Cell Types of The Nervous System Case File

Cell Types of The Nervous System Case File

EUGENE C.TOY, MD, RAHUL JANDIAL, MD, PhD, EVAN YALE SNYDER, MD, PhD, MARTIN T. PAUKERT, MD

CASE 1

A 53-year-old male presents to the emergency department following a newonset generalized seizure. After recovery from the seizure period, he is alert and oriented to person, place, and time, although he has no specific memory of the seizure. There are no neurological deficits noted on physical examination and laboratory values are unremarkable. The patient undergoes surgery for resection of the malignancy and is diagnosed with a malignant primary brain tumor, which is read as a glioblastoma multiforme (GBM). The neurosurgeon’s plan is to place the patient on long-term seizure prophylaxis and steroids, and radiation treatment to the operative bed.

• What other types of tumors are most closely related to this patient’s malignancy?
• What are the imaging findings most characteristic of these types of tumors?
• What are the hallmark pathological findings of these types of tumors?

ANSWERS TO CASE 1: CELL TYPES OF THE NERVOUS SYSTEM

Summary: 53-year-old male with new-onset seizure and a left parietal lobe mass undergoes surgery to resect a primary brain tumor, diagnosed as a GBM. He also receives adjuvant radiation treatment.

• Related tumors: Low-grade astrocytomas and anaplastic astrocytomas.
• Imaging characteristics: A ring-enhancing lesion in the left parietal lobe with surrounding edema and mass effect.
• Neuropathological findings: GBMs exhibit marked hypercellularity, nuclear pleomorphism, vascular proliferation, and pseudopalisading of tumor cells around areas of necrosis.

CLINICAL CORRELATION

The clinical presentation of the patient in this case is very typical for GBM, a severe and aggressive form of primary brain cancer. Astrocytomas encompass a group of primary brain tumors which, as the name implies, are derived from astrocytes, a star-shaped glial cell with multiple supportive roles that assist neurons in efficiently relaying messages through the neural network (see discussion). The World Health Organization (WHO) grades astrocytomas based upon pathological findings along a continuum from grades I to IV with grades I and II consisting of low-grade astrocytomas, grade III consisting of anaplastic astrocytomas, and finally grade IV consisting of GBMs. As tumor types progress according to the WHO classification, they begin to exhibit progressively more hypercellularity and nuclear pleomorphism (a nonhomogeneous group of cells with nuclei of various sizes and shapes). Proliferation of tumor cells around vascular structures along white matter tracts occurs in either anaplastic astrocytomas or GBMs. Necrosis with pseudopalisading of tumor cells is only found in GBMs. Treatment consists of surgery, radiation treatment, and/or chemotherapy either individually or in combination. Despite the advances in all three modalities of treatment, median survival for patients with astrocytomas has remained consistent (Table 1-1).

Oligodendrogliomas are another type of primary brain tumor which arise from the oligodendrocytes, another form of glial cells which provide myelin sheaths around the axons of neurons in the central nervous system. These tumors generally affect adults in their fifth decade of life, present with seizures, and have a characteristic appearance on both radiographs and microscopic examination from calcifications in the tumor. Treatment consists of an appropriate surgical procedure followed by chemotherapy. The presence or absence of specific chromosomal deletions on the long arm of chromosome 1 or the short arm of chromosome 19 has been shown to affect the sensitivity of these tumors to chemotherapy. Oligodendrogliomas tend to have a better prognosis with 10-year survival of 10%-30% reported in the literature.

Table 1-1 SURVIVAL ESTIMATES FOR ASTROCYTOMAS
ASTROCYTOMA TYPE  (WHO GRADE)	MEDIAN SURVIVAL
Low-grade astrocytomas (I)	8-10 years
Low-grade astrocytomas (II)	7-8 years
Anaplastic astrocytomas (III)	~2 years
Glioblastoma multiforme (IV)	<1 year

Additional tumors arising from cells of the nervous system include mixed tumors with oligodendral and astrocytic components, schwannomas arising from Schwann cells of the peripheral nervous system, and gangliogliomas arising from both glial cells and neurons. This list is certainly not exhaustive, but is representative of the breadth of pathology found in primary brain tumors.

APPROACH TO CELL TYPES OF THE NERVOUS SYSTEM

Objectives

1. Differentiate between the central and peripheral nervous system.
2. Know the names of each cell type in the nervous system.
3. Describe the role of each cell type within the nervous system.
4. Identify the components that make up the blood-brain barrier (BBB).

Definitions

Meninges: A series of three membranes which encapsulates the central nervous system (CNS).

Glial cells: Cells that support neurons and form the structural framework for the nervous system.

Myelin: A phospholipid bilayer which insulates the axon and allows for faster conduction of an action potential.

DISCUSSION

The human nervous system can be divided into two main components: the central nervous system (CNS) and the peripheral nervous system (PNS) (see Figure 1-1). The CNS is contained entirely within the meninges, a series of three membranes which encapsulates the CNS, while the PNS is distributed outside of the meninges. The meningeal layers consist of the dura mater, pia mater, and the arachnoid layers.

There are two main types of cells within the nervous system: nerve cells (neurons) and glial cells (glia). Glia, which far outnumber neurons, support neurons and form the structural framework for the nervous system. 

• Oligodendrocytes, found only in the central nervous system, and Schwann cells, found only in the peripheral nervous system, are two types of glial cells that have similar functions. They produce myelin, which insulate the axons of neurons for faster conduction of electrical signals. One oligodendrocyte can provide myelin sheaths for multiple axons, while one Schwann cell provides myelin for only one axon.

