350 British Journal of Ophthalmology 1996; 80: 350-355 Ocular neuromyotonia Br J Ophthalmol: first published as 10.1136/bjo.80.4.350 on 1 April 1996. Downloaded from

Eric Ezra, David Spalton, Michael D Sanders, Elizabeth M Graham, Gordon T Plant

Abstract revealed a neurogenic pattern and they con- Aims/Background-Ocular neuromyo- cluded that neuromyotonic activity resulted tonia is characterised by spontaneous from spontaneous electrical activity in unstable spasm of extraocular muscles and has motor nerve membranes, followed by ephatic been described in only 14 patients. Three transmission of electrical activity to adjacent further cases, two with unique features, nerves, causing co-firing of different muscles are described, and the underlying mech- supplied by the third nerve. This hypothesis anism reviewed in the light of recent was supported by the fact that both patients experimental evidence implicating extra- responded and became asymptomatic after cellular potassium concentration in treatment with carbamazepine, an anticonvul- causing spontaneous firing in normal and sant. The term 'ocular neuromyotonia' was demyelinated axons. used to describe the syndrome. Further reports Methods-Two patients had third nerve in the literature have been sparse3-6 as sum- neuromyotonia, one due to compression marised in Table 1. by an internal carotid artery aneurysm, The condition is distinct from superior which has not been reported previously, oblique myokymia, which is characterised by while the other followed irradiation of a oscillopsia and microtremor due to phasic pituitary tumour, a common association rather than tonic activity.7 8 It is also distinct in the published reports. Selective activa- from cyclical oculomotor spasm, which occurs tion occurred in both, where neuro- in the setting of a congenital third nerve pare- myotonic activity was triggered by sis, where cycles have characteristic pupillary prolonged voluntary activation of specific involvement without tonic adduction.9 extraocular muscles with or without Although surgery or, more specifically, irradia- spread of activity to other third nerve tion for pituitary fossa and other intracranial muscles. The other patient had fourth tumours is the usual aetiology, ocular neuro- nerve involvement, where spasms of the mytonia may occur with other intracranial superior oblique muscle were induced compressive lesions, or in the absence of any only by alcohol, a phenomenon which has causative factors.1-5 Any of the ocular motor not been described. nerves may be affected, often in the setting of a http://bjo.bmj.com/ Results-The two patients with third chronic nerve paresis and episodes may be nerve involvement responded to carba- elicited by sustained activity of the extraocular mazepine and in one, an improvement in muscle supplied by the nerve involved or may a chronic partial third nerve paresis occur spontaneously. 1-6 occurred. The other has not required The diagnosis may be easily overlooked in a treatment and remains asymptomatic by patient complaining of paroxysmal diplopia refraining from alcohol. because a careful examination of ocular motil- on September 23, 2021 by guest. Protected copyright. Conclusions-A careful examination, ity, including the effects of sustained action of including the effects of prolonged volun- individual muscles, is required. Furthermore, tary muscle action is required to initiate effective treatment with anticonvulsants is episodes and to demonstrate selective available. Our experience suggests that where activation. Imaging is mandatory to the cause is not clear (particularly if there is no exclude compressive intracranial lesions, previous history of radiation therapy) all particularly where there is no history of patients should be investigated for intracranial pituitary fossa irradiation. A trial of anti- disease. Medical Eye Unit, St convulsants should be considered in all These points are illustrated with a descrip- Thomas's Hospital, Extracellular tion of three further London patients. potassium may cases. E Ezra play a role in spontaneous firing and D Spalton ephatic transmission in ocular neuro- M D Sanders myotonia. Methods and patients E M Graham G T Plant (BrJ Ophthalmol 1996; 80: 350-355) The three patients in this study were all referred following an initial examination by The National Hospital their ophthalmologist. All patients had a full for Neurological Diseases, London In 1970 Ricker and Mertensl described a ophthalmic, neurological, and general exami- M D Sanders patient with idiopathic paroxysmal diplopia. nation. Ophthalmic examination included E M Graham During episodes, they noted a tonic unilateral careful assessment of ocular motility, with par- G T Plant esodeviation with restriction of elevation and ticular attention to the following: Correspondence to: abduction due to overaction of the medial and (1) Ocular motility during quiescent peri- Dr Gordon Plant, The National Hospital for inferior rectus muscles. Papst2 in 1972 ods, with careful documentation of chronic Neurology and described a similar patient with involvement of nerve pareses, including signs of oculomotor Neurosurgery, Queen Square, London WC 1 3BG. the medial, inferior and superior recti, and the synkinesis ('aberrant regeneration') in third Accepted for publication levator muscle. Electromyographic recordings nerve involvement. A Hess examination was 21 December 1995 in both patients during quiescent periods performed on all patients. Pupillary synkinesis Ocular neuromyotonia 351

