Tremor and Other Hyperkinetic Movements

Brief Reports

Improvement of Post-hypoxic Myoclonus with Bilateral Pallidal Deep Brain Stimulation: A Case Report and Review of the Literature

Ritesh A. Ramdhani1,2*, Steven J. Frucht1 & Brian H. Kopell1,2,3,4

1Division of Movement Disorders, Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY, USA, 2Department of Neurosurgery, Icahn School of Medicine at Mount Sinai, New York, NY, USA, 3Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA, 4Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, USA


Background: Post-hypoxic myoclonus (PHM) is a syndrome that occurs when a patient has suffered hypoxic brain injury. The myoclonus is usually multifocal and generalized, often stemming from both cortical and subcortical origins. In severe cases, pharmacological treatments with antiepileptic medications may not satisfactorily control the myoclonus.

Methods: We present a case of a 23-year-old male with chronic medication refractory PHM following a cardiopulmonary arrest related to an asthmatic attack who improved with bilateral globus pallidus internus (GPi) deep brain stimulation (DBS). We review the clinical features of PHM, as well as the preoperative and postoperative Unified Myoclonus Rating Scale scores and DBS programming parameters in this patient and compare them with the three other published PHM-DBS cases in the literature.

Results: This patient experienced an alleviation of myoclonic jerks at rest and a 39% reduction in action myoclonus with improvement in both positive and negative myoclonus with bilateral GPi-DBS. High frequency stimulation (130 Hz) with amplitudes >2.5 V were needed for the therapeutic response.

Discussion: We demonstrate a robust improvement in a medication refractory PHM patient with bilateral GPi-DBS, and suggest that it is a viable therapeutic option for debilitating post-hypoxic myoclonus.

Keywords: Post-hypoxic myoclonus, deep brain stimulation, globus pallidus internus

Citation: Ramdhani RA, Frucht SJ, Kopell BH. Improvement of post-hypoxic myoclonus with bilateral pallidal deep brain stimulation: a case report and review of the literature. Tremor Other Hyperkinet Mov. 2017; 7. doi: 10.7916/D8NZ8DXP

*To whom correspondence should be addressed. E-mail:

Editor: Elan D. Louis, Yale University, USA

Received: March 09, 2017 Accepted: April 20, 2017 Published: May 19, 2017

Copyright: © 2017 Ramdhani et al. This is an open-access article distributed under the terms of the Creative Commons Attribution–Noncommercial–No Derivatives License, which permits the user to copy, distribute, and transmit the work provided that the original authors and source are credited; that no commercial use is made of the work; and that the work is not altered or transformed.

Funding: None.

Financial Disclosures: None.

Conflict of Interest: The authors report no conflict of interest.

Ethics Statement: All patients that appear on video have provided written informed consent; authorization for the videotaping and for publication of the videotape was provided.


The syndrome of post-hypoxic myoclonus (PHM) emerges within days to weeks of a patient suffering hypoxic brain injury, usually from cardiopulmonary arrest (CPA).1,2 PHM is commonly cortical, manifesting as multifocal, generalized muscle jerks that increase during movement and/or accentuate with sensory stimuli.3 Subcortical, brainstem myoclonus can often coexist. First described by Lance and Adams,1 PHM can also be associated with other neurological symptoms including cerebellar ataxia and seizures. Myoclonus may be positive or negative, and patients usually have a combination of cortical/subcortical and positive/negative myoclonus.

Treatment for chronic myoclonus is difficult, requiring a polypharmacy approach using antiepileptic medications such as leviteracetam, piracetam, clonazepam, and valproate.4,5 Primidone, valproate, and clonazepam are usually insufficient monotherapies and their side effects can exacerbate the underlying myoclonus.6 Levetiracetam and piracetam have been shown in clinical trials to be tolerable and effective in cortical myoclonus,7,8 but the high doses needed for these drugs can engender non-compliance. As a result, patients with PHM usually require a combination of the classes of aforementioned medications with variable responses. Deep brain stimulation (DBS) has been suggested in patients with chronic PHM, but there have been only three reported cases of PHM treated with DBS.911 We report a fourth case of a patient with PHM following an asthmatic attack and CPA who was effectively treated with DBS, and only the second case to utilize bilateral globus pallidus internus (GPi) stimulation. We suggest that this approach should be considered in patients with severe disability from PHM when medications fail.


