PNS STUDENT - Sheppard
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Transcript of PNS STUDENT - Sheppard
Chapter 27: Peripheral Nerves
and Skeletal Muscles
Robbins and Cotran Pathologic Basis of Disease
Sierra Sheppard
Objectives Recall the structure and anatomy of peripheral nerves. Understand the types of connective tissue that bundle
axons together. Describe the clinical features of myasthenia gravis and
indicate which part of the neuromuscular junction the antibodies are directed against.
Identify gross, histologic, and clinical features of schwannomas, neurofibromas and malignant peripheral nerve sheath tumors.
Diagnose neurofibromatosis type 1 and neurofibromatosis type 2.
Peripheral Nerve Structure
Axons Myelin Sheaths
Peripheral Nerve Function
PNS is divided into somatic (voluntary) and autonomic (involuntary) components
Somatic Nervous System Both sensory and motor
Sensory nerves Dorsal root ganglia
Motor nerves Anterior (ventral) horn of spinal cord
Peripheral Nerve Structure
Somatic motor function is carried out by the motor unit: Motor neuron Axon Neuromuscular junction Myofibers
Peripheral Nerve Structure
Peripheral Nerve Structure
Somatic sensory function depends on: Distal nerve endings Axon that travels to the dorsal root ganglia Proximal axon that synapses on neurons in spinal
cord or brainstem
Autonomic nerve fibers outnumber somatic fibers in the PNS, but signs and symptoms are generally not prominent features of peripheral neuropathies
Peripheral Nerve Structure
Myelinated axons: One Schwann cell wraps around the axon
multiple times to create the sheath Separated from the next by a small space =
Node of Ranvier
Peripheral Nerve Structure
Axons are bundled together by three types of connective tissue: Epineurium Perineurium Endoneurium
General Types of Peripheral Nerve Injury
Axonal Neuropathies Axons are primary target of
damage Wallerian degeneration
Axons distal to point of transection degenerate
Axons begin to fragment and myelin sheaths unravel Myelin ovoids
Regeneration begins at site of transection 1mm per day toward distal
target Thinner and shorter
General Types of Peripheral Nerve Injury
Demyelinating Neuropathies Schwann cells with myelin
sheaths are primary targets Axons are preserved Myelin sheaths degenerate in
random pattern Schwann cells initiate repair
and form new myelin sheaths Shorter and thinner
Slowed nerve conduction velocity
Giullain-Barre Syndrome (Acute Inflammatory Demyelinating Neuropathy)
General Types of Peripheral Nerve
Injury Neuronopathies Destruction of neurons Leads to secondary degeneration of axonal
processes Caused by infections and toxins Affects proximal and distal parts of the body
Anatomic Patterns of Peripheral
Neuropathies Mononeuropathies Affect a single nerve Trauma, entrapment, infections
Polyneuropathies Symmetrically affects multiple nerves Deficits start in feet and ascend
Guillain-Barre – “ascending paralysis”
Mononeuritis Multiplex Damages several nerves in a haphazard fashion
Polyradiculoneuropathies Affect nerve roots and peripheral nerves Diffuse symmetric symptoms Proximal and distal parts of the body
Diseases of the Neuromuscular
Junction
Diseases of the NMJ Antibody mediated
Myasthenia Gravis Lambert-Eaton Myasthenic Syndrome
Congenital myasthenic syndromes Disorders caused by toxins
Botulism Curare
Myasthenia Gravis Autoimmune Antibodies against postsynaptic acetycholine receptors
Thymic abnormalities
Fluctuating weakness that worsens with exertion and over the course of the day
Diplopia and ptosis are common Repeated electrophysiologic stimulation does not
increase muscle response
Acetylcholinesterase inhibitors have reduced mortality rates
Myasthenia Gravis
Lambert-Eaton Myasthenic Syndrome Autoimmune
Antibodies block acetylcholine release by inhibiting a presynaptic calcium channel
Rapid repeated stimulation does increase muscle response Muscle strength is improved after a few seconds of
muscle activity
Present with weakness of extremities In half of cases, there is an underlying
neuroendocrine carcinoma of the lung Paraneoplastic syndrome
Peripheral Nerve Sheath Tumors
Schwannomas Benign tumors that exhibit Schwann cell
differentiation and often arise directly from peripheral nerves
Component of NF2 Loss of expression of merlin Cells hyperproliferate in response to growth
factors
Schwannomas Morphology:
Well-circumscribed, encapsulated Abut nerve without invading it Firm, gray masses
Schwannomas Morphology:
Microscopically, consist of areas referred to Antoni A and Antoni B areas
Recurrence is common if incompletely resected Malignant transformation is extremely rare
Schwannomas Symptoms from local compression of involved
nerve, brainstem or spinal cord Within the cranial vault, most occur at the
cerebellopontine angle, attached to the vestibular branch of the eighth nerve
