An epidemiological survey of moyamoya disease,unilateral moyamoya disease and quasi-moyamoya disease in Japan

Objectives

Moyamoya disease (MMD) is a unique occlusive disease of the bilateral internal carotid arteries in which, compensation for occlusion results in an enrichment of collateral arteries at the base of the brain. However, the epidemiology of unilateral MMD (typical angiographic evidence of MMD unilaterally with equivocal contralateral findings), and quasi-MMD (MMD present with inherited or acquired disorders) is poorly known. Here, a nationwide epidemiological survey was conducted to estimate the total numbers of patients, the annual incidence rates and prevalences of MMD, unilateral MMD and quasi-MMD in Japan.

Patients and methods

The neurosurgery, neurology and pediatrics departments that were listed in Japanese resident training programs were recruited to participate in this survey. Questionnaires were directly mailed to 2998 departments in February 2006.

Results

A total of 1183 departments replied to the questionnaire (39.5% response rate). It was estimated that there were 6670.9 MMD patients, 840.5 unilateral MMD patients and 430.4 quasi-MMD patients in Japan. The annual incidence rates of MMD, unilateral MMD and quasi-MMD are 1.13, 0.23 and 0.11/100,000, respectively, and the prevalences are 5.22, 0.66 and 0.34/100,000, respectively. These patients were mainly treated by neurosurgeons. An estimated total of 929.1 surgical interventions are performed in Japan annually.

Conclusion

This nationwide study reports the current epidemiologic status of MMD, unilateral MMD and quasi-MMD in Japan.     

Efficacy of the revascularization surgery for adult-onset moyamoya disease with the progression of cerebrovascular lesions

Object

In moyamoya disease, despite its progressive nature of the occlusive lesions in pediatric patients, the prevalence of the progression in adult patients is undetermined. Furthermore, the optimal timing of the revascularization surgery for progressive cases is controversial. To address these issues, we retrospectively investigate four cases with the adult-onset moyamoya disease manifesting as progression before revascularization surgery.

Methods

From March 2004 to May 2007, 49 patients with adult-onset moyamoya disease aged from 19 to 62 years old (mean 40.5) underwent superficial temporal artery–middle cerebral artery (STA–MCA) anastomosis on 63 hemispheres. All patients were strictly followed up by magnetic resonance (MR) imaging/angiography postoperatively. Twenty-seven hemispheres of 15 adult patients without surgery were also followed up at outpatient service during the same period. If the patients manifest as the progression of the steno-occlusive lesion on the hemisphere without surgery, they undergo revascularization surgery after the confirmation of hemodynamic compromise.

Results

During this period, 47 hemispheres including those of outpatient cases were conservatively followed up after initial diagnosis. Among them, six hemispheres (12.8%) of four patients had been proven to show apparent progression of steno-occlusive lesion and were subjected to revascularization surgery. Postoperative courses were uneventful in all four cases, and no patient suffered cerebrovascular event on the operated hemisphere after surgery.

Conclusion

Adult-onset moyamoya disease, either bilateral or unilateral, has a substantial risk for progression, and careful follow-up is necessary for asymptomatic hemisphere. Once the patient manifests as the progression of cerebrovascular occlusive lesions or ischemic symptoms, we recommend revascularization surgery after the confirmation of the hemodynamic compromise.     

Postoperative changes in the superficial temporal artery and the external carotid artery duplex sonography after extra-intracranial bypass surgery in European Moyamoya disease

Introduction

Despite Duplex ultrasonography being a noninvasive, easily repeatable, readily available and economical tool, this examination and its normal ranges are rarely described in Moyamoya disease (MMD).

Methods

Duplex ultrasonography examinations of the superficial temporal artery (STA) and external carotid artery (ECA) were performed preoperatively, postoperatively (within 30 days) and as follow-up exams (6 months postoperatively) after 32 cerebral revascularization procedures in 20 European patients with MMD.

