Lower Arterial Cross-Sectional Area of Carotid and Vertebral Arteries and Higher Frequency of Secondary Neck Vessels Are Associated with Multiple Sclerosis.

BACKGROUND AND PURPOSE: Arterial and neck vessel system characteristics of patients with multiple sclerosis have not been previously investigated. Therefore, the aim of this study was to examine the frequency of neck vessels and their cross-sectional areas (in square millimeters) between patients with MS and healthy controls. MATERIALS AND METHODS: In this study, 193 patients with MS and 193 age- and sex-matched healthy controls underwent 2D TOF venography at 3T. The main arterial (carotid and vertebral), venous (internal jugular), and secondary neck vessels were examined at 4 separate cervical levels (C2/3, C4, C5/6, and C7/T1). The ANCOVA adjusted for age, body mass index, smoking status, hypertension, and heart disease was used to compare the differences between patients with MS and healthy controls. RESULTS: After controlling for all confounding factors, patients with MS had significantly lower cross-sectional areas of the carotid arteries at the C2/3 (P = .03), C5/6 (P = .026), and C7/T1 (P = .005) levels as well as of the vertebral arteries at the C2/3 (P = .02), C4 (P = .012), and C7/T1 (P = .006) levels, compared with healthy controls. A higher frequency of secondary neck vessels was found at all 4 levels in patients with MS: C2/3 (12.9 versus 10, P < .001), C4 (9.1 versus 7.5, P < .001), C5/6 (7.8 versus 6.8, P = .012), and C7/T1 (8.8 versus 6, P < .001). The total cross-sectional areas of secondary neck vessels were also significantly higher at all 4 levels (P < .03). No significant differences in the cross-sectional areas of jugular veins were found between patients with MS and healthy controls. CONCLUSIONS: Patients with MS showed lower cross-sectional areas of the carotid and vertebral arteries and a higher frequency of secondary neck vessels and their cross-sectional areas compared with healthy controls.

Effect of age on MRI phase behavior in the subcortical deep gray matter of healthy individuals.

BACKGROUND AND PURPOSE: It has been demonstrated that increased levels of iron in the brain occur with aging. In this study we investigated the nature of the association between age and SWI-filtered phase values, indicative of iron content, in the subcortical deep gray matter of healthy individuals. MATERIALS AND METHODS: A total of 210 healthy individuals (men: n = 89, women: n = 121), mean age, 39.8 years (standard deviation = 15.5; range = 6-76 years), were imaged on a 3T scanner. Mean MRI phase, mean phase of low-phase voxels, and normalized volumes were determined for total subcortical deep gray matter, caudate, putamen, globus pallidus, thalamus, pulvinar nucleus, hippocampus, amygdala, nucleus accumbens, red nucleus, and substantia nigra. Linear and nonlinear regression models were used to explore the relationship between phase and volume measures, and aging. RESULTS: Mean phase values of subcortical deep gray matter structures showed a quadratic relationship, with individuals in late middle age (40-59 years) having the lowest mean phase values, followed by a reversal of this trend in the elderly. In contrast, mean phase of low-phase voxel measurements showed strong negative linear relationships with aging. Significantly lower phase values were detected in women compared with men (P < .001), whereas no sex differences were observed for mean phase of low-phase voxels. Normalized volume measurements were also linearly related to aging, and women showed smaller normalized volumes of subcortical deep gray matter structures than men (P < .001). Lower mean phase of low-phase voxels was related to decreased volume measures. CONCLUSIONS: A strong association between phase (quadratic effect; phase decreases are followed by increases), mean phase of low-phase voxels (linear effect), volume (linear effect), and age was observed. Low phase was related to brain atrophy.

Iron deposition on SWI-filtered phase in the subcortical deep gray matter of patients with clinically isolated syndrome may precede structure-specific atrophy.

