Movement Disorders Vol. 6, No. 2, 1991, pp. 180-182. 0 1991 Movement Disorder Society
Brief Report
Hereditary Paroxysmal Ataxia with Neuromyotonia J. Vaamonde, J. Artieda, and J. A. Obeso Movement Disorders Unit and Neurophysiology Service, Department of Neurology, Clinica Universitaria, Pamplona, Spain
Summary: The clinical manifestations of a patient with hereditary paroxysmal ataxia and neuromyotonia are described. Generalized tremor, triggered by sudden movements, and spasms of hand and foot muscles were the main clinical findings. Electromyogram (EMG) and nerve blocking studies led to the diagnosis of neuromyotonia. Treatment with acetozolamide was of no therapeutic value, confirming previous observations about the difference in response of paroxysmal ataxia with and without neuromyotonia. Key Words: Paroxysmal ataxia-Neuromyotonia.
The mother and one sister suffered from exactly the same complaint. One other sister is normal. It was impossible by history to ascertain whether or not the same problem existed in previous generations. A typical episode (summarized in the videotape segment) consisted of dysarthria and blurred vision, followed by unsteadiness and jerking movements of the head and limbs. Concomitantly, the hands and feet adopted an exaggerated flexor posture resembling carpopedal spasm. During attacks, the patient was fully alert and showed no evidence of cognitive dysfunction. Examination between attacks revealed continuous dysfunction. Examination between attacks revealed continuous muscle activity characterised by rippling, ondulatory twitches of orbicularis oculis, peribuccal, and hand muscles, and abduction of the thumb. No nystagmus or any other oculomotor abnormality was present. An electroencephalogram (EEG) recorded during one episode did not show any abnormality. The following laboratory studies were normal: complete blood count, Ca, Mg, P, Ph, and bicarbonate; serum B,, and folate, serum total protein, immunoglobulins, creatine phosphokinase (CPK), lactic dehydrogenase (LDH), serum glutamate oxaloacetate transaminase (SGOT), creatinine, blood urea nitrogen (BUN), uric acid, cholesterol, triglycerides, electrolytes, alkaline phosphatase, total bilirubin, 24-h urinary amino acid excretion, pyruvic and lactic acid, T3T4, Cu, and ceruloplasmin, arylsulfatase A and hexosaminidase. A muscle biopsy was reported as normal. Computed tomography (CT) brain scan revealed no abnormality. Both motor (MCV) and sensory (SCV) nerve conduction velocities in the limbs were studied in detail and found absolutely normal. For example, median nerve (elbow-wrist) MCV was 68 (right arm) and 66 (left arm) d s ; the motor potentials evoked by median nerve stim-
Hereditary paroxysmal ataxia (HPA) is a rarely recognized syndrome. Only 14 families have been previously described ( 1 4 ) . It is characterized by recurrent episodes of ataxia lasting from minutes to several hours. The ataxia may be accompanied by shaking, dysarthria, and vertigo. Patients may be normal in between episodes but may also have nystagmus and neuromyotonia. Treatment with acetazolamide usually allows total control of the episodes ( 4 3 , except in families with HPA and neuromyotonia (1-3). We describe the clinical manifestations and response to treatment of a family with hereditary paroxysmal ataxia and neuromyotonia similar to the families with myokymia and periodic ataxia reported by Van Dyke et al. (1) and Hanson et al. (2) and the family with “episodic ataxia and neuromyotonia” described by Gancher and Nutt (3).
CASE REPORT A 26-year-old woman has had episodic unsteadiness lasting for a few minutes since the age of 6 years. The frequency of attacks varied widely from several times weekly to attack-free periods of over 1 month. Susceptibility of attacks was increased by fatigue, emotional stress, hyperventilation, and fever. However, sudden postural changes have been the only triggering factor.
A videotape segment accompanies this article. Address correspondence and reprint requests to Dr. J . A. Obeso at Department of Neurology, Clinica Universitaria, Apdo 192, 31080 Pamplona, Spain.
180
HEREDITARY PAROXYSMAL ATAXIA WITH NEUROMYOTONIA ulation in the wrist had an amplitude of 3 (right) and 3.3 (left) mV and a latency of 2.2 (right) and 2.1 (left) ms. The sensory action potential recorded in the wrist with surface electrodes, after stimulating with ring electrodes the right index finger, had an amplitude of 13.2 nV and a latency of 1.8 ms. Antidromic recording stimulation of the right sensory action potential evoked by superficial radial nerve in the distal forearm showed an amplitude of 18 nV and a latency of 2.2 ms. Similar values were obtained for MCV and SCV in the ulnar nerve and in the lower limbs. The EMG with a concentric needle electrode revealed high frequency double and triple discharges in orbicularis oculis, thenar, hypothenar, and tibialis anterior muscles at rest (Fig. 1). Such discharges were not enhanced during active muscle contraction. No evidence of denervation was seen in the EMG. Anesthetic blockade (mepivocaina HCl, 2%) of the ulnar nerve in the elbow did not modify the continuous EMG discharges in abductor digiti quinti. Treatment with acetazolamide (200 mg daily p.0.) for 4 weeks did not reduce the severity or frequency of attacks. Phenytoin (200 mg/daily) during 2 weeks produced some improvement but had to be discontinued shortly after beginning treatment due to dizziness and nausea. Treatment with flunarizine (10 mgfday) for 9 months reduced the frequency and intensity of the attacks in the affected sister but had not been tried yet in this patient.
