Introduction

Creutzfeldt-Jakob Disease (CJD) is a rapidly progressing, transmissible, and fatal neurodegenerative disease caused by prions, which are misfolded infectious proteins. Among its many devastating symptoms, CJD significantly affects motor functions, leading to movement disorders such as ataxia, myoclonus, and spasticity. These movement disorders significantly impact the quality of life of affected patients, and cause disturbances in their everyday life. This article explores the correlation between CJD and these specific motor problems, detailing their symptoms, diagnosis, and potential treatment options.

What Is Creutzfeldt-Jakob disease?

Creutzfeldt-Jakob Disease (CJD) is a very rapidly progressing, transmissible, rare, and fatal neurodegenerative disease. It is caused by the unique infectious agent prions.¹ The accumulation of misfolded prion proteins leads to severe brain damage, rapidly worsening over time as the prions accumulate.¹

Symptoms²

People diagnosed with CJD often die within a year of their symptoms starting, with symptoms getting worse and worse over time.

Symptoms include:

• Loss of intellect and memory
• Progressive loss of mobility & brain function
• Changes in personality
• Blindness or vision problems

The symptoms related to movement disorders include:

• Loss of balance and coordination
• Slurred speech
• Abnormal jerking of muscles or problems with muscles

What causes Creutzfeldt-Jakob disease?

The actual cause of CJD is prions, which are abnormal infectious agents that are proteins, and specifically cause neurological diseases by causing damage to nerve cells. 

There are 4 different types of CJD, with various ways of obtaining the disease:

• Sporadic CJD: Sporadic CJD accounts for 85% of the cases,³ and this is when the cause of CJD is unknown. The cause of this is still being researched as it is still unknown, but it is believed that it is possible a normal prion brain protein misfolds and becomes an infectious prion on its own.² This normally affects people later in life, around the age of 60³
• Variant CJD: Variant CJD is believed to be caused by eating meat containing prions, particularly from cows that have had the bovine spongiform encephalopathy, another common prion disease which is found in cows and can be passed onto humans. Patients with variant CJD often experience their symptoms earlier in life. They also present unique psychiatric symptoms and behavioural  changes¹
• Familial CJD: Familial CJD is an incredibly rare genetic condition, where the offspring inherits a mutation from their parent that makes prions start forming in their brain when they reach early adulthood. Patients with familial CJD often experience symptoms earlier on in life¹
• Iatrogenic CJD: Iatrogenic CJD is another form of acquired CJD where the disease is accidentally spread through medical equipment. This can often be with surgeries involving the brain such as surgical grafts of brain tissue, transplanted corneas, or improperly sterilised medical equipment.³ Due to the structure of prions, it is significantly more difficult to sterilise equipment that has come in touch with it, and previously, medical instruments have not been sterilised properly due to lack of information.³ However, this is no longer a problem due to higher awareness

Diagnosis

How does one know if they have CJD? Oftentimes, it’s hard to give a fully correct diagnosis until the autopsy,⁴ but looking at the symptoms along with taking the following tests might make it possible to differentiate CJD from other neurodegenerative diseases:¹

• Complete blood count
• Complete metabolic panel
• Blood magnesium
• Rapid plasma reagin
• Erythrocyte sedimentation rate
• Antinuclear antibody
• C-reactive protein
• Thyroid function tests
• Vitamin B12 level
• HIV test
• Lyme disease titer
• Autoimmune antibodies
• Urinalysis
• Cerebrospinal fluid studies, including glucose, oligoclonal bands, and cell count with differential
• Cerebrospinal fluid 14-3-3 protein (a test for prion disease)
• Venereal disease research laboratory (VDRL) test

Prion diseases can be quite challenging to diagnose, but with the correct steps, it can be straightforward to find the correct diagnosis and treatments for improving symptoms.

Treatment

There is currently no cure for CJD, and everyone with CJD dies, with 70% of patients dying within one year of symptoms appearing or diagnosis.³ Treatment for CJD aims to make the patient as comfortable as possible alleviate any uncomfortable symptoms, and provide aid in their daily life. Various treatments to address the symptoms of movement disorders as a result of CJD will be explored further down in this article.

Prions and their role in Creutzfeldt-Jakob Disease

Prions are an incredibly fascinating infectious agent, with a unique way of functioning compared to other infectious agents.

