Levodopa-carbidopa intestinal gel infusion (LCIG) in Parkinson disease with genetic mutations.

BACKGROUND: Levodopa-carbidopa intestinal gel infusion (LCIG) is a therapeutic option for advanced Parkinson disease (PD) patients with troublesome motor complications, unresponsive to conventional oral treatment. There is some evidence to suggest that the genetic background may influence the clinical presentation and rate of progression of PD. Whether the genetic background influences the outcome of device-assisted therapies is currently debated. Some studies have investigated the effectiveness of deep brain stimulation (DBS) in PD patients with different genetic background, while evidence is lacking regarding LCIG. METHODS: A cohort of LCIG patients underwent genetic testing. The motor and neuropsychological outcomes of LCIG were retrospectively analyzed. RESULTS: Fifty-six patients were analyzed, nine of them (15%) had at least one mutation/variant in a PD-associated gene: five GBA1, two SNCA, one LRRK2, one PRKN; 13 (23%) carried the BDNF Val66Met polymorphism. The mean duration of follow-up was 4.9 ± 2.6 years. There were no significant differences in motor or neuropsychological outcomes between patients with and without these gene mutations/variants. No cognitive worsening was observed at follow-up among GBA-PD patients, and they responded well to LCIG in terms of motor symptoms. CONCLUSIONS: Overall, we observed a significant benefit in terms of motor complications in our cohort, including patients carrying genetic mutations/variants. Due to the small sample and limited number of patients carrying genetic mutations/variants, no definitive conclusions can be drawn yet on the genotype impact on LCIG outcome. A careful selection of patients, regardless of the genetic background, is pivotal for an optimal outcome of LCIG.

Levodopa/carbidopa intestinal gel infusion and weight loss in Parkinson's disease.

BACKGROUND AND PURPOSE: Weight loss (WL) is a frequent yet under-recognized complication of levodopa/carbidopa intestinal gel (LCIG) infusion, as well as a milestone of Parkinson's disease (PD) disability progression. The complex association between WL, poor nutritional status, motor complications and PD progression, however, remains unclear. METHODS: Consecutive consenting patients with PD treated with LCIG (n = 44; PD duration, 18.3 ± 6.5 years) were enrolled in an open-label observational study assessing the extent of WL occurring during LCIG treatment. As secondary aims, we correlated the nutritional status, as detected by the Mini Nutritional Assessment, with the severity of motor symptoms [Movement Disorder Society Unified Parkinson's Disease Rating Scale part III], motor complications (Unified Parkinson's Disease Rating Scale part IV), activities of daily living (Schwab and England scale), cognitive impairment (Mini Mental State Examination), depression (Beck Depression Inventory), difficulties in feeding (Edinburgh Feeding Evaluation in Dementia Questionnaire) and levodopa equivalent daily dose (LEDD). RESULTS: There was an average WL of 9.9 ± 10.5% (7.6 ± 7.1 kg) over an LCIG treatment period of 51.6 ± 28.5 months. The extent of WL correlated with the percentage of the waking day spent with dyskinesia (P < 0.05). The nutritional status correlated with motor symptom severity (P < 0.01), dysphagia (P < 0.01) and LEDD (P < 0.01). CONCLUSIONS: Weight loss may occur in patients with PD undergoing LCIG in correlation with the percentage of the waking day spent with dyskinesia. Regardless of the extent of WL, the nutritional status correlated with higher LEDD, as well as with indices of disease progression, such as motor symptom severity and dysphagia.

Subthalamic deep brain stimulation and trunk posture in Parkinson's disease.

OBJECTIVES: We sought to assess the efficacy of subthalamic nucleus deep brain stimulation (STN-DBS) in Parkinson's disease (PD)-associated trunk posture abnormalities retrospectively analyzing data from 101 patients reporting mild-to-severe trunk posture abnormalities of a cohort of 216 PD patients treated with STN-DBS at our center. METHODS: Abnormal trunk posture was rated on a scale of 0 (normal) to 4 (marked flexion with an extreme abnormality of posture) as per the grading score reported in the Unified Parkinson's Disease Rating Scale. The independent effect of STN-DBS on trunk posture was assessed comparing Medication-Off (presurgery) vs Stimulation-On/Medication-Off (post-surgery). The combined effect of STN-DBS plus levodopa was evaluated comparing Medication-On (presurgery) vs Stimulation-On/Medication-On (post-surgery). Analyses were conducted considering both the entire cohort of patients and the subgroup with camptocormia (CMC) and Pisa syndrome (PS). RESULTS: The independent effect of STN-DBS resulted in a 41.4% improvement in abnormal trunk posture severity (P < .001), with 78.2% of patients (n = 79) reporting an improvement of at least 1 point. The combined effect of STN-DBS and levodopa resulted in a 30.9% improvement (P = .061), with 54.5% of patients (n = 55) reporting an improvement of at least 1 point. The subanalysis of patients with CMC (n = 23) and PS (n = 5) showed a 42.7% improvement in abnormal posture severity when considering the independent effect of STN-DBS (P < .001) and 30.5% when considering the combined effect of STN-DBS and levodopa (P < .001). CONCLUSIONS: STN-DBS may have the potential for improving posture in patients with advanced PD.

Peripheral neuropathy associated with levodopa-carbidopa intestinal infusion: a long-term prospective assessment.

