7 T Lesion-Attenuated Magnetization-Prepared Gradient Echo Acquisition for Detection of Posterior Fossa Demyelinating Lesions in Multiple Sclerosis.

OBJECTIVES: Detection of infratentorial demyelinating lesions in multiple sclerosis (MS) presents a challenge in magnetic resonance imaging (MRI), a difficulty that is further heightened in 7 T MRI. This study aimed to assess the efficacy of a novel MRI approach, lesion-attenuated magnetization-prepared gradient echo acquisition (LAMA), for detecting demyelinating lesions within the posterior fossa and upper cervical spine on 7 T MRI and contrast its performance with conventional double-inversion recovery (DIR) and T2-weighted turbo spin echo sequences. MATERIALS AND METHODS: We conducted a retrospective cross-sectional study in 42 patients with a confirmed diagnosis of MS. All patients had 7 T MRI that incorporated LAMA, 3D DIR, and 2D T2-weighted turbo spin echo sequences. Three readers assessed lesion count in the brainstem, cerebellum, and upper cervical spinal cord using both DIR and T2-weighted images in one session. In a separate session, LAMA was analyzed alone. Contrast-to-noise ratio was also compared between LAMA and the conventional sequences. Lesion counts between methods were assessed using nonparametric Wilcoxon signed rank test. Interrater agreement in lesion detection was estimated by intraclass correlation coefficients. RESULTS: LAMA identified a significantly greater number of lesions than DIR + T2 (mean 6.4 vs 3.0; P < 0.001). LAMA also exhibited better interrater agreement (intraclass correlation coefficient [95% confidence interval], 0.75 [0.41-0.88] vs 0.61 [0.35-0.78]). The contrast-to-noise ratio for LAMA (3.7 ± 0.9) significantly exceeded that of DIR (1.94 ± 0.7) and T2 (1.2 ± 0.7) (all P's < 0.001). In cases with no lesions detected using DIR + T2, at least 1 lesion was identified in 83.3% with LAMA. Across all analyzed brain regions, LAMA consistently detected more lesions than DIR + T2. CONCLUSIONS: LAMA significantly improves the detection of infratentorial demyelinating lesions in MS patients compared with traditional methods. Integrating LAMA with standard magnetization-prepared 2 rapid acquisition gradient echo acquisition provides a valuable tool for accurately characterizing the extent of MS disease.

Toward allele-specific targeting therapy and pharmacodynamic marker for spinocerebellar ataxia type 3.

Spinocerebellar ataxia type 3 (SCA3), caused by a CAG repeat expansion in the ataxin-3 gene (ATXN3), is characterized by neuronal polyglutamine (polyQ) ATXN3 protein aggregates. Although there is no cure for SCA3, gene-silencing approaches to reduce toxic polyQ ATXN3 showed promise in preclinical models. However, a major limitation in translating putative treatments for this rare disease to the clinic is the lack of pharmacodynamic markers for use in clinical trials. Here, we developed an immunoassay that readily detects polyQ ATXN3 proteins in human biological fluids and discriminates patients with SCA3 from healthy controls and individuals with other ataxias. We show that polyQ ATXN3 serves as a marker of target engagement in human fibroblasts, which may bode well for its use in clinical trials. Last, we identified a single-nucleotide polymorphism that strongly associates with the expanded allele, thus providing an exciting drug target to abrogate detrimental events initiated by mutant ATXN3. Gene-silencing strategies for several repeat diseases are well under way, and our results are expected to improve clinical trial preparedness for SCA3 therapies.

Facial Myokymia and Hemifacial Spasm in Multiple Sclerosis: A Descriptive Study on Clinical Features and Treatment Outcomes.

OBJECTIVE: Facial Myokymia and hemifacial spasm have been associated with multiple sclerosis; however, their etiology and clinical outcome is uncertain. Here, we describe the clinical, radiologic features, and treatment outcomes of a cohort of patients with multiple sclerosis and history of facial myokymia or hemifacial spasm. METHODOLOGY: We reviewed the clinical features, radiologic features, and treatment outcomes of 35 patients with a diagnosis of multiple sclerosis and facial myokymia (28) or hemifacial spasm (7) seen at Mayo Clinic (Rochester, MN). RESULTS: Facial myokymia was associated with a clinical or radiologic relapse in 11 of 28 patients. In 27 of 28 patients with facial myokymia, symptom resolution occurred within months regardless of treatment. An ipsilateral pontine lesion was found in 3 of 7 cases with hemifacial spasm. Hemifacial spasm was associated with a clinical or radiologic relapse in 3 of 7 cases. Hemifacial spasm resolved within 4 years in 5 of 7 cases, with the remaining cases persisting up to 9 years despite treatment. CONCLUSIONS: Facial myokymia and hemifacial spasm occurring in patients with multiple sclerosis is associated with an ipsilateral pontine MRI lesion in a minority of patients. Facial myokymia is a self-limited process while hemifacial spasm can be persistent in a minority of patients, despite treatment.