EEG in Dementia and Encephalopathy

EEG in Dementia and Encephalopathy
Author: Eli S Neiman, DO; Chief Editor: Selim R Benbadis, MD more...

Updated: Dec 17, 2013
Overview
For some time, electroencephalography (EEG) has been employed clinically as a measure of brain function in the
hope of determining and differentiating certain functional conditions of the brain. It is used in patients with cognitive
dysfunction involving either a general decline of overall brain function or a localized or lateralized deficit. This article
primarily addresses the clinical use of EEG in the evaluation of dementias and encephalopathies. In addition,
aspects of digital EEG and other newer developments are discussed briefly.
Definiti on of dementia
Criteria from Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR)
should be used in the diagnosis of dementia. Clinical dementia is a fairly broad-based decline of brain function, and
most definitions center on the patient's intellectual decline and memory dysfunction. This is, however, a fairly
simplistic approach, in that dementia encompasses much more than these fundamental deficits. Many dementias
have specific distinguishing features.
The process that constitutes normal aging is still an ongoing debate. As our understanding and testing procedures
develop, more people are being classified as suffering from some type of dementia.
In 1998, Widagdo et al performed a quantitative EEG (QEEG) study of age-related changes during cognitive tasks.
[1]
This study revealed no conclusive differences between the young and the elderly. Cognitive decline, unlike normal
aging, is associated with alterations in the temporospatial characteristics of EEG. The diagnosis of the initial stages
of dementia is based mainly on neuropsychological testing and clinical suspicion. The EEG findings are nonspecific
(see the image below).
EEG in dementia.
EEG findings in dementi a
In early dementia, the resting alpha frequency declines. Most authors agree that the lower limit of normal alpha
frequency is 8 Hz (cycles per second). Medications can slow the posterior dominant rhythm; therefore, medication
effect should always be excluded. In assessing the frequency of the alpha rhythm, alerting maneuvers are essential
in order to ensure that the patient is in the best awake state and not drowsy. Computerized methods, such as EEG
spectral analysis, coherence, and complexity (ie, correlation dimension), have been demonstrated to correspond to
cognitive function.
[2]
Stevens et al recorded EEGs during 2 resting conditions (eyes closed and eyes opened) and 2 tasks (mental
arithmetic and a lexical decision), with the aim of determining which temporal and spatial EEG descriptors change
with cognitive decline and normal aging.
[3]
The EEGs were analyzed by using EEG microstates. The primary findings
were a significant increase in the number of ultrashort EEG microstates and a reduction in the average duration of
EEG microstates in cognitively impaired and demented patients.
Cognitive impairment was associated with a reduction or loss of EEG reactivity.
[3]
In contrast, no alterations in
temporal or spatial EEG descriptors were found in normal aging. Cognitive tasks did not add to the information
already obtained during the resting states. The reduction in EEG microstate duration correlated with loss of cognitive
function.
Therefore, temporospatial analysis of the EEG record is a useful indicator of cortical dysfunction in dementia and
correlates with the degree of cognitive impairment. Apparently, temporospatial analysis may be useful in
distinguishing patients with dementia from those experiencing normal aging. Whether these data contribute
significant additional information to the clinical data in evaluating dementia is unclear.
Definiti on of encephalopathy
Encephalopathy represents a brain state in which normal functioning of the brain is disturbed temporarily or
permanently. Encephalopathy encompasses a number of conditions that lead to cognitive dysfunction. Some of
these conditions are multifactorial, and some have an established cause, such as hepatic or uremic encephalopathy.
Because the EEG patterns in most dementias and encephalopathies demonstrate few specific features, they are
discussed together.
Some notable exceptions include Creutzfeldt-J akob disease (CJ D) and subacute sclerosing panencephalitis (SSPE);
however, no specific patterns exist for most dementias and encephalopathies. Other conditions, such as hepatic and
renal encephalopathies, carry distinguishing features; nevertheless, similar patterns may be seen in a fairly wide
range of illnesses under certain conditions.
EEG findings in encephalopathy
In general, the most prominent feature of the EEG record in encephalopathies (if there is a change) is slowing of the
normal background frequency. Over the course of the disease if serial EEGs are performed, disorganization of the

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record may develop gradually. Reactivity to photic or other type of external stimulation may be altered. If a QEEG is
performed, it may show a frequency shift or decreased interhemispheric coherence of background frequencies.
Some conditions are associated with an increase in seizure frequency, and in such cases, epileptic activity may be
recorded.
[4]
In a given context, EEG can play a clinically useful role, especially because functional MRI, positron emission
tomography (PET), and single-photon emission computed tomography (SPECT) are either still in an experimental
stage or require special settings that are not widely available.
Use of digital EEG data
Although the following sections frequently cite digital EEG data, these data primarily represent digital analysis of
clinical EEG recordings. The referenced data are presumed to be based on an EEG recording that is read by a
clinician; presently, recording is done with computerized technology for ease and also for availability for further
analysis. Various mathematical transforms are available after the initial clinical interpretation (eg, coherence, Fourier
transform, wavelets, and microstates; see Digital EEG). These allow further comparisons with norms and control
groups but should be interpreted in conjunction with the primary EEG reading.
Dementia
Alzheimer di sease
Electroencephalography (EEG) is the only clinical diagnostic instrument that directly reflects cortical neuronal
functioning. Although the EEG may be normal or minimally disturbed in a number of patients in the initial stages of
Alzheimer disease (AD), an abnormal EEG usually is recorded later in the course. A large percentage of patients
with moderately severe to severe AD exhibit abnormal EEGs.
In 1981, Stigsby reported diffuse increases of delta and theta frequencies in AD, as well as decreases in the alpha
and beta frequency ranges. Frontal slowing was also seen and was more prominent anterior to the sylvian fissure,
whereas decreased blood flow was more prominent posterior to the sylvian fissure. These findings may be explained
by the observation that EEG reflects the functional decline of the anterior structures, whereas the flow decrease
correlates more with the structural damage to the parietal lobe. Frontal slowing probably reflects the loss of
functioning of the frontal cholinergic system.
[5]
Wada et al showed that EEG coherence provides a measure of functional correlation between 2 EEG signals.
[6]
They examined intrahemispheric EEG coherence at rest and during photic stimulation in 10 patients with dementia of
the Alzheimer type. In the resting EEG, patients with AD had significantly lower coherence than gender and
age-matched healthy control subjects in the alpha-1, alpha-2, and beta-1 frequency bands.
EEG analysis during photic stimulation demonstrated that the patients had significantly lower coherence irrespective
of the stimulus frequency.
[6]
The changes in coherence from the resting state to the stimulus condition showed
significant group differences in the region of the brain primarily involved in visual functioning. The patients had
significantly lower coherence of their EEG reactivity to photic stimulation at 5 and 15 Hz over the posterior head
regions.
Thus, patients with AD may have an impairment of interhemispheric functional connectivity in both nonstimulus and
stimulus conditions, which suggests a failure of normal stimulation-related brain activation in AD.
J elic et al found a positive correlation between levels of tau protein in the cerebrospinal fluid (CSF) and the EEG
alpha/delta ratio. In a subgroup with high CSF tau levels, a strong relationship between EEG alpha/theta and
alpha/delta power was found. No such correlation was found in healthy controls and mildly cognitively impaired
individuals with elevated CSF tau levels.
[7]
Locatelli et al used EEG coherence to evaluate the functionality of cortical connections and to obtain information
about synchronization of regional cortical activity in patients with suspected AD.
[8]
Alpha coherence was decreased
significantly in 6 patients. Significant delta coherence increase was found in a few patients between frontal and
posterior regions. The group with AD demonstrated a significant decrease of alpha-band coherence in the temporal-
parietal-occipital areas; this was expressed to a greater extent in patients with more severe cognitive impairment.
The investigators theorized that these abnormalities could reflect 2 different pathophysiologic changes, as follows
[8]
:
The alpha coherence decrease could be related to alterations in corticocortical connections
The delta coherence increase suggests lack of influence of subcortical cholinergic structures on cortical
electrical activity
Strik et al found that the microstates of the resting EEG of patients presenting with mild or moderately severe
dementia of the Alzheimer type demonstrated a significant anteriorization of the microstate fields, and the duration of
sustained microstates was reduced.
[9]
These differences were more important than the diffuse slowing. The
measurements of microstates may be useful in the early diagnosis of AD.
[9]
Muller et al conducted a study comparing single-photon emission computed tomography (SPECT) and quantitative
EEG (QEEG) and concluded that whereas QEEG might be as useful as SPECT brain scanning in staging the
disease, the correlation with clinical status was weak.
[10]
Akrofi et al, employing an automated coherence-based pattern recognition system involving multiple discriminant
analysis (MDA) and k-means clustering coherence features from EEG obtained from 56 subjects, were able to
distinguish patients with AD from patients with mild cognitive impairment (MCI) and from age-matched controls. This
suggests that patients with AD may have a greater number of damaged cortical neurons than patients with MCI and
that MCI may be an intermediate step in the development of AD.
[11]
Siennicki-Lantz et al studied the relation of cerebral white-matter lesions to AD and found that cerebral blood flow
(CBF) in white matter correlated with systolic blood pressure and multichannel EEG in senile dementia of the
Alzheimer type.
[12]
The presence and functional significance of white-matter lesions in the aging brain or in dementia and the relation of
these lesions to blood pressure are unsettled issues. White-matter lesions occur in both cerebrovascular disease
and AD. Probably, the white-matter lesions in hypertensive patients are not related to AD but are simply coexisting
with it. Their influence on the overall expression of the degree of dementia is unclear; however, it seems intuitively
plausible that the lesions should be causing additional cognitive dysfunction.