Results

A significant higher mean diastolic flow of STA compared to preoperative values was found in postoperative (p < .000) and follow-up exams (p < .001) in Duplex ultrasonography. Postoperative and follow-up Duplex sonography of STA also showed a significantly higher mean systolic flow compared to preoperative values (p < .05 and p < .05). Also ECA showed significantly changes after bypass surgery (p < .05).

Conclusion

Duplex ultrasonography of STA is a reliable and non-invasive tool to investigate hemodynamic changes after bypass surgery and to detect bypass patency in European patients with MMD.     

A genome-wide study of moyamoya-type cerebrovascular disease in the korean population

Objective

Structural genetic variation, including copy-number variation (CNV), constitutes a substantial fraction of total genetic variability, and the importance of structural variants in modulating susceptibility is increasingly being recognized. CNV can change biological function and contribute to pathophysiological conditions of human disease. Its relationship with common, complex human disease in particular is not fully understood. Here, we searched the human genome to identify copy number variants that predispose to moya-moya type cerebrovascular disease.

Methods

We retrospectively analyzed patients who had unilateral or bilateral steno-occlusive lesions at the cerebral artery from March, 2007, to September, 2009. For the 20 subjects, including patients with moyamoya type pathologies and three normal healthy controls, we divided the subjects into 4 groups : typical moyamoya (n=6), unilateral moyamoya (n=9), progression unilateral to typical moyamoya (n=2) and non-moyamoya (n=3). Fragmented DNA was hybridized on Human610Quad v1.0 DNA analysis BeadChips (Illumina). Data analysis was performed with GenomeStudio v2009.1, Genotyping 1.1.9, cnvPartition_v2.3.4 software. Overall call rates were more than 99.8%.

Results

In total, 1258 CNVs were identified across the whole genome. The average number of CNV was 45.55 per subject (CNV region was 45.4). The gain/loss of CNV was 52/249, having 4.7 fold higher frequencies in loss calls. The total CNV size was 904,657,868, and average size was 993,038. The largest portion of CNVs (613 calls) were 1M-10M in length. Interestingly, significant association between unilateral moyamoya disease (MMD) and progression of unilateral to typical moyamoya was observed.

Conclusion

Significant association between unilateral MMD and progression of unilateral to typical moyamoya was observed. The finding was confirmed again with clustering analysis. These data demonstrate that certain CNV associate with moyamoya-type cerebrovascular disease.     

Comparative Analysis of Serum Proteomes of Moyamoya Disease and Normal Controls

Objective

The etiology and pathogenesis of moyamoya disease remain unclear. Furthermore, the definitive diagnostic protein-biomarkers for moyamoya disease are still unknown. The present study analyzed serum proteomes from normal controls and moyamoya patients to identify novel serological biomarkers for diagnosing moyamoya disease.

Methods

We compared the two-dimensional electrophoresis patterns of sera from moyamoya disease patients and normal controls and identified the differentially-expressed spots by matrix-assisted laser desorption/ionization-time-of flight mass spectrometry and electrospray ionization quadruple time-of-flight mass spectrometry.

Results

We found and analyzed 22 differently-expressed proteomes. Two proteins were up-regulated. Twenty proteins were down-regulated. Complement C1 inhibitor protein and apolipoprotein C-III showed predominantly changed expressions (complement C1 inhibitor protein averaged a 7.23-fold expression in moyamoya patients as compared to controls, while apolipoprotein C-III averaged a 0.066-fold expression).

Conclusion

Although our study had a small sample size, our proteomic data provide serologic clue proteins for understanding moyamoya disease.     

Preliminary Study of Neurocognitive Dysfunction in Adult Moyamoya Disease and Improvement after Superficial Temporal Artery-Middle Cerebral Artery Bypass

Objective

Moyamoya disease (MMD) is a chronic cerebrovascular occlusive disease of unknown etiology. In addition, the neurocognitive impairment of adults with MMD is infrequently reported and, to date, has not been well described. We attempted to determine both the neurocognitive profile of adult moyamoya disease and whether a superficial temporal artery-middle cerebral artery (STA-MCA) anastomosis can improve the neurocognitive impairment in exhibiting hemodynamic disturbance without stroke.

