Neuropathy& myopathy

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  • LONGITUDINAL H&E section of a peripheral myelinated nerve
  • TRANSVERSE H&E section of a peripheral myelinated nerve
  • SILVER STAIN showing black axons surrounded by washed out fat (myelin)
  • MYELIN stain showing the REVERSE of the previous slide
  • Medium sized nerve, transverse section, showing a finite number of myelinated axons and schwann cells
  • How many axons are in this nerve section? Perhaps around 20?
  • Classical neurovascular “triad”: Artery, Vein, Nerve
  • Smaller neurovascular triad, or “bundle”. How many axons are in this small nerve? Perhaps 5-8?
  • The more longitudinally a nerve happens to be sectioned, the more “wavy” it appears.
  • Electron microscope section, peripheral nerve. How many axons are myelinated? Perhaps about 7?
  • Please differentiate between microtubules (small circles) and neurofilaments (dots). Find the schwann cell nucleus, find an UNmyelinated axon, find a mitochondrion.
  • Note that the myelin “layering” has to start (INNER mesaxon) and end (OUTER mesaxon) somewhere!
  • It looks like one micrometer (micron) would span about 60 layers of myelin? True or false?
  • Slam dunk classical appearance of skeletal muscle. Why is skeletal muscle or voluntary striated muscle a better name for this than just striated muscle?
  • Is the peripheral nature of skeletal muscle nuclei more apparent from cross or longitudinal sections? Ans: Cross Why? Ans: Simple geometry! Are striations better seen on cross or longitudinal sections? Ans: Longitudinal Why? Ans: Simple geometry again!
  • EM, skeletal muscle, the sarcomere, like America, extends from “Z” to shining “Z”! Find glycogen. Find Mitochondria.
  • Find the sarcoplasmic reticulum, which is the endoplasmic reticulum of skeletal muscle. Find MYOSIN filaments, find ACTIN.
  • These are NONSPECIFIC reactions of nerve and skeletal muscle to injury
  • Extremely important concepts of nerve demyelinization, axonal damage, and regeneration
  • Muscle fiber necrosis
  • Muscle fiber vacuolization
  • Muscle fiber hypertrophy/atrophy. Certain fiber hypertrophy to make up for the loss of atrophic fibers
  • Why is auto-amputation common in severe leprosy? Ans: Nerve destructioon
  • CMT is a very HETEROGENEOUS group of hereditary diseases involved with defective myelination, e.g., CMT1, CMT2, CMT3, CMT4, X-linked CMT
  • Peroneal muscle involvement and HIGH arching is common in CMT.
  • BOTH demyelination AND a direct TOXIC effect to peripheral nerves are seen in diabetes, which is the MOST COMMON cause of neuropathy
  • Morton’s Neuromas most commonly occur in the 3 rd common digital branch of the MEDIAL plantar nerve, i.e., 3 rd and 4 th toe at the distal metatarsal level.
  • Schwannoma
  • Hypertrophy/Atrophy scenario
  • What is myotonia?
  • Dystrophin, an intracellular protein, forms an interface between the cytoskeletal proteins and a group of transmembrane proteins
  • Note again the atrophy/hypertrophy scenario
  • Half of dermatomyositis patients also have cancer, many are young adults and therefore there is a juvenile variant. Note the eyelid appearance and eyelid edema.
  • No skin changes, only in adults, no big association with cancer, and the inflammation is ENDOMYSEAL rather than PERIVASCULAR.
  • Very obscure disease, but said to be the most common acquired myopathy in people over the age of 50. Quads and wrist flexors, asymmetrically, is the rule.
  • Exceedingly RARE tumors, you may see, possibly ONE rhabdomyosarcoma in your life, perhapos.
