- Email: [email protected]
Pathophysiology of congenital mirror movements
C-P angle cavernoma / Mirror movements
Case reports outcome. In: Tos M, ThomsonJ (eds). Acoustic Neuroma. Copenhagen: Proceedings of the First International Conference on Acoustic Neuroma, 1991: 423-427. 14. Simard M, Garcia-Bengochea F, Ballinger WE, MickleJR Quisling RG. Cavernous angioma: a review of 126 collected and 12 new clinical cases. Neurosurgery 1986; 18: 162-172. 15. Mawhinney RR, BuckleyJH, Worthington BS. Magnetic resonance imaging of the cerebellopontine angle. BrJ Radiol 1986; 59: 961-969. 16. Osborn AG. Brain tumours and tumour-like masses. In: Osborn A (ed). Diagnostic Neuroradiology. St Louis: Mosby, 1994: 437-450.
Fig. 4 Well circumscribed dural cavernous angioma without signs of intraparenchymal bleeding or calcification. The vessels were partly closed with thrombotic material and are lined by a single layer of endothelium (haematoxylin and eosin).
Pathophysiology of congenital mirror movements
References 1. Brackmann DE, Bartels LJ. Rare tumours of the cerebellopontine angle. Otolaryngol Head Neck Surg 1980; 88: 555-559. 2. Rengachary SS, Klyan-Raman UR Other cranial intradural angiomas. In: Wilkins RH, Rengachary SS (eds). Neurosurgery, Baltimore: McGraw-Hill, 1985: 1465-1473. 3. Burger PC, Scheithauer BW. Cavernous Angioma. Tumours of the Central Nervous System. Washington: Armed Forces Institute of Pathology, 1993: 290-291. 4. Russell DS, Rubinstein LJ. Pathology of Turnouts of the Nervous System, 5th edn. London: Edward Arnold, 1989: 730-735. 5. Mangham CA, CarberryJN, Brackmann DE. Management of intratemporal vascular turnouts. Laryngoscope 1981; 91: 86%876. 6. Pappas DG, Schneiderman TS, Brackmann DE, Simpson LC, Chandra-Sekar B, Sofferman R. Cavernous haemangiomas of the internal auditory canal. Otolaryngol Head Neck Surg 1989; 101: 27-32. 7. Schott B, Morgon A, Bady B, Bernard PA. Cavernome de L'angle ponto-cerebelleux. J Fr Otolrhinolaryngol 1970; 19: 339-342. 8. Sundaresan N, Eller T, Ciric I. Haemangiomas of the internal auditory canal. Surg Neurol 1976; 6: 119-121. 9. Bordi L, Pires M, Symon L, Cheesman AD. Cavernous angioma of the cerebellopontine angle: a case report. BrJ Neurosurg 1991; 5: 83-86. 10. Dale AJ. The cerebellopontine angle syndrome. Med Clin North Am 1968; 52: 789-795. 11. Iplikcioglu AC, Benli K, Bertan V, Ruacan S. Cystic cavernous haemangioma of the cerebellopontine angle: case report. Neurosurgery 1986; 19: 641-642. 12. Ohkuma A, Sugimoto S, Murase S, Iwama T, Miwa Y. Cavernous angioma of the cerebellopontine angle: a case report. Neurol Surg 1993; 21: 367-371. 13. Pfaltz CR, Gratzl O. The retrosigmoid approach in the cerebellopontine angle surgery: otological procedure and
S. R. D . W a t s o n FRACP, J. G. C o l e b a t c h PhD FRACP Institute of Neurological Sciences, Prince of Wales Hospital, Randwick, Sydney 9031, Australia
A case of congenital mirror movements occurring in association with lnild hemiparesis and unilateral schizencephaly was investigated using focal transcranial magnetic stimulation. The cortical motor representations for first dorsal interosseous, abductor digiti minimi and biceps brachii were mapped for both cerebral hemispheres: bilateral short latency EMG responses were elicited with stimulation over the nonschizencephalic hemisphere while no short latency responses were obtained with stimulation over the schizencephalic hemisphere. The cortical representations for all three homologous muscle pairs studied were colocalized, and the responses occurred at identical latencies bilaterally. Our findings, plus previous observations suggesting a single functional motor cortex in schizencephaly, are consistent with the suggestion that mirror movements are the result o f branched corticospinal projections to distal muscle groups. Journal of Clinical Neuroscience 1997, 4 (1) : 69-74 © Pearson Professional Ltd 1997 Keywords: mirror movements, magnetics, pyramidal tracts, schizencephaly
Introduction Mirror movements are characterized by an association of intended movements of one limb with simultaneous non-suppressible 'mirror image' movements of the other, due to contraction of homologous muscles. 1-5 These findings are usually most obvious for the hands, although fractionated movements of the fingers are preserved. Mirror movements have also been
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Case reports described in proximal arm and in distal lower limb muscles) Congenital mirror movements are recognised from infancy and are non-progressive.1-5Mirror movements may occur in normal infants,< 6 but are considered pathological if they are particularly prominent or persist beyond 10 years of age. 4 Congenital mirror movements may occur in isolation, most often as a familial trait, 2,7 or in association with developmental abnormalities, such as the Klippel-Feil syndrome8,9 or Kallman's syndrom@ °, 11 as well as with some types o f congenital hemiparesis. 19-14 There is a strong association between the presence of congenital mirror movements and electrophysiological evidence of ipsilaterally projecting corticospinal fibres, so that stimulation of the motor cortex evokes bilateral short latency electromyographic (EMG) responses. This may be demonstrable for one 12,13 or, more often, both hemispheres. 5,s, 10,15-1a We recently had the opportunity to study a subject with typical congenital mirror movements occurring in the context of hemiparetic cerebral palsy and schizencephaly. We describe the clinical features and the results of a motor cortex mapping study using transcranial magnetic stimulation, and conclude with a discussion of the pathophysiology of congenital mirror movements.
