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 DOI: 10.1177/1550059411433612

2012 43: 161 originally published online 16 March 2012Clin EEG NeurosciJudith van Vliet, Wim Mulleners and Jan Meulstee

EEG Leading to the Diagnosis of Limbic Encephalitis  

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EEG Leading to the Diagnosis of LimbicEncephalitis

Judith van Vliet1, Wim Mulleners1, and Jan Meulstee1

AbstractLimbic encephalitis is characterized by subacute onset of short-term memory loss, seizures, sleep disturbances, as well as psychiatricand behavioral symptoms. A subgroup is associatedwith voltage-gated potassium channel antibodies (VGKC-Abs). Inmany cases, brainmagnetic resonance imaging (MRI) demonstrates hyperintense areas in the medial part of the temporal lobe. Also, pleiocytosis is fre-quently found. In this study, we describe a 69-year-old man with VGKC-Abs limbic encephalitis with generalized tonic–clonicseizures, increasing memory deficits, visual hallucinations, depression, and severe insomnia. Brain MRI and cerebrospinal fluid(CSF) were normal, while the electroencephalogram (EEG) showed bilateral frontal and temporal intermittent rhythmic delta activitywith disorganization and slowing of background activity, ultimately leading to the diagnosis of limbic encephalitis. The patient improvedmarkedly after starting immunosuppressive therapy, both clinically andelectrophysiologically. In addition to temporal lobe involvementon the brain MRI and CSF inflammation, we propose EEG abnormalities as an additional diagnostic criterion for limbic encephalitis.

Keywordselectroencephalography, limbic encephalitis, voltage-gated potassium channel, antibodies

Received March 1, 2011; accepted June 17, 2011.

Introduction

Limbic encephalitis is a rare disorder characterized by seizures,

short-term memory loss, as well as psychiatric and behavioral

symptoms such as depression, hallucinations, anxiety, and per-

sonality changes. Sleep disturbances have been reported as well,

both hypersomnia and insomnia. Onset is subacute in a few weeks

to months but may also evolve in a few days. Among others, lim-

bic encephalitis is linked to N-methyl-D-aspartate-receptor anti-

bodies (anti-NMDA-receptors)1 and to VGKC-Abs.2,3 The

latter are also associated with 2 other neurological syndromes,

acquired neuromyotonia, and Morvan syndrome.4 Morvan

syndrome is characterized by autonomic and central nervous

system involvement and neuromyotonia. Symptoms consist of

weight loss, hyperhidrosis, severe insomnia, and hallucinations.

Suggested diagnostic criteria for limbic encephalitis consist of

a typical clinical picture as described above, and at least one of the

following: (1) neuroimaging with evidence of temporal lobe

involvement, (2) CSF inflammation, and (3) detection of limbic

encephalitis–associated antibodies.5 In this study, we describe a

69-year-old man with VGKC-Abs limbic encephalitis, with a nor-

mal MRI and CSF examination, in which the EEG eventually led

to the diagnosis of limbic encephalitis.

Case Report

A 69-year-old man was known to have a renal cell carcinoma

on both sides, in 2002 and 2009, respectively, which resulted

in bilateral nephrectomy and peritoneal dialysis. In May

2010, the patient presented at the emergency room with 2

generalized tonic–clonic seizures. For a few weeks, he had

progressive insomnia, and on the last days he demonstrated

confused and aggressive behavior.

The patient showed severe postictal confusion, resulting in

temporary admission to the intensive care unit for sedation and

intubation. Neurological examination was otherwise normal.

White blood cell count, C-reactive protein, electrolytes, and

glucose were all normal. His creatinine was 958 mmol/L, blood

urea nitrogen (BUN) was 14.3 mmol/L, comparable to previous

values. Contrast-enhanced brain computed tomography (CT)

was uneventful. Analysis of CSF showed normal white blood

cell count (1 � 106) and normal protein level. An EEG,

performed during sedation with propofol to rule out a noncon-

vulsive status epilepticus, demonstrated diffuse slow-wave

activity without epileptic discharges. On the assumption of ure-

mic encephalopathy as the cause of his seizures, he was treated

with phenytoin.

1 Department of Neurology and Clinical Neurophysiology, Canisius Wilhel-

mina Hospital, Nijmegen, The Netherlands

Corresponding Author:

Judith van Vliet, Department of Neurology and Clinical Neurophysiology,

Canisius Wilhelmina Hospital, PO Box 9015, 6500 GS Nijmegen, The

Netherlands

Email: j.v.vliet@cwz.nl.

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Six weeks later, he was admitted with pneumonia and a third

generalized tonic–clonic seizure. The brain MRI with gadoli-

nium was normal. Over the next few weeks, he visited the

emergency department several times, with symptoms of

depression and increasing memory deficits. He had visual

hallucinations and worsening insomnia and showed aggressive

behavior. All symptoms fluctuated during the day.

To rule out partial seizures as the cause of his fluctuating

confused behavior, a 24-hour ambulatory EEG was repeated

(Figure 1). No epileptic discharges were seen. However, the

EEG demonstrated marked worsening compared to the previous

recording, showing disorganization of the background, with

bilateral frontal and temporal intermittent rhythmic delta activity

(FIRDA and TIRDA). Remarkably, during 24 hours, sleep was

nearly absent, showing only a few periods of light drowsiness

without any vertex waves, sleep spindles or K complexes.

