Acquired Metabolic and Systemic Disorders

Main Text

Preamble

In this chapter, we focus on acquired metabolic and systemic disorders that involve the CNS. We begin with the most common—hypertension—before turning our attention to abnormalities of glucose metabolism and thyroid/parathyroid function.

We then discuss seizure disorders, as sustained ictal activity with hypermetabolism can have profound effects on the brain. We finish the section by exploring cytotoxic corpus callosum injury and transient global amnesia.

We close with miscellaneous but important acquired metabolic diseases, such as hepatic encephalopathy (HE) (both acute and chronic) and the osmotic demyelination syndromes.

Hypertensive Encephalopathies

Preamble

If not recognized and treated, the effects of both acutely elevated blood pressure and chronic hypertension (HTN) on the brain can be devastating. We begin this section with a discussion of acute hypertensive encephalopathy, then delve into the CNS damage caused by chronic HTN.

Acute Hypertensive Encephalopathy

Terminology

The most common manifestation of acute hypertensive encephalopathy is posterior reversible encephalopathy syndrome (PRES) (37-1). Despite the syndrome’s name, lesions are rarely limited to the “posterior” (parietooccipital) aspects of the brain, and atypical is more common than “classic” PRES (37-3).

Etiology

General Concepts

The pathogenesis of PRES is not yet completely understood. The most common explanation is that severe HTN leads to failed cerebral autoregulation and breakthrough hyperperfusion with vasodilatation. However, between 15-20% of patients with PRES are normotensive or even hypotensive, whereas < 1/2 have a mean arterial pressure > 140-150 mm Hg.

Alternative theories for the development of PRES invoke vasculopathy with vascular endothelial injury and dysfunction.

Associated Conditions

PRES is associated with a multitude of diverse clinical entities, the most common of which are eclampsia, HTN, and immunosuppressive treatment.

Other conditions associated with PRES include renal failure with hemolytic-uremic syndrome (HUS), thrombotic thrombocytopenic purpura (TTP), autoimmune disorders (e.g., lupus nephropathy and acute glomerulonephritis), shock/sepsis syndrome, postcarotid endarterectomy with reperfusion syndrome, endocrine disorders, stimulant drugs, such as ephedrine and pseudoephedrine, and ingestion of some food products (e.g., licorice).

Pathology

Autopsied brains from patients with complicated PRES show diffuse cerebral edema. Intracranial hemorrhage complicates 15-25% of PRES cases. The most common finding is multiple bilateral petechial microhemorrhages in the occipital lobes (37-1).

Microvascular pathology includes fibrinoid arteriolar necrosis with petechial hemorrhages, proteinaceous exudates, and macrophage infiltration along the perivascular spaces.

Pathologic evidence of partial irreversible damage has been documented in PRES despite radiographic resolution of abnormalities. Scattered microinfarcts, white matter (WM) rarefaction with subpial gliosis, and hemosiderin deposition—especially in the posterior cerebrum—have been reported.

Clinical Issues

Epidemiology and Demographics

Although the peak age of onset is 20-40 years, PRES can affect patients of all ages from infants to older adults. There is a moderate female predominance, largely because of the strong association of PRES and preeclampsia.

Preeclampsia is the most common overall cause of PRES. HTN (blood pressure > 140/90 mm Hg) and proteinuria are typical. Progression from preeclampsia to eclampsia (mean systolic ≥ 160 mm Hg) occurs in 0.5% of patients with mild and 2-3% of patients with severe preeclampsia.

Presentation

Although 92% of patients with PRES have acutely elevated blood pressure, PRES can also occur in the absence of HTN. The most common clinical symptoms and signs in patients with PRES are encephalopathy (50-80%), seizure (60-75%), headache (50%), visual disturbances (33%), and focal neurologic deficit (10-15%).

Natural History and Treatment Options

Reversibility is a typical feature of PRES and is associated with good prognosis. If the inciting substances or precipitating conditions are eliminated and any existing HTN is promptly treated, PRES often resolves with minimal or no residual abnormalities.