Materials and methods The patient, a 29-year-old male New Zealander, was admitted to the Prince of Wales Hospital febrile and confused, several weeks following a holiday in Bali. The acute features were attributed to typhoid fever (laboratory proven) and settled rapidly with therapy. O n presentation he was noted to have mild left-sided hyperreflexia, a left-sided extensor plantar response and mild hypoplasia of the left arm, together with a long history of leftsided motor difficulties. A cerebral CT scan showed right-sided schizencephaly. Once the confusion resolved, the patient was able to confirm that his neurological disorder was long-standing. He had been adopted soon after birth and no obstetric or family history was available, but problems with his left arm and leg were noted from infancy. He started walking at around 3 years but dragged his left leg and throughout primary school wore a calliper and received regular physiotherapy. Over his high school years there was a degree of functional improvement and eventually he was able to walk near normally without aids but continued to have difficulty with running. He had always been strongly righthanded and aware that the left hand was clumsy and weak. Despite these limitations he completed high school at a moderately high level and was working successfully as manager and bookkeeper for a hardware store. Mirror movements had been present for as long as he could recall. When he used a given hand, particularly for delicate tasks, the other hand closely 'mirrored' its movements. This occurred whether he was intending movement of his right hand or of his clumsy left hand and led to a variety of functional difficulties. He typed proficiently with his right hand, but was unable to type two-handed because when a finger of one hand would strike a key, the homologous finger of the other hand would strike an unwanted key involuntarily. He was also unable to eat with a knife and fork because when he tried to cut food using the knife in his right hand the fork in his left hand shifted the food away. For most activities he was able to use the left hand to stabilize the object while any delicate manipulation was performed by the right, e.g. tying shoelaces or doing up buttons. In general he felt that he had adapted well to his circumstances, but problems still occurred. He described a recent episode in which, while holding a power drill in his left hand,
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Mirror movements
Fig. 1 An axial Tl-weighted image showing the right-sided cleft extending from the cortical margin to the lateral ventricle. The cortex adjoining the cleft is thickened and lacks normal architecture. he picked up a screwdriver with his right hand. The fingers of his left hand involuntarilytightened on the drill handle, switching on the drill and moving it towards his groin. The drill cut through the fly of his pants and he was able to avoid injury only by dropping the screwdriver from his right hand, thereby releasing his left hand's grip. On physical examination a mild left-sided spasticity was found, with very mild hand weakness and impairment of proprioception at the distal interphalangealjoints of the left hand. Rapid fractionated movements of the left hand were slower and of lower amplitude than those of the right. With active movements of either arm, at or distal to the wrist, mirror movements were visible in homologous muscles of the opposite arm. The mirror movements were of comparable amplitude to the intended movements for movements of the thumb and fingers, and were equally prominent for both hands. Mirror movements were not observed for more proximal arm movements, nor for movements of the face or legs. A cerebral magnetic resonance imaging (MRI) scan was performed, confirming right-sided schizencephaly with the abnormal cleft extending from the Sylvian fissure to the lateral ventricle at a site corresponding to the central sulcus of the left hemisphere. The cleft was lined by thickened cortex without a normal gyral pattern. No associated abnormalities such as agenesis of the corpus callosum were found (Fig. 1). Normal somatosensory evoked responses were obtained from over the left hemisphere following stimulation of the right median nerve, but no reproducible cerebral response was found over either hemisphere following stimulation of the left median nerve, despite well formed peripheral potentials. A MagStim Model 200 (MagStim Co., Dyffed, Wales) magnetic stimulator with a focal (figure-of-eight) 70 m m coil was used for the study. Unrectified surface EMG was recorded on 6 channels: right and left first dorsal interosseous (FDI), abductor digiti minimi (ADM) and biceps. The threshold for response was 50% of maximal stimulator output for both the right and left FDI at a point 1 cm anterior to the vertex and 5 cm to the left, while no response was seen in any of the sampled muscles with stimulation at 100% of stimulator output over the right hemisphere. The cortical mapping study was performed using a grid of 27 stimulation sites separated by 2.5-cm intervals, spanning 5 cm in the sagittal plane from 2 cm posterior to the vertex r u n n i n g anteriorly and 20 cm in the coronal plane r u n n i n g
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R BICEPS
L BICEPS
R FDI
L FDI
For each muscle an average latency (SD) was calculated from the latencies of the 6 largest responses obtained at 70% stimulator output. For FDI the latency for the right was at 22.3 (_+ 1.2) ms and for the left 22.0 (+ 0.9) ms, for ADM the right was 22.7 (-+ 2.0) ms and the left 21.2 (_+ 1.5) ms, and for biceps the right was 13.3 (_+ 0.5) ms and the left 14.2 (_+ 0.4) ms. The differences between the sides were not significant. Responses in upper limb muscles for the normal controls were only found with stimulation over the contralateral hemisphere. The extent of the sites over the left hemisphere from which responses were obtained for the controls' right-sided muscles, the response thresholds and latencies were similar to those found (for both right- and left-sided muscles) following stimulation over the left hemisphere of our patient.
Discussion
10m$
Fig. 2 Simultaneous recordings from the right and left first dorsal interosseous and biceps brachii muscles following magnetic stimulation at 70% of maximal output at a site 0.5 cm anterior to the vertex in the sagittal plane and 5 cm to the left in the coronal plane. The vertical dashed lines indicate the time of delivery of the stimulus, and portions of the traces have been emphasized to highlight the responses.
10 cm from the midline on either side. The figure-of-eight coil was held tangential to the scalp and with the handle to the left side for all stimulation sites. Studies were performed with muscles relaxed at each of 60%, 65 % and 70% of stimulator output, and for each study all 97 sites were stimulated sequentially three times. For each EMG response the amplitude was measured peak to peak, and the latency was determined visually as the point of clear deviation from baseline. For each muscle at each site and for each stimulus intensity, three response amplitudes were averaged. For each stimulus, level, each average was divided by the largest obtained for that muscle, and these rescaled values (0-1) were displayed in graphical form. Three normal controls (31 M, 28 M, 27 F) were also studied using the same stimulation and recording protocols (at 20% above their respective response thresholds).
Results Responses in all muscles were found with focal magnetic stimulation over the left hemisphere (Fig. 2) of the patient, but no responses were found with stimulation over the right side. For all stimulus intensities and for all muscles studied, very similar topographical patterns of response amplitudes were found for homologous muscles bilaterally (Fig. 3). This was equally so for biceps, in which mirror movements were not apparent clinically, as for FDI and ADM. The largest averaged responses were 5.7 mVfor right FDI and 9.0 mVfor left FDI (both at 2 cm posterior to the vertex and 10 cm to the left), 2.9 mVfor right ADM and 3.4 mV for left ADM (both at 0.5 cm anterior to the vertex and 5 cm to the left) and 1.9 mV for right biceps and 1.1 mV for left biceps (both at the site 2 cm posterior to the vertex and 5 cm to the left).
Schizencephaly is a disorder of neuronal migration and therefore the pathogenic mechanism must operate between 7 and 16 weeks postconception, the period of cortical neuronal migration) 9-21 Most cases of schizencephaly are idiopathic although familial cases have been described 22 and recent evidence suggests that in some cases it is due to a focal ischaemic insult early in the period of neuronal migration. 2°,~1The congenital mirror movements in our subject were typical: they were present from early life, they were non-progressive and they showed no voluntary suppression. Distal, fractionated movements of the upper limbs were predominantly involved, and there was marked dissociation between the preservation of relatively i n d e p e n d e n t movements between the fingers of a given hand, and the loss of independence between the hands.I, 2,4.5.s In our subject the mirror movements occurred in association with mild congenital hemiparesis due to the schizencephaly and, despite their prominence, caused only mild motor disability. His developmental motor delay was probably due to the associated hemiparesis, although swimming and running, tasks requiring alternating movements of proximal limb muscles, may be affected in some subjects with mirror movements. 1,5 The motor cortex mapping study in our subject demonstrated colocalization of responses in FDI, ADM and biceps brachii muscles with stimulation over the non-schizencephalic left hemisphere. Furthermore, the responses in homologous muscles were at the same latency and within the normal range for these muscles. In contrast, no responses were obtained with stimulation over the schizencephalic right hemisphere. This study has found no evidence of two separate representations for the two upper limbs within the one hemisphere, nor, unlike one case described in the literature, ~for an enlargement of the cortical representation of these muscle groups. Although we suspect that the right hemisphere carries no short latency projections to the upper limbs, we cannot completely exclude the possibility that functioning motpr cortex is buried within the schizencephalic cleft and cannot be stimulated transcranially. However, a case of schizencephaly with mirror movements has been described in whom a Wada test was performed during evaluation for epilepsy surgery.19 With infusion of methohexital into the carotid artery on the schizencephalic left side, no deficits were seen, but with infusion on the (normal) right side there was severe aphasia and profound bilateral limb weakness, implying that the motor representation for both limbs as well as language function were located within the one, non-schizencephalic, hemisphere. Electrophysiological investigations of subjects with mirror movements have provided important evidence as to their origin. The almost universal finding has been the presence of
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Case reports
Mirror movements
R BICEPS
L BICEPS
L-1Ocm
Ant
Ant
R FDI
L FDI
L-lOcm
Ant
Ant
Fig. 3 A graphical representation of the responses found for the right and left first dorsal interosseous and biceps muscles with stimulation at 70% of maximal output. Each bar represents the average of three responses for a given stimulation site, normalized in relation to the largest average response for that particular muscle. Stimulation sites were 2.5 cm apart in the sagittal plane, from 2 cm posterior to the vertex (Post) to 3 cm anterior to the vertex (Ant), and were also 2.5 cm apart in the coronal plane, from 10 cm to the left of midline to 10 cm to the right. Colocalization for the responses in homologous muscles is apparent with stimulation over the left hemisphere.
