A novel HYLS1 homozygous mutation in living siblings with Joubert syndrome.

The p.Asp211Gly homozygous HYLS1 mutation is so far known to cause only hydrolethalus syndrome, a lethal malformation syndrome. We report living sibling patients with a homozygous no-stop mutation in exon 4 of HYLS1, NM_145014.2:c.900A>C (p.Ter300TyrextTer11) in the second decade of life. The proband has Joubert syndrome (JS). The younger brother also has JS and an enlarged posterior fossa that was initially diagnosed as Dandy-Walker malformation. The present mutation is unique as it affects the stop codon. The product protein HYLS1 plays an essential role in the formation of the primary cilium. This report provides insight into the spectrum of disorders involving midline brain defects closely related to cilium dysfunction or ciliopathy.

Autosomal recessive cystinuria caused by genome-wide paternal uniparental isodisomy in a patient with Beckwith-Wiedemann syndrome.

Approximately 20% of Beckwith-Wiedemann syndrome (BWS) cases are caused by mosaic paternal uniparental disomy of chromosome 11 (pUPD11). Although pUPD11 is usually limited to the short arm of chromosome 11, a small minority of BWS cases show genome-wide mosaic pUPD (GWpUPD). These patients show variable clinical features depending on mosaic ratio, imprinting status of other chromosomes, and paternally inherited recessive mutations. To date, there have been no reports of a mosaic GWpUPD patient with an autosomal recessive disease caused by a paternally inherited recessive mutation. Here, we describe a patient concurrently showing the clinical features of BWS and autosomal recessive cystinuria. Genetic analyses revealed that the patient has mosaic GWpUPD and an inherited paternal homozygous mutation in SLC7A9. This is the first report indicating that a paternally inherited recessive mutation can cause an autosomal recessive disease in cases of GWpUPD mosaicism. Investigation into recessive mutations and the dysregulation of imprinting domains is critical in understanding precise clinical conditions of patients with mosaic GWpUPD.

Abnormal fast activity before the onset of West syndrome.

In our sequential EEG study performed on 68 infants with various pre- and perinatal brain insults, we found peculiar abnormal fast activity (AFAs) in 12 patients. 9 of the 12 patients with AFAs later developed West syndrome (WS) compared with only 3 of the 56 patients without AFAs (p<0.001, χ(2) test). We analyzed these AFAs using EEG topography, and compared them with ictal fast activity (IFA) corresponding to tonic spasms observed later in the same patients after they had developed WS. We also investigated the clinical and EEG features in these patients. AFAs were first observed commonly at 4-5 months of CA, before the onset of WS. AFA topographic maps revealed posterior predominance in 11 of the 12 patients; IFA maps also showed posterior predominance but were more widely distributed. We propose that, though AFAs and IFAs are different, they share certain aspects of their pathophysiology, and that the maturational process of the occipital cortex plays an important role in the shared aspects. Since AFAs are observed before the onset of WS, they can be considered a sign that WS is imminent.

A phantom experiment for the evaluation of whole body exposure during BNCT using cyclotron-based epithermal neutron source (C-BENS).

At Kyoto University Research Reactor Institute (KURRI), cyclotron-based epithermal neutron source was installed in December 2008, and the supplementary construction works have been performed. As of December 2010, the various irradiation characteristics important for BNCT were mostly evaluated. The whole body exposure during BNCT medical irradiation is one of the important characteristics. In this article, measurements of absorbed dose for thermal and fast neutrons and gamma-ray at ten positions corresponding to important organs are reported.

Relation of spasms and myoclonus to suppression-burst on EEG in epileptic encephalopathy in early infancy.

PURPOSE: This study was intended to clarify the relation between spasms in series and a suppression-burst (SB) EEG pattern which have a common nature of repetitive bursting activity in epileptic encephalopathy in early infancy. METHODS: The ictal EEG traces of spasms were temporally compressed and expanded to study the beginning and ending phases of series along with their spectral analysis in two patients with Ohtahara syndrome (OS) and one with early myoclonic encephalopathy (EME). The EEG bursts associated with myoclonus were also investigated. RESULTS: A mutual transition was indicated between the ictal activity of spasms and the bursts in the peri-series SB on EEG. Gamma rhythm was detected in common in the ictal activity and the peri-series and interictal bursts on EEG, and also in the bursts with myoclonus. CONCLUSION: The relation between the ictal activity of spasms and SB on EEG was shown to be close. The generative mechanisms of spasms and myoclonus might be linked to the bursting tendency intrinsic to immature brain function.