Table 1 Summary ofthe 17 cases ofocular neuromyotonia in the literature

Chronic palsyl Neuromyotonic muscle Treatment Treatment

Case Radiation Time to aberrant involvement (and response response (chronic Br J Ophthalmol: first published as 10.1136/bjo.80.4.350 on 1 April 1996. Downloaded from Age/sex Aetiology (Gy) onset Nerve regeneration triggering muscles) (symptoms) nerve palsy) Ricker and Mertens' 1 Nil Nil III Nil MR, IR Full resolution Papst2 2 Nil Nil III Nil MR, IR, SR, LP Full resolution Shults et al3 3 Pituitary adenoma, 75 9 Months III AR lid only MR, IR, SR, LP, P Full resolution Full resolution 60M craniotomy (triggered by MR, IR) 4 Pituitary adenoma, 45-6 7 Years III Partial III MR, IR, SR, LP No response No response 62F craniotomy AR lid (triggered by MR, IR) 5 Pituitary adenoma, 50 4 3 Years III AR lid only MR, IR, SR, LP Partial response ? 52M TSA 6 Nil Nil - III AR lid only MR, IR, SR, LP Partial response Full resolution 74F (triggered by IR) 7 Nil Nil - IV Nil SO ? ? 12M 8 Pituitary adenoma, 66 3 Years VI Nil LR (triggered by LR) No response 46M craniotomy Lessell et a14 9 Craniopharyngioma, 50 05 2 Years III Nil SR? ? ? 19F craniotomy 10 Pit adenoma, TSA 54 11 Months III Nil MR ? ? 17F 11 Skull base sarcoma 70-2 2 Months VI Partial VI LR ? ? 51F (no surgery) 12 Skull base 40 4 Years VI Nil LR No treatment, 1IF rhabdomyosarcoma partial resolution Salmon et al5 13 Pituitary adenoma, 45 7 Years III Nil IR, SR, LP Full resolution 36F TSA Barroso and Hoyt6 14 Thalamic glioma (no 77 16 Months VI Nil LR (triggered by LR) No treatment, full 7M surgery) resolution Ezra et al (this study) 15 Internal carotid Nil - III Partial III MR, LP (triggered by Partial response Unchanged 60M aneurysm MR, LP) 16 Pituitary adenoma, 36 9 Years III Partial III MR, IR, SR, LP, P Partial response Partial 44M craniotomy AR (triggered by MR, IR) improvement 17 Nil Nil - IV Nil SO No treatment, 40M unchanged TSA=trans-sphenoidal adenohypophysectomy, AR=aberrant regeneration, MR=medial rectus, IR=inferior rectus, SR=superior rectus, LR=lateral rectus, SO=superior oblique, LP=levator palpebrae, P=pupillomotor, ?=unknown.

