Quantification of Oscillatory Shear Stress from Reciprocating CSF Motion on 4D Flow Imaging.

BACKGROUND AND PURPOSE: Oscillatory shear stress could not be directly measured in consideration of direction, although cerebrospinal fluid has repetitive movements synchronized with heartbeat. Our aim was to evaluate the important of oscillatory shear stress in the cerebral aqueduct and foramen magnum in idiopathic normal pressure hydrocephalus by comparing it with wall shear stress and the oscillatory shear index in patients with idiopathic normal pressure hydrocephalus. MATERIALS AND METHODS: By means of the 4D flow application, oscillatory shear stress, wall shear stress, and the oscillatory shear index were measured in 41 patients with idiopathic normal pressure hydrocephalus, 23 with co-occurrence of idiopathic normal pressure hydrocephalus and Alzheimer-type dementia, and 9 age-matched controls. These shear stress parameters at the cerebral aqueduct were compared with apertures and stroke volumes at the foramen of Magendie and cerebral aqueduct. RESULTS: Two wall shear stress magnitude peaks during a heartbeat were changed to periodic oscillation by converting oscillatory shear stress. The mean oscillatory shear stress amplitude and time-averaged wall shear stress values at the dorsal and ventral regions of the cerebral aqueduct in the idiopathic normal pressure hydrocephalus groups were significantly higher than those in controls. Furthermore, those at the ventral region of the cerebral aqueduct in the idiopathic normal pressure hydrocephalus group were also significantly higher than those in the co-occurrence of idiopathic normal pressure hydrocephalus with Alzheimer-type dementia group. The oscillatory shear stress amplitude at the dorsal region of the cerebral aqueduct was significantly associated with foramen of Magendie diameters, whereas it was strongly associated with the stroke volume at the upper end of the cerebral aqueduct rather than that at the foramen of Magendie. CONCLUSIONS: Oscillatory shear stress, which reflects wall shear stress vector changes better than the conventional wall shear stress magnitude and the oscillatory shear index, can be directly measured on 4D flow MR imaging. Oscillatory shear stress at the cerebral aqueduct was considerably higher in patients with idiopathic normal pressure hydrocephalus.

Mineral trioxide aggregate suppresses pro-inflammatory cytokine expression via the calcineurin/nuclear factor of activated T cells/early growth response 2 pathway in lipopolysaccharide-stimulated macrophages.

AIM: To elucidate mechanisms by which mineral trioxide aggregate (MTA) suppresses pro-inflammatory cytokine mRNA expression in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages. METHODOLOGY: Mineral trioxide aggregate extracts were prepared by immersing set ProRoot MTA in culture medium. RAW264.7 cells were cultured in the presence of LPS and MTA extracts. mRNA expression levels of interleukin (IL)-1α, IL-6, early growth response 2 (Egr2), suppressor of cytokine signalling 3 (Socs3) and IL-10 were quantified with reverse transcription-quantitative polymerase chain reaction. Phosphorylation of nuclear factor-kappa B (NF-κB) p65 in RAW264.7 cells was analysed by Western blotting. Intracellular calcium imaging was performed with Fluo-4 AM. The activity of nuclear factor of activated T cells (NFAT) was determined by luciferase assays. Enforced expression and silencing of Egr2 in RAW264.7 cells were carried out using an expression vector and specific RNAi, respectively. In vivo kinetics of Egr2+ cells in MTA-treated rat molar pulp tissues were examined using immunohistochemistry. Data were analysed by one-way analysis of variance, followed by the Tukey-Kramer test (P < 0.05). RESULTS: Exposure to MTA extracts resulted in reduced mRNA expression levels of IL-1α and IL-6, as well as reduced expression of phosphorylated NF-κB, in LPS-stimulated RAW264.7 cells. Exposure to MTA extracts induced Ca2+ influx, which was blocked by NPS2143, an antagonist of calcium-sensing receptor (CaSR); Ca2+ influx then triggered activation of calcineurin/NFAT signalling and enhanced mRNA expression of Egr2. Enforced expression of Egr2 in RAW264.7 cells promoted the expression of both IL-10 and Socs3. In vivo application of MTA onto rat molar pulp tissue resulted in the appearance of Egr2-expressing cells that coexpressed CD163, a typical M2 macrophage marker. CONCLUSIONS: Mineral trioxide aggregate extracts induced downregulation of IL-1α and IL-6 in LPS-stimulated RAW264.7 cells via CaSR-induced activation of calcineurin/NFAT/Egr2 signalling and subsequent upregulation of IL-10 and Socs3.

