Brain, Vol. 125, No. 8, 1751-1759,
August 2002
© 2002 Guarantors of Brain
The natural history of Rasmussen’s encephalitis
Departments of 1 Epileptology, 2 Radiology/Neuroradiology, 3 Neuropathology and 4 Neurosurgery, University of Bonn, Bonn, Germany
Correspondence to: C. G. Bien, Department of Epileptology, University of Bonn, Sigmund-Freud-Strasse 25, D-53105 Bonn, Germany E-mail: christian.bien{at}ukb.uni-bonn.de
Received November 21, 2001. Revised February 11, 2002. Accepted February 20, 2002.
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Summary |
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Rasmussen’s encephalitis (RE) is a chronic inflammatory disease of unknown origin, usually affecting one brain hemisphere. In the present study, a comprehensive assessment of the natural history of the disorder is presented. Seizure frequency, degree of hemiparesis and degree of cerebral hemiatrophy in 13 patients with histopathologically proven RE are analysed over the time course prior to resective epilepsy surgery or introduction of long-term immunosuppressive pharmacotherapy. For the assessment of the degree of cerebral hemiatrophy, on defined slices comprising the Sylvian fissure of hard copies of serial MRI investigations, the hemispheric ratio (HR) was determined. The data show an initial prodromal phase with an intermediate frequency of focal onset seizures and mostly no hemiparesis. The occurrence of this stage was mainly observed in the adolescent and adult patients. All patients went through an acute phase with a median duration of 8 months. During this stage, there were frequent simple partial motor seizures, development of hemiparesis and volume loss of the affected hemisphere. After this, the patients passed into a residual stage with a marked decrease in seizure frequency. Twelve months after the onset of the acute stage, the average HR was 0.72. These data allow an estimation of the prognosis of newly affected patients, and demonstrate that most of the brain damage in RE occurs during the first 8–12 months. These findings should be taken into consideration when future therapeutic approaches to RE are evaluated.
Keywords: epilepsy; hemiparesis; MRI; natural history; Rasmussen’s encephalitis
Abbreviations: EPC = epilepsia partialis continua; HR = hemispheric ratio; MNI = Montreal Neurological Institute; RE = Rasmussen’s encephalitis; SPMS = simple partial motor seizures
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Introduction |
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TopSummaryIntroductionPatients and methodsResultsDiscussionReferences |
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Rasmussen’s encephalitis (RE) is a chronic inflammatory disease of unknown origin, usually affecting one brain hemisphere. Rasmussen and co-workers in their original description assumed a viral cause of the disease (Rasmussen et al., 1958
). Later, the condition was linked to circulating auto-antibodies (Rogers et al., 1994; Twyman et al., 1995; He et al., 1998; Levite et al., 1999). More recently, however, a cytotoxic T cell reaction against neurons was demonstrated to play a causative role in RE (Bien et al., 2002a). Serial MRI of RE patients reveals a spread of the inflammatory lesion over the affected hemisphere. In a given brain region, a characteristic course from increased volume and T2/FLAIR signal to a final stage of atrophy without signal abnormalities occurs. This course could be correlated to a decreasing number of T cells and reactive astrocytes as assessed by quantitative histopathology (Bien et al., 2002b). These findings support the hypothesis of an early active inflammation that ‘burns out’ later on (Robitaille, 1991). Clinically, RE is characterized by intractable focal onset seizures, namely epilepsia partialis continua (EPC) (Koshewnikow, 1895), and deterioration of functions associated with the affected hemisphere (Hart and Andermann, 2000; Oguni et al., 1992). RE was initially described as a condition affecting children (Rasmussen et al., 1958). Later, adolescent and adult cases were reported (McLachlan et al., 1993b; Larner et al., 1995; Hart et al., 1997; Leach et al., 1999; Vadlamudi et al., 2000; Hennessy et al., 2001). The most effective treatment of RE with regard to seizure freedom is hemispherectomy. This procedure, however, is usually performed only at later stages of the disease when a patient has developed a fixed hemiparesis with loss of fine finger movements (Villemure et al., 1991; Honavar et al., 1992). In recent years, various attempts at immunotherapy for RE patients have been reported. These open trials were mostly