A 23-year-old male with a history of asthma and gastric bypass surgery suffered an asthmatic attack en route to a scheduled endoscopy. He went into cardiopulmonary arrest and was resuscitated after three rounds of defibrillation and cardiopulmonary resuscitation for 15 minutes. Within 24 hours of this event, he developed generalized and multifocal myoclonus while in intensive care and was comatose for approximately 1 month before regaining consciousness. Electroencephalogram monitoring did not reveal seizure activity. He underwent a tracheostomy and a percutaneous endoscopic gastrostomy, both of which were eventually reversed. He was referred to our center 2 years after the hypoxic and despite early gains in his mental status, respiratory function and dysphagia, his myoclonus persisted—occurring at rest and worsened with movement of his hands and legs. He was unable to hold a cup with either hand because of action myoclonus (Video 1). He required assistance with all activities of daily living and was unable to ambulate more than a few steps even using a walker. Throughout the day he had several episodes of myoclonic “volleys,” characterized as frequent, relentless flurries of generalized myoclonus that would last 20 minutes to 1 hour (Video 2). The patient would sweat profusely during these events and consumption of several shots of vodka was found to substantially dampen the myoclonus. A regimen of levetiracetam 1,500 mg twice a day, clonazepam 2 mg three times a day, and valproate 250 mg three times a day provided only modest control of his rest and action myoclonus and further increases failed to decrease the severity or frequency of his myoclonic volleys.

On examination, while in the seated position, there were mild spontaneous myoclonic jerks in his arms and hands. His speech was incomprehensible with frequent arrests. He had one or two jerks of his neck when rotating his head and infrequent facial myoclonus. Action myoclonus emerged when his arms were outstretched and increased on finger to nose movements with myoclonic jerks in flexor more than extensor muscle groups. There was no stimulus-induced myoclonus with tactile or pinprick stimulation of the arms or legs. He required two-person assistance to stand, which triggered negative myoclonus in his legs with frequent truncal jerks (Video 3). His stance was broad based and he was unable to take a step forward.

Following a multidisciplinary deliberation that took into consideration this patient’s preserved cognition, lack of other medical comorbidity, and severity of disability stemming from medication refractory myoclonus, a recommendation for DBS was taken as an attempt to recuperate some level of meaningful quality of life. The decision to choose bilateral GPi as the target for implantation was in part based on our experience along with published data of treating myoclonus in myoclonus–dystonia patients with GPi-DBS.1215


The patient underwent staged implantation of bilateral DBS electrodes (Medtronic 3389, Medtronic Inc., St. Paul, MN) 3 years after his anoxic event. The electrodes were placed into the posteroventrolateral globus pallidus internus using a Leksell stereotactic frame and O-Arm guidance. The operative target was localized as 20 mm lateral to the midline, 2.5 mm anterior to the middle cerebral peduncle (MCP), and 4 mm inferior to the commissural line. The target was then cross correlated with the reformatted Schaltenbrand and Wahren atlas and with the Quantitative Susceptibility Mapping (QSM)16 images showing the GPi. Intraoperative microelectrode recording provided further targeting refinement and a postoperative CT co-registered with preoperative magnetic resonance imaging provided confirmation of electrode placement (Figure 1).


Postoperative programming commenced 2 weeks after the pulse generators were implanted. Of note, there was no objective clinical change in the patient’s physical condition or functional improvement before stimulation started. Initial programming consisted of a monopolar review (pulse width (PW) 90 ms, frequency 130 Hz) that evaluated each contact and mapped their myoclonus reduction along with any unwanted side effects. There was immediate reduction of both rest and action myoclonus, greater on the left hemibody during initial programming. However, he developed an infection of the left implanted pulse generator (IPG) 2 months from initial programming that spared the left electrode. The IPG was removed, and as a result his right upper extremity rest and action myoclonus returned. Following 6 weeks of antibiotics, his IPG was reimplanted.

Six months from the first programming session, there was only mild action myoclonus in both his arms and legs. His lower extremity negative myoclonus also showed improvement by this time following a very modest rate of response up until that point. This allowed him to stand by pushing off with both hands and walk several meters using a walker in physical therapy with one-person assistance. He was able to hold items with each hand, drink from a cup with one hand, and open a bottle cap (Video 4). He started brushing his teeth independently and assisted his caretakers with dressing and hygiene. In addition, his myoclonic volleys were no longer a daily occurrence.

