- Email: [email protected]
Report of a delayed seizure after low frequency repetitive Transcranial Magnetic Stimulation in a chronic stroke patient
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Letters to the Editor / Clinical Neurophysiology 127 (2016) 1734–1756
Hina Sharma Department of Neurology, All India Institute of Medical Sciences, New Delhi, India Tamonud Modak Department of Psychiatry, All India Institute of Medical Sciences, New Delhi, India Available online 26 July 2015 1388-2457/Ó 2015 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved. http://dx.doi.org/10.1016/j.clinph.2015.06.033
Report of a delayed seizure after low frequency repetitive Transcranial Magnetic Stimulation in a chronic stroke patient
We report a seizure in a stroke patient 24 h after exposure to 1 Hz repetitive Transcranial Magnetic Stimulation (rTMS). This 56-year-old man (initials: BS) had suffered a right parietal stroke 8 months prior. MRI scan showed an ischemic lesion in the region of the right middle cerebral artery mainly involving the parieto-temporal areas. The neuropsychological evaluation three months after the stroke showed evidence of visual hemispatial neglect and extinction and he was enrolled in a research study where rTMS was used to relieve the symptoms of visual extinction. He met all inclusion criteria, had no risk factor for TMS, was not taking antiepileptic or epileptogenic drugs, and had never had a seizure. At the time of the enrolment in the study he was suffering from essential hypertension for which he was taking nebivolol and irbesartan; he was also treated with statins and acetylsalicylic acid. The study was three weeks long. During the first week we completed baseline behavioral testing, which consisted of computerized tasks and a complete neuropsychological evaluation that confirmed the presence of visual extinction deficits. In addition, we determined resting motor threshold (RMT) to set the intensity of TMS for the subsequent intervention sessions. RMT was defined as the minimum TMS intensity necessary to elicit a motor response on 5 out of 10 consecutive trials. Stimulation was performed using a 70 mm figure-8-coil connected to a Magstim Rapid2 (Magstim Co., UK), and his RMT was 74% of machine output intensity. During the second week he underwent 5 days of sham stimulation sessions followed, during the third week, by 5 days of daily active stimulation sessions. Stimulation was applied as 1-Hz rTMS and 90% RMT intensity over the intact left parietal cortex for 20 min (with the coil centered over the electrode location P3 identified using the 10/20 EEG measurement system). For the active stimulation condition, the coil was held with the handle pointing toward the back of the head and positioned perpendicularly to the stimulated region, while for the sham stimulation the coil was tilted at 90 deg, oriented perpendicular to the scalp, with the border of one wing placed against the subject’s scalp. On day 5 of each week he was re-tested on the computerized tests as well as on the neuropsychological tests battery. Moreover, he was screened for possible side effects and asked if he had headache, neck pain, scalp pain, hearing difficulties, trouble concentrating or mood changes. He reported none. On Saturday, 24 h after he completed the third week of the experimental protocol, thus following the week of active rTMS sessions, he experienced tonic and then clonic movements of the left
