Levodopa-carbidopa intestinal gel (LCIG) treatment in routine care of patients with advanced Parkinson's disease: An open-label prospective observational study of effectiveness, tolerability and healthcare costs.

BACKGROUND: Continuous infusion of levodopa-carbidopa intestinal gel (LCIG) can effectively manage motor and non-motor complications in advanced Parkinson's disease (PD). Healthcare costs, quality of life (QoL), effectiveness, and tolerability were assessed in routine care treatment with LCIG. METHODS: The seventy-seven patients enrolled in this prospective, open-label, 3-year study in routine medical care were LCIG-naïve (N = 37), or had previous LCIG treatment for <2 (N = 22), or ≥2 (N = 18) years. Healthcare costs were collected monthly. PD symptoms and QoL were assessed with the Unified Parkinson's Disease Rating Scale (UPDRS), 39-item Parkinson's Disease Questionnaire (PDQ-39), and EuroQoL 5-Dimension Visual Analog Scale (EQ-5D VAS); LCIG dose, safety, and tolerability were monitored. RESULTS: Mean monthly costs per patient (€8226 ± 5952) were similar across cohorts, remained steady during 3-year follow-up, and increased with PD severity and QoL impairment. In LCIG-naïve patients, significant improvements compared to baseline were observed on the UPDRS total score and PDQ-39 summary index score through 18 months (n = 24; UPDRS, p = 0.033; PDQ-39, p = 0.049). Symptom control was maintained during 3-year follow-up in LCIG-experienced cohorts. Small changes in mean daily LCIG dose were observed. Adverse events were common and generally related to the device, procedure, levodopa, or laboratory evaluations. CONCLUSIONS: Costs in LCIG-treated patients were stable over 3 years. LCIG treatment led to significant improvements in motor function and QoL over 18 months in LCIG-naïve patients and no worsening was observed in LCIG-experienced patients over 3 years despite natural PD progression over time. The long-term safety was consistent with the established LCIG profile.

A comparison of gray matter density in restless legs syndrome patients and matched controls using voxel-based morphometry.

BACKGROUND: Restless legs syndrome (RLS) is a common neurological disorder the pathophysiology of which is incompletely understood. Four studies have examined structural differences between the brains of RLS patients and healthy controls, using voxel-based morphometry (VBM). All 4 studies have provided different results. METHODS: Optimized VBM was used to search for structural differences in gray matter density. Sixteen RLS patients naïve to dopaminergic drugs and 16 age- and sex-matched controls received structural T1-weighted MR scans. Structural data were analyzed using FSL-VBM. RESULTS: No difference in gray matter density was detected between the two groups (voxel-wise significance: no significant voxels at P= .89 (whole brain Family Wise Error (FWE) corrected); no significant voxels at P < .05 (whole brain False Discovery Rate (FDR) corrected; smallest achievable FDR threshold .99). CONCLUSION/DISCUSSION: The present study did not replicate (confirm) previous findings of structural brain changes in RLS, but instead supported the findings of a recent study showing a lack of gray matter alteration in an elderly RLS population. More specifically, the results do not support neuronal loss as an underlying disease mechanism in RLS. Potential limitations in the application of VBM are also discussed.

HMPAO SPECT in Parkinson's disease (PD) with major depression (MD) before and after antidepressant treatment.

Previously we suggested that major depression (MD) in Parkinson's disease (PD) could be an indication of a more advanced and widespread neurodegenerative process, as PD symptoms were more severe in those with depression. We also found a different antidepressant response with SSRI medication in PD patients with depression compared to depressed patients without PD. This indicates diverse underlying pathophysiological mechanisms. Investigations using single-photon emission computed tomography (SPECT), measuring regional cerebral blood flow (rCBF), may contribute to enlighten the neurobiological substrates linked to depressive symptoms. SPECT was performed in order to compare rCBF in MD patients with and without PD. The study included 11 MD patients with PD, 14 non-depressed PD patients and 12 MD patients without PD. All patients were followed for 12 weeks with repeated evaluation of depressive as well as PD symptoms. Anti-Parkinsonian treatment remained unchanged during the study. Antidepressant treatment with SSRI (citalopram) was given to all patients with MD. SPECT was performed before and after 12 weeks of antidepressant treatment. rCBF was found to differ between PD patients with and without MD, as well as between MD patients with and without PD, both at baseline and concerning the response to treatment with SSRI (citalopram). In patients with PD the rCBF was found to be decreased in preoccipital and occipital regions, a finding more common when PD was combined with MD. In summary, larger cortical areas were found to be involved in depressed PD patients, both with hyperactivity (reciprocal to basal degeneration in PD and maybe dopaminergic treatment) and with hypoactivity (probably due to organic lesions leading to hypoperfusion). These observations support our hypothesis that PD combined with MD is an expression of a more advanced and widespread neurodegenerative disorder.

Support for dopaminergic hypoactivity in restless legs syndrome: a PET study on D2-receptor binding.

Clinical observations support a central role of the dopamine system in restless legs syndrome (RLS) but previous imaging studies of striatal dopamine D2-receptors have yielded inconclusive results. Extrastriatal dopaminergic function has hitherto not been investigated. Sixteen RLS patients naïve to dopaminergic drugs and sixteen matched control subjects were examined with PET. [11C]Raclopride and [11C]FLB 457 were used to estimate D2-receptor availability in striatum and extrastriatal regions, respectively. Examinations were performed both in the morning (starting between 10:00 and 12:00 h) and evening (starting at 18:00 h). Measures were taken to monitor and control for head movement during data acquisition. In the striatum, patients had significantly higher [11C]raclopride binding potential (BP) values than controls. In extrastriatal regions, [11C]FLB 457 BP was higher in patients than controls, and in the regional analysis the difference was statistically significant in subregions of thalamus and the anterior cingulate cortex. The diurnal variability in BP with [11C]FLB 457 and [11C]raclopride was within the previously reported test-retest reproducibility for both radioligands. The study supports involvement of the dopamine system in both striatal and extrastriatal brain regions in the pathophysiology of RLS. The brain regions where differences in D2-receptor binding were shown are implicated in the regulation of affective and motivational aspects of sensory processing, suggesting a possible pathway for sensory symptoms in RLS. Increased D2-receptor availability in RLS may correspond to higher receptor densities or lower levels of endogenous dopamine. Both interpretations are consistent with the hypothesis of hypoactive dopaminergic neurotransmission in RLS, as increased receptor levels can be owing to receptor upregulation in response to low levels of endogenous dopamine. The results do not support variations in dopamine D2-receptor availability as a correlate to the diurnal rhythm of RLS symptoms.