performed in patients who were not yet disabled enough to be eligible for hemispherectomy (Walsh, 1991; Maria et al., 1993; Chinchilla et al., 1994; Hart et al., 1994; Wise et al., 1996; Palcoux et al., 1997; Antozzi et al., 1998; Leach et al., 1999). These studies report some, albeit transient, effect on different disease symptoms. It must be assumed that today most physicians caring for RE patients undertake an attempt of immunotherapy prior to hemispherectomy on the basis of such reports. The interpretation of uncontrolled trials in RE, however, is in particular hampered by the fact that only very few data on the long term course of untreated RE patients are available (Oguni et al., 1992). The present study was designed to close this gap. It intends to comprehensively summarize the course of 13 patients with the typical clinical course and histopathological signs of RE prior to surgical or immunotherapeutical treatment of RE. In addition to clinical parameters (seizure frequency, degree of hemiparesis), a new tool is used for assessing the degree of hemiatrophy in RE, termed hemispheric ratio. This parameter is applied to document the destructive disease process underlying the signs and symptoms of RE. |
Patients and methods |
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TopSummaryIntroductionPatients and methodsResultsDiscussionReferences |
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Patients
Sixteen patients with the clinical course (Oguni et al., 1992
; So and Andermann, 1998) and neuroradiological features (Nakasu et al., 1997; Yacubian et al., 1997) typical of RE were treated at the Epilepsy Centre of the University of Bonn between January 1990 and May 2001. Thirteen of them were histopathologically studied. All exhibited the typical histopathological features of RE (Robitaille, 1991; Honavar et al., 1992; Farrell et al., 1995). These 13 patients were included in this analysis. The period of their disease course prior to resective brain surgery or long-term (>2 weeks) immunosuppressive therapies was studied.
Clinical parameters
From each patient’s records, the seizure frequencies and the degrees of hemiparesis were obtained at each documented clinic visit for the period from the first seizure until 3 years after the beginning of the acute stage (see below). Seizure frequency was documented whereby the average frequency of simple partial motor seizures (SPMS) during the previous month was recorded as number of seizures per day. EPC was defined as regular or irregular clonic muscular twitches affecting a limited part of the body, occurring for a minimum of 1 h, and recurring at intervals of no more than 10 s (Thomas et al., 1977). A total of 52 seizure frequency values were obtained for all 13 cases (median per patient 4; range 2–6). The frequency of other seizure types (complex partial, generalized tonic-clonic) during the previous month was also recorded. The degree of hemiparesis was scored according to the motor item scale of the NIH stroke scale for arm or leg (whatever was more paretic; 0 = no drift; 1 = limb drift; 2 = some effort against gravity; 3 = no effect against gravity; 4 = no movement) (Brott et al., 1989). A total of 51 hemiparesis values were obtained for all 13 patients (median per patient 4; range 2–6). The clinical staging was carried out similar to the Montreal Neurological Institute (MNI) stages of RE (Oguni et al., 1992). Stage 1 is the period from the first epileptic seizure until the beginning of stage 2. Stage 2 is defined as the acute phase of RE, with a rapid increase in seizure frequency (to >10 SPMS per day) accompanied by the development or deterioration of a hemiparesis until the completion of neurological deterioration. Stage 3 is defined as relatively stable state with a permanent hemiparesis and a seizure frequency lower than during stage 2.
Imaging
MRI scans of a total of 37 investigations from different institutions (0.5 Tesla, n = 3; 1.0 Tesla, n = 1; 1.5 Tesla, n = 33) from the period from the first seizure of a patient until 3 years after the beginning of the acute stage (see below) were available for evaluation (median number per patient 3; range 1–5). From four investigations, only axial slices but no coronal ones were available. Axial slices were angulated along the AC–PC line in 30 investigations and along the hippocampal axis in seven investigations. Coronal slices were angulated along the brainstem in 25 investigations and perpendicularly to the hippocampal axis in eight investigations.
Qualitative analysis
An experienced neuroradiologist (H.U.) determined for each patient the site of the initial inflammatory lesion.
