- Email: [email protected]
The abduction deficit of functional convergence spasm
The abduction deficit of functional convergence spasm E. Anagnostou, P. Katsika, E. Kemanetzoglou, S. Vassilopoulou, K. Spengos PII: DOI: Reference:
S0022-510X(16)30093-4 doi: 10.1016/j.jns.2016.02.027 JNS 14381
To appear in:
Journal of the Neurological Sciences
Received date: Revised date: Accepted date:
15 December 2015 17 January 2016 11 February 2016
Please cite this article as: E. Anagnostou, P. Katsika, E. Kemanetzoglou, S. Vassilopoulou, K. Spengos, The abduction deficit of functional convergence spasm, Journal of the Neurological Sciences (2016), doi: 10.1016/j.jns.2016.02.027
This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT The abduction deficit of functional convergence spasm
Department of Neurology, University of Athens, Eginition Hospital, Athens, Greece
NU
SC R
IP
1
T
Anagnostou E1, Katsika P1, Kemanetzoglou E1, Vassilopoulou S1, Spengos K1
Corresponding Author:
MA
Dr. Evangelos Anagnostou Department of Neurology
11528 Athens, Greece
TE
Vas. Sophias Avenue 74,
D
Eginition Hospital, University of Athens
CE P
Email: [email protected]
AC
Tel: +302107289291
Word count: Main text = 956 Keywords: Convergence spasm; abducens palsy; eye movements; functional disorders
ACCEPTED MANUSCRIPT
Bilateral sixth-nerve palsy may be a sign of sinister central nervous system pathology. In most instances, patients with an apparent bilateral weakness of abduction of the
T
eyes frequently enter the hospital on an emergency basis for extensive investigation.
IP
Upon careful examination, however, many patients turn out to have convergence
SC R
spasm (CS) or “spasm of the near reflex”. CS has been described in various pathologies of the posterior fossa, but occurs much more frequently as a manifestation of a conversion disorder [1,2]. Indeed, organic CS occurs so much rarer than its functional variety, that Keane proposed to reserve the term CS only for functional CS,
NU
while symptomatic cases should always be labeled explicitly as “organic CS” [3]. It should be noted that in many cases CS is a sign detected by examination, while the
MA
patients might not complain about double vision. The frequency of occurrence of diplopia in CS is unknown.
In order to rule out sixth nerve palsy, clinicians look for the presence of the triad of
D
the near response (convergence, excessive accommodation and miosis). Onset of
TE
vergence upon lateral eye movements may not be easy to differentiate from lateral rectus weakness. Excessive accommodation manifests as a sudden appearance of
CE P
myopia, which is also hard to assess due to its transient nature. Finally, the observation of miosis during attempted abduction seems to be the most reliable sign at bedside examination, but in many cases there is concomitant narrowing of the
AC
palpebral fissures, changes of fixation and significant discomfort, all of which make the assessment of miosis difficult [1]. This is further complicated by the fact that the three components of the near reflex do not always present in the same fixed proportion or degree [1]. Therefore, we aimed to analyze the abduction deficit per se, in order to identify differences between CS and abducens palsy. A 41-year-old woman presented with sudden onset of painless diplopia 12 hours prior to admission. Upon brief clinical assessment in the emergency room a preliminary diagnosis of bilateral abducens palsy has been made. On careful examination, however, we noted an intermittent esotropia in primary position with concomitant miosis. Leftward and rightward versions showed weakness of the abducting eye that partially improved upon monocular testing. Vertical versions were full and there was no nystagmus. When no attention was paid to testing her eye movements, esotropia
ACCEPTED MANUSCRIPT was less manifest. The rest of the neurological examination was unremarkable. These signs made CS the most likely diagnosis. Recording of eye movements revealed interesting features (figure 1, left panel).
