Abstract Objective Late‐onset GM2 gangliosidosis (LOGG) subtypes late‐onset Tay‐Sachs (LOTS) and Sandhoff disease (LOSD) are ultra‐rare neurodegenerative lysosomal storage disorders presenting with weakness, ataxia, and neuropsychiatric symptoms. Previous studies considered LOTS and LOSD clinically indistinguishable; recent studies have challenged this. We performed a scoping review to ascertain whether imaging and clinical features may differentiate these diseases. Methods We examined MEDLINE/non‐MEDLINE databases up to May 2022. Articles reporting brain imaging findings in genetically/enzymatically confirmed LOGG, symptom onset at age ≥ 10 years (or evaluated at least once ≥18 years) were included, yielding 170 LOGG patients (LOTS = 127, LOSD = 43) across 68 papers. We compared LOTS versus LOSD and performed regression analyses. Results were corrected for multiple comparisons. Results Age of onset was lower in LOTS versus LOSD (17.9 ± 8.2 vs. 23.9 ± 14.4 years, p = 0.017), although disease duration was similar ( p = 0.34). LOTS more commonly had psychosis/bipolar symptoms (35.0% vs. 9.30%, p = 0.011) but less frequent swallowing problems (4.10% vs. 18.60%, p = 0.041). Cerebellar atrophy was more common in LOTS (89.0%) versus LOSD (60.5%), p < 0.0001, with more severe atrophy in LOTS ( p = 0.0005). Brainstem atrophy was documented only in LOTS (14.2%). Independent predictors of LOTS versus LOSD (odds ratio [95% confidence interval]) included the presence of psychosis/bipolar symptoms (4.95 [1.59–19.52], p = 0.011), no swallowing symptoms (0.16 [0.036–0.64], p = 0.011), and cerebellar atrophy (5.81 [2.10–17.08], p = 0.0009). Lower age of onset (0.96 [0.93–1.00], p = 0.075) and tremor (2.50 [0.94–7.43], p = 0.078) were marginally statistically significant but felt relevant to include in the model. Interpretation These data suggest significant differences in symptomatology, disease course, and imaging findings between LOTS and LOSD.
Magnetic resonance imaging (MRI) of peripheral nerves can provide image-based anatomical information and quantitative measurement. The aim of this pilot study was to investigate the feasibility of high-resolution anatomical and quantitative MRI assessment of sciatic nerve fascicles in patients with Charcot-Marie-Tooth (CMT) 1A using 7T field strength.Six patients with CMT1A underwent imaging on a high-gradient 7T MRI scanner using a 28-channel knee coil. Two high-resolution axial images were simultaneously acquired using a quantitative double-echo in steady-state (DESS) sequence. By comparing the two DESS echoes, T2 and apparent diffusion coefficient (ADC) maps were calculated. The cross-sectional areas and mean T2 and ADC were measured in individual fascicles of the tibial and fibular (peroneal) portions of the sciatic nerve at its bifurcation and 10 mm distally. Disease severity was measured using Charcot-Marie-Tooth Examination Score (CMTES) version 2 and compared to imaging findings.We demonstrated the feasibility of 7T MRI of the proximal sciatic nerve in patients with CMT1A. Using the higher field, it was possible to measure individual bundles in the tibial and fibular divisions of the sciatic nerve. There was no apparent correlation between diffusion measures and disease severity in this small cohort.This pilot study indicated that high-resolution MRI that allows for combined anatomical and quantitative imaging in one scan is feasible at 7T field strengths and can be used to investigate the microstructure of individual nerve fascicles.
