1071
Letters to the Editor / Clinical Neurophysiology 125 (2014) 1065–1074
patient scalp EEG recording revealed right hemispheric rhythmic slowing with episodic suppression suggestive of non-convulsive status epileptics. In our patient brain MRI, CSF analyses, EEG recordings and paraneoplastic panel were not suggestive of encephalitis. Furthermore, PSH has been reported in the absence of obvious structural brain lesions and normal CSF opening pressures (Fox et al., 1973). Our patient had no clinical evidence of increased intracranial pressure; nevertheless, we cannot exclude the possibility of transient elevations in intracranial pressure (plateau-waves) to account for the hyperadrenergic state. PSH remains poorly understood and under recognized despite distinctive and characteristic features (Perkes et al., 2010). Originally, Penfield speculated that the constellation of symptoms in PSH originated from epileptic discharges emanating from thalamic nuclei (Penfield, 1929). However, subsequent studies didn’t support his model of epilepsy (Boeve et al., 1998). In fact, the seizure like events in PSH are now considered to be ‘‘non-epileptic’’ as evidenced by the lack of epileptiform discharges on surface EEG and failure to respond to AEDs (Boeve et al., 1998); thus the waning use of terms ‘‘diencephalic autonomic seizure or epilepsy’’. Nevertheless, given the recent renewed interest in subcortical epilepsies (Badaway et al., 2013), the latter theory may be challenged in the future. Further studies utilizing depth electrodes (albeit less practical) and functional brain imaging such as ictal SPECT and interictal PET may help to address the contentious possibility of seizure arising from deep brain areas such as the diencephalon and brain stem in PSH. Our patient was initially managed as a case of status epilepticus because of the recurrent abnormal posturing and accompanying confusion. The lack of response to multiple AEDs and cVEEG analysis led to the diagnosis of PSH. Once the diagnosis of PSH was established, 2 mg IV morphine sulfate was tried and it successfully ceased the abnormal posturing along with restoration of patient’s vital signs. Taken together, the clinical presentation along with the rapid response to IV morphine sulfate fits the syndrome of PSH. Clinicians should be aware of this rare yet potentially fatal syndrome as it can be easily misdiagnosed as status epilepticus. Early diagnosis of this syndrome using cVEEG will preclude needless administration of potentially toxic AEDs, especially in cancer patients receiving chemotherapy. Lack of recognition and undertreatment of this syndrome will lead to morbidity and mortality resulting from the autonomic dysfunction. This report highlights the key role of cVEEG in the diagnosis and management of PSH. Moreover, our case study may reignite an age-old debate on the nature of the abnormal movements in PSH: non-epileptic vs. epileptic events. We are also hopeful that future studies in patients with PSH will attempt to undertake functional brain imaging studies and/or depth electrode recording (when applicable) to further elucidate the pathophysiology of this syndrome. Disclosure This study received no external funding. Acknowledgment The authors would like to thank Maranatha R. McLean, a third year medical student at University of Texas medical branch at Galveston, for editing the video (Supplementary Movie S1) and video still. Appendix A. Supplementary data Supplementary data associated with this article can be found, in the online version, at http://dx.doi.org/10.1016/ j.clinph.2013.09.023.
References Blackman JA, Patrick PD, Buck ML, Rust Jr RS. Paroxysmal autonomic instability with dystonia after brain injury. Arch Neurol 2004;61:321–8. Boeve BF, Wijdicks EF, Benarroch EE, Schmidt KD. Paroxysmal sympathetic storms (‘‘diencephalic seizures’’) after severe diffuse axonal head injury. Mayo Clin Proc 1998;73:148–52. Badawy RA, Lai A, Vogrin SJ, Cook MJ. Subcortical epilepsy? Neurology 2013;80:1901–7. Fox RH, Wilkins DC, Bell JA, Bradley RD, Browse NL, Cranston WI, et al. Spontaneous periodic hypothermia: diencephalic epilepsy. BMJ 1973;2:693–5. Hinson HE, Takahashi C, Altowaijri G, Baguley IJ, Bourdette D. Anti-NMDA receptor encephalitis with paroxysmal sympathetic hyperactivity: an under-recognized association? Clin Auton Res 2013;23:109–11. Penfield W. Diencephalic autonomic epilepsy. Arch Neurol Psychiatry 1929;22:358–74. Perkes I, Baguley IJ, Nott MT, Menon DK. A review of paroxysmal sympathetic hyperactivity after acquired brain injury. Ann Neurol 2010;68:126–35. Soriano A, Gutgsell TL, Davis MP. Diencephalic storms from leptomeningeal metastases and leukoencephalopathy: a rare and clinically important complication. Am J Hosp Palliat Care 2013. Available from: http:// ajh.sagepub.com/content/early/2013/01/07/1049909112472047.
