RESUMEN
OBJECTIVES: We aimed to characterize worldwide electroconvulsive therapy (ECT) practice and compare practice across nations and global regions. METHOD: Our anonymous survey was open on SurveyMonkey.com from January to June 2022. We sent invitations to providers identified using a Medicare provider database, an advanced PubMed search function, and professional group listservs. Participants were instructed to submit one survey per ECT site. Response frequencies were pooled by global region and compared using nonparametric methods. RESULTS: Responses came from 126 sites, mostly in the United States (59%, n = 74), Europe (18%, n = 23), Canada (10%, n = 12), and South/East Asia (6%, n = 8). With some exceptions, sites were broadly consistent in practice as indicated by: a likely shift internationally from bitemporal to right unilateral electrode placement; predominant use of pulse widths <1 ms; preference for seizure threshold titration over age-based dosing methods; widespread availability of continuation/maintenance ECT (97%); and frequent use of quantitative outcome measures for depressive symptoms (88%) and cognitive adverse effects (80%). CONCLUSIONS: This is the first, published survey that aimed to characterize worldwide ECT practice. With some exceptions, responses suggest a concordance in practice. However, responses were primarily from the Global North. To obtain a truly worldwide characterization of practice, future surveys should include more responses from the Global South.
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Terapia Electroconvulsiva , Humanos , Canadá , Encuestas y Cuestionarios , Pautas de la Práctica en Medicina/estadística & datos numéricos , Estados Unidos , Europa (Continente)RESUMEN
OBJECTIVES: This study aimed to describe current US electroconvulsive therapy (ECT) practice, identify practice changes over time, and inform discussion of practice. METHOD: Our anonymous survey was open on SurveyMonkey.com from January to June 2022. We sent invitations to providers identified using a Medicare provider database, an advanced PubMed search function, and professional group listservs. Participants were instructed to submit 1 survey per ECT site. We examined frequency of responses, tabulated individual comments, and grouped data for comparison. RESULTS: We received responses from 74 US practice sites encompassing 283 providers. Forty-nine percent (n = 36) of respondents practiced at general academic medical centers, 23% (n = 17) at general medical centers, 16% (n = 12) at freestanding psychiatric hospitals, and 7% (n = 5) at Veterans Affairs medical centers. Proportions of female (29%) and Black or African American (AA) (1%) ECT providers were markedly lower than proportions of female (60%) and Black or African American ECT patients (10%). The median number of treatments for a major depressive episode was 10. The preferred electrode placement was right unilateral (66%, n = 45). The favored dosing strategy was seizure threshold titration. Quantitative outcome measures were used by 89% (n = 66) of sites for depressive symptoms and 84% (n = 62) for cognitive adverse effects. CONCLUSIONS: This survey is the first nationwide survey of ECT practice in nearly 40 years. Our results describe changes in practice over time and highlight the need to increase the number of female and Black or African American ECT providers. A comprehensive network of ECT sites could facilitate more frequent nationwide surveys.
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Terapia Electroconvulsiva , Humanos , Estados Unidos , Femenino , Masculino , Pautas de la Práctica en Medicina/estadística & datos numéricos , Trastorno Depresivo Mayor/terapia , Encuestas y CuestionariosRESUMEN
ABSTRACT: Repetitive transcranial magnetic stimulation (rTMS) is Food and Drug Administration cleared for clinical use in treatment-resistant depression and a growing list of other disorders. The clinical uptake of rTMS has been facilitated by its relatively benign adverse-effect profile compared with other treatment modalities. Seizure is a rare but serious adverse event that has been reported with rTMS, when dosage exceeds safety guidelines or in individuals at increased risk for seizure. Fortunately, most rTMS-induced seizures are typically transient, with no adverse sequelae, but they may lead to treatment discontinuation. Seizure is not the only cause of loss of conscious and abnormal movements induced by rTMS. Convulsive syncope, a more common adverse event that involves loss of consciousness associated with myoclonic movements, can be difficult to differentiate from an rTMS-induced seizure. We report the case of a 52-year-old man with no known seizure risk factors, enrolled in an institutional review board-approved research study who developed what appeared to be a convulsive syncopal episode lasting 10 to 15 seconds during day 2 of a 30-day rTMS protocol (10 Hz, 120% of motor threshold, 4-second pulse train, 26-second intertrain interval, 3000 pulses per session), with no adverse sequelae. The patient's history, screening, physical examination, pertinent laboratory, neurology consult, electroencephalogram, and imaging findings are discussed. This case demonstrates that distinguishing between convulsive syncope and rTMS-induced seizure can be a diagnostic challenge. Clinicians and researchers delivering rTMS should be familiar with the risk factors for rTMS-induced seizures and rTMS-induced convulsive syncope, to screen for predisposing factors and to manage these rare adverse events if they occur.
