What Is Gerstmann Straussler Scheinker Disease?

Overview

Gerstman-Straussler-Scheinker disease (GSS) is a rare, inherited, progressive, untreatable and therefore fatal prion neurodegenerative disorder. It usually develops between the ages of 35 and 55.¹^,² Although GSS is not as well known as some other neurological diseases like Alzheimer's or Parkinson's, it likewise bears profound impacts on those affected and their families.

Historical background

The German neurologist Hans Gerstmann identified GSS first in 1936, where subsequently, Ernst Straussler and Igor Sheinker, via their research, contributed to the development of the understanding of this disease. They discovered that it was a heredo-familial disease of the central nervous system. Post-mortem studies of family members of the individual where the condition was initially identified showed similar symptoms to those of Kuru - an extremely rare transmissible prion disease.³^,⁴ Therefore, upon further study, GSS was declared a variant of the Transmissible Spongiform Encephalopathies (TSEs); these are a family of rare progressive neurodegenerative brain disorders affecting both humans and animals.⁵^,⁶

Causes and risk factors

Prion diseases are caused by prions, which are small infectious particles that promote the prion protein, which is normally found within the nerves in the central nervous system (this encompasses the spinal cord and the brain), to fold abnormally. These prion proteins then aggregate and form long, insoluble clumps known as fibrils that may trigger the death of neurons in the nervous system.⁷

GSS, a type of prion disease, results from an abnormal variant of the prion protein (PRPN) gene, which encodes for the human prion protein (PrPSc). Alterations to this gene produce the toxic version of the protein due to a misfolding of the prion protein (PrPSc). These build up in the brain, leading to the progressive loss of nerve cells (neurons), subsequently leading to the physical and neurological symptoms observed in affected individuals.⁸ 

The critical aspect of this disorder is its inheritance pattern of dominant autosomal; meaning that an affected individual has at least a 50% chance of passing on the mutated gene to their offspring.⁸

Symptoms and clinical presentation¹⁰

The progression of GSS is slow but relentless, making it an emotionally challenging condition for the individual and their loved ones.

Primary symptoms:

• Progressive loss of coordination
  • Presented as unsteadiness, difficulty walking, clumsiness
• Problems with coordinating voluntary movements (ataxia)
• Mild difficulty with speech (dysarthria)
  • Presented as slurred speech, and in severe cases, affects the ability to speak and understand what they are attempting to say
• Potential problems with swallowing (dysphagia) due to the lack of coordination of the muscles

Additional early signs may include:

• Diminished reflexes (hyporeflexia)
• Progressive weakness in the legs
• Burning or tingling sensation and/or discomfort under the skin (dysesthesia)

Moreover, as the disorder progresses, individuals develop spasticity. This is characterised by rigid muscle tone and muscle stiffness and weakness; as a result, some individuals may display reduced facial expression (hypomimia), abnormal writhing movements, and abnormal slowness of movement (bradykinesia). Furthermore, the loss of muscle control may lead to rapid, involuntary eye movements (nystagmus) and difficulties judging distance or scale (ocular dysmetria), potentially leading to more eyesight problems where, in some cases, it can progress to blindness. In some cases, people may also experience seizures, paralysis of certain cranial nerves and movement disorders, including jerky muscle spasms (myoclonus) or slow, writhing, involuntary movements (athetosis).

As the condition continues progressing, the affected individual experiences a deterioration of their cognitive ability, including the diminishing of their ability to think, remember, reason, imagine, and process thoughts. Concentration and focus are also heavily affected, causing individuals to demonstrate slow thought processing (bradyphrenia). In addition, other symptoms like dementia may also be apparent with the development of the disease.

To summarise, GSS causes the slow progressive physical and mental deterioration of the affected individual, resulting in them becoming bedridden and unable to eat independently and communicate, leading ultimately to the onset of a coma and eventually death.

Diagnosis

Diagnosing GSS can be challenging due to symptoms overlapping with other neurodegenerative diseases, the wide spectrum of clinical phenotypes (observable characteristics) and imaging findings, as well as ambiguity in family history.¹¹^,¹²

Therefore, its diagnosis relies on a combination of clinical evaluation and exams: the identification of symptoms, patient history, clinical evaluation and a variety of specialised tests.