COMMENTS This is the fourth reported family with a combination of episodic ataxia and continuous muscular
181
activity. This latter manifestation is typical of neuromyotonia on the basis of EMG and anesthetic nerve blocking studies, but is clinically indistinguishable from tetany (7). The study of this patient does not provide any clue to explain the association of symptoms originated in both peripheral nerve (neuromyotonia) and CNS (tremor, ataxia). We do not believe that the unsteadiness and tremor could be due to an exaggeration of neuromyotonia. Thus, the episodes were preceded by CNS symptoms such as blurring of vision and dysarthria and it is extremely difficult to envisage how sudden postural changes could trigger and synchronise the EMG discharges originating in the peripheral nerves to produce a tremor like activity. Exacerbation of the very fast EMG double-triple discharges could conceivably produce muscle spasms, as occurred in the hands and feet of our patient. Previous descriptions of HPA included shaking, dysarthria, and vertigo as part of the clinical manifestations, but commonly the diagnosis is made by history without the chance of witnessing the paroxystic episodes. The main features of the patient described here were generalized tremor and unsteadiness, induced by sudden postural changes. Assessment of limb coordination and gait was extremely difficult due to the seventy of the tremor. Indeed, a
FIG. 1. Electromyographic recording of first dorsal interosseous in the right hand showing continuous spontaneous activity of motor units at rest. Recurrent “grouped discharges” (doublets, triplets, and multiplets) are also seen. These continuous muscle discharges persisted after ulnar nerve blockade.
YY
25 ms
Movement Disorders, Vol. 6 , No. 2, 1991
182
J . VAAMONDE ET AL.
diagnosis of ataxia could not be established in this patient with certainty. The usual labeling of “episode ataxia” could be, therefore, considered misleading and cause confusion and difficulty in the clinical recognition of this syndrome. Phenytoin has produced good control of the symptoms in families with a combination of episodic ataxia and neuromyotonia, but acetazolamide was ineffective (1,3). Our family confirms such previous experience. The possible therapeutic value of flunarizine requires further evaluation, but it may be an useful therapeutic alternative for hereditary paroxysmal ataxia with neuromyotonia (8). Acknowledgment: Mrs. M. Mar Lopez and Carol Elsden were, as usual, very helpful in editing this report. Addendum: While this paper was in press Brunt and van Weerden described a large family with hereditary paroxysmal ataxia and myokymia (Brain 1990;113:136182). It seems that our family is clinically identical to Brunt and van Weerden’s extensively investigated patients.
Movement Disorders, Vol. 6 , N o . 2, 1991
LEGEND TO THE VIDEOTAPE This video shows the patient at rest having slept for only 4 h the previous night and after drinking several cups of coffee. After standing up quickly, she developed generalized tremor and unsteadiness, accompanied by contracture of hand muscles.
REFERENCES 1. Van Dyke DH, Griggs RC, Murphy MJ, Goldstein MH. Hereditary myokymia and periodic ataxia. J Neurol Sci 1975;25:109-18. 2. Hanson PA, Martinez LB, Cassidy R. Contractured continuous muscle discharges and titubation. Ann Neurol 1977; I: 120-4. 3. Gancher ST, Nutt JG. Autosomal dominant episodic ataxia. Movement Disorders 1986;1:23%53. 4. Zasorin NL, Balch RW, Myers LB. Acetozolamide responsive episodic ataxia syndrome. Neurology 1983;33:1212-4. 5. Friedman JH, Hollmann. Acetozolamide responsive hereditary paroxysmal ataxia. Movement Disorders 1987;2:67-72. 6. Mertens HG, Zschocke S. Neuromyotonie. Klin Wochenschr 1965;43:917-25. 7. Harati Y , Ashizawa T. Cramps and myalgia. In: Jankovic J, Tolosa E, eds. Parkinson’s disease and movement disorders. Baltimore: Urban and Schwarzenberg, 1988:395-424. 8 . Boel MN, Casaer P. Familiar periodic ataxia responsive to flunarizine. Neuropediatrics 1988;19:2 18-20.
