Bovine Spongiform Encephalopathy: Symptoms, Types, Causes and Treatment

Bovine Spongiform Encephalopathy (BSE), commonly known as “mad cow disease,” is a progressive and fatal neurodegenerative disorder that affects cattle. While the name conjures images of frenzied animals, the reality is a complex disease with a unique clinical course, multiple forms, and a dramatic impact on animal health, food safety, and public perception. This article explores BSE’s symptoms, types, causes, and treatment, synthesizing insights from scientific research and real-world outbreaks.

Symptoms of Bovine Spongiform Encephalopathy

BSE presents with a range of neurological and behavioral symptoms, typically observed in adult cattle. Early detection relies on familiarity with individual animal behaviors, making herdsmen and those who regularly handle the cattle best positioned to notice the subtle changes that herald the onset of disease.

Symptom	Description	Frequency/Notes	Source(s)
Apprehension	Increased nervousness, fearfulness	Most frequent early sign	1 3
Hyperaesthesia	Heightened sensitivity to stimuli	To sound, touch, light; may kick when touched	1 2 3
Ataxia	Loss of coordination	Hindlimb ataxia, unsteady gait, falling	1 3 9
Behavioral Changes	Frenzy, reluctance at doorways	Subtle at first, followed by more obvious signs	3 9

Table 1: Key Symptoms

Progression and Variability of Symptoms

The clinical picture of BSE evolves over time, beginning with subtle behavioral changes and progressing to pronounced neurological deficits. The earliest signs often include apprehension and nervousness, sometimes detected only by those well-acquainted with the animal’s normal demeanor. As the disease advances, symptoms such as hyperaesthesia—a marked increase in sensitivity to touch, sound, and light—become apparent. For example, cattle may react nervously to being touched on the head or may kick when their limbs are brushed 1 2 3.

Ataxia, or loss of coordination, typically manifests later, most notably with a low head carriage, unsteady gait, tremors, and the tendency to fall. Other signs can include behavioral abnormalities such as reluctance to enter doorways, frenzy, and restlessness 3 9. Weight loss is also commonly observed, and while pruritus (itching) has been reported, it is not a predominant symptom 9.

Subclinical and Non-Specific Findings

It is important to note that abnormal findings—such as nervousness and mild hypersensitivity—can occur in otherwise healthy cattle and are not, on their own, diagnostic of BSE. In studies of progeny from BSE-affected cows, most animals showed no clinical or neurological evidence of BSE, underlining the challenge of relying solely on symptoms for diagnosis 2. Further, the duration of clinical signs can range from just a week to over a year, although most cases last one to two months before progressing to fatality 3.

Types of Bovine Spongiform Encephalopathy

While BSE was once considered a homogeneous disease, research has revealed several distinct types, each with unique molecular and pathological characteristics.

Type	Molecular Profile	Geographic Occurrence	Source(s)
Classical	Standard PrPSc pattern	Historically widespread	4 7
H-type	Higher mass unglycosylated PrPSc	Europe, North America, Japan	4 5 6 8
L-type	Lower mass unglycosylated PrPSc	Europe, notably France	4 5 7

Table 2: BSE Types

Classical (C-type) BSE

Classical BSE is the form responsible for the major epidemic in the United Kingdom and other affected countries starting in the 1980s. It is characterized by a distinctive pattern of the disease-associated prion protein (PrPSc) on Western blot analysis 4. Most surveillance programs and diagnostic tests have historically targeted this form.

Atypical BSE: H-type and L-type

In the past two decades, advanced molecular techniques have identified atypical forms of BSE, labeled H-type and L-type due to the higher or lower migration of the unglycosylated PrPSc band in Western blot tests, compared to classical BSE 4 5.

• H-type BSE: This form shows a unique higher molecular mass of the unglycosylated prion protein. It is associated with distinct pathological features, such as the presence of amyloid plaques and different patterns of prion protein deposition in the brain and peripheral nervous tissues 6 8. H-type BSE has been identified in Europe, North America, and Japan.

• L-type BSE: Also called "bovine amyloidotic spongiform encephalopathy" (BASE), L-type is characterized by a lower molecular mass for the unglycosylated PrPSc band. It has been reported in several European countries, including France, where active surveillance has detected sporadic cases 4 5 7.

Diagnostic Challenges and Disease Diversity

The discovery of atypical BSE forms has significant implications for surveillance, as these variants may not always be detected by tests designed for classical BSE. Molecular discrimination using specific antibodies and pH conditions is now an essential part of distinguishing these forms and understanding their epidemiology 4 7. Both H- and L-type BSE are considered rare and may arise sporadically, suggesting that BSE, like human prion diseases, could have multiple origins 5 7 8.

Causes of Bovine Spongiform Encephalopathy

The origins of BSE are central to understanding its spread, prevention, and ongoing risk. While the classical epidemic has been thoroughly investigated, questions remain about the emergence of atypical forms.

