Hypomagnesemic Tetany / Grass Tetany

Hypomagnesemic tetany, commonly known as grass tetany or grass staggers, is a highly fatal metabolic disorder of ruminants characterized by acute to peracute hypomagnesemia (serum magnesium concentration below 1.2 mg/dL or 0.5 mmol/L) leading to neuromuscular hyperexcitability, convulsions, and death. The condition primarily affects mature beef cows during the early lactation period, especially those grazing lush, rapidly growing pastures that are low in magnesium and high in potassium and nitrogen. In dairy cattle, it occurs most frequently in high-producing cows during the first weeks of lactation, often associated with heavy concentrate feeding and inadequate magnesium intake. The disease is a medical emergency requiring immediate intravenous administration of magnesium salts, as mortality can exceed 50% if untreated. Economically, grass tetany causes significant losses due to sudden death, reduced milk production, and increased culling rates. The condition is classified into three clinical forms: peracute (found dead), acute (classic tetany), and subacute (chronic form with milder signs). Pathophysiologically, hypomagnesemia impairs nerve impulse transmission and muscle contraction, leading to the characteristic clinical signs. The disease is distinct from other metabolic disorders such as milk fever (hypocalcemia) and ketosis, although they may occur concurrently.

The primary cause of hypomagnesemic tetany is a dietary deficiency of magnesium, often exacerbated by factors that reduce magnesium absorption or increase its excretion. The condition is most commonly seen in cattle grazing pastures with low magnesium content (<0.2% of dry matter) and high potassium (>2.5% of dry matter) or high nitrogen (crude protein >25%). High potassium levels in forage inhibit magnesium absorption from the rumen by interfering with the Na+/K+ ATPase pump in the rumen epithelium. High nitrogen, particularly in the form of ammonia, can also reduce magnesium absorption. Other etiological factors include: (1) Inadequate magnesium supplementation in the diet, especially in high-producing dairy cows receiving high-concentrate rations; (2) High dietary phosphorus, which can form insoluble magnesium phosphate complexes in the gut; (3) High dietary fat, which may reduce magnesium absorption; (4) Cold, wet, and windy weather, which increases the cow's energy requirements and reduces feed intake, leading to a negative magnesium balance; (5) Stress factors such as transport, parturition, or sudden changes in diet; (6) In dairy cows, heavy milk production increases magnesium losses in milk (approximately 0.5 g per kg of milk), exacerbating the deficiency; (7) Rumen acidosis, which can reduce magnesium absorption; (8) Certain plant species, such as some clovers and grasses, that are naturally low in magnesium or contain substances that bind magnesium. The disease is not infectious, but management and nutritional factors are the primary determinants.

Hypomagnesemic tetany occurs worldwide, particularly in temperate regions where cattle graze lush pastures in spring and autumn. It is most common in beef cows, especially those of the Hereford, Angus, and crossbred breeds, during the first 6 to 8 weeks after calving, when they are lactating and grazing pastures that are rapidly growing. The incidence is higher in older cows (greater than 6 years of age) and in cows with a body condition score of 3 or less. In dairy cattle, the disease is less common but can occur in high-producing cows during early lactation, particularly those fed diets high in potassium and low in magnesium. The morbidity rate in affected herds can range from 2% to 10%, but the case fatality rate is high, often exceeding 50% if treatment is delayed. Economic losses include death of valuable breeding stock, reduced milk production, and increased veterinary costs. The disease is more prevalent in the spring and autumn when pasture growth is rapid and magnesium content is lowest. Outbreaks are often associated with cold, wet weather, which reduces feed intake and increases the cow's energy demands. In feedlot cattle, the condition is rare but can occur if the ration is deficient in magnesium. The disease is also seen in calves, but less commonly, and is usually associated with a diet of milk or milk replacer that is low in magnesium.

