P. Hildenbrand

Lyme Neuroborreliosis: Manifestations of a Rapidly Emerging Zoonosis

SUMMARY:Lyme disease has a worldwide distribution and is the most common vector-borne disease in the United States. Incidence, clinical manifestations, and presentations vary by geography, season, and recreational habits. Lyme neuroborreliosis (LNB) is neurologic involvement secondary to systemic infection by the spirochete Borrelia burgdorferi in the United States and by Borrelia garinii or Borrelia afzelii species in Europe. Enhanced awareness of the clinical presentation of Lyme disease allows inclusion of LNB in the imaging differential diagnosis of facial neuritis, multiple enhancing cranial nerves, enhancing noncompressive radiculitis, and pediatric leptomeningitis with white matter hyperintensities on MR imaging. The MR imaging white matter appearance of successfully treated LNB and multiple sclerosis display sufficient similarity to suggest a common autoimmune pathogenesis for both. This review highlights differences in the epidemiology, clinical manifestations, diagnosis, and management of Lyme disease in the United States, Europe, and Asia, with an emphasis on neurologic manifestations and neuroimaging.

Brain regional lesion burden and impaired mobility in the elderly

This study investigated the relationship of brain white matter (WM) lesions affecting specific neural networks with decreased mobility in ninety-nine healthy community-dwelling subjects ≥75 years old prospectively enrolled by age and mobility status. We assessed lesion burden in the genu, body and splenium of corpus callosum; anterior, superior and posterior corona radiata; anterior and posterior limbs of internal capsule; corticospinal tract; and superior longitudinal fasciculus. Burden in the splenium of corpus callosum (SCC) demonstrated the highest correlation particularly with walking speed (r=0.4, p<10(-4)), and in logistic regression it was the best regional predictor of low mobility performance. We also found that independent of mobility, corona radiata has the largest lesion burden with anterior (ACR) and posterior (PCR) aspects being the most frequently affected. The results suggest that compromised inter-hemispheric integration of visuospatial information through the SCC plays an important role in mobility impairment in the elderly. The relatively high lesion susceptibility of ACR and PCR in all subjects may obscure the importance of these lesions in mobility impairment.

Identification and Clinical Impact of Multiple Sclerosis Cortical Lesions as Assessed by Routine 3T MR Imaging

It is possible that many if not most clinical symptoms of multiple sclerosis patients are due to plaques in the gray matter and not in the white matter as commonly believed (remember that myelinated fibers are found in cortical and deep gray matter). Could it be that because cortical plaques are not routinely seen at 1.5T we do not think about this issue? Here, the authors studied 26 patients with 3D FLAIR and inversion recovery spoiled gradient recalled sequences at 3T and found cortical plaques in 24 of them. The volume and load of these cortical plaques correlated with those seen in white matter. Cortical lesions also correlated with verbal learning test disability scale results better than white matter lesion load. Conclusion: routinely detectable cortical lesions were related to physical disability and cognitive impairment. BACKGROUND AND PURPOSE: Histopathologic studies have reported widespread cortical lesions in MS; however, in vivo detection by using routinely available pulse sequences is challenging. We investigated the relative frequency and subtypes of cortical lesions and their relationships to white matter lesions and cognitive and physical disability. MATERIALS AND METHODS: Cortical lesions were identified and classified on the basis of concurrent review of 3D FLAIR and 3D T1-weighted IR-SPGR 3T MR images in 26 patients with MS. Twenty-five patients completed the MACFIMS battery. White matter lesion volume, cortical lesion number, and cortical lesion volume were assessed. RESULTS: Overall, 249 cortical lesions were detected. Cortical lesions were present in 24/26 patients (92.3%) (range per patient, 0–30; mean, 9.6 ± 8.8). Most (94.4%, n = 235) cortical lesions were classified as mixed cortical-subcortical (type I); the remaining 5.6% (n = 14) were classified as purely intracortical (type II). Subpial cortical lesions (type III) were not detected. White matter lesion volume correlated with cortical lesion number and cortical lesion volume (rS = 0.652, rS = 0.705, respectively; both P < .001). After controlling for age, depression, and premorbid intelligence, we found that all MR imaging variables (cortical lesion number, cortical lesion volume, white matter lesion volume) correlated with the SDMT score (R2 = 0.513, R2 = 0.449, R2 = 0.418, respectively; P < .014); cortical lesion number also correlated with the CVLT-II scores (R2 = 0.542–0.461, P < .043). The EDSS scores correlated with cortical lesion number and cortical lesion volume (rS = 0.472, rS = 0.404, respectively; P < .05), but not with white matter lesion volume. CONCLUSIONS: Our routinely available imaging method detected many cortical lesions in patients with MS and was useful in their precise topographic characterization in the context of the gray matter−white matter junction. Routinely detectable cortical lesions were related to physical disability and cognitive impairment.

On the development of a well-defined source of superoxide ion for studies with biological systems.

