The startle disease or hyperekplexia

523

Journal of the neurological Sciences

Elsevier Publishing Company, Amsterdam-Printed in The Netherlands

The Startle Disease or Hyperekplexia* Pathological Surprise Reaction H. G A S T A U T AND A. VILLENEUVE Unit~ de Recherches Neurobiologiques, Institut National de la Santd et de la Recherche Me'dicale, Marseille (France)

(Received 6 January, 1967)

INTRODUCTION The startle or surprise reaction following an unexpected stimulus is a phenomenon that has been experienced by everyone. That reaction can however reach such a degree in frequency, in intensity or both as to become pathological. After mentioning the existence of such a clinical entity in 1878, BEARD published in 1880 his famous observations based on 50 cases of"jumping Frenchmen of Maine". Widespread interest was aroused by this account and in 1884 HAMMOND described a similar syndrome occurring in Siberia. In 1884, GILLES DE LA TOURETTE,who had translated BEARD'S report into French in 1881, contrasted in an article entitled "Jumping, Latah, Myriachit" these three entities and cautiously avoided the conclusion that all three constituted the same illness. As pointed out by STEVENS, who reviewed this topic in 1965 and reported 3 new cases of pathological startle reaction, reference to this syndrome decreased in the literature after 1912 and faded away thereafter, In his paper STEVENSmentioned that another physician (FITCH) recalled having also observed 5 cases of such a disease, Finally in 1966, StJHREN et al., in a report based upon a detailed study of 25 cases. have described a hereditary startle syndrome transmitted by a dominant autosomal gene and suggested that it be called hyperexplexia. They claimed that this entity was different from the one described in the articles of BEARD and STEVENSas well as from myriachit.

The pathological startle reaction, a rare entity sometimes encountered in the course of medical practice, is often mistaken for an epileptic manifestation because of a lack of knowledge of its electroclinical semeiology. Moreover a variety of epilepsy either having some similarity to a jump or triggered by an unexpected stimulus ("startle epilepsy") does exist and can be diagnosed relatively easily (GASTAUTAND TASSINARI 1966). * 8~¢p: above measure; cZ-rr).~: jerk, jump. A. VILLENEUVE: Recipient of a bursary from the Quebec Psychiatric Services, Quebec, Canada. J. neurol. Sci. (1967) 5:523-542

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In an attempt to shed further light on the pathological startle reaction or hyperekplexia we will report 12 cases of non-hereditary, non-familial startle disease, that is "essential startle disease", seen in the practice of one of us (H.G.). Five cases were carefully investigated from the neurophysiological view-point. The differential diagnosis and the physiopathogeny of this affection will also be discussed. INCIDENCE

Nine patients were females and 3 were males. The disorder began in 1 case before the age of 10 (7 years old), in 4 cases between the ages of 10 and 15 (12, 13, 14, 15 years old), in 4 cases between the ages of 16 and20 (18, 19, 19, 20 years old) andin the 3 other cases between the ages of 21 and 25 (21, 23, 25 years old). In our group of patients the disorder was not found to be familial in contradistinction to BEARD'Sfindings, to 2 of STEVENS'Spatients and to the 5 affected sibs mentioned by FITCH. CLINICAL SEMEIOLOGY

The disease is characterized by diurnal and nocturnal jumps differing from the physiological startle reaction only in their increased frequency and intensity.

Diurnal jumps (1) Types of stimuli. The stimulus inducing the jump was always unexpected and most frequently auditory. In all cases an auditory stimulus, light or loud, could trigger a jump, e.g., slamming of a door, clapping of the hands, noise of a falling object, honking of a horn, ringing of the telephone, etc. In 9 cases a proprioceptive somaesthetic stimulus was also able to provoke a jump, e.g. loss of equilibrium etc., and in 8 cases an exteroceptive one could cause it, e.g. unexpected touching or a drop of water falling on the patient's hand. In 6 cases a visual stimulus had the same effect, e.g. unexpected passage before the eyes of an object, of a shadow or of a flash of light, vision of a scene engendering a reaction of surprise such as a cup or a man in danger of falling, a bicycle swerving, etc.. In none of our patients did the jumps occur spontaneously during wakefulness. The necessity of a sensory triggering factor indicates clearly that we are dealing with a surprise reaction. Only during sleep seemingly spontaneous jumps were observed. (2) Frequency of the jumps. The number of jumps was high, ranging from 10 to 100 daily. It could vary from day to day and some patients detected a relationship between the number of jumps and their emotional state. For example the jumps were more numerous when the patient was worried or upset and 5 females noted an augmented frequency during the menses. There was no habituation or very little to the triggering factors and some subjects jumped each time the telephone rang even if it did so 10 to 20 times daily. (3) Intensity of the jumps. The intensity of the jumps is great. The cephalic extremity and the upper limbs are always involved. The contraction of the muscles of the face (mostly the frontal and masseter muscles) with closing of the eyelids and elevation of the eyeballs is accompanied by a flexion of the head over the chest, a lifting of the shoulders, a symmetrical flexion of the arms and clenched fists.

