Multidisciplinary Study Based on Clinical, Electrophysiological and Psycological Evaluations Combined with Advanced Neuroimaging in Gaucher Disease Patients

Gaucher Disease (GD) is an autosomal recessive metabolic disorder due to glucocerebrosidase deficit. There are three main clinical phenotypes: type I (GD1: non-neuronopathic form), characterized by a visceral involvement that can mimic a hematologic disease; type II (GD2: acute neuropathic form) and type III (GD3) characterized by a slower and progressive neurological involvement. Hematologists have often involved in diagnosis and management of the GD1 patients. Increasing data and our experience show that patients with GD1 may present manifestations of Parkinson's disease or Parkinsonism symptoms (tremor, bradykinesia and rigidity), frequently combined with cognitive impairment and behavioral alterations. The aim of this study is to deeply investigate the neurological and neuropsychiatric aspects in GD1 patients in order to identify clinical and subclinical neurological manifestations, including cognitive impairment and behavioral alterations in this category of patients. This observational, monocentric, and prospective study is planned to enroll 22 GD patients (19 GD1 patients and 3 GD3 patients with or without active neurological signs) aged >12 years. Neurological assessments include: clinical evaluation including Severity Scoring Tool Unified Parkinson's Disease Rating scale and Epworth Sleepiness scale, psycho-diagnostic tests and psychiatric evaluation using cognitive test battery and two psychiatric (BPRS) and psychological (CBA 2.0) questionnaires, Somatosensory and Motors Evoked Potentials, Electroencephalography (EEG) and magnetic resonance (MR) 3Tesla, at baseline, after 12 months and 24 months. Preliminary results concerning the baseline evaluation of first cohort of patients are here reported. Since June 2019, 11 patients (10 GD1 and 1 symptomatic GD3) have been enrolled. Neurological impairment according to the major features (Gaucher severity score tool) was found in 4/11 patients: signs of Parkinson disease in 1 GD1 patient, motoneuron disease in 1 GD3 patients, abnormalities in ocular motility and psycho-cognitive disturbances in 2 GD1 patients. Minor features of a neurological impairment was found as follows: bradykinesia in 5 GD1 patients, excessive daytime sleepiness in 5 GD1 patients, and saccadic slowness in 1 GD1 patient. EEG revealed focal or diffuse slow waves in 6 patien patients (5 GD1 and 1 GD3). Cognitive and psychological evaluations revealed the presence of significant psychiatric symptoms such as depression, anxiety, and ph