Neuropathology

慈濟大學 醫學系 台中慈濟醫院 神經內科神經內科 曾啟育 Abstract

• Muscle disease • Peripheral neuropathy •Tumor • Neurodegenerative disease Muscle disease and Muscle biopsy

H & E stain

Modified Gomori trichrome stain Muscle: blue - green

Oxidative enzyme NADH Cytochrome C oxidase (CCO)

Fiber grouping Angulated fiber Nuclear clumps Fiber grouping ATPase Central nuclei, Split fiber Necrotic fiber, Central myocytic necrosis

Spinal muscular atrophy Werdnig - Hoffman Inflammatory

Dermatomyositis Perifascicular atrophy Perivascular inflammatory infiltration Microinfarction, Ischemic focal loss Polymyositis

Dermatomyositis: CD4 lymphocyte Polymyositis: CD8 lymphocyte Inclusion body myositis Rimmed vacuole

Inclusion body myopathy

• deficiency • Duchenne muscular dystrophy • Becker muscular dystrophy

• Limb-girdle muscular dystrophy • • Regional form of Muscular dystrophy • X-link Emery-Dreifuss dystrophy • Facioscapulohumeral muscular dystrophy • Scapuloperoneal muscular dystrophy • Oculopharyngeal muscular dystrophy

• Congenital muscular dystrophy

• Distal muscular dystrophy, Distal myopathy

• Myotonic muscular dystrophy Muscular dystrophy

Immunocytochemistry

Dystrophin – deficiency dystrophy Duchenne muscular dystrophy Becker muscular dystrophy (Gower sign, Pseudohypertrophy, Contracture) Connective tissue, Adipose tissue Pseudohypertrophy Limb-girdle muscular dystrophy

• AD Limb-girdle muscular dystrophy, LMGD type 1 (AD) • LGMD 1A, Myotilin deficiency (Pharyngeal weakness) • LGMD 1B, Lamin A/C deficiency (AD Emery-Dreifuss, Cardiomyopathy) • LGMD 1C, Caveolin-3 deficiency (Myalgia)

• AR Limb-girdle muscular dystrophy, LMGD type 2 (AR) • LGMD 2A, Calpain-3 deficiency • LGMD 2B, Dysferlin deficiency • LGMD 2CDEF, Sarcoglycan deficiency •LGMD 2GHIJL • LGMD 2KMNO, α-Dystroglycanopathy, Congenital muscular dystrophy

• Myofibrillar myopathy, myopathy Limb-girdle muscularvdystrophy (LGMD) Alpha-sacroglycanopathy Muscular dystrophy

• Dystrophin deficiency • Duchenne muscular dystrophy • Becker muscular dystrophy

• Limb-girdle muscular dystrophy • • Regional form of Muscular dystrophy • X-link Emery-Dreifuss dystrophy (Cardica complication) • Facioscapulohumeral muscular dystrophy, AD • (Open lip, Chicken wing, Deltoid preserved) • Scapuloperoneal muscular dystrophy (Facial spared) • Oculopharyngeal muscular dystrophy • (GCG, 40-60 y/o, Ptosis, EOM)

• Congenital muscular dystrophy • Distal muscular dystrophy, Distal myopathy • Myotonic muscular dystrophy Facioscapulohumeral muscular dystrophy

Whorled fiber, Split fiber Pseudoneurogenic change (Angulated fiber) Oculopharyngeal muscular dystrophy (GCG, 40-60 y/o, Ptosis, EOM, Rimmed vacuole) Distal muscular dystrophy, Distal myopathy

• Miyoshi myopathy • (AR, Early adult, Gastrocenemius atrophy, Thin leg) • Welander myopathy • (AD, 40-60 y/o, Hand & drop wrist, Small fiber polyneuropathy) • Udd myopathy • (AD, 35 y/o, Anterior tibialis, Drop foot, Rimmed vacuole) • Markesbery myopathy • (Udd + Cardiomyopathy) • Nonaka myopathy • (AR, Early adult, Hereditary inclusion body myopathy)

Distal myopathy Distal muscular dystrophy Myotonic muscular dystrophy

Striated annulet (Ring fiber) Lateral sarcoplasmic mass Myofibril aggregation Central nucleus

Nemaline myopathy (Z-Disc) (Nucleus) Central core myopathy (Sarcomere) Fiber type disproportion Muscular dystrophy

Fiber type disproportion Channopathy

• Calcium channopathy • Hypokalemic Type 1 • Sodium channopathy • Hyperkalemic periodic paralysis • • Potassium-aggravated • Myotonia fluctuan, Myotonia permanen • Potassium channopathy • Andersen-Tawil syndrome • Chloride channopathy • Metabolic myopathy