part of the body lasting about 4–5 min. There were no preceding symptoms, no nausea and no postictal confusion; he only reported to be exhausted. He was rapidly assisted by the doctor in charge and laid down. The episode ended spontaneously. There was no loss or alteration of consciousness. Postictally, detailed physical examination did not reveal any neurological or cardiovascular abnormal findings or symptoms. BS was started on the antiepileptic drug (levetiracetam) the same day. This was a non-standard clinical decision of the neurologist on call. Four days after the seizure he underwent electroencephalographic recording (EEG) that showed moderate voltage relative focal theta and delta slowing in the right hemisphere, with some low voltage sharply contoured waveforms consistent with probable spike waves noted maximally in the right posterior quadrant and centro-parietal regions. These EEG findings are consistent with likely focal dysfunction in those regions with underlying cortical irritability. To our knowledge this is the first report of a delayed seizure (24 h from the end of the treatment) following consecutive rTMS therapeutic sessions in a chronic stroke patient. Delayed seizures following single pulse TMS three and four weeks after stimulation were described by Kandler (1990) in two multiple sclerosis (MS) patients over a total of 108 patients. Given the prevalence of epileptic seizures in MS patients (1.1–4.5%) these cases were considered in the normal range. Figiel et al. (1998) also reported a major depression patient who developed a left motor seizure 6 h after 10 Hz rTMS stimulation. In this case the use of antidepressant might have increased the risk of seizures. In addition, one case has been reported of a subject suffering from chronic tinnitus who developed a seizure after one 580-pulses session of 1 Hz rTMS (Nowak et al., 2006), however the seizure in this latter case developed immediately after stimulation. Our patient experienced a focal, simple seizure, arising from the damaged right hemisphere, following a course of 1 Hz rTMS to the left, undamaged hemisphere. Following the stroke, our patient had an increased risk of seizures arising from the right hemisphere. The course of rTMS might have contributed to the seizure by suppressing activity in the intact hemisphere and interhemispherically promoting an increase in excitability in the damaged, right hemisphere (Agosta et al., 2014; Oliveri et al., 1999). Since the time interval between the end of the stimulation session and the seizure was about 24 h, we cannot completely rule out other causes for the ictal episode. It is however unlikely because, according to his medical record and from the patient’s report and he never had seizures before the study. In conclusion, we believe precautions should be taken even when unilateral stroke patients are enrolled in studies where low frequency stimulation is delivered over the undamaged hemisphere. We recommend that patients undergoing multiple rTMS sessions should be monitored up to 24 h after the end of the clinical/experimental trial. It is also worth to point out that notwithstanding the present report, the risk of low-frequency rTMS-induced seizures remains very low at the current state of knowledge. Conflict of interest None of the authors have potential conflicts of interest to be disclosed. References Agosta S, Herpich F, Miceli G, Ferraro F, Battelli L. Contralesional rTMS relieves visual extinction in chronic stroke patients. Neuropsychologia 2014;62: 269–76.
Letters to the Editor / Clinical Neurophysiology 127 (2016) 1734–1756 Figiel GS, Epstein C, McDonald WM, Amazon-Leece J, Figiel L, Saldivia A, Glover MD. The use of rapid-rate transcranial magnetic stimulation (rTMS) in refractory depressed patients. J Neuropsychiatry Clin Neurosci 1998;10:20–5. Kandler R. Safety of transcranial magnetic stimulation. Lancet 1990;335: 469–70. Nowak DA, Hoffmann U, Connemann BJ, Schonfeldt-Lecuona C. Epileptic seizure following 1 Hz repetitive transcranial magnetic stimulation. Clin Neurophysiol 2006;117:1631–3. Oliveri M, Rossini PM, Traversa R, Cicinelli P, Filippi MM, Pasqualetti P, Tomaiuolo F, Caltagirone C. Left frontal transcranial magnetic stimulation reduces contralesional extinction in patients with unilateral right brain damage. Brain 1999;122:1731–9.