Association between excessive supraventricular ectopy and subclinical cerebrovascular disease: a population-based study.

BACKGROUND AND PURPOSE: The association between an increased supraventricular ectopic beat (SVEB) and subclinical cerebrovascular disease remains unclear. Given the emerging concept that an increased SVEB is a marker of atrial cardiomyopathy or atherosclerosis burden, we sought to determine whether excessive supraventricular ectopic activity (ESVEA) is associated with a higher burden of subclinical cerebrovascular disease in the middle-aged to older cohort with neither apparent stroke nor atrial fibrillation. METHODS: We conducted a cross-sectional population-based study of 462 men (mean age, 68.1 years) who underwent 24-h Holter electrocardiography and brain magnetic resonance imaging. ESVEA was defined as the presence of >10 SVEBs/h. Subclinical cerebrovascular diseases were defined as silent brain infarct (SBI), white matter hyperintensity (WMH) and intracranial atherosclerotic stenosis (ICAS). The association of ESVEA with the presence of subclinical cerebrovascular diseases was adjusted for potential confounding covariates. RESULTS: A total of 88 (19.0%) participants had ESVEA and 81 (17.5%), 91 (19.7%) and 109 (23.6%) had SBI, WMH and ICAS, respectively. In multivariable-adjusted Poisson regression with robust error variance, ESVEA was associated with the presence of WMH (relative risk, 1.58; 95% confidence interval, 1.06-2.36) and ICAS (relative risk, 1.49; 95% confidence interval, 1.02-2.18), but not with that of SBI (relative risk, 1.32; 95% confidence interval, 0.86-2.01). These associations were consistent when the graded distributions of subclinical cerebrovascular diseases were applied as outcomes in ordinal logistic regression. CONCLUSIONS: The ESVEA was independently associated with higher burdens of WMH and ICAS. This suggests that increased SVEBs might improve risk stratification of individuals at high risk of subclinical cerebrovascular disease and consequently apparent ischaemic stroke.

Prognostic usefulness of arm circumference and nutritional screening tools in older patients with cardiovascular disease.

BACKGROUND AND AIM: Arm circumference (AC) and nutritional screening tools have been shown to have prognostic capability in patients with cardiovascular disease (CVD). This study aimed to compare the prognostic predictive capabilities of AC and nutritional screening tools in older patients with CVD. METHODS AND RESULTS: The study population consisted of 949 admitted patients ≥60 years old with CVD. Patients underwent AC measurement and nutritional screening before hospital discharge. We used the controlling nutritional status index (CONUT), the geriatric nutritional risk index (GNRI), and the prognostic nutritional index (PNI) as nutritional screening tools. The end point of the study was all-cause mortality. The mean age of the study population was 72.3 ± 7.2 years, and 68.2% of the patients were male. A total of 130 deaths occurred over a median follow-up period of 2.2 years (interquartile range, 1.1-3.8 years). After adjusting for other prognostic factors, AC (hazard ratio [HR]: 0.59; p < 0.001), CONUT (HR: 0.82; p = 0.016), GNRI (HR: 0.77; p = 0.040), and PNI (HR: 0.80; p = 0.014) were significant predictors of mortality. However, adding AC to the multivariate-adjusted model (0.739 vs. 0.714, respectively; p = 0.037), but not CONUT, GNRI, or PNI (0.724, 0.717, and 0.723 vs. 0.714; p = 0.072, p = 0.306, and p = 0.127, respectively), significantly increased the area under the curve on receiver operating characteristic curve. CONCLUSIONS: AC, but not nutritional screening tools, plays a complementary role to preexisting prognostic factors for predicting prognosis in older patients with CVD.

Copolymerisation of ethylene with polar monomers by using palladium catalysts bearing an N-heterocyclic carbene-phosphine oxide bidentate ligand.

We report the synthesis and characterisation of palladium complexes bearing an N-heterocyclic carbene-phosphine oxide bidentate ligand and their use as catalysts for ethylene polymerisation and ethylene/polar monomer copolymerisation.

Fungal meningitis caused by Lomentospora prolificans after allogeneic hematopoietic stem cell transplantation.

Central nervous system lomentosporiosis is a rare pathological condition in immunocompromised patients. We describe a fatal case of meningitis caused by Lomentospora prolificans (which was previously named Scedosporium prolificans), after an allogeneic hematopoietic stem cell transplantation (allo-HSCT). To our knowledge, no cases of Lomentospora meningitis following allo-HSCT have been reported previously. Particularly in neutropenic patients, it is important to consider L. prolificans when a fungal infection is suspected and antifungal agents are ineffective.