Quantitative analysis
To assess the volume of the affected hemisphere in relation to the unaffected one, the following procedure was performed on T1 scans (if no T1 scan was available, FLAIR images were used, or, if no FLAIR images were available, T2 images were used). From each MRI investigation, one axial and (if available) one coronal slice were selected (axial: T1 n = 20, FLAIR n = 8, T2 n = 10; coronal: T1 n = 18, FLAIR n = 10, T2 n = 6; no coronal scan available: n = 4). The selection criteria for the slices aimed at including the Sylvian fissure into analysis, because the perisylvian tissue is usually most strongly affected by the atrophic process (Tampieri et al., 1991). From the axial slices, the one that showed the third ventricle at its largest extent was selected. Selection criteria for the coronal slices were as follows: in investigations angulated along the brainstem, the slice that was closest to the optic chiasm was chosen. From sections angulated perpendicularly to the hippocampal axis, the one that was closest to the anterior commissure was used. The selected axial and coronal slices were scanned with an A3 flatbed scanner at a resolution of 300 x 300 pixel (ScanMaker 9600XL, Microtek International Inc., Taiwan). The following steps were done on the axial and coronal slices by two of the authors independently (C.G.B. and G.W.). The two hemispheres were manually segmented using an image processing software (Picture Publisher 7; Micrografx Inc., Richardson, TX, USA). The threshold function of another image processing software (Scion Image for Windows, Scion Corp., Frederick, MD, USA—free download from www.scioncorp.com) was applied to the segmented brain image. Using the ‘Analyze Particles’ function, the size of each hemisphere (in pixels of the scanned picture) was determined. The ratio of the pixels of the affected and the unaffected hemisphere was computed. Finally, the mean of the four (or two) determined values [two investigators; axial and coronal slices (or only axial slices)] was calculated and termed hemispheric ratio (HR). The HR is dimensionless, it can be calculated independently from the size of the original MRI film, and different investigations can be compared. A value of 1.0 indicates that the both hemispheres on the assessed slices were of equal size, values >1.0 indicate that the affected hemisphere was larger than the unaffected one and values <1.0 indicate atrophy of the affected hemisphere.
Brain specimen collection
Specimens were collected during diagnostic brain biopsies (n = 6), temporal lobe resection (n = 1), subtotal multi-lobar disconnection (n = 1), functional hemispherectomies (n = 4), and hemispherical deafferentations (n = 3) (Schramm et al., 1995). Two patients underwent two surgical procedures (focal resection, functional hemispherectomy), and one patient three surgical procedures (biopsy, subtotal multi-lobar disconnection and total hemispherical deafferentation) due to insufficient seizure control after the initial resections.
Histopathological evaluation
Specimens were embedded, 4-µm sections were cut from paraffin blocks and used for haematoxylin–eosin stain and immunohistochemistry. Antibodies against the following molecules were used for immunohistochemical reactions (all from Dakopatts, Hamburg, Germany): CD3, CD68, HLA-DR and glial fibrillary acidic protein (GFAP). An avidin–peroxidase complex protocol was used for the demonstration of all antibodies, as described previously (Deckert-Schlüter et al., 1998).
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Results |
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Clinical, neuroradiological and neuropathological data of the patients are summarized in Table 1. A characteristic MRI course demonstrating the method of determining the HR is shown in Fig. 1.
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Stage-wise course of RE
Even though no continuous documentation of seizure frequency and development of seizure frequency was available, it was, in all patients, possible to distinguish the following stages (information was very limited in Patient 05 only; see Table 1).
Prodromal phase
An initial prodromal phase (MNI stage 1) was characterized by a relatively low seizure frequency and only rarely some degree of hemiparesis. It had a median duration of 7.1 months (range 0 months to 8.1 years) and was clearly longer in the adolescent and adult patients compared with the children (see below).
Acute disease
All patients went through a period of acute disease (equivalent to MNI stage 2), with frequent SPMS (in 69% of the patients in the form of EPC) and development of hemiparesis (only one patient did not develop a hemiparesis). The median duration of this acute period was 8 months (range 4–8 months). The initial MRI scans, usually performed during this stage, showed that the inflammatory lesions (hyperintense T2/FLAIR signal) in all patients had a monofocal onset. The initial lesions were in all but one patient found in between the Rolandic and the temporo-medial area (see Table 1 for details). The lesions then spread across the ipsilateral hemisphere, or parts of it. Assessment of the HR showed that during this acute period, most of the hemispheric volume loss occurred. In some patients, there was a short-term swelling of the affected hemisphere during the earliest scans within the first 6 months of the acute phase before atrophy began. One year after the onset of the acute stage, the average HR was 0.72 (see Fig. 2).
