RESUMEN
Genetic factors alone cannot explain the pathophysiology of moyamoya disease (MMD), and environmental factors such as an immune response are thought to be involved. Oral and gut microbiomes have attracted attention as environmental factors in the pathophysiology of some vascular and autoimmune diseases. However, the relationship between MMD and these microbiomes is yet to be thoroughly investigated. This prospective case-control study aimed to compare the microbiomes of Japanese patients with MMD with those of healthy individuals to identify the specific bacteria involved in MMD. Saliva and fecal samples were collected from 16 patients with MMD who had not undergone revascularization surgery. Fifteen healthy individuals were matched for age, sex, and body mass index. The microbiomes were determined using 16S rRNA sequencing and analyzed using QIIME2. Differentially abundant microbes were identified using LEfSE and ANCOM-BC. In the oral microbiome, the two analytical methods showed that Campylobacter was more abundant in patients with MMD than in healthy individuals. Differences in the gut microbiome were smaller than those in the oral microbiome. In conclusion, the oral microbiome profiles of patients with MMD significantly differ from those of healthy individuals. Campylobacter spp. could be a substantial environmental factor in the pathophysiology of MMD.
Asunto(s)
Campylobacter , Microbiota , Enfermedad de Moyamoya , Saliva , Humanos , Campylobacter/genética , Campylobacter/aislamiento & purificación , Estudios de Casos y Controles , Pueblos del Este de Asia , Enfermedad de Moyamoya/genética , Enfermedad de Moyamoya/microbiología , ARN Ribosómico 16S/genética , Saliva/microbiología , Heces/microbiologíaRESUMEN
BACKGROUND: Transient neurological deficits (TNDs) develop after cerebral revascularization in patients with moyamoya disease (MMD). The authors report a rare pediatric MMD case with extensive decreased cerebral blood flow (CBF) and prolonged TNDs after combined revascularization. OBSERVATIONS: A 9-year-old boy presented with transient left upper limb weakness, and MMD was diagnosed. A right-sided combined surgery was performed. Two years after the surgery, frequent but transient facial (right-sided) and upper limb weakness appeared. The left internal carotid artery terminal stenosis had progressed. Therefore, a left combined revascularization was performed. The patient's motor aphasia and right upper limb weakness persisted for approximately 10 days after surgery. Magnetic resonance angiography showed that the direct bypass was patent, but extensive decreases in left CBF were observed using single photon emission tomography. With adequate fluid therapy and blood pressure control, the neurological symptoms eventually disappeared, and CBF improved. LESSONS: The environment of cerebral hemodynamics is heterogeneous after cerebral revascularization for MMD, and the exact mechanism of CBF decreases was not identified. TNDs are significantly associated with the onset of stroke during the early postoperative period. Therefore, appropriate treatment is desired after determining complex cerebral hemodynamics using CBF studies.
RESUMEN
Balloon test occlusion (BTO) is an angiographic test to evaluate ischemic tolerance after permanent occlusion of an internal carotid artery (ICA). BTO can simulate ischemia caused by parent artery occlusion and can be used to select a suitable bypass surgery using specific criteria. On the other hand, a postoperative thrombus can form despite proper case selection, optimal radiological evaluation, and an appropriate surgical strategy. Postoperative ischemic complications related to perforating branches are clinically significant. This simulation study aimed to analyze postoperative flow characteristics and elucidate the cause of ischemic complications related to the perforating branch using computational fluid dynamics (CFD). An unexpected postoperative thrombus formation related to the perforating branch occurred after treating a giant aneurysm in the cavernous portion of the ICA in a patient. Three-dimensional digital subtraction angiography was used to acquire flow data and set up the CFD simulation. The flow simulations were performed at various bypass flow rates. The CFD analysis indicated flow stagnation in the ICA only when surgical treatment using a low-flow bypass graft was performed. Thrombus formation may lead to ischemic complications related to the perforating branch, such as the anterior choroidal artery. BTO did not reflect the influence of bypass blood flow. Therefore, recognizing that blood flow stagnation may occur and comprehensively deciding on the surgical strategy by CFD analysis can be helpful to prevent ischemic complications in patients with giant aneurysms.
