Letters to the Editor / Clinical Neurophysiology 125 (2014) 1065–1074
1067
Palatal motor evoked potentials: Description of a new technique
nerve (Benecke et al., 1988; Cruccu et al., 1990; Rösler et al., 1989; Muellbacher et al., 1994). Herein we describe an original technique to record MEPs at the level of the palate, which could be useful for the study of swallowing disorders.
1. Introduction
2. Methods
Motor evoked potentials (MEPs) to transcranial magnetic stimulation are usually recorded in limb muscles (Chen et al., 2008), but MEP recording techniques have been published for various head muscles innervated by the trigeminal, facial, or hypoglossal
In 15 healthy subjects (11 men), aged from 22 to 45 years (mean: 30 years), palatal MEPs were recorded (bandpass filter 20 Hz–2 kHz) using a pair of pre-gelled disposable adhesive surface electrodes (ref 9013S0242, Natus, Skovlunde, Denmark). After
Fig. 1. (A) Placement of a pair of pre-gelled disposable adhesive surface electrodes at the midline of the palatal dimple to record motor evoked potentials. (B) Motor evoked potentials recorded at the midline of the palate to peripheral and cortical magnetic stimulation. (C and D) Illustrative cases of motor evoked potentials recorded on the lateral (right or left) aspects of the tongue and the midline palate in patients with dysphagia due to altered motor control caused by amyotrophic lateral sclerosis (ALS, patient 1) and left capsular stroke (patient 2).
1068
Letters to the Editor / Clinical Neurophysiology 125 (2014) 1065–1074
Table 1 Mean (SD) amplitude and latency values and range of values of the motor evoked potentials recorded on the midline of the palate to peripheral and cortical magnetic stimulations.
Stimulation Peripheral Cortical Peripheral Cortical
Mean (SD)
Min–Max
Amplitude (mV) 0.2 (0.2) 0.9 (0.3)
0.1–1.0 0.4–1.8
Latency (ms) 4.0 (0.4) 9.5 (1.3) Central conduction time (ms) 5.5 (1.2)
3.3–4.9 7.3–12.7 3.3–8.3
having gently dried the palate, the electrodes were positioned 2 cm apart at the midline of the palatal dimple, the active electrode being anterior (Fig. 1). Motor cortex was stimulated with a circular coil (90 mm diameter) connected to a monophasic magnetic stimulator (Magstim 200, Magstim Co., Carmarthenshire, UK). Palatal MEPs of maximal amplitude were obtained by positioning the centre of the coil 2–6 cm lateral and 1–4 cm anterior to the vertex, with coil handle pointing backwards, and by asking the subject to firmly apply the tongue against the palate. The left hemisphere was stimulated by placing the coil to induce clockwise current flow in the brain and the coil positioning was reversed to preferentially activate the right hemisphere. Peripheral stimulation of the cranial nerves innervating the palate was performed by positioning the circular coil over the parieto-occipital region (the bottom of the coil overlying the mastoid, the handle pointing antero-laterally). In four subjects, the electromyographic crosstalk between head muscles was studied by performing focal cortical stimulation with a figure-of-eight coil and by recording MEPs concomitantly in palatal muscles and in orbicularis oris, masseter, or tongue muscles, according to previously described methods (Cruccu et al., 1990; Muellbacher et al., 1994; Guggisberg et al., 2001). Finally, the diagnostic value of palatal MEPs was illustrated by two clinical cases: a 78-year woman (patient 1) who had dysphagia for a few months in the context of definite amyotrophic lateral sclerosis (ALS); a 38-year man (patient 2) who had dysphagia and right hemiparesis secondary to an ischemic infarct, which occurred three days before the investigation and located in the posterior limb of the left internal capsule. 3. Results Palatal MEP amplitude and latency values are presented in Table 1 and typical responses to peripheral and cortical magnetic stimulation are shown in Fig. 1. Reliable MEPs were obtained at relatively low intensity for ‘‘peripheral’’ stimulation (30–35% of maximal stimulator output), while ‘‘cortical’’ MEPs required higher stimulation intensity (50–80% of maximal stimulator output) but were of greater amplitude than ‘‘peripheral’’ MEPs. Palatal MEPs were selectively recorded without crosstalk from facial or lingual muscles to focal cortical stimulation, at a scalp site more antero-lateral than that producing selective MEPs in the orbicularis oris muscle for example. A significant but incomplete overlap of the cortical representation of palatal, facial, masseter, and tongue muscles was observed. The two illustrative clinical cases were characterized by altered palatal MEPs with normal lingual MEPs to cortical stimulation, proving the specificity and diagnostic sensitivity of palatal MEPs in the context of dysphagia (Fig. 1). In addition, palatal MEPs showed that the disease process affected upper rather than lower motor neurons in the oral region in patient 1 and that a lateralized palatal paresis resulted from contralateral left hemispheric stroke in patient 2.