  • Neuropathy& myopathy

    1. 1. MYOPATHIES & NEUROPATHIES www.freelivedoctor.com
    2. 2. NEUROPATHIES, MYOPATHIES <ul><li>NEUROPATHIES (7) </li></ul><ul><ul><li>Inflammatory </li></ul></ul><ul><ul><li>Infectious </li></ul></ul><ul><ul><li>Hereditary (HMSN-I) </li></ul></ul><ul><ul><li>HMSN-II, HMSN-III </li></ul></ul><ul><ul><li>Acquired Toxic/Metabolic </li></ul></ul><ul><ul><li>Traumatic </li></ul></ul><ul><ul><li>Neoplasms </li></ul></ul><ul><li>MYOPATHIES (9) </li></ul><ul><ul><li>Denervation </li></ul></ul><ul><ul><li>Dystrophies </li></ul></ul><ul><ul><li>Ion Channel </li></ul></ul><ul><ul><li>Congenital </li></ul></ul><ul><ul><li>Genetic Metabolic </li></ul></ul><ul><ul><li>Inflammatory </li></ul></ul><ul><ul><li>Toxic </li></ul></ul><ul><ul><li>NeuroMuscular Junction </li></ul></ul><ul><ul><li>Neoplasms </li></ul></ul>www.freelivedoctor.com
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    22. 22. GENERAL Reactions <ul><li>NERVE </li></ul><ul><ul><li>DEMYELINATION (segmental) </li></ul></ul><ul><ul><li>AXONAL DEGENERATION </li></ul></ul><ul><ul><li>NERVE REGENERATION </li></ul></ul><ul><ul><li>REINNERVATION </li></ul></ul><ul><li>MUSCLE FIBER </li></ul><ul><ul><li>NECROSIS </li></ul></ul><ul><ul><li>VACUOLIZATION </li></ul></ul><ul><ul><li>REGENERATION </li></ul></ul><ul><ul><li>ATROPHY </li></ul></ul><ul><ul><li>HYPERTROPHY </li></ul></ul>www.freelivedoctor.com
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    27. 27. HYPERTROPHY, ATROPHY www.freelivedoctor.com
    28. 28. NEUROPATHIES, MYOPATHIES <ul><li>NEUROPATHIES (7) </li></ul><ul><ul><li>Inflammatory </li></ul></ul><ul><ul><li>Infectious </li></ul></ul><ul><ul><li>Hereditary (HMSN-I) </li></ul></ul><ul><ul><li>HMSN-II, HMSN-III </li></ul></ul><ul><ul><li>Acquired Toxic/Metabolic </li></ul></ul><ul><ul><li>Traumatic </li></ul></ul><ul><ul><li>Neoplasms </li></ul></ul><ul><li>MYOPATHIES (9) </li></ul><ul><ul><li>Denervation </li></ul></ul><ul><ul><li>Dystrophies </li></ul></ul><ul><ul><li>Ion Channel </li></ul></ul><ul><ul><li>Congenital </li></ul></ul><ul><ul><li>Genetic Metabolic </li></ul></ul><ul><ul><li>Inflammatory </li></ul></ul><ul><ul><li>Toxic </li></ul></ul><ul><ul><li>NeuroMuscular Junction </li></ul></ul><ul><ul><li>Neoplasms </li></ul></ul>www.freelivedoctor.com
    29. 29. NEUROPATHY , Inflammatory <ul><li>Guillain-Barr é </li></ul><ul><ul><li>Preceded by “influenza”-like illness </li></ul></ul><ul><ul><li>NO actual specific etiologic agent isolated, autoimmume disease to myelin gangliosides most likely </li></ul></ul><ul><ul><li>Inflammation of a peripheral nerve </li></ul></ul><ul><ul><li>DEMYELINATION </li></ul></ul><ul><ul><li>“ ASCENDING” paralysis </li></ul></ul>www.freelivedoctor.com
    30. 30. Guillain-Barr é, (AIDP), A cute I nflammatory D emyelinating P olyneuropathy www.freelivedoctor.com
    31. 31. NEUROPATHY , Infectious <ul><li>Leprosy </li></ul><ul><li>Diphtheria </li></ul><ul><li>V/Z (Varicella-Zoster) </li></ul>www.freelivedoctor.com
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    34. 34. N E U R O T O X I N C. DIPHTHERIAE www.freelivedoctor.com
    35. 35. Z O S T E R POSTHERPETIC NEURALGIA ZOSTER in DRG www.freelivedoctor.com
    36. 36. NEUROPATHY , Hereditary (defective myelination) ( H ereditary M otor and S ensory N europathy) <ul><li>HMSN-I (Charcot-Marie-Tooth) </li></ul><ul><li>HMSN-II (Like CMT of the neurons) </li></ul><ul><li>HMSN-III (Palpable Nerves) (aka, Dejerine-Sottas) </li></ul>www.freelivedoctor.com
