- Email: [email protected]
Differences between `congenital mirror movements' and `associated movements' in normal children: a neurophysiological case study
Neuroscience Letters 256 (1998) 69–72
Differences between ‘congenital mirror movements’ and ‘associated movements’ in normal children: a neurophysiological case study Michaela Reitz, Kristina Mu¨ller* Medizinische Einrichtungen der Heinrich-Heine-Universita¨t, Zentrum fu¨r Kinderheilkunde, Moorenstrasse 5, D-40225 Du¨sseldorf, Germany Received 15 June 1998; received in revised form 26 August 1998; accepted 14 September 1998
Abstract In this study we analysed how far physiological associated movements in normal children (which may be present up to the age of 10 years) share the same physiological mechanism with clinically apparent mirror movements. Transcranial magnetic stimulation (TMS) and kinematic movement analysis were applied in a 4-year-old child with congenital mirror movements (CMM). The results were compared with a normative data base of clinically normal children. In the child with CMM focal TMS of one motor cortex induced bilaterally symmetrical responses in distal and proximal upper extremities muscles with identical ipsi- and contralateral latencies. Also kinematic analysis showed a precise symmetrical onset of intended and unintended contralateral movements, whereas normal children with associated movements showed a variable movement onset delay between extremities. The data suggest a different physiological mechanism underlying these two varieties of elementary associated motor activity in childhood. 1998 Elsevier Science Ireland Ltd. All rights reserved
Keywords: Congenital mirror movements; Associated movements; Transcranial magnetic stimulation in children; Motor development; Corticospinal tract
Involuntary movements in homologous contralateral muscles after intended ipsilateral muscle activation are a frequent phenomenon in normal children. These physiological associated movements are partially suppressible, increase with effort and disappear after the childhood period [22]. These associated movements can normally be observed in children up to 10 years of age, suggesting maturational changes of the motor system and completion of myelination of the corpus callosum [6,17,18,23]. The question arises in how far ‘true’ mirror movements which cause clinical problems and tend to persist into adulthood are related to physiological associated movements. In adults, the persistence of mirror movements is always considered abnormal. This condition is often associated with Klippel–Feil syndrome, Kallmann’s syndrome and other rare neurological syndromes [7,11,22]. Mirror move-
* Corresponding author. Tel.: +49 211 8117685; fax: +49 211 8116441; e-mail: [email protected]
ments may be acquired after ischemic stroke or hemispherectomy [1,12,13] and are seen in children with hemiplegic cerebral palsy [4]. Congenital mirror movements (CMM) without any other neurological abnormality are rare. They may be familial or sporadic [20,22]. The pathophysiology remains unclear. Transcranial magnetic stimulation (TMS) has been used in adults to clarify possible abnormalities in wiring of the upper motor neuron in adults with CMM; here bilateral motor evoked potentials (MEP) with identical latencies after TMS have been reported [2,5,13]. In the following study we describe neurophysiological and kinematic data in a child with CMM in contrast to a normative data base of TMS and kinematic data of physiological associated movements in normal children. The 4-year-old girl was born after an uneventful pregnancy and delivery to unrelated healthy parents. She achieved normal developmental milestones and her past medical history was unremarkable. At about 6 months of age the parents observed that voluntary movements of one
0304-3940/98/$19.00 1998 Elsevier Science Ireland Ltd. All rights reserved PII S0304- 3940(98) 00748- 4
70
M. Reitz, K. Mu¨ller / Neuroscience Letters 256 (1998) 69–72
hand were accompanied by similar movements of the other hand, e.g. when grasping food. Neurological examination was normal except for the distinct mirror movements in the hand and fingers which occurred symmetrically on both sides and extended to proximal parts of the arms when more complex movements were performed. No mirror movements were seen in the lower limbs. The mirror activity could be suppressed by gross motor activity, e.g. by making a fist on the contralateral side. Handedness was determined by the Denckla score [8] which assigned her to be right handed. An MRI of the brain was normal, especially as there was no evidence of callosal malformations. There was no family history of mirror movements and the girl’s parents did not show any clinical evidence of mirror motor activity. Focal TMS was performed using a Cadwell MES 10 stimulator with a maximum output of 2.2 T following the methods described in Mu¨ller et al. (1997). Briefly the optimal position of the ‘figure of eight’ coil over the presumed hand area of the motor cortex was determined as the site where the largest reproducible MEPs could be evoked. This was 4–5 cm lateral and 1 cm posterior to Cz. Stimulus intensity was 90% of the maximal output and 10 stimuli were delivered over each hemisphere with an