The effect of denture installation at mandibular rest position on unsteady motion of the centre of pressure in postural sway.

Wearing dentures has been believed to decrease the instability of the postural sway using the total length of centre of pressure (CoP) trajectory or the magnitude of its variability. However, the physical aspects of the postural sway have not been taken into account while evaluating the CoP in patients who wear dentures. The CoP fluctuations are found to show a random walk process. Therefore, changes in the random movement of CoP caused by wearing dentures should be examined by nonlinear dynamics that enables analysis of the characteristics found in the random movement. We evaluated the effect of complete denture installation on CoP sway for twenty-six edentulous patients by performing the following steps. First, we excluded subjects who did not show crossover in spectral analyses. Then, we evaluated the spectral characteristics and phase shifts of the velocities of CoP sway for the subjects who showed crossover. We found that wearing complete dentures decreased the fluctuations in the high-frequency part of the power spectral density (PSD) and the phase shift in the mediolateral direction. On the other hand, we also found that the use of complete dentures decreased the fluctuations of PSD amplitude in the anteroposterior direction. From the point of view of the kinetic energy of the musculoskeletal system, we suggested that the use of complete dentures could reduce the energy consumption for the standing posture.

Estimation of minimum oral tract constriction area in sibilant fricatives from aerodynamic data.

Speech screening of sibilant fricative phonemes is an important tool for oral health care. Nevertheless, screening as a function of quantitative geometrical markers is mostly limited to teeth features whereas the minimum area of the narrowed air passage upstream from the tooth is known to be a key production feature. The minimum area is estimated from non-invasive aerodynamic measurements using a laminar flow model. The influence of viscid flow losses on the area estimation is shown to be negligible. Current data suggest that speech screening is most effective for phoneme /s/, which supports common practice in oral health care.

Isoquinolino[4,3,2-de]phenanthridine: synthesis and its use in 1,3-dipolar cycloadditions to form nitrogen-containing polyaromatic hydrocarbons.

The synthesis of the novel azomethine ylide, isoquinolino[4,3,2-de]phenanthridine, and its use in 1,3-dipolar cycloaddition with various alkenes and alkynes to form the corresponding fused pyrrolidines and pyrroles is reported.

Dielectric properties of fluorine substituted hydroxyapatite: the effect of the substitution on configuration of hydroxide ion chains.

Hydroxyapatite (HAp) [Ca5(PO4)3OH] is an extremely popular biomaterial. Moreover, HAp durability is well-known to be enhanced by fluoridation. We prepared fluoridated HAp (F-HAp; Ca5(PO4)3(OH)1-xFx) ceramics by substituting F- ions for OH- ions of HAp. F-substitution dependence of dielectric properties in F-HAp was measured to detect the configuration change of OH- ion chains. Dielectric relaxation of two kinds was observed. Each kind had a different relaxation time. Faster relaxation, which is associated with the reorientation motion of OH- ions, was only observed at the low F-substitution range (0 ≤x < 0.35). The relaxation strength decreased as the F-substitution increased. It became zero at x = 0.35, suggesting that F-substitution induces hydrogen bonds. One F- ion substituted for an OH- ion forms two hydrogen bonds with the two neighboring OH- ions and inhibits the motion of OH- ions, which results in some kind of ordered configuration in F-HAp. The configuration might be an origin that enhances the durability of the F-HAp.

Sibilant /s/ simulator based on computed tomography images and dental casts.

The sibilant /s/ is produced by raising the tongue against the roof of the mouth to form a narrow constriction, which is adjusted so that the airstream emerging from it impinges on the incisors. However, the location where the sibilant sound occurs is unclear, as are the details of the mechanisms of its generation. In this study, we used a realistically shaped replica produced with a three-dimensional printer and demonstrated that turbulent flow was generated in the oral tract near the incisors and lips and that sufficiently developed turbulent flow generated a sound source up to 20,000 Hz at 333, 500, and 667 cm(3)/sec, which agrees with the range of physiological flow rates typical for /s/. The characteristics of the sound spectra agreed with those of the sibilant /s/ sound emitted by our control individual. Such a physical perspective could yield knowledge useful for oral surgery and speech science - for example, to predict how the generation of sibilants may be occasionally affected by orthodontic and prosthodontic treatments.