Figure 1-1. Schematic illustration of nerve cell types. A shows motor and sensory

neurons, whereas B shows preganglionic cells.

• Microglia, the phagocytes of the nervous system, mobilize following insults to the CNS and remove debris following neuronal injury or death. They arise from macrophages outside of the nervous system and are physiologically unrelated to other glial cells.
• Astrocytes, the most numerous type of glial cell, are star-shaped cells that fill the interneuronal space in the CNS. They provide structural support for the neurons in the CNS, insulate and separate neurons from one another, and help to regulate the potassium ion concentration in the extracellular space around neurons.
• Tight junctions between the foot processes of astrocytes, along with the endothelial membrane of the vessels, help to maintain the bloodbrain barrier, an almost impermeable lining of the brain’s capillaries and venules that prevents certain toxic substances in the blood from entering the brain.
• Glial cells also assist with the migration of neurons during embryological development and direct the outgrowth of axons.

Neurons are the signaling unit within the nervous system and are the only cells in the nervous system involved with the conduction of electrical impulses. While there are a number of morphologically different types of neurons, they all share the same cellular phenotype consisting of a cell body or soma, multiple dendrites, axon, and a presynaptic terminal.

COMPREHENSION QUESTIONS

[1.1] A 37-year-old woman comes to see you in your family medicine clinic because the medication she is taking for her moderately severe seasonal allergies makes her extremely drowsy. You advise her to switch from the current first-generation antihistamine she is taking to a newer second-generation antihistamine because you know the latter has less incidence of drowsiness as it cannot penetrate the BBB. What cell type in the CNS is responsible for forming this BBB?

A. Astrocytes

B. Microglia

C. Oligodendrocytes

D. Schwann cells

[1.2] A 45-year-old man presents to his primary care physician with complaints of persistent headache for the past several months. After extensive workup, he is found to have an intraparenchymal brain tumor. On biopsy, the pathologist reports that the tumor has myelin elements. From what cell type in the CNS did this tumor likely arise?

A. Astrocyte

B. Microglia

C. Schwann cell

D. Oligodendrocyte

[1.3] A 21-year-old college student is brought into the emergency room complaining of the worst headache of his life. On examination he is noted to have a stiff neck and photophobia. As the physician on duty, you are concerned that this young man may have bleeding from a ruptured aneurysm. You perform a CT scan followed by a lumbar puncture which returns bloody cerebrospinal fluid (CSF), confirming your suspicion. Neurosurgery is called and the patient is rushed to surgery. From where was this bloody CSF obtained?

A. Epidural space

B. Intraparenchymally

C. Subarachnoid space

D. Subdural space

Answers

[1.1] A. Astrocytes extend foot processes that, in adition to the endothelial cells of the cerebral capillaries, are a critical component of the BBB. The BBB is a very important structure that, as the name implies, restricts access of molecules from the blood to the brain. This restriction is generally based on size and lipid solubility such that small, lipophilic molecules can cross, whereas larger, lipophobic molecules cannot. The BBB also is active in preventing bacteria and viruses from entering the brain. Oligodendrocytes are responsible for myelinating CNS axons, Schwann cells for myelinating PNS axons, and microglia are the phagocytes of the CNS.

[1.2] D. Tumors arising from oligodendrocytes will contain myelin elements and be located in the CNS. In the analysis of tumors, it is important to remember that dysfunctional tumor cells arise from normal cells and thus express the same markers as the cells from which they arise. In this case, the tumor contains myelin elements, and thus most likely arises from a cell that produces myelin: either an oligodendrocyte or a Schwann cell. Because the question refers specifically to the CNS, the correct answer is oligodendrocyte. The other cell types listed do not produce myelin.

[1.3] C. Because CSF flows in the subarachnoid space between the arachnoid mater and the pia mater, bloody CSF represents blood from the subarachnoid space. Bleeding into the CNS is an emergency situation with a grave prognosis despite appropriate and timely management. Epidural bleeds typically present acutely following trauma, and are commonly associated with a laceration of the middle meningeal artery. Subdural bleeds often present subacutely, several weeks following minor head trauma especially in the elderly. Intraparenchymal bleeds present in a variety of ways, depending on the size and location of the bleeding in the brain parenchyma.

NEUROSCIENCE PEARLS ❖ The Central nervous system is contained in the meninges (consisting of the dura mater, pia mater, and arachnoid layers) while the peripheral nervous system is distributed outside of the meninges. ❖ Neurons conduct electrical impulses throughout the nervous system. ❖ Glial cells support neurons and form the structural framework for the neurons. ❖ Oligodendrocytes produce myelin in the CNS while Schwann cells produce myelin in the PNS. ❖ Microglia arise from macrophages and phagocytose debris following neuronal injury or death. ❖ Astrocytes provide structural support for the neurons in the CNS, insulate and separate neurons from one another, and help to regulate the potassium ion concentration in the extracellular space around neurons. ❖ Tight junctions between the foot processes of astrocytes, along with the endothelial membrane of the vessels, help to maintain the BBB.

REFERENCES

Bear MF, Connors B, Paradiso M, eds. Neuroscience: Exploring the Brain. 3rd ed. Baltimore, MD: Lippincott Williams & Wilkins; 2006. 

Kandel E, Schwartz J, Jessell T, eds. Principles of Neural Science. 5th ed. New York: McGraw-Hill; 2000. 

Zigmond MJ, Squire LR, Bloom FE, Landis SC, Roberts JL, eds. Fundamental Neuroscience. 2nd ed. San Diego, CA: Academic Press; 1999.

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