Vol. 36 No.
4 October 2008 Letters
References
1. De Graeff A, Dean M. Palliative sedation therapy
in the last weeks of life: a literature review and rec-
ommendations for standards. J Palliat Med 2007;10:
67e85.
2. Anon. Prescribing in palliative care. In: British
National Formulary, Vol. 53. London: BMJ Publish-
ing Group, 2007.
3. Orentlicher D. The Supreme Court and physi-
cian-assisted suicidedrejecting assisted suicide but
embracing euthanasia. N Engl J Med 1997;337:
1236e1239.
4. Mistraletti G, Donatelli F, Carli F. Metabolic and
endocrine effects of sedative agents. Curr Opin Crit
Care 2005;11:312e317.
5. Berger JM, Ryan A, Vadivelu N, et al. Ketamine--
fentanyl-midazolam infusion for the control of
symptoms in terminal life care. Am J Hosp Palliat
Care 2000;17(2):127e132.
6. Okon T. Ketamine: an introduction for the pain
and palliative medicine physician. Pain Physician
2007;10:493e500.
7. Rang HP, Dale MM, Ritter JM, Moore P. Pharma-
cology, 5th ed. Edinburgh: Churchill Livingstone,
2003.
8. Mercadante S, Arcuri E, Tirelli W, Casuccio A.
Analgesic effect of intravenous ketamine in cancer
patients on morphine therapy: a randomised, con-
trolled, double-blind, crossover, double-dose study.
J Pain Symptom Manage 2000;4:246e251.
9. Yang CY, Wong CS, Chang JY. Intrathecal ket-
amine reduces morphine requirements in patients
with terminal cancer pain. Can J Anaesth 1996;43:
379e383.
10. Bell R, Eccleston C, Kalso E. Ketamine as an ad-
juvant to opioids for cancer pain. Cochrane Data-
base Syst Rev 2003;1. CD003351.
Spinal Myoclonus in Advanced
Cancer
To the Editor:
Spinal myoclonus is a rare but extremely dis-
tressing clinical scenario. To our knowledge,
we report the first case of spinal myoclonus
heralding a terminal event in advanced
malignancy.
Case
A 39-year-old male surfing instructor, with
a history of rapidly progressive metastatic
e3
melanoma and a history of oligodendroglioma
and complex partial seizures, was transferred
to a tertiary-referral oncology hospital for reha-
bilitation after undergoing surgical decom-
pressive laminectomy and spinal fixation to
treat malignant spinal cord compression. This
had been diagnosed one month previously af-
ter magnetic resonance imaging (MRI) had
demonstrated vertebral metastatic disease at
T9 and impending cord compression at L2.
The initial postoperative period was uncom-
plicated and the patient mobilized with the aid
of a spinal brace. After two weeks, however, he
developed shooting pain and progressive weak-
ness affecting his right leg. His weakness pro-
gressed and power in both legs was assessed
as 1/5 on a 6-point scale, where 0 represents
complete paralysis and 5 normal power, 18
days postoperatively. In addition, he was found
to have bilateral lower limb hypertonia, hyper-
reflexia, and foot paresthesia. MRI demon-
strated progressive malignant disease at T9
and L2, and given that no further surgical in-
tervention was possible, treatment with high-
dose dexamethasone and radiotherapy (16 Gy;
T8eL3) was started.
Over the following days, the patient’s pain
was treated with dose adjustment of his long-
standing antiepileptic medications, carbama-
zepine and levetiracetam, in addition to
gabapentin, ketamine, and morphine sulfate,
with good effect. The morphine sulfate was sub-
sequently converted to subcutaneous alfentanil
after he developed an intestinal ileus, primarily
as a result of the spinal cord compression, but
contributed to by morphine’s gastrointestinal
motility-inhibitory effects. His bowel motility
improved after this change, and during
radiotherapy.
On the last day of radiotherapy, the patient
developed bilateral, severe, intermittent lower
limb twitching, with a frequency of up to 40
twitches per minute. This was associated with
severe, episodic back pain and bilateral, shoot-
ing leg pain. He indicated that he had experi-
enced similar symptoms before surgery but
that they had always been mild and short-lived.