Anteneh M. Feyissa University of Texas Medical Branch at Galveston, 301 University Blvd, Suite JSA 9.128, Galveston, TX 77555, USA Tel: +1 409 772 8053; fax: +1 409 772 6940. Department of Neuro-Oncology, The University of Texas, MD Anderson Cancer Center, 1515 Holcombe Blvd, Unit #431, Room#FC7.3000, Houston, TX 77030-4009, USA E-mail addresses: [email protected], [email protected] Sudhakar Tummala Department of Neuro-Oncology, The University of Texas, MD Anderson Cancer Center, 1515 Holcombe Blvd, Unit #431, Room#FC7.3000, Houston, TX 77030-4009, United States Available online 19 October 2013 1388-2457/$36.00 Published by Elsevier Ltd. on behalf of International Federation of Clinical Neurophysiology. doi:http://dx.doi.org/10.1016/j.clinph.2013.09.023
Artifact avoidance for head impulse testing
The head impulse test (HIT) consists of a brisk head turn while the subject is looking at a target. If the vestibulo-ocular reflex (VOR) is normal and stabilizes the gaze in space, when the head stops the eyes are on the target and do not move; if not, a saccade is needed for refixation and can be detected by the examiner (Halmagyi and Curthoys, 1988). If saccades are triggered after the head has stopped, they are called ‘‘overt saccades’’, yet during vestibular compensation saccades are produced even during the head movement; these are called ‘‘covert saccades’’. The HIT is clinically very important (Kattah et al., 2009), but the detection of small overt and of covert saccades may be difficult and some authors set up instrumental versions that combine head and eye movement recording and analysis to improve saccade detection and the sensitivity of the test. The recording of eye movements was initially based on the magneto oculographic (MOG) technique, which unfortunately is quite expensive and slightly invasive, and is not well suited for clinical vestibular routine. Then it was suggested that the video-oculographic (VOG) technique could be used, and it was proved that the results obtained by simultaneous MOG and VOG recording were strictly correlated and comparable (MacDougall et al., 2009). However, the gain values (namely the ratio of eye to head velocity) were slightly higher for VOG than for
1072
Letters to the Editor / Clinical Neurophysiology 125 (2014) 1065–1074
MOG, and could be higher than 1; this was considered to be an artifact, possibly due to the slippage of the goggle that carries the video-cameras and the inertial measurement unit, and could be overcome by a different and lighter frame (Weber et al., 2009). This flaw is inherent in all frame-based HIT devices, but we suggest that it can be minimized by placing on the bridge of the nose a cast made of dental paste (Honigum-putty rigid fast; DMG Dental; Hamburg, Germany) that can be impressed by the frame. Approximately 5–10 g of dental paste (Fig. 1, panel a) is moulded and placed on the nose, then the goggles are placed so as to impress the paste; after approximately 1 min, when the paste becomes rigid the test can be started (Fig. 1, panel b). The whole procedure lasts about 5 min. The cast is tailored to the subject’s nose, and can stabilize the frame and prevent it from slipping during the quick head turns (Fig. 1, panels c and d). We used the EyeSeeCam device with and without the dental paste cast to test HIT twice in 13 normal subjects (20 thrusts for
each direction and for each stabilization condition). The mean gain values were 0.98 (standard deviation: 0.06) clockwise (CW) and 1.03 (SD 0.06) counter-clockwise (CCW) with the cast, and 1.06 (SD 0.13) and 1.11 (SD 0.1) respectively without the cast. The repeated measure ANOVA (two, 2-level within-subject factors, direction and frame stabilization), showed a significant effect only for frame stabilization (larger gain values without stabilization, F(1,12) = 15.1, p = 0.002). All subjects showed a gain decrease ranging from 0 to 0.4, with the sole exception of one subject in one direction showing a gain increase of 0.1. The stabilization effect is likely to be inversely related to how well the goggles fit the nose and the orbital region of the subject. During HIT we also asked the subject to read a letter (viewing distance 1 m) that briefly (80 ± 8 ms) appeared on the screen when predefined head angular acceleration and velocity thresholds were overcome (Ramat et al., 2012). The percentage of correct answers, which is related to the real gain value, is expected to be
Fig. 1. Panel a shows the small amount of Honigum- putty rigid fast (DMG Dental, Hamburg Germany) needed for the cast. Panel b shows the cast of dental impression paste on the bridge of the nose that stabilize the EyeSeeCam frame. Panels c and d show the head (thick line) and the eye (thin line) velocity; the eye tracing was flipped horizontally for a better comparison with head tracing. The recordings of Panel c have been obtained without frame stabilization, and the movement of the eyes apparently leads that of the head. This artifact is not detectable after the frame has been stabilized by dental paste cast (Panel d).