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Terapia Electroconvulsiva , Estimulación Magnética Transcraneal , Masculino , Humanos , Persona de Mediana Edad , Estimulación Magnética Transcraneal/efectos adversos , Estimulación Magnética Transcraneal/métodos , Convulsiones/diagnóstico , Convulsiones/etiología , Convulsiones/terapia , Síncope/etiología , Síncope/complicaciones , Factores de RiesgoRESUMEN
Approximately half of stroke survivors suffer from clinically significant fatigue, contributing to poor quality of life, depression, dependency, and increased mortality. The etiology of post-stroke fatigue is not well understood and treatment is limited. This study tested the hypothesis that systemic aerobic energy metabolism, as reflected by platelet oxygen consumption, is negatively associated with fatigue and systemic inflammation is positively associated with fatigue in chronic ischemic stroke survivors. Data on self-reported level of fatigue, platelet oxygen consumption rates (OCR) and plasma inflammatory markers were analyzed from 20 ischemic stroke survivors. DNA copy number for two mitochondrial genes was measured as a marker of platelet mitochondrial content. Basal and protonophore-stimulated maximal platelet OCR showed a biphasic relationship to fatigue. Platelet OCR was negatively associated with low to moderate fatigue but was positively associated with moderate to high fatigue. DNA copy number was not associated with either fatigue or platelet OCR. Fatigue was negatively associated with C-reactive protein but not with other inflammatory markers. Post-stroke fatigue may be indicative of a systemic cellular energy dysfunction that is reflected in platelet energy metabolism. The biphasic relationship of fatigue to platelet OCR may indicate an ineffective bioenergetic compensatory response that has been observed in other pathological states.
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Plaquetas/metabolismo , Isquemia Encefálica/sangre , Metabolismo Energético , Fatiga/sangre , Consumo de Oxígeno , Accidente Cerebrovascular/sangre , Anciano , Anciano de 80 o más Años , Biomarcadores/sangre , Plaquetas/patología , Isquemia Encefálica/patología , Enfermedad Crónica , Fatiga/patología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Accidente Cerebrovascular/patologíaRESUMEN
Currently there is no consensus statement about the safety of electroconvulsive therapy in patients who have implanted electrodes for deep brain stimulation. We present a summary of the existing literature on this topic, consisting of 21 cases, and then report a case performed at the University of Maryland Medical Center. Notably, with appropriate safety precautions and careful patient selection, there were no adverse events reported in the literature that were related to the presence of the deep brain stimulation device in any of the cases. Based on our review of the literature and the case we present, we have found no evidence so far to indicate that electroconvulsive therapy in patients with an implanted deep brain stimulator is unsafe.
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Estimulación Encefálica Profunda , Terapia Electroconvulsiva/efectos adversos , Terapia Electroconvulsiva/métodos , Trastorno Depresivo Mayor/complicaciones , Trastorno Depresivo Mayor/terapia , Electrodos Implantados , Femenino , Humanos , Persona de Mediana Edad , Enfermedad de Parkinson/complicaciones , Enfermedad de Parkinson/terapia , Seguridad del PacienteRESUMEN
The safety of electroconvulsive therapy (ECT) is improving with advances in anesthesia and ECT technique. There are published case reports of successful treatment of depression in patients who were once considered at high medical risk. Recent cerebral hemorrhage is one of the conditions considered to significantly increase the risk of ECT treatment. Literature search did not indicate any case reports of ECT treatment in patients with recent subarachnoid hemorrhage. We report the successful ECT treatment of depression in an older man who had developed a subarachnoid hemorrhage after a suicide attempt by ingestion of antifreeze.
