Cerebellar hematoma in a carrier of the A3243G MELAS mutation

Abstract

Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) is often related to the A3243G mutation of the mitochondrial DNA, accounting for about 80% of typical cases, with a relevant phenotypic variability. Hemorrhagic strokes are quite unusual in these patients. A case of recurrent brain hematomas has been reported in a MELAS patient carrying the G13513A mutation, with clinical onset at age 31 [1]. Another fatal case of intracerebral hemorrhage was reported in a MERRF/MELAS overlap syndrome due to a T8356C mutation [2]. Finally, a putaminal hemorrhagic stroke was described in a MERRF patient carrying the A8344G mutation, with clinical onset at age 26 [3]. Here, we report the case of a 37-year-old male arriving to our attention because of a two-week history of headache associated with nausea, vomiting, and dizziness. A brain MRI scan showed a left hemispheric cerebellar hemorrhage at a stage compatible with the onset of the symptoms. The patient neither had history of arterial hypertension, any hemorrhagic risk-factor, diabetes, nor was taking any medication. A few years before, he was found to be asymptomatic carrier of the A3243G mitochondrial DNA mutation (heteroplasmy confirmed on a blood sample), since a MELAS diagnosis was made on his younger brother expressing a typical phenotype. On current examination, our patient presented slight left ataxic hemiparesis and hypoesthesia. A cerebral angiography failed to show any vascular abnormality. Since our patient was carrier of a MELAS mutation, we decided to assess its putative clinical burden. An EEG showed generalized electrogenetic dysfunction with a single generalized epileptic spike discharge; EMG suggested slight myopathic signs; mild perceptive bilateral deafness was also present. A venous lactic acid test with compression of the right arm was significant (baseline values 2.9 mmol/L; increase up to 7.5 mmol/L after 3 min; NV 0.44–2.22 mmol/L). No hearth conduction defects were present. A week later, on a control CT scan, progressive blood reabsorption was noted and basal ganglia calcifications were not observed; the headache had improved and the neurological examination was normal. Iizuka et al. [4] demonstrated cortical laminar necrosis and focal HMPAO SPET hyperperfusion during subacute stages of stroke-like episodes; moreover, they reported several cases of microhemorrhages and at least one case of intracortical gyral hemorrhage, suggesting that stroke-like episodes are characterized by increased capillary permeability and focal hyperemia [5]. Consistently, vasogenic edema has been reported during stroke-like episodes [6]. Anyhow, in our case, the aspect of the lesion does not suggest the hemorrhagic transformation of a stroke-like episode; this also considering that the hematoma was confined in a specific vascular territory, which is not a characteristic of stroke-like episodes [4]. Conversely, we cannot exclude a hemorrhagic coincidental event in a patient carrying the A3243G mutation with a subclinical MELAS phenotype. However, mitochondrial angiopathy in E. Saracchi L. Tremolizzo J. C. DiFrancesco L. Brighina G. Costantino B. Frigeni M. Brioschi M. L. Piatti L. Fumagalli L. Marzorati N. A. Curto C. Ferrarese Department of Neurology, S. Gerardo Hospital, Monza, Italy