Barbara F. Westmoreland

Clinical, Magnetic Resonance Imaging, and Electroencephalographic Findings in Paraneoplastic Limbic Encephalitis

OBJECTIVE To analyze clinical presentation of and paraclinical test abnormalities in patients with paraneoplastic limbic encephalitis (PLE). PATIENTS AND METHODS We retrospectively reviewed 24 patients seen at the Mayo Clinic in Rochester, Minn, between 1985 and 2002 in whom PLE was suspected. Patients were identified on the basis of clinical history and presence of cancer. Data were reviewed from magnetic resonance imaging (MRI), cerebrospinal fluid (CSF) analysis, electroencephalography (EEG), and paraneoplastic serologic studies. RESULTS Common manifestations were cognitive dysfunction (92%), seizures (58%), and psychiatric symptoms (50%); 13 patients had small cell lung carcinoma; 11 had other malignancies. Paraneoplastic neuronal autoantibodies were found in 14 (64%) of 22 patients tested. Electroencephalography showed focal or generalized slowing and/or epileptiform activity, maximal in the temporal regions, in all 22 patients tested. Magnetic resonance imaging revealed increased T2 signal involving one or both temporal lobes in 15 (83%) of 18 patients. Cerebrospinal fluid test results were abnormal in 18 (78%) of 23 patients tested. Clinical or radiographic evidence of extralimbic involvement was documented in 12 (55%) of 22 patients. No abnormality on EEG, MRI, or CSF analysis correlated with a specific cancer type or with a specific paraneoplastic autoantibody. CONCLUSIONS In patients with suspected PLE, EEG is invaluable for confirming cerebral dysfunction. Magnetic resonance imaging can show unequivocal involvement of temporolimbic structures and helps exclude other diagnoses. When EEG and cranial MRI are both normal, PLE is unlikely. Comprehensive testing for paraneoplastic neuronal nuclear, cytoplasmic, and ion channel autoantibodies is an important part of the evaluation, but negative results do not rule out PLE.

EEG findings in steroid-responsive encephalopathy associated with autoimmune thyroiditis

OBJECTIVE To analyze the electroencephalogram (EEG) findings of patients with steroid-responsive encephalopathy associated with autoimmune (Hashimoto) thyroiditis. METHODS We reviewed 51 EEGs and the clinical records of 17 patients (5 men and 12 women, 27-84 years old). RESULTS All patients had mild to severe generalized slowing on the EEG which corresponded to the clinical severity of the underlying encephalopathy. Other findings included triphasic waves, epileptiform abnormalities, photomyogenic response, and photoparoxysmal response. Follow-up EEGs of 13 patients showed slowing in 7 and a return to normal in 6. Myoclonic jerks were recorded during the EEG study of 8 patients but did not have an EEG correlate. The EEG and clinical condition improved after treatment with corticosteroids. When encephalopathy recurred, the EEG showed corresponding abnormalities. CONCLUSIONS EEG findings in steroid-responsive encephalopathy associated with autoimmune thyroiditis consist mainly of slow wave abnormalities that reflect the degree of severity of the underlying encephalopathy. The EEG findings often paralleled the course of the disease, showing improvement with improvement in the clinical condition and worsening with recurrence of symptoms. SIGNIFICANCE The EEG is helpful in evaluating and following patients with steroid-responsive encephalopathy associated with autoimmune thyroiditis in reflecting the degree of central nervous system (CNS) involvement, in determining whether their condition is better or worse, and in ruling out other causes of encephalopathy.

A distinctive rhythmic EEG discharge of adults

An unusual transient electroencephalographic pattern consisting of repetitive sharp-contoured wave forms in the range of 4--7 c/sec was seen in recordings from 65 patients who were between 42 and 80 years of age. This pattern was usually predominant over the parietal and temporal regions. No clinical alteration was associated with the pattern. Although the pattern resembled a subclinical EEG seizure discharge, it did not correlate with clinical seizures. The pattern occurred in patients with diverse clinical complaints, and although its mechanism of origin remains uncertain, it appears to represent a benign EEG phenomenon that has little diagnostic significance.

Electroencephalographic Abnormalities in Interferon Encephalopathy: A Preliminary Report

Although several studies have shown that interferon does not readily cross the blood-brain barrier, recent reports have described central nervous system effects in patients receiving interferon. At our institution, we encountered three patients who had symptoms of toxicity of the central nervous system (somnolence, confusion, and gait difficulties) in association with electroencephalographic abnormalities while receiving alpha 2-interferon therapy for multiple myeloma. The electroencephalogram showed diffuse slow-wave abnormalities in two of the patients and generalized sharp-wave discharges in the third patient. Because the use of interferon is increasing, physicians should be aware of the central nervous system complications and the electroencephalographic changes that can be associated with such therapy.

Unusual EEG Patterns

Some of the unusual patterns that can be encountered on the EEG are described briefly. The patterns are grouped according to the predominant frequencies involved and/or by distinctive morphology or distribution. Those involving predominantly the alpha frequency range are alpha squeak, retained alpha, alpha-delta sleep, unilateral decrease in reactivity of alpha activity, and extreme spindles. The patterns involving the beta frequency range are the fast alpha variant, posterior temporal fast activity in children, the fast spiky spindle variant, central fast activity, and diffuse paroxysmal or continuous fast activity. The patterns of predominant theta frequencies are the slow alpha variant, frontal arousal rhythm, rhythmic temporal theta activity of drowsiness, midline theta rhythms, and focal parietal theta activity. Activity in the delta range includes the transient rhythmic slowing occurring after eye closure and the more continuous posterior rhythmic slowing. Patterns with a distinct morphology or distribution include the breach rhythm, wicket spikes, zeta waves, periodic frontal sharp complexes, subclinical rhythmic electrographic discharge of adults, and the EEG pattern of holoprosencephaly.