Introduction Patients diagnosed with Mild Cognitive Impairment (MCI) often go on to develop dementia, however many do not. Although cognitive tests are widely used in the clinic, there is limited research on their potential to help predict which patients may progress to Alzheimer's disease (AD) from those that do not.Methods MCI patients (n = 325) from the longitudinal Alzheimer's Disease Neuroimaging Initiative (ADNI-2) dataset were tracked across a 5 year period. Upon initial diagnosis, all patients underwent a series of cognitive tests including the Mini Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA) and Alzheimer's Disease Assessment Scale-Cognitive (ADAS-Cog 13). Twenty-five percent (n = 83) of those initially diagnosed with MCI subsequently developed AD within 5 years.Results We showed that those individuals that progressed to AD had significantly lower scores upon baseline testing on the MMSE and MoCA, and higher scores on the ADAS-13, compared to those that did not convert. However, not all tests were equivalent. We showed that the ADAS-13 offers the best predictability of conversion (Adjusted Odds ratio (AOR) = 3.91). This predictability was higher than that offered by the two primary biomarker Amyloid-beta (Aβ, AOR = 1.99) and phospho-tau (Ptau, AOR = 1.72). Further analysis on the ADAS-13 showed that MCI patients that subsequently converted to AD performed particularly poorly on delayed-recall (AOR = 1.93), word recognition (AOR = 1.66), word finding difficulty (AOR = 1.55) and orientation (1.38) test items.Conclusions Cognitive testing using the ADAS-13 may offer a simpler, less invasive, more clinically relevant and a more effective method of determining those that are in danger of converting from MCI to AD.
The ability to estimate neurological disease progression based on objective quantitative measurements could be of great value for assessing treatment efficacy. Here, we demonstrate the feasibility of acquiring high-resolution anatomic and quantitative images at 7T in the sciatic, tibial, and fibular nerves, allowing quantitative assessment of individual fascicles. We also measure the quantities of fascicle cross-sectional area, T2, ADC, and fat fraction for CMT1A patients and healthy controls and investigate any between-group differences.
Abstract The relationship between motor cortex (M1) and upper limb movements has been investigated extensively using functional MRI (fMRI). While most research has focused on applications, very few studies have focused on practical aspects related to developing the fMRI protocol. Thus, the effect of scan length on M1 activations during various upper limb movements remains unclear. Scan length constraints are important for conducting motor experiments within a 60- or 90-min scan session. We targeted this gap by studying 7T fMRI activations in a male participant while performing eight different upper limb movements (of the fingers, wrist, and elbow) across 16 task runs (8 with the left arm, 8 with the right arm, 88 mins total fMRI duration). Standard activation analyses were performed ( Z >3.1, p <0.01, cluster thresholded) independently for 14 different cases (2 runs through 8 runs, left and right arm) and compared. We found diminishing returns with higher number of runs (activations gradually plateaued with runs). We observed two clusters of movements, one with generally higher activation (more activated voxels and higher Z-stats) and the other with lower activation. To achieve similar statistical power, movements with lower activation required longer scanning (more runs). Based on these observations, we propose a ‘ one size does not fit all ’ practical protocol within a 60-, 75-, or 90-min scan session, wherein different number of runs are assigned for different movements. Our study could benefit researchers who are designing upper limb fMRI experiments.
Patients with Alzheimer's disease (AD) demonstrate progressive white matter atrophy and myelin loss. Restoring myelin content or preventing demyelination has been suggested as a therapeutic approach for AD.
Abstract Magnetic resonance spectroscopy (MRS) and functional MRI (fMRI), related through common biophysical bases, provide complementary information about brain function. The link between MRS and fMRI measures is of interest, especially in the ultra-rare, metabolic disease late-onset GM2 gangliosidosis (LOGG). Imaging studies on LOGG have been few and far between, with cerebellar atrophy and neurochemical impairments being the most prominent findings. However, it remains unknown as to how these neurochemical aberrations relate to neurofunctional characteristics. The goal of this study (7 LOGG, 7 age/sex matched controls) was to assess the relationship between MRS concentrations and fMRI measures derived from the same MRS ROI (cerebellum, thalamus, precuneus) in LOGG. To quantify the communication between MRS regions and rest of the brain, we employed graph measures estimated from resting-state fMRI functional connectivity. We found that one such measure, local efficiency, which quantifies the aggregate relationship between a MRS region and rest of the brain, was significantly associated with N-acetylaspartate (NAA) in the cerebellum and thalamus ( p <0.05, FDR corrected). Poorer neuronal health, neuronal loss (NAA), and neuroinflammation (myo-inositol) were related to poorer cerebellum-brain communication. Likewise, reduced thalamus-brain communication was also associated with poorer neuronal health and longer disease duration ( p =0.002). These findings hint at a model of impaired neurochemical concentrations in these regions, leading to aberrant communication between them and rest of the brain, which may exacerbate disease progression. Future research must replicate these findings in larger cohorts, and further investigate such abnormalities in the cerebellum, thalamus and precuneus in this ultra-rare neurological disease.
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