ABSTRACT: Posthypoxic coma is often associated with cortical and brain-

stem hyperexcitability. Five months following cardiopulmonary resuscitation

after myocardial infarction and ventricular arrhythmia, a 47-year-old man
presented with posthypoxic cerebral dysfunction, minimal responsiveness,
severe spastic-dystonic tetraparesis, and stimulus-sensitive muscle spasms
upon acoustic and sensory stimulation. Neurophysiological examination
revealed increased long-loop reflexes in abductor pollicis brevis muscle
following median nerve stimulation at the wrist, consistent with cortical
hyperexcitability. Exaggerated startle responses provided evidence of con-
comitant brainstem disinhibition. Levetiracetam up to 3,000 mg per day
suppressed transcortical long-loop reflexes in a dose-dependent manner
without concomitant suppression of the H-reflex and only mild attenuation of
the startle response. The present findings suggest a suppressive effect of
levetiracetam on cortical neurons in the absence of a spinal effect on
monosynaptic reflexes, and thus support the drug’s efficacy in posthypoxic
cortical hyperexcitability.
Muscle Nerve 33: 785–791, 2006

LEVETIRACETAM SUPPRESSES LONG-LOOP

REFLEXES AT THE CORTICAL LEVEL
MARKUS KOFLER, MD

Department of Neurology, Hospital Hochzirl, A-6170 Zirl, Austria

Accepted 24 January 2006

Posthypoxic coma is often associated with cortical CASE REPORT

and brainstem hyperexcitability.3 Clinical manifesta-
tions may comprise seizures, cortical or brainstem
myoclonus, and exaggerated startle reactions to vari-
able degrees. Neurophysiological techniques may
help to localize the origin of myoclonic jerks,24 but
may also provide evidence of subclinical forms of
neuronal hyperexcitability. Levetiracetam has been
used to treat epilepsy and myoclonus following cere-
bral hypoxia,4,10,12,22 and has recently been sug-
gested for the treatment of spasticity and paroxysmal
stiffness.5,21 The mechanism of action of levetirac-
etam is not fully known. Investigation of spinal,
brainstem, and cortical reflexes, as well as somato-
sensory evoked potentials, during administration of
increasing doses of levetiracetam may show a differ-
ential and dose-dependent suppressive effect on cer-
tain parameters, and may thus help to localize the
site of action of levetiracetam.
Abbreviations: ANOVA, analysis of variance; ASR, auditory startle re-
sponse; LLR, long-loop reflex; SEP, somatosensory evoked potential
Key words: auditory startle response; levetiracetam; long-loop reflex;
somatosensory evoked potential
Correspondence to: M. Kofler; e-mail: markus.kofler@uibk.ac.at
© 2006 Wiley Periodicals, Inc.
Published online 3 March 2006 in Wiley InterScience (www.interscience.wiley.
com). DOI 10.1002/mus.20533
A 47-year-old man developed severe posthypoxic ce-
rebral dysfunction following cardiopulmonary resus-
citation after anteroseptal myocardial infarction and
ventricular arrhythmia. Resuscitation was begun 10
min after initial loss of consciousness, at which point
the Glasgow Coma Score was 5. Cerebral magnetic
resonance imaging 1 and 4 months posthypoxia re-
vealed mild progressive cerebral atrophy but no lo-
calized lesions. Single photon emission computer-
ized tomography with technetium, performed 1
month posthypoxia, showed reduced perfusion of
cerebral cortex, basal ganglia, and left cerebellum,
which was more pronounced on repeat evaluation 2
months later. Electroencephalography at 1 month
posthypoxia was reported abnormal with diffuse
theta-delta slowing, but preserved reactions to exog-
enous stimuli. Two months later electroencephalo-
graphic reactivity diminished, and it was also less
reproducible in a repeat study 3 months thereafter.
None of the electroencephalograms showed spikes
or epileptiform activity.
After 5 months the patient was referred to our
institution for further evaluation and treatment. On
clinical examination he showed minimal responsive-
ness: when spoken to or touched, he developed pro-
longed head elevation, hyperventilation, and slow

Long-Loop Reflexes MUSCLE & NERVE June 2006 785

tonic flexion of the upper and lower extremities,
without an auditory or somatosensory startle blink.
