RESUMO
Familial cerebral cavernous malformations due to the common Hispanic mutation (FCCM1-CHM) is an endemic condition among the Hispanic population of the Southwestern United States associated with significant morbidity and mortality. Cutaneous vascular malformations (CVMs) can be found in individuals with FCCM1-CHM, but their morphology, prevalence, and association with cerebral cavernous malformations (CCMs) has not been well characterized. A cross-sectional study of 140 individuals with confirmed FCCM1-CHM was performed with statistical analyses of CVM, CCM, and patient characteristics. We then compared these findings to other cohorts with Familial cerebral cavernous malformations (FCCM) due to other mutations. We observed a higher overall prevalence and a different predominant morphological subtype of CVM compared to previous FCCM cohorts. While the number of CVMs was not a reliable indicator of the number of CCMs present, each person with one or more CVMs had evidence of central nervous system (CNS) disease. Awareness of the morphology of these cutaneous lesions can aid in the diagnosis of individuals with FCCM-CHM in Hispanic patients or those with family history of CCM.
Assuntos
Hemangioma Cavernoso do Sistema Nervoso Central/genética , Proteína KRIT1/genética , Dermatopatias Vasculares/genética , Adolescente , Adulto , Idoso , Criança , Feminino , Hemangioma Cavernoso do Sistema Nervoso Central/diagnóstico por imagem , Hemangioma Cavernoso do Sistema Nervoso Central/patologia , Hispânico ou Latino/genética , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Mutação/genética , Linhagem , Dermatopatias Vasculares/tratamento farmacológico , Dermatopatias Vasculares/patologia , Adulto JovemRESUMO
OBJECTIVE. The purpose of this study was to investigate whether MRI-typical and MRI-atypical intraosseous vascular malformations are associated with familial cerebral cavernous malformation (FCCM). MATERIALS AND METHODS. In a retrospective matched case-control study, two radiologists reviewed the spinal imaging, both CT and MRI, of 22 patients with FCCM seen between 2006 and 2017 and of age- and sex-matched control subjects for MRI-typical and MRI-atypical intraosseous vascular malformations. Quantitative analysis of lesions identified included vertebral level, size, and number of lesions. Pathologic samples from two lesions were analyzed for histologic and immunohistochemical features. Whether the presence of typical, atypical, and total intraosseous vascular malformations differed between patients and control subjects was tested. For patients with complete spinal imaging, whether intraosseous vascular malformations were associated with age, sex, brain lesion count, and spinal lesion count was also tested. RESULTS. MRI-atypical intraosseous vertebral malformations were more commonly present in patients with FCCM (p = 0.003). Sixteen lesions were found in nine patients and none in the control group. The numbers of MRI-typical intraosseous vascular malformations were similar between patients and control subjects (p = 0.480). Age was associated with typical intraosseous vascular malformations (p = 0.027), though not with atypical malformations. MRI-atypical malformations were larger (mean diameter double) than MRI-typical malformations (p = 0.023). Histologic analysis of two lesions from different patients with pathologic collapse revealed the same histologic features consistent with combined capillary-venous malformations. CONCLUSION. Vertebral capillary-venous malformations (MRI-atypical intraosseous vascular malformations) are common in patients with FCCM and may have a more aggressive clinical course than MRI-typical malformations.
Assuntos
Hemangioma Cavernoso do Sistema Nervoso Central/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Coluna Vertebral/anormalidades , Coluna Vertebral/irrigação sanguínea , Tomografia Computadorizada por Raios X/métodos , Adolescente , Adulto , Idoso , Estudos de Casos e Controles , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos RetrospectivosRESUMO
Purpose To determine if adrenal calcifications seen at computed tomography (CT) are associated with familial cerebral cavernous malformations (fCCMs) in carriers of the CCM1 Common Hispanic Mutation. Materials and Methods This study was approved by the institutional review board. The authors retrospectively reviewed abdominal CT scans in 38 patients with fCCM, 38 unaffected age- and sex-matched control subjects, and 13 patients with sporadic, nonfamilial cerebral cavernous malformation (CCM). The size, number, and laterality of calcifications and the morphologic characteristics of the adrenal gland were recorded. Brain lesion count was recorded from brain magnetic resonance (MR) imaging in patients with fCCM. The prevalence of adrenal calcifications in patients with fCCM was compared with that in unaffected control subjects and those with sporadic CCM by using the Fisher exact test. Additional analyses were performed to determine whether age and brain lesion count were associated with adrenal findings in patients with fCCM. Results Small focal calcifications (SFCs) (≤5 mm) were seen in one or both adrenal glands in 19 of the 38 patients with fCCM (50%), compared with 0 of the 38 unaffected control subjects (P < .001) and 0 of the 13 subjects with sporadic CCM (P = .001). Adrenal calcifications in patients with fCCM were more frequently left sided, with 17 of 19 patients having more SFCs in the left adrenal gland than the right adrenal gland and 50 of the 61 observed SFCs (82%) found in the left adrenal gland. No subjects had SFCs on the right side only. In patients with fCCM, the presence of SFCs showed a positive correlation with age (P < .001) and number of brain lesions (P < .001). Conclusion Adrenal calcifications identified on CT scans are common in patients with fCCM and may be a clinically silent manifestation of disease. © RSNA, 2017.
