Sporadic Creutzfeldt-Jakob Disease - Causes, Symptoms, Diagnosis, and Management

What Is Creutzfeldt-Jakob Disease?

Creutzfeldt-Jakob disease (CJD) is a rare disorder affecting the brain that progresses quickly and leads to distinct changes in the brain's tissues. It affects memory, muscle coordination, and thinking. In the United States, there are around 350 cases reported each year. It is classified as a neurodegenerative disorder known as prion disease or transmissible spongiform encephalopathies. These conditions have the potential to be fatal. The infectious agent involved in CJD is a protein called a prion. Transmission can occur through direct contact with contaminated tissue (iatrogenic) or through inheriting a mutation in the prion protein gene (familial). However, most cases of CJD are sporadic, meaning they arise without a known cause.

What Are the Types of CJD?

Different Types of CJD are as below:

1. Sporadic CJD:

• The most common type accounts for 85 percent of cases.

• Occurs spontaneously without a known cause.

• Typically affects individuals aged 55 to 75, with an average age of onset at 61 years.

• The median survival time is four to eight months; about 90 percent of patients pass away within a year.

2. Genetic CJD:

• The second most common type, making up 10 percent to 15 percent of cases.

• May have a family history and a positive genetic mutation test.

• Caused by inherited autosomal dominant mutations in the PRNP gene, which encodes the prion protein.

3. Acquired CJD:

• This type can result from iatrogenic (medical procedure-related) or oral transmission from humans or animals.

• Transmission can occur during surgical procedures or exposure to infected brain or nervous tissue.

What Are the Symptoms of CJD?

1. Main Symptoms:

• Severe mental deterioration and dementia.

• Involuntary muscle jerks (myoclonus) or muscle movement.

2. Early Symptoms:

• Lack of coordination.

• Problems with walking and balance.

• Impaired thinking, memory, and judgment.

• Behavior changes.

• Depression, mood swings, and anxiety.

• Confusion.

• Insomnia or changes in sleeping patterns.

• Unusual sensations.

• Changes in vision.

3. Progressing Symptoms:

• Weakness of the arms and legs.

• Blindness.

• Loss of ability to move or speak.

• Pneumonia and other infections.

• Coma.

4. Comparison to Other Neurological Disorders:

• Some symptoms may resemble those of other progressive neurological disorders like Alzheimer's and Huntington's disease.

• However, symptoms tend to worsen more rapidly in CJD compared to Alzheimer's disease or most other types of dementia.

How Is CJD Diagnosed?

CJD can be challenging to diagnose as it resembles rapidly progressing dementia. The doctors typically recommend Initial screening tests for rapidly progressive dementia. These tests may include the following investigations:

• Complete blood count (CBC).

• Basic metabolic panel (BMP), including magnesium level.

• Liver function tests.

• Rapid plasma reagin.

• Erythrocyte sedimentation rate (ESR).

• Antinuclear antibody.

• C-reactive protein (CRP)

• Thyroid function tests (TFTs).

• Vitamin B-12 level.

• HIV (human immunodeficiency virus) test.

• Lyme disease titer.

• Autoimmune antibody tests.

• Urinalysis.

• Cerebrospinal fluid (CSF) studies include glucose, oligoclonal bands, cell count, and differential count.

• VDRL (Venereal Disease Research Laboratory) test.

• MRI (magnetic resonance imaging) of the brain, including diffusion-weighted imaging (DWI) and fluid-attenuated inversion recovery (FLAIR) with and without contrast.

• EEG (electroencephalogram).

What Are the Diagnostic Criteria and Tests for CJD?

• Diagnostic Criteria: WHO (world health organization) published criteria relying on clinical examination, EEG, and CSF findings. However, advancements in medicine suggest the need for updated criteria.

• Diagnostic Tests: MRI brain, CSF-based tests, and EEG.

• MRI Findings in CJD: MRI with DWI or FLAIR imaging reveals abnormalities in cortical gray matter and deep nuclei. DWI MRI has a sensitivity of 98 percent and a specificity of 93 percent.

• CSF Protein Biomarkers and Studies: 14-3-3 protein, total tau (t-tau), and neuron-specific enolase (NSE). These markers indicate rapid neurodegeneration but are not specific to CJD.

• Routine CSF studies: Glucose, total protein, white blood cell count, total cell count, and oligoclonal IgG are usually unremarkable in CJD patients.

• Real Time-Quaking-Induced Conversion (RT-QuIC) Test: Detects pathogenic prion protein in CSF with high accuracy. More specific than traditional markers like 14-3-3 protein or tau proteins.

• EEG: EEG is the least sensitive test compared to MRI and CSF studies. It may show periodic sharp wave complexes.

• Brain Tissue Biopsy: Brain tissue biopsy confirms the diagnosis of CJD but is risky and not always feasible.

How Is CJD Treated and Managed?

Currently, there is no specific treatment available for CJD. The primary focus of management is to provide symptomatic and supportive care to improve the patient's quality of life. While researchers have conducted drug trials for CJD, none have demonstrated significant benefits thus far. Further research is necessary to develop effective treatments for this fatal condition.

What Is the Differential Diagnosis of CJD?

• Differential diagnosis of rapidly progressive dementia (RPD) can have various underlying causes, including different types of conditions affecting the brain. These conditions may include vascular, neurodegenerative, autoimmune, infectious, thromboembolic, metastasis/neoplasm, iatrogenic, and toxic metabolic conditions. Here are some examples:

• Vascular Causes: Conditions like strokes, multiple infarcts, cerebral myeloid angioplasty, or hypertensive encephalopathy can lead to progressive dementia. Vasculitis (inflammation of blood vessels) and intravascular lymphoma are also possible causes. Brain MRI and vascular imaging studies like MRI angiography and CT angiography can help diagnose vascular-related causes.

• Infectious Causes: Viral encephalitis (such as herpes simplex virus), HIV dementia, progressive multifocal leukoencephalopathy, fungal infections like central nervous system (CNS) aspergillosis, syphilis, Lyme disease, and subacute sclerosing panencephalitis can cause rapidly progressive dementia. Appropriate blood and serological studies can aid in diagnosing infectious causes.

• Neurodegenerative Causes: Conditions such as Creutzfeldt-Jakob disease (iatrogenic and familial forms), Alzheimer's disease, dementia with Lewy bodies, progressive supranuclear palsy, corticobasal degeneration, neurofilament inclusion body disease, and progressive subcortical gliosis can lead to rapidly progressive dementia.

What Is the Prognosis of CJD?

The prognosis for CJD is very poor. The disease is ultimately fatal, and most individuals with CJD do not survive beyond one year from the onset of symptoms. Despite advancements in our understanding of the disease, no cure or effective treatment is currently available.

Conclusion:

CJD can occur sporadically, genetically, or through the transmission of infectious prions. It presents a diagnostic challenge due to its resemblance to other forms of dementia. While there is no definitive treatment for CJD, management focuses on providing symptomatic and supportive care to improve the patient's quality of life.