There was no optic fixation. He reacted to visual
threat by blinking without concomitant contraction
of the body musculature. Opening of the mouth was
impeded by a trismus-like, markedly increased tone
of the masseter muscles. Severe spastic-dystonic tet-
raparesis was apparent, with the upper limbs flexed
at the elbows, wrists, and fingers bilaterally, and the
lower limbs flexed at the hips and knees with bilat-
eral plantar extension. The passive range of motion
was limited in upper and lower limbs by shortened
tendons, more marked on the right side. Minimal
spontaneous movements were present in the left leg.
Tendon reflexes were not elicitable due to increased
muscle tone and fixed contractures. There was no
clinical evidence of myoclonus.
Oral medication comprising baclofen (75 mg/
d), tizanidine (24 mg/d), diazepam (20 mg/d),
gabapentin (1,200 mg/d), fentanyl (75 ␮g/h), alpra-
zolam (2 mg/d), and nabilone (2 mg/d) failed to
alleviate his spasticity, as did intrathecal baclofen up
to 1,000 ␮g/d. Based on neurophysiological findings
(see below) and the author’s previous experience
with levetiracetam in the treatment of posthypoxic
cortical hyperexcitability,10,22 levetiracetam was in-
troduced and titrated up to 3,000 mg/day. The ef-
fect was monitored by weekly recordings of H-re-
flexes, long-loop reflexes (LLRs), somatosensory
evoked potentials (SEPs), and auditory startle re-
sponses (ASRs). This medication led to a slight re-
duction of spastic-dystonic posturing upon exoge-
nous stimulation, but also rendered the patient less
vigilant. Clinical responsiveness remained minimal
over 6 weeks, and levetiracetam was therefore ta-
pered off and finally discontinued. On clinical fol-
low-up 18 months later, the patient was able to fixate
and follow objects visually, to understand simple
verbal instructions, and to follow, although inconsis-
tently, simple commands such as to close the eyes,
and he had begun to communicate basic needs by
pressing buttons on a special keyboard.
Neurophysiological Methods. Neurophysiological in-
vestigations were performed using routine electrodi-
agnostic equipment (Viking; Nicolet Biomedical,
Madison, Wisconsin) according to previously pub-
lished standards.7,9,11 H-reflexes and LLRs in abduc-
tor pollicis brevis muscle, median nerve SEPs, motor
evoked potentials from the abductor digiti minimi
muscle, and ASRs were studied 5 months posthy-
poxia, before introducing and 18 months after dis-
continuation of levetiracetam medication. H-re-
flexes, LLRs, cortical SEPs, and ASRs were
786 Long-Loop Reflexes
repeatedly studied following each increase in the
patient’s levetiracetam dosage.
H-reflexes and LLRs were recorded from the
slightly contracted right abductor pollicis brevis mus-
cle following bipolar stimulation of the right median
nerve at the wrist (0.2-ms duration, 2.3-Hz stimula-
tion rate, intensity adjusted to yield nonrectified M-
wave amplitudes of 200 ␮V). The level of muscle
contraction was estimated by auditory feedback, as
the patient was unable to follow verbal commands,
and was adjusted if necessary by gently applying re-
sistance to the patient’s thumb. Concomitant SEP
recordings were obtained from the contralateral pa-
rietal cortex with a frontal reference. Two series of
200 responses with sweeps of 200 ms were amplified,
averaged, and superimposed, with filters set at 10
and 10,000 Hz.
SEPs were also elicited at rest following median
nerve stimulation at the wrist (electrical monopolar
square waves, 0.2-ms duration, 3.7-Hz stimulation
rate, intensity sufficient to elicit a maximum anti-
dromic sensory action potential recorded from the
index finger). Recordings were obtained from Erb’s
point (contralateral reference), fifth cervical verte-
bra (suprasternal and frontal reference), frontal cor-
tex (linked-ear reference), and contralateral parietal
cortex (linked-ear and frontal reference). Electrodes
were placed according to the International 10 –20
System. Impedance was kept below 2 k ohms at all
electrode sites (in this and all subsequent studies).
Two series of 500 responses with sweeps of 50 ms
were amplified, averaged, and superimposed to en-
sure reproducibility. The filters were set at 20 and
3,000 Hz for subcortical and at 5 and 3,000 Hz for
cortical SEP recordings.