interval of at least 20 s between successive stimuli. Responses were recorded from the first dorsal interosseus (FDI), brachioradialis (BR) and biceps brachii (BB) muscles. The stimulus was triggered when the child lifted a 0.5 kg weight by flexion of the elbows to yield a reproducible background muscle activity. An average of three to five usable MEP’s was recorded in each muscle. Latencies and amplitudes were determined from the superimposed MEPs. For comparison a data base from a control group of 50 normal children examined with the same stimulation protocol [18] was used. In the child with CMM stimulation of the left or right hemisphere evoked ‘early’ contra- and ipsilateral MEP’s at absolutely identical latencies and with similar amplitudes. These findings were the same in all three recorded muscles (Fig. 1). The latencies were in the range of the control group. In some recordings in the proximal muscles (BR and BB) ipsi- and contralateral responses with a longer latency were induced instead of the early synchronous response (Fig. 1). The latency difference between the ‘early’ ipsilateral and the ‘late’ ipsilateral MEP was 10– 12 ms. These identical contra- and ipsilateral latencies are in contrast to findings in the normal control group where two of three patients under 10 years showed ipsilateral responses which however occurred at a latency difference of 12–14 ms compared to the contralateral side [18]. Three-dimensional movement recordings were performed using a Selspot (system measuring signals of infrared light emitting diodes (LED). LED’s were attached to different parts of the right and left upper extremity. The
Fig. 1. ‘Early’ MEPs after right hemispheric stimulation of the motor cortex in a child with congenital mirror movements: contralateral and ipsilateral responses occur at same latencies in left and right upper extremity muscles (FDI, first dorsal interosseus; BR, brachioradialis; BB, biceps brachii). Depending on the stimulation site ‘late’ ipsi -and contralateral responses could be evoked.
child was asked to perform simple isolated movements of the right or left body side: Index finger abduction, extension, elbow flexion and shoulder abduction were recorded. Averages over 10 movement recordings per side and movement were worked out with a registration-time of 2 s (time resolution 100 Hz, spatial resolution 0.1 mm). For comparison, a control group of 30 healthy children aged from 3 to 10 years was investigated under the same conditions [21]. Fig. 2A shows an example of a recording of voluntary abduction of the left index finger in the CMM child. The figure illustrates simultaneous onset of the left index finger abduction and a smaller amplitude ‘mirror’ movement of the contralateral right side. Such mirror movements with simultaneous onset could be recorded for left and right index finger abduction and index finger extension. No mir-
M. Reitz, K. Mu¨ller / Neuroscience Letters 256 (1998) 69–72
71
Fig. 2. Kinematic analysis (z-coordinate) while performing left index finger abduction. Note the symmetrical beginning of the intended and unintended movement in the patient (A). The normal child shows a latency difference of the associated movement of 12 ms to the intended side (B).
ror movements were however recorded for elbow flexion or shoulder abduction. In contrast to these findings in the CMM patient, in normal children associated movements could be detected only after latency delays of 12 up to 200 ms between the intended and non-intended side. Such associated movements were restricted to distal parts of the upper extremity [21] (Fig. 2B). In the CMM child focal TMS of the motor cortex of one hemisphere elicited MEPs with the same latency in both ipsi- and contralateral muscles of the upper extremities. This is in contrast to findings in normal adults where only contralateral MEPs can be evoked according to the anatomical distribution of the descending corticospinal connections. Even with invasive electrical stimulation there are only contralateral responses in the distal part of the upper extremity [10]. However in adults with congenital mirror movements the same finding as in our patient including bilateral symmetrical responses after focal TMS have been reported [2,5,13]. This points to an abnormal organisation of the descending motor pathways in people with mirror movements. In autopsies of patients with Klippel–Feil syndrome and mirror movements an incomplete pyramidal decussation has been found [11]. Mayston et al. (1997) performed reflex and TMS studies in patients with Kallmann’s syndrome and mirror movements and concluded that an ipsilateral corticospinal tract is responsible for the mirroring in these patients. The fact that latencies of the ipsi and- contralateral responses are identical does not allow for a trancallosal pathway considering a transcallosal conduction time of about 10–13 ms [16]. Also a possible migration disorder of callosal fibres in Kallmann’s Syndrome can not explain the identical latencies in these patients [7], e.g. by an impaired transcallosal inhibition of ipsilaterally projecting neurons. Hence the most likely origin of the ipsilateral corticospinal connections are uncrossed axon collaterals or novel corticospinal connections [3,9,15].