BACKGROUND AND PURPOSE: Increasing evidence suggests that iron deposition is present in the later stages of MS. In this study we examined abnormal phase values, indicative of increased iron content on SWI-filtered phase images of the SDGM in CIS patients and HC. We also examined the association of abnormal phase with conventional MR imaging outcomes at first clinical onset. MATERIALS AND METHODS: Forty-two patients with CIS (31 female, 11 male) and 65 age and sex-matched HC (41 female, 24 male) were scanned on a 3T scanner. Mean age was 40.1 (SD = 10.4) years in patients with CIS, and 42.8 (SD = 14) years in HC, while mean disease duration was 1.2 years (SD = 1.3) in patients with CIS. MP-APT, NPTV, and normalized volume measurements were derived for all SDGM structures. Parametric and nonparametric group-wise comparisons were performed, and associations were determined with other MR imaging metrics. RESULTS: Patients with CIS had significantly increased MP-APT (P = .029) and MP-APT volume (P = .045) in the pulvinar nucleus of the thalamus compared with HC. Furthermore, the putamen (P = .004), caudate (P = .035), and total SDGM (P = .048) displayed significant increases in MP-APT volume, while MP-APT was also significantly increased in the putamen (P = .029). No global or regional volumetric MR imaging differences were found between the study groups. Significant correlations were observed between increased MP-APT volumes of total SDGM, caudate, thalamus, hippocampus, and substantia nigra with white matter atrophy and increased T2 lesion volume (P < .05). CONCLUSION: Patients with CIS showed significantly increased content and volume of iron, as determined by abnormal SWI-phase measurement, in the various SDGM structures, suggesting that iron deposition may precede structure-specific atrophy.

Assessing abnormal iron content in the deep gray matter of patients with multiple sclerosis versus healthy controls.

BACKGROUND AND PURPOSE: It is well known that patients with MS tend to have abnormal iron deposition in and around the MS plaques, in the basal ganglia and the THA. In this study, we used SWI to quantify iron content in patients with MS and healthy volunteers. MATERIALS AND METHODS: Fifty-two patients with MS were recruited to assess abnormal iron content in their basal ganglia and THA structures. One hundred twenty-two healthy subjects were recruited to establish a baseline of normal iron content in deep GM structures. Each structure was separated into 2 regions: a low-iron-content region and a high-iron-content region. The average phase, the percentage area, and the total phase of the high-iron-content region were evaluated. A weighting was also assigned to each subject depending on the level of iron content and its deviation from the normal range. RESULTS: A clear separation between iron content in healthy subjects versus patients with MS was seen. For healthy subjects 13% and for patients with MS 65% showed an iron-weighting factor >3 SDs from the normal mean (P < .05). The results for those patients younger than 40 years are even more impressive. In these cases, only 1% of healthy subjects and 67% of patients with RRMS showed abnormally high iron content. CONCLUSIONS: Iron-weighting factors in the basal ganglia, THA, and the midbrain appeared to be abnormal in roughly two-thirds of patients with MS as measured by SWI.

Value of MR venography for detection of internal jugular vein anomalies in multiple sclerosis: a pilot longitudinal study.

BACKGROUND AND PURPOSE: CCSVI was recently described in patients with MS. CCSVI is diagnosed noninvasively by Doppler sonography and invasively by catheter venography. We assessed the role of conventional MRV for the detection of IJV anomalies in patients with MS diagnosed with CCSVI and in healthy controls who underwent MRV and Doppler sonography examinations during 6 months. MATERIALS AND METHODS: Ten patients with MS underwent TOF, TRICKS, Doppler sonography, and catheter venography at baseline. They were treated at baseline with percutaneous angioplasty and re-evaluated 6 months' posttreatment with MRV and Doppler sonography. In addition, 6 healthy controls underwent a baseline and a 6-month follow-up evaluation by Doppler sonography and MRV. RESULTS: At baseline, the sensitivity, specificity, PPV, and NPV of Doppler sonography for detecting IJV abnormalities relative to catheter venography in patients with MS were calculated, respectively, at 82%, 100%, 99%, and 95%. The figures were 99%, 33%, 33%, 99% for TOF and 99%, 39%, 35%, and 99% for TRICKS. Venous anomalies included the annulus, septum, membrane, and malformed valve. No agreement was found between TOF and catheter venography in 70% of patients with MS and between TRICKS and catheter venography in 60% of patients with MS. At follow-up, 50% of the patients with MS presented with abnormalities on Doppler sonography but only 30% were diagnosed with restenosis. CONCLUSIONS: Conventional MRV has limited value for assessing IJV anomalies for both diagnostic and posttreatment purposes.

Use of neck magnetic resonance venography, Doppler sonography and selective venography for diagnosis of chronic cerebrospinal venous insufficiency: a pilot study in multiple sclerosis patients and healthy controls.