The prion protein, often called PrPC, is a completely normal and harmless neuron protein that exists in your brain. The actual purpose of PrPC is still unknown, but it is believed to aid in functions such as cell adhesion, synaptic function, and more.⁵ The structure of PrPC mainly consists of alpha-helices and random coils. It should be noted that a protein’s structure and folding are incredibly important in the function of the protein. Here is where prions come in. Prion stands for proteinaceous infectious particles, and it is a misfolded protein that has become infectious. Prions typically have mainly beta-sheets as their structure, they are K-resistant meaning they are resistant to being broken down, and they form aggregates meaning they clump together to form clusters.¹ When these prions come in contact with PrPC, they make the PrPC turn from alpha-helices to insoluble protease-resistant beta-sheets, making them also turn into infectious prions. This is how the disease and the neurodegeneration progresses, with the self-propagating prions spreading to various parts of the brain continuously forming aggregates and plaques.¹ These plaques then disrupt cell functions and cell signalling, killing neurons, and giving the brain that commonly seen “spongy”  appearance due to the extreme damage it causes, also known as spongiform encephalopathy.¹

Understanding this, we know that prions are not only incredibly hard to break down and remove, but they also self-propagate. This causes prions to be incredibly infectious and easy to spread between humans. It should be noted that knowledge about prions is still fairly limited due to it being first only discovered in 1982,⁶ and its mechanisms are still being investigated by researchers due to it being such a recent discovery. 

The correlation between Creutzfeldt-Jakob disease and movement disorders

Different forms and mutations of prions determine the disease that one will get, as different types of prions will aggregate and accumulate in different parts of the brain. There are multiple types of prion diseases, such as Kuru and Fatal Insomnia in humans, and other animal diseases such as mad cow disease which can also be spread to humans.

In CJD in particular, the prions are seen to accumulate mostly in the cerebral contrex.⁷ The cerebral cortex is a very important structure and carries many of the important brain regions. A region in the cerebral cortex particularly relevant to this article is the frontal lobe. The frontal lobe carries the premotor cortex and the primary motor cortex, which are responsible for motor functions, and the disruption of these areas can lead to movement disorders.⁷ This means that with CJD not only are many basic functions disrupted due to the cerebral cortex being primarily affected, but one of the regions largely responsible for movement and motor skills is damaged by prions.⁷

The movement disorder we will be exploring today, Brare differently affected by CJD.

• Ataxia: Having balance and coordination is a result of the complex circuitry of the cerebral cortex with the cerebellum and the basal ganglia. When any of these components is disrupted, this leads to incoordination or ataxia⁸
• Myoclonus: Although there are different types of myoclonus, in the case of CJD, it is cortical myoclonus, which is the result of abnormal electrical signals and disruptions in the cerebral cortex⁹
• Spasticity: It has been seen that lesions in the premotor cortex, or damage to any other motor nerves, can lead to spasticity⁹

Ataxia

Ataxia is a neurological movement disorder characterised by a lack of coordination and balance, which affects voluntary actions such as walking, speaking, and performing daily tasks. Ataxia is usually caused by damage to the cerebellum, However, in the case of CJD, the damage to the cerebral cortex also affects the function of the cerebellum due to their important circuitry.¹⁰ This leads to dysfunction in the signalling in the cerebellum that is necessary for balance and coordination.

Symptoms

Symptoms include:¹⁰

• Balance and coordination problems (this gets affected first)
• Poor coordination of hands, arms, and legs
• Difficulty with writing and eating
• Slurring of speech
• Wide-based manner of walking
• Slow eye movements

Diagnosis

To get a diagnosis, a thorough family history and medical history are needed along with a full neurological and physical exam. Alongside this, your healthcare provider may recommend:¹¹

• Lab Tests: Blood tests and urine tests are beneficial as they can provide insight into possible metabolic or other systemic issues that may be worsening symptoms. Genetic testing also requires blood or saliva samples
• Diagnostic tests: Using diagnostic tests such as magnetic resonance imaging (MRI) scan, computed tomography (CT) scan, or an electromyogram, your healthcare provider can look at your brain and your nerves for a better diagnosis

Treatment

Similarly to the rest of the movement disorders in this article, ataxia cannot be fully cured. In most situations, the original cause of the ataxia is addressed and treated, however, since there is no cure for CJD, the aim is to simply relieve symptoms as much as possible. Using assistive devices to allow the patient to have as much independence as possible is ideal, with some examples being a cane, wheelchair, walker, or various types of therapies such as physical therapy or speech therapy to improve symptoms. Medication might also be used, to aid in sleep, tremor, stiffness, depression, or any other side effects the ataxia might have.¹¹

Myoclonus

Myoclonus refers to any involuntary sudden brief muscle jerking or movement. This can be very normal and happen to anyone, however in CJD it can be severe, and it is primarily cortical myoclonus that happens, or sometimes subcortical. In CJD it is primarily positive myoclonus that occurs, meaning it is the muscles contract or flex suddenly rather than relaxing. 

