Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome has various presentations. We report on a case of MELAS in which alternate-sided homonymous hemianopia was the main symptom of recurrent neurological defects. A 19-year-old woman suffered from blurred vision, headaches, vomiting, and fever that subsided within days. The ophthalmic examination demonstrated right homonymous hemianopia. One month later a similar episode occurred again. Computed tomography (CT) and magnetic resonance imaging (MRI) of her brain revealed an infarct in the left temporo-occipital lobes. Exercise tests showed lactic acidosis, and a muscle biopsy confirmed the diagnosis of mitochondrial myopathy. Half a month later, a third episode occurred. Visual field examination demonstrated left homonymous hemianopia and partial recovery of the right visual field. The infarct in the brain, as revealed by CT and MRI, was compatible with the visual field changes. MELAS should be ruled out in young patients who present with homonymous hemianopia accompanied by recurrent headaches or other recurrent symptoms. (Chang Gung Med J 2003;26:199-203)

Key words:
mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome, homonymous hemianopia, alternating sides.

CASE REPORT

A 19-year-old woman, who had generally been well in the past, suffered from sudden-onset blurred vision in November 2001. Headaches, nausea, and vomiting associated with fever were noted initially, but they subsided in a few days. Because of the persistence of the right hemianopia, she was referred for ocular examinations. Her visual acuity with her glasses was 20/20 in the right eye, and 20/50 in the left; these values were subjectively comparable with her vision before the attack. No limitations in extraocular muscle movements were found. The light reflex of both pupils was normal. No abnormality was found with slit-lamp and fundus examinations. Right homonymous hemianopia was revealed by examination of the visual field. The findings of visual evoked potential were normal.
The visual field defect was stable for a month. However, a similar episode with headaches, vomiting, and blurred vision occurred in December 2001, but symptoms improved within 1 day. She went to the emergency department, and was admitted to the neurology ward for further evaluation. She had no family history of stroke or seizures. Physical examinations revealed a short stature with a height of 154 cm and a body weight of 35 kg. No neurological motor defects were detected. Neither sign of dementia nor hearing loss was noted. Her visual acuity with her glasses was 20/30 in the right eye and 20/50 in the left. The results of a slit-lamp exam and direct ophthalmoscopy were unremarkable. Right homonymous hemianopia was found using a visual field examination (Fig. 1A). A computed tomographic (CT) scan of her brain showed encephalomalacic changes in the left occipital lobe. A magnetic resonance imaging (MRI) scan of the brain demonstrated a left posterior temporo-occipital lesion that was compatible with an infarction (Fig. 2A). Visual evoked potential performed later showed an abnormality in left visual pathway conduction.
To identify the cause of the recurrent stroke, hematological examinations, carotid artery echogram, and transcranial Doppler study were performed, but no abnormality was found. Under a suspicion of MELAS, an exercise test was performed which revealed lactic acidosis. The lactate level before exercise was 1.86 mmol/L (normal, 0.63-2.44 mmol/L), and the pyruvate level was 27.36 mmol/L (normal, 34.2-102.6 mmol/L). After exercise, the lactate level increased to 8.42 mmol/L, and the pyruvate level increased to 101.46 mmol/L. Thus muscle biopsy was performed to confirm the diagnosis. Gomori-trichrome stain showed increased subsarcolemmal mitochondrial accumulation, which was further confirmed by reduced nicotinamide-adenine dinucleotide (NADH) staining. There were no apparent decreases in activities by cytochrome C oxidase stain. The pathologic changes in the muscle were compatible with mitochondrial myopathy.
Unfortunately another episode occurred in January 2002. She was re-admitted due to severe headaches and blurred vision. She felt that her vision had become worse. There was no other sensory loss or motor defect, except for left homonymous hemianopia. The best-corrected vision in the right eye was 20/50, and 20/100 in the left. The results of a visual field examination showed left homonymous hemianopia, and moderate depression of the right-side visual field (Fig. 1B). Brain CT showed infarcts at the bilateral parieto-occipital lobes. An MRI of the brain revealed sequela of an infarct in the left occipitoparietal lobes, and subacute infarct in the right occipital, parietal, and temporal lobes (Fig. 2B). Diffuse cortical dysfunction with epileptic activities on the right side was found by electroencephalography. Visual evoked potential suggested a bilateral visual pathway conduction abnormality. Her condition stabilized, and she was followed up in the clinic after discharge from the hospital.