    37. 37. PES CAVUM(S), in CMT www.freelivedoctor.com
    38. 38. NEUROPATHY , Toxic/Metabolic <ul><li>Symmetric, Asymmetric </li></ul><ul><li>Sensory, Sensorimotor </li></ul><ul><li>Somatic, Autonomic </li></ul><ul><li>Focal, Multifocal </li></ul>www.freelivedoctor.com
    39. 39. NEUROPATHY , Toxic/Metabolic <ul><li>Diabetes Mellitus </li></ul><ul><li>Vitamin Deficiencies (many Bs, E) </li></ul><ul><li>Heavy Metals, Pb, As, etc. </li></ul><ul><li>Organic Compounds </li></ul><ul><li>CHEMO </li></ul>www.freelivedoctor.com
    40. 40. DEMYELINATION www.freelivedoctor.com
    41. 41. NEUROPATHY , Traumatic <ul><li>Laceration </li></ul><ul><li>Avulsion </li></ul><ul><li>Carpal Tunnel </li></ul><ul><li>Traumatic (amputation) “Neuroma” </li></ul><ul><li>“ Saturday Night” Palsy </li></ul><ul><li>Morton “Neuroma” </li></ul>www.freelivedoctor.com
    42. 42. TRAUMATIC NEUROMA “ Regenerating Axons and Glia (Schwann Cells), but with no direction” www.freelivedoctor.com
    43. 43. MORTON’S NEUROMA Traumatic Compression F>M Interdigital Intermetatarsal MEDIAL Plantar Nerve 3 rd COMMON digital branch www.freelivedoctor.com
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    45. 45. NEUROPATHY , Neoplastic <ul><li>Benign: Schwannoma </li></ul><ul><li>Malignant: Malignant Schwannoma </li></ul>www.freelivedoctor.com
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    47. 47. Antoni A : “Palisaded” Antoni B : NON-Palisaded www.freelivedoctor.com
    48. 48. MYOPATHIES www.freelivedoctor.com
    49. 49. MYOPATHY , Denervation MUSCLE FIBERS CANNOT SURVIVE UNLESS THEY ARE INNERVATED PERIPHERAL NERVE PATHOLOGY ANTERIOR HORN CELL PATHOLOGY www.freelivedoctor.com
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    51. 51. S PINAL M USCULAR A TROPHY <ul><li>Childhood diseases </li></ul><ul><li>Chromosome #5 that harbors the survival motor neuron gene ( SMN1 ) </li></ul><ul><li>Anterior Horn Cells </li></ul><ul><li>Often PAN-fascicular </li></ul><ul><li>More peripheral muscles </li></ul>www.freelivedoctor.com
    52. 52. MYOPATHY , “Dystrophic” <ul><li>Jerry’s kids, no “DYSTROPHIN” </li></ul><ul><li>DUCHENNE (DMD), x-linked </li></ul><ul><li>BECKER (BMD) (less common, less severe, same chromosome) </li></ul><ul><li>Many others also, all of which have complex genetic patterns which have all been precisely defined </li></ul><ul><li>MYOTONIA is a common feature </li></ul>www.freelivedoctor.com
    53. 53. NORMAL DMD www.freelivedoctor.com
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    56. 56. www.freelivedoctor.com Limb Girdle Muscular Dystrophies Inheritance Locus Gene Clinicopathologic Features 1A Autosomal-dominant 5q31 Myotilin Onset in adult life with slow progression of limb weakness, but sparing of facial muscles; dysarthric speech 1B Autosomal-dominant 1q21 Lamin A/C Onset before the age of 20 years in lower limbs, progression during many years with cardiac involvement 1C Autosomal-dominant 3p25 Caveolin-3 (M-caveolin) Onset before the age of 20, clinically similar to type 1B 1D Autosomal-dominant 7p Unknown Limb girdle muscle weakness, adult onset 2A Autosomal-recessive 15q15.1-21.1 Calpain 3 Onset in late childhood to middle age; slow progression during 20–30 years 2B Autosomal-recessive 2p13.3-q13.1 Dysferlin Mild clinical course with onset in early adulthood 2C Autosomal-recessive 