KEY FACTS Terminology Acute/subacute/chronic toxic effects of EtOH on CNS Wernicke encephalopathy (WE) Marchifava-Bignami disease (MBD) Imaging EtOH: Disproportionate superior vermian atrophy, enlargement of lateral ventricles, sulci with chronic EtOH WE: Mammillary body, medial thalamus, hypothalamus, periaqueductal gray abnormal signal/enhancement/diffusion restriction MBD: Abnormal signal and later necrosis in corpus callosum Top Differential Diagnoses Nonalcoholic atrophy Demyelination (toxic, acquired/inherited metabolic) Corpus callosal hyperintensity Status epilepticus Drug toxicity…

KEY FACTS Terminology Fahr disease (FD) a.k.a. cerebrovascular ferrocalcinosis, bilateral striopallidodentate calcification Rare degenerative neurological disorder Extensive bilateral basal ganglia (BG) calcifications (Ca++) ± progressive dystonia, parkinsonism, neuropsychiatric manifestations Imaging Bilateral symmetric Ca++ in BG, thalami, dentate nuclei, and cerebral white matter on CT Top Differential Diagnoses Normal (physiologic) Symmetrical BG Ca++ in middle-aged, elderly patients Pathologic BG Ca++ (e.g., endocrinological) Pathology FD is often familial…

KEY FACTS Terminology CNS manifestations related to parathyroid hormone (PTH) metabolic abnormalities Hyperparathyroid (HPTH); hypoparathyroid (HP) Imaging Bilateral symmetric calcifications in globi pallidi, putamen, caudate nuclei Diffuse patchy “salt & pepper” lesions in skull in primary HPTH Plaque-like dural calcification, “pipestem” calcifications of carotid arteries in secondary HPTH Brown tumors: Focal expansile lytic lesions with nonsclerotic margins in primary HPTH and secondary HPTH T2WI: Hypointensity involving…

KEY FACTS Terminology Hashimoto encephalopathy (HE) HE synonym: Steroid-responsive encephalopathy associated with autoimmune thyroiditis Imaging Pituitary hyperplasia (PH): Symmetrical pituitary enlargement that is reversible with thyroid hormone replacement therapy Basal ganglia variably hyperintense (Ca++) HE: Bilateral patchy or confluent subcortical and periventricular white matter T2 hyperintensity with relative sparing of occipital lobes, bilateral and symmetric or unilateral mesial temporal lobe edema Top Differential Diagnoses Pituitary macroadenoma…

KEY FACTS Terminology Adult hypoglycemic encephalopathy Imbalance between glucose supply, utilization → brain injury Hypoglycemia: Sudden decrease in serum glucose level < 50 mg/dL Imaging Stroke/coma in adult diabetic on insulin replacement therapy (IRT) Parietal/temporal/occipital lobes, basal ganglia, ± hippocampi Hyperintensity in parietooccipital cortex and basal ganglia Thalami, subcortical/deep white matter and cerebellum generally spared Restricted diffusion, ↓ ADC (may be transient) MRS shows ↓ NAA,…

Approach to Toxic and Metabolic Disorders Acquired toxic and metabolic disorders of the brain result from a wide variety of agents, including toxic exposures, substance abuse, radiation, and chemotherapy, as well as metabolic alterations, including hypertension, hepatic failure, hypoglycemia, and osmotic demyelination. The vast majority of toxic and metabolic disorders of the brain involve the deep gray nuclei (basal ganglia and thalamus) or the cerebral white…

KEY FACTS Terminology Wilson disease is also known as hepatolenticular degeneration Autosomal recessive disorder of copper metabolism Abnormal accumulation of copper in various tissues Particularly in liver, basal ganglia (BG), midbrain Imaging Usually normal MR in presymptomatic patients T1WI: Normal or BG hyperintensity (similar to chronic hepatic encephalopathy) T2/FLAIR: Symmetric hyperintensity in putamina (with hyperintense peripheral putaminal rim), caudate nuclei, ventrolateral thalami Characteristic face of giant…

KEY FACTS Terminology Autosomal dominant neurodegenerative disease Loss of GABAergic neurons of basal ganglia (BG) Imaging Diffuse cerebral atrophy Caudate nucleus (CN) atrophy → frontal horns enlarged ↑ “Bicaudate” ratio (BCR) or Evans ratio Intercaudate distance divided by distance between inner tables of skull BCR = 0.18 in Huntington disease (HD) vs. 0.09 controls Most specific & sensitive anatomic measure for HD Hyperintense signal in CN,…

KEY FACTS Terminology Pantothenate kinase-associated neurodegeneration (PKAN) Most common form of neurodegeneration with brain iron accumulation (NBIA) Mutated pantothenate kinase 2 gene ( PANK2 ) Formerly known as Hallovorden-Spatz disease Imaging Best diagnostic clue Highly suggestive of PKAN is eye-of-the-tiger sign – Diffuse pallidal T2 hypointensity with medial foci ↑ T2 signal Top Differential Diagnoses Disorders with ↑ T2 signal globus pallidus Metabolic – Methylmalonic acidemia,…

KEY FACTS Terminology Group of neurodegenerative disorders characterized by dystonia, parkinsonism, and spasticity Caused by mutations in L-ferritin gene FTL All characterized by abnormal Fe accumulation in basal ganglia – Lewy bodies, axonal swellings, hyperphosphorylated tau in some subtypes Includes (among others) – Pantothenate kinase-associated neurodegeneration (PKAN) – Infantile neuroaxonal dystrophy (INAD) – Aceruloplasminemia Imaging Globus pallidus (GP) T2 hypointensity with central hyperintensity of GP: Eye…