Methods

From September 2010 through November 2012, 12 patients with angiographically diagnosed MMD underwent STA-MCA anastomosis for hemodynamic impairment. Patients with hypoperfusion and impaired cerebrovascular reserve (CVR) capacity but without evidence of ischemic stroke underwent a cognitive function test, the Seoul Neuropsychological Screening Battery (SNSB). Five patients agreed to undergo a follow-up SNSB test. Data from preoperative and postoperative neurocognitive function tests were compared and analyzed.

Results

Five of 12 patients were enrolled. The median age was 45 years (range, 24-55 years). A comparison of preoperative to postoperative status of SNSB, memory domain, especially delayed recall showed significant improvement. Although most of the domains showed improvement after surgery, the results were not statistically significant.

Conclusion

In our preliminary study, large proportions of adult patients with MMD demonstrate disruption of cognitive function. This suggests the possibility of chronic hypoperfusion as a primary cause of the neurocognitive impairment. When preoperative and postoperative status of cognitive function was compared, memory domain showed remarkable improvement. Although further study is needed, neurocognitive impairment may be an indication for earlier intervention with reperfusion procedures that can improve cognitive function.     

An institutional experience of 26 patients with Moyamoya disease: A study from Northwest India

Aim:

Moyamoya disease (MMD) is a slowly progressive bilateral stenocclusive process of the distal internal carotid and proximal portions of the anterior and middle cerebral arteries and the formation of an abnormal vascular network at the base of the brain. The purpose of this retrospective study was to identify clinical features, salient features, radiological features and yield of diagnostic cerebral angiography in MMD.

Materials and Methods:

We analyzed the records of 26 patients with MMD evaluated and treated at our institute from August 2010 until March 2013. Diagnosis of MMD was made on the basis of features of angiographic findings. Cerebral angiography showed typically fine network of vessels at the base of the brain with puff of smoke appearance suggestive of MMD. CT angiography (CTA) was done in 25 (96.15%) patients where as Digital substraction angiography (DSA) was done in 18 (69.23%) patients.

Results:

Out of the 26 patients 13 were in the pediatric age group and 13 were adults. At presentation 14 patients had infarcts and 10 patients had hemorrhages. Among the hemorrhagic group 20% had isolated intracerebral hemorrhage (ICH), 50% patients had ICH with intraventricular extension (IVE) and 30% patients had primary intraventricular hemorrhage (PIVH). 50 % of the patients had involvement of the posterior circulation.

Conclusion:

Posterior circulation involvement is frequent in MMD. Though parenchymal bleed with/without intraventricular extension is the usual presentation of hemorrhagic MMD, isolated intraventricular hemorrhage could also be the mode of presentation.     

Analysis of ischemic cerebral lesions using 3.0-T diffusion-weighted imaging and magnetic resonance angiography after revascularization surgery for ischemic disease

Background

Cerebral revascularization surgery (CRS) is increasingly recognized as an important component in the treatment of complex cerebral vascular disease and tumors. CRS requires that the incidence of perioperative neurological complications should be minimized, because CRS for ischemic disease is often not the goal of treatment, but rather a prophylactic surgery. CRS carries the risk of focal postoperative neurological deficits. Little has been established concerning mechanisms of post-CRS ischemia. We used 3.0-T diffusion-weighted magnetic resonance imaging (DWI) and magnetic resonance angiography (MRA) to analyze the incidence and mechanism of ischemic lesions.

Methods

We studied the anterior circulation territory after 20 CRS procedures involving 33 vascular anastomosis procedures (13 double anastomoses and 7 single anastomoses) in 12 men and 8 women between June 2007 and October 2011. The operations included single or double superficial temporal artery–middle cerebral artery (STA–MCA) anastomosis to treat internal carotid artery/MCA occlusions or severe MCA stenosis. A combined STA–MCA anastomosis and indirect bypass were performed for moyamoya disease. Postoperative DWI and MRA were obtained in all patients between 24 and 96 h after surgery to detect thromboembolism, hypoperfusion, or procedural ischemic complications and vasospasms of the donor STA.