Ipsilateral MEPs occurring at somewhat longer latencies than the contralateral response have been reported as a phenomenon of reorganisation of the motor cortex after stroke or hemispherectomy [1,12,19]. In children with congenital hemiplegic cerebral palsy due to early prenatal lesions and marked mirror movements the origin of the ipsilateral projections at the same latency as the contralateral corticospinal projection are branched axon collaterals probably at the level of the motor neuron pool [4]. It is still not clear, if these ipsilateral corticospinal projections are the only neuroanatomical correlate for mirror movements. There is evidence for bilateral cortical activation in some normal adults performing a strictly unilateral hand movement [3]. In patients with CMM an unilateral movement provokes a bilateral premovement potential and bilateral metabolic activity of the motor cortex detected by positron emission tomography [3,5,14]. The role of a bilateral activation of the motor cortex in patients with mirror movements remains unclear [3]. In two-thirds of the normal children population we found ipsilateral MEPs in distal and proximal muscles of the upper extremity which however occurred at a considerably longer latency than the contralateral responses [18]. These ipsilateral responses can be explained by ipsilateral projecting corticospinal or corticorubrospinal connections. These connections are likely to underlie increasing transcallosal inhibitory influences during ontogeny and therefore disappear after the first decade of life. The timing of these ipsilateral connections makes it unlikely that they are responsible for mirror movements. Depending on the stimulation site we could detect ‘late’ responses in our patient as well. Nevertheless in our patient there again was no time lag between ipsi- and contralateral responses also for these late MEPs. This points to the presence of at least two different populations of neurons which may exert bilateral control through axon collaterals in CMM. The ‘late’ responses may correspond to a slower conducting population of ipsilateral corticospinal connec-
72
M. Reitz, K. Mu¨ller / Neuroscience Letters 256 (1998) 69–72
tions in normal children [18] but similar to the ‘early’ responses they are organised bilaterally (i.e. with axon collaterals) in CMM. Associated movements are present in normal children in the first decade [6]. In these normal children a significant time lag is present between the intended and the not intended associated movements. In our CMM patient however a symmetrical start of the intended and unintended movement was present corresponding to the TMS findings. Also the kinematic finding points against a common neural mechanism of mirror movements and so called associated movements. The results of this study demonstrates an abnormal organisation of the corticospinal tract possibly responsible for CMM. The pattern of motor performance in this condition is different from that of associated movements in normal children. We are grateful to Professor Karch Maulbroun for referring the patient to us. [1] Benecke, R., Meyer, B.-U. and Freund, H.-J., Reorganisation of descending motor pathways in patients after hemispherectomy and severe hemispheric lesions demonstrated by magnetic brain stimulation, Exp. Brain. Res., 83 (1991) 419–426. [2] Britton, T.C., Meyer, B.U. and Benecke, R., Central motor pathways in patients with mirror movements, J. Neurol. Neurosurg. Psychiat., 54 (1991) 505–510. [3] Bouloux, P.M., Quinton, R., Mayston, M.J., Harrison, L.M., Dolan, R.J., Bouloux, P.M., Stephens, J.A., Frackowiak, R.S. and Passingham, R.E., Mirror movements in X-linked Kallman’s syndrome, II. A PET study, Brain, 120 (1997) 1217–1228. [4] Carr, L.J., Harrison, L.M., Evans, A.L. and Stephens, J.A., Patterns of central motor reorganisation in hemiplegic cerebral palsy, Brain, 116 (1993) 1223–1247. [5] Cohen, L.G., Meer, J., Tarkka, I., Bierner, S., Leidermann, D.B., Dubinski, R.M., Sanes, J.N., Jabbari, B., Branscum, B. and Hallet, M., Congenital mirror movements, Brain, 114 (1991) 381–403. [6] Connolly, S. and Stratton, P., Developmental changes in associated movements, Dev. Med. Child Neurol., 10 (1968) 49–56. [7] Danek, A., Heye, B. and Schroedter, R., Cortically evoked motor responses in patients with Xp22.3-linked Kallmann´s Syndrome and in female gene carriers, Ann. Neurol., 31 (1992) 299–304. [8] Denckla, M.B., Revised neurological examination for subtle signs, Psychopharmacol. Bull., 4 (1985) 773–800.