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Trastorno Depresivo Mayor/terapia , Terapia Electroconvulsiva/métodos , Hemorragia Subaracnoidea/complicaciones , Anciano , Encéfalo/diagnóstico por imagen , Encéfalo/patología , Trastorno Depresivo Mayor/complicaciones , Glicol de Etileno/envenenamiento , Humanos , Masculino , Suicidio , Tomografía Computarizada por Rayos XRESUMEN
Major depressive disorder (MDD) is an important public health problem affecting 350 million people worldwide. After decades of study, the pathophysiology of MDD remains elusive, resulting in treatments that are only 30-60% effective. This review summarizes the emerging evidence that implicates impaired mitochondrial bioenergetics as a basis for MDD. It is suggested that impaired mitochondrial bioenergetic function contributes to the pathophysiology of MDD via several potential pathways including: genetics/genomics, inflammation, oxidative stress, and alterations in neuroplasticity. A discussion of mitochondrial bioenergetic pathways that lead to MDD is provided. Evidence is reviewed regarding the mito-toxic or mito-protective impact of various antidepressant medications currently in use. Opportunities for further research on novel therapeutic approaches, including mitochondrial modulators, as stand-alone or adjunct therapy for reducing depression are suggested. In conclusion, while there is substantial evidence linking mitochondrial bioenergetics and MDD, there are currently no clear mitochondrial phenotypes or biomarkers to use as guides in targeting therapies beyond individuals with MDD and known mitochondrial disorders toward the general population of individuals with MDD. Further study is needed to develop these phenotypes and biomarkers, to identify therapeutic targets, and to test therapies aimed at improving mitochondrial function in individuals whose MDD is to some extent symptomatic of impaired mitochondrial bioenergetics.
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Trastorno Depresivo Mayor , Metabolismo Energético/genética , Mitocondrias , Enfermedades Mitocondriales , Animales , Trastorno Depresivo Mayor/genética , Trastorno Depresivo Mayor/metabolismo , Trastorno Depresivo Mayor/patología , Humanos , Mitocondrias/genética , Mitocondrias/metabolismo , Mitocondrias/patología , Enfermedades Mitocondriales/genética , Enfermedades Mitocondriales/metabolismo , Enfermedades Mitocondriales/patologíaRESUMEN
BACKGROUND: Brain-derived neurotrophic factor (BDNF) protein levels decline in the brain during senescence and are also shown to be reduced in schizophrenia patients. BDNF is present in both the gray and white matters of the brain. It is unclear whether BDNF abnormalities in schizophrenia are specific to gray and/or white matter. OBJECTIVE: We hypothesized that the age-related BDNF decline is abnormal and contributes to the reduced BDNF in schizophrenia. METHODS: We tested this hypothesis by measuring BDNF protein levels in postmortem gray and white matter, using the prefrontal cortex (PFC) and the genu of the corpus callosum as regions of interests, from 20 schizophrenia patients and 20 matched nonpsychiatric controls. Samples were selected across the adult lifespan--from 20 to 80 years of age. RESULTS: PFC gray matter BDNF protein levels were significantly lower in older age in both nonpsychiatric comparisons and patients, while BDNF in white matter did not decrease significantly with age in either group. PFC BDNF was linearly lower from 20 to 80 years of age in nonpsychiatric comparisons. In schizophrenia, the age effect was similarly linear in younger patients but a decline did not occur in older patients. CONCLUSION: PFC BDNF does not follow a normative linear age effect in schizophrenia patients as they grow older, which may represent a 'floor effect' due to earlier decline or a survivor cohort of older patient donors who are less susceptible to a schizophrenia-related pathological aging process.
