ABSTRACT
INTRODUCTION: Mitochondrial diseases exhibit wide phenotypic heterogeneity, and can present as progressive myoclonic epilepsy. SUMMARY: We report a case of adult-onset drug-resistant epilepsy, cortical myoclonus and bilateral optic neuropathies due to m.14487T>C, a rare mitochondrial gene mutation identified on whole-genome sequencing. This mutation, which affects the NADH dehydrogenase 6 (ND6) subunit of the mitochondrial respiratory chain, is most commonly implicated in cases of infantile-onset Leigh syndrome, although a broader phenotypic spectrum including migraine with aura and progressive myoclonic epilepsy have been described. Serial MRI scans over a 2-year period demonstrated the interval development of bihemispheric stroke-like lesions. Giant somatosensory evoked potentials and short-duration myoclonic jerks with craniocaudal spread on surface electromyography were consistent with cortical myoclonus. Optical coherence tomography showed bilateral symmetric thinning of the nerve fibre layer in the papillomacular bundles. CONCLUSION: Whole-genome sequencing can help to provide a definitive diagnosis for mitochondrial disease and should be considered in situations where clinical suspicion remains high despite normal genetic panels or muscle histopathology. Mitochondrial disease can present as adult-onset progressive myoclonic epilepsy, and bilateral optic neuropathies can be a striking feature of ND6 mitochondrial gene mutations. In our case, severe cortical myoclonus affecting speech and swallowing remained highly drug-resistant, however, symptomatic benefit was derived from targeted onabotulinum toxin A injections.
ABSTRACT
OBJECTIVE: The relationship between cannabis use and the onset of psychosis is well established. Aberrant salience processing is widely thought to underpin many of these symptoms. Literature explicitly investigating the relationship between aberrant salience processing and cannabis use is scarce; with those few studies finding that acute tetrahydrocannabinol (THC) administration (the main psychoactive component of cannabis) can result in abnormal salience processing in healthy cohorts, mirroring that observed in psychosis. Nevertheless, the extent of and mechanisms through which cannabis has a modulatory effect on aberrant salience, following both acute and chronic use, remain unclear. METHODS: Here, we systematically review recent findings on the effects of cannabis use - either through acute THC administration or in chronic users - on brain regions associated with salience processing (through functional MRI data); and performance in cognitive tasks that could be used as either direct or indirect measures of salience processing. We identified 13 studies either directly or indirectly exploring salience processing. Three types of salience were identified and discussed - incentive/motivational, emotional/affective, and attentional salience. RESULTS: The results demonstrated an impairment of immediate salience processing, following acute THC administration. Amongst the long-term cannabis users, normal salience performance appeared to be underpinned by abnormal neural processes. CONCLUSIONS: Overall, the lack of research specifically exploring the effects of cannabis use on salience processing, weaken any conclusions drawn. Additional research explicitly focussed on salience processing and cannabis use is required to advance our understanding of the neurocognitive mechanisms underlying the association between cannabis use and development of psychosis.