[9] Farmer, S.F., Ingram, D.A. and Stephens, J.A., Mirror movements studied in a patient with Klippel–Feil Syndrome, J. Physiol., 237 (1990) 107–109. [10] Foerster, O., Motorische Felder und Bahnen. In O. Bumke and O. Foerster (Eds.), Allgemeine Neurologie VI, Springer, Berlin, 1936, pp. 1–357. [11] Gunderson, C.H. and Solitare, G.B., Mirror movements in patients with the Klippel–Feil syndrome, Arch. Neurol., 18 (1968) 675–679. [12] Ho¨mberg, V., Stephan, K.M. and Netz, J., Transcranial stimulation of motor cortex in upper motor neurone syndrome: its relation to the motor deficit, Electroenceph. clin. Neurophysiol., 81 (1991) 377–388. [13] Konagaya, Y., Mano, Y. and Konagaya, M., Magnetic stimulation study in mirror movements, Neurology, 237 (1990) 107– 109. [14] Leinsinger, G.L., Heiss, D.T., Jassoy, A.G., Pfluger, T., Hahn, K. and Danek, A., Persistent mirror movements: functional MR imaging of the hand motor cortex, Radiology, 203 (1997) 545– 552. [15] Mayston, M.J., Harrison, L.M., Quinton, R., Stephens, J.A., Krams, M. and Bouloux, P.M., Mirror movements in X-linked Kallman’s syndrome. I. A neurophysiological study, Brain, 120 (1997) 1199–1216. [16] Meyer, B.U., Ro¨richt, S., Einsiedel Gra¨fin von, H., Kruggel, F. and Weindl, A., Inhibitory and excitatory interhemispheric transfers between motor cortical areas in normal humans and patients with abnormalities of the corpus callosum, Brain, 118 (1995) 429–440. [17] Mu¨ller, K., Ho¨mberg, V. and Lenard, H.-G., Magnetic stimulation of motor cortex and nerve roots in children: maturation of cortico-motoneuronal projections, Electroenceph. clin. Neurophysiol., 81 (1991) 63–70. [18] Mu¨ller, K., Kass-Iliyya, F. and Reitz, M., Ontogeny of ipsilateral corticospinal projections: a developmental study with transcranial magnetic stimulation, Ann. Neurol., 42 (1997) 705–711. [19] Netz, J., Lammers, T. and Ho¨mberg, V., Reorganisation of motor output in the non-affected hemisphere after stroke, Brain, 120 (1997) 1579–1586. [20] Regli, F., Filippa, G. and Wiesendanger, M., Hereditary mirror movements, Arch. Neurol., 16 (1967) 620–623. [21] Reitz, M., Kass-Iliyya, F. and Mu¨ller, K., Are ipsilateral corticospinal connections a correlate to associated movements?, Electroenceph. clin. Neurophysiol., 102 (1997) 51P. [22] Scott, G.D. and Wyke, M.A., Congenital mirror movements, J. Neurol. Neurosurg. Psychiat., 44 (1981) 586–599. [23] Yakovlev, P.I. and Lecours, A.R., The myelogenetic cycles of regional maturation of the brain. In A. Minowski (Ed.), Regional Development of the Brain in Early Life, Blackwell, Oxford, 1967, pp. 3–77.
