Akihiko Tateno

Early onset epileptic encephalopathy caused by de novo SCN8A mutations.

De novo SCN8A mutations have been reported in patients with epileptic encephalopathy. Herein we report seven patients with de novo heterozygous SCN8A mutations, which were found in our comprehensive genetic analysis (target capture or whole‐exome sequencing) for early onset epileptic encephalopathies (EOEEs).

A missense mutation in SCN1A in brothers with severe myoclonic epilepsy in infancy (SMEI) inherited from a father with febrile seizures.

Severe myoclonic epilepsy in infancy (SMEI) is an age-dependent epileptic encephalopathy occurring in the first year of life and is one of the intractable epilepsies. Heterozygous mutations in the voltage-gated sodium channel alpha subunit type1 gene (SCN1A) are frequently identified in patients with SMEI; two-thirds of these mutations are truncation mutations (non-sense and frameshift), and one-third are missense mutations. Although most reported SMEI cases arise as sporadic mutations, close relatives of SMEI patients have also been shown to manifest other types of epilepsies at a higher rate than that in the general population. Here, we report a familial case of SMEI, in which two brothers were affected with SMEI while their father had previously experienced simple febrile seizures. A gene-based analysis identified a novel missense mutation in the SCN1A gene (c.5138G>A, S1713N) in both brothers and in their father. Clinically, both siblings showed failure in locomotion, an impairment of the sleep-wake cycle after late infancy, and the subsequent appearance of frontal foci. The similarity in clinical manifestations in both brothers suggests that the impairment of elements of the brainstem, particularly aminergic neurons, develops after late infancy in SMEI. However, the siblings differed in age at onset of SMEI and of myoclonic seizures, as well as in the severity of speech delay. Our molecular and clinical findings suggest that different genetic backgrounds and/or environmental factors may critically affect the clinical features of patients with SCN1A mutations, consistent with the heterogeneity prevalent in this disorder.

Plasma levodopa peak delay and impaired gastric emptying in Parkinson's disease

OBJECTIVES Whereas delayed gastric emptying is believed to be a causative factor for producing delayed-on and motor fluctuation in Parkinsons disease (PD), few studies have directly measured levodopa pharmacodynamics and gastric emptying together. In order to determine the relationship, we measured these two parameters in a single PD patients cohort. METHODS Thirty-one patients with PD were enrolled in the study. They were 11 men and 20 women; age, 68.1 ± 7.8 years; disease duration, 4.2 ± 3.8 years; Unified Parkinsons Disease Rating Scale Part 3 Motor Score 18.37 ± 8.60; bowel movement <3 times a week in 20; all taking 301 mg ± 94 mg/day levodopa/carbidopa. All patients underwent levodopa pharmacokinetic study and the gastric emptying study using (13)C-octanoic acid expiration breath test. Statistical analysis was performed by Students t-test and Mann-Whitneys U test. RESULTS Pharmacokinetic study showed that the plasma levodopa peak was at 2 hours in 42% (13/31 patients) whereas at 1 hour in 58% (18/31 patients), total of 50.7 ± 16.4 min (mean ± standard deviation) in all 31 patients. The gastric emptying study showed that T(max) ((13)C)>60 min was more common in patients with a plasma levodopa peak at 2 hours (14/18, 69%) than in those with a plasma levodopa peak at 1 hour (4/13, 22%) (p<0.05), total of 50.7 ± 16.4 min in all 31 patients. CONCLUSION We found a significant relationship between levodopa pharmacokinetics and gastric emptying in PD patients, suggesting that delayed gastric emptying is a causative factor for producing delayed-on in PD. Therefore, studies of improved gastric emptying in order to ameliorate delayed-on in PD are warranted.

Tears From Children With Chronic Hepatitis B Virus (HBV) Infection Are Infectious Vehicles of HBV Transmission: Experimental Transmission of HBV by Tears, Using Mice With Chimeric Human Livers

BACKGROUND Body fluids such as saliva, urine, sweat, and tears from hepatitis B virus (HBV) carriers are potential sources of HBV transmission. METHODS Thirty-nine children and 8 adults who were chronically infected with HBV were enrolled. Real-time polymerase chain reaction was used for the quantification of HBV DNA. RESULTS HBV DNA was detected in 73.7% of urine samples (14 of 19), 86.8% of saliva samples (33 of 38), 100% of tear samples (11 of 11), and 100% of sweat samples (9 of 9). Mean HBV DNA levels (±SD) in urine, saliva, tears, and sweat were 4.3 ± 1.1 log copies/mL, 5.9 ± 1.2 log copies/mL, 6.2 ± 0.7 log copies/mL, and 5.2 ± 0.6 log copies/mL, respectively. A statistically significant correlation was observed between the HBV DNA level in serum specimens and HBV DNA levels in saliva and tear specimens (r = 0.88; P < .001). Tear specimens from a child were injected intravenously into 2 human hepatocyte-transplanted chimeric mice. One week after inoculation, both chimeric mice had serum positive for HBV DNA. CONCLUSIONS The levels of HBV DNA in tear specimens from young children were high. Tears were confirmed to be infectious, using chimeric mice. Strict precautions should be taken against direct contact with body fluids from HBV carriers with high-level viremia.