Results

Follow-up DWI and MRA were carried out 1.8 ± 0.6 days after CRS (range, 1–4 days). Temporary occlusion time for anastomoses averaged 18.9 min (range, 16–32 min). Asymptomatic new hyperintensities occurred in the ipsilateral hemisphere of 2 patients on postoperative DWI (10% patients/6.0% anastomoses), and 1 moyamoya patient (5.0% patients/3.0% anastomoses) developed a symptomatic hyperintensity in the ipsilateral occipital lobe in response to the operation. Two abnormal small (<5 mm) cortical DWI lesions were caused by sacrifices of a small branch of the recipient MCA.

Conclusion

This study is the first postoperative 3.0-T DWI study of CRS and related clinical events. The incidence of symptomatic postoperative DWI abnormalities was restricted to 1 moyamoya patient representing 5.0% of total patients and 3.0% anastomoses. Although some postoperative DWI abnormalities occurred, CRS was found to be safe with a low risk of symptomatic ischemia.     

Comparison of quantitative EEG between patients with Alzheimer’s disease and those with Parkinson’s disease dementia

Objective

Dementia frequently occurs in Parkinson’s disease (PD) but its pathophysiological basis is little known. Comparative EEG studies of Alzheimer’s disease (AD) and Parkinson’s disease dementia (PDD) are still rare, but could provide knowledge on the different pathophysiological mechanisms involved. The objective of the present study was to comparatively evaluate the absolute power and coherence on the EEG for patients with AD and PDD.

Methods

This study assessed 38 adults with AD, 12 with PDD, 31 with Parkinson’s disease without dementia, and 37 controls (CG) by a neurological evaluation, CERAD neuropsychological battery, executive functions tests and qEEG, calculating global absolute powers for the delta, theta, alpha and beta bands and inter- and intra-hemispheric coherences.

Results

The delta and theta powers were highest in PDD and lowest in CG (p < 0.05). The beta frontal-occipital inter-hemispheric coherence was highest in PDD (p < 0.05). Whereas, alpha and beta frontal inter-hemispheric coherence was highest in PDD and lowest in AD (p < 0.05).

Conclusion

These results suggest that qEEG power and coherence measures are different in AD and PDD.

Significance

These qEEG differences must be related to the distinct mechanisms of cortical neural connections in AD and PDD.     

Decisions under risk in Parkinson’s disease: Preserved evaluation of probability and magnitude

Introduction

Unmedicated Parkinson’s disease patients tend to be risk-averse while dopaminergic treatment causes a tendency to take risks. While dopamine agonists may result in clinically apparent impulse control disorders, treatment with levodopa also causes shift in behaviour associated with an enhanced response to rewards. Two important determinants in decision-making are how subjects perceive the magnitude and probability of outcomes. Our objective was to determine if patients with Parkinson’s disease on or off levodopa showed differences in their perception of value when making decisions under risk.

Methods

The Vancouver Gambling task presents subjects with a choice between one prospect with larger outcome and a second with higher probability. Eighteen age-matched controls and eighteen patients with Parkinson’s disease before and after levodopa were tested. In the Gain Phase subjects chose between one prospect with higher probability and another with larger reward to maximize their gains. In the Loss Phase, subjects played to minimize their losses.

Results

Patients with Parkinson’s disease, on or off levodopa, were similar to controls when evaluating gains. However, in the Loss Phase before levodopa, they were more likely to avoid the prospect with lower probability but larger loss, as indicated by the steeper slope of their group psychometric function (t₍₂₄₎=2.21, p=0.04). Modelling with prospect theory suggested that this was attributable to a 28% overestimation of the magnitude of loss, rather than an altered perception of its probability.

Conclusion

While pre-medicated patients with Parkinson’s disease show risk-aversion for large losses, patients on levodopa have normal perception of magnitude and probability for both loss and gain. The finding of accurate and normally biased decisions under risk in medicated patients with PD is important because it indicates that, if there is indeed anomalous risk-seeking behaviour in such a cohort, it may derive from abnormalities in components of decision making that are separate from evaluations of size and probability.     