DISCUSSION

The clinical presentation of MELAS syndrome is variable. It has been reported to mimic herpes encephalitis which presents with cognitive decline, hemiparesis, and hemianopia after herpes infection.(7) It could also be confused with a migrainous stroke, which presents as pulsatile headache and hemiparesis.(8) Although hemianopia and cortical blindness are the most common symptoms, they are usually accompanied by other neurological defects, such as hemiparesis, dementia, and seizures.(2,3,6) In addition to headaches and vomiting, our patient presented with homonymous hemianopia as the only focal neurological sign in all 3 attacks. With CT and MRI scans, a parieto-occipital infarction was diagnosed. Without the associated neurological symptoms, MELAS was not initially suspected. It was the occurrence of a visual cortex infarction and the pathologic results of a muscle biopsy that drew us toward the final diagnosis.
The stroke-like episodes in MELAS have a propensity for the occipital area,(3,9) and about 10% of patients with mitochondrial disorders suffer from an occipital stroke before the age of 45 years.(10) The occipital cortex might be more susceptible to metabolic derangement secondary to mitochondrial dysfunction.(3) In the 3 episodes of our case, the hemianopia developed first on one side and then the other, representing alternate involvement of both occipital lobes. The visual field examination performed after the third episode revealed not only left homonymous hemianopia, but also the incomplete recovery from right hemianopia. This suggested that infarcts of each episode did not recover fully and left the sequela of moderate visual field depression.
MELAS syndrome may present in various forms, and should be suspected in patients with unusual strokes. Homonymous hemianopia may be the only focal neurological sign of MELAS syndrome, thus ophthalmologists should remain aware of this when managing patients with hemianopia accompanied by headaches, vomiting, or seizures.

REFERENCES

1. Shapira Y, Harel S, Russell A. Mitochondrial encephalomyopathies: a group of neuromuscular disorders with defects in the oxidative metabolism. Isr J Med Sci. 1977;13:161-4.
2. Ciafaloni E, Ricci E, Shanske S, Moraes CT, Silvestri G, Hirano M, Simonetti S, Angelini C, Donati A, Garcia C, Martinuzzi A, Mosewich R, Servidei S, Zammarchi E, Bonilla E, DeVivo DC, Rowland LP, Schon EA, DiMauro S. MELAS: clinical features, biochemistry, and molecular genetics. Ann Neurol 1992;31:391-8.
3. Koo B, Becker LE, Chuang S, Merante F, Robinson BH, MacGregor D, Tei I, Ho VB, McGreal DA, Wherrett JR, Logan WJ. Mitochondrial encephalomyopathy, lactic acidosis, stroke-like episodes (MELAS): clinical, radiological, pathological, and genetic observations. Ann Neurol 1993;34:25-32.
4. DiMauro S, Moraes CT. Mitochondrial encephalomyopathies. Ann Neurol 1993;50:1197-208.
5. Pavlakis SG, Phillips PC, DiMauro S, DeVivo DC, Rowland LP. Mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes: a distinctive clinical syndrome. Ann Neurol 1984;16:481-8.
6. DiMauro S, Bonilla E. Mitochondrial encephalomyopathies. In: Rosenberg RN, Prusiner SB, DiMauro S, Barchi RL, eds. The molecular and genetic basis of neurological disease. 2nd ed. Boston: Butterworth-Heinemann Co., 1997:222-3.
7. Sharfstein SR, Gordon MF, Libman RB, Malkin ES. Adult-onset MELAS presenting as herpes encephalitis. Arch Neurol 1999;56:241-3.
8. Ohno K, Isotani E, Hirakawa K. MELAS presenting as migraine complicated by stroke: case report. Neuroradiology 1997;39:781-4.
9. Allard JC, Tilak S, Carter AP. CT and MR of MELAS syndrome. Am J Neuroradiol 1988;9:1234-8.
10. Majamaa K, Turkka, J, Karppa M, Winqvist S, Hassinen IE. The common MELAS mutation A3243G in mitochondrial DNA among young patients with an occipital brain infarct. Neurology 1997;49:1331-4.

From the Department of Ophthalmology, 1Department of Neurology, Chang Gung Memorial Hospital, Taoyuan.
Received: Mar. 19, 2002
Accepted: Jul. 12, 2002
Address for reprints: Dr. Ling-Yuh Kao, Department of Ophthalmology, Chang Gung Memorial Hospital. 5, Fushing Street, Gueishan Shiang, Taoyuan, Taiwan 333, R.O.C.
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