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Residual stage
The acute phase was followed by a residual stage (MNI stage 3) with a permanent and stable hemiparesis. In three patients, treatment had been performed during the acute stage, they thus did not reach the residual stage in the sense of this study. Of the remaining 10, five were children and five were adolescents or adults. Five of these 10 patients had a grade 4 hemiparesis [four children, one adolescent (Patient 08)]; one patient (an adult) had a grade 3 hemiparesis; and two patients had a grade 2 hemiparesis (one child, one adolescent). The remaining two adult patients had no hemiparesis (in one of them, a degree 1 hemiparesis had been present during the acute phase and disappeared then). Seizure frequency decreased in all patients during the residual stage, and one patient even became seizure free. In two patients (03 and 10), however, EPC recurred after a period of remission with fixed neurological deficit, and led to surgical treatment. Figure 2 depicts all available seizure frequency figures, the hemiparesis degrees and the HR values of all patients.
Type 1 and 2 patients
There were two groups of patients with marked differences with regard to age, duration of the prodromal stage and outcome. To account for these differences, a distinction between type 1 and type 2 patients is suggested.
The type 1 patients (n = 7, Patients 01–07) had a median age of 5.3 years (range 1.6–6.1 years) at their first seizure. They had been healthy until the disease became manifest by the first epileptic seizure. The prodromal phase was omitted or was short (median 0 months, range 0–7 months). The median duration of the acute period in the four patients in whom no surgical or immunosuppressive treatment was performed in this phase was 8 months (range 4–8 months). In Patient 06, the acute phase was still ongoing when he was operated on 15 months after the beginning of the acute stage. The average HR 12 months after the onset of the acute period was 0.60 (see Fig. 3A). Dual pathology (a small old infarction, most probably dating back prior to the manifestation of RE) was found in Patient 04. Five type 1 patients underwent hemispherectomy or one of its variants.
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The type 2 patients (n = 6, Patients 08–13) had a median age of 18.9 years (range 6.4–40.9 years) at disease manifestation. During the prodromal stage (median duration 3.2 years, range 1.3–8.1 years), they had a focal epilepsy with complex partial seizures or secondarily generalized tonic-clonic seizures, but rare (if any) simple partial motor seizures. Hemiparesis during this stage was present in only one patient (Patient 08), who had developed it even prior to her first seizure. In those five patients, in whom neither surgery nor immunosuppression was performed during the acute phase, it lasted a median of 7.5 months (range 7–8 months). Hemiparesis and hemispheric atrophy during the acute stage did not reach the same degree as in the type 1 patients. The average HR 12 months after the onset of the acute stage was 0.88 (see Fig. 3B). No case with dual pathology was identified in this group. The course of these type 2 patients was less uniform than that of the type 1 cases. Only two type 2 patients underwent hemispherectomy.
On histopathological examination of the specimens, the two groups did not differ. Chronic inflammation in a manner typical of RE (Robitaille, 1991; Honavar et al., 1992; Farrell et al., 1995) was found in all patients. There were perivascular and parenchymal CD3+ T lymphocytes, CD68 and HLA-DR positive microglial cells (diffuse and in nodules) and GFAP+ astrocytes, the majority of which were of the ‘reactive phenotype’, with hyperplastic cytoplasm and star-like processes (Kreutzberg et al., 1997). Neuronal cell density appeared to be reduced, particularly in chronic cases.
Reliability of HR
The mean difference between the two raters in the assessment of the HR values was for the axial slices 0.031 (SD ± 0.035; range 0.001–0.143) and for the coronal slices 0.026 (SD ± 0.022; range 0.001–0.095).
Correlation of clinical parameters to the HR
The course of hemispheric volume loss during the acute stage was correlated to the evolution of hemiparesis (see Fig. 2). During the process of hemispheric destruction, the seizure frequency was high. During stages of relatively stable hemispheric ratios (prodromal stage and residual stage), the seizure frequency was lower.
