Camelidae and Cervidae Ryegrass Staggers – NAVLE Study Guide

Overview and Clinical Importance

Ryegrass staggers is a neurological syndrome affecting grazing livestock caused by ingestion of perennial ryegrass (Lolium perenne) infected with the endophytic fungus Epichloë festucae var. lolii (formerly Neotyphodium lolii). The fungus produces tremorgenic mycotoxins, primarily lolitrem B, which causes characteristic tremors, ataxia, and incoordination in affected animals.

Camelids (alpacas and llamas) and cervids (farmed deer) are highly susceptible species commonly affected in regions where perennial ryegrass pastures predominate, particularly New Zealand, Australia, and increasingly in the United States. Young animals under 2 years of age appear most susceptible, and some genetic predisposition exists.

Etiology and Pathophysiology

Causative Agent

The condition results from ingestion of perennial ryegrass infected with the endophytic fungus Epichloë festucae var. lolii. This fungus lives entirely within the plant, growing intercellularly, and cannot spread from plant to plant in the field. Transmission occurs only through infected seed. The fungus-grass relationship is mutualistic: the fungus provides the plant with enhanced insect resistance and drought tolerance, while the grass provides nutrients and habitat.

Key Toxins Produced

Mechanism of Action

Lolitrem B is the primary tremorgenic neurotoxin responsible for ryegrass staggers. It acts by potently inhibiting large conductance calcium-activated potassium (BK) channels (also known as BKCa, Maxi-K, or Slo1 channels) in the central nervous system. The IC50 for lolitrem B inhibition of human BK channels (hSlo) is approximately 3.7 nM, making it an extremely potent blocker.

BK channels normally function to repolarize neurons after action potential firing by allowing potassium efflux. When lolitrem B blocks these channels, it prevents the neuron from properly resetting after depolarization, leading to prolonged cellular excitation and disrupted neurotransmitter release. This results in the characteristic tremors, ataxia, and motor dysfunction seen clinically.

Key Pathophysiological Features

• Fat-soluble toxin: Lolitrem B accumulates in adipose tissue, causing slow onset and prolonged duration of clinical signs
• Reversible effects: Neurological signs are generally reversible upon removal from toxic pasture
• Open-state preference: Lolitrem B preferentially blocks BK channels in their open configuration
• Cardiovascular effects: BK channel blockade can decrease heart rate (30-42% reduction) and cause vasoconstriction

Toxin Distribution in Plants

Lolitrem B concentration varies within the plant and is influenced by environmental conditions:

• Highest concentration: Leaf sheaths (base of plant) and seed heads
• Lowest concentration: Upper leaf blades
• Peak season: Late summer through autumn (warm temperatures increase toxin production)
• Persistence: Toxins persist in hay and silage made from infected grass
• Risk factors: Overgrazing, drought conditions, or fresh regrowth after drought

Species Susceptibility

Camelids (Llamas and Alpacas)

Camelids are highly susceptible to ryegrass staggers, with outbreaks commonly reported in New Zealand, Australia, the United Kingdom, and increasingly in the United States (particularly Ohio). Several factors contribute to their susceptibility:

• Grazing behavior: Alpacas tend to graze selectively, often preferring tender ryegrass shoots over other forages
• Age predilection: Animals under 12 months of age are most commonly affected; nursing crias as young as a few weeks old can be affected
• Genetic susceptibility: Some individual animals and genetic lines appear more susceptible than others
• Anecdotal observation: Lighter-colored alpacas may be more susceptible (unconfirmed scientifically)

Cervids (Deer)

Farmed deer, including red deer and fallow deer, are susceptible to ryegrass staggers, though they appear only moderately susceptible compared to sheep. Key points include:

• Red and fallow deer: Moderately susceptible; commonly affected in New Zealand deer farming operations
• Genetic variation: Some genetic lines are less prone to staggers and can be selected for breeding
• AR37 endophyte caution: Novel endophyte strains (like AR37) are not recommended for deer pastures as they may still cause staggers

Toxicity Thresholds

Clinical Signs

Clinical signs typically develop 7-14 days after animals begin grazing toxic pastures and are characteristically precipitated or exacerbated by stress, exercise, or sudden stimuli. Animals may appear normal at rest but show dramatic signs when disturbed.

