Middle cerebral artery resistivity and pulsatility indices in systemic lupus erythematosus: evidence for hyperperfusion.

BACKGROUND AND PURPOSE: Systemic lupus erythematosus (SLE) is associated with significant cerebrovascular and neuropsychiatric disease for which multiple pathogeneses have been proposed. Although global cerebral hypoperfusion has been proposed, there are limited data about intracerebral arterial hemodynamics. Transcranial Doppler (TCD) allows portable, high temporal and spatial resolution, noninvasive blood velocity measurements in the middle cerebral arteries, and calculations of standard resistivity (RI) and pulsatility (PI) indices. RI and PI correlate with cerebral hemispheric arteriolar tone, blood flow resistances, and impedances. Accordingly, we hypothesized that there would be significant differences (p < 0.05) in RI and PI between SLE patients and healthy, age and gender matched controls. METHODS: TCD was used to measure RI and PI bilaterally on 34 stable SLE patients (35 ± 11 years) and 15 control subjects (34 ± 10 years). Patients and controls had similar, normal blood pressures and were examined in the supine position during normal, resting respiration. RI and PI were determined by a blinded, experienced observer. RESULTS: There were no significant differences in RI and PI bilaterally within each cohort. However, SLE patients had significantly lower average RI and PI values compared with controls: 0.45 ± 0.10 versus 0.52 ± 0.05 (p < 0.05); and 0.65 ± 0.19 versus 0.77 ± 0.12, (p < 0.05); respectively. CONCLUSIONS: These preliminary data suggest that RI and PI values in the human middle cerebral artery are significantly lower in SLE compared with controls. These indices indicate that middle cerebral arterial resistances and impedances are decreased in SLE. Under normotensive conditions, the results are consistent with hyperperfusion in SLE with increased arteriolar dilation and increased cerebral blood flow.

Does ultrasound guidance improve the outcomes of arthrocentesis and corticosteroid injection of the knee?

OBJECTIVE: The present randomized controlled trial compared arthrocentesis of the effusive knee followed by corticosteroid injection performed by the conventional anatomic landmark palpation-guided technique to the same procedure performed with ultrasound (US) needle guidance. METHODS: Sixty-four palpably effusive knees were randomized to (i) palpation-guided arthrocentesis with a conventional 20-mL syringe (22 knees), (ii) US-guided arthrocentesis with a 25-mL reciprocating procedure device (RPD) mechanical aspirating syringe (22 knees), or (iii) US-guided arthrocentesis with a 60-mL automatic aspirating syringe (20 knees). The one-needle two-syringe technique was used. Outcome measures included patient pain by the Visual Analogue Scale (VAS) for pain (0-10 cm), the proportion of diagnostic samples, synovial fluid volume yield, complications, and therapeutic outcome at 2 weeks. RESULTS: Sonographic guidance resulted in 48% less procedural pan (VAS; palpation-guided: 5.8 ± 3.0 cm, US-guided: 3.0 ± 2.8 cm, p < 0.001), 183% increased aspirated synovial fluid volumes (palpation-guided: 12 ± 10 mL, US-guided: 34 ± 25 mL, p < 0.0001), and improved outcomes at 2 weeks (VAS; palpation-guided: 2.8 ± 2.4 cm, US-guided: 1.5 ± 1.9 cm, p = 0.034). Outcomes of sonographic guidance with the mechanical syringe and automatic syringe were comparable in all outcome measures. CONCLUSIONS: US-guided arthrocentesis and injection of the knee are superior to anatomic landmark palpation-guided arthrocentesis, resulting in significantly less procedural pain, improved arthrocentesis success, greater synovial fluid yield, more complete joint decompression, and improved clinical outcomes.

Pressure generated by syringes: implications for hydrodissection and injection of dense connective tissue lesions.