Motor evoked potentials were recorded at rest
from abductor pollicis brevis muscle following con-
tralateral transcranial magnetic stimulation (Mag-
stim 200; Whitland, UK) using a round coil with an
outer diameter of 14 cm centered over the vertex.
The current direction was counterclockwise for pref-
erential activation of the left hemisphere and vice
versa. Test stimulus intensities were 40%, 60%, 80%,
and 100% stimulator output. At least two responses
were recorded for each intensity. Filters were set at
10 Hz and 10,000 Hz.
ASRs were elicited by eight binaurally presented
tone bursts with random tonal frequency and inten-
sity (250 Hz, 90 dB nHL; 500 Hz, 105 dB nHL; 750
Hz, 105 dB nHL, 1,000 Hz, 110 dB nHL; 2 cycles rise
time, 400 cycles duration), separated by 2 to 3 min.
Single sweeps of nonrectified surface electromyo-
graphic recordings were simultaneously obtained
following each stimulus from orbicularis oculi, mas-
MUSCLE & NERVE June 2006
FIGURE 1. Cortical somatosensory evoked potentials recorded between C3’ and Fz (A), and direct (M), spinally (H), and transcortically
(LLR) mediated muscle responses in right abductor pollicis brevis muscle (B) following right median nerve stimulation at baseline (left)
and during treatment with 2,000 mg levetiracetam daily (right).
seter, sternocleidomastoid, biceps brachii, abductor
pollicis brevis, rectus femoris, tibialis anterior, and
soleus muscles. Silver–silver chloride cup electrodes
were attached over muscle belly and tendon where
applicable. Single sweeps of 500 ms including 20 ms
prestimulus delay were recorded with filters set at 10
and 10,000 Hz. ASR probability was calculated by
dividing the number of all reflex responses in all
eight muscles following all eight stimuli by the total
number of recorded traces multiplied by 100. ASR
latencies were measured from stimulus onset to ASR
onset. ASR area under the curve was calculated dur-
ing the first 100 ms following response onset.
RESULTS
Baseline Studies. Median nerve stimulation at the
wrist at a rate of 2.3 Hz and an intensity of 6.3 mA
evoked a direct M-wave in slightly contracted right
abductor pollicis brevis muscle of 200 ␮V peak-to-
peak amplitude. An H-reflex was elicited with a la-
tency of 29.6 ms and a peak-to-peak amplitude of 290
␮V, followed by an exaggerated LLR with a latency of
43.6 ms and a peak-to-peak amplitude of 1,195 ␮V.
Contralateral cortical SEPs N20 –P25, concomitantly
recorded with a frontal reference, were marginally
enlarged with 8.04 ␮V (normal range obtained in 53
healthy subjects: 1.51–7.47 ␮V) (Figs. 1, 2).
Right and left median nerve stimulation at rest
elicited SEPs with normal absolute and interpeak
latencies over brachial plexus, cervical spinal cord,
and contralateral cortex. In noncephalic reference
Long-Loop Reflexes
recordings the amplitude of the postcentral cortical
N20 –P25 response was 6.5 ␮V following right-sided
stimulation, and 7.9 ␮V following left-sided stimula-
tion (normal, 0.03–7.11 ␮V), with a P25 baseline–
peak amplitude of 5.1 ␮V and 6.5 ␮V, respectively
(normal, – 0.13 to 5.49 ␮V). Precentral P21–N30
responses were in the normal range bilaterally with
2.3 ␮V and 2.5 ␮V following right- and left-sided
stimulation, respectively (normal, 0.08 – 4.87 ␮V).
Transcranial magnetic stimulation evoked motor
responses of normal latency from right and left ab-
ductor digiti minimi muscles (21.4 and 20.4 ms,
respectively; upper normal limit, 25.9 ms7). The am-
plitude on the right side was smaller than the left
side (2.8 vs. 5.9 mV with 100% stimulator output
intensity).
Binaural acoustic stimulation elicited brisk gen-
eralized muscle responses typical of an auditory star-
tle reaction (Fig. 3). ASR probability was 100% in
each muscle, clearly exceeding the normal range
particularly in extremity muscles, as obtained in 10
age- and gender-matched8,9 control subjects (Fig.
4A). ASR onset latencies were shorter than normal
median values in masseter and sternocleidomastoid
muscles, and below the normal range in all extremity
muscles (Fig. 4B). ASR area under the curve was
larger than normal median values in orbicularis oc-
uli and abductor pollicis brevis muscles, and above
the normal range in all other muscles (Fig. 4C). The
observed abnormalities were consistent with brain-
stem hyperexcitability.
MUSCLE & NERVE June 2006 787

FIGURE 2. Amplitudes of H-reflex (A), long-loop reflex (LLR) (B),
and the N20 –P25 (black columns) and P25–N34 (white columns)
components of the somatosensory evoked potential (SEP) in
C3’–Fz (D), as well as the ratio of LLR and H-reflex amplitudes
(%) (C) following right median nerve stimulation at baseline,
during levetiracetam treatment (1,000, 2,000, 3,000 mg daily),
and 18 months following cessation of levetiracetam treatment.
Follow-up Studies during Levetiracetam Treatment.
Levetiracetam was started at 1,000 mg and increased
up to 3,000 mg per day in weekly increments of 1,000
mg. With increasing doses of levetiracetam H-re-
flexes were unchanged, but LLR amplitudes, LLR/H
ratios, and cortical SEPs were suppressed in a dose-
dependent manner (Fig. 2A–D). There was a high
correlation of the reduction of the LLR/H ampli-
tude ratio with that of cortical N20 –P25 and P25–
N34 SEPs following median nerve stimulation, with
788 Long-Loop Reflexes
Pearson’s correlation coefficients of 0.90 (N20 –P25)
and 0.89 (P25–N34), respectively. ASR probability
remained abnormally high with only a small decline
in probability with 3,000 mg levetiracetam daily in
the biceps brachii, abductor pollicis brevis, and rec-
tus femoris muscles (Fig. 4A). ASR latencies were not
consistently influenced by increasing doses of levetirac-
etam (Fig. 4B). Mean area-under-the-curve was mildly
reduced by levetiracetam, particularly in sternocleido-
mastoid and biceps brachii muscles, but remained ab-
normally increased even up to 3,000 mg levetiracetam
daily in lower-extremity muscles (Fig. 4C).
Follow-up Studies after Cessation of Levetiracetam
Treatment. Eighteen months after discontinuation
of levetiracetam, H-reflexes remained unchanged,
but LLRs were exaggerated again similar to baseline
values, as was the LLR/H ratio (Fig. 2A–C). Cortical
SEPs, however, were similar to those obtained with
3,000 mg levetiracetam daily, and clearly smaller
FIGURE 3. Recording of auditory startle responses before leve-
tiracetam treatment. The thick arrow indicates stimulus onset,
thin arrows indicate response onset in MSS, masseter; OOc,
orbicularis oculi; SCM, sternocleidomastoid; BB, biceps brachii;
APB, abductor pollicis brevis; RF, rectus femoris; TA, tibialis
anterior; SOL, soleus. Two responses are superimposed.
MUSCLE & NERVE June 2006

FIGURE 4. Auditory startle response probability (A), onset la-
tency (B), and area-under-the-curve during 100 ms following
response onset (C), recorded from right masseter (MSS), orbic-
ularis oculi (OOc), sternocleidomastoid (SCM), biceps brachii
(BB), abductor pollicis brevis (APB), rectus femoris (RF), tibialis
anterior (TA), and soleus (SOL) muscles at baseline (open rect-
angles) and during treatment with 1,000 mg (black triangles),
2,000 mg (open circles), and 3,000 mg (black rectangles) leveti-
racetam daily, and 18 months after cessation of levetiracetam
treatment (open rhomboids). Normal values obtained in 10
healthy age-matched male control subjects are indicated by rect-
angular boxes in the background (upper and lower normal range,
intersected by median values).
than those at baseline (Fig. 2D). Motor evoked po-
tentials following transcranial magnetic stimulation
were of normal latency and amplitude in right and
left abductor digiti minimi muscles. ASR probability
Long-Loop Reflexes
was again 100% in all muscles, ASR latencies were
longer compared to baseline (P ⬍ 0.001, analysis of
variance, ANOVA), and ASR area-under-the-curve
was larger compared to levetiracetam treatment and
to baseline (P ⬍ 0.001, each), indicating again ex-
aggerated transcortical and brainstem reflexes (Fig.