T
Abducting saccades of 10-deg magnitude showed normal initial slope, but then
IP
decelerated abruptly before reaching the eccentric target due to the onset of the convergence signal. We tested five consecutive saccades and observed that secondary
SC R
and occasionally tertiary saccades took the eye then towards the target after the primary eye movement. Even then, most final positions were either hypo- or hypermetric. Characteristically, primary saccades were of markedly different
NU
amplitude, indicating that the convergence signal intermingled with the saccade at different time points. Compared to normal saccades (figure 1, right panel), eye
MA
velocity in our patient had normal amplitude and waveform. Abducting movements in a 45-year-old male patient with microvascular sixth nerve palsy, recorded three days after diplopia onset, showed a completely different pattern (figure 1, middle panel).
D
Here, all primary saccades were hypometric with diminished velocities. Nonetheless,
TE
amplitudes and velocities were relatively fixed. In all five saccades, the eye approached the target with a secondary slow saccade. A small onward drift occurring
CE P
at the end of the primary saccades resulted in positively skewed velocity profiles, a feature which was absent in the CS patient. This is also in contrast to the rather symmetrical profiles seen in small and medium amplitude saccades in healthy humans ([5] and example in figure 1 - right panel ).
AC
In the present case, a negative brain MRI which was done one day after admission and reassuring the patient that she is not in physical danger and, was sufficient to completely resolve the symptoms within 48 hours. On follow-up one month later ocular motility remained unremarkable. In the meantime the patient underwent a psychiatric evaluation and was diagnosed with a depressive disorder. Hence, three features characterize the abduction deficit of CS, which are not found in true sixth nerve palsy [6]: (a) normal peak saccadic velocities, (b) marked endpoint variability in both primary and corrective saccades and (c) absence of post-saccadic drift. These properties reflect the pathomechanism of functional CS consisting of intrusion of convergence at variable time points on the course of horizontal centrifugal eye movements and of a lack of true muscle weakness. Although the above oculographic parameters may be useful in clinically ambiguous cases, they only confirm the absence of sixth nerve palsy, but they cannot exclude the
ACCEPTED MANUSCRIPT presence of an organic CS. Indeed, rare cases with organic CS after brainstem stroke, multiple sclerosis and Wernicke’s encephalopathy have been described [7-9] and from the viewpoint of psychogenic disorders, the differential diagnosis between functional
T
and organic CS is more important than that between functional CS and abducens
IP
palsy [10]. Possible differences in saccade kinematics between functional and organic CS remain to be determined. We hypothesize that in organic CS, saccade steepness
SC R
will be low right from the onset, while other abduction abnormalities should appear more stereotypically, yielding lower variability values in terms of velocity and displacement.
NU
Focusing on the abduction deficit, the present case demonstrated the differences in horizontal saccadic eye movements between abducens and pseudo-abducens (i.e.
MA
functional CS) palsy. Such recordings are easy to perform and to evaluate in any oculographic laboratory since the differences are obvious in both the amplitude and the velocity channel. The reproducibility and reliability of this test, however, should
AC
CE P
TE
D
be addressed in larger case series.
ACCEPTED MANUSCRIPT References 1. Goldstein JH, Schneekloth BB. Spasm of the near reflex: a spectrum of anomalies. Surv Ophthalmol 1996;40:269-278. 2. Fekete R, Baizabal-Carvallo JF, Ha AD, Davidson A, Jankovic J.
T
Convergence spasm in conversion disorders: prevalence in psychogenic and
IP
other movement disorders compared with controls. J Neurol Neurosurg
SC R
Psychiatry 2012;83:202-204.
3. Keane JR. Reply from the author. Neurology 1983;33:1637. 4. Anagnostou E, Kemanetzoglou E, Papadimas G, Kararizou E, Evdokimidis I.
NU
Extraocular muscle function in adult-onset Pompe disease tested by saccadic eye movements. Neuromuscul Disord 2014;24:1073-1078. 5. Baloh RW, Sills AW, Kumley WE, Honrubia V. Quantitative measurement of
MA
saccade amplitude, duration, and velocity. Neurology 1975;25:1065-1070. 6. Abel LA, Schmidt D, Dell’Osso LF, Daroff RB. Saccadic system plasticity in
D
humans. Ann Neurol 1978;4:313-318.