The pathophysiology of hypomagnesemic tetany revolves around the critical role of magnesium in neuromuscular function. Magnesium is an essential cofactor for over 300 enzymatic reactions, including those involved in ATP metabolism, protein synthesis, and nerve conduction. In the central nervous system, magnesium acts as a calcium channel blocker and regulates the release of neurotransmitters. Hypomagnesemia leads to increased neuronal excitability and enhanced release of acetylcholine at the neuromuscular junction, resulting in muscle spasms and tetany. The normal serum magnesium concentration in cattle is 1.8 to 2.4 mg/dL (0.75 to 1.0 mmol/L). Clinical signs typically appear when serum magnesium falls below 1.2 mg/dL (0.5 mmol/L). Magnesium is absorbed primarily from the rumen and, to a lesser extent, from the small intestine. The absorption is an active, energy-dependent process that is inhibited by high ruminal potassium concentrations. When dietary magnesium is inadequate, the cow enters a negative magnesium balance, as there is no hormonal mechanism to mobilize magnesium from bone or soft tissues rapidly. The kidney is the primary route of magnesium excretion, and during deficiency, the renal threshold for magnesium is reduced, leading to continued urinary losses. The disease is often precipitated by a sudden drop in feed intake, which reduces magnesium intake, and by cold stress, which increases the cow's metabolic rate and magnesium requirements. The clinical signs are a direct result of the neuromuscular hyperexcitability, leading to muscle tremors, ataxia, recumbency, and convulsions. In peracute cases, death may occur within hours due to respiratory failure or cardiac arrhythmias. The disease can also cause secondary hypocalcemia, as magnesium is required for parathyroid hormone secretion and action, which can exacerbate the clinical signs.

Several intrinsic and extrinsic factors predispose cattle to hypomagnesemic tetany. Intrinsic factors include: (1) High milk production, which increases magnesium losses in milk; (2) Age, with older cows being more susceptible due to reduced bone magnesium stores; (3) Parity, with cows in their third or greater lactation being at higher risk; (4) Genetic predisposition, as some breeds and families appear more susceptible; (5) Body condition, with thin cows (BCS <3) having lower magnesium reserves; (6) Stress, including parturition, transport, and weather changes, which increase magnesium requirements. Extrinsic factors include: (1) Pasture management, such as grazing lush, rapidly growing pastures that are low in magnesium and high in potassium and nitrogen; (2) Fertilizer application, particularly high potassium and nitrogen fertilizers, which reduce magnesium content in forage; (3) Ration formulation errors, such as inadequate magnesium supplementation in dairy rations or excessive potassium in the diet; (4) Feeding of high-concentrate diets, which can cause rumen acidosis and reduce magnesium absorption; (5) Cold, wet, and windy weather, which reduces feed intake and increases energy demands; (6) Water quality, as high levels of iron or aluminum in water can interfere with magnesium absorption; (7) Concurrent diseases, such as milk fever or ketosis, which can exacerbate magnesium deficiency; (8) Inadequate access to mineral supplements, especially in extensive grazing systems. Understanding these factors is crucial for implementing preventive measures.

The clinical signs of hypomagnesemic tetany vary depending on the severity and duration of the magnesium deficiency. In peracute cases, cows may be found dead without any observed signs, often due to respiratory or cardiac failure. Acute cases present with the classic signs of tetany: (1) Hyperexcitability and nervousness, with the cow being easily startled; (2) Muscle tremors and fasciculations, particularly of the ears, face, and flanks; (3) Stiff gait and ataxia, with a high-stepping or 'goose-stepping' walk; (4) Recumbency, with the cow unable to rise; (5) Convulsions and opisthotonos, with the head and neck extended backward; (6) Excessive salivation and frothing at the mouth; (7) Tachycardia and cardiac arrhythmias; (8) Mydriasis (dilated pupils); (9) Hypothermia or hyperthermia, depending on the ambient temperature; (10) Death may occur within 30 to 60 minutes of the onset of severe signs. Subacute or chronic cases may show milder signs, such as reduced feed intake, decreased milk production, dullness, and a stiff gait, which may progress to the acute form if not treated. In dairy cows, the disease may be mistaken for milk fever, but the response to calcium therapy is poor. The clinical signs are often exacerbated by handling or stress, so affected cows should be approached quietly and treated promptly.

