What is the appropriate work‑up and management for a patient presenting with headache and bilateral lentiform‑nucleus hyperdensities on CT?

Bilateral Lentiform Nucleus Hyperdensities with Headache: Diagnostic Work-Up and Management

In a patient presenting with headache and bilateral lentiform nucleus (basal ganglia) hyperdensities on CT, immediately obtain serum calcium, phosphate, parathyroid hormone (PTH), and vitamin D levels to evaluate for metabolic disorders causing pathologic calcifications, as these represent the most common treatable etiologies of Fahr's syndrome. 1, 2, 3

Initial Laboratory Evaluation

The presence of bilateral basal ganglia calcifications with headache mandates urgent metabolic workup:

• Serum calcium (corrected) - to detect both hypocalcemia and hypercalcemia, as both hypoparathyroidism and primary hyperparathyroidism can cause basal ganglia calcifications 1, 2, 3
• Parathyroid hormone (PTH) - elevated PTH with normal or high calcium suggests primary hyperparathyroidism; low PTH with low calcium indicates hypoparathyroidism 1, 2, 3
• Phosphate levels - abnormal calcium-phosphorus homeostasis is central to pathologic brain calcification 1, 2, 4
• Vitamin D (25-OH) - deficiency can contribute to ectopic calcifications even with normal calcium 1, 3
• Thyroid function (TSH, free T4) - as thyroid disorders may coexist with parathyroid pathology 1

Neuroimaging Considerations

While CT has already identified the hyperdensities, additional imaging may be warranted:

• MRI brain with and without contrast is preferred over CT for superior soft-tissue characterization and to exclude underlying vascular malformations, masses, or infectious etiologies that could present with calcifications 5
• CT remains the gold standard for detecting and characterizing calcifications, showing their distribution pattern (bilateral basal ganglia, dentate nuclei, periventricular regions) which helps narrow the differential diagnosis 2, 4

Red Flag Assessment

Evaluate for secondary headache red flags that would necessitate urgent intervention 5, 6:

• Thunderclap onset - suggests subarachnoid hemorrhage or cerebral venous thrombosis 5, 6
• Focal neurological deficits - may indicate stroke, mass effect, or structural lesion 5, 6
• Altered consciousness or seizures - common presentations of Fahr's syndrome but require exclusion of acute intracranial pathology 2, 4
• Fever or neck stiffness - mandates evaluation for meningitis or encephalitis 5, 6

If any red flags are present beyond the calcifications themselves, proceed with lumbar puncture (after imaging excludes mass effect) and blood cultures as clinically indicated 5.

Differential Diagnosis of Bilateral Basal Ganglia Calcifications

Primary Metabolic Causes (Most Common and Treatable)

Hypoparathyroidism presents with:

• Low serum calcium and low PTH 2, 4
• Seizures (often generalized tonic-clonic) and headache as presenting symptoms 2, 4
• Calcifications typically in basal ganglia, dentate nuclei, and periventricular regions 2, 4

Primary hyperparathyroidism (including normocalcemic variant) presents with:

• Elevated PTH with normal or elevated calcium 1, 3
• Ectopic calcifications from calcium-phosphorus dysregulation 1, 3
• Headache, vertigo, and occasionally seizures 1, 3
• Parathyroid adenoma often identified on ultrasound or sestamibi scan 3

Secondary Causes to Consider

• Fahr's disease (primary familial brain calcification) - diagnosed when metabolic causes excluded and family history present 2, 4
• Infectious etiologies - congenital TORCH infections, HIV, tuberculosis 4
• Celiac disease with folate deficiency - rare association with occipital calcifications and migraine-like headache 7
• Sturge-Weber syndrome - typically with cutaneous angiomas, though atypical forms exist 7

Management Algorithm

Step 1: Stabilize and Treat Acute Symptoms

• If seizures present: initiate anticonvulsant therapy (levetiracetam 500-1000 mg is commonly used) 1, 2
• If severe headache: provide symptomatic relief while completing diagnostic workup 1, 3
• Monitor for signs of increased intracranial pressure - though mass effect is uncommon with calcifications alone 5

Step 2: Treat Underlying Metabolic Disorder

For hypoparathyroidism:

• Calcium supplementation to normalize serum levels 2, 4
• Vitamin D replacement (calcitriol preferred for hypoparathyroidism) 2
• Seizures typically remit once calcium normalized 2, 4

For primary hyperparathyroidism:

• Refer to endocrine surgery for parathyroidectomy 1, 3
• Parathyroid imaging (ultrasound and/or sestamibi scan) to localize adenoma 3
• Post-operative monitoring shows normalization of PTH and calcium within months 3

For normocalcemic hyperparathyroidism:

• Consider parathyroidectomy even with normal calcium if PTH persistently elevated and symptomatic 1
• Vitamin D optimization may be needed 1

Step 3: Long-Term Monitoring

• Repeat neuroimaging is generally not indicated unless new neurological symptoms develop, as calcifications may persist or progress slowly despite metabolic correction 2, 3
• Monitor calcium, phosphate, and PTH levels every 3-6 months initially, then annually once stable 1, 3
• Anticonvulsant therapy may be discontinued if seizures were solely due to metabolic derangement and levels remain normalized 2

Common Pitfalls to Avoid

Do not assume calcifications are benign or age-related without metabolic workup - treatable causes like hypoparathyroidism and hyperparathyroidism are frequently missed, delaying appropriate therapy 1, 2, 3

Do not rely solely on serum calcium - normocalcemic primary hyperparathyroidism can cause Fahr's syndrome, requiring PTH measurement for diagnosis 1

Do not overlook vitamin D status - deficiency contributes to ectopic calcifications and must be corrected alongside calcium-PTH abnormalities 1, 3

Do not perform lumbar puncture before imaging in patients with headache and suspected intracranial pathology, as mass effect must be excluded first 5

Do not attribute all symptoms to calcifications - evaluate for coexisting conditions like thyroid dysfunction, which commonly accompanies parathyroid disorders 1

Prognosis and Expected Outcomes

When metabolic causes are identified and corrected:

• Seizures typically resolve with normalization of calcium levels 2, 4
• Headaches improve with treatment of underlying endocrinopathy 1, 3
• Neurological symptoms stabilize though pre-existing calcifications may not fully resolve 2, 3
• Quality of life significantly improves with targeted management of the metabolic disorder 1

Early diagnosis and treatment of metabolic causes can prevent progression and improve symptom control, making thorough laboratory evaluation essential in all cases of bilateral basal ganglia calcifications with headache 1, 2, 3.