4. Discussion Herein we describe for the first time, a simple, noninvasive, and reliable technique for assessing motor cortical projections to the palate. The technique was well tolerated and produced well individualized and reproducible MEPs in all subjects. In particular, the pre-gelled disposable adhesive surface electrodes we used really guarantee stable recordings over time without detachment, despite the effect of saliva. Palatal MEPs were easily obtained in response to non-focal cortical stimulation using a circular coil. Focal cortical stimulation with a figure-of-eight coil showed the possibility to record palatal MEPs selectively without any crosstalk from facial or lingual muscles. The latency and central conduction time of palatal MEPs had the same range of values and variability as previously reported for facial and lingual MEPs (Rösler et al., 1989; Muellbacher et al., 1994). As also previously described for lingual MEPs (Muellbacher et al., 1994), peripheral stimulation was submaximal and produced smaller MEPs than cortical stimulation. Electrical nerve stimulation should be used to achieve supramaximal stimulation but was unsuccessful for palatal recordings, probably because palatal muscles are innervated by multiple cranial nerves including the facial, glossopharyngeal, and vagus nerves (Broomhead, 1951; Prodvinec, 1952; Nishio et al., 1976). Facial electrical stimulation was not able to recruit simultaneously these multiple nerve branches. The two clinical cases presented in this paper support the diagnostic value of our technique in the investigation of dysphagia. Motor control of swallowing was previously studied by recording MEPs either superficially in the submental, suprahyoid (mylohyoid–stylohyoid–geniohyoid–digastricus) muscle complex or invasively in the pharyngeal constrictor muscles using ring electrodes placed onto a swallowed catheter (Hamdy et al., 1997; PlowmanPrine et al., 2008; Doeltgen et al., 2009). Palatal and submental MEP recordings are clearly easier to perform than pharyngeal MEPs and could be complementary to study disorders affecting the oral or pharyngeal phases of swallowing such as stroke and motor neuron disease. In particular, recording palatal MEPs could help: (i) predict recovery from post-stroke dysphagia according to their presence or absence in the acute/postacute post-stroke phase and understand the underlying mechanisms of motor function recovery, as previously described for limb MEPs (Lefaucheur, 2006; Talelli et al., 2006; Stinear, 2010); (ii) give evidence for upper or lower motor neuron involvement in ALS patients with bulbar symptoms. The perspectives opened by palatal MEP recordings remain to be confirmed in further studies. Conflict of interest statement The authors report no conflict of interest related to this work. References Benecke R, Meyer BU, Schönle P, Conrad B. Transcranial magnetic stimulation of the human brain: responses in muscles supplied by cranial nerves. Exp Brain Res 1988;71:623–32. Broomhead IW. The nerve supply of the muscles of the soft palate. Brit J Plast Surg 1951;4:1–5. Chen R, Cros D, Curra A, Di Lazzaro V, Lefaucheur JP, Magistris MR, et al. The clinical diagnostic utility of transcranial magnetic stimulation: report of an IFCN committee. Clin Neurophysiol 2008;119:504–32. Doeltgen SH, Ridding MC, O’Beirne GA, Dalrymple-Alford J, Huckabee ML. Testretest reliability of motor evoked potentials (MEPs) at the submental muscle group during volitional swallowing. J Neurosci Methods 2009;178:134–7. Cruccu G, Berardelli A, Inghilleri M, Manfredi M. Corticobulbar projections to upper and lower facial motoneurons. A study by magnetic transcranial stimulation in man. Neurosci Lett 1990;117:68–73. Guggisberg AG, Dubach P, Hess CW, Wüthrich C, Mathis J. Motor evoked potentials from masseter muscle induced by transcranial magnetic stimulation of the pyramidal tract: the importance of coil orientation. Clin Neurophysiol 2001;112:2312–9.