bilateral short latency projections to hand muscles; most commonly these are demonstrable from both cerebral hemispheres, 5, s, 10,15-18but when associated with congenital hemiparesis, bilateral short latency projections are evident from stimulation over a single hemisphere only, as with our patient) 2,13 Although ipsilateral excitatory responses may sometimes occur in normals with unilateral cortical stimulation, the responses are generally delayed, are 0£ low amplitude and are most p r o m i n e n t for proximal muscles. 23T h e r e is general a g r e e m e n t that subjects with mirror movements have normal spinal reflex circuitry, assessed using H reflexes and f waves J, 8, 12 O n the other hand, long latency stretch reflexes from the t h u m b and cutaneous reflexes s, 12,13,24 can be recorded bilaterally following stimulation of a single side,
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findings which have in turn b e e n used as additional evidence for transcranial pathways of these reflexes. T h e distal p r e d o m i n a n c e of muscle involvement in mirror movements is similar to reports of the relative strength of pyramidal outflow to muscles of the arm as assessed by the amplitude of corticomotoneuronal excitatory postsynaptic potential (EPSPs) recorded from m o t o n e u r o n s 25'26 and by the relative size of responses to cortical stimulation, 18,27 although there is some evidence to suggest that the proximal-distal gradation may be less marked in humans. 28 Direct corticomotoneuronal projections are held to be of critical importance for fractionated movemerits of hand muscles. 29, 3o Given the distal p r e d o m i n a n c e of mirroring, either the large diameter corticomotoneuronal
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neurons projecting to intrinsic hand muscles are more likely to be involved in alterations underlying mirroring, or these rapidly conducting fibres are relatively more effective in activating distal muscles than similar fibres innervating more proximal muscles. Abnormalities of the motor 'command' have also been proposed as a possible basis for mirroring. Studies of premovement potentials in mirror movements have found evidence of bilateral motor cortical activation5' 31 and a positron emission tomographic (PET) activation study demonstrated bilateral sensorimotor cortical activation with intended movement of one side, in one subject3 One group has proposed that the abnormality underlying mirror movements is failure of the normal inhibition of the motor command reaching the ipsilateral motor cortex 15. Monkeys with experimental lesions of the supplementary motor area show characteristic deficits in which both hands tend to behave similarly?2 Such an abnormality of motor command is not, of course, incompatible with coexistent abnormalities of the corticospinal system and, indeed, may be responsible for the more widespread mirroring which may occur in these patients as children? The patients possibly learn with experience to direct their command to the desired muscle groups. However, it is difficult to see why mirroring should be confined to distal muscles if it is primarily due to an abnormality of motor command: if it is possible for the patients to learn to 'focus' their command to most muscle groups why should they not be able to do so for distal muscles too? We believe that the main basis for the motor syndrome of mirroring as seen in adults is not an abnormality of the motor command but an abnormality of lateralization within the corticospinal system. In addition to the evidence given above, one EMG study showed a correlation between the reaction times of the right and left sides when the patients were asked to move each thumb individually, but not when they were asked to move both together, suggesting that two separate motor commands could be generated. 3There have also been two cases with familial mirror movements described in whom mirror movements persisted in the plegic arm following a major stroke in adult life, even though no voluntary movement of the limb was possible.< 7 In this situation corticospinal projections from the intact (ipsilateral) motor cortex must be responsible for the mirror movements. We favour the mechanism first proposed by Farmer et al8 as being the most likely to explain the clinical features. These authors showed peaks in the cross-correlograms of the discharges of motor units in hand muscles, that were largest for distal muscles and not detectable for more proximal ones. They proposed that their findings were most likely to be due to branching of individual corticospinal tract fibres to supply motoneuron pools on both sides of the cord. In a large study of patients with congenital or juvenile onset hemiparesis, some of whom showed mirror movements, Carr et a112 showed that it was only those patients with bilateral projections and peaks in the cross-correlograms who demonstrated prominent mirror movements. Such an abnormality would explain why the patients can never overcome the mirroring: because individual corticospinal fibres project bilaterally, it is not possible to learn to direct the motor command in a way to avoid mirroring. For isolated congenital mirror movements a primary failure of pyramidal lateralization may be responsible but for cases associated with congenital hemiparesis it has been proposed that axonal branching occurs as a secondary p h e n o m e n o n , to innervate motor neurons that would normally be innervated by the damaged motor cortex) 2 From the results of clinical12 and animaP3, 34 research, it appears likely that such compensatory branching can only occur early in central nervous system development, perhaps during the first 29 weeks postconception) 2
The remarkable clinical features of congenital mirror movements and the colocalization we have described suggest that the same pattern of connectivity between axons and motor neurons is established for the ipsilateral projections as for the contralateral projections. In this regard, it has been shown that following unilateral pyramidal section in the neonatal hamster, a normal pattern of arborization and synapse formation is seen for the axons that cross the midline at the segmental level to pass into the denervated cord. 33 We propose that in our subject with congenital mirror movements, mild left hemiparesis, mild left-sided sensory disturbance and schizencephaly, the right sensorimotor cortex was damaged early in utero, at a time of considerable neuronal plasticity. Alterations, probably branching, of corticospinal axons projecting from the intact left motor cortex occurred, resulting in functional innervation of left-sided motor neurons and the clinical p h e n o m e n o n of mirror movements.
Addendum We have recently become aware of a study by Maegaki et als5 in which motor cortex mapping was performed in a subject with unilateral cortical dysplasia and mirror movements and which showed colocalized, bilateral responses from the normal hemisphere.
Acknowledgments We thank Dr P. Spira for allowing us to study his patient. Ms D. Wagener gave expert technical assistance. Dr Watson was recipient of the Whitmont Fellowship of the Australian Brain Foundation during the period of this study.
Received25 March 1996; Accepted 17 April 1996
Correspondence and offprint requests: DrJ. G. Colehatch, Institute of Neurological Sciences, Prince of Wales Hospital, High Street, Randwick, Sydney2031, Australia, Tel: 61 2 382 2422, Fax: 61 2 9382 2428, E-mail:[email protected] References 1. Schott GD, Wyke MA. Congenital mirror movements. J Neurol Neurosurg Psychiatry 1981, 44: 586-599. 2. Regli F, Filippa G, Weisendanger M. Hereditary mirror movements. Arch Neurol 1967; 16: 620-623. 3. Forget R, Boghen D, Attig E, Lamarre Y. Electromyographic studies of congenital mirror movements. Neurology 1986; 36: 1316-1322. 4. Rasmussen R Persistent mirror movements: a clinical study of 17 children, adolescents and young adults. Dev Med Child Neurol 1993; 35: 699-707. 5. Cohen LG, MeerJ, Tarkka I, et al. Congenital mirror movements. Abnormal organisation of motor pathways in two patients. Brain 1991; 114: 381-403. 6. Connolly K, Stratton R Developmental changes in associated movements. Dev Med Child Neurol 1968; 10: 49-56. 7. Haerer AF, Currier RD. Mirror movements. Neurology 1966; 16: 757-760. 8. Farmer SF, Ingram DA, StephensJA. Mirror movements studied in a patient with Klippel-Feil syndrome. J Physiol 1990; 428: 467-484. 9. Gunderson CH, Soitare GB. Mirror movements in patients with Klippel-Feil syndrome. Arch Neurol 1968; 18: 675-679. 10. Danek A, Heye B, Schroeter R. Cortically evoked motor responses in patients with Xp22.3-1inked Kallmann's syndrome and in female gene carriers. Ann Neurol 1992; 31: 299-304.