Lateralized and focal clinical, EEG, and FLAIR MRI abnormalities in Creutzfeldt–Jakob disease

OBJECTIVE Creutzfeldt-Jakob disease (CJD) is a rapidly progressive fatal prion disorder with typical clinical findings of dementia, motor dysfunction, and myoclonus and characteristic electroencephalographic (EEG) findings of bilateral synchronous periodic sharp waves. Advances in neuroimaging capabilities with diffusion-weighted and fluid-attenuated inversion recovery (FLAIR) magnetic resonance imaging (MRI) techniques have shown promise in the non-invasive diagnosis of CJD. This series illustrates the correlation between the lateralized and focal clinical, EEG, and MRI FLAIR sequence abnormalities in 8 patients (7 men and one woman 55-73 years old) with CJD. METHODS A case series of 8 patients, evaluated at Mayo Clinic, who had a history of rapidly progressive lateralized or focal neurologic dysfunction and laboratory findings consistent with CJD between 1996 and 1999 were identified. EEG, MRI of the head with FLAIR sequence, and cerebrospinal fluid studies were performed in all patients. RESULTS Mean time to death from symptom onset was 4 months. Symptoms were lateralized to the left hemisphere in 5 patients and to the right hemisphere in two. One patient showed bilateral occipital lobe involvement. In all patients, the EEG showed lateralized or focal periodic sharp waves that colocalized with clinical cerebral dysfunction. FLAIR MRI images revealed increased signal in the cortical ribbon and deep gray matter corresponding to the lateralized clinical and EEG findings in 7 patients. The other patient had bilateral occipital increased signal on FLAIR MRI. CONCLUSIONS CJD may present with lateralized or focal cortical syndromes with colocalizing EEG and MRI findings. With the appropriate clinical history and laboratory evaluation, the corresponding areas of increased signal on FLAIR MRI provide supportive evidence of the disease. SIGNIFICANCE CJD can sometimes present with more focal or lateralized clinical findings, and the colocalizing EEG and MRI findings can help make or confirm the diagnosis of CJD.

Tuberous sclerosis, early onset of seizures, and mental subnormality Study of discordant homozygous twins

In two sets of male homozygous twins with tuberous sclerosis, one twin in each set suffered frequent generalized seizures from early life, and the second either had no seizures or had only short-lived seizures. One twin of each pair is of normal intelligence, and the other is mentally subnormal. We propose that generalized seizures occurring in early life are an important mechanism in an apparently progressive dementing process in some infants and children with tuberous sclerosis. If our assumption is correct, an early attempt to control generalized seizures in these patients is indicated even in the presence of the cortical, subcortical, and subependymal pathologic changes characteristic of cerebral tuberous sclerosis.

Epileptiform abnormalities in hepatic encephalopathy.

Epileptiform abnormalities are uncommon in patients with hepatic encephalopathy. A review of EEGs in patients with hepatic encephalopathy over a 10-year period identified 18 (15%) with epileptiform abnormalities. Thirteen patients had interictal discharges consisting of focal spike and sharp wave discharges, bilateral independent discharges, and generalized spike and wave discharges. A total of 10 patients had electrographic seizure discharges, focal in 6 and generalized in 5 (some patients had more than one abnormality). Twelve patients had clinical seizures, partial in four and generalized in eight. Neuroimaging failed to provide an etiology for the generation of epileptiform discharges in most patients, including those with focal abnormalities. Most patients with epileptiform discharges died or deteriorated. We conclude that epileptiform can be seen in patients with hepatic encephalopathy, and when present imply a poor prognosis.

The EEG findings in Extratemporal seizures

Summary: Extratemporal seizures originate from the frontal, central, parietal, occipital, and midline regions of the brain. The scalp EEG can show various types of interictal and ictal discharges consisting of spikes, spike and wave sharp waves, paroxysmal fast activity, or rhythmic activity in the β, α, θ, or δ frequency ranges. The discharges can occur as focal, regional, lateralized, or secondarily generalized discharges. Discharges arising from the frontal region are varied and at times complex. Centro‐temporal spikes associated with benign epilepsy of childhood have a characteristic blunt spike and wave appearance. Centro‐parietal spikes can occur in children with benign childhood epilepsy or in association with symptomatic epilepsies at any age. Occipital spike discharges have been seen in young children with visual problems, benign occipital epilepsy of childhood, the Sturge‐Weber syndrome, and other symptomatic or structural lesions involving the occipital lobe. There may be problems with detection of the source of origin of seizures secondary to the anatomy of the various regions, deep foci, small restricted foci, rapid spread of epileptiform discharges, and contaminating effects of muscle and movement artifact. Depth or intracranial recordings may help in further localization of foci.

Unusual variants of subclinical rhythmic electrographic discharge of adults (SREDA)

Since 1981, when we first described a group of patients with subclinical rhythmic electrographic discharge of adults (SREDA), we have seen 108 patients with SREDA. Nineteen of these patients had unusual or atypical features of SREDA. The typical pattern consists of a non-evolving theta rhythm occurring in a widespread manner but maximal over the parietal and posterior temporal regions and lasting for a few seconds to a minute without clinical manifestations or symptoms. The unusual variants consist of predominantly delta frequencies, notched waveforms, a frontal or more focal distribution, a more prolonged duration, and presence during sleep. There was no significant difference in the patient group that had the atypical pattern compared with those with the typical pattern. Although the mechanism of the SREDA is unclear, it appears to represent a benign EEG phenomenon that has little diagnostic significance and should be distinguished from seizure discharges.