1069
Letters to the Editor / Clinical Neurophysiology 125 (2014) 1065–1074 Hamdy S, Aziz Q, Rothwell JC, Hobson A, Barlow J, Thompson DG. Cranial nerve modulation of human cortical swallowing motor pathways. Am J Physiol 1997;272:G802–8. Lefaucheur JP. Stroke recovery can be enhanced by using repetitive transcranial magnetic stimulation (rTMS). Neurophysiol Clin 2006;36:105–15. Muellbacher W, Mathis J, Hess CW. Electrophysiological assessment of central and peripheral motor routes to the lingual muscles. J Neurol Neurosurg Psychiatry 1994;57:309–15. Nishio J, Matsuya T, Machida J, Miyazaki T. The motor supply of the velopharyngeal muscles. Cleft Palate J 1976;13:20–30. Plowman-Prine EK, Triggs WJ, Malcolm MP, Rosenbek JC. Reliability of transcranial magnetic stimulation for mapping swallowing musculature in the human motor cortex. Clin Neurophysiol 2008;119:2298–303. Prodvinec S. The physiology and pathology of the soft palate. J Laryngol 1952;66:452–61. Rösler KM, Hess CW, Schmid UD. Investigation of facial motor pathways by electrical and magnetic stimulation: sites and mechanisms of excitation. J Neurol Neurosurg Psychiatry 1989;52:1149–56. Stinear C. Prediction of recovery of motor function after stroke. Lancet Neurol 2010;9:1228–32. Talelli P, Greenwood RJ, Rothwell JC. Arm function after stroke: neurophysiological correlates and recovery mechanisms assessed by transcranial magnetic stimulation. Clin Neurophysiol 2006;117:1641–59.
Rechdi Ahdab EA 4391, Excitabilité Nerveuse et Thérapeutique, Université Paris-Est-Créteil, Créteil, France Service de Physiologie – Explorations Fonctionnelles, Hôpital Henri Mondor, Assistance Publique – Hôpitaux de Paris, Créteil, France Neuroscience Department, University Medical Center Rizk Hospital, Beirut, Lebanon Samar S. Ayache EA 4391, Excitabilité Nerveuse et Thérapeutique, Université Paris-Est-Créteil, Créteil, France Service de Physiologie – Explorations Fonctionnelles, Hôpital Henri Mondor, Assistance Publique – Hôpitaux de Paris, Créteil, France Wassim H. Farhat EA 4391, Excitabilité Nerveuse et Thérapeutique, Université Paris-Est-Créteil, Créteil, France Service de Neurologie, Hôpital Henri Mondor, Assistance Publique – Hôpitaux de Paris, Créteil, France Philippe Kerschen EA 4391, Excitabilité Nerveuse et Thérapeutique, Université Paris-Est-Créteil, Créteil, France Service de Neurologie, Hôpital Henri Mondor, Assistance Publique – Hôpitaux de Paris, Créteil, France Jean-Pascal Lefaucheur EA 4391, Excitabilité Nerveuse et Thérapeutique, Université Paris-Est-Créteil, Créteil, France Service de Physiologie – Explorations Fonctionnelles, Hôpital Henri Mondor, Assistance Publique – Hôpitaux de Paris, 51 avenue de Lattre de Tassigny, 94010 Créteil, France Tel.: +33 1 4981 2694; fax: +33 1 4981 4660. E-mail address: [email protected] (J.-P. Lefaucheur).