(case 2) was confirmed by pupillometry. Upper (Tensilon) test to exclude myasthenia gravis, lid position and retraction on downgaze, a sign was performed in all patients, where an intra-

of upper lid synkinesis, were recorded. venous injection during a quiescent period was http://bjo.bmj.com/ (2) Episodes of neuromyotonic spasms followed by a careful examination of ocular were induced by prolonged voluntary activity motility to determine whether edrophonium of individual extraocular muscles in turn. Each could abolish neuromyotonic triggering. muscle was tested to determine whether it could act as the triggering muscle. (3) During neuromyotonic episodes the fol- Results

lowing were recorded: (i) duration and symp- on September 23, 2021 by guest. Protected copyright. toms, particularly the nature of the diplopia; CASE 1 (ii) which muscles were co-firing - this could A 60-year-old man was referred with a 1 year be determined by ocular deviation in all posi- history of right supraorbital pain. The family tions of gaze and by eliciting mechanical had noted that, from time to time, his right eye restriction of the antagonists; (iii) upper lid would appear to stare. Direct questioning position in primary gaze and the effects of revealed episodes ofintermittent diplopia, with downgaze, which accentuates any spasm of variable horizontal and vertical components the levator palpebrae; (iv) pupillary spasm; and no precipitating factors of which the (v) globe retraction due to co-firing of extra- patient was aware. He also had a history of ocular muscles; (vi) the presence of torsional hypertension, ischaemic heart disease, and diplopia, intorsion, and hypodeviation were peripheral vascular disease. Alcohol consump- taken as a sign of superior oblique spasm (case tion had been high, in excess of 40 units per 3) and microtremor was sought by slit-lamp week for several years, though episodes were examination. not related to alcohol consumption. Neuro- (4) In case 3, episodes could not be elicited ophthalmic examination showed a partial right during several examinations. The patient was third nerve palsy and signs of oculomotor syn- therefore asked to drink approximately 100 ml kinesis, with upper lid retraction on downgaze of spirit in order to allow observation of an (Fig 1 A-C) and pupillary synkinesis. The episode. right corneal reflex was reduced but there were All patients underwent computed tomogra- no other abnormal neuro-ophthalmic or phy (CT) or magnetic resonance imaging neurological signs. Systemic examination (MRI) with contrast, and MRI cerebral vessel revealed bilateral carotid bruits and hyperten- angiography was performed to confirm sus- sion but was otherwise unremarkable. pected vascular lesions (case 1). All patients Sustained elevation of the right eye resulted also had neurological examination, including in paroxysmal spasm of the right levator full blood screening. An edrophonium muscle, the upper lid becoming markedly 352 Ezra, Spalton, Sanders, Graham, Plant Br J Ophthalmol: first published as 10.1136/bjo.80.4.350 on 1 April 1996. Downloaded from Figure I Case 1. (A-C) A partial chronic right third nerve paresis is present during quiescent periods, with a right hypotropia and ptosis (A), right upper lid retraction on downgaze (B) and weakness ofright elevation (C). (C-E) Right levator neuromyotonia. On sustained upgaze (C), levator spasm is induced, resulting in increased upper lid retraction, particularly on downgaze (D, E). (F-I) Right medial rectus neuromyotonia. During quiescent periods, right lateral gaze isfull (F). Sustained left gaze (G) induces right medial rectus neuromyotonia with restriction ofright lateral rectus action (H). With U resolution of the episode, full abduction ofthe right eye is restored (I). Simultaneous neuromyotonia ofthe superior rectus/levator complex and the medial rectus could not be elicited. E

retracted, particularly on attempted downgaze scotoma, and right optic disc pallor and afferent (Fig 1 C-E). Ocular motility and pupillary pupillary defect, suggesting anterior chiasmal responses remained unchanged during these compression. Ocular motility and neurological episodes. A different pattern of activity could examinations were unremarkable and general be provoked by sustained adduction of the examination revealed signs of panhypopitu- right eye. During these episodes, paroxysmal itarism. A CT scan confirmed the presence of a