OBJECTIVE: Hydrodissection and high-pressure injection are important for the treatment of dense connective tissue lesions including rheumatoid nodules, Dupuytren's contracture, and trigger finger. The present study determined the optimal syringes for high-pressure injection of dense connective tissue lesions. METHODS: Different sizes (1, 3, 5, 10, 20, and 60 mL) of a mechanical syringe (reciprocating procedure device) with a luer-lock fitting were studied. Twenty operators generated maximum pressure with each mechanical syringe size, and pressure was measured in pounds per square inch (psi). Subsequently, 223 dense connective tissue lesions were injected with different sizes of syringes (1, 3, or 10 mL). Outcomes included (i) successful intralesional injection and (ii) clinical response at 2 weeks. RESULTS: Smaller syringes generated significantly more injection pressure than did larger syringes: 1 mL (363 ± 197 psi), 3 mL (177 ± 96 psi), 5 mL (73 ± 40 psi), 10 mL (53 ± 29 psi), 20 mL (32 ± 18 psi), and 60 mL (19 ± 12 psi). Similarly, smaller syringes were superior to larger syringes for intralesional injection success: 10 mL: 34% (15/44) vs. 1 mL: 100% (70/70) (p < 0.001) and 3 mL: 91% (99/109) (p < 0.001). CONCLUSION: Smaller syringes (≤ 3 mL) are superior to larger syringes (≥ 5 mL) for successful hydrodissection and high-pressure intralesional injection of dense connective tissue lesions.

Premature aortic stiffness in systemic lupus erythematosus by transesophageal echocardiography.

To assess aortic stiffness by transesophageal echocardiography (TEE) and to determine its clinical predictors and relation to age, blood pressure, renal function, and atherosclerosis, 50 patients with systemic lupus erythematosus (SLE), 94% women, with a mean age of 38 ± 12 years, and 22 age and gender-matched healthy controls underwent clinical and laboratory evaluations and multiplane TEE to assess stiffness, intima-media thickness (IMT), and plaques of the proximal, mid, and distal descending thoracic aorta. Stiffness at each level and overall aortic stiffness by the pressure-strain elastic modulus was higher in patients than in controls after adjusting for age (overall, 8.25 ± 4.13 versus 6.1 ± 2.5 Pascal units, p = 0.01). Patients had higher aortic stiffness than controls after adjusting both groups to the same mean age, blood pressure, creatinine, and aortic IMT (p = 0.005). Neither IMT nor plaques were predictors of aortic stiffness. Moreover, normotensive patients, those without aortic plaques, and non-smokers had higher stiffness than controls (all p < 0.05). Age at SLE diagnosis and non-neurologic damage score were the only SLE-specific independent predictors of aortic stiffness (both p ≤ 0.01). Thus, increased aortic stiffness is an early manifestation of lupus vasculopathy that seems to precede the development of hypertension and atherosclerosis.

Reciprocating procedure device for thyroid cyst aspiration and ablative sclerotherapy.

Most thyroid cysts are benign; however, they require aspiration if symptomatic or atypical on ultrasound scanning, and ablation with ethanol injection if recurrent. We have systematically studied the use of new safety technologies for surgical procedures, which protect both the surgeon and the patient. Here, we describe the use of one such technology, the reciprocating procedure device, which enables simpler, safer, more efficient and less painful thyroid cyst aspiration and therapeutic ablation.

Accumulation of acetyl groups following cycling: a 1H-MR spectroscopy study.

Using in vivo proton magnetic resonance spectroscopy (1H-MRS), a new peak resonating at 2.13 ppm post-exercise has been attributed in the literature to the acetyl groups of acetylcarnitine. Since this peak is inconsistently generated by various submaximal exercise regimens, this study aimed at (a) verification of the previous chemical assignment, (b) determination of exercise conditions necessary for its induction, and (c) documentation of the recovery kinetics through 60 minutes following exercise. Ten healthy males (31 +/- 4 yr) cycled continuously for 45 minutes with intensity alternating between 50% (3 min) and 110% (2 min) of ventilatory threshold (VT). 1H-MR spectra were acquired from the vastus lateralis before and for 60 minutes following exercise. The peak at 2.13 ppm was not quantifiable at rest in any subject. However, it was present in all subjects following intense exercise (p < 0.0001), and expressed the chemical characteristics of an acetyl-containing compound. The estimated concentration, accumulation with high-intensity exercise, the presence as a single peak at 2.13 ppm, and the chemical shift were all consistent with the chemical and biophysical characteristics of acetyl groups associated with acetylcarnitine. This study provides further evidence that acetyl groups are robustly generated by intense exercise, and that the accumulation of acetyl groups in healthy subjects is dependent on the degree of exercise intensity. 1H-MRS may be used for the noninvasive study of muscle metabolism during exercise and recovery and may have special applications for studying the generation and transport of acetyl compounds, including acetylcarnitine.

Cigarette smoking, alcohol consumption, and the risk of systemic lupus erythematosus: a case-control study.