Extensive vasogenic edema, hemorrhage, and restricted diffusion on initial imaging are associated with worse clinical outcomes. Severe PRES can be life threatening. In rare cases, lesions are irreversible and permanent damage occurs, typically hemorrhagic cortical/subcortical or basal ganglionic infarcts.

Imaging

General Features

Three distinct imaging patterns of PRES have been described. The most common is a dominant parietal-occipital pattern (classic or typical PRES). Two less common (atypical) patterns are a superior frontal sulcus pattern (involvement of the mid and posterior aspects of the superior frontal sulcus) and a holohemispheric watershed pattern (involvement of the frontal, parietal, and occipital lobes along the internal watershed zones). Combinations of these three patterns as well as involvement of other anatomic areas are also common (37-3).

The parietooccipital lobes are involved in > 90% of PRES cases (37-1) (37-2) (37-4B). The frontal lobes are involved in 75-77% of cases with the temporal lobes (65%) and cerebellum (50-55%) also commonly affected. Other atypical distributions include the basal ganglia and thalami, deep WM, corpus callosum splenium, brainstem, and cervical spinal cord.

CT Findings

NECT scans are commonly obtained as an initial screening study (37-4A) (37-2A). It is therefore extremely important to identify even subtle abnormalities that may be suggestive of PRES. If the screening NECT is normal and PRES is suspected on clinical grounds, an MR scan with DWI and T2* in addition to the routine sequences (T1 and T2/FLAIR) should be obtained.

Screening NECTs are normal in ~ 1/4 of all PRES cases (37-4). Subtle, patchy cortical/subcortical hypodensities—usually in the parietooccipital lobes, watershed zones, &/or cerebellum—may be the only visible abnormalities on NECT (37-2A). PRES-associated intracranial hemorrhage is uncommon.

MR Findings

PRES has both classic and atypical (i.e., variant) MR features. Keep in mind that (1) atypical PRES is actually more common than classic (i.e., purely parietooccipital) PRES; (2) PRES is rarely just posterior; and (3) PRES is not always reversible.

Classic PRES demonstrates bilateral parietooccipital cortical/subcortical hypointensities that are hypointense on T1WI and hyperintense on T2/FLAIR (37-2B) (37-4B). T2* (GRE or SWI) sequences may demonstrate hemorrhagic foci. Transient patchy cortical-subcortical enhancement on T1 C+ may occur.

Imaging findings in atypical PRES include involvement of the frontal lobes, watershed zones, basal ganglia &/or thalami, brainstem, cerebellum, and even the spinal cord (37-6) (37-7). Findings of both classic and atypical PRES very commonly occur together.

In unusual cases, brainstem &/or cerebellar lesions may be the only abnormality present. The spinal cord has been reported as a rare site of isolated PRES involvement.

Frank infarction is quite rare in PRES. Because most cases of PRES are caused by vasogenic—not cytotoxic—edema, DWI is usually negative (37-5). However, PRES with restricted diffusion occurs in 15-30% of cases and is usually seen as small foci of restricted diffusion within larger regions of nonrestricting vasogenic edema.

Following blood pressure normalization, imaging findings in most cases of PRES resolve completely. Irreversible lesions are relatively uncommon, occurring in ~ 15% of cases.

Differential Diagnosis

The major differential diagnoses of PRES include acute cerebral ischemia-infarction, vasculitis, hypoglycemia, status epilepticus (SE), sinovenous thrombosis, reversible cerebral vasoconstriction syndrome (RCVS), and the thrombotic microangiopathies.

PRES rarely involves just the posterior circulation, so acute cerebral ischemia-infarction is often easily distinguished. Vasculitis can resemble PRES-induced vasculopathy on CTA or DSA.

The distribution of lesions in vasculitis is much more random and less symmetric, usually does not demonstrate the parietooccipital predominance seen in PRES, and more often enhances following contrast administration. Vasculitis may have associated hemorrhage. In contrast to vasculitis, high-resolution vessel wall imaging is usually negative in PRES.

Hypoglycemia typically affects the parietooccipital cortex and subcortical WM, so the clinical laboratory findings (i.e., low serum glucose, lack of systemic HTN) are important differentiating features. SE can cause transient gyral edema but is rarely bilateral and can affect any part of the cortex.

Less common entities that can mimic PRES include RCVS. RCVS shares some features (e.g., convexal subarachnoid hemorrhage) with PRES but is typically limited to a solitary sulcus or just a few adjacent sulci. On DSA, RCVS involves large and medium-sized arteries with diffuse, multifocal, segmental narrowing. Small infarcts are often seen on DWI/DTI.

Malignant Hypertension

Terminology and Etiology

Malignant HTN (mHTN), a.k.a. acute hypertensive crisis, is characterized clinically by extreme blood pressure elevation and papilledema. Diastolic levels often exceed 130-140 mm Hg. The abruptness of blood pressure elevation seems to be more important than the absolute level of either systolic or mean arterial blood pressure.

Pathology

Macroscopically, the brain appears swollen and edematous. Gross parenchymal hematomas and perivascular petechial microhemorrhages may be present. Acute microinfarcts, especially in the basal ganglia and pons, are common.

Imaging

Imaging findings in mHTN range from classic PRES to “atypical” features. “Atypical” features are more common in mHTN. Brainstem-dominant hypertensive encephalopathy and basal ganglia &/or watershed lesions are common cerebral manifestations of mHTN.

Lobar &/or multifocal parenchymal microhemorrhages in the cortex, basal ganglia, pons, and cerebellum are common in mHTN and are best seen as “blooming” foci on T2* sequences (GRE, SWI) (37-8). Convexal subarachnoid hemorrhage has been reported in a few cases of mHTN. Contrast images may show striking multifocal patchy enhancement related to widespread blood-brain barrier disruption (37-9).

Chronic Hypertensive Encephalopathy

Although the clinical and imaging manifestations of PRES and mHTN can be dramatic and life threatening, the effects of longstanding untreated or poorly treated HTN on end-organ function can be equally devastating and are far more common.

Pathology

The most consistent histopathologic feature of chronic hypertensive encephalopathy is a microvasculopathy characterized by arteriolosclerosis and lipohyalinosis (see Chapter 10). The microvasculopathy is accompanied by myelin pallor, gliosis, and spongiform WM volume loss. Multiple lacunar infarcts are common.

Clinical Issues

Chronic hypertensive encephalopathy is most common in middle-aged and older adult patients. In addition to age and chronically elevated blood pressure, smoking is an independent risk factor as is metabolic syndrome (impaired glucose metabolism, elevated blood pressure, central obesity, and dyslipidemia).

Imaging

The two cardinal imaging features of chronic hypertensive encephalopathy are (1) diffuse patchy &/or confluent WM lesions and (2) multifocal microbleeds. The WM lesions are concentrated in the corona radiata and deep periventricular WM—especially around the atria of the lateral ventricles. The damaged WM appears hypodense on NECT scans and hyperintense on T2/FLAIR imaging.

Multiple petechial bleeds (“microhemorrhages”) are the second most common manifestation of chronic hypertensive encephalopathy. These are not usually identifiable on NECT and may be invisible on standard MR sequences (FSE T2WI and FLAIR). T2* (GRE, SWI) scans show multiple “blooming” hypointensities (“black dots”) that tend to be concentrated in the basal ganglia and cerebellum (37-10).

Differential Diagnosis

The major differential diagnosis of chronic hypertensive encephalopathy is cerebral amyloid angiopathy (CAA). The WM lesions in both diseases often appear similar, and both disorders can cause hemorrhagic microangiopathy. The microbleeds of CAA are more often peripheral (e.g., cortex, siderosis of the leptomeninges) and rarely affect the brainstem or cerebellum. Hypertensive microhemorrhages are most common in the basal ganglia, pons, and cerebellum.

Cerebral autosomal dominant arteriopathy without subcortical infarcts and leukoencephalopathy (CADASIL) can also mimic chronic hypertensive encephalopathy. CADASIL typically presents in younger patients and causes multiple subcortical lacunar infarcts. Lesions in the anterior temporal lobes and external capsules are classic imaging findings of CADASIL.

Glucose Disorders

Preamble

The brain is a glucose glutton, consuming > 1/2 of the body’s total glucose. Because the brain does not store excess energy as glycogen, CNS function is highly dependent on a steady, continuous supply of blood glucose (see next box).

Blood glucose levels are tightly regulated and are normally maintained within a narrow physiologic range. Disorders of glucose metabolism—both hypo glycemia and hyper glycemia—can injure the CNS.

The neurologic manifestations of deranged glucose metabolism range from mild, reversible focal deficits to SE, coma, and death. Because the clinical and imaging manifestations differ in neonates from those of older children and adults, hypoglycemia in these two age groups is discussed separately.

Pediatric/Adult Hypoglycemic Encephalopathy

Terminology

Hypoglycemia literally means low blood sugar and is caused by an imbalance between glucose supply and glucose utilization. Acute hypoglycemic brain injury is called hypoglycemic encephalopathy.

Etiology

Childhood hypoglycemic encephalopathy is most commonly associated with type 1 diabetes mellitus. In its most common adult setting—advanced type 2 diabetes—hypoglycemia typically results from the interplay between absolute or relative insulin excess and compromised glucose counterregulation; insulin in and of itself is not neurotoxic. Most cases of adult hypoglycemia occur as a side effect of diabetes treatment with insulin and sulfonylureas.

Pathology

Cortical necrosis is the most common gross finding in hypoglycemic encephalopathy. Although the entire cortical ribbon can be affected, the parietooccipital regions are usually the most severely involved (37-11). Other especially vulnerable areas include the basal ganglia, hippocampi, and amygdalae. The thalami, WM, brainstem, and cerebellum are typically spared.

Clinical Issues

The typical hypoglycemic patient is an older diabetic patient on insulin replacement therapy with altered dietary glucose intake. Deliberate or accidental insulin overdose is more common in children and young or middle-aged adults.

Imaging

CT Findings

NECT scans typically show symmetrically hypodense parietal and occipital lobes. The putamina frequently appear hypodense, whereas the thalami are spared (37-12A). In severe cases, diffuse cerebral edema with near-total sulcal effacement and blurred gray matter (GM)-WM interfaces can be seen.

MR Findings

T2/FLAIR hyperintensity in the parietooccipital cortex and basal ganglia is typical of acute hypoglycemic encephalopathy. The thalami, subcortical/deep WM, and cerebellum are generally spared. T2* scans generally show minimal or no “blooming” to suggest hemorrhage. Enhancement on T1 C+ is variable and, when present, usually mild.

DWI scans show restricted diffusion in the affected areas, predominately the posterior parietal and occipital cortex (37-12B). Cytotoxic corpus callosum splenium lesions with restricted diffusion have also been reported in association with hypoglycemia.

Differential Diagnosis

The most important differential diagnosis of hypoglycemic encephalopathy is hypoxic-ischemic encephalopathy (HIE). HIE typically occurs following cardiac arrest or global hypoperfusion. In contrast to hypoglycemic encephalopathy, the thalami and cerebellum are often affected in HIE. Acute cerebral ischemia-infarction is wedge-shaped, involving both the cortex and underlying WM. Acute hypertensive encephalopathy typically affects the parietooccipital cortex but spares most of the underlying WM and rarely restricts on DWI.

Neonatal/Infantile Hypoglycemia

Unlike older children and adults, neonates have lower absolute glucose demands and can utilize other substrates, such as lactate, to produce energy. Nevertheless, prolonged &/or severe hypoglycemia can result in devastating brain injury in newborn infants.

Neonatal/infantile hypoglycemic encephalopathy typically presents in the first three days of life, usually within the first 24 hours, and is most often caused by maternal diabetes with poor glycemic control. Uncontrolled maternal diabetes leads to chronic fetal hyperglycemia in utero . This results in transient neonatal hyperinsulinemia and hypoglycemia of varying severity. Congenital hyperinsulinism (HI) is the most common, most severe cause of persistent hypoglycemia in neonates and children.

MR scans in the acute stages of neonatal hypoglycemic encephalopathy show T2/FLAIR hyperintensity and restricted diffusion in the parietooccipital cortex, subcortical WM, and corpus callosum splenium (37-13).