On examination, he was found to have hyper-
reflexia, with clonus to light touch, hypertonia
and allodynia below both knees. Based on
findings from the history, examination, and
previous investigations, a diagnosis of spinal
myoclonus was made.
e4
The patient’s opioid requirement increased
markedly, from a total 24-hour dose of 35 mg
of alfentanil subcutaneously (equivalent to
approximately 350 mg diamorphine) to a 24-
hour dose of 82 mg alfentanil. In addition,
he had received a total of 50 mg of subcutane-
ous midazolam over that period to treat his
pain, myoclonus, and distress. These agents
provided only minimal pain relief, and did
not reduce the myoclonic frequency. The most
helpful measure at this stage was a positional
adjustment, whereby his legs were flexed at
the hip and knee and pushed proximally.
Advice was sought from a local neurology
unit, after which 1 mg of subcutaneous clona-
zepam was given and the levetiracetam dose
was increased from 500 mg twice a day to
750 mg twice a day. A single dose of 100 mg
of subcutaneous phenobarbitone was adminis-
tered, and the ketamine dose was converted to
40 mg subcutaneously over 24 hours.
Despite these measures, the patient became
increasingly distressed and requested sedation
to relieve him of his symptoms. An epidural
was considered but was not possible due to ex-
tensive disease throughout the spine.
After urgent multidisciplinary discussion
with the patient and his wife, the decision to
sedate for symptom control was taken. He
was transferred to the Critical Care Unit for
close monitoring of his condition and to en-
able easy and rapid titration of the sedation.
Sedation was carried out using the intravenous
anesthetic agent propofol. The initial aim was
to attempt reversal of the sedation once the
antimyoclonus medications began to take ef-
fect. After further specialist neurological ad-
vice, baclofen, starting at a dose of 5 mg
three times a day, was added to the treatment
regimen, administered via a nasogastric tube
in addition to his other oral medications.
The myoclonus resolved after propofol was
started and titrated upward, but any attempt
to reduce the dose below 300 mg per hour re-
sulted in its return, accompanied by severe
pain and distress. At this dose, the patient
was unable to communicate. After two days
of close monitoring and discussions with his
wife and with the patient himself, when possi-
ble, his symptoms began to worsen and re-
quired the dose of propofol to be further
increased. It became apparent that this was
a terminal event and a decision to continue
Letters Vol. 36 No. 4 October 2008
sedation on the palliative care ward was agreed
to by all parties. The patient remained com-
fortable, with no further evidence of myoclo-
nus until his death three days later.
Before staring sedation with propofol, the
patient asked the authors to write up his case
with the aim of increasing awareness of spinal
myoclonus, in the hope that others would not
have to suffer as he had from this rare and
distressing symptom.
Comment
This case demonstrates a rare but significant
sequela of disease affecting the spinal cord,
more commonly discussed in relation to non-
malignant disease. To the authors’ knowledge,
this is the first report of spinal myoclonus as
a terminal event in a patient with advanced
malignancy.
Myoclonus, a sudden involuntary jerking of
a muscle or group of muscles, may arise in
any region of the central nervous system.1
Spinal myoclonus, also sometimes referred
to as propriospinal myoclonus, refers to invol-
untary rapid movements of the extremities
that may be caused by any insult to the spinal
cord, usually occurring 30 to 40 times per
minute. Cases have been documented as a re-
sult of spinal anesthesia, intrathecal catheteri-
zation, trauma, disc herniation, tumors, and
syringomyelia. In these cases, myoclonus has
usually occurred in those areas supplied by
nerves originating at or below the level of
the spinal lesion.2
The movements show considerable variation
in their precipitants and nature, and may be
rhythmic or dysrhythmic,3 and spontaneous
or related to changes in body position, acous-
tic startle, or tendon strike. Generalized jerk-
ing is usually absent during sleep, but
insomnia is often a feature of this disruptive
and distressing symptom. In some cases, the
myoclonus is temporary but it can persist.