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Siennicki-Lantz et al observed significantly lower white-matter CBF (WMCBF) in patients with AD than in controls.
[12]
This was more obvious in the posterior cerebral region (ie, the parietal-temporal-occipital area). QEEG from the
posterior cerebral regions correlated with WMCBF. Systolic blood pressure was significantly lower in the AD group
and was correlated positively with WMCBF in the posterior and anterior brain regions.
Epileptiform activity may occur more frequently in patients with AD than in the general population; clinical tonic-clonic
seizures can occur. Bilateral synchronous periodic epileptiform discharges (BiPEDs) (see the first image below),
such as triphasic waves (TWs) (see the second image below), may be recorded in AD, usually in the late stages (see
Triphasic Waveforms).
Bilateral periodic epileptiform discharges (BiPEDs).
Triphasic waves, maximum amplitude bilateral frontal.
These findings are not specific for AD because they most often are observed in metabolic disorders, particularly
hepatic encephalopathy and other degenerative diseases, such as Creutzfeldt-J akob disease (CJ D). Although there
is a good correlation between severity of EEG abnormalities and cognitive impairment, epileptiform discharges or
TWs are not predictors of seizures. EEG often can be useful for excluding a superimposed reversible metabolic
etiology of dementia and for confirming CJ D when the dementia is rapidly progressive.
To investigate the relation between QEEG band powers and CBF, Rodriguez et al studied 42 patients with suspected
AD and 18 healthy elderly controls and attempted to differentiate patients with AD from the controls by measuring
QEEG and CBF.
[13]
Regional CBF and QEEG were correlated, especially in the right hemisphere. Significant
correlations were found between Mini Mental State Examination (MMSE) scores and relative power of the 2- to 6-Hz
and 6.5- to 12-Hz bands on either side and between MMSE scores and left regional CBF; the correlation between
MMSE scores and right regional CBF was less strong.
Used together, QEEG and regional CBF had a sensitivity of 88% and a specificity of 89%, with a total accuracy of
88.3%.
[13]
. QEEG alone showed an accuracy of 77% in the whole group and 69% in those with mild AD; regional
CBF alone had an accuracy of 75% in the whole group and 71% in those with mild AD. This study suggests that
QEEG and regional CBF measurements, when used together, are reasonably accurate in differentiating AD from
healthy aging.
Scheriter et al used clinical examinations, QEEG, neuropsychological testing and neuroimaging to see if distinctions
could be made between patients with AD, mixed dementia (vascular), and controls; they found that as would be
expected, patients with mixed dementias had more subcortical lesions with increased slow frequency power, which
suggested subcortical pathology.
[14]
The QEEG high-frequency power was normal in mixed dementia and decreased in AD, probably reflecting the
cortical pathology seen in AD.
[14]
Hachinski scores and neuropsychological testing showed little difference between
mixed dementia and AD. QEEG and neuroimaging may be of great use in diagnosing and differentiating these
dementia types.
A study that presented a frequency band analysis of AD EEG signals suggested that optimized frequency bands
may improve existing EEG-based diagnostic tools for AD, though additional testing on larger AD datasets will be
required to verify the effectiveness of the proposed approach.
[15]
Oscillatory brain dynamics in AD appear to differ according to age at onset. Young AD patients present with more
severe slowing of spontaneous oscillatory activity than old AD patients, which is most pronounced in the posterior
brain areas. This finding supports the hypothesis that early-onset AD presents with a distinct endophenotype.
[16]
The apolipoprotein E (ApoE) sigma-4 allele is a risk factor for late-onset AD and may have an impact on cholinergic
function in AD. Because the cholinergic system has an important role in modulating EEG, impairment of this system
may have some relation to the EEG slowing that is characteristic of AD progression.
Lehtovirta et al studied the relation of ApoE to EEG changes.
[17, 18]
The QEEG of 31 patients with AD was recorded
at the early stage of the disease and after a 3-year follow-up. Patients with AD were divided into several subgroups
according to the ApoE sigma-4 allele (ie, 2 sigma-4, 1 sigma-4, and 0 sigma-4). These subgroups did not differ in
clinical severity or duration of dementia.
The AD patients carrying the sigma-4 allele had more pronounced slow-wave activity than AD patients without the
sigma-4 allele, although the disease progression rate did not change.
[17, 18]
These differences in EEG may suggest
differences in the degree of the cholinergic deficit in these subgroups.
The typical electrophysiologic correlates of myoclonus in AD are similar to those of cortical reflex myoclonus, with a
focal, contralateral negativity in the EEG preceding the myoclonic jerk. The electrophysiologic correlate of
polymyoclonus that can be seen in AD and other pathologic states is a bifrontal negativity in the EEG that precedes
the myoclonic jerk. This new type of electrophysiologic correlate of myoclonus may reflect activity of a subcortical
generator.
Dementia with Lewy bodies
In a study comparing patients with dementia with Lewy bodies (DLB) and patients with AD, Briel et al found that 17
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of the total 19 records from the patients with DLB) were abnormal.
[19]
Thirteen showed loss of alpha activity as the
dominant rhythm, and half had slow wave transient activity in the temporal lobe areas. This slow wave transient
activity correlated with a clinical history of loss of consciousness. The patients with AD were less likely to show
transient slow waves and tended to have less marked slowing of dominant rhythm.
The greater slowing of the EEG in DLB than in AD may be related to a greater loss of choline acetyltransferase
found in DLB. Temporal slow wave transients may be a useful diagnostic feature in DLB and may help to explain the
transient disturbance of consciousness, which is characteristic of DLB.
Pick disease
Pick disease, which is a frontotemporal dementia, is much less common than AD. The age of onset is earlier than
that of AD. The EEG is less abnormal than in AD, especially in the early stages. Posterior alpha rhythm is more
preserved. Theta and delta are increased. Frequency analysis may demonstrate a difference at a time when simple
visual reading may not pick up a clear abnormality. The major feature of Pick disease is a decline in judgment and
insight with relative early preservation of memory.
Because EEG correlates poorly with the clinical symptoms, impressive EEG changes are not observed in this
condition. Blood flow measurements correlate with thinking processes; Ingvar demonstrated these changes in
1977.
[20]
Stigsby demonstrated a decrease in anterior blood flow in patients with Pick disease.
[5]
Because the
anterior cholinergic system is relatively preserved in Pick disease, the EEG changes are not prominent frontally.
Gemignani et al studied sleep in Pick disease with a longitudinal polysomnographic and fluorodeoxyglucose positron
emission tomography (FDG-PET) study,
[21]
documenting sleep fragmentation, short rapid-eye-movement (REM)
latency, and a severe reduction of slow wave sleep, with relatively preserved non-REM (NREM)-REM sleep cycles.
PET scan revealed severe cerebral glucose metabolic reductions in the frontal and temporal areas.
Postmortem study showed severe neuronal loss, spongiosis, and gliosis most marked in cortical layers I, II, V, and
VI.
[21]
In vivo, neurometabolic and postmortem neuropathologic data are consistent with and indicative of a severe
dysfunction of intra- and transhemispheric regional connectivity and of corticothalamic circuits. These findings
suggest that the decreased cortical and subcortical connectivity may have been the main pathophysiologic
mechanism responsible for delta sleep reduction and the cognitive decline.
Huntington disease
Huntington disease is a genetic condition characterized by movement disorder (primarily chorea), cognitive
impairment, and psychotic features. The degree of such symptoms varies widely. The EEG changes show gradual
and progressive slowing over time. The amplitude also attenuates as the disease progresses. About 30% of the
patients have very-low-voltage EEGs, with amplitudes below 10 V. Hyperventilation as a rule does not increase the
background voltage as it usually does in healthy subjects. About 3% of the patients show epileptiform activity; they
tend to be juvenile cases.
The EEG has not been proven to be of any predictive value in identifying future affected family members. Genetic
testing is far more useful.
Progressive supranuclear palsy
Progressive supranuclear palsy (PSP) causes decreased ocular motility, rigidity, dementia, impaired postural
reflexes, and, histologically, midbrain atrophy and abnormal tau deposition. Usually, the degree of dementia is not
severe. The EEG in PSP may initially be normal but eventually shows increasing delta and theta activity, as was the
most common finding reported by Fowler and Harrison in 1986. These authors found that the delta often was
rhythmic with frontal accentuation.
Gross et al found a decrease in background frequency of 6-7 Hz and delta activity over the temporal regions.
[22]
Su
and Goldstein et al found initial EEG patterns to be normal in 8 of 12 (67%) of patients with PSP.
[23]
With disease
progression, they found background slowing and frontal intermittent rhythmic delta activity (FIRDA) (see below) in
this population.
Frontal intermittent rhythmic delta activity (FIRDA).
Through the use of QEEG recordings in 6 patients with PSP compared with controls, Montplaisir et al found slowing
over the frontal lobes in the waking state, with neuropsychological testing confirming this frontal lobe dysfunction.
Abnormalities of sleep architecture with REM sleep abnormalities were seen as well.
Corticobasal degeneration
Corticobasal degeneration (CBD) is a neurodegenerative disorder and tauopathy characterized by progressive
dementia and asymmetrical rigidity and limb apraxia. Tashiro et al found prominent focal slowing on EEG in the
anterior and temporal head regions in early CBD in 8 of 10 patients studied.
[24]
Frontal intermittent rhythmic delta
activity was also observed but was not found to be specific to CBD.
Roche et al evaluated 5 patients with CBD, of whom none had REM behavioral disorder (as is often seen in many
neurodegenerative disorders) or excessive daytime sleepiness. All 5 patients with CBD had insomnia, 4 had periodic
limb movements or restless legs syndrome, and 2 had sleep respiratory disorders.
