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PRACTICAL NEUROLOGY
NEUROLOGICAL RARITIES
Startles, jumps
Andrea Lindahl*
*Specialist Registrar in Neurology, Department of Neurology, Gloucester Royal Hospital,
Great Western Road, Gloucester, GL1 3NN; E-mail: [email protected]
Practical Neurology, 5, 2005, 292–297
INTRODUCTION
We are all personally familiar with the startle response – the
abrupt ‘start’ or ‘jump’ in response to sudden unexpected stimuli,
like a loud noise. This startle is a nonsuppressible reflex, which
alerts us to abrupt changes in our environment that may threaten
our safety. It is a reflex with survival value. But, if excessive or too
easily triggered, it can interfere with daily functioning, or cause
falls or injuries, and it is then a pathological response. The startle
reflex is thought to be mediated at the level of the midbrain or
below, because it is still elicited in decerebrate animals (Forbes &
Sherrington 1914). The intensity of the startle reflex in humans
varies between individuals and is increased by anxiety, fatigue or
emotion (consider your response to a door slamming as you are
watching a late night horror movie).
Pathological startle syndromes can be divided into (Fig. 1):
• Primary startle syndromes (startle disease and startle epilepsy)
• Startle secondary to other pathologies
• Psychogenic startle
• The culturally linked startle syndromes
Pathological startle
Primary startle
syndromes
Hyperekplexia
Major
Minor
Startle epilepsy
Secondary startle
syndromes
Psychogenic
startle
Brain disease
!
!
!
!
Compression of
cervico-medullary
junction
Brainstem lesions
- stroke
- encephalitis
- multiple
sclerosis
Post-anoxic
encephalopathy
thalamic infarct
Fig. 1. A framework for classifying the startle syndromes
© 2005 Blackwell Publishing Ltd
Cultural startle
syndromes
!
!
Lâtah
Jumping Frenchmen of
Maine
Latency between
stimuli and jerks
longer than in startle
reflex
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OCTOBER 2005
ps,
s, falls and fits
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PRACTICAL NEUROLOGY
Recognition of the condition
is important because affected
families can be referred for genetic
counselling.
This review will provide an overview of the different types of
startle syndromes, which are uncommon but interesting – and
potentially treatable. But not everything that jumps is startle
disease.
STARTLE DISEASE (HYPEREKPLEXIA)
Hyperekplexia is uncommon (the exact prevalence is unknown)
and is one of the few treatable neurogenetic disorders. The diagnosis
is usually straightforward -once one is aware of the clinical features.
Early diagnosis and treatment can prevent much of the morbidity
and mortality. Recognition of the condition is also important because affected families can be referred for genetic counselling.
Illustrative case history
A 26-year-old right-handed man was seen in the neurology clinic,
having suffered with ‘drop attacks’ since childhood. His mother
had become concerned about his frequent falls at the age of six,
particularly as he made no obvious attempt to save himself and
had sustained a number of facial injuries. She said he did not
seem to stumble and there was no loss of consciousness, but she
had noticed that loud noises often precipitated a fall. He had been
seen at the age of three and diagnosed with a spastic diplegia and
equinovarus deformity of the right foot. At the time of review in
the adult clinic, neurological examination was entirely normal.
A detailed family history revealed that a number of other family
members were also affected (Fig. 2) and the patient reported that
his 2-year-old daughter had been ‘stiff ’ when she was born. She
was just starting to walk and he was concerned by the fact that she
also seemed to fall frequently.
Inheritance and pathophysiology
Hyperekplexia is usually inherited in an autosomal dominant
fashion (as in the case history above), although there have been
reports of recessive inheritance, and sporadic cases. The genetic
defect is linked to chromosome 5 and different mutations in the
inhibitory glycine receptor (GLRA1) gene have been identified in
a number of affected families (Shiang et al. 1993). Mutations of
GLRA1 uncouple ligand binding and chloride channel function
of the inhibitory glycine receptor. The result is thought to be an
increase in excitability of the pontomedullary reticular neurons
and abnormal spinal inhibition.
