Large-Fiber Neuropathy in Parkinson’s Disease: Clinical, Biological, and Electroneurographic Assessment of a Romanian Cohort

Abstract

(1) Background: Increased attention has lately been given to polyneuropathy in Parkinson’s Disease (PD). Several papers postulated that large-fiber neuropathy (PNP) in PD is related to vitamin B12 deficiency and L-Dopa exposure. (2) Methods: Using a cross-sectional, observational study, we evaluated 73 PD patients without a previously known cause of PNP using clinical scores (UPDRS II and III and Toronto Clinical Scoring System), biological evaluation of vitamin B12 and folic acid, and nerve conduction studies to assess the prevalence and features of PNP. (3) Results: The prevalence of PNP was 49.3% in the study group. In the L-Dopa group, the frequency of PNP was 67.3% as compared to PNP in the non-L-Dopa group, where one subject had PNP (χ2 = 23.41, p < 0.01). PNP was predominantly sensory with mild to moderate axonal loss. Cyanocobalamin correlated with L-Dopa daily dose (r = −0.287, p < 0.05) and L-Dopa duration of administration (r = −0.316, p < 0.05). L-Dopa daily dose correlated with the amplitudes of sensory nerve action potentials of the superficial peroneal and radial nerves (r = −0.312, p < 0.05) (r = −0.336, p < 0.05), respectively. (4) Conclusions: PNP is more frequent in L-Dopa-treated patients than in L-Dopa-naïve patients. The results imply that longer exposure to high doses of L-Dopa may cause vitamin B12 and folate imbalance and PNP, secondarily.

Parkinson’s disease with restless legs syndrome—an in vivo corneal confocal microscopy study

“…These results are in contrast to previous studies, where an increased prevalence of large fiber neuropathy in PD has been reported, when evaluated with both NCS and clinical rating scales 16,23,24 . In those studies, neuropathy was suggested to be associated with alterations in the vitamin B12-dependent methionine cycle, mediated by chronic exposure to L-dopa and thus associated with elevated levels of p-homocysteine and s-MMA 16,23,24 . In the present study, 60% of the PD patients were taking vitamin B12 or multivitamin supplements, and the median levels of p-homocysteine and s-MMA were within normal range.…”

Parkinson’s disease with restless legs syndrome—an in vivo corneal confocal microscopy study

“…These results are in contrast to previous studies, where an increased prevalence of large fiber neuropathy in PD has been reported, when evaluated with both NCS and clinical rating scales 16,23,24 . In those studies, neuropathy was suggested to be associated with alterations in the vitamin B12-dependent methionine cycle, mediated by chronic exposure to L-dopa and thus associated with elevated levels of p-homocysteine and s-MMA 16,23,24 . In the present study, 60% of the PD patients were taking vitamin B12 or multivitamin supplements, and the median levels of p-homocysteine and s-MMA were within normal range.…”

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

“…Patients in the PN group were older, in more advanced stages, with longer PD duration and scored higher in the UPDRS scale, than those in the non-PN group. PN in this cohort was previously shown to be related to L-Dopa intake; possible causes and relations of PN to PD in this cohort were previously discussed and PN was linked to vitamin B12 and folate deficiencies and high daily doses of L-Dopa (46). Nevertheless, PN in PD seems to be more common in advanced stages of PD and linked to higher doses of L-Dopa and might represent a more severe phenotype of PD (49).…”

“…Seventy-three PD patients (49.3% females, mean age 65.44 (9.87)) from the previous study were included (46). Two patients scored below 24 points on MMse but due to motor impairment and 10 patients received medication for anxiety or depression.…”

Parkinson-related neuropathy

“…PDRNP may also be caused by long-term usage of L-DOPA. L-DOPA may not only cause vitamin-B12 deficiency (L-DOPA induced vitamin-B12 deficiency), but also folate deficiency (10). The notion that L-DOPA causes vitamin-B12 or folate deficiency, and thus secondary PDRNP, has been challenged by findings from third world countries showing that low vitamin-B12 and folate levels do not play a significant role in the development of PDRNP (11).…”

