PFBC also demonstrates calcification in other locations, such as the thalami, dentate nuclei, and cerebral and cerebellar WM.

Parathyroid disorders (i.e., hyperparathyroidism, hypoparathyroidism, pseudohypoparathyroidism, and pseudopseudohypoparathyroidism) can all have calcification in a distribution similar to that of PFBC. In cases with severe hypocalcemia, acquired dystrophic brain calcifications can be so extensive that they mimic the appearance and distribution seen in PFBC. Serum calcium, phosphorus, and PTH levels are normal in PFBC and pseudo-pseudohypoparathyroidism.

Mineralizing microangiopathy is a late complication of radiation-induced brain injury. Some cases exhibit extensive symmetric cerebral calcifications with striopallidodentate, occipital, cerebellar, and U-fiber involvement that mimic PFBC.

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Seizures and Related Disorders

Seizures can be precipitated by many infective, metabolic, toxic, developmental, neoplastic, or degenerative conditions and can affect numerous different areas of the brain. Because the temporal lobe is the most commonly affected site, we begin this section with a brief review of its normal gross and imaging anatomy. Special attention is given to the hippocampus as the site involved in mesial temporal sclerosis, an important imaging diagnosis.

We next consider the imaging manifestations of seizure activity. Two classic disorders represent the effects of chronic repeated seizures (mesial temporal sclerosis) and prolonged acute seizure activity (status epilepticus) on the brain.

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We then discuss a newly described abnormality that can be seen with seizures (as well as a variety of other disorders), the "transient lesion of the corpus callosum splenium." The section concludes with a consideration of imaging findings in transient global amnesia, which specifically affects the hippocampus.

Normal Anatomy of the Temporal

Lobe

Here, we briefly review general anatomy of the temporal lobe before focusing in greater detail on the hippocampus.

Gross Anatomy

Temporal Lobe. The temporal lobe lies inferior to the sylvian fissure. Its lateral surface presents three gyri: the superior temporal gyrus (contains the primary auditory cortex), the middle temporal gyrus (connects with auditory,

somatosensory, visual association pathways), and the inferior temporal gyrus (contains the higher visual association area).

The temporal lobe also contains major subdivisions of the limbic system (32-37). The parahippocampal gyrus lies on the medial surface of the temporal lobe and merges into the uncus (32-38).

Hippocampus. The human hippocampus is a phylogenetically older part of the brain that plays a key role in memory. It can be affected by many common neurologic disorders, including acute ischemic stroke, transient global amnesia, epilepsy, and encephalitis.

The hippocampus is part of the limbic system, three nested C- shaped arches that surround the diencephalon and basal ganglia (32-37). The hippocampus proper is part of the middle arch, which extends from the temporal to the frontal lobes.

(32-41) Coronal graphic depicts typical mesial temporal sclerosis. The right hippocampus is atrophied and sclerotic with loss of normal internal architecture. The right temporal horn is enlarged, and the ipsilateral fornix is small.

The hippocampus lies on the medial aspect of the temporal horn and bulges into its floor. The hippocampus has three anatomic segments: the head (pes hippocampus, the digitated anterior part), the body (cylindrical), and a posterior tail that narrows and curves around the corpus callosum splenium (32-37).

On coronal sections through the body, the hippocampus is composed of two interlocking U-shaped layers of gray matter: the Ammon horn and the dentate gyrus. The Ammon horn—the hippocampus proper—forms the more superolateral, upside-down "U," while the dentate gyrus forms the inferomedial "U" (32-39).

The Ammon horn is subdivided into four zones based on width, cell size, and cell density. These zones are designated as CA1, CA2, CA3, and CA4. CA1 (also known as the Sommer sector) is the lateral, outermost zone and consists of small pyramidal cells that are especially vulnerable to anoxia. CA2 curves superomedially from CA1 and consists of a narrow band of cells that are relatively resistant to anoxia. CA3 is a wide loose band that merges into CA4, the innermost zone. CA4 is enveloped by the dentate gyrus.

Imaging Anatomy

The superior, middle, and inferior temporal gyri are best seen on sagittal MR scans.

The hippocampus is best depicted on coronal MR scans performed perpendicular to the long axis of the hippocampus. Thin-section true IR (or 3D T1 SPGR), high-resolution T2WI, and coronal whole-brain FLAIR scans are recommended.

Coronal scans show the hippocampus as a seahorse-shaped structure immediately below the choroid fissure and temporal

(32-42) Coronal T2WI in a 27y man with history of intractable epilepsy and remote closed head trauma shows temporal lobe encephalomalacia . The shrunken, hyperintense right hippocampus is consistent with MTS.

horn of the lateral ventricle (32-40). The parahippocampal gyrus is separated from the dentate gyrus by the hippocampal sulcus. The collateral sulcus is an important landmark that lies just inferolateral to the parahippocampal gyrus.