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Envejecimiento/metabolismo , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Encéfalo/metabolismo , Enfermedades Neurodegenerativas/metabolismo , Esquizofrenia/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Autopsia , Estudios de Casos y Controles , Cuerpo Calloso/metabolismo , Diagnóstico Diferencial , Femenino , Sustancia Gris/metabolismo , Humanos , Masculino , Persona de Mediana Edad , Enfermedades Neurodegenerativas/diagnóstico , Corteza Prefrontal/metabolismo , Esquizofrenia/diagnóstico , Sustancia Blanca/metabolismoRESUMEN
The smoking rate is high in patients with schizophrenia. Brain stimulation targeting conventional brain circuits associated with nicotine addiction has also yielded mixed results. We aimed to identify alternative circuitries associated with nicotine addiction in both the general population and schizophrenia, and then test whether modulation of such circuitries may alter nicotine addiction behaviors in schizophrenia. In Study I of 40 schizophrenia smokers and 51 non-psychiatric smokers, cross-sectional neuroimaging analysis identified resting state functional connectivity (rsFC) between the dorsomedial prefrontal cortex (dmPFC) and multiple extended amygdala regions to be most robustly associated with nicotine addiction severity in healthy controls and schizophrenia patients (p = 0.006 to 0.07). In Study II with another 30 patient smokers, a proof-of-concept, patient- and rater-blind, randomized, sham-controlled rTMS design was used to test whether targeting the newly identified dmPFC location may causally enhance the rsFC and reduce nicotine addiction in schizophrenia. Although significant interactions were not observed, exploratory analyses showed that this dmPFC-extended amygdala rsFC was enhanced by 4-week active 10Hz rTMS (p = 0.05) compared to baseline; the severity of nicotine addiction showed trends of reduction after 3 and 4 weeks (p ≤ 0.05) of active rTMS compared to sham; Increased rsFC by active rTMS predicted reduction of cigarettes/day (R = -0.56, p = 0.025 uncorrected) and morning smoking severity (R = -0.59, p = 0.016 uncorrected). These results suggest that the dmPFC-extended amygdala circuit may be linked to nicotine addiction in schizophrenia and healthy individuals, and future efforts targeting its underlying pathophysiological mechanisms may yield more effective treatment for nicotine addiction.
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Imagen por Resonancia Magnética , Esquizofrenia , Tabaquismo , Estimulación Magnética Transcraneal , Humanos , Esquizofrenia/diagnóstico por imagen , Esquizofrenia/fisiopatología , Esquizofrenia/terapia , Tabaquismo/terapia , Tabaquismo/diagnóstico por imagen , Tabaquismo/fisiopatología , Masculino , Adulto , Femenino , Estimulación Magnética Transcraneal/métodos , Corteza Prefrontal/diagnóstico por imagen , Corteza Prefrontal/fisiopatología , Persona de Mediana Edad , Amígdala del Cerebelo/diagnóstico por imagen , Amígdala del Cerebelo/fisiopatología , Neuroimagen , Estudios TransversalesAsunto(s)
Encefalopatías , Hiperamonemia , Trastornos Mentales , Anticonvulsivantes , Hospitales Generales , Humanos , Ácido ValproicoAsunto(s)
Enfermedad de Alzheimer/tratamiento farmacológico , Inhibidores de la Colinesterasa , Esquema de Medicación , Inhibidores de la Colinesterasa/administración & dosificación , Inhibidores de la Colinesterasa/efectos adversos , Inhibidores de la Colinesterasa/clasificación , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/prevención & control , HumanosRESUMEN
OBJECTIVE: An association between allergic disease and depression has been consistently reported, but whether the key mediating ingredients are predominantly biological, psychological, or mere artifacts remains unknown. In the current study, we examined a hypothesized relationship between allergen-specific immunoglobulin E (IgE) status and changes in allergy symptoms with worsening in depression scores. METHODS: In patients with recurrent mood disorders, we individually coupled sensitization to specific seasonal aeroallergens (as assessed by allergen-specific IgE) with temporal windows of exposure to aeroallergens (low versus high tree or ragweed pollen counts, measured according to the National Allergy Bureau guidelines). We compared Structured Interview Guide for the Hamilton Depression Rating Scale-Seasonal Affective Disorder Version (SIGH-SAD) depression score changes in 41 patients with mood disorders [25 with major depression and 16 with bipolar I disorder, diagnosed by Structured Clinical Interview for DSM (SCID)] seropositive for tree or ragweed pollen-specific IgE antibody versus 53 patients with mood disorders (30 with major depression and 23 with bipolar I disorder) seronegative for aeroallergen-specific IgE. RESULTS: Worsening in total depressive scores from low to high pollen exposure was greater in allergen-specific IgE-positive patients as compared to allergen-specific IgE antibody-negative patients (p = 0.01). When stratified by polarity, the association was significant only in patients with bipolar I disorder (p = 0.004). This relationship was resilient to adjustment for changes in allergy symptom scores. CONCLUSION: To our knowledge, this is the first report of coupling a molecular marker of vulnerability (allergen-specific IgE) with a specific environmental trigger (airborne allergens) leading to exacerbation of depression in patients with bipolar I disorder.