AIM: Chronic cerebrospinal venous insufficiency (CCSVI) is a vascular condition characterized by anomalies of primary veins outside the skull that restrict normal outflow of blood from the brain. CCSVI was recently described as highly prevalent in patients with multiple sclerosis (MS), and can be non-invasively diagnosed by Doppler sonography (DS) and invasively by selective venography (SV). The aim of this paper was to investigate the value of neck magnetic resonance venography (MRV) for the diagnosis of CCSVI compared to DS and SV in patients with MS and in healthy controls (HC). METHODS: Ten MS patients and 7 HC underwent DS, 2D-Time-Of-Flight venography (TOF) and 3D-Time Resolved Imaging of Contrast Kinetics angiography (TRICKS). MS patients also underwent SV. The internal jugular veins (IJVs) and the vertebral veins (VVs) were assessed by both MRV sequences, and the findings were validated against SV and DS. SV has been considered the diagnostic gold standard for MS patients. RESULTS: All MS patients and none of the HC presented CCSVI, according to the DS criteria. This was confirmed by SV. For CCSVI diagnosis, DS showed sensitivity, specificity, accuracy, PPV and NPV of 100%, whereas the figures were 40%, 85%, 58%, 80% and 50% for 3D-TRICKS, and 30%, 85%, 52%, 75% and 46% for 2D-TOF in the IJVs. In MS patients, compared to SV, DS showed sensitivity, specificity, accuracy, PPV and NPV of 100%, 75%, 95%, 94% and 100%, whereas the figures were 31%, 100%, 45%, 100% and 26% for 3D-TRICKS and 25%, 100%, 40%, 100% and 25% for 2D-TOF in the IJVs. CONCLUSION: The use of MRV for diagnosis of CCSVI in MS patients has limited value, and the findings should be interpreted with caution and confirmed by other imaging techniques such as DS and SV.

Chronic cerebrospinal venous insufficiency and iron deposition on susceptibility-weighted imaging in patients with multiple sclerosis: a pilot case-control study.

AIM: Chronic cerebrospinal venous insufficiency (CCSVI) is a vascular phenomenon recently described in multiple sclerosis (MS) that is characterized by stenoses affecting the main extracranial venous outflow pathways and by a high rate of cerebral venous reflux that may lead to increased iron deposition in the brain. Aim of this study was to investigate the relationship between CCSVI and iron deposition in the brain of MS patients by correlating venous hemodynamic (VH) parameters and iron concentration in deep-gray matter structures and lesions, as measured by susceptibility-weighted imaging (SWI), and to preliminarily define the relationship between iron measures and clinical and other magnetic resonance imaging (MRI) outcomes. METHODS: Sixteen (16) consecutive relapsing-remitting MS patients and 8 age- and sex-matched healthy controls (HC) were scanned on a GE 3T scanner, using SWI. RESULTS: All 16 MS patients fulfilled the diagnosis of CCSVI (median VH=4), compared to none of the HC. In MS patients, the higher iron concentration in the pulvinar nucleus of the thalamus, thalamus, globus pallidus, and hippocampus was related to a higher number of VH criteria (P<0.05). There was also a significant association between a higher number of VH criteria and higher iron concentration of overlapping T2 (r=-0.64, P=0.007) and T1 (r=-0.56, P=0.023) phase lesions. Iron concentration measures were related to longer disease duration and increased disability as measured by EDSS and MSFC, and to increased MRI lesion burden and decreased brain volume. CONCLUSION: The findings from this pilot study suggest that CCSVI may be an important mechanism related to iron deposition in the brain parenchyma of MS patients. In turn, iron deposition, as measured by SWI, is a modest-to-strong predictor of disability progression, lesion volume accumulation and atrophy development in patients with MS.

The incidence and natural course of transfusion-associated GB virus C/hepatitis G virus infection in a cohort of thalassemic patients. The Cooleycare Cooperative Group.

To evaluate the risk of transmitting blood-borne GB virus C/hepatitis G virus (GBV-C/HGV) and to define the natural course of infection, we performed a prospective study in a cohort of multitransfused beta-thalassemics during a 6-year follow-up period. We analyzed serum samples of 150 patients collected at 3-year intervals from 1990 to 1996. GBV-C/HGV RNA was determined by reverse transcriptase-polymerase chain reaction and antibodies to E2-protein by an enzyme immunoassay. At baseline, 14.5% of patients had viremia and 18.5% anti-E2. None of the patients with anti-E2 in 1990 subsequently became viremic. Of the 100 GBV-C/HGV RNA-, anti-E2- patients, 10 acquired infection during follow-up, as indicated by positivity of GBV-C/HGV RNA (n = 2), anti-E2 (n = 7), or both markers (n = 1) in 1996. The incidence was 1.7 per 100 person-years (95% confidence interval [CI], 0.8 to 3). Since approximately 19,000 blood units were transfused to these patients during follow-up, the risk of infection was 5.3 in 10,000 units (95% CI, 2 to 8.5). Six of 22 viremic patients cleared the virus during follow-up; 4 of them became anti-E2+. Twelve of 28 patients lost anti-E2 reactivity during follow-up. In conclusion, more than 25% of infections resolve within 6 years; the presence of anti-E2 seems to be protective against infection. Anti-E2 reactivity may decrease with time.