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Discussion |
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TopSummaryIntroductionPatients and methodsResultsDiscussionReferences |
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In this study we describe the natural history of RE in 13 histopathologically studied patients. All patients go through an acute period with frequent SPMS and development of hemiparesis, which has a median duration of 8 months, and then pass into a residual stage (documented in 10 patients, three were treated during the acute phase and were thus excluded from further analysis). In our experience, the three stages are clinically reliably distinguishable as follows, even under retrospective conditions: (i) the onset of an epilepsy with a medium seizure frequency (stage 1) is almost always clearly remembered by the patient or his parents and documented by a physician; (ii) the massive increase in seizure frequency with beginning hemiparesis (stage 2) almost always leads to an admission to a hospital with documentation of the clinical status; (iii) only the transition to the residual stage 3 (decrease in seizure frequency, stabilization of the hemiparesis) may sometimes be less sharply delimited from the previous acute stage. Two patterns of the disease course could be distinguished: the type 1 patients (children) have a more rapid and severe disease, whereas the type 2 patients (adolescents and adults) have a more protracted and milder course with a longer, relatively unspecific, prodromal phase. The differences in the clinical and neuroradiological course are quite distinct in the patients reported here. However, due to the relatively small number of patients with this rare condition studied here, it is still possible that one or two atypical cases may have biased the results to a certain extent.
The clinical parameters seizure frequency and hemiparesis have previously been used for a depiction of the natural history of RE (Oguni et al., 1992). MRI investigations have gained increasing importance in the diagnosis of RE (Zupanc et al., 1990; Tampieri et al., 1991; Tien et al., 1992; Chinchilla et al., 1994; Cendes et al., 1995; Geller et al., 1998; So and Andermann, 1998; Koehn and Zupanc, 1999; Sundgren et al., 1999; Kaiboriboon et al., 2000; Vadlamudi et al., 2000), but serial MRI investigations have only rarely been reported (Nakasu et al., 1997; Yacubian et al., 1997; Türkdogan-Sözüer et al., 2000; Bien et al., 2002b). A parameter like the HR, reflecting the degree of cerebral hemiatrophy in RE, has not previously been used in published RE cases. The HR as described here can be applied to MRI hard copies, which are usually the only available depiction of previous stages of the disease process once a RE patient is transferred to an epilepsy centre. This parameter, which is obtained by measuring a coronal and an axial MRI slice including the most strongly affected perisylvian tissue, appears to be a sensitive marker of the underlying destructive process correlated to the degree of neurological deficit. The procedure of determining the HR has a high inter-rater reliability. Its usefulness in predicting disease activity will require further study. The interpretation of the HR may be difficult in the apparently rare cases of RE affecting both hemispheres (we have not encountered such a case yet), and perhaps in some patients with double pathology.
The time periods of the three disease phases reported here are comparable to those of the MNI stages. The definition of the acute period (corresponding to the MNI stage 2) used here adds the rapid increase in seizure frequency at its onset to the MNI criteria of the development of a fixed neurological deficit, which may be difficult to assess, especially at the beginning. In their 1992 study, Oguni and co-workers did not distinguish between the two types of disease course as described here (Oguni et al., 1992). In subsequent reports, ‘late-onset’ RE cases with a milder disease course were described (McLachlan et al., 1993; Hart et al., 1997; Vadlamudi et al., 2000). It is open to discussion how the dichotomy of type 1 patients (children) and type 2 patients (adolescents and adults) can be explained. The following are possibilities. (i) The two types represent different pathogenic forms of chronic encephalitis. This is unlikely, however, since the differences between the two types are less striking than the features they have in common (affection of only one hemisphere, EPC as typical seizure type, identical inflammatory histopathological findings). (ii) Type 2 RE represents basically the same disease process as type 1 RE. This process, however, is slower and less aggressive in type 2 patients (perhaps because of the higher age of the patients, at which the brain may be less vulnerable than during childhood). The prodromal period, which is particularly evident in type 2 patients, with non-specific focal onset seizures, may then lead to the assumption that RE patients initially (during the prodromal phase) have a non-encephalitic brain disorder. According to this hypothesis, brain inflammation would be superimposed on a pre-existing focal abnormality, e.g. via a disruption of the blood–brain barrier. This secondary inflammation would lead to the acute stage and ‘burn itself out’ later on (Robitaille, 1991; Hart and Andermann, 2000). This pathogenic concept has recently been discussed by the MNI group in their study on double pathology in RE. Cases with additional, non-inflammatory lesions accounted for 
10% of all MNI RE patients (Hart et al., 1998) and one patient (8%) in the sample described here; two other patients in the present series had evidence of another pre-existing cerebral disorder (in addition to the focal epilepsy during the prodromal stage): one developed initially a hemiparesis, and one had migraine attacks with visual auras (this patient developed unusual occipito-parietal onset RE). However, the hypothesis of a non-inflammatory brain dysfunction as a prerequisite of RE cannot as yet be proven.
