Use of gadolinium-based contrast agents in multiple sclerosis: a review by the ESMRMB-GREC and ESNR Multiple Sclerosis Working Group.

Magnetic resonance imaging (MRI) is the most sensitive technique for detecting inflammatory demyelinating lesions in multiple sclerosis (MS) and plays a crucial role in diagnosis and monitoring treatment effectiveness, and for predicting the disease course. In clinical practice, detection of MS lesions is mainly based on T2-weighted and contrast-enhanced T1-weighted sequences. Contrast-enhancing lesions (CEL) on T1-weighted sequences are related to (sub)acute inflammation, while new or enlarging T2 lesions reflect the permanent footprint from a previous acute inflammatory demyelinating event. These two types of MRI features provide redundant information, at least in regular monitoring of the disease. Due to the concern of gadolinium deposition after repetitive injections of gadolinium-based contrast agents (GBCAs), scientific organizations and regulatory agencies in Europe and North America have proposed that these contrast agents should be administered only if clinically necessary. In this article, we provide data on the mode of action of GBCAs in MS, the indications of the use of these agents in clinical practice, their value in MS for diagnostic, prognostic, and monitoring purposes, and their use in specific populations (children, pregnant women, and breast-feeders). We discuss imaging strategies that achieve the highest sensitivity for detecting CELs in compliance with the safety regulations established by different regulatory agencies. Finally, we will briefly discuss some alternatives to the use of GBCA for detecting blood-brain barrier disruption in MS lesions. CLINICAL RELEVANCE STATEMENT: Although use of GBCA at diagnostic workup of suspected MS is highly valuable for diagnostic and prognostic purposes, their use in routine monitoring is not mandatory and must be reduced, as detection of disease activity can be based on the identification of new or enlarging lesions on T2-weighted images. KEY POINTS: • Both the EMA and the FDA state that the use of GBCA in medicine should be restricted to clinical scenarios in which the additional information offered by the contrast agent is required. • The use of GBCA is generally recommended in the diagnostic workup in subjects with suspected MS and is generally not necessary for routine monitoring in clinical practice. • Alternative MRI-based approaches for detecting acute focal inflammatory MS lesions are not yet ready to be used in clinical practice.

Editorial Comment: Free water corrected diffusion tensor imaging discriminates between good and poor outcome of comatose patients after cardiac arrest.

KEY POINTS: • Prediction of neurological outcome after cardiac arrest is a major ethical challenge. • Diffusion tensor imaging (DTI) is a promising prognostic tool in comatose patients assessing brain microstructural damages. • The combination of clinical data with whole-brain fractional anisotropy and mean diffusivity values appears more accurate to predict poor outcome.

Multiple sclerosis imaging in clinical practice: a European-wide survey of 428 centers and conclusions by the ESNR Working Group.

OBJECTIVES: To evaluate compliance with the available recommendations, we assessed the current clinical practice of imaging in the evaluation of multiple sclerosis (MS). METHODS: An online questionnaire was emailed to all members and affiliates. Information was gathered on applied MR imaging protocols, gadolinium-based contrast agents (GBCA) use and image analysis. We compared the survey results with the Magnetic Resonance Imaging in MS (MAGNIMS) recommendations considered as the reference standard. RESULTS: A total of 428 entries were received from 44 countries. Of these, 82% of responders were neuroradiologists. 55% performed more than ten scans per week for MS imaging. The systematic use of 3 T is rare (18%). Over 90% follow specific protocol recommendations with 3D FLAIR, T2-weighted and DWI being the most frequently used sequences. Over 50% use SWI at initial diagnosis and 3D gradient-echo T1-weighted imaging is the most used MRI sequence for pre- and post-contrast imaging. Mismatches with recommendations were identified including the use of only one sagittal T2-weighted sequence for spinal cord imaging, the systematic use of GBCA at follow-up (over 30% of institutions), a delay time shorter than 5 min after GBCA administration (25%) and an inadequate follow-up duration in pediatric acute disseminated encephalomyelitis (80%). There is scarce use of automated software to compare images or to assess atrophy (13% and 7%). The proportions do not differ significantly between academic and non-academic institutions. CONCLUSIONS: While current practice in MS imaging is rather homogeneous across Europe, our survey suggests that recommendations are only partially followed. CLINICAL RELEVANCE STATEMENT: Hurdles were identified, mainly in the areas of GBCA use, spinal cord imaging, underuse of specific MRI sequences and monitoring strategies. This work will help radiologists to identify the mismatches between their own practices and the recommendations and act upon them. KEY POINTS: • While current practice in MS imaging is rather homogeneous across Europe, our survey suggests that available recommendations are only partially followed. • Several hurdles have been identified through the survey that mainly lies in the areas of GBCA use, spinal cord imaging, underuse of specific MRI sequences and monitoring strategies.