As with older children and adults, the major differential diagnosis of neonatal hypoglycemic encephalopathy is term hypoxic-ischemic injury (HII). Hypoglycemic encephalopathy and HII often coexist, potentiating the extent of brain injury. Imaging findings in the two disorders may be indistinguishable.

Inherited mitochondrial disorders, such as mitochondrial encephalopathy with lactic acidosis and stroke-like episodes (MELAS), may present with cortical swelling that spares the underlying WM. MELAS is rarely bilaterally symmetric and demonstrates much more markedly elevated lactate on MRS.

Hyperglycemia-Associated Disorders

Hyperglycemia-induced brain injury can be chronic or acute. With the worldwide rise in obesity and the soaring prevalence of diabetes mellitus type 2 (DM2), the effects of chronic hyperglycemia on the brain are increasingly recognized. Patients with DM2 have accelerated arteriolosclerosis and lipohyalinosis with silent infarcts, brain volume loss, and decreased cognitive functioning.

MR in chronic hyperglycemia shows increased numbers of T2/FLAIR subcortical and periventricular hyperintensities, especially in the frontal WM, pons, and cerebellum. DTI demonstrates loss of microstructural integrity with decreased fractional anisotropy. Elevated myoinositol on MRS reflects gliosis, an indicator of brain injury.

Acute hyperglycemic brain injury can manifest as diabetic ketoacidosis (DKA). Imaging is nonspecific with vasogenic cerebral edema the most common abnormality. Hyperglycemic hyperosmolar state with overrapid correction may also develop osmotic demyelination with typical findings of central pontine myelinolysis.

Hyperglycemia-induced hemichorea-hemiballismus (HIHH), a.k.a. delayed-onset diabetic striatopathy, is characterized by involuntary unilateral movements. It is a complication of nonketotic hyperglycemia. MR classically shows T1 shortening in the unilateral basal ganglia with sparing of thalamus (37-14). T2 may show hyperintensity and T2* may show hypointensity in the affected striatum (37-15B). CT may show unilateral basal ganglia hyperdensity (37-15).

Thyroid Disorders

Preamble

Thyroid disorders are relatively common metabolic disturbances that are usually mild and rarely affect brain function. However, several imaging findings—some of them striking—have been associated with thyroid disease. Some can be mistaken for more serious disease (e.g., hypothyroid-induced pituitary hyperplasia mimicking pituitary adenoma), and a few (e.g., Hashimoto encephalopathy) can be life threatening. Hypothyroidism may be congenital or acquired.

Congenital Hypothyroidism

Hypothyroidism is one of the most frequent congenital endocrine disorders. It occurs in 1:2,000-4,000 newborns and is one of the most common preventable causes of intellectual disability. In resource-rich countries, infant screening programs allow early identification of congenital hypothyroidism. If treated within a few weeks of birth, neurodevelopmental outcome is generally normal.

Newborns with congenital hypothyroidism normally have some initial thyroid function related to the maternal T4, which crosses the placenta to the fetus. Congenital hypothyroidism may be caused by thyroid dysgenesis, dyshormonogenesis, or central hypothyroidism (37-16). Maternal factors may cause transient hypothyroidism in preterm infants in areas with endemic iodine deficiency or in families with a goiter history.

Thyroid dysgenesis is the most common cause of congenital hypothyroidism, representing 70-75% of cases. There is failure of normal thyroid gland development, which includes both abnormal gland formation and aberrant descent.

Ectopic thyroid tissue represents 25-50% of cases with thyroid dysgenesis. Ectopia may occur anywhere along the embryonic thyroglossal duct, the path the developing thyroid follows as it descends from the tongue to the infrahyoid neck. Rarely, ectopic thyroid tissue may occur in the substernal region or superior mediastinum (37-17). Hormone production in ectopic thyroids is often low but not absent.

Thyroid agenesis or hypoplasia accounts for 20-50% and causes severe hypothyroidism. Dyshormonogenesis, a.k.a. inborn errors of thyroid hormone biosynthesis, accounts for 5-15% of congenital hypothyroidism. Central hypothyroidism, a.k.a. secondary hypothyroidism related to pituitary or hypothalamic disfunction, causes 10-15% of cases.