Sara Agosta Center for Neuroscience and Cognitive Systems@UniTn, Istituto Italiano di Tecnologia, Corso Bettini 31, 38068 Rovereto (TN), Italy E-mail address: [email protected] Emanuela Galante Francesco Ferraro Neuro-motor Rehabilitation Unit, Neuroscience Department, Carlo Poma Hospital, via XXV Aprile 71, Bozzolo, Mantova, Italy Alvaro Pascual-Leone Berenson-Allen Center for Noninvasive Brain Stimulation and Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Ave, Boston, MA 02215, USA Joel Oster Department of Neurology, Lahey Clinic and Tufts University School of Medicine, Burlington, Boston, MA, USA Lorella Battelli Center for Neuroscience and Cognitive Systems@UniTn, Istituto Italiano di Tecnologia, Corso Bettini 31, 38068 Rovereto (TN), Italy Berenson-Allen Center for Noninvasive Brain Stimulation and Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Ave, Boston, MA 02215, USA Available online 7 August 2015 1388-2457/Ó 2015 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved. http://dx.doi.org/10.1016/j.clinph.2014.11.029
Letter in response to ‘‘High-frequency ultrasound in guiding needle insertion for microneurography’’ by Granata and colleagues
The recent letter by Granata and colleagues (2016) provides further evidence in support of ultrasound guidance for the insertion and placement of microneurography electrodes. The authors note the promise of this technique shown previously (Curry and Charkoudian, 2011) and address the previously overlooked details of microelectrode diameter and the optimal frequency of the ultrasound probe. Single-fibre microneurography is a notoriously difficult and low-yield technique with a steep learning curve. Ultrasound guidance could prove invaluable during this period, providing confidence for the novice microneurographer and reassurance for their participant. The use of ultrasound is designed to facilitate only the first phase of microneurography, the insertion and placement of the microelectrode. It cannot facilitate the identification of a stable site that permits recording or stimulation of a single axon without external fixation of the microelectrode, or the final data collection phase. The aim of combining
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microneurography and ultrasound is twofold: to reduce the time between microelectrode insertion and the initiation of data collection, and to minimise microelectrode movements within the test limb. The standard practice of microelectrode insertion has been detailed elsewhere for intraneural motor axon microstimulation (McNulty and Macefield, 2005). The initial insertion and placement of the microelectrode is similar regardless of the nature of the subsequent investigation. It is assumed that the microelectrode is within the epineurium once appropriate pulse synchronous responses are obtained at currents 650–100 lA using 0.1 ms pulse widths. An experienced operator can perform the final microelectrode positioning for single large-diameter afferent fibre recordings based on audio feedback of the neurogram in conjunction with external mechanical stimulation. Recordings of Ad, sympathetic and other C fibre activity can be identified and differentiated according to the responses to appropriate physiological, psychological, electrical or mechanical stimuli. In brief, microelectrode insertion begins with palpation of the nerve trunk before the location and course of the nerve are confirmed with percutaneous electrical stimulation, although palpation alone may be sufficient at some sites. This rarely takes more than 1–2 min in healthy subjects. The microelectrode is inserted at the site of the strongest response to stimulation, usually orthogonal to the skin surface. Positioning the microelectrode within the nerve trunk is relatively quick and easy for an experienced microneurographer, the more difficult and challenging aspect to the technique is finding a suitable and stable site for data collection. The site of insertion should not be altered to facilitate ultrasound guidance if this compromises the potential for stable recordings. The insertion site commonly used for microneurography of the median nerve in the upper arm is approximately 10 cm proximal to the elbow. Here the nerve lies deeper, on the medial aspect of the plane between the biceps brachii and the long head of the triceps muscle, affording a more stable site for productive recordings. The gross regional anatomy at this site may preclude the hyperacute angle of microelectrode insertion used by Granata and colleagues which was presumably used to facilitate ultrasound visualisation. In addition, the anatomical arrangement identified in their Fig. 1C is unusual with the brachial artery immediately anterior and superficial to the tendon of the biceps brachii muscle rather than its more typical location medial and slightly posterior to the biceps brachii muscle or its tendon. Finally, the authors suggest that ultrasound can help guide intrafascicular placement of the electrode tip. This is unclear from their Fig. 1A and the utility is doubtful due to the absence of any somatotopic arrangement within the median nerve at this level (see Sunderland, 1978). This is in stark contrast to the median nerve at the wrist where the afferent fibres arising from each hemi-digit are gathered in separate somatotopically organised fascicles. Granata and colleagues aimed to provide greater technical detail for the use of ultrasound imaging than that provided by Curry and Charkoudian (2011). In the latter work the ultrasound probe frequency was not provided in the text, but each figure legend specifies a 12 MHz rate that permits clear visualisation of the microelectrode in the peroneal nerve at the fibular head (see their Fig. 3). In contrast, Granata and colleagues found the microelectrode was visible only when an 18 MHz ultrasound frequency was used, with only tissue displacement visible using a 14 MHz probe. The disparity between studies could reflect differences between ultrasound systems and probes; device-specific operational settings including focus number and depth, and time gain compensation; the width of the probe (which neither study reports, but influences lateral spatial resolution); and operator skill.