3-T MR neurography of lumbo-sacral plexus in hereditary transthyretin-related amyloidosis with polyneuropathy.

OBJECTIVES: Our aim was to evaluate the ability of magnetic resonance neurography (MRN) of the lumbo-sacral plexus (LSP) to distinguish patients with hereditary transthyretin-related amyloidosis with polyneuropathy (ATTRv-PN) from asymptomatic variant carriers (AVC) and healthy controls and to assess its prognostic value. METHODS: Three-Tesla MRN was performed in 25 consecutive ATTRv-PN patients, 18 AVC, and 10 controls including T2-w DIXON and DWI MR sequences. Two blinded readers independently assessed LSP root diameter and intraneural signal on the MRN images of each subject. MRN findings were compared between groups and correlated with clinical impairment scored on the Neuropathy Impairment Score (NIS) and the modified Polyneuropathy Disability score (mPND). RESULTS: The agreement between readers on MRN images was excellent (Cohen's kappa = 0.82). LSP root enlargement was significantly more frequent in ATTRv-PN patients compared to AVC (ratio = 4.38, p = 0.038). Increased LSP root intraneural signal on T2-w images was significantly more frequent in ATTRv-PN patients compared to AVC (ratio = 3.4, p = 0.016). In contrast, there were no MRN abnormalities in controls. In ATTRv-PN patients, LSP root enlargement was associated with higher mPND scores (p = 0.03) and increased intraneural signal on T2-w images was associated with significantly higher NIS and mPND scores (p = 0.004 and 0.02, respectively). CONCLUSIONS: MRN of the LSP can help differentiate ATTRv-PN patients from AVC. LSP root enlargement and increased intraneural signal are significantly associated with clinical impairment, suggesting potential implications for patient care. KEY POINTS: • ATTRv-PN patients showed abnormal LSP changes on MRN. • MRN of the LSP can help to differentiate ATTRv-PN patients from AVC and healthy controls. • LSP root enlargement and increased intraneural signal were significantly associated with clinical impairment in ATTRv-PN patients.

Diffusion tensor imaging MR neurography in patients with acute or chronic plexopathy.

The nerve plexus is susceptible to various pathological processes. In addition to clinical and electrophysiological findings, magnetic resonance neurography (MRN) may contribute to characterize plexus involvement. Diffusion tensor imaging (DTI) was reported feasible for the nerve plexuses imaging but its value in the clinical practice remains uncertain. From 2014 to 2020, we routinely performed MRN including DTI at 3T in patients with acute or chronic plexopathy. DTI images were co-registered with conventional MRN images. MRN images including DTI were reviewed by consensus by two neuroradiologists and one neurologist. They retrospectively identified cases for whom the use of DTI had a potential impact on the diagnostic workup, seven of these clinical cases are presented here. Compared to conventional MRN, the added value of DTI consisted in: (i) improved detection of signal/morphological abnormalities of the plexus (due to removal of background structures, multiplanar reformatted views and large field of view), (ii) additional information regarding the microarchitecture of nerve fibers provided by DTI metrics, (iii) potential alternative for the use of gadolinium. This case series supports the implementation of DTI in MRN protocols.

Phosphorus magnetic resonance spectroscopy and fatigue in multiple sclerosis.

Fatigue stands among the most debilitating multiple sclerosis (MS) manifestations. Several pathophysiological mechanisms have been proposed at its origin. However, unmet needs still exist, and further investigations are required to better understand and manage this complaint. A new imaging modality-the phosphorous magnetic resonance spectroscopy (31P-MRS)-might help studying fatigue by allowing the measurement of energy metabolites of various cerebral regions. Therefore, this work aimed to explore the association between fatigue and brain energy status. Thirty MS patients with progressive disease forms completed the study. Their sociodemographic and clinical data including fatigue and disability scores [i.e., Fatigue Severity Scale (FSS) and Expanded Disability Status Scale (EDSS)] were collected. 31P-MRS spectra of (1) bilateral frontoparietal area and (2) centrum semiovale normal appearing white matter (NAWM) were obtained. Percentages of phosphocratine and ß-adenosine triphosphate (ß-ATP) were calculated. FSS scores were found to be directly correlated with the frontoparietal ß-ATP % (p < 0.05). However, there were no significant correlations between FSS scores and NAWM energy metabolites or clinical data (i.e., age, EDSS scores or disease duration). These findings point toward the existence of a link between fatigue severity and the amount of cerebral ATP metabolites. Such a link might reflect either a high production or low utilization of ATP, both of which were paralleled with increased fatigue perception. While the former would be due to a redistribution of ion channels along demyelinated axons and subsequent changes in mitochondrial activity; the latter could be interpreted in the light of neuronal loss which would lead to a decrease in ATP utilization and accumulation of its metabolites.

Non-COVID-19 emergencies: where have all the patients gone?

KEY POINTS: • Early in the pandemic, numbers of patients undergoing non-COVID-19 emergent CTs dropped sharply but diagnostic yield did not increase, suggesting potentially undiagnosed emergencies in patients not seen in healthcare institutions.

Optical coherence tomography: a window to the optic nerve in clinically isolated syndrome.

In this study, we aimed to evaluate the association of asymptomatic optic nerve demyelinating lesion in patients presenting a clinically isolated syndrome with the asymptomatic retinal neuro-axonal loss previously reported at clinically isolated syndrome. We prospectively recruited 66 patients presenting a clinically isolated syndrome and 66 healthy control subjects matched according to age and gender. All patients underwent brain magnetic resonance imaging including 3D-double inversion recovery (DIR) sequence, optical coherence tomography examination and visual function evaluation, at 2.5-4.5 months after CIS. Evaluation criteria were presence and length of optic nerve DIR hypersignal, retinal layers (including ganglion cell inner plexiform layer and inner nuclear layer) thickness/volume, and low contrast monocular vision acuity (number of letters correctly identified). All clinically isolated syndrome eyes with past history of optic neuritis (CIS-ON) presented an optic nerve DIR hypersignal. We observed asymptomatic optic nerve DIR hypersignal in 22.2% of clinically isolated syndrome eyes without optic neuritis (CIS-NON). In comparison with healthy control, GCIPL volume (in mm3) was significantly lower in CIS-ON eyes [ß (95% confidence interval, CI) = -0.121 (-0.168 to -0.074); P < 0.0001], and to a lesser extent in CIS-NON [ß (95% CI) = -0.023 (-0.039 to -0.008); P = 0.004]. In comparison to healthy controls, eyes with asymptomatic optic nerve DIR hypersignal presented significantly lower macular ganglion cell inner plexiform layer volume [ß (95% CI) = -0.043 (-0.068 to -0.019); P = 0.001], and eyes without did not [ß (95% CI) = -0.016 (-0.034 to 0.003); P = 0.083]. Among CIS-NON, macular ganglion cell inner plexiform layer volume decrease was associated with asymptomatic optic nerve DIR hypersignal independently of optic radiations T2 lesions and primary visual cortex volumes (P = 0.012). Symptomatic optic nerve DIR hypersignal were significantly longer (13.8 ± 6.7 mm) than asymptomatic optic nerve hypersignal (10.0 ± 5.5 mm; P = 0.047). Length of optic nerve DIR hypersignal was significantly associated with thinner inner retinal layers (P ≤ 0.001), thicker inner nuclear layer (P = 0.017) and lower low contrast monocular vision acuity (P < 0.05). Compared to healthy control, low contrast monocular vision acuity was significantly lower in CIS-ON eyes (P < 0.0001) and CIS-NON eyes with (P = 0.03) or without asymptomatic optic nerve DIR hypersignal (P = 0.0005). Asymptomatic demyelinating optic nerve DIR hypersignal at the earliest clinical stage of multiple sclerosis is frequent and associated with asymptomatic retinal neuro-axonal loss reported at clinically isolated syndrome stage. Length of optic nerve DIR hypersignal is a biomarker of retinal neuro-axonal loss and visual disability at clinically isolated syndrome stage. Visual disability of clinically isolated syndrome eyes without clinical and subclinical optic nerve involvement might be due to missed optic nerve lesions on MRI. At the earliest clinical stage of multiple sclerosis, our results support considering optical coherence tomography as a window to the optic nerve rather than to the brain.