Imaging studies of the face and neck demonstrate an ectopic thyroid in up to 50% of congenital hypothyroid cases. Nearly 90% occur at the tongue base as a midline hyperdense mass on NECT (37-18)and a T2-hyperintense mass on MR. Avid enhancement is typical following contrast (37-19). Nuclear medicine studies (Tc-99m pertechnetate or I-123 thyroid scan) are best for diagnosis of agenesis or hypoplasia. In agenesis, there is no focal radiotracer uptake between the base of tongue and upper chest. In hypoplasia/partial agenesis, there is decreased or normal uptake in a small, abnormally shaped gland in a normal location.

Acquired Hypothyroid Disorders

Acquired hypothyroidism is much more common than the congenital variety. Acquired hypothyroidism has two important imaging manifestations: Pituitary hyperplasia and Hashimoto thyroiditis/encephalopathy.

Pituitary Hyperplasia

Physiologically enlarged pituitary glands are common in young menstruating female patients and pregnant/lactating female patients. Non physiologic increase in pituitary volume—pathologic pituitary enlargement—is much less common and typically occurs in response to end-organ failure (37-20).

Both physiologic and nonphysiologic pituitary hyperplasia are discussed in detail in Chapter 30. Most cases of hypothyroid-induced pituitary hyperplasia reverse with thyroid hormone replacement therapy (see Fig. 30-5). Caution: Any prepubescent male patient thought to harbor a “pituitary macroadenoma” on imaging studies should undergo comprehensive endocrine evaluation, as macroadenomas are exceptionally rare in this age group!

Hashimoto Encephalopathy

Hashimoto encephalopathy is a rare but treatable condition typically associated with Hashimoto thyroiditis. Hashimoto encephalitis is also called “steroid-responsive encephalopathy with autoimmune thyroiditis.” It is a well-recognized neurologic complication of autoimmune thyroid disease and is the most common cause of acquired hypothyroidism.

Hashimoto encephalopathy occurs in both children and adults. Psychiatric symptoms (“myxedema madness”) are common. Approximately 50% of patients demonstrate imaging abnormalities. The most typical MR findings are diffuse confluent or focal T2/FLAIR hyperintensities in the subcortical and deep periventricular WM with sparing of the occipital lobes (37-21).

Hyperthyroidism

The most common manifestation of hyperthyroidism in the head and neck is thyroid ophthalmopathy (Graves disease). Brain involvement in hyperthyroidism occurs but is very rare. A few cases of acute idiopathic intracranial HTN (“pseudotumor cerebri”) associated with hyperthyroidism have been reported.

Because of its effect on factor VIII activity, hyperthyroidism has also been reported as an independent risk factor for dural venous sinus thrombosis. Graves disease has been reported as a rare cause of transient corpus callosum splenium hyperintensity and an MS-like multiphasic demyelinating autoimmune syndrome.

Parathyroid and Related Disorders

Preamble

Metabolic abnormalities related to parathyroid hormone (PTH) dysfunction include primary and secondary hyperparathyroidism (HPTH) as well as hypoparathyroidism (HP), pseudohypoparathyroidism (PHP), and pseudo-pseudohypoparathyroidism (PPHP).

Hyperparathyroidism

The parathyroid glands control calcium metabolism by producing PTH. HPTH is the classic disease of bone resorption, so imaging abnormalities may be seen in both the skull and brain. The most common cause of primary HPTH is a parathyroid adenoma, representing 75-85% of cases.

HPTH can be an acquired (common) or inherited disorder (rare). HPTH can also be primary, secondary, or even tertiary. Because of the increasing number of patients on dialysis, the most common type is now secondary HPTH. Sporadic primary HPTH is more common than hereditary. The most important syndromes associated with primary HPTH are multiple endocrine neoplasia (MEN)type 1, MEN type 2A, and familial isolated HPTH. Major features of MEN1include parathyroid tumors (95%), pancreatic neuroendocrine tumor (40%), and pituitary neoplasms (30%). MEN2ais characterized by medullary thyroid carcinoma (99%), pheochromocytoma (50%), and parathyroid tumors (20-30%).