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Case reports 11. SchwankhausJD, CurrieJ,Jaffe MJ, Rose SR, Sherins RJ. Neurologic findings in men with isolated hypogonadotropic hypogonadism. Neurology 1989; 39: 223-226. 12. Carr LJ, Harrison LM, Evans AL, StephensJA. Patterns of central motor reorganisation in hemiplegic cerebral palsy. Brain 1993; 116: 1223-1247. 13. RothwellJC, ColebatchJ, Britton TC, et al. Physiological studies in a patient with mirror movements and agenesis of the corpus callosum. J Physiol 1991; 438: 34P. 14. GreenJB. An electromyographic study of mirror movements. Neurology 1967; 17: 91-94. 15. HermsdorferJ, Danek A, Winter T, Marquardt C, Mai N. Persistent mirror movements: force and timing of 'mirroring' are task dependent. Exp Brain Res 1995; 104: 126-134. 16. Konagaya Y, Mano Y, Konagaya M. Magnetic stimulation study in mirror movements.J Neurol 1990; 237: 107-109. 17. Britton TC, Meyer B-U, Benecke R. Central motor pathways in patients with mirror movements. J Neurol Neurosurg Psychiatry 1991; 54: 505-510. 18. Cohen LG, Roth BJ, Wasserman EM, et al. Magnetic stimulation of the human cerebral cortex, an indicator of reorganisation in motor pathways in certain pathological conditions.J Clin Neurophysiol 1991; 8: 56-65. 19. Brown MC, Levin BE, Ramsay RE, Landy HJ. Comprehensive evaluation of left hemisphere type 1 schizencephaly. Arch Neurol 1993; 50: 667-669. 20. Suchet IB. Schizencephaly: antenatal and postnatal assessment with colour-flow Doppler imaging. Can Assoc RadiolJ 1994; 45: 193-200. 21. Landieu P, Lacroix C. Schizencephaly, consequence of a developmental vasculopathy? A clinicopathological report. Clin Neuropath 1994; 13: 192-196. 22. Hilburger AC, WillisJK, Bouldin E, Henderson-Tilton A. Familial schizencephaly. Brain Dev 1993; 15: 234-236. 23. Wasserman EM, Fuhr P, Cohen LG, Hallett M. Effects of transcranial magnetic stimulation on ipsilateral muscles. Neurology 1991; 41: 1795-1799. 24. Capaday C, Forget R, Fraser R, Lamarre Y. Evidence for a contribution of the motor cortex to the long-latency stretch reflex of the human thumb. J Physiol 1991; 440: 243-255. 25. Phillips CG, Porter R. The pyramidal projection to motoneurones of some muscle groups of the baboon's forelimb. Prog Brain Res 1964; 12: 222-242. 26. CloughJFM, Kernell D, Phillips CG. The distribution of monosynaptic excitation from the pyramidal tract and from primary spindle afferents to motoneurones of the baboon's hand and forearm.J Physiol 1968; 198: 145-166. 27. RothwellJC, Thompson PD, Day BL, et al. Motor cortex stimulation in intact man. 1. General characteristics of EMG responses in different muscles. Brain 1987; 110: 1173-1190. 28. ColebatchJG, RothwellJC, Day BL, Thompson PD, Marsden CD. Cortical outflow to proximal arm muscles in man. Brain 1990; 113: 1843-1856. 29. Lawrence D, Hopkins D. The development of motor control in the rhesus monkey: evidence concerning the role of corticomotoneuronal connections. Brain 1976; 99: 235-254. 30. Kuypers HGJM. A new look at the organisation of the motor system. Prog Brain Res 1982; 57: 381-403. 31. Shibasaki H, Nagae IC Mirror movement: application of movement-related cortical potentials. Ann Neurol 1984; 15: 299-302. 32. Brinkman C. Supplementary motor area of the monkey's cerebral cortex: short- and long-term deficits after unilateral ablation and the effects of subsequent callosal section.J Neurosci 1984; 4: 918-929. 33. Gomez-Pinilla F, VillablancaJR, Sonnier BJ, Levine M. Reorganisation of pericruciate projections to the spinal cord and dorsal column nuclei after neonatal or adult cerebral hemispherectomy in cats. Brain Res 1986; 385: 343-355.
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Mirror movements / Hashimoto's encephalopathy 34. Kuang RZ, Kalil tC Specificity of corticospinal axon arbors sprouting into denervated contralateral spinal cord. J Comp Neurol 1990; 302: 461-472. 35. Maegaki Y, Yamamoto T, Takeshita K. Plasticity of central motor and sensory pathways in a case of unilateral extensive cortical dysplasia: investigation of magnetic resonance imaging, transcranial magnetic stimulation and short-latency somatosensory evoked potentials. Neurology 1995; 45: 2255-2261.
Hashimoto's encephalopathy C. M . S u e 1 FRACP, V. F u n g 1 FRACP, J. P. H a l p e r n 1 PhD, S. C. B o y a g e s 2 PhD, C. Yiannikas ~, 3 FRACP 1Department of Neurology, Westmead Hospital, Sydney, Australia 2Department of Diabetes and Endocrinology, Westmead Hospital, Sydney, Australia 3Current address: Department of Neurology, Repatriation General Hospital, Concord, Sydney, Australia
We describe a 59-year-old female with Hashimoto's eneephalopathy whose presentation was characterized by a subacute onset of confusion, depressed level of consciousness, tremor and pyramidal signs. She was euthyroid on presentation but antithyroid antibodies were elevated. Hashimoto's thyroiditis was confirmed by thyroid biopsy. There was a spontaneous remission of the neurological disorder. Subacute encephalopathy is often investigated with thyroid function tests only. In cases of unexplained encephalopathy, thyroid antibodies and/or thyroid biopsy should be performed to exclude this condition. Journal of ClinicalNeuroscience1997, 4(1): 74-77 © Pearson Professional Ltd 1997
Keywords: Hashimoto's thyroiditis, subacute encephalopathy, antimicrosomal antibody Introduction Hashimoto's encephalopathy is a rare neurological complication associated with Hashimoto's thyroiditis. It was first described by Lord Brain in 19661 and since then only a small number of cases have been reported in the literature?-3' 7 It has a distinctive clinical picture which is characterized by an altered level of consciousness, confusional state, seizures, movement disorders such as myoclonus or tremor, pyramidal tracts signs and stroke-like episodes which follow a subacute relapsing and remitting course. In most of the cases reported the patient has been euthyroid, but often goitrous, with serological evidence of active Hashimoto's thyroiditis. Elevated antithyroid antibodies may be the only manifestation of Hashimoto's thyroiditis and indeed seronegative cases have also been described. Investigative findings are non-specific in this condition, but the presentation of this encephalopathy and its relapses may be related to elevations in the level of antithyroid antibodies.