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Alérgenos/inmunología , Trastorno Bipolar/inmunología , Depresión/inmunología , Inmunoglobulina E/sangre , Polen/inmunología , Rinitis Alérgica Estacional/psicología , Adulto , Ambrosia/inmunología , Trastorno Bipolar/psicología , Depresión/psicología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estaciones del Año , Índice de Severidad de la Enfermedad , Árboles/inmunologíaRESUMEN
Vitamin B12 deficiency is a common cause of neuropsychiatric symptoms in elderly persons. Malabsorption accounts for the majority of cases. Vitamin B12 deficiency has been associated with neurologic, cognitive, psychotic, and mood symptoms, as well as treatment-resistance. Clinician awareness should be raised to accurately diagnose and treat early deficiencies to prevent irreversible structural brain damage, because current practice can be ineffective at identifying cases leading to neuropsychiatric sequelae. This clinical review focuses on important aspects of the recognition and treatment of vitamin B12 deficiency and neuropsychiatric manifestations of this preventable illness in elderly patients.
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Envejecimiento , Trastornos del Conocimiento/etiología , Enfermedades del Sistema Nervioso/etiología , Neuropsiquiatría , Trastornos Psicóticos/etiología , Deficiencia de Vitamina B 12/complicaciones , Sistema Nervioso Central/patología , Humanos , Síndromes de Malabsorción/epidemiología , Síndromes de Malabsorción/etiología , Enfermedades del Sistema Nervioso/epidemiología , Trastornos Psicóticos/epidemiología , PubMed/estadística & datos numéricos , Deficiencia de Vitamina B 12/epidemiologíaRESUMEN
More than any other brain region, the prefrontal cortex (PFC) gives rise to the singularity of human experience. It is therefore frequently implicated in the most distinctly human of all disorders, those of mental health. Noninvasive neuromodulation, including electroconvulsive therapy (ECT), repetitive transcranial magnetic stimulation (rTMS), and transcranial direct current stimulation (tDCS) among others, can-unlike pharmacotherapy-directly target the PFC and its neural circuits. Direct targeting enables significantly greater on-target therapeutic effects compared with off-target adverse effects. In contrast to invasive neuromodulation approaches, such as deep-brain stimulation (DBS), noninvasive neuromodulation can reversibly modulate neural activity from outside the scalp. This combination of direct targeting and reversibility enables noninvasive neuromodulation to iteratively change activity in the PFC and its neural circuits to reveal causal mechanisms of both disease processes and healthy function. When coupled with neuronavigation and neurophysiological readouts, noninvasive neuromodulation holds promise for personalizing PFC neuromodulation to relieve symptoms of mental health disorders by optimizing the function of the PFC and its neural circuits. ClinicalTrials.gov Identifier: NCT03191058.
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Estimulación Transcraneal de Corriente Directa , Encéfalo , Humanos , Salud Mental , Corteza Prefrontal , Estimulación Magnética TranscranealRESUMEN
Glucose-6-phosphate dehydrogenase (G6PD) is the first and rate-limiting enzyme of the pentose phosphate pathway that is essential to maintaining cellular redox balance. G6PD is especially plentiful in brain, and its deficiency has been linked to mood and psychotic disorders. We measured G6PD activity spectrophotometrically in four groups of 15 parietal somatosensory association cortex [Brodmann area (BA) 7] tissue samples (Nâ¯=â¯60) from individuals with bipolar disorder (BPD); nonpsychotic unipolar major depression (UPD); schizophrenia (SCZ), and controls without psychiatric illness (CON). We report for the first time brain G6PD activity levels in these disorders. G6PD activity did not differ by brain group. In BPD and SCZ brains, however, it correlated significantly and inversely with percent of hexokinase 1 (HK1) in the tissue homogenate mitochondrial fraction as determined previously in another set of tissue samples obtained from the same brains and brain region. The correlation in SCZ brains lost statistical significance after controlling for brain pH. This finding indicates a positive relationship in BPD brains between G6PD activity and HK1 mitochondrial detachment, an indicator of mitochondrial impairment associated with increased mitochondrial generation of reactive oxygen species. We speculate that this relationship could be evidence that G6PD activity is proportionate to and may be a compensatory response to oxidative stress in the BA7 region of BPD brains. Future research should focus on clarifying the relationships among G6PD activity, markers of oxidative stress, brain pH, and evidence of mitochondrial impairment, particularly HK1 mitochondrial detachment, in brains of individuals with G6PD deficiency, BPD and SCZ.