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Letters to the Editor / Clinical Neurophysiology 125 (2014) 1065–1074
independent from frame stabilization, and it in fact was: CW 94.2% (SD 9.5) and CCW 92.7% (SD 8.3) with stabilization; CW 96.9% (SD 5.8) and CCW 90.1% (SD 10) without stabilization. In conclusion, the instrumental evaluation of HIT can be a very useful tool for VOR evaluation, and artifacts due to slippage can be easily controlled by stabilizing the frame on the subject’s nose by using a personalized cast made of dental impression paste. References Halmagyi GM, Curthoys IS. A clinical sign of canal paresis. Arch Neurol 1988;45:737–9. Kattah JC, Talkad AV, Wang DZ, Hsieh YH, Newman-Toker DE. HINTS to diagnose stroke in the acute vestibular syndrome: three steps bedside oculomotor examination more sensitive than early MRI diffusion-weighted imaging. Stroke 2009;40:3504–10. MacDougall HG, Weber KP, McGarvie LA, Halmagyi GM, Curthoys IS. The video head impulse test. Diagnostic accuracy in peripheral vestibulopathy. Neurology 2009;73:1134–41. Ramat S, Colnaghi S, Boehler A, Astore S, Falco P, Mandala M, et al. A device for the functional evaluation of the VOR in clinical settings. Front Neurol 2012;3:39. Weber KP, MacDougall HG, Halmagyi GM, Curthoys IS. Impulsive testing of semicircular-canal function using video-oculography. Basic and Clinical Aspects of Vertigo and Dizziness: Ann N Y Acad Sci 2009;1164:486–91.
⇑
Maurizio Versino C. Mondino National Neurological Institute, Pavia, Italy Department of Brain and Behavioural Sciences, University of Pavia, Italy ⇑ Corresponding author at: Department of Brain and Behavioural Sciences, University of Pavia, Italy. Tel.: +39 0382 380340; fax: +39 0382 24714. E-mail address: [email protected] Paolo Colagiorgio Department of Electrical, Computer and Biomedical Engineering, University of Pavia, Italy Simone Sacco Department of Brain and Behavioural Sciences, University of Pavia, Italy Silvia Colnaghi C. Mondino National Neurological Institute, Pavia, Italy Stefano Ramat Department of Electrical, Computer and Biomedical Engineering, University of Pavia, Italy Available online 13 October 2013 1388-2457/$36.00 Ó 2013 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved. doi:http://dx.doi.org/10.1016/j.clinph.2013.09.024
The significance of significance: Overstating in the setting of many comparisons
As a neurologist and neurophysiologist with special interests in peripheral neuropathies I was attracted to a recent article in Clinical Neurophysiology on clinical–neurophysiological correlations among patients with IgM-related neuropathies by Luigetti et al. (2013). The article reported on a case series of moderate size and divided patients into two groups, those with typical and those atypical clinical features. The authors then assessed neurophysiological data and report a number of significant differences between the two groups. My concern with the interpretation of the neurophysiologic data that led to conclusions about differences between the two groups is that a large number of statistical comparisons were
made, 32 in Table 2 of the text and 49 in Supplementary Table S2, and statistical significance was based on a p value
Letters to the Editor / Clinical Neurophysiology 125 (2014) 1065–1074
patient scalp EEG recording revealed right hemispheric rhythmic slowing with episodic suppression suggestive of non-convulsive status epileptics. In our patient brain MRI, CSF analyses, EEG recordings and paraneoplastic panel were not suggestive of encephalitis. Furthermore, PSH has been reported in the absence of obvious structural brain lesions and normal CSF opening pressures (Fox et al., 1973). Our patient had no clinical evidence of increased intracranial pressure; nevertheless, we cannot exclude the possibility of transient elevations in intracranial pressure (plateau-waves) to account for the hyperadrenergic state. PSH remains poorly understood and under recognized despite distinctive and characteristic features (Perkes et al., 