PGE(2) -EP(2) signalling in endothelium is activated by haemodynamic stress and induces cerebral aneurysm through an amplifying loop via NF-κB.

BACKGROUND AND PURPOSE: Cerebral aneurysm is a frequent cerebrovascular event and a major cause of fatal subarachnoid haemorrhage, but there is no medical treatment for this condition. Haemodynamic stress and, recently, chronic inflammation have been proposed as major causes of cerebral aneurysm. Nevertheless, links between haemodynamic stress and chronic inflammation remain ill-defined, and to clarify such links, we evaluated the effects of prostaglandin E(2) (PGE(2) ), a mediator of inflammation, on the formation of cerebral aneurysms. EXPERIMENTAL APPROACH: Expression of COX and prostaglandin E synthase (PGES) and PGE receptors were examined in human and rodent cerebral aneurysm. The incidence, size and inflammation of cerebral aneurysms were evaluated in rats treated with COX-2 inhibitors and mice lacking each prostaglandin receptor. Effects of shear stress and PGE receptor signalling on expression of pro-inflammatory molecules were studied in primary cultures of human endothelial cells (ECs). KEY RESULTS: COX-2, microsomal PGES-1 and prostaglandin E receptor 2 (EP(2) ) were induced in ECs in the walls of cerebral aneurysms. Shear stress applied to primary ECs induced COX-2 and EP(2) . Inhibition or loss of COX-2 or EP(2) in vivo attenuated each other's expression, suppressed nuclear factor κB (NF-κB)-mediated chronic inflammation and reduced incidence of cerebral aneurysm. EP(2) stimulation in primary ECs induced NF-κB activation and expression of the chemokine (C-C motif) ligand 2, essential for cerebral aneurysm. CONCLUSIONS AND IMPLICATIONS: These results suggest that shear stress activated PGE(2) -EP(2) pathway in ECs and amplified chronic inflammation via NF-κB. We propose EP(2) as a therapeutic target in cerebral aneurysm.

Treatment of spontaneous intradural vertebral artery dissections.

Spontaneous intradural vertebral artery dissections may cause subarachnoid hemorrhage and often result in devastating damage. Increased use of noninvasive imaging studies has allowed larger numbers of patients to be diagnosed. In addition, intracranial vertebral artery dissection tends to induce multiple lesions affecting both intracranial vertebral arteries recurrently. Although unruptured dissections in this area usually have a benign nature, some authors have reported on the incidence of rupture from this lesion. Once hemorrhage from a dissecting vessel wall has occurred, it needs to be treated in the acute phase because of the high risk of rebleeding resulting in high morbidity and mortality. From December 2004 to July 2010, we managed 47 patients with spontaneous vertebral artery dissection, 31 patients were ruptured and 16 were unruptured. All patients who suffered from subarachnoid hemorrhage were treated with endovascular procedures. Most of the patients with unruptured dissection received medical therapy, but if the aneurysmal dilatation persisted or grew, surgical interventions were performed. Stenting with or without coils was deployed for 13 patients with posterior inferior cerebellar artery involvement at the site of dissection and/or were affected on the dominant side. In some patients, stenting was performed even if they were in the acute phase. For other ruptured patients, internal coil trappings were performed. Six patients died due to severe initial subarachnoid hemorrhage and one patient, who underwent stent deployment with coils for the dominant vertebral artery, with bilateral dissection continuing to the basilar artery died due to rerupture while the next additional coiling was planning. There were two cases of complications related to the intervention. During the follow-up period no bleeding occurred in any of the patients except for the previously mentioned patient. In conclusion, internal coil trapping or stent placement with or without coils was effective in preventing rebleeding of ruptured vertebral artery dissection. If the dissection is unruptured, it is necessary to detect the risk of bleeding with careful watching and when progress appears to be made, patients should be treated promptly. Stent-assisted therapy for preserving the patency of the parent artery and major branches is a promising treatment for vertebral artery dissection, even in the acute stage of subarachnoid hemorrhage. However, the risk of acute rerupture and recurrence remains even with the porous stent placement with or without coils.

Effect of cyclic mechanical loading on osteoclast recruitment in periodontal tissue.