Available online 22 December 2013 1388-2457/$36.00 Ó 2014 Published by Elsevier Ireland Ltd. on behalf of International Federation of Clinical Neurophysiology. doi:http://dx.doi.org/10.1016/j.clinph.2013.08.029
Unusual case of paroxysmal sympathetic hyperactivity in a patient with leukemia
A 53 year old female patient with history of therapy-related acute myeloid leukemia after treatment for ovarian cancer presented to MD Anderson Cancer Center, Houston, TX, USA, with acute recurrent episodes of staring spells and jerky movements of the upper extremities accompanied by elevations in blood pressure (systolic blood pressure range: 140–190 mm Hg), hyperthermia (range: 38–39 degree Celsius), tachycardia (range: 110–160 beats per minute), and tachypnea (range: 20–28 breath per minute). Symptoms started two days prior to her admission and lasted between 5–30 min and occurred 2–4 times per day. Initial neurologic examination revealed altered mental status; confusion. Blood and urine cultures, serum chemistries, and paraneoplastic panel were normal. Lumbar puncture revealed normal opening pressure. CSF glucose, protein, cell count, cytology and infectious work up were negative. Transcranial Doppler and brain MRI and MRV were unremarkable. MRI studies were acquired on 1.5 Tesla scanners and multiple sequences were applied: Sagittal T1, axial T1 and T2, ADC, DWI, axial FLAIR, and T-1 post contrast. Continuous video electroencephalography (cVEEG) revealed brief staring spells, head bobbing, and bilateral upper extremity jerking activity with no significant EEG abnormalities other than generalized slowing and high amplitude EMG artifact (see Supplementary Movie S1; Fig. 1A and B). Use of high frequency filter and review of the central regions failed to demonstrate any obvious epileptiform activity. Despite therapeutic doses of intravenous (IV) levetiracetam, phenytoin, and diazepam, the episodic abnormal posturing didn’t abate. The lack of response to multiple anti-epileptic drugs (AEDs) and cVEEG analysis led to the diagnosis of paroxysmal sympathetic hyperactivity (PSH). IV Morphine sulfate (2 mg every 4 h) successfully restored the patient’s vital signs to normal with cessation of the abnormal movements. Two days after initial presentation, the patient was weaned off of morphine because she was no longer having vital sign abnormalities and abnormal posturing. Patient received a total dose of 28 mg of morphine sulfate and there were no relapses on follow-ups. PSH is characterized by marked agitation, episodic hypertension, diaphoresis, hyperthermia, tachycardia, tachypnea and abnormal posturing. In 1929, Wilder Penfield described a patient with diaphoresis, pupillary dilation, hypertension, and shivering associated with a tumor at the foramen of Monro and coined the term ‘‘diencepahlic autonomic epilepsy’’ (Penfield, 1929). Since then, various labels have been applied to this phenomenon including paroxysmal autonomic instability with dystonia, hypothalamicmidbrain dysregulation syndrome, hyperpyrexia associated with sustained muscle contractions, dysautonomia, sympathetic storms, paroxysmal sympathetic storms, diencephalic seizures, and diencephalic epilepsy (Blackman et al., 2004; Boeve et al., 1998). The constellation of episodic hyperadrenergic signs, abnormal posturing, EEG findings, and response to morphine sulfate in our patient is consistent with PSH as described in the contemporary literature (Blackman et al., 2004; Perkes et al., 2010). The frequency of PSH is not known, however, traumatic and/or non-traumatic brain injuries account for most cases (Perkes
1067
Palatal motor evoked potentials: Description of a new technique
nerve (Benecke et al., 1988; Cruccu et al., 1990; Rösler et al., 1989; Muellbacher et al., 1994). Herein we describe an original technique to record MEPs at the level of the palate, which could be useful for the study of swallowing disorders.
