Multimodal MRI Longitudinal Assessment of White and Gray Matter in Different SPG Types of Hereditary Spastic Paraparesis.

Hereditary spastic paraplegias (HSP) are a group of genetically and clinically heterogeneous neurologic disorders. Hereby we describe a relatively large group of patients (pts) affected by HSP studied at baseline (31 pts) and at follow-up (mean period 28.9 ± 8.4 months; 23 pts) with multimodal advanced MRI: high-resolution T1 images for voxel-based morphometry (VBM) analysis, magnetic resonance spectroscopy (MRS), and diffusion tensor imaging (DTI). An age-matched healthy control (HC) group underwent the same neuroimaging protocol in a time schedule matched with the HSP patients. At baseline, VBM showed gray matter (GM) reduction in HSP in the right pre-frontal cortex and bilaterally in the thalami. MRS at baseline depicted in HSP patients compared to the HC group reduction of NAA/Cr ratio in the right pre-frontal region, increase of Cho/Cr ratio in the right pre-central regions, and increase of mI/Cr ratio on the left pre-central area. At cross-sectional follow-up analysis and longitudinal evaluation, no VBM and MRS statistically significant results were obtained. Tract-based spatial statistics (TBSS) analysis showed widespread DTI brain white matter (WM) alterations in patients compared to HC at baseline, which are characterized by reduction of fractional anisotropy (FA) and increase of mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity, as confirmed on cross-analysis of the follow-up dataset. A longitudinal analysis with TBSS in HSP patients did not show significant variations, while upon applying region-based analysis we found increased FA and decreased MD and AD in specific brain WM fiber complex during follow-up. The changes were not correlated with the clinical presentation (pure vs complicated HSP), motor function, and motility indexes or history of specific treatments (botulinum toxin). In conclusion, the cross-sectional analysis of the multiparametric MRI data in our HSP patients confirmed the non-prominent involvement of the cortex in the primary motor regions but rather of other more associative areas. On the contrary, DTI demonstrated a widespread involvement of the brain WM, including the primary motor regions, which was confirmed at follow-up. The longitudinal analysis revealed an apparent inversion of tendency when considering the expected evolution of a neurodegenerative process: we detected an increase of FA and a decrease of MD and AD. These time-related modifications may suggest a repair attempt by the residual central WM fibers, which requires confirmation with a larger group of patients and with a longer time interval.

Is there evidence of bradykinesia in essential tremor?

BACKGROUND AND PURPOSE: Essential tremor (ET) is a movement disorder primarily characterized by upper limb postural and kinetic tremor. Although still under-investigated, bradykinesia may be part of the phenotypic spectrum of ET. The aim was to evaluate bradykinesia features in ET through clinical examination and kinematic analysis of repetitive finger movements. Data collected in ET patients were compared with those recorded in Parkinson's disease patients and healthy controls. METHODS: Overall, 258 subjects participated in the study (90 ET patients, 84 Parkinson's disease patients and 84 healthy controls). Repetitive finger tapping was kinematically recorded using a motion analysis system. Movement velocity, amplitude and decrement (sequence effect) were measured. The three groups were first compared by one-way analysis of variance. A cluster analysis was also performed to better address the data variability observed in ET patients. Possible relationships between kinematic and clinical data were assessed in ET patients. RESULTS: Essential tremor patients were slower than healthy controls. Movement slowness in ET did not correlate with postural or kinetic tremor severity. It was also found that movement slowness in ET was not associated with a sequence effect, which instead is a common feature in Parkinson's disease. Cluster analysis showed that a proportion of ET patients may have movement abnormalities similar to those observed in Parkinson's disease. CONCLUSIONS: Movement slowness without sequence effect is a common feature in ET patients. The present findings are relevant when interpreted in the context of the new tremor classification system and in the development of a more accurate bradykinesia definition.

Brain white matter involvement in hereditary spastic paraplegias: analysis with multiple diffusion tensor indices.