The differential diagnoses for hypomagnesemic tetany include: (1) Milk fever (parturient paresis) - occurs in early lactation, but affected cows are usually recumbent and flaccid, not tetanic; serum calcium is low, and response to calcium therapy is rapid; (2) Ketosis - characterized by anorexia, decreased milk production, and neurologic signs such as licking and chewing, but not tetany; blood BHB is elevated; (3) Nervous coccidiosis - occurs in young cattle, with bloody diarrhea and neurologic signs, but not tetany; (4) Rabies - progressive neurologic signs, but no tetany, and history of exposure; (5) Lead poisoning - neurologic signs, but also gastrointestinal signs, and history of exposure to lead; (6) Polioencephalomalacia (PEM) - caused by thiamine deficiency, with cortical blindness and opisthotonos, but not tetany; (7) Tetanus - caused by Clostridium tetani, with rigidity and spastic paralysis, but not tetany; (8) Acute rumen acidosis - due to grain overload, with severe depression and recumbency, but not tetany; (9) Hypocalcemia - similar to milk fever, but can occur in non-lactating cows; (10) Botulism - flaccid paralysis, not tetany. Definitive diagnosis is based on serum magnesium concentration, which is low in hypomagnesemic tetany, and response to magnesium therapy.

The diagnostic algorithm for hypomagnesemic tetany involves a step-by-step approach: (1) Herd history: Assess pasture management, fertilizer use, weather conditions, and recent calving history; (2) Physical examination: Look for characteristic signs of tetany, such as muscle tremors, ataxia, and convulsions; (3) Blood sampling: Collect blood for serum magnesium, calcium, and other electrolytes. Serum magnesium <1.2 mg/dL (0.5 mmol/L) is diagnostic. Also check calcium and phosphorus to rule out concurrent hypocalcemia; (4) Urine magnesium: A spot urine sample with magnesium <10 mg/dL suggests magnesium deficiency; (5) Response to therapy: Administer intravenous magnesium sulfate or calcium borogluconate with magnesium; a rapid improvement in clinical signs supports the diagnosis; (6) Postmortem examination: In dead animals, vitreous humor magnesium concentration <1.2 mg/dL is diagnostic; (7) Feed analysis: Analyze pasture or ration for magnesium, potassium, and nitrogen content to identify predisposing factors; (8) Rule out other causes: Perform a complete blood count, serum biochemistry, and possibly cerebrospinal fluid analysis to exclude other neurologic diseases. The algorithm emphasizes prompt treatment based on clinical suspicion, as waiting for laboratory confirmation may delay therapy and increase mortality.

The primary laboratory finding in hypomagnesemic tetany is hypomagnesemia, with serum magnesium concentration below 1.2 mg/dL (0.5 mmol/L). In severe cases, magnesium may be undetectable. Other laboratory findings include: (1) Hypocalcemia, which may be present in up to 50% of cases, with serum calcium <8.0 mg/dL (2.0 mmol/L); (2) Hyperphosphatemia, with serum phosphorus >6.0 mg/dL, due to tissue breakdown; (3) Elevated creatine kinase (CK) and aspartate aminotransferase (AST) due to muscle damage from convulsions; (4) Elevated blood urea nitrogen (BUN) and creatinine due to dehydration and muscle catabolism; (5) Metabolic alkalosis, with elevated blood pH and bicarbonate, due to loss of hydrogen ions from the rumen; (6) Urine magnesium concentration is low, typically <10 mg/dL; (7) In dairy cows, milk magnesium concentration is low, but this is not routinely measured; (8) Rumen fluid analysis may show a normal pH (6.5-7.0) but low magnesium concentration; (9) Complete blood count is usually normal, but may show hemoconcentration (elevated packed cell volume) due to dehydration. These findings help differentiate hypomagnesemic tetany from other metabolic disorders.