1. Introduction
2. Methods
Motor evoked potentials (MEPs) to transcranial magnetic stimulation are usually recorded in limb muscles (Chen et al., 2008), but MEP recording techniques have been published for various head muscles innervated by the trigeminal, facial, or hypoglossal
In 15 healthy subjects (11 men), aged from 22 to 45 years (mean: 30 years), palatal MEPs were recorded (bandpass filter 20 Hz–2 kHz) using a pair of pre-gelled disposable adhesive surface electrodes (ref 9013S0242, Natus, Skovlunde, Denmark). After
Fig. 1. (A) Placement of a pair of pre-gelled disposable adhesive surface electrodes at the midline of the palatal dimple to record motor evoked potentials. (B) Motor evoked potentials recorded at the midline of the palate to peripheral and cortical magnetic stimulation. (C and D) Illustrative cases of motor evoked potentials recorded on the lateral (right or left) aspects of the tongue and the midline palate in patients with dysphagia due to altered motor control caused by amyotrophic lateral sclerosis (ALS, patient 1) and left capsular stroke (patient 2).
1068
Letters to the Editor / Clinical Neurophysiology 125 (2014) 1065–1074
Table 1 Mean (SD) amplitude and latency values and range of values of the motor evoked potentials recorded on the midline of the palate to peripheral and cortical magnetic stimulations.
Stimulation Peripheral Cortical Peripheral Cortical
Mean (SD)
Min–Max
Amplitude (mV) 0.2 (0.2) 0.9 (0.3)
0.1–1.0 0.4–1.8
Latency (ms) 4.0 (0.4) 9.5 (1.3) Central conduction time (ms) 5.5 (1.2)
3.3–4.9 7.3–12.7 3.3–8.3
having gently dried the palate, the electrodes were positioned 2 cm apart at the midline of the palatal dimple, the active electrode being anterior (Fig. 1). Motor cortex was stimulated with a circular coil (90 mm diameter) connected to a monophasic magnetic stimulator (Magstim 200, Magstim Co., Carmarthenshire, UK). Palatal MEPs of maximal amplitude were obtained by positioning the centre of the coil 2–6 cm lateral and 1–4 cm anterior to the vertex, with coil handle pointing backwards, and by asking the subject to firmly apply the tongue against the palate. The left hemisphere was stimulated by placing the coil to induce clockwise current flow in the brain and the coil positioning was reversed to preferentially activate the right hemisphere. Peripheral stimulation of the cranial nerves innervating the palate was performed by positioning the circular coil over the parieto-occipital region (the bottom of the coil overlying the mastoid, the handle pointing antero-laterally). In four subjects, the electromyographic crosstalk between head muscles was studied by performing focal cortical stimulation with a figure-of-eight coil and by recording MEPs concomitantly in palatal muscles and in orbicularis oris, masseter, or tongue muscles, according to previously described methods (Cruccu et al., 1990; Muellbacher et al., 1994; Guggisberg et al., 2001). Finally, the diagnostic value of palatal MEPs was illustrated by two clinical cases: a 78-year woman (patient 1) who had dysphagia for a few months in the context of definite amyotrophic lateral sclerosis (ALS); a 38-year man (patient 2) who had dysphagia and right hemiparesis secondary to an ischemic infarct, which occurred three days before the investigation and located in the posterior limb of the left internal capsule. 3. Results Palatal MEP amplitude and latency values are presented in Table 1 and typical responses to peripheral and cortical magnetic stimulation are shown in Fig. 1. Reliable MEPs were obtained at relatively low intensity for ‘‘peripheral’’ stimulation (30–35% of maximal stimulator output), while ‘‘cortical’’ MEPs required higher stimulation intensity (50–80% of maximal stimulator output) but were of greater amplitude than ‘‘peripheral’’ MEPs. Palatal MEPs were selectively recorded without crosstalk from facial or lingual muscles to focal cortical stimulation, at a scalp site more antero-lateral than that producing selective MEPs in the orbicularis oris muscle for example. A significant but incomplete overlap of the cortical representation of palatal, facial, masseter, and tongue muscles was observed. The two illustrative clinical cases were characterized by altered palatal MEPs with normal lingual MEPs to cortical stimulation, proving the specificity and diagnostic sensitivity of palatal MEPs in the context of dysphagia (Fig. 1). In addition, palatal MEPs showed that the disease process affected upper rather than lower motor neurons in the oral region in patient 1 and that a lateralized palatal paresis resulted from contralateral left hemispheric stroke in patient 2.
