paroxysmal symptoms in multiple sclerosis · journial ofneurology, neurosurgery, andpsychiatry,...

Journial of Neurology, Neurosurgery, and Psychiatry, 1975, 38, 617-623

Paroxysmal symptoms in multiple sclerosisW. B. MATTHEWS

From the Department of Clinical Neurology, University of Oxford.The Churchill Hospital, Oxford

SYNOPSIS The clinical features of paroxysmal symptoms occurring in 26 patients with multiplesclerosis are reviewed. The findings are considered to provide further support for the concept oflateral spread of axonal excitation within demyelinated plaques.

The familiar symptoms of multiple sclerosis(MS) are those due either to impaired axonalconduction, temporary or permanent, or to therelease of exaggerated reflex activity. Apparentlyin a different category, not easily attributable toeither cause, are brief paroxysmal symptoms.Epilepsy occasionally occurs in MS (Matthews,1962) and trigeminal neuralgia is well docu-mented but neither presents any distinctivefeatures. In contrast, tonic seizures (Matthews,1958), paroxysmal dysarthria (Andermann et al.,1959), and certain sensory symptoms (Espir etal., 1966) are highly characteristic of MS, beingseldom identifiable in other conditions. I proposeto review, from personal experience, the range ofparoxysmal phenomena encountered and theirsignificance.

METHODS

Detailed notes were available of 26 patients seenpersonally between 1956 and 1974 and regarded ashaving paroxysmal symptoms of MS other thanepilepsy or trigeminal neuralgia. The criterionadopted was that of repeated stereotyped symptomsof no more than two minutes' duration, thus exclud-ing many patients with episodic symptoms of lessclearly defined character, in particular recurrentpain. The patients were seen in three different centresand no attempt can be made to estimate the inci-dence of these symptoms in patients with MS.Although three patients are known to have died inhospital after prolonged detailed observation, nonecropsy confirmation of the diagnosis could beobtained. Many of the patients were seen before

(Accepted 24 January 1975.)617

estimation of protein fractions in the cerebrospinalfluid was possible and the diagnosis was establishedon clinical grounds. Direct observation of motorphenomena was not always possible and reliancesometimes had to be placed on the patient's descrip-tion.Four types of paroxysmal symptom that might

occur in isolation or in various combinations wereidentified; tonic seizures, dysarthria, sensory symp-toms, and segmental loss of use of the limbs.

TONIC SEIZURES As originally described (Matthews,1958) tonic seizures were brief, frequent, usuallyintensely painful episodes in which the limbs on oneside adopted the tetanic posture, often precipitatedby movement or sensory stimulation and remittingcompletely in a few weeks. In the present series 15patients, including five previously published (Mat-thews, 1958; 1962), had seizures recognizably of thistype but the original description must be modified inthe light of these observations.

In 11 patients the diagnosis of MS was 'definite'and in one 'probable' (McAlpine et al., 1972) eitherat the time of the seizures or subsequently. In threepatients the diagnosis of MS might well not havebeen considered in the absence of recognizableparoxysmal symptoms and must remain in doubt atthe time of reporting. The seizures were the firstsymptoms in two patients.The seizures were unilateral in all patients, the

arm being invariably affected while in six the lowerlimb was not involved in spasm. In nine patients thehand adopted the tetanic posture, being observed todo so in six, but in two the fist was clenched and intwo further patients the fingers were extended at themetacarpophalangeal joints, producing a claw hand.In two patients the posture of the hand could not beascertained. The arm was usually flexed at the elbow

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and wrist and adducted at the shoulder, but in onepatient the arm was extended and in another stronglyabducted. When involved, the lower limb was ex-tended at hip and knee and the foot was plantar-flexed. Involvement of the facial muscles wasprobable in four patients but the face was often con-torted by pain, rendering interpretation difficult. Theresemblance to the tetanic posture, while oftenstriking, was, therefore, less consistent than at firstreported.The seizures were extremely painful in seven

patients, the pain having the same distribution as thespasm. It seemed unlikely that the pain was entirelydue to the intense muscular contraction as in twopatients pain was experienced before the spasm wasfully developed, while eight patients, in whomcontraction was not obviously less severe, had nopain. Paraesthesiae in the affected limbs were notcommented on apart from one patient who experi-enced a tickling sensation. Thirteen patients ob-served precipitation of the seizures by movement orsensory stimulation, the two often being indistin-guishable. Putting the foot to the ground on stand-ing up or turning over in bed onto the affected sidewere the actions most frequently noted but therewere also spontaneous complaints of seizures in-duced by typing, carrying shopping, or tying shoe-laces. Overbreathing for a brief period was observedto trigger the seizures in three of the seven patients inwhom this was attempted.