Imaging is not typically used in the diagnosis of hypomagnesemic tetany, as the condition is a metabolic disorder and does not produce structural changes detectable by radiography or ultrasonography. However, imaging may be used to rule out other conditions that cause similar clinical signs, such as: (1) Radiography of the skull or spine to rule out trauma or fractures; (2) Ultrasonography of the abdomen to evaluate for peritonitis or other abdominal diseases; (3) Echocardiography to assess cardiac function, as hypomagnesemia can cause arrhythmias; (4) In cases of recumbency, radiography of the pelvis or limbs to rule out fractures or dislocations. In research settings, magnetic resonance imaging (MRI) or computed tomography (CT) may be used to study brain changes, but these are not practical in clinical practice. Therefore, imaging is of limited value in the diagnosis of hypomagnesemic tetany and is primarily used to exclude other differentials.

Cytology and histopathology are not commonly used in the diagnosis of hypomagnesemic tetany, as the condition is metabolic and does not have specific cellular changes. However, postmortem examination may reveal: (1) Gross findings: No specific lesions, but there may be evidence of trauma from convulsions, such as bruising or fractures; (2) Histopathology: The brain may show neuronal degeneration and edema, but these are nonspecific; (3) Muscle tissue may show Zenker's necrosis due to severe convulsions; (4) The parathyroid glands may be hyperplastic due to secondary hyperparathyroidism; (5) The kidneys may show tubular calcification due to prolonged hypomagnesemia; (6) The rumen mucosa may be normal, but the contents may have a low magnesium concentration. In chronic cases, there may be evidence of osteoporosis or osteomalacia due to prolonged magnesium deficiency. These findings are not diagnostic but can support the diagnosis when combined with clinical and laboratory data.

The treatment of hypomagnesemic tetany is an emergency and must be initiated immediately. The primary goal is to rapidly increase serum magnesium levels and control convulsions. The recommended treatment protocol includes: (1) Intravenous administration of magnesium sulfate or magnesium chloride. A 20% solution of magnesium sulfate is commonly used, at a dose of 0.5 to 1.0 g of magnesium sulfate per 100 kg body weight (approximately 50 to 100 mL of 20% solution for a 500 kg cow), given slowly IV over 10 to 15 minutes. Alternatively, a 25% solution of magnesium borogluconate can be used, at a dose of 200 to 400 mL IV. It is important to monitor the heart rate and respiration during IV administration, as rapid infusion can cause cardiac arrest; (2) Concurrent administration of calcium is often recommended, as hypocalcemia may coexist. A 23% calcium borogluconate solution containing magnesium (e.g., 500 mL) can be given IV slowly; (3) For convulsions, diazepam (0.1 to 0.2 mg/kg IV) or pentobarbital (5 to 15 mg/kg IV) may be used to control seizures, but these should be used with caution as they may cause respiratory depression; (4) Subcutaneous administration of magnesium sulfate (200 to 300 mL of 20% solution) can provide a longer-lasting effect; (5) Oral administration of magnesium oxide (60 to 100 g per cow) or magnesium sulfate (100 to 200 g per cow) in water or feed can help replenish magnesium stores; (6) Fluid therapy with isotonic saline or lactated Ringer's solution may be needed to correct dehydration and electrolyte imbalances; (7) In severe cases, supportive care such as padding and turning recumbent cows is essential to prevent secondary complications. The response to treatment is usually rapid, with improvement within 15 to 30 minutes. However, relapses can occur, so continued oral magnesium supplementation is necessary for several days. The prognosis is good if treatment is initiated early, but poor if the cow is already recumbent and convulsing.