4. Discussion Herein we describe for the first time, a simple, noninvasive, and reliable technique for assessing motor cortical projections to the palate. The technique was well tolerated and produced well individualized and reproducible MEPs in all subjects. In particular, the pre-gelled disposable adhesive surface electrodes we used really guarantee stable recordings over time without detachment, despite the effect of saliva. Palatal MEPs were easily obtained in response to non-focal cortical stimulation using a circular coil. Focal cortical stimulation with a figure-of-eight coil showed the possibility to record palatal MEPs selectively without any crosstalk from facial or lingual muscles. The latency and central conduction time of palatal MEPs had the same range of values and variability as previously reported for facial and lingual MEPs (Rösler et al., 1989; Muellbacher et al., 1994). As also previously described for lingual MEPs (Muellbacher et al., 1994), peripheral stimulation was submaximal and produced smaller MEPs than cortical stimulation. Electrical nerve stimulation should be used to achieve supramaximal stimulation but was unsuccessful for palatal recordings, probably because palatal muscles are innervated by multiple cranial nerves including the facial, glossopharyngeal, and vagus nerves (Broomhead, 1951; Prodvinec, 1952; Nishio et al., 1976). Facial electrical stimulation was not able to recruit simultaneously these multiple nerve branches. The two clinical cases presented in this paper support the diagnostic value of our technique in the investigation of dysphagia. Motor control of swallowing was previously studied by recording MEPs either superficially in the submental, suprahyoid (mylohyoid–stylohyoid–geniohyoid–digastricus) muscle complex or invasively in the pharyngeal constrictor muscles using ring electrodes placed onto a swallowed catheter (Hamdy et al., 1997; PlowmanPrine et al., 2008; Doeltgen et al., 2009). Palatal and submental MEP recordings are clearly easier to perform than pharyngeal MEPs and could be complementary to study disorders affecting the oral or pharyngeal phases of swallowing such as stroke and motor neuron disease. In particular, recording palatal MEPs could help: (i) predict recovery from post-stroke dysphagia according to their presence or absence in the acute/postacute post-stroke phase and understand the underlying mechanisms of motor function recovery, as previously described for limb MEPs (Lefaucheur, 2006; Talelli et al., 2006; Stinear, 2010); (ii) give evidence for upper or lower motor neuron involvement in ALS patients with bulbar symptoms. The perspectives opened by palatal MEP recordings remain to be confirmed in further studies. Conflict of interest statement The authors report no conflict of interest related to this work. References Benecke R, Meyer BU, Schönle P, Conrad B. Transcranial magnetic stimulation of the human brain: responses in muscles supplied by cranial nerves. Exp Brain Res 1988;71:623–32. Broomhead IW. The nerve supply of the muscles of the soft palate. Brit J Plast Surg 1951;4:1–5. Chen R, Cros D, Curra A, Di Lazzaro V, Lefaucheur JP, Magistris MR, et al. The clinical diagnostic utility of transcranial magnetic stimulation: report of an IFCN committee. Clin Neurophysiol 2008;119:504–32. Doeltgen SH, Ridding MC, O’Beirne GA, Dalrymple-Alford J, Huckabee ML. Testretest reliability of motor evoked potentials (MEPs) at the submental muscle group during volitional swallowing. J Neurosci Methods 2009;178:134–7. Cruccu G, Berardelli A, Inghilleri M, Manfredi M. Corticobulbar projections to upper and lower facial motoneurons. A study by magnetic transcranial stimulation in man. Neurosci Lett 1990;117:68–73. Guggisberg AG, Dubach P, Hess CW, Wüthrich C, Mathis J. Motor evoked potentials from masseter muscle induced by transcranial magnetic stimulation of the pyramidal tract: the importance of coil orientation. Clin Neurophysiol 2001;112:2312–9.
