2 Neurophysiology

General

1. How does magnesium prevent excitotoxicity in brain injury?

Magnesium readily crosses the blood-brain barrier (BBB) and blocks various subtypes of calcium and N-methyl-d-aspartate (NMDA) channels.1

2. What is the most abundant excitatory neurotransmitter in the brain?

Glutamate.

3. What cellular elements compose the BBB?

Endothelial cells, astrocyte end-feet, and pericytes. The capillary endothelial cells are connected by tight junctions (Fig. 2.1).

4. What happens to platelet function after a subarachnoid hemorrhage?

It is enhanced, leading to an increase in platelet aggregates in the cerebral microcirculation.3

5. What happens to cerebral blood flow immediately after a subarachnoid hemorrhage?

Decreases.3

6. What is GPHb/HIa?

A platelet surface integrin, which is a mediator of platelet aggregation.

7. What is in the dense granules of platelets?

Serotonin, adenosine triphosphate (ATP), and plateletderived growth factor.

8. It is thought that a disturbed balance between which peptide and molecule plays a major role in the development of vasospasm?

Endothelin-1 (vasoconstriction) and nitric oxide (vasodilatation).3

9. What is the name of the reaction that states that a highly reactive hydroxyl radical could be generated from an interaction between superoxide and hydrogen peroxide?

The Haber-Weiss reaction.4

10. What is deferoxamine?

An iron chelator. Because intracerebral hemorrhage may result in iron toxicity to the brain, iron chelation may help to reduce brain damage in these cases.5

11. What is the proposed mechanism of action of steroid treatment in blunt spinal cord injury?

Steroid treatment in blunt spinal cord injury is controversial. Steroids (when given within 8 hours of injury) are thought to have effects on local blood flow, inhibition of immunologic injury, and free radical-mediated lipid peroxidation and neuronal damage.6

12. What is S100B and how is it related to traumatic brain injury?

S100B is a protein belonging to a multigenic family of low-molecular-weight calcium-binding S100 proteins abundant in astrocytes. After traumatic brain injury, S100B protein is released by astrocytes; this protein may be neuroprotective and/or neurotrophic.7

13. What is factor XIII and in what diseases is it deficient?

Factor XIII is an enzyme (protransglutaminase) that stabilizes the fibrin clot and is important for cross-linking fibrin in the clotting cascade. It is deficient in leukemia, liver disease, malaria, inflammatory bowel disease, disseminated intravascular coagulopathy, and Henoch-Schönlein purpura (Fig. 2.2).

14. What is the (intracranial) Windkessel phenomenon?

The Windkessel phenomenon is the ability of the cerebral vasculature to expand and the ability of the cerebrospinal fluid (CSF) and venous blood to translocate to accommodate arterial pulsations and provide a smooth capillary flow in the brain.9

15. What is the ischemic penumbra?

The term ischemic penumbra has been used to define a region in which cerebral blood flow reduction has passed the threshold that leads to the failure of electrical but not membrane function. The neuron is functionally disturbed, but remains structurally intact.10

16. What is the role of infiltration with local anesthetic at the beginning of a case?

Infiltration with local anesthetic prevents the activation of nociceptors during surgery and substantially lessens the need for analgesic medication.11

17. Local anesthetic molecules are composed of a benzene ring and a quaternary amine separated by an intermediate chain. Which part of the molecule determines the metabolic pathway of the drug?

The intermediate chain.11

18. What is the structural unit of a gap junction?

The connexon is a proteinaceous cylinder with a hydrophilic channel and is the structural unit of the gap junction. Direct electrical communication between cells occurs through gap junctions and may be important in the pathogenesis of diseases of the nervous system including epilepsy (Fig. 2.3).12

19. What are the functions of transforming growth factor β (TGF-β)?

TGF-β is a multifunctional polypeptide implicated in the regulation of various cellular processes including growth, differentiation, apoptosis, adhesion, and motility. Abnormalities in the TGF-β signaling pathway are implicated in the development and progression of brain tumors.

20. What enzyme is inhibited by acetazolamide?

Carbonic anhydrase.13

21. What is the difference between a bioactive Guglielmi detachable coil (GDC) and a platinum GDC?

The bioactive coil accelerates clot maturation and promotes the development of mature connective tissue and neointimal formation. The polymer used in bioactive coils is polyglycolic/poly-L-lactic acid.14

22. What are matrix metalloproteinases?

A family of zinc-dependent endopeptidases that mediate vascular remodeling by degrading extracellular matrix components, such as collagen and elastin.15

23. What is the causative mutation in Crouzon’s syndrome?

Crouzon’s syndrome is caused by mutations in fibroblast growth factor receptor 2 (FGFR2), leading to constitutive activation of receptors in the absence of ligand binding. This syndrome is characterized by premature fusion of the cranial sutures that leads to abnormal cranium shape, restricted brain growth, and increased intracranial pressure.

24. How does baclofen work?

Baclofen is an agonist of γ-aminobutyric acid (GABA); it reduces the release of presynaptic neurotransmitters in excitatory spinal pathways.

25. What is hypsarrhythmia?

A chaotic, high-amplitude, generalized electroencephalographic pattern characteristic of infantile spasms.16

26. What is “subsidence” in relation to the aging spine?

Subsidence is the loss of vertebral column height that occurs normally with aging; it may also refer to the loss of graft height after surgery. The use of dynamic plates allows normal subsidence to occur and may help bony fusion, resulting in decreased incidence of construct failures.

27. What is the genetic defect in Gorlin’s syndrome?

Gorlin’s syndrome is an autosomal dominant disorder resulting from mutations in the patched (PTCH) gene that predisposes to neoplasias and widespread congenital malformations.17

28. What is rFVIIa?

Recombinant activated factor VII can help to prevent bleeding episodes especially in hemophilic patients with inhibitors to coagulation factors VIII and IX. Administration of rFVIIa (off-label) given within 4 hours of a spontaneous intracranial hemorrhage can result in reduced hematoma growth and less intraventricular extension of the hematoma.

29. What is the name of the water channel proteins of the central nervous system (CNS), which provide a major pathway for osmotically driven water movement across plasma membranes?

Aquaporins are the water channel proteins of the brain. In normal brain, aquaporin 1 is expressed on the ventricle surface by the choroid plexus. The predominant water channel in normal brain is aquaporin 4, which is strongly expressed in the plasma membranes of astrocytes. Aquaporin proteins could be a therapeutic target for pharmacologic treatment of hydrocephalus.18

30. What is the most common agent used for the pharmacologic dilatation of vasospastic cerebral vessels?

Papaverine hydrochloride is a potent, nonspecific, endothelium-independent smooth muscle relaxant that produces dilatation of arteries and arterioles, as well as veins. Intra-arterial papaverine is usually administered superselectively via a microcatheter positioned proximal to the spastic vessel.

31. How do intervertebral disks receive their nutrition?

Intervertebral disks receive nutrition through passive diffusion from a network of capillary beds in the subchondral end plate region of the vertebral body.

32. What is the composition of a PEEK cage?

Polyetheretherketone (PEEK) spacers have a modulus of elasticity close to that of cortical bone. PEEK is a strong polymer that is able to withstand the compressive load of the vertebral column. Its hollow center allows for packing of autologous bone and/or demineralized bone matrix.19

33. What are common areas of leptomeningeal dissemination for tumors?

The most common areas of leptomeningeal dissemination of CNS tumors are the basilar cisterns, sylvian fissures, and cauda equina, most likely because of both gravity and slower rate of CSF flow in these areas.

34. What is the resting membrane potential in myelinated peripheral nerves and in the...