OBJECTIVE: To investigate the effects of cigarette smoking and alcohol consumption on the development of systemic lupus erythematosus (SLE). METHODS: We interviewed 125 patients with SLE and 125 controls in a case-control study. Demographically similar controls randomly selected from outpatient clinics were matched to SLE cases for sex and age. Clinical data, including cigarette smoking, drinking habits, and other demographic variables, were collected by an interview-administered questionnaire. RESULTS: To minimize bias associated with reactive habits induced by disease, cigarette smoking before the diagnosis of SLE was the primary variable for subsequent analysis. Analysis of the data by multivariate conditional logistic regression revealed that both cigarette smoking before SLE diagnosis and ex-smoking before SLE diagnosis significantly increased the risk of development of SLE (OR 6.69, 95% CI 2.59, 17.28, p < 0.001; and OR 3.62, 95% CI 1.22, 10.70, p = 0.02, respectively). This association remained even when statistically controlling for the effects of family history and education, indicating an independent effect. Alcohol did not place an individual at increased risk nor did it have a protective role. CONCLUSION: The results of this study provide further evidence that cigarette smoking may be an associated risk factor for the development of SLE.

Gerstmann syndrome in systemic lupus erythematosus: neuropsychological, neuroimaging and spectroscopic findings.

Gerstmann syndrome (GS) comprises four interlaced neuropsychological symptoms including finger agnosia, right-left confusion, agraphia, and acalculia. While GS is commonly associated with focal lesions to the region of the left angular gyrus, it has also been associated with numerous diffuse etiologies including atrophy, alcoholism, carbon monoxide poisoning, lead intoxication and anaphylactic shock. Thus, a vigorous debate has emerged as to whether GS represents a syndrome arising from general brain decline or a distinct and localizing lesion. We report a right-handed patient who developed neuropsychological dysfunction secondary to systemic lupus erythematosus (SLE). Neuropsychological evaluation found the patient to exhibit symptoms consistent with the GS tetrad, as well as general cognitive decline. Magnetic resonance imaging revealed a distinct focal lesion of the left parieto-occipital white matter underlying the angular gyrus as well as diffuse atrophy. (1)H-magnetic resonance spectroscopy revealed substantial metabolic derangement in a voxel placed within the visible lesion, although substantial metabolic derangement was observed in regions remote from the focal pathology. Thus, GS in this first case in SLE would appear to comprise a focal neurological tetrad of disorders within a more general pattern of cognitive decline and metabolic derangement.

Metabolic and cognitive response to human traumatic brain injury: a quantitative proton magnetic resonance study.

Proton magnetic resonance spectroscopy (1H-MRS) offers a unique insight into brain cellular metabolism following traumatic brain injury (TBI). The aim of the present study was to assess change in neurometabolite markers of brain injury during the recovery period following TBI. We studied 19 TBI patients at 1.5, 3, and 6 months postinjury and 28 controls. We used 1H-MRS to quantify N-acetylaspartate (NAA), creatine (Cre), choline (Cho), and myoinositol (mIns) in occipitoparietal gray matter (GM) and white matter (WM) remote from the primary injury focus. Neuropsychological testing quantified cognitive impairment and recovery. At 1.5 months, we found cognitive impairment (mean z score = -1.36 vs. 0.18,p < 0.01), lower NAA (GM: 12.42 mM vs. 13.03, p = 0.01; WM: 11.75 vs. 12.81, p < 0.01), and elevated Cho (GM: 1.51 vs. 1.25, p < 0.01; WM: 1.98 vs. 1.79, p < 0.01) in TBI patients compared with controls. GM NAA at 1.5 months predicted cognitive function at outcome (6 months postinjury; r = 0.63, p = 0.04). GM NAA continued to fall by 0.46 mM between 1.5 and 3 months (p = 0.02) indicating continuing neuronal loss, metabolic dysfunction, or both. Between 3 and 6 months, WM NAA increased by 0.55 mM (p = 0.06) suggesting metabolic recovery. Patients with poorer outcomes had elevated mean GM Cho at 3 months postinjury, suggesting active inflammation, as compared to patients with better outcomes (p = 0.002). 1H-MRS offers a noninvasive approach to assessing neuronal injury and inflammation following TBI, and may provide unique data for patient management and assessment of therapeutic efficacy.

Myths of neuropsychology: intelligence, neurometabolism, and cognitive ability.