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Objects held in the hands are not usually dropped; however many incidents can happen if the individual is accomplishing an action, for example if he is eating, drinking or writing, when startled. The tongue may be bitten if it is outside the mouth at the time of the jump. In 11 patients the most violent jumps also involved the lower limbs and provoked a fall. Six patients injured themselves more or less seriously when falling. Two of them fell so often that they adopted a wide-based gait and always looked for a point of support; one even walked on all fours during the periods of exacerbation of the disease. Accessory phenomena accompanied the jumps. Five patients emitted occasionally a little glottic sound when jumping but were not concerned by it. The most intense jumps provoked in 4 patients a loss of urine. Either a few drops were lost or the bladder was completely emptied: 2 female patients were obliged to wear continually several sanitary napkins in order to absorb the urinary flow. In 3 patients the jump was followed by a vasomotor episode giving a sensation of facial warmth and in another case by sweating. None of our cases presented at the time of the jumps or during the intervals between them phenomena of echolalia, echomimia or automatic obedience. There was never any alteration of consciousness either. Nocturnal jumps (during sleep) Nine patients had nocturnal jumps, sometimes intense and with a loss of urine in 1 ease. These were at times triggered by a noise, a light or an unexpected somaesthetic stimulus (for example a sudden move of the spouse in the bed). More often these jumps occurred, seemingly spontaneously, during the phase of falling asleep (hypnagogic jump) or during actual sleep. As reported by the spouse the nocturnal jumps might or might not awaken the patient. If they did the patient could rarely recall if a dream had preceded his awakening and he had no feeling of anxiety. Only 1 individual pointed out a relationship between awakening and dreams liable to engender a surprise reaction e.g. a threat, blow, fall, etc., in his dream. It is possible that in fact all our patients had nocturnal jumps. The 3 patients who did not report any were individuals sleeping alone in their rooms and no-one, for example a spouse, could notice the occurrence of jumps. Four patients presented other periodical nocturnal phenomena: somnambulism, somniloquism or nightmares. Ictal manifestations Only 1 patient, now 44 years old, had had with certainty periodic epileptic manifestations associated with her pathological startle reaction: both had begun at the age of 19. She had 2-3 characteristic seizures, grand mal type, happening just prior to or during the menses. Treatment with primidone and phenobarbitone controlled both the jumps in response to unexpected stimuli and the grand mal seizures. This patient did not show any electroencephalographic (EEG) abnormalities suggestive of epilepsy but had an extremely low convulsive threshold (3 ml of metrazol intravenously sufficed to trigger an epileptic seizure). 3. neuroL Sci. (1967) 5:523-542

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Another female patient had likewise mentioned the occurrence of "seizures" coinciding with the menstrual period but she described them so vaguely that it was impossible to ascertain if these were epileptic in nature. Like the previous patient her EEG did not contain any abnormality indicative of epilepsy but she too had a very low convulsive threshold. Treatment with phenobarbitone did not modify this symptom and had no action on her pathological startle reaction. Neurological examination was always normal. Laboratory tests and other investigations were also within normal limits, more particularly radiographic and EEG studies. Onepatient had a questionable unilateralventricular dilatation and another calcification of the falx cerebri.

Psychological examination Psychological testing could be carried out on only 5 patients. A mild degree of mental deficiency was detected in 2 cases, one tested by the Cattel Intelligence Test and the other by the Wechsler Adult Intelligence Scale (WAIS). Some degree of mental deficiency was also suspected in two patients who were not tested. Projective tests (Rorschach, thematic apperception test) revealed a passive-aggressive personality in 1 instance and a hysterical structure in the 4 other ones. Three patients in the latter category gave to the psychologist a definite impression of exploiting their illness in order to get special attention from their family. Only 2 of these 5 patients were subjected to a formal psychiatric examination and the attending psychiatrist made a diagnosis of hysteria. The staff members (physicians, psychologists) with whom the remaining 7 patients came into contact felt that all had affective and personality problems but that none ever presented any symptom indicative of a psychotic process. POLYGRAPHIC SEMEIOLOGY

A polygraphic study of the jump has been done on 5 patients during the day while they were awake. In 3 of them the procedure was repeated during nocturnal sleep.

Polygraphic study during wakefulness (Figs. 1 and 2) (1) Jumps could be induced in all subjects with the usual signs of the surprise reaction as described in 1957, 1958 and 1960 by GASTAUTand co-workers. (i) The electromyogram (EMG) showed: (a) A precocious muscle potential, isolated or grouped in volleys of 2-10 elements. Depending upon the muscles investigated there was a latency ranging from 10-40 msec (starting from the frontal muscle and going to those of the leg). According to the number of motor units recruited, the amplitude varied from 1-10 mVwhile the duration was of 20-60 msec. (b) Activity of interferential type followed, sometimes after an interval of about 20 msec, and lasted from a fraction of a second to several seconds thus lengthening the initial jerk. These muscle potentials were generalized to the agonist and antagonist muscular systems without reciprocal innervation. Their amplitude decreased from the head and neck to the trunk, from the root of the limbs to their extremities and from the upper to the lower limbs.

