Subacute Sclerosing Panencephalitis

What Causes Subacute Sclerosing Panencephalitis?

Scientists are not sure of the precise causes of SSPE, but the disorder is undoubtedly a reaction to the measles virus. Some cases may occur when the body’s immune system has an inappropriate response to the virus and begins attacking healthy cells. It is also possible that SSPE is caused by a mutated form of the virus that lies dormant in the body for an extended period and is then reactivated by some unknown trigger.

Is Subacute Sclerosing Panencephalitis Hereditary?

Some scientists believe that genetic predispositions may make certain people more likely to develop SSPE after a measles infection. In addition, studies have found an association between cases of SSPE and mutations in genes involved in the immune system. However, research into these genetic connections is still in the early stages, and a definitive genetic relationship has not yet been identified.

How Is Subacute Sclerosing Panencephalitis Detected?

Early signs of SSPE are often subtle and may be overlooked until the more obvious neurological symptoms begin to emerge. Behavioral symptoms are also similar to those of other disorders, so misdiagnosis may also be a problem.

Early symptoms of SSPE often include:

• A decline in school performance
• Irritability, anger, or other personality changes
• Problems with concentration
• Poor judgment
• Speech or language difficulties

How Is Subacute Sclerosing Panencephalitis Diagnosed?

A doctor may suspect SSPE when a child shows behavioral symptoms, experiences neurological symptoms such as jerking muscles, and has had measles in the past. Several exams and tests can detect signs of SSPE.

Diagnostic steps may include:

• Blood tests to look for evidence of a past measles infection
• Electroencephalogram (EEG) to look for abnormal brain activity
• Examination of the cerebrospinal fluid (CSF) to look for signs of inflammation in the central nervous system
• Imaging scans such as magnetic resonance imaging (MRI) or computerized tomography (CT) to look for structural deterioration in the brain

PLEASE CONSULT A PHYSICIAN FOR MORE INFORMATION.

How Is Subacute Sclerosing Panencephalitis Treated?

SSPE has no cure, and no treatment will stop or reverse its symptoms. Treatment options will focus on managing symptoms, preventing complications for as long as possible, and improving quality of life. Anti-convulsant medications may be prescribed to control seizures and jerking muscles.

Some trials of antiviral drugs have shown effectiveness at slowing the progression of symptoms and prolonging life, but other trials have been unsuccessful. Research on the efficacy of these medications as a treatment for SSPE is ongoing.

How Does Subacute Sclerosing Panencephalitis Progress?

SSPE is a progressive disorder, meaning that its symptoms worsen over time. Neurological symptoms get worse, and complications of the condition are eventually fatal. In most cases, the condition is fatal within 1-3 years, but individual cases may progress faster or more slowly.

Long-term symptoms and complications of SSPE include:

• Muscle rigidity
• Loss of the ability to walk
• Swallowing difficulties
• Breathing difficulties
• Blindness
• Elevated body temperature, heart rate, and blood pressure
• Coma and persistent vegetative state
• Pneumonia
• Heart failure

How Is Subacute Sclerosing Panencephalitis Prevented?

Prevention of measles infection is the only way to prevent SSPE. The disorder is rare in countries with a widespread measles vaccination program and more common in countries where vaccination is less accessible. In addition, SSPE seems to be more common in children who have had measles before two, so early vaccination is vital. The CDC currently recommends that children be vaccinated against measles between the ages of 12 and 15 months.

Subacute Sclerosing Panencephalitis Caregiver Tips

• Vaccinate your children. SSPE is rare in the United States because of widely available measles vaccines. However, failing to follow your doctor’s guidelines about when and how to vaccinate puts your child and the rest of the community at risk.
• Reach out for the help you need. Caring for a child with SSPE is a monumental task, and you shouldn’t try to go it alone. Don’t hesitate to ask for help from family and friends, and ask your child’s medical providers about resources and support groups to help you cope.

Some people with SSPE also suffer from other brain-related issues, a condition called co-morbidity. Here are a few of the disorders commonly associated with SSPE:

• Dementia and coma may be complications of SSPE.
• Sleep disruptions, including insomnia, are often a symptom of SSPE.

Subacute Sclerosing Panencephalitis Brain Science

SSPE symptoms appear long after the initial infection seems to have passed, but studies have suggested that the measles virus may infect the brain soon after the initial infection. The virus may spread throughout the brain, where it will lie dormant and, in SSPE cases, reactivate because of an unknown trigger years later.