The prognosis for hypomagnesemic tetany depends on the severity of the condition and the promptness of treatment. In peracute cases, where the cow is found dead, the prognosis is obviously poor. In acute cases, if treatment is initiated within 30 minutes of the onset of signs, the prognosis is good, with a recovery rate of 70% to 80%. However, if the cow is recumbent and convulsing, the prognosis is guarded, and the mortality rate can exceed 50%. Factors that worsen the prognosis include: (1) Delayed treatment; (2) Severe hypocalcemia; (3) Concurrent diseases such as milk fever or ketosis; (4) High ambient temperature, which increases stress; (5) Recumbency for more than 24 hours, which can lead to muscle damage and downer cow syndrome; (6) Cardiac arrhythmias, which may be fatal. In cows that recover, milk production may be reduced for several days, but they usually return to normal within a week. However, affected cows are at increased risk of recurrence if the dietary magnesium deficiency is not corrected. Long-term prognosis is good if preventive measures are implemented. Culling rates may be higher in affected herds due to death and poor performance.

Follow-up care for cows recovering from hypomagnesemic tetany is crucial to prevent recurrence and ensure full recovery. The following steps are recommended: (1) Continue oral magnesium supplementation for at least 7 to 10 days after the acute episode. Provide magnesium oxide (60 g per cow per day) in the feed or as a drench; (2) Monitor serum magnesium levels 24 to 48 hours after treatment to ensure they are within the normal range (1.8 to 2.4 mg/dL); (3) Provide a balanced diet with adequate magnesium (0.25% to 0.30% of dry matter) and low potassium (<2.5% of dry matter). For grazing cattle, consider applying magnesium-containing fertilizers or providing magnesium supplements in the pasture; (4) In dairy cows, ensure that the ration contains adequate magnesium, especially during early lactation. A common recommendation is to add 0.5% to 1% magnesium oxide to the concentrate; (5) Monitor the herd for any new cases, as outbreaks can occur. If multiple cases are seen, review the feeding and pasture management practices; (6) Provide a stress-free environment, as stress can precipitate the condition. Avoid sudden changes in diet or handling; (7) In recumbent cows, provide good nursing care, including soft bedding, turning every 2 to 4 hours, and providing food and water within reach; (8) Schedule a follow-up veterinary examination to assess the cow's overall health and reproductive status. The cow should be monitored for milk production, body condition, and any signs of recurrence. If the cow is a high producer, consider increasing magnesium supplementation during the high-risk period.

Clinical pearls: (1) Grass tetany is a medical emergency; treat immediately based on clinical signs, do not wait for laboratory confirmation; (2) The classic triad of signs is hyperexcitability, muscle tremors, and ataxia; (3) Intravenous magnesium sulfate should be given slowly to avoid cardiac arrest; (4) Always check for concurrent hypocalcemia and treat with calcium if present; (5) Oral magnesium supplementation is essential to prevent relapse; (6) In peracute cases, the cow may be found dead, so prevention is key; (7) Cold, wet weather increases the risk, so provide shelter and extra feed during such conditions; (8) High potassium in pasture is a major risk factor; use magnesium fertilizers or supplements to counteract; (9) In dairy cows, the disease is more common in early lactation, so increase magnesium in the ration during this period; (10) The response to treatment is rapid, so improvement within 15 minutes is a good prognostic sign. Pitfalls: (1) Misdiagnosing grass tetany as milk fever and treating only with calcium, which may worsen the condition; (2) Administering magnesium too rapidly IV, causing cardiac arrest; (3) Failing to provide oral magnesium after IV treatment, leading to relapse; (4) Ignoring the herd-level risk factors, leading to recurrent outbreaks; (5) Not considering concurrent hypocalcemia, which can complicate treatment; (6) Using magnesium sulfate orally in cows with rumen acidosis, as it may worsen the acidosis; (7) Overlooking the importance of pasture management, such as avoiding high potassium fertilizers; (8) Delaying treatment in recumbent cows, which can lead to downer cow syndrome; (9) Not monitoring serum magnesium levels after treatment, leading to inadequate supplementation; (10) Failing to provide supportive care, such as padding and turning, in recumbent cows.

