Vitamins and Infusion of Levodopa-Carbidopa Intestinal Gel.

Levodopa-carbidopa intestinal gel infusion (LCIG) is an established therapy for advanced Parkinson disease (PD), resulting in a significant improvement of quality of life. With increased LCIG adoption worldwide, potential complications due to abnormal vitamin absorption or metabolism have been reported in these patients. Neurologists are unfamiliar with vitamins physiology and pathophysiological mechanisms in case of their deficiency. Unfortunately, clinical and laboratory guidelines related to vitamin monitoring and supplementation in the context of treatment with LCIG are not available. We herein summarize the current knowledge on three vitamins that are reduced with LCIG therapy reporting on their physiology, laboratory testing, and clinical impact of their deficiency/excess. In addition, we proposed an opinion-based recommendation for clinicians treating LCIG patients. Patients and caregivers should be informed about the risk of vitamin deficiency. Vitamin B12, homocysteine, and methylmalonic acid (MMA) should be tested before starting LCIG, six months after and once/year thereafter. Vitamin B6 and folate testing is not universally available but it should be considered if homocysteine is elevated but MMA and/or total vitamin B12 are normal. Prophylaxis of vitamin deficiency should be started as soon as LCIG is implemented, possibly even before. Dietary recommendations are enough in most patients although a subgroup of patients is at higher risk and should receive Vitamin B12 regularly and cycles of B6. Finally, once diagnosed a vitamin deficiency should be readily treated and accompanied by clinical and laboratory monitoring. Resistant cases should receive non-oral routes of administration and possibly discontinue LCIG, even temporarily.

Levodopa-Induced Neuropathy: A Systematic Review.

BACKGROUND: Clinical, neurophysiological, and pathological evidence suggest an association between Parkinson's disease (PD) and peripheral neuropathy (PNP), with a possible causative role of levodopa metabolic products, such as homocysteine and methylmalonic acid. METHODS: We conducted a systematic review of studies reporting cases of PNP in l-dopa-treated PD patients indexed in PubMed between January 1990 and March 2018. RESULTS: We identified 38 articles reporting cases of PNP in PD patients treated with oral l-dopa or with l-dopa/carbidopa intestinal gel infusion (LCIG). Prevalence of PNP was 30.2% in the former group and 42.1% in the latter. Oral l-dopa was mostly associated with slowly progressive PNP, whereas LCIG showed an acute or subacute onset in 35.7% of cases. In both groups, there was an association between PNP and higher l-dopa doses, as well as with the following biochemical alterations: increased homocysteine; reduced vitamin B12; increased methylmalonic acid; and reduced vitamin B6. A skin biopsy was performed in 181 patients, showing signs of small fibers neuropathy in 169 (93.4%). Positive, yet preliminary, results were observed in patients receiving periodic vitamin supplementation. CONCLUSIONS: Over one third of PD patients in treatment with l-dopa may develop PNP, with a significantly higher prevalence of acute and subacute forms in those receiving LCIG. Pathogenic mechanisms remain unclear, but possibly related to a complex interplay between peripheral neurodegenerative processes and l-dopa neurotoxic metabolites. Prospective, randomized, clinical trials are required to identify factors associated with the onset and progression of PD-associated PNP and clarify the protective role of B-group vitamin supplementation.

Telemedicine in Neurological Disorders: Opportunities and Challenges.

Introduction: Telemedicine represents an emerging model for the assessment and management of various neurological disorders. Methods: We sought to discuss opportunities and challenges for the integration of telemedicine in the management of common and uncommon neurological disorders by reviewing and appraising studies that evaluate telemedicine as a means to facilitate the access to care, deliver highly specialized visits, diagnostic consultations, rehabilitation, and remote monitoring of neurological disorders. Results: Opportunities for telemedicine in neurological disorders include the replacement of or complement to in-office evaluations, decreased time between follow-up visits, reduction in disparities in access to healthcare, and promotion of education and training through interactions between primary care physicians and tertiary referral centers. Critical challenges include the integration of the systems for data monitoring with an easy-to-use, secure, and cost-effective platform that is both widely adopted by patients and healthcare systems and embraced by international scientific societies. Conclusions: Multiple applications may spawn from a model based on digitalized healthcare services. Integrated efforts from multiple stakeholders will be required to develop an interoperable software platform capable of providing not only a holistic approach to care but also one that reduces disparities in the access to care.

Advanced therapies in Parkinson's disease: Long-term retrospective study.

BACKGROUND: Levodopa/carbidopa intestinal gel infusion (LCIG) and subthalamic nucleus deep brain stimulation (STN-DBS) are approved therapies for advanced Parkinson's disease (PD) whose long-term comparability remains unclear. METHODS: We reviewed the 5-year data on activities of daily living (ADL) and motor complications (OFF time, dyskinesia duration, and dyskinesia severity), as measured by the Unified Parkinson Disease Rating Scale (UPDRS) section-II and section-IV (items 39, 32, and 33, respectively) in 60 PD patients exposed to STN-DBS (n = 20), LCIG (n = 20), and oral medical therapy (OMT) (n = 20) at similar baseline disability and cognitive state. RESULTS: STN-DBS and LCIG showed a similar magnitude of deterioration in ADL (+6.1 vs. +5.7 UPDRS-II; p = 0.709), but lesser than with OMT (+13.7 UPDRS-II; p = 0.005). OFF time also improved to the same extent in STN-DBS and LCIG (-62% vs. -54.5%; p = 0.830), while worsened with OMT (+78.6%; p < 0.001). STN-DBS and LCIG yielded greater improvement on dyskinesia compared to OMT (dyskinesia duration: -66.1% vs. -9.0% vs. +24.2% [p = 0.001]; dyskinesia severity: -68.8% vs. -18.0% vs. +16.2% [p = 0.002]), with relative superiority of STN-DBS over LCIG (p = 0.004 for duration; p = 0.014 for severity). The annualized rate of complication was lower in STN-DBS vs. LCIG (0.13 vs. 0.68; p < 0.001) but not different between STN-DBS and OMT (0.13 vs. 0.10; p = 0.795). CONCLUSIONS: STN-DBS and LCIG showed comparable efficacy in ADL and OFF time, superior to OMT. STN-DBS yielded greater improvement in dyskinesia and lower long-term rate of complications than LCIG.