Assuntos
Doenças das Glândulas Suprarrenais/diagnóstico por imagem , Doenças das Glândulas Suprarrenais/etiologia , Doenças das Glândulas Suprarrenais/genética , Calcinose/diagnóstico por imagem , Calcinose/etiologia , Calcinose/genética , Hemangioma Cavernoso do Sistema Nervoso Central/complicações , Hemangioma Cavernoso do Sistema Nervoso Central/diagnóstico por imagem , Hemangioma Cavernoso do Sistema Nervoso Central/genética , Proteínas Associadas aos Microtúbulos/genética , Proteínas Proto-Oncogênicas/genética , Tomografia Computadorizada por Raios X/métodos , Adolescente , Adulto , Biomarcadores/análise , Estudos de Casos e Controles , Criança , Meios de Contraste , Diagnóstico Diferencial , Feminino , Humanos , Proteína KRIT1 , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-IdadeRESUMO
PURPOSE: Familial cerebral cavernous malformation (CCM) patients present with multiple lesions that can grow both in number and size over time and are reliably detected on susceptibility-weighted imaging (SWI). Manual counting of lesions is arduous and subject to high variability. We aimed to develop an automated algorithm for counting CCM microbleeds (lesions <5 mm in diameter) on SWI images. METHODS: Fifty-seven familial CCM type-1 patients were included in this institutional review board-approved study. Baseline SWI (n = 57) and follow-up SWI (n = 17) were performed on a 3T Siemens MR scanner with lesions counted manually by the study neuroradiologist. We modified an algorithm for detecting radiation-induced microbleeds on SWI images in brain tumor patients, using a training set of 22 manually delineated CCM microbleeds from two random scans. Manual and automated counts were compared using linear regression with robust standard errors, intra-class correlation (ICC), and paired t tests. A validation analysis comparing the automated counting algorithm and a consensus read from two neuroradiologists was used to calculate sensitivity, the proportion of microbleeds correctly identified by the automated algorithm. RESULTS: Automated and manual microbleed counts were in strong agreement in both baseline (ICC = 0.95, p < 0.001) and longitudinal (ICC = 0.88, p < 0.001) analyses, with no significant difference between average counts (baseline p = 0.11, longitudinal p = 0.29). In the validation analysis, the algorithm correctly identified 662 of 1325 microbleeds (sensitivity=50%), again with strong agreement between approaches (ICC = 0.77, p < 0.001). CONCLUSION: The automated algorithm is a consistent method for counting microbleeds in familial CCM patients that can facilitate lesion quantification and tracking.