Multiple encephalogaleoperiosteal synangiosis for bilateral carotid artery stenosis in a 13-year-old girl: a case report

Introduction

Encephalogaleoperiosteal synangiosis (EGS) has been widely used to treat children with moyamoya disease (MMD). We present the first case of successful multiple EGS in a patient with brain ischemic disease who presented with different cerebrovascular findings from MMD.

Methods

A 13-year-old girl had an increased frequency of transient ischemic attacks that affected her right extremities. Digital subtraction angiography showed tapering of the internal carotid artery (ICA). The anterior cerebral artery (ACA) and middle cerebral artery (MCA) were visible on vertebral angiogram, but not on carotid angiogram. The intact circle of Willis and lack of hypervascularity of the lenticulostriate arteries were observed. Decreased regional cerebral blood flow (CBF) in the bilateral ACA and MCA territories quantified by ¹²³I-N-isopropyl-p-iodoamphetamine-single photon emission computed tomography indicated the need for extracranial-intracranial bypass surgery. Multiple EGS procedures were performed instead of direct anastomosis, which is the standard procedure for intracranial ICA stenosis, because the space for the craniotomy was limited by transdural anastomosis.

Results

Despite the fact that the diagnosis of MMD was questionable, the hemispheres were well vascularized, and the neurology and CBF improved postoperatively.

Conclusion

The preserved circle of Willis and lack of moyamoya vessels were inconsistent with the features of MMD. However, childhood onset, bilateralness, chronic intracranial ICA stenosis, and transdural anastomosis indicated the same underling pathogenicity as MMD. It is hypothesized that ICA stenosis occurred immediately proximal to the posterior communicating artery in this case. This would have produced the atypical finding of the remaining circle of Willis without growth of the basal moyamoya vessels.

     

Varied presentations of moyamoya disease in a tertiary care hospital of north-east India

Introduction:

Moyamoya disease is a chronic progressive cerebrovascular disorder, characterized by stenosis or occlusion of bilateral internal carotid arteries (ICAs), anterior cerebral arteries (ACAs) and middle cerebral arteries (MCAs), accompanied by a collateral network of vessels formed at the base of the brain. Ischemia and intracranial hemorrhage are the common typical manifestations. However moyamoya disease has been associated with atypical presentations like headache, seizures and involuntary movements. Although frequently reported from Asian countries like Japan, China and Korea, only few studies reported on clinical manifestations of moyamoya disease from India.

Objectives:

To study the varied presentations of moyamoya disease in a tertiary care hospital of north-east India.

Material and Methods:

Relevant investigations were done to rule out other causes of moyamoya syndrome.

Results:

We report 6 cases of moyamoya disease with varied presentations from a tertiary care referral government hospital. Case 1, 2 and 6 presented with alternating hemiparesis. Case 3 had amaurosis fugax. Case 4 had history suggestive of ischemic stroke and presented with hemichorea. Case 4 had focal seizure as the only manifestation. Cases 4 and 5 notably had stenosis of posterior cerebral artery (PCA) in addition to stenosis of bilateral ICAs, ACAs and MCAs.

Conclusion:

Owing to its low incidence in India, moyamoya disease is easily overlooked as a possible diagnosis. However, because of its progressive nature, it is imperative to diagnose this disease early and offer surgical treatment to the patients.     

Comparison of Effects between Clopidogrel and Cilostazol on Cerebral Perfusion in Nonsurgical Adult Patients with Symptomatically Ischemic Moyamoya Disease: Subanalysis of a Prospective Cohort

Background and purpose

Adult patients with symptomatically ischemic moyamoya disease (MMD) initially undergo medical treatment alone including antiplatelet drugs when symptomatic cerebral hemispheres do not exhibit hemodynamic compromise. The purpose of the present study subanalyzing the same patient cohort used in a previous study was to determine which antiplatelet drug, clopidogrel or cilostazol, provides better improvement of cerebral perfusion in such patients.

