691 Alternative Treatments TABLE 38–3 How to obtain quality alternative compounds Compound Brand/company Source Galantamine/Rhodiola A/P Formula/Ameriden 888-405-3336; http://www.ameriden.com Huperzine-A GNC (General Nutrition Centers) http://www.gnc.com Centrophenoxine Lucidril/International Antiaging Systems (IAS) http://www.antiaging-systems.com; Fax: 011-44870-151-4145 Acetyl-L-carnitine Life Extension Foundation (LEF) 800-544-4440; http://www.lef.org Citicholine Smart Nutrition (SN); LEF http://www.smart-nutrition.net S-adenosylmethionine Donnamet/IAS See above NatureMade (tosylate and butanedisulfonate) http://www.naturemade.com, pharmacies, chain stores, buyer’s clubs, Costco, BJs LEF See above Pyritinol SN 800-479-2107; http://www.smart-nutrition.net Idebenone SN; Thorne Research 800-932-2953 (Thorne) Vinpocetine LEF; SN; Intensive Nutrition See above Rhodiola rosea Rosavin/Ameriden 888-405-3336; http://www.ameriden.com Energy Kare/Kare-N-Herbs http://www.Kare=N-herbs.com Rodax/Pinnacle GNC Rhodiola Force/New Chapter Health food stores or online Ginkgold/Nature’s Way Health food stores, pharmacies Ginkgo Ginkoba/Pharmaton Ginseng (Panax/ Korean) Hsu’s Ginseng 800-388-3818; http://www.hsuginseng.com Power Max 4x/Action Labs 800-932-2953 Piracetam (all racetams) IAS See above L-Deprenyl Jumex tabs, Cyprenil (liquid)/IAS Deprenyl, Selegiline, Eldepryl B vitamins By prescription from U.S pharmacies Bio-Strath/Nature’s Answer 800-681-7099 or health food stores Note This list of specific brands is not comprehensive It simply represents easily available brands that we have used and found to be consistently of good quality Because brands and companies may change, the physician should reevaluate each product over time See Table 38–4 for independent evaluations of many brands and check www.consumerlab.com or www.supplementwatch.com B-vitamin supplement at double the usual adult dose, was given to 75 patients age 55–85 years with mild dementia in a 3-month DBRPC trial The placebo group deteriorated In contrast, the Bio-Strath group showed improvement in short-term memory with physical and emotional benefits at 3 months (Pelka and Leuchtgens 1995) The relationship between B vitamins and cognitive function persuades us to treat brain-injured patients with B vitamins Homeopathy A pilot study (at Spaulding Rehabilitation Hospital in Boston) of 50 patients with mild TBI found that homeo- pathic treatment significantly reduced the intensity of patients’ symptoms (P=0.01) and reduced difficulty functioning (P=0.0008) (Chapman et al 1999) Limitations of this study include the small number of patients, the variety of symptoms, duration of treatment, the use of different combinations of multiple homeopathic preparations in different patients, and questions about the validity and reliability of the measures used (Chapman 2001) Nevertheless, the finding of statistically significant differences in this PC study is intriguing The investigators acknowledged the need for a larger collaborative MC study to validate these findings, but such a study has not been funded as of this date It is not possible to place this study within 692 TABLE 38–4 Resources for information on alternative medicine The Desktop Guide to Complementary and Alternative Medicine: An Evidence Based Approach Edited by Edzard Ernst New York, Mosby, 2001 Focus on Alternative and Complementary Therapies, Pharmaceutical Press, P.O Box 151, Wallingford, OX10 8QU, UK; Phone: +440 1491 829272; Fax: +440 1491 829292; rpsgb@cabi.org Martindale: The Complete Drug Reference Pharmaceutical Press, 1 Lambeth High St., London SE17JN, UK American Botanical Council, P.O Box 144345, Austin, TX, 78714; Phone: 512-926-4900; http://www.herbalgram.org ConsumerLab, http://www.ConsumerLab.com FDA MedWatch, http://www.fda.gov/medwatch Herb Research Foundation, 1007 Pearl St., Suite 200, Boulder, CO 80302; Phone: 303-449-2265; http://www.herbs.org Natural Medicines Comprehensive Database, Therapeutic Research Facility, 3120 W March Lane, PO Box 8190, Stockton, CA 95208; Phone: 209-472-2244; Fax: 209-4722249; Mail@NaturalDatabase.com; http:// www.NaturalDatabase.com TEXTBOOK OF TRAUMATIC BRAIN INJURY and L-deprenyl The brands of the herbs, ginkgo, and ginseng have been assessed