There has been one previously reported case
of myoclonus associated with a thoracic verte-
bral fracture, which progressed into a myo-
clonic ‘‘status’’ associated with respiratory
failure and loss of consciousness, resolving
after intravenous infusion of lorazepam.4
The exact pathophysiology of spinal myoclo-
nus is unclear, but it is thought that
Vol. 36 No. 4 October 2008
spontaneous repetitive discharges of cells in
the anterior horn or loss of inhibitory function
of local dorsal horn neurons5 may contribute.
An association with alterations in glycine or
GABAergic transmission in the spinal cord
has been postulated.6
Most of the literature on spinal myoclonus is
based on case reports and small case series.
There is little evidence underlying the pharma-
cological treatment of myoclonus, and symp-
tomatic treatment is often unsuccessful. The
use of several agents has been reported, with
varying degrees of success. Clonazepam, in
doses up to 6 mg per day, has been found to
have some symptomatic benefit,4 as has levetir-
acetam (500e1250 mg per day) in patients
with subacute, evolving spinal cord injuries.6
A recent case report has, however, suggested
that levetiracetam may actually worsen myoclo-
nus in some patients.7 Baclofen, a g-aminobu-
tyric acid (GABA) analog with spinal reflex
inhibitory activity, which has a long history of
use in the treatment of spasticity, has been
used orally and intrathecally to treat spinal my-
oclonus.8 Intramuscular botulinum toxin in-
jection has been used with lasting success in
one case,5 and valproate has been found to
give a partial response in up to 50% of cases.9
Other successful agents include diazepam,
carbamazepine, tetrabenazine, gabapentin
and topiramate.
There have been several case reports of spi-
nal myoclonus but this is the first as a terminal
event in a palliative care setting. The lack of
clear, evidence-based treatment options in
this setting and the rapid progression of the
patient’s disease contributed to a significant
amount of distress for him, his wife, and the
staff caring for him, at a time when alleviation
of these factors was paramount. It is unclear
whether his symptoms would have improved
if his condition had allowed more time for
antimyoclonus medication, such as baclofen,
to have its desired effect. Given his advanced,
progressive malignancy, time was severely re-
stricted. Although the patient suffered greatly
during the final stages of his life, we believe
that his suffering would have been much
worse had he not been an inpatient in an en-
vironment with the means to safely and effec-
tively sedate patients intravenously. We advise
that, especially in palliative care settings, early
identification, assessment, and treatment are
Letters e5
essential to avoid the severe pain and distress
that can result from spinal myoclonus.
Joanne Droney, MB BCh, MRCP
Vinnie Nambisan, MB BCh, MRCP
Anne-Louise Jennings, MA, MB BS,
MRCGP, FRCP
Julia Riley, MB, BCh, MRCGP, FRCP
Royal Marsden Hospital
London, United Kingdom
doi:10.1016/j.jpainsymman.2008.07.001
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lonus. Neurophysiol Clin 2006;36(5e6):281e291.
2. Borg M. Symptomatic myoclonus. Neurophysiol
Clin 2006;36(5-6):309e318.
3. Celik Y, Bekir DC, Karaca S, Kose Y. Transient seg-
mental spinal myoclonus due to spinal anaesthesia
with bupivacaine. J Postgrad Med 2003;49(3):286.
4. Manconi M, Sferrazza B, Iannaccone S, et al. Case
of symptomatic propriospinal myoclonus evolving
toward acute ‘‘myoclonic status. Mov Disord 2005;
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5. Campos CR, Limongi JC, Machado FC,
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6. Keswani SC, Kossoff EH, Krauss GL, Hagerty C.
Amelioration of spinal myoclonus with levetirace-
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457e458.
7. Lim LL, Ahmed A. Limited efficacy of levetirace-
tam on myoclonus of different etiologies. Parkin-
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8. Fouillet N, Wiart L, Arne P, et al. Propriospinal
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9. Krauss GL, Mathews GC. Similarities in mecha-
nisms and treatments for epileptic and nonepileptic
myoclonus. Epilepsy Curr 2003;3(1):19e21.
Re: Relief of Incident Dyspnea
in Palliative Cancer Patients
To the Editor:
I have read with great interest the excellent
study carried out by Charles et al.,1 which con-
tributes greatly to attempts to alleviate breath-
lessness toward the end of life. There are very
few randomized studies on this topic, and even