Longitudinal study of auditory brainstem response in leigh syndrome.

To assess the utility of auditory brainstem response (ABR) in diagnosing brainstem changes in patients with Leigh syndrome (LS), we performed a longitudinal study of five patients with LS using both ABR and neuroimaging techniques (CT and MRI). The brainstem components of the initial ABRs we performed on the patients were abnormal in all five patients. In four of the patients, these abnormal findings preceded any clinical signs of brainstem impairment. Improvements in clinical findings were reflected in improvements in ABR findings in three patients. In one of these three patients, improvements in clinical findings were also reflected in improvements in MRI findings. In the other two patients, MRI findings showed no improvements, despite the improvements in clinical findings. In two of our patients, ABR clearly revealed functional improvements in the brainstem which were not revealed by MRI. Therefore, we conclude that ABR is an essential diagnostic technique for patients with LS.

Waist-to-height ratio, a simple and practical index for assessing central fat distribution and metabolic risk in Japanese men and women.

OBJECTIVE: The normal body mass index (BMI) range, as defined by the World Health Organization (WHO), is quite wide, and some people within this range may have excessive central fat accumulation and elevated metabolic risks. We hypothesize that the waist-to-height ratio (W/Ht), an effective index for assessing central fat distribution among Japanese people, can be used to identify subjects who are at higher metabolic risk within the normal as well as the overweight range. METHODS: We investigated: (1). the values of BMI, waist circumference, and W/Ht in 6141 men and 2137 women at various age intervals and calculated gender (female to male) ratios for all these anthropometric indices; (2). the relation between age and each anthropometric index, between age and morbidity index for coronary risk factors (sum of the scores for hyperglycemia, hypertension, hypertriglyceridemia, hypercholesterolemia, and low HDL cholesterol; one point for each condition if present), and between morbidity index for coronary risk factors and each anthropometric index; (3). the distributions of the subjects, using various proposed indices of waist circumference (those suggested by WHO, the Japan Society for the Study of Obesity, and the Asia-Pacific perspective), and our proposed boundary value, W/Ht 0.5, among the WHO categories based on BMI; (4). the metabolic risks (coronary risk factors, hyperuricemia, high gamma-glutamyltransferase, and fatty liver diagnosed by ultrasonography), and exercise habits among normal-weight subjects with W/Ht<0.5 or >or=0.5. RESULTS: (1). For the various anthropometric indices in all age groups, the gender ratio for W/Ht was closest to 1, indicating that a single set of values for W/Ht can be used for men and women. (2). Height correlated negatively with age. Among the anthropometric indices, only W/Ht correlated positively with age for both men and women, while age and all anthropometric indices, except height, correlated positively with the morbidity index for coronary risk factors. For both men and women, the highest correlation coefficient was between W/Ht and the morbidity index for coronary risk factors. (3). Nearly all overweight men and women (BMI>or=25) had W/Ht>or=0.5 (98.5% of men and 97.5% of women). None of the underweight subjects had W/Ht>or=0.5. However, 45.5% of men and 28.3% of women of normal weight (BMI 18.5-<25) had W/Ht>or=0.5. W/Ht, of all the indices investigated, was the best index for signaling metabolic risk in the normal-weight subjects as well as the overweight subjects. (4). Age- and BMI-adjusted odds ratios for multiple metabolic risks, and history of no habitual exercise were significantly higher in normal-weight men and women with W/Ht>or=0.5 than in others of normal weight. CONCLUSIONS: Waist circumference is improved by relating it to height to categorized fat distribution of different genders and ages. W/Ht is a simple and practical anthropometric index to identify higher metabolic risks in normal and overweight Japanese men and women.

Prevalence of atopic dermatitis in Japanese adults.