4A–C).
DISCUSSION
In this patient, neurophysiological examination was
consistent with cortical hyperexcitability based on
exaggerated LLRs and increased cortical SEP ampli-
tudes following median nerve stimulation.24 Exag-
gerated ASRs suggested additional brainstem hyper-
excitability, as is often seen in posthypoxic brain
damage.3 There was, however, no clinical evidence
of cortical or reticular reflex myoclonus.24 The dim-
inution of LLR amplitude in the absence of concom-
itant H-reflex suppression, as indicated by a dose-
dependent reduction of the LLR/H ratio, provides
further human in vivo evidence of an inhibitory
effect of the antiepileptic drug levetiracetam on hy-
perexcitable cortical neurons. This is further sup-
ported by the suppression of increased cortical SEPs,
but contrasts with a relatively minor suppressive ef-
fect on the ASR, which is a brainstem reflex.8,9
The piracetam analog levetiracetam has been
found to be helpful in both short- and long-term
suppression of postanoxic myoclonus,4,10,12,22 and
has recently been suggested for the treatment of
spasticity and rigidity.5,21 Its mechanism of action has
not yet been fully elucidated, but seems to differ
from established mechanisms of other antiepileptic
drugs. The antimyoclonic effect has been related to
blocking of negative GABAA-receptor modulators
such as zinc,13 whereas antiepileptic effects have
been attributed to the inhibition of high-voltage-
gated N-type calcium channels15 and the reduction
of voltage-operated potassium currents.16
Neurophysiological investigation of the action of
levetiracetam in humans is scarce and has so far
been limited to the motor system.19,26,27 Resting and
active motor thresholds were found to be increased
by a single oral dose of 2,000 mg levetiracetam.19
Recruitment curve measurements revealed reduced
motor evoked potential amplitudes, particularly fol-
lowing high-intensity transcranial magnetic stimula-
tion,26,27 whereas cortical silent periods and intracor-
tical inhibition and facilitation remained unaffected
by a single oral dose of 3,000 mg levetiracetam.27
Thus, levetiracetam suppressed the corticospinal
neuronal response to transcranial magnetic stimula-
tion by preferentially affecting less excitable neu-
MUSCLE & NERVE June 2006 789
rons. Complete suppression of motor evoked poten-
tials following transcranial magnetic, but not
electrical, stimulation was encountered in a patient
receiving 3,000 mg levetiracetam daily over 2 years.10
The primary motor cortex is essential in early con-
solidation of motor learning,17 a process which
seems to be blocked by levetiracetam: pinch grip
acceleration, but not pinch force, was suppressed by
a single oral dose of 3,000 mg levetiracetam in a task
of rapid motor learning presumably by influencing
long-term potentiation of horizontal excitatory con-
nections within the primary motor cortex.26 The
confinement of suppressive effects of levetiracetam
to the cerebral cortex was supported by the lack of
concomitant changes in spinal and peripheral excit-
ability as measured by amplitude and persistence of
F-waves and compound muscle action potentials,26,27
according with the present findings of unchanged
H-reflexes with chronic levetiracetam up to 3,000 mg
daily.
Median nerve SEPs and LLRs are often enhanced
in cortical myoclonus, indicating cortical hyperexcit-
ability.24 In most cases, the larger the SEP, the more
conspicuous and widespread is the LLR24; however,
these two phenomena do not always correlate with
each other in this way.20 In the present patient with
no clinically manifest myoclonus, the LLR was much
more enhanced than the corresponding cortical SEP
before and after levetiracetam treatment (Fig. 1).