BACKGROUND AND PURPOSE: Subacute and chronic peripheral neuropathies (PNP) have been reported in Parkinson's disease (PD) patients treated with levodopa/carbidopa intestinal gel infusion (LCIG), although several aspects of their incidence and pathogenesis still remain to be clarified. This study main objective is to prospectively report the 2-year incidence of PNP in patients treated with LCIG. METHODS AND RESULTS: The clinical, hematological, nutritional and electrophysiological assessments of 33 consecutive patients have been prospectively collected and evaluated. At baseline (before the start of LCIG therapy), 3/33 (9%) patients showed symptomatic PNP and 7/33 (21%) subclinical PNP. During a follow-up of 24.36 ± 12.18 months, 2/23 patients with normal baseline clinical-electrophysiological assessment developed a subacute PNP, 2/23 developed a chronic PNP and 7/23 developed a subclinical PNP. LCIG was immediately halted in the subacute cases, while the infusion therapy was not interrupted in chronic and subclinical forms. All PNP were supplemented with vitamin B1 and B12, showing a clinical improvement and/or substantial stability at the following evaluations. Higher levodopa-equivalent daily dose (P: 0.024) and homocysteine levels (P: 0.041) were found in chronic PNP, while no correlations were observed with vitamin B12, folate and UPDRS values. A trend towards BMI reduction was observed in both PNP and unaffected subjects and one patient developed a symptomatic PNP associated with a relevant weight loss. CONCLUSIONS: Serial clinical-electrophysiological evaluations are mandatory in patients treated with LCIG, given the possible risk of subacute and chronic PNP. No clear causative factors has been recognized in the subacute forms, whilst homocysteine-mediated neurotoxicity seems to underlie the pathogenesis of chronic forms.

Machine learning applied to ambulatory blood pressure monitoring: a new tool to diagnose autonomic failure?

BACKGROUND: Autonomic failure (AF) complicates Parkinson's disease (PD) in one-third of cases, resulting in complex blood pressure (BP) abnormalities. While autonomic testing represents the diagnostic gold standard for AF, accessibility to this examination remains limited to a few tertiary referral centers. OBJECTIVE: The present study sought to investigate the accuracy of a machine learning algorithm applied to 24-h ambulatory BP monitoring (ABPM) as a tool to facilitate the diagnosis of AF in patients with PD. METHODS: Consecutive PD patients naïve to vasoactive medications underwent 24 h-ABPM and autonomic testing. The diagnostic accuracy of a Linear Discriminant Analysis (LDA) model exploiting ABPM parameters was compared to autonomic testing (as per a modified version of the Composite Autonomic Symptom Score not including the sudomotor score) in the diagnosis of AF. RESULTS: The study population consisted of n = 80 PD patients (33% female) with a mean age of 64 ± 10 years old and disease duration of 6.2 ± 4 years. The prevalence of AF at the autonomic testing was 36%. The LDA model showed 91.3% accuracy (98.0% specificity, 79.3% sensitivity) in predicting AF, significantly higher than any of the ABPM variables considered individually (hypotensive episodes = 82%; reverse dipping = 79%; awakening hypotension = 74%). CONCLUSION: LDA model based on 24-h ABPM parameters can effectively predict AF, allowing greater accessibility to an accurate and easy to administer test for AF. Potential applications range from systematic AF screening to monitoring and treating blood pressure dysregulation caused by PD and other neurodegenerative disorders.

Multiple sclerosis relapses: a multivariable analysis of residual disability determinants.

BACKGROUND: Recovery from multiple sclerosis (MS) relapses is variable. The factors influencing persistence of residual disability (RD) after a relapse are still to be thoroughly elucidated. AIMS OF STUDY: To assess RD after MS relapses and to define the factors associated with persistence of RD. METHODS: Data were retrospectively collected for all relapses in a population of relapsing-remitting MS patients during 3 years. Relapse severity and RD after 1 year were calculated on Expanded Disability Status Scale basis. A multivariable analysis for factors influencing RD and relapse severity was performed (variables: age, gender, disease duration, oligoclonal bands, relapse severity, monosymptomatic/polysymptomatic relapse, immunomodulating treatment, incomplete recovery at 1 month). RESULTS: A total of 174 relapses were assessed. RD after 1 year was observed in 54.5% of the relapses. Higher risk of RD was associated with occurrence of a severe relapse (P = 0.024). Incomplete recovery at 1 month was highly predictive of RD at 1 year (P < 0.0001). Risk of a severe relapse was associated with age

The carpal ligaments in MR arthrography of the wrist: correlation with standard MRI and wrist arthroscopy.

We assessed the value of three-compartment magnetic resonance (MR) wrist arthrography in comparison with non-enhanced magnetic resonance imaging (MRI) for the evaluation of 13 individual wrist ligaments in 35 patients with refractory wrist pain. In 20 of these patients MR findings were correlated with the findings from multiportal wrist arthroscopy. For MR imaging (1.5-T magnet) a three-dimensional volume acquisition with a gradient-recalled echo sequence and 0.6-1.0 mm effective slice thickness was used. The delineation of individual wrist ligaments was rated as "good" in 10% of non-enhanced MR and 90% of MR arthrography images. Ligament evaluation was possible with high diagnostic confidence in 11% by non-enhanced MR imaging and 90% by MR arthrography. With wrist arthroscopy as the standard of reference, average sensitivities/specificities/accuracies for the diagnosis of full-thickness ligamentous defects were 0.81/0.75/0.77 for non-enhanced MR imaging and 0.97/0.96/0.96 for MR arthrography. Our findings suggest that MR arthrography is more accurate than standard MRI in delineating and evaluating the ligaments of the wrist.