Superoxide ion has recently been shown to be formed in several biochemical reactions involving molecular oxygen [l-8] , and it has been proposed that this free radical is a potent cytogenic agent [9] . However, the latter point remains a matter OS some debate, and while its chemistry has not been completely explored, most previous work suggests that superoxide ion is itself a fairly innocuous species [ 7, lo121 . In order to investigate the biochemical reactivity of 0~ it is necessary to have reliable, simple, and well-understood methods for its synthesis and introduction to biological systems. The ideal source of 0~ would: (1) be able to provide a pulse of a fairly high concentration (2 1 mM) of 0, ; (2) have no associated reactive substances; (3) allow spectrophotometric observation of the 02 ; and (4) have no requirements for expensive, specialized equipment. Superoxide ion has been generated in situ by enzymatic [ 131, photochemical [l] , and chemical [ 141 techniques but these are not well defined and they may involve reactive intermediates which would interfere in the processes under investigation. In the presence of suitable radical scavenging substances, pulse radiolytic techniques can provide a well defined solution of 0, but specialized equipment is required [ 151 . We report here in preliminary form, some of our results on the preparation and properties of 0, in some water-miscible organic solvents [ 161 .

Medulla Oblongata Volume: A Biomarker of Spinal Cord Damage and Disability in Multiple Sclerosis

BACKGROUND AND PURPOSE: While brain MR imaging is routinely performed, the MR imaging assessment of spinal cord pathology in multiple sclerosis (MS) is less frequent in clinical practice. The purpose of this study was to determine whether measurements of medulla oblongata volume (MOV) on routine brain MR imaging could serve as a biomarker of spinal cord damage and disability in MS. MATERIALS AND METHODS: We identified 45 patients with MS with both head and cervical spinal cord MR imaging and 29 age-matched and sex-matched healthy control subjects with head MR imaging. Disability was assessed by the expanded disability status scale (EDSS) and ambulation index (AI). MOV and upper cervical cord volume (UCCV) were manually segmented; semiautomated segmentation was used for brain parenchymal fraction (BPF). These measures were compared between groups, and linear regression models were built to predict disability. RESULTS: In the patients, MOV correlated significantly with UCCV (r = 0.67), BPF (r = 0.45), disease duration (r = −0.64), age (r = −0.47), EDSS score (r = −0.49) and AI (r = −0.52). Volume loss of the medulla oblongata was −0.008 cm3/year of age in patients with MS, but no significant linear relationship with age was found for healthy control subjects. The patients had a smaller MOV (mean ± SD, 1.02 ± 0.17 cm3) than healthy control subjects (1.15 ± 0.15 cm3), though BPF was unable to distinguish between these 2 groups. MOV was smaller in patients with progressive MS (secondary- progressive MS, 0.88 ± 0.19 cm3 and primary-progressive MS, 0.95 ± 0.30 cm3) than in patients with relapsing-remitting MS (1.08 ± 0.15 cm3). A model including both MOV and BPF better predicted AI than BPF alone (P = .04). Good reproducibility in MOV measurements was demonstrated for intrarater (intraclass correlation coefficient, 0.97), interrater (0.79), and scan rescan data (0.81). CONCLUSION: MOV is associated with disability in MS and can serve as a biomarker of spinal cord damage.

Segmentation of subtraction images for the measurement of lesion change in multiple sclerosis.

BACKGROUND AND PURPOSE: Lesion volume change (LVC) assessment is essential in monitoring MS progression. LVC is usually measured by independently segmenting serial MR imaging examinations. Subtraction imaging has been proposed for improved visualization and characterization of lesion change. We compare segmentation of subtraction images (SSEG) with serial single time-point conventional segmentation (CSEG) by assessing the LVC relationship to brain atrophy and disease duration, as well as scan-rescan reproducibility and annual rates of lesion accrual. MATERIALS AND METHODS: Pairs of scans were acquired 1.5 to 4.7 years apart in 21 patients with multiple sclerosis (MS). Scan-rescan MR images were acquired within 30 minutes in 10 patients with MS. LVC was measured with CSEG and SSEG after coregistration and normalization. Coefficient of variation (COV) and Bland-Altman analyses estimated method reproducibility. Spearman rank correlations probed associations between LVC and other measures. RESULTS: Atrophy rate and net LVC were associated for SSEG (R = −0.446; P < .05) but not when using CSEG (R = −0.180; P = .421). Disease duration did not show an association with net lesion volume change per year measured by CSEG (R = −0.360; P = .11) but showed an inverse correlation with SSEG-derived measurements (R = −0.508; P < .05). Scan-rescan COV was lower for SSEG (0.98% ± 1.55%) than for CSEG (8.64% ± 9.91%). CONCLUSION: SSEG unveiled a relationship between T2 LVC and concomitant brain atrophy and demonstrated significantly higher measurement reproducibility. SSEG, a promising tool providing detailed analysis of subtle alterations in lesion size and intensity, may provide critical outcome measures for clinical trials of novel treatments, and may provide further insight into progression patterns in MS.