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Case reports outcome. In: Tos M, ThomsonJ (eds). Acoustic Neuroma. Copenhagen: Proceedings of the First International Conference on Acoustic Neuroma, 1991: 423-427. 14. Simard M, Garcia-Bengochea F, Ballinger WE, MickleJR Quisling RG. Cavernous angioma: a review of 126 collected and 12 new clinical cases. Neurosurgery 1986; 18: 162-172. 15. Mawhinney RR, BuckleyJH, Worthington BS. Magnetic resonance imaging of the cerebellopontine angle. BrJ Radiol 1986; 59: 961-969. 16. Osborn AG. Brain tumours and tumour-like masses. In: Osborn A (ed). Diagnostic Neuroradiology. St Louis: Mosby, 1994: 437-450.
Fig. 4 Well circumscribed dural cavernous angioma without signs of intraparenchymal bleeding or calcification. The vessels were partly closed with thrombotic material and are lined by a single layer of endothelium (haematoxylin and eosin).
Pathophysiology of congenital mirror movements
References 1. Brackmann DE, Bartels LJ. Rare tumours of the cerebellopontine angle. Otolaryngol Head Neck Surg 1980; 88: 555-559. 2. Rengachary SS, Klyan-Raman UR Other cranial intradural angiomas. In: Wilkins RH, Rengachary SS (eds). Neurosurgery, Baltimore: McGraw-Hill, 1985: 1465-1473. 3. Burger PC, Scheithauer BW. Cavernous Angioma. Tumours of the Central Nervous System. Washington: Armed Forces Institute of Pathology, 1993: 290-291. 4. Russell DS, Rubinstein LJ. Pathology of Turnouts of the Nervous System, 5th edn. London: Edward Arnold, 1989: 730-735. 5. Mangham CA, CarberryJN, Brackmann DE. Management of intratemporal vascular turnouts. Laryngoscope 1981; 91: 86%876. 6. Pappas DG, Schneiderman TS, Brackmann DE, Simpson LC, Chandra-Sekar B, Sofferman R. Cavernous haemangiomas of the internal auditory canal. Otolaryngol Head Neck Surg 1989; 101: 27-32. 7. Schott B, Morgon A, Bady B, Bernard PA. Cavernome de L'angle ponto-cerebelleux. J Fr Otolrhinolaryngol 1970; 19: 339-342. 8. Sundaresan N, Eller T, Ciric I. Haemangiomas of the internal auditory canal. Surg Neurol 1976; 6: 119-121. 9. Bordi L, Pires M, Symon L, Cheesman AD. Cavernous angioma of the cerebellopontine angle: a case report. BrJ Neurosurg 1991; 5: 83-86. 10. Dale AJ. The cerebellopontine angle syndrome. Med Clin North Am 1968; 52: 789-795. 11. Iplikcioglu AC, Benli K, Bertan V, Ruacan S. Cystic cavernous haemangioma of the cerebellopontine angle: case report. Neurosurgery 1986; 19: 641-642. 12. Ohkuma A, Sugimoto S, Murase S, Iwama T, Miwa Y. Cavernous angioma of the cerebellopontine angle: a case report. Neurol Surg 1993; 21: 367-371. 13. Pfaltz CR, Gratzl O. The retrosigmoid approach in the cerebellopontine angle surgery: otological procedure and
S. R. D . W a t s o n FRACP, J. G. C o l e b a t c h PhD FRACP Institute of Neurological Sciences, Prince of Wales Hospital, Randwick, Sydney 9031, Australia
A case of congenital mirror movements occurring in association with lnild hemiparesis and unilateral schizencephaly was investigated using focal transcranial magnetic stimulation. The cortical motor representations for first dorsal interosseous, abductor digiti minimi and biceps brachii were mapped for both cerebral hemispheres: bilateral short latency EMG responses were elicited with stimulation over the nonschizencephalic hemisphere while no short latency responses were obtained with stimulation over the schizencephalic hemisphere. The cortical representations for all three homologous muscle pairs studied were colocalized, and the responses occurred at identical latencies bilaterally. Our findings, plus previous observations suggesting a single functional motor cortex in schizencephaly, are consistent with the suggestion that mirror movements are the result o f branched corticospinal projections to distal muscle groups. Journal of Clinical Neuroscience 1997, 4 (1) : 69-74 © Pearson Professional Ltd 1997 Keywords: mirror movements, magnetics, pyramidal tracts, schizencephaly
Introduction Mirror movements are characterized by an association of intended movements of one limb with simultaneous non-suppressible 'mirror image' movements of the other, due to contraction of homologous muscles. 1-5 These findings are usually most obvious for the hands, although fractionated movements of the fingers are preserved. Mirror movements have also been
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Case reports described in proximal arm and in distal lower limb muscles) Congenital mirror movements are recognised from infancy and are non-progressive.1-5Mirror movements may occur in normal infants,< 6 but are considered pathological if they are particularly prominent or persist beyond 10 years of age. 4 Congenital mirror movements may occur in isolation, most often as a familial trait, 2,7 or in association with developmental abnormalities, such as the Klippel-Feil syndrome8,9 or Kallman's syndrom@ °, 11 as well as with some types o f congenital hemiparesis. 19-14 There is a strong association between the presence of congenital mirror movements and electrophysiological evidence of ipsilaterally projecting corticospinal fibres, so that stimulation of the motor cortex evokes bilateral short latency electromyographic (EMG) responses. This may be demonstrable for one 12,13 or, more often, both hemispheres. 5,s, 10,15-1a We recently had the opportunity to study a subject with typical congenital mirror movements occurring in the context of hemiparetic cerebral palsy and schizencephaly. We describe the clinical features and the results of a motor cortex mapping study using transcranial magnetic stimulation, and conclude with a discussion of the pathophysiology of congenital mirror movements.