• Disorder of carbohydrate metabolism • Myophosphorylase deficiency (McArdle disease), AR • (Exercise intolerance, Painful contracture, Second-wind) • Acid maltase, Alpha-glucosidase deficiency (Pompe disease), AR • (Juvenile, Adult 36.5 y/o, D/D Duchene, LGMD, Polymyositis, Respiratory muscle)

• Disorder of lipid metabolism • Carnitine palmitoyl transferase deficiency, AR • (Myoglobinuria, exercise in fasting)

• Disorder of abnormal nucleotide metabolism Glycogen storage disease

Pompe disease Large empty vacuole Periodic acid – Schiff stain (PAS)

Mitochondrial myopathy

• Myoclonic epilepsy with ragged-red fiber (MERRF) • Mitochondrial encephalopathy, lactic acidosis, stroke-like episode (MELAS) • Kearn-Sayer syndrome (KSS) • Progressive external ophthalmoplegia (PEO) Mitochondria disease

Ragged red fiber (Gomori trichrome stain) COX negative fiber (Cytochrome oxidase)

Hereditary Neuropathy

• Charcot-Marie-Tooth Disease, CMT • Hereditary motor and sensory neuropathy

• Hereditary neuropathy with liability to pressure palsy, HNPP •

• Hereditary sensory and autonomic neuropathy

• Familial amyloid polyneuropathy

• Porphyric neuropathy • Fabry disease • Leukodystrophy with neuropathy • with neuropathy • Refsum disease, Phytanic acid storage disease • Tangier disease • Abetalipoproteinemia, Bassen-Kornzweig syndrome Charcot-Marie-Tooth Disease, CMT Hereditary motor and sensory neuropathy

CMT1: Demyelinating form, AD CMT1A: PMP22 CMT1B: myelin protein zero, MPZ CMT2: Axonal form, AD CMT2A1: weakness, atrophy CMT2A2: optic neuropathy CMT2B: sensory loss (HSN) CMT2C: phargngeal, laryngeal, respiratory CMT2D: hand CMT2E: giant axon CMT2F: late onset, 35-60 y/o CMT3: Dejerine-Sottas syndrome, DSS, AR CMT4: hypomyelination, dysmyelination, AR X-link CMT: CNS white matter, metabolic stress , connexin 32, Cx32

Neuropathy Wallerian degeneration, Dysmyelination Hereditary neuropathy with liability to pressure palsy HNPP, PMP 22, AD Tomaculous neuropathy Congo red Tumor of Nervous System

Astrocytic tumor Oligodendroglial tumor Ependymal tumor Choroid plexus tumor Neuroblastic tumor: Medulloblastoma

Schwannoma Neurofibroma

Meningioma Hemangiopericytoma Hemangioblastoma Astrocytoma: Rosenthal fiber Oligodendroglioma: Microcalcification Astrocytoma

Astrocytoma GFAP: Glial fibrillary acidic protein Ki-67/MIB-1 labeling index (cellular proliferation)

Fibrillary astrocytoma Protoplasmic astrocytoma Pilocystic astrocytoma Anaplastic astrocytoma Subependymal giant cell astrocytoma Glioblastoma multiform, GBM Fibrillary astrocytoma Protoplasmic astrocytoma Pilocystic astrocytoma Subependymal giant cell astrocytoma Anaplastic astrocytoma Glioblastoma multiform, GBM Oligodendroglioma Microcalcification Microvascular proliferation Ependymoma: Perivascular pseudorosettes Choroid plexus papilloma: Elongated papillae Schwannoma (Neurilemmoma)

Antoni A Dense fibrillary tissue Palisading cell

Antoni B Loose reticulated tissue vaculated cell Neurofibroma Meningioma: Whorls, Psammoma body (-associated protein Tau) Alzheimer disease Progressive supranuclear palsy, PSP Corticobasal ganglion degeneration, CBGD Pick disease

Synucleinopathy (Synaptic-associated α-synuclein) Parkinson disease Lewy body dementia Multiple system atrophy

Polyglutamine disease Spinocerebellar atrophy, SCA Huntington disease Neurofibrillary tangle Neurofibrillary tangle Alzheimer plaque Pick disease Progressive supranuclear palsy, PSP Corticobasal ganglion degeneration, CBGD Alpha-synuclein Multiple system atrophy Alpha-synuclein Lewy body dementia Lewy body

CJD Florid plaque

Lafora body, Periodic acid Schiff stain Amyloid angiopathy Niemann – Pick disease: Foamy cell Tay – Sachs disease Mucopolysaccharidosis: Zebra body

感恩