Perampanel-Induced Cataplexy in a Young Male with Generalized Epilepsy

Abstract

Description Perampanel (Fycompa) is a newer anti-epileptic drug believed to exert its effects in the central nervous system by inhibiting post-synaptic glutamate receptors. However, the precise therapeutic mechanism is unknown. The most common neuropsychiatric side effect is affective dysregulation; there are also reports of psychosis. We describe a 32 year old African American male with recurring generalized tonic-clonic (GTC) seizures, who presented to our hospital with onset of mood lability for several months, after Perampanel was added to his antiepileptic medications. Perampanel administration was temporarily withheld, and subsequently on restarting, noted to be coincident with neuropsychiatric symptomatology, including motor weakness in emotional contexts. The mechanisms underlying cataplexy are complex and, in our patient, most likely induced by an interaction between Perampanel and the wakeful inhibition of the sublaterodorsal nucleus projections.

Keywords: Fycompa; REM sleep behavior disorder; cataplexy; disorders of excessive somnolence; drug-related side effects and adverse reactions; epilepsy; hypocretin; narcolepsy; orexins; perampanel; seizures; sleep wake disorders.

Figure 1

Suggested pathway for normal muscle tone. During normal wake periods in noncataleptic individuals, orexin stimulation of the vlPAG/LPT nuclei and monoaminergic centers, leads to adequate inhibition of the sublaterodorsal nuclei and hence, maintenance of normal muscle tone. Adapted with permission from Burgess et al. vlPAG: ventrolateral periaqueductal grey, LPT: lateral pedunculopontine tegmentum, NE: norepinephrine, 5HT: 5-hydroxytryptamine (Serotonin), SLD: sublaterodorsal nuclei. Solid line: stimulation; Dashed line: inhibition; line thickness correlates with strength

Figure 2

Suggested pathway for muscle atonia. In cataplectic patients, it is hypothesized that processing of positive (and some negative) stimuli by the CeA, inhibits the vlPAG/LPT and stimulates the SLD, overcoming the vlPAG/LPT and monoaminergic inhibition. This leads to REM-type atonia during wakefulness and symptoms of cataplexy. Adapted with permission from Burgess et al. vlPAG: ventrolateral periaqueductal grey, LPT: lateral pedunculopontine tegmentum, NE: norepinephrine, 5HT: 5-hydroxytryptamine (Serotonin), SLD: sublaterodorsal nuclei, CeA: contral nucleus of the amygdala. Solid line: stimulation; Dashed line: inhibition; line thickness correlates with strength