7. Caplan LR. '"Top of the basilar" syndrome. Neurology 1980;30:72-79.
TE
8. Postert T, McMonagle U, Büttner T, Pöhlau D, Meves S, Przuntek H. Paroxysmal convergence spasm in multiple sclerosis. Acta Neurol Scand
CE P
1996;94:35-37.
9. Thompson RA, Lynde RH. Convergence spasm associated with Wernicke's encephalopathy. Neurology 1969;19:711-712.
AC
10. Kaski D, Bronstein AM, Edwards MJ, Stone J. Cranial functional (psychogenic) movement disorders. Lancet Neurol 2015;14:1196-1205.
ACCEPTED MANUSCRIPT Figure 1 (legend) Five rightward saccades to a visible target 10 degrees from fixation were recorded. Eye movements were aligned on saccade onset. The upper panel
T
depicts eye displacement, the lower panel eye velocity. For details on
IP
recording and analysis see [4]. Briefly, Eye movements were recorded with an infrared corneal reflection device (IRIS, Skalar, Delft), A/D converted at 500
SC R
Hz with a National Instruments external card with 14 bit resolution. Data were digitally low pass filtered at 70 Hz and smoothed with a Savtizky Golay filter. The patient was seated in a dimly illuminated room with her head immobilized
throughout the measurement.
NU
by a head-chin rest. Targets were red LEDs that were continuously present
MA
Left: Patient with CS. Range of amplitudes for primary saccades: 3.35 deg (6.75 - 10.1), for final position: 3.75 deg (8 - 11.75). Range of peak velocities for primary saccades: 113 deg/s (165 - 278).
D
Middle: Patient with right sixth nerve palsy. Range of amplitudes for primary
TE
saccades: 0.5 deg (6.7 – 7.2), for final position: 1.5 deg (8.25 - 9.75). Range of peak velocities for primary saccades: 25.5 deg/s (52.5 - 78).
CE P
Right: Healthy control (37-year-old). Range of amplitudes for primary saccades: 1.45 deg (9.25 - 10.7), for final position: 0.6 deg (10.2 - 10.8).
AC
Range of peak velocities for primary saccades: 9.5 deg/s (239.5 - 249).
IP
T
ACCEPTED MANUSCRIPT
AC
CE P
TE
D
MA
NU
SC R
Figure 1
S0022-510X(16)30093-4 doi: 10.1016/j.jns.2016.02.027 JNS 14381
To appear in:
Journal of the Neurological Sciences
Received date: Revised date: Accepted date:
15 December 2015 17 January 2016 11 February 2016
Please cite this article as: E. Anagnostou, P. Katsika, E. Kemanetzoglou, S. Vassilopoulou, K. Spengos, The abduction deficit of functional convergence spasm, Journal of the Neurological Sciences (2016), doi: 10.1016/j.jns.2016.02.027
This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT The abduction deficit of functional convergence spasm
Department of Neurology, University of Athens, Eginition Hospital, Athens, Greece
NU
SC R
IP
1
T
Anagnostou E1, Katsika P1, Kemanetzoglou E1, Vassilopoulou S1, Spengos K1
Corresponding Author:
MA
Dr. Evangelos Anagnostou Department of Neurology
11528 Athens, Greece
TE
Vas. Sophias Avenue 74,
D
Eginition Hospital, University of Athens
CE P
Email: [email protected]
AC
Tel: +302107289291
Word count: Main text = 956 Keywords: Convergence spasm; abducens palsy; eye movements; functional disorders
ACCEPTED MANUSCRIPT
Bilateral sixth-nerve palsy may be a sign of sinister central nervous system pathology. In most instances, patients with an apparent bilateral weakness of abduction of the
T
eyes frequently enter the hospital on an emergency basis for extensive investigation.
IP
Upon careful examination, however, many patients turn out to have convergence
SC R
spasm (CS) or “spasm of the near reflex”. CS has been described in various pathologies of the posterior fossa, but occurs much more frequently as a manifestation of a conversion disorder [1,2]. Indeed, organic CS occurs so much rarer than its functional variety, that Keane proposed to reserve the term CS only for functional CS,
NU
while symptomatic cases should always be labeled explicitly as “organic CS” [3]. It should be noted that in many cases CS is a sign detected by examination, while the
MA
patients might not complain about double vision. The frequency of occurrence of diplopia in CS is unknown.