BACKGROUND: Adult atopic dermatitis (AD) in Japan has become a significant social problem, with as many as one-third of adult patients with severe AD absenting themselves from work or classes due to aggravation of the disease. Reports of such patients have become increasingly common in recent years. Despite the pressing need for epidemiological studies to clarify the prevalence and distribution of AD and to determine its aetiology, no previous research has been carried out on the prevalence of AD within the adult population in Japan. OBJECTIVES: To clarify the prevalence of adult AD in Japan, using the U.K. Working Party's diagnostic criteria. METHODS: The subjects of this study were mostly government officials or their family members visiting the Medical Center of Health Science, Toranomon Hospital in Tokyo for annual health check-ups in the period from September 1997 to August 1998. Questionnaires completed by 10 762 persons (8076 men and 2686 women) aged 30 years or above were analysed. The questionnaire consisted of 14 questions on allergic disease. The U.K. Working Party's diagnostic criteria were used after translation into Japanese. Three types of prevalence were used as indicators of prevalence: point, 1-year and lifetime prevalence. RESULTS: The point prevalence, 1-year prevalence and lifetime prevalence of AD in Japanese adults were 2.9%, 3.0% and 3.3%, respectively. No significant statistical differences were observed between the sexes or among age groups within each sex. The survey indicated that 88.6% of those who had ever had AD were currently affected by active AD, while 93.4% of those who had had at least one episode of AD in the past had experienced an episode over the previous year. CONCLUSIONS: This study gives the first indication of the prevalence of adult AD among the Japanese, based on the U.K. criteria. Both the internal and external validity of this study are believed to be high; it would be safe to conclude that the 1-year prevalence of AD in Japanese adult populations living in urban areas is 3.0%.

The relationship between paroxysmal kinesigenic choreoathetosis and epilepsy.

PURPOSE: To clarify the relationship between paroxysmal kinesigenic choreoathetosis (PKC) and epilepsy, we investigated the clinical and electroencephalographic (EEG) findings of patients with familial PKC and epilepsy, as well as sporadic cases with both PKC and epilepsy. PATIENTS AND METHODS: Patients consisted of 12 familial cases from seven families and three sporadic cases. The period of follow-up ranged from 17 months to 33 years, 7 months (average: 16 years, 8 months). During the follow-up, a total of 163 EEGs (11 EEGs per subject) were studied, including interictal and ictal EEGs. RESULTS: Transient epileptic discharges were found in ten of the 15 patients (66.7 %) during the clinical course. As for focus, centro-midtemporal and frontal spikes were most often observed. The ictal EEG of an afebrile convulsion in one patient showed a partial seizure with secondary generalization which originated from the frontal area. CONCLUSIONS: It appears that patients who suffer from both PKC and epilepsy have a functional abnormality of the cerebral cortex, particularly in the perirolandic and frontal regions.

Clinical spectrum of epileptic spasms associated with cortical malformation.

The spectrum of clinico-electrical characteristics of epileptic spasms associated with cortical malformation was studied in detail. The subjects were 15 patients suffering from spasms and cortical malformation demonstrated by MRI. The types of cortical malformation causing spasms were various, including hemimegalencephaly, diffuse pachygyria, focal cortical dysplasia, and polymicrogyria. Ohtahara syndrome was diagnosed in 3 patients, and West syndrome in 8. Symptomatic localization-related epilepsy preceded West syndrome in 4 patients, and a transition from Ohtahara syndrome to West syndrome was observed in one. West syndrome was followed by symptomatic generalized epilepsy including Lennox-Gastaut syndrome in 4 patients. Nine patients showed a condition which was labeled "epilepsy with partial seizures and spasms" (EPS) and characterized by the coexistence of partial seizures and spasms, and multifocal epileptic discharges on EEG. Spasms occurred only as EPS in 5 patients. EPS appeared following Ohtahara syndrome or West syndrome in 4 patients, and showed a transition to symptomatic localization-related epilepsy in 4. However, EPS did not evolve into generalized epilepsy, and persisted until the time of last follow-up in 5 patients. Therefore, the clinico-electrical pictures of patients with spasms and cortical malformation were diverse and not always limited within those of typical generalized epilepsy.

Incidence of epileptic discharge in various epileptic syndromes.

Three hundred eight patients with childhood and adolescent epilepsy were examined to clarify the incidence of epileptic discharges on initial and follow-up electroencephalograms. Epileptic discharges were found in 75.6% patients on the initial electroencephalogram, which is higher than figures previously reported for adults. The cumulative incidence of epileptic discharges was 92.3% by the third electroencephalogram recording. However, in 17.1% patients with nonspecific idiopathic generalized epilepsy, no epileptic discharges were found even after three electroencephalogram recordings. The incidence of epileptic discharges in patients with generalized epilepsy (84.3%) was significantly higher than in patients with localization-related epilepsy (71.6%). The incidence of epileptic discharges in patients with partial seizures was lower than those in patients with generalized seizures. The incidence of epileptic discharges was low in the 0- to 3-year-old and 15- to 20-year-old groups, and high in the 3- to 12-year-old groups. In the positive epileptic discharge patients, 38.8% of electroencephalograms were abnormal only during the waking or sleeping portion of the recordings. Knowing the incidence of epileptic discharges for each type of epilepsy will be useful in planning further electroencephalogram research and performing electroencephalograms in the clinical setting.