Assuntos
Hemorragia Cerebral/diagnóstico por imagem , Hemangioma Cavernoso do Sistema Nervoso Central/diagnóstico por imagem , Interpretação de Imagem Assistida por Computador/métodos , Imageamento por Ressonância Magnética/métodos , Algoritmos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de RiscoRESUMO
PURPOSE: To evaluate factors that affect eyelid crease formation before and after frontalis suspension. DESIGN: Nonrandomized, comparative, interventional case series. METHODS: Sixty-three patients (125 eyes) with myogenic ptosis were included. Data collected included age, gender, previous surgeries, follow up, as well as pre- and postoperative margin reflex distance, palpebral fissure height, and levator function. Intraoperative maneuvers of incorporation of the levator aponeurosis into the skin closure, conservative fat excision, and conservative skin excision were recorded. Pre- and postoperative eyelid creases were graded by 2 masked, independent observers as "good," "fair," or "poor." RESULTS: The weighted κ coefficient between the graders was 0.68 (95% CI, 0.58-0.79) preoperatively and 0.70 (95% CI, 0.61-0.79) postoperatively. Evaluating preoperative eyelid crease grades, there was no significant difference with regard to age or gender (p = 0.83 or 0.69, respectively). Eyelid crease grade correlated with margin reflex distance (p = 0.0004) and palpebral fissure height (p = 0.002). There was no significant correlation of eyelid crease with levator function (p = 0.104). After frontalis sling, intraoperative maneuvers of incorporation of the levator aponeurosis into the incision, skin preservation, and fat preservation correlated with postoperative eyelid crease (p = 0.0004, 0.059, and 0.033, respectively). CONCLUSIONS: Preoperative levator function in patients with adult onset myogenic ptosis may be an inaccurate measure of true levator palpebrae strength. Reliance on levator function alone in decision making for surgical intervention in these patients may be misguided. The inclusion of the intraoperative maneuvers of incorporation of the levator aponeurosis into the skin incision and preservation of fat and skin results in a stronger eyelid crease after frontalis sling surgery.
Assuntos
Blefaroptose/cirurgia , Doenças Palpebrais/patologia , Distrofia Muscular Oculofaríngea/cirurgia , Músculos Oculomotores/cirurgia , Oftalmoplegia Externa Progressiva Crônica/cirurgia , Implantação de Prótese , Elastômeros de Silicone , Idoso , Blefaroptose/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Distrofia Muscular Oculofaríngea/fisiopatologia , Músculos Oculomotores/fisiopatologia , Oftalmoplegia Externa Progressiva Crônica/fisiopatologia , Próteses e Implantes , Técnicas de SuturaRESUMO
Importance: Cerebral cavernous malformations (CCMs) are vascular lesions of the brain that may lead to hemorrhage, seizures, and neurologic deficits. Most are linked to loss-of-function mutations in 1 of 3 genes, namely CCM1 (originally called KRIT1), CCM2 (MGC4607), or CCM3 (PDCD10), that can either occur as sporadic events or are inherited in an autosomal dominant pattern with incomplete penetrance. Familial forms originate from germline mutations, often have multiple intracranial lesions that grow in size and number over time, and cause an earlier and more severe presentation. Despite active preclinical research on a few pharmacologic agents, clinical translation has been slow. Open surgery and, in some cases, stereotactic radiosurgery remain the only effective treatments, but these options are limited by lesion accessibility and are associated with nonnegligible rates of morbidity and mortality. Observations: We discuss the limits of CCM management and introduce findings from in vitro and in vivo studies that provide insight into CCM pathogenesis and indicate molecular mechanisms as potential therapeutic targets. These studies report dysregulated cellular pathways shared between CCM, cardiovascular diseases, and cancer. They also suggest the potential effectiveness of proper drug repurposing in association with, or as an alternative to, targeted interventions. Conclusions and Relevance: We propose methods to exploit specific molecular pathways to design patient-tailored therapeutic approaches in CCM, with the aim to alter its natural progression. In this scenario, the lack of effective pharmacologic options remains a critical barrier that poses an unfulfilled and urgent medical need.
