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Of these 10 mg rizatriptan fast delivery,tiagabine (gabitril) order 10 mg rizatriptan fast delivery,a derivative of nipecotic acid that acts preferentially on GAT-1,has proved clinically useful in cases of refractory epilepsy. METABOLISM OF GABA Once recovered into GABAergic nerve terminals or glia,GABA is metabolised to succinic semialdehyde and then to succinate. As detailed above,these reactions are catalysed by GABA-T and SSADH,respectively. Aminotransferase reactions are reversible but GABA-T breaks down GABA,rather than producing it,because the irreversible action of SSADH rapidly oxidises the product SSA to succinate (Fig. SSA may also be reduced by the enzyme succinic semialdehyde reductase (SSAR) to form g-hydroxybutyric acid (GHB). Inhibitors of GABA-T include aminooxyacetic acid,5-amino-1,3-cyclohexadi- enenecarboxylic acid (gabaculine), g-vinyl GABA (vigabatrin) and 2-propylpenatanoic acid (valproate). The first two are PLP antagonists and are of experimental interest only. Vigabatrin is an irreversible inhibitor of GABA-T and has been used clinically as an anticonvulsant. Valproate is a widely used anticonvulsant but it is not clear to what extent inhibition of GABA-T contributes to its therapeutic properties,as it also inhibits SSADH and SSAR,and inhibits Na‡ currents,thus limiting neuronal firing. GABA RECEPTORS The actions of GABA are mediated by receptors belonging to three distinct classes, termed GABAA,GABAB and GABAC. GABAA and GABAC receptors form membrane channels (ionotropic receptors) and their activation leads to an increased permeability to chloride (ClÀ) and bicarbonate (HCOÀ) ions. GABA receptors belong 3 B to the family of G-protein-coupled receptors (metabotropic receptors) and can modify the activity of the enzyme adenylate cyclase,suppress transmitter release by directly inhibiting calcium channels or hyperpolarise postsynaptic cells by directly activating potassium channels. GABAA RECEPTORS GABAA receptors are the most widely expressed of the GABA receptors in the CNS and are found at the vast majority of GABAergic synapses. Binding of two molecules of GABA to the receptor causes the opening of an integral transmembrane anion channel (Bormann,Hamill and Sakmann 1987). As the ClÀ permeability of the channel is approximately five times that of HCO À,under most circumstances the net flux is 3 dominated by ClÀ. Because of this the amplitude and direction of GABA-gated currents,and the resultant transmembrane potential changes,are determined largely by the sign and magnitude of the difference between the membrane potential (Vm) and the chloride equilibrium potential (ECl). If ClÀ were passively distributed across the neuronal membrane E would equal V. Cl m However,neurons possess a variety of transport mechanisms for extrusion or uptake of ClÀ (Kaila 1994). The value of E is dictated by the net result of these chloride- Cl extruding or accumulating mechanisms. Mature central neurons tend to maintain a low intracellular ClÀ through the activity of a ClÀ-extruding K‡/ClÀ co-transporter (KCC2). Thus,in many neurons,ECl is more negative than Vm (although variable, typical values would be À70 and À65 mV,respectively). Under these circumstances,an increase in chloride conductance (g ) leads to an influx of ClÀ that results in membrane Cl hyperpolarisation (a movement towards ECl). This is the classic GABA-mediated inhibitory postsynaptic potential (IPSP). The IPSP transiently (tens of milliseconds) moves the membrane potential to a more hyperpolarised value,away from the threshold for action potential initiation (Fig. In cells in which the net ClÀ extrusion is less (because KCC2 or other ClÀ-extruding mechanisms are less active), E Cl may be very close to,or slightly positive to,Vm. The effect of GABA is still inhibitory, 234 NEUROTRANSMITTERS,DRUGS AND BRAIN FUNCTION as the increase in gCl tends to hold the membrane potential close to ECl,thus making it more difficult to trigger an action potential. Activity of NKCC1 can result in ECl being positive to Vm,such that an increase in gCl leads to chloride exit from the cell and membrane depolarisation. GABA may still be inhibitory,as long as ECl is below the threshold for spike initiation.

