Tomoko Toyota

Tandemly repeated sequences are highly mutable and variable features of genomes. Tandem repeat expansions are responsible for a growing list of human diseases, even though it is hard to determine tandem repeat sequences with current DNA sequencing technology. Recent long-read technologies are promising, because the DNA reads are often longer than the repetitive regions, but are hampered by high error rates. Here, we report robust detection of human repeat expansions from careful alignments of long (PacBio and nanopore) reads to a reference genome. Our method (tandem-genotypes) is robust to systematic sequencing errors, inexact repeats with fuzzy boundaries, and low sequencing coverage. By comparing to healthy controls, we can prioritize pathological expansions within the top 10 out of 700000 tandem repeats in the genome. This may help to elucidate the many genetic diseases whose causes remain unknown.

症例は67歳女性．家族歴なし．2009年より進行性の脊椎側弯が出現し2013年他院で体幹ジストニアの診断でトリヘキシフェニジル内服とボツリヌス注射が行われたが改善はなく，2015年に歩行障害が出現した．同年5月当科での［¹²³I］-イオフルパンシンチグラフィー（以後DATスキャン）で異常をみとめ，6月当科入院時は運動緩慢，筋強剛，右優位の静止時振戦，姿勢反射障害をみとめ頭部MRIで異常なくレボドパで運動症状の改善をみとめたことからパーキンソン病と診断した．本例は体幹ジストニアが先行したパーキソニズムでありDATスキャンが診断の一助となりえた症例である．貴重な症例であり文献的考察を加え報告する．

Background: The incidence of epilepsy is highest in older adults and exceeds that observed in children. Seizure disorders are also more common among older adults. However, there are few reports of interictal epileptiform discharges in new‐onset epilepsy among older adults.Aim: To investigate the rate of interictal epileptiform discharges in elderly patients with new‐onset epilepsy.Methods: We defined elderly patients with new‐onset epilepsy as those who developed epilepsy after the age of 65 years. We reviewed the interictal electroencephalographic characteristics of patients with new‐onset epilepsy treated between April 2005 and December 2011 at a tertiary referral center. Both outpatients and inpatients were included in this study. Epilepsy was diagnosed on the basis of clinical history, scalp‐recorded electroencephalography, physical findings, brain 3.0‐T magnetic resonance imaging/computed tomography, single‐photon emission tomography and neuropsychological evaluation. Epilepsy and seizure classifications, and age of onset were also reviewed.Results: We included 112 patients (58 men and 54 women) in this study. The mean age of seizure onset was 73.5 ± 6.7 years. Interictal epileptiform discharges were detected in 82 patients (73.2%). Temporal lobe epilepsy (odds ratio 6.3, P = 0.004) and complex partial seizures (odds ratio 8.0, P = 0.033) were associated with interictal epileptiform discharges.Conclusion: Interictal epileptiform discharges were present in 73.2% of the elderly patients with new‐onset epilepsy in our cohort, which was higher than the previously reported rate. Temporal lobe epilepsy was the most frequent epilepsy diagnosis among the interictal epileptiform discharge‐positive patients.

We report the case of a 72‐year‐old woman with a first epileptic seizure at the age of 70 years. Neuronal intranuclear inclusion disease was subsequently diagnosed based on characteristic magnetic resonance imaging findings and intranuclear inclusions on skin biopsy histology. Neuronal intranuclear inclusion disease is a rare neurodegenerative disease with a diverse range of clinical manifestations, including epilepsy. It is categorized into three categories: infantile, juvenile and adult forms. Epileptic seizure is the third most common neurological disorder in the elderly after stroke and dementia. To our knowledge, this is the first case of a patient presenting with epileptic seizures as a manifestation of the adult form of neuronal intranuclear inclusion disease. We further showed intranuclear inclusions in keratinocytes by skin biopsy histology. We report neuronal intranuclear inclusion disease as a cause of new‐onset epilepsy in the elderly.

As the elderly constitute the most rapidly growing population, epilepsy in this group is an important health issue worldwide. We identified 70 patients who developed epilepsy after the age of 65 years at our institution. Complex partial seizures (CPS) without secondarily generalization were most frequent. The most frequent diagnosis was temporal lobe epilepsy. Etiological diagnosis was possible in nearly 50% patients, including those with cerebrovascular disease. Interictal EEG revealed focal epileptiform discharges in 66.7% of patients. Forty-two patients were on antiepileptic monotherapy and 52 patients had been seizure-free for more than 1 year. Epileptogenecity was relatively low in elderly patients and they responded well to antiepileptic medication.

Recently, some reports have indicated that limbic encephalitis associated with anti-voltage-gated potassium channel complex antibodies (VGKC-Ab) is a cause of adult-onset mesial temporal lobe epilepsy (MTLE). We report a 53-year-old woman who had her first epileptic seizure at the age of 50 years old. Examination by 3-Tesla brain MRI revealed left hippocampal high signal intensity and swelling on fluid-attenuated inversion recovery (FLAIR) and T2-weighted imaging at 2 months after her first seizure. The patient received intravenous methylprednisolone and carbamazepine 300 mg/day. One month later, MRI revealed improvement of her left hippocampal abnormalities. Thereafter, she had no seizures, however, three years after her first seizure, EEG revealed a seizure pattern in the left temporal region. Brain MRI revealed left hippocampal high signal intensity and brain fluorodeoxyglucose positron emission tomography revealed hypermetabolism. Her serum VGKC-Ab levels were 118 pM(normal < 100 pM). Intravenous methylprednisolone therapy was reinitiated. Two months later, her hippocampal abnormalities had improved and 3 months later her VGKC-Ab levels decreased to 4.4 pM. Remission of the epileptic seizures was also observed. This MTLE in the middle age was considered as limbic encephalitis associated with anti- VGKC-Ab. In cases of unexplained adult-onset MTLE, limbic encephalitis associated with anti-VGKC-Ab, which responds well to immunotherapy, should be considered in the differential diagnosis.

Summary: In this study, we aimed to investigate the types of seizures and epilepsy associated with systemic lupus erythematosus (SLE). We searched the medical records at a tertiary referral center to identify a cohort of epilepsy patients with SLE who were treated between January 2000 and August 2011. We analyzed the clinical and immunologic profiles of these patients, their seizure and epilepsy classifications, electroencephalography (EEG) and magnetic resonance imaging (MRI) assessments, and the treatment administered for epilepsy and SLE. As the result, 17 patients with SLE and epilepsy were identified. Seven patients had mesial temporal lobe epilepsy (MTLE), eight had epilepsy secondary to stroke, and two had generalized epilepsy. Of the seven patients with MTLE, anteriotemporal spikes were noted in all patients with EEG, and MRI findings suggesting hippocampal sclerosis were noted in four patients. Clobazam and levetiracetam were effective in treating three patients, and one patient underwent amygdalohippocampectomy. In conclusion, MTLE may be a characteristic manifestation of neuropsychiatric syndrome of systemic lupus erythematosus.