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…

KEY FACTS Terminology C hronic l ymphocytic i nflammation with p ontine p erivascular e nhancement r esponsive to s teroids (CLIPPERS) Predominantly involving brainstem, adjacent rhombencephalic structures Shows clinical, imaging response to glucocorticosteroids Imaging Location: Predominately pons May extend into cerebellar peduncles, hemispheres Caudally into medulla, spinal cord Rostrally into midbrain MR Classic: Enhancing punctate/curvilinear lesions; pons often appears “peppered”; may exhibit subtle radiating pattern…

KEY FACTS Terminology Autoimmune-mediated white matter (WM) demyelination of brain &/or spinal cord, usually with remyelination Imaging Best diagnostic clue: Multifocal WM and deep gray lesions days to weeks following infection/vaccination May involve both brain and spinal cord; WM > gray matter, but usually both affected Deep/juxtacortical WM > periventricular WM Both supratentorial and infratentorial lesions Multifocal punctate to large flocculent FLAIR hyperintensities Do not usually…

KEY FACTS Terminology Synonyms: Devic disease, optic-spinal multiple sclerosis Definition: Autoimmune inflammatory disorder involving myelin of neurons of optic nerves and spinal cord, with limited brain parenchymal involvement Imaging Longitudinally extensive (> 3 vertebral segments) T2 hyperintensity within cord + enhancement of optic nerves (85% of cases) T2 abnormality tends to involve entire cross section of cord, unlike more focal involvement of MS Top Differential Diagnoses…

KEY FACTS Imaging Multiple perpendicular callososeptal T2 hyperintensities characteristic of multiple sclerosis (MS) Perivenular extension: “Dawson fingers” Bilateral, asymmetric linear/ovoid FLAIR hyperintensities > 85% periventricular/perivenular 50-90% callososeptal interface May also commonly involve subcortical U fibers, brachium pontis, brainstem, spinal cord common Transient enhancement during active demyelination > 90% disappear within 6 months Rare: Large tumefactive enhancing rings T1: Hypointense lesions suggest worse prognosis Correlate with disability,…

KEY FACTS Terminology HIV/AIDS-related opportunistic infections and neoplasms Imaging Findings Primary CNS lymphoma: Enhancing lesions, often hemorrhagic/necrotic within basal ganglia, periventricular white matter Kaposi sarcoma: Intense enhancing soft tissue mass in scalp Bacterial abscesses: Ring-enhancing lesion with ↑ signal on DWI Aspergillosis: Multiple ring-enhancing lesions Neurosyphilis: Cortical/subcortical infarcts, granulomas, leptomeningeal enhancement Benign lymphoepithelial lesions of HIV: Multiple cystic masses enlarging both parotid glands MR is most…

KEY FACTS Terminology I mmune R econstitution I nflammatory S yndrome (IRIS) Atypical/worsening opportunistic infection HIV/AIDS patients following commencement of HAART Patients with MS, immunomodulatory therapy Imaging Progressive multifocal leukoencephalopathy (PML)-IRIS White matter (WM) hypodensities with ↑ mass Patchy atypical enhancement TB-IRIS ↑ leptomeningeal enhancement ↑ size of ring-/nodular-enhancing tuberculomas Crypto-IRIS ↑ nodular meningeal/subependymal enhancement ↑ in size of “gelatinous” pseudocysts Top Differential Diagnoses Diffuse/patchy WM…

KEY FACTS Terminology Progressive multifocal leukoencephalopathy (PML) Subacute opportunistic infection caused by DNA virus JC polyomavirus (JCV) JCV infects oligodendrocytes, causes demyelination in immunocompromised patients Associated with immunosuppression, often AIDS Organ transplant, cancer, chemotherapy, myeloproliferative disease, and steroid treatment Reported in treatment for multiple sclerosis and in rheumatic diseases Imaging Multifocal T2-hyperintense demyelinating plaques involve subcortical white matter (WM), extend to deep WM; gray matter often…

KEY FACTS Terminology Cryptococcus neoformans infection Opportunistic fungal infection that typically affects HIV and other immunosuppressed patients Cryptococci spread along perivascular spaces (PVS) to deep brain: Basal ganglia, thalamus, brainstem, cerebellum, dentate nucleus, periventricular WM Imaging Dilated PVS in deep gray nuclei of AIDS patient, often no enhancement Degree of enhancement depends on cell-mediated immunity of host May see miliary or leptomeningeal enhancing nodules + gelatinous…