Programming parameters and changes in his Unified Myoclonus Rating Scale Motor scores from an unblinded rater are shown in Table 1 along with the three other published PHM-DBS cases. His action myoclonus in his arms required large stimulation amplitudes. Furthermore, a tripolar configuration of the left DBS was used to create a broad stimulation field as a means to attenuate his right upper extremity myoclonus.

As a result of reduced PHM, the patient’s underlying mild appendicular dysmetria and gait ataxia, which were not initially appreciated because of the extent of his muscle jerks, were unmasked, and remained unresponsive to stimulation. His myoclonic medications also remained unchanged as attempts to reduce them increased his myoclonus.


Though neurophysiological studies were not conducted, phenomenologically this patient manifested both chronic cortical and subcortical myoclonus. The presence of multifocal, distal muscle jerks that increased with movement was consistent with a cortical process. Subcortical or reticular myoclonus was evident with observed jerks in his face, neck, and proximal upper extremity flexor muscles during movement, as well as negative myoclonus in his legs.17,18

Pallidal and thalamic DBS have been shown to be quite effective in suppressing myoclonus, especially in patients with myoclonus–dystonia.12,13 However, to the best of our knowledge, there have only been three reported cases of PHM treated with DBS (Table 1). Two of those cases were pallidal stimulation—one of which was unilateral to treat hemimyoclonus following a stroke,9 while the other was a bilateral implantation that effectively treated CPA-induced myoclonus in all extremities.11 Khobayashi et al.10 reported a case of perinatal anoxia-induced action myoclonus successfully treated with bilateral VIM-DBS. The programming parameters for these cases all utilized a bipolar configuration to achieve therapeutic gain, whereas a monopolar and tripolar configuration in our patient, produced robust responses at amplitudes >2.5 V without any side effects.

The pathophysiology of post-hypoxic myoclonus remains unknown. However, the rat arrest model with myoclonus19 demonstrated degeneration in pyramidal cells of layers III and IV of the cerebral cortex and reticular thalamus along with extensive Purkinje cell damage in the cerebellum. Concomitantly, decreases in 5-HTP (hydroxytryptophan), 5-HT (hydroxytryptamine receptors), and 5-HIAA (hydroxyindoleacetic acid) in the cortex, mesencephalic regions, striatum, and cerebellum highlighted a potential role of the serotonergic system in the pathophysiology of PHM. Recent human brain imaging studies in PHM showed minimal anatomical changes but significant cortical and cerebellar connectivity, metabolic, and blood flow changes2,2025 (Table 2). Of note, fludeoxyglucose positron emission tomography findings by Frucht and colleagues20 revealed elevated glucose metabolism in the ventrolateral thalamus and pontine tegmentum in seven patients with PHM, suggesting involvement of the basal ganglia-thalamocortical network. When compared to myoclonus–dystonia (DYT-11), shared metabolic increases were seen in the parasagittal cerebellar nuclei.21 Combining these findings with the neuronal injury in the paravermal and vermal regions of the rat arrest model, suggests that dysfunctional ascending pathways intricate to motor execution19 are contributory to the generation of PHM. Furthermore, the unmasking of cerebellar symptoms following attenuation of our patient’s myoclonus underscores the potential putative role of the cerebellum in the pathogenesis of myoclonus, especially cortical myoclonus.

There are limited data regarding the neuronal activity of the GPi in the context of PHM. However, aberrations in GPi neuronal recordings have been reported in a constellation of hyperkinetic disorders such as myoclonus–dystonia,26 generalized and secondary dystonia, and hemiballismus.27,28 The response of cortical myoclonus to pallidal stimulation in this patient suggests the possibility that dysfunctional motor cortical relays and/or cerebellar efferents converge on the basal ganglia–thalamocortical network triggering changes in the nature of neuronal processing. Unlike cortical myoclonus, the pathophysiology of subcortical myoclonus is less clear; however, its response to stimulation infers a possible role for this network in its pathogenesis.