In order to rule out sixth nerve palsy, clinicians look for the presence of the triad of
D
the near response (convergence, excessive accommodation and miosis). Onset of
TE
vergence upon lateral eye movements may not be easy to differentiate from lateral rectus weakness. Excessive accommodation manifests as a sudden appearance of
CE P
myopia, which is also hard to assess due to its transient nature. Finally, the observation of miosis during attempted abduction seems to be the most reliable sign at bedside examination, but in many cases there is concomitant narrowing of the
AC
palpebral fissures, changes of fixation and significant discomfort, all of which make the assessment of miosis difficult [1]. This is further complicated by the fact that the three components of the near reflex do not always present in the same fixed proportion or degree [1]. Therefore, we aimed to analyze the abduction deficit per se, in order to identify differences between CS and abducens palsy. A 41-year-old woman presented with sudden onset of painless diplopia 12 hours prior to admission. Upon brief clinical assessment in the emergency room a preliminary diagnosis of bilateral abducens palsy has been made. On careful examination, however, we noted an intermittent esotropia in primary position with concomitant miosis. Leftward and rightward versions showed weakness of the abducting eye that partially improved upon monocular testing. Vertical versions were full and there was no nystagmus. When no attention was paid to testing her eye movements, esotropia
ACCEPTED MANUSCRIPT was less manifest. The rest of the neurological examination was unremarkable. These signs made CS the most likely diagnosis. Recording of eye movements revealed interesting features (figure 1, left panel).
T
Abducting saccades of 10-deg magnitude showed normal initial slope, but then
IP
decelerated abruptly before reaching the eccentric target due to the onset of the convergence signal. We tested five consecutive saccades and observed that secondary
SC R
and occasionally tertiary saccades took the eye then towards the target after the primary eye movement. Even then, most final positions were either hypo- or hypermetric. Characteristically, primary saccades were of markedly different
NU
amplitude, indicating that the convergence signal intermingled with the saccade at different time points. Compared to normal saccades (figure 1, right panel), eye
MA
velocity in our patient had normal amplitude and waveform. Abducting movements in a 45-year-old male patient with microvascular sixth nerve palsy, recorded three days after diplopia onset, showed a completely different pattern (figure 1, middle panel).
D
Here, all primary saccades were hypometric with diminished velocities. Nonetheless,
TE
amplitudes and velocities were relatively fixed. In all five saccades, the eye approached the target with a secondary slow saccade. A small onward drift occurring
CE P
at the end of the primary saccades resulted in positively skewed velocity profiles, a feature which was absent in the CS patient. This is also in contrast to the rather symmetrical profiles seen in small and medium amplitude saccades in healthy humans ([5] and example in figure 1 - right panel ).
AC
In the present case, a negative brain MRI which was done one day after admission and reassuring the patient that she is not in physical danger and, was sufficient to completely resolve the symptoms within 48 hours. On follow-up one month later ocular motility remained unremarkable. In the meantime the patient underwent a psychiatric evaluation and was diagnosed with a depressive disorder. Hence, three features characterize the abduction deficit of CS, which are not found in true sixth nerve palsy [6]: (a) normal peak saccadic velocities, (b) marked endpoint variability in both primary and corrective saccades and (c) absence of post-saccadic drift. These properties reflect the pathomechanism of functional CS consisting of intrusion of convergence at variable time points on the course of horizontal centrifugal eye movements and of a lack of true muscle weakness. Although the above oculographic parameters may be useful in clinically ambiguous cases, they only confirm the absence of sixth nerve palsy, but they cannot exclude the
ACCEPTED MANUSCRIPT presence of an organic CS. Indeed, rare cases with organic CS after brainstem stroke, multiple sclerosis and Wernicke’s encephalopathy have been described [7-9] and from the viewpoint of psychogenic disorders, the differential diagnosis between functional
T
and organic CS is more important than that between functional CS and abducens
IP
palsy [10]. Possible differences in saccade kinematics between functional and organic CS remain to be determined. We hypothesize that in organic CS, saccade steepness
SC R
will be low right from the onset, while other abduction abnormalities should appear more stereotypically, yielding lower variability values in terms of velocity and displacement.