Letters to the Editor / Clinical Neurophysiology 127 (2016) 1734–1756
Hina Sharma Department of Neurology, All India Institute of Medical Sciences, New Delhi, India Tamonud Modak Department of Psychiatry, All India Institute of Medical Sciences, New Delhi, India Available online 26 July 2015 1388-2457/Ó 2015 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved. http://dx.doi.org/10.1016/j.clinph.2015.06.033
Report of a delayed seizure after low frequency repetitive Transcranial Magnetic Stimulation in a chronic stroke patient
We report a seizure in a stroke patient 24 h after exposure to 1 Hz repetitive Transcranial Magnetic Stimulation (rTMS). This 56-year-old man (initials: BS) had suffered a right parietal stroke 8 months prior. MRI scan showed an ischemic lesion in the region of the right middle cerebral artery mainly involving the parieto-temporal areas. The neuropsychological evaluation three months after the stroke showed evidence of visual hemispatial neglect and extinction and he was enrolled in a research study where rTMS was used to relieve the symptoms of visual extinction. He met all inclusion criteria, had no risk factor for TMS, was not taking antiepileptic or epileptogenic drugs, and had never had a seizure. At the time of the enrolment in the study he was suffering from essential hypertension for which he was taking nebivolol and irbesartan; he was also treated with statins and acetylsalicylic acid. The study was three weeks long. During the first week we completed baseline behavioral testing, which consisted of computerized tasks and a complete neuropsychological evaluation that confirmed the presence of visual extinction deficits. In addition, we determined resting motor threshold (RMT) to set the intensity of TMS for the subsequent intervention sessions. RMT was defined as the minimum TMS intensity necessary to elicit a motor response on 5 out of 10 consecutive trials. Stimulation was performed using a 70 mm figure-8-coil connected to a Magstim Rapid2 (Magstim Co., UK), and his RMT was 74% of machine output intensity. During the second week he underwent 5 days of sham stimulation sessions followed, during the third week, by 5 days of daily active stimulation sessions. Stimulation was applied as 1-Hz rTMS and 90% RMT intensity over the intact left parietal cortex for 20 min (with the coil centered over the electrode location P3 identified using the 10/20 EEG measurement system). For the active stimulation condition, the coil was held with the handle pointing toward the back of the head and positioned perpendicularly to the stimulated region, while for the sham stimulation the coil was tilted at 90 deg, oriented perpendicular to the scalp, with the border of one wing placed against the subject’s scalp. On day 5 of each week he was re-tested on the computerized tests as well as on the neuropsychological tests battery. Moreover, he was screened for possible side effects and asked if he had headache, neck pain, scalp pain, hearing difficulties, trouble concentrating or mood changes. He reported none. On Saturday, 24 h after he completed the third week of the experimental protocol, thus following the week of active rTMS sessions, he experienced tonic and then clonic movements of the left