In conclusion, this study provides data on the clinical natural history and, for the first time, on the time course of brain destruction, in a sample of 13 patients. These observations may have the following implications: (i) for clinical purposes, the data permit an estimation of the prognosis of RE patients, including a distinction between type 1 and type 2 cases (prognosis somewhat better for the latter); and (ii) the period of the most extensive brain damage is, on average, the 8 months of the acute disease phase. Future therapeutic interventions should therefore focus on this time period rather than on later ‘burnt out’ stages, during which the majority of brain atrophy has already taken place. Clinical improvement in RE patients after this time period is most probably due to the natural course of the disease, with a decrease of seizure frequency and possible adaptive processes (as, for example, in patients after a stroke), and probably not due to immunotherapeutic interventions. It is suggested that future immunotherapy trials in RE assess the hemispheric volume loss as an additional surrogate parameter for the underlying destructive disease process of RE.
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Acknowledgements |
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The authors thank Karin Schmidt, Hannelore Storma, Gerd Thüner and Rüdiger Schmidt for expert technical assistance with the artwork.
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References |
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|
TopSummaryIntroductionPatients and methodsResultsDiscussionReferences |
|---|
Antozzi C, Granata T, Aurisano N, Zardini G, Confalonieri P, Airaghi G, et al. Long-term selective IgG immuno-adsorption improves Rasmussen’s encephalitis. Neurology 1998; 51: 302–5.
Bien CG, Bauer J, Deckwerth TL, Wiendl H, Deckert M, Wiestler OD, et al. Destruction of neurons by cytotoxic T cells: a new pathogenic mechanism in Rasmussen’s encephalitis. Ann Neurol 2002a; 51: 311–8.[Web of Science][Medline]
Bien CG, Urbach H, Deckert M, Schramm J, Wiestler OD, Lassmann H, et al. Diagnosis and staging of Rasmussen’s encephalitis by serial MRI and histopathology. Neurology 2002b; 58: 250–7.
Brott T, Adams HP, Olinger CP, Marler JR, Barsan WG, Biller J, et al. Measurements of acute cerebral infarction: a clinical examination scale. Stroke 1989; 20: 864–70.
Cendes F, Andermann F, Silver K, Arnold DL. Imaging of axonal damage in vivo in Rasmussen’s syndrome. Brain 1995; 118: 753–8.
Chinchilla D, Dulac O, Robain O, Plouin P, Ponsot G, Pinel JF, et al. Reappraisal of Rasmussen’s syndrome with special emphasis on treatment with high doses of steroids. J Neurol Neurosurg Psychiatry 1994; 57: 1325–33.
Deckert-Schlüter M, Rang A, Wiestler OD. Apoptosis and apoptosis-related gene products in primary non-Hodgkin’s lymphoma of the central nervous system. Acta Neuropathol (Berl) 1998; 96: 157–62.[Medline]
Farrell MA, Droogan O, Secor DL, Poukens V, Quinn B, Vinters HV. Chronic encephalitis associated with epilepsy: immunohistochemical and ultrastructural studies. Acta Neuropathol (Berl) 1995; 89: 313–21.[Medline]
Geller E, Faerber EN, Legido A, Melvin JJ, Hunter JV, Wang Z, et al. Rasmussen encephalitis: complementary role of multitechnique neuroimaging. AJNR Am J Neuroradiol 1998; 19: 445–9.[Abstract]
Hart Y, Andermann F. Rasmussen syndrome. In: Oxbury JM, Polkey CE, Duchowny M, editors. Intractable focal epilepsy. London: W. B. Saunders; 2000. p. 233–48.