spasm of the medial rectus would occur, with large pituitary fossa mass with suprasellar http://bjo.bmj.com/ restriction of abduction, and unaffected lid extension, and a markedly raised serum pro- position (Fig 1 F-I). Both types of episodes lactin indicated a prolactinoma. At the time, typically lasted between 2 and 3 minutes. The bromocriptine therapy was not available and clinical pattern reflected levator and medial he underwent a frontal craniotomy and rectus involvement, although simultaneous hypophysectomy, followed by postoperative overaction of these could not be elicited in a irradiation with 36 Gy. Thereafter, he single episode and co-firing of other muscles remained well on endocrine replacement ther- on September 23, 2021 by guest. Protected copyright. supplied by the third nerve did not occur. Both apy and showed improvement in visual fields types of episodes could be easily reproduced. and acuity of the right eye. A Ti MRI scan revealed a supraclinoid Nine years later he presented with episodes mass on the right, with a mixed signal sug- of paroxysmal vertical and horizontal diplopia, gestive of a partially thrombosed aneurysm associated with a 'pulling' sensation in the (Fig 2). This was confirmed by MRI angio- right eye usually occurring while driving long graphy which showed an aneurysm of the distances and looking in the rear mirror or internal carotid artery at its junction with the when tired or under extreme stress. During posterior communicating artery, impinging on these episodes he invariably noted that the the roof of the right cavernous sinus where the right eye would 'stare'. Typically, episodes third nerve enters the sinus (Fig 3). Treatment would last between seconds and minutes and with carbamazepine 200 mg twice daily resolve spontaneously, with several occurring resulted in full resolution of symptoms within a over a period of several hours. At the time, week, but the partial third nerve paresis ocular motility and eyelids were reported as remained unchanged. An attempt to reduce normal, though the effects of sustained muscle the dosage resulted in recurrence of symptoms activity were not sought. Visual field and CT and the original dose was recommenced. He examination on three occasions failed to show has had no further attacks on treatment after any change or tumour recurrence. Over the 1 year. next 3 years, episodes became increasingly frequent, to the extent that he was no longer able to drive without symptoms. He also devel- CASE 2 oped a mild chronic third nerve paresis, a A 44-year-old man with headache, right visual 2 mm ptosis, pupillary dilatation, and oculo- disturbance and gynaecomastia was found to motor synkinesis (aberrant regeneration), have visual acuities of 6/12 right and 6/6 left, with lid retraction on downgaze and pupillary with a bitemporal hemianopia, a right central synkinesis confirmed by pupillometry. Ocular neuromyotonia 353 Br J Ophthalmol: first published as 10.1136/bjo.80.4.350 on 1 April 1996. Downloaded from

Figure 2 Case 1. Magnetic resonance imaging scan Figure 3 Case 1. Magnetic resonance cerebral showing a mixed signal lesion impinging on the roofofthe angiography showing the lesion to be a partially thrombosed cavernous sinus posteriorly (arrow). aneurysm (arrow). Attacks could be provoked by sustained diplopia, without torsion, during these attacks, adduction and depression of the right eye. which lasted a variable period from seconds to During episodes, the right eye would become minutes. The clinical pattern therefore tonically deviated in adduction, with restric- reflected co-firing of pupillomotor, levator and tion of all ocular movements, particularly medial, inferior and superior rectus muscle abduction and elevation, and marked upper lid fibres, triggered by sustained voluntary activity retraction due to levator overaction. In addi- of the medial and inferior recti. tion pupillary involvement would occur, the Treatment with carbamazepine 200 mg pupil becoming fixed in partial miosis, failing twice daily resulted in a dramatic improvement to react to light or accommodation. The of symptoms within a week. In addition, the

patient reported vertical and horizontal chronic third nerve paresis improved markedly http://bjo.bmj.com/ (Fig 4), with only mild limitation of upgaze, and mild upper lid retraction on downgaze remaining after 2 months of treatment. Although he reported occasional symptoms on f -.p" Itt., treatment, no further attacks could be elicited. t~~~~~~~~~~~~~~~.'- on September 23, 2021 by guest. Protected copyright.