KEY FACTS Terminology Rare inherited leukoencephalopathy characterized by Rosenthal fibers (eosinophilic intracytoplasmic inclusions) 3 clinical forms Infantile (most common) Juvenile Adult Imaging Infantile: Symmetric ↑ T2 bifrontal white matter (WM) including subcortical U fibers Juvenile/adult: ↑ T2 brainstem (especially medulla), cerebellum, cervical cord Other findings: ↓ T2, ↑ T1 enhancing nodular periventricular rim 1 of few metabolic disorders that enhance Top Differential Diagnoses Canavan disease Megaloencephalic…

KEY FACTS Terminology Progressive autosomal-recessive spongiform leukodystrophy a.k.a. spongy degeneration of infancy Aspartoacyclase deficiency (autosomal recessive) Imaging White matter Involves subcortical U fibers Spares internal capsule and corpus callosum Gray matter Thalami, globi pallidi (GP), ± dentate nuclei Spares caudate, putamen ↑ T2 + DWI signal, normal to ↓ apparent diffusion coefficient in involved areas MRS shows ↑ NAA/Cr, ↓Ch/Cr Top Differential Diagnoses Maple syrup urine…

KEY FACTS Terminology Abbreviations X-linked adrenoleukodystrophy (X-ALD) Classic childhood ALD (CCALD) Inherited peroxisomal disorder ABCD1 mutation → impaired β-oxidation of very-long-chain fatty acids (VLCFAs) Accumulation of VLCFAs in white matter causes severe inflammatory demyelination Several clinical forms of ALD and related disorders Classic X-ALD – Severe form almost exclusively in boys 5-12 years old At least 6 variants other than classic childhood X-ALD – Presymptomatic X-ALD,…

KEY FACTS Terminology Fabry disease (FD) Imaging NECT Ca++ in lateral pulvinar, globus pallidus, putamen, substantia nigra, dentate nuclei MR may show earlier changes ↑ T1 signal in deep gray nuclei T1 lateral pulvinar hyperintensity considered pathognomonic of FD T2/FLAIR hyperintensities in periventricular white matter, deep gray matter Top Differential Diagnoses Endocrinologic disorders Hyperparathyroidism, hypoparathyroidism, pseudohypoparathyroidism, hypothyroidism HIV-associated mineralizing calcific microangiopathy Fahr disease Pathology X-linked disorder…

KEY FACTS Terminology Lysosomal storage disorder Caused by ↓ arylsulfatase A Results in CNS, PNS demyelination 3 clinical forms Late infantile (most common), juvenile, adult Imaging Best diagnostic clue: Confluent butterfly-shaped ↑ T2 signal in deep cerebral hemispheric white matter (WM) Early: Spares subcortical U fibers – Corpus callosum splenium, parietooccipital WM initially – Rapid centrifugal spread to frontal, temporal WM Late: Involves subcortical U fibers…

KEY FACTS Terminology Mucopolysaccharidoses (MPS): 1-9 Group of lysosomal storage disorders Characterized by inability to break down glycosaminoglycans (GAGs) Undegraded GAGs toxic, accumulate in multiple organs Each type of MPS causes accumulation of particular GAG in lysosomes, extracellular matrix 11 known enzyme deficiencies, resulting in 7 distinct forms of MPS – Prototype MPS = MPS 1H (Hurler) Imaging Perivascular spaces (PVS) dilated by accumulated GAG Favored…

KEY FACTS Terminology Clinical phenotypes associated with single large-scale mtDNA deletions (SLSMDs) Kearns-Sayre syndrome (KSS) Chronic progressive external ophthalmoplegia Pearson syndrome – Multisystem disorder characterized by bone marrow failure, pancreatic insufficiency – Children who survive develop KSS later in life SLSMDs often exhibit overlapping disease spectrum Most common non-CNS disease; anemia, renal impairment, endocrine disturbance Imaging Can be normal (especially early in disease) Diffuse symmetric Ca++…

KEY FACTS Terminology M itochondrial myopathy, e ncephalopathy, l actic a cidosis, and s troke-like episodes (MELAS) Inherited disorder of intracellular energy production caused by point mutation in mtDNA Imaging Stroke-like cortical lesions crossing vascular territories Posterior location most common “Shifting spread” (appearance, disappearance, reappearance elsewhere) is classic Lactate “doublet” at 1.3 ppm in 60-65% Elevated lactate in cerebrospinal fluid, “normal” brain on MRS Basal ganglia…

KEY FACTS Terminology a.k.a. subacute necrotizing encephalomyelopathy Genetically heterogeneous mitochondrial disorder characterized by progressive neurodegeneration Imaging Best imaging: MR with DWI/MRS Bilateral, symmetric ↑ T2/FLAIR corpora striata (putamen > caudate) > globi pallidi, periaqueductal gray matter, substantia nigra/subthalamic nuclei, dorsal pons, cerebellar nuclei Reduced diffusion in regions of acute disease Lactate peak often present on MRS; may be large Uncommon appearance: Predominant white matter disease (simulates…

Overview Inherited metabolic disorders (IMD) are very difficult to diagnose. Affected patients can present at any age; symptoms vary depending on age of onset and severity of the biochemical defect. Completely different parts of the brain may be involved in less severely affected patients compared with more severely affected patients. The same enzyme may perform different functions, in different parts of the brain, as the person…