Hart YM, Cortez M, Andermann F, Hwang P, Fish DR, Dulac O, et al. Medical treatment of Rasmussen’s syndrome (chronic encephalitis and epilepsy): effect of high-dose steroids or immunoglobulins in 19 patients. Neurology 1994; 44: 1030–6.
Hart YM, Andermann F, Fish DR, Dubeau F, Robitaille Y, Rasmussen T, et al. Chronic encephalitis and epilepsy in adults and adolescents: a variant of Rasmussen’s syndrome? Neurology 1997; 48: 418–24.
Hart YM, Andermann F, Robitaille Y, Laxer KD, Rasmussen T, Davis R. Double pathology in Rasmussen’s syndrome: a window on the etiology? Neurology 1998; 50: 731–5.
He XP, Patel M, Whitney KD, Janumpalli S, Tenner A, McNamara JO. Glutamate receptor GluR3 antibodies and death of cortical cells. Neuron 1998; 20: 153–63.[Web of Science][Medline]
Hennessy MJ, Koutroumanidis M, Dean AF, Jarosz J, Elwes RD, Binnie CD, et al. Chronic encephalitis and temporal lobe epilepsy: a variant of Rasmussen’s syndrome? Neurology 2001; 56: 678–81.
Honavar M, Janota I, Polkey CE. Rasmussen’s encephalitis in surgery for epilepsy. Dev Med Child Neurol 1992; 34: 3–14.[Web of Science][Medline]
Kaiboriboon K, Cortese C, Hogan RE. Magnetic resonance and positron emission tomography changes during the clinical progression of Rasmussen encephalitis. J Neuroimaging 2000; 10: 122–5.[Web of Science][Medline]
Koehn MA, Zupanc ML. Unusual presentation and MRI findings in Rasmussen’s syndrome. Pediatr Neurol 1999; 21: 839–42.[Web of Science][Medline]
Koshewnikow AJ. Eine besondere Form von corticaler Epilepsie. Neurol Centralbl 1895; 14: 47–8.
Kreutzberg GW, Blakemore WF, Graeber MB. Cellular pathology of the central nervous system. In: Graham DI, Lantos PL, editors. Greenfield’s neuropathology, Vol. 1. 6th ed. London: Arnold; 1997. p. 115–56.
Larner AJ, Smith SJ, Duncan JS, Howard RS. Late-onset Rasmussen’s syndrome with first seizure during pregnancy [letter]. Eur Neurol 1995; 35: 172.[Web of Science][Medline]
Leach JP, Chadwick DW, Miles JB, Hart IK. Improvement in adult-onset Rasmussen’s encephalitis with long-term immunomodulatory therapy. Neurology 1999; 52: 738–42.
Levite M, Fleidervish IA, Schwarz A, Pelled D, Futerman AH. Autoantibodies to the glutamate receptor kill neurons via activation of the receptor ion channel. J Autoimmun 1999; 13: 61–72.[Web of Science][Medline]
Maria BL, Ringdahl DM, Mickle JP, Smith LJ, Reuman PD, Gilmore RL, et al. Intraventricular alpha interferon therapy for Rasmussen’s syndrome. Can J Neurol Sci 1993; 20: 333–6.[Web of Science][Medline]
McLachlan RS, Girvin JP, Blume WT, Reichman H. Rasmussen’s chronic encephalitis in adults. Arch Neurol 1993; 50: 269–74.
Nakasu S, Isozumi T, Yamamoto A, Okada K, Takano T, Nakasu Y. Serial magnetic resonance imaging findings of Rasmussen’s encephalitis—case report. Neurol Med Chir (Tokyo) 1997; 37: 924–8.[Medline]
Oguni H, Andermann F, Rasmussen TB. The syndrome of chronic encephalitis and epilepsy. A study based on the MNI series of 48 cases. Adv Neurol 1992; 57: 419–33.[Medline]
Palcoux JB, Carla H, Tardieu M, Carpentier C, Sebire G, Garcier JM, et al. Plasma exchange in Rasmussen’s encephalitis. Ther Apher 1997; 1: 79–82.[Medline]
Rasmussen T, Olszewski J, Lloyd-Smith D. Focal seizures due to chronic localized encephalitis. Neurology 1958; 8: 435–45.