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(ii) The electroencephalogram (EEG) showed the phenomenon described in the surprise reaction by Y. GASTAUT(1953); i.e. a vertex spike* followed by a general desynchronisation of the cortical rhythms in the central regions (fl-rhythm) as well as in the parietal, temporal and occipital areas (o~-rhythm). Several other phenomena were observed: (iii) an important electrodermographic reaction signifying a sudden lowering of cutaneous resistance; (iv) a variable but often persistent tachycardia; (v) a very brief apnoea followed by a variable polypnoea; (vi) a rise of arterial blood pressure (mainly systolic); (vii) a fall in systolic peripheral blood flow as measured by impedance plethysmography. (2) The polygraphic signs of the startle reaction as well as the jump itself were quite marked and could barely be attenuated by repeating the stimulus. All the polygraphic signs mentioned above were always observed in the 5 patients investigated although some signs, especially tachycardia and apnoea, are often very difficult to identify in a normal individual. In addition, the most intense stimuli induced frequently, after the precocious muscular potential, an interferential muscular activity sufficient to engender a tonic spasm lasting several seconds. The spasm was accompanied by a vegetative discharge bringing on an apnoea lasting several seconds and a heart rate accelerated by 100 ~o. Habituation to the repetition of a stimulus was so poor that pistol shots or even light auditory stimuli provoked, if not a jump, at least vegetative phenomena when repeated 20-30 times. By contrast, such a stimulus, when repeated 2-5 times to a normal individual, becomes ineffective (GASTAtJTAND RO~ER 1960). If in our patients some habituation could be obtained it sufficed in order again to trigger a jump, to vary slightly the characteristics of the noise (tonality or intensity) or to introduce a new stimulus, the latter creating an external inhibition in the Pavlovian sense (GASTAtJT AND ROGER 1960). The intravesical pressure of 2 patients was also measured and was found to be increased during the jump. The rise of intravesical pressure could explain the loss of urine that 4 patients experienced at the moment of the jump. (3) In the 3 cases in which diazepam (Valium) was tried (10 mg intravenously) it suppressed temporarily the pathological startle reaction and its polygraphic signs. This effect began about 10 sec after injection of the drug and waned progressively within 5-10 min.

Polygraphic studies during sleep The 3 patients whose sleep was recorded during a whole night fell asleep and slept normally with normal sleep activity in the EEG. Two of them had spontaneous jumps during their sleep, identical to but more intense and frequent than those observed in certain normal subjects by GASTAUTet al. * The summation methods have demonstrated that the vertex spike seen in conventional EEG is only the relatively belated part of a polyphasic response the first element of which has a very brief latency (15-20 msec). J. neurol. Sci. (1967) 5:523-542

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Fig. 1. Electroencephalographic (EEG) and electromyographic (EMG) recording during jumps provoked by noises in a 19-year-old adolescent severely af"ected by the essentialstartle disease. Note the absence of habituation to the auditory stimulus in spite of its repetition (12 times). In the EEG only muscular artefact is 9resent except at the vertex where it is less intense and one can see the vertex spike and the brief desynchronization of the normal rhythms that are the only EEG signs of the startle reaction. In the E M G the generalized muscular contraction during the jump is visible with its clonic and tonic elements while the elec:rocardiogram (EKG) shows the induced tachycardia. Abbreviations (for Figs. 1, 2, 5, 6 and 7): A C T O G : actogram (motions of the bed on which the patient ies); BICEPS: m. biceps brachii; DELT: m. deltoid; E K G : electrocardiogram; EXT D I G : m. extensor digitorum, F A C I A L I N F : m. facialis inferior, FLEX DIG: m. flexor digitorum communis; F R O N T A L : m. frontalis; I N T E G R : integrated muscular activity of the left quadriceps; IPS: intermittent photic ;timulation; MYLO: m. mylohyoidius; N." noise; O C U L O G (VERT/LAT): vertical/lateral oculogram; Q U A D R : m. quadriceps femoris; STERNO: m. sternocleidomastoidius; T R A P : m. trapezius; TRICEPS: m. triceps brachii.

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Fig. 2. Effect of tactile stimuli (same patient as in Fig. 1). As well as noises tactile stimuli provoked jumps. Tactile stimuli on the vertex and the forehead triggered the jumps having the greatest intensity. Stimuli applied on the chest or the abdomen provoked a less intense jump affecting mostly the frontal muscle. Given on the genitals the stimulus induced a fairly intense jump but affecting mostly the lower limbs. (Same key as Fig. 1 .)

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Fig. 3. Spontaneous jumps during sleep (same patient as in Figs. 1 and 2). The three samples of records on the left (A, B and C) show three spontaneous jumps occurring during the phase I (REM) of sleep. The two samples on the right (D and E) show two jumps during phase III of deep sleep.

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Fig. 4. Jumps provoked by noises during various phases of sleep (same patient as in Figs. 1-3). Jumps provoked by noises while falling asleep (I; non-REM), during light sleep (II), during very deep sleep (IV) and during the REM phase of sleep (I; REM) as compared to those when awakened (A).

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Fig. 5. Very intense jump provoked by a noise during sleep. The j ump was triggered by a noise (at the same time a camera photographing the patient was set in motion) during phase IV of very deep sleep. N o t e the marked tachycardia (passage from 72 to 150 beats/min) and especially the long tonic phase (about 10 see) of the jump. During such an intense jump the patient (the same one as for Figs. 1 4 ) would sometimes bite his tongue and pass some urine. (Same key as Fig. 1 .)

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(1964). The first patient had spontaneous jumps without awakening during phase I ( R E M : rapid eye movements) and during phase III of deep sleep (Fig. 3). The second patient had two jumps only; one during phase IV 30 min after falling asleep and the other during another phase IV 45 min after he fell asleep again following his brief awakening resulting from the first jump. Awakened by both jumps he had no recollection of a dream and no feeling of anxiety. Jumps during sleep could be provoked by noises in the 3 patients. They occurred during the phase of falling asleep (I: non-REM), during the slow EEG phases II, III and IV and during the fast EEG phase with REM (Fig. 4). None of these induced jumps, although intense and accompanied by important vegetative reactions (Fig. 5), brought on clinical awakening except on one occasion when stimulation during a R E M phase awoke the patient in the middle of a trivial dream.