Inflammatory pseudotumor of the skull base

INTRODUCTION: Inflammatory pseudotumor is an idiopathic, non-neoplastic mass lesion with few cases reported in the literature involving only the skull base and related structures. Imaging of skull-base pseudotumors shows characteristics similar to that of nasopharyngeal carcinoma and lymphoma, thereby requiring a biopsy to exclude malignancy. Surgical versus medical management relates to the location of the mass, the extent of bony invasion, and the involvement of corresponding anatomic structures. METHODS: A retrospective chart review of patients diagnosed with inflammatory pseudotumor of the skull base from a single tertiary care institution over a five-year period. RESULTS: Five cases of skull-base pseudotumor have been identified and followed from one to four years. In our clinical experience, maintenance oral corticosteroids have proven effective in improving symptoms and significantly reducing radiologic tumor dimensions. CONCLUSION: Inflammatory pseudotumor of the skull base is a challenging diagnosis due to its occult anatomic location, vague associated symptoms, and nonspecific histology. Low-dose oral corticosteroids are often very effective in management.

One year activity on subtraction MRI predicts subsequent 4 year activity and progression in multiple sclerosis

Objective To investigate the predictive value of 1 year subtraction MRI (sMRI) on activity and progression over the next 4 years in early phase multiple sclerosis (MS). To compare sensitivity of sMRI and contrast enhanced MRI towards disease activity. Methods The study was performed on 127 MS patients with brain MRI within 5 years of symptom onset (y0), after 1 year (y1) and after 5 years (y5). Measures of clinical (Expanded Disability Status Scale, relapse rate) and conventional MRI outcomes (brain parenchyma fraction (BPF); T2 lesion volume (T2LV); contrast enhancing lesions (CEL)) were available at all time points. sMRI was obtained from y1–y0, y5–y1 and y5–y0 image pairs and the number of new, enlarged, resolved and regressed lesions was counted. Results One year lesion change measured by sMRI predicted sMRI lesion change (p<0.0001), BPF and T2LV (p<0.05) changes, as well as clinical relapse rate (p<0.02) in the subsequent 4 years. sMRI measures were retained in stepwise predictive models that included other candidate MRI predictors. Active lesions on sMRI over a 1, 4 or 5 year interval provided a more sensitive assessment of disease activity than number of CEL at y0, y1 and/or y5: 83%, 93% and 90% of patients without CEL showed sMRI activity during the y1–y0, y5–y1, and y5–y0 intervals. Conclusions sMRI is a feasible and sensitive tool for detecting MS activity and may provide an alternative to contrast enhanced MRI in clinical practice, particularly in cases where CEL are not available or inconclusive. Furthermore, sMRI metrics combined with conventional MRI outcomes (CEL, T2LV, BPF) can increase the prediction of longer term MRI activity and progression.

Regional White Matter Atrophy−Based Classification of Multiple Sclerosis in Cross-Sectional and Longitudinal Data

BACKGROUND AND PURPOSE: The different clinical subtypes of multiple sclerosis (MS) may reflect underlying differences in affected neuroanatomic regions. Our aim was to analyze the effectiveness of jointly using the inferior subolivary medulla oblongata volume (MOV) and the cross-sectional area of the corpus callosum in distinguishing patients with relapsing-remitting multiple sclerosis (RRMS), secondary-progressive multiple sclerosis (SPMS), and primary-progressive multiple sclerosis (PPMS). MATERIALS AND METHODS: We analyzed a cross-sectional dataset of 64 patients (30 RRMS, 14 SPMS, 20 PPMS) and a separate longitudinal dataset of 25 patients (114 MR imaging examinations). Twelve patients in the longitudinal dataset had converted from RRMS to SPMS. For all images, the MOV and corpus callosum were delineated manually and the corpus callosum was parcellated into 5 segments. Patients from the cross-sectional dataset were classified as RRMS, SPMS, or PPMS by using a decision tree algorithm with the following input features: brain parenchymal fraction, age, disease duration, MOV, total corpus callosum area and areas of 5 segments of the corpus callosum. To test the robustness of the classification technique, we applied the results derived from the cross-sectional analysis to the longitudinal dataset. RESULTS: MOV and central corpus callosum segment area were the 2 features retained by the decision tree. Patients with MOV >0.94 cm3 were classified as having RRMS. Patients with progressive MS were further subclassified as having SPMS if the central corpus callosum segment area was <55.12 mm2, and as having PPMS otherwise. In the cross-sectional dataset, 51/64 (80%) patients were correctly classified. For the longitudinal dataset, 88/114 (77%) patient time points were correctly classified as RRMS or SPMS. CONCLUSIONS: Classification techniques revealed differences in affected neuroanatomic regions in subtypes of multiple sclerosis. The combination of central corpus callosum segment area and MOV provides good discrimination among patients with RRMS, SPMS, and PPMS.

Reversible Kernohan notch.

A 55-year-old patient experienced episodic headaches, left facial twitching, and increasing falls over 2 years. Multiple yearly brain MRs (figure 1, top panels) revealed a large right frontal arachnoid cyst with evolving …