Mesial Temporal (Hippocampal)

Sclerosis

Temporal lobe epilepsy (TLE) is the most common form of partial complex epilepsy and can occur with or without mesial temporal sclerosis.

Terminology

Mesial temporal sclerosis (MTS), also known as hippocampal sclerosis (HS) is the most common overall localization-related form of epilepsy (32-41). Its most common manifestation is complex partial seizures.

Etiology

A variety of events such as trauma or infection may precipitate intractable complex partial seizures (32-42). The end result is MTS. Although the precise pathophysiology of how and why MTS develops is unclear, inflammatory processes or prolonged seizures with hippocampal hypoxic-ischemic injury are considered the most likely candidates.

Pathology

MTS is characterized grossly by atrophy of the hippocampus and adjacent structures (32-41). The hippocampal body (8590%) is the most commonly affected site, followed by the tail (60%) and head (50%). Approximately 15-20% of cases are bilateral but usually asymmetric.

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The CA1 and CA4 areas are the most susceptible to hypoxicischemic damage, but all regions of the hippocampus can be affected. Neuronal loss with chronic astrogliosis is the typical histologic finding.

Clinical Issues

Epidemiology. Nearly 10% of all individuals experience a seizure in their lifetime. Two-thirds of these are nonrecurrent febrile/nonfebrile seizures. Peak prevalence is bimodal (< 1 year and > 55 years of age). One-third of patients develop repeated seizures ("epilepsy").

Approximately 20% of patients with epilepsy have complex partial seizures. Of these, 35-50% are pharmacoresistant and are refractory to anticonvulsant therapy. Current estimates based on a USA population of 325 million indicate that as many as 143,000-191,000 patients suffer from drug-resistant HS-TLE.

MTS is one of the most common types of localization-related epilepsy and accounts for the majority of patients undergoing temporal lobectomy for seizure disorder.

Demographics. MTS is a disease of older children and young adults. There is no sex predominance.

Presentation. Most patients with MTS present with complex partial seizures lasting 1-2 minutes. Preceding "auras" with fear, anxiety, and associated autonomic symptoms are common.

Treatment Options. Anteromedial temporal lobectomy is the most common treatment for MTS with drug-resistant TLE and is successful in reducing or eliminating seizures in 70-90% of patients.

Imaging

MR Findings. Imaging markers of MTS are found in 60-70% of patients with TLE. True coronal IR or 3D SPGR sequences show a shrunken hippocampus with atrophy of the ipsilateral fornix and widening of the adjacent temporal horn and/or choroid fissure (32-43). Abnormal T2/FLAIR hyperintensity with obscuration of the internal hippocampal architecture is typical (32-42). MTS typically does not enhance following contrast administration.

DWI shows increased diffusivity on ADC and hyperintensity on DWI (T2 "shine-through"). The spectroscopic hallmark of TLE is reduced NAA in the epileptogenic focus, presumably secondary to neuronal loss. Cho and Cr are typically unchanged. In MTS, NAA is reduced—and not just in the hippocampus.

Widespread alterations in extrahippocampal and even extratemporal regions can be demonstrated in MTS. Highresolution DTI shows evidence of diffusion abnormalities of the ipsilateral fimbria-fornix, parahippocampal WM bundle, and the uncinate fasciculus and is helpful in predicting postoperative seizure outcome. Resting-state fMR demonstrates that the inferior cingulum bundle undergoes degeneration in tandem with ipsilateral hippocampal volume loss.

Nuclear Medicine Findings. FDG PET is one of the most sensitive imaging procedures for diagnosing MTS. Temporal lobe hypometabolism is the typical finding (32-43). SPECT shows hyperperfusion in the epileptogenic zone during seizure activity; hypoperfusion in the interictal period is common.

Angiography. In the past, most patients with intractable TLE who were candidates for temporal lobe resection underwent a Wada test (intracarotid amobarbital test) to evaluate language lateralization and assess risk for postoperative memory disorders. With new noninvasive techniques such as resting fMR mapping, the utilization of Wada testing is declining precipitously. It is no longer used in many epilepsy centers.

Differential Diagnosis

The major differential diagnosis of MTS is status epilepticus. Status epilepticus can be subclinical and may cause transient gyral edema with T2/FLAIR hyperintensity and/or enhancement in the affected cortex as well as the hippocampus.

A low-grade glioma (WHO grade II astrocytoma, oligodendroglioma, or oligoastrocytoma) in the temporal lobe can cause drug-resistant TLE. Gliomas are usually T2/FLAIR hyperintense and cause mass effect, not volume loss. Cortically based neoplasms associated with TLE include dysembryoplastic neuroepithelial tumor (DNET). DNET typically is a well-demarcated, "bubbly" mass that is often associated with adjacent cortical dysplasia. Cortical dysplasia is isointense with GM but frequently causes T2 hyperintensity in the underlying temporal lobe WM.

