What is Subacute Sclerosing Panencephalitis?
Subacute Sclerosing Panencephalitis, also known as SSPE, is a rare but dangerous condition that can happen after a measles infection. It affects the nervous system, typically shows up in young teenagers, and usually gets worse over time. Unfortunately, it also has a high chance of causing death. The good news is that measles vaccines have helped reduce the number of both measles and SSPE cases. However, measles is still common in many places that lack access to vaccines. In addition, in some developed nations, people refusing to get vaccinated is causing a comeback of measles.
What Causes Subacute Sclerosing Panencephalitis?
Subacute sclerosing panencephalitis, a condition affecting the brain, is caused by the measles virus. This virus is so contagious that one infected person can spread it to 12 to 18 other people. It is spread when infected persons cough or sneeze, releasing tiny droplets, called aerosols, into the air that others can breathe in.
Measles can lead to various health complications, both immediately and over time. Some of these complications affect the nervous system, like Subacute sclerosing panencephalitis. Children under five years old and adults older than 20 are at a higher risk of death from measles and these complications.
Risk Factors and Frequency for Subacute Sclerosing Panencephalitis
Subacute sclerosing panencephalitis (SSPE) is a disease that has become less common since the introduction of the measles vaccination. Essentially, as the number of measles cases decreases, so does the number of SSPE cases. In the United States, we usually see only 4 to 5 cases of SSPE each year. However, with some people choosing to not get vaccinated, this could change. In fact, in 2019, there was a 3-fold increase in measles cases compared to the previous year. Keep in mind that the measles virus is quite serious and has caused over 100,000 deaths annually since 2010, most of them children under 5 years old. Measles is still a problem in many developing countries in Africa and Asia where it’s not easy to get vaccines.
Out of every 100,000 measles cases, between 4 to 11 result in SSPE. This increases to 18 if the measles infection occurs in a child under 5 years old. SSPE also appears to be more prevalent in males, with a delayed onset and increased latency in females.
- Risk factors for SSPE include living in rural or poverty-stricken areas, overcrowding, and having many siblings or a higher birth order, which increases the chance of exposure and infection at a younger age (less than 5 years old).
- SSPE tends to occur earlier and progress more aggressively in individuals with compromised immune systems, children whose mothers had measles during pregnancy, or if there was incomplete transfer of measles antibodies during gestation.
It’s important to note that getting vaccinated against measles does not cause SSPE. You can only get SSPE through a direct measles infection. This has been proven in studies where no traces of the vaccine strain of the virus were found in tissue samples from patients with SSPE. To put it simply, the risks of getting measles far outweigh any risks associated with the vaccine.
Signs and Symptoms of Subacute Sclerosing Panencephalitis
Subacute sclerosing panencephalitis (SSPE) is a condition that often follows a measles infection. Commonly showing up around 8 to 11 years post-measles, it involves a progressive decline in mental abilities. Early signs include changes in personality and behavior, difficulty with school work, and intellectual decline. Over time, patients may experience a general decrease in motor function, spasms and jerks in muscles, autonomic dysfunction, and even paralysis in some areas. Seizures, either focused or generalized, may occur in some cases, and about a third of those with SSPE develop epilepsy.
The disease progresses through several stages, each highlighting a different phase of SSPE:
- Stage I: This phase is known for changes in personality or behavior, such as irritability, dementia, lethargy, social withdrawal, or speech regression.
- Stage II: This phase is marked by further decline in motor function, including myoclonus (sudden, involuntary jerking of a muscle or muscles), dyskinesia (difficulty in performing voluntary movements), and dystonia (abnormal muscle tone resulting in muscular spasm and abnormal posture).
- Stage III: In this stage, patients progress to extrapyramidal symptoms, abnormal body posture, and spasticity.
- Stage IV: The final stage occurs when patients develop akinetic mutism (a condition in which a person cannot speak or move), autonomic failure, or enter a vegetative state.
Visual symptoms may appear a couple of years before other obvious disease symptoms kick in. These could range from retinal hemorrhages to complete vision loss. However, it’s worth noting that there is never inflammation in the jelly-like substance (vitreous) that fills the eyeball.