LLR latency and amplitude were compatible with
either LLR I or LLR II.2 Enhancement of the LLR, as
typically seen in cortical myoclonus, usually affects
the earlier LLR I2 rather than LLR II.23 The path-
ways mediating both SEPs and LLRs involve fast-
conducting cutaneous and Ia afferents, and subse-
quently dorsal columns to nucleus cuneatus, and
lemniscal pathways to the thalamus. The LLR II
pathway is then to the somatosensory cortex, then via
intracortical connections to the motor cortex, and
via corticospinal neurons to spinal motoneurons.2
The pathways for LLR I are less clear, but are also
transcortical.2 As both cortical SEPs and LLRs were
suppressed in a highly correlated, dose-dependent
manner within a relatively short period of time, a
common cortical site of action of levetiracetam
seems possible— but not provable—at the somato-
sensory cortex. LLR amplitude and LLR/H-ratio had
returned to near-baseline values 18 months after
cessation of levetiracetam treatment, confirming the
suppressive effect of the drug. Cortical SEP ampli-
tudes remained normal at follow-up, but this may be
attributed to the natural course of posthypoxic en-
cephalopathy rather than a long-term effect of leve-
tiracetam. Posthypoxic myoclonus may spontaneously
790 Long-Loop Reflexes
improve over time.3,29 The rate of improvement, how-
ever, is not known, and it remains speculative whether
cortical hyperexcitability without myoclonus decreases
over time as well. We are not aware of other reports
about potential effects of levetiracetam on SEPs or
LLRs.
Exaggerated ASRs may be the result of either
brainstem hyperexcitability or diminished inhibi-
tion. The cerebral cortex exerts powerful tonic and
phasic influences on brainstem auditory reflex cen-
ters via direct corticofugal projections to mesence-
phalic, pontine, and medullary reticular nuclei.30
Animal studies suggest that the sensory cortex likely
has a facilitatory effect on brainstem reflexes.1 The
temporal lobe also facilitates ASRs, as revealed by
audiospinal facilitation of the H-reflex.14 Exagger-
ated ASRs were observed on the hemiparetic side
following vascular hemispheric lesions of motor
pathways,6,28 in cerebral palsy,25 and following cere-
bral hypoxia.18 Thus, a disinhibited cerebral cortex
may subserve exaggerated ASRs, as seen before and
after levetiracetam treatment, which had a mild sup-
pressive effect on ASR magnitude, as indicated by a
tendency toward normal area-under-the-curve in
most muscles investigated. It remains speculative,
however, whether the observed reflex suppression is
due to direct influence at the brainstem level or to
an indirect effect via cortical structures.
In conclusion, the findings reported here local-
ize the site of action of levetiracetam to supraspinal,
likely cortical, structures, in agreement with its
known inhibitory effects on cortical motoneurons,
and support the drug’s efficacy in posthypoxic cor-
tical hyperexcitability.
Presented in part at the 8th International Congress of Parkinson’s
Disease and Movement Disorders, June 2004, Rome, Italy. The
author thanks Maria Hoch for expert technical assistance and
Ellen Quirbach for help with editing the article.
REFERENCES
1. Ascher P, Jassik-Gerschenfeld D, Buser P. Participation des
aires corticales sensorielles à l’elaboration de reponses motri-
ces extrapyramidales. Electroencephalogr Clin Neurophysiol
1963;15:246 –264.
2. Deuschl G. Long-latency reflexes following stretch and nerve
stimulation. In: Daube JR, Mauguière F, editors. Handbook of
clinical neurophysiology, Vol 1. Hallett M, editor. Movement
disorders. Amsterdam: Elsevier; 2003. p 285–294.
3. Frucht S, Fahn S. The clinical spectrum of posthypoxic my-
oclonus. Mov Disord 2000;15(Suppl 1):2–7.
4. Genton P, Gelisse P. Suppression of post-hypoxic and post-
encephalitic myoclonus with levetiracetam. Neurology 2001;
57:1144 –1145.
5. Hawker K, Frohman E, Racke M. Levetiracetam for phasic
spasticity in multiple sclerosis. Arch Neurol 2003;60:1772–
1774.
MUSCLE & NERVE June 2006
 6. Jankelowitz SK, Colebatch JG. The acoustic startle reflex in
ischemic stroke. Neurology 2004;62:114 –116.
7. Kofler M. Evozierte Potentiale. In: Hufschmidt A, Lücking
CH, editors. Neurologie compact. Stuttgart: Thieme; 2003. p
452– 462.
8. Kofler M, Müller J, Reggiani L, Valls-Solé J. Influence of
gender on auditory startle responses. Brain Res 2001;921:
206 –210.
9. Kofler M, Müller J, Reggiani L, Valls-Solé J. Influence of age
on auditory startle responses in humans. Neurosci Lett 2001;
307:65– 68.
