Biomedical subjects

Maria L Stromillo

Publications and source records attributed to Maria L Stromillo.

7 recordsLinked to original sources

PubMed2007

Cardiac autonomic nervous system and risk of arrhythmias in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL).

BACKGROUND AND PURPOSE: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an inherited systemic microangiopathy with prevalently cerebral manifestations. Among the causes of death, sudden unexpected death seems to occur in a significant number of CADASIL patients. Because potential causes of sudden unexpected death may include cardiac arrhythmias and myocardial infarction, we evaluated risk factors for life-threatening arrhythmias, such as reduced heart rate variability, sympathetic overactivity and QT interval (QTc) prolongation, in 23 CADASIL patients. The relationship of these changes with brain MRI pattern was also investigated. METHODS: Frequency domain measures of heart rate variability (10 minutes recordings) and QTc interval were recorded in 23 CADASIL patients (17 males, 6 females) and 22 healthy age- and sex-matched control subjects. The following heart rate variability spectral parameters were considered at rest during spontaneous and controlled breathing (Cb): total power, very-low-frequency component, low-frequency component, high-frequency component, low-frequency/high-frequency ratio, and Cb-total power, Cb-very-low-frequency component, Cb-low-frequency component, Cb-high-frequency component, Cb-low-frequency/high-frequency ratio. R-to-R wave and QTc interval were also analyzed. All data were statistically compared between CADASIL and control subjects. Conventional brain MRI was performed in patients with CADASIL and T1-weighted and T2-weighted lesion volumes, and were compared with each spectral component of the tachogram. RESULTS: During spontaneous and controlled breathing, total power spectrum and all spectral components (very low frequency component, high-frequency component, low-frequency component) of heart rate variability were significantly reduced in CADASIL patients with respect to controls (P<0.05). The low-frequency/high-frequency component ratio was significantly higher in CADASIL patients than in controls. No significant correlation between heart rate variability spectral parameters and other variables including total brain T2-weighted and T1-weighted lesion volumes were observed in CADASIL subjects. CONCLUSIONS: We found a statistically significant reduction in all frequency domain parameters of heart rate variability associated with a higher low frequency/high frequency ratio for CADASIL patients with respect to normal subjects. These data are consistent with autonomic derangement and suggests that CADASIL patients may be at risk for life-threatening arrhythmias. This could at least in part explain their higher recurrence of sudden unexpected death and should be taken into account in planning therapy.

Adult↗

PubMed2006

Cortical damage in brains of patients with adult-form of myotonic dystrophy type 1 and no or minimal MRI abnormalities.

OBJECTIVE: To evaluate, by using quantitative MRI metrics, subtle cortical changes in brains of patients with the adult form of myotonic dystrophy type I (DM1) who showed no or minimal abnormalities on MRI. BACKGROUND: DM1 is an autosomal dominant multisystem disorder caused by the expansion of CTG repeats in the myotonic dystrophy-protein kinase gene. Mild to severe involvement of the CNS can be part of the clinical features of the disease. Several MRI studies have demonstrated that both focal white matter (WM) lesions and diffuse grey matter atrophy can be found in the brains of DM1 patients. However, whether these two processes are related or may occur independently is not clear. DESIGN/METHODS: Ten genetically-proven DM1 patients who showed no or minimal abnormalities on MRI underwent a new brain MRI examination to obtain computerized measures of total and regional brain volumes normalized to head size and regional measurements of the magnetization transfer ratio (MTr). RESULTS: Normalized brain volumes (NBV) were significantly (p < 0.0001) lower in DM1 subjects than in a group of age- and sex-matched normal controls. Normalized cortical volumes (NCV) also were lower (p = 0.003) in DM1 subjects than in normal controls, whereas normalized WM volumes were not different between the two groups (p = 0.3). In agreement with this, values of MTr in the neocortex (cortical-MTr) were significantly (p = 0.006) lower in DM1 patients than in normal controls and this difference was not found in the WM tissue (p = 0.8). CONCLUSIONS: Neocortical damage seems to be evident in the absence of visible WM lesions suggesting that a neocortical pathology, unrelated to WM lesion formation, occurs in DM1 brains.

Adult↗

PubMed2006

Diffuse structural and metabolic brain changes in Fabry disease.

OBJECTIVES: To assess structural and metabolic brain changes in subjects affected by Fabry disease (FD) or carrying the disease mutation. BACKGROUND: FD is an X-linked metabolic disorder due to alpha-galactosidase A deficiency, which leads to storage of glycosphingolipids in many tissues and organs. Previous MR studies have shown structural and metabolic brain abnormalities in FD patients. It is not clear, however, whether tissue damage can be seen in both the brains of hemizygous and heterozygous and whether quantitative MR metrics are useful to monitor disease evolution. DESIGN/METHODS: We studied 4 males and 4 females with FD. Each subject underwent brain proton MRI/MR spectroscopic imaging (MRSI) examinations to obtain measures of total brain volumes, total brain lesion volumes, magnetization transfer ratios (MTr) in WM and central brain levels of N-acetylaspartate (NAA) to creatine (Cr). A second MR examination was performed in five subjects after 2 years. RESULTS: Focal WM lesions were found in 2 males and 1 female. The MTr values were always low in the WM lesions of FD subjects (p < 0.001) and also were low in the normal-appearing WM of 2 affected males. Total brain volumes were never decreased in FD subjects. Brain NAA/Cr values were significantly (p = 0.005) lower in FD subjects than in normal controls and correlated closely with Rankin scale measures (r = -0.79). On follow-up examinations, no significant MR changes were found. However, the small changes in NAA/Cr correlated closely with changes in Rankin scores (r = -0.86). CONCLUSIONS: Subtle structural and metabolic tissue damage can extend beyond WM lesions in FD subjects. Diffuse brain NAA/Cr decrease can be found in FD subjects in relation to the degree of their CNS involvement and its evolution over time.

