Interest in muscle MRI has been largely stimulated in the last few years by the recognition of an increasing number of genetic defects in the field of inherited neuromuscular disorders. Muscle ultrasound (US) and computed tomography (CT) have been used to detect the presence of muscle involvement in patients affected by these disorders, but until recently the use of muscle MRI has been, with a few exceptions, limited to detecting inflammatory forms. The aim of this review is to illustrate how muscle MRI, in combination with clinical evaluation, can contribute to the selection of appropriate genetic tests and more generally in the differential diagnosis of genetically distinct forms of neuromuscular disorders. Possible future applications of muscle MRI are also discussed. J. Magn. Reson. Imaging 2007.

Background: Congenital muscular dystrophies (CMD) with reduced glycosylation of alpha-dystroglycan (α-DG) are a heterogeneous group of conditions associated with mutations in six genes encoding proven or putative glycosyltransferases.

Objective To delineate the electroclinical features of SCN8A infantile developmental and epileptic encephalopathy (EIEE13, OMIM #614558). Methods Twenty-two patients, aged 19 months to 22 years, underwent electroclinical assessment. Results Sixteen of 22 patients had mildly delayed development since birth. Drug-resistant epilepsy started at a median age of 4 months, followed by developmental slowing, pyramidal/extrapyramidal signs (22/22), movement disorders (12/22), cortical blindness (17/22), sialorrhea, and severe gastrointestinal symptoms (15/22), worsening during early childhood and plateauing at age 5 to 9 years. Death occurred in 4 children, following extreme neurologic deterioration, at 22 months to 5.5 years. Nonconvulsive status epilepticus recurred in 14 of 22 patients. The most effective antiepileptic drugs were oxcarbazepine, carbamazepine, phenytoin, and benzodiazepines. EEG showed background deterioration, epileptiform abnormalities with a temporo-occipital predominance, and posterior delta/beta activity correlating with visual impairment. Video-EEG documented focal seizures (FS) (22/22), spasm-like episodes (8/22), cortical myoclonus (8/22), and myoclonic absences (1/22). FS typically clustered and were prolonged (<20 minutes) with (1) cyanosis, hypomotor, and vegetative semiology, sometimes unnoticed, followed by (2) tonic-vibratory and (3) (hemi)-clonic manifestations ± evolution to a bilateral tonic-clonic seizure. FS had posterior-temporal/occipital onset, slowly spreading and sometimes migrating between hemispheres. Brain MRI showed progressive parenchymal atrophy and restriction of the optic radiations. Conclusions: SCN8A developmental and epileptic encephalopathy has strikingly consistent electroclinical features, suggesting a global progressive brain dysfunction primarily affecting the temporo-occipital regions. Both uncontrolled epilepsy and developmental compromise contribute to the profound impairment (increasing risk of death) during early childhood, but stabilization occurs in late childhood.

To describe the occurrence of abnormal hyperintensity in the dentate nucleus on T1-weighted magnetic resonance (MR) images in patients with multiple sclerosis (MS) as a neuroradiologic sign of gray matter involvement. Presence of the finding was evaluated for association with disability, clinical MS subtype, total lesion volume on T1- and T2-weighted MR images (lesion load), and brain atrophy. Written informed consent was waived by the Ethics Committee because of the retrospective nature of this single-center Institutional Review Board-approved study. MR examinations of 185 patients with MS were reviewed, and 119 patients were included for analysis. Two neuroimagers, who were blinded to clinical data, assessed the presence of a hyperintense dentate nucleus on T1-weighted MR images. The presence of this radiologic alteration was then evaluated in relation to MS subtype, clinical disability, T1 and T2 lesion load, and whole-brain atrophy measurements. Fisher exact, chi(2), and Mann-Whitney U tests were used to evaluate differences in clinical and imaging features between patients with and those without a T1 hyperintense dentate nucleus. Twenty-three (19.3%) of the 119 patients had a hyperintense dentate nucleus on unenhanced T1-weighted MR images. This finding was related to the secondary progressive subtype of the disease, a higher score on the Expanded Disability Status Scale, a higher brain lesion load, and tissue loss. None of the patients with primary progressive MS had a hypterintense dentate nucleus. Hyperintensity of the dentate nucleus may be present on unenhanced T1-weighted MR images of patients with MS and is associated with the secondary progressive disease subtype and with increased clinical disability, lesion load, and brain atrophy.

Enzyme replacement therapy is currently the only approved treatment for Pompe disease, due to acid α-glucosidase deficiency. Clinical efficacy of this approach is variable, and more effective therapies are needed. We showed in preclinical studies that chaperones stabilize the recombinant enzyme used for enzyme replacement therapy. Here, we evaluated the effects of a combination of enzyme therapy and a chaperone on α-glucosidase activity in Pompe disease patients. α-Glucosidase activity was analyzed by tandem-mass spectrometry in dried blood spots from patients treated with enzyme replacement therapy, either alone or in combination with the chaperone N-butyldeoxynojirimycin given at the time of the enzyme infusion. Thirteen patients with different presentations (3 infantile-onset, 10 late-onset) were enrolled. In 11 patients, the combination treatment resulted in α-glucosidase activities greater than 1.85-fold the activities with enzyme replacement therapy alone. In the whole patient population, α-glucosidase activity was significantly increased at 12 hours (2.19-fold, P = 0.002), 24 hours (6.07-fold, P = 0.001), and 36 hours (3.95-fold, P = 0.003). The areas under the curve were also significantly increased (6.78-fold, P = 0.002). These results suggest improved stability of recombinant α-glucosidase in blood in the presence of the chaperone.