Second edition

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Treatment
In the case of medication-associated tremor, dose reduction
is often sufficient; when this is not practical, for example
in lithium treatment, consideration may be given to
symptomatic treatment with propranolol (Lapierre 1976).
Treatment is otherwise directed at the underlying cause,
and most of these are discussed in the respective chapters.
For primary writing tremor, consideration may be given to
propranolol or primidone (Bain et al. 1995), botulinum
injections (Singer et al. 2005), or the use of a writing device
(Espay et al. 2005a). Orthostatic tremor may respond to
clonazepam or gabapentin (Onofrj et al. 1998; Rodrigues
et al. 2006), and Holmes’ tremor may respond to carbidopa/levodopa
(Remy et al. 1995; Samie et al. 1990; Tan
et al. 2001; Velez et al. 2002), clonazepam (Jacob and
Pratap Chand 1998), trihexyphenidyl (Krack et al. 1994),
or levetiracetam (Striano et al. 2007).
3.2 MYOCLONUS
Myoclonus is an important diagnostic sign, and, in addition
to close observation during the interview and examination,
patients should be questioned as to whether or not
they have had any jerking motions. In patients with delirium
the presence of myoclonus immediately suggests the
serotonin syndrome or Hashimoto’s encephalopathy; in
patients with dementia its presence immediately raises the
possibility of Creutzfeldt–Jakob disease.
Clinical description
Myoclonus consists of sudden rapid muscular jerks, followed
by a slower relaxation phase. These myoclonic jerks
may be focal, multifocal, or generalized, and they vary in
amplitude from being almost imperceptible to a gross
movement that can, in severe cases, throw an arm up or
knock a patient off balance. Although occasionally rhythmic
myoclonus may be seen, myoclonic jerks, in most cases,
occur at irregular intervals with a frequency varying from
only several per day up to multiple occurrences every
minute. Although in most cases myoclonus occurs spontaneously,
at times one may see stimulus-sensitive myoclonus
to either a sudden touch or a loud noise; furthermore, in
some cases myoclonus only occurs with ‘action’, as for
example when the patient extends the arms.
Etiology
In attempting to determine the cause of myoclonus, it is
useful to consider first whether the patient has a delirium
or a dementia, or has epilepsy. If the cause is still unclear
then one should consider the possibility of medication
toxicity and, if the diagnosis remains obscure, a number of
3.2 Myoclonus 75
other miscellaneous causes may be considered. Each of
these diagnostic possibilities is listed in Table 3.2 and
discussed further below.
In patients with delirium, the presence of myoclonus
strongly suggests the serotonin syndrome and a diligent
search should be made for recent use of a combination of
serotoninergic drugs. Hashimoto’s encephalopathy should
also be considered, especially in cases with ataxia or
seizures, and anti-thyroid antibodies should be tested for.
Metabolic deliria associated with myoclonus include uremic
encephalopathy and hyperosmolar non-ketotic hyperglycemia,
and these will be revealed on a chemistry profile.
Encephalopathic pellagra should be considered in alcoholics
with delirium, especially when there is also an associated,
albeit mild, parkinsonism. Baclofen withdrawal delirium, as
may occur when chronic, high-dose baclofen is abruptly
discontinued, or when a baclofen pump malfunctions, is
characterized, in addition to delirium, by myoclonus and
fever, and in many respects, including treatment response,
resembles the serotonin syndrome. Myoclonus may play a
minor role in the overall clinical picture of an arbovirus
encephalitis or an episode of complex partial status epilepticus.
Bismuth intoxication is rare but myoclonus plays a
prominent role in its symptomatology. Other intoxications
that may be characterized by myoclonus include those with
leaded gasoline, bromide, or mercury.
In patients with dementia, myoclonus immediately suggests
Creutzfeldt–Jakob disease; consideration should also
be given to post-anoxic encephalopathy. Subacute sclerosing
panencephalitis, in either children or adults, is rare but
is classically associated with myoclonus. A large number of
other disorders capable of causing dementia may also be
associated with myoclonus (see Table 3.2); however, in
these the myoclonus plays only a very minor role in the
overall clinical picture.
Certain epilepsies are characterized by myoclonus, and in
patients with grand mal or petit mal seizures the presence
of myoclonus should suggest the diagnosis of juvenile
myoclonic epilepsy or one of the progressive myoclonic
epilepsies, such as Unverricht–Lundborg disease, myoclonic
epilepsy with ragged red fibers, or Lafora body disease. In
adults, the very rare Kufs’ disease should also be considered.
Medications that are capable of causing myoclonus are
listed in Table 3.2 and of these the anti-epileptic drugs
gabapentin and lamotrigine stand out, as do the opioids
meperidine and hydromorphone. With regard to the
opioids, in some cases myoclonus may appear early on in
treatment; however, in others it is only after prolonged treatment
that the myoclonus appears; in these cases it is
suspected that the myoclonus is occurring due to the accumulation
of toxic metabolites and not secondary to the parent
compound (Mercadante 1998). This same late evolution
has also been noted with fluoxetine, with which years of treatment
may pass before myoclonus appears. Although little
need be said regarding the other medications, some words are
in order regarding tardive myoclonus. Tardive myoclonus is
a rare variant of tardive dyskinesia and, like all the tardive