Adult↗

PubMed2006

Diffuse metabolic changes in the brain of patients with familial amyloid polyneuropathy. A proton MRSI study.

OBJECTIVES: To assess brain metabolic abnormalities in patients with familial amyloid polyneuropathy (FAP) due to the transthyretin (TTR) gene mutations. BACKGROUND: The TTR-FAP has variable phenotypic expression, which includes abnormalities of the central nervous system (CNS). Several conventional MRI studies have shown brain abnormalities, probably secondary to amyloid accumulation in leptomeningeal and subarachnoid vessels. However, TTR-related amyloid deposits do not seem to significantly affect the brain parenchyma and a prominent CNS impairment is considered to be rare in TTR amyloidosis. METHODS: We performed proton MR spectroscopic imaging (1H-MRSI) in the central brain of four unrelated TTR-FAP patients with either minimal or no signs of neurological involvement and eight age- and sex-matched normal controls (NC). Metabolic changes were assessed in the entire volume of interest (VOI) and in the frontal, periventricular and posterior white matter (WM). RESULTS: Conventional MRI was normal in 2 patients and showed minimal WM lesions in the remaining 2 patients. 1H-MRSI showed N-acetylaspartate to creatine ratio (NAA/Cr) decreases in the central brain VOI in all TTR-FAP patients (p < 0.005). These NAA/Cr decreases were homogeneous in all WM regions (p < 0.05 for all). CONCLUSIONS: 1H-MRSI findings suggest that diffuse metabolic changes, probably related to axonal damage, are present in brains of TTR-FAP patients even when they have no or minimal clinical and MRI signs of CNS involvement. The mechanism leading to sub-clinical metabolic brain changes needs to be identified.

Adult↗

PubMed2006

Imaging brain damage in first-degree relatives of sporadic and familial multiple sclerosis.

OBJECTIVE: Our objective was to assess brain damage in first-degree relatives of patients with sporadic and familial multiple sclerosis (MS). METHODS: Asymptomatic first-degree relatives of sporadic (sMS, n = 152) and familial MS (fMS, n = 88) and healthy volunteers (NC, n = 56) underwent brain MRI and magnetization transfer (MT) imaging on a mobile MR scan. On MR examinations, we visually assessed white matter (WM) lesions and quantified WM lesion volumes, brain volumes, and MT ratio (MTr) in lesions and normal-appearing WM (NAWM). RESULTS: A lesional MR pattern similar to that of MS patients was found in 4% sMS and 10% fMS. In these WM lesions, MTr was lower (p < 0.0001) than in the WM of NC. In contrast, there was no difference in NAWM-MTr and brain volume values between the three groups. INTERPRETATION: Focal brain abnormalities indistinguishable from those of MS occur in asymptomatic first-degree relatives of MS patients. These are twice more frequent in fMS than in sMS but do not lead to the widespread tissue damage commonly found in MS patients. Although there is a genetic susceptibility to develop brain abnormalities suggestive of focal demyelination in first-degree relatives of MS patients, other factors are probably critical for the development of a diffuse, clinically relevant, pathology.

Adult↗

PubMed2005

Magnetic resonance spectroscopy as a measure of brain damage in multiple sclerosis.

Recent MR studies have emphasised the importance of neuronal and axonal damage in multiple sclerosis. In this respect, proton MR spectroscopy (by monitoring levels of N-acetylaspartate, a putative marker of axonal integrity) has been particularly illuminating by showing indirect evidence of neurodegeneration in both lesional and non-lesional brain tissues from the earliest stages of the disease. The importance of these changes to patients' clinical disability argues for the primary role of neuronal pathology in the pathogenesis of the disease.

Aspartic Acid↗

PubMed2003

MR evidence of structural and metabolic changes in brains of patients with Werner's syndrome.

OBJECTIVE: To assess CNS abnormalities in patients with Werner's syndrome (WS) using MR metrics specific for tissue damage. BACKGROUND: WS is a rare autosomal recessive disorder that causes premature aging. The CNS involvement in this disease is still debated. METHODS: Two siblings who showed signs of neurological involvement underwent MR spectroscopic imaging (MRSI) and magnetization transfer (MT) imaging. Also, on conventional T1-weighted MR images, measurements of total brain volume were performed. RESULTS: Conventional MR images of both WS patients did not show abnormalities on visual inspection. However, both WS patients showed significantly lower values of normalized total brain volume and MT ratio in the white matter than age-matched normal controls. Also, proton MRSI showed significantly lower values of central brain NAA/Cr in WS patients than in normal controls. CONCLUSIONS: Our findings suggest that, despite normal appearance on conventional MRI, diffuse structural and metabolic tissue damage can be demonstrated in WS brains by means of sensitive MR methods even in patients with moderate or subclinical CNS involvement.

Adult↗