2010). Originally, Penfield speculated that the constellation of symptoms in PSH originated from epileptic discharges emanating from thalamic nuclei (Penfield, 1929). However, subsequent studies didn’t support his model of epilepsy (Boeve et al., 1998). In fact, the seizure like events in PSH are now considered to be ‘‘non-epileptic’’ as evidenced by the lack of epileptiform discharges on surface EEG and failure to respond to AEDs (Boeve et al., 1998); thus the waning use of terms ‘‘diencephalic autonomic seizure or epilepsy’’. Nevertheless, given the recent renewed interest in subcortical epilepsies (Badaway et al., 2013), the latter theory may be challenged in the future. Further studies utilizing depth electrodes (albeit less practical) and functional brain imaging such as ictal SPECT and interictal PET may help to address the contentious possibility of seizure arising from deep brain areas such as the diencephalon and brain stem in PSH. Our patient was initially managed as a case of status epilepticus because of the recurrent abnormal posturing and accompanying confusion. The lack of response to multiple AEDs and cVEEG analysis led to the diagnosis of PSH. Once the diagnosis of PSH was established, 2 mg IV morphine sulfate was tried and it successfully ceased the abnormal posturing along with restoration of patient’s vital signs. Taken together, the clinical presentation along with the rapid response to IV morphine sulfate fits the syndrome of PSH. Clinicians should be aware of this rare yet potentially fatal syndrome as it can be easily misdiagnosed as status epilepticus. Early diagnosis of this syndrome using cVEEG will preclude needless administration of potentially toxic AEDs, especially in cancer patients receiving chemotherapy. Lack of recognition and undertreatment of this syndrome will lead to morbidity and mortality resulting from the autonomic dysfunction. This report highlights the key role of cVEEG in the diagnosis and management of PSH. Moreover, our case study may reignite an age-old debate on the nature of the abnormal movements in PSH: non-epileptic vs. epileptic events. We are also hopeful that future studies in patients with PSH will attempt to undertake functional brain imaging studies and/or depth electrode recording (when applicable) to further elucidate the pathophysiology of this syndrome. Disclosure This study received no external funding. Acknowledgment The authors would like to thank Maranatha R. McLean, a third year medical student at University of Texas medical branch at Galveston, for editing the video (Supplementary Movie S1) and video still. Appendix A. Supplementary data Supplementary data associated with this article can be found, in the online version, at http://dx.doi.org/10.1016/ j.clinph.2013.09.023.
References Blackman JA, Patrick PD, Buck ML, Rust Jr RS. Paroxysmal autonomic instability with dystonia after brain injury. Arch Neurol 2004;61:321–8. Boeve BF, Wijdicks EF, Benarroch EE, Schmidt KD. Paroxysmal sympathetic storms (‘‘diencephalic seizures’’) after severe diffuse axonal head injury. Mayo Clin Proc 1998;73:148–52. Badawy RA, Lai A, Vogrin SJ, Cook MJ. Subcortical epilepsy? Neurology 2013;80:1901–7. Fox RH, Wilkins DC, Bell JA, Bradley RD, Browse NL, Cranston WI, et al. Spontaneous periodic hypothermia: diencephalic epilepsy. BMJ 1973;2:693–5. Hinson HE, Takahashi C, Altowaijri G, Baguley IJ, Bourdette D. Anti-NMDA receptor encephalitis with paroxysmal sympathetic hyperactivity: an under-recognized association? Clin Auton Res 2013;23:109–11. Penfield W. Diencephalic autonomic epilepsy. Arch Neurol Psychiatry 1929;22:358–74. Perkes I, Baguley IJ, Nott MT, Menon DK. A review of paroxysmal sympathetic hyperactivity after acquired brain injury. Ann Neurol 2010;68:126–35. Soriano A, Gutgsell TL, Davis MP. Diencephalic storms from leptomeningeal metastases and leukoencephalopathy: a rare and clinically important complication. Am J Hosp Palliat Care 2013. Available from: http:// ajh.sagepub.com/content/early/2013/01/07/1049909112472047.
