{'fraction_non_alphanumeric': 0.03562482605065405, 'fraction_numerical': 0.01224603395491233, 'mean_word_length': 5.175257731958763, 'pattern_counts': {'":': 0, '<': 0, '<?xml version=': 0, '>': 0, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 0, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
Response to Letter to the Editor: Can MR spectroscopy and muscle biopsy findings be correlated in MELAS and CPEO?

1. MELAS is not the most common subtype of mitochondrial dis‐ order (MID).Response: “Mitochondrial encephalomyopathy” (ME) is defined as a multisystem inherited disorder affecting tissues with high energy requirements, such as the muscle and central nervous systems.1 It is widely accepted that the subtypes of ME include mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS); myoclonic epilepsy and ragged red fiber disease (MERRF); chronic progressive external ophthal‐ moplegia (CPEO), Leigh syndrome, and others. MELAS is rec‐ ognized as one of the more common ME disorders.2 Thus, the definition of an MID given by Dr. Finsterer and Dr. ZarroukMahjoub is their own and not entirely applicable to our article. An extensive discussion of the function and genetics of MIDs is beyond the scope of this study. 2. CPEO results from single large-scale mtDNA depletion, as well as nDNA mutation.Response: Yes, we know that CPEO can result from both mtDNA and nDNA mutations (most commonly a 4977bp mtDNA deletion, as well as POLG, TWNK, RRM2B, and SLC25A4 nDNA mutations).3,4 The purpose of our study was to select CPEO patients and not to identify definite genetic mutations in CPEO. Hence, if patients had a history of chronic progressive external ophthalmoplegia, short stature, and mtDNA depletion, they satisfied the criteria for CPEO diagnosis, irrespective of the presence of nDNA mutations. 3. Leigh syndrome is not uncommon and is associated with specific cerebral abnormalities.Response: (i) Leigh syndrome occurs mostly between the ages of 3 and 12 months (childhood) and is reported to affect 1 in 40 000 live births.5 As most ME patients in our study were adolescents and adults, Leigh syndrome was relatively rare compared to MELAS, which is estimated to occur in as many as 60 in 100 000 individuals.6 (ii) Cerebral abnormalities in patients with Leigh syndrome include symmetric alterations to the basal ganglia or brain stem. However, these abnormalities are only suggestive of Leigh syndrome and are not diagnostic criteria, given their lack of specificity. Other pathological conditions such as hepatolenticular degeneration (Wilson’s disease) or carbon monoxide (CO) poison‐ ing demonstrate magnetic resonance imaging (MRI) characteristics similar to those of symmetric basal ganglia degeneration (Figure 1). 4. The disease durations were not mentioned.Response: In the pre‐ sent study, we focused on the peak period of the disease course rather than the entire disease duration of ME. Thus, the MRI exami‐ nations and muscle biopsies were performed at the peak clinical stage of disease, to avoid variations in lactate and N-acetylaspartate (NAA) values. Moreover, as the possibility of evaluating lactate lev‐ els by means of 1H-magnetic resonance spectroscopy (MRS) is re‐ lated to the concentration threshold of lactate methyl protons, the ideal time to perform MRS is the peak period of the disease course.7 5. There was unclear reasoning as to why only 13 of 19 MELAS pa‐ tients had cerebral involvement.Response: All of our patients had abnormal MRS imaging, with increased lactate levels or decreased NAA levels. However, these subtle metabolic changes may not be completely observed as clinical central nervous systems (CNS) manifestations, which include delayed development, skill loss, stroke-like episodes, migraines, seizures, myoclonus, cortical blind‐ ness, and others (Table S2 in our original article). The original