Taken together the clinical signs and the EEG pattern with

intermittent rhythmic frontotemporal delta activity, suggested

limbic encephalitis. The brain MRI and lumbar puncture were

repeated and again showed no abnormalities. Then, VGKC-

Abs testing was positive, and the diagnosis of limbic encephalitis

was confirmed.

The patient was treated with high doses of prednisolone

(60 mg/d). In a week, there was complete resolution of hal-

lucinations and confusion. Over the next few weeks, his insomnia

improved markedly. A repeated EEG (Figure 2) a few weeks after

starting treatment showed obvious improvement, with recurrence

of background organization. Diffuse slow-wave activity with

FIRDA was still present but far less pronounced compared to the

previous recording. Also, sleep had partially returned with recur-

rence of rapid eye movement (REM) sleep and non-REM light

sleep stages. Immunoglobulins were added as therapy, and the

patient showed further improvement.

Discussion

We report a male patient with a typical clinical picture of lim-

bic encephalitis. Of interest is the fact that EEG eventually led

to this diagnosis, while brain MRI and CSF examination were

normal.

Abnormalities on EEGs are frequently found in limbic

encephalitis, although recordings may be normal as well.6

The EEG may show nonspecific changes with generalized

slowing or uni- or bilateral temporal lobe epileptiform activ-

ity. Focal slow-wave activity in one or both temporal lobes

is another frequently noted feature.7,8 Dalmau et al1

described 92 patients with anti-NMDA-receptor encephali-

tis. All patients showed abnormalities on the EEGs, 23%had epileptic discharges and all other patients showed gen-

eralized or predominantly frontotemporal slow or disorga-

nized activity.

Diagnostic criteria have been formulated for limbic ence-

phalitis.5,9 These consist of typical clinical features (subacute

onset within 12 weeks of seizures, confusion, short-term

memory loss, and psychiatric symptoms), and at least one of

the following: (1) neuroimaging with evidence of temporal

lobe involvement, (2) CSF inflammation, and (3) detection of

limbic encephalitis–associated antibodies. Our patient does

meet these criteria, as VGKC-Abs was positive. However, the

normal findings of brain MRI and CSF examination caused a

delay in definite diagnosis. Therefore, we propose EEG

abnormalities as an additional diagnostic criterion to avoid a

Figure 1. Electroencephalogram (EEG) before treatment, 70 Hz, 0.1 Hz band-pass filter. EEG showing disorganization of the background withdiffuse slowing and intermittent rhythmic delta waves, most pronounced in both temporal areas.

162 Clinical EEG and Neuroscience 43(2)

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delay in treatment. Generalized slowing, temporal lobe epilepti-

form activity, and uni- or bilateral predominantly frontotemporal

slow-wave activity may support the diagnosis. These findings

may be helpful not only in diagnosing limbic encephalitis but

also used to evaluate the effect of treatment during follow-up,

as demonstrated in this case.

A striking symptom in this case was insomnia, demonstrated

by ambulatory EEG recording, which showed hardly any sleep

apart from some short periods of drowsiness. During treatment,

the EEG showed partial improvement with recurrence of REM

sleep and non-REM light sleep stages. However, non-REM

deep sleep stages remained notably absent. Sleep disturbances

have been reported as symptom of limbic encephalitis. Mostly,

hypersomnia is reported,8,10 and severe insomnia is described

as well.11 Two other neurological syndromes are associated

with VGKC-Abs; acquired neuromyotonia, and Morvan

syndrome.4 Morvan syndrome is characterized by

neuromyotonia and involvement of autonomic and central

nervous system, with severe insomnia as an important symp-

tom. In Morvan syndrome, a lack of deep sleep is described,

as well as abnormal REM sleep with lack of atonia. There

seems to be some overlap between the features of limbic ence-

phalitis and Morvan syndrome.

In conclusion, abnormalities on EEG may help diagnose

limbic encephalitis in clinically suspected cases, notably in

patients with normal findings on neuroimaging and CSF anal-

ysis. Generalized slowing, temporal lobe epileptiform activity,

and uni- or bilateral predominantly frontotemporal slow-wave

activity support the diagnosis. Moreover, EEG may be used to

monitor clinical improvement after treatment. We believe that

the EEG as a diagnostic tool deserves greater attention in this

patient population.

It would be interesting to perform a large cohort study to

determine whether certain more specific EEG abnormalities

may point to the diagnosis limbic encephalitis.

Acknowledgment

We thank Ms S. Ruiter and Ms J. ten Cate, EEG technologists, for

recording the EEGs.

Declaration of Conflicting Interests

The authors declared no potential conflicts of interest with respect to

the research, authorship, and/or publication of this article.

Funding

The authors received no financial support for the research, authorship,

and/or publication of this article.

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Figure 2. Electroencephalogram (EEG) during treatment, 70 Hz, 0.1 Hz band-pass filter. EEG after several weeks of treatment with prednisolon,showing strikingly less delta wave activity compared to the previous one. Instead, background organization has returned, and it demonstrates ahigh index of theta activity.

van Vliet et al. 163

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