Symptoms

Typically cortical myoclonus is mostly seen in limbs that have the most cortical representation, particularly in the digits and the face, however, it could still happen anywhere. The cortical myoclonus is particularly sensitive to touch and action triggers it, and it can much easier elicit tendon reflexes.¹²

Diagnosis

Myoclonus can be determined to be cortical and caused by CJD by doing an electroencephalogram(EEG), which records brain activity. By identifying patterns in the EEG and looking at the timings of the muscle contraction and electrical brain discharge, the source of the myoclonus can be determined. If there always is a cortical discharge right before the muscle contraction, it can be determined that it is cortical myoclonus.⁹

Treatment

Since it is believed that the cause of myoclonus in CJD is caused by a loss of specifically gabanergic cells in the brain, the symptoms of myoclonus can be reduced by gabanergic drugs. Sodium valproate is the most common one, with benzodiazepines also being quite helpful in improving symptoms. If it is subcortical myoclonus rather than cortical, the most popular drug is clonazepam.⁹

Spasticity

Spasticity is the abnormal muscle tightness that is caused by prolonged muscle contraction. It is caused by issues in the signals sent from the brain to the muscles, as disruptions or damage to areas of the brain that are responsible for motor function means those neurons will not be able to signal normally.

Symptoms

Symptoms of spasticity can range from mild and manageable stiffness or tightness to uncontrollable and very painful spasms. Pain or tightness in joints is quite a common symptom, with other symptoms including:¹³

• Muscle stiffness which causes movements to be less precise, making certain tasks difficult to perform
• Muscle spasms that cause uncontrollable and often painful muscle contractions
• Involuntary crossing of the legs
• Muscle and joint deformities
• Muscle fatigue
• Inhibition of longitudinal muscle growth
• Inhibition of protein synthesis in muscle cells

Diagnosis

Due to how different spasticity can be from case to case, it can be quite difficult to diagnose. However, by doing neuroimaging such as magnetic resonance imaging (MRI), one can gain more information about the cause of the spasticity and to what extent the brain is damaged to be affecting the muscles.¹³ An MRI alongside a physical examination can provide a good thorough diagnosis.

Treatment

Although there is no treatment to fully cure spasticity, there are many options available for improving symptoms and quality of life for patients with spasticity.

Treatments include:¹⁴

• Physical therapy: Physical therapy can greatly aid in building mobility, strength, and flexibility in the lower body
• Occupational therapy: Occupational therapy aids in building mobility and strength in the upper body, to make daily tasks easier to do
• Speech therapy: If the spasticity affects the face, mouth, or throat muscles, speech therapy can aid in important skills such as speech or swallowing
• Casting or bracing: Using a cast or brace can help in maintaining a stretch in the affected area, to facilitate function or improve range of motion
• Assistive devices: Assistive devices aid patients with spasticity in moving around and performing daily functions
• Oral medications: Oral medications are often prescribed when the spasticity disrupts important daily functioning such as sleep
• Botox treatment: Doing local injections of the botulinum toxin, also known as botox, can greatly improve symptoms of spasticity and the severity of the spasticity
• Surgical treatment: In extreme cases, surgery might be needed to improve symptoms

Summary

Creutzfeldt-Jakob Disease (CJD) is a rare, fatal neurodegenerative disorder caused by the accumulation of misfolded prion proteins, leading to severe and rapid brain damage. Among its many symptoms, CJD prominently features movement disorders such as ataxia, myoclonus, and spasticity, as the prions of CJD primarily accumulate in the cerebral cortex. Ataxia involves a loss of coordination and balance, resulting from damage to the circuitry between the cerebral cortex and the cerebellum. Myoclonus presents as sudden, involuntary muscle jerks triggered by abnormal cortical discharges. Spasticity is characterised by abnormal muscle tightness and prolonged contraction due to disrupted motor signals from the brain. Diagnosis of these disorders relies on clinical examination, neuroimaging, and electrophysiological studies, while treatment focuses on alleviating symptoms and improving patient quality of life. Understanding these movement disorders and how they can be treated can help improve the quality of life and provide a comfortable life for CJD patients.