Timothy C. Hain, MD
•Most recent update: March 7, 2021
An unusual source of unsteadiness (not
dizziness), is an excessive startle reflex. This goes under the very
obscure and difficult to spell name of "hyperekplexia". These
people are unsteady because they develop uncontrollable spasms or postures
of their body, usually as a result of a loud noise or perhaps an
emotionally disturbing event. This can occasionally cause unsteady
gait (Rouco et al, 2014) but more commonly results in individuals who
adopt unusual body postures after startle. Intellectually, these are
interesting conditions as there are a myriad of possible explanations (see
below). Practically though, they are almost all treated similarly
with benzodiazepine type drugs. There are many medical
publications about Hyperekplexia or excessive startle (262 as of
2020). Hyperekplexia was recently reviewed by Saini and Pandey
(2020). This page is an online review of literature about hyperekplexia,
particularly concerning situations where it might disturb balance.
Hyperekplexia manifests as eye blinking and a
flexion of the trunk to unexpected innocuous (particularly auditory)
stimuli. It typically does not habituate. It is one of the
"startle" syndromes which also includes neuropsychiatric startle and
startle induced epilepsy. (Bakker et al, 2006). While auditory
stimuli can also cause dizziness in persons with ear disorders (such as
Superior canal dehiscence), these disorders are easily differentiated by
the strong trunk movements seen in Hyperekplexia.
Causes of Hyperekplexia
Hyperekplexia is divided into acquired and congenital forms. The
congenital forms are mainly due to genetic defects in the glycine
receptor, due to loss of function, but may also be due to complex
disorders (see below). The acquired forms can involve processes that
affect the glycine receptor, as well as psychological disturbances
involving anxiety and unusual responses to startle, and miscellaneous
Laboratory findings in Hyperekplexia
The causes of hyperkplexia are diverse, and the literature offers a
large number of tests, sometimes found positive in cases here and
there. An MRI and EEG seems rather reasonable, looking for
structural brainstem causes, and brain disturbances with abnormal
excitability (such as Jakob Creutzfeldt). Genetic testing may be
productive in cases with early childhood onset (which leaves out the
acquired ones). Antibody testing would seem most appropriate for severe
and progressive cases (such as PERM -- see below).
Differential Diagnosis of Hyperekplexia
- Genetic causes -- these are generally very early onset in
life. One does not need to test for these in cases acquired
later in life.
- Specific mutations involving the glycine receptor
- GLRA1 (about 60%)
- GLRB (12-14%)
- SLC6A5 (25%)
- Complex neurodevelopmental conditions with an excessive startle
response (see Balint and Thomas (1993, and updates) for a detailed
- Autoimmune -- if these are found, "immunotherapy" may be offered.
- Glycine receptor antibodies such as in PERM -- progressive
encephalomyelitis with rigidity and myoclonus. (Carvajal-Gonzalez et
- GAD antibodies (these are very common in other disorders, such as
- amphiphysin antibodies
- DPPX antibodies
- Psychological (e.g. see Howard and Ford, 1992) -- this is usually a
"wastebasket" diagnosis -- similar to "no other reasonable
- Tic disorder (Gilles de la Tourette) -- this may be genetic or
- Culture specific disorders involving exaggerated startle responses
(Bhidayasiri and Truong, 2011)
- Jumping Frenchmen of Maine among the Franco-Canadian lumberjack
- Latah in Southeast Asia
- Focal neurological disturbances
- Post-anoxic myoclonus, infarct, hemorrhage, medullary compression,
- Startle epilepsy
- Paroxysmal kinesiogenic choreoathetosis -- symptoms are induced by
- Tetanus, which prevents release of glycine
- Creutzfeldt-Jakob disease (cortical hyperexcitability due to this
prion disorder) (Graveline et al, 2019)
- Subacute sclerosing panencephalitis
- Other encephalitus (e.g. Fenzi et al, 1988)
- Strychnine poisoning (this is a inhibitor of the glycine receptor)
Treatment of Hyperekplexia
The main treatment for hyperekplexia is benzodiazepines, such as
low dose clonazepam. Other drugs that have been tried include
seizure medications (e.g carmabazepine, phenytoin, valproate,
levetiracetam, piracetam, phenobarbital). (Bakker et al, 2006;
Dooley and Andermann, 1989; McAbee 2015)
Hyperekplexia is a rare cause of unsteady gait and posturing. It
is treated with low dose clonazepam.
- Bakker, M. J., et al. (2006). "Startle syndromes." Lancet Neurol
- Bakker, M. J., et al. (2009). "Clonazepam is an effective treatment
for hyperekplexia due to a SLC6A5 (GlyT2) mutation." Mov Disord
- Balint, B. and R. Thomas (1993). Hereditary Hyperekplexia Overview.
GeneReviews((R)). M. P. Adam, H. H. Ardinger, R. A. Pagon et al.
Seattle (WA). This article is available online and has been
- Bhidayasiri, R. and D. D. Truong (2011). "Startle syndromes." Handb
Clin Neurol 100: 421-430.
- Carvajal-Gonzalez, A., et al. (2014). "Glycine receptor antibodies
in PERM and related syndromes: characteristics, clinical features and
outcomes." Brain 137(Pt 8): 2178-2192.
- Dooley, J. M. and F. Andermann (1989). "Startle disease or
hyperekplexia: adolescent onset and response to valproate." Pediatr
Neurol 5(2): 126-127.
- Fenzi, F., et al. (1988). "Anatomical and clinical study of a case
of subacute encephalomyelitis with hyperekplexia syndrome." Ital J
Neurol Sci 9(5): 505-508.
- Graveline, J., et al. (2019). "Creutzfeldt-Jakob disease presenting
with encephalopathy, rigidity, and hyperekplexia." Neurol Clin Pract
- Howard, R. and R. Ford (1992). "From the jumping Frenchmen of Maine
to post-traumatic stress disorder: the startle response in
neuropsychiatry." Psychol Med 22(3): 695-707.
- McAbee, G. N. (2015). "Clobazam-clonazepam combination effective for
stimulus-induced falling in hyperekplexia." J Child Neurol 30(1):
- Rouco, I., et al. (2014). "Sporadic hyperekplexia presenting with an
ataxic gait." J Clin Neurosci 21(2): 345-346.
- Saini, A. G. and S. Pandey (2020). "Hyperekplexia and other startle
syndromes." J Neurol Sci 416: 117051.