Hypercalcemia is a condition where the total serum calcium concentration rises above the normal range of approximately 8.5 to 10.5 milligrams per deciliter (mg/dL). While calcium is vital for many bodily functions, including bone health and muscle contraction, elevated levels can disrupt the nervous system. Severe hypercalcemia can indeed cause a range of neurological symptoms, including confusion, lethargy, and in rare cases, seizures. This seizure activity is usually associated with calcium concentrations exceeding 14.0 mg/dL, which constitutes a medical emergency.
Understanding Hypercalcemia
Calcium is a fundamental mineral involved in bone structure, muscle contraction, and nerve signaling. The body maintains tight control over blood calcium levels using hormones like parathyroid hormone and calcitonin. When this balance is disrupted, hypercalcemia develops, categorized by severity based on the total serum calcium level.
Mild hypercalcemia (10.5 to 11.9 mg/dL) is often asymptomatic. Moderate hypercalcemia (12.0 to 13.9 mg/dL) often presents with symptoms like fatigue and muscle weakness. Severe hypercalcemia, or hypercalcemic crisis (levels exceeding 14.0 mg/dL), is the range most commonly associated with profound neurological complications like stupor, coma, and seizures.
The Neurological Mechanism How High Calcium Affects Brain Cells
High extracellular calcium levels depress the overall excitability of the central nervous system, despite calcium being required for neurotransmitter release. This depression occurs because high calcium ions stabilize the nerve cell membrane by altering voltage-gated sodium channels. This makes it more difficult for the nerve cell to depolarize and fire an action potential.
This reduced excitability typically manifests as generalized neurological slowing, causing confusion, lethargy, and muscle weakness. The rare occurrence of seizures in severe hypercalcemia is not due to direct neuronal hyperexcitability, but rather a complication known as hypercalcemic encephalopathy. One proposed mechanism is that high calcium levels cause significant cerebral vasoconstriction, or narrowing of the blood vessels in the brain. This vasoconstriction can lead to Posterior Reversible Encephalopathy Syndrome (PRES), which is known to cause seizures and other acute neurological deficits.
Primary Causes of Severe Hypercalcemia
Two main diseases account for over 90% of cases where calcium levels rise high enough to induce severe neurological symptoms. The most common cause is primary hyperparathyroidism, involving the overproduction of parathyroid hormone (PTH), usually by a benign tumor. Excess PTH signals the body to release calcium from bones and increase kidney reabsorption, leading to chronically high, often mild, calcium levels.
The second major cause, often acute and severe, is malignancy-associated hypercalcemia. This condition is common in patients with cancers such as lung, breast, kidney cancer, and multiple myeloma. Tumors often secrete parathyroid hormone-related peptide (PTHrP), which mimics PTH action and causes rapid increases in blood calcium.
Less Common Causes
Less common causes include excessive intake of Vitamin D or Vitamin A, certain medications like thiazide diuretics or lithium, and granulomatous diseases such as sarcoidosis.
Diagnosis and Management of Hypercalcemia-Induced Seizures
When a patient presents with new-onset seizures and neurological symptoms, a rapid diagnosis is necessary to identify the high calcium as the cause. Initial blood tests are performed to measure total serum calcium, along with parathyroid hormone (PTH) and phosphate levels, to confirm the diagnosis and help identify the underlying cause. Electroencephalography (EEG) may be used to assess the brain’s electrical activity, which often shows diffuse slowing or abnormal wave patterns when calcium levels are significantly elevated.
The immediate management is focused on rapidly and safely lowering the serum calcium concentration to prevent irreversible organ damage and resolve the seizure activity. Intravenous (IV) fluid hydration with normal saline is the first step, as it helps dilute the calcium and increase its excretion through the kidneys. Medications are then administered, with bisphosphonates being a common treatment because they inhibit the release of calcium from the bone, though they take several days to reach their full effect. Calcitonin is often used alongside these drugs for a more immediate, though short-lived, calcium-lowering effect.