CIRCUMSTANCESOF ONSETAND EVOLUTION By scrutinizing our clinical records we have been able in some patients to ascertain the circumstances of onset of their illness. In 1 case an affective trauma was obviously connected with the onset of the disease. A 20-year-old girl sufferedfrom her firstjumps one hour after the death of her mother to whom she was very attached. In the case of a dependent mildly mentally defective and sexually-dissatisfied woman her proneness to jump appeared shortly after the death of her young infant delivered like her first one by Caesarean section. As for the female patient who, at the age of 19, began to present catamenial grand mal seizures and a pathological startle reaction, she had a disturbed childhood and adolescence. Since she was 4-5 years old, her parents, particularly her father, quarrelled with her and even injured her. He was sexually curious about her and used to burst into the bathroom while she was there. She was also the victim of two attempts at rape between the ages of 17 and 19. She attended medical school for two years and gave up. Now 44, her marital life has been unstable and she remarried not long ago for the third time. In the case of a 19-year-old male adolescent who had 8 sisters but no brother his illness began at puberty coinciding with sexual conflicts and problems over his masculine identification. The remote possibility of a traumatic experience is doubtful in the case of a girl whose genitals a man attempted to fondle when she was 13 years old; she began to jump in response to unexpected stimuli only two years later, one year after a panic attack at an amusement park while in the "scenic railway". All our patients came for consultation from 1½ months to 30 years after the onset of their illness. There had been no lasting remission during this time. Six patients were followed by one of us (H.G.) for a length of time varying from 3 months to 3 years. No lasting improvement was noted in 4 of these patients after administration of various drugs (barbiturates, diazepam, haloperidol, etc.). A noticeable amelioration, obtained over a week with a few sessions of psychotherapy, was reported by the staff psychiatrist in the case of the 20-year-old girl, diagnosed as an hysteric, who began to jump after her mother's death. This treatment had to be discontinued because the patient went back to her home in another town. As previously stated with regard to the female patient suffering both from catamenial grand mal seizures and pathological startle reaction, these manifestations disappeared after treatment by phenobarbitone and primidone instituted by her general practitioner. They recurred briefly later when the dosage of her medication was temporarily reduced. J. neurol. Sci. (1967) 5:523-542

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H. GASTAUT,A. VILLENEUVE DIFFERENTIALDIAGNOSIS

The essential startle disease (non-hereditary, non-familial)just described is fairly easy to diagnose when one is aware of its existence and knows its semeiology. The illness must not be confused with myoclonic epilepsy, with the syndrome of GILLES DE LA TOURETTE, with the "imitation neuroses" or with "hyperexplexia". It must also be differentiated from the more or less frequent and intense jumps occurring in some individuals suffering from a central nervous system disease of organic origin.

(1) Myoclonic epilepsy As stated before the essential startle disease is unfortunately often mistaken for myoclonic epilepsy. Yet there are clues helping to establish the differential diagnosis (GASTAUT AND TASSINARI 1966). (i) The massive myoclonias, often associated with "absences" and grand mal seizures in the usual type of generalized epilepsy sometimes called "idiopathic", are only exceptionally observed without the above two varieties of seizures. When it does occur the clinical picture of "myoclonic petit mal" is realized and in this type of epilepsy the massive myoclonias cannot be differentiated from a jump from the clinical and E M G standpoints. They are, however, characterized in the EEG by a discharge ofpolyspikes or polyspike-waves. Besides they appear spontaneously and are not consecutive to an unexpected sensory stimulus. In the laboratory they are not induced by noises while intermittent photic stimulation can provoke them fairly easily. (ii) Diagnosis can be more difficult in the rare cases of epilepsy in which the seizures are triggered by a noise or by any other stimulus able to engender a surprise reaction. (a) There is, however, little difficulty in recognizing the acoustico-motor seizures of infants suffering from Tay-Sachs disease. (b) Startle-epilepsy, as described by ALAJOUANINEAND GASTAUT(1958a, b) occurring in individuals afflicted with a hemiplegia or a hemiparesis, is a relatively frequent type of epilepsy and is diagnosed easily. A startle reaction is accompanied in these patients by a tonic seizure, lasting 5-10 sec, localized mostly to the disabled half of the body, and by the usual EEG signs of such seizures. (c) The rare cases of startle-epilepsy, where unexpected noises trigger a massive myoclonic attack which is impossible to differentiate clinically and with the E M G from a jump, have an EEG record characterized by slow polyspikes or polyspike-waves (GASTAUTAND TASSlNARI1966).

(2) Syndrome of Gilles de la Tourette (tie convulsif) This illness, in which CLARK has found a remarkably strong startle response (1966), is nevertheless easily distinguished from the startle disease. In addition to echolalia and coprolalia not found in the latter, the choreiform and myoclonic movements, segmental, localized and not induced by an unexpected stimulus constitute the main feature of the tic convulsif. (3) Imitation neuroses Ethnopsychiatry (ELLENBERGER1965) has brought to our attention several psychiatric disorders encountered in primitive societies and grouped under the heading of

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"imitation neuroses". It is reported that in some of these diseases a startle reaction can trigger the attack (Latah) or that the individuals afflicted jump upon hearing the slightest noise (menerik, omftrax). The clinical signs characterizing all these neuroses are: echolalia, echomimia, automatic obedience (even to the most absurd and dangerous orders) and sometimes coprophilia. The cases described by BEARD, in addition to the jump in response to an unexpected stimulus, could present echolalia and automatic obedience: 1 patient of STEVENShad the combination of jumps and echolalia. By pointing this out we do not intend to classify these cases with the imitation neuroses. In our patients who exhibited only jumps we do not feel that their illness is related to the group of the imitation neuroses.