10. Kofler M, Schauer R, Saltuari L. Long-term efficacy of leveti-
racetam in cortical myoclonus. Mov Disord 2002;17:S331.
11. Kofler M, Wenning GK, Poewe W. Cortical and brain stem
hyperexcitability in striatonigral degeneration. Mov Disord
1998;13:602– 607.
12. Krauss GL, Bergin A, Kramer RE, Cho YW, Reich SG. Sup-
pression of posthypoxic and postencephalitic myoclonus with
levetiracetam. Neurology 2001;56:411– 412.
13. Krauss GL, Mathews GC. Similarities in mechanisms and treat-
ments for epileptic and nonepileptic myoclonus. Epilepsy
Curr 2003;3:19 –21.
14. Liegeois-Chauvel C, Morin C, Musolino A, Bancaud J, Chau-
vel P. Evidence for a contribution of the auditory cortex to
audiospinal facilitation in man. Brain 1989;112:375–391.
15. Lukyanetz EA, Shkryl VM, Kostyuk PG. Selective blockade of
N-type calcium channels by levetiracetam. Epilepsia 2002;43:
9 –18.
16. Madeja M, Margineanu DG, Gorji A, Siep E, Boerrigter P,
Klitgaard H, et al. Reduction of voltage-operated potassium
currents by levetiracetam: a novel antiepileptic mechanism of
action? Neuropharmacology 2003;45:661– 671.
17. Muellbacher W, Ziemann U, Wissel J, Dang N, Kofler M,
Facchini S et al. Early consolidation in human primary motor
cortex. Nature 2002;415:640 – 644.
18. Paumgarten K, Kofler M, Nehkam-Heis D, Zorowka P, Felber
S, Saltuari L. Supraspinal origin of dysphagia in cerebral
hypoxia. Neurorehabil Neural Repair 2002;16:144.
Long-Loop Reflexes
19. Reis J, Wentrup A, Hamer HM, Mueller HH, Knake S, Tergau
F, et al. Levetiracetam influences human motor cortex excit-
ability mainly by modulation of ion channel function — a
TMS study. Epilepsy Res 2004;62:41–51.
20. Rothwell JC, Obeso JA, Marsden CD. On the significance of
giant somatosensory evoked potentials in cortical myoclonus.
J Neurol Neurosurg Psychiatry 1984;47:33– 42.
21. Rüegg SJ, Steck AJ, Fuhr P. Levetiracetam improves paroxys-
mal symptoms in a patient with stiff-person syndrome. Neu-
rology 2004;62:338.
22. Schauer R, Singer M, Saltuari L, Kofler M. Suppression of
cortical myoclonus by levetiracetam. Mov Disord 2002;17:
411– 415.
23. Shibasaki H. Myoclonus. Curr Opin Neurol 1995;8:331–
334.
24. Shibasaki H, Hallett M. Electrophysiological studies of myoc-
lonus. Muscle Nerve 2005;31:157–174.
25. Shimamura M. Neural mechanisms of the startle reflex in
cerebral palsy, with special reference to its relationship with
spino-bulbo-spinal reflexes. In: Desmedt JE, editor. New de-
velopments in electromyography and clinical neurophysiol-
ogy, Vol 3. Basel: Karger; 1973. p 761–766.
26. Sohn YH, Jung HY, Kaelin-Lang A, Hallett M. Effect of leve-
tiracetam on rapid motor learning in humans. Arch Neurol
2002;59:1909 –1912.
27. Sohn YH, Kaelin-Lang A, Jung HY, Hallett M. Effect of leve-
tiracetam on human corticospinal excitability. Neurology
2001;57:858 – 863.
28. Voordecker P, Mavroudakis N, Blecic S, Hildebrand J, De Beyl
DZ. Audiogenic startle reflex in acute hemiplegia. Neurology
1997;49:470 – 473.
29. Werhahn KJ, Brown P, Thompson PD, Marsden CD. The
clinical features and prognosis of chronic posthypoxic myoc-
lonus. Mov Disord 1997;12:216 –220.
30. Wright CG, Barnes CD. Audio-spinal reflex responses in de-
cerebrate and chloralose anesthetized cats. Brain Res 1972;
36:307–331.
MUSCLE & NERVE June 2006 791