Utility of the scalp-recorded ictal EEG in childhood epilepsy.

PURPOSE: To evaluate the usefulness of the scalp-recorded ictal EEGs in diagnosing childhood epilepsy. METHODS: We analyzed the ictal EEGs of 259 seizures in 183 patients who visited the department of child neurology, Okayama University Medical School, during the past 6 years. RESULTS: We divided all seizures into the following four categories, according to the diagnostic usefulness of ictal EEGs in determining the seizure type: 1. (a) Ictal EEGs confirmed the diagnosis of the seizure type based on seizure symptoms (101 seizures); (b) Ictal EEGs aided in the classification of the seizure type based on the seizure symptoms (101 seizures); (c) Ictal EEGs corrected errors in the classification (37 seizures); and (d) Ictal EEGs revealed previously unreported/undocumented seizure type (20 seizures). 2. Of the 37 misdiagnosed seizures (group C), 11 were nonepileptic seizures misdiagnosed as epileptic seizures, eight were complex partial seizures (CPS) misdiagnosed as the other seizure types, and 10 were other seizure types misdiagnosed as CPSs. 3. Of the 20 previously unreported/undocumented seizures (group D), nine were myoclonic seizures, five were absence seizures, five were CPS, and one was tonic spasms. 4. Seventy-two patients had CPS. Among them, 11 patients showed no epileptic spikes in their interictal EEG recordings. Therefore, ictal recordings confirmed the diagnosis of epilepsy. CONCLUSIONS: Ictal EEG recording is a very useful diagnostic tool not only for determining seizure types, but also for uncovering the existence of the unsuspected seizure types. It supplies the physician with useful information for the classification and the treatment of epilepsy. In particular, ictal EEGs are useful in diagnosing patients with CPS.

Combined use of sphenoidal electrodes and the dipole localization method for the identification of the mesial temporal focus.

UNLABELLED: We attempted to sub-classify four cases who show temporal spikes on standard scalp electroencephalogram (EEG), using sphenoidal electrodes and the dipole localization METHOD: In a case with mesial temporal epilepsy, spikes showed phase reversal in a sphenoidal electrode, and the spike dipoles were estimated to be in the mesial temporal lobe. In a case with lateral temporal epilepsy, spikes showed no phase reversal in a sphenoidal electrode, and the spike dipoles were estimated to be in the lateral temporal lobe. In two cases out of four, spikes showed phase reversal in sphenoidal electrodes, whilst the dipoles were estimated to be in the frontal lobe. Clinical features also suggested a diagnosis of frontal lobe epilepsy. In one of the two cases in which frontal lobe epilepsy was suspected, ictal dipoles as well as interictal spike dipoles indicated participation of the frontal lobe in the genesis of seizures. Nevertheless, only mesial temporal lobectomy was performed based on results obtained by invasive subdural electrodes. As a result, seizures were not controlled. Although sphenoidal electrodes were useful for differentiating between mesial and lateral temporal lobe foci, it is advisable to use them in combination with the dipole localization method to identify frontal lobe foci.

Predictors and underlying causes of medically intractable localization-related epilepsy in childhood.

The goal of this study is to clarify the prognostic factors in childhood localization-related epilepsy in a tertiary medical center. Children (n = 113) with symptomatic and cryptogenic localization-related epilepsy were divided into groups of intractable patients (average seizure frequency: one or more per month during the 6 months before the last follow-up; n = 40) and well-controlled patients (no seizures for at least 1 year before the last follow-up; n = 73). Clinical and electroencephalogram (EEG) factors were examined to elucidate prognostic factors. The subtypes of epilepsies and causes were also investigated. Univariate analyses indicated that the following factors were correlated with seizure outcome: (1) seizure type at the first visit; (2) seizure frequency; (3) underlying cause; (4) age at onset of epilepsy; (5) status epilepticus occurring as the first seizure and before the first visit; and (6) diffuse epileptic discharges on first visit interictal EEGs. Multivariate analyses revealed that seizure type at the first visit, seizure frequency, status epilepticus before the first visit, and underlying causes were significant independent predictive factors. The rate of intractable patients was highest in multilobar epilepsy, followed by frontal-lobe epilepsy. Regarding etiologies, the intractable group contained nine patients with encephalitis of unknown origin and three each with localized cortical malformation and mesial temporal sclerosis.