High-risk areas such as northern and central Europe 10 mg rizatriptan mastercard, 17 18 NURSING PRACTICE IN MULTIPLE SCLEROSIS: A CORE CURRICULUM Italy order 10mg rizatriptan with mastercard, the northern United States, Canada, southeastern Australia, New Zealand, and parts of the former Soviet Union are considered high risk, with rates greater than 30 per 100,000 populations. Low-risk areas (less than 5 per 100,000) include other areas of Africa and Asia, the Caribbean, Mexico, and possibly northern South America. In general, people who reside in temperate climates in economically developed occidental countries tend to have a higher rate of MS. There is a seven-fold decrease in exacerbations during pregnancy and a seven-fold increased risk during the six months after delivery. No data strongly link associations but anecdotal reports CHAPTER 5: EPIDEMIOLOGY 19 exist of relationships to diabetes mellitus, rheumatoid arthritis, myasthenia gravis, and bipolar illness. Incidence and death rates refer to new cases and to deaths per unit time and population. Those migrating before the age of 15 acquire the lower risk of their new residence. This page intentionally left blank Chapter 6 The Complete Neurologic Examination Objectives: Upon completion of this chapter, the learner will: Describe key components of a neurologic examination Discuss clinical implications of positive findings Cite the importance of patient and family education to explain the neuropathology of diseaseTaking the history: A. The first and most important step in a focused assessment is gathering a detailed and accurate history in chronologic order. Assess level of consciousness, orientation memory, intellectual status, and speech. Each evaluation is scored with regard to the number of tasks per- 21 22 NURSING PRACTICE IN MULTIPLE SCLEROSIS: A CORE CURRICULUM formed correctly. For example, if a patient is able to correct- ly recall only two of the three objects, a score of 2 is given. A mental status score of less than 20 points out of a maxi- mum of 30 indicates a cognitive deficit. CNII—Optic nerve involves assessment of visual acuity and gross visual fields as well as an ophthalmosopic examination. CNIII, IV, and VI are responsible for pupillary constriction elicited by shining a light into each eye. Each pupil should constrict directly and consensually (constriction of the opposite pupil). A pupillary difference (aniscoria) up to 20% may be pre-existing and normal. This nerve also innervates the extraocular muscles that affect lateral and vertical gaze and is tested with CN IV, which innervates the superior oblique muscle and aids in depression of the eye and looking downward, and CNVI, which innervates the lateral rectus muscle of the eye (abduction). Testing these three nerves involves testing the extraocular eye movements (nystagmus and isolated paralysis). Trigeminal neuralgia is a common problem in MS, and occurs when this nerve is affected. The motor portion innervates the muscles of the face and scalp; the sensory portion supplies the sense of taste on the anterior 2/3 of the tongue and sensation to the ear canal and behind the ear. CNVIII is the acoustic nerve, which involves hearing and influences equilibrium. CNIX supplies sensory sensation to the pharynx, tonsils, and posterior 2/3 of the tongue. CNX is the vagus nerve; it is involved in the gag reflex and is tested with CNIX. CNXI controls the movement of the sternocleidomastoid and trapezius muscles of the neck and shoulders. Evaluation of arm drift is a sensitive test for weakness in the upper extremities. Other sensitive tests for extremity weakness include hand grasp, plantar flexion of the foot, and dorsiflexion of the foot. Atrophy—observe large muscle groups for symmetry and deter- mine if their size is appropriate for the person’s age. Rigidity presents as stiffness regardless of the rate of passive movement. Basic sensory examination consists of pain, light touch, proprioception, stereognosis, and vibration: 1. Proprioception measures posterior column defects (position of toe—up or down, etc. Stereognosis is dependent on touch and position sense (identification of a familiar object in one’s hand).