[25]
Parkinson disease
The EEG is frequently normal in Parkinson disease (PD). In advanced cases, however, marked slowing is noted.
Sleep may be markedly abnormal with frequent awakenings, prolonged sleep latency, reduced REM sleep, periodic
leg movements and increased frequency of REM behavioral disorder.
Wszolek et al studied patients with rapidly progressive familial parkinsonism and dementia with pallidopontonigral
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degeneration (PPND).
[26]
The patients had PPND linked to chromosome 17q21-22; 11 EEGs of 9 patients were
studied. EEGs revealed normal findings early in the disease and diffuse slowing that became more prominent with
disease progression.
Serizawa et al, using QEEG to compare PD patients with age-adjusted controls, also found diffuse slowing in the
patients with PD.
[27]
Electromyography (EMG) and nerve conduction studies (NCSs) showed no abnormalities.
Visual evoked potentials (VEPs) and sensory evoked potentials (SEPs) were normal. The clinical neurophysiologic
study findings were consistent with a cortical and subcortical degenerative process.
With clinical deterioration, progressive decline is seen in the mean parietal frequency and background rhythms.
Theta and theta-delta mixture may be recorded bilaterally in the posterior head regions. After stereotactic surgery,
focal theta or delta slowing may be observed.
Korsakov syndrome
Obraztsova et al, in a study involving 32 patients (21 with reversible and 11 with chronic Korsakov syndrome of
traumatic origin) and 20 healthy controls, found that EEG beta activity (13-20 Hz) in the frontobasal and brainstem
locations had negative prognostic significance in Korsakov syndrome. Most typically, patients with Korsakov
syndrome have abnormal EEGs with slowing in the theta and delta frequencies.
[28]
Vascular Dementia
Binswanger disease
Binswanger disease usually demonstrates slowing of background and a nonspecific pattern. Kuroda et al reported
other patterns, describing a 72-year-old patient with von Recklinghausen disease who exhibited akinetic mutism
within 6 months of the onset of dementia. Encephalography (EEG) demonstrated periodic synchronous discharges
(PSDs), suggesting Creutzfeldt-J akob disease (CJ D). Computed tomography (CT) of the brain identified diffuse
cerebral atrophy. Autopsy findings revealed diffuse subcortical white matter disease and marked arteriosclerotic
changes of the subcortical arterioles.
[29]
The cortex was relatively spared, and the pathologic diagnosis confirmed Binswanger disease. Binswanger disease,
therefore, can present with PSDs and should be included in the differential diagnosis of dementia. On the other
hand, Dzialek et al described a group of 15 patients with Binswanger subcortical atherosclerotic encephalopathy who
showed a different EEG appearance. The EEG records were pathological in most cases, with varying degrees of
slow activity that was distributed symmetrically.
[30]
Circulatory encephalopathy
Atherosclerosis
Plachinda et al studied the correlations of cognitive disorders and the EEGs of elderly patients with circulatory
encephalopathy. They explored the possibilities of using EEG for evaluating intellectual-mnemonic disorders in
elderly patients with cerebral atherosclerosis. Ninety-five patients (aged 60-74 y) with atherosclerotic encephalopathy
but without stroke were included in the study. Statistical analysis of the data demonstrated a correlation between
psychological test results and EEG readings and computerized EEG data.
[31]
In cerebrovascular disease, focal slowing is far more frequent than in nonvascular dementia; therefore, EEG can be
useful in distinguishing the 2 conditions.
Multi-infarct dementia
No specific EEG pattern is associated with multi-infarct dementia. Some background slowing may be observed,
especially in advanced disease. These changes are less prominent and do not show the progressive course
observed in Alzheimer disease (AD).
Iznak et al used quantitative EEG (QEEG) to reveal the specific features of and study amplitude-frequency
parameters in patients with mild dementia of different origins compared with healthy elderly individuals.
[32]
They
found that alpha rhythm was suppressed in AD and vascular dementia and that alpha rhythm was slower and theta
activity higher in AD. Patients with AD were characterized by desynchronized EEG.
Transient global amnesia
A variety of records have been reported from normal to even epileptiform potentials in transient global amnesia
(TGA). Nonepileptiform activity, such as bitemporal delta or bioccipital theta, has been reported. Kushner described
patients with normal activity, one with occasional epileptic activity, and one with asymmetric alpha depression, while
2 patients had intermittent rhythmic slowing.
[33]
TGA caused by a seizure is uncommon, and is believed to be caused
by a vascular etiology or spreading depression.
Hereditary Encephalopathies
Action myoclonus
Action myoclonus consists of arrhythmic muscular jerking induced by voluntary movement. It can be made worse by
attempts at precise or coordinated movement (ie, intention myoclonus) and may be elicited by sensory stimuli. The
effective stimulus for action myoclonus is thought to be feedback from muscle afferents, although it may be related to
activity in the motor cortex relayed to the reticular formation preceding or coinciding with voluntary movement.
The condition usually is associated with diffuse neuronal diseases, such as posthypoxic encephalopathy, uremia,
and the various forms of peripheral neuroepithelioma, although action myoclonus may be limited to one limb in some
cases of focal cerebral damage. It is caused by hyperexcitability of the sensorimotor cortex (ie, cortical reflex
myoclonus) or reticular formation (ie, reticular reflex myoclonus), or both. Autopsied cases have failed to reveal a
clear pathology. Theories include loss of inhibitory mechanisms involving serotonin and possibly gamma-
aminobutyric acid (GABA) transmitters.
Myoclonus may be seen in degenerative disorders of the nervous system. It may be associated with tonic-clonic
seizures or dementia. Myoclonus has been described in cases with Lafora inclusion bodies and cerebral storage
diseases, as well as system degenerations: cerebellodentatorubral, pyramidal, extrapyramidal, optic, auditory,
posterior columns and gracile and cuneate nuclei, spinocerebellar pathways, motor neurons of cranial nerves and
anterior horns, and muscle fibers.
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Action myoclonus usually responds to sodium valproate or clonazepam, and some patients with posthypoxic action
myoclonus may improve with serotonin precursors.
Generalized myoclonus
Generalized myoclonus in comatose survivors after CPR implies a poor prognosis despite improvement of the critical
care of patients.
[34]
This transient, self-limited phenomenon reflects dysfunction of lethally damaged neurons.
Propofol often controls myoclonus but does not change the underlying condition. Clinical, pathologic, and
electroencephalographic (EEG) findings indicate that these patients die of severe hypoxic-ischemic damage.
Abnormal EEG patterns, especially burst suppression EEG (BS-EEG) and alpha-coma EEG, are seen in these
patients. The EEG abnormalities include BS-EEG, generalized epileptiform discharges, alpha-coma EEG.
[35]
Unverricht-Lundborg di sease
Unverricht-Lundborg disease (ULD) (ie, Baltic myoclonus) is an autosomal recessive progressive myoclonic epilepsy
syndrome. ULD is found sporadically worldwide, but is common in Finland. The myoclonus is severe and generalized
seizures occur that are difficult to control. Progressive background slowing, generalized spike and wave and
polyspike and wave complexes, and focal occipital spikes are found on EEG.
[36]
Mi tochondrial encephalopathy with lactic acidosis and stroke (MELAS) and myoclonus
epi lepsy with ragged red fibers (MERRF)
Isozumi et al described a 50-year-old woman with subacute dementia and myoclonus in whom computed
tomography (CT) revealed brain atrophy and EEG revealed periodic synchronous discharges (PSDs). She initially
was thought to be suffering from Creutzfeldt-J akob disease (CJ D) but dramatically recovered over 5 months. On the
basis of further investigations, the final diagnosis was mitochondrial encephalomyopathy. In general, the EEG
changes were described as background slowing, multifocal epileptiform discharges, and photosensitivity.
Post stereotactic surgery
Patients developed EEG slowing of different degrees about 50% of the time.
Alpers disease
Alpers disease, an autosomal recessive inherited disorder consisting of progressive neuronal degeneration of
childhood with liver disease, has been studied by Boyd et al.
[37]
The onset is in early childhood and consists of
intractable fits, progressive dementia, and brain atrophy. EEG studies have been carried out on 12 children with this
condition. The EEGs were similar and demonstrated abnormal patterns with high-amplitude slow activity as well as
lower amplitude polyspikes. The flash visual evoked potential (VEP) was usually abnormal and often asymmetrical.
In the appropriate clinical setting, the neurophysiologic features may aid the clinician in the diagnosis of this disease.
Adrenoleukodystrophy
Multifocal paroxysmal discharges, hypsarrhythmic pattern, and prominent arrhythmic delta are present in temporal-
occipital areas. Epileptic discharges usually do not occur in adrenoleukodystrophy.
Zellweger syndrome
This syndrome is characterized by diffuse slowing.
Infantile neuroaxonal dystrophy
This condition is characterized by a high-voltage, 14- to 22-Hz activity that is not reactive to environmental stimuli.
Pantothenate kinase-associated neurodegeneration (PKAN)
In PKAN, formerly known as neurodegeneration with brain iron accumulation type I, the EEG is normal to slow.
Neuronal ceroid lipofuscinosi s
In the infantile form, the EEG is slow and early, and posterior spikes may be present. Photic response is excessive
and evokes high-voltage spikes that are polyphasic. The EEG abnormalities in the juvenile form are not as marked.
Gaucher disease
In patients with type III disease, posterior spikes and sharp waves, diffuse spike and waves, and photomyoclonic and
photoparoxysmal responses may be present.
Metachromatic leukodystrophy
Diffuse slowing progresses to high-voltage generalized delta activity. Epileptic activity is rare; however,
hypsarrhythmia may be observed.
Tay-Sachs disease
EEG is generally slow. Generalized or multifocal spikes accompany the seizures.