1069
Letters to the Editor / Clinical Neurophysiology 125 (2014) 1065–1074 Hamdy S, Aziz Q, Rothwell JC, Hobson A, Barlow J, Thompson DG. Cranial nerve modulation of human cortical swallowing motor pathways. Am J Physiol 1997;272:G802–8. Lefaucheur JP. Stroke recovery can be enhanced by using repetitive transcranial magnetic stimulation (rTMS). Neurophysiol Clin 2006;36:105–15. Muellbacher W, Mathis J, Hess CW. Electrophysiological assessment of central and peripheral motor routes to the lingual muscles. J Neurol Neurosurg Psychiatry 1994;57:309–15. Nishio J, Matsuya T, Machida J, Miyazaki T. The motor supply of the velopharyngeal muscles. Cleft Palate J 1976;13:20–30. Plowman-Prine EK, Triggs WJ, Malcolm MP, Rosenbek JC. Reliability of transcranial magnetic stimulation for mapping swallowing musculature in the human motor cortex. Clin Neurophysiol 2008;119:2298–303. Prodvinec S. The physiology and pathology of the soft palate. J Laryngol 1952;66:452–61. Rösler KM, Hess CW, Schmid UD. Investigation of facial motor pathways by electrical and magnetic stimulation: sites and mechanisms of excitation. J Neurol Neurosurg Psychiatry 1989;52:1149–56. Stinear C. Prediction of recovery of motor function after stroke. Lancet Neurol 2010;9:1228–32. Talelli P, Greenwood RJ, Rothwell JC. Arm function after stroke: neurophysiological correlates and recovery mechanisms assessed by transcranial magnetic stimulation. Clin Neurophysiol 2006;117:1641–59.
Rechdi Ahdab EA 4391, Excitabilité Nerveuse et Thérapeutique, Université Paris-Est-Créteil, Créteil, France Service de Physiologie – Explorations Fonctionnelles, Hôpital Henri Mondor, Assistance Publique – Hôpitaux de Paris, Créteil, France Neuroscience Department, University Medical Center Rizk Hospital, Beirut, Lebanon Samar S. Ayache EA 4391, Excitabilité Nerveuse et Thérapeutique, Université Paris-Est-Créteil, Créteil, France Service de Physiologie – Explorations Fonctionnelles, Hôpital Henri Mondor, Assistance Publique – Hôpitaux de Paris, Créteil, France Wassim H. Farhat EA 4391, Excitabilité Nerveuse et Thérapeutique, Université Paris-Est-Créteil, Créteil, France Service de Neurologie, Hôpital Henri Mondor, Assistance Publique – Hôpitaux de Paris, Créteil, France Philippe Kerschen EA 4391, Excitabilité Nerveuse et Thérapeutique, Université Paris-Est-Créteil, Créteil, France Service de Neurologie, Hôpital Henri Mondor, Assistance Publique – Hôpitaux de Paris, Créteil, France Jean-Pascal Lefaucheur EA 4391, Excitabilité Nerveuse et Thérapeutique, Université Paris-Est-Créteil, Créteil, France Service de Physiologie – Explorations Fonctionnelles, Hôpital Henri Mondor, Assistance Publique – Hôpitaux de Paris, 51 avenue de Lattre de Tassigny, 94010 Créteil, France Tel.: +33 1 4981 2694; fax: +33 1 4981 4660. E-mail address: [email protected] (J.-P. Lefaucheur).
