Perhexiline neuropathy: A clinicopathological study

Abstract

Five patients developed a mild to severe polyneuropathy while under treatment with perhexiline maleate, a drug used in long-term treatment of angina pectoris. Recovery took place within a few months after drug withdrawal. We performed qualitative and quantitative light and electron microscopical studies, including teased fiber preparations, in different patients; 16 to 90% of the fibers showed segmental demyelination, an unusual feature in drug-induced neuropathies, and 3 to 20% were undergoing wallerian degeneration. Severe loss of myelinated axons was noted in all 5 patients. In these patients clinical symptoms occurred only when a great number of fibers had already been lost and most of the surviving fibers showed demyelination.

Targeting NOX enzymes in the central nervous system: therapeutic opportunities

“…However, such an indication should, unfortunately, not be recommended for this compound because in many cases it induces drug-induced neuropathies [49,133]. NOX inhibitors are currently developed by both academic [18] and industrial laboratories, such as Shionogi or Mitsubishi, for which only patents have been published (for review, see [69,75], but, unfortunately, BBB penetration or efficacy in CNS indications has to our knowledge not been published.…”

Toward therapeutic targets for SCA3: Insight into the role of Machado–Joseph disease protein ataxin-3 in misfolded proteins clearance

“…No significant treatment effects are seen on the UHDRS or the ADAS-cog (Kieburtz et al, 2010) In patients with mild to moderate Huntington disease and cognitive impairment, treatment with latrepirdine for 6 months is safe and well tolerated but does not improve cognition or global function relative to placebo (NCT00920946) ( Wistar rats receiving an increasing concentration of amiodarone results in conduction block and significant axon degeneration. A high concentration results in severe acute motor axon degeneration followed by complete but delayed regeneration (Silva Oropeza et al, 1997) Causes a sensorimotor neuropathy with distal predominance, and other secondary effects of amiodarone and axonal degeneration changes, segmental demyelination and remyelination in some of the patients taking amiodarone (Pellissier et al, 1984), it also causes optic neuropathyin eyes (Turdumambetova et al, 2005) Causing segmental demyelination, an unusual feature in drug-induced neuropathies, and wallerian degeneration in some of users (Said, 1978) Reduces inositol and IP3 levels; mTORindependent Prolonged use of VPA at specific dose partly prevents eye depigmentation, alleviates climbing disability, and extends the average lifespan of SCA3/MJD transgenic Drosophila. It both increases the acetylation levels of histone H3 and histone H4 and reduces the early apoptotic rate of cells without inhibiting the aggregation of mutant ataxin-3 proteins in MJDtr-Q68-expressing cells (Yi et al, 2013) VPA treatment does not delay emergence of agitation or psychosis or slows cognitive or functional decline in AD patients with moderate disease and is associated with significant toxic effects (Tariot et al, 2011) VPA does not affect survival or the rate of decline of functional status.…”

“…However perhexiline and amiodarone are likely to have a neurotoxic rather than neuroprotective effect both in patients and animal models. Perhexiline is a drug used in long-term treatment of angina pectoris, which may cause severe adverse effects on peripheral neuropathy, like Segmental demyelination, Wallerian degeneration and severe loss of myelinated axons, in a small proportion of patients (Said, 1978). Moreover, perhexiline treatment in rats also causes a cellular lesion in the central nervous system (Jung and Suzuki, 1978).…”

Neuronal and Muscular Inclusions in Rats with Hindlimb Dysfunction after Treating with Difluorobenzhydrylpiperadine

“…These cationic amphiphilic drugs are considered to form complexes with phospholipids and to form lamellar structures within lysosomes (25,29). Such lamellar body formation was reported in affected nerves and muscles of patients with peripheral neuropathy after treatment with amiodarone, chloroquine, or perhexiline (11,20,27,31,34). This paper describes light and electron microscopy of the peripheral nerves and skeletal muscles of DFBP-treated rats.…”