Rett syndrome
Rett syndrome is a slowly progressive encephalopathy that occurs only in girls and is characterized by early
deterioration of higher brain function with dementia, autistic behavior, loss of purposeful use of the hands, and
deceleration of head growth. Al-Mateen et al reported 15 cases of Rett syndrome.
[38]
When affected girls are aged
2-4 years, epilepsy may develop with minor motor seizures. Additional features may include an extrapyramidal
disorder with dystonia and choreoathetosis and lactic acidemia. A precise biochemical marker of this disorder has
not been identified.
According to McIntosh et al, Rett syndrome consists of a progressive encephalopathy and psychomotor deterioration
in young girls who have appeared clinically normal until age 6-18 months.
[39]
The incidence is similar to that of
phenylketonuria and autism in females. When the child is at least 6 months old, head growth decelerates in
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association with severe dementia, autism, apraxia, stereotypic handwashing movements, and loss of previously
acquired skills. Other signs include breathing dysfunction, seizures, EEG abnormalities, and growth retardation. It
appears to be sporadic in occurrence.
The EEG may demonstrate slowing, a variety of nonspecific patterns, and epileptiform discharges. The epileptic
activity may include multifocal spikes, slow-wave spikes, and paroxysmal delta slowing with spikes that may appear
in sleep; in certain cases, however, sleep may attenuate the EEG abnormalities. Background flattening occurs to
some degree, corresponding with the stage of dementia and cognitive decline. Rolandic spikes may be elicited by
noise.
Infectious Encephalopathies
Creutzfeldt-Jakob disease
In Creutzfeldt-J akob disease (CJ D), electroencephalography (EEG) shows a fairly typical repetitive pattern of
bilateral synchronous periodic epileptiform discharges (BiPEDs; see the first image below) such as triphasic waves
(TWs; see the second image below) approximately 1-1.5 seconds apart. These usually are present during
wakefulness and disappear during sleep.
Bilateral periodic epileptiform discharges (BiPEDs).
Periodic synchronous discharges (PSDs) seem to be the EEG hallmark of CJ D; however, a number of atypical EEG
presentations have been reported without these waveforms.
Aoki et al reported giant spikes with photic stimulation.
[40]
These photic-stimulated giant spikes simultaneously
suppressed PSDs. Necropsy exhibited extensive gray and white matter lesions. Both lateral geniculate bodies and
pregeniculate bodies were involved preferentially. The superior colliculus, optic nerve, and optic tracts were not
affected. The cortices of the occipital lobes were damaged severely. The Gennari line was spared. The lesion of the
lateral geniculate body appeared to be associated with the unusual EEG feature.
These findings indicate that the visual pathway may be involved in the generation of PSD in CJ D (see the image
below).
MRI axial diffusion weighted image: Cortical ribbon sign in CJ D.
The EEG findings and the evolution of clinical signs were investigated by Hansen et al in 7 patients with CJ D who
underwent serial EEG recordings.
[41]
At the onset (mean 8.7 weeks) of periodic slow-wave complexes (PSWC), 5
patients already had progressed to akinetic mutism characterized by loss of verbal contact and movement disorders
(ie, myoclonus, exaggerated startle reaction, or focal dyskinesia started in 5 patients).
When akinetic mutism commenced (average 7.5 weeks), runs of frontal intermittent rhythmic delta activity (FIRDA),
like that shown below, were found in all cases. These were later replaced by PSWC in 6 patients. Occurrence of
PSWC often related negatively to external stimuli and sedative medication.
[41]
These data help in the selection of EEG recording dates to detect PSWC in patients in whom CJ D is suspected. The
survival time is short after the onset of PSWC (average 8 weeks). In earlier disease stages, FIRDA-like EEG
activities should be regarded as compatible with the diagnosis of CJ D and should encourage further EEG studies for
the demonstration of PSWC in a more advanced stage of CJ D.
EEG characteristics of CJ D and its differential diagnosis were studied by Steinhoff et al, who found some nonspecific
EEG findings and also typical PSWC in the course of the disease,
[42]
obtaining a sensitivity of 67% and a specificity
of 86%. With the exception of one familial variant of CJ D, PSWC are usually absent in all other human prion
diseases.
The authors presented a pathophysiologic hypothesis on the development of PSWC based on the assumption that
the specific periodicity of PSWC results from a still functionally active but greatly impaired subcortical-cortical circuit
of neuronal excitability.
[42]
They stressed the use of clinical signs, laboratory data, and EEG correlation and
suggested that the clinical diagnosis of CJ D should be reconsidered if repeated EEG recordings fail to reveal PSWC
under technically adequate conditions. Some patients with CJ D presented with visual blurring, diplopia, and visual
lossie, the Heidenhain 5 variant.
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Focal EEG abnormalities as described in the Heidenhain variant of CJ D are uncommon. Lee et al reported a
73-year-old man presenting with visual symptoms, right hemianopia, and rapidly progressive dementia. Myoclonus
was synchronous with generalized periodic epileptiform discharges on EEG (see the image below).
Generalized periodic epileptiform discharges (GPED).
In addition, periodic focal sharp waves were present at the left occipital region. Diffusion-weighted magnetic
resonance imaging (MRI) of the brain showed slightly increased signal intensity in the occipital parasagittal area, left
more than right. The 14-3-3 protein was detected in the cerebrospinal fluid (CSF). The patient died within 5 months
of presentation.
[43]
Subacute spongiform encephalopathy
Aguglia et al described 20 patients with subacute spongiform encephalopathy and periodic paroxysmal activities in
the EEG. Evolution of clinical and EEG abnormalities were analyzed in all 20 (16 pathologically confirmed). Illness
duration was less than 4 months in 65% and greater than 17 months in 10%. The early clinical stage was
characterized by gradual gait disturbances, mental deterioration, and sensory or autonomic changes. In 10 EEG
recordings from 7 patients examined in the early clinical stage, no periodic discharges were present.
[44]
Early periodic paroxysmal activity appeared within 12 weeks of the onset of the disease in 88% of the patients who
underwent EEG recordings. This early periodic paroxysmal activity usually occurred at an intermediary stage, when
the patients demonstrated marked worsening of the clinical picture. Focal, segmental, and/or generalized myoclonic
jerks were observed in 15%, 53%, and 100% of cases at prodromal, intermediary, and terminal stages, respectively.
Different kinds of periodic paroxysmal activity were observed:
Biphasic or triphasic periodic complexes
Periodic complexes with multiphasic configuration
Periodic polyspiking discharges
Abnormal "pacing" by slowly repeated flashes was found in 4 patients presenting with visual hallucinations or cortical
blindness. Burst-suppression activity was observed frequently in the terminal stage in decorticate patients.
AIDS dementia
EEG abnormalities usually precede brain atrophy on computed tomography (CT) of the brain. Generalized or
multifocal slowing may be observed. Computerized EEG is abnormal in most cases. About one half of patients who
have normal neurologic findings on physical examination exhibit abnormal EEGs.
Thomas et al described a 40-year-old HIV-positive, right-handed homosexual man who was admitted for progressive
mental deterioration coexisting with permanent, segmental, middle-amplitude, arrhythmic, asynchronous, and
asymmetrical myoclonic jerks. EEG demonstrated frontocentral bursts of rhythmic triphasic 1.5- to 2-Hz sharp waves
similar to the characteristic periodic pattern of CJ D. Biological investigations were negative, thus ruling out a
metabolic encephalopathy.
[45]
Dramatic neurological improvement occurred shortly after initiation of intravenous and then oral zidovudine, which
produced absolute EEG normalization. This unusual electroclinical presentation of the AIDS dementia complex
underlines the fact that this condition presents a diagnostic challenge, particularly in individuals in whom HIV
infection has not been diagnosed previously.
Canafoglia et al described a case of a HIV-seropositive patient with ataxia and upper limb rhythmic myoclonus.
[46]
Electromyographic (EMG) recordings of the forearm muscles correlated with frontocentral rhythmic activity on EEG.
This movement disorder should be considered a rhythmic variant of cortical myoclonus. HIV infection may have
caused a dysfunction in the central nervous system pathways similar to that occurring in genetically determined
conditions characterized by cortical myoclonus.
Sinha et al described various electrophysiologic abnormalities in HIV encephalopathy.
[47]
Polich et al found greater frontal delta power in HIV cases than in control subjects.
[48]
Ferrari et al described 2 patients with HIV type 1 infection who presented new-onset epilepsia partialis continua
(EPC) as an early manifestation of progressive multifocal leukoencephalopathy (PML).
[49]
PML represents an
increasingly recognized cause of new-onset seizures in both seropositive and seronegative patients.
Diehl et al followed 117 HIV patients with EEG. Serial EEGs on 117 HIV patients without any clinical signs of
secondary neuromanifestations were studied in order to document EEG changes in the course of HIV infection.
Clinical signs of HIV-associated encephalopathy presented in 18 patients at the first examination and 23 at
reexamination. Significant slowing of background activity occurred in the course of the disease. The results of this
study indicated progressive central nervous system (CNS) dysfunction with worsening of the immunostatus.
[50]
Chronic rubella encephalitis
This condition is characterized by myoclonus, mental deterioration, ataxia, and chorea, with diffuse slowing on EEG.
Intermittent rhythmic delta activity (IRDA) has been described. Periodic activity with spikes and slow-wave spikes
may occur.
Viral encephalitis
Viral encephalitis frequently causes EEG abnormalities. If the cortical gray-matter involvement is predominant, more
polymorphic delta activity is observed, while with subcortical involvement, a rhythmic pattern (IRDA) is more
common. In herpes simplex encephalitis (HSE; see the first image below), temporal intermittent rhythmic delta
slowing (TIRDA; see the second image below), nonrhythmic temporal slowing, and frontotemporal slowing are
characteristic; a periodic pattern may develop as the disease evolves.
8 of 19 10/7/2014 11:30 AM
MRI axial FLAIR with gadolinium; herpes encephalitis, left temporal.
Left temporal intermittent rhythmic delta (TIRDA).
Hsieh et al found abnormal EEG findings and abnormal neuroimaging in three fifths of children (n=26) with HSE
aged 1-6 years correlated with poorer outcomes.
[51]
In a retrospective review of EEG in HSE, Al Shekhlee et al found periodic lateralized epileptiform discharges
(PLEDs) (see the image below) or focal temporal slowing to be present in 90% of the PCR-positive group (PCR
testing for the herpes virus from spinal fluid being the most sensitive and specific test for the diagnosis of HSE) at
symptom onset as compared with 30% of the PCR-negative group.
[52]
Periodic lateralized epileptiform discharges.
The investigators found that the sensitivity of the EEG recording for these focal and epileptiform findings decreases
after 48 hours. The MRI results were consistent with HSE in 86% of those with HSE-positive PCR results obtained
48 hours from symptom onset. They found the EEG to be of important diagnostic use when obtained within the first
24-48 hours of HSE symptom onset.
[52]
Serial EEGs usually capture PLED activity, but in the later stages of the disease course, the EEG may revert to
normal.
St Louis encephalitis
Wasay et al, using EEG and MRI to study patients, found that of the 9 patients who were examined with EEG, all 9
had seizures or other abnormalities, and 1 had nonconvulsive status epilepticus. The MRI findings in 2 of the 9
patients showed edema. One of the 9 patients had HIV coinfection.
[53]
Subacute sclerosing panencephalitis
Subacute sclerosing panencephalitis (SSPE) is a progressive neurodegenerative disorder caused by defective
measles virus replication in the brain as a consequence of measles immunization.
The EEG may provide an important clue regarding SSPE and demonstrates bilaterally synchronous, high-amplitude
spike or slow-wave bursts that often correlate with clinical myoclonus. As SSPE progresses, the background activity
becomes suppressed, resulting in a burst-suppression pattern. Neuroimaging studies demonstrate nonspecific
abnormalities or diffuse atrophy, although T2 prolongation can be detected by MRI symmetrically in the cerebral
white matter or multifocally in the subcortical white matter or cortex.
Flaherty et al described a 17-year-old boy with SSPE discovered when he presented with confusion after a mild head
injury. The EEG strongly suggested the diagnosis. Repeated CT scans of the head were normal. The boy had a
3-year history of decreased vision, associated with a focal pigmentary retinopathy. On assessment, the patient
demonstrated visual agnosia and early dementia. MRI demonstrated symmetrical demyelination of the white matter,
particularly in the occipital lobes. The typical EEG findings and the presence of measles antibodies in the CSF
confirmed the diagnosis of SSPE.
[54]
SSPE should be considered in young patients who have persisting cognitive dysfunction that is not proportional to
the severity of the initial trauma. A focal pigmentary retinopathy, especially with macular involvement, should raise
the possibility of SSPE, even if neurologic symptoms are absent initially. The longest interval (to date) between the
visual symptoms and onset of neurological signs of SSPE was reported by the author.
Koppel et al reported on the relation of SSPE and HIV. At one time largely eliminated from the United States by
nearly universal measles vaccination, SSPE has reemerged in HIV-infected children. Two children with SSPE were
described. The first was HIV-positive and presented with seizures and encephalopathy at the age of 21 months. The
second developed myoclonus and dementia at 4 years of age; she was not infected with HIV, but her mother had
AIDS. MRI brain scans were nonspecific. EEG was characteristic of SSPE, showing high-voltage PSWCs and
background slowing. Brain biopsy and high measles antibody titers in the CSF confirmed the diagnosis of SSPE.
[55]
Metabolic Encephalopathies
Metabolic disorders
9 of 19 10/7/2014 11:30 AM
Anoxic encephalopathy
Hypoxia causes diffuse slowing on the electroencephalogram (EEG). The acute and prolonged anoxia of cardiac
arrest exhibits no changes initially. In 7-10 seconds, slow waves appear. This is followed by rhythmic, high-voltage
delta activity; subsequently, attenuation and EEG flattening occurs. As a rule, irreversible brain damage results in 4-8
minutes.
In some cases, establishing the completeness and duration of anoxia is difficult. Certain patterns carry a poor
outcome: flat EEG, burst-suppression patterns, and burst suppression patterns with epileptiform discharges (see the
image below) nearly always carry a poor prognosis. Postanoxic EEGs may exhibit a variety of abnormal patterns:
triphasic activity, alpha coma pattern, repetitive complexes, and bilateral PLEDs.
Anoxic encephalopathy. Burst suppression pattern with bursts of spike and wave and polyspike wave discharges with voltage
suppression.
Takahashi et al reported a 47-year-old man admitted to the hospital for depression, who suddenly developed
cardiopulmonary arrest of unknown etiology and entered a chronic vegetative state as a result of anoxic
encephalopathy. Periodic synchronous discharges (PSDs) were present for as long as 5 months. The wave pattern,
periodicity, and duration of appearance of PSDs were similar to those of PSDs seen in Creutzfeldt-J akob disease
(CJ D). The PSDs were prolonged gradually, with a course similar to that of the discharges observed in CJ D. The
mechanism of occurrence is considered to be similar to that of PSDs in CJ D.
[56]
Fernandez-Torre et al described the clinical and electroencephalographic features of a comatose patient with severe
anoxic encephalopathy who experienced acute reflex myoclonus precipitated by passive eye opening/closure and
painful stimulation. Acute stimulus-sensitive postanoxic myoclonus is an underdiagnosed epileptic condition. Shortly
after the anoxic insult, the diagnosis should be based on EEG evaluation and various types of stimulation. These
should include passive eye opening/closure and painful stimuli.
[57]
Comatose intensive care patients
Young et al investigated the usefulness of continuous EEG monitoring. Twenty percent of patients recorded seizures.
The study suggests that continuous EEG monitoring may be more valuable for detection of seizures in patients with
acute structural brain lesions (ASBLs) than in patients with metabolic encephalopathies.
[58]
Hyponatremic encephalopathy
Usually, nonspecific slowing is observed in hyponatremic encephalopathy. A variety of other patterns have been
described: triphasic waves (TWs); burst of high-voltage rhythmic delta; central, high-voltage, 5- to 7-Hz rhythm; and
sensory stimulation-induced, high-voltage delta activity. Epileptic activity is very rare, even in cases of clinical
seizure.
Kameda et al reported a case of frontal intermittent delta activity (FIRDA) in the EEG of a patient with pituitary
adenoma, hyponatremic encephalopathy, and major depression. The pituitary adenoma is thought to be a major
factor for FIRDA in this case. Complicating factors included diffuse encephalopathy and use of antipsychotic drugs;
FIRDA remained in the EEG after these factors diminished. The size of the pituitary adenoma that was proposed to
be associated with FIRDA in the EEG recording was not noted. FIRDA may be associated with a small pituitary
adenoma less than 10 mm in size.
[59]
Hypocalcemia and hypercalcemia
Paresthesias, tetany, muscle spasm and, rarely, seizures may occur in hypocalcemia. EEG findings include theta
and polymorphic delta slowing, polyspikes, sharp waves, and paroxysmal activity. Hypercalcemia is associated with
renal failure, neoplasms, bone destruction, parathyroid hormone (PTH)-releasing tumors, and hypervitaminosis D.
Muscle weakness, polydipsia, polyuria, nausea, anorexia, and coma may develop. EEG changes appear when
serum calcium level is approximately 13 mg/dL; slowing and intermittent rhythmic delta activity is seen. Photic driving
may be prominent, and TWs may be recorded.
When serum calcium is normalized, the EEG usually improves but not immediately. A hypercalcemic condition can
be observed in association with hyperthyroidism. Confusional state and EEG alterations, among which diffuse
monomorphic delta rhythms were remarkable, were shown by J uvarra.
[60]
As soon as normalization of calcium
serum level was achieved, rapid clinical and EEG improvement ensued.
Endocrine conditions
Adrenal disease
EEG pattern is nonspecific.
Cushing disease
EEG changes are uncommon.
Addison disease
Nonspecific slowing and diffuse theta and delta may be seen in a disorganized manner.
Pheochromocytoma
No particular EEG pattern has been noted.
Hypoglycemia
The EEG resembles changes described with hypoxia; hyperventilation response is exaggerated and FIRDA may be
observed. If prolonged coma ensues, the EEG changes persist and may become permanent. In most cases of
hypoglycemia, a generalized disorganization of record occurs; in patients with long-term diabetes, the EEG is usually
10 of 19 10/7/2014 11:30 AM
mildly to moderately diffusely disorganized and slow.
Hyperglycemia
Similar slowing is the rule; however, epileptic activity may be observed with clinical seizure.
Wang et al described hyperglycemia with occipital seizures. They described acute and follow-up visual evoked
potential (VEP) and magnetic resonance imaging (MRI) findings of a patient with hyperglycemia-related visual SE of
occipital origin. Occipital seizures and hemianopsia can be caused by hyperglycemia and may be accompanied by
special MRI and VEP findings.
[61]
Glutaric aciduria type I
Neurophysiologic abnormalities are frequently seen in organic acidemias. Yalnizoglu et al studied EEG, VEP, and
brain-stem auditory evoked response (BAER) in 7 children with glutaric aciduria type I (GA1).
[62]
Three of the 7
patients showed abnormal EEG findings; 2 showed asymmetry with intermittent occipital delta slowing in 1
hemisphere. This finding probably indicates underlying cerebral dysfunction and is not a specific feature. One patient
showed high amplitude bursts of beta in the occipital regions with left predominance while on clonazepam and
baclofen.
Hyperthyroidism
This has a nonspecific pattern, including slowing and FIRDA. Depending on the severity of the thyroid dysfunction,
seizures and epileptiform discharges can be seen.
[36]
Hypothyroidism
Low-voltage theta is the rule with reduced photic driving response.
Nutritional deficiency syndromes
Pyridoxine deficiency causes severe, and at times, fatal convulsions in infants. The underlying metabolic problem
has been suggested to be insufficient gamma-aminobutyric acid (GABA) synthesis. Thiamine deficiency causes
diffuse slowing in Wernicke encephalopathy. Malnutrition results in EEG slowing, proportional and corresponding to
the clinical alertness of the patient.
Toxic agents
Aluminum toxicity
Flaten et al reported a wide range of toxic effects of aluminum. This element has been demonstrated in plants and
aquatic animals in nature, in experimental animals by several routes of exposure, and under different clinical
conditions in humans.
[63]
Aluminum toxicity is a major problem in agriculture, affecting perhaps as much as 40% of
arable soil in the world. In fresh waters acidified by acid rain, aluminum toxicity has led to fish extinction. Aluminum is
a very potent neurotoxin. Subtle neurocognitive and psychomotor effects and EEG abnormalities have been reported
at plasma aluminum levels as low as 50 g/L.
Infants and patients with impaired renal function could be particularly susceptible to aluminum accumulation and
toxicity. Evidence exists to suggest that aluminum may be the causative agent in the development of dementia in
patients with chronic renal failure who are on dialysis (ie, dialysis dementia). The EEG may become abnormal
months before the full-blown dementia develops. Aluminum also is associated with dialysis encephalopathy, which
often is accompanied by osteomalacia and anemia. Such effects also have been reported in certain patient groups
without renal failure.
Aluminum accumulation occurs in the tissues of workers with long-term occupational exposure to aluminum dusts or
fumes. Such exposure may cause neurologic effects.
In dialysis dementia, the EEG abnormalities usually are diffuse slowing, although TWs may occur. When seizure
develops, high-voltage spike and slow-wave complexes and paroxysmal bursts with a frequency of 2-4 Hz have
been observed. Polymorphic frontally dominant delta often is observed. The background slowing usually correlates
with severity of mental status impairment. Subcortical dysfunction may be present with FIRDA.
Carmofur
Carmofur, an antineoplastic derivative of 5-fluorouracil, has been reported to cause subacute leukoencephalopathy.
Kuzuhara described 3 individuals who developed subacute leukoencephalopathy after carmofur (l-hexylcarbamoyl-
5-fluorouracil) administration.
[64]
Initial symptoms were unsteady gait and dementia, developing several weeks or
months after administration of carmofur. Symptoms increased gradually even after stopping the drug.
Severe encephalopathy with confusion, delirium, or coma developed. Symptoms were usually reversible but
occasionally resulted in death. The EEG demonstrated marked slowing. CT scan of the brains of severely intoxicated
patients showed marked hypodensity of the entire cerebral white matter.
[64]
Carmofur must be discontinued
immediately if any psychomotor symptoms develop.
Cefepime
Status epilepticus and encephalopathy have been reported with use of cephalosporins in patients with renal failure.
Maganti et al reported the case of a 79-year-old patient with normal renal function who developed subtle mental
status changes during cefepime therapy for urinary tract infection. EEG showed nonconvulsive status epilepticus
(NCSE).
[65]
Lead
The heavy metal lead is usually absorbed into the body by ingestion and/or inhalation. Symptoms from acute
poisoning may range from lethargy, seizures, coma, and death to cognitive impairment, delirium, ataxia and distal
motor neuropathy with chronic exposure.
[66, 67]
Stewart et al found lead to be linked to neurodegeneration with
cumulative exposure leading to decreased brain volumes and white matter lesions.
[68]
Treatment includes chelation
therapy and removing the source of the lead exposure from the patient's environment (see Lead Encephalopathy).
Lithium
Encephalopathy, confusional states, and nonconvulsive status epilepticus due to lithium toxicity and overdose is well
documented.
[69]
In a report by Bellesi et al, a patient presented in nonconvulsive status epilepticus with a normal
serum lithium level that resolved with benzodiazepine administration and withdrawal of the lithium. After 2 months ,
11 of 19 10/7/2014 11:30 AM
the lithium was restarted with therapeutic levels attained. The patient again was found to be in NCSE with 3-4 Hz
diffuse spike and wave discharges. The lithium was stopped, never to be readministered.
[70]
Manganese encephalopathy
Excess manganese (Mn) can cause several neurotoxic effects. Herrero Hernandez et al described an epileptic
syndrome due to manganese intoxication in a 3-year-old boy. EEG showed progressive encephalopathy. The patient
developed epileptic status. Chelating treatment promptly succeeded in reverting epileptic symptoms.
[71]
Neuroleptic encephalopathy
Treatment of psychiatric patients often necessitates overlapping neuroleptic medication. Lambreva et al reported a
60-year-old woman suffering from schizoaffective disorder who temporarily received 3 neuroleptics, together with
lithium. She developed neurotoxic encephalopathy with symptoms of a malignant neuroleptic syndrome. The authors
recommended frequent EEG controls for early detection of neurotoxicity.
Tiagabine
Tiagabine hydrochloride (TGB) (an antiepileptic medication) is a selective GABA reuptake inhibitor that is used as an
add-on therapy for partial seizures. The risk of NCSE can be elevated by TGB (comedication 7.8% vs TGB alone
2.7%).
[72]
Kellinghaus et al reported 3 cases of recent increase in TGB doses causing nonconvulsive status
epilepticus with the EEG of one of the patients demonstrating rhythmic delta waves.
[73]
Vinton et al reported TGB-induced NCSE in 3 patients with focal lesional epilepsies1 with initiation of the
medication and 2 with recent dose escalation. All of these patients had continuous high amplitude and generalized
2-4 Hz delta activity with intermingled spikes seen with episodes of unresponsiveness. After dose reduction or
withdrawal of the TGB and administration of intravenous (IV) clonazepam, EEG and clinical signs normalized.
[74]
Valproate and topiramate encephalopathy
Panda et al reported 2 children with encephalopathy and slowing of EEG background activity, which promptly
reverted to normal along with clinical improvement following withdrawal of valproate (VPA).
[75]
According to Segura-Bruna et al, VPA-induced hyperammonemic encephalopathy (VHE) is VPA treatment that
results in elevated serum ammonium levels, which leads to a decreased level of consciousness, cognitive slowing,
vomiting, drowsiness, lethargy, and increased seizure frequency. If VHE is suspected, serum ammonium levels
should be evaluated and the existence of a possible urea cycle enzyme deficiency, such as ornithine
carbamoyltransferase deficiency, should be considered. Generalized slowing in the theta and delta frequencies,
FIRDA, and TWs can be found on EEG. These findings and other clinical symptoms usually resolve after VPA is
withdrawn.
[76]
Cheung et al proposed a novel term, topiramate-valproate induced hyperammonemic encephalopathy, to describe
the clinical features of patients on concomitant topiramate and valproate therapy. With this specific encephalopathic
syndrome those on the above therapy may display excessive sleepiness or somnolence, increased seizure activity,
hyperammonemia, and an absence of TWs on EEG.
[77]
Liver transplantation
The EEG in hepatic encephalopathy may consist of slow waves and TWs; epileptic activity may be observed. Adams
et al studied patients after liver transplantation; 17 (33%) of 52 patients who underwent 56 consecutive orthotopic
liver transplants had serious postoperative neurologic complications.
[78]
Seizures were described in 13 (25%) patients; of these, 50% had onset of seizures within the first week. In 3
patients, the seizures were associated with postoperative metabolic encephalopathy and fatal progressive
neurological deterioration. Cyclosporine was thought to be causing the seizures in some of these patients. In others,
electrolyte disturbances, steroid treatment for graft rejection, and cerebral infarction could have contributed to the
occurrence of seizures.
[78]
Autoimmune Encephalopathy
Scleroderma
CNS involvement and psychiatric manifestations can occur in systemic sclerosis (ie, scleroderma). Hietaharju et al
evaluated CNS and psychiatric involvement in 32 patients. Severe CNS or psychiatric symptoms were present in 5
patients (16%), including encephalopathy, psychosis, anxiety disorder, grand mal seizures, and transient ischemic
attacks. In addition, abnormal VEPs were recorded in 5 of 32 patients (16%), suggesting optic neuropathy. EEGs
were mainly normal or showed only slight nonspecific changes.
[79]
Anti-NMDAR encephalopathy
Anti N -methyl-d-aspartate receptor (NMDAR) encephalitis is a neuroimmune syndrome in patients with
autoantibodies recognizing extracellular epitopes of NMDAR, and the autoantibodies attenuate NMDAR function
through the internalization of NMDAR.
[80]
This autoimmune encephalitis is characterized by headache, confusion, memory deficits, psychiatric disturbance,
including psychosis, dyskinesias, coma, autonomic instability, and seizures.
[80, 81, 82]
Anti-NMDAR encephalopathy is
often due to ovarian teratomas in young women, with children less likely to have the above tumors.
[80]
Many patients
need ICU admission and close monitoring because of autonomic instability, coma, and seizures.
[80, 82]
Extreme care
must be taken when evaluating the abnormal movements often seen in anti-NMDAR encephalitis. In one study, false
impressions of status epilepticus rather than encephalopathy were reported in 6% of the cases reviewed.