BACKGROUND AND OBJECTIVE: It is well accepted that cyclic mechanical loading induces osteoclastogenesis in periodontal tissue, but its molecular mechanisms are not well understood, in part because of a lack of appropriate models. In this study, we investigated a novel device that allows cyclic mechanical loading to be performed in a well-controlled manner. Furthermore, by employing this model, the effect of cyclic loading on osteoclast recruitment in the periodontal tissue was described. MATERIAL AND METHODS: By using a newly developed device, the cyclic loading of 20 n (reference loading corresponding to the fracture hardness of dietary pellets) and two excessive loadings (i.e. 30 and 40 n) were applied to maxillary right molars in rats for up to 7 d, and osteoclast recruitment in the periodontal tissue was evaluated by analyzing relevant marker proteins using immunohistochemistry. RESULTS: Osteoclastogenesis was induced by day 3 within alveolar bone subjected to a compression force of 30 n. With both 30 and 40 n loadings, cells that were positive to for tartrate-resistant acid phosphate, receptor activator of nuclear factor-kappaB ligand and osteoprotegerin were significantly increased in the alveolar bone/periodontal ligament in a time-dependent manner. CONCLUSION: A new device was developed that allows various levels of cyclic mechanical loading to be exerted. By using this device in rats, early events of osteoclast recruitment in the periodontal tissues were observed with excessive loadings in a time-dependent manner, indicating the usefulness of this model.

High aldolase with normal creatine kinase in serum predicts a myopathy with perimysial pathology.

OBJECTIVE: To study the clinical and pathological correlations of neuromuscular patients with a high aldolase and normal creatine kinase (CK) in serum at presentation or during a symptomatic exacerbation. METHODS: Records and muscle biopsies were retrospectively reviewed in a consecutive series of 12 patients. Pathological results were compared to 75 abnormal muscle biopsies associated with acquired immune or inflammatory myopathy syndromes and 14 muscle biopsies from patients with myopathies associated with serum anti-Jo-1 antibodies. RESULTS: All patients with selectively elevated serum aldolase had muscle discomfort (92%), weakness (proximal and distal) (50%), or both. Frequent systemic features included joint pain (75%), skin disorders (75%) and pulmonary involvement (50%). Electromyography patterns included normal (36%), non-irritable myopathy (45%) and irritable myopathy (18%). Jo-1 antibodies were not found in the five patients tested. The distinctive feature of muscle biopsies was perimysial pathology (92%), including acid phosphatase positive cellularity (83%) and fragmented connective tissue (75%). CONCLUSIONS: Selectively elevated serum aldolase is associated with syndromes including myopathies with discomfort and weakness, systemic disorders and myopathology in perimysial connective tissue. The myopathy with perimysial pathology and the associated clinical syndromes seen in our patients are similar to disorders associated with antisynthetase antibodies. In patients with muscle discomfort or mild weakness and a normal CK, measurement of serum aldolase can be useful in the evaluation of possible myopathies.

Plical resection in pre-temporal approach for basilar bifurcation aneurysms: preliminary surgical experience and cadaveric study.

OBJECT: Although a pre-temporal approach (PA) can provide a wide space for preservation of thalamoperforating atrteries in direct surgery for basilar bifurcation aneurysms (BBAs), it cannot always secure adequate proximal control. The authors described the advantages of plical resection added to PA for BBAs. METHODS: Between October 1998 and April 2000, eight consecutive patients with BBAs were treated in the neurosurgical department of Kurashiki Central Hospital. Among them, five patients received direct clipping using this method. There were four females and one male, ages ranging from 61 to 77 (mean 70.8 years). Mean aneurysmal size and distance between the in"terclinoidal line and the aneurysmal neck was 4.5 and 9.5 mm, respectively. The operative procedures consisted of the following components; 1) fronto-temporal craniotomy with translocation of orbito-zygomatico-malar bone for PA, 2) preservation of lateral branches of the superficial sylvian veins, 3) resection of plica dural folds to increase the operative field up to the oculomotor nerve (OMN). RESULTS: Complete clipping was achieved without thalamic infarction or temporal contusion in all patients. Three of the five patients suffered from transient right OMN palsy which recovered within two months after surgery. CONCLUSION: Plical resection in the pre-temporal approach might be beneficial in the surgical treatment of BBAs when proximal control seems difficult.

Autosomal dominant moyamoya disease maps to chromosome 17q25.3.