Some cases of SSPE may not follow the typical course or symptoms. These “atypical” cases often involve psychiatric symptoms or poorly controlled seizures. It progresses rapidly with neurological deficits appearing within the first 3 months and death within 6 months in about two-thirds of cases. Risks for this severe and unusual progress include having had the measles virus before the age of 2, increased virulence of the virus, and co-infection with other viruses.
Diagnosing SSPE can be tough due to its variable presentation. However, it’s vital to consider it a possibility in many circumstances. For instance, it can develop in older patients who are experiencing psychiatric symptoms that turn into progressive dementia. Children suffering acute cognitive decline, muscle jerks, or new-onset epileptic syndromes should also be screened for SSPE. It can even appear during pregnancy, manifesting as cognitive dysfunction or difficulty with simple tasks. However, children born to mothers having SSPE are usually healthy.
Testing for Subacute Sclerosing Panencephalitis
The process of diagnosing Subacute Sclerosing Panencephalitis (SSPE), a brain condition, is complex. Ideally, a brain biopsy, a test where a small sample of brain tissue is removed for examination, would be the definitive way to diagnose it. However, due to the invasiveness of this procedure, doctors typically use a series of criteria instead.
Initially, a set of measures called the Dyken criteria were used, which needed at least 3 of 5 specific symptoms and test results to diagnose SSPE. But given the varying ways SSPE can present itself, newer criteria were developed in 2010.
The updated criteria include a combination of major and minor factors. For a diagnosis, two major and one minor factor are required. If criteria are not entirely met but SSPE is still considered likely, additional tests at the molecular level can be carried out.
Major factors include typical or atypical presentation of symptoms, where typical presentation can be acute, rapid, or progressively chronic, while atypical includes seizures, extended stage I, or unusual age at onset. Another significant factor is the presence of anti-measles antibodies, which are disease-fighting proteins, in certain concentrations within the cerebrospinal fluid (CSF) or serum, i.e., the clear liquid part of the blood.
The minor criteria cover supporting evidence like specific types of patterns in an electroencephalogram (EEG) – a test to measure electrical activity in the brain. Another minor factor is if the CSF has a high percentage of globulin, a protein that helps fight off infections. Useful supplementary evidence can also come from biomolecular testing to identify mutations in the measles virus and brain biopsy.
The accuracy of these new criteria hasn’t been assessed for the general public or pregnant women yet. As part of these criteria, certain results from testing the CSF can include a higher than normal number of specific cells and increased antibodies related to SSPE.
About 65% to 83% of the SSPE cases have the EEG findings described in the criteria. Imaging can also provide supportive evidence of SSPE, although the pictures may not always reveal abnormal results. Brain scans using magnetic resonance imaging (MRI) can show shrinkage of brain tissue, shadows indicating damage, and significant enlargement of brain cavities. MRI aids doctors in tracking the progression of the disease.
It is also possible to utilize magnetic resonance spectroscopy to help diagnose SSPE. Detecting early-stage SSPE will show decreased N-acetyl-aspartate and increased choline levels, suggesting inflammation and weakening of the myelin, the protective covering of nerve cells. As the disease progresses, there should be elevated levels of certain chemicals, which are linked to reduced brain volume.
Treatment Options for Subacute Sclerosing Panencephalitis
Subacute sclerosing panencephalitis (SSPE), a progressive brain disorder, doesn’t have a cure. The main aim of the treatments is to reduce symptoms and in few patients, treatments have shown to slow down the disease’s progression, stabilize its course, lengthen life span, or bring about clinical improvement, even if this is rare.
Several supportive measures have been employed to manage SSPE. Though there are no specific therapeutic guidelines or suggestions, multiple drugs are often used side by side.
Inosine pranobex, an antiviral medication you take orally, can halt the multiplication of the virus and influence the immune response. However, this medication could increase uric acid levels in urine and blood and sometimes lead to nausea.
Another option is Interferon-alpha (INF-alpha), a medicine that adjusts the immune system response, typically used alongside Inosine Pranobex. It needs to be given intrathecal (directly into the spinal cord) every week, and its maximum benefits can be reaped only with long-term use. Studies haven’t shown any added advantages of using Inosine Pranobex and INF-alpha together daily over using Inosine Pranobex alone.