Differences between ‘congenital mirror movements’ and ‘associated movements’ in normal children: a neurophysiological case study Michaela Reitz, Kristina Mu¨ller* Medizinische Einrichtungen der Heinrich-Heine-Universita¨t, Zentrum fu¨r Kinderheilkunde, Moorenstrasse 5, D-40225 Du¨sseldorf, Germany Received 15 June 1998; received in revised form 26 August 1998; accepted 14 September 1998
Abstract In this study we analysed how far physiological associated movements in normal children (which may be present up to the age of 10 years) share the same physiological mechanism with clinically apparent mirror movements. Transcranial magnetic stimulation (TMS) and kinematic movement analysis were applied in a 4-year-old child with congenital mirror movements (CMM). The results were compared with a normative data base of clinically normal children. In the child with CMM focal TMS of one motor cortex induced bilaterally symmetrical responses in distal and proximal upper extremities muscles with identical ipsi- and contralateral latencies. Also kinematic analysis showed a precise symmetrical onset of intended and unintended contralateral movements, whereas normal children with associated movements showed a variable movement onset delay between extremities. The data suggest a different physiological mechanism underlying these two varieties of elementary associated motor activity in childhood. 1998 Elsevier Science Ireland Ltd. All rights reserved
Keywords: Congenital mirror movements; Associated movements; Transcranial magnetic stimulation in children; Motor development; Corticospinal tract
Involuntary movements in homologous contralateral muscles after intended ipsilateral muscle activation are a frequent phenomenon in normal children. These physiological associated movements are partially suppressible, increase with effort and disappear after the childhood period [22]. These associated movements can normally be observed in children up to 10 years of age, suggesting maturational changes of the motor system and completion of myelination of the corpus callosum [6,17,18,23]. The question arises in how far ‘true’ mirror movements which cause clinical problems and tend to persist into adulthood are related to physiological associated movements. In adults, the persistence of mirror movements is always considered abnormal. This condition is often associated with Klippel–Feil syndrome, Kallmann’s syndrome and other rare neurological syndromes [7,11,22]. Mirror move-
* Corresponding author. Tel.: +49 211 8117685; fax: +49 211 8116441; e-mail: [email protected]
ments may be acquired after ischemic stroke or hemispherectomy [1,12,13] and are seen in children with hemiplegic cerebral palsy [4]. Congenital mirror movements (CMM) without any other neurological abnormality are rare. They may be familial or sporadic [20,22]. The pathophysiology remains unclear. Transcranial magnetic stimulation (TMS) has been used in adults to clarify possible abnormalities in wiring of the upper motor neuron in adults with CMM; here bilateral motor evoked potentials (MEP) with identical latencies after TMS have been reported [2,5,13]. In the following study we describe neurophysiological and kinematic data in a child with CMM in contrast to a normative data base of TMS and kinematic data of physiological associated movements in normal children. The 4-year-old girl was born after an uneventful pregnancy and delivery to unrelated healthy parents. She achieved normal developmental milestones and her past medical history was unremarkable. At about 6 months of age the parents observed that voluntary movements of one
0304-3940/98/$19.00 1998 Elsevier Science Ireland Ltd. All rights reserved PII S0304- 3940(98) 00748- 4
70
M. Reitz, K. Mu¨ller / Neuroscience Letters 256 (1998) 69–72
hand were accompanied by similar movements of the other hand, e.g. when grasping food. Neurological examination was normal except for the distinct mirror movements in the hand and fingers which occurred symmetrically on both sides and extended to proximal parts of the arms when more complex movements were performed. No mirror movements were seen in the lower limbs. The mirror activity could be suppressed by gross motor activity, e.g. by making a fist on the contralateral side. Handedness was determined by the Denckla score [8] which assigned her to be right handed. An MRI of the brain was normal, especially as there was no evidence of callosal malformations. There was no family history of mirror movements and the girl’s parents did not show any clinical evidence of mirror motor activity. Focal TMS was performed using a Cadwell MES 10 stimulator with a maximum output of 2.2 T following the methods described in Mu¨ller et al. (1997). Briefly the optimal position of the ‘figure of eight’ coil over the presumed hand area of the motor cortex was determined as the site where the largest reproducible MEPs could be evoked. This was 4–5 cm lateral and 1 cm posterior to Cz. Stimulus intensity was 90% of the maximal output and 10 stimuli were delivered over each hemisphere with an interval of at least 20 s between successive stimuli. Responses were recorded from the first dorsal interosseus (FDI), brachioradialis (BR) and biceps brachii (BB) muscles. The stimulus was triggered when the child lifted a 0.5 kg weight by flexion of the elbows to yield a reproducible background muscle activity. An average of three to five usable MEP’s was recorded in each muscle. Latencies and amplitudes were determined from the superimposed MEPs. For comparison a data base from a control group of 50 normal children examined with the same stimulation protocol [18] was used. In the child with CMM stimulation of the left or right hemisphere evoked ‘early’ contra- and ipsilateral MEP’s at absolutely identical latencies and with similar amplitudes. These findings were the same in all three recorded muscles (Fig. 1). The latencies were in the range of the control group. In some recordings in the proximal muscles (BR and BB) ipsi- and contralateral responses with a longer latency were induced instead of the early synchronous response (Fig. 1). The latency difference between the ‘early’ ipsilateral and the ‘late’ ipsilateral MEP was 10– 12 ms. These identical contra- and ipsilateral latencies are in contrast to findings in the normal control group where two of three patients under 10 years showed ipsilateral responses which however occurred at a latency difference of 12–14 ms compared to the contralateral side [18]. Three-dimensional movement recordings were performed using a Selspot (system measuring signals of infrared light emitting diodes (LED). LED’s were attached to different parts of the right and left upper extremity. The
Fig. 1. ‘Early’ MEPs after right hemispheric stimulation of the motor cortex in a child with congenital mirror movements: contralateral and ipsilateral responses occur at same latencies in left and right upper extremity muscles (FDI, first dorsal interosseus; BR, brachioradialis; BB, biceps brachii). Depending on the stimulation site ‘late’ ipsi -and contralateral responses could be evoked.
child was asked to perform simple isolated movements of the right or left body side: Index finger abduction, extension, elbow flexion and shoulder abduction were recorded. Averages over 10 movement recordings per side and movement were worked out with a registration-time of 2 s (time resolution 100 Hz, spatial resolution 0.1 mm). For comparison, a control group of 30 healthy children aged from 3 to 10 years was investigated under the same conditions [21]. Fig. 2A shows an example of a recording of voluntary abduction of the left index finger in the CMM child. The figure illustrates simultaneous onset of the left index finger abduction and a smaller amplitude ‘mirror’ movement of the contralateral right side. Such mirror movements with simultaneous onset could be recorded for left and right index finger abduction and index finger extension. No mir-
M. Reitz, K. Mu¨ller / Neuroscience Letters 256 (1998) 69–72
71
Fig. 2. Kinematic analysis (z-coordinate) while performing left index finger abduction. Note the symmetrical beginning of the intended and unintended movement in the patient (A). The normal child shows a latency difference of the associated movement of 12 ms to the intended side (B).
ror movements were however recorded for elbow flexion or shoulder abduction. In contrast to these findings in the CMM patient, in normal children associated movements could be detected only after latency delays of 12 up to 200 ms between the intended and non-intended side. Such associated movements were restricted to distal parts of the upper extremity [21] (Fig. 2B). In the CMM child focal TMS of the motor cortex of one hemisphere elicited MEPs with the same latency in both ipsi- and contralateral muscles of the upper extremities. This is in contrast to findings in normal adults where only contralateral MEPs can be evoked according to the anatomical distribution of the descending corticospinal connections. Even with invasive electrical stimulation there are only contralateral responses in the distal part of the upper extremity [10]. However in adults with congenital mirror movements the same finding as in our patient including bilateral symmetrical responses after focal TMS have been reported [2,5,13]. This points to an abnormal organisation of the descending motor pathways in people with mirror movements. In autopsies of patients with Klippel–Feil syndrome and mirror movements an incomplete pyramidal decussation has been found [11]. Mayston et al. (1997) performed reflex and TMS studies in patients with Kallmann’s syndrome and mirror movements and concluded that an ipsilateral corticospinal tract is responsible for the mirroring in these patients. The fact that latencies of the ipsi and- contralateral responses are identical does not allow for a trancallosal pathway considering a transcallosal conduction time of about 10–13 ms [16]. Also a possible migration disorder of callosal fibres in Kallmann’s Syndrome can not explain the identical latencies in these patients [7], e.g. by an impaired transcallosal inhibition of ipsilaterally projecting neurons. Hence the most likely origin of the ipsilateral corticospinal connections are uncrossed axon collaterals or novel corticospinal connections [3,9,15].