BACKGROUND AND PURPOSE: The hereditary spastic paraplegias are a group of genetically heterogeneous neurodegenerative disorders, characterized by progressive spasticity and weakness of the lower limbs. Although conventional brain MR imaging findings are normal in patients with pure hereditary spastic paraplegia, microstructural alteration in the cerebral WM can be revealed with DTI. Concomitant investigation of multiple intrinsic diffusivities may shed light on the neurobiologic substrate of the WM degeneration pattern in patients with pure hereditary spastic paraplegia across the whole brain. MATERIALS AND METHODS: Tract-based spatial statistics analysis was performed to compare fractional anisotropy and mean, axial, and radial diffusivities of the WM skeleton in a group of 12 patients with pure hereditary spastic paraplegia and 12 healthy volunteers. Data were analyzed counting age and sex as nuisance covariates. The threshold-free cluster-enhancement option was applied, and the family-wise error rate was controlled by using permutation tests for nonparametric statistics. RESULTS: In pure hereditary spastic paraplegia, group widespread fractional anisotropy decreases and radial diffusivity and mean diffusivity increases (P < .05, corrected) were found. No voxelwise difference was observed for the axial diffusivity map. Percentage of voxels within the WM skeleton that passed the significance threshold were 51%, 41.6%, and 11.9%, respectively, for radial diffusivity, fractional anisotropy, and mean diffusivity clusters. An anteroposterior pattern with preferential decrease of fractional anisotropy in the frontal circuitry was detected. CONCLUSIONS: In patients with pure hereditary spastic paraplegia, alterations in multiple DTI indices were found. Radial diffusivity seems more sensitive to hereditary spastic paraplegia-related WM pathology and, in line with the lack of axial diffusivity changes, might indicate a widespread loss of myelin integrity. A decrease of fractional anisotropy alone in the frontal circuitry may reflect subtle disruption of the frontal connections.

Brugada syndrome: the prognostic dilemma and value of sincope.

Since its first description in 1992 as a new clinical entity, the Brugada syndrome has stimulated great interest among physicians and basic scientists. In 2002 and 2005, two consensus conferences have respectively defined the diagnostic criteria for the syndrome. Currently the diagnosis of Brugada syndrome is based on a combination of clinical events (syncope and/or sudden cardiac death due to malignant ventricular arrhythmias) and electrocardiographic features (pathognomonic ST-segment elevation morphology). In the last years, many advances have been done in the knowledge about the genetic basis, the cellular mechanisms responsible for the typical electrocardiography features, susceptibility to ventricular arrhythmias and risk stratification. The implantable cardioverter defibrillator remains the only therapeutic option of proven efficacy for primary and secondary prophylaxis of sudden cardiac death. Identification of high risk subjects is one of the major goals in clinical decision-making. Syncope is ubiquitously recognized as a bad prognostic marker in Brugada syndrome. However, young individuals with this disease may suffer from vaso-vagal instead of arrhythmic syncope. The prognostic significance of syncope in patients with Brugada syndrome is discussed in this review.

Intraoperative transesophageal echo-Doppler evaluation of stentless aortic xenografts. Incidence and significance of moderate gradients.

BACKGROUND: The aim of this study was to assess the utility of intraoperative transesophageal echocardiography (TEE) in the evaluation of patients undergoing aortic valve replacement with the CryoLife-O'Brien (CLOB) Stentless Porcine Aortic Bioprosthesis. METHODS: Between May 1994 and March 1995, 26 patients (15 men, mean age 68.4+/-10.78 years) had a CLOB valve in the aortic position. Transprosthetic gradients and valve regurgitation were detected by intraoperative TEE. Prosthetic regurgitation and transvalvular gradients were evaluated at six-month intervals using transthoracic echo-Doppler (TTE). RESULTS: The majority of implants resulted in low gradients (83.7%), with only four patients exhibiting a moderate gradient (15.3%). Color flow Doppler imaging showed central aortic regurgitation in only four of 25 patients (trivial, n=4; mild, n=1). There was one paravalvular leak (trivial, n=1). At follow-up examination (mean 37+/-12 months), 24 of 25 patients exhibited low mean gradients (7.25+/-2.81 mmHg). At follow-up one patient who had low velocities in the LVOT at perioperative evaluation exibited a moderate gradient (45 mmHg) with an effective orifice area of 0.8-0.9 cm(2). CONCLUSIONS: Intraoperative TEE was effective in assessing prosthetic stentless valve function.