Anteneh M. Feyissa University of Texas Medical Branch at Galveston, 301 University Blvd, Suite JSA 9.128, Galveston, TX 77555, USA Tel: +1 409 772 8053; fax: +1 409 772 6940. Department of Neuro-Oncology, The University of Texas, MD Anderson Cancer Center, 1515 Holcombe Blvd, Unit #431, Room#FC7.3000, Houston, TX 77030-4009, USA E-mail addresses: [email protected], [email protected] Sudhakar Tummala Department of Neuro-Oncology, The University of Texas, MD Anderson Cancer Center, 1515 Holcombe Blvd, Unit #431, Room#FC7.3000, Houston, TX 77030-4009, United States Available online 19 October 2013 1388-2457/$36.00 Published by Elsevier Ltd. on behalf of International Federation of Clinical Neurophysiology. doi:http://dx.doi.org/10.1016/j.clinph.2013.09.023
Artifact avoidance for head impulse testing
The head impulse test (HIT) consists of a brisk head turn while the subject is looking at a target. If the vestibulo-ocular reflex (VOR) is normal and stabilizes the gaze in space, when the head stops the eyes are on the target and do not move; if not, a saccade is needed for refixation and can be detected by the examiner (Halmagyi and Curthoys, 1988). If saccades are triggered after the head has stopped, they are called ‘‘overt saccades’’, yet during vestibular compensation saccades are produced even during the head movement; these are called ‘‘covert saccades’’. The HIT is clinically very important (Kattah et al., 2009), but the detection of small overt and of covert saccades may be difficult and some authors set up instrumental versions that combine head and eye movement recording and analysis to improve saccade detection and the sensitivity of the test. The recording of eye movements was initially based on the magneto oculographic (MOG) technique, which unfortunately is quite expensive and slightly invasive, and is not well suited for clinical vestibular routine. Then it was suggested that the video-oculographic (VOG) technique could be used, and it was proved that the results obtained by simultaneous MOG and VOG recording were strictly correlated and comparable (MacDougall et al., 2009). However, the gain values (namely the ratio of eye to head velocity) were slightly higher for VOG than for
1072
Letters to the Editor / Clinical Neurophysiology 125 (2014) 1065–1074
MOG, and could be higher than 1; this was considered to be an artifact, possibly due to the slippage of the goggle that carries the video-cameras and the inertial measurement unit, and could be overcome by a different and lighter frame (Weber et al., 2009). This flaw is inherent in all frame-based HIT devices, but we suggest that it can be minimized by placing on the bridge of the nose a cast made of dental paste (Honigum-putty rigid fast; DMG Dental; Hamburg, Germany) that can be impressed by the frame. Approximately 5–10 g of dental paste (Fig. 1, panel a) is moulded and placed on the nose, then the goggles are placed so as to impress the paste; after approximately 1 min, when the paste becomes rigid the test can be started (Fig. 1, panel b). The whole procedure lasts about 5 min. The cast is tailored to the subject’s nose, and can stabilize the frame and prevent it from slipping during the quick head turns (Fig. 1, panels c and d). We used the EyeSeeCam device with and without the dental paste cast to test HIT twice in 13 normal subjects (20 thrusts for
each direction and for each stabilization condition). The mean gain values were 0.98 (standard deviation: 0.06) clockwise (CW) and 1.03 (SD 0.06) counter-clockwise (CCW) with the cast, and 1.06 (SD 0.13) and 1.11 (SD 0.1) respectively without the cast. The repeated measure ANOVA (two, 2-level within-subject factors, direction and frame stabilization), showed a significant effect only for frame stabilization (larger gain values without stabilization, F(1,12) = 15.1, p = 0.002). All subjects showed a gain decrease ranging from 0 to 0.4, with the sole exception of one subject in one direction showing a gain increase of 0.1. The stabilization effect is likely to be inversely related to how well the goggles fit the nose and the orbital region of the subject. During HIT we also asked the subject to read a letter (viewing distance 1 m) that briefly (80 ± 8 ms) appeared on the screen when predefined head angular acceleration and velocity thresholds were overcome (Ramat et al., 2012). The percentage of correct answers, which is related to the real gain value, is expected to be
Fig. 1. Panel a shows the small amount of Honigum- putty rigid fast (DMG Dental, Hamburg Germany) needed for the cast. Panel b shows the cast of dental impression paste on the bridge of the nose that stabilize the EyeSeeCam frame. Panels c and d show the head (thick line) and the eye (thin line) velocity; the eye tracing was flipped horizontally for a better comparison with head tracing. The recordings of Panel c have been obtained without frame stabilization, and the movement of the eyes apparently leads that of the head. This artifact is not detectable after the frame has been stabilized by dental paste cast (Panel d).