Assuntos
Neoplasias do Sistema Nervoso Central/tratamento farmacológico , Hemangioma Cavernoso do Sistema Nervoso Central/tratamento farmacológico , Animais , Neoplasias do Sistema Nervoso Central/metabolismo , Neoplasias do Sistema Nervoso Central/patologia , Neoplasias do Sistema Nervoso Central/fisiopatologia , Hemangioma Cavernoso do Sistema Nervoso Central/metabolismo , Hemangioma Cavernoso do Sistema Nervoso Central/patologia , Hemangioma Cavernoso do Sistema Nervoso Central/fisiopatologia , HumanosRESUMO
BACKGROUND: Familial Cerebral Cavernous Malformation type 1 (CCM1) is an autosomal dominant disease caused by mutations in the Krev Interaction Trapped 1 (KRIT1/CCM1) gene, and characterized by multiple brain lesions. CCM lesions manifest across a range of different phenotypes, including wide differences in lesion number, size and susceptibility to intracerebral hemorrhage (ICH). Oxidative stress plays an important role in cerebrovascular disease pathogenesis, raising the possibility that inter-individual variability in genes related to oxidative stress may contribute to the phenotypic differences observed in CCM1 disease. Here, we investigated whether candidate oxidative stress-related cytochrome P450 (CYP) and matrix metalloproteinase (MMP) genetic markers grouped by superfamilies, families or genes, or analyzed individually influence the severity of CCM1 disease. METHODS: Clinical assessment and cerebral susceptibility-weighted magnetic resonance imaging (SWI) were performed to determine total and large (≥5mm in diameter) lesion counts as well as ICH in 188 Hispanic CCM1 patients harboring the founder KRIT1/CCM1 'common Hispanic mutation' (CCM1-CHM). Samples were genotyped on the Affymetrix Axiom Genome-Wide LAT1 Human Array. We analyzed 1,122 genetic markers (both single nucleotide polymorphisms (SNPs) and insertion/deletions) grouped by CYP and MMP superfamily, family or gene for association with total or large lesion count and ICH adjusted for age at enrollment and gender. Genetic markers bearing the associations were then analyzed individually. RESULTS: The CYP superfamily showed a trend toward association with total lesion count (P=0.057) and large lesion count (P=0.088) in contrast to the MMP superfamily. The CYP4 and CYP8 families were associated with either large lesion count or total lesion count (P=0.014), and two other families (CYP46 and the MMP Stromelysins) were associated with ICH (P=0.011 and 0.007, respectively). CYP4F12 rs11085971, CYP8A1 rs5628, CYP46A1 rs10151332, and MMP3 rs117153070 single SNPs, mainly bearing the above-mentioned associations, were also individually associated with CCM1 disease severity. CONCLUSIONS: Overall, our candidate oxidative stress-related genetic markers set approach outlined CYP and MMP families and identified suggestive SNPs that may impact the severity of CCM1 disease, including the development of numerous and large CCM lesions and ICH. These novel genetic risk factors of prognostic value could serve as early objective predictors of disease outcome and might ultimately provide better options for disease prevention and treatment.
Assuntos
Encéfalo/metabolismo , Sistema Enzimático do Citocromo P-450/genética , Hemangioma Cavernoso do Sistema Nervoso Central/genética , Metaloproteinases da Matriz/genética , Estresse Oxidativo/genética , Adulto , Idoso , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Feminino , Genótipo , Hemangioma Cavernoso do Sistema Nervoso Central/diagnóstico por imagem , Hemangioma Cavernoso do Sistema Nervoso Central/patologia , Heterozigoto , Humanos , Proteína KRIT1 , Imageamento por Ressonância Magnética , Masculino , Proteínas Associadas aos Microtúbulos/genética , Pessoa de Meia-Idade , Família Multigênica/genética , Mutação , Fenótipo , Polimorfismo de Nucleotídeo Único , Proteínas Proto-Oncogênicas/genética , Índice de Gravidade de DoençaRESUMO
PURPOSE: To describe the demographics of part-time faculty at U.S. medical schools and to examine their satisfaction with and perceptions of their workplace. METHOD: Faculty from 14 Liaison Committee on Medical Education-accredited U.S. medical schools participated in the 2011-2012 Faculty Forward Engagement Survey. The authors calculated descriptive statistics of part-time faculty respondents and used ANOVA and t test analyses to assess significant differences between and among demographic groups. RESULTS: The survey yielded an overall response rate of 62% (9,600/15,490). Of the part-time faculty respondents, most had appointments in clinical departments (634/674; 94%) and were female (415/674; 62%). Just over 80% (384/474) reported a full-time equivalent of 0.5 or higher. The majority of part-time faculty respondents reported satisfaction with their department and medical school as a place to work (372/496 [75%] and 325/492 [66%]); approximately half agreed that their institution had clear expectations for part-time faculty (210/456; 46%) and provided the resources they needed (232/457; 51%). Significant differences existed between part- and full-time faculty respondents regarding perceptions of growth opportunities and compensation and benefits, with part-time faculty respondents feeling less satisfied in these areas. CONCLUSIONS: As institutions work to improve the satisfaction of full-time faculty, they should do the same for part-time faculty. Understanding why faculty choose part-time work is important in encouraging the recruitment and retention of the most talented faculty. The findings of this study indicate multiple opportunities to improve the satisfaction and engagement of part-time faculty.
