Rasmussen syndrome (RS) or Rasmussen encephalitis (chronic encephalitis and epilepsy) was first described by Rasmussen et al in 1958.¹ It is an unusual condition typically developing in childhood, and is characterized by the occurrence of refractory partial epilepsy, often with epilepsia partialis continua (EPC), associated with progressive hemiparesis and cognitive impairment. Changes of unilateral hemispheric atrophy are seen on neuroimaging.

Based on the largest available patient series, the “average” RS patient can be described as follows: he or she (there is no gender predominance in RS) starts experiencing intractable unilateral focal motor seizures or temporal lobe seizures at the age of 6 years. Later on, when the inflammatory process spreads across the affected hemisphere, new seizure semiologies indicating new epileptogenic areas are observed. EPC, that is, more or less continuous myoclonic twitching of the distal extremities or the face, is frequent. Within a few months of epilepsy onset there is a progressive loss of neurological function associated with one hemisphere, typically hemiparesis, hemianopia, and (if the dominant side is affected) aphasia.^2,3

Serial brain magnetic resonance imaging (MRI) shows focal cortical and subcortical signal increase on T2 and fluid attenuated inversion recovery (FLAIR) images followed by progressive, centrifugal hemiatrophy of the cerebral hemisphere contralateral to the affected side of the body. The initial changes are usually peri-Sylvian; a frequent early MRI feature is volume loss of the head of the ipsilateral caudate nucleus.^4,5 After a year or so, the main decline remits, and there is a residual stage of stable neurological deficit and cerebral hemiatrophy. Seizure frequency remains high but is lower than in the “acute stage.”³ In reality, this “average” or “typical” RS patient is uncommon. Due to the complexity of potential symptoms, the presentation of RS can take a variety of different forms.

LESS COMMON PRESENTATIONS OF RS

Since the original description of RS, other presentations have been recognized. Although RS typically develops in children, a similar presentation has been described in adults.^6,7,8 although the course is often slower and less severe. Villani et al distinguished two phenotypes in adults: an “epileptic” form characterized by focal motor epilepsy refractory to antiepileptic drug treatment, and a “myoclonic” form with EPC and/or unilateral cortical myoclonus (focal or multifocal).

Although secondary spread of seizures to the contralateral side, or a minor degree of contralateral atrophy is sometimes seen in patients with RS, true bilateral involvement in the form of bilateral inflammation has only rarely been described,^9,10 and no case of subsequent spread to the opposite side has been reported following the successful surgical treatment of unilateral RS.¹¹ The bilateral nature of RS is usually apparent within 13 months of onset of the disorder.

Dual pathology, in which there is a second cerebral abnormality such as cortical dysplasia, vascular abnormality, or tuberous sclerosis, occurs in approximately 10% of patients,¹² leading to speculation that a breach in the blood-brain barrier may play a part in the genesis of the disease. Recent observations suggest that otherwise typical RS may occur in patients with delayed seizure onset,¹³ or in the absence of seizures.¹⁴ In a few patients, movement disorders including hemiathetosis and hemidystonia have been described in addition to EPC.^15,16

The most characteristic and unique feature of RS is the progressive unilateral loss of function and hemispheric atrophy occurring over several months or years. This acute stage is followed by a stable residual stage. Prior to the acute stage, a nonspecific prodromal period with less frequent seizures and occasional mild neurological deficit may be observed.³

Given the rarity of the syndrome, it is difficult to distinguish “typical” from “atypical” cases. To standardize the diagnosis of RS, a European consensus panel recently proposed formal diagnostic criteria¹⁷ which are given in Table 37–1.

NEUROIMAGING

As in many other brain disorders, MR imaging is a diagnostic mainstay in suspected cases. Within the first 4 months after disease onset, most patients exhibit unilateral enlargement of the inner and outer cerebrospinal fluid (CSF) compartments, most marked in the insular and peri-insular regions. Atrophy of the head of the ipsilateral caudate nucleus is a typical feature of hemispheric atrophy. T2 and FLAIR signals are focally enhanced in cortical and subcortical regions, or both.

Serial MRIs reveal that during the acute stage regions of signal increase spread across the affected hemisphere leaving behind further atrophic areas.^4,5 A typical MRI course is shown in Figure 37–1. Other modern neuroimaging techniques including positron emission tomography (PET), single-photon emission computed tomography (SPECT), and magnetic resonance spectroscopy (MRS) cannot adequately define the inflammatory nature of the condition but may help confirm the unihemispheric nature in suspected early RS cases.

EEG

Pathological electroencephalography (EEG) changes in RS are characterized by polymorphic delta waves over the affected hemisphere, mainly in a centrotemporal distribution. Epileptiform abnormalities are frequent and not infrequently evolve into (subclinical) electrographic seizures. During disease evolution, initially impoverished background activity shows further flattening. Contralateral asynchronous slow waves and epileptiform discharges occur in the majority of patients.¹⁸ Later, they may be more frequent than the ipsilateral abnormalities (which may falsely rise the suspicion of “bilateral disease”).¹⁹ As in other conditions, EPC in RS is not always accompanied by rhythmic EEG discharges on surface EEG.²⁰

LABORATORY TESTS

The serum test for GluR3 antibodies, published in the mid 1990s,²¹ can no longer be regarded as a useful diagnostic method. These antibodies are neither specific nor sensitive for the disease.^22,23,24 CSF cell counts and protein content are normal in 50% of examinations. In the remainder, moderately elevated cell counts (16–70 cells/μL, predominantly lymphocytes), and moderately increased protein concentrations (50–100 mg/dL) are observed.²⁵ Oligoclonal bands are an inconsistent finding ranging from 0% to 67% in three small series.^18,26,27 Therefore, standard CSF tests are insufficient to exclude or confirm the diagnosis of RE. In combination with serological tests, they can exclude central nervous system (CNS) infection by a known neurotropic agent.