Can Intestinal Pseudo-Obstruction Drive Recurrent Stroke-Like Episodes in Late-Onset MELAS Syndrome? A Case Report and Review of the Literature

Abstract

Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome is a maternally inherited mitochondrial disorder that is most commonly caused by the m. 3243A>G mutation in the MT-TL1 mitochondrial DNA gene, resulting in impairment of mitochondrial energy metabolism. Although childhood is the typical age of onset, a small fraction (1-6%) of individuals manifest the disease after 40 years of age and usually have a less aggressive disease course. The clinical manifestations are variable and mainly depend on the degree of heteroplasmy in the patient's tissues and organs. They include muscle weakness, diabetes, lactic acidemia, gastrointestinal disturbances, and stroke-like episodes, which are the most commonly observed symptom. We describe the case of a 50-year-old male patient who presented with relapsing intestinal pseudo-obstruction (IPO) episodes, which led to a late diagnosis of MELAS. After diagnosis, he presented several stroke-like episodes in a short time period and developed a rapidly progressive cognitive decline, which unfortunately resulted in his death. We describe the variable clinical manifestations of MELAS syndrome in this atypical and relatively old patient, with a focus on paralytic ileus and stroke-like episodes; the first symptom may have driven the others, leading to a relentless decline. Moreover, we provide a brief revision of previous reports of IPO occurrence in MELAS patients with the m.3243A>G mutation, and we investigate its relationship with stroke-like episodes. Our findings underscore the importance of recognizing gastrointestinal disturbance to prevent neurological comorbidities.

Keywords: MELAS; gastrointestinal disturbance; intestinal pseudo-obstruction; mitochondrial disorders; stroke-like episodes.

Figure 1

Temporal evolution of brain magnetic resonance imaging (MRI). FLAIR (fluid attenuated recovery) sequences are shown in the upper line, and DWI (diffusion-weighted imaging) sequences are shown in the lower line. (A) First stroke-like episode initially interpreted as an ischemic stroke. A high signal occurred in the diffusion-weighted imaging (DWI) sequences in the right temporo-occipital lobes and the corresponding fluid attenuated recovery (FLAIR) sequence. (B) Second stroke-like episode: three months later, evidence of a wider lesion was found in the right temporal, parietal and occipital lobes together with initial enlargement of the ventricular spaces. (C) Third stroke-like episode: a new cortical DWI abnormality was observed in the left medial temporal and occipital lobes; marked and diffuse atrophy was found in the brain parenchyma.

Figure 2

Diagnostic assessment of MELAS syndrome. (A–B) Cortical diffusion-weighted imaging abnormalities in the right temporal, parietal and occipital lobes with corresponding fluid attenuated inversion recovery hyperintensity. (C) Brain positron emission tomography (PET) revealed a severe reduction in cortical glucose metabolism in the posterior right hemisphere. (D) MR spectroscopy (MRS) showed elevation of the lactate peak within the abnormal lesion. (E–H) Muscle biopsies. (E) Modified Gomori Trichrome stain (40X) showing a typical Ragged Red muscle fiber (RRF) containing mitochondrial hyperproliferation. (F) Succinate dehydrogenase (SDH) stain (40X) confirming mitochondrial hyperproliferation in the same fiber. (G) Cytochrome C oxidase (COX) stain (40X) demonstrating muscle cells with decreased mitochondrial activity. (H) COX/SDH combo reaction (20X) showing diffuse fibers with COX deficiency and SDH positivity scattered in the muscle.

Figure 3

Timeline representing the clinical disease course. Major clinical episodes are shown in the first line, and the diagnostic assessments performed and treatments are reported in the second and third lines, respectively. IPO, intestinal pseudo-obstruction; MELAS, mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes; PLED, period lateralized epileptiform discharges.