NU
Focusing on the abduction deficit, the present case demonstrated the differences in horizontal saccadic eye movements between abducens and pseudo-abducens (i.e.
MA
functional CS) palsy. Such recordings are easy to perform and to evaluate in any oculographic laboratory since the differences are obvious in both the amplitude and the velocity channel. The reproducibility and reliability of this test, however, should
AC
CE P
TE
D
be addressed in larger case series.
ACCEPTED MANUSCRIPT References 1. Goldstein JH, Schneekloth BB. Spasm of the near reflex: a spectrum of anomalies. Surv Ophthalmol 1996;40:269-278. 2. Fekete R, Baizabal-Carvallo JF, Ha AD, Davidson A, Jankovic J.
T
Convergence spasm in conversion disorders: prevalence in psychogenic and
IP
other movement disorders compared with controls. J Neurol Neurosurg
SC R
Psychiatry 2012;83:202-204.
3. Keane JR. Reply from the author. Neurology 1983;33:1637. 4. Anagnostou E, Kemanetzoglou E, Papadimas G, Kararizou E, Evdokimidis I.
NU
Extraocular muscle function in adult-onset Pompe disease tested by saccadic eye movements. Neuromuscul Disord 2014;24:1073-1078. 5. Baloh RW, Sills AW, Kumley WE, Honrubia V. Quantitative measurement of
MA
saccade amplitude, duration, and velocity. Neurology 1975;25:1065-1070. 6. Abel LA, Schmidt D, Dell’Osso LF, Daroff RB. Saccadic system plasticity in
D
humans. Ann Neurol 1978;4:313-318.
7. Caplan LR. '"Top of the basilar" syndrome. Neurology 1980;30:72-79.
TE
8. Postert T, McMonagle U, Büttner T, Pöhlau D, Meves S, Przuntek H. Paroxysmal convergence spasm in multiple sclerosis. Acta Neurol Scand
CE P
1996;94:35-37.
9. Thompson RA, Lynde RH. Convergence spasm associated with Wernicke's encephalopathy. Neurology 1969;19:711-712.
AC
10. Kaski D, Bronstein AM, Edwards MJ, Stone J. Cranial functional (psychogenic) movement disorders. Lancet Neurol 2015;14:1196-1205.
ACCEPTED MANUSCRIPT Figure 1 (legend) Five rightward saccades to a visible target 10 degrees from fixation were recorded. Eye movements were aligned on saccade onset. The upper panel
T
depicts eye displacement, the lower panel eye velocity. For details on
IP
recording and analysis see [4]. Briefly, Eye movements were recorded with an infrared corneal reflection device (IRIS, Skalar, Delft), A/D converted at 500
SC R
Hz with a National Instruments external card with 14 bit resolution. Data were digitally low pass filtered at 70 Hz and smoothed with a Savtizky Golay filter. The patient was seated in a dimly illuminated room with her head immobilized
throughout the measurement.
NU
by a head-chin rest. Targets were red LEDs that were continuously present
MA
Left: Patient with CS. Range of amplitudes for primary saccades: 3.35 deg (6.75 - 10.1), for final position: 3.75 deg (8 - 11.75). Range of peak velocities for primary saccades: 113 deg/s (165 - 278).
D
Middle: Patient with right sixth nerve palsy. Range of amplitudes for primary
TE
saccades: 0.5 deg (6.7 – 7.2), for final position: 1.5 deg (8.25 - 9.75). Range of peak velocities for primary saccades: 25.5 deg/s (52.5 - 78).
CE P
Right: Healthy control (37-year-old). Range of amplitudes for primary saccades: 1.45 deg (9.25 - 10.7), for final position: 0.6 deg (10.2 - 10.8).
AC
Range of peak velocities for primary saccades: 9.5 deg/s (239.5 - 249).
IP
T
ACCEPTED MANUSCRIPT
AC
CE P
TE
D
MA
NU
SC R
Figure 1