The pos- to the fornix purchase 10 mg rizatriptan visa, and the crus of the fornix is found along the mid- terior commissure is located at the caudal aspect of the third ven- line superior to the thalamus order 10 mg rizatriptan amex. The anterior limb of the internal tricle just above the opening of the cerebral aqueduct, and the capsule is found between the head of the caudate nucleus and the Massa intermedia bridges the third ventricle in about 80% of indi- lenticular nucleus (mainly the putamen). The rostral wall of the third ventricle is formed by the lus contains pallidothalamic fibers and traverses the posterior lamina terminalis and the septum pellucidum forms the medial limb of the internal capsule en route to the dorsal thalamus. Answer A: The amygdaloid complex is located immediately in- ternal to the uncus. Bilateral damage to rostral portions of the temporal lobe may include the amygdala and result in a constella- Review and Study Questions for tion of deficits known as the Klüver-Bucy syndrome. The hip- Chapter 5 pocampal formation is internal to the cortex of the parahip- pocampal gyrus, and the anterior thalamic nucleus is internal to the anterior thalamic tubercle. A 16-year-old boy is brought to the emergency department fol- longitudinally oriented fibers of the cingulum and the gracile tu- lowing a diving accident at a local quarry. The examination reveals bercle is the external elevation formed by the gracile nucleus. At 36 hours after the accident the boy is able to dorsiflex his toes, barely move his right lower extremity at the knee, and is able to perceive pinprick stimulation of the perianal 17. Answer D: The optic radiations are located in the lateral wall of skin (sacral sparing). Which of the following most specifically de- the posterior horn of the lateral ventricle as they pass through the scribes the spinal cord lesion in this patient? A thin layer of white (A) Central cord matter, the tapetum, separates the optic radiations from the wall (B) Complete of the ventricle. The cisterns at the midbrain on the basal aspect of (C) Hemisection the hemisphere contain the optic tract. The other ventricular (D) Incomplete spaces listed have no direct relationship to the optic radiations. Which of the following represents the most likely level of damage the emergency department after experiencing sudden onset of to the spinal cord resulting from the fracture to the vertebral col- weakness of his left upper and lower extremities. Damage to which of the following (A) T6 on the left tracts or fiber bundles of the medulla would most likely explain (B) T8 on the left this deficit? The artery of Adamkiewicz is an especially large spinal medullary (E) Vestibulospinal fibers artery supplementing the arterial blood supply to the spinal cord. Which of the following represents the most consistent location of this vessel? A 78-year-old healthy, active woman experiences a sudden weak- ness of her right upper extremity during an angiogram to deter- (A) At C7–C8 on the left mine the patency of her carotid bifurcation. The immediate ex- (B) At L5–S1 on the left amination reveals weakness of both extremities on the right and a (C) At L5–S1 on the right partial loss of vision in both eyes (homonymous hemianopsia). The CT of a 73-year-old woman shows an infarcted area in the ros- points to the occlusion of one vessel. Which of the following ves- tral portions of the dorsomedial nucleus, the anterior nucleus, and sels is most likely occluded? Which of the following arteries sup- (A) Anterior cerebral artery ply blood to this area of the brain? A 69-year-old man is brought to the emergency department by his wife after complaining of a bad headache and becoming stuporous. Which of the following structures is insinuated between the ex- CT shows a hemorrhage into the head of the caudate nucleus that ternal and extreme capsules and is functionally related to the in- has ruptured into the anterior horn of the lateral ventricle. An 83-year-old man is brought to the emergency department by his (E) Thalamoperforating artery(ies) daughter, who explains that her father started having “fits”. The ex- amination reveals an alert, otherwise healthy, man who frequently Questions 5 and 6 are based on the following patient. Which of the A 23-year-old man is brought to the emergency department from the following structures is most likely involved in this lesion? The neurologic examination reveals (A) Cerebellar cortex plus nuclei weakness of the right lower extremity and a loss of pain and thermal (B) Lenticular nucleus sensations on the left side beginning at the level of the umbilicus.