Brief Report
Hereditary Paroxysmal Ataxia with Neuromyotonia J. Vaamonde, J. Artieda, and J. A. Obeso Movement Disorders Unit and Neurophysiology Service, Department of Neurology, Clinica Universitaria, Pamplona, Spain
Summary: The clinical manifestations of a patient with hereditary paroxysmal ataxia and neuromyotonia are described. Generalized tremor, triggered by sudden movements, and spasms of hand and foot muscles were the main clinical findings. Electromyogram (EMG) and nerve blocking studies led to the diagnosis of neuromyotonia. Treatment with acetozolamide was of no therapeutic value, confirming previous observations about the difference in response of paroxysmal ataxia with and without neuromyotonia. Key Words: Paroxysmal ataxia-Neuromyotonia.
The mother and one sister suffered from exactly the same complaint. One other sister is normal. It was impossible by history to ascertain whether or not the same problem existed in previous generations. A typical episode (summarized in the videotape segment) consisted of dysarthria and blurred vision, followed by unsteadiness and jerking movements of the head and limbs. Concomitantly, the hands and feet adopted an exaggerated flexor posture resembling carpopedal spasm. During attacks, the patient was fully alert and showed no evidence of cognitive dysfunction. Examination between attacks revealed continuous dysfunction. Examination between attacks revealed continuous muscle activity characterised by rippling, ondulatory twitches of orbicularis oculis, peribuccal, and hand muscles, and abduction of the thumb. No nystagmus or any other oculomotor abnormality was present. An electroencephalogram (EEG) recorded during one episode did not show any abnormality. The following laboratory studies were normal: complete blood count, Ca, Mg, P, Ph, and bicarbonate; serum B,, and folate, serum total protein, immunoglobulins, creatine phosphokinase (CPK), lactic dehydrogenase (LDH), serum glutamate oxaloacetate transaminase (SGOT), creatinine, blood urea nitrogen (BUN), uric acid, cholesterol, triglycerides, electrolytes, alkaline phosphatase, total bilirubin, 24-h urinary amino acid excretion, pyruvic and lactic acid, T3T4, Cu, and ceruloplasmin, arylsulfatase A and hexosaminidase. A muscle biopsy was reported as normal. Computed tomography (CT) brain scan revealed no abnormality. Both motor (MCV) and sensory (SCV) nerve conduction velocities in the limbs were studied in detail and found absolutely normal. For example, median nerve (elbow-wrist) MCV was 68 (right arm) and 66 (left arm) d s ; the motor potentials evoked by median nerve stim-
Hereditary paroxysmal ataxia (HPA) is a rarely recognized syndrome. Only 14 families have been previously described ( 1 4 ) . It is characterized by recurrent episodes of ataxia lasting from minutes to several hours. The ataxia may be accompanied by shaking, dysarthria, and vertigo. Patients may be normal in between episodes but may also have nystagmus and neuromyotonia. Treatment with acetazolamide usually allows total control of the episodes ( 4 3 , except in families with HPA and neuromyotonia (1-3). We describe the clinical manifestations and response to treatment of a family with hereditary paroxysmal ataxia and neuromyotonia similar to the families with myokymia and periodic ataxia reported by Van Dyke et al. (1) and Hanson et al. (2) and the family with “episodic ataxia and neuromyotonia” described by Gancher and Nutt (3).
CASE REPORT A 26-year-old woman has had episodic unsteadiness lasting for a few minutes since the age of 6 years. The frequency of attacks varied widely from several times weekly to attack-free periods of over 1 month. Susceptibility of attacks was increased by fatigue, emotional stress, hyperventilation, and fever. However, sudden postural changes have been the only triggering factor.
A videotape segment accompanies this article. Address correspondence and reprint requests to Dr. J . A. Obeso at Department of Neurology, Clinica Universitaria, Apdo 192, 31080 Pamplona, Spain.
180
HEREDITARY PAROXYSMAL ATAXIA WITH NEUROMYOTONIA ulation in the wrist had an amplitude of 3 (right) and 3.3 (left) mV and a latency of 2.2 (right) and 2.1 (left) ms. The sensory action potential recorded in the wrist with surface electrodes, after stimulating with ring electrodes the right index finger, had an amplitude of 13.2 nV and a latency of 1.8 ms. Antidromic recording stimulation of the right sensory action potential evoked by superficial radial nerve in the distal forearm showed an amplitude of 18 nV and a latency of 2.2 ms. Similar values were obtained for MCV and SCV in the ulnar nerve and in the lower limbs. The EMG with a concentric needle electrode revealed high frequency double and triple discharges in orbicularis oculis, thenar, hypothenar, and tibialis anterior muscles at rest (Fig. 1). Such discharges were not enhanced during active muscle contraction. No evidence of denervation was seen in the EMG. Anesthetic blockade (mepivocaina HCl, 2%) of the ulnar nerve in the elbow did not modify the continuous EMG discharges in abductor digiti quinti. Treatment with acetazolamide (200 mg daily p.0.) for 4 weeks did not reduce the severity or frequency of attacks. Phenytoin (200 mg/daily) during 2 weeks produced some improvement but had to be discontinued shortly after beginning treatment due to dizziness and nausea. Treatment with flunarizine (10 mgfday) for 9 months reduced the frequency and intensity of the attacks in the affected sister but had not been tried yet in this patient.
