**2. Materials and Methods**

### *2.1. Trial Design*

In this case report, a ten-year-old girl with right hemiparesis following ischemic stroke caused by probable primary central nervous system angioitis was enrolled to undergo 10 sessions of RMT with Gloreha Sinfonia.

The aim of this study was to provide an account of the efficacy of RMT using Gloreha Sinfonia in terms of improvements in the range of motion, spasticity, force modulation capability and functionality of the hemiplegic hand in pediatric stroke patients. This paper was organized according to CARE guidelines [20]. Figure 1 presents the timeline.

#### **Figure 1.** Timeline.

#### *2.2. Participant*

A nine-year and eleven-month-old girl on 24 March 2020, who apparently was in a state of full wellbeing, fell to the ground and lost consciousness after feeling a severe headache while she was playing with her brother; then, she had generalized hypertonus, trismus and emission of noises for about 10 min with apparent resolution. When the ambulance arrived, the little girl had regained consciousness and was able to carry out simple orders with her 4 limbs. When she arrived in the Umberto I ER, her speech appeared fluid and there were no evident cranial nerve deficits. Later, the girl complained of headaches again, and she had a reduced ability to move on the right side, deviation of the buccal rim and dysarthria. She underwent brain MRI in urgency, which highlighted "ischemic acute lesion in the left Rolandic area". Her parents reported a history of mild and sporadic headache in the previous days. Transferred for competence to the ER of the Pediatric Hospital Bambino Gesù of Rome, the girl appeared alert, oriented and responsive to verbal stimulus. The right side was compromised, with deviation of the buccal rim and a deficit of tone and strength that was greater in the upper limb than in the lower limb; moreover, she had difficulty in trunk control in sitting positions and had no problems with dysphagia and desaturation. She started low molecular weight heparin, as per the hematological prescription and according to Pediatric Stroke Guidelines [8]. As soon as possible, the child was transferred to the Department of Neurology of the same hospital to complete the investigations planned for this case. During neurological hospitalization, the girl underwent another brain MRI, which confirmed recent ischemic lesions. In particular, they were in the territory of the left Middle Cerebral Artery (MCA) with greater extension compared to the first MRI examination, associated with a reduction in the left Internal Carotid Artery (ICA) caliber and left M1 and Al flow profile irregularities (left MCA and Anterior Cerebral Artery—ACA—arteritis). The baby was subjected to ultrasound of the neck vessels, evaluation and cardiological examinations, immuno-infectious examinations, thrombophilia screening, trace oligoclonal bands and platelet aggregation tests. In consideration of the exclusion of secondary causes and of vasculitis alterations in other parts of the body, the diagnostic suspicion of primary CNS angiitis was conducted, for which, to complete the diagnosis, and further in-depth examinations were carried out according to the national protocol for primary vasculitis [8]. By 27 March 2020 to 4 April 2020, the child had also started treatment with intravenous cortisone. In a short period of time, the child showed an improvement in clinical conditions, in particular in dysarthria and in the ability to make minimal movements with the right lower limbs. Upon discharge from neurology, she was prescribed aspirin, heparin suspension and cortisone scaling. On 4 April 2020, the child was transferred to the Pediatric Neurorehabilitation Department of the same hospital located in Palidoro (near Rome) to begin an intensive neuro-motor rehabilitative treatment. She was admitted to Bambino Gesù Rehab Department from 4 April 2020 to 12 June 2020.

Therefore, after 15 days from the stroke onset, she began intensive rehabilitation treatment consisting of 5 sessions/week of neuro-motor therapy, 2 sessions/week of speech therapy and 1 session/week of occupational therapy. In addition to conventional motor treatments, she performed robotic motor training for the upper limb (Mit Manus). The proposals were recognition activities of different textures, heights and shapes to stimulate the sensitivity of the right upper limb, activate the intrinsic muscles of the hand, and to improve the pronation–supination of the forearm and coordination of the two upper limbs in simple gestures of daily life. At the last MRI examinations on 10 April and 19 May 2020, respectively, there was a reduction in the known ischemic lesions in the left hemisphere and a reduction in the size of ICA, the M1/M2 sections of the MCA and the A1 section of the ACA. Upon discharge, the condition of the child improved overall, reached a moderate static and dynamic control of the trunk and started ambulatory training with the help of an ankle-foot orthosis, but right hemiparesis and dysarthria persisted.

Followed a period of non-in-patient rehabilitation at the Fondazione Santa Lucia in Rome, there she performed a neuro-motor rehabilitative treatment of 180 days, 4 times a week, including speech therapy and occupational therapy as well.

After 180 days of treatment and with respect for the recovery of the right upper limb, the girl was able to perform movements against gravity flexo-extension and abduction– adduction of the shoulder with extended elbow and spinal compensation. In addition, she was able to perform movements against gravity elbow flexo-extension, while hinting at muscle recruitment at the level of the wrist and hand extensor muscles and first finger opponent. However, the girl was able to find strategies to solve practical problems of daily life and involving the right upper limb in base activities.

In January 2021, the child began, in association with the conventional treatment and in progress at the Fondazione Santa Lucia, a treatment with the Gloreha robotic glove for the right upper limb at the Campus Bio-Medico University. The objective of the robotic treatment was to recover the movements of extension of the fingers and wrist and improve hand-wrist bending and manual dexterity movements. The use of Gloreha aimed also at recovering the sensory skills of the hand, improving its muscle tone and functionality. Moreover, the use of non-immersive virtual reality through interactive video games had the objective of stimulating cognitive abilities, such as attention, visual-spatial analysis, working memory and executive functions as well.