(4) Hereditary hyperexplexia In this hereditary syndrome (SUHREN et al. 1966), transmitted by a dominant autosomal gene, congenital hypertonia and hypokinesia in the waking state is noticed during the first 3-4 months of life. Subsequently the patients develop a startle reaction quantitatively exaggerated or qualitatively different from normal. The disorder is afterwards variable in severity during life: some patients are most affected in their youth and then the disease stabilizes at a given level or a remission occurs: in some cases after a progressive increase in intensity the symptoms lessen: finally in other instances the condition worsens progressively. As in the essential startle disease, the abnormal startle reaction can be so intense as to cause the patient to fall, no epileptic attack can be provoked by a startle, there is no alteration of consciousness (in only 2 cases of hyperexplexia was a slight transitory disturbance of consciousness reported), the occurrence of excessive startle reactions is facilitated by factors such as emotional tension, nervousness and fatigue, the EEG is normal or subnormal without any epileptic features and there are often generalized jerks that can be very violent at the moment of falling asleep. However in hereditary hyperexplexia the brain-stem reflexes are markedly hyperactive and there is an unexplained higher incidence of inguinal, umbilical and epigastric hernias than in the normal population. Finally the administration of phenobarbitone or of chlordiazepoxide (Librium) effects a marked improvement in the illness in the waking state and suppresses the jerkings at the moment of falling asleep. In summary, in spite of many similarities with the essential startle disease, differences can be noted in hereditary hyperexplexia: (i) well-defined hereditary transmission; (ii) hypertonia and hypokinesia in the waking state during the first 3-4 months of life (this finding has not been reported by the mothers of our younger patients); (iii) improvement of the illness with phenobarbitone or chlordiazepoxide (Librium); (iv) markedly hyperactive brain-stem reflexes; (v) higher incidence of inguinal, umbilical and/or epigastric hernias than in the normal population.

(5) Jumps in organic lesions of the CNS Abnormally intense and frequent jumps may exceptionally occur during the course of a disease of the central nervous system and are often wrongly ascribed to epilepsy. We have observed 6 cases in which jumps happened during a disease of the central J. neurol. Sci. (1967) 5:523-542

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Fig. 6. Jumps provoked by a noise in a 19-year-old adolescent suffering from spastic diplegia with myoclonias, spinal in origin, localized to the right arm. Note that the induced jumps have the same characteristics as those occurring during the essential startle disease. The jumps were provoked while the patient had spontaneous segmental myoclonias of the right biceps and of the right flexor digitorum in order to clearly differentiate between the features o f these partial myoclonias and those of the jumps. (Same key as Fig. 1.)

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nervous system and 2 of these patients underwent diurnal and nocturnal polygraphic studies. This allowed us to ascertain that the jumps had the same clinical and polygraphic features as those of the essential startle disease (frequency, intensity, poor habituation, diurnal and nocturnal occurrence). In the first instance a 10-year-old boy suffered from brain damage due to obstetric trauma, with subsequent mental and motor retardation, diffuse hyper-reflexia and hypotonia. In the second instance a 19year-old young man was affected by Little's disease and by myoclonias, spinal in origin, localized almost exclusively to the biceps of the right arm (Fig. 6). The brain damage was demonstrated by the presence in the EEG in the first case of left temporal spikes and in the second one of generalized spike-wave discharges occurring during sleep only. In both patients the EEG abnormalities bore no temporal relationship to the jumps. PHYSIOPATHOGENESIS The essential startle disease or hyperekplexia could be seen as an exaggeration of the physiological reaction of surprise. The jump which is the somato-motor expression of this reaction was studied by GASTAUT(1958) and by GASTAtJTAND ROGER (1960) and was attributed to the reticular formation of the brain stem. Giving the reasons that led him to formulate this hypothesis GASTAUT explained the mechanism of the surprise reaction as follows: The afferents circulating in the collaterals coming from the specific pathways reach the reticular formation and are most likely responsible for the various manifestations of the surprise reaction. They provoke in this formation an intense excitation spreading at a distance by its rostral and caudal projections. The reticular excitation is propagated caudally along the reticulo-bulbo-spinal pathways that provoke: (a) the peripheral motor activation responsible for the jump: (b) the activation of the preganglionic vegetative centres accountable for the respiratory, cardiac and secretory modifications. The reticular excitation is also propagated rostrally in the direction of the cortex and the subcortical structures along the activating ascending pathways that give rise to: (a) the vertex spike and the desynchronization of the cortical rhythms: (b) in all likelihood a transient reinforcement of the wakefulness state... Considered from a finalist standpoint the surprise reaction appears as a very archaic reaction which is rapidly inhibited during ontogenesis. This would explain its common occurrence in the newborn, the premature or the protuberantial anencephalic child but its rarity in the adult where it is observed only during the phase of falling asleep or under the influence of intense and unexpected stimuli during very particular vigilance states (anxiety, fear). The real role of the surprise reaction would be to defend the organism and the backward movement in the jump could be considered as its most elementary component while the vegetative reactions preparing a better adapted activity to take place (fight or flight) could be regarded as more developed ones (GASTAOT1958)". In a recent publication, BOSER and co-workers (1966) have demonstrated that the startle reflex, previously investigated by MORUZZI (1944) is essentially elaborated within the subcortical centres of the brain stem (inferior colliculi for the jump consecutive to a noise) since it persists after neo-decortication. They also showed that this subcortical startle reflex is under the control of the cerebral cortex. The cortical area, specific for the sensory modality used to provoke the reflex, can, depending upon its excitation or depression, increase or decrease the jump. When directly excited, the subcortical centre liberates itself from cortical control and always gives rise to a startle reflex of maximum intensity which is not attenuated by the repetition of the stimulus. In the light of these observations it is difficult to avoid the conclusion that in man the essential startle disease could result from a functional hyperexcitability of the J. neurol. Sci. (1967) 5:523-542