*1' es CASE 3 A 40-year-old man was referred with a 4 year history of paroxysmal vertical diplopia. Episodes typically lasted between 10 and 20 seconds and would occur repetitively after moderate to high alcohol consumption. He did not report any oscillopsia or eyelid abnormali- (7m-z- btco Wr ct ties during attacks. No relevant medical history was elicited. Neuro-ophthalmic and neurological exami- Left E.r nation proved unremarkable initially, but after consumption of about 100 ml of spirit under observation, a series of attacks occurred over the space of 20 minutes. During episodes, which occurred spontaneously and indepen- dently of eye position, he would develop a right hypotropia due to superior oblique overaction with torsional and vertical diplopia. No oscil- lopsia or microtremor occurred and eyelid position and pupillary reactions remained normal throughout. Each episode was extremely short lived, thereby precluding a more detailed examination. Activity could not be induced in the absence of alcohol. Figure 4 Case 2. Hess charts comparing basal third nerve function before (above) and after (below) treatment with carbamazepine. After treatment, marked improvement in MRI studies failed to reveal any intracranial third nemve function occurred, though mild weakness in elevation ofthe right eye persists. abnormality and an edrophonium test during 354 Ezra, Spalton, Sanders, Graham, Plant

an episode proved negative. He did not receive neuromyotonia provoked by alcohol. The case treatment and remains asymptomatic if he described by Clark" as superior oblique over-

abstains from alcohol. action without oscillopsia or microtremor, was Br J Ophthalmol: first published as 10.1136/bjo.80.4.350 on 1 April 1996. Downloaded from probably the first case of fourth nerve neuro- myotonia to be described in the literature, as Discussion has been pointed out by previous authors.3 All 17 cases of ocular neuromyotonia in the As a clinical syndrome, fourth nerve neuro- literature,'-6including the three reported here, myotonia may be differentiated from superior are summarised in Table 1. Eleven had oblique myokymia. In addition to a hypo- intracranial tumours treated with surgery tropia, the symptom of oscillopsia, in associa- and/or radiotherapy, the period between treat- tion with microtremor and intorsion, which are ment and onset of symptoms ranging from 2 best observed by slit-lamp examination, is months to 9 years. Four patients had no iden- typical of myokymia and reflects phasic neural tifiable cause and two associations are reported activity rather than the tonic activity seen in here for the first time - oculomotor nerve com- neuromyotonia. However, both conditions pression (case 1) and an association with may represent a spectrum of disease with a alcohol consumption (case 3). Case 1 in our common underlying mechanism, with the dis- series is the first patient with ocular neuro- tinction being purely clinical. myotonia to be described in association with a Sixth nerve neuromyotonia has been compressive lesion. However, the patient described in four patients. It involves intermit- described by Bateman and Saunders,'0 a tent exotropia with restriction of adduction, patient with a supraclinoid aneurysm, a and is triggered by sustained action of the chronic third nerve paresis with synkinesis, and lateral rectus muscle. The patient described by paroxysmal third nerve spasm was interpreted Barroso and Hoyt6 is unique in that this is the as having a cyclical oculomotor palsy but may only reported case where resolution of neuro- well have been a case ofocular neuromyotonia, myotonia occurred spontaneously without as has been suggested by previous authors.3 anticonvulsant therapy. Metz and Sterns'2 Eleven patients had involvement ofthe third described a woman with a chronic sixth nerve nerve, two of the fourth nerve, and four of the paresis, following pituitary surgery and irradia- sixth nerve. Ten patients in total received anti- tion, who developed 'variable esotropia- convulsant therapy, eight showing a reduction exotropia'. The clinical picture would be in the frequency of symptoms. Perhaps more consistent with sixth nerve neuromyotonia. remarkably, three patients, our case 2 and two In ocular neuromyotonia the spasm results patients described by Shults et al,3 showed from spontaneous neural firing in a single improvement of chronic nerve paresis on treat- neuron or a group of neurons supplying the ment. Of the 11 patients with third nerve activating muscle or muscles. Interneural