Interestingly, hyperekplexia is known in animals, which provide experimental models for the condition. (Healey et al. 2002)
described a bovine form of myoclonus (with an accompanying
video supplement), which closely resembles human hyperekplexia. Affected animals have myoclonic jerks in response to
sensory stimuli and heightened responsiveness. Lifting them
causes excessive stiffness and extensor spasm, but with no loss
of consciousness, and recovery is rapid. This, too, is the result of
a mutation in the glycine receptor α-subunit leading to a failure
of glycine-mediated inhibitory neurotransmission in the spinal
cord and brainstem. There are also three strains of mice (spastic,
spasmodic and oscillator) that have a phenotype resembling hyperekplexia, all of which have a genetic defect involving glycine
receptors (Ryan et al. 1994; Kingsmore et al. 1994).
Affected female
Unaffected female
Affected male
Unaffected male
Fig. 2. The family history of the illustrated case, clearly showing autosomal dominant
transmission
© 2005 Blackwell Publishing Ltd
Clinical features
Human hyperekplexia often appears in the
neonatal period. Affected neonates are diffusely
hypertonic and hyperreflexic and have an exaggerated startle response to noise and handling,
usually head retraction and tonic flexion of the
body. Hernia may be associated due to raised
intra-abdominal pressure. Startle during feeding can result in aspiration, apnoea and sudden
death – it is therefore important that affected
neonates are monitored closely. Muscle stiffness
tends to settle during the first year, but walking
may be delayed due to fear of falling. Children
may crawl around on their knees or bottoms
before adopting a normal gait. Parents may also
notice clonic jerking, particularly of the legs,
during sleep. This is not associated with epileptiform discharges on the EEG and does not
respond to antiepileptic drugs.
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OCTOBER 2005
Why does an adult neurologist need to be aware of the paediatric manifestations of this condition? Firstly, paediatric patients
with hyperekplexia may well be handed on to adult clinics in adolescence. Secondly, it is important to ask about these clinical features in patients’ children when taking the family history. Thirdly,
in patients with established hyperekplexia, it is important to alert
them to the possibility of neonatal problems if they are planning
a family, particularly the need for vigilance during feeding and
apnoea monitoring at night.
Adults with untreated hyperekplexia continue to have excessive startle and run the risk of severe injury from frequent falls.
In response to a sudden, unexpected stimulus (usually noise, although attacks can be precipitated by sudden tactile stimuli), the
patient suddenly stiffens and then falls to the floor without loss
of consciousness. The arms are held rigidly by the sides and the
patients are unable to save themselves. Falls can result in severe
facial lacerations, skull or limb fractures, and some patients may
even take to a wheelchair to avoid falling.
The demonstration of other affected members in the family
can be difficult because major and minor forms may coexist in
the same family. The major form of hyperekplexia is associated
with generalized hypertonia in the first year of life, exaggerated
startle and falls, whereas in the minor form, exaggerated startle
and hypnic jerks are the only features (Suhren et al. 1966).
Neurological examination in adults is generally entirely normal. Affected neonates may show hypertonicity, and tapping
their nose may precipitate their exaggerated startle in the form
of sudden head retraction and tonic flexion of the body. This
excessive backward jerking of the head in response to tapping
the nose or forehead persists into adulthood (Shahar & Raviv
2004).
Investigation
Atypical features in the history or examination are reasons for
magnetic resonance imaging (MRI) of the brain to rule out central nervous system causes of startle (Fig. 1 and below). EEG correlates of startle have been described (Suhren et al. 1966; Gastaut
1967): centroparietal vertex spikes followed by slow waves and
desynchronization of background activity lasting a few seconds.
However, the diagnosis still remains largely clinical.
Treatment
Hyperekplexia is one of the few eminently treatable neurogenetic disorders. Clonazepam will reduce the exaggerated startle
response and therefore the risk of falling (Anderman et al. 1980;
Dubowitz et al. 1992). However, there is little information on the
optimum dose or duration of treatment. In the paediatric literature, 9 severely affected infants were treated with 0.2 mg/kg/day
of clonazepam and 7 showed complete recovery allowing treatment to be discontinued after 6 months (Shahar & Raviv 2004).
Ryan et al. treated 16 patients in a large kindred with clonazepam
and found a dramatic and sustained response (Ryan et al. 1992).
Sedation may occur as an adverse effect and one case report described the effectiveness of clobazam (0.25–0.3 mg/kg/day) in
two affected infants unable to tolerate clonazepam (Stewart et al.