Asunto(s)
Enfermedades de las Arterias Carótidas , Revascularización Cerebral , Aneurisma Intracraneal , Enfermedades de las Arterias Carótidas/complicaciones , Enfermedades de las Arterias Carótidas/diagnóstico por imagen , Enfermedades de las Arterias Carótidas/cirugía , Arteria Carótida Interna/diagnóstico por imagen , Arteria Carótida Interna/cirugía , Revascularización Cerebral/efectos adversos , Revascularización Cerebral/métodos , Humanos , Hidrodinámica , Aneurisma Intracraneal/complicaciones , Aneurisma Intracraneal/diagnóstico por imagen , Aneurisma Intracraneal/cirugía , Complicaciones Posoperatorias/etiologíaRESUMEN
The purpose of this study was to examine the effects of combined revascularization for ischaemic-onset moyamoya disease (MMD) on cerebral haemodynamics by comparing cerebral blood flow (CBF) during the postoperative chronic phase with preoperative CBF. A retrospective cohort of 24 MMD patients (representing 31 surgeries) who received single photon emission computed tomography (SPECT) before and more than 6 months after surgery was investigated. The CBF value of each vascular territory was extracted from SPECT data, and the value relative to the ipsilateral cerebellar value (relative CBF, or RCBF) was calculated. The correlation between the revascularization effect and the proportional change in RCBF before and after surgery (calculated as post-RCBF/pre-RCBF ("post/pre-RCBF")) was analysed. Furthermore, the relationships between changes in neurological symptoms and post/pre-RCBF were investigated. Preoperative and postoperative mean RCBF values were 0.92 ± 0.15 and 0.96 ± 0.13 (p = 0.619) in the anterior cerebral artery territory, 0.99 ± 0.17 and 1.01 ± 0.17 (p = 0.598) in the middle cerebral artery territory and 1.15 ± 0.22 and 1.14 ± 0.19 (p = 0.062) in the posterior cerebral artery territory, respectively. No significant correlation was found between the revascularization score and post/pre-RCBF. The revascularization score and post/pre-RCBF were not significant predictors of worsening neurological symptoms postoperatively. No significant change in RCBF was observed in any vascular territory in the chronic phase after revascularization. Combined revascularization may assist in the redirection of blood flow from the internal to the external carotid system and contribute to CBF maintenance.
Asunto(s)
Revascularización Cerebral , Enfermedad de Moyamoya , Revascularización Cerebral/métodos , Circulación Cerebrovascular/fisiología , Humanos , Enfermedad de Moyamoya/cirugía , Estudios Retrospectivos , Tomografía Computarizada de Emisión de Fotón ÚnicoRESUMEN
OBJECTIVE: Cerebral revascularization is necessary for pediatric patients younger than 5 years with moyamoya disease (MMD). However, they have a high risk of developing cerebral infarction early after surgery. This study aimed to analyze the risk factors for developing cerebral infarction among these patients. METHODS: The charts of 21 consecutive patients with MMD (39 surgeries) younger than 5 years who had undergone revascularization at our hospital were retrospectively analyzed. Because cerebral infarction occurring within 1 month after surgery was the primary end point, other clinical information was evaluated, including each surgical procedure. Multivariate analysis of the risk factors for postoperative cerebral infarction was performed. RESULTS: Cerebral infarction occurred after 7 of 39 surgeries (17.9%). Of the 39 surgeries, 23 (59%) included direct and indirect combined revascularization. The incidence of cerebral infarction did not differ significantly between the combined (21.7%) and indirect (12.5%) groups (P = 0.46). Logistic regression showed no association between the revascularization procedure and the occurrence of cerebral infarction after surgery (P = 0.3). However, younger age at surgery was correlated with a higher risk of developing cerebral infarction in the early postoperative period (P = 0.05). CONCLUSIONS: No differences were found in the risk of developing cerebral infarction early after surgery as a result of surgical procedures. However, younger patients had higher postoperative risk. Further multicenter research should examine this issue for young pediatric patients with moyamoya at high risk of developing cerebral infarction.
