Brief Communication Depressive Episode With Catatonic Features in a Case of Mitochondrial Myopathy, Encephalopathy, Lactic Acidosis, and Stroke-Like Episodes (MELAS) Journal of Child Neurology Volume 24 Number 10 October 2009 1307-1309 # 2009 The Author(s) 10.1177/0883073809334380 http://jcn.sagepub.com Ju Seok Ryu, MD, Sook Joung Lee, MD, In Young Sung, MD, PhD, Tae Sung Ko, MD, PhD, and Han Ik Yoo, MD, PhD Three months previously, a 17-year-old girl had complained of right-hand side hemiparesis, and her brain magnetic resonance imaging (MRI) showed a signal change in the left temporoparietooccipital area. The 3243A>G mutation was found in mitochondrial DNA. She was diagnosed with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) and was prescribed dichloroacetic acid to treat lactic acidosis. Her health improved. Two months later, she developed drowsiness and generalized weakness. A New lesion was not found on brain MRI, and electrodiagnostic findings were compatible with acute motor sensory axonal neuropathy. Her negative symptoms, such as depressed mood, loss of interest in activities, psychomotor retardation, and hypersomnia, were aggravated. She was prescribed antidepressants and psychostimulants by a psychiatrist after diagnosis of severe depression episode with catatonic features. One month later, her catatonic condition had improved with medication. Our experience shows that psychiatric diagnostic evaluation of abruptly regressed neurologic and clinical features is important, even in a patient with devastating underlying disease. M ophthalmoplegia (CPEO), mitochondrial diabetes mellitus, hypertrophic cardiomyopathy, sensorineural hearing loss, a subtype of Leigh syndrome, severe retarded depression, bipolar disorder, and schizophrenia.2-5 In a previous study of 8 patients, the clinical course of the 3243A>G mutation was devastating, with death in 50% of cases and mental retardation in 25% within 7 years of diagnosis.6 We describe the first case of severe depressive episode with catatonic features associated with MELAS and show that the clinical course improved with medication. itochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) is a devastating multisystemic syndrome characterized by progressive encephalopathy and stroke-like episodes leading to disability and early death. The condition has a genetic basis; the most common mutation occurs at mitochondrial base pair 3243, accounting for 45% to 80% of MELAS cases.1 MELAS is thus one of the classic mitochondrial encephalopathies.2,3 The 3243A>G mutation is associated with variable clinical symptoms such as those of typical MELAS, myoclonic epilepsy with ragged red fibers (MERRF), chronic progressive external Keywords: MELAS; A3243G; depression Case Report Received November 26, 2008. Received revised February 12, 2009. Accepted for publication February 13, 2009. From the Departments of Rehabilitation Medicine (JSR, SJL, IYS), Pediatrics (TSK), and Psychiatrics, (HIY), University of Ulsan College of Medicine, Seoul, Korea. The authors have no conflicts of interest to disclose with regard to this article. Address correspondence to: In Young Sung, Department of Physical Medicine and Rehabilitation, Asan Medical Center, Ulsan University College of Medicine, 388-1 Pungnap-2dong, Songpa-gu, Seoul 138-736, Korea; e-mail: iysung@amc.seoul.kr. Ryu JS, Lee SJ, Sung IY, Ko TS, Yoo HI. depressive episode with catatonic features in a case of mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS). J Child Neurol. 2009;24:1307-1309. On June 2, 2008, a 17-year-old girl diagnosed with MELAS was transferred to our department of rehabilitation medicine for evaluation of and rehabilitation for quadriplegia from the department of pediatrics. In February 2008, she complained of headache and right upper extremity weakness. At the local tertiary hospital, brain magnetic resonance imaging (MRI) showed a T2hyperintense lesion in the left temporoparietooccipital area, with cortical swelling, water diffusion restriction on apparent diffusion coefficient measurement, and increased vascular enhancement. Brain magnetic resonance angiography showed no intracranial vascular abnormality. A genetic 1307 Downloaded from jcn.sagepub.com at UCSF LIBRARY & CKM on May 1, 2015 1308 Journal of Child Neurology / Vol. 24, No. 10, October 2009 Figure 1. Transverse T2-weighted magnetic resonance image (MRI) obtained on February 11, 2008, reveals a signal change in the left temporoparietooccipital area. Figure 2. Transverse T2-weighted magnetic resonance image (MRI) obtained on May 21, 2008, shows no change from the earlier scans. analysis revealed the 3243A>G mutation in mitochondrial DNA (Figure 1). She was diagnosed with MELAS and transferred to Asan Medical Center. She was prescribed dichloroacetic acid (25 mg/kg per day) to treat lactic acidosis and was discharged. Her health improved and she returned to school. On April 18, she presented with drowsiness and progressive weakness of all extremities and was again admitted to the local tertiary hospital. Brain MRI showed no definite change from the previous scan. She was discharged and stayed at home with supportive care. On May 21, limb weakness had markedly worsened, and she could not walk. She became unresponsive to her environment and stopped speaking. She was admitted to Asan Medical Center again. On admission, physical examination showed general weakness (poor-to-nil grade) of both upper and low extremities, and deep tendon reflexes were absent from all limbs. Sensory testing was unreliable because of cognitive impairment. Brain MRI showed no change from the earlier scans (Figure 2). Blood cell count; serum chemical, electrolyte, and coagulation batteries; and serum lactic acid level were normal. The quadriparesis and cognitive deterioration were thought to be associated with MELAS. On June 2, she was transferred to our