FEATURES OF STARTLE DISEASE
(HYPEREKPLEXIA)
• Hyperekplexia is a treatable neurogenetic condition
• It is usually inherited in an autosomal dominant fashion
and is one of the channelopathies
• Exaggerated startle causes falls which can result in severe
injury
• Affected neonates run the risk of aspiration and apnoea due
to startle responses during feeding, and they require close
monitoring
• Early and accurate diagnosis significantly improves quality
of life and reduces risk of injury
• Liaison with obstetric and paediatric teams can raise awareness of the particular risks that are associated with delivery
and the neonatal period
• Hyperekplexia responds well to clonazepam, which is usually well tolerated and does not lose efficacy with time
• Affected patients should have genetic counselling
• Unexpected features in the history or examination should
prompt a search for underlying CNS pathology
2002). There is some evidence to suggest that valproate and piracetam may also be helpful (Dooley & Andermann 1989; SaenzLope et al. 1984).
SECONDARY STARTLE DISORDERS
Exaggerated startle has been reported in association with brainstem pathology such as multiple sclerosis (Ruprecht et al. 2002),
vascular anomalies (Gambardella et al. 1999), paraneoplastic
brainstem encephalitis, subacute viral encephalomyelitis, brainstem haemorrhage and sarcoidosis (Matsumoto et al. 1994). It
can occur with cervicomedullary compression (Salvi et al. 2000)
(Matsumoto et al. 1994), and in one case improved after decompressive surgery (Winston 1983). Ischaemic lesions such as posterior thalamic artery occlusion (Fariello et al. 1983) or pontine
infarction may result in hyperekplexia, possibly as a result of disinhibition of the normal startle reflex. Hyperekplexia may also
occur as a component of generalized tetanus (Warren et al. 2003),
after head injury, or in association with postanoxic encephalopathy (Joachim et al. 1997).
PSYCHOGENIC STARTLE RESPONSES
Psychogenic startle has been described when stimulus-induced
jerking occurrs as part of an apparent myoclonic or pathological
startle syndrome (Thompson et al. 1992). In two of the five patients described, jerking followed minor injuries to the head and
neck; a further two patients had a background of neurological illness. Clinical suspicion of a psychogenic origin was aroused when
close observation of the patients revealed that their symptoms
were not typical of either myoclonus or hyperekplexia. In three
of the patients in whom jerking occurred in response to sudden
stimuli, there had been no falls. In two of the patients, the pattern
of jerks was altered when the patient was distracted and in one,
the exaggerated startle occurred in response to loud noises on
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the ward, but not when walking in the street in the company of
medical staff.
Neurophysiological studies provided further evidence that the
abnormal movements were not secondary to hyperekplexia or
myoclonus. The latencies to onset of jerking were long and variable and there was a variable pattern of muscle recruitment. The
responses also tended to habituate. The authors compared these
responses to those of normal volunteers, asked to imitate a generalized jerk in response to sensory or auditory stimuli. The patients
with psychogenic jerks had longer reaction times than the fastest
voluntary reaction time of normal subjects and a similar pattern
of muscle recruitment. In one patient, the jerks resolved when the
possibility of a psychogenic origin was discussed with her. The
diagnosis of psychogenic movement disorders can be difficult but
simple neurophysiological testing is helpful.
CULTURALLY LINKED STARTLE
SYNDROMES
The culturally linked startle syndromes are interesting and remain controversial (Joseph et al. 1992). The ‘Jumping Frenchmen
of Maine’ and Lâtah have been the most extensively studied, but
other similar disorders have been described worldwide. These
disorders are characterized by pathological startle associated
with echolalia, echopraxia, coprolalia and automatic obedience
behaviour, and were in fact described by Gilles de la Tourette in
1885.
The ‘Jumping Frenchmen of Maine’
The ‘Jumping Frenchmen of Maine’ were first described in the
late 19th century, when George Beard came across a group of men
with an abnormal startle response consisting of jumping, raising their arms, hitting, vocalization and repetition of sentences
(Anon 1980). This same phenomenon was also seen in a group
of lumberjacks who were teased by their colleagues in lumber
camps. In both cases, the men were noted to be excessively ticklish. The enhanced startle in the lumberjacks was enhanced by the
attention it attracted and was felt to be a conditioned response
because when they left the environment in which stimuli and
positive reinforcement were frequent their responses became less
intense and less complex (Joseph et al. 1992).
Treatment of startle induced
seizures is difficult although
some patients respond well
to carbamazepine or sodium
valproate, and response to
lamotrigine has been reported.