BACKGROUND: Moyamoya disease (MMD) is an idiopathic steno-occlusive cerebrovascular disease that represents an important cause of stroke. However, etiology of the disease has remained largely unknown. METHODS: We previously showed that the inheritance pattern of MMD is autosomal dominant with incomplete penetrance. Here, we report the genome-wide parametric linkage analysis for MMD in 15 extended Japanese families. We conducted linkage analyses under two diagnostic classifications: narrow and broad. Affected member-only analysis was applied due to incomplete and age-dependent penetrance of the disease. RESULTS: Under both classifications, significant evidence of linkage was only observed on chromosome 17q25.3, with maximum multipoint logarithm of odds (lod) scores of 6.57 (under the narrow classification) and 8.07 (under the broad classification) at D17S704. Haplotype analysis revealed segregation of a disease haplotype in all families but one, and informative crossovers enabled mapping of the MMD locus to a 3.5-Mb region between D17S1806 and the telomere of 17q, encompassing 94 annotated genes. CONCLUSIONS: Our data suggest that there is a major gene locus for autosomal dominant moyamoya disease on chromosome 17q25.3.

Introduction to tractography-guided navigation: using 3-tesla magnetic resonance tractography in surgery for cerebral arteriovenous malformations.

OBJECTIVE: To examine the effectiveness of magnetic resonance (MR) tractography in surgery for cerebral arteriovenous malformations (AVMs). METHODS: A preoperative evaluation of major neural tracts around the nidus was carried out with 3-tesla (3 T) MR tractography in 25 consecutive patients with cerebral AVMs. The patients were 12 men and 13 women ranging in age from 4 to 60 years of age (mean age: 31.2 +/- 14.1 years). Twelve presented with hemorrhage. Images were obtained with T2-weighted turbo spin echo sequences, axial T1-weighted three-dimensional magnetization-prepared rapid acquisition gradient-echo (MPRAGE) sequences, three-dimensional time-of-flight MR angiography (3D TOF MRA), and thin-section diffusion-tensor imaging (DTI). RESULTS: The AVMs were obliterated in 22 of the 25 patients. A postoperative study of the MR tractography was carried out in 24 patients. In 21 patients, tracts were preserved and no postoperative neurological worsening was observed. Disruption of the tracts was found in 3 patients, and postoperative worsening was observed in 2 patients. However, no deterioration occurred in 1 patient with cerebellar AVM. CONCLUSIONS: Notwithstanding the limitations of this method, MR tractography can be considered useful for confirming the integrity of deviated tracts, for localizing deviated tracts, and for evaluating surgical risk, especially in cases of non-hemorrhagic AVM.

u-SHARE: web-based decision support/risk communication tool for healthcare consumers with unruptured intracranial aneurysms.

PURPOSE: Clinical management for unruptured intracranial aneurysms (UIA) is controversial and requires professional knowledge which is the main reason that patients have difficulty in making decisions. The purpose of this study is to develop a tool that aids healthcare consumers in making optimal shared decisions with decision analysis. METHODS: The decision model and relevant data were derived from published literature. A web-based decision analytic tool was designed to provide a systematic guide for patients to understand favorable treatment options, intrinsic uncertainty, and critical factors for decision making. Twenty-nine testers evaluated content appropriateness, usability and clinical usefulness of the tool. RESULTS: The decision analytic tool has been successfully implemented and evaluated. Testers generally judged the web-based decision analytic tool as functional and useful. Acceptance rate for decision analysis was higher in nonhealthcare professionals than health care professionals. CONCLUSIONS: Our decision analytic tool was well accepted especially by healthcare consumers. The tool enables UIA patients to enhance their knowledge and understanding toward optimal shared decision making and can be an alternative "structured informed consent tool".

Inheritance pattern of familial moyamoya disease: autosomal dominant mode and genomic imprinting.

BACKGROUND: Although the aetiology of moyamoya disease (MMD) has not been fully clarified, genetic analysis of familial MMD (F-MMD) has considerable potential to disclose it. OBJECTIVE: To determine the inheritance pattern and clinical characteristics of F-MMD to enable precise genetic analyses of the disease. METHODS: 15 highly aggregated Japanese families (52 patients; 38 women and 14 men) with three or more affected members were examined. The difference in categories of age at onset (child onset, adult onset and asymptomatic) between paternal and maternal transmission was compared by chi2 statistics. RESULTS: In all families there had been three or more generations without consanguinity, and all types of transmission, including father-to-son, were observed. Among a total of 135 offspring of affected people, 59 (43.7%) were patients with MMD or obligatory carriers. Affected mothers were more likely to produce late-onset (adult-onset or asymptomatic) female offspring (p = 0.007). CONCLUSIONS: The mode of inheritance of F-MMD is autosomal dominant with incomplete penetrance. Thus, in future genetic studies on F-MMD, parametric linkage analyses using large families with an autosomal dominant mode of inheritance are recommended. Genomic imprinting may be associated with the disease.