part of the body lasting about 4–5 min. There were no preceding symptoms, no nausea and no postictal confusion; he only reported to be exhausted. He was rapidly assisted by the doctor in charge and laid down. The episode ended spontaneously. There was no loss or alteration of consciousness. Postictally, detailed physical examination did not reveal any neurological or cardiovascular abnormal findings or symptoms. BS was started on the antiepileptic drug (levetiracetam) the same day. This was a non-standard clinical decision of the neurologist on call. Four days after the seizure he underwent electroencephalographic recording (EEG) that showed moderate voltage relative focal theta and delta slowing in the right hemisphere, with some low voltage sharply contoured waveforms consistent with probable spike waves noted maximally in the right posterior quadrant and centro-parietal regions. These EEG findings are consistent with likely focal dysfunction in those regions with underlying cortical irritability. To our knowledge this is the first report of a delayed seizure (24 h from the end of the treatment) following consecutive rTMS therapeutic sessions in a chronic stroke patient. Delayed seizures following single pulse TMS three and four weeks after stimulation were described by Kandler (1990) in two multiple sclerosis (MS) patients over a total of 108 patients. Given the prevalence of epileptic seizures in MS patients (1.1–4.5%) these cases were considered in the normal range. Figiel et al. (1998) also reported a major depression patient who developed a left motor seizure 6 h after 10 Hz rTMS stimulation. In this case the use of antidepressant might have increased the risk of seizures. In addition, one case has been reported of a subject suffering from chronic tinnitus who developed a seizure after one 580-pulses session of 1 Hz rTMS (Nowak et al., 2006), however the seizure in this latter case developed immediately after stimulation. Our patient experienced a focal, simple seizure, arising from the damaged right hemisphere, following a course of 1 Hz rTMS to the left, undamaged hemisphere. Following the stroke, our patient had an increased risk of seizures arising from the right hemisphere. The course of rTMS might have contributed to the seizure by suppressing activity in the intact hemisphere and interhemispherically promoting an increase in excitability in the damaged, right hemisphere (Agosta et al., 2014; Oliveri et al., 1999). Since the time interval between the end of the stimulation session and the seizure was about 24 h, we cannot completely rule out other causes for the ictal episode. It is however unlikely because, according to his medical record and from the patient’s report and he never had seizures before the study. In conclusion, we believe precautions should be taken even when unilateral stroke patients are enrolled in studies where low frequency stimulation is delivered over the undamaged hemisphere. We recommend that patients undergoing multiple rTMS sessions should be monitored up to 24 h after the end of the clinical/experimental trial. It is also worth to point out that notwithstanding the present report, the risk of low-frequency rTMS-induced seizures remains very low at the current state of knowledge. Conflict of interest None of the authors have potential conflicts of interest to be disclosed. References Agosta S, Herpich F, Miceli G, Ferraro F, Battelli L. Contralesional rTMS relieves visual extinction in chronic stroke patients. Neuropsychologia 2014;62: 269–76.
Letters to the Editor / Clinical Neurophysiology 127 (2016) 1734–1756 Figiel GS, Epstein C, McDonald WM, Amazon-Leece J, Figiel L, Saldivia A, Glover MD. The use of rapid-rate transcranial magnetic stimulation (rTMS) in refractory depressed patients. J Neuropsychiatry Clin Neurosci 1998;10:20–5. Kandler R. Safety of transcranial magnetic stimulation. Lancet 1990;335: 469–70. Nowak DA, Hoffmann U, Connemann BJ, Schonfeldt-Lecuona C. Epileptic seizure following 1 Hz repetitive transcranial magnetic stimulation. Clin Neurophysiol 2006;117:1631–3. Oliveri M, Rossini PM, Traversa R, Cicinelli P, Filippi MM, Pasqualetti P, Tomaiuolo F, Caltagirone C. Left frontal transcranial magnetic stimulation reduces contralesional extinction in patients with unilateral right brain damage. Brain 1999;122:1731–9.