Seizures were always brief, the longest observedbeing 90 seconds and the longest estimate by apatient being two minutes, many claiming a durationof 30 seconds or less. In 11 patients the seizuresappeared abruptly and persisted for from two daysto two months, remitting either spontaneously or inresponse to treatment, without recurrence whentreatment was eventually stopped. In these patientsseizures occurred with great frequency, 30 times aday being common, and sometimes every few minutesfor many hours. In four patients the pattern wasdifferent, with relatively infrequent seizures recur-ring for from one to over three years.The physical signs present at the time of onset of

the seizures did not indicate any specific pattern ofdistribution of lesions. In five patients, signs wereconfined to those of mild or moderate pyramidaltract involvement ipsilateral to the seizures. In twopatients abnormal signs were restricted to the opticnerves; three showed evidence of widespread in-volvement of the spinal cord and brain-stem; onehad a severe cervical spinal cord lesion; two hadspastic paraparesis with little sensory loss; and twohad sensory loss alone.

In five patients tonic seizures were accompaniedby other paroxysmal symptoms. Two patients with

painless tonic seizures, not involving the face, weredysarthric during the attacks. In one patient tonicseizures involving the left upper limb were invariablypreceded by a burning sensation behind the rightscapula. In another patient the initial symptom hadbeen brief episodes of loss of use of the left foot,without spasm or change in posture, often precipi-tated by putting the foot to the ground. After sixmonths these episodes began to be accompanied bypainless tonic seizures affecting the left upper limb.In a girl of 16 her second attack of retrobulbarneuritis was accompanied by typical tonic seizures ofthe left upper limb and simultaneous 'jumping'movements of the right upper limb, unfortunatelynot witnessed.Tonic seizures were not accompanied by any

disturbance of consciousness and the electro-encephalogram recorded both between and duringseizures was not disturbed. In one patient, however,there was an unexpected link with epilepsy.

CASE 1

Devic's syndrome followed by paroxysmaldysarthria and later by tonic seizures and epilepsy

A man aged 18 years developed a severe illness lead-ing within three days to bilateral blindness from opticneuritis and paraplegia with an upper dorsal motorand sensory level. In the course of a few months bothvision and strength partially recovered. Four yearslater he had an episode of diplopia. A month later hedeveloped attacks of slurred speech during which hefelt light headed and unable to control his limbs.These lasted a few seconds only and occurred up to20 times a day. Attacks could be precipitated byabout 20 deep breaths. They were abolished by asmall dose of carbamazepine and did not recur whenthis was stopped six weeks later. Four months laterhe developed tonic seizures of the right arm whichadopted a tetanic posture. These were regularlyprecipitated by using the hand and were accom-panied by dysarthria. While demonstrating thattying his shoelace would cause a seizure the localtonic spasm was immediately succeeded by ageneralized convulsion. He was stuporose for fourdays and subsequently had a right hemiparesis thatrecovered over the next five months. During thistime he had two further major fits but no moretonic seizures. Anticonvulsants had to be withdrawnbecause of repeated deliberate overdosage but no illeffects resulted.

In addition to the 15 patients with seizures affect-ing the limbs one patient had a different form oftonic seizure.

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Paroxysmal symptoms in multiple sclerosis

CASE 2

Tonic seizures of neck and eye musclesafter relapse ofMS affecting brain-stem

At the age of 24 years this woman had diplopia andparaesthesiae in the left side of the face and tonguefor three weeks and a similar episode a year laterwith recovery. Two years later, in the course of twoweeks, she developed a severe brain-stem syndromeat the height of which she was drowsy, unable toswallow, and had almost complete external ophthal-moplegia, bilateral facial weakness, and weakness ofall limbs with bilateral extensor plantar reflexes. Amonth later, when she was recovering from thisrelapse and when the ocular palsies had resolved shebegan to have attacks in which she felt as if her eyeswere turning in. Her head would turn slightly to theright and the left eye would adduct (Figure). Theseattacks lasted about 10 seconds and were extremelydistressing, although not painful. For many daysthey occurred approximately every 10 minutes and

t X ..P<. X ~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~...As. .

FIGURE Case 2 experiencing a paroxysm in which thehead is turned slightly to the right and the left eye isadducted. Between paroxysms the position of the eyeswas normal and there was no ocular paresis.

could be regularly induced by overbreathing but alsoby virtually any form of sensory stimulation, render-ing nursing care and feeding difficult. Phenobarbi-tone and phenytoin did not reduce the number ofattacks which gradually lessened and stopped aftertwo months. Carbamazepine was not available. Herimprovement continued but she subsequently hadrepeated relapses and died at the age of 35 years.

DYSARTHRIA Ten patients experienced paroxysmaldysarthria including the two already mentioned whohad concurrent tonic seizures, one of whom had hada previous series of dysarthric attacks (case 1). Eightwere eventually classified as definite cases of MS andtwo as probable cases, the diagnosis sometimes onlybeing established after prolonged follow-up. Forexample, the patient who was reported as a possibleexample ofMS occurring with ankylosing spondylitis(Matthews, 1968) later developed characteristicsymptoms and signs of the disease (Dr MichaelEspir, personal communication). In this patient andin one other the paroxysms were the presentingsymptom.The attacks began suddenly and occurred from

one to 50 times a day for a period varying from oneweek to 12 months. In those in whom the paroxysmsremitted spontaneously the frequency declinedgradually from the initial high level. The attackswere always brief, varying from an observed fiveseconds to the longest estimate by a patient of twominutes. Excluding those paroxysms that occurredwith tonic spasms, five additional patients hadnoted precipitating factors. Sudden movement of anypart of the body was the usual trigger in four patientsand one believed that even changing his train ofthought was sufficient. One woman complained ofattacks immediately after sexual intercourse. In fourof the five patients in whom it was attempted over-breathing for a brief period induced a paroxysm.Despite these precipitating factors in all patients themajority of paroxysms appeared to be spontaneous.Less observant patients would describe the attacks as'dizziness' and their nature could only be deter-mined by detailed questioning.The speech disturbance was variously described by

the patients as slurring, stammering, or loss of con-trol. The six patients whose attacks were observedwere reluctant to continue speaking and preciseobservation was also limited by the brevity of theepisodes. The slurred disjointed syllables that couldsometimes be recognized certainly suggested dys-arthria rather than dysphasia but no detailed analysiswas possible. Dysarthria was never the only com-ponent of the paroxysms. As noted, in two patientsdysarthria was accompanied by tonic seizures. Threepatients complained of feeling faint or light headed,

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combined with a sensation of generalized loss ofcontrol of the limbs, sometimes causing stumbling.One of these patients fell off his bicycle in a numberof attacks. Consciousness did not seem to be dis-turbed, even momentarily.

In six patients the paroxysms began with sensorysymptoms in the face, variously described as burning,numbness, or tingling. These sensations were alwaysconfined to one side of the face, the left in fivepatients and the right in one, and in three patientsinvariably began in a specific restricted site such asthe forehead or upper lip. In four patients, apparentlysimultaneously with the onset of dysarthria, similarsensory symptoms developed in the upper limb, intwo ipsilateral and two contralateral to the facialsensations. Again the paraesthesiae were oftensharply localized, affecting the identical digits onevery occasion. Two patients said that during anattack they were unable to use the arm contralateralto the paraesthesiae but it was not possible to deter-mine, even when witnessing an attack, whether thiswas due to weakness or ataxia. Most patients foundthe paroxysms highly distressing.At the time of development of the paroxysmal

dysarthria four patients had widespread signs of MS,including evidence of brain-stem lesions, but in twothere were no abnormal signs and in the remainingfour only minor signs, not specifically related to thebrain stem.

SENSORY SYMPTOMS One patient had paroxysmalsensory symptoms in isolation.

CASE 3

Paroxysmal sensory systomsas first symptom ofMS

A man of 45 years of age began to experience asensation of quivering in the right side of the face,spreading to the right arm, index finger, and thumb.This would last for a few seconds and was notaccompanied by any involuntary movement or bydysarthria. The sensation, which was highly un-pleasant, was not precipitated by any obvious factor.The frequency gradually increased until after about ayear he suddenly began to have attacks 'every fewseconds' causing such distress that his doctor had tobe called out twice in one night and eventually gavean injection of morphia that allowed the patient tofall asleep. The attacks continued many times a daybut on treatment with carbamazepine rapidly sub-sided after a total duration of 15 months and did notreturn when treatment was stopped some monthslater.Soon after the onset of these symptoms he

developed progressive difficulty in walking. When

examined after the severe exacerbation of hisparoxysms he was found to have pallor of the rightoptic disc, increased tendon reflexes in the left limbs,absent abdominal reflexes, bilateral extensor plantarreflexes, and an ataxic gait.

LOSS OF USE Two patients with probable MS, one ofwhom had previously had paroxysmal dysarthria,experienced attacks of a sensation of loss of use ofthe limbs on one side. These bore many points ofresemblance to other paroxysmal symptoms in thatthey were brief, began suddenly, and occurred withgreat frequency for two weeks in one patient and forone week in the other, in whom they respondedimmediately to carbamazepine. It was not possibleto determine the precise nature of the loss of usecomplained of even when an attack was witnessed.There is some resemblance to the motor accompani-ment described by two patients with paroxysmaldysarthria but more obviously to the paroxysmalloss of use of the foot described by one patient withupper limb tonic seizures.

TREATMENT These 26 patients had 28 episodes ofparoxysmal symptoms. Of these, 12 stopped spon-taneously without the effect of drugs being observed.Conventional anticonvulsants, phenobarbitone, andphenytoin, appeared to arrest the paroxysms in sixpatients, three with tonic seizures, one with combinedtonic seizures and dysarthria and two with paroxys-mal dysarthria. The response was sometimesobvious, with complete relief immediately onbeginning treatment and temporary relapse onattempted withdrawal of the drug. In four patients,two with tonic seizures, one with dysarthria and onewith motor symptoms involving the eyes and headthere was no response to these drugs in full dosage.Carbamazepine was immediately effective in the sixpatients in whom it was used, comprising onepatient with sensory symptoms, one with tonicseizures, and four with dysarthria, in one of whomphenobarbitone had proved ineffective. Carbamaze-pine was not available for use in the other threepatients in whom phenobarbitone and phenytoinhad failed. The effect of carbamazepine on paroxys-mal dysarthria was particularly striking. In onepatient who was having up to 50 attacks a day therewas complete relief within an hour of the first doseof 100 mg. The maintenance dose required was low,seldom exceeding 300 mg a day in divided dosage.

DISCUSSION

Paroxysmal symptoms of the type describedhere must be distinguished from other symp-

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toms of brief duration encountered in MS. Manypatients describe unsystematized fluctuation intheir symptoms, and more specific entities in-clude Lhermitte's sign, flexor and extensorspasms and, in particular, the transient deteriora-tion in vision or walking induced by heat orexertion. These appear to be related to thedemyelinating process but the duration andprecipitating factors are distinctive. Many of thebrief episodes of weakness described by Zeldo-wicz (1961) were probably of this nature as werethe visual symptoms reported by Franklin andBrickner (1947).The frequency of paroxysmal symptoms has

been variously estimated. Kuroiwa and Araki(1963) reported that 13% of 56 patients withdemyelinating disease had tonic seizures andShibasaki and Kuroiwa (1974) 17% of 64patients with MS, there apparently being littleoverlap between these two series from the samecentre in Japan. Espir and Millac (1970) reported13 patients with tonic seizures or paroxysmaldysarthria in approximately 600 patients withMS in addition to nine with trigeminal neuralgia.Identical paroxysmal symptoms undoubtedlyoccur in patients who appear to have acutedisseminated encephalomyelitis rather thanclassical MS (Ekbom et al., 1968).The full range of paroxysmal symptoms has

almost certainly not been recognized. In manyof the examples of tonic seizures reported fromJapan (Kuroiwa and Araki, 1963; Shibasaki andKuroiwa, 1974) the spasm has been widespread,involving both arms or one arm and both legs oreven all four limbs. Kreindler et al. (1962) alsoreported bilateral involvement. The paroxysmalsensation of loss of use of the limbs described bytwo patients in the present series as an isolatedphenomenon was also reported by Castaigne etal. (1970) one of whose patients would be unableto move for 20 seconds, although he did not fall.This brief akinesia is described by patients indifferent terms from the loss of control com-plained of by some patients during paroxysmaldysarthria which is probably cerebellar ataxia.Distressing paraesthesiae can occur as an isolatedparoxysmal symptom as in the patient reportedhere (case 3) and in Espir and Millac's (1970)case 4, but less convincingly in their otherexamples. In personal experience, episodic painin MS, other than trigeminal neuralgia, has

different characteristics, the attacks lasting formuch longer and showing little response totherapeutic agents effective in preventing otherparoxysmal symptoms, although partial successwas claimed by Espir and Millac (1970).The association of tonic seizures with a partial

Brown-Sequard syndrome (Matthews, 1958) thatwas originally suggested could not be confirmedin this larger series. A number of authors haveemphasized the importance of spinal cord lesions(Kreindler et al., 1962; Shibasaki and Kuroiwa,1974) and the association with Lhermitte's signnoted by Kuroiwa and Araki (1963) could beregarded as supporting evidence of spinal corddisease. The simultaneous occurrence of tonicseizures and dysarthria in two patients in thepresent series could not be accounted for by anydisturbance of function resulting from a singlespinal cord lesion.The nature of these paroxysmal symptoms is a

matter of some interest. Epilepsy of corticalorigin is an unlikely explanation, althoughclosely similar tonic seizures can result fromfocal lesions of the medial surface of the hemi-spheres (Kennedy, 1959). The patient in thepresent series in whom a tonic seizure induced bymovement was observed to lead immediately togeneralized status epilepticus appears to beunique. The confused literature of tonic fits as aform of subcortical epilepsy was reviewed byMatthews (1958) who concluded that unilateraltonic seizures were not characteristic of fitsoriginating in any subcortical structure. Thequestion of epilepsy of spinal cord origin islargely a matter of definition. Certainly tonicspasms not readily explained as due to reflexactivity have been described in spinal cord com-pression (Nathanson, 1962) but their epilepticnature is problematical.

In some patients with paroxysmal symptomsfeatures are detectable that could not be attri-buted to neuronal discharge from any single sitein the cerebral hemisphere. Ekbom et al. (1968)drew attention to tonic seizures accompanied orpreceded by contralateral paraesthesiae of thetype associated with lesions of the spinothalamictract. They postulated lateral spread of excita-tion between axons in the lateral column of thespinal cord as a cause for this sequence. In thebrain-stem a similar possibility is even morestrongly suggested by the facial paraesthesiae

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followed by crossed brachial paraesthesiae andipsilateral ataxia that occurred in two patientswith paroxysmal dysarthria. Sensory symptomscontralateral to tonic seizures are relatively rare,occurring in only one patient in the presentseries, but, if this hypothesis is correct, isolatedtonic spasm could result from lateral axonalspread in plaques in the corticospinal pathwaynot involving the spinothalamic tract, or perhapscausing ipsilateral pain or other sensory symp-toms from spread into the posterior columns. Ifthis were so, similar motor symptoms mightresult from involvement of the corticospinalpathway at any level, brain-stem plaquesaccounting for tonic seizures accompanying dys-arthria and a plaque subjacent to the cortexbeing responsible for the sequence in the patientdescribed here in whom epilepsy immediatelyfollowed a tonic seizure.

All authors have noted that paroxysmalsymptoms of every type are frequently precipi-tated by sensory stimulation or movement.Shibasaki and Kuroiwa (1974) were able toidentify trigger zones in some patients but inpersonal experience these seldom approach thespecificity found in trigeminal neuralgia. Al-though in any patient many paroxysms appearto be spontaneous, this effect of the sensoryinput must be taken into account in any theoryof causation. A possible explanation is thatafferent impulses reaching an area of demyelina-tion spread laterally to neighbouring afferentand efferent axons within the plaque, resulting inthe clinical phenomena of the paroxysm.The clinical resemblance of tonic seizures to

hemitetany of metabolic origin has been notedby all observers and the possible significance ofthis fact was reviewed by Matthews (1958). Thisresemblance is sometimes less precise than atfirst described but the implications may yet besomething more than 'assez superficielles'(Castaigne et al., 1970). Both tetany and tonicseizures may be precipitated by overbreathing.From clinical evidence overbreathing and othermethods of reducing ionic calcium appear tofacilitate transmission through plaques of de-myelination (Davis et al., 1970; Becker et al.,1974). The precise action of carbamazepine thatis so effective in controlling all forms of paroxys-mal symptoms has been little investigated atcellular level but an effect on ionic concentra-

tions in the axon has been established (Schaufet al., 1974). Phenytoin, that has a similar butless pronounced effect on paroxysmal symp-toms, is known to exert its effect on reducingaxonal excitability by limiting membrane perme-ability to calcium (Pincus and Lee, 1973). It istherefore at least plausible that the mechanism ofthe postulated lateral spread of excitation indemyelinated plaques (Ekbom et al., 1968) bearssome resemblance to the state of axonal hyper-excitability induced by reduction of ionic calciumthat causes tetany.