1073
Letters to the Editor / Clinical Neurophysiology 125 (2014) 1065–1074
independent from frame stabilization, and it in fact was: CW 94.2% (SD 9.5) and CCW 92.7% (SD 8.3) with stabilization; CW 96.9% (SD 5.8) and CCW 90.1% (SD 10) without stabilization. In conclusion, the instrumental evaluation of HIT can be a very useful tool for VOR evaluation, and artifacts due to slippage can be easily controlled by stabilizing the frame on the subject’s nose by using a personalized cast made of dental impression paste. References Halmagyi GM, Curthoys IS. A clinical sign of canal paresis. Arch Neurol 1988;45:737–9. Kattah JC, Talkad AV, Wang DZ, Hsieh YH, Newman-Toker DE. HINTS to diagnose stroke in the acute vestibular syndrome: three steps bedside oculomotor examination more sensitive than early MRI diffusion-weighted imaging. Stroke 2009;40:3504–10. MacDougall HG, Weber KP, McGarvie LA, Halmagyi GM, Curthoys IS. The video head impulse test. Diagnostic accuracy in peripheral vestibulopathy. Neurology 2009;73:1134–41. Ramat S, Colnaghi S, Boehler A, Astore S, Falco P, Mandala M, et al. A device for the functional evaluation of the VOR in clinical settings. Front Neurol 2012;3:39. Weber KP, MacDougall HG, Halmagyi GM, Curthoys IS. Impulsive testing of semicircular-canal function using video-oculography. Basic and Clinical Aspects of Vertigo and Dizziness: Ann N Y Acad Sci 2009;1164:486–91.
⇑
Maurizio Versino C. Mondino National Neurological Institute, Pavia, Italy Department of Brain and Behavioural Sciences, University of Pavia, Italy ⇑ Corresponding author at: Department of Brain and Behavioural Sciences, University of Pavia, Italy. Tel.: +39 0382 380340; fax: +39 0382 24714. E-mail address: [email protected] Paolo Colagiorgio Department of Electrical, Computer and Biomedical Engineering, University of Pavia, Italy Simone Sacco Department of Brain and Behavioural Sciences, University of Pavia, Italy Silvia Colnaghi C. Mondino National Neurological Institute, Pavia, Italy Stefano Ramat Department of Electrical, Computer and Biomedical Engineering, University of Pavia, Italy Available online 13 October 2013 1388-2457/$36.00 Ó 2013 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved. doi:http://dx.doi.org/10.1016/j.clinph.2013.09.024
The significance of significance: Overstating in the setting of many comparisons
As a neurologist and neurophysiologist with special interests in peripheral neuropathies I was attracted to a recent article in Clinical Neurophysiology on clinical–neurophysiological correlations among patients with IgM-related neuropathies by Luigetti et al. (2013). The article reported on a case series of moderate size and divided patients into two groups, those with typical and those atypical clinical features. The authors then assessed neurophysiological data and report a number of significant differences between the two groups. My concern with the interpretation of the neurophysiologic data that led to conclusions about differences between the two groups is that a large number of statistical comparisons were
made, 32 in Table 2 of the text and 49 in Supplementary Table S2, and statistical significance was based on a p value