Ribavirin, another medication, has also been used in SSPE treatment, with modest success. It appeared to be mildly beneficial in patients when used in combination with INF-alpha. Antiepileptic drugs have been used to control seizures, muscular spasms, and brain-related symptoms. There’s ongoing research about the potential of antiapoptotic agents- that prevent cell death, and small interfering RNA that appears to inhibit viral replication in cells.
Some studies suggest that blocking membrane fusion- the combining of the viral and host cell membranes, could help halt the progress of brain infections caused by the measles virus.
An alternative option that some case reports suggest is the ketogenic diet- a diet high in fats and low in carbs. This diet seems to have helped reduce muscle spasms in some SSPE patients who haven’t seen success with other treatments. The diet could protect brain health by reducing damage caused by oxygen-related stress, enhancing the activity of small cell parts that produce energy (mitochondria), and by suppressing factors that cause cell death. Though this diet has shown promising results in some cases, its effectiveness in treating SSPE still requires further investigation.
The best way to tackle SSPE is by preventing it from occurring in the first place. A very secure and productive way to prevent the initial infection is by vaccinating against the measles virus. The vaccine is administered in two doses- the first between the ages of 12 to 15 months, and the second dose between the ages of 3 to 5. However, those with compromised immune systems cannot receive this vaccine since it’s a live-weakened vaccine. The World Health Organization (WHO) recommends giving the vaccine to HIV-positive patients, provided they don’t have severe immune suppression. For eradication of the measles virus from a population, it is necessary for 95% of that population to exhibit immunity with anti-measles antibodies. Even though effective, vaccination rates have unfortunately seen a downturn in recent years due to hesitancy about vaccines, leading to a resurgence of the measles virus in developed countries.
What else can Subacute Sclerosing Panencephalitis be?
Subacute sclerosing panencephalitis (SSPE) can have different symptoms and can be linked to various clinical conditions. It’s typically found in children, but occasionally occurs in adults, including pregnant women. Early stages of the disease can be mistaken for epilepsy or mental health disorders.
If someone starts to show sudden and worsening symptoms like jerkiness, memory problems, or seizures, doctors need to consider a variety of conditions. These might include:
- Viral encephalitis (brain inflammation caused by a virus)
- Autoimmune encephalitis (brain inflammation caused by the body’s immune system)
- Multiple sclerosis that’s not typical
- Creutzfeldt-Jakob disease (a rare and fatal brain disorder)
- NMDA receptor encephalitis (brain inflammation caused by antibodies)
- Neurometabolic encephalopathies (brain diseases caused by metabolism problems)
- Cancerous tumours (neoplasms)
- Paraneoplastic syndromes (rare disorders triggered by a reaction to cancer in the body)
- Leukodystrophies (rare progressive metabolic disorders affecting the brain, spinal cord and often the peripheral nerves)
This list isn’t exhaustive, but it provides a wide range of possibilities that should be considered alongside SSPE.
What to expect with Subacute Sclerosing Panencephalitis
SSPE, a serious medical condition, has an especially high mortality rate at around 95%. Only a small percentage of cases naturally get better. Once the symptoms first show, the average life expectancy is around 3.8 years, though this can vary widely from as little as 45 days to as long as 12 years.
Possible Complications When Diagnosed with Subacute Sclerosing Panencephalitis
SSPE is a condition that can occur when the measles virus infects the nervous system for a long time. Patients with SSPE will gradually experience issues related to their nervous system, and sadly, this condition eventually leads to death. Certain treatments aim to extend the life span and improve the life quality of patients despite some possible side effects. For instance, interferon-alpha may result in symptoms similar to the flu or cause a rebound of the symptoms due to the body developing antibodies against the medication. Ribavirin, on the other hand, may cause oral sores, headache, tiredness, and a type of anemia that can be reversed.
Treatment Side Effects:
- Flu-like symptoms from Interferon-alpha
- Rebound of symptoms due to antibodies to Interferon-alpha
- Oral sores from Ribavirin
- Headache from Ribavirin
- Fatigue from Ribavirin
- Reversible anemia from Ribavirin
Preventing Subacute Sclerosing Panencephalitis
Families should keep learning about vaccination programs, particularly the possible outcomes of getting infected with the measles virus and the long-term complications that can happen. In this situation, the advantages of getting vaccinated far exceed the risks associated with potentially contracting SSPE, a rare but serious disease that can develop years after a person has had measles.
