• tetany is a medical condition characterized by an increased excitability of neuronal and muscle membranes
    • hyperexcitability occurs at all levels of the nervous system, including the central nervous system
  • tetany presents with extremely diverse clinical symptoms and can result from various underlying causes that disrupt the normal balance of calcium and other electrolytes in the body
    • a tetanic seizure (hands and feet crumps with limb paresthesia) is clinically the most notable symptom of tetany
    • other typical symptoms include:
      • fatigue and irritability
      • palpitations
      • tingling, burning
      • chronic cramps
  • acute hypocalcemia is a medical emergency and, unless treated promptly, may progress to bronchospasm and cardiovascular instability  (Sehgal, 2011)
  • muscle spasms caused by tetanus are not classified as tetany
  • some manifestations of tetany can resemble a stroke (so it is classified as a potential stroke mimic)

Etiopathogenesis

  • the primary cause of tetany is electrolyte imbalance (most commonly hypocalcemia, but also hypomagnesemia), which rapidly and significantly increases the excitability of neuronal and muscle membranes

Hypocalcemia

  • tetany most commonly occurs when the total serum calcium is decreased (corrected calcium is standard laboratory value)
  • hypocalcemia is defined as total serum calcium level < 8.5 mg/dL (2.12 mmol/L) or ionized calcium level < 4.4 mg/dL (1.1 mmol/L)
  • in clinical signs of tetany occur and no evident abnormality in standard ionogram (Ca, Cl, K, Na, Mg) are detected, ionized calcium levels must be determined (Alanazi, 2023)

    • decreased ionized calcium levels are caused by increased calcium binding to albumin, usually provoked by hyperventilation  ⇒  typical cause of “normocalcemic” tetany
    • the corrected (total) calcium may need to be raised above the normal range to maintain normal ionized calcium in the context of metabolic alkalosis
    • ionized Ca levels are not always available; if clinical tetany occurs, start supplementation therapy despite normal total calcium in serum
  • factors that determine the severity of symptoms include acid-base status (hypocalcemia and alkalosis act synergistically)

Normocalcemic tetany

  • most “normocalcemic” tetany attacks are caused by undetected hypocalcemia
  • tetany due to hypomagnesemia is a complex metabolic disturbance characterized by hypomagnesemia (plasma total magnesium< 1.5 mg/dL [< 0.65 mmol/L]) leading to hyperexcitability, muscular spasms, seizures, respiratory distress, etc. (Unandh, 2021)
  • another possible cause of normocalcemic tetany is a paraneoplastic syndrome (probably mostly due to secondary hypocalcemia)  (Partanen, 1980)
  • hypocalcemia refers to a condition characterized by low levels of corrected (total) calcium in the blood
  • calcium is an essential mineral involved in various physiological processes, including muscle contraction, nerve transmission, blood clotting, and bone formation
  • hypocalcemia can result from several underlying causes
  • hypoparathyroidism (without enough PTH, calcium levels drop)

    • congenital (DiGeorge syndrome)
    • acquired
      • surgical removal of the parathyroid glands as a complication of neck surgery, particularly thyroidectomy
      • autoimmune diseases
      • radiation-induced damage
      • magnesium deficiency can impair PTH secretion
  • vitamin D deficiency due to decreased production or increased degradation (vitamin D plays a crucial role in calcium absorption from the intestines)
  • malabsorbtion syndromes
    • intestinal calcium resorption disorders
    • increased gastrointestinal calcium loss
  • deficient dietary calcium intake
  • hypercalcitoninemia
  • increased Ca2+ uptake in bones or inhibition of bone resorption
  • Ca2+ sequestration in acute pancreatitis
  • hypocalcemic factors produced by tumor cells
  • advanced renal failure
  • respiratory alkalosis (caused by hyperventilation)
  • corrected calcium and ionized calcium are two different measures of calcium levels in the blood
  • corrected calcium accounts for albumin levels (as calcium binds to albumin ) and provides a more accurate total calcium level
  • ionized calcium measures the free, biologically active form of calcium in the blood; it represents the fraction of calcium that is readily available for physiological functions
  • in tetany, the focus is often on the ionized calcium level because it reflects the biologically active form of calcium that directly affects neuromuscular excitability
  • hypomagnesemia can contribute to the development of tetany, although it is not as common as hypocalcemia
  • magnesium plays a crucial role in neuromuscular function, and its deficiency can lead to neuromuscular hyperexcitability and muscle spasms, similar to tetany
  • when magnesium levels are low, there is an impaired regulation of calcium channels and decreased parathyroid hormone (PTH) release, which can disrupt calcium homeostasis. This disruption can lead to increased neuromuscular irritability and the development of tetanic muscle contractions or spasms
  • in addition to tetany, other symptoms of hypomagnesemia may include muscle weakness, tremors, convulsions, cardiac arrhythmias, and altered mental status
  • hypercalcemia, hyperparathyroidism (increased urinary excretion of magnesium)
  • malabsorption syndromes  (celiac disease, Crohn’s disease, etc.)
  • inadequate dietary intake
  • medication
    • loop and thiazide diuretics
    • proton pump inhibitors (PPIs)
    • certain antibiotics (e.g., aminoglycosides)
  • hyperaldosteronism (increased urinary excretion of magnesium)
  • inherited disorders (such as familial hypomagnesemia with secondary hypocalcemia (FHHNC) and Gitelman syndrome)
  • renal disorders (chronic kidney disease, renal tubular dysfunction, and certain medications used to treat kidney disorders can interfere with magnesium reabsorption in the kidneys)
  • alcoholism (increased urinary excretion and reduced intestinal absorption of magnesium)