• Clinical evaluation: provides detailed information about the patient's medical history, physical and neurological assessment will provide evidence of the characteristic symptoms of GSS.¹³
• Molecular genetic testing: can detect the abnormal variant of the PRPN gene that causes GSS.¹⁴
• Electroencephalogram (EEG): the measurement of the electrical of the brain may show changes in brain functioning; for example, its slowing down.¹⁵
• Magnetic Resonance Imaging (MRI): can demonstrate abnormalities in the brain, providing supporting evidence for the prion disease, or it may be used to rule out other possible conditions with similar symptoms.¹⁶
• Cerebrospinal fluid (CFS) testing: CFS can be collected and tested for markers associated with neurodegeneration.¹⁷^,¹⁸

Moreover, it is important to reinforce that GSS is rare; therefore, it may not always be immediately recognised, leading to delays in diagnosis.

Treatment and Management

At the moment, there is no cure for GSS. The current treatment options are limited and require the collaborative work of a variety of specialists, including neurologists, psychiatrists, psychologists, pain specialists, social workers and other healthcare professionals, to develop a patient-centred plan on how to manage their symptoms. Moreover, as this condition affects not only the diagnosed individual but also their family, psychosocial support may be essential to be provided, as well as genetic counselling.¹⁹

Due to its rarity, there are no standardised treatment protocols or guidelines. Therefore, the possible treatment options address the associated symptoms of GSS; these may include:

• Anti-seizure medication such as anti-epileptics or anti-convulsants²º^,²¹ 
• Medication to treat muscle spasms²²
• Feeding tube in case if there are swallowing issues.²³^,²⁴ 

In addition, clinical trials and research may also be a way to have access to the most up-to-date treatments for GSS.²⁵^,²⁶ By accessing these, you will be able to learn about the new findings that may provide invaluable insights into the disease and potential treatments that could improve the prognosis of affected individuals in the future.

For more information regarding having access to clinical trials in the UK, see this link: https://www.nhs.uk/conditions/clinical-trials/. For trials in other countries (and in the UK), follow this link: https://clinicaltrials.gov/search

Prognosis

Gerstman-Straussler-Scheinker has a poor prognosis due to it being a progressive neurodegenerative disease that leads to severe disability and drastically diminishes the quality of life of the affected individual, given the resulting symptoms. As a result, GSS causes the shortening of life expectancy, typically ranging between 2 to 10 years upon the onset of the symptoms. In due course, as a result of the severe disability that the condition causes, the individual ends up dying²⁷,²⁷

Nevertheless, with the ongoing research in this field, in the future, we might not only have access to new findings regarding the condition but also potential treatments that could improve the patient's prognosis.

Prevention and genetic counselling

Given the genetic nature of GSS, genetic counselling can play a vital role in managing the condition.

Genetic counselling provides detailed information about conditions that affect families. This is achieved via the collection of personal and family history, which helps them determine the likelihood of the individual or their family being affected by a genetic condition. This may be particularly important when planning a pregnancy, during pregnancy, child caring, and managing your own health.²⁸

Moreover, the genetic counsellor can assist you in deciding whether or not you should proceed with genetic testing. This will be the case if you have a family history of GSS.²⁹

FAQ

How many people have Gerstmann-Straussler-Scheinker disease?

GSS has a prevalence of 1 to 10% per 100 million.³º

Is GSS contagious?

GSS can be contagious, which is the reason why it is considered to be a transmissible spongiform encephalopathy (TSE). However, these are only transmittable via direct contact with affected brain tissue. Therefore, GSS is not a contagious disease like most other infectious diseases.³¹

Why can’t prion diseases be cured?

Prion diseases are irreversible and cannot be overcome by the body’s immune system, so they require the development of a drug or other treatments, which are yet to be developed, in order to be cured.³²

Conclusion

In conclusion, Gerstmann-Straussler-Scheinker disease is a rare and devastating neurodegenerative disorder that results from genetic mutations causing a range of both physical and cognitive symptoms. Currently, there is no cure, but ongoing research offers hope for future findings that increase our understanding of the disorder, allowing the development of a potential treatment. The greatest component for the management of GSS is genetic counselling for the affected families, which with the aid of research, may develop strategies of both prevention and intervention to reduce the impact of the disease.

Despite GSS being a rare disease, it has a profound impact on the affected individuals and families, highlighting this way the importance of continuing to do research in this field so that more families can be helped.

Here is another source of support:

• Creutzfeldt-Jakob Disease Foundation, inc. To register, send an email to help@CJDFoundation.org
• United Brain Association - GSS information and support