Recently, Dodrill (1999) revised a previously described "Myth of neuropsychology" (1997) to state: "Just as below average performances on neuropsychological tests are found when intelligence is below average, to that same degree above average performances on neuropsychological tests are expected when intellectual abilities are above average." This study addresses the relationship between intellectual and neuropsychological performance in the context of Magnetic Resonance Spectroscopy (MRS) measurements of the neurometabolite N-acetylaspartate (NAA). When subjects were stratified by Full Scale IQ (Average, High Average, Superior) they differed significantly in terms of total neuropsychological performance [F(2,47) = 17.63; p <.001] and the neuronal marker NAA [F(2,47) = 3.25; p <.05]. Regression analysis across groups demonstrated that FSIQ and NAA were independently related to Total z-score [F(1,47) = 29.43; p <.0001] and accounted for over half the variance (r(2) of model =.56). The concurrent relationship of FSIQ and NAA to total neuropsychological performance suggests that the relationship between measures sensitive to intellectual ability and neuropsychological performance is real, and does not reflect arbitrary psychometric or scaling properties of the WAIS-III.

Biochemical markers of cognition: a proton MR spectroscopy study of normal human brain.

In the current study we explored the relationship between neurometabolites measured by proton magnetic resonance spectroscopy (1H-MRS) and cognitive ability assessed with a battery of neuropsychological tests. Forty-five participants were recruited from the local college community, and examined utilizing neuropsychological testing and 1H-MRS. Our central finding was that N-acetylaspartate (NAA) was associated with overall neuropsychological performance (F(1,42) = 23.16, p < 0.0001], r2 = 0.35. We found an even stronger association between timed neuropsychological measures and NAA (F(1,42) = 31.15, p < 0.0001], r = 0.43. These results reveal the specific relationship of NAA to neuropsychological functioning in normal human brain. The current observations in healthy individuals are consistent with the hypothesis that variability in NAA levels and neuropsychological performance may be related to mitochondrial function.

Biochemical markers of intelligence: a proton MR spectroscopy study of normal human brain.

Proton magnetic resonance spectroscopy (1H-MRS) offers a unique non-invasive approach to measurement of N-acetylaspartate (NAA) and choline (Cho), putative markers of neuronal and glial integrity. Previous studies revealed that these neurochemicals predict cognitive impairment in diseased subjects, although little is known about their relationship to cognitive functioning in healthy people. We measured the concentrations of NAA and Cho in the left occipitoparietal white matter of 26 healthy adults and compared them with intellectual performance assessed by the Wechsler Adult Intelligence Scale-3. We found that NAA (b = 0.6, p < 0.01) and Cho (b = -0.42, p < 0.01) were independently associated with the Full-Scale Intelligence Quotient. Together, these metabolites accounted for a large proportion of the variance in intelligence (r2 = 0.45). Possible mechanisms underlying these correlations, such as mitochondrial function and myelin turnover, are discussed. 1H-MRS is a sensitive new tool to assess the neuronal underpinnings of cognitive function non-invasively.

Neuropsychiatric systemic lupus erythematosus.

The systemic lupus erythematosus (SLE) patients with neuropsychiatric complaints requires a comprehensive and timely diagnostic approach. Despite the obvious difficulties in diagnosing neuropsychiatric SLE, the neurologic complications of SLE can be approached in a careful, logical manner with gratifying results.

Automated T2 quantitation in neuropsychiatric lupus erythematosus: a marker of active disease.

Active neuropsychiatric systemic lupus erythematosus (NPSLE) is characterized by brain edema as measured by manual quantitative magnetic resonance (MR) relaxometry. An automated image processing method was developed to segment gray matter (GM), while minimizing the effects of confounding factors, specifically cerebral atrophy and volume averaging artifacts. Twenty patients with SLE (10 major, 10 minor), matched for atrophy, were studied. We compared T2 calculated for GM segmented by manual and automated methods. Both methods demonstrated a marked increase in GM T2 in patients with major NPSLE (P < 0.001), confirming the presence of cerebral edema. The results from each method were highly correlated, (r = 0.64, P = 0.002). The automated method effectively identifies GM, minimizes volume averaging artifacts, and produces results similar to the manual method. This method markedly decreases analysis time and will make quantitative relaxometry a valuable contribution to the clinical management of NPSLE.

Relationship between neurometabolite derangement and neurocognitive dysfunction in systemic lupus erythematosus.