Parkinson’s disease with restless legs syndrome—an in vivo corneal confocal microscopy study

“…These results are in contrast to previous studies, where an increased prevalence of large fiber neuropathy in PD has been reported, when evaluated with both NCS and clinical rating scales 16,23,24 . In those studies, neuropathy was suggested to be associated with alterations in the vitamin B12-dependent methionine cycle, mediated by chronic exposure to L-dopa and thus associated with elevated levels of p-homocysteine and s-MMA 16,23,24 . In the present study, 60% of the PD patients were taking vitamin B12 or multivitamin supplements, and the median levels of p-homocysteine and s-MMA were within normal range.…”

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

“…Patients in the PN group were older, in more advanced stages, with longer PD duration and scored higher in the UPDRS scale, than those in the non-PN group. PN in this cohort was previously shown to be related to L-Dopa intake; possible causes and relations of PN to PD in this cohort were previously discussed and PN was linked to vitamin B12 and folate deficiencies and high daily doses of L-Dopa (46). Nevertheless, PN in PD seems to be more common in advanced stages of PD and linked to higher doses of L-Dopa and might represent a more severe phenotype of PD (49).…”

“…Seventy-three PD patients (49.3% females, mean age 65.44 (9.87)) from the previous study were included (46). Two patients scored below 24 points on MMse but due to motor impairment and 10 patients received medication for anxiety or depression.…”

Parkinson-related neuropathy

“…PDRNP may also be caused by long-term usage of L-DOPA. L-DOPA may not only cause vitamin-B12 deficiency (L-DOPA induced vitamin-B12 deficiency), but also folate deficiency (10). The notion that L-DOPA causes vitamin-B12 or folate deficiency, and thus secondary PDRNP, has been challenged by findings from third world countries showing that low vitamin-B12 and folate levels do not play a significant role in the development of PDRNP (11).…”

Parkinson’s disease with restless legs syndrome—an in vivo corneal confocal microscopy study

“…These results are in contrast to previous studies, where an increased prevalence of large fiber neuropathy in PD has been reported, when evaluated with both NCS and clinical rating scales 16,23,24 . In those studies, neuropathy was suggested to be associated with alterations in the vitamin B12-dependent methionine cycle, mediated by chronic exposure to L-dopa and thus associated with elevated levels of p-homocysteine and s-MMA 16,23,24 . In the present study, 60% of the PD patients were taking vitamin B12 or multivitamin supplements, and the median levels of p-homocysteine and s-MMA were within normal range.…”

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

“…Patients in the PN group were older, in more advanced stages, with longer PD duration and scored higher in the UPDRS scale, than those in the non-PN group. PN in this cohort was previously shown to be related to L-Dopa intake; possible causes and relations of PN to PD in this cohort were previously discussed and PN was linked to vitamin B12 and folate deficiencies and high daily doses of L-Dopa (46). Nevertheless, PN in PD seems to be more common in advanced stages of PD and linked to higher doses of L-Dopa and might represent a more severe phenotype of PD (49).…”

“…Seventy-three PD patients (49.3% females, mean age 65.44 (9.87)) from the previous study were included (46). Two patients scored below 24 points on MMse but due to motor impairment and 10 patients received medication for anxiety or depression.…”

Parkinson-related neuropathy

“…PDRNP may also be caused by long-term usage of L-DOPA. L-DOPA may not only cause vitamin-B12 deficiency (L-DOPA induced vitamin-B12 deficiency), but also folate deficiency (10). The notion that L-DOPA causes vitamin-B12 or folate deficiency, and thus secondary PDRNP, has been challenged by findings from third world countries showing that low vitamin-B12 and folate levels do not play a significant role in the development of PDRNP (11).…”