13q12 γ-Sarcoglycan Severe weakness during childhood, rapid progression; dystrophic myopathy on muscle biopsy 2D Autosomal-recessive 17q21 α-Sarcoglycan (adhalin) Severe weakness during childhood, rapid progression; dystrophic myopathy on muscle biopsy 2E Autosomal-recessive 4q12 β-Sarcoglycan Onset in early childhood, with Duchenne-like clinical course 2F Autosomal-recessive 5q33 δ-Sarcoglycan Early onset and severe myopathy; dystrophic myopathy on muscle biopsy 2G Autosomal-recessive 17q11-q12 Telethonin Distal weakness with limb-girdle weakness in late childhood to adulthood; rimmed vacuoles in muscle cells 2H Autosomal-recessive 9q31-q34.1 Tripartite motif-containing protein 32 (TRIM32) Limb-girdle and facial weakness with onset in childhood, mild, slowly progressive course
    57. 57. MYOPATHY , Ion Channel “Channelopathies” <ul><li>MYOTONIA/HYPOTONIC PARALYSIS </li></ul><ul><li>FAMILIAL, (genetic) DISEASES </li></ul><ul><li>TRIGGERED BY: </li></ul><ul><ul><li>Exercise </li></ul></ul><ul><ul><li>Cold </li></ul></ul><ul><ul><li>Carb Intake </li></ul></ul><ul><li>Classified by K+, ↑ K+, ↓ K+ </li></ul><ul><li>MALIGNANT HYPERTHERMIA can be triggered off by anesthetic halogenated inhalation agents in some of these patients!!! </li></ul>www.freelivedoctor.com
    58. 58. MYOPATHY , Congenital “Floppy Babies” <ul><li>HYPOTONIC </li></ul><ul><li>FAMILIAL, (genetic) DISEASES </li></ul><ul><li>MANY TYPES, in most of which the precise genetic defects have been identified </li></ul>www.freelivedoctor.com
    59. 59. MYOPATHY , Metabolic (genetic also) <ul><li>LIPID </li></ul><ul><ul><li>Mitoch. Enz. Def.  LIPID ACCUMULATION </li></ul></ul><ul><li>MITOCHONDRIAL </li></ul><ul><ul><li>“ PARKING LOT ” mitochondria </li></ul></ul>www.freelivedoctor.com
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    61. 61. PARKING LOT MITOCH. www.freelivedoctor.com
    62. 62. MYOPATHY , Inflammatory <ul><li>DERMATOMYOSITIS </li></ul><ul><li>POLYMYOSITIS </li></ul><ul><li>INCLUSION BODY MYOSITIS </li></ul><ul><li>ALL HAVE UNCLEAR ETIOLOGIES </li></ul>www.freelivedoctor.com
    63. 63. DERMATOMYOSITIS (often peri-vascular) www.freelivedoctor.com
    64. 64. POLYMYOSITIS, usually endo- myseal www.freelivedoctor.com
    65. 65. INCLUSION BODY MYOSITIS, “rimmed” vacuole www.freelivedoctor.com
    66. 66. MYOPATHY , Toxic <ul><li>THYROTOXICOSIS </li></ul><ul><li>ETHANOL </li></ul><ul><li>DRUGS ( steroids , chloroquine) </li></ul><ul><li>DRUGS ( MANY MANY others) </li></ul>www.freelivedoctor.com
    67. 67. MYOPATHY , NeuroMuscular Junction <ul><li>Myasthenia Gravis </li></ul><ul><ul><li>Associated with thymomas </li></ul></ul><ul><ul><li>Thymectomies often useful Rx: </li></ul></ul><ul><ul><li>AUTOIMMUNE DISEASE, CLEARLY </li></ul></ul><ul><ul><li>Ab’s to ANTI-CHOLINESTERASE RECEPTORS </li></ul></ul><ul><ul><li>Anticholinesterase test is very diagnostic </li></ul></ul><ul><ul><li>YOUNG WOMEN WITH EYE MUSCLE: </li></ul></ul><ul><ul><ul><li>Ptosis  </li></ul></ul></ul><ul><ul><ul><li>Diplopia  </li></ul></ul></ul><ul><ul><ul><li>General Weakness </li></ul></ul></ul><ul><li>Lambert-Eaton Syndrome (paraneoplastic) </li></ul>www.freelivedoctor.com
    68. 68. MYOPATHY , Neoplastic <ul><li>Benign </li></ul><ul><ul><li>Rhabdomyoma </li></ul></ul><ul><li>Malignant </li></ul><ul><ul><li>Rhabdomyosarcoma </li></ul></ul>www.freelivedoctor.com

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