Published Ahead of Print on December 18, 2015 as 10.1212/WNL.0000000000002293 Clinical/Scientific Notes Kanako Muraga, MD, PhD* Satoshi Suda, MD, PhD* Hiroshi Nagayama, MD, PhD Seiji Okubo, MD, PhD Arata Abe, MD, PhD Junya Aoki, MD, PhD Akane Nogami, MD Kentaro Suzuki, MD Yuki Sakamoto, MD Masayuki Ueda, MD, PhD Masahiro Mishina, MD, PhD Kazumi Kimura, MD, PhD LIMB-SHAKING TIA: CORTICAL MYOCLONUS ASSOCIATED WITH ICA STENOSIS Limb-shaking associated with steno-occlusion of the internal carotid artery (ICA) was first reported by Miller Fisher1 in 1962, and is characterized by brief, jerky, coarse, involuntary movements involving an arm or leg. Limb-shaking TIA is an under-recognized manifestation of an intracranial and extracranial carotid occlusion or severe stenosis. Although hemodynamic compromise has been suggested to be associated with shaking movements, the pathogenic nature of this symptom remains unclear. Neurophysiologic evaluation of this movement disorder would be useful, but the attack is rare and typically lasts less than 5 minutes.2 Thus, few reports have investigated this hyperkinetic phenomenon under neurophysiologic assessment.3 We describe a patient who presented with limbshaking TIA who was diagnosed with a cortical myoclonus via electrophysiology using the jerk-locked back-averaging (JLBA) method. Case report. An 84-year-old man who had hypertension was admitted to our hospital with sudden onset recurrent involuntary movements upon standing up from a supine position. A neurologic examination disclosed myoclonus-like involuntary movement of the left distal upper limb that was jerky, purposeless, and rhythmic, but no involvement of the face or right side of the limb. This was the second episode of involuntary movement, the first having occurred 3 weeks prior. The patient was alert and well-oriented, but exhibited slight left hemiparesis. No other neurologic deficits such as parkinsonism or dementia were found. There was no family history of neurologic disorders. MRI of the brain showed a minimum chronic ischemic lesion in the left temporal lobe without any evidence of acute or past vascular pathology in the basal ganglia (figure, A and B). A transfemoral cerebral angiogram demonstrated severe right ICA stenosis (figure, F). No epileptiform discharge was seen on the ictal EEG recording. However, JLBA demonstrated EEG discharges over the contralateral sensorimotor region 20 milliseconds prior to myoclonic EMG discharges of the bicep muscle (figure, F). Therefore, the patient was diagnosed with cortical myoclonus associated with ICA stenosis. The patient was given fluid replacement therapy, antiplatelet therapy, and statin. The symptom gradually improved and had disappeared by the following day (lasting about 10 hours in total duration). Brain N-isopropyl-4-[123I] iodoamphetamine SPECT demonstrated severely impaired perfusion of the frontoparietal cortex, but the basal ganglia and thalamus exhibited relatively preserved perfusion (figure, C and D). Discussion. Hyperkinetic movement disorders seem to be related to a secondary lesion in the basal ganglia or thalamus in the majority of patients,4 whereas the underlying anatomical origin and pathogenesis of limb-shaking TIA is uncertain. Most previous reports suggest that shaking movements are related to transient focal cerebral ischemia. Precipitation of symptoms is caused by specific circumstances, such as rising from a supine to a standing position, walking, running, or hyperextension of the neck, that may lower cerebral blood flow in patients with intracranial and extracranial carotid occlusions or severe stenosis. However, few reports have investigated these symptoms using electrophysiologic methods and no reports have investigated this phenomenon with the use of JLBA, which is able to directly determine the cortical origin of myoclonus. In the present case, JLBA showed a spike prior to a myoclonic jerk, suggesting that hyperexcitability was most likely present at the primary motor cortex. We could not perform SPECT scans during the shaking movement, but postictal SPECT showed severe hypoperfusion in the frontoparietal cortex. Meanwhile, the basal ganglia and thalamus displayed relatively preserved perfusion, which is consistent with previous reports.5 At its simplest level, hyperkinetic movement may represent either the loss of inhibition or a state of primary hyperexcitability. Ischemic damage to neurons may increase membrane instability, excitatory neurotransmitter release, neuronal depolarization, and electrically irritable tissue.6 Moreover, ictal and postacetazolamide SPECT scans showed increased local hyperperfusion of the cortex and an impaired hemodynamic reserve in the vicinity of the same ischemic area.7 Therefore, in the present case, we speculated that ischemia-induced neuronal hyperexcitability of the cerebral cortex, rather than that of the basal ganglia or thalamus, was associated with contralateral shaking movements. Myoclonus has a wide differential diagnosis, including epileptic diseases, infections, neurodegenerative Neurology 86 January 19, 2016 ª 2015 American Academy of Neurology. Unauthorized reproduction of this article is prohibited. 