Differences in salivary cortisol levels in cocaine-exposed and noncocaine-exposed NICU infants.

To assess whether cocaine exposure in utero affected adrenocortical responsiveness in the neonatal period, salivary cortisol levels were compared between noncocaine-exposed (n = 35) and cocaine-exposed (n = 11) healthy preterm infants just prior to hospital discharge. Cortisol levels were measured under three conditions: Basal--120 min after no disrupting event or behavioral distress; Noninvasive Stressor--30 min after a neurobehavioral examination; Invasive Stressor--30 min after a heel-stick procedure. There were no differences in Basal cortisol levels between the noncocaine-exposed and cocaine-exposed infants, but the cocaine-exposed infants had significantly lower levels in both the Noninvasive and Invasive Stressor conditions. The suppressed cortisol responding to stressful events in cocaine-exposed infants suggests that these infants may have decreased modulation capability to normally stressful events, which could underlie some of the subtle state regulation problems reported.

[Radiology of thalassemic syndrome in the transition from the old to the new therapeutic transfusion regimen]. / La sindrome radiologica talassemica di transizione fra vecchio e nuovo regime terapeutico trasfusionale.

The authors have evaluated the skull, thorax, wrist and hand standard radiographs of 29 patients affected by Cooley's disease who were treated up to 1983 with a low transfusion regimen, rather with a high transfusion regimen (Hb level greater than 9.5 g/dl). The patients have been divided into two groups, according to the prevalence of the first or the second transfusion regimen. Almost all the changes described in the literature have been found in the radiographs, but completely modified; some of these, like rib notchings, in higher percentage than known. In the youngest patients the most significant appearances were ribs and hand changes, that can be considered the most important feature in their radiological monitoring. However this new transitional radiological syndrome will rapidly modify with the establishment "ab initio" of the high transfusional regimen.

[The endocrine complications in thalassemia major]. / Complicanze endocrine nella thalassemia major.

Based on a review of the literature and personal observation, the authors discuss the most frequent endocrine complication that occur in patients with thalassemia major given blood transfusion and chelating therapy. All the complication are attributed to iron overload in the endocrine glands. The authors conclude that an adequate chelating therapy protects against hemosiderosis and thus against endocrine pathologies.

Use of salivary cortisol measurements in young infants: a note of caution.

In order to investigate possible contamination of saliva samples with formula or breast milk obtained from young infants for cortisol assays, we measured cortisol concentrations in 3 common infant milk formulas and in breast milk before and after defatting and extraction using a commercial radioimmunoassay kit. Cortisol concentrations obtained prior to defatting and extraction were equal to or higher than (1.64-82.80 micrograms/dL) levels reported for salivary cortisol levels reported in newborn infants (0.09-2.08 micrograms/dL). Cortisol concentrations obtained after the defatting and extraction were lower (0.02-0.15 micrograms/dL), indicating that values obtained prior to defatting and extraction were due to cross-reacting substances as well as cortisol. As saliva samples are not routinely defatted or extracted prior to being assayed, high cortisol levels and interfering substances in formula and breast milk could contaminate salivary cortisol measurements in young infants. The present study suggests that appropriate controls should be taken when making salivary cortisol measurements in young infants to help ensure accurate results.

Brain-stem auditory evoked responses as indicators of early brain insult.

The relationship between cranial ultrasonograms (SONOs) and brain-stem auditory evoked responses (BAERs) was evaluated in 2 independent samples of newborn infants at risk for brain injury (n = 113 and 203). Features of the BAER wave forms subjected to stepwise linear discriminant analysis formed the basis of an algorithm used to detect and follow early brain injury. Using this algorithm, information derived from BAERs reliably predicted SONO abnormalities at least 82.3% of the time in the initial study which was replicated with the second sample (77.3%). The wave I component latency (CL) and the wave III-V inter-peak latency interval (IPL) were independent of each other, and both contributed to a prediction of SONO abnormality. Possible mechanisms for these BAER results include compromise to the cochlear membrane or to the auditory nerve itself as well as prolongation of transmission in the brain-stem due to brain-stem hemorrhage, edema, or compression. Normative BAER values and non-linear regression functions for the wave I, III and V CLs, and the I-III, III-V, and I-V IPLs were calculated across age using data from 109 infants who demonstrated normal BAER patterns and had no history of SONO abnormalities. Our analyses indicate BAER techniques, where a single higher intensity is used to produce the BAER wave form, are both valid and efficient for use in the evaluation of early brain injury.