Asunto(s)
Revascularización Cerebral , Enfermedad de Moyamoya , Infarto Cerebral/epidemiología , Infarto Cerebral/etiología , Revascularización Cerebral/efectos adversos , Revascularización Cerebral/métodos , Niño , Humanos , Enfermedad de Moyamoya/complicaciones , Enfermedad de Moyamoya/epidemiología , Enfermedad de Moyamoya/cirugía , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Estudios Retrospectivos , Factores de Riesgo , Resultado del TratamientoRESUMEN
Cerebral revascularization for moyamoya disease (MMD) is an effective treatment for improving cerebral ischaemia and preventing rebleeding. Although direct bypass surgery is commonly performed on older children and adults, it is challenging in very young children due to the high difficulty level of the procedure. The subjects were MMD patients under 3 years of age on whom surgery was performed by a single surgeon (Y.A.). Preoperative clinical findings, information related to direct bypass surgery, bypass patency, and the incidence of postoperative stroke were investigated. Combined revascularization, including direct bypass surgery, was performed on 3 MMD patients (3 sides) under 3 years of age. The average diameter of the grafts used in direct bypass was 0.8 mm. The average recipient diameter was 0.8 ± 0.17 (range 0.6-1) mm. In all cases, the anastomotic procedure was completed using 11-0 monofilament nylon thread, and patency was confirmed. Direct bypass for MMD patients under 3 years old is technically challenging. However, despite the anatomical differences between very young children and elderly individuals, direct bypass surgery could certainly be completed. In addition, a rapid recovery from cerebral blood flow insufficiency could yield a promising neurological outcome.
Asunto(s)
Isquemia Encefálica , Revascularización Cerebral , Enfermedad de Moyamoya , Adolescente , Adulto , Anciano , Anastomosis Quirúrgica/métodos , Isquemia Encefálica/complicaciones , Isquemia Encefálica/cirugía , Revascularización Cerebral/métodos , Niño , Preescolar , Humanos , Enfermedad de Moyamoya/complicaciones , Enfermedad de Moyamoya/cirugía , Complicaciones Posoperatorias/etiología , Resultado del TratamientoRESUMEN
BACKGROUND: Ipsilateral late stroke events occurring after cerebral revascularization for Moyamoya disease (MMD) and their risk factors have not been fully investigated. METHODS: We retrospectively analyzed 123 patients with MMD who underwent 212 revascularizations. We investigated preoperative demographic data, surgical procedures, and ipsilateral stroke events occurring more than 1 month after surgery. The effect of revascularization and the residual Moyamoya vessel (MMV) score were examined using magnetic resonance angiography (MRA). Then, predictive factors for postoperative late stroke occurrence were evaluated by logistic regression. RESULTS: The mean age was 26 ± 18.4 years (range 1 to 66 years). Ipsilateral late stroke events were present in 11 of 123 (9%) patients. Stroke occurred in 11 out of 212 surgeries (5.2%) on a hemispheric basis. During the 1300.1 hemisphere-years of follow-up more than 1 month after surgery, the annual stroke rate was 0.84%. The postoperative MRA time-of-flight image showed a mean revascularization score of 1.82 ± 0.6 and a mean residual MMV score of 1.91 ± 0.83. Postoperative strokes occurring within 1 month after cerebral revascularization (36.4%, p = 0.0026) and lower revascularization scores (1.82 ± 0.6 vs 2.51 ± 0.59, p = 0.0006) were significant factors related to the presence of ipsilateral late stroke. Logistic regression showed that stroke events within 1 month after revascularization (odds ratio [OR], 9.79; 95% confidence interval [CI], 0.02-0.57; p = 0.0103), low revascularization score (OR, 0.15; 95% CI, 0.001-0.37; p = 0.0069), and high residual MMV score (OR, 16.2; 95% CI, 1.88-187.4; p = 0.0107) were risk factors for ipsilateral stroke more than 1 month after revascularization. CONCLUSIONS: MMD patients who have a stroke within 1 month after cerebral revascularization are at high risk for late strokes. Less effective revascularization or remarkable residual MMV are risk factors for late stroke events. Additional revascularization may be considered for patients in such situations. CLINICAL TRIAL REGISTRATION: This study was approved by the Bioethics Review Committee of Nagoya University Hospital for the treatment and prognosis of Moyamoya disease (2016-0327).