1 Figure MRI, SPECT, angiogram, and jerk-locked back-averaging findings associated with limb-shaking TIA (A, B) Axial diffusion-weighted and fluid-attenuated inversion recovery images show no evidence of vascular pathology in the basal ganglia. (C, D) Postictal brain SPECT shows hypoperfusion areas in the frontoparietal cortex, but relatively preserved perfusion in the basal ganglia and thalamus. (E) Right common carotid artery angiography shows severe stenosis of the internal carotid artery. (F) Jerk-locked back-averaging demonstrates positive EEG waves over the sensorimotor region 20 milliseconds prior to myoclonic EMG discharges of the bicep muscle. 2 disorders, drug exposure, metabolic diseases, and neoplasm. Together, our present findings and other previous reports suggest the importance of taking good medical history into account in order to consider vascular imaging studies for the early identification of carotid occlusive disease in patients with unilateral myoclonus. Thus, a detailed observation of symptoms, as well as neuroradiologic and electrophysiologic features, is warranted to further clarify the pathogenesis of limb-shaking TIA. Dr. Suzuki: analysis and interpretation and critical revision of the manuscript for important intellectual content. Dr. Sakamoto: analysis and interpretation and critical revision of the manuscript for important intellectual content. Dr. Ueda: analysis and interpretation and critical revision of the manuscript for important intellectual content. Dr. Mishina: acquisition of data, analysis and interpretation, and critical revision of the manuscript for important intellectual content. Dr. Kimura: study concept and design, acquisition of data, analysis and interpretation, critical revision of the manuscript for important intellectual content, and study supervision. *These authors contributed equally to this work. Received May 9, 2015. Accepted in final form September 21, 2015. From the Graduate School of Medicine, Nippon Medical School, Tokyo, Japan. Correspondence to Dr. Suda: suda-sa@nms.ac.jp Author contributions: Dr. Muraga: study concept and design, acquisition of data, analysis and interpretation, and drafting/revising the manuscript for content, including medical writing for content. Dr. Suda: study concept and design, acquisition of data, analysis and interpretation, and drafting/revising the manuscript for content, including medical writing for content. Dr. Nagayama: analysis and interpretation and critical revision of the manuscript for important intellectual content. Dr. Okubo: analysis and interpretation and critical revision of the manuscript for important intellectual content. Dr. Abe: analysis and interpretation and critical revision of the manuscript for important intellectual content. Dr. Aoki: analysis and interpretation and critical revision of the manuscript for important intellectual content. Dr. Nogami: analysis and interpretation and critical revision of the manuscript for important intellectual content. © 2015 American Academy of Neurology Neurology 86 Study funding: No targeted funding reported. Disclosure: The authors report no disclosures relevant to the manuscript. Go to Neurology.org for full disclosures. 1. 2. 3. 4. Miller Fisher C. Concerning recurrent transient cerebral ischemic attacks. CMAJ 1962;86:1091–1099. Persoon S, Kappelle LJ, Klijn CJ. Limb-shaking transient ischaemic attacks in patients with internal carotid artery occlusion: a case-control study. Brain 2010;133:915–922. Lee MS, Kim WJ, Lyoo CH, Kim SJ, Suh G. 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Neurology 86 January 19, 2016 ª 2015 American Academy of Neurology. Unauthorized reproduction of this article is prohibited. 3 Limb-shaking TIA: Cortical myoclonus associated with ICA stenosis Kanako Muraga, Satoshi Suda, Hiroshi Nagayama, et al. Neurology published online December 18, 2015 DOI 10.1212/WNL.0000000000002293 This information is current as of December 18, 2015 Updated Information & Services including high resolution figures, can be found at: http://www.neurology.org/content/early/2015/12/18/WNL.0000000000 002293.full.html Permissions & Licensing Information about reproducing this article in parts (figures,tables) or in its entirety can be found online at: http://www.neurology.org/misc/about.xhtml#permissions Reprints Information about ordering reprints can be found online: http://www.neurology.org/misc/addir.xhtml#reprintsus Neurology ® is the official journal of the American Academy of Neurology. 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