Robitaille Y. Neuropathologic aspects of chronic encephalitis. In: Andermann F, editor. Chronic encephalitis and epilepsy. Rasmussen’s syndrome. Boston: Butterworth-Heinemann; 1991. p. 79–110.
Rogers SW, Andrews PI, Gahring LC, Whisenand T, Cauley K, Crain B, et al. Autoantibodies to glutamate receptor GluR3 in Rasmussen’s encephalitis. Science 1994; 265: 648–51.
Schramm J, Behrens E, Entzian W. Hemispherical deafferentation: an alternative to functional hemispherectomy. Neurosurgery 1995; 36: 509–15.[Web of Science][Medline]
So NK, Andermann F. Rasmussen’s syndrome. In: Engel J Jr, Pedley TA, editors. Epilepsy. A comprehensive textbook. Philadelphia: Lippincott-Raven; 1998. p. 2379–88.
Sundgren PC, Burtscher IM, Lundgren J, Geijer B, Holtas S. MRI and proton spectroscopy in a child with Rasmussen’s encephalitis. Case report. Neuroradiology 1999; 41: 935–40.[Web of Science][Medline]
Tampieri D, Melanson D, Ethier R. Imaging of chronic encephalitis. In: Andermann F, editor. Chronic encephalitis and epilepsy. Rasmussen’s syndrome. Boston: Butterworth-Heinemann; 1991; p. 47–60.
Thomas JE, Reagan TJ, Klass DW. Epilepsia partialis continua. A review of 32 cases. Arch Neurol 1977; 34: 266–75.
Tien RD, Ashdown BC, Lewis DV Jr, Atkins MR, Burger PC. Rasmussen’s encephalitis: neuroimaging findings in four patients. AJR Am J Roentgenol 1992; 158: 1329–32.
Türkdogan-Sözüer D, Özek MM, Sav A, Dincer A, Pamir MN. Serial MRI and MRS studies with unusual findings in Rasmussen’s encephalitis. Eur Radiol 2000; 10: 962–6.[Web of Science][Medline]
Twyman RE, Gahring LC, Spiess J, Rogers SW. Glutamate receptor antibodies activate a subset of receptors and reveal an agonist binding site. Neuron 1995; 14: 755–62.[Web of Science][Medline]
Vadlamudi L, Galton CJ, Jeavons SJ, Tannenberg AE, Boyle RS. Rasmussen’s syndrome in a 54 year old female: more support for an adult variant. J Clin Neurosci 2000; 7: 154–6.[Web of Science][Medline]
Villemure J-G, Andermann F, Rasmussen TB. Hemispherectomy for the treatment of epilepsy due to chronic encephalitis. In: Andermann F, editor. Chronic encephalitis and epilepsy. Rasmussen’s syndrome. Boston: Butterworth-Heinemann; 1991. p. 235–41.
Walsh PJ. Treatment of Rasmussen’s syndrome with intravenous gammaglobulin. In: Andermann F, editor. Chronic encephalitis and epilepsy. Rasmussen’s syndrome. Boston: Butterworth-Heinemann; 1991. p. 201–4.
Wise MS, Rutledge SL, Kuzniecky RI. Rasmussen syndrome and long-term response to gamma globulin. Pediatr Neurol 1996; 14: 149–52.[Web of Science][Medline]
Yacubian EM, Marie SK, Valerio RM, Jorge CL, Yamaga L, Buchpiguel CA. Neuroimaging findings in Rasmussen’s syndrome. J Neuroimaging 1997; 7: 16–22.[Web of Science][Medline]
Zupanc ML, Handler EG, Levine RL, Jahn TW, ZuRhein GM, Rozental JM, et al. Rasmussen encephalitis: epilepsia partialis continua secondary to chronic encephalitis. Pediatr Neurol 1990; 6: 397–401.[Web of Science][Medline]
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