department of rehabilitation medicine because of sustained quadriparesis, and electrophysiologic studies were performed to determine the cause of her weakness. The electrophysiologic findings were compatible with acute motor sensory axonal neuropathy. Her negative symptoms such as depressed mood, loss of interest in activities, psychomotor retardation, hypersomnia, and dysphagia became aggravated. We were unable to institute any rehabilitation program except for a range of passive motion exercises. Because she could not eat or swallow, we inserted a Levin tube for parenteral nutrition. The Montgomery Asberg Depression Rating Scale was 60. We could not evaluate our patient with the Beck Depression Inventory, which is a self-reported test, because of her severe catatonic features. After consultation with the department of psychiatry, an experienced psychiatrist prescribed, from June 11, escitalopram once daily and methylphenidate 2 times per day, as our patient had a history of severe depressive episode with catatonic features, according to the Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition).7 The maximum doses of escitalopram and methylphenidate were 20 and 60 mg/day, respectively. She had never been diagnosed with or treated for psychiatric Downloaded from jcn.sagepub.com at UCSF LIBRARY & CKM on May 1, 2015 Depressive Episode With Catatonic Features / Ryu et al disorders and also denied involvement of familial factors. Before this episode, she had performed well at school. On June 20, the hypersomnia and poor verbal expression improved slightly. She began rehabilitation therapy consisting of progressive strengthening exercises, balancing training, activities of daily living training, speech therapy, and swallowing therapy. On August 10, her muscle strength was much improved, from nil grade to poor-fair grade, on the bilateral upper and lower extremities. Her sitting balance became stable, and she began to eat with assistive devices such as universal cuff and a dorsal cock-up splint under the supervision. Her verbal expression, motivation, and thought expression also improved. The Montgomery Asberg Depression Rating Scale improved to 25 and the Beck Depression Inventory was 23. She was discharged from our hospital. On September 8, she visited our outpatient clinic for follow-up and we found that her depressive symptoms were much improved; she was able to partake in nearly normal conversation. Her motivation had also improved; she could perform eating and grooming independently, despite poor motor recovery. Discussion Our patient was characterized by acute motor sensory axonal neuropathy and severe depressive episode with catatonic features associated with MELAS. Initially, the diagnosis of severe depressive episode with catatonic features was confused with cognitive deterioration caused by MELAS itself. In a previous study, upregulation of LARS2 was a hallmark of the 3243A>G mutation and this mutation was correlated with the presence of bipolar disorder and schizophrenia.5 To the best of our knowledge, only 2 patients with depression have been shown to have mutations in mitochondrial DNA.4,8 Her recurrent, progressive, weakness, and the underlying 3243A>G mutation, may have provoked both the development and aggravation of severe depressive episode with catatonic features. Delirium and drug side effects were considered as differential diagnoses of depression. However, our patient showed no symptoms of delirium, such as mood fluctuation over the course of the day, disorientation, vivid perceptual disturbances, nocturnal exacerbation, or brief episode duration. In addition, our patient took no medication apart from dichloroacetic acid. Therefore, we could rule out delirium and drug side effects as causes of her condition.7 It is important to note that her depression improved after medication and recovery from motor weakness. The Montgomery Asberg Depression Rating Scale dropped 1309 from 60 to 25 and the Beck Depression Inventory improved from an uncheckable state to 23. Escitalopram is an antidepressant that increases intrasynaptic levels of the neurotransmitter serotonin by blocking reuptake of the neurotransmitter into the neuron.9 Methylphenidate is a norepinephrine and dopamine reuptake inhibitor, which potentiates the effects of antidepressants.10 We assumed that administration of escitalopram and methylphenidate regulated brain neurotransmitter levels and assisted in patient recovery over several weeks. Our patient taught us that we should not regard symptoms in MELAS cases as untreatable even though the underlying disease is devastating. We here describe the first patient who developed severe depressive episode with catatonic features associated with MELAS but who showed an improving course with antidepressant treatment. References 1. Hirano M, Pavlaskis SG. Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS): current concepts. J Child Neurol. 1994;9(1):4-13. 2. Goto Y, Horai S, Matsuoka T, et al. 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J Biomed Sci. 2002;9(6 pt 1):527-533. 7. Sadock BJ, Sadock VA. Kaplan & Sadock’s Synopsis of Psychiatry: Behavioral Science/Clinical Psychiatry. 10th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2007. 8. Miyaoka H, Suzuki Y, Taniyama M, et al. Mental disorders in diabetic patients with mitochondrial Transfer RNA Leu(UUR) Mutation at position 3243. Biol Psychiatry. 1997;42(6):524-526. 9. Hoschl C, Svestka J. Escitalopram for the treatment of major depression and anxiety disorders. Expert Rev Neurother. 2008;8(4):537-552. 10. Frye CB. Methylphenidate for depression in the elderly, medically ill patient. Am J Health Syst Pharm. 1997;54(21): 2510-2511. For reprints and permissions queries, please visit SAGE’s Web site at http://www.sagepub.com/journalsPermissions.nav Downloaded from jcn.sagepub.com at UCSF LIBRARY & CKM on May 1, 2015