Electroencephalographic changes and their regional differences during pediatric cardiovascular surgery with hypothermia.

Monitoring brain function by EEG is an important means of preventing cerebral insults in pediatric cardiovascular surgery. We studied intraoperative EEG changes and their regional differences associated with hypothermia and brain ischemia. The subjects of this study consisted of 13 children ranging in age from 4 months to 4 years and 6 months. Multi-channel EEGs were recorded using a portable digital EEG system, and the EEG changes were examined by visual inspection and computerized analyses. The results were as follows. (1) During cooling, a discontinuous EEG pattern was transiently observed in four patients, and this phenomenon indicated rapid suppression of cerebral function and subsequent adaptation. (2) Regarding the patterns of change in equivalent potentials induced by hypothermia, there were two different patterns depending on the degree of hypothermia, and the borderline rectal temperature was found to be around 32 degrees C. (3) During cooling, regional differences in the changes in equivalent potentials were observed in nine patients. A decrease in slow waves was marked in the occipital head area, and a decrease in fast waves was prominent in the anterior head area. (4) Arterial hypotension caused transient EEG abnormalities. Of them, bilaterally synchronous rhythmic high voltage slow waves were remarkable and exhibited bifrontal or bicentral dominance. (5) The EEG changes induced by hypothermia were influenced not only by the rectal temperature itself, but also by the rate of change in rectal temperature, and we speculated that this phenomenon was a result of adaptation. In intraoperative EEG monitoring, these findings constitute the basis for early detection of a cerebral hypoxic-ischemic state during pediatric cardiovascular surgery.

Frequent presence of Helicobacter pylori genome in the saliva of patients with hyperemesis gravidarum.

Recently, possible involvement of Helicobacter pylori (H. pylori) in hyperemesis gravidarum have been reported based on serological studies and the therapeutic effects of antibiotics. In this study, we examined for the presence of H. pylori genome [by (PCR) of saliva] in combination with serological techniques. Thirty-four patients with hyperemesis and 29 normal pregnant subjects were examined for serum anti-H. pylori IgG antibodies and PCR of saliva. By serum antibody test, 16 of 34 hyperemesis patients (47.5%) were positive for anti-H. pylori IgG antibody, while 6 of 29 control subjects (20.6%) were positive (chi2 p < 0.0005). PCR revealed positive H. pylori genome in 21 cases out of 34 hyperemesis (61.8%, 14 of 16 patients positive for H. pylori antibody and 7 of H. pylori-antibody-negative 18 patients) and 8 of 29 control subjects (27.6%) (chi2 p < 0.000001). We suggest chronic infection of H. pylori as one of the important factors on the pathogenesis of hyperemesis gravidarum even though it may not be the single cause of the disorder.

Myoclonic seizures combined with partial seizures and probable pathophysiology of secondary bilateral synchrony.

OBJECTIVE: We report on a patient who showed an unusual transition from complex partial seizures to a combination of myoclonic seizures and partial seizures, and then to isolated myoclonic seizures. The pathophysiological mechanism of the myoclonic seizures in this uncommon condition was studied. METHODS: The interhemispheric small time differences were estimated in the ictal EEG discharges of myoclonic seizures for differentiation between primary and secondary bilateral synchrony. The estimation was performed by coherence and phase analysis based on the two-dimensional autoregressive model. RESULTS: The estimated interhemispheric time differences were at most 27.4 ms. The ictal activity of the myoclonic seizures was suggested to originate from a cortical focus in the right hemisphere, which was also the origin of the partial seizures. CONCLUSION: The patient was considered to have an unusual type of myoclonic seizures with a probable pathophysiological mechanism of secondary bilateral synchrony.

High density cultivation of two strains of iron-oxidizing bacteria through reduction of ferric iron by intermittent electrolysis.

Electrolytic cultivation was applied to Leptospirillum ferrooxidans strains P3A and CF27, which use ferrous iron to respire aerobically. Ferrous iron was supplied to the bacteria by intermittent electrolytic reduction of ferric iron as electron shuttle using an electrode. The yield of L. ferrooxidans and strain CF27 reached 20- and 50-fold, respectively, higher density than were achievable yields without electrolysis. The time required to obtain high density depended not on the growth ratio, but rather on the original growth rate of each strain.