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TitleMotor cortex stimulation for enhancement of recovery after stroke: case report.

Permalinkhttps://escholarship.org/uc/item/9nv1c51p

JournalNeurological research, 25(8)

ISSN0161-6412

AuthorsBrown, Jeffrey ALutsep, HelmiCramer, Steven Cet al.

Publication Date2003-12-01

DOI10.1179/016164103771953907

Copyright InformationThis work is made available under the terms of a Creative Commons Attribution License, availalbe at https://creativecommons.org/licenses/by/4.0/ Peer reviewed

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Motor cortex stimulation for enhancement ofrecovery after stroke: Case report

Jeffrey A. Brown*, Helmi Lutsep{, Steven C. Cramer{ and Martin Weinand§

*Department of Neurological Surgery, Wayne State University, Detroit, MI{Department of Neurology, Oregon Health Sciences University, Portland, OR

{Department of Neurology, University of California, Irvine, CA§Department of Neurological Surgery, University of Arizona, Tucson, AZ, USA

We present a case report of a 65-year-old patient who had a subcortical infarct and a right spastichemiparesis that occurred 19 months before being treated with an investigational therapy consisting of lowfrequency subthreshold epidural motor cortex electrical stimulation delivered during structuredoccupational therapy repeated daily for three weeks. Before treatment the patient’s affected arm restedin a �exion posture and he was unable to �ex or extend the �ngers. After three weeks of treatment, theresting tone of his arm had improved and he was able to grasp a pen and write letters. The Fugl–Meyermotor scale score improved from 36 to 46 and this improvement was sustained for four weeks after theconclusion of rehabilitation therapy. This is the �rst patient to be entered into a randomized clinicalfeasibility and safety study assessing functional improvement in stroke patients treated with epiduralcortical stimulation concurrent with occupational therapy (an investigational therapy). [Neurol Res 2003;25: 815–818]

Keywords: Stroke; electrical stimulation; motor cortex; rehabilitation

INTRODUCTIONPre-clinical evaluation, in both rodent and primatestroke models, of the functional improvement providedby subthreshold epidural cortical stimulation (CS) ofcortex adjacent to damaged motor cortex showssigni�cant functional improvements. (see companionpapers in this issue). These investigations were per-formed because of a number of anecdotal reports notingimproved motor function in patients being treated forcentral pain that had developed after thalamic infarc-tion1–3. The Wayne State University Institutional ReviewBoard approved this clinical trial sponsored by NorthstarNeuroscience, Inc. (Seattle, WA, USA) to evaluate thesafety of CS concurrent with occupational therapy inpatients with a chronic neurological de�cit from eithercortical or subcortical stroke. The Food and DrugAdministration has approved an Investigational DeviceExemption (IDE) for this feasibility study. This case reportpresents results from the �rst subject entered into thisrandomized clinical trial.

CASE REPORTA 65-year-old, right-handed male developed a subcor-tical cerebral infarction. A right hemiparesis was presentwith his right arm more severely affected than his leg. Hehad co-existing adult onset Diabetes Mellitus andhypercholesterolemia. Initially he was treated withphysical and occupational therapy that improved his

arm and leg function, but the improvement stabilized.Despite therapy, he was only able to extend his wristagainst gravity. There was no voluntary �nger �exion orextension.

Nineteen months after his stroke he was enrolled inthe clinical study after meeting extensive entrancecriteria. Some relevant baseline data were: arm Fugl–Meyer score 36/66, the (normalized) Stroke Impact ScaleHandicap was 35/100. An anatomic magnetic reso-nance imaging study (MRI) showed a sub-cortical infarctlateral to the mid-body of the lateral ventricle (Figure 1)and his functional MRI (fMRI) performed while extend-ing the right wrist at preset intervals localized the site ofactivity in the pre-central gyrus of the affected hemi-sphere (Figure 2).

After randomization to surgical treatment, a cranio-tomy �ap was created using neuronavigational tech-nique and sited over the region corresponding to thecenter of pre-central BOLD activity seen on fMRIidentifying the motor cortical representation of wrist�exion. An investigational epidural 3£3 plate gridelectrode array (Northstar Neuroscience Inc., Seattle,WA, USA) was implanted. Stimulation through selectiveelectrode contacts evoked contralateral �nger �exioncon�rming placement on the primary motor cortex. Thisalso con�rmed that direct cortical spinal projectionswere intact although the patient could not voluntarilycontrol �nger movement. The electrode lead wastunneled to a sub clavicular exit site and the craniotomy�ap replaced.

Three days after surgery the patient began an intensiveroutine of daily occupational therapy directed atimproving activities of daily living and involving the

Correspondence and reprint requests to: Jeffrey A. Brown, MD,Department of Neurological Surgery, Wayne State University Schoolof Medicine, 4160 John R. Suite 930, Detroit, MI 48201, USA.[jbrown@neurosurgery.wayne.edu] Accepted for publication June2003.

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paretic hand and arm. During these sessions aninvestigational external pulse generator was attachedto the electrode lead and worn in a chest harness, andsub-threshold cortical stimulation was delivered con-current with occupational therapy. At the end of eachdaily session, the pulse generator was turned off andremoved. During stimulation the pulse generator was setto deliver continuous stimulation at a rate of 50 Hz,pulse duration of 100 sec, and a current level of 4.5 mA.

