The cognitive profile of type 1 Gaucher disease patients

BACKGROUND: The absence of neurological symptoms and signs is traditionally considered mandatory for a diagnosis of type 1 Gaucher disease (GD1), but in recent years many reports have emerged on neurological manifestations in GD1 patients. Nevertheless, it has been unclear whether cognitive deficits are part of the disease as well. METHODS: Cognitive function was assessed in a large cohort of GD1 patients with the use of the CDR system, a set of computerised cognitive tests. Testing was performed at baseline and every 6 months thereafter during a two-year study period. RESULTS: Our patient cohort (84 patients, median age 40 years, median time from diagnosis 15 years) showed mild deficits relative to healthy age-matched subjects on the composite scores: power of attention (Z-score (mean ± SD) -0.9 ± 1.37) and speed of memory (Z-score (mean ± SD) -1.39 ± 1.49). No decline in cognitive function was seen during the two-year period. Age correlated with the composite scores variability of attention and quality of working memory. Moreover, severely affected patients (Zimran severity score (SSI) ≥ 15) scored more poorly compared to mildly affected patients (SSI ≤ 5) on the composite measure power of attention, reflecting the ability to concentrate. CONCLUSIONS: GD1 patients exhibit mild deficits in power of attention and speed of memory, reflecting a decreased ability to focus attention and process information, together with a slowing in the speed of retrieval of items from memory. The clinical relevance of these findings is uncertain

Peripheral neuropathy in adult type 1 Gaucher disease: a 2-year prospective observational study

Type 1 Gaucher disease is currently categorized as non-neuronopathic, although recent studies suggest peripheral neurological manifestations. We report prevalence and incidence data for peripheral neuropathy and associated conditions from a multinational, prospective, longitudinal, observational cohort study in patients with type 1 Gaucher disease, either untreated or receiving enzyme replacement therapy. The primary outcome parameters were the prevalence and incidence of polyneuropathy, evaluated by standardized assessments of neurological symptoms and signs, and electrophysiological studies. All diagnoses of polyneuropathy were adjudicated centrally. Secondary outcome parameters included the prevalence and incidence of mononeuropathy, other neurological or electrophysiological abnormalities not fulfilling the criteria for a mono- or polyneuropathy and general type 1 Gaucher disease symptoms. Furthermore, a literature search was performed to identify all studies reporting on prevalence and incidence of polyneuropathy in the general population. One hundred and three patients were enrolled [median (range) age: 42 (18-75) years; disease duration: 15 (0-56) years; 52% female]; 14 (13.6%) were untreated and 89 (86.4%) were on enzyme replacement therapy. At baseline, 11 patients [10.7%; 95% confidence interval (CI): 5.9-18.3] were diagnosed with sensory motor axonal polyneuropathy. Two (1.9%; 95% CI: 0.1-7.2) had a mononeuropathy of the ulnar nerve. The 2-year follow-up period revealed another six cases of polyneuropathy (2.9 per 100 person-years; 95% CI: 1.2-6.3). Patients with polyneuropathy were older than those without (P <0.001). Conditions possibly associated with polyneuropathy were identified in four patients only, being monoclonal gammopathy, vitamin B-1 deficiency, folic acid deficiency, type 2 diabetes mellitus, renal insufficiency, alcohol abuse and exposure to toxins related to profession. The 11 cases of polyneuropathy found at baseline were confirmed during follow-up. According to the literature, the prevalence of polyneuropathy in the general population was estimated between 0.09 and 1.3% and the incidence was estimated between 0.0046 and 0.015 per 100 person-years. Thus, we conclude that the prevalence and incidence of polyneuropathy in patients with type 1 Gaucher disease is increased compared with the general populatio