In summary, we present a patient with medication-refractory post-hypoxic myoclonus following cardiopulmonary arrest manifesting with cortical (positive and negative myoclonus) and subcortical myoclonus who experienced significant improvement with pallidal deep brain stimulation. Based on our growing understanding of the pathophysiology of cortical myoclonus as well as the robust nature by which it responds to DBS in myoclonus–dystonia and a small cohort of published PHM cases, it is not unreasonable to consider DBS as a therapeutic option in debilitating Lance Adam’s syndrome.


1. Lance JW, Adams RD. The syndrome of intention or action myoclonus as a sequel to hypoxic encephalopathy. Brain 1963;86:111–136. doi: 10.1093/brain/86.1.111

2. Werhahn KJ, Brown P, Thompson PD, Marsden CD. The clinical features and prognosis of chronic posthypoxic myoclonus. Mov Disord 1997;12:216–20. doi: 10.1002/mds.870120212

3. Hallett M. Physiology of human posthypoxic myoclonus. Mov Disord 2000;15 (Suppl. 1):8–13. doi: 10.1002/mds.870150703

4. Fahn S. Post-anoxic action myoclonus: improvement with valproic acid. N Engl J Med 1978;299:313–314.

5. Obeso JA. Therapy of myoclonus. Clin Neurosci 1995;3:253–257.

6. Ikeda A, Shibasaki H, Tashiro K, Mizuno Y, Kimura J. Clinical trial of piracetam in patients with myoclonus: nationwide multiinstitution study in Japan. The Myoclonus/Piracetam Study Group. Mov Disord 1996;11:691–700. doi: 10.1002/mds.870110615

7. Striano P, Manganelli F, Boccella P, Perretti A, Striano S. Levetiracetam in patients with cortical myoclonus: a clinical and electrophysiological study. Mov Disord 2005;20:1610–1614. doi: 10.1002/mds.20530

8. Frucht SJ, Louis ED, Chuang C, Fahn S. A pilot tolerability and efficacy study of levetiracetam in patients with chronic myoclonus. Neurology 2001;57:1112–1114. doi: 10.1212/WNL.57.6.1112

9. Yamada K, Sakurama T, Soyama N, Kuratsu J. Gpi pallidal stimulation for Lance-Adams syndrome. Neurology 2011;76:1270–1272. doi: 10.1212/WNL.0b013e31821482f4

10. Kobayashi K, Katayama Y, Otaka T, et al. Thalamic deep brain stimulation for the treatment of action myoclonus caused by perinatal anoxia. Stereotact Funct Neurosurg 2010;88:259–263. doi: 10.1159/000315464

11. Asahi T, Kashiwazaki D, Dougu N, et al. Alleviation of myoclonus after bilateral pallidal deep brain stimulation for Lance-Adams syndrome. J Neurol 2015;262:1581–1583. doi: 10.1007/s00415-015-7748-x

12. Ramdhani RA, Frucht SJ, Behnegar A, Kopell BH. Improvement of isolated myoclonus phenotype in myoclonus dystonia after pallidal deep brain stimulation. Tremor Other Hyperkinet Mov 2016;6. doi: 10.7916/D8F47P0C

13. Gruber D, Kuhn AA, Schoenecker T, et al. Pallidal and thalamic deep brain stimulation in myoclonus-dystonia. Mov Disord 2010;25:1733–17343. doi: 10.1002/mds.23312

14. Azoulay-Zyss J, Roze E, Welter ML, et al. Bilateral deep brain stimulation of the pallidum for myoclonus-dystonia due to epsilon-sarcoglycan mutations: a pilot study. Arch Neurol 2011;68:94–98. doi: 10.1001/archneurol.2010.338

15. Kurtis MM, San Luciano M, Yu Q, et al. Clinical and neurophysiological improvement of SGCE myoclonus-dystonia with GPi deep brain stimulation. Clin Neurol Neurosurg 2010;112:149–152. doi: 10.1016/j.clineuro.2009.10.001

16. Deistung A, Schafer A, Schweser F, Biedermann U, Turner R, Reichenbach JR. Toward in vivo histology: a comparison of quantitative susceptibility mapping (QSM) with magnitude-, phase-, and R2∗-imaging at ultra-high magnetic field strength. Neuroimage 2013;65:299–314. doi: 10.1016/j.neuroimage.2012.09.055

