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BackgroundMutations in SACS, leading to autosomal-recessive spastic ataxia of Charlevoix-Saguenay (ARSACS), have been identified as a frequent cause of recessive early-onset ataxia around the world. Here we aimed to enlarge the spectrum of SACS mutations outside Quebec, to establish the pathogenicity of novel variants, and to expand the clinical and imaging phenotype.MethodsSequencing of SACS in 22 patients with unexplained early-onset ataxia, assessment of novel SACS variants in 3.500 European control chromosomes and extensive phenotypic investigations of all SACS carriers.ResultsWe identified 11 index patients harbouring 17 novel SACS variants. 9/11 patients harboured two variants of at least probable pathogenicity which were not observed in controls and, in case of missense mutations, were located in highly conserved domains. These 9 patients accounted for at least 11% (9/83) in our series of unexplained early onset ataxia subjects. While most patients (7/9) showed the classical ARSACS triad, the presenting phenotype reached from pure neuropathy (leading to the initial diagnosis of Charcot-Marie-Tooth disease) in one subject to the absence of any signs of neuropathy in another. In contrast to its name “spastic ataxia”, neither spasticity (absent in 2/9=22%) nor extensor plantar response (absent in 3/9=33%) nor cerebellar ataxia (absent in 1/9=11%) were obligate features. Autonomic features included urine urge incontinence and erectile dysfunction. Apart from the well-established MRI finding of pontine hypointensities, all patients (100%) showed hyperintensities of the lateral pons merging into the (thickened) middle cerebellar peduncles. In addition, 63% exhibited bilateral parietal cerebral atrophy, and 63% a short circumscribed thinning of the posterior midbody of the corpus callosum. In 2 further patients with differences in important clinical features, VUS class 3 variants (c.1373C>T [p.Thr458Ile] and c.2983 G>T [p.Val995Phe]) were identified. These variants were, however, also observed in controls, thus questioning their pathogenic relevance.ConclusionsWe here demonstrate that each feature of the classical ARSACS triad (cerebellar ataxia, spasticity and peripheral neuropathy) might be missing in ARSACS. Nevertheless, characteristic MRI features – which also extend to supratentorial regions and involve the cerebral cortex – will help to establish the diagnosis in most cases.

Pallidal deep brain stimulation is a safe and effective long-term treatment in patients with medically refractory tardive dystonia.

The aim of this study was to compare CT, MRI and FDG-PET in the prediction of outcome of neoadjuvant radiochemotherapy in patients with locally advanced primary rectal cancer. A total of 23 patients with T3/4 rectal cancer underwent a preoperative radiochemotherapy combined with regional hyperthermia. Staging was performed using four-slice CT (n=23), 1.5-T MRI (n=10), and (18)F-FDG-PET (n=23) before and 2-4 weeks after completion of neoadjuvant treatment. Response criteria were a change in T category and tumour volume for CT and MRI and a change in glucose uptake (standard uptake value) within the tumour for FDG-PET. Imaging results were compared with those of pretherapy endorectal ultrasound and histopathological findings. Histopathology showed a response to neoadjuvant therapy in 13 patients whereas 10 patients were classified as nonresponders. The mean SUV reduction in responders (60+/-14%) was significantly higher than in nonresponders (37+/-31%; P=0.030). The sensitivity and specificity of FDG-PET in identifying response was 100% (CT 54%, MRI 71%) and 60% (CT 80%, MRT 67%). Positive and negative predictive values were 77% (CT 78%, MRI 83%) and 100% (CT 57%, MRI 50%) (PET P=0.002, CT P=0.197, MRI P=0.500). These results suggest that FDG-PET is superior to CT and MRI in predicting response to preoperative multimodal treatment of locally advanced primary rectal cancer.

ObjectiveTo generate high-resolution maps of the viscoelastic properties of human brain parenchyma for presurgical quantitative assessment in glioblastoma (GB).MethodsTwenty-two GB patients underwent routine presurgical work-up supplemented by additional multifrequency magnetic resonance elastography. Two three-dimensional viscoelastic parameter maps, magnitude |G*|, and phase angle φ of the complex shear modulus were reconstructed by inversion of full wave field data in 2-mm isotropic resolution at seven harmonic drive frequencies ranging from 30 to 60 Hz.ResultsMechanical brain maps confirmed that GB are composed of stiff and soft compartments, resulting in high intratumor heterogeneity. GB could be easily differentiated from healthy reference tissue by their reduced viscous behavior quantified by φ (0.37±0.08 vs. 0.58±0.07). |G*|, which in solids more relates to the material's stiffness, was significantly reduced in GB with a mean value of 1.32±0.26 kPa compared to 1.54±0.27 kPa in healthy tissue (P = 0.001). However, some GB (5 of 22) showed increased stiffness.ConclusionGB are generally less viscous and softer than healthy brain parenchyma. Unrelated to the morphology-based contrast of standard magnetic resonance imaging, elastography provides an entirely new neuroradiological marker and contrast related to the biomechanical properties of tumors.