Jugular venous reflux may mimic type I dural arterio-venous fistula on arterial spin labeling magnetic resonance images.

PURPOSE: Previous studies have shown that arterial spin-labeling (ASL) has high sensitivity and specificity for detecting dural arteriovenous fistulas (DAVFs). However, in case of jugular venous reflux (JVR), the labeled protons in the jugular vein may lead to a venous hypersignal in the jugular vein, sigmoid, and transverse sinus on ASL images and mimic DAVF. METHODS: To ascertain this hypothesis, two blinded senior neuroradiologists independently and retrospectively reviewed randomized ASL images and graded the likelihood of DAVF on a 5-point Likert scale in 2 groups of patients: (i) 13 patients with angiographically proven type I DAVF; and (ii) 11 patients with typical JVR diagnosed on the basis of clinical and MR imaging data, first using ASL alone, and second using ASL together with all of the sequences including 4D CE MRA. RESULT: A dural venous ASL signal was seen in 11 patients with type I DAVF and in all the 11 patients with JVR, with no distinctive pattern between the two. The mean Likert score was "very likely" in DAVF and JVR patients when using ASL alone (k = 0.71), and "very unlikely" for JVR versus "very likely" for DAVF when using all the sequences available (k = 0.92). CONCLUSION: Our study shows that JVR can mimic DAVF on ASL images with potential implications for patient care. The detection of DAVFs should be based on additional MR sequences such as TOF-MRA and 4D CE MRA to exclude JVR and to avoid unnecessary DSAs.

Intracranial aneurysms in sickle cell disease: Aneurysms characteristics and modalities of endovascular approach to treat these patients.

INTRODUCTION: The neurological complications of Sickle Cell Disease (SCD) include cerebral infarction and haemorrhage with rarely subarachnoid haemorrhage due to cerebral aneurysms. MATERIALS AND METHODS: In our interventional department, working with SCD referral department, we reported our experience concerning management of adult's patients with cerebral aneurysms. We identified 26 adults with 48 intracranial aneurysms documented by imaging. RESULTS: 18 patients, with 26 cerebral aneurysms were treated by endovascular approach for their aneurysms. No patient was treated by surgical way in our institution. 50% of patients had multiple aneurysms. Locations of aneurysms treated were typical with 70% of cerebral anterior artery and 30% of posterior artery. Three patients suffered from subarachnoid haemorrhage. Two procedure-related complications occurred during the treatment: one thrombo-embolic event with good recovery after medical treatment and one aneurismal perforation leading to the death of patient. Hypercoagulability is a major specific risk in SCD and use of permanent device as stent of flow diverter should be discussed to prevent complications. CONCLUSION: Endovascular management of these aneurysms seems to be a good alternative to treat these patients, with stability of occlusion at follow-up.

