Sleep Medicine 13 (2012) 115–117
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Video-Clinical Corners
Introduction This section is a new feature of Sleep Medicine allowing readers to submit unique sleep related cases with video segments as a way to enhance educational value in a manner unattainable through paper format. Please see our web site’s (http://ees.elsevier.com/ sleep/) Guide for Authors for instructions. We hope this section
will be enriched by the contributions of our colleagues who wish to offer stimulating opportunities for discussion and new insights into the field of sleep. doi:10.1016/S1389-9457(11)00418-7
Sleep induced abnormal motor behaviors caused by medium-chain acyl-CoA dehydrogenase deficiency: A case report q Xianghong Meng 1, Wei Mao 1, Wei Sun, Liping Li, Shuqin Zhan, Xun Wu, Zhaoyang Huang, Xiating Zhang, Yunchuan Ma, Yuping Wang ⇑ Department of Neurology, Xuanwu Hospital, Capital Medical University, No. 45 Changchunjie Road, Beijing 100053, China
a r t i c l e
i n f o
a b s t r a c t
Article history: Received 15 November 2010 Received in revised form 9 April 2011 Accepted 22 April 2011 Available online 3 December 2011
Ó 2011 Elsevier B.V. All rights reserved.
Keywords: Sleep MCADD Abnormal motor behaviors Video-polysomnography Video-electroencephalography Fatty metabolism
1. Introduction Inherited medium-chain acyl-CoA dehydrogenase deficiency (MCADD) is a severe, sometimes fatal autosomal recessive disorder, which can cause mitochondrial fatty b-oxidation disorder. The symptoms for MCADD are non-specific, including feeding difficulty, lethargy, vomiting, tachypnea or respiratory arrest,
q
The patient and her family have agreed with this report.
⇑ Corresponding author. Tel.: +86 10 83198273; fax: +86 10 83157841. E-mail addresses:
[email protected],
[email protected] (Y. Wang). 1 Co-first author. 1389-9457/$ - see front matter Ó 2011 Elsevier B.V. All rights reserved. doi:10.1016/j.sleep.2011.04.017
hypotonia, hypoglycemia, metabolic acidosis, coma, encephalopathy, seizures, sudden and unexpected death, and Reye-like syndrome [1–4]. However, the symptom of sleep abnormality has not been reported until now. Here we present the case of a patient whose chief complaint was sleep-induced paroxysmal motor behaviors during non-REM sleep, which is a rare phenomenon in other sleep disorders.
2. Case description We report an 18-year-old girl with normal developmental milestones who suffered from paroxysmal motor behaviors induced by
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X. Meng et al. / Sleep Medicine 13 (2012) 115–117
Fig. 1. Polysomnographic recording of an episode of the patient (the upper picture) showing that this episode happened in stage II of non-REM sleep with intermittent trunk rolling combining with irregular limbs movement.
sleep during both the day and night. However, she was normal when awake. Her abnormal motor behaviors during sleep first occurred when she was four months old and were characterized by trunk vermicular movements lasting several minutes per night. As she grew these episodes became more and more intensive, frequent, and complicated. At present, the patient exhibits various episodic manifestations, such as uttered guttural sounds, trunk torsion, turning over or vermicular movement, choreic limb movements, and leg treading or shaking movements during sleep (see video ‘‘episode recorded in hospital’’ and ‘‘episode recorded at home’’). Occasionally, she would sit up or fall out of bed during sleep. All the episodes could be disturbed by waking her (see video ‘‘episode recorded in hospital-part 2’’ and Supplementary Fig. B). These episodes occurred several dozen times per night, occupying nearly the entire night, and the duration of each episode was from a few seconds to 40 min. Neurological examination, wake and sleep EEGs, interictal MEG, and brain magnetic resonance imaging were normal, but deep tendon reflexes of lower limbs were 3+ and bilateral ankle clonus were positive. Her family history was normal. Psychometric evaluation showed a borderline mental level (Wechsler Adult Intelligence Scale: Full scale IQ 83, verbal IQ 88, performance IQ 78). The initial treatment with Carbamazepine (70 mg/kg d) was ineffective, as were the treatments with Valproic, Clonazepam, Trihexyphenidyl, and Dopamine. Blood organic acid analysis by tandem mass spectrometry (MS) showed several-fold increased values of C8 and C10 (C8: 0.87, nor-