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brain stem structures responsible for the surprise reaction. Of course an epileptic process has nothing to do with this hyperexcitability and with the exaggerated surprise reaction of the individuals suffering from the startle disease. Even though the massive epileptic myoclonias and the jumps may look peculiarly alike from the clinical and EMG viewpoints (this would support the assumption that both follow a final common pathway that can be blocked by diazepam) they have nevertheless definite differences: (i) during an epileptic myoclonic seizure a generalized epileptic discharge is recorded in the EEG while it is absent during a jump; (ii) intense and unexpected auditory stimuli always induce a jump in people with startle disease but only exceptionally a myoclonia in epileptics, the latter being usually triggered in epileptics by intermittent photic stimulation which does not provoke a jump in people suffering from essential startle disease; (iii) in the laboratory repeated unexpected stimuli fail after a while to induce a surprise reaction, under the effect of a habituation process which is very rapid in normal subjects and very slow in individuals affected by essential startle disease. On the other hand, repeated intermittent photic stimulation in photosensitive epileptics continues to provoke myoclonic seizures without any habituation; (iv) it is possible to produce experimentally in any normal subject a real startle disease by administration of strychnine whereas this substance has no effect on the myoclonias triggered by intermittent photic stimulation in photosensitive epileptics or in normal subjects after injection of metrazol. By contrast, metrazol which produces in any normal subject epileptic myoclonias triggered by light is without effect on the jump induced by a noise in patients suffering from startle disease or in normal subjects after the injection of strychnine (Fig. 7). It is interesting to note that individuals suffering from the essential startle disease can have quite a low convulsive threshold. As estimated in 4 patients by intravenous metrazol injection, 1, 2, 4 and 5 ml respectively were sufficient to cause polyspike-wave discharges and massive myoclonias characteristic of the convulsive threshold. As pointed out earlier, as little as 3 ml of metrazol could trigger an epileptic seizure in the female patient who, in addition to her excessive proneness to jump, had catamenial grand mal seizures. It is therefore possible that the convulsive threshold of some individuals affected by the essential startle disease is so low as to allow the occurrence of typical grand real seizures. Thus exceptionally a combination of essential startle disease and generalized functional epilepsy can occur. However one of us has demonstrated long ago that a low convulsive threshold is not specific to epilepsy and that it can also be found in schizophrenics (catatonic type) and more particularly in some neurotics (hysterics) (GASTAUT 1950). The hyperexcitability of the brain stem structures responsible for the exaggerated surprise reaction in individuals affected by the essential startle disease remains to be explained. PAVLOV'Spsychopathological concept of hysteria (1941) as an exaggerated excitability of the subcortical centres secondary to a functional deficiency of the cortex is a possible explanation if one believes that the essential startle disease is a manifestation of hysteria. Emotional disturbances disrupting the normal functioning of subcortical structures, would however be more likely to be an important facilitating factor J. neurol. Sci.

(1967) 5:523-542

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Fig. 7. Comparison of experimentally induced jump in response to an unexpected noise and experimentally-induced epileptic myoclonias triggered by light in a normal subject. Before the experimental procedure this subject did not have any myoclonia in response to intermittent photic stimulation (IPS) and reacted with a very light jump, quite physiological, to an unexpected and loud noise. The first part of the record at left, before the injection of strychnine, shows that a noise provoked a physiological startle reaction expressed by a light revulsion of the eyeballs (see oculogram) and a very small jerk of the right deltoid (very small muscular potential). The second part, 30 min after the injection of strychnine, shows that the slightest noise induced a violent and generalized jump with no other sign on the EEG than the vertex spike and the desynchronization of the normal rhythms. The third part, 35 rain after the injection, demonstrates that IPS was unable to provoke a jump while noise still could do so, but with progressively decreasing efficiency 40 and 60 min after the injection (fourth and fifth parts). On the sixth part it can be observed that strychnine no longer exerted any effect and that the intensity of the jump had returned to normal. The next day, before the injection of metrazol, the response to an unexpected noise was again normal (seventh part). As seen in the EEG after 7 ml of metrazol, IPS provoked important spike-wave discharges, some of them accompanied by violent and massive myoclonias that could not have been differentiated from jumps on the basis of the EMG alone (eighth part). The spike-wave discharges had however established the epileptic nature of the myoclonias and a grand mal seizure began to develop (end of eighth part) and was obvious 10 sec later (last part of record at right). (Same key as Fig. 1.)