Sara Agosta Center for Neuroscience and Cognitive Systems@UniTn, Istituto Italiano di Tecnologia, Corso Bettini 31, 38068 Rovereto (TN), Italy E-mail address: [email protected] Emanuela Galante Francesco Ferraro Neuro-motor Rehabilitation Unit, Neuroscience Department, Carlo Poma Hospital, via XXV Aprile 71, Bozzolo, Mantova, Italy Alvaro Pascual-Leone Berenson-Allen Center for Noninvasive Brain Stimulation and Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Ave, Boston, MA 02215, USA Joel Oster Department of Neurology, Lahey Clinic and Tufts University School of Medicine, Burlington, Boston, MA, USA Lorella Battelli Center for Neuroscience and Cognitive Systems@UniTn, Istituto Italiano di Tecnologia, Corso Bettini 31, 38068 Rovereto (TN), Italy Berenson-Allen Center for Noninvasive Brain Stimulation and Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Ave, Boston, MA 02215, USA Available online 7 August 2015 1388-2457/Ó 2015 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved. http://dx.doi.org/10.1016/j.clinph.2014.11.029
Letter in response to ‘‘High-frequency ultrasound in guiding needle insertion for microneurography’’ by Granata and colleagues
The recent letter by Granata and colleagues (2016) provides further evidence in support of ultrasound guidance for the insertion and placement of microneurography electrodes. The authors note the promise of this technique shown previously (Curry and Charkoudian, 2011) and address the previously overlooked details of microelectrode diameter and the optimal frequency of the ultrasound probe. Single-fibre microneurography is a notoriously difficult and low-yield technique with a steep learning curve. Ultrasound guidance could prove invaluable during this period, providing confidence for the novice microneurographer and reassurance for their participant. The use of ultrasound is designed to facilitate only the first phase of microneurography, the insertion and placement of the microelectrode. It cannot facilitate the identification of a stable site that permits recording or stimulation of a single axon without external fixation of the microelectrode, or the final data collection phase. The aim of combining
1737
microneurography and ultrasound is twofold: to reduce the time between microelectrode insertion and the initiation of data collection, and to minimise microelectrode movements within the test limb. The standard practice of microelectrode insertion has been detailed elsewhere for intraneural motor axon microstimulation (McNulty and Macefield, 2005). The initial insertion and placement of the microelectrode is similar regardless of the nature of the subsequent investigation. It is assumed that the microelectrode is within the epineurium once appropriate pulse synchronous responses are obtained at currents 650–100 lA using 0.1 ms pulse widths. An experienced operator can perform the final microelectrode positioning for single large-diameter afferent fibre recordings based on audio feedback of the neurogram in conjunction with external mechanical stimulation. Recordings of Ad, sympathetic and other C fibre activity can be identified and differentiated according to the responses to appropriate physiological, psychological, electrical or mechanical stimuli. In brief, microelectrode insertion begins with palpation of the nerve trunk before the location and course of the nerve are confirmed with percutaneous electrical stimulation, although palpation alone may be sufficient at some sites. This rarely takes more than 1–2 min in healthy subjects. The microelectrode is inserted at the site of the strongest response to stimulation, usually orthogonal to the skin surface. Positioning the microelectrode within the nerve trunk is relatively quick and easy for an experienced microneurographer, the more difficult and challenging aspect to the technique is finding a suitable and stable site for data collection. The site of insertion should not be altered to facilitate ultrasound guidance if this compromises the potential for stable recordings. The insertion site commonly used for microneurography of the median nerve in the upper arm is approximately 10 cm proximal to the elbow. Here the nerve lies deeper, on the medial aspect of the plane between the biceps brachii and the long head of the triceps muscle, affording a more stable site for productive recordings. The gross regional anatomy at this site may preclude the hyperacute angle of microelectrode insertion used by Granata and colleagues which was presumably used to facilitate ultrasound visualisation. In addition, the anatomical arrangement identified in their Fig. 1C is unusual with the brachial artery immediately anterior and superficial to the tendon of the biceps brachii muscle rather than its more typical location medial and slightly posterior to the biceps brachii muscle or its tendon. Finally, the authors suggest that ultrasound can help guide intrafascicular placement of the electrode tip. This is unclear from their Fig. 1A and the utility is doubtful due to the absence of any somatotopic arrangement within the median nerve at this level (see Sunderland, 1978). This is in stark contrast to the median nerve at the wrist where the afferent fibres arising from each hemi-digit are gathered in separate somatotopically organised fascicles. Granata and colleagues aimed to provide greater technical detail for the use of ultrasound imaging than that provided by Curry and Charkoudian (2011). In the latter work the ultrasound probe frequency was not provided in the text, but each figure legend specifies a 12 MHz rate that permits clear visualisation of the microelectrode in the peroneal nerve at the fibular head (see their Fig. 3). In contrast, Granata and colleagues found the microelectrode was visible only when an 18 MHz ultrasound frequency was used, with only tissue displacement visible using a 14 MHz probe. The disparity between studies could reflect differences between ultrasound systems and probes; device-specific operational settings including focus number and depth, and time gain compensation; the width of the probe (which neither study reports, but influences lateral spatial resolution); and operator skill.