This paper was prepared by Dr Ian Hart Senior Lecturer in Neurology Neuroimmunology
Group, University Department of Neurological Science Clinical Sciences Building,
Walton Centre, Lower Lane Liverpool
Introduction
Rasmussen’s encephalitis (RE; also called Rasmussen’s syndrome) is a
progressive inflammation of the part of the brain called the cerebral cortex, which
is made up of a right and a left hemisphere. The disease starts at one site in one
hemisphere and spreads to adjoining areas on the same side. Curiously, it does not
spread to the other hemisphere. The inflammation leads to loss of nerve cells and
scar formation and usually results in severe disability. Although RE is most often
diagnosed in children under the age of 10 years, it can also start in adolescence
and adulthood. It is a rare disorder and probably affects one person in every 500
000 to 1 000 000.
Clinical features
The clinical problems in RE are determined by which areas of the affected hemisphere
are inflamed: each area has different functions. As the disease spreads, more areas
are damaged and the greater the severity and range of the disabilities. Typically,
the disease progresses relentlessly until most of one hemisphere is affected. The
inflammation burns out by itself only rarely before severe disability has occurred.
However, the speed of the spread varies between patients. At one end of the spectrum,
the disease advances rapidly over a few weeks or months. At the other end, progression
occurs slowly over several years. This slower clinical variant seems to be more
common in adolescents and adults than in children. It is possible that there are
milder forms of RE that we fail to recognize.
The typical clinical features are:
Epilepsy
Usually, the first sign of the disease is focal epilepsy. If the motor cortex (the
area that controls movement) is affected, the patients have motor seizures with
jerking of one side of the body. Sometimes the motor seizures become continuous,
and this state is called continuous partial epilepsy. Similarly, if the temporal
cortex is affected, patients have temporal lobe seizures (complex partial seizures)
with altered awareness of their surroundings.
Although the seizures start at one site, they can spread to the rest of the brain
and cause generalized epilepsy with loss of consciousness. As the disease progresses,
the seizures become more frequent, more severe, and more difficult to treat with
standard anti-epileptic drugs.
Neurological deficits
Hemiparesis. The wiring of the nervous system determines that a lesion of one side
of the brain causes problems on the opposite side of the body. Thus, involvement
of the motor cortex in one hemisphere causes weakness of the other side of the body.
If the sensory cortex is affected the patient has numbness of the other side of
the body (hemianaesthesia).
Visual loss. Damage to the visual areas in one hemisphere causes loss of vision
in the opposite direction (hemianopia)
Speech problems. If the speech areas are affected, patients may be unable
to translate their thoughts into words (expressive dysphasia) and have difficulty
understanding what others say to them (receptive dysphasia).
Cognitive deficits Patients can develop memory problems, intellectual impairment,
and other neuropsychological deficits.
Causes
There is convincing evidence that in most patients RE is an autoimmune disorder.
Many patients have antibodies in their blood that bind to nerve cells and which
are capable of damaging the brain. Of particular interest is an antibody that binds
to an important nerve protein called the type-3 glutamate receptor (GluR3). In addition,
activated immune cells called T cells that are toxic to nerve cells are found in
inflammatory brain tissue in biopsies from RE patients.
In most patients, it is not clear what triggers the abnormal immune response, although
sometimes RE has followed an otherwise minor bacterial or viral infection, or head
injury.
Diagnosis
A serious disease needs intensive investigation. The tests are designed to confirm
RE and to exclude other conditions. Diseases that can mimic RE include viral and
toxoplasma encephalitis, autoimmune disorders such as vasculitis, and tumours.
The most useful investigations are
- Brain scans. MR, SPECT, and if available PET scans are useful. Figure 1 shows an
MR brain scan of severe RE.
- Blood tests. These include assays for a range of antibodies and tests to exclude
infection.
- Lumbar puncture. Spinal fluid is examined for evidence of inflammation and infection.
- Brain biopsy. This is needed to confirm the diagnosis.
-
Electroencephalogram (EEG). This records the electrical activity of the brain and
is useful in characterising the type of seizures the patient has.
Treatment
Because in RE the seizures often do not improve with anti-epilepsy drugs and the
disease only ends with destruction of the affected cerebral hemisphere, surgical
removal of large areas, sometimes all, of the hemisphere became a standard treatment.
However, the research evidence of autoimmune abnormalities in many patients, and
the clear need for effective medical therapy early in the disease to prevent progression,
helped prompt trials of immune therapy.
Immune therapy
Trials of various combinations of powerful drugs that suppress the immune system
(prednisolone, azathioprine, methotrexate, and cyclophosphamide) and therapies that
modulate the function of the immune system (plasma exchange and intravenous immunoglobulin)
have been tried. However, these trials have usually been performed in individual
patients and there are no good data on the optimum combination, dosing, or duration
of immune treatments.
It seems likely that to modify or arrest the progression of a chronic, destructive
disease such as RE, most patients will need a combination of therapies at high dose
for prolonged periods – perhaps indefinitely.
The combination of daily oral prednisolone (a steroid) and monthly pulses of intravenous
immunoglobulin appears promising. All eight patients, mostly with adult-onset RE,
that we have treated in this way for up to five years have had useful improvement
in their epilepsy control and, so far, have not developed any new disabilities.
Sometimes, the disabilities that were present before treatment have improved.
Regardless of the type of immune therapy used, the outcome is likely to be better
the earlier the treatment is started. The decision to start immune therapy is not
taken lightly. These treatments have many potentially serious side effects, especially
in children, and require very careful monitoring.
Surgery
This is the traditional treatment for advanced RE, and is used mainly to improve
seizure control in patients with established disability. The extent of the surgery
is determined by the severity, duration, rate of progression, and site of the disease,
and the age of the patient. In patients with severe disease, all of the affected
hemisphere may be removed (hemispherectomy).
When we find out more about the best use of immune therapy in RE, it is hoped that
fewer patients will need surgery.
Anti-epileptic drugs
As epilepsy in RE is usually difficult to control, patients often try many drugs
before the best combination is found. These drugs have no effect on progression
of the underlying encephalitis.
Other therapies
Various anti-viral drugs have been tried in some patients thought to have RE. However,
they are likely to be useful only when the patient has a viral encephalitis rather
than autoimmune RE.
Last modified: July 2005