Objectives: Whether or not stroke-like-episodes also involve the optic nerve is under debate. Results: However, it is conceivable that oxidative stress also affects structures of the optic nerve and lead to visual impairment. Conclusions: the term stroke-like-episode should be restricted to typical stroke-like lesions in the cerebrum, which are radiologically well defined.
We read with interest the article by Scarcella et al. on a 55 year-old female who presented with acute, left-sided, painful visual impairment, headache, and myalgia and was diagnosed with ischemic neuropathy respectively stroke-like episode (SLE) of the left optic nerve [1]. Like the index patient’s brother, who was diagnosed with mitochondrial encephalopathy, lactic acidosis, and stroke-like episode (MELAS) syndrome due to the variant m.3243A>G, she carried the same mtDNA variant with a heteroplasmy rate of 12% in urinary epithelial cells [1]. The visual defect remained unchanged under L-arginine and ubidecarenone [1]. The study is compelling but has limitations that should be discussed.
A limitation of the study is that heteroplasmy rates were only determined in urine epithelial cells where it was low (12%) [1]. Heteroplasmy rates were not determined in skin fibroblasts, hair follicles, buccal mucosa cells, leukocytes, or muscle. Knowing heteroplasmy rates in clinically affected tissues, particularly muscle, is crucial not only to explain the phenotype, to predict the course of the disease and thus the outcome of the condition, but also for genetic counselling. Regarding the low heteroplasmy rate in urine, it is hardly conceivable that the clinical manifestations were due to the m.3243A>G variant.
A second limitation is that the current medication was not provided. Since the patient had a history of arterial hypertension and hyperlipidemia, it is conceivable that she received a novel drug for either of these conditions. From statins it is well-known that they can cause myalgia (statin myopathy), particularly in patients with a mitochondrial disorder (MID) [2]. A shortcoming in this respect is that creatine-kinase, lactate-dehydrogenase, aldolase, and myoglobin levels were not provided. Was there any indication for rhabdomyolysis? Was the urine ever cola-coloured?
A third limitation is that no lactate stress test (LST) was performed to assess whether or not serum lactate increased under workload below the anerobic threshold on a bicycle ergometer [3].
A fourth limitation is that cerebrospinal fluid (CSF) lactate was not reported. CSF exam is described as “unremarkable” [1]. However, it was not reported, whether or not CSF lactate was determined. CSF lactate can be elevated in MELAS patients even if serum lactate is normal. CSF lactate is particularly elevated if thereis a SLE. An argument for elevated CSF lactate is that magnetic resonance spectroscopy (MRS) depicted a lactate peak [1].
A fifth limitation is that no electroencephalography (EEG) was recorded. Since MELAS is characterised by the occurrence of seizures and SLEs, and SLEs can be triggered by seizures, it is crucial to know whether or not epileptiform discharges were recorded on EEG.
There is a discrepancy regarding the diagnosis in the abstract (“SLE”) and the diagnosis in the title respectively case description (“ischemic optic neuropathy”) [1]. These are two completely different entities. SLEs are triggered by seizures or metabolic stress but are unrelated to impaired arterial perfusion. This discrepancy should be clarified not to confuse the reader.
Not considered as pathophysiological mechanisms were spasms of arterioles supplying the optic nerve or enlargement of endothelial mitochondria in arterioles of the optic nerve [4].
Because the case is set during the SARS-CoV-2 pandemic and COVID infection or vaccination can be complicated by optic neuritis [5], it is crucial that SARS-CoV-2 infection or vaccination has been ruled out.
Overall, the interesting study has limitations that put the results and their interpretation into perspective. Addressing these issues would strengthen the conclusions and could improve the status of the study. SLEs of the optic nerve are not imaginable per definition. Alternative pathophysiologies of unilateral visual impairment in m.3243A>G carriers should be considered.
Download PDF
Download XML
