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


Somatic motor function is carried out by the motor unit: Motor neuron Axon Neuromuscular junction Myofibers



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


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


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


Clinical features: Mental retardation or seizures Skeletal defects Lisch nodules Café au lait spots


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.

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