During the three weeks of therapy, the patient showedimprovement in pincer movement of the thumb and �rst�nger, which he had not been able to do prior toelectrode implantation and stimulation. By the end ofthe three weeks, his arm Fugl–Meyer motor scale scorehad improved from the baseline value of 36 points (of atotal possible score of 66) to 46 at the one-week post-therapy follow-up visit. His normalized Stroke ImpactScale (SIS; for handicap) improved from a baseline levelof 35 (maximum possible score of 100), to a post-treatment level of 75. The normalized SIS strength scaleimproved from a baseline of 42 to 75 four weeks aftercessation of treatment. The occupational therapist andthe attending neurologist observed other changes thatcould not be objectively documented in outcomemeasures. For example, the patient’s upper extremity�exor posture gave way to a more natural posture,

although the Ashworth Spasticity Scale did not demon-strate any signi�cant change. The 9-Hole Pegboard Testwas also an outcome measure. There was no signi�cantchange in the pre- to post-therapy scores, because thepatient’s disability was too great to participate in thistask. At the end of therapy he could pick up a pencil andprint block letters and he could pick up a ball bearing.Both tasks were impossible before therapy one monthearlier. This study was primarily performed to evaluatethe safety of cortical stimulation to enhance motorrecovery after stroke. There were no adverse effectsrelated either to the surgery or to the cortical stimulation.

DISCUSSIONThis is a report of the �rst patient to be treated by aninvestigational restorative neurosurgical proceduredesigned to enhance recovery of the functional injurythat occurs after stroke. The study extends observationsmade of motor improvements during treatment of centralpain and information gained from pre-clinical studies(see companion papers in this issue) showing thatsubthreshold electrical stimulation of perilesion cortexconcurrent with behavioral training can lead to thereturn of a signi�cant portion of lost function. Thisappears to be due to neuroplasticity but the underlying

Figure 1: T1 weighted MRI demonstrating infarct just lateral to the mid-body of the lateral ventricle. This scan was taken19 months after the patient‘s stroke

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basis for this neuroplasticity is not completely under-stood. The pre-clinical data suggests that it may involveincreasing or facilitating the effectiveness of corticalprojections to the appropriate spinal segments.

These data from our �rst human subject indirectlysupport this neuroplasticity hypothesis. Although thepatient had no willful �nger function prior to therapy,the area targeted for stimulation corresponded to thepre-central gyrus involved with the only hand functionthe patient was capable of performing – wrist extension.This was �rst demonstrated by fMRI. What wasintriguing about this stimulation was that a brief trainof pulses delivered intra-operatively evoked individual�nger �exion, thus implying that the cortico–spinalprojection remained intact. The synaptic connectionsneeded to willfully execute movements via this �nalcommon pathway were either not intact before stimula-tion, or were incapable of initiating movement. It ishypothesized that the sub-threshold electrical stimula-tion at the time of occupational therapy may depolarizethe underlying neurons to a level that previously

ineffective pathways became capable of eliciting move-ment. As the synaptic circuits are reinforced bystructured rehabilitation, their ef�ciency improves,leading to the improved ability to �ex and extendotherwise paretic muscles.

Animal data also suggests that CS induces newdendrite formation4. New dendrites may form functionalsynapses leading to motor improvements. Primate androdent studies5 have shown that CS induces changes inthe motor cortical representation areas so that uninjuredareas of the motor cortex take on increased function ofthe damaged motor cortex. The anatomical and motorcortex representation area changes observed in animalsmay also occur in humans leading to enhanced recoveryof function.

It is interesting that this �rst patient had a subcorticalstroke. From a large series of patients treated with motorcortex stimulation for refractory pain, Katayama et al.6

reviewed the results of treatment of 50 patients with avariety of concomitant movement disorders. For many ofthese patients subcortical stroke was the presumed

Figure 2: fMRI images demonstrating four areas of activation as a result of a wrist extension paradigm during scanning.The largest area corresponds to the SMA, a small activation area exists just anterior to the pre-centralgyrus, a larger areain the posterior portion of the pre-central gyrus, and a smaller area in the parietal region

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etiology of both their pain and movement disorders. Afew of these patients also suffered hemiparesis as a resultof the lesions. Anecdotally, Katayama noted that severalof these patients’ paresis improved following CS for paincontrol. The clinical outcome of these patients wasprobably similar to our �rst patient in the study.

CONCLUSIONAlthough preliminary, the results presented here suggestthat there is the potential to enhance motor recoveryafter stroke that occurred months to years earlier.

ACKNOWLEDGEMENTSThis research is part of a feasibility study supported by NorthstarNeuroscience, Inc., Seattle, Washington, USA.

REFERENCES1 Tsubokawa T, Katayama Y, Yamamoto T, Hirayama T, Koyama S.

Chronic motor cortex stimulation in patients with thalamic pain.J Neurosurg 1993; 78: 393–401

2 Katayama Y, Fukaya C, Yamamoto T. Control of poststrokeinvoluntary and voluntary movement disorders with deep brain orepidural cortical stimulation. Stereotact Funct Neurosurg 1997; 69:73–79

3 Brown J. Guest Editorial. Neurol Res 2003; 25: 115–1174 Adkins DeAL, Jones TA. Cortical electrical stimulation combined

with rehabilitative training: Enhanced functional recovery anddendritic plasticity following focal cortical ischemia in rats. NeurolRes 2003; 25: this issue

5 Plautz EJ, Barby S, et al. Post-infarctcortical plasticityand behavioralrecovery using concurrent cortical stimulation and rehabilitativetraining: A feasibility study in primates. Neurol Res 2003; 25: 801–810

6 Katayama Y, Tsubokawa T, Yamamoto T. Chronic motor cortexstimulation for central deafferentation pain: Experience with bulbarpain secondary to Wallenberg syndrome. Stereotact Funct Neuro-surg 1994; 62: 295–299

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