Materials and methods The patient, a 29-year-old male New Zealander, was admitted to the Prince of Wales Hospital febrile and confused, several weeks following a holiday in Bali. The acute features were attributed to typhoid fever (laboratory proven) and settled rapidly with therapy. O n presentation he was noted to have mild left-sided hyperreflexia, a left-sided extensor plantar response and mild hypoplasia of the left arm, together with a long history of leftsided motor difficulties. A cerebral CT scan showed right-sided schizencephaly. Once the confusion resolved, the patient was able to confirm that his neurological disorder was long-standing. He had been adopted soon after birth and no obstetric or family history was available, but problems with his left arm and leg were noted from infancy. He started walking at around 3 years but dragged his left leg and throughout primary school wore a calliper and received regular physiotherapy. Over his high school years there was a degree of functional improvement and eventually he was able to walk near normally without aids but continued to have difficulty with running. He had always been strongly righthanded and aware that the left hand was clumsy and weak. Despite these limitations he completed high school at a moderately high level and was working successfully as manager and bookkeeper for a hardware store. Mirror movements had been present for as long as he could recall. When he used a given hand, particularly for delicate tasks, the other hand closely 'mirrored' its movements. This occurred whether he was intending movement of his right hand or of his clumsy left hand and led to a variety of functional difficulties. He typed proficiently with his right hand, but was unable to type two-handed because when a finger of one hand would strike a key, the homologous finger of the other hand would strike an unwanted key involuntarily. He was also unable to eat with a knife and fork because when he tried to cut food using the knife in his right hand the fork in his left hand shifted the food away. For most activities he was able to use the left hand to stabilize the object while any delicate manipulation was performed by the right, e.g. tying shoelaces or doing up buttons. In general he felt that he had adapted well to his circumstances, but problems still occurred. He described a recent episode in which, while holding a power drill in his left hand,
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Mirror movements
Fig. 1 An axial Tl-weighted image showing the right-sided cleft extending from the cortical margin to the lateral ventricle. The cortex adjoining the cleft is thickened and lacks normal architecture. he picked up a screwdriver with his right hand. The fingers of his left hand involuntarilytightened on the drill handle, switching on the drill and moving it towards his groin. The drill cut through the fly of his pants and he was able to avoid injury only by dropping the screwdriver from his right hand, thereby releasing his left hand's grip. On physical examination a mild left-sided spasticity was found, with very mild hand weakness and impairment of proprioception at the distal interphalangealjoints of the left hand. Rapid fractionated movements of the left hand were slower and of lower amplitude than those of the right. With active movements of either arm, at or distal to the wrist, mirror movements were visible in homologous muscles of the opposite arm. The mirror movements were of comparable amplitude to the intended movements for movements of the thumb and fingers, and were equally prominent for both hands. Mirror movements were not observed for more proximal arm movements, nor for movements of the face or legs. A cerebral magnetic resonance imaging (MRI) scan was performed, confirming right-sided schizencephaly with the abnormal cleft extending from the Sylvian fissure to the lateral ventricle at a site corresponding to the central sulcus of the left hemisphere. The cleft was lined by thickened cortex without a normal gyral pattern. No associated abnormalities such as agenesis of the corpus callosum were found (Fig. 1). Normal somatosensory evoked responses were obtained from over the left hemisphere following stimulation of the right median nerve, but no reproducible cerebral response was found over either hemisphere following stimulation of the left median nerve, despite well formed peripheral potentials. A MagStim Model 200 (MagStim Co., Dyffed, Wales) magnetic stimulator with a focal (figure-of-eight) 70 m m coil was used for the study. Unrectified surface EMG was recorded on 6 channels: right and left first dorsal interosseous (FDI), abductor digiti minimi (ADM) and biceps. The threshold for response was 50% of maximal stimulator output for both the right and left FDI at a point 1 cm anterior to the vertex and 5 cm to the left, while no response was seen in any of the sampled muscles with stimulation at 100% of stimulator output over the right hemisphere. The cortical mapping study was performed using a grid of 27 stimulation sites separated by 2.5-cm intervals, spanning 5 cm in the sagittal plane from 2 cm posterior to the vertex r u n n i n g anteriorly and 20 cm in the coronal plane r u n n i n g
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R BICEPS
L BICEPS
R FDI
L FDI
For each muscle an average latency (SD) was calculated from the latencies of the 6 largest responses obtained at 70% stimulator output. For FDI the latency for the right was at 22.3 (_+ 1.2) ms and for the left 22.0 (+ 0.9) ms, for ADM the right was 22.7 (-+ 2.0) ms and the left 21.2 (_+ 1.5) ms, and for biceps the right was 13.3 (_+ 0.5) ms and the left 14.2 (_+ 0.4) ms. The differences between the sides were not significant. Responses in upper limb muscles for the normal controls were only found with stimulation over the contralateral hemisphere. The extent of the sites over the left hemisphere from which responses were obtained for the controls' right-sided muscles, the response thresholds and latencies were similar to those found (for both right- and left-sided muscles) following stimulation over the left hemisphere of our patient.
Discussion
10m$
Fig. 2 Simultaneous recordings from the right and left first dorsal interosseous and biceps brachii muscles following magnetic stimulation at 70% of maximal output at a site 0.5 cm anterior to the vertex in the sagittal plane and 5 cm to the left in the coronal plane. The vertical dashed lines indicate the time of delivery of the stimulus, and portions of the traces have been emphasized to highlight the responses.
10 cm from the midline on either side. The figure-of-eight coil was held tangential to the scalp and with the handle to the left side for all stimulation sites. Studies were performed with muscles relaxed at each of 60%, 65 % and 70% of stimulator output, and for each study all 97 sites were stimulated sequentially three times. For each EMG response the amplitude was measured peak to peak, and the latency was determined visually as the point of clear deviation from baseline. For each muscle at each site and for each stimulus intensity, three response amplitudes were averaged. For each stimulus, level, each average was divided by the largest obtained for that muscle, and these rescaled values (0-1) were displayed in graphical form. Three normal controls (31 M, 28 M, 27 F) were also studied using the same stimulation and recording protocols (at 20% above their respective response thresholds).
Results Responses in all muscles were found with focal magnetic stimulation over the left hemisphere (Fig. 2) of the patient, but no responses were found with stimulation over the right side. For all stimulus intensities and for all muscles studied, very similar topographical patterns of response amplitudes were found for homologous muscles bilaterally (Fig. 3). This was equally so for biceps, in which mirror movements were not apparent clinically, as for FDI and ADM. The largest averaged responses were 5.7 mVfor right FDI and 9.0 mVfor left FDI (both at 2 cm posterior to the vertex and 10 cm to the left), 2.9 mVfor right ADM and 3.4 mV for left ADM (both at 0.5 cm anterior to the vertex and 5 cm to the left) and 1.9 mV for right biceps and 1.1 mV for left biceps (both at the site 2 cm posterior to the vertex and 5 cm to the left).
Schizencephaly is a disorder of neuronal migration and therefore the pathogenic mechanism must operate between 7 and 16 weeks postconception, the period of cortical neuronal migration) 9-21 Most cases of schizencephaly are idiopathic although familial cases have been described 22 and recent evidence suggests that in some cases it is due to a focal ischaemic insult early in the period of neuronal migration. 2°,~1The congenital mirror movements in our subject were typical: they were present from early life, they were non-progressive and they showed no voluntary suppression. Distal, fractionated movements of the upper limbs were predominantly involved, and there was marked dissociation between the preservation of relatively i n d e p e n d e n t movements between the fingers of a given hand, and the loss of independence between the hands.I, 2,4.5.s In our subject the mirror movements occurred in association with mild congenital hemiparesis due to the schizencephaly and, despite their prominence, caused only mild motor disability. His developmental motor delay was probably due to the associated hemiparesis, although swimming and running, tasks requiring alternating movements of proximal limb muscles, may be affected in some subjects with mirror movements. 1,5 The motor cortex mapping study in our subject demonstrated colocalization of responses in FDI, ADM and biceps brachii muscles with stimulation over the non-schizencephalic left hemisphere. Furthermore, the responses in homologous muscles were at the same latency and within the normal range for these muscles. In contrast, no responses were obtained with stimulation over the schizencephalic right hemisphere. This study has found no evidence of two separate representations for the two upper limbs within the one hemisphere, nor, unlike one case described in the literature, ~for an enlargement of the cortical representation of these muscle groups. Although we suspect that the right hemisphere carries no short latency projections to the upper limbs, we cannot completely exclude the possibility that functioning motpr cortex is buried within the schizencephalic cleft and cannot be stimulated transcranially. However, a case of schizencephaly with mirror movements has been described in whom a Wada test was performed during evaluation for epilepsy surgery.19 With infusion of methohexital into the carotid artery on the schizencephalic left side, no deficits were seen, but with infusion on the (normal) right side there was severe aphasia and profound bilateral limb weakness, implying that the motor representation for both limbs as well as language function were located within the one, non-schizencephalic, hemisphere. Electrophysiological investigations of subjects with mirror movements have provided important evidence as to their origin. The almost universal finding has been the presence of
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R BICEPS
L BICEPS
L-1Ocm
Ant
Ant
R FDI
L FDI
L-lOcm
Ant
Ant
Fig. 3 A graphical representation of the responses found for the right and left first dorsal interosseous and biceps muscles with stimulation at 70% of maximal output. Each bar represents the average of three responses for a given stimulation site, normalized in relation to the largest average response for that particular muscle. Stimulation sites were 2.5 cm apart in the sagittal plane, from 2 cm posterior to the vertex (Post) to 3 cm anterior to the vertex (Ant), and were also 2.5 cm apart in the coronal plane, from 10 cm to the left of midline to 10 cm to the right. Colocalization for the responses in homologous muscles is apparent with stimulation over the left hemisphere.