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in the genesis and maintenance of the startle disease. In this respect it should be borne in mind that the reticular formation of the brain stem plays a role not only in the elaboration of the surprise reaction but also in that of the basic emotions, fear and rage (GASTAUT 1958; GASTAUTAND ROGER 1960). As observed in natives in the past b y DARWIN,a heightened state of vigilance and anxiety in the face of a potential danger sensitizes the individual, renders him hyper-receptive to any stimulus and more prone to jump. Therefore threatening conscious or unconscious anxiety, heightening the level of vigilance and muscular tension, could give rise to that exaggerated propensity to jump in individuals whose diffuse cerebral hyperexcitability is proven by their very low convulsive threshold. Along this trend of throught, from a psychodynamic viewpoint, the pathological startle reaction could be viewed as a maladaptive defence against a danger perceived as coming from within the self or from the environment. As to muscle tone BICKFORDand his co-workers (1964) have recently shown that a barely perceptible startle reaction could be detected by means of a special recording technique but only in muscles under some degree of tonicity and it is well known that emotions like anxiety and anger produce muscular tension. Incidentally, SUHRENet al. (1966) have also implicated subcortical structures in the exaggerated startle reaction of hereditary hyperexplexia. They have assumed that there was a retardation of maturational control by higher areas of the brain stem, particularly the rhombo-mesencephalic reticular formation, preventing them from exerting their inhibitory action. They have interpreted their data (high-speed filming analysis, EEG and EMG findings) as "indicating the dominance of an inhibited primitive nociceptive reflex pattern due to a deficient maturational control by higher nervous system activity, and subserved by a fairly direct pathway from the central sensory nuclei to the o~-motoneurons". Following the same argument, CLARK (1966) states that "in the tic syndromes, including those often described as GILLESDELATOURETTE'Sdisease there is a high level of cortical inhibition which mediates deficient smoothing of motor responses themselves triggered by strong impulses - - of hostility for example - - that overwhelm the regulatory capacity of the basal ganglia". CONCLUSION

Due to the restrictions imposed upon us by the various settings in which the cases were seen, our investigation was limited in scope particularly with respect to psychiatric and psychological data. It is nevertheless evident that the essential startle disease or hyperekplexia is not an illness that can be explained solely on a neurological basis. Emotional and psychological factors also appear to play a role in its inception and its course. The difficulties in social adaptation brought about by the disease, their noxious psychological repercussions on the patient and at times the exploitation by the latter of his illness complicate further the problem. We are of course aware that there is a large gamut of responses to an unexpected or surprising stimulus and that some apparently well-adjusted individuals exhibit a constant tendency to jump quite readily while some neurotic persons will have, usually unnoticed amongst their other symptoms, that propensity. A patient should be considered as suffering from a pathological startle reaction only when the jump is the J. neurol. Sci.

(1967) 5:523-542

STARTLE DISEASE OR HYPEREKPLEXIA

541

most prominent or unique clinical sign and is the reason for medical consultation. The essential startle disease is not believed to be hereditary or familial, nor related to the imitation neuroses, nor limited to any race or culture. In order to identify its exact place in neuropsychiatric pathology a more systematic psychiatric study of patients suffering from this disease coupled with thorough clinical and laboratory investigations and a long-term follow-up will be needed. Although it has been reported that hysterics have a greater tendency to jump in response to an unexpected stimulus (DoNGIER et al. 1957) the corollary is not necessarily so, that the excessive startle reaction constituting the essential startle disease is symptomatic of hysteria and is a conversion phenomenon. The relationship between the essential startle disease and hereditary hyperexplexia, the former appearing functional, the latter seeming organic and hereditary will warrant further consideration. As for the exaggerated startle reaction encountered in some organic brain diseases it is possible that the cerebral lesion causes the hyperexcitability of the subcortical structures responsible for the jump. SUMMARY

The essential startle disease or hyperekplexia is a rare entity and 12 cases are reported here. The illness is characterized by jumps of abnormal intensity and/or frequency, without alteration of consciousness, following', unexpected stimuli. The jumps occur not only during the day but also during sleep. Emotional and psychological factors appear to play a role in the genesis and in the course of the disease. For diagnostic purposes this illness should be differentiated from myoclonic epilepsy with which it is usually mistaken, from the syndrome of GILLESDE LA TOURETTE(tic convulsif), from hereditary hyperexplexia and from the exaggerated startle reaction encountered in some organic brain diseases. The knowledge of the existence and of the electroclinical semeiology of the essential startle disease renders its diagnosis fairly easy. The main diagnostic clues are as follows: (1) Jumps of abnormal intensity and/or frequency in response to unexpected stimuli suddenly appear. Sometimes it is possible to link an emotional factor with their onset. The investigation of hereditary antecedents is negative. (2) Any unexpected stimulus provokes the jump and little or no habituation can be obtained by multiple successive repetition of the stimulus. (3) Neurological examination, laboratory tests and radiographic studies are either completely negative, this being the most frequent case, or do not yield any relevant information. (4) EEG shows only a vertex spike followed by a general desynchronization of the cortical rhythms in the central regions (fl-rhythm) as well as in the parietal, temporal and occipital areas (s-rhythm). (5) Polygraphic and other investigations reveal various neurovegetative changes accompanying the jump and characteristic of the surprise reaction. (6) Intravenous metrazol injection may disclose a low convulsive threshold in some cases. Relying upon experimental studies by BUSER and co-workers, the hypothesis is J. neurol. Sci. (1967) 5:523-542

