Early skeletal outcomes after hematopoietic stem and progenitor cell gene therapy for Hurler syndrome.

Mucopolysaccharidosis type I Hurler (MPSIH) is characterized by severe and progressive skeletal dysplasia that is not fully addressed by allogeneic hematopoietic stem cell transplantation (HSCT). Autologous hematopoietic stem progenitor cell-gene therapy (HSPC-GT) provides superior metabolic correction in patients with MPSIH compared with HSCT; however, its ability to affect skeletal manifestations is unknown. Eight patients with MPSIH (mean age at treatment: 1.9 years) received lentiviral-based HSPC-GT in a phase 1/2 clinical trial (NCT03488394). Clinical (growth, measures of kyphosis and genu velgum), functional (motor function, joint range of motion), and radiological [acetabular index (AI), migration percentage (MP) in hip x-rays and MRIs and spine MRI score] parameters of skeletal dysplasia were evaluated at baseline and multiple time points up to 4 years after treatment. Specific skeletal measures were retrospectively compared with an external cohort of HSCT-treated patients. At a median follow-up of 3.78 years after HSPC-GT, all patients treated with HSPC-GT exhibited longitudinal growth within WHO reference ranges and a median height gain greater than that observed in patients treated with HSCT after 3-year follow-up. Patients receiving HSPC-GT experienced complete and earlier normalization of joint mobility compared with patients treated with HSCT. Mean AI and MP showed progressive decreases after HSPC-GT, suggesting a reduction in acetabular dysplasia. Typical spine alterations measured through a spine MRI score stabilized after HSPC-GT. Clinical, functional, and radiological measures suggested an early beneficial effect of HSPC-GT on MPSIH-typical skeletal features. Longer follow-up is needed to draw definitive conclusions on HSPC-GT's impact on MPSIH skeletal dysplasia.

Robot-Assisted Training for Upper Limb in Stroke (ROBOTAS): An Observational, Multicenter Study to Identify Determinants of Efficacy.

BACKGROUND: The loss of arm function is a common and disabling outcome after stroke. Robot-assisted upper limb (UL) training may improve outcomes. The aim of this study was to explore the effect of robot-assisted training using end-effector and exoskeleton robots on UL function following a stroke in real-life clinical practice. METHODS: A total of 105 patients affected by a first-ever supratentorial stroke were enrolled in 18 neurorehabilitation centers and treated with electromechanically assisted arm training as an add-on to conventional therapy. Both interventions provided either an exoskeleton or an end-effector device (as per clinical practice) and consisted of 20 sessions (3/5 times per week; 6-8 weeks). Patients were assessed by validated UL scales at baseline (T0), post-treatment (T1), and at three-month follow-up (T2). The primary outcome was the Fugl-Meyer Assessment for the upper extremity (FMA-UE). RESULTS: FMA-UE improved at T1 by 6 points on average in the end-effector group and 11 points on average in the exoskeleton group (p < 0.0001). Exoskeletons were more effective in the subacute phase, whereas the end-effectors were more effective in the chronic phase (p < 0.0001). CONCLUSIONS: robot-assisted training might help improve UL function in stroke patients as an add-on treatment in both subacute and chronic stages. Pragmatic and highmethodological studies are needed to confirm the showed effectiveness of the exoskeleton and end-effector devices.

Body schema and corporeal self-recognition in the alien hand syndrome.

OBJECTIVE: The alien hand syndrome (AHS) is a rare neuropsychological disorder characterized by involuntary, yet purposeful, hand movements. Patients with the AHS typically complain about a loss of agency associated with a feeling of estrangement for actions performed by the affected limb. The present study explores the integrity of the body representation in AHS, focusing on 2 main processes: multisensory integration and visual self-recognition of body parts. Three patients affected by AHS following a right-hemisphere stroke, with clinical symptoms akin to the posterior variant of AHS, were tested and their performance was compared with that of 18 age-matched healthy controls. METHOD: AHS patients and controls underwent 2 experimental tasks: a same-different visual matching task for body postures, which assessed the ability of using your own body schema for encoding others' body postural changes (Experiment 1), and an explicit self-hand recognition task, which assessed the ability to visually recognize your own hands (Experiment 2). RESULTS: As compared to controls, all AHS patients were unable to access a reliable multisensory representation of their alien hand and use it for decoding others' postural changes; however, they could rely on an efficient multisensory representation of their intact (ipsilesional) hand. Two AHS patients also presented with a specific impairment in the visual self-recognition of their alien hand, but normal recognition of their intact hand. CONCLUSION: This evidence suggests that the AHS following a right-hemisphere stroke may involve a disruption of the multisensory representation of the alien limb; instead, self-hand recognition mechanisms may be spared. (PsycINFO Database Record

Enzymatic replacement therapy for Hunter disease: Up to 9 years experience with 17 patients.

Hunter disease is an X-linked lysosomal storage disorder characterized by progressive storage of glycosaminoglycans (GAGs) and multi-organ impairment. The central nervous system (CNS) is involved in at least 50% of cases. Since 2006, the enzymatic replacement therapy (ERT) is available but with no effect on the cognitive impairment, as the present formulation does not cross the blood-brain barrier. Here we report the outcome of 17 Hunter patients treated in a single center. Most of them (11) started ERT in 2006, 3 had started it earlier in 2004, enrolled in the phase III trial, and 3 after 2006, as soon as the diagnosis was made. The liver and spleen sizes and urinary GAGs significantly decreased and normalized throughout the treatment. Heart parameters improved, in particular the left ventricular mass index/m(2) decreased significantly. Amelioration of hearing was seen in many patients. Joint range of motion improved in all patients. However, no improvement on respiratory function, eye, skeletal and CNS disease was found. The developmental quotient of patients with a CNS involvement showed a fast decline. These patients were no more testable after 6 years of age and, albeit the benefits drawn from ERT, their quality of life worsened throughout the years. The whole group of patients showed a consistent residual disease burden mainly represented by persistent skeletal disease and frequent need of surgery. This study suggests that early diagnosis and treatment and other different therapies which are able to cross the blood-brain barrier, might in the future improve the MPS II outcome.

Intramural aortic hematoma: no flap no warning?

We report a case of type A intramural aortic hematoma (IMH) occurred in a 78 years old female. The clinical scenario (medical history of hypertension, severe substernal chest pain, early diastolic decrescendo murmur as for aortic insufficiency), the laboratory results (no significant troponin level), ECG and transthoracic echocardiography findings (no signs of myocardial ischemia) shifted the initial diagnostic suspicion from acute coronary syndrome to the acute aortic syndrome (AAS) and triggered further imaging tests. Computed tomography revealed an aneurismatic dilatation with thickening of the wall of the ascending aorta without intimal flap. No particular "warning message" for evidence of AAS was sent to the clinician on call. Subsequently, due to the persisting high clinical suspicion transesophageal echocardiography (TEE) was performed. TEE confirmed the aneurysm of the ascending aorta and highlighted an extended and marked aortic wall thickness, consisting with the diagnosis of type A IMH. Patient underwent urgent cardiac surgery that confirmed the diagnosis.