Post-contrast 3D T1-weighted TSE MR sequences (SPACE, CUBE, VISTA/BRAINVIEW, isoFSE, 3D MVOX): Technical aspects and clinical applications.

Post-contrast three-dimensional T1-weighted imaging of the brain is widely used for a broad range of vascular, inflammatory or tumoral diseases. The variable flip angle 3D TSE sequence is now available from several manufacturers (CUBE, General Electric; SPACE, Siemens; VISTA/BRAINVIEW, Philips; isoFSE, Itachi; 3D MVOX, Canon). Compared to gradient-echo (GRE) techniques, 3D TSE offers the advantages of useful image contrasts and reduction of artifacts from static field inhomogeneity. However, the respective role of 3D TSE and GRE MR sequences remains to be elucidated, particularly in the setting of post-contrast imaging. The purpose of this review was (1) to describe the technical aspects of 3D TSE sequences, (2) to illustrate the main clinical applications of the post-contrast 3D T1-w TSE sequence through clinical cases, (3) to discuss the respective role of post-contrast 3D TSE and GRE imaging in the field of neuroimaging.

Diffusion-Weighted Imaging Hyperintensities in Subtypes of Acute Intracerebral Hemorrhage: Meta-Analysis.

Background and Purpose- Diffusion-weighted imaging (DWI) hyperintensities in intracerebral hemorrhage (ICH) are associated with increased risk of recurrent ICH, cognitive impairment, and death, but whether these lesions are specific to a subtype of ICH remains uncertain. We investigated the association between DWI lesions and ICH subtype and explored the risk factors for DWI lesions. Methods- In a systematic review of ICH studies, we identified those reporting prevalence of DWI lesions. Two reviewers independently assessed study eligibility and risk of bias and collected data. We determined the pooled prevalence of DWI lesions within 90 days after ICH onset for cerebral amyloid angiopathy- and hypertensive angiopathy-related ICH using random-effects meta-analysis. We calculated odds ratios to compare prevalence of DWI lesions by ICH subtype and to assess risk factors for DWI lesions. Results- Eleven studies (1910 patients) were included. The pooled prevalence of DWI lesions was 18.9% (95% CI, 11.1-26.7) in cerebral amyloid angiopathy- and 21.0% (95% CI, 15.3-26.6) in hypertensive angiopathy-related ICH. There was no difference in the prevalence of DWI lesions between cerebral amyloid angiopathy- (64/292 [21.9%]) and hypertensive angiopathy-related ICH (79/370 [21.4%]; odds ratio, 1.25; 95% CI, 0.73-2.15) in the 5 studies reporting data on both ICH pathogeneses. In all ICH, presence of DWI lesions was associated with neuroimaging features of microangiopathy (leukoaraiosis extension, previous ICH, and presence, and number of microbleeds) but not with vascular risk factors or the use of antithrombotic therapies. Conclusions- Prevalence of DWI lesions in acute ICH averages 20%, with no difference between cerebral amyloid angiopathy- and hypertensive angiopathy-related ICH. Detection of DWI lesions may add valuable information to assess the progression of the underlying microangiopathy.

Optic nerve double inversion recovery hypersignal in patients with clinically isolated syndrome is associated with asymptomatic gadolinium-enhanced lesion.