involvement, six had evidence of a chronic transmission to other neurons supplying the http://bjo.bmj.com/ nerve paresis with signs of oculomotor syn- same or other muscles may then occur result- kinesis and five had normal ocular motility ing in a self perpetuating circuit.13 This would during quiescent periods. eight had levator explain 'selective activation' by specific involvement, nine medial rectus, eight superior muscles and subsequent co-firing of other rectus, and eight inferior rectus involvement muscles in third nerve neuromyotonia and during episodes. Only two patients had pupil- tonic activity in fourth and sixth nerve involve- lary involvement. ment. on September 23, 2021 by guest. Protected copyright. In the two patients we have described with Support for this mechanism has come from third nerve neuromyotonia, the phenomenon evidence in other neurological conditions such of selective activation occurred, that is to say as radiation plexopathy,13 peripheral neuro- sustained action of certain muscles provoked pathy,14 15 traumatic neuropathy,16 and hemi- the spasms. This was also described in four of facial spasm,'7 where spontaneous firing has the six patients in the series of Shults et al,3 been shown to occur in segmentally demy- with activation most commonly occurring elinated axons. Patients with limb myokymia through action of the medial and inferior recti. due to radiation plexopathy exhibit similar In case 2 medial and inferior rectus overaction electromyographic activity to those with ocular resulted in co-firing of the other muscles. Case neuromyotonia. 13 1 showed two quite distinct patterns of neuro- In experimental models, spontaneous firing myotonic activity, where sustained upgaze in demyelinated axons has been demonstrated triggered overaction of the levator and activity in rat spinal root axons,18 cat dorsal columns,'9 of the medial rectus triggered overaction of and rat trigeminal nerve.20 Ectopic action that muscle only. Activity did not 'spread' from potentials also occur in normal, myelinated the medial rectus to the levator or vice versa. mammalian axons where extracellular potas- This pattern has not been previously reported sium concentration has been elevated2l includ- and some degree of co-activation is the rule. ing following sustained tetanic activation.22 In Ocular neuromyotonia of the fourth nerve ocular neuromyotonia, therefore, it is possible has only been described in two patients, that damaged axons become susceptible to including case 3 in our series, and typically spontaneous firing. Extracellular potassium involves spontaneous superior oblique over- may be elevated when axons are subjected to action without microtremor or oscillopsia, sustained activity, thus explaining the trigger- reflecting the tonic, rather than phasic, ing that occurs with sustained muscle activity. nature of the neural discharges in neuromyo- For co-firing of neurons supplying other tonia. This patient is the only case of ocular muscles to be initiated interneural electrical Ocular neuromyotonia 355