[82]
Anti-NMDAR encephalitis can sometimes be reversed with immunotherapy, including steroid treatment, intravenous
immunotherapy, and surgery (removal of the teratoma). When able, physical, occupational, speech, cognitive, and
behavioral therapies are often required. Recovery can be slow, with cognitive and motor deficits sometimes
significant.
[80]
EEG patterns seen in this autoimmune encephalopathy can include focal or hemispheric slowing and often diffuse
background slowing.
[83]
With more prolonged hospitalization, a unique delta brushtype pattern has been observed
in up to 30% of adults with anti-NMDAR encephalitis in one study of 23 patients.
[84]
This pattern can be continuous
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or become rhythmic and is often quite refractory to anticonvulsant therapy. Focal nonconvulsive or convulsive status
epilepticus can be seen as well, requiring video or continuous EEG monitoring for closer surveillance.
[81, 82]
Hashimoto myoclonic encephalopathy
Ghika-Schmid et al reported 2 patients with subacute diffuse encephalopathy characterized by confusion, myoclonic
encephalopathy, and mild akineto-rigid extrapyramidal signs in one case and by apathy, memory deficit, and partial
complex seizures in the other. Hashimoto thyroiditis with high titers of antithyroglobulin antibodies was diagnosed in
both patients, who were not responsive to anticonvulsant medication but exhibited rapid neurologic improvement
following steroid treatment. On neuropsychological examination, predominant frontotemporal dysfunction was
noted.
[85]
EEG activity was remarkable for its rhythmic delta activity, which was unresponsive to, or even paradoxically
increased by, anticonvulsant treatment. Atrophy with temporal predominance was observed on MRI. These
observations support the idea that this potentially treatable dementia and movement disorder should be classified as
a separate clinical entity.
Kothbauer-Margreiter et al reported 6 patients with Hashimoto thyroiditis and associated encephalopathy and
compared with 14 well-documented cases identified in the literature.
[86]
Encephalopathy typically affects patients
when they are euthyroid and in an appropriate clinical situation; antithyroid autoantibodies are the main indicators of
the encephalopathy. Since clinical features of Hashimoto encephalopathy are nonspecific, other etiologies, such as
infectious, metabolic, toxic, vascular, neoplastic, and paraneoplastic causes, must be considered.
Two types of initial clinical presentation can be differentiated:
A vasculitic type with strokelike episodes and mild cognitive impairment
A diffuse progressive type with dementia, seizures, psychotic episodes, or altered consciousness
These types may overlap, particularly over the long term in untreated patients. A strong female predominance
existed in the study by Kothbauer-Margreiter et al ; 18 of the 20 patients were women. The EEG was abnormal in
90% of cases; it showed nonspecific changes. The condition is steroid-responsive.
Triphasic Waveforms
Triphasic waves (TWs; see the image below) were initially described by Foley et al in hepatic encephalopathy. They
later were described in other metabolic states and brain tumors.
[87]
Most electroencephalographers now agree that
TWs are a relatively nonspecific pattern observed in a number of metabolic conditions, degenerative dementias, and
anoxia. In a bipolar montage, TWs usually comprise a high-voltage, positive wave followed by a smaller negative
deflection; they usually are bilaterally synchronous and maximal frontally. A fronto-occipital (anteroposterior) phase
lag varies from 25 to 140 ms; this is expressed less in referential montages.
TWs have not been reported in children. Generally, the TW pattern carries a poor prognosis with a high mortality if it
occurs in association with rapid neurologic and clinical deterioration.
However, TWs in a psychiatric population described by Blatt and Brenner carried a different prognosis. In a large
retrospective study consisting of 15,326 electroencephalograms (EEGs) performed from 1983 to 1992 in a
psychiatric institute, 83 EEGs (62 patients13 men and 49 women aged 59-90 years, with a mean age of 74 years)
had TWs.
All 62 patients were awake, though they often were confused. Most (n=56) had dementia, usually severe; 15 also
had delirium. Six patients had no dementia. Infrequent etiologies included neuroleptic malignant syndrome (n=1) and
hepatic encephalopathy (n=1); in 4, the cause was uncertain, although all were receiving lithium.
[88]
EEG features analyzed included frequency of background rhythms, distribution of the TWs, periodicity, and
epileptiform abnormalities.
[88]
Background rhythms were slow in all but 7 patients. TWs were maximal posteriorly in
47 patients and anteriorly in 6 and were diffuse in 9. Neuroimaging studies demonstrated prominent posterior
abnormalities in only 1 individual. Periodicity was prominent in 4 patients; in 2, the TWs were maximal anteriorly.
Interictal epileptiform activity was present in 6 patients, a history of seizures in 8, and myoclonus in 4. TWs are
uncommon in psychiatric populations; they occur primarily in elderly and severely demented patients.
Aguglia et al discussed nonmetabolic causes of TWs and described 2 patients with TWs on their EEGs in the
absence of metabolic disturbances.
[89]
One patient had coma associated with cerebellar hematoma, the other had
mild dementia associated with idiopathic calcifications of the basal ganglia and healthy auditory brainstem responses
and subcortical and cortical SEPs. Neurologic examination revealed no asterixis in either patient.
The literature on nonmetabolic causes of TWs also was reviewed, and the clinical and anatomic reports of 10
patients were analyzed.
[89]
Seven patients had focal brainstem-diencephalic lesions: craniopharyngioma (2),
thalamic gliomas (3), or pontine stroke (2). Three patients suffered from diffuse subcortical or multifocal
encephalopathies: Binswanger encephalopathy (1), cerebral carcinomatosis (1), or multifocal cerebral lymphoma (1).
From the clinical point of view, patients with nonmetabolic diseases causing TWs presented with either disturbance
of higher cerebral functions with no asterixis or sudden onset of coma. Aguglia et al concluded that TWs may result
from focal brainstem/diencephalic lesions or from diffuse subcortical or multifocal encephalopathies in the absence of
concomitant metabolic abnormalities.
[89]
Nonmetabolic causes of TW should be suspected in patients presenting
with neurologic disturbances not associated with asterixis.
TWs also were evaluated by Sundaram et al, and their clinical correlates and morphology were assessed.
[90]
Of 63
consecutive patients with TWs, 26 (41%) had various types of metabolic encephalopathies, and 37 patients (59%)
had nonmetabolic encephalopathies, usually senile dementia. TWs were not found to be specific for any single type
of metabolic encephalopathy. Etiology was linked more closely to level of consciousness at recording than to any
13 of 19 10/7/2014 11:30 AM
morphologic or distributional feature of the TWs themselves. Thus, all 31 alert patients had nonmetabolic
encephalopathies, and all 13 comatose patients had metabolic encephalopathies.
The second, positive component (wave II) most often had the highest voltage, while equally maximal waves I and II
occurred next most commonly.
[90]
In these patients, TWs most often were expressed maximally anteriorly. Among
patients with metabolic encephalopathies, a posterior-anterior delay or lag of the wave II peak occurred more
commonly than did the better known anterior-posterior lag. Lags occurred with both metabolic and nonmetabolic
conditions but were more common with the former. No difference in quantity or mode of appearance existed between
the metabolic and nonmetabolic groups when matched for consciousness level.
Prognosis for patients with either metabolic or nonmetabolic encephalopathies was unfavorable.
[90]
Only 4 of 24
patients with metabolic encephalopathy and 1 of 35 patients with nonmetabolic encephalopathy were well at
follow-up more than 2 years later. Forty percent of EEGs with sharp and slow-wave complexes (slow spike waves)
had sporadically appearing TWs. The relative amplitudes of the 3 components differed from those of TWs in other
conditions; equally maximal waves II and III were the most usual form.
Digital EEG
As stated in the assessment report of the American Academy of Neurology and the American Clinical
Neurophysiology Society, digital electroencephalography (EEG) is an established substitute for recording, reviewing,
and storing a paper EEG record. In this sense, digital EEG simply replaces and improves the paper record, much as
word processing has improved letter writing over what could be done by hand or even by a typewriter. However,
routine digital recording of the clinical EEG does not add new information that was not present in the paper record.
Once the paper recording is made, various options are available for further analysis. Some processing methods,
such as different montage displays and digital filtering, simply enhance the visibility of the record. Others, such as
calculating the mean band frequencies and different band-energy spectra, may bring into the forefront information
that was already there in the paper record but is too tedious and time-consuming to calculate without use of a
computer.
Spike recognition is an important enhancement and a great time saver but needs careful review by the interpreting
physician. Lately, technologic developments have enabled the authors to record long-term monitoring on small
storage devices, making the diagnosis of syncope, seizures, and sleep disorders much easier.
EEG brain mapping visualizes a selected electrical event in the brain and maps its geographic distribution. Attempts
have been made to standardize some aspects of brain mapping; however, no clear uniform recommendation has yet
emerged. Although frequency bands are fairly well standardized, different ways of calculating the data exist.
Normative values are being developed; however, most brain maps are not time locked to an event or brain state;
therefore, comparisons of frequency bands are difficult to accomplish across groups or disease states.
A clear definition for the clinical correlation of the brain maps is still needed; therefore, EEG brain mapping and other
advanced quantitative EEG (QEEG) techniques should be used only by physicians highly skilled in clinical EEG and
only as an adjunct to traditional EEG interpretation.
These tests may be clinically useful only for patients who have been carefully selected on the basis of their clinical
presentation. Certain QEEG techniques are considered established as an addition to the digital EEG and include
screening for possible epileptic spikes or seizures, long-term EEG monitoring or ambulatory recording, and operating
room (OR) and intensive care unit (ICU) monitoring.
Continuous EEG monitoring by frequency trending helps to detect early intracranial processes in the OR or ICU (eg,
screening for possible epileptic seizures in high-risk ICU patients). QEEG frequency analysis may be a useful
adjunct to interpretation of the routine EEG. In a number of conditions (eg, postconcussion syndrome, head injury,
learning disability, attention disorders, schizophrenia, depression, alcoholism, and drug abuse), QEEG remains
investigational. On the basis of available clinical and scientific evidence and expert opinions, QEEG is not currently
useful in civil or criminal cases.
QEEG is a derivative of regular EEG. The original data must be evaluated before any further mathematical
translation of this same data set is done. A thorough understanding and firm knowledge of clinical EEG diagnosis
may help prevent erroneous interpretations of digitally displayed mathematical constructs (eg, brain maps and
coherence maps).
Ideally, only physicians properly trained in EEG and, in addition, sufficiently well trained in mathematics and
computing science should use these new technologies. A substantial risk of erroneous interpretations exists if any of
the elements required is missing. Clinical use of any of the EEG brain mapping or other QEEG techniques by
practitioners who are not physicians highly skilled and properly trained in clinical EEG interpretation or who have not
reviewed the original record should be unacceptable.
Conclusion
Electroencephalography (EEG) is regarded as a fairly nonspecific measure of clinical states. A limited number of
abnormalities that can be recognized in widely varied disease states exist.
On the other hand, an abnormal EEG is a sensitive measure of brain function. When the patient has clinically
symptomatic encephalopathy or moderate dementia, the EEG is almost always abnormal.
Accordingly, the clinical utility of EEG must be appreciated in a different way from that of some other diagnostic
procedures. In medicine, clear correlations and specific answers are desired; however, depending on the modality
and the underlying principle of measurement, this goal cannot always be achieved.
In addition to EEG, magnetic resonance imaging (MRI) scan is very sensitive in showing various lesions in the brain.
However, it is difficult to know exactly what these lesions represent on the basis of mere appearance. When
interpreting MRI images, the clinician relies to a large extent on other relevant clinical information.
EEG measures electrical field variations, and a number of clinical conditions can disturb the normal electrical field of
the brain. Simple state or electrolyte changes may alter the appearance and time variation of the brain-generated
electrical fields; hence, a large number of conditions cause the EEG to appear abnormal. In EEG practice, the
clinician has to rely to a large extent on the clinical history and the neurologic examination findings to make a
clinically meaningful conclusion.
In most instances, the correct question may be whether the EEG is normal or abnormal. The next step is to decide
how an abnormal EEG would help the clinical diagnosis; therefore, the EEG can be used to confirm clinical
observation or suspicion or to determine the extent of the abnormality for prognostic purposes (ie, in attempting to
predict outcome). Sometimes, EEGs serve as a "proof" to families that the patient's brain function is indeed so
14 of 19 10/7/2014 11:30 AM
greatly disturbed that recovery is doubtful. In such cases, the EEG helps resolve anxiety and supports a more correct
ethical decision.
Newer EEG techniques offer a number of conveniences and also enhance communication between the
electroencephalographer and other clinical specialists. However, they may not make the record more specific but
merely render it more easily understandable. Computer analysis, on the other hand, may offer features that, although
present in the regular record, are difficult or time-consuming to extract and display.
EEG has a definite role in evaluating changes in mental states. It can confirm or rule out nonconvulsive status
epilepticus (NCSE). EEG changes are usually proportional to the degree of metabolic, hepatic, or renal
encephalopathy. EEG often is abnormal in subdural hematoma, normal pressure hydrocephalus (NPH), and
Creutzfeldt-J akob disease (CJ D).
Computer analysis of the EEG may help reveal subtle changes in Alzheimer disease (AD). This application is
promising and, it is to be hoped, will soon become clinically useful and available. In cases of clinical dementia, a
normal EEG with preserved alpha might help establish the diagnosis of Pick disease, whereas a slowed and shifted
alpha frequency is seen in AD and progressive supranuclear palsy (PSP). Low-voltage, flat EEG and the appropriate
clinical presentation may raise the suspicion of Huntington disease.
EEG study should be requested if clear clinical indications are present or if the clinician has a reasonable
presumption that it may give clinically relevant information. Such information would be expected to alter the clinical
decision-making process. It would also help the referring source in diagnosis and treatment.
Another role is to help the patient or family to understand the ongoing disease process. EEG frequently is ordered to
evaluate patients with different degrees of mental and behavioral changes and encephalopathy or coma. Usually,
nonspecific abnormalities are present that do not give definite information about the cause of the underlying process
but do provide information on its location and severity; therefore, unless epileptic seizures are a consideration, the
EEG does not give direct unequivocal information on the cause of the patient's condition.
Nevertheless, EEG may differentiate between a generalized and a focal abnormality. This may guide the clinician to
further appropriate imaging studies. On the other hand, if the abnormality is generalized, the EEG can be used to
characterize and monitor the disease process. With coma, the EEG may help in predicting the neurologic prognosis.
EEG is an important diagnostic tool in dementias in which specific morphologic lesions are not apparent on imaging
studies.
Personal perspective
EEG often is compared with MRI; when this comparison is made, it usually refers to clinical MRI rather than
functional MRI. This comparison is puzzling, in that a primarily anatomic test is being compared with a functional
one.
In general, MRI is good at telling us where the lesion is, whereas EEG is good at separating normal and abnormal
primarily cortical function. The topologic usefulness of EEG is limited, although it may be improved with
computerization. The purpose of MRI is to provide precise localization of a lesion, usually one that has passed a
certain stage of evolution. The EEG, on the other hand, captures the changing electrical characteristics of a
functioning brain, primarily those of the cortex.
Conditions can be identified with EEG that as a rule cannot be seen on the MRI; therefore, the use of these studies
is not exclusive but complementary. The EEG may be used for the following purposes:
To exclude nonconvulsive status epilepticus
To identify focal interictal epileptiform activity to confirm clinical suspicion that seizures may contribute to the
condition in question
To attempt to record functional disturbance in individuals whose brain MRI is "normal" but in whom brain
dysfunction is clinically evident (eg, metabolic encephalopathies)
To attempt to record disease-specific patterns in the proper clinical setting, such as progressive myoclonic
epilepsies, CJ D, SSPE
To help a psychiatrist with the multitude of complex disorders masking as potential epilepsy or
encephalopathy (eg, lithium intoxication may present with BiPEDs)
To identify focal or lateralized changes that suggest a structural cause to the encephalopathy
The truism that EEG is nonspecific and cannot diagnose etiology or localization well (eg, the cause of coma) is often
cited. However, in general medical practice, nonspecificity is often not the question, because most of the referrals in
general neurology are individuals in whom the cause is fairly clear, or reasonably suspected, on the basis of clinical
history and laboratory chemistry. The questions from the clinician are whether the brain is involved and what is the
extent of brain damage (if any). At present, for answering these questions, no clinical tool is more useful than the
EEG.

Contributor Informati on and Disclosures
Author
Eli S Neiman, DO Neurologist and Clinical Neurophysiologist, Specialty Care, Inc; Assistant Professor of
Neurology, Seton Hall University School of Health and Medical Sciences; Clinical Associate Professor of
Neurology, Department of Neurology, Kansas City University of Medicine and Biosciences College of Osteopathic
Medicine
Eli S Neiman, DO is a member of the following medical societies: American Academy of Neurology, American
Epilepsy Society, and American Osteopathic Association
Disclosure: UCB Pharma Honoraria Review panel membership; UCB Pharma Honoraria Speaking and teaching;
Cyberonics, Inc Honoraria Speaking and teaching
Coauthor(s)
Philip A Hanna, MD Associate Professor, Department of Neuroscience, Seton Hall University School of
Graduate Medical Education; Residency Program Director, New J ersey Neuroscience Institute, J FK Medical
Center; Neurology Director, Huntington's Disease Unit, J FK Hartwyck-Cedarbrook
Philip A Hanna, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of
Neurology, and Movement Disorders Society
Disclosure: Nothing to disclose.
Chief Editor
Selim R Benbadis, MD Professor, Director of Comprehensive Epilepsy Program, Departments of Neurology and
15 of 19 10/7/2014 11:30 AM
Neurosurgery, Tampa General Hospital, University of South Florida College of Medicine
Selim R Benbadis, MD is a member of the following medical societies: American Academy of Neurology,
American Academy of Sleep Medicine, American Clinical Neurophysiology Society, American Epilepsy Society,
and American Medical Association
Disclosure: UCB Pharma Honoraria Speaking, consulting; Lundbeck Honoraria Speaking, consulting; Cyberonics
Honoraria Speaking, consulting; Glaxo Smith Kline Honoraria Speaking, consulting; Sleepmed/DigiTrace
Honoraria Consulting; Sunovion Consulting fee None; Supernus Speaking, consulting; Upsher-Smith
Grant/research funds None
Additional Contributors
Leslie Huszar, MD Consulting Staff, Department of Neurology, Indian River Memorial Hospital
Leslie Huszar, MD is a member of the following medical societies: American Academy of Neurology, American
Association for the Advancement of Science, and American Medical Electroencephalographic Association
Disclosure: Nothing to disclose.
Erasmo A Passaro, MD, FAAN Director, Comprehensive Epilepsy Program/Clinical Neurophysiology Lab,
Bayfront Medical Center, Florida Center for Neurology
Erasmo A Passaro, MD, FAAN is a member of the following medical societies: American Academy of Neurology,
American Academy of Sleep Medicine, American Clinical Neurophysiology Society, American Epilepsy Society,
American Medical Association, and American Society of Neuroimaging
Disclosure: Glaxo Smith Kline Honoraria Speaking and teaching; UCB Honoraria Speaking and teaching; Pfizer
Honoraria Speaking and teaching; Forest Honoraria Speaking and teaching
Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College
of Pharmacy; Editor-in-Chief, Medscape Drug Reference
Disclosure: Medscape Salary Employment
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