EEG similarities between TWs and epileptiform sharp and slow wave
complexes were already noted by Foley (1950), who thought that TWs could
not always be clearly distinguished from ictal patterns associated with
petit mal epilepsy (hence the term "blunted spike and wave" he used in
describing TWs).
As a matter of fact,
differentiating NCSE from
triphasic wave encephalopathy (metabolic or structural) may be difficult
since TWs straddle the borders between epilepsy and encephalopathy
(Kaplan 1999). Especially when TWs have a frequency higher than I Hz
(Figure 4), the distinction between encephalopathy and NCSE may be
particularly difficult (Kaplan 1999).
Several investigators
proposed EEG criteria in order to clearly differentiate "triphasic-like
waves" in NCSE from nonepileptiform "true TWs" in encephalopathies. Litt
et al. (1998) reported that monorhythmic TWs could be distinguished
from epileptic patterns. An antero-posterior lag was considered to be
specific for hepatic encephalopathy (Reiher 1970, Karnze and Bickford
1984), but it was later demonstrated that this time lag is neither a
consistent feature of TWs nor of specific value regarding the type of
metabolic encephalopathy (Fisch and Klass 1988). The appearance of TWs
after noxious stimulation, which was considered a criterium to
differentiate nonepileptiform "true TWs" from the epileptic pattern, has
been recently challenged by the finding of stimulus-induced rhythmic,
periodic or ictal discharges
(SIRPIDs) (Hirsch et al. 2004). In a study
conducted by Husain et al. (1999) epileptic "triphasic-like waves" in
NCSE differed from nonepileptiform "true TWs" with an atypical
morphology and variable periods of amplitude suppression between
successive waveforms. Boulanger et al. (2006) conducted a retrospective
study comparing EEG patterns in patients with diagnosis of NCSE and in
patients with metabolic encephalopathy. Authors concluded that when
compared with nonepileptiform "true TWs", epileptiform discharges
associated with NCSE had a higher frequency, a shorter duration of phase
one, extra spike components, and less generalized background slowing.
Amplitude predominance of positive phase (wave 2) was similar. A phase
lag was absent in all cases of NCSE but present in 40.8% of patients
with nonepileptiform "true TWs." Noxious or auditory stimulation
frequently increased the nonepileptiform "true TWs" (51%) without effect
on epileptic "triphasic-like waves."
Unfortunately none of these
criteria, which would be of great utility, have been validated in an
observer-blinded study (Bauer and Trinka 2010), so that definitive
conclusions are still lacking.
CLINICAL AND DIAGNOSTIC ASPECTS
TWs
may be encountered in many conditions, especially in metabolic/toxic
disorders, but also in structural encephalopathies, and "triphasic-like
waves" may occur during status epilepticus. The most common
metabolic/toxic disturbances associated with this pattern are hepatic
failure, renal failure, and anoxia. Other metabolic disorders which must
be taken into account are hyponatremia, hypernatremia, hypercalcamia,
and hypoglycaemia. Sporadic TWs may also occur in stroke, cerebral
tumors, and elderly subjects with clinically advanced dementia. Physical
and neurological examinations usually show a decline of consciousness
ranging from mild confusion to stupor and coma with decreased
responsiveness.
Postanoxic TWs are frequently associated with myoclonus,
whereas TWs during hepatic or renal failure may be accompanied by
asterixis, a neurological sign consisting of recurrent sudden loss of
muscle tone in the outstretched and dorsiflexed hands.
The
following laboratory studies may be useful to determine the presence of a
metabolic encephalopathy: electrolytes, liver function tests, blood
urea urea nitrogen, creatinine, and lithium levels.
When laboratory
tests are not suggestive of a metabolic/toxic disorder and when
neurological examination shows focal neurological deficits, neuroimaging
studies (CT or MRI) should be performed to rule out a structural
encephalopathy.
The most useful way to distinguish between
"triphasic-like waves" occurring during status epilepticus and
nonepileptiform "true TWs" occurring during nonepileptic
encephalopathies is to evaluate whether electroclinical improvement
following benzodiazepine administration occurs.
CLINICAL AND TECHNICAL TIPS FOR A CORRECT INTERPRETATION OF TRIPHASIC WAVES
Improvement
in EEG pattern after intravenous administration of benzodiazepine may
occur in both NCSE and metabolic encephalopathies (Fountain and Waldman
2001, Brenner 2002), being therefore of limited utility in the
differential diagnosis.
As a matter of fact, instead of
considering only EEG modification after benzodiazepine or antiepileptic
drug administration, an electroclinical response should be taken into
account.
After intravenous antiepileptic drug or benzodiazepine
administration a clearly marked clinical improvement may occur in NCSE;
such a clinical improvement does not occur in metabolic
encephalopathies. The clinical response to benzodiazepines should be
considered when interpreting TWs.
The evaluation of the patient's
consciousness impairment is another clinical aspect which should be
considered when interpreting TWs.
In metabolic encephalopathies, the
impairment of consciousness is mild or moderate when TWs are seen,
almost never reaching the level of coma. On the other hand, patients
with anoxic encephalopathy following cardiopulmonary arrest are often in
deep coma, at the time when "triphasic-like waves" are recorded. The
epileptic nature of TWs may be suspected if they are associated with
spikes (which, however, may be absent in 31% of the cases [Boulanger et
al. 2006]). There are still no valid criteria for a differential
diagnosis between epileptic and nonepileptic TWs in coma following
cardiopulmonary arrest (Bauer and Trinka 2010).
As a consequence,
it is essential to interpret the EEG recording always considering
clinical features and laboratory data. When only EEG is taken into
account, electroencephalographers should not be dogmatic in
distinguishing metabolic periodic discharges from seizure-related
periodic discharges, because such a distinction is often not possible
(Chong and Hirsch 2005).
CONCLUSION
In conclusion,
nonepileptic "true TWs" with sharply contoured morphology may resemble
epileptic patterns encountered in NCSE and may lead to misinterpretation
and overinterpretation of this pattern as epileptic "triphasic-like
waves" if only EEG is considered.
Both the electroclinical response to
benzodiazepines and evaluation of consciousness impairment should be
considered when interpreting TWs. Evaluating only the EEG without
considering also clinical and laboratory findings is not only useless
and meaningless, but it may even lead to serious consequences.