OBJECTIVE: To determine the relationship between neurochemical markers of brain injury and brain dysfunction associated with systemic lupus erythematosus (SLE). METHODS: Patients with SLE (n = 12) were studied using magnetic resonance spectroscopic imaging at 1.5 Tesla to determine neurochemistry and a neurocognitive testing battery to determine brain dysfunction. N-acetylaspartate (NAA), creatine (Cre), and choline (Cho) concentrations were measured in white (WM) and gray (GM) matter and expressed as the ratios NAA/Cho, NAA/Cre, and Cho/Cre. Neurocognitive testing results were expressed as a composite z score. Disease activity was quantified by SLE Disease Activity Index (SLEDAI) and disease injury by Systemic Lupus International Collaborating Clinics (SLICC)/American College of Rheumatology Damage Index. RESULTS: Neurochemical measures of brain injury were correlated with neurocognitive testing z scores: NAA/Cho in WM (r = 0.77, p = 0.003) and GM (r = 0.67, p = 0.017); WM Cho/Cre also correlated with total z score (r = -0.74, p = 0.006). Neurometabolite ratios and SLICC were correlated: GM NAA/Cho (r = -0.70, p = 0.011 ) and NAA/Cre (r = -0.71, p = 0.01) and WM Cho/Cre (r = 0.66, p = 0.02). Correlations between neurometabolite ratios and SLEDAI did not reach significance. CONCLUSION: Brain function is closely correlated with brain injury assessed noninvasively by proton magnetic resonance spectroscopy. This important finding further supports the use of magnetic resonance spectroscopy to evaluate brain injury in SLE.

Neurometabolite markers of cerebral injury in the antiphospholipid antibody syndrome of systemic lupus erythematosus.

BACKGROUND AND PURPOSE: To determine the neurometabolic patterns of brain injury in systemic lupus erythematosus with antiphospholipid antibody syndrome (SLE-aPLS). METHODS: Forty-nine SLE patients (12 SLE-aPLS) and 23 control subjects were studied using magnetic resonance imaging and spectroscopy. N-Acetylaspartate/creatine (NAA/Cre) and choline/Cre (Cho/Cre) were measured in normal-appearing tissue. IgG and IgM antiphospholipid antibodies (aPL) were measured by enzyme-linked immunosorbent assay. RESULTS: Stroke, epilepsy, and elevated IgG-aPL were more common in SLE-aPLS patients than in SLE patients (P<0.001). NAA/Cre was lower (P<0.05) and Cho/Cre higher (P<0.001) in SLE-aPLS patients than in SLE patients without aPLS. Regression models showed NAA/Cre was most related to injury seen by imaging (P<0.01), disease duration (P<0. 05), and prior neuropsychiatric SLE (NPSLE) (P=0.07). Reduced NAA/Cre was more closely related to IgG-aPL (P<0.01) than the presence of stroke or aPLS. When adjusted for all factors, Cho/Cre was most associated with the presence of aPLS (P=0.05). CONCLUSIONS: SLE and SLE-aPLS are actually a clinical continuum describing brain injury in SLE, with SLE-aPLS being characterized by increased aPL, NPSLE, stroke, epilepsy, and disturbed neurochemistry. An elevated IgG-aPL level is a potent risk factor for brain injury as measured by NAA/Cre in SLE that is independent of stroke and aPLS. However, thrombotic phenomena and the presence of aPL (aPLS) are most closely associated with increased Cho/Cre in SLE. These results suggest that aPLs exacerbate SLE, resulting in increased thrombotic and nonthrombotic brain injuries. Spectroscopy detects brain injury in SLE and may permit better understanding of the neurological consequences of SLE and SLE-aPLS.

Neurologic, MR imaging, and MR spectroscopic findings in eosinophilia myalgia syndrome.

BACKGROUND AND PURPOSE: Eosinophilia myalgia syndrome (EMS), a multisystemic disease induced by exposure to L-tryptophan, may result in serious CNS abnormalities. The purpose of this study was to determine the pattern of neurologic characteristics, MR imaging abnormalities, and brain neurometabolites in EMS. METHODS: Sixteen patients with EMS and CNS abnormalities (CNS-EMS) and 12 control subjects underwent evaluation, including medical and neurologic examination, proton MR spectroscopy, and MR imaging. RESULTS: Neurologic findings that were increased in CNS-EMS included minor depression (100%), amnesia (88%), and intermittent confusion (38%), although fatigue (31%), motor disorders (31%), recurrent headache (19%), major depression (13%), and dementia (6%) also occurred, but at a lesser significance. Self-reported disability was markedly increased in CNS-EMS. MR imaging findings included subcortical focal lesions, focal lesions in deep white matter, cortical atrophy, ventricular dilatation, and diffuse and periventricular white matter abnormalities. MR spectroscopic findings established two distinct spectral patterns: 1) increased choline-containing compounds, decreased N-acetylaspartate, and increased lipid-macromolecules, consistent with inflammatory cerebrovascular disease; and 2) increased glutamine, decreased myo-inositol, and decreased choline, consistent with acute CNS injury or metabolic encephalopathy. CONCLUSION: Neurologic abnormalities, self-reported disability, brain lesions, and MR spectroscopic abnormalities are common in CNS-EMS. The pattern of cerebral lesions and neurometabolites is consistent with widespread inflammatory cerebrovascular disease. However, a subgroup of patients with CNS-EMS have neurometabolic changes consistent with a metabolic encephalopathy identical or similar to hepatic encephalopathy. The neurologic abnormalities in EMS and related hypereosinophilic syndromes should be interpreted cautiously, with the recognition that both cerebrovascular injury and secondary metabolic encephalopathies may be involved.