Primary Hyperparathyroidism

Primary HPTH is most common in middle-aged to older adults and relatively rare in children. There is a striking female predominance. Primary HPTH is characterized by hypercalcemia and hypophosphatemia (serum calcium is elevated; serum phosphorus is normal or decreased). HPTH is usually asymptomatic. General signs of symptomatic HPTH have been characterized as “stones, bones, abdominal groans, and psychic moans.”

Bone CT demonstrates diffuse patchy salt and pepper lesions in the skull (37-22). Foci of bone resorption are interspersed with variable patchy sclerosis. The most common findings in the brain are basal ganglia calcifications on NECT. Bilateral symmetric deposits in the globi pallidi, putamen, and caudate nuclei are typical. The thalami, subcortical WM, and dentate nuclei may also be affected (37-23).

MR shows symmetric T1 shortening and T2 hypointensity in the basal ganglia. Mild to moderate “blooming” on T2* (GRE, SWI) sequences is typical. “Brown tumors”—solitary or multiple nonneoplastic lesions in the skull—are common (37-24).

Secondary Hyperparathyroidism

The most common cause of secondary HPTH is chronic renal disease (CRD). The majority of dialysis patients eventually develop secondary HPTH. Other etiologies of secondary HPTH include dietary calcium deficiency, vitamin D disorders, disrupted phosphate metabolism, and hypomagnesemia.

Most patients with secondary HPTH are older than 40 years at the time of initial diagnosis. Serum calcium is normal or low, serum phosphorus is increased, and calcium-phosphate product is elevated. Vitamin D is low, almost always secondary to renal disease rather than dietary deficiency.

A common manifestation of CRD is renal osteodystrophy. Massive thickening of the calvarium and skull base narrows neural and vascular channels. Progressive cranial nerve involvement—most commonly compressive optic neuropathy—and carotid stenosis with ischemic symptoms are typical.

Secondary HPTH primarily affects the skull and dura; the brain parenchyma itself is usually normal. NECT scans show markedly thickened skull and facial bones, a condition sometimes referred to as “uremic leontiasis ossea”or “big head disease”(37-24).

“Brown tumors”can be seen in both primary and secondary HPTH. Fibrous replacement, hemorrhage, and necrosis lead to formation of brownish-appearing cysts. Solitary or multiple “brown tumors” are seen on bone CT as focal, expansile, lytic lesions with nonsclerotic margins. Signal intensity on MR is highly variable, reflecting the age and amount of hemorrhage as well as the presence of fibrous tissue and cyst formation.

The classic intracranial finding in secondary HPTH is unusually extensive, plaque-like dural thickening (37-25). Longstanding CRD can also result in extensive “pipestem” calcifications in the internal and external carotid arteries.

Hypoparathyroid Disorders

Three types of hypoparathyroid disorders are recognized: HP, PHP, and PPHP. All three disorders share common features on brain imaging, although their clinical presentation and laboratory findings vary.

HP is characterized by brain calcifications. The basal ganglia and thalami are the most common sites (37-26) followed by the cerebrum and cerebellum.

PHP is characterized by elevated PTH levels and PTH-resistant hypocalcemia and hyperphosphatemia. Bilateral symmetric calcifications in the basal ganglia and thalami (37-27), cerebellar hemispheres, subcortical WM, and, occasionally, the cerebral cortex are typical findings in both PHP and PPHP. PPHP typically shows no laboratory abnormalities, so calcium and phosphate levels are normal.

PARATHYROID DISORDERS

Hyperparathyroidism

• Primary HPTH (parathyroid adenomas)

 Salt and pepper skull, “brown tumors”

Basal ganglia calcifications

• Secondary HPTH (chronic renal failure)

 Thick skull, face (“big head” disease) ± “brown tumors”

 Plaque-like dural thickening, calcification

Hypoparathyroid Disorders

• 3 types (distinguished by clinical, laboratory findings)

HP

PHP

PPHP

• All have calcifications in basal ganglia > cerebrum, cerebellum

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