Cause	Mechanism	Evidence/Details	Source(s)
Contaminated Feed	Consumption of MBM with prions	Linked to rendering process changes, spread in UK	9 10 12
Scrapie-like Agent	Cross-species transmission	BSE agent similar to sheep scrapie prion	9 12
Human Prion Disease	Possible introduction via feed	Hypothesis: imported feed contaminated with human TSE	13
Atypical/Sporadic	Spontaneous prion misfolding	H- and L-type BSE may arise independently	4 5 7

Table 3: BSE Causes

Feed Contamination and the Classical Epidemic

The overwhelming evidence points to the consumption of meat and bone meal (MBM) contaminated with prions as the principal cause of the classical BSE epidemic 9 10 12. Changes in rendering processes in the early 1980s, especially the cessation of organic solvent extraction, failed to inactivate prions, enabling their persistence in animal feed. This allowed prions—originally from sheep scrapie or possibly other sources—to infect cattle, leading to a common source epidemic that began around 1981-82 and peaked in the early 1990s 10 12.

• The epidemic’s broad geographic onset and its subsequent restriction to countries with high MBM use (especially the UK) underscore the central role of contaminated feed 12.
• Genetic studies and epidemiological data have excluded simple Mendelian inheritance or introduction by imported cattle as primary causes 9.

Theories on BSE Origin

While the scrapie hypothesis is widely accepted, alternative origins have been proposed:

• Human Prion Disease Hypothesis: Some researchers suggest BSE might have originated from human prion diseases, with infection introduced via imported animal feed containing mammalian material contaminated with human remains 13. This theory remains unproven but highlights the need for vigilance regarding feed ingredients.
• Atypical BSE: The identification of H- and L-type BSE cases not linked to contaminated feed suggests that sporadic or spontaneous prion misfolding may also occur in cattle, analogous to sporadic Creutzfeldt-Jakob disease in humans 4 5 7.

Pathogenesis and Transmission

Infection typically occurs in calfhood via oral ingestion of prion-contaminated feed. Prions accumulate in lymphoid and neural tissues before spreading to the central nervous system, where they cause the characteristic spongiform changes and neurological symptoms 11. There is no strong evidence for vertical (mother-to-calf) transmission, as studies have shown progeny of BSE-affected cows rarely develop clinical BSE 2.

Treatment of Bovine Spongiform Encephalopathy

BSE remains a fatal disease with no known cure or effective treatment. The focus is on prevention, surveillance, and control to protect both animal and public health.

Approach	Description	Notes on Effectiveness	Source(s)
Feed Ban	Prohibit ruminant protein in feed	Cornerstone of epidemic control	12
Culling	Remove affected animals	Prevents further spread	3
Surveillance	Active testing and monitoring	Essential for detection, especially atypical BSE	5 7
Prion Inactivation	High-temperature dry-heat	Complete inactivation at ≥600°C	14

Table 4: BSE Treatments and Controls

No Effective Medical Treatment

There is currently no cure for BSE. Once clinical signs appear, the disease is invariably fatal, with progressive neurological deterioration leading to death 3.

Prevention and Control Measures

• Feed Ban: The single most effective measure has been the ban on feeding ruminant-derived protein to cattle, introduced in the UK in July 1988. This practice drastically reduced new BSE cases, as evidenced by the marked decline in the epidemic curve following the ban 12.
• Culling: Immediate removal and destruction of clinically affected animals and those exposed to contaminated feed prevent further spread within herds 3.
• Surveillance: Rigorous active surveillance, including rapid tests and molecular techniques capable of distinguishing between BSE types, remains essential—especially for detecting the rare atypical forms 5 7.
• Prion Decontamination: BSE prions are notably resistant to standard heat and chemical treatments. Research indicates that only dry-heat treatment at temperatures of 600°C or higher can completely eliminate prion infectivity from contaminated tissues. Lower temperatures are insufficient for inactivation 14.

Research Directions

While treatment is not currently possible, ongoing research focuses on understanding prion biology, improving diagnostic accuracy, and exploring potential decontamination and inactivation strategies. There is also active investigation into the zoonotic potential of BSE and its relationship to human prion diseases, such as variant Creutzfeldt-Jakob disease (vCJD) 12.

Conclusion

Bovine Spongiform Encephalopathy is a complex and devastating disease with significant implications for cattle health, food safety, and public trust in agriculture. Understanding its symptoms, types, causes, and control measures is essential for effective management and prevention.

Key takeaways:

• Symptoms: BSE manifests with progressive behavioral and neurological signs, including apprehension, hyperaesthesia, ataxia, and weight loss 1 3 9.
• Types: In addition to the classical form, atypical H- and L-type BSEs have been identified, each with unique molecular traits 4 5 6 7 8.
• Causes: The classical epidemic was driven by prion-contaminated feed, with evidence supporting a scrapie-like agent as the source; atypical BSE may arise sporadically 9 10 12.
• Treatment: There is no cure; prevention relies on feed bans, culling, surveillance, and proper decontamination of materials 12 14.

Ongoing vigilance, research, and strict adherence to preventive measures remain vital to safeguarding both animal and human health from the risks posed by BSE.