Ipsilateral MEPs occurring at somewhat longer latencies than the contralateral response have been reported as a phenomenon of reorganisation of the motor cortex after stroke or hemispherectomy [1,12,19]. In children with congenital hemiplegic cerebral palsy due to early prenatal lesions and marked mirror movements the origin of the ipsilateral projections at the same latency as the contralateral corticospinal projection are branched axon collaterals probably at the level of the motor neuron pool [4]. It is still not clear, if these ipsilateral corticospinal projections are the only neuroanatomical correlate for mirror movements. There is evidence for bilateral cortical activation in some normal adults performing a strictly unilateral hand movement [3]. In patients with CMM an unilateral movement provokes a bilateral premovement potential and bilateral metabolic activity of the motor cortex detected by positron emission tomography [3,5,14]. The role of a bilateral activation of the motor cortex in patients with mirror movements remains unclear [3]. In two-thirds of the normal children population we found ipsilateral MEPs in distal and proximal muscles of the upper extremity which however occurred at a considerably longer latency than the contralateral responses [18]. These ipsilateral responses can be explained by ipsilateral projecting corticospinal or corticorubrospinal connections. These connections are likely to underlie increasing transcallosal inhibitory influences during ontogeny and therefore disappear after the first decade of life. The timing of these ipsilateral connections makes it unlikely that they are responsible for mirror movements. Depending on the stimulation site we could detect ‘late’ responses in our patient as well. Nevertheless in our patient there again was no time lag between ipsi- and contralateral responses also for these late MEPs. This points to the presence of at least two different populations of neurons which may exert bilateral control through axon collaterals in CMM. The ‘late’ responses may correspond to a slower conducting population of ipsilateral corticospinal connec-
72
M. Reitz, K. Mu¨ller / Neuroscience Letters 256 (1998) 69–72
tions in normal children [18] but similar to the ‘early’ responses they are organised bilaterally (i.e. with axon collaterals) in CMM. Associated movements are present in normal children in the first decade [6]. In these normal children a significant time lag is present between the intended and the not intended associated movements. In our CMM patient however a symmetrical start of the intended and unintended movement was present corresponding to the TMS findings. Also the kinematic finding points against a common neural mechanism of mirror movements and so called associated movements. The results of this study demonstrates an abnormal organisation of the corticospinal tract possibly responsible for CMM. The pattern of motor performance in this condition is different from that of associated movements in normal children. We are grateful to Professor Karch Maulbroun for referring the patient to us. [1] Benecke, R., Meyer, B.-U. and Freund, H.-J., Reorganisation of descending motor pathways in patients after hemispherectomy and severe hemispheric lesions demonstrated by magnetic brain stimulation, Exp. Brain. Res., 83 (1991) 419–426. [2] Britton, T.C., Meyer, B.U. and Benecke, R., Central motor pathways in patients with mirror movements, J. Neurol. Neurosurg. Psychiat., 54 (1991) 505–510. [3] Bouloux, P.M., Quinton, R., Mayston, M.J., Harrison, L.M., Dolan, R.J., Bouloux, P.M., Stephens, J.A., Frackowiak, R.S. and Passingham, R.E., Mirror movements in X-linked Kallman’s syndrome, II. A PET study, Brain, 120 (1997) 1217–1228. [4] Carr, L.J., Harrison, L.M., Evans, A.L. and Stephens, J.A., Patterns of central motor reorganisation in hemiplegic cerebral palsy, Brain, 116 (1993) 1223–1247. [5] Cohen, L.G., Meer, J., Tarkka, I., Bierner, S., Leidermann, D.B., Dubinski, R.M., Sanes, J.N., Jabbari, B., Branscum, B. and Hallet, M., Congenital mirror movements, Brain, 114 (1991) 381–403. [6] Connolly, S. and Stratton, P., Developmental changes in associated movements, Dev. Med. Child Neurol., 10 (1968) 49–56. [7] Danek, A., Heye, B. and Schroedter, R., Cortically evoked motor responses in patients with Xp22.3-linked Kallmann´s Syndrome and in female gene carriers, Ann. Neurol., 31 (1992) 299–304. [8] Denckla, M.B., Revised neurological examination for subtle signs, Psychopharmacol. Bull., 4 (1985) 773–800.