© 2005 Blackwell Publishing Ltd
Lâtah
Lâtah has been recognized in Malaysia since the fifteenth century,
and by contrast affects females more than males. Affected females
are timid and passive, but the clinical features are very similar
to ‘jumping’. In addition to exaggerated startle, the women have
automatic obedience behaviour, which can range from dancing
to more bizarre behaviour, sometimes mimicking sexual actions
(Simons 1996). The female preponderance in Lâtah may be because both men and women preferred to startle women because
they could do so with impunity (Simons 1996), not always the
case when Lâtah men were startled! There has been some controversy as to whether Lâtah is an organic disorder because people
with Lâtah have been observed exaggerating their dysfunction
either to attract attention or to have an excuse for behaviour that
may otherwise be culturally unacceptable.
Bartholomew (1994) described 37 cases of Lâtah from his own
extended Malay family, 33 of whom had coprolalia in response
to startle, and 4 had bizarre behaviour and automatic obedience
for up to 10 min The first group were categorized as ‘habitual’
Lâtah and the second group as ‘performance’ Lâtah. The author
hypothesized that the first group constituted a conditioned habit
as part of a response to stress and the second group were exhibiting a conscious ritual for social gain (i.e. attention-seeking behaviour).
STARTLE EPILEPSY
Startle-provoked seizures are rare but well described. The purpose of this overview is to highlight the distinction between startle disease (hyperekplexia) and startle epilepsy. Startle epilepsy is
recognized as a syndrome, but patients with startle-induced seizures are, in fact, a heterogeneous group with variable aetiologies
and EEG correlates (Panayiotopoulos 2002). Startle epilepsy is a
form of reflex seizure in which startle activates the epileptiform
discharge.
Clinical features
Startle epilepsy was originally thought to be rare in those with
normal intellect and neurological function. The first description
of abnormal startle associated with seizures was by Alajouanine
and Gastaut (1955, cited in Anderman et al. 1980). They described
STARTLE EPILPEPSY
• It is important to distinguish between startle disease (hypertplexia) and startle epilepsy and once aware of the clinical
manifestations of these two separate conditions, the clinical
diagnosis is relatively straightforward
• The preservation of consciousness and absence of epileptiform discharges on EEG distinguish hyperekplexia from
startle epilepsy
• Whilst startle epilepsy is often resistant to treatment, hyperekplexia, by contrast usually responds well to clonazepam
• Abnormal features in the history or examination should
prompt a search for underlying brain pathology.
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OCTOBER 2005
two types in children with infantile hemiparesis or quadriparesis
and diffuse cerebral dysfunction:
• Startle synkinesis, where the weak limb undergoes a 5–10 second tonic contraction, often causing falls
• Startle epilepsy where in addition to startle and tonic contraction, there were other clinical or electrophysiological signs of
seizure activity
Startle seizures are asymmetrical in 25% of patients. The initial
tonic contraction of the paretic limb may spread to the contralateral side and there may be other symptoms such as automatisms,
laughter or autonomic manifestations. Seizures are frequent,
may progress to status epilepticus and are typically refractory to
medical treatment. Spontaneous (non-startle provoked) seizures
occur in many patients with startle epilepsy, but are infrequent.
Prognosis tends to be poor, particularly for those with severe preexisting brian damage (Panayiotopoulos 2002). Startle epilepsy
has been described in association with Sturge–Weber syndrome
These days, it has been suggested that startle-provoked seizures may occur more frequently than previously thought in the
context of normal neurological function. Manford et al. (1996)
described 19 patients with startle epilepsy, 10 of whom had no
abnormal neurological signs. There was no difference in seizure
frequency, severity or response to treatment between the groups
with and without a neurological deficit. Onset was usually in
childhood or adolescence, but could occur in adulthood. Seizures
tended to be brief but frequent and in most patients evolved into
tonic motor activity and asymmetrical posturing. Interictal EEG
abnormalities varied within and between patients, but tended to
affect the frontal, temporal and central regions. In patients with a
hemiparesis, a porencephalic cyst or focal atrophy was seen in the
contralateral hemisphere. In a number of patients with normal
CT scans, high resolution MRI demonstrated dysplastic brain lesions.
Treatment of startle induced seizures is difficult although some
patients respond well to carbamazepine or sodium valproate
(Sainz-Lope et al. 1984), and response to lamotrigine has been
reported (Faught 1999). Surgery may be considered in patients
with focal brain lesions.
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Startles, jumps, falls and fits
Andrea Lindahl
Pract Neurol 2005 5: 292-297
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