17. Tassinari CA, Rubboli G, Shibasaki H. Neurophysiology of positive and negative myoclonus. Electroencephalogr Clin Neurophysiol 1998;107:181–195. doi: 10.1016/S0013-4694(98)00058-3

18. Rubboli G, Tassinari CA. Negative myoclonus. An overview of its clinical features, pathophysiological mechanisms, and management. Neurophysiol Clin 2006;36:337–343. doi: 10.1016/j.neucli.2006.12.001

19. Tai KK, Bhidayasiri R, Truong DD. Post-hypoxic animal model of myoclonus. Parkinsonism Relat Disord 2007;13:377–381. doi: 10.1016/j.parkreldis.2007.07.001

20. Frucht SJ, Trost M, Ma Y, Eidelberg D. The metabolic topography of posthypoxic myoclonus. Neurology 2004;62:1879–1881. doi: 10.1212/01.WNL.0000125336.05001.23

21. Carbon M, Raymond D, Ozelius L, et al. Metabolic changes in DYT11 myoclonus-dystonia. Neurology 2013;80:385–391. doi: 10.1212/WNL.0b013e31827f0798

22. Park KM, Han YH, Kim TH, et al. Increased functional connectivity between motor and sensory cortex in a patient with Lance-Adams syndrome. Clin Neurol Neurosurg 2015;139:241–243. doi: 10.1016/j.clineuro.2015.10.021

23. Ferlazzo E, Gasparini S, Cianci V, Cherubini A, Aguglia U. Serial MRI findings in brain anoxia leading to Lance-Adams syndrome: a case report. Neurol Sci 2013;34:2047–2050. doi: 10.1007/s10072-013-1356-2

24. Zhang YX, Liu JR, Jiang B, et al. Lance-Adams syndrome: a report of two cases. J Zhejiang Univ Sci B 2007;8:715–720. doi: 10.1631/jzus.2007.B0715

25. Huang HC, Chen JC, Lu MK, Chen JM, Tsai CH. Post-hypoxic cortical myoclonus mimicking spinal myoclonus - electrophysiological and functional MRI manifestations. Eur J Neurol 2011;18:e4–5. doi: 10.1111/j.1468-1331.2010.03186.x

26. Welter ML, Grabli D, Karachi C, et al. Pallidal activity in myoclonus dystonia correlates with motor signs. Mov Disord 2015;30:992–926. doi: 10.1002/mds.26244

27. Vitek JL, Chockkan V, Zhang JY, et al. Neuronal activity in the basal ganglia in patients with generalized dystonia and hemiballismus. Ann Neurol 1999;46:22–35. doi: 3.0.CO;2-Z"$10#?>10.1002/1531-8249(199907)46:1<22::AID-ANA6>3.0.CO;2-Z

28. Sanghera MK, Grossman RG, Kalhorn CG, Hamilton WJ, Ondo WG, Jankovic J. Basal ganglia neuronal discharge in primary and secondary dystonia in patients undergoing pallidotomy. Neurosurgery 2003;52:1358–70; discussion 1370–133. doi: 10.1227/01.NEU.0000064805.91249.F5

Table 1. Post-hypoxic Myoclonus Cases Treated with Deep Brain Stimulation

Age/Gender Etiology Body Region Affected Preoperative UMRS Postoperative UMRS Medication DBS Target/Electrode DBS Parameters (contacts: amplitude/PW/Freq)
Rest Action Stimulus Sensitive Rest Action Stimulus Sensitive

Abbreviations: CPA, Cardiopulmonary Arrest; LLE, Left Lower Extremity; LUE, Left Upper Extremity; NA, Not Available; RLE, Right Lower Extremity; RUE, Right Upper Extremity; UMRS, Unified Myoclonus Rating Scale.

1Assessed during an episode of a myoclonic volley.