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Cystic-appearing lesions in the temporal lobe that are hyperintense on T2WI include prominent perivascular spaces, hippocampal sulcus remnants, and choroid fissure cysts. These "leave me alone" lesions all behave like CSF and suppress on FLAIR.

Status Epilepticus

Terminology

Status epilepticus (SE) is a prolonged (more than 30 minutes), continuously active seizure with EEG-demonstrated seizure activity. Two or more seizures without full recovery between the events is also considered SE. SE can be focal or generalized; generalized convulsive SE is potentially lifethreatening if not controlled.

Etiology

Prolonged ictal activity induces hypermetabolism with increased glucose utilization. Perfusion increases but is still insufficient to match glucose demand. The result is compromised cellular energy production, cytotoxic cell swelling, and vasogenic edema. With prolonged severe seizure activity, the blood-brain barrier may become permeable, permitting leakage of fluid and macromolecules into the extracellular spaces.

Pathology

Transient vasogenic and/or cytotoxic edema causes cortical swelling that typically spares the underlying WM.

Imaging

General Features. Imaging findings in SE vary with acuity and severity. Most acute periictal abnormalities are reversible and normalize within a few days. Irreversible changes do occur, especially with generalized convulsive SE.

CT Findings. Initial NECT scans may be normal or show gyral swelling with sulcal effacement and parenchymal hypodensity. CECT may demonstrate gyral enhancement in a nonvascular distribution.

MR Findings. Periictal MR shows T2/FLAIR hyperintensity with gyral swelling (32-44). The subcortical and deep WM is relatively spared. Crossed cerebellar diaschisis, ipsilateral thalamic involvement, and basal ganglia lesions are seen in some cases.

Gyriform enhancement on T1 C+ varies from none to striking. Diffusion restriction with unior bilateral hippocampal, thalamic, and cortical lesions is common (32-45) (32-46). Ictal DWI and pMR demonstrating hyperperfusion can be especially useful in the diagnosis of nonconvulsive SE.

Scans performed a week to several months following SE may show permanent abnormalities, including focal brain atrophy, cortical laminar necrosis, and mesial temporal sclerosis.

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Differential Diagnosis

The major differential diagnosis of periictal brain swelling is acute cerebral ischemia-infarction. Acute cerebral ischemia occurs in a typical vascular territorial distribution, is wedgeshaped (involving both GM and WM), and is positive on DWI before T2/FLAIR hyperintensity develops. In ongoing SE, DWI and T2 signal changes typically occur simultaneously.

Cerebritis may cause a T2/FLAIR hyperintense mass that restricts on DWI. Cerebritis typically involves the subcortical WM as well as the cortex. Herpes encephalitis is typically preceded by a viral prodrome, affects the limbic system, is frequently bilateral but asymmetric, and often demonstrates petechial hemorrhage.

Acute onset of mitochondrial encephalopathy with lactic acidosis and stroke-like episodes (MELAS) may affect the cortex in a nonvascular distribution. MRS in the noninvolved brain usually demonstrates a lactate peak. Transient global

amnesia causes tiny dot-like foci of restricted diffusion in the lateral hippocampus.

IMAGING IN SEIZURE DISORDERS

Mesial Temporal Sclerosis

•Hippocampal ± fornix volume loss

○80-85% unilateral

•Loss of internal architecture

○T2/FLAIR hyperintensity

○FDG PET hypometabolic

Status Epilepticus

•Gyriform T2/FLAIR hyperintensity, spares WM

•Nonvascular distribution

•May restrict on DWI, exhibit hyperperfusion

•Subacute/chronic effects

○Atrophy, cortical laminar necrosis

○Mesial temporal sclerosis

(32-47) A patient taken off antiseizure medications 3 weeks prior to imaging shows round FLAIR hyperintense lesion in CC splenium (top L) that restricts on DWI (top R). Repeat scan 2 weeks later shows that the lesions have resolved. This is CLCC.

Cytotoxic Lesions of the Corpus

Callosum

Terminology

Cytotoxic lesions of the corpus callosum (CLCCs) are acquired lesions that have been associated with a number of different entities. Because they are (1) often reversible and (2) most common in the corpus callosum splenium, they have also been called transient or reversible splenial lesions.

Pathoetiology

Precisely how and why CLCCs appear and then disappear is unknown. Most investigators believe CLCCs are a cytokinopathy with secondary excitotoxic glutaminergicassociated intracellular edema. The corpus callosum—especially the splenium—has a high density of excitatory amino acid, toxin, and drug receptors and is hence more vulnerable to the development of cytotoxic edema.