Failure to distinguish systemic-onset juvenile idiopathic arthritis from incomplete Kawasaki disease in an infant

Abstract:  In an infant, an initial diagnosis of incomplete Kawasaki disease was made according to the American Heart Association guidelines. However, the diagnosis of systemic‐onset juvenile idiopathic arthritis was established later. Physicians need to recognize that systemic‐onset juvenile idiopathic arthritis can be mistaken for incomplete Kawasaki disease, even when the guidelines are used.

Dietary Herb Extract Rikkunshi-To Ameliorates Gastroparesis in Parkinson's Disease: A Pilot Study

Objective: To perform an open trial on the effects of the extract of the dietary herb Rikkunshi-to (RKT) on gastroparesis in Parkinsons disease (PD) patients, using objective parameters given by the 13C-sodium acetate expiration breath test (gastric emptying study). Methods: Twenty patients with PD were enrolled into this study. Eleven patients were male and 9 were female, with the following characteristics (mean ± SD): age, 69.4 ± 8.17 years; disease duration, 4.34 ± 4.03 years; modified Hoehn and Yahr stage, 2.37 ± 0.98, and Unified Parkinsons Disease Rating Scale Part 3 motor score, 16.6 ± 7.37. Fourteen patients came to the clinic due to constipation; 16 patients were taking 288 ± 72 mg/day levodopa/carbidopa, 2 were taking dopamine agonists, and the others were not treated yet. All patients underwent the breath test. Statistical analysis was performed using Students t test. Results: RKT was well tolerated by all patients and none experienced abdominal pain or other adverse effects, except for its bitter taste. RKT significantly reduced the peak time of the 13C-dose-excess curve (p < 0.05). Conclusion: In this pilot trial, we found a significant shortening of the gastric emptying time after administration of the dietary herb extract RKT in PD patients. Further studies examining both gastric emptying and delayed-on in PD are warranted.

Weak detrusor contractility correlates with motor disorders in Parkinson's disease

Limited attention has been paid to the relationship between urinary symptoms or urodynamic findings and motor disorders in Parkinsons disease (PD). We aimed to correlate pressure‐flow urodynamic parameters with video‐gait analysis parameters in PD. We recruited 41 patients with PD (25 men and 16 women; age, 70.6 ± 8.5 years; H & Y motor grading: 2 [range, 1–3]; disease duration: 4 years [range, 1–7]; taking levodopa 300 mg/day [range, 100–400]). All patients underwent pressure‐flow urodynamics (parameters: first sensation, bladder capacity, detrusor overactivity [noted in 24 patients], and Watts factor [WF]) and video‐gait analysis (parameters: time and number of strides for 5‐m gait [simple task] and time for timed up and go [complex task]). Statistical analysis was made by Mann‐Whitneys U‐test for analyzing the relation between detrusor overactivity and gait as well as Spearmans rank‐correlation coefficient test for analyzing the relation between the remaining parameters and gait. We found no relation between filling‐phase urodynamics (detrusor overactivity, first sensation, and bladder capacity) and video‐gait analysis parameters. By contrast, we found a significant relation between voiding‐phase urodynamics (WF, reflecting detrusor power) and all three video‐gait analysis parameters (reflecting lower‐half bradykinesia and loss of postural reflex) in our PD patients (P < 0.01). The close relation between the WF and motor disorders in the present study suggests that, though clinically mild, a weak detrusor in PD might have a central origin. We should follow postvoid residual volume carefully in PD patients with advanced gait disorder, because postvoid residual volume might increase in such patients.

Meningitis-retention syndrome: a review.

A peculiar combination of acute urinary retention and aseptic meningitis has been described. This combination is referred to as meningitis‐retention syndrome (MRS), since patients with this syndrome exhibited no other abnormalities, except for mild pyramidal involvement. We aimed to delineate this syndrome by reviewing literatures.

Rett's syndrome: progression of symptoms from infancy to childhood.

The results of studies of seven girls with Retts syndrome and two additional cases suggestive of Retts syndrome are presented. After normal neurological development up to the age of 7 to 20 months, there was a rapid regression of higher cortical function. Retts syndrome was initially manifested by a delay of further motor development and the appearance of autistic traits. As the disease progressed, there was loss of ability to crawl, loss of purposeful hand movements, abnormal respirations, truncal ataxia, seizures, and spastic increase in muscle tone. Blood chemistries, including ammonia levels, were normal. Metabolic interference, a recently hypothesized form of inheritance, may occur in this syndrome. (J Child Neurol 1986;1:137-141)

Two siblings with multiple intracranial haemangiomatosis with calcification

SummaryTwo siblings with multiple intracranial haemangiomatosis are reported, each having psychomotor retardation, epilepsy and gyriform type calcification in the occipital and frontal lobes. There were haemangiomas in one autopsy case with calcification in the deep layers of the cortex and subcortical white matter.