Once reactivated, the infection causes widespread damage to brain tissue in several ways, including:

• Loss of nerve cells (neurons)
• Loss of nerve cells’ protective covering (myelin)
• Degeneration of dendrites (structures that aid in communication between nerve cells)
• Abnormal tangled proteins inside brain cells
• Abnormal accumulation of cells called astrocytes
• Infiltration of immune system cells into the brain

Subacute Sclerosing Panencephalitis Research

Title:  The ExTINGUISH Trial of Inebilizumab in NMDAR Encephalitis (ExTINGUISH)

Stage: Not yet recruiting

Contact: Stacey L. Clardy, MD, PhD

University of Utah

Salt Lake City, UT

N-methyl-D-aspartate receptor (NMDAR) encephalitis is one of the most common causes of autoimmune encephalitis, with prevalence exceeding herpes encephalitis in industrialized nations. Typically, the disease affects patients age 10-50 causing prominent psychiatric symptoms, altered consciousness, seizures, movement disorders, and life-threatening dysautonomia. Intensive care, including cardiorespiratory support, is required in 75% of cases. The diagnosis is confirmed by the detection of IgG autoantibodies against central nervous system NMDAR in the cerebrospinal fluid. Despite the severity of the illness, NMDAR encephalitis is a treatable neurological disease, with retrospective case series establishing the benefit of off-label intravenous steroids and immunoglobulins. These treatments are presumed to work through effects on IgG NMDAR autoantibody levels in the CSF, although prospective data informing predictors of treatment responses are limited. Even with prompt treatment, ~50% of patients remain disabled, requiring prolonged hospital admissions. Various off-label therapies have been proposed as “second-line” treatments in NMDAR encephalitis. Most second-line treatments target circulating B-cells with various degrees of blood-brain penetrance and efficacy and poor consensus on the timing, dose, and route of delivery of candidate agents. High-quality evidence is needed to inform the treatment of NMDAR encephalitis. Inebilizumab is a promising therapeutic monoclonal antibody for the treatment of NMDAR encephalitis. This humanized monoclonal antibody against the B-cell surface antigen CD19 was recently shown to be safe and efficacious in treating neuromyelitis optica spectrum disorder-another antibody-mediated disorder of the central nervous system. Compared to other off-label B-cell depleting therapies, such as rituximab, inebilizumab not only depletes CD20+ B-cells, but also CD20- plasmablasts and plasma cells, resulting in robust and sustained suppression of B-cell expression. The ExTINGUISH Trial will randomize 116 participants with moderate-to-severe NMDAR encephalitis to receive either inebilizumab or placebo in addition to first-line therapies. Patient outcomes will be ascertained at standard intervals using the modified Rankin scale and accepted safety measures (primary outcomes at 16 weeks), together with comprehensive, validated neuropsychological tests, bedside cognitive screening tools, quality of life/ functional indices, and outcome prediction measures. Clinical data will be combined with quantitative measures of NMDAR autoantibody titers and cytokines implicated in B-cell activation and antibody production within the intrathecal compartment to identify treatment responders, inform the biologic contributors to outcomes, and evaluate for biomarkers that may serve as early predictors of favorable outcomes in future clinical trials in NMDAR encephalitis. The ExTINGUISH Trial will prospectively study an optimized B-cell depletion therapy to promote better long-term outcomes in NMDAR encephalitis, to determine more meaningful cognitive endpoints, and to identify better biologic biomarkers to predict outcome.

Title: Biomarkers of Trained Immunity Following MMR Vaccination

Stage: Recruiting

Principal investigator: Michael S. Avidan, MD

Washington University School of Medicine

Saint Louis, MO

This is a substudy of NCT04333732. This sub-study aims to identify and characterize biomarkers of trained immunity by measuring, in vitro, immune responses to heterologous products, especially viral associated products, in the MMR vaccinated compared placebo groups.

All participants are randomly assigned to MMR or placebo injection at baseline, followed by SARS-CoV-2 specific vaccination. Blood is drawn around 60 to 90 days after the last SARS-CoV-2 specific vaccine injection.

A sub-study of the CROWN CORONATION Trial (COVID-19 Research Outcomes Worldwide Network for CORONAvirus prevenTION; NCT04333732). The goal of this sub-study is to identify and characterize biomarkers of trained immunity by measuring, in vitro, immune responses to heterologous products, especially virally associated products, in those exposed to MMR vaccine injection compared to those exposed to 0.9% sodium chloride (‘normal saline’) placebo injection.

A secondary objective is the comparison of SARS-CoV-2 neutralization assays between MMR and placebo comparison groups around 60 to 90 days after the last SARS-CoV-2 specific vaccine injection.