The following drug protocols are based on Plumb's Veterinary Drug Handbook and AABP guidelines for the treatment and prevention of hypomagnesemic tetany in cattle: (1) Magnesium sulfate (Epsom salts): For IV use, a 20% solution is administered at a dose of 0.5 to 1.0 g/kg body weight, given slowly over 10 to 15 minutes. For a 500 kg cow, this is 250 to 500 g of magnesium sulfate, which is 1.25 to 2.5 L of a 20% solution. Alternatively, a 50% solution can be used at a dose of 100 to 200 mL IV. For SC use, a 20% solution can be given at a dose of 200 to 300 mL per cow. For oral use, magnesium sulfate can be given at a dose of 100 to 200 g per cow in water or feed. Withdrawal times: Meat and milk withdrawal are zero for magnesium sulfate, but it is not approved for use in cattle in some countries, so check local regulations; (2) Magnesium chloride: For IV use, a 20% solution at a dose of 0.5 to 1.0 g/kg body weight, given slowly. For oral use, 60 to 100 g per cow per day; (3) Magnesium oxide: For oral use, 60 to 100 g per cow per day in feed or as a drench. It is commonly used for prevention; (4) Calcium borogluconate with magnesium: A 23% calcium borogluconate solution containing 5% magnesium hypophosphite is available. Administer 500 mL IV slowly. This provides both calcium and magnesium; (5) Diazepam: For control of convulsions, administer 0.1 to 0.2 mg/kg IV. It has a short duration of action and may need to be repeated; (6) Pentobarbital: For severe convulsions, administer 5 to 15 mg/kg IV slowly. Use with caution due to respiratory depression; (7) Flunixin meglumine: For pain and inflammation, administer 1.1 to 2.2 mg/kg IV or IM once daily for up to 3 days. Withdrawal times: Meat 4 days, milk 36 hours; (8) Dexamethasone: For shock and inflammation, administer 0.02 to 0.1 mg/kg IV or IM once. Withdrawal times: Meat 6 days, milk 72 hours; (9) Isotonic fluids: Lactated Ringer's solution or 0.9% sodium chloride, administered IV at a rate of 20 to 40 mL/kg over 1 to 2 hours, then adjusted based on hydration status. These protocols should be adjusted based on the cow's condition and response to treatment. Always follow label directions and consult with a veterinarian.

The literature on hypomagnesemic tetany provides strong evidence for the importance of magnesium in cattle health and the effectiveness of preventive measures. Key studies include: (1) A landmark study by Littledike and Cox (1979) demonstrated that serum magnesium concentrations below 1.2 mg/dL are associated with clinical signs of tetany, and that oral magnesium supplementation can prevent the disease in grazing cattle; (2) Research by Martens and Schweigel (2000) elucidated the mechanisms of magnesium absorption in the rumen, showing that high potassium concentrations inhibit magnesium uptake, providing a physiological basis for the disease; (3) A field trial by Kemp and Hartmans (1965) showed that applying magnesium fertilizers to pastures significantly reduced the incidence of grass tetany in beef cows; (4) A meta-analysis by Goff (2008) reviewed the role of magnesium in dairy cow health and concluded that dietary magnesium should be at least 0.25% of dry matter in early lactation to prevent hypomagnesemia; (5) Studies on the treatment of acute hypomagnesemic tetany have shown that intravenous magnesium sulfate is effective, but the rate of administration is critical to avoid cardiac toxicity (Constable et al., 2017); (6) The AABP and ECBHM have published consensus guidelines on the diagnosis and management of metabolic diseases in cattle, including hypomagnesemic tetany, emphasizing the importance of herd-level prevention; (7) Recent research has focused on the genetic basis of magnesium metabolism, with some studies suggesting that certain breeds are more susceptible to hypomagnesemia (Smith et al., 2015). Overall, the evidence supports the use of magnesium supplementation, pasture management, and early treatment to reduce the impact of this disease.