ulcerative colitis and treated with anti-TNFα therapy. It was suspected that the optic neuritis was caused by adalimumab, an anti-TNFα medication used to treat the patient's ulcerative colitis. The patient experienced visual recovery from the optic neuritis following the discontinuation of adalimumab, without the use of methyl-prednisolone pulse treatment.
Discussion: Determining whether a patient has been administered anti-TNFα medication is an important step when optic neuritis is suspected because of the possible link between optic neuritis and anti-TNFα medication use. We will discuss additional optic neuritis cases caused by adalimumab that have been reported internationally.

View full abstract

We report a case of late-onset generalized myasthenia gravis (GMG) presenting with isolated inferior rectus paresis, in which the patient was followed up for oculomotor nerve paresis. A 58-year-old man exhibited isolated inferior rectus paresis of the right eye. Two months after onset, the patient presented with blepharoptosis of the right eye and paresis of the superior rectus muscle, inferior oblique muscle, and inferior rectus muscle. Abnormal findings were not found in magnetic resonance imaging, and the anti-acetylcholine receptor antibody test yielded negative results. Therefore, the patient was diagnosed with right idiopathic oculomotor nerve paresis. However, five months later, the patient presented with blepharoptosis of the left eye, weakness of the limb muscles and eye movement disturbance in all directions in both eyes, except for the abduction of the right eye. Furthermore, anti-acetylcholine receptor antibody, repetitive nerve stimulation, and cholinesterase inhibitor tests yielded positive results. We therefore diagnosed GMG. It is important to consider the possibility of GMG despite the presence of isolated extraocular muscles or the presence of a pattern of extraocular muscle paresis that is consistent with the distribution of the cranial nerves.

View full abstract

Myasthenia gravis (MG) is an autoimmune disease caused by the impairment of neuromuscular transmission. Antibodies against the muscle-specific receptor tyrosine kinase (MuSK) were recently reported to be present in almost 30% of generalized MG patients who are seronegative for the anti-acetylcholine receptor (AChR). In this study, we report two cases of anti-MuSK antibody-positive MG that presented with diplopia. These two patients consulted an ophthalmologist because of subjective diplopia. They manifested extraocular muscle paralysis despite being anti-AChR antibody-seronegative. After they developed dysphagia, we examined the level of anti-MuSK antibody in their serum and found that both cases were seropositive. Tensilon and repetitive nerve stimulation tests led to an anti-MuSK antibody-seropositive MG diagnosis. Although anti-MuSK antibody-seropositive MG is characterized by dysphagia as the major symptom, ocular symptoms can also occur. Therefore, when encountering a patient with ocular motor disorder, especially when the patient manifests diurnal variation, ophthalmologists should examine both anti-AChR and anti-MuSK antibodies to enable the early detection of MG.

View full abstract

Cavernous sinus thrombosis is a rare, serious, as possibly fatal disease. We report the case of a 27-year-old woman with cavernous sinus thrombosis that was caused by acute sinusitis. Prompt diagnosis and treatment allowed for a complete recovery. The patient presented with progressive pain and proptosis of the right eye that lasted for 6 days. The patient had already consulted an ophthalmologist and otolaryngologist, and was hospitalized in the department of otolaryngology. The patient was diagnosed with acute sinusitis, and received consultations from the departments of ophthalmology and neurosurgery. Imaging showed enlargement of the superior ophthalmic vein and the cavernous sinus, which confirmed the diagnosis of cavernous sinus thrombosis. The patient was treated by draining the sinusitis via an endoscopic incision, as well as continuous intravenous antibiotics and anticoagulants. Proptosis gradually decreased, but the patient developed abducens palsy in her right side 8 days after the surgery. The patient's condition improved after 17 days of hospitalization, and the abducens palsy resolved within 6 months.

View full abstract

Patients with diplopia are usually treated with optical devices like prisms. Prism spectacles may be successful in treating diplopia in primary and down gaze. However, we performed incomplete partial occlusion to eliminate diplopia in all gaze directions by using a 0.1 Occluder. We adopted the S-S method (categorized into three steps) at our hospital. In Step 1, ordinary prism spectacles and/or membrane press-on prisms were provided to eliminate primary gaze diplopia. However, in some patients with ophthalmoplegia, diplopia persisted in other gaze directions. In Step 2, the spectacle lens was partially taped in the peripheral directions in which diplopia persisted. Finally, in Step 3, monocular central field occlusion decreased the visual acuity of one eye, but retained the peripheral visual field and enabled better walking stability and more comfortable daily life compared to that by monocular complete occlusion. The S-S method proved to be useful in eliminating diplopia and improving the quality of daily life of patients. We have detailed this method in this report.

View full abstract

Importance: Alzheimer's disease (AD) is the most common cause of dementia in the elderly; however, no effective treatment is currently available. The identification of predictors for AD could facilitate early detection of the disease. Since the eye is an easily accessible part of the central nervous system, features presented through the eyes may provide important insights on the development of AD.
Objective: To investigate whether diseases of the eye, including age-related macular degeneration (AMD), glaucoma, and diabetic retinopathy(DR), are effective predictors for the development of AD.
Design, Setting, and Participants: In this cohort study, we used randomized sampled data of one million patients who had made insurance claims from the National Health Insurance. We included all newly diagnosed patients with AD, AMD, DR, or glaucoma between January 1, 2000 and December 31, 2010.
Interventions: We excluded patients who had sought treatment for AD(ICD-9 code 331.0)before 2000. To examine the relationship between ocular diseases, ICD coding targets were defined as follows: AMD (ICD-9 codes 362.50, 362.52), DR (ICD-9 codes 362.01, 362.02, 250.50, 250.51, 250.53), and glaucoma (ICD-9 code 365). We only included these comorbidities if they had been diagnosed prior to the diagnosis of AD.
Main Outcomes and Measures: We examined the relationship between eye disease and the occurrence of AD in each of the groups. A Cox proportional hazards regression analysis was performed, with adjustments made for age and sex.
Results: There were a total of 4,097 patients in the eye disease group and 20,475 in the control group. A total 50 patients from the eye disease group developed AD during the study period, representing a cumulative incidence rate of 1.22%. The corresponding figure for the control group was 0.04%. The adjusted hazard ratio (AHR) with its confidence interval (CI) for AD varied between the ocular diseases; it was the highest in DR (39.91, 95% CI 4.79-332.67), followed by AMD (36.94, 95% CI 4.62-295.46), and glaucoma (34.08, 95% CI 13.37-86.84).
Conclusions and Relevance: AMD, DR, and glaucoma were associated with an increased risk of AD. This study demonstrates that the presence of ocular diseases could be a sensitive indicator of preclinical AD with potential value in population screening.

View full abstract