Asunto(s)
Revascularización Cerebral/efectos adversos , Enfermedad de Moyamoya/cirugía , Complicaciones Posoperatorias/etiología , Accidente Cerebrovascular/etiología , Adolescente , Adulto , Anciano , Niño , Preescolar , Humanos , Lactante , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/epidemiología , Accidente Cerebrovascular/epidemiologíaRESUMEN
Stroke and neurological outcomes in the early phase following revascularization for moyamoya disease (MMD) may depend on the patient's age. In this study, an age-stratified comparative analysis was performed to clarify this issue. We reviewed 105 MMD patients who underwent 179 revascularization surgeries. The demographic characteristics were collected in four age groups (≤ 5 and 6-17 years for pediatric patients and 18-49 and ≥ 50 years for adults). Additionally, we assessed the incidence of subsequent stroke and deterioration of modified Rankin Scale (mRS) score. Then, we evaluated predictors of postoperative stroke and mRS deterioration using logistic regression. The mean patient age was 26.2 ± 18.5 years. No significant difference in the incidence of postoperative stroke was observed between age groups; however, the incidence tended to be increased among patients aged ≤ 5 years (17.9%) and patients aged ≥ 50 years (16.7%). Deterioration of mRS scores was significantly associated with ages ≤ 5 years (17.9%) and ≥ 50 years (11.1%). Logistic regression showed that posterior cerebral artery involvement (odds ratio [OR], 4.6) and postoperative transient neurological events (TNEs) (OR, 5.93) were risk factors for postoperative stroke. Age ≤ 5 years (OR, 9.73), postoperative TNEs (OR, 7.38), and postoperative stroke (OR, 49) were identified as predictors of unfavorable neurological outcomes. The novel feature of this comparative analysis by age group is that membership in the early-childhood MMD patient group (under 5 years old) was an independent risk factor for unfavorable short-term neurological outcomes and was mainly associated with the incidence of postoperative severe cerebral infarction.
Asunto(s)
Revascularización Cerebral , Enfermedad de Moyamoya , Accidente Cerebrovascular , Adulto , Revascularización Cerebral/efectos adversos , Niño , Humanos , Recién Nacido , Enfermedad de Moyamoya/epidemiología , Enfermedad de Moyamoya/cirugía , Arteria Cerebral Posterior , Complicaciones Posoperatorias/epidemiología , Estudios Retrospectivos , Accidente Cerebrovascular/epidemiología , Accidente Cerebrovascular/etiología , Resultado del Tratamiento , Procedimientos Quirúrgicos VascularesRESUMEN
OBJECTIVE: Cerebral revascularization surgery has been established as an effective treatment for moyamoya disease. On the other hand, harvesting grafts and tissues to nourish the scalp may increase the risk of postoperative wound-related complications. The purpose of this study was to clarify risk factors for wound-related complications after examining the relationship with the surgical design. METHODS: We retrospectively analyzed 115 patients who underwent 197 revascularization procedures between October 2004 and March 2019. The design of the revascularization was classified into 6 types, then further classified according to the number of grafts harvested, resulting in 11 subtypes. Incidences of minor and major wound-related complications for the 11 different surgical designs were assessed. The risk of complications from each design was statistically examined. In addition, the yearly transition rate of complications was also investigated. RESULTS: Wound-related complications occurred in 38 of the 195 operations (19.5%), including 10 major events (26.3%) and 28 minor events (73.7%). Significant differences in the incidence of complications were seen according to surgical design (P < 0.05), with complications significantly more frequent for L(a) double type and L(p) double type and less frequent for L(a) single type and L(p) single type. In addition, significant differences were found in the incidence and degree of complications according to the number of grafts (0-2) (P < 0.05). The incidence of wound-related complications has clearly decreased since 2015. CONCLUSIONS: Wound-related complications were more frequent and tended to become more severe with double-bypass procedures but were clearly improved under a plastic surgery approach.