Available online 22 December 2013 1388-2457/$36.00 Ó 2014 Published by Elsevier Ireland Ltd. on behalf of International Federation of Clinical Neurophysiology. doi:http://dx.doi.org/10.1016/j.clinph.2013.08.029
Unusual case of paroxysmal sympathetic hyperactivity in a patient with leukemia
A 53 year old female patient with history of therapy-related acute myeloid leukemia after treatment for ovarian cancer presented to MD Anderson Cancer Center, Houston, TX, USA, with acute recurrent episodes of staring spells and jerky movements of the upper extremities accompanied by elevations in blood pressure (systolic blood pressure range: 140–190 mm Hg), hyperthermia (range: 38–39 degree Celsius), tachycardia (range: 110–160 beats per minute), and tachypnea (range: 20–28 breath per minute). Symptoms started two days prior to her admission and lasted between 5–30 min and occurred 2–4 times per day. Initial neurologic examination revealed altered mental status; confusion. Blood and urine cultures, serum chemistries, and paraneoplastic panel were normal. Lumbar puncture revealed normal opening pressure. CSF glucose, protein, cell count, cytology and infectious work up were negative. Transcranial Doppler and brain MRI and MRV were unremarkable. MRI studies were acquired on 1.5 Tesla scanners and multiple sequences were applied: Sagittal T1, axial T1 and T2, ADC, DWI, axial FLAIR, and T-1 post contrast. Continuous video electroencephalography (cVEEG) revealed brief staring spells, head bobbing, and bilateral upper extremity jerking activity with no significant EEG abnormalities other than generalized slowing and high amplitude EMG artifact (see Supplementary Movie S1; Fig. 1A and B). Use of high frequency filter and review of the central regions failed to demonstrate any obvious epileptiform activity. Despite therapeutic doses of intravenous (IV) levetiracetam, phenytoin, and diazepam, the episodic abnormal posturing didn’t abate. The lack of response to multiple anti-epileptic drugs (AEDs) and cVEEG analysis led to the diagnosis of paroxysmal sympathetic hyperactivity (PSH). IV Morphine sulfate (2 mg every 4 h) successfully restored the patient’s vital signs to normal with cessation of the abnormal movements. Two days after initial presentation, the patient was weaned off of morphine because she was no longer having vital sign abnormalities and abnormal posturing. Patient received a total dose of 28 mg of morphine sulfate and there were no relapses on follow-ups. PSH is characterized by marked agitation, episodic hypertension, diaphoresis, hyperthermia, tachycardia, tachypnea and abnormal posturing. In 1929, Wilder Penfield described a patient with diaphoresis, pupillary dilation, hypertension, and shivering associated with a tumor at the foramen of Monro and coined the term ‘‘diencepahlic autonomic epilepsy’’ (Penfield, 1929). Since then, various labels have been applied to this phenomenon including paroxysmal autonomic instability with dystonia, hypothalamicmidbrain dysregulation syndrome, hyperpyrexia associated with sustained muscle contractions, dysautonomia, sympathetic storms, paroxysmal sympathetic storms, diencephalic seizures, and diencephalic epilepsy (Blackman et al., 2004; Boeve et al., 1998). The constellation of episodic hyperadrenergic signs, abnormal posturing, EEG findings, and response to morphine sulfate in our patient is consistent with PSH as described in the contemporary literature (Blackman et al., 2004; Perkes et al., 2010). The frequency of PSH is not known, however, traumatic and/or non-traumatic brain injuries account for most cases (Perkes