Yamada et al.9 71M Right putaminal hemorrhage and CPA Right Hemibody 24 52 NA 6 15 NA Clonazepam (1.5 mg/day) Valproate (800 mg/day) Gabapentin (400 mg/day) Left Gpi (Medtronic 3387) L: 1–2+1, 8V/450 µs/130 Hz
Kobayashi et al.10 36M Perinatal anoxia Upper limbs NA LUE 12 RUE 9 NA NA LUE 2 RUE 2 NA N/A B/L VIM (Medtronic 3387) R: 1–3+ settings unavailable L: 1–3+ settings unavailable
Asahi et al.11 54M CPA Generalized 8 25 5 0 5 0 Valproate acid Clonazepam Intrathecal Baclofen BL Gpi (Medtronic 3387) Interleaved R: 1(–) 2(+) 2.5 V/60 µsec/125 Hz L: 0(–) 1(+) 2.0 V/60 µs/125 Hz
Current case 26M Asthmatic attack and CPA Generalized 751 52 RUE 6 RLE 2 LUE 6 LLE 2 0 0 32 RUE 2 RLE 2 LUE 0 LLE 2 0 Clonazepam (6 mg/day) Levetiracetam (3,000 mg/day) Valproate (750 mg/day) BL Gpi Medtronic/3389 R: 3-c+: 2.8 V/90 µs/130 Hz L: 1-2-3-C+: 2.5 V/60 µs/130 Hz

Table 2. Neuroimaging Findings in Post-Hypoxic Myoclonus

Study No. Patients Imaging Modality Results

Abbreviations: BOLD, Blood Oxygenation Level Dependent; CPA, Cardiopulmonary Arrest; DWI, Diffusion-weighted Image; FDG-PET, [18F]-fludeoxyglucose-positron Emission Tomography; MRS, Magnetic Resonance Spectroscopy; PET, Positron Emission Tomography; rs-fMRI, Resting State Functional Magnetic Resonance Imaging; SPECT - Single-photon emission computed tomography.

aOne post-hypoxic myoclonus patient compared with four age matched controls

b12 of 14 PHM patients had brain MRI.

Frucht et al.20 7 FDG-PET Bilateral increase in glucose metabolism in pontine tegmentum, ventrolateral thalamus, and medial temporal lobes
Carbon et al.21 7 FDG-PET Conjunction analysis with DYT-11 revealed shared increases in parasagittal cerebellar nuclei bilaterally
Park et al.22,a 1 rs-fMRI Increased connectivity between: 1) primary motor cortex and right somatosensory association cortex 2) primary sensory cortex and left visual association cortex 3) supplementary motor cortex and right inferior temporal, right orbito-temporal, left primary auditory, and left somatosensory association cortex
Ferlazzo et al.23 1 Serial MRIs 4 days after CPA, DWI lesions in cerebellum and thalami, FLAIR was normal 20 days after CPA–DWI and FLAIR normal 6 months after CPA–3T MRI with quantitative volumetric analysis no atrophy of thalami, cerebellum, caudate nuclei, putamina, pallidus nuclei, hippocampi, as well as normal volumes of whole encephalic tissue, gray and white matter
Werhahn et al.2,b 14 MRI Mean 2.5 years from CPA: 4 patients – mild cortical and cerebellar atrophy 4 patients – hemispheric or cerebellar infarcts 4 patients – normal
Zhang et al.24 2 SPECT MRS FDG-PET 1 patient 2 months from CPA SPECT – revealed mild left temporal lobe hypoperfusion 1 patient 10 months from CPA MRS – moderate reduction in N-acetyl aspartate peak in her left hippocampus and a mild decrease in the right hippocampus PET – metabolic reduction in frontal lobes
Huang et al.25 1 fMRI Increased BOLD bilateral cortical areas, particularly the motor cortex of legs. Of note patient has only muscle jerks in her legs

Bilateral DBS electrode position. Preoperative magnetic resonance imaging quantitative susceptibility mapping of coronal sequences showing the co-registered postoperative computed tomography location of the centroid (red dot) of the left (A) and right (B) electrodes in the globus pallidus internus.

Video 1. Myoclonus at rest and with action. Cortical and subcortical myoclonus affecting the patient’s speech and limb movements.

Video 2. Myoclonic volley. Episode of myoclonic volley with frequent generalized myoclonus at rest and with action.

Video 3. Myoclonus when standing. Negative myoclonus observed in the patient’s legs when standing.

Video 4. 6 months after with Bilateral GPi-DBS. Reduction in myoclonus with pallidal deep brain stimulation. The patient is able to drink from a water bottle, push himself up to stand, and takes a few steps with assistance.

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