Objective To investigate the clinical features and laboratory results in a patient with late onset autosomal recessive spastic ataxia of Charlevoix-Saguenay ( ARSACS ) carrying novel SACS ( spastic ataxia of Charlevoix-Saguenay ) gene heterozygous mutations .Methods A 26-year-old Chinese man developed since the age of 13 a progressive weakness and stiffness of his bilateral lower limbs and gait unsteadiness.He had pyramidal tract sign in his bilateral lower limbs , cerebellar ataxia and sensory-motor polyneuropathy , with hyperelastica and swan neck-like deformities of the fingers , pes cavus and hammer toes.Funduscopy and optical coherence tomography , brain and cervical MRI , conduction velocity of peripheral nerve , motor evoked potentials , visual and brainstem auditory evoked potentials , ultrasound of peripheral nerve , hips and legs MRI , electronystagmography , and targeted capture and next generation sequencing were performed .Results Funduscopy and optical coherence tomography revealed thickening of the retinal nerve fiber layer with unclear margined optic disc .MRI revealed symmetrical linear hypointensity lesions in the pons on T 2 and T2 FLAIR weighted images , thickened bilateral cerebellar peduncles , and flattened and atrophied cervical and upper thoracic spinal cord .Nerve conduction studies showed sensory nerve action potentials were absent in four limbs , motor conduction velocity was slowed , amplitude of muscle response was significantly decreased in lower-limb nerves ( decreased by 80% -100%) but normal in upper-limb nerves.Central motor conduction time of motor evoked potential was prolonged .Targeted capture and next generation sequencing revealed novel SACS compound heterozygous mutations , c.12637 _12638delGA (p.Glu4213ArgFs*3) and c.11274_11276delAAC (p.Ile3758_Thr3759delinsMet) derived from each parent respectively , which were confirmed by Sanger sequencing analyses . Conclusions Recognizing ARSACS triad and its characteristics on fundus and brain MRI is helpful for correct diagnosis . Our findings expand the clinical and genetic spectrum of ARSACS .

Objective To assess the dosimetric impact on the target volumes and organs at risk ( OARs) using simultaneous integrated boost ( SIB ) for the hypoxic regions of the pancreatic cancer patients treated with stereotactic body radiotherapy ( SBRT ) , and to predict an optimal way of SIB. Methods The setup corrections guided by 100 sets of CBCT scans of 10 patients previously treated with SBRT were imported to the treatment planning system ( TPS ) to recalculate the dose to the target and OARs. Two tumor control probability ( TCP ) models were applied to calculate the TCP under various hypoxic situations. The correlations between the TCP and target dose were analyzed. Results Without setup corrections, the PTV and ITV were underdosed by 8. 9％ and 9. 2％ on average respectively relative to planed dose. With setup corrections, the mean dose to PTV and ITV coverage were 1. 6％ and 1. 3％lower than planned respectively. The mean deviations of OAR dose were between -0. 11 Gy and 0. 26 Gy for all plans. The predictive values of Dmean on hypoxic regions were 31. 4, 34. 0 and 37. 2 Gy (Niemierko model) or 31. 6, 33. 9 and 37. 2 Gy (Poisson model) when the oxygen enhancement ratios (OERs) were 1, 1. 5 and 3 respectively. Conclusions With CBCT setup corrections, the dosimetric impacts of setup errors on the target and OARs can be neglected. Significant deviations of TCP calculation were observed without accounting for tumor hypoxia. To counteract the impacts of hypoxia, the mean dose to the hypoxic regions should be at least 1. 24 times of prescribed dose.