KEY FACTS Terminology Coccidioidomycosis, histoplasmosis (sporadic, common) Blastomycosis (rare, sporadic, generally lungs/skin) Invasive fungal infection (immunocompromised) Candidiasis (common) Aspergillus, mucormycosis (angioinvasive) Imaging Varies with type, site of infection, immune status MR ± contrast (add T2* for hemorrhage) Invasive fungal sinusitis Most common in immunocompromised patient Aspergillus, mucormycosis most common Bone CT shows sinus/orbit/skull base involvement Look for occluded carotid, thrombosed cavernous sinus Meningitis Most common presentation…

KEY FACTS Terminology Acquired CNS cytomegalovirus (CMV) infections: Meningitis, encephalitis, ventriculitis, transverse myelitis, radiculomyelitis, chorioretinitis Immunocompromised (AIDS, organ transplant) patients are at risk → reactivation of previously silent infection Imaging Best diagnostic clue: Ventriculitis with fluid-debris level and ependymal enhancement in immunocompromised patient Encephalitis: Ill-defined T2-hyperintense area, variable enhancement May mimic HIV encephalitis with patchy nonspecific T2-hyperintense lesions Contrast should be used for imaging of all…

KEY FACTS Terminology Opportunistic infection Caused by parasite Toxoplasma gondii Most common opportunistic CNS infection in AIDS Imaging CT Ill-defined, hypodense lesions and edema Basal ganglia, thalamus, cerebellum Rim, nodular, target enhancement MR T2 hypointense T1 C+ target sign highly suggestive Thallium-201 SPECT and 18F-FDG PET: Toxoplasmosis lesions are hypometabolic Top Differential Diagnoses Lymphoma Solitary mass in patient with HIV/AIDS? Lymphoma > toxoplasmosis Lymphoma often restricts…

KEY FACTS Terminology HIV-1 encephalitis/HIV-1 encephalopathy HIV-associated neurocognitive disorders Imaging CT Atrophy Bilateral periventricular/diffuse WM hypointensities Basal ganglia, cerebellum, brainstem hypodensity MR Diffuse “hazy” hyperintense WM on T2/FLAIR Nonenhancing (if enhancement present, consider opportunistic infections, immune reconstitution inflammatory syndrome) Pathology HIV has ability to cause neurologic disease Does not replicate within neural/glial cells Microglial nodules with multinucleated giant cells WM pallor early, neocortical infection/atrophy late Clinical…

KEY FACTS Terminology Lyme disease, Lyme neuroborreliosis (LNB) Multisystem inflammatory disease Caused by spirochete Borrelia burgdorferi (USA) Transmitted by Ixodes tick bite Reservoirs = white tail deer/field mouse Imaging MS-like white matter (WM) lesions (may enhance) 2-8 mm (large “tumefactive” lesions rare) ± multiple enhancing cranial nerves ± cauda equina, meningeal enhancement Top Differential Diagnoses Demyelinating disease Vasculitis Sarcoidosis Bell's palsy (solitary CN 7 enhancement) Chronic…

KEY FACTS Terminology Intracranial parasitic infection caused by pork tapeworm Taenia solium 4 pathologic stages: Vesicular, colloidal vesicular, granular nodular, and nodular calcified Imaging Best diagnostic clue: Cyst with “dot” inside Convexity subarachnoid spaces most common location Inflammatory response around cyst may seal sulcus, making lesions appear intraaxial May involve cisterns > parenchyma > ventricles Intraventricular cysts are often isolated Basal cistern cysts may be racemose…

KEY FACTS Terminology Typically causes tuberculous meningitis &/or localized CNS infection, tuberculoma Imaging Basilar meningitis + extracerebral TB (pulmonary) Meningitis + parenchymal lesions highly suggestive Tuberculomas Supratentorial parenchyma most common Usually T2 hypointense Enhances strongly (solid or ring enhancing) Tuberculous abscess: Multiloculated ring enhancement MR with FLAIR, DWI, T1 C+, ± MRA, MRS TB abscess has prominent lipid, lactate but no amino acid resonances Top Differential…