Present with tinnitus and hearing loss Surgical removal is curative
Schwannomas
Neurofibromas Benign More heterogeneous than schwannomas Three growth patterns:
Superficial cutaneous neurofibromas Pedunculated, isolated or multiple
Diffuse neurofibromas Plaquelike skin lesion
Plexiform neurofibromas Deep or superficial Only type that can undergo malignant transformation
Neurofibromas Schwann cells show complete loss of NF1
gene product, neurofibromin Schwann cells are the neoplastic cells
Neurofibromas:Morphology
Localized cutaneous neurofibroma Small, well-delineated Unencapsulated Arise in dermis and subcutaneous fat
Neurofibromas: Morphology
Diffuse neurofibroma: Morphologically similar, but distinct growth
pattern from cutaneous neurofibromas Diffusely infiltrates dermis and subcutaneous
tissue Entrap fat and appendage structures Produces a plaquelike appearance Can grow to large sizes
Neurofibromas: Morphology
Plexiform neurofibromas: Grow within and expand nerve fascicles Entrap associated axons Perineurial layer is preserved
Encapsulated appearance “Bag of worms” = ropy thickening of multiple
fascicles “Shredded carrot” = collagen bundles
Malignant Peripheral Nerve Sheath Tumors
(MPNST) 85% high grade Half arise in NF1 patients
Malignant transformation of plexiform neurofibroma
MPNST Morphology Poorly defined Infiltrate parent nerve Invade adjacent soft tissues Fasciculated arrangement of spindle cells Appears “marbleized” at low power due to variations in
cellularity Can undergo “divergent differentiation”
Triton tumor
Distinction from undifferentiated sarcoma may be difficult
Neurofibromatosis Type 1
Systemic disease 1 in 3000 Non-neoplastic manifestations and a variety of tumors
Neurofibromas (all types) MPNSTs Gliomas of optic nerves Other glial tumors and hamartomatous lesions Pheochromocytomas
NF1 loss-of-function mutations Encodes tumor suppressor neurofibromin
Neurofibromatosis Type 1
Clinical features: Mental retardation or seizures Skeletal defects Lisch nodules Café au lait spots
Neurofibromatosis Type 2
Results in a range of tumors Bilateral eighth-nerve schwannomas Multiple meningiomas Also, gliomas, typically ependymomas of
spinal cord
Non-neoplastic lesions Much less common than NF1
Question 1 What are the four parts of a somatic motor
unit?
Question 2 What three types of tissue bundle axons
together?
Question 3 Myasthenia Gravis characteristically has
antibodies directed against: A. Presynaptic calcium channels to block
acetylcholine release B. Presynaptic acetylcholine receptors C. Postsynaptic acetylcholine receptors D. Presynaptic neurons to block acetylcholine
release
Question 4 What peripheral nerve sheath tumor is
described as a benign well-circumscribed, encapsulated, gray mass that abuts the nerve without invading it?
Question 5 What type of neurofibroma can undergo
malignant transformation?
Question 6 Lisch nodules and café au lait spots are
associated with:
Question 7 Bilateral eighth-nerve schwannomas and
multiple meningiomas are associated with:
Question 8 True or False: Repeated electrophysiologic
stimulation in a patient with myasthenia gravis increases the muscular response.
Question 9 Microscopically, Antoni A and Antoni B areas
are associated with what tumor?
Question 10 Within the cranial vault, where do most
schwannomas occur?
Bibliography Kumar, Vinay, Abul K. Abbas, Jon C. Aster, and James A. Perkins.
Robbins and Cotran Pathologic Basis of Disease. 9th ed. Philadelphia, PA: Elsevier, 2015. 1227-49. Print.
Motor Unit Image: https://www.google.com/search?q=motor+unit&espv=2&biw=977&bih=783&source=lnms&tbm=isch&sa=X&ved=0CAYQ_AUoAWoVChMIv5SaoILixgIV0LeACh1XUgg8#imgrc=xLKxBnBz64HvRM%3A
Peripheral Nerve Structure: http://www.quia.com/files/quia/users/lmcgee/Systems/endocrine-nervous/neuronstructure2_L.gif
Axon Connective Tissue: http://www.muskingum.edu/~asantas/Biology%20228/Chapter14_spinalcord_part2_files/slide0060_image010.jpg
Myasthenia Gravis: http://www.beverlydoc.com/wp-content/uploads/2014/01/Myasthenia-Gravis.jpg
Schwannoma, Gross Image: http://www.tumorlibrary.com/case/images/2357.jpg
Bibliography Cerebellopontine Angle Images:
http://www.bmc.med.utoronto.ca/cranialnerves/wp-content/images/c_08/Vestibulo-viii12_labelled768.jpg, http://education.vrad.com/wp-content/uploads/2011/12/IC-angle-mass-1.jpg
Neurofibroma, Gross Image: http://atlasgeneticsoncology.org/Tumors/Images/NeurofibromFig1.jpg
Plexiform Neurofibroma, Bag of Worms: http://ebooks.cambridge.org/content/978/11/3968/078/3/html_chunk/Images/03816fig8_4hi-res.jpeg
Lisch Nodules: https://41.media.tumblr.com/fdf48b12af4e8418914595ed30278076/tumblr_noxo38SZUo1s1vn29o1_1280.jpg
Café au Lait Spots: http://www.e-ijd.org/articles/2011/56/4/images/IndianJDermatol_2011_56_4_375_84721_u4.jpg
Malignant Peripheral Nerve Sheath Tumor; Peripheral Nerve Function: Falcon, Justin.