Asunto(s)
Revascularización Cerebral/métodos , Enfermedad de Moyamoya/cirugía , Procedimientos Neuroquirúrgicos/métodos , Adolescente , Adulto , Anciano , Revascularización Cerebral/efectos adversos , Niño , Preescolar , Femenino , Humanos , Incidencia , Lactante , Masculino , Persona de Mediana Edad , Procedimientos Neuroquirúrgicos/efectos adversos , Complicaciones Posoperatorias/epidemiología , Periodo Posoperatorio , Estudios Retrospectivos , Factores de Riesgo , Accidente Cerebrovascular/epidemiología , Colgajos Quirúrgicos/cirugía , Infección de la Herida Quirúrgica/epidemiología , Resultado del Tratamiento , Adulto JovenRESUMEN
BACKGROUND: In moyamoya disease (MMD), the causes of differences in clinical features between children and adults and of the dramatic temporal changes in moyamoya vessels are poorly understood. We previously discovered elevated levels of m/z 4588 and m/z 4473 peptides in cerebrospinal fluid (CSF) in patients with MMD. This study examined the amino acid sequences of these peptides and quantified in specimens. METHODS: The m/z 4588 and m/z 4473 peptides in CSF from patients with MMD were purified and concentrated by high-performance liquid chromatography and ultrafiltration. Liquid chromatography coupled with tandem mass spectrometry analysis was performed to identify the amino acid sequences of these peptides. We quantified these peptides in samples using sandwich enzyme-linked immunosorbent assay, and concentrations in CSF were compared between MMD (n = 40, 19 male; median age, 37 years) and non-MMD intracranial disease (n = 40, 19 male; median age, 39 years) as controls. RESULTS: These peptides were identified as proenkephalin 143-183 (PENK 143-183). The concentration of PENK 143-183 was significantly greater in patients with MMD (median, 8,270 pmol/L) than control patients (median, 3,760 pmol/L; P < 0.001) and decreased in an age-dependent manner in MMD (r = -0.57; P < 0.001). The area under the receiver operating characteristic curve in children (age <18 years) was 0.885 (95% confidence interval 0.741-1). The correlation between proenkephalin concentration and temporal changes in moyamoya vessels was suggested. CONCLUSIONS: Proenkephalin 143-183 in CSF may offer a helpful diagnostic biomarker in pediatric MMD. The effect of enkephalin peptides through opioid growth factor receptor or delta opioid receptor might be associated with the pathophysiology of MMD.
Asunto(s)
Encefalinas/líquido cefalorraquídeo , Enfermedad de Moyamoya/líquido cefalorraquídeo , Fragmentos de Péptidos/líquido cefalorraquídeo , Precursores de Proteínas/líquido cefalorraquídeo , Adolescente , Adulto , Anciano , Estudios de Casos y Controles , Niño , Preescolar , Cromatografía Liquida , Femenino , Humanos , Lactante , Masculino , Persona de Mediana Edad , Espectrometría de Masas en Tándem , Adulto JovenRESUMEN
BACKGROUND: Bilateral cavernous carotid aneurysms (CCAs) are very rare. A treatment strategy for symptomatic bilateral CCAs has not been established because of their complex pathogenesis. Here we report our treatment strategy and long-term results for 6 cases of symptomatic bilateral CCAs. METHODS: From January 2007 to December 2013, we treated 6 patients (2 men and 4 women; mean age at first treatment, 56.0 years) with symptomatic bilateral CCAs. RESULTS: All patients began to experience unilateral symptoms. Five of the 6 underwent high-flow bypass (HFB) with parent artery occlusion (PAO), and 1 received PAO only. Mean follow-up period after the first treatment was 61.3 months. All symptoms improved after the treatment. Five contralateral CCAs became enlarged during the follow-up period. Of these, 4 became symptomatic. One patient received superficial temporal-middle cerebral artery bypass with PAO, 2 received HFB with PAO, and 1 refused treatment. Final modified Rankin Scale scores were 0 in 4 patients, 1 in 1 patient, and 2 in 1 patient. There was no mortality in this series. CONCLUSIONS: HFB with PAO is feasible as the first treatment for symptomatic bilateral CCAs. This treatment strategy steadies and simplifies future treatment of contralateral CCAs should they become symptomatic.
Asunto(s)
Aneurisma/complicaciones , Aneurisma/terapia , Enfermedades de las Arterias Carótidas/complicaciones , Enfermedades de las Arterias Carótidas/terapia , Seno Cavernoso/patología , Revascularización Cerebral/métodos , Adulto , Anciano , Femenino , Humanos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
Moyamoya disease (MMD) is a rare cerebrovascular disease characterized by steno-occlusive change in bilateral internal carotid arteries with unknown etiology. To discover biomarker candidates in cerebrospinal fluid from MMD patients, proteome analysis was performed by the surface-enhanced laser desorption/ionization time-of-flight mass spectrometry. Three peptides, 4473Da, 4475Da, and 6253Da, were significantly elevated in MMD group. A positive correlation between 4473Da peptide and postoperative angiogenesis was determined. Twenty MMD patients were enrolled in this pilot study, including 11 pediatric cases less than 18 years of age (mean age, 8.67 years) and 9 adult MMD patients (mean age, 38.1 years). This study also includes 17 control cases with the mean age of 27.9 years old. In conclusion, 4473Da peptide is supposed to be a reliable biomarker of MMD. 4473Da peptide showed higher intensity peaks especially in younger MMD patients, and it was proved to be highly related to postoperative angiogenesis. Further study is needed to show how 4473Da peptide is involved with the etiology and the onset of MMD.