Assuntos
Docentes de Medicina/organização & administração , Satisfação no Emprego , Gestão de Recursos Humanos , Faculdades de Medicina , Emprego , Feminino , Humanos , Masculino , Estados UnidosRESUMO
The aim of this study is to quantitatively evaluate the behavior of CNS cavernous malformations (CCMs) using a dynamic contrast-enhanced MRI (DCEMRI) technique sensitive for slow transfer rates of gadolinium. The prospective study was approved by the institutional review board and was HIPPA compliant. Written informed consent was obtained from 14 subjects with familial CCMs (4 men and 10 women, ages 22-76 years, mean 48.1 years). Following routine anatomic MRI of the brain, DCEMRI was performed for six slices, using T1 mapping with partial inversion recovery (TAPIR) to calculate T1 values, following administration of 0.025 mmol/kg gadolinium DTPA. The transfer rate (Ki) was calculated using the Patlak model, and Ki within CCMs was compared to normal-appearing white matter as well as to 17 normal control subjects previously studied. All subjects had typical MRI appearance of CCMs. Thirty-nine CCMs were studied using DCEMRI. Ki was low or normal in 12 lesions and elevated from 1.4 to 12 times higher than background in the remaining 27 lesions. Ki ranged from 2.1E-6 to 9.63E-4 min(-1), mean 3.55E-4. Normal-appearing white matter in the CCM patients had a mean Ki of 1.57E-4, not statistically different from mean WM Ki of 1.47E-4 in controls. TAPIR-based DCEMRI technique permits quantifiable assessment of CCMs in vivo and reveals considerable differences not seen with conventional MRI. Potential applications include correlation with biologic behavior such as lesion growth or hemorrage, and measurement of drug effects.
Assuntos
Malformações Vasculares do Sistema Nervoso Central/diagnóstico , Meios de Contraste , Gadolínio DTPA , Imageamento por Ressonância Magnética/métodos , Adulto , Idoso , Neoplasias do Sistema Nervoso Central/diagnóstico , Feminino , Hemangioma Cavernoso do Sistema Nervoso Central/diagnóstico , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Adulto JovemRESUMO
AIM: To evaluate outcomes of patients with oculopharyngeal muscular dystrophy (OPMD) with levator function (LF) ≥ 10mm who underwent primary bilateral silicone frontalis suspension. METHODS: 31 patients with OPMD satisfied the following inclusion criteria: LF ≥ 10 mm; no previous eyelid surgery; and pre-operative measurements, silcone frontalis suspension and post-operative measurements performed by a single individual. The following data were collected: age; gender; pre-operative margin reflex distance (MRD), palpebral fissure height (PF), and LF; post-operative MRD, PF and lagophthalmos; follow-up; and complications. RESULTS: Mean age at surgery was 61.5 ± 5.8 years. Pre-operative measurements for MRD, PF and LF were -0.05 ± 0.82 mm (OD), -0.13 ± 0.91 mm (OS); 5.2 ± 1.2 mm (OD), 5.2 ± 1.3 mm (OS); 11.6 ± 1.3 mm (OD), and 11.7 ± 1.3 mm (OS), respectively. Post-operative measurements for MRD and PF were 2.23 ± 0.97 mm (OD), 2.10 ± 1.09 mm (OS), 7.9 ± 1.4 mm (OD), and 7.7 ± 1.6 mm (OS), respectively (all p < 0.0001). The mean follow-up period was 22.8 ± 22.4 months. There was no sling (infection or extrusion) or ophthalmic (significant corneal compromise) complication after the surgery. Six patients (19%) underwent early (within 3 months) tightening of their slings for under correction. Three patients (10%) underwent late (> 39 months) tightening of their frontalis slings for recurrent ptosis after their initial surgery. CONCLUSIONS: Primary bilateral silicone frontalis suspension for good LF ptosis secondary to OPMD appears to be an effective, safe treatment which gives symmetrical upper lid elevation. Early sling adjustment may be required to attain optimal eyelid height and late tightening for expectant loosening of the sling is safe and effective.
