Identification of causative mutations in patients with Leigh syndrome and MERRF by mitochondrial DNA-targeted next-generation sequencing

PURPOSE: Mitochondrial diseases are clinically and genetically heterogeneous disorders, which make their exact diagnosis and classification difficult. The purpose of this study was to identify pathogenic mitochondrial DNA (mtDNA) mutations in 2 Korean families with myoclonic epilepsy with ragged-red fibers (MERRF) and Leigh syndrome, respectively. MATERIALS AND METHODS: Whole mtDNAs were sequenced by the method of mtDNA-targeted next-generation sequencing (NGS). RESULTS: Two causative mtDNA mutations were identified from the NGS data. An m.8344A>G mutation in the tRNA-Lys gene (MT-TK ) was detected in a MERRF patient (family ID: MT132), and an m.9176T>C (p.Leu217Pro) mutation in the mitochondrial ATP6 gene (MT-ATP6) was detected in a Leigh syndrome patient (family ID: MT130). Both mutations, which have been reported several times before in affected individuals, were not found in the control samples. CONCLUSION: This study suggests that mtDNA-targeted NGS will be helpful for the molecular diagnosis of genetically heterogeneous mitochondrial diseases with complex phenotypes.

Arterial Stiffness and Functional Outcome in Acute Ischemic Stroke

OBJECTIVE: Arterial stiffness is a common change associated with aging and can be evaluated by measuring pulse wave velocity (PWV) between sites in the arterial tree, with the stiffer artery having the higher PWV. Arterial stiffness is associated with the risk of stroke in the general population and of fatal stroke in hypertensive patients. This study is to clarify whether PWV value predicts functional outcome of acute ischemic stroke. METHODS: One hundred patients were enrolled with a diagnosis of acute ischemic stroke and categorized into two groups: large-artery atherosclerosis (LAAS) or small vessel disease (SVD) subtype of Trial of Org 10172 in Acute Stroke Treatment (TOAST) classification. Each group was divided into two sub-groups based on the functional outcome of acute ischemic stroke, indicated by modified Rankin Scale (mRS) at discharge. Poor functional outcome group was defined as a mRS > or = 3 at discharge. Student's t-test or Mann-Whitney U-test were used to compare maximal brachial-ankle PWV (baPWV) values. RESULTS: Twenty-four patients whose state was inadequate to assess baPWV or mRS were excluded. There were 38 patients with good functional outcome (mRS or = 3). The baPWV values were significantly higher in patients with poor outcome (2,070.05 +/- 518.37 cm/s) compared with those with good outcome (1,838.63 +/- 436.65) (p = 0.039). In patients with SVD subtype, there was a significant difference of baPWV values between groups (2,163.18 +/- 412.71 vs. 1,789.80 +/- 421.91, p = 0.022), while there was no significant difference of baPWV among patients with LAAS subtype (2,071.76 +/- 618.42 vs. 1,878.00 +/- 365.35, p = 0.579). CONCLUSIONS: Arterial stiffness indicated by baPWV is associated with the functional outcome of acute ischemic stroke. This finding suggests that measurement of baPWV predicts functional outcome in patients with stroke especially those whose TOAST classification was confirmed as SVD subtype.

Intracranial Cystic Metastasis Mimicking Neurocysticercosis in a Pregnant Woman

Brain metastasis can form large cystic lesions, and its differentiation on the basis of imaging findings alone is difficult. A 36-year-old woman with headache visited emergency room. Two years ago, she was diagnosed as neurocysticercosis and had taken anti-parasite medications. However, in the current visit, the sizes of intracranial cystic lesions increased. Brain biopsy reported metastatic neuroendocrine tumor, and chest CT showed the primary site of the tumor. Cystic brain metastasis should be considered in cases with cystic brain lesions.

Vertebrobasilar Occlusion Presenting as Sudden Isolated Bilateral Sensorineural Hearing Loss: Case Report

Isolated bilateral deafness is a rare but possible symptom of vertebrobasilar ischemia, primarily due to occlusion of the anterior inferior cerebellar arteries or their branch, the internal auditory artery. We reported on uncommon case of sudden bilateral sensorineural hearing loss without typical neurological symptoms resulting from vertebrobasilar ischemia. We performed the available examinations, including otoscopy, laboratory tests, and pure tone audiogram, however we were not able to identify the cause of bilateral sensorineural hearing loss. Brain magnetic resonance image showed the cerebellar infarction of the posterior inferior cerebellar artery territory. Brain magnetic resonance angiography showed bilateral vertebral and basilar artery occlusion. We suggest vertebrobasilar ischemia as a cause of sudden isolated deafness.

Vertebrobasilar Occlusion Presenting as Sudden Isolated Bilateral Sensorineural Hearing Loss: Case Report

Isolated bilateral deafness is a rare but possible symptom of vertebrobasilar ischemia, primarily due to occlusion of the anterior inferior cerebellar arteries or their branch, the internal auditory artery. We reported on uncommon case of sudden bilateral sensorineural hearing loss without typical neurological symptoms resulting from vertebrobasilar ischemia. We performed the available examinations, including otoscopy, laboratory tests, and pure tone audiogram, however we were not able to identify the cause of bilateral sensorineural hearing loss. Brain magnetic resonance image showed the cerebellar infarction of the posterior inferior cerebellar artery territory. Brain magnetic resonance angiography showed bilateral vertebral and basilar artery occlusion. We suggest vertebrobasilar ischemia as a cause of sudden isolated deafness.