transmission must occur; perhaps this may also Corbett JJ. Ocular neyromyotonia. A clinical description of six cases. Arch Ophthalmol 1986; 104: 1028-34. occur as a result of changes in extracellular 4 Lessell S, Lessell IM, Rizzo JF. Ocular neuromyotonia after radiation Am 102: 766-70. potassium. therapy. J Ophthalmol 1986; Br J Ophthalmol: first published as 10.1136/bjo.80.4.350 on 1 April 1996. Downloaded from 5 Salmon JF, Steven P, Abrahamson MJ. Ocular neuro- In oculomotor synkinesis, it has previously myotonia. Neuro-ophthalmol 1988; 4: 181-5. been argued that aberrant regeneration or 6 Barroso L, Hoyt WF. Episodic exotropia from lateral rectus neuromyotonia - Appearance and remission after radia- axonal misdirection may not account for co- tion therapy for a thalamic glioma. J7 Paediatr Ophthalmol firing. Two alternative mechanisms have been Strabismus 1993; 30: 56-7. 7 Rosenberg ML, GlaserJS. Superior oblique myokymia. Ann proposed.23 The first is ephaptic (lateral) Neurol 1983; 13: 667-9. transmission between axons and the second 8 Lee JP. Superior oblique myokymia: a possible aetiological factor. Arch Ophthalmol 1984; 102: 1178-9. involves central synaptic reorganisation follow- 9 Lowenfeld IE, Thompson HS. Oculomotor paresis with ing injury. As most patients with third nerve cyclical spasms: a critical review of the literature and a new case. Surv Ophthalmol 1975; 20: 81-124. neuromyotonia also show signs of synkinesis 10 Bateman DE, Saunders M. Cyclic oculomotor palsy. during quiescent periods ephaptic transmis- Description of a case and hypothesis of the mechanism. J Neurol Neurosurg Psychiatry 1983; 46: 451-4. sion may be relevant to both phenomena. This 11 Clark E. A case of apparent intermittent overaction of the may account for the disappearance of syn- superior oblique. Br OrthopticsJ1 1966; 23: 116-7. 12 Metz HS, Stems G. Varying esotropia-exotropia. Y Paediatr kinesis in case 2 following anticonvulsant Ophthalmol Strabismus 1985; 22: 97-9. therapy - its disappearance has also been 13 Albers JW, Allen AA, Bastron JA, Daube JR. Limb myokymia. Musde Nerve 1981; 4: 494-504. described following treatment of a lymphoma 14 Lance JW, Burke D, Pollard J. Hyperexcitability of motor causing oculomotor nerve synkinesis.24 It and sensory neurons in neuromyotonia. Ann Neurol 1979; 5: 523-32. would be difficult to explain these observations 15 Warmolts JR, Mendell JR. Neurotonia: impulse induced if the synkinesis were due to a 'hard wired' repetitive discharges in motor nerves in peripheral neuropathy. Ann Neurol 1980; 7: 245-50. aberrant regeneration. 16 Stohr M. Repetitive impulse induced EMG discharges in The role of alcohol consumption in precipi- neuromuscular disease. Ann Neurol 1981; 9: 204-10. 17 Nielsen VK. Pathophysiology of hemifacial spasm: I. tating attacks in patient 3 is unknown. Studies Ephatic transmission and ectopic excitation. Neurology examining the effects of alcohol on human 1984; 34: 418-26. 18 Baker M, Bostock H. Ectopic activity in demyelinated peripheral nerve function have not shown spinal root axons of the rat. J Physiol 1992; 451: 539-52. similar effects in peripheral nerves.25-27 19 Smith KJ, Macdonald WI. Spontaneous and evoked electri- cal discharges from a central demyelinating lesion. Finally, the marked improvement in basal JNeurol Sci 1982; 55: 39-47. nerve function with anticonvulsant treatment 20 Buchiel KJ. Abnormal impulse generation in focally demyelinated trigeminal roots. J Neurosurg 1980; 53: in case 2 and in the two other patients 647-83. described in the literature,3 implies that 21 Kapoor R, Smith KJ, Felts PA, Davies M. Internodal potas- sium currents can generate ectopic in mammalian myeli- chronic paresis is at least in part due to nerve nated axons. Brain Res 1993; 611: 165-9. membrane instability. The improvement of 22 Bostock H, Bergmans J. Post-tetanic excitability changes and ectopic discharges in a human motor axon. Brain such a paresis may have wider implications for 1994; 117: 913-28. the treatment of other peripheral and central 23 Lepore FE, Glaser JS. Misdirection revisited. A critical appraisal of acquired oculomotor nerve synkinesis. neuropathies and demyelinating disorders. Arch Ophthalmol 1980; 98: 2206-9. 24 Sze HL, Yew KY, Chai BT, Tjia H. Transient oculomotor We are grateful to Dr Raju Kapoor for his contribution to the nerve synkinesis in non-Hodgkin's lymphoma. J Clin http://bjo.bmj.com/ discussion and to the orthoptic department at St Thomas's Neuro-ophthalmol 1992; 12: 203-6. Hospital for their contributions. 25 Letz R, Gerr F. Covariates of human peripheral nerve function: I. Nerve conduction velocity and amplitude. Neurotoxicol Teratol 1994; 16: 95-104. 26 Letz R, Gerr F. Covariates ofhuman peripheral nerve func- 1 Ricker VK, Mertens HG. Okulare Neuromyotonie. Kin tion: II. Vibrotactile and thermal thresholds. Neurotoxicol MonatsblAugenheilkd 1970; 156: 837-42. Teratol 1994; 16: 105-12. 2 Papst W. Zur differentialdiagnose der okularen neuro- 27 Letz R, Gerr F. Covariates of human peripheral nerve func- myotonie. Ophthalmologica 1972; 164: 252-63. tion: III. Effects of reported drinking. Neurotoxicol Teratol 3 Shults WT, Hoyt WF, Behrens M, Maclean J, Saul RF, 1994; 16: 113-22. on September 23, 2021 by guest. Protected copyright.