Asunto(s)
Biomarcadores/líquido cefalorraquídeo , Enfermedad de Moyamoya/líquido cefalorraquídeo , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción/métodos , Adolescente , Adulto , Niño , Preescolar , Femenino , Humanos , Lactante , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Enfermedad de Moyamoya/patología , Neovascularización Patológica/patología , Proyectos Piloto , Proteómica/métodos , Adulto JovenRESUMEN
A 30-year-old female developed moyamoya syndrome after gamma knife surgery (GKS) for cerebral arteriovenous malformation (AVM), and was treated with bypass surgery. She suffered from flittering scotoma, right transient hemianopsia, and headache for 1 year. Cerebral angiography revealed a Spetzler-Martin grade III AVM located in the left occipital lobe. After staged embolization, GKS was performed with a minimum dose of 20 Gy to the periphery of the nidus at the 50% isodose level of the maximum target dose. Gradual nidus regression was achieved, and the clinical symptoms disappeared completely. However, at 30 months after GKS, the patient suffered transient ischemic attack. Cerebral angiography showed left middle cerebral artery occlusion with moyamoya vessels. The patient underwent direct and indirect bypass surgery. After surgery, the patient was free from ischemic symptoms. Chronic inflammation and long-term changes in expression of cytokines and growth factors after GKS may have triggered this case.
Asunto(s)
Malformaciones Arteriovenosas Intracraneales/cirugía , Enfermedad de Moyamoya/diagnóstico , Enfermedad de Moyamoya/fisiopatología , Complicaciones Posoperatorias/diagnóstico , Complicaciones Posoperatorias/fisiopatología , Radiocirugia/efectos adversos , Adulto , Revascularización Cerebral/métodos , Femenino , Humanos , Infarto de la Arteria Cerebral Media/diagnóstico , Infarto de la Arteria Cerebral Media/etiología , Infarto de la Arteria Cerebral Media/fisiopatología , Malformaciones Arteriovenosas Intracraneales/diagnóstico por imagen , Malformaciones Arteriovenosas Intracraneales/patología , Ataque Isquémico Transitorio/etiología , Ataque Isquémico Transitorio/fisiopatología , Enfermedad de Moyamoya/etiología , Lóbulo Occipital/irrigación sanguínea , Lóbulo Occipital/patología , Lóbulo Occipital/fisiopatología , Complicaciones Posoperatorias/etiología , Dosis de Radiación , Radiografía , Radiocirugia/métodos , Resultado del Tratamiento , Vasculitis del Sistema Nervioso Central/complicaciones , Vasculitis del Sistema Nervioso Central/inmunología , Vasculitis del Sistema Nervioso Central/fisiopatologíaRESUMEN
BACKGROUND: Moyamoya disease (MMD) is an uncommon cerebrovascular condition with unknown etiology characterized by slowly progressive stenosis or occlusion of the bilateral internal carotid arteries associated with an abnormal vascular network. MMD is a major cause of stroke, specifically in the younger population. Diagnosis is based on only radiological features as no other clinical data are available. The purpose of this study was to identify novel biomarker candidate proteins differentially expressed in the cerebrospinal fluid (CSF) of patients with MMD using proteomic analysis. METHODS: For detection of biomarkers, CSF samples were obtained from 20 patients with MMD and 12 control patients. Mass spectral data were generated by surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF-MS) with an anion exchange chip in three different buffer conditions. After expression difference mapping was undertaken using the obtained protein profiles, a comparative analysis was performed. RESULTS: A statistically significant number of proteins (34) were recognized as single biomarker candidate proteins which were differentially detected in the CSF of patients with MMD, compared to the control patients (p < 0.05). All peak intensity profiles of the biomarker candidates underwent classification and regression tree (CART) analysis to produce prediction models. Two important biomarkers could successfully classify the patients with MMD and control patients. CONCLUSIONS: In this study, several novel biomarker candidate proteins differentially expressed in the CSF of patients with MMD were identified by a recently developed proteomic approach. This is a pilot study of CSF proteomics for MMD using SELDI technology. These biomarker candidates have the potential to shed light on the underlying pathogenesis of MMD.