bilateral short latency projections to hand muscles; most commonly these are demonstrable from both cerebral hemispheres, 5, s, 10,15-18but when associated with congenital hemiparesis, bilateral short latency projections are evident from stimulation over a single hemisphere only, as with our patient) 2,13 Although ipsilateral excitatory responses may sometimes occur in normals with unilateral cortical stimulation, the responses are generally delayed, are 0£ low amplitude and are most p r o m i n e n t for proximal muscles. 23T h e r e is general a g r e e m e n t that subjects with mirror movements have normal spinal reflex circuitry, assessed using H reflexes and f waves J, 8, 12 O n the other hand, long latency stretch reflexes from the t h u m b and cutaneous reflexes s, 12,13,24 can be recorded bilaterally following stimulation of a single side,
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findings which have in turn b e e n used as additional evidence for transcranial pathways of these reflexes. T h e distal p r e d o m i n a n c e of muscle involvement in mirror movements is similar to reports of the relative strength of pyramidal outflow to muscles of the arm as assessed by the amplitude of corticomotoneuronal excitatory postsynaptic potential (EPSPs) recorded from m o t o n e u r o n s 25'26 and by the relative size of responses to cortical stimulation, 18,27 although there is some evidence to suggest that the proximal-distal gradation may be less marked in humans. 28 Direct corticomotoneuronal projections are held to be of critical importance for fractionated movemerits of hand muscles. 29, 3o Given the distal p r e d o m i n a n c e of mirroring, either the large diameter corticomotoneuronal
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neurons projecting to intrinsic hand muscles are more likely to be involved in alterations underlying mirroring, or these rapidly conducting fibres are relatively more effective in activating distal muscles than similar fibres innervating more proximal muscles. Abnormalities of the motor 'command' have also been proposed as a possible basis for mirroring. Studies of premovement potentials in mirror movements have found evidence of bilateral motor cortical activation5' 31 and a positron emission tomographic (PET) activation study demonstrated bilateral sensorimotor cortical activation with intended movement of one side, in one subject3 One group has proposed that the abnormality underlying mirror movements is failure of the normal inhibition of the motor command reaching the ipsilateral motor cortex 15. Monkeys with experimental lesions of the supplementary motor area show characteristic deficits in which both hands tend to behave similarly?2 Such an abnormality of motor command is not, of course, incompatible with coexistent abnormalities of the corticospinal system and, indeed, may be responsible for the more widespread mirroring which may occur in these patients as children? The patients possibly learn with experience to direct their command to the desired muscle groups. However, it is difficult to see why mirroring should be confined to distal muscles if it is primarily due to an abnormality of motor command: if it is possible for the patients to learn to 'focus' their command to most muscle groups why should they not be able to do so for distal muscles too? We believe that the main basis for the motor syndrome of mirroring as seen in adults is not an abnormality of the motor command but an abnormality of lateralization within the corticospinal system. In addition to the evidence given above, one EMG study showed a correlation between the reaction times of the right and left sides when the patients were asked to move each thumb individually, but not when they were asked to move both together, suggesting that two separate motor commands could be generated. 3There have also been two cases with familial mirror movements described in whom mirror movements persisted in the plegic arm following a major stroke in adult life, even though no voluntary movement of the limb was possible.< 7 In this situation corticospinal projections from the intact (ipsilateral) motor cortex must be responsible for the mirror movements. We favour the mechanism first proposed by Farmer et al8 as being the most likely to explain the clinical features. These authors showed peaks in the cross-correlograms of the discharges of motor units in hand muscles, that were largest for distal muscles and not detectable for more proximal ones. They proposed that their findings were most likely to be due to branching of individual corticospinal tract fibres to supply motoneuron pools on both sides of the cord. In a large study of patients with congenital or juvenile onset hemiparesis, some of whom showed mirror movements, Carr et a112 showed that it was only those patients with bilateral projections and peaks in the cross-correlograms who demonstrated prominent mirror movements. Such an abnormality would explain why the patients can never overcome the mirroring: because individual corticospinal fibres project bilaterally, it is not possible to learn to direct the motor command in a way to avoid mirroring. For isolated congenital mirror movements a primary failure of pyramidal lateralization may be responsible but for cases associated with congenital hemiparesis it has been proposed that axonal branching occurs as a secondary p h e n o m e n o n , to innervate motor neurons that would normally be innervated by the damaged motor cortex) 2 From the results of clinical12 and animaP3, 34 research, it appears likely that such compensatory branching can only occur early in central nervous system development, perhaps during the first 29 weeks postconception) 2
The remarkable clinical features of congenital mirror movements and the colocalization we have described suggest that the same pattern of connectivity between axons and motor neurons is established for the ipsilateral projections as for the contralateral projections. In this regard, it has been shown that following unilateral pyramidal section in the neonatal hamster, a normal pattern of arborization and synapse formation is seen for the axons that cross the midline at the segmental level to pass into the denervated cord. 33 We propose that in our subject with congenital mirror movements, mild left hemiparesis, mild left-sided sensory disturbance and schizencephaly, the right sensorimotor cortex was damaged early in utero, at a time of considerable neuronal plasticity. Alterations, probably branching, of corticospinal axons projecting from the intact left motor cortex occurred, resulting in functional innervation of left-sided motor neurons and the clinical p h e n o m e n o n of mirror movements.
Addendum We have recently become aware of a study by Maegaki et als5 in which motor cortex mapping was performed in a subject with unilateral cortical dysplasia and mirror movements and which showed colocalized, bilateral responses from the normal hemisphere.
Acknowledgments We thank Dr P. Spira for allowing us to study his patient. Ms D. Wagener gave expert technical assistance. Dr Watson was recipient of the Whitmont Fellowship of the Australian Brain Foundation during the period of this study.
Received25 March 1996; Accepted 17 April 1996
Correspondence and offprint requests: DrJ. G. Colehatch, Institute of Neurological Sciences, Prince of Wales Hospital, High Street, Randwick, Sydney2031, Australia, Tel: 61 2 382 2422, Fax: 61 2 9382 2428, E-mail:[email protected] References 1. Schott GD, Wyke MA. Congenital mirror movements. J Neurol Neurosurg Psychiatry 1981, 44: 586-599. 2. Regli F, Filippa G, Weisendanger M. Hereditary mirror movements. Arch Neurol 1967; 16: 620-623. 3. Forget R, Boghen D, Attig E, Lamarre Y. Electromyographic studies of congenital mirror movements. Neurology 1986; 36: 1316-1322. 4. Rasmussen R Persistent mirror movements: a clinical study of 17 children, adolescents and young adults. Dev Med Child Neurol 1993; 35: 699-707. 5. Cohen LG, MeerJ, Tarkka I, et al. Congenital mirror movements. Abnormal organisation of motor pathways in two patients. Brain 1991; 114: 381-403. 6. Connolly K, Stratton R Developmental changes in associated movements. Dev Med Child Neurol 1968; 10: 49-56. 7. Haerer AF, Currier RD. Mirror movements. Neurology 1966; 16: 757-760. 8. Farmer SF, Ingram DA, StephensJA. Mirror movements studied in a patient with Klippel-Feil syndrome. J Physiol 1990; 428: 467-484. 9. Gunderson CH, Soitare GB. Mirror movements in patients with Klippel-Feil syndrome. Arch Neurol 1968; 18: 675-679. 10. Danek A, Heye B, Schroeter R. Cortically evoked motor responses in patients with Xp22.3-1inked Kallmann's syndrome and in female gene carriers. Ann Neurol 1992; 31: 299-304.