by independent laboratories as reported by ConsumerLab.com The authors have personally contacted the manufacturers of Rhodiola rosea, galantamine, and SAMe to obtain adequate information regarding standardization, content, purity, and batch testing procedures (including shelf life) to be reasonably assured of the quality and reliability of these products Invariably, some products and companies will change over time Physicians should stay current by using unbiased sources of product evaluation and rigorous studies Table 38–4 provides resources for those interested in reliable information on alternative compounds Anyone interested in an alternative product may contact the manufacturer and request information about content, purity, testing, and quality control, as well as consulting independent sources of evaluation when available Alternative compounds can offer significant benefits with few side effects in some patients with TBI Certain agents may help repair the nervous system and enhance plasticity In practice, it often requires several attempts to design an effective combination of treatments Many patients and families can participate in the development of an alternative treatment regimen Supplement Watch, http://www.supplementwatch.com References the framework of the other treatments in this chapter because the pathophysiological basis of homeopathy is unproven Biological effects are inferred from observations of change after treatment is administered For a discussion of the state of homeopathic research, we refer the reader to Alternative and Complementary Treatment in Neurological Illness (Weintraub 2001) Summary Doctors and consumers are concerned about the quality of herbs and nutrients Advances in biochemistry have improved the purity and stability of many products (Wagner 1999) Although the publication of specific brands is not the norm in a text of this kind, in the field of alternative medicine it is particularly important to choose products that have proven to be of good quality To help clinicians find their way through the morass of unreliable, ineffective lookalikes, Table 38–3 lists brands that we have investigated The following compounds in the brands we have listed are pharmaceutical grade, regulated by European governmental agencies: centrophenoxine, acetyl-Lcarnitine, citicholine, S-adenosylmethionine (SAMe), Picamilon, pyritinol, idebenone, vinpocetine, racetams, Ackerman PT, Dykman RA, Holloway C, et al: A trial of piracetam in two subgroups of students with dyslexia enrolled in summer tutoring J Learn Disabil 24:542–549, 1991 al-Zuhair H, Abd el-Fattah A, el-Sayed MI: The effect of meclofenoxate with ginkgo biloba extract or zinc on lipid peroxide, some free radical scavengers and the cardiovascular system of aged rats Pharmacol Res 38:65–72, 1998 Alvarez XA, Mouzo R, Pichel V, et al: Double-blind placebocontrolled study with citicoline in APOE genotyped Alzheimer’s disease patients: effects on cognitive performance, brain bioelectrical activity and cerebral perfusion Methods Find Exp Clin Pharmacol 21:633–644, 1999 Amano T, Terao S, Imada I: Effects of 6-(10-hydroxydecyl)-2,3dimethoxy-5-methyl-1,4-benzoquinone (idebenone) and related benzoquinones on porcine pancreas phospholipase A2 activity Biol Pharm Bull 18:779–781, 1995 Anonymous: Acetyl-L-carnitine Altern Med Rev 4:438–441, 1999 Arciniegas DB: Traumatic brain injury and cognitive impairment: the cholinergic hypothesis Neuropsychiatry Reviews 17–20, 2001 Arrigo A, Casale R, Buonocore M, et al: Effects of acetyl-L-carnitine on reaction times in patients with cerebrovascular insufficiency Int J Clin Pharmacol Res 10:133–137, 1990 Bacci-Ballerini F, Lopez-Anguera A, Accarezy N, et al: Tratiamiento del sindrome posconmocional con SAMe Med Clin (Barc) 80:161–164, 1983 694 Fischhof PK, Saletu B, Ruther E, et al: Therapeutic efficacy of pyritinol in patients with senile dementia of the Alzheimer type (SDAT) and multi-infarct dementia (MID) Neuropsychobiology 26:65–70, 1992 Flicker L, Grimley-Evans G: Piracetam for dementia or cognitive impairment (Cochrane Review) Cochrane Database Syst Rev 2:CD0010112001 Furmanowa M, Oledzka H, Michalska M, et al: Rhodiola rosea L (Roseroot): in vitro regeneration and the biological activity of roