Folia Psychiatrica et Neurologica Japonica, Vol. 33, No. 1, 1979
Paroxysmal Dysesthesia in Multiple Sclerosis Seiso Yabuki, M.D. and Toshiyuki Hayabara, M.D.* Department of Neurology, Kochi Prefectural Central Hospital, Kochi *National Okayama Sanatorium, Okayarna
INTRODUCTION
There have been numerous reports of various paroxysmal symptoms occurring during the course of multiple sclerosis (MS) ever since paroxysmal attacks were first described by Matthews.” Tonic seizure, trigeminal neuralgia and paroxysmal dysarthria are among the most common of such symptoms whereas spinal sensorimotor seizures,l paroxysmal pain or dysesthesia3 and paroxysmal akinesia, diplopia and itching8 are more rarely seen. Although the mode of the attacks is quite diverse, all of these paroxysmal symptoms in MS have common clinical features such as short duration of the attacks, eliciting factors and effect of anticonvulsant medication. It is therefore assumed that all such paroxysmal symptoms share common pathophysiological mechanisms. In this report seven patients with MS who developed paroxysmal dysesthesias of an upper extremity during the course of the disease are presented. The clinical features and the mechanism of development of this particular symptom in comparison with tonic seizures and spinal sensorimotor seizures in MS are considered. CASE REPORTS
Cuse I : u 27-yeur-old femule
The disease began suddenly with pain and Received for publicatiQn Sept. 25, 1978.
impaired vision in the left eye at the age of 20. Complete remission occurred within three months but she had repeated episodes of visual loss thereafter. At the age of 25 she developed weakness of her lower extremities and anuria, and she was admitted to the hospital for the first time. Bilateral optic atrophy, spastic paraplegia and hypesthesia at the level of Tn and below were also noted. After about three months of therapy with prednisolone she was discharged in a state of remission. She remained stable until the following year when she began to have attacks of excruciating pain over the whole left upper extremity (apparently precipitated by doing laundry work in the morning). Within three months the attacks were occurring several times a day. By four months after the painful attacks began she began slurring her speech and gradually developed weakness of the extremities and disturbance in gait, which thus precipitated hospitalization. Neurological examination on admission revealed optic atrophy in the left eye, a positive Lhermitte’s sign, decreased muscular strength and hyperreflexia of the right upper and lower extremities and a bilaterally positive Babinski sign. CSF was free from abnormalities but diffuse slowing was noted on EEG. Paroxysmal Dysesthesia : The attack consisted of a ‘squeezing’ or ‘tearing’ pain of several to many seconds duration occurring in an area extending down from the left shoulder to the entire
98
S. Yabuki and T.
left upper extremity. This pain did not radiate and the area involved did not conform to a specific peripheral nerve distribution. Although there was no associated motor weakness nor convulsive activity the patient usually stopped her motion of the left arm though capable of voluntary movements during the attack. These paroxysms always occurred suddenly immediately after a rapid unintentional movement of the left upper extremity and were never induced by hyperventilation, sensory stimuli or local ischemia. The attacks disappeared on an oral regimen of 200mg carbamazepine and medication was withdrawn two weeks later with no relapses thereafter. Case 2: a 33-year-old female
The onset of MS occurred with dysarthria and hypesthesia of the lower extremities at the age of 23. After one month there was a remission but two months later she developed loss of vision in her left eye, tonic seizures of the upper and lower extremities and gait disturbance. With these symptoms she was hospitalized. Neurological examination on admission revealed bilateral optic atrophy, horizontal nystagmus, a positive Lhermitte’s sign, spastic paraplegia, muscular atrophy of both hands, a zone of hyperesthesia at the neck (C,,,), paresthesia of the right hand, and decrease of all forms of sensation from TI, and below. The total protein content of the CSF was increased to 115 mg/dl; electromyogram of the hand showed evidence of lower motor neuron damage. Tonic seizures involving upper and lower limbs bilaterally, about 20 seconds in duration, and apparently provoked by a change of position, hyperventilation, or stimulation of the skin, were frequently observed at the time of hospitalization. These attacks were completely suppressed by medication with 300 mg carbamazepine, but four months later paroxysms of dysesthesia in the right upper limb developed.
Hayabara
Paroxysmal Dysesthesia: Spells of dysesthesia occurred suddenly upon brushing the teeth or moving the right arm continuously. They were felt by the patient as a sensation of “being compressed by her surroundings” or a “tingling” sensation and were occasionally transmitted to the right side of the neck. The attack usually lasted for about 15 seconds and became resolved spontaneously. During the attacks consciousness was unimpaired Once an attack began the patient usually held her elbow joint flexed but still capable of voluntary movement. The addition of diphenylhydantoin to the carbamazepine regimen for tonic seizures resulted in obliteration of the attacks. Carre 3: a 35-year-old housewife
At the age of 27 she developed numbness in the chest and lower parts of the body and gait disturbance, which disappeared in one month. Subsequently she experienced several episodes of numbness in both lower limbs, each lasting for one to two months. She consulted us after three weeks of progressive numbness in both hands and both legs and a disturbance in gait. At the time of our first examination, dysarthria, intention tremors of both hands, spastic quadriplegia, loss of superficial sensations over the right upper limb and the ulnar side of the left forearm and loss of all forms of sensation over all the limbs and the trunk up to the level of Cs were noted. The CSF was free from gross abnormalities. Paroxysmal Dysesthesia: About three months after first being seen she began to have many very brief daily attacks of a dull pain-like sensation in her right upper extremity. The attack could be provoked by a voluntary movement of the right arm or by bending the neck but never by sensory stimuli, hyperventilation or ischemia of the right upper extremity. After one month the attacks disappeared spontaneously without any anticonvulsant medication.
Paroxysmal Dysesthesia in Multiple Sclerosis
99
Case 4: a 35-year-old unmarried woman
Case 5: a 37-year-old housewife
She had suffered from impaired vision in both eyes eight years previously. Although she had rapidly recovered vision in her right eye, impairment of vision in the left eye had persisted. She had experienced two episodes of weakness of all extremities with gait disturbance four and two years, previously. In both instances remission occurred after several months but a slight weakness of the right leg remained. Four months prior to admission she began to feel numbness in the chest and back, which extended gradually to involve both upper limbs, abdomen and lower limbs; in addition, disturbances in gait and urination developed three weeks prior to admission, which led to her hospitalization. Examination on admission revealed the presence of the following signs: bilateral optic atrophy, nystagmus, dysarthria, intention tremor and other mild cerebellar symptoms, a positive Lhermitte sign, BrownSCquard paralysis between the C, and Th, segments, and loss of superficial sensation on the ulnar side of both forearms. The cerebrospinal fluid showed a slight lymphocytosis but there were normal values for total protein and y-globulin.
In the evening 17 days before hospitalization the patient felt a smarting pain in the left lower leg when she stood up from a sofa. The pain lasted for about 10 seconds but did not impair her ability to walk. For the next four days paroxysms of dysesthesia below the left knee occurred frequently, each time disappearing spontaneously. Seven days prior to hospitalization her left shoulder felt heavy on awakening. As soon as she moved her left arm, a smarting pain occurred over the whole left upper limb, lasting about 10-12 seconds. Subsequently similar attacks of pain occurred when taking a bath which led her to seek medical evaluation. At the time of her admission vertical nystagmus was noted but otherwise there were no gross neurological deficiencies. Paroxysmal dysesthesias of the left upper extremity and attacks of itching on the left side of the face occurred frequently and independently of each other. Ten days later there was an exacerbation of the symptoms and thereafter cerebellar ataxia, spastic tetraplegia dominant on the right side, left precordial zones of hyperesthesia (G-C,), paresthesia in the fingers of both hands and a partial loss of all forms of sensation below the abdomen on the left side developed.
Paroxysmal Dysesthesia: About one month after hospitalization the patient began to feel a momentary boring pain in her left upper extremity when she turned in the bed or moved her left arm. The attacks occurred several times daily but were not accompanied by motor disturbances or convulsions. Because the attacks provoked marked discomfort, 300 mg of carbamazepine was prescribed, which completely controlled the attacks. Six days later, however, she developed fever and leukopenia, and thus the medication was discontinued. No recurrence of the attack has since been observed.
Paroxysmal Dysesthesia : This consisted of spells of fulgurant pain of 2-12 seconds duration. Although an attempt to provoke the pain by manipulation of the left arm failed, the abnormal sensation was liable to occur immediately after movement of the left arm and occasionally even at rest. Voluntary movements were totally unaffected by the attack. The patient became entirely free from the attacks of pain and paroxysmal itching after she was placed on 400 mg carbamazepine. Case 6: a 64-year-old housewife Ever since the age of 53 years she had experienced occasional generalized convul-
100
S.
Yabuki and T. Hayabara
sive seizures. From 60 years of age she had suffered impaired vision in her left eye. At the age of 61 she developed generalized convulsive seizures, followed by motor paralysis of all limbs, urinary incontinence and inability to walk. Remission of these symptoms occurred several months later, but three years later she developed similar symptoms which led to her hospitalization. Significant neurologic findings on admission included optic atrophy and total loss of vision in the left eye, slight weakness of both upper extremities and complete paralysis of both lower extremities, dulling of superficial sensation in the right 3rd to 5th fingers and all over the left forearm and 105s of all forms of sensation below the chest (Th,) on both sides. Tendon reflexes were diminished in the upper extremities and absent in the lower extremities and the plantar response was extensor on both sides. Paroxysmal Dysesthesia: There were attacks of pain, occurring in the left shoulder and radiating to the left arm of about 10 seconds duration. The attacks were not accompanied by convulsions nor precipitated by voluntary movements of the arm. After the attacks initially appeared they ceased for three months but then reappeared and finally were controlled completely with carbamazepine. Unfortunately, the neurologic symptoms became worse two months later and the patient died of respiratory paralysis. Autopsy was not permitted. Case 7: a 61-year-old housewife The disease began at the age of 59 years with a sudden onset of numbness and weakness in both legs and gait disturbance. Following a period of remission there was a reexacerbation of similar symptoms one year later, resulting in inability to walk, urinary incontinence and impaired vision in the right eye. With these symptoms she was admitted to the hospital. Neurologically, bilateral optic atrophy,
spastic total paralysis of both lower extremities, bilateral impairment of all modalities of sensation below T, and anuria were present. Paroxysmal Dysesthesia : After hospitalization she began to have frequent paroxysms, several to 10 seconds in duration, of a boring pain in an area extending from the right shoulder to the right upper arm. The attacks were apparently precipitated by voluntary movements of the upper limb or bodily movements and not associated with convulsions and motor disturbance. Carbamazepine therapy stopped the attacks. Seventeen months later the attacks recurred and were again controlled by carbamazepine. Both of these episodes of paroxysmal dysesthesia coincided with a remission of the neurologic symptoms. In less than one month after the 2nd episode there was symptomatic exacerbation with increased impairment of vision and hypesthesia of the neck and the ulnar aspect of the forearm on the right side. DISCUSSION
Fluctuating periods of exacerbation and remission is one of the important ciinical features of multiple sclerosis (MS), Transitory neurologic manifestations, apparently distinct from long-standing symptoms, may occasionally be observed during the course of MS. McAlpine and associates' classified transient symptoms associated with MS into two groups, i.e., transient symptomatic worsening due to extrinsic factors such as fever and fatigue and paroxysmal symptoms. Among the symptoms which belong to the latter group, various types of epileptic seizures, paroxysmal dysarthria, tonic seizures and trigeminal neuralgia have been commonly reported. The clinical features of paroxysmal dysesthesias in the seven cases presented above can be briefly summarized as follows: ( 1 ) the dysesthesia consists of a burning sensation
Paroxysmal Dysesthesia in Multiple Sclerosis
101
Table 1 : Clinical Features of Seven Patients with Paroxysmal Dysesthesia Case/Sex/ (Yr.) Age
Estimated Site of Lesion Cere- Brain Spinal Optic bellar Stem (levels)
1/F/21 1/F/33
+
+
+
3/F/35
-
4/F/35
7/F/61
+ -
+ +
(C3, Thlo-)
+
-
+
(Ca-Ths,
+
-
-
+
(C4-1
-
+
+
(Ca-1
+
-
-
+
(C7-a. Ths-)
+
+
-
+
(G-, Th7-)
-
Tho-)
or a fulgurant pain and is provoked by voluntary movement of the extremity involved in the attack, (2) the pathological sensation is usually confined to one arm but may at times extend to the shoulder or neck, (3) there is no associated convulsive activity nor disturbance of voluntary movements, (4) the attacks are of short duration (a few seconds to less than one minute) but occur many times a day, and ( 5 ) the attacks are controlled by carbamazepine. Consciousness was retained during the attacks and no paroxysmal abnormalities were noted on EEG in five of seven cases where such examinations were feasible. These attacks bear a resemblance to Lhermitte’s sign but differ from the latter in the method of provocation, distribution and duration. Unlike radiating pain from cervical root stimulation, the distribution of pain does not correspond to a specific dermatomal pattern. However, these attacks share the follow-
Neurolo ical Signs in the Limb A&cted with the Paroxysmal Dy sesthesia
(-1
paresthesia of the neckandhand, hyperreflexia, weakness, and muscle atrophy hyperesthesia between G-Ths, sensory loss of the ulnar side, and weakness superficial sensory loss of the ulnar side, deceased deep sensation, hyperreflexia, weakness, and ataxia hyperesthesia between C8-C4,hyperreflexia, weakness, and ataxia superficial sensory loss in the 3rd to 5th finger, hyporeflexia, and weakners superficial sensory loss of the neck and ulnar side of the right hand
ing characteristics with other forms of paroxysmal symptoms seen in MS: they are provoked by movement, are short in duration and of frquent occurrence, and responsive to antiwnvulsant medication. The attacks also Mer from tonic seizures in that they are purely sensory and of very short duration. As regards the pathogenetic mechanism of tonic seizures in MS, epileptic theory gained wide acceptance initially. From the fact that this type of seizure manifests itself as choreo-athetotic movements, it was speculated that a lesion in the subcortical area or basal ganglia might be responsible for tonic seizures in MS.4 l1 However, Matthews,O who first noticed the relationship between such seizures and MS, surmised that tonic seizures might represent a kind of tetany resulting from structural lesions of the central nervous system. Kuroiwa and Shibasaki reported four cases of tonic seizures in 19686 and an
102
S. Yabuki and T. Hayabara
additional 10 cases in 1974,"' postulating that a spinal cord reflex mechanism was responsible for this paroxysmal disturbance. In 1968 Ekbom et d 2 described two cases of spinal sensorimotor seizure with simultaneous occurrence of tonic spasms on one side and dysesthesia on the other. They suggested that these motor and sensory disturbances could be explained by (1) a centrifugal stream of impulses along a motor path in the central nervous system and (2) a centripetal stream of impulses along a sensory path in the central nervous system, and they proposed the hypothesis that the attacks were caused by a transversely spreading activation of damaged axons in the fibre tracts of the spinal cord. In 1974 we studied the relationship between the types of tonic seizures and other neurologic symptoms in 3 of our own cases of MS and another 25 reported in literature." The result led us to postulate that tonic seizure is a sign whose motor and sensory factors derive from the pyramidal tract and spinothalamic tract, respectively. In 1975, Osterman et al.x reported 22 cases of MS exhibiting a variety of paroxysmal symptoms. According to them, all types of paroxysmal symptoms occurring in MS might be explained by a transversely spreading ephatic activation of axons within a partially demyelinated lesion in the fibre tracts somewhere in the central nervous system. Ekbom, the present authors and Osterman agree with each other in theorizing that tonic seizures of MS represent paroxysmal symptoms which result from spontaneous axonal discharge from a demyelinating lesion with subsequent spread along the motor and sensory tracts, thus resulting in motor and sensory symptomatology. Turning, in retrospect, to the neurologic symptoms present at the time of the occurrence of paroxysmal dysesthesia in the seven cases described above, symptoms arising from the spinal cord were observed in six cases, optic atrophy was seen in five cases,
cerebellar symptoms and Lhermitte's sign were present in three cases each, and symptoms involving the brain stem were noted in only one case. Thus, symptoms of a spinal cord lesion, notably at the level of the cervical region, were most common. As regards signs involving the upper extremity from which the seizure arose, neurologic symptoms were present in six of the seven cases. More particularly, sensory disturbances were present in six cases, hyperreflexia, diminished muscular power and pyramidal sign were noted in three cases and a slight to moderate degree of cerebellar ataxia in two cases. The sensory disturbances included impairment of superficial senses localized at the ulnar side of the forearm observed in four cases, dysesthesia of the whole palm in two cases and segmental zones of dysesthesia at the level of the cervical region in five cases. These clinical findings can be interpreted as suggesting the possibility that paroxysmal dysesthesia originates in a lesion of the cervical spinal cord. As already referred to above, paroxysmal dysesthesia differs from tonic seizures in that it is purely sensory in nature. Furthermore, these two types of paroxysms tend to be distinct from each other in the distribution of the areas involved. Thus, tonic seizures usually occur bilaterally or in both upper and lower extremities and are rarely confined to a single limb. This is consistent with the hypothesis that tonic seizures have their origin in the long tract of the central nervous system. The paroxysms of dysesthesia observed in the present seven cases, on the other hand, were all localized at a single extremity. The seven cases of paroxysmal pain described by Espir et al.:j seem to bear a resemblance to the seizures in the present cases. And it should be noted that in all cases in their series the paroxysms were also localized at one limb. If such a distribution pattern is one of the characteristics of paroxysmal dysesthesia, then it is difficult to implicate a lesion of the white matter of
Paroxysmal Dysesthesia in Multiple Sclerosis
103
il i x-
paroxysmal dysesthesia
anterior horn
stimuli
Fig. 1: Schematic illustration of the concept ( 1 ) : motor stimuli from the upper extremity could be transmitted to the posterior horn via the anterior horn of the spinal cord.
the spinal cord in its mechanism of development. This is because the paroxysm occurs in the upper extremity on the side receiving the motor stimuli. Furthermore, since the most common clinical symptoms in the seven cases would be localized in the cervical spinal cord, it is quite unlikely that the seizure would originate from the brain stem or above. These clinical observations and neurophysiological considerations have led the present authors to regard the paroxysmal dysesthesias in question as segmental signs due to lesions in or about the spinal cord. In this instance there are two possibilities, i.e., (1) impulses are transmitted to the peripheral sensory fibre via the spinal cord or ( 2 ) they are transmitted, in an abnormal manner, from the peripheral motor fibres directly to the peripheral sensory fibres. Although it is uncertain which of these two modes of transmission is actually the case, it does not seem likely that the focus of excitation lies in the distal portion of the peripheral nerves in view of the fact that in all seven cases the paroxysmal dysesthesia
occurred over an entire upper limb, even extending to the shoulder and neck in occasional cases. Fig. 1 is a diagrammatic representation of the concept (1 ). As can be seen, the motor fibres from an upper extremity leave the anterior horn of the spinal cord via the anterior root. Motor stimuli could be transmitted in a retrograde fashion directly to the posterior horn and thereby give rise to excitation of sensory fibres peripheral to the dorsal root. If this hypothesis is correct it can be seen that the paroxysmal dysesthesias occur ipsilaterally to the motor stimuli and are confined to the upper extremity without extending to the lower extremity. On the other hand, MS has recently been reported to also be associated with impaired myelinization of the peripheral nerves." Evidence of lower motor neuron damage was obtained on electromyography of the finger muscles in Case 2 of the present series. In view of these findings the possibility that paroxysmal dysesthesias are of peripheral origin cannot be ruled out.
S. Yabuki and T. Hayabara
104
SUMMARY
Seven cases of multiple sclerosis with paroxysmal dysesthesias of an upper extremity were reported. This seizure characteristically is a purely sensory one induced by movements and is not accompanied by convulsions or a disorder of voluntary movements. In other ways it shares some features with other paroxysmal manifestations seen in MS. Clinical observations with subsequent neurophysiologic considerations have led to the hypothesis that paroxysmal dysesthesias are segmental symptoms with their foci lying in or about the spinal cord. REFERENCES 1 Castaigne, P., Cambier, J. and Brunet, P.:
1970. 4 Guillain, G., Alajouanine, T., Bertrand, I.
and Garcin, R.: Sur une forme anatomoclinique speciale de neuro-myblite optique nbcrotique aigue avec crises toniques tbtanoides, Ann Med, 24: 24-57, 1928. 5 Kuroiwa, Y. and Shibasaki, H.: Painful tonic seizure in multiple sclerosis, Treatment with diphenylhydantoin and carbamazepine, Folia Psychiat Neurol Jap, 22: 107-119, 1968. 6 Matthews, W. B.: Tonic seizure in disseminated sclerosis, Brain, 81: 193-206, 1958. 7 McAlpine, D., Lumsden, C.E. and Ache-
8 9 10
Spinal sensory-motor seizures, Lancet, I: 357, 1968. 2 Ekbom, K. A.,
Westerberg, C.-E. and Osterman, P. 0.: Focal sensory-motor seizures of spinal origin, Lancet, I: 67, 1968. 3 Espir, M.L.E. and Millac, P.: Treatment of paroxysmal disorders in multiple sclerosis with carbamazepine (Tegretol), J Neurol Neurosurg Psychat, 33: 528-53 1,
11
son, E. D.: Multiple Sclerosis, A Reappraisal, p. 143, 1965, Livingstone, Edinburgh and London. Osterman, P. 0. and Westerberg, C.-E.: Paroxysmal attacks in multiple sclerosis, Brain, 98: 189-202, 1975. Pollac, M., Calder, C. and Allpress, S.: Peripheral nerve abnormality in multiple sclerosis, Ann Neurol, 2: 41-48, 1977. Shibasaki, H. and Kuroiwa, Y.: Painful tonic seizure in multiple sclerosis, Arch Neurol, 30: 47-51, 1974. Spiller, W. G.: Subcortical epilepsy, Brain,
50: 171-177, 1927. 12 Yabuki, S., Hayabara, T., Ikeda, H., Ishino, H. and Otsuki, S.: Clinical obser-
vation of the tonic seizure in multiple sclerosis, Psychiat Neurol Jap, 76: 207-220, 1974 (in Japanese).
Paroxysmal Dysesthesia in Multiple Sclerosis Seiso Yabuki, M.D. and Toshiyuki Hayabara, M.D.* Department of Neurology, Kochi Prefectural Central Hospital, Kochi *National Okayama Sanatorium, Okayarna
INTRODUCTION
There have been numerous reports of various paroxysmal symptoms occurring during the course of multiple sclerosis (MS) ever since paroxysmal attacks were first described by Matthews.” Tonic seizure, trigeminal neuralgia and paroxysmal dysarthria are among the most common of such symptoms whereas spinal sensorimotor seizures,l paroxysmal pain or dysesthesia3 and paroxysmal akinesia, diplopia and itching8 are more rarely seen. Although the mode of the attacks is quite diverse, all of these paroxysmal symptoms in MS have common clinical features such as short duration of the attacks, eliciting factors and effect of anticonvulsant medication. It is therefore assumed that all such paroxysmal symptoms share common pathophysiological mechanisms. In this report seven patients with MS who developed paroxysmal dysesthesias of an upper extremity during the course of the disease are presented. The clinical features and the mechanism of development of this particular symptom in comparison with tonic seizures and spinal sensorimotor seizures in MS are considered. CASE REPORTS
Cuse I : u 27-yeur-old femule
The disease began suddenly with pain and Received for publicatiQn Sept. 25, 1978.
impaired vision in the left eye at the age of 20. Complete remission occurred within three months but she had repeated episodes of visual loss thereafter. At the age of 25 she developed weakness of her lower extremities and anuria, and she was admitted to the hospital for the first time. Bilateral optic atrophy, spastic paraplegia and hypesthesia at the level of Tn and below were also noted. After about three months of therapy with prednisolone she was discharged in a state of remission. She remained stable until the following year when she began to have attacks of excruciating pain over the whole left upper extremity (apparently precipitated by doing laundry work in the morning). Within three months the attacks were occurring several times a day. By four months after the painful attacks began she began slurring her speech and gradually developed weakness of the extremities and disturbance in gait, which thus precipitated hospitalization. Neurological examination on admission revealed optic atrophy in the left eye, a positive Lhermitte’s sign, decreased muscular strength and hyperreflexia of the right upper and lower extremities and a bilaterally positive Babinski sign. CSF was free from abnormalities but diffuse slowing was noted on EEG. Paroxysmal Dysesthesia : The attack consisted of a ‘squeezing’ or ‘tearing’ pain of several to many seconds duration occurring in an area extending down from the left shoulder to the entire
98
S. Yabuki and T.
left upper extremity. This pain did not radiate and the area involved did not conform to a specific peripheral nerve distribution. Although there was no associated motor weakness nor convulsive activity the patient usually stopped her motion of the left arm though capable of voluntary movements during the attack. These paroxysms always occurred suddenly immediately after a rapid unintentional movement of the left upper extremity and were never induced by hyperventilation, sensory stimuli or local ischemia. The attacks disappeared on an oral regimen of 200mg carbamazepine and medication was withdrawn two weeks later with no relapses thereafter. Case 2: a 33-year-old female
The onset of MS occurred with dysarthria and hypesthesia of the lower extremities at the age of 23. After one month there was a remission but two months later she developed loss of vision in her left eye, tonic seizures of the upper and lower extremities and gait disturbance. With these symptoms she was hospitalized. Neurological examination on admission revealed bilateral optic atrophy, horizontal nystagmus, a positive Lhermitte’s sign, spastic paraplegia, muscular atrophy of both hands, a zone of hyperesthesia at the neck (C,,,), paresthesia of the right hand, and decrease of all forms of sensation from TI, and below. The total protein content of the CSF was increased to 115 mg/dl; electromyogram of the hand showed evidence of lower motor neuron damage. Tonic seizures involving upper and lower limbs bilaterally, about 20 seconds in duration, and apparently provoked by a change of position, hyperventilation, or stimulation of the skin, were frequently observed at the time of hospitalization. These attacks were completely suppressed by medication with 300 mg carbamazepine, but four months later paroxysms of dysesthesia in the right upper limb developed.
Hayabara
Paroxysmal Dysesthesia: Spells of dysesthesia occurred suddenly upon brushing the teeth or moving the right arm continuously. They were felt by the patient as a sensation of “being compressed by her surroundings” or a “tingling” sensation and were occasionally transmitted to the right side of the neck. The attack usually lasted for about 15 seconds and became resolved spontaneously. During the attacks consciousness was unimpaired Once an attack began the patient usually held her elbow joint flexed but still capable of voluntary movement. The addition of diphenylhydantoin to the carbamazepine regimen for tonic seizures resulted in obliteration of the attacks. Carre 3: a 35-year-old housewife
At the age of 27 she developed numbness in the chest and lower parts of the body and gait disturbance, which disappeared in one month. Subsequently she experienced several episodes of numbness in both lower limbs, each lasting for one to two months. She consulted us after three weeks of progressive numbness in both hands and both legs and a disturbance in gait. At the time of our first examination, dysarthria, intention tremors of both hands, spastic quadriplegia, loss of superficial sensations over the right upper limb and the ulnar side of the left forearm and loss of all forms of sensation over all the limbs and the trunk up to the level of Cs were noted. The CSF was free from gross abnormalities. Paroxysmal Dysesthesia: About three months after first being seen she began to have many very brief daily attacks of a dull pain-like sensation in her right upper extremity. The attack could be provoked by a voluntary movement of the right arm or by bending the neck but never by sensory stimuli, hyperventilation or ischemia of the right upper extremity. After one month the attacks disappeared spontaneously without any anticonvulsant medication.
Paroxysmal Dysesthesia in Multiple Sclerosis
99
Case 4: a 35-year-old unmarried woman
Case 5: a 37-year-old housewife
She had suffered from impaired vision in both eyes eight years previously. Although she had rapidly recovered vision in her right eye, impairment of vision in the left eye had persisted. She had experienced two episodes of weakness of all extremities with gait disturbance four and two years, previously. In both instances remission occurred after several months but a slight weakness of the right leg remained. Four months prior to admission she began to feel numbness in the chest and back, which extended gradually to involve both upper limbs, abdomen and lower limbs; in addition, disturbances in gait and urination developed three weeks prior to admission, which led to her hospitalization. Examination on admission revealed the presence of the following signs: bilateral optic atrophy, nystagmus, dysarthria, intention tremor and other mild cerebellar symptoms, a positive Lhermitte sign, BrownSCquard paralysis between the C, and Th, segments, and loss of superficial sensation on the ulnar side of both forearms. The cerebrospinal fluid showed a slight lymphocytosis but there were normal values for total protein and y-globulin.
In the evening 17 days before hospitalization the patient felt a smarting pain in the left lower leg when she stood up from a sofa. The pain lasted for about 10 seconds but did not impair her ability to walk. For the next four days paroxysms of dysesthesia below the left knee occurred frequently, each time disappearing spontaneously. Seven days prior to hospitalization her left shoulder felt heavy on awakening. As soon as she moved her left arm, a smarting pain occurred over the whole left upper limb, lasting about 10-12 seconds. Subsequently similar attacks of pain occurred when taking a bath which led her to seek medical evaluation. At the time of her admission vertical nystagmus was noted but otherwise there were no gross neurological deficiencies. Paroxysmal dysesthesias of the left upper extremity and attacks of itching on the left side of the face occurred frequently and independently of each other. Ten days later there was an exacerbation of the symptoms and thereafter cerebellar ataxia, spastic tetraplegia dominant on the right side, left precordial zones of hyperesthesia (G-C,), paresthesia in the fingers of both hands and a partial loss of all forms of sensation below the abdomen on the left side developed.
Paroxysmal Dysesthesia: About one month after hospitalization the patient began to feel a momentary boring pain in her left upper extremity when she turned in the bed or moved her left arm. The attacks occurred several times daily but were not accompanied by motor disturbances or convulsions. Because the attacks provoked marked discomfort, 300 mg of carbamazepine was prescribed, which completely controlled the attacks. Six days later, however, she developed fever and leukopenia, and thus the medication was discontinued. No recurrence of the attack has since been observed.
Paroxysmal Dysesthesia : This consisted of spells of fulgurant pain of 2-12 seconds duration. Although an attempt to provoke the pain by manipulation of the left arm failed, the abnormal sensation was liable to occur immediately after movement of the left arm and occasionally even at rest. Voluntary movements were totally unaffected by the attack. The patient became entirely free from the attacks of pain and paroxysmal itching after she was placed on 400 mg carbamazepine. Case 6: a 64-year-old housewife Ever since the age of 53 years she had experienced occasional generalized convul-
100
S.
Yabuki and T. Hayabara
sive seizures. From 60 years of age she had suffered impaired vision in her left eye. At the age of 61 she developed generalized convulsive seizures, followed by motor paralysis of all limbs, urinary incontinence and inability to walk. Remission of these symptoms occurred several months later, but three years later she developed similar symptoms which led to her hospitalization. Significant neurologic findings on admission included optic atrophy and total loss of vision in the left eye, slight weakness of both upper extremities and complete paralysis of both lower extremities, dulling of superficial sensation in the right 3rd to 5th fingers and all over the left forearm and 105s of all forms of sensation below the chest (Th,) on both sides. Tendon reflexes were diminished in the upper extremities and absent in the lower extremities and the plantar response was extensor on both sides. Paroxysmal Dysesthesia: There were attacks of pain, occurring in the left shoulder and radiating to the left arm of about 10 seconds duration. The attacks were not accompanied by convulsions nor precipitated by voluntary movements of the arm. After the attacks initially appeared they ceased for three months but then reappeared and finally were controlled completely with carbamazepine. Unfortunately, the neurologic symptoms became worse two months later and the patient died of respiratory paralysis. Autopsy was not permitted. Case 7: a 61-year-old housewife The disease began at the age of 59 years with a sudden onset of numbness and weakness in both legs and gait disturbance. Following a period of remission there was a reexacerbation of similar symptoms one year later, resulting in inability to walk, urinary incontinence and impaired vision in the right eye. With these symptoms she was admitted to the hospital. Neurologically, bilateral optic atrophy,
spastic total paralysis of both lower extremities, bilateral impairment of all modalities of sensation below T, and anuria were present. Paroxysmal Dysesthesia : After hospitalization she began to have frequent paroxysms, several to 10 seconds in duration, of a boring pain in an area extending from the right shoulder to the right upper arm. The attacks were apparently precipitated by voluntary movements of the upper limb or bodily movements and not associated with convulsions and motor disturbance. Carbamazepine therapy stopped the attacks. Seventeen months later the attacks recurred and were again controlled by carbamazepine. Both of these episodes of paroxysmal dysesthesia coincided with a remission of the neurologic symptoms. In less than one month after the 2nd episode there was symptomatic exacerbation with increased impairment of vision and hypesthesia of the neck and the ulnar aspect of the forearm on the right side. DISCUSSION
Fluctuating periods of exacerbation and remission is one of the important ciinical features of multiple sclerosis (MS), Transitory neurologic manifestations, apparently distinct from long-standing symptoms, may occasionally be observed during the course of MS. McAlpine and associates' classified transient symptoms associated with MS into two groups, i.e., transient symptomatic worsening due to extrinsic factors such as fever and fatigue and paroxysmal symptoms. Among the symptoms which belong to the latter group, various types of epileptic seizures, paroxysmal dysarthria, tonic seizures and trigeminal neuralgia have been commonly reported. The clinical features of paroxysmal dysesthesias in the seven cases presented above can be briefly summarized as follows: ( 1 ) the dysesthesia consists of a burning sensation
Paroxysmal Dysesthesia in Multiple Sclerosis
101
Table 1 : Clinical Features of Seven Patients with Paroxysmal Dysesthesia Case/Sex/ (Yr.) Age
Estimated Site of Lesion Cere- Brain Spinal Optic bellar Stem (levels)
1/F/21 1/F/33
+
+
+
3/F/35
-
4/F/35
7/F/61
+ -
+ +
(C3, Thlo-)
+
-
+
(Ca-Ths,
+
-
-
+
(C4-1
-
+
+
(Ca-1
+
-
-
+
(C7-a. Ths-)
+
+
-
+
(G-, Th7-)
-
Tho-)
or a fulgurant pain and is provoked by voluntary movement of the extremity involved in the attack, (2) the pathological sensation is usually confined to one arm but may at times extend to the shoulder or neck, (3) there is no associated convulsive activity nor disturbance of voluntary movements, (4) the attacks are of short duration (a few seconds to less than one minute) but occur many times a day, and ( 5 ) the attacks are controlled by carbamazepine. Consciousness was retained during the attacks and no paroxysmal abnormalities were noted on EEG in five of seven cases where such examinations were feasible. These attacks bear a resemblance to Lhermitte’s sign but differ from the latter in the method of provocation, distribution and duration. Unlike radiating pain from cervical root stimulation, the distribution of pain does not correspond to a specific dermatomal pattern. However, these attacks share the follow-
Neurolo ical Signs in the Limb A&cted with the Paroxysmal Dy sesthesia
(-1
paresthesia of the neckandhand, hyperreflexia, weakness, and muscle atrophy hyperesthesia between G-Ths, sensory loss of the ulnar side, and weakness superficial sensory loss of the ulnar side, deceased deep sensation, hyperreflexia, weakness, and ataxia hyperesthesia between C8-C4,hyperreflexia, weakness, and ataxia superficial sensory loss in the 3rd to 5th finger, hyporeflexia, and weakners superficial sensory loss of the neck and ulnar side of the right hand
ing characteristics with other forms of paroxysmal symptoms seen in MS: they are provoked by movement, are short in duration and of frquent occurrence, and responsive to antiwnvulsant medication. The attacks also Mer from tonic seizures in that they are purely sensory and of very short duration. As regards the pathogenetic mechanism of tonic seizures in MS, epileptic theory gained wide acceptance initially. From the fact that this type of seizure manifests itself as choreo-athetotic movements, it was speculated that a lesion in the subcortical area or basal ganglia might be responsible for tonic seizures in MS.4 l1 However, Matthews,O who first noticed the relationship between such seizures and MS, surmised that tonic seizures might represent a kind of tetany resulting from structural lesions of the central nervous system. Kuroiwa and Shibasaki reported four cases of tonic seizures in 19686 and an
102
S. Yabuki and T. Hayabara
additional 10 cases in 1974,"' postulating that a spinal cord reflex mechanism was responsible for this paroxysmal disturbance. In 1968 Ekbom et d 2 described two cases of spinal sensorimotor seizure with simultaneous occurrence of tonic spasms on one side and dysesthesia on the other. They suggested that these motor and sensory disturbances could be explained by (1) a centrifugal stream of impulses along a motor path in the central nervous system and (2) a centripetal stream of impulses along a sensory path in the central nervous system, and they proposed the hypothesis that the attacks were caused by a transversely spreading activation of damaged axons in the fibre tracts of the spinal cord. In 1974 we studied the relationship between the types of tonic seizures and other neurologic symptoms in 3 of our own cases of MS and another 25 reported in literature." The result led us to postulate that tonic seizure is a sign whose motor and sensory factors derive from the pyramidal tract and spinothalamic tract, respectively. In 1975, Osterman et al.x reported 22 cases of MS exhibiting a variety of paroxysmal symptoms. According to them, all types of paroxysmal symptoms occurring in MS might be explained by a transversely spreading ephatic activation of axons within a partially demyelinated lesion in the fibre tracts somewhere in the central nervous system. Ekbom, the present authors and Osterman agree with each other in theorizing that tonic seizures of MS represent paroxysmal symptoms which result from spontaneous axonal discharge from a demyelinating lesion with subsequent spread along the motor and sensory tracts, thus resulting in motor and sensory symptomatology. Turning, in retrospect, to the neurologic symptoms present at the time of the occurrence of paroxysmal dysesthesia in the seven cases described above, symptoms arising from the spinal cord were observed in six cases, optic atrophy was seen in five cases,
cerebellar symptoms and Lhermitte's sign were present in three cases each, and symptoms involving the brain stem were noted in only one case. Thus, symptoms of a spinal cord lesion, notably at the level of the cervical region, were most common. As regards signs involving the upper extremity from which the seizure arose, neurologic symptoms were present in six of the seven cases. More particularly, sensory disturbances were present in six cases, hyperreflexia, diminished muscular power and pyramidal sign were noted in three cases and a slight to moderate degree of cerebellar ataxia in two cases. The sensory disturbances included impairment of superficial senses localized at the ulnar side of the forearm observed in four cases, dysesthesia of the whole palm in two cases and segmental zones of dysesthesia at the level of the cervical region in five cases. These clinical findings can be interpreted as suggesting the possibility that paroxysmal dysesthesia originates in a lesion of the cervical spinal cord. As already referred to above, paroxysmal dysesthesia differs from tonic seizures in that it is purely sensory in nature. Furthermore, these two types of paroxysms tend to be distinct from each other in the distribution of the areas involved. Thus, tonic seizures usually occur bilaterally or in both upper and lower extremities and are rarely confined to a single limb. This is consistent with the hypothesis that tonic seizures have their origin in the long tract of the central nervous system. The paroxysms of dysesthesia observed in the present seven cases, on the other hand, were all localized at a single extremity. The seven cases of paroxysmal pain described by Espir et al.:j seem to bear a resemblance to the seizures in the present cases. And it should be noted that in all cases in their series the paroxysms were also localized at one limb. If such a distribution pattern is one of the characteristics of paroxysmal dysesthesia, then it is difficult to implicate a lesion of the white matter of
Paroxysmal Dysesthesia in Multiple Sclerosis
103
il i x-
paroxysmal dysesthesia
anterior horn
stimuli
Fig. 1: Schematic illustration of the concept ( 1 ) : motor stimuli from the upper extremity could be transmitted to the posterior horn via the anterior horn of the spinal cord.
the spinal cord in its mechanism of development. This is because the paroxysm occurs in the upper extremity on the side receiving the motor stimuli. Furthermore, since the most common clinical symptoms in the seven cases would be localized in the cervical spinal cord, it is quite unlikely that the seizure would originate from the brain stem or above. These clinical observations and neurophysiological considerations have led the present authors to regard the paroxysmal dysesthesias in question as segmental signs due to lesions in or about the spinal cord. In this instance there are two possibilities, i.e., (1) impulses are transmitted to the peripheral sensory fibre via the spinal cord or ( 2 ) they are transmitted, in an abnormal manner, from the peripheral motor fibres directly to the peripheral sensory fibres. Although it is uncertain which of these two modes of transmission is actually the case, it does not seem likely that the focus of excitation lies in the distal portion of the peripheral nerves in view of the fact that in all seven cases the paroxysmal dysesthesia
occurred over an entire upper limb, even extending to the shoulder and neck in occasional cases. Fig. 1 is a diagrammatic representation of the concept (1 ). As can be seen, the motor fibres from an upper extremity leave the anterior horn of the spinal cord via the anterior root. Motor stimuli could be transmitted in a retrograde fashion directly to the posterior horn and thereby give rise to excitation of sensory fibres peripheral to the dorsal root. If this hypothesis is correct it can be seen that the paroxysmal dysesthesias occur ipsilaterally to the motor stimuli and are confined to the upper extremity without extending to the lower extremity. On the other hand, MS has recently been reported to also be associated with impaired myelinization of the peripheral nerves." Evidence of lower motor neuron damage was obtained on electromyography of the finger muscles in Case 2 of the present series. In view of these findings the possibility that paroxysmal dysesthesias are of peripheral origin cannot be ruled out.
S. Yabuki and T. Hayabara
104
SUMMARY
Seven cases of multiple sclerosis with paroxysmal dysesthesias of an upper extremity were reported. This seizure characteristically is a purely sensory one induced by movements and is not accompanied by convulsions or a disorder of voluntary movements. In other ways it shares some features with other paroxysmal manifestations seen in MS. Clinical observations with subsequent neurophysiologic considerations have led to the hypothesis that paroxysmal dysesthesias are segmental symptoms with their foci lying in or about the spinal cord. REFERENCES 1 Castaigne, P., Cambier, J. and Brunet, P.:
1970. 4 Guillain, G., Alajouanine, T., Bertrand, I.
and Garcin, R.: Sur une forme anatomoclinique speciale de neuro-myblite optique nbcrotique aigue avec crises toniques tbtanoides, Ann Med, 24: 24-57, 1928. 5 Kuroiwa, Y. and Shibasaki, H.: Painful tonic seizure in multiple sclerosis, Treatment with diphenylhydantoin and carbamazepine, Folia Psychiat Neurol Jap, 22: 107-119, 1968. 6 Matthews, W. B.: Tonic seizure in disseminated sclerosis, Brain, 81: 193-206, 1958. 7 McAlpine, D., Lumsden, C.E. and Ache-
8 9 10
Spinal sensory-motor seizures, Lancet, I: 357, 1968. 2 Ekbom, K. A.,
Westerberg, C.-E. and Osterman, P. 0.: Focal sensory-motor seizures of spinal origin, Lancet, I: 67, 1968. 3 Espir, M.L.E. and Millac, P.: Treatment of paroxysmal disorders in multiple sclerosis with carbamazepine (Tegretol), J Neurol Neurosurg Psychat, 33: 528-53 1,
11
son, E. D.: Multiple Sclerosis, A Reappraisal, p. 143, 1965, Livingstone, Edinburgh and London. Osterman, P. 0. and Westerberg, C.-E.: Paroxysmal attacks in multiple sclerosis, Brain, 98: 189-202, 1975. Pollac, M., Calder, C. and Allpress, S.: Peripheral nerve abnormality in multiple sclerosis, Ann Neurol, 2: 41-48, 1977. Shibasaki, H. and Kuroiwa, Y.: Painful tonic seizure in multiple sclerosis, Arch Neurol, 30: 47-51, 1974. Spiller, W. G.: Subcortical epilepsy, Brain,
50: 171-177, 1927. 12 Yabuki, S., Hayabara, T., Ikeda, H., Ishino, H. and Otsuki, S.: Clinical obser-
vation of the tonic seizure in multiple sclerosis, Psychiat Neurol Jap, 76: 207-220, 1974 (in Japanese).