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Case reports 11. SchwankhausJD, CurrieJ,Jaffe MJ, Rose SR, Sherins RJ. Neurologic findings in men with isolated hypogonadotropic hypogonadism. Neurology 1989; 39: 223-226. 12. Carr LJ, Harrison LM, Evans AL, StephensJA. Patterns of central motor reorganisation in hemiplegic cerebral palsy. Brain 1993; 116: 1223-1247. 13. RothwellJC, ColebatchJ, Britton TC, et al. Physiological studies in a patient with mirror movements and agenesis of the corpus callosum. J Physiol 1991; 438: 34P. 14. GreenJB. An electromyographic study of mirror movements. Neurology 1967; 17: 91-94. 15. HermsdorferJ, Danek A, Winter T, Marquardt C, Mai N. Persistent mirror movements: force and timing of 'mirroring' are task dependent. Exp Brain Res 1995; 104: 126-134. 16. Konagaya Y, Mano Y, Konagaya M. Magnetic stimulation study in mirror movements.J Neurol 1990; 237: 107-109. 17. Britton TC, Meyer B-U, Benecke R. Central motor pathways in patients with mirror movements. J Neurol Neurosurg Psychiatry 1991; 54: 505-510. 18. Cohen LG, Roth BJ, Wasserman EM, et al. Magnetic stimulation of the human cerebral cortex, an indicator of reorganisation in motor pathways in certain pathological conditions.J Clin Neurophysiol 1991; 8: 56-65. 19. Brown MC, Levin BE, Ramsay RE, Landy HJ. Comprehensive evaluation of left hemisphere type 1 schizencephaly. Arch Neurol 1993; 50: 667-669. 20. Suchet IB. Schizencephaly: antenatal and postnatal assessment with colour-flow Doppler imaging. Can Assoc RadiolJ 1994; 45: 193-200. 21. Landieu P, Lacroix C. Schizencephaly, consequence of a developmental vasculopathy? A clinicopathological report. Clin Neuropath 1994; 13: 192-196. 22. Hilburger AC, WillisJK, Bouldin E, Henderson-Tilton A. Familial schizencephaly. Brain Dev 1993; 15: 234-236. 23. Wasserman EM, Fuhr P, Cohen LG, Hallett M. Effects of transcranial magnetic stimulation on ipsilateral muscles. Neurology 1991; 41: 1795-1799. 24. Capaday C, Forget R, Fraser R, Lamarre Y. Evidence for a contribution of the motor cortex to the long-latency stretch reflex of the human thumb. J Physiol 1991; 440: 243-255. 25. Phillips CG, Porter R. The pyramidal projection to motoneurones of some muscle groups of the baboon's forelimb. Prog Brain Res 1964; 12: 222-242. 26. CloughJFM, Kernell D, Phillips CG. The distribution of monosynaptic excitation from the pyramidal tract and from primary spindle afferents to motoneurones of the baboon's hand and forearm.J Physiol 1968; 198: 145-166. 27. RothwellJC, Thompson PD, Day BL, et al. Motor cortex stimulation in intact man. 1. General characteristics of EMG responses in different muscles. Brain 1987; 110: 1173-1190. 28. ColebatchJG, RothwellJC, Day BL, Thompson PD, Marsden CD. Cortical outflow to proximal arm muscles in man. Brain 1990; 113: 1843-1856. 29. Lawrence D, Hopkins D. The development of motor control in the rhesus monkey: evidence concerning the role of corticomotoneuronal connections. Brain 1976; 99: 235-254. 30. Kuypers HGJM. A new look at the organisation of the motor system. Prog Brain Res 1982; 57: 381-403. 31. Shibasaki H, Nagae IC Mirror movement: application of movement-related cortical potentials. Ann Neurol 1984; 15: 299-302. 32. Brinkman C. Supplementary motor area of the monkey's cerebral cortex: short- and long-term deficits after unilateral ablation and the effects of subsequent callosal section.J Neurosci 1984; 4: 918-929. 33. Gomez-Pinilla F, VillablancaJR, Sonnier BJ, Levine M. Reorganisation of pericruciate projections to the spinal cord and dorsal column nuclei after neonatal or adult cerebral hemispherectomy in cats. Brain Res 1986; 385: 343-355.
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Mirror movements / Hashimoto's encephalopathy 34. Kuang RZ, Kalil tC Specificity of corticospinal axon arbors sprouting into denervated contralateral spinal cord. J Comp Neurol 1990; 302: 461-472. 35. Maegaki Y, Yamamoto T, Takeshita K. Plasticity of central motor and sensory pathways in a case of unilateral extensive cortical dysplasia: investigation of magnetic resonance imaging, transcranial magnetic stimulation and short-latency somatosensory evoked potentials. Neurology 1995; 45: 2255-2261.
Hashimoto's encephalopathy C. M . S u e 1 FRACP, V. F u n g 1 FRACP, J. P. H a l p e r n 1 PhD, S. C. B o y a g e s 2 PhD, C. Yiannikas ~, 3 FRACP 1Department of Neurology, Westmead Hospital, Sydney, Australia 2Department of Diabetes and Endocrinology, Westmead Hospital, Sydney, Australia 3Current address: Department of Neurology, Repatriation General Hospital, Concord, Sydney, Australia
We describe a 59-year-old female with Hashimoto's eneephalopathy whose presentation was characterized by a subacute onset of confusion, depressed level of consciousness, tremor and pyramidal signs. She was euthyroid on presentation but antithyroid antibodies were elevated. Hashimoto's thyroiditis was confirmed by thyroid biopsy. There was a spontaneous remission of the neurological disorder. Subacute encephalopathy is often investigated with thyroid function tests only. In cases of unexplained encephalopathy, thyroid antibodies and/or thyroid biopsy should be performed to exclude this condition. Journal of ClinicalNeuroscience1997, 4(1): 74-77 © Pearson Professional Ltd 1997
Keywords: Hashimoto's thyroiditis, subacute encephalopathy, antimicrosomal antibody Introduction Hashimoto's encephalopathy is a rare neurological complication associated with Hashimoto's thyroiditis. It was first described by Lord Brain in 19661 and since then only a small number of cases have been reported in the literature?-3' 7 It has a distinctive clinical picture which is characterized by an altered level of consciousness, confusional state, seizures, movement disorders such as myoclonus or tremor, pyramidal tracts signs and stroke-like episodes which follow a subacute relapsing and remitting course. In most of the cases reported the patient has been euthyroid, but often goitrous, with serological evidence of active Hashimoto's thyroiditis. Elevated antithyroid antibodies may be the only manifestation of Hashimoto's thyroiditis and indeed seronegative cases have also been described. Investigative findings are non-specific in this condition, but the presentation of this encephalopathy and its relapses may be related to elevations in the level of antithyroid antibodies.
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