Proton MR spectroscopic measurement of neurometabolites in hepatic encephalopathy during oral lactulose therapy.

BACKGROUND AND PURPOSE: MR imaging and MR spectroscopy are increasingly being used to determine response to pharmacologic therapy. Hepatic encephalopathy (HE) is characterized by abnormal cerebral metabolites, yet the response to lactulose and other anti-HE measures is still primarily determined by using arbitrary categorical clinical rating scales, rather than MR spectroscopy. The purpose of this study was to determine whether MR spectroscopy could demonstrate relevant neurometabolic changes associated with lactulose therapy and thereby provide further support for the use of MR spectroscopy in clinical trials. METHODS: Ten control subjects and 23 patients with grades I to III HE were studied by proton MR spectroscopy with imaging parameters of 2000/26 (TR/TE). Metabolic ratios were calculated for myo-inositol (mI)/creatine (Cre), choline (Cho)/Cre, (glutamine + glutamate) (Glx)/Cre, N-acetylaspartate (NAA)/Cre, and (Cho + mI)/Glx. A time series design trial was used in which eight patients with HE were compared before and after lactulose therapy (60 mL by mouth three times per day). RESULTS: Relative to control subjects, HE was characterized by 43%, 64%, and 5% reductions, respectively, in mI/Cre, (Cho + mI)/Glx, and Cho/Cre. In comparison, Glx/Cre was increased by 75% and NAA/Cre was not changed. Therapy with lactulose was associated with increases of 29%, 37%, and 7%, respectively, in mI/Cre, (Cho + mI)/Glx, and Cho/Cre, as well as respective decreases of 15% and 42%, respectively, in Glx/Cre and HE grade. NAA/Cre did not change with lactulose therapy. CONCLUSION: MR spectroscopy detects neurometabolic changes associated with pharmacologic therapy for HE. The metabolic ratios ml/Cre and (Cho + mI)/Glx are the most sensitive measures of lactulose effect. These data support the expanded use of MR spectroscopy as an adjunctive technique in pharmaceutical development and clinical trials for HE.

Brain injury and neurometabolic abnormalities in systemic lupus erythematosus.

PURPOSE: To investigate with statistical analysis the relationship between brain injury measured with magnetic resonance (MR) imaging and that measured with proton (hydrogen-1) MR spectroscopy. MATERIALS AND METHODS: Forty-two patients (34 female, eight male; mean age +/- SD, 38.7 years +/- 13.1; age range, 6-60 years) with systemic lupus erythematosus (SLE) were examined with H-1 MR spectroscopy to measure N-acetylaspartate (NAA), creatine (Cr), and choline (Cho) levels in normal-appearing white matter and with MR imaging to detect anatomic abnormalities. RESULTS: Results of linear regression analysis revealed an association between the NAA/Cr ratio and anatomic abnormalities (P = .03). However, only small focal lesions were independently related to NAA/Cr ratio changes (P = .04). Results of a similar analysis showed associations between the Cho/Cr ratio and anatomic abnormalities (P = .002). An elevated Cho/Cr ratio and cerebral infarction were independently associated (P = .02), as were a decreased Cho/Cr ratio and severe cortical atrophy (P = .02). CONCLUSION: Cerebrovascular abnormalities underlie diffuse cerebral injury in SLE, with small vessel injury (i.e., small focal lesions) primarily associated with a decreased NAA/Cr ratio and medium vessel injury (i.e., infarct) primarily associated with an increased Cho/Cr ratio. Statistical integration of H-1 MR spectroscopic and MR imaging findings over large data sets provides insights into the relevance of individual MR imaging-visible brain abnormalities in SLE. This statistical approach may be applicable to other systemic diseases complicated by brain injury.