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advanced that the illness could result from a f u n c t i o n a l hyperexcitability of the b r a i n stem structures responsible for the n o r m a l startle reaction. E m o t i o n a l factors could play a n i m p o r t a n t role in the inception a n d the course of the disease which is believed to be unrelated to the i m i t a t i o n neuroses, to be n o t hereditary or familial, n o r limited to a n y race or culture. The essential startle disease is long-lasting a n d little i m p r o v e m e n t was obtained with drugs currently available i n the cases treated. One case treated by a few sessions o f psychotherapy showed some i m p r o v e m e n t while a n o t h e r who presented the association of c a t a m e n i a l g r a n d m a l seizures a n d pathological startle reaction had these manifestations b r o u g h t u n d e r c o n t r o l with p h e n o b a r b i t o n e c o m b i n e d with primidone. REFERENCES ALAJOUANINE,TH. AND H. GASTAUT(1958a) La syncinrsie-surtautet l'rpilepsie-sursaut ~t drclenchement sensitif ou sensoriel inopin& Les fairs anatomo-cliniques, Rev. neuroL, 93 : 29-41. ALAJOUANrNE,TH. ANt) H. GASTAtrr(1958b) La syncinrsie-sursaut et l'rpilepsie-sursaut/t drclenchemerit sensitif ou sensoriel inopinr. Considrrations physiopathogrniques. In: Bases Physiologiques et Aspects Cliniques de l'l~pilepsie, Masson, Paris, pp. 199-231. BEARD, G. M. (1878)Remarks upon "jumpers, or jumping Frenchmen", J. nerv. ment. Dis., 5: 526. BEARO, G. M. (1880)Experiments with "jumpers" of Maine, Pop. Sci. Monthly (N.Y.), 18" 170-178. BICgFORD, R., J. JACOBSON,D. COPY AND E. LAMBERT(1964) Fast motor systems in men; physiopathology of the sonomotor response, Trans. Amer. neuroL Ass., 89: 56-58. BtrsER, F., J. SrLAURENTANDC8. MENINI(1966) Intervention du colliculus inf&ieur dans l'61aboration et le contrrle cortical sprcifique des drcharges cliniques au son chez le chat sous chloralose, Exp. Brain Res., 1 : 102-126. CLARK, D. F. (1966) Behaviour therapy of Gilles de la Tourette's syndrome, Brit. J. Psychiat., 112: 771-778. DONatoR, S., Y. GASTAUTANI) M. DONGIER(1957) Enregistrement polygraphique de l'effet de surprise. Relations entre les rrsultats obtenus et les dormres cliniques. In: Conditionnement et Rdactivitd en l~lectroenc~phalographie, Masson, Paris, pp. 125-132. ELLENaERG~R,H. F. (1965) Ethnopsychiatrie. In: Encyclopddie Mddico-Chirurgicale, Vol. Psychiatrie, Tome 3, fasc. 37725 A10 et Blo. GASTAUT, H. (1950) Combined photic and metrazol activation of the brain, Electroenceph. clin. Neurophysiol., 2: 249-261. GASTAtrr, H. (1958) Donnres actuelles sur les mrcanismes physiologiques centraux de l'rmotion, Rev. psychoL franf., 3 : 1-21. GASTAUT,H. AND A. RO~ER (1960) Les mrcanismes de l'activit6 nerveuse suprrieure. In" H. H. JASPERAND G. D. SMIRNOV(Eds.), The Moscow Colloquium on Electroencephalography of Higher Nervous Activity, October 1958, Moscow (Electroenceph. clin. Neurophysiol., SuppL 13), Elsevier, Amsterdam, pp. 13-38. GASTAtrr, H. AND C. A. TASSrNAPd(1966) Triggering mechanisms in epilepsy, Epilepsia, 7: 85-138. GASTAtrr,H., C. BATINI,R. BROUGrlTON,I. FRESSYANt)C. A. TASSINAPa(1965)Etuderlectroencrphalographique du phrnomrne 6pisodique non 6pileptique au cours du sommeil. In: Le Sommeil de Nuit Normal et Pathologique. Masson, Paris, pp. 215-236. GASrAUT, Y. (1953) Les pointes nrgatives 6voqures sur le vertex: leur signification psychologique, Rev. neuroL, 89: 382-399. GILLESDELATOURETTE,G. (1881) Les "sauteurs" du Maine (Etats-Unis) par G. BEARD,Arch. Neurol. (Paris), 2: 146-150. GXLLESDE LA TOURz'rrE, G. (1884) Jumping, Latah, Myriachit, Arch. NeuroL (Paris), 8: 68-74. HAMMOND,W. A. (1884) Miryachit: a newly described disease of the nervous system and its analogues, N.Y. reed. J., 39: 191-192. PAV~V, I. P. (1941) Conditioned Reflexes and Psychiatry (translated by W. H. GANTT),International Publishers, New York, pp. 106-107. STEVENS,H. (1965) "Jumping Frenchmen of Maine", Arch. neuroL, 12: 311-314. SLrnREN,O., G. W. BRUYNm'qDJ. A. TUYNMAN(1966) Hyperexplexia: a hereditary startle syndrome, J. neuroL ScL, 3: 577-605.

J. neurol. Sci. (1967) 5:523-542