Psychiatric factors related to sexual functioning in patients with Parkinson's disease

Introduction

This research deals with the topic of sexual life among people suffering from Parkinson's disease (PD) and with selected factors related to sexual functioning in these patients. Parkinson's disease is a serious chronic disease whose symptoms as well as treatment substantially affect the sexual life of the patients. Despite this fact, very little published work has dealt with this topic.

Aim

This research focuses on describing the structure of deterioration of sexual functions of the patients suffering from PD, and statistical analysis of the interdependence of selected factors (age, duration of the disease, subjective score of the impact of the disease, depression, anxiety) as well as the patients’ sexual satisfaction. The most substantial factors influencing sexual satisfaction of men and women with PD are analysed and their impact assessed, the greatest stress being put on psychiatric factors.

Methods

The research project examined a group of 103 people with PD. In order to identify the specifics of the patients’ sexual lives, two questionnaire-sets were designed (separate for men and women), containing psychological (BDI-II, STAI) and sexological (FSFI, IIEF, GRISS) questionnaires.

Main outcome measures

The main outcome measures were depression, state and trait anxiety, sexual satisfaction, erectile function, the Female Sexual Function Index.

Results

The acquired data was statistically elaborated using the programme SPSS. The results of the sexological questionnaires show a decrease in overall sexual functioning and the presence of sexual dysfunctions related to PD. With the help of regression models it was elicited that in case of men with this illness, the most influential factor on their sexual life is depression and their subjective scoring of the illness, in the case of women the prevailing factors are depression and anxiety.

Conclusions

Sexuality for people suffering from Parkinson's disease is a very complex issue and psychiatric factors (depression, anxiety) have an important impact on the sexual functioning of the patients.     

Involuntary movement in pediatric moyamoya disease patients: consideration of pathogenetic mechanism using neuroimaging studies

Purpose

Involuntary movement is a rare symptom of moyamoya disease (MMD). No consensus has been reached regarding its clinical features and pathogenetic mechanism. Therefore, pediatric MMD patients presenting with involuntary movement were retrospectively analyzed, focusing on the image findings.

Methods

A total of 513 patients who were treated for MMD were reviewed. After exclusion of MMD syndromes and those with accompanying conditions related to involuntary movements, five patients (mean age: 11.6 years, range: 5–13 years) were evaluated.

Results

All of the patients improved their symptoms rapidly after the indirect bypass operations to the contralateral hemisphere. All remained symptom-free during the long follow-up period. Comprehensive evaluation of the preoperative imaging findings failed to suggest a characteristic feature in common, corresponding to the existing hypotheses or a new hypothesis. Only one patient showed infarction preoperatively, and only one patient showed prominently enhanced collateral vessels in the basal ganglia. Although a decrease in vascular reserve was observed in all patients, the location and laterality were nonspecific.

Conclusion

There still appears to be confusion regarding the pathogenetic mechanism of involuntary movement in MMD with no repetitive, established imaging features to explain the phenomenon. Nonetheless, with its excellent response to surgical treatment, clinical awareness of this rare symptom of MMD should be emphasized as a differential diagnosis for secondary movement disorder in children.     

Trends of Antiplatelet Therapy for the Management of Moyamoya Disease in Japan: Results of a Nationwide Survey

Background

The efficacy and safety of antiplatelet drugs in the treatment of moyamoya disease remain unclear. This study reports results of a nationwide survey conducted in 2016 on the trends of antiplatelet therapy for moyamoya disease in Japan.

Perceptual and response interference in Alzheimer’s disease and mild cognitive impairment

Objectives

The ability to resolve conflicts is indispensable to the function of daily life and decreases with cognitive decline. We hypothesized that subjects with different levels of cognitive impairment exhibit different conflict resolution performances and may be susceptible to interference effects at different stages.

Methods

Sixteen normal controls (NC), 15 mild cognitive impairment (MCI) and seven Alzheimer’s disease (AD) patients were recruited to perform in a modified Eriksen flanker task.