REFERENCES

Andermann, F., Cosgrove, J. B. R., Lloyd-Smith, D., andWalters, A. M. (1959). Paroxysmal dysarthria and ataxia inmultiple sclerosis. A report of 2 unusual cases. Neurology(Minneap.), 9, 211-215.

Becker, F. O., Michael, J. A., and Davis, F. A. (1974).Acute effects of oral phosphate on visual function inmultiple sclerosis. Neurology (Minneap.), 24, 601-607.

Castaigne, P., Cambier, J., Masson, M., Brunet, P.,Lechevallier, B., Delaporte, P., and Dehen, H. (1970). Lesmanifestations motrices paroxystiques de la sclerose enplaques. Presse Me'dicale, 78, 1921-1924.

Davis, F. A., Becker, F. O., Michael, J. A., and Sorensen, E.(1970). Effect of intravenous sodium bicarbonate, di-sodium edetate (Na2EDTA), and hyperventilation onvisual and oculomotor signs in multiple sclerosis. Journalof Neurology, Neurosurgery, and Psychiatry, 33, 723-732.

Ekbom, K. A., Westerberg, C.-E., and Osterman, P. 0.(1968). Focal sensory-motor seizures of spinal origin.Lancet, 1, 67.

Espir, M. L. E., and Millac, P. (1970). Treatment of paroxys-mal disorders in multiple sclerosis with carbamazepine(Tegretol). Journal of Neurology, Neurosurgery, andPsychiatry, 33, 528-531.

Espir, M. L. E., Watkins, S. M., and Smith, H. V. (1966).Paroxysmal dysarthria and other transient neurologicaldisturbances in disseminated sclerosis. JournalofNeurology,Neurosurgery, and Psychiatry, 29, 323-330.

Franklin, C. R., and Brickner, R. M. (1947). Vasospasmassociated with multiple sclerosis. Archives of Neurologyand Psychiatry (Chic.), 58, 125-162.

Kennedy, W. A. (1959). Clinical and electroencephalo-graphic aspects of epileptogenic lesions of the medial sur-face and superior border of the cerebral hemisphere.Brain, 82, 147-161.

Kreindler, A., Cardas, M., Petresco, A., and Botez, M. I.(1962). Consid6rations sur 1'6tiopathogenie des crisestoniques dans l'encephalomyelite dissemin6e. RevueNeurologique, 107, 353-369.

Kuroiwa, Y., and Araki, S. (1963). Lhermitte's sign andreflex tonic spasm in demyelinating diseases with specialreference to their localizing value. Kyushu Journal ofMedical Science, 14, 29-38.

McAlpine, D., Lumsden, C. E., and Acheson, E. D. (1972).Multiple Sclerosis. A Reappraisal, 2nd edn, p. 202. Living-stone: Edinburgh.

Matthews, W. B. (1958). Tonic seizures in disseminatedsclerosis. Brain, 81, 193-206.

Matthews, W. B. (1962). Epilepsy and disseminated sclerosis.Quarterly Journal of Medicine, 31, 141-155.

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Matthews, W. B. (1968). The neurological complications ofankylosing spondylitis. Journal of the NeurologicalSciences, 6, 561-573.

Nathanson, M. (1962). Paroxysmal phenomena resemblingseizures, related to spinal cord and root pathology. Journalof the Mount Sinai Hospital, 29, 147-151.

Pincus, J. H., and Lee, S. (1973). Diphenylhydantoin andcalcium. Archives of Neuirology (Chic.), 29, 239-244.

Schauf, C. L., Davis, F. A., and Marder, J. (1974). Effects of

carbamazepine on the ionic conductances of Myxicolagiant axons. Journal of Pharmacology and ExperimentalTherapeutics, 189, 538-543.

Shibasaki, H., and Kuroiwa, Y. (1974). Painful tonic seizurein multiple sclerosis. Archives of Neurology (Chic.), 30,47-51.

Zeldowicz, L. (1961). Paroxysmal motor episodes as earlymanifestations of multiple sclerosis. Canadian MedicalAssociation Journal, 84, 937-941.

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