BACKGROUND: Optic nerve involvement is not considered in dissemination in space (DIS) or time (DIT) of multiple sclerosis (MS) lesions. OBJECTIVES: To evaluate frequency of optic nerve involvement using three-dimensional (3D)-double inversion recovery (DIR) sequence in clinically isolated syndrome (CIS) and to measure its relationship with DIS and DIT (2010 and 2017 McDonald criteria). METHODS: From November 2013 to August 2016, 57 CIS patients underwent 3T-magnetic resonance imaging (3T-MRI) including 3D-DIR sequence and optical coherence tomography (OCT) at 3 months after CIS. We assessed signal abnormalities of the optic nerves on DIR sequence and collected data for DIS and DIT criteria according to 2010 and 2017 McDonald criteria. RESULTS: Among the 57 recruited patients, the presence of ⩾1 DIR hypersignal in optic nerve was observed in 36 (63%; 48 optic nerves) including asymptomatic hypersignal in 22 (38.5%; 25 optic nerves). Optic nerve involvement was significantly associated with DIT (p = 0.006) and MS according to 2010 criteria (p = 0.01) but was not significantly associated with presence of DIS criteria according to 2010 and 2017 McDonald criteria. We identified a significant (p < 0.001) temporal peripapillary retinal nerve fiber layer thinning on eyes with optic nerve involvement versus healthy controls. CONCLUSIONS: Optic nerve involvement is very frequent at the earliest clinical stage of MS. It is associated with the presence of asymptomatic gadolinium-enhancement and retinal axonal loss and may reflect the inflammatory disease activity level.

Correction to: A rare presentation of skull-base osteomyelitis with neurovascular sheath extension following external otitis resolved by PET/MRI.

The figure in the original published version of this article was omitted.

Magnetic resonance imaging changes following natalizumab discontinuation in multiple sclerosis patients with progressive multifocal leukoencephalopathy.

BACKGROUND: Detecting early progressive multifocal leukoencephalopathy-immune reconstitution inflammatory syndrome (PML-IRIS) is clinically relevant. OBJECTIVE: Evaluating magnetic resonance imaging (MRI) changes following natalizumab (NTZ) discontinuation and preceding PML-IRIS. METHODS: MRIs (including diffusion-weighted imaging (DWI), T2-weighted fluid-attenuated inversion recovery (T2-FLAIR), post-contrast T1-weighted sequences) were performed every week following PML diagnosis in 11 consecutive NTZ-PML patients. PML expansion, punctate lesions, contrast-enhancement, and mass-effect/edema were evaluated on each MRI sequence, following NTZ discontinuation. RESULTS: PML-IRIS occurred from 26 to 89 days after NTZ discontinuation. MRI changes prior to early PML-IRIS appeared significantly more pronounced using DWI compared to T2-FLAIR imaging (p < 0.003). Two DWI features (marked PML expansion, punctate lesions) systematically preceded contrast-enhancement. CONCLUSION: Subtle changes may occur on DWI preceding contrast-enhancement.

Ventriculomegaly in the Elderly: Who Needs a Shunt? A MRI Study on 90 Patients.

OBJECTIVE: In the case of ventriculomegaly in the elderly, it is often difficult to differentiate between communicating chronic hydrocephalus (CCH) and brain atrophy. The aim of this study is to describe the MRI criteria of CCH, defined by a symptomatic patient with ventriculomegaly and that improved after shunt placement. MATERIALS AND METHODS: Magnetic resonance imaging was prospectively evaluated in 90 patients with ventriculomegaly. Patients were classified into three groups: patients without clinical signs of CCH (control, n = 47), patients with CCH treated by shunt placement with clinical improvement (responders, n = 36), and patients with CCH treated using a shunt without clinical improvement (nonresponders, n = 7). MRI parameters of the two groups of interest (responders vs. controls) were compared. RESULTS: Compared with controls, Evans' index (p = 0.029), ventricular area (p < 0.01), and volume (p = 0.0001) were higher in the responders. In this group, the callosal angle was smaller (p ≤ 0.0001) and the aqueductal stroke volume (SVa) of CSF was higher (p ≤ 0.0001) than in controls. On the ROC curves, the optimal cut-off values for differentiating between responders and controls were a ventricular area >33.5 cm2, a callosal angle <90.8° and a SVa > 136.5 µL/R-R. In multivariate analysis, responders remained associated with SVa and callosal angle, with a c-statistic of 0.90 (95%CI, 0.83-0.98). CONCLUSION: On suspicion of CCH, a large ventricular area, a small callosal angle, and an increased aqueductal stroke volume are important MRI arguments that can be associated with the clinical evaluation and dynamic testing of CSF to confirm the indication for a shunt.

