Effects of levodopa/carbidopa intestinal gel versus oral levodopa/carbidopa on B vitamin levels and neuropathy

Abstract

ObjectivesTo determine the possible interactions between levodopa therapy and plasma levels of B vitamins in patients with advanced idiopathic Parkinson's disease (IPD) in the context of either oral levodopa therapy or levodopa/carbidopa intestinal gel (LCIG). Secondly, to determine the prevalence of neuropathy and its relation to plasma levels of B vitamins and homocysteine.MethodsMedication doses, neurographies, and serum levels of pyridoxine, cobalamin, folate, and homocysteine of eight LCIG and 13 orally treated advanced IPD patients matched for age, Hoehn & Yahr stage, and UPRDS III were collected. This data was analyzed for correlation with daily levodopa dose (LDD).Results LICG patients had a longer disease duration and higher LDD. All LCIG patients and most orally treated patients had sensorimotor axonal polyneuropathy. Of all plasma vitamin levels, pyridoxine was decreased most and significantly lower in the LCIG group. Cobalamin and folate, however, were within the lower reference range, and homocysteine highly elevated, all without any significant difference between both groups. LDD correlated significantly with pyridoxine deficiency (p = .02) irrespective of the route of application and with hyperhomocysteinemia in the LCIG group (p = .03). At LDDs above 2,000 mg, pyridoxine deficiency was almost always detectable.ConclusionsPyridoxine deficiency and hyperhomocysteinemia are dependent on the daily levodopa/carbidopa dose, while levels of cobalamin and folate are not. The mode of application of levodopa/carbidopa has no impact on B‐vitamin levels. Neuropathy is very frequent in advanced IPD; however, it remains to be investigated further whether neuropathy is more frequent in LCIG than in orally levodopa/carbidopa‐treated advanced IPD patients.

Levodopa‐Induced Neuropathy: A Systematic Review

“…The association between PNP and oral l ‐dopa was evaluated in 19 studies, , including a total of 1,137 patients. A total of 353 PNPs were described, with a large predominance of slowly progressive axonal neuropathy selectively involving the sensory fibers.…”

“…The association between PNP and l ‐dopa dosage was evaluated in 16 studies: 12 found an association between PNP and higher doses of l ‐dopa, whereas four showed negative results . Three studies did not provide any measures of association between PNP and l ‐dopa dosage …”

“…In 2008, Toth and colleagues described, for the first time, an unexpectedly high prevalence of peripheral neuropathy (PNP) in patients with Parkinson's disease (PD) . Since then, several studies confirmed a pathological association between PNP, PD, and dopamine‐replacement therapies, estimating that up to 55% of patients treated with oral levodopa, and 75% of those treated with l ‐dopa/carbidopa intestinal gel (LCIG) infusion, may develop clinical or subclinical signs of PNP during the course of the disease …”

Nutritional neuropathies

“…Metabolism of levodopa consumes pyridoxine, folate, and cobalamin. Some studies have provided evidence supporting that levodopa neuropathy is dose‐dependent, with higher doses causing more severe axonal loss and widespread damage . With doses of levodopa 2000 mg per day or higher, nearly all patients develop pyridoxine deficiency regardless of the route of administration .…”

The impact of associated large-fiber peripheral neuropathy on health-related quality of life in Parkinson’s disease – results from a Romanian cohort

“…New data have found a higher prevalence of polyneuropathy in PD patients than in age-matched controls (4)(5)(6)(7). Peripheral nerve fiber impairment in PD can take the form of large fiber neuropathy (PN) in L-Dopa treated patients (5)(6)(7)(8)(9)(10)(11)(12) or small fiber neuropathy (SFN) in all PD patients (13)(14)(15). A se-ries of data consider PN to be secondary to L-Dopa intake that determines the accumulation of homocysteine and methylmalonic acid, and cyanocobalamin, pyridoxine or folate plasma deficits (4,(6)(7)(8)11,(16)(17)(18).…”