Results

We observed that the AD and MCI patients exhibited smaller accuracy rate and longer response time compared to NC subjects. Longer N2 and P300 latencies were observed in the AD group. Furthermore, the MCI group showed a longer latency than the NC group in the P300 latency. The magnitude of the perceptual and response interference effects was larger in the AD group than the other groups, and the MCI group significantly differed from the NC group at the perceptual level.

Conclusion

The ability to resolve conflict decreased with impaired cognition and the perceptual and response interference effects may be useful in distinguishing MCI and AD.

Significance

The perceptual or response interference effect may potentially be employed as a useful non-invasive probe for the clinical diagnosis of MCI and AD.     

Experiencia y resultados de las técnicas de revascularización en patología cerebral isquémica: enfermedad de moyamoya y oclusión carotídea

Introduction

Cerebral revascularization techniques are an indispensable tool in the current armamentarium of vascular neurosurgeons. We present revascularization surgery experience and results in both moyamoya disease and occlusive cerebral ischaemia.

Quantitative EEG and apolipoprotein E-genotype improve classification of patients with suspected Alzheimer’s disease

Objective

To establish a model for better identification of patients in very early stages of Alzheimer’s disease, AD (including patients with amnestic MCI) using high-resolution EEG and genetic data.

Methods

A total of 26 patients in early stages of probable AD and 12 patients with amnestic MCI were included. Both groups were similar in age and education. All patients had a comprehensive neuropsychological examination and a high resolution EEG. Relative band power characteristics were calculated in source space (LORETA inverse solution for spectral data) and compared between groups. A logistic regression model was calculated including relative band-power at the most significant location, ApoE status, age, education and gender.

Results

Differences in the delta band at 34 temporo-posterior source locations (p < .01) between AD and MCI groups were detected after correction for multiple comparisons. Classification slightly increased when ApoE status was added (p = .06 maximum likelihood test). Adjustment of analyses for the confounding factors age, gender and education did not alter results.

Conclusions

Quantitative EEG (qEEG) separates between patients with amnestic MCI and patients in early stages of probable AD. Adding information about Apo ε4 allele frequency slightly enhances diagnostic accuracy.

Significance

qEEG may help identifying patients who are candidates for possible benefit from future disease modifying treatments.     

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 χ² 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.Moyamoya disease (MMD) is an idiopathic progressive angiopathy characterised by progressive stenosis or occlusion and affecting the terminal portions of the bilateral internal carotid artery and the circle of Willis. Collateral vessels develop at the base of the brain to compensate for the progressive stenosis. These enlarged collaterals appear as a puff of smoke on angiography, which gives the disease its name.MMD is predominantly found in East Asian populations, with most reported cases originating from Japan, Korea and China. The estimated annual incidence in Japan in 1994 was 0.35 per 100 000 population,¹ whereas that in Europe was one tenth of this.² It is well known that MMD has been observed predominantly in women, with a female‐to‐male ratio of 1.8.^1,3 Recently, MMD has been diagnosed by magnetic resonance imaging (MRI) and magnetic resonance angiography (MRA),^4,5 which makes it possible to detect asymptomatic patients. Accordingly, familial occurrence has been increasing; it was observed in 12.1% of the patients in 2004.³ The female predominance, East Asian distribution and familial occurrence of the disease imply the existence of genetic risk factors.To clarify the genetic background of MMD, several non‐parametric linkage analyses using mainly affected sibling pairs have been carried out, showing linkages to 3p24.2–p26, 6q25, 8q23, 12p12 and 17q25.^6,7,8,9 The association analysis of tissue inhibitor of metalloproteinase 2 in 17q25 showed that a polymorphism in the promoter region was markedly associated with familial MMD (F‐MMD).¹⁰To make further progress in genetic analysis of the disease, it is important to enrol highly aggregated families with MMD to characterise the clinical features and inheritance patterns in F‐MMD. Some unresolved issues are as follows:

1. The mode of inheritance has not yet been determined.
2. Some reports mention that paternal transmission led to earlier onset than maternal transmission.¹¹ However, the difference between maternal and paternal transmission has not been proved by a statistical analysis.

The aim of this study is to resolve these issues, to enable precise genetic analyses of F‐MMD.