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Trastorno Bipolar/metabolismo , Trastorno Depresivo Mayor/metabolismo , Glucosafosfato Deshidrogenasa/metabolismo , Hexoquinasa/metabolismo , Enfermedades Mitocondriales/metabolismo , Estrés Oxidativo , Esquizofrenia/metabolismo , Corteza Somatosensorial/metabolismo , Adulto , Autopsia , Femenino , Humanos , MasculinoRESUMEN
OBJECTIVES: Both diabetes mellitus and magnetic resonance image (MRI) deep white matter hyperintensities (WMHs) are more common in bipolar disorder (BD) patients than in matched controls. Deep-as opposed to periventricular--WMHs and diabetes are associated with treatment resistance and poorer outcome. This study investigated whether brain glucose metabolism by the polyol pathway--a pathway linked to nervous tissue disease in diabetes--is related to deep WMH volume and treatment resistance in BD patients. METHODS: Volumes of fluid-attenuated inversion recovery WMHs were quantified and correlated with cerebrospinal fluid (CSF) concentrations of glucose metabolites in 20 nondiabetic patients with BD and nondiabetic comparison subjects with schizophrenia (n = 15) or transient neurologic symptoms (neurologic controls, n = 15). RESULTS: BD patients, but not schizophrenic patients, had significantly greater volumes of deep but not periventricular WMHs compared to neurologic controls. BD subjects also had significantly greater CSF concentrations of sorbitol and fructose (the polyol pathway metabolites of glucose) compared to controls. Significant positive correlations between CSF metabolites and WMH volumes were found only in the BD group and were between deep WMH volumes and CSF sorbitol (rho = 0.487, p = 0.029) and fructose (rho = 0.474, p = 0.035). An index of treatment resistance correlated significantly with deep WMH volume (rho = 0.578, p = 0.008), sorbitol (rho = 0.542, p = 0.013), and fructose (rho = 0.692, p = 0.001) in BD subjects but not in other subjects. CONCLUSIONS: This is the first reported evidence of relationships between abnormal brain glucose metabolism and both deep WMHs and treatment resistance in a group of BD patients. Further studies are necessary to determine the significance of these findings to BD pathophysiology.
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Trastorno Bipolar/líquido cefalorraquídeo , Trastorno Bipolar/patología , Glucosa/líquido cefalorraquídeo , Fibras Nerviosas Mielínicas/patología , Adolescente , Adulto , Análisis de Varianza , Trastorno Bipolar/sangre , Femenino , Fructosa/sangre , Fructosa/líquido cefalorraquídeo , Cromatografía de Gases y Espectrometría de Masas/métodos , Humanos , Imagen por Resonancia Magnética/métodos , Masculino , Persona de Mediana Edad , Esquizofrenia/líquido cefalorraquídeo , Esquizofrenia/patología , Sorbitol/sangre , Sorbitol/líquido cefalorraquídeo , Estadística como Asunto , Adulto JovenRESUMEN
In contrast to relapse, the mechanisms of multiple sclerosis (MS) disease progression are less understood and appear not to be exclusively inflammatory in nature. In this pilot study we investigated the relationship between disturbed CNS energy metabolism and MS disease progression. We tested the hypothesis that cerebrospinal fluid (CSF) concentrations of sorbitol, fructose, and lactate, all metabolites of extra-mitochondrial glucose metabolism, would be elevated in secondary progressive (SP) MS patients and would be associated with worsening neurologic disability. We measured metabolite concentrations by gas chromatographic/mass spectrometric and enzymatic methods in archived CSF samples from 85 MS patients [31 relapsing-remitting (RR) and 54 SP patients] and 18 healthy controls. We found that concentrations of all three metabolites, but not concentrations of glucose or myoinositol, were significantly increased in CSF from SP and, to a lesser degree, RR patients, compared to controls. Furthermore, CSF concentrations of sorbitol and fructose (polyol pathway metabolites), but not lactate (anaerobic glycolysis metabolite), correlated positively and significantly with Expanded Disability Status Scale (EDSS) score, an index of neurologic disability in MS patients. We conclude that extra-mitochondrial glucose metabolism is increased in MS patients and is associated with disease progression evidenced by increasing EDSS score. As extra-mitochondrial glucose metabolism increases with impaired mitochondrial metabolism of glucose, these findings implicate mitochondrial dysfunction in the pathogenesis of MS disease progression. CSF metabolic profiling may be useful in clarifying the role of mitochondrial pathology in progression and in targeting and monitoring therapies for disease progression that aim to preserve or boost mitochondrial glucose metabolism.