Associated Conditions

CLCCs were first identified in patients with epilepsy and were initially considered a seizureand/or drug-related reversible abnormality. The use and subsequent withdrawal of antiepileptic drugs is the most commonly associated condition. CLCCs typically appear between 24 hours and 3 weeks after antiepileptic therapy is discontinued.

The second most common cause of CLCC is infection, usually a viral encephalitis that may also cause a mild febrile encephalopathy (sometimes termed MERS, or mild encephalopathy with reversible splenial lesion). Influenza

(32-48) Series of FLAIR scans in viral encephalitis shows lesionsin pons, peduncles, and cerebellar hemisphere. Corpus callosum splenium lesion restricts on DWI . This is virusassociated CLCC.

virus, rotavirus, measles, human herpesvirus-6, West Nile virus, Epstein-Barr virus, varicella-zoster virus, mumps, and adenoviruses have all been reported with CLCCs as have bacterial meningoencephalitis and malaria.

Metabolic derangements such as hypoglycemia and hypernatremia, acute alcohol poisoning, malnutrition, and vitamin B12 deficiency are the third most common group of CLCC-associated disorders. Eclampsia and hemolytic-uremic syndrome have been reported as rare possible causes.

Miscellaneous reported associations include migraine headache, trauma, high-altitude cerebral edema, systemic lupus erythematosus, internal cerebral vein occlusion, Charcot-Marie-Tooth disease, and neoplasms.

Clinical Issues

CLCCs themselves are usually asymptomatic and discovered incidentally on imaging studies. Variable degrees of encephalopathy reported with CLCCs may be caused by the inciting pathology, not the lesion itself.

Most CLCCs resolve spontaneously and disappear although not all lesions are completely reversible.

Imaging

On imaging studies, typical CLCCs are round to ovoid homogeneous, nonhemorrhagic lesions centered in the corpus callosum splenium. They are mildly hypointense on T1WI, hyperintense on T2/FLAIR, do not enhance, and demonstrate restricted diffusion (32-47) (32-48). A variant type of CLCC that involves the entire corpus callosum splenium and extending into the forceps major has been

termed the "boomerang" sign. Rarely, CLCCs extend anteriorly from the splenium into the corpus callosum body.

CLCCs typically resolve completely within a few days or weeks, and follow-up imaging studies are normal.

CYTOTOXIC LESIONS OF THE CORPUS CALLOSUM

Terminology

• Also called reversible or transient splenial lesions

Pathoetiology

•Cytokinopathy with glutamate-induced intracellular edema

•Associated with

○Seizures

○Drugs (antiepileptic, metronidazole, etc.)

○Infections (often but not invariably viral)

○Metabolic disorders (alcohol, Wernicke, osmotic)

○Neoplasms, chemotherapy

○Trauma

Clinical Features

•Usually asymptomatic, incidental

•Typically (but not invariably) resolves spontaneously

Imaging Findings

•Round, ovoid or "boomerang-shaped" lesion

•Splenium > > > body, central > > eccentric

•T2/FLAIR hyperintense

•Restricts on DWI

•Does not enhance

Transient Global Amnesia

Terminology

Transient global amnesia (TGA) is a unique neurologic disorder characterized by (1) sudden memory loss without other signs of cognitive or neurologic impairment and (2) complete clinical recovery within 24 hours.

As a clinical syndrome, TGA is easily recognized. The patient has isolated transient amnesia with normal consciousness and no other neurologic or cognitive disturbances.

Etiology

The underlying etiology of TGA is unknown. Paroxysmal neuronal discharges or epileptic phenomena (e.g., spreading cortical depression, seizure with delayed neuronal injury), migraine with aura, ischemic stroke or hypoxia, local nonischemic energy failures, and venous congestion have all been proposed as possible pathologic mechanisms.

Clinical Issues

Most TGA patients are between 50 and 70 years; TGA is rare under the age of 40. There is no sex predilection. A typical scenario is a middle-aged patient who suddenly starts forgetting conversations within minutes and tends to repeat the same questions. Isolated anterograde amnesia with preserved alertness, attention, and personal identity are consistent features. EEGs are normal in 80-90% of cases with the remainder showing minor nonepileptiform activity. Symptoms resolve in 24 hours or less.

Recurrences are relatively rare (5-10% per year). Population-based studies have demonstrated that having a TGA episode does not increase the risk of

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(32-49A) Axial FLAIR in a 70y woman with sudden onset of confusion and amnesia is normal.

(32-49B) DWI shows small focus of restricted diffusion in right hippocampus . Symptoms resolved; follow-up scan was normal. This is TGA.

(32-50) DWI in 65y man with sudden anterograde memory loss shows foci of restricted diffusion in both hippocampi . This is TGA.