COMMENTS This is the fourth reported family with a combination of episodic ataxia and continuous muscular
181
activity. This latter manifestation is typical of neuromyotonia on the basis of EMG and anesthetic nerve blocking studies, but is clinically indistinguishable from tetany (7). The study of this patient does not provide any clue to explain the association of symptoms originated in both peripheral nerve (neuromyotonia) and CNS (tremor, ataxia). We do not believe that the unsteadiness and tremor could be due to an exaggeration of neuromyotonia. Thus, the episodes were preceded by CNS symptoms such as blurring of vision and dysarthria and it is extremely difficult to envisage how sudden postural changes could trigger and synchronise the EMG discharges originating in the peripheral nerves to produce a tremor like activity. Exacerbation of the very fast EMG double-triple discharges could conceivably produce muscle spasms, as occurred in the hands and feet of our patient. Previous descriptions of HPA included shaking, dysarthria, and vertigo as part of the clinical manifestations, but commonly the diagnosis is made by history without the chance of witnessing the paroxystic episodes. The main features of the patient described here were generalized tremor and unsteadiness, induced by sudden postural changes. Assessment of limb coordination and gait was extremely difficult due to the seventy of the tremor. Indeed, a
FIG. 1. Electromyographic recording of first dorsal interosseous in the right hand showing continuous spontaneous activity of motor units at rest. Recurrent “grouped discharges” (doublets, triplets, and multiplets) are also seen. These continuous muscle discharges persisted after ulnar nerve blockade.
YY
25 ms
Movement Disorders, Vol. 6 , No. 2, 1991
182
J . VAAMONDE ET AL.
diagnosis of ataxia could not be established in this patient with certainty. The usual labeling of “episode ataxia” could be, therefore, considered misleading and cause confusion and difficulty in the clinical recognition of this syndrome. Phenytoin has produced good control of the symptoms in families with a combination of episodic ataxia and neuromyotonia, but acetazolamide was ineffective (1,3). Our family confirms such previous experience. The possible therapeutic value of flunarizine requires further evaluation, but it may be an useful therapeutic alternative for hereditary paroxysmal ataxia with neuromyotonia (8). Acknowledgment: Mrs. M. Mar Lopez and Carol Elsden were, as usual, very helpful in editing this report. Addendum: While this paper was in press Brunt and van Weerden described a large family with hereditary paroxysmal ataxia and myokymia (Brain 1990;113:136182). It seems that our family is clinically identical to Brunt and van Weerden’s extensively investigated patients.
Movement Disorders, Vol. 6 , N o . 2, 1991
LEGEND TO THE VIDEOTAPE This video shows the patient at rest having slept for only 4 h the previous night and after drinking several cups of coffee. After standing up quickly, she developed generalized tremor and unsteadiness, accompanied by contracture of hand muscles.
REFERENCES 1. Van Dyke DH, Griggs RC, Murphy MJ, Goldstein MH. Hereditary myokymia and periodic ataxia. J Neurol Sci 1975;25:109-18. 2. Hanson PA, Martinez LB, Cassidy R. Contractured continuous muscle discharges and titubation. Ann Neurol 1977; I: 120-4. 3. Gancher ST, Nutt JG. Autosomal dominant episodic ataxia. Movement Disorders 1986;1:23%53. 4. Zasorin NL, Balch RW, Myers LB. Acetozolamide responsive episodic ataxia syndrome. Neurology 1983;33:1212-4. 5. Friedman JH, Hollmann. Acetozolamide responsive hereditary paroxysmal ataxia. Movement Disorders 1987;2:67-72. 6. Mertens HG, Zschocke S. Neuromyotonie. Klin Wochenschr 1965;43:917-25. 7. Harati Y , Ashizawa T. Cramps and myalgia. In: Jankovic J, Tolosa E, eds. Parkinson’s disease and movement disorders. Baltimore: Urban and Schwarzenberg, 1988:395-424. 8 . Boel MN, Casaer P. Familiar periodic ataxia responsive to flunarizine. Neuropediatrics 1988;19:2 18-20.