This portion of the internal intercostals lies under closed in a fibrous sheath formed from the aponeuroses of the other the external intercostals cheap 10mg rizatriptan mastercard, and its fibers are directed downward three abdominal muscles buy discount rizatriptan 10mg line. The abdominal muscles may also contract during sue on the midline of the abdomen that separates the two rectus ab- forced expiration, which increases pressure within the abdominal dominis muscles. Tendinous inscriptions transect the rectus abdominis cavity and forces the diaphragm superiorly, squeezing additional muscles at several points, causing the abdominal region of a well- air out of the lungs. Muscular System © The McGraw−Hill Anatomy, Sixth Edition Companies, 2001 Chapter 9 Muscular System 259 FIGURE 9. The mammary gland is an integumentary structure positioned over the pectoralis major muscle. Skin Anterior layer of rectus sheath Subcutaneous fat Creek External abdominal oblique Internal abdominal Linea alba oblique Transversalis fascia Rectus Transversus abdominis abdominis Posterior layer of rectus sheath FIGURE 9. Muscular System © The McGraw−Hill Anatomy, Sixth Edition Companies, 2001 260 Unit 4 Support and Movement TABLE 9. The external anal sphincter is a funnel-shaped constrictor muscle that surrounds the anal Muscles of the Pelvic Outlet canal. The Inferior to the pelvic diaphragm are the perineal muscles, pelvic outlet—the entire muscular wall at the bottom of the pelvic which provide the skeletal muscular support to the genitalia. The urogenital diaphragm lies immediately deep to the ficial transversus perinei muscles (fig. The muscles of the external genitalia; the pelvic diaphragm is situated closer to the pelvic diaphragm and the urogenital diaphragm are similar in the internal viscera. Together, these sheets of muscle provide support male and female, but the perineal muscles exhibit marked sex- for pelvic viscera and help regulate the passage of urine and feces. The pelvic diaphragm consists of the levator ani and the In males, the bulbospongiosus (bul'bo-spon'je-o-sus) of coccygeus muscles (table 9. When con- pelvic viscera and constrict the lower part of the rectum, pulling tracted, the two muscles constrict the urethral canal and assist it forward and aiding defecation. The ischiocavernosus (is'ke-o-ka˘'ver-no-sus) muscle An episiotomy is a surgical incision,for obstetrical purposes,of inserts onto the pubic arch and crus of the penis in the male the vaginal orifice and a portion of the levator ani muscle of the perineum. Following a pudendal nerve block,an episiotomy may be and the pubic arch and crus of the clitoris of the female. This done during childbirth to accommodate the head of an emerging fetus muscle assists the erection of the penis and clitoris during sex- with minimal tearing of the tissues. Muscular System © The McGraw−Hill Anatomy, Sixth Edition Companies, 2001 Chapter 9 Muscular System 261 (a) (b) Pubococcygeus Symphysis pubis Levator ani Iliococcygeus Urogenital diaphragm Urethra Vagina Obturator canal Anal canal Obturator internus Ischial spine Coccygeus Coccyx Piriformis Ilium Sacroiliac articulation Sacrum (c) FIGURE 9. Muscles of the Vertebral Column ready been described as a long, straplike muscle of the anterior abdominal wall. The extensor muscles located on the posterior The strong, complex muscles of the vertebral column are side of the vertebral column have to be stronger than the flexors adapted to provide support and movement in resistance to the because extension (such as lifting an object) is in opposition to effect of gravity. The extensor muscles consist of a superficial group and a The vertebral column can be flexed, extended, hyperex- deep group. Only some of the muscles of the vertebral column tended, rotated, and laterally flexed (right or left). Muscular System © The McGraw−Hill Anatomy, Sixth Edition Companies, 2001 262 Unit 4 Support and Movement FIGURE 9. The superficial neck muscles and erector spinae group of muscles are illustrated on the right, and the deep neck and back muscles are illustrated on the left. A heavy object should not be lifted with the vertebral column flexed; instead, the hip and knee joints should be actually consists of three groups of muscles: the iliocostalis, flexed so that the pelvic and leg muscles can aid in the task. Each Pregnancy may also put a strain on the erector spinae mus- of these groups, in turn, consists of overlapping slips of muscle. Pregnant women will try to counterbalance the effect of a pro- The iliocostalis is the most lateral group, the longissimus is inter- truding abdomen by hyperextending the vertebral column. This results in an exaggerated lumbar curvature, strained muscles, and a mediate in position, and the spinalis, in the medial position, peculiar gait.