Altered signal intensity of active enhancing inflammatory lesions using post-contrast double inversion recovery MR sequence.

OBJECTIVES: We aimed at establishing the impact upon gadolinium administration on the conspicuity of active enhancing multiple sclerosis (MS) lesions using double inversion recovery (DIR) at 3T. METHODS: 15 consecutive patients with MS (n=8) or a clinically isolated syndrome (n=7) underwent pre and post-contrast DIR in addition to T2-weighted, FLAIR, pre and post-contrast T1-weighted sequences. First, two neuroradiologists located and marked all the enhancing MS lesions visible in consensus. Second, two other neuroradiologists, blinded to other sequences than DIR, independently assessed the SI changes from pre to post-contrast DIR images for each enhancing lesion, according to a 4-point-scale: increased SI (grade 1), absence of change (grade 2), lesion being partially (grade 3) or completely masked on post-contrast DIR images (grade 4). RESULTS: 246 MS lesions were detected including 26 enhancing on post-contrast T1-weighted images in 9 patients. The two blinded readers concluded to a decreased signal-intensity on post-contrast DIR images for all the 26 enhancing MS lesions (14 of grade 3 and 12 of grade 4). Inter-observer agreement was excellent, Kappa=0.85 (0.75 - 0.94). Using DIR post-contrast leads to altered signal-intensity of enhancing active MS lesions, ranging from partial to complete signal-loss. CONCLUSION: Our study strongly suggests the use of DIR before gadolinium administration. KEY POINTS: • DIR has gained widespread use in MS. • MRI protocols for MS patients usually contain several post-contrast sequences. • Signal-intensity of enhancing MS lesions is altered using DIR post-contrast. • Our study strongly suggests the use of DIR before gadolinium administration.

Adenosine Triphosphate Metabolism Measured by Phosphorus Magnetic Resonance Spectroscopy: A Potential Biomarker for Multiple Sclerosis Severity.

BACKGROUND/AIMS: Phosphorus magnetic resonance spectroscopy (31P-MRS) has previously shown abnormal changes in energy metabolites in the brain of multiple sclerosis (MS) patients. However, the relationship between these energy metabolites - particularly adenosine triphosphate (ATP) - and the disease severity remains unclear. The objective of this study was to determine whether measuring ATP metabolites can help to predict disease severity in MS patients. METHODS: 31P-MRS at 3 tesla was performed in 9 relapsing remitting (RRMS), 9 secondary progressive MS patients (SPMS), and 10 age-matched healthy controls. ATP metabolites (expressed as %) in normally appearing white matter of the centrum semiovale were compared between patients and healthy controls. The relationship between Expanded Disability Status Scale (EDSS) and ATP metabolites was evaluated. RESULTS: RRMS and SPMS patients had higher phosphocreatine (PCr) and lower phosphodiesters than healthy controls. In addition, RRMS patients had higher ß-ATP% than SPMS patients. ß-ATP% was negatively correlated with EDSS in all patients. CONCLUSION: Our findings suggest a defective PCr metabolism in both patient groups, and a higher state of energy production in RRMS that might reflect a compensatory mechanism in face of the increased needs. The correlation of ß-ATP with EDSS makes it a candidate biomarker for assessing MS disease severity.