mal range 0.04–0.2; C10: 0.97, normal range 0.04–0.35), and Urinary gas chromatographic mass spectrometric analysis showed that Ethylmalonic acid-2 was increased dramatically (14.35, normal range 0–6.2), which indicated that fatty acid metabolism was abnormal. DNA analysis by PCR amplification of the exons of MCAD (result comparing to the ACADM reference sequence [NCBI Reference Sequence: NM_001127328.1]) revealed a single nucleotide mutation of 2586 T > Y. Video-electroencephalography showed that the episodes happened during stage II of NREM sleep, the motor episodes of the patient did not interrupt NREM sleep and the main symptoms were intermittent trunk torsion and twisting combined with irregular limbs choreic movement (see video ‘‘episode recorded in hospital-part 1’’ and Fig. 1). There was no hypoxemia event during episodes (see Supplementary Figs. A and B). The patient was treated with diet therapy (low fat diet, high glucose, and high protein diet), oral carnitine, Vit B2 and Vit B12 supplementation, and intravenous glucose and Coenzyme complex infusion. Her clinical symptoms were improved gradually. After a one-week treatment, the motor activity became less frequent and pronounced. 3. Discussion We diagnosed MCADD based mainly on the result of blood test, gene mutation, and urine organic acid analysis and the effect of therapy. The increased deep tendon reflex and positive ankle clo-
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nus indicated impairment of the upper motor neurons. It was difficult to differentiate the episodes of our patient from nocturnal paroxysmal dystonia (NPD) and nocturnal frontal lobe epilepsy (NFLE), which are characterized by complex, bizarre motor patterns. NPD was recognized to be a manifestation of NFLE beginning as paroxysmal arousal and lasting less than two min [5,6]. However, several factors could suggest non-epileptic episodes, including the long-lasting attacks, wide spectrum of abnormal motor activity without a stereotypical pattern and without arousal at the episodic onset, negative EEG and MEG findings and resistance to Carbamazepine. Additionally, this abnormal motor activity could be disturbed and stopped either at the onset or during an episode. Our case highlights the need for health care professionals to be aware of this uncommon manifestation of MCADD. Early diagnosis and prompt initiation of treatment appear to be effective in improving clinical symptoms and life quality of patients. In addition, we wonder why the abnormality of fatty metabolism influences sleep exclusively and what the mechanism of this influence is. In order to stimulate the discussion of these issues by medical doctors and researchers, we have provided a video documenting the case presented in this paper. Conflicts of interest The ICMJE Uniform Disclosure Form for Potential Conflicts of Interest associated with this article can be viewed by clicking on the following link: doi:10.1016/j.sleep.2011.04.017.
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Acknowledgement This study was supported by the National Natural Science Foundation of China (30800366). Appendix A. Supplementary data Supplementary data associated with this article can be found, in the online version, at doi:10.1016/j.sleep.2011.04.017. References [1] Wang SS, Fernhoff PM, Hannon WH, Khoury MJ. Medium chain acyl-CoA dehydrogenase deficiency human genome epidemiology review. Genet Med 1999;1:332–9. [2] Gosalakkal JA, Kamoji V. Reye Syndrome and Reye-Like Syndrome. Pediatr Neurol 2008;39:198–200. [3] Yusuf K, Jirapradittha J, Amin HJ, Yu WM, Hasan SU. Neonatal ventricular tachyarrhythmias in medium chain acyl-coa dehydrogenase deficiency. Neonatology 2010;98:260–4. [4] Beresford MW, Pourfarzam M, Turnbull DM, Davidson JE. So doctor, what exactly is wrong with my muscles? Glutaric aciduria type II presenting in a teenager. Neuromuscul Disord 2006;16:269–73. [5] Provini F, Plazzi G, Lugaresi E. From nocturnal paroxysmal dystonia to nocturnal frontal lobe epilepsy. Clin Neurophysiol 2000;111(Suppl. 2):2–8. [6] Derry CP, Duncan JS, Berkovic SF. Paroxysmal motor disorders of sleep: The clinical spectrum and differentiation from epilepsy. Epilepsia 2006;47: 1775–91.
