Rasmussen syndrome (Rasmussen’s encephalitis) is a rare, chronic neurological disorder typically affecting children between two and ten years old. This progressive disease involves chronic inflammation localized almost exclusively to one hemisphere of the brain. The inflammation causes irreversible damage to brain tissue, resulting in severe, frequent, and drug-resistant epilepsy. This form of chronic focal encephalitis is defined by continuous, debilitating seizure activity that resists conventional anti-seizure medications.
The Underlying Mechanism of Rasmussen Syndrome
The precise cause of Rasmussen Syndrome remains unknown, but current understanding points to an underlying autoimmune or inflammatory process. It is considered a T-cell-mediated autoimmune encephalitis, where the body’s immune system mistakenly attacks brain tissue. Histological analysis consistently reveals an infiltration of cytotoxic CD8+ T lymphocytes, which are immune cells that directly target and destroy neurons and glial cells.
These T-cells release substances like granzyme B and perforin, inducing neuronal death and progressive loss of brain matter. The resulting inflammation is multifocal, causing neuronal loss, gliosis, and microglial nodules within the affected hemisphere. Although a viral infection theory was proposed, extensive testing for various viruses has yielded negative results.
The fact that the damage is almost always confined to a single hemisphere is a major mystery in the disease’s pathogenesis, suggesting an unknown factor limits the inflammatory process to one side. Researchers hypothesize that an initial focal event, such as a seizure, may damage the blood-brain barrier on one side. This damage allows immune cells and inflammatory molecules to infiltrate and begin the destructive cycle. The presence of specific autoantibodies has been investigated, but these are generally considered a secondary consequence of the tissue damage rather than the primary cause.
Clinical Manifestation and Disease Progression
The progression of Rasmussen Syndrome is described in three sequential stages: prodromal, acute/active, and residual. The prodromal stage may last for months or years, presenting with infrequent, mild focal seizures and subtle weakness on one side of the body. Neurological deficits are minimal during this initial phase, and seizures may initially respond to standard anti-epileptic medications.
The disease then enters the acute or active stage, characterized by a rapid escalation in seizure frequency and severity, often lasting four to eight months. The hallmark symptom of this stage is Epilepsia Partialis Continua (EPC), a relentless focal seizure involving continuous rhythmic twitching of a localized body part, such as the face, arm, or leg. Approximately half of all patients experience this constant seizure activity.
During this active phase, patients develop progressive hemiparesis, the gradual weakening and eventual paralysis of the side of the body opposite the affected hemisphere. This motor deficit worsens as inflammation causes increasing atrophy and permanent damage to the motor cortex. Patients also experience cognitive decline, including functional and intellectual deterioration, and if the dominant hemisphere is affected, they may develop aphasia, or difficulty with language. The final residual stage stabilizes the neurological deficits; seizures may decrease, but severe hemiparesis and cognitive impairment become permanent.
Diagnostic Procedures and Confirmation
The diagnosis of Rasmussen Syndrome is primarily clinical, supported by imaging and electrophysiological tests. Electroencephalography (EEG) monitors brain activity and typically reveals continuous focal seizure activity, or a pattern of persistent high-amplitude slow-wave activity, often called delta activity, over the affected hemisphere. The EEG confirms the presence of a chronic, unilateral seizure focus.
Magnetic Resonance Imaging (MRI) is essential for diagnosis and monitoring progression. Early MRI may show inflammation and swelling in the affected hemisphere. As the condition advances, the MRI characteristically reveals progressive unilateral cerebral atrophy, where the affected hemisphere shrinks and the fluid-filled spaces, like the ventricles, appear enlarged.
A brain biopsy is occasionally performed but is not always necessary when clinical and radiological evidence is strong. A biopsy confirms the diagnosis by showing characteristic pathological features, including chronic inflammation, T-cell infiltration, and neuronal loss confined to one hemisphere. The combination of drug-resistant EPC, progressive hemiparesis, and unilateral atrophy on MRI is usually sufficient for a definitive diagnosis.
Therapeutic Approaches and Management
Initial management focuses on pharmacological strategies to control seizures and suppress inflammation. Anti-epileptic drugs (AEDs) are the first line of defense, but they have limited efficacy against the severe, chronic seizures characteristic of this condition. Because of the disease’s inflammatory nature, treatments directed at the immune system are necessary.
Immunomodulatory therapies are used to slow inflammatory destruction, particularly in the early stages. These include high-dose corticosteroids, intravenous immunoglobulin (IVIG), and plasma exchange. While these treatments may temporarily reduce seizure frequency or slow neurological deficits, they are generally not curative and do not halt the long-term course of the disease. For many patients, these medical therapies serve as a bridge while the disease progresses to a point where a more definitive treatment is required.
For cases progressing despite medical management, the only definitive treatment for long-term seizure freedom is a surgical procedure: hemispherectomy or hemispherotomy. This operation surgically disconnects the affected hemisphere from the healthy side of the brain, eliminating the seizure source. Although highly effective at stopping seizures, the procedure inevitably results in permanent loss of function controlled by that hemisphere, including dense hemiparesis and potential vision loss. Post-operative rehabilitation, including physical and occupational therapy, is necessary to maximize functional recovery and adaptation.