Assuntos
Blefaroplastia/métodos , Blefaroptose/cirurgia , Distrofia Muscular Oculofaríngea/cirurgia , Músculos Oculomotores/cirurgia , Elastômeros de Silicone , Idoso , Anestesia Local/métodos , Blefaroptose/fisiopatologia , Pálpebras/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Músculos Oculomotores/fisiopatologia , Retalhos Cirúrgicos , Resultado do TratamentoRESUMO
PURPOSE: To examine the current state of satisfaction with the academic medicine workplace among U.S. medical school faculty and the workplace factors that have the greatest influence on global satisfaction. METHOD: The authors used data from the 2009 administration of a medical school faculty job satisfaction survey and used descriptive statistics and χ analyses to assess levels of overall satisfaction within faculty subgroups. Multiple regressions used the mean scores of the 18 survey dimensions and demographic variables to predict three global satisfaction measures. RESULTS: The survey was completed by 9,638 full-time faculty from 23 U.S. medical schools. Respondents were mostly satisfied on global satisfaction measures including satisfaction with their department (6,506/9,128; 71.3%) and medical school (5,796/9,124; 63.5%) and whether they would again choose to work at their medical school (5,968/8,506; 70.2%). The survey dimensions predicted global satisfaction well, with the final models explaining 51% to 67% of the variance in the dependent measures. Predictors across models include organization, governance, and transparency; focus of mission; recruitment and retention effectiveness; department relationships; workplace culture; and nature of work. CONCLUSIONS: Despite the relatively unpredictable environmental challenges facing medical schools today, leaders have opportunities to influence and improve the workplace satisfaction of their faculty. Examples of opportunities include fostering a culture characterized by open communication and occasions for faculty input, and remaining vigilant regarding factors contributing to faculty burnout. Understanding what drives faculty satisfaction is crucial for medical schools as they continue to seek excellence in all missions and recruit and retain high-quality faculty.
Assuntos
Docentes de Medicina , Satisfação no Emprego , Faculdades de Medicina , Carga de Trabalho/psicologia , Local de Trabalho/normas , Feminino , Humanos , Masculino , Inquéritos e Questionários , Estados Unidos , Recursos HumanosRESUMO
Recent progress in scientific research has facilitated accurate genetic and neuropathological diagnosis of congenital myopathies. However, given their relatively low incidence, congenital myopathies remain unfamiliar to the majority of care providers, and the levels of patient care are extremely variable. This consensus statement aims to provide care guidelines for congenital myopathies. The International Standard of Care Committee for Congenital Myopathies worked through frequent e-mail correspondences, periodic conference calls, 2 rounds of online surveys, and a 3-day workshop to achieve a consensus for diagnostic and clinical care recommendations. The committee includes 59 members from 10 medical disciplines. They are organized into 5 working groups: genetics/diagnosis, neurology, pulmonology, gastroenterology/nutrition/speech/oral care, and orthopedics/rehabilitation. In each care area the authors summarize the committee's recommendations for symptom assessments and therapeutic interventions. It is the committee's goal that through these recommendations, patients with congenital myopathies will receive optimal care and improve their disease outcome.
Assuntos
Protocolos Clínicos/normas , Saúde Global , Distrofias Musculares/diagnóstico , Distrofias Musculares/terapia , Padrão de Cuidado/normas , Congressos como Assunto , Humanos , Distrofias Musculares/complicações , Distrofias Musculares/congênitoRESUMO
A strategy for using tissue water as a concentration standard in (1)H magnetic resonance spectroscopic imaging studies on the brain is presented, and the potential errors that may arise when the method is used are examined. The sensitivity of the method to errors in estimates of the different water compartment relaxation times is shown to be small at short echo times (TEs). Using data from healthy human subjects, it is shown that different image segmentation approaches that are commonly used to account for partial volume effects (SPM2, FSL's FAST, and K-means) lead to different estimates of metabolite levels, particularly in gray matter (GM), owing primarily to variability in the estimates of the cerebrospinal fluid (CSF) fraction. While consistency does not necessarily validate a method, a multispectral segmentation approach using FAST yielded the lowest intersubject variability in the estimates of GM metabolites. The mean GM and white matter (WM) levels of N-acetyl groups (NAc, primarily N-acetylaspartate), choline (Ch), and creatine (Cr) obtained in these subjects using the described method with FAST multispectral segmentation are reported: GM [NAc] = 17.16 +/- 1.19 mM; WM [NAc] = 14.26 +/- 1.38 mM; GM [Ch] = 3.27 +/- 0.47 mM; WM [Ch] = 2.65 +/- 0.25 mM; GM [Cr] = 13.98 +/- 1.20 mM; and WM [Cr] = 7.10 +/- 0.67 mM.