[9] Farmer, S.F., Ingram, D.A. and Stephens, J.A., Mirror movements studied in a patient with Klippel–Feil Syndrome, J. Physiol., 237 (1990) 107–109. [10] Foerster, O., Motorische Felder und Bahnen. In O. Bumke and O. Foerster (Eds.), Allgemeine Neurologie VI, Springer, Berlin, 1936, pp. 1–357. [11] Gunderson, C.H. and Solitare, G.B., Mirror movements in patients with the Klippel–Feil syndrome, Arch. Neurol., 18 (1968) 675–679. [12] Ho¨mberg, V., Stephan, K.M. and Netz, J., Transcranial stimulation of motor cortex in upper motor neurone syndrome: its relation to the motor deficit, Electroenceph. clin. Neurophysiol., 81 (1991) 377–388. [13] Konagaya, Y., Mano, Y. and Konagaya, M., Magnetic stimulation study in mirror movements, Neurology, 237 (1990) 107– 109. [14] Leinsinger, G.L., Heiss, D.T., Jassoy, A.G., Pfluger, T., Hahn, K. and Danek, A., Persistent mirror movements: functional MR imaging of the hand motor cortex, Radiology, 203 (1997) 545– 552. [15] Mayston, M.J., Harrison, L.M., Quinton, R., Stephens, J.A., Krams, M. and Bouloux, P.M., Mirror movements in X-linked Kallman’s syndrome. I. A neurophysiological study, Brain, 120 (1997) 1199–1216. [16] Meyer, B.U., Ro¨richt, S., Einsiedel Gra¨fin von, H., Kruggel, F. and Weindl, A., Inhibitory and excitatory interhemispheric transfers between motor cortical areas in normal humans and patients with abnormalities of the corpus callosum, Brain, 118 (1995) 429–440. [17] Mu¨ller, K., Ho¨mberg, V. and Lenard, H.-G., Magnetic stimulation of motor cortex and nerve roots in children: maturation of cortico-motoneuronal projections, Electroenceph. clin. Neurophysiol., 81 (1991) 63–70. [18] Mu¨ller, K., Kass-Iliyya, F. and Reitz, M., Ontogeny of ipsilateral corticospinal projections: a developmental study with transcranial magnetic stimulation, Ann. Neurol., 42 (1997) 705–711. [19] Netz, J., Lammers, T. and Ho¨mberg, V., Reorganisation of motor output in the non-affected hemisphere after stroke, Brain, 120 (1997) 1579–1586. [20] Regli, F., Filippa, G. and Wiesendanger, M., Hereditary mirror movements, Arch. Neurol., 16 (1967) 620–623. [21] Reitz, M., Kass-Iliyya, F. and Mu¨ller, K., Are ipsilateral corticospinal connections a correlate to associated movements?, Electroenceph. clin. Neurophysiol., 102 (1997) 51P. [22] Scott, G.D. and Wyke, M.A., Congenital mirror movements, J. Neurol. Neurosurg. Psychiat., 44 (1981) 586–599. [23] Yakovlev, P.I. and Lecours, A.R., The myelogenetic cycles of regional maturation of the brain. In A. Minowski (Ed.), Regional Development of the Brain in Early Life, Blackwell, Oxford, 1967, pp. 3–77.