Clinical Signs in Camelids

Mild Signs

• Subtle head tremor or wobbling (most common initial sign)
• Head and neck tremors that worsen with excitement
• May appear normal until stressed or agitated

Moderate Signs

• High-stepping gait
• Stiffness and incoordination (ataxia)
• Swaying and staggering when walking
• Tendency to fall, stand with legs splayed

Severe Signs

• Collapse with tetanic extension of limbs
• Opisthotonos
• Inability to rise
• Convulsions (especially with external stimuli)
• May kneel on forelegs or dogsit on hindlegs

Clinical Signs in Cervids (Deer)

• Slight head tremor or trembling of neck, shoulder, and back muscles at rest
• Exaggerated tremors and shaking when moved or yarded
• Stiff-legged stance with visible shaking or nodding
• Falling and thrashing or convulsions in severe cases
• Not all deer in a group are affected to the same degree

Diagnosis

Diagnosis is primarily based on clinical signs, history of exposure to perennial ryegrass, and pasture evaluation. There is no definitive live-animal test.

Diagnostic Approach

Clinical Presentation

• Characteristic stress-induced tremors and ataxia
• Multiple animals often affected simultaneously
• Recovery when animals removed from pasture (supports diagnosis)

Pasture and Feed Evaluation

• Confirm presence of perennial ryegrass in pasture
• Microscopic examination for endophyte hyphae (aniline blue staining of leaf sheaths)
• Note: Most perennial ryegrass pastures contain some endophyte infection

Laboratory Testing

• Lolitrem B quantification: HPLC with fluorescence detection on feed/pasture samples
• Fat tissue analysis: Lolitrem B concentrations in perirenal fat (post-mortem)
• ELISA: Plasma lolitrem B testing (experimental; may have diagnostic value)
• Histopathology: Often unremarkable; chronic cases may show myodegeneration, Purkinje cell vacuolation

Differential Diagnoses

Treatment and Management

There is no specific antidote for lolitrem B toxicosis. Treatment is primarily supportive and focuses on removing the source of toxin and minimizing stress.

Prognosis and Recovery

• Recovery time: 1-3 weeks after removal from toxic pasture
• Prognosis: Good if caught early; most animals recover fully
• Chronic exposure: May result in permanent neurological damage
• Mortality: Death uncommon and usually due to accidents (drowning, trauma, starvation) rather than direct toxicity

Prevention

Pasture Management Strategies

• Maintain grazing height: Prevent overgrazing; keep grass above 4 inches (toxin concentrated at base)
• Avoid seed heads: Do not allow animals to graze ryegrass going to seed
• Mixed pastures: Encourage growth of clovers, other legumes, and non-ryegrass species
• Alternative pastures: Have non-ryegrass paddocks available during high-risk periods
• Monitor conditions: Increase vigilance in late summer/autumn and after drought

Novel (Safe) Endophyte Varieties

Plant breeders have developed perennial ryegrass cultivars infected with novel endophyte strains that provide pest resistance without producing lolitrem B:

Memory Aids

STAGGERS Mnemonic for Clinical Features:

• S - Stress-induced (signs worsen with excitement)
• T - Tremors (head, neck, whole body)
• A - Ataxia and incoordination
• G - Grazing on ryegrass (history)
• G - Good prognosis if removed early
• E - Endophyte fungus (Epichloë) is cause
• R - Recovery in 1-3 weeks
• S - Summer/autumn peak season

BK Channel = Big K = Big Problem:

Lolitrem B Blocks BK (Big K+) channels, causing neurons to stay excited (tremors). Think 'B' in lolitrem B blocks 'B'K channels!