Clinical Presentation

Tetanic seizure

  • seizures occur spontaneously or as a result of excitement or other provoking moments
  • they last ~ 5-20 minutes, the patient is fully conscious but restless, and the seizure is accompanied by autonomic reactions, tachycardia, sweating, sometimes nausea, and global discomfort
  • typical signs:
    • sensory manifestations – paresthesia and tingling of the hands and feet, perioral numbness, gradually increasing in extent and intensity
    • carpopedal spasms

      • with extension of the interphalangeal joints and adduction and flexion of the metacarpophalangeal joints
    • bronchospasm, laryngospasm, or generalized tonic muscle contractions in severe cases (must be distinguished from generalized seizures)
  • seizure may be accompanied by hyperventilation, which accentuates its course by inducing respiratory alkalosis and hypocapnia (in susceptible individuals, a tetanic seizure can be provoked by voluntary hyperventilation alone)

Other manifestations of increased neuromuscular excitability

  • increased deep tendon reflexes
  • neurovegetative lability, e.g., positive dermographism
  • signs of increased neuromuscular excitability
    • Chvostek’s sign – contraction of the ipsilateral facial muscles, particularly the upper lip, in response to tapping or percussing the facial nerve just anterior to the ear
    • Trousseau’s sign – carpal spasm (flexion of the wrist and metacarpophalangeal joints, extension of the interphalangeal joints) induced by inflating a blood pressure cuff on the upper arm above systolic pressure for 3-5 minutes
      • it may also be induced by voluntary hyperventilation for one to two minutes after releasing the cuff
    • both signs may be negative in hypocalcemic patients and, vice versa, may occur in healthy individuals (Chvostek’s sign in ~10%)

In addition, there are a lot of less specific symptoms of increased neuromuscular excitability, such as:

  • headaches
  • chest pain, palpitations
    • in case of negative coronary findings, EMG for tetany should be performed, and appropriate therapy should be administered
  • hyperirritability, anxiety, and moodiness
  • fatigue
  • decreased concentration and work performance
  • persistent or intermittent paresthesias of the limbs and around the mouth
  • hyperhidrosis
  • sleep disturbance

Diagnostic evaluation

  • EMG
    • spontaneous motor activity with short-duration, high-frequency motor unit action potentials, especially in small hand muscles after provoking tests (limb ischemia, hyperventilation)
    • nerves and muscles may show increased sensitivity to electrical stimulation during nerve conduction studies, resulting in lower thresholds for evoking muscle responses
    • motor unit recruitment patterns may remain relatively normal or decrease during voluntary muscle contractions
  • EEG – abnormal, nonspecific
  • repeated examination of ionogram, incl. ionized fractions of Ca2+ and Mg 2+

    • Ca2+ 4.5-5.3 mg/dL (1.15-1.35 mmol/L), total Ca 8.6-10.2 mg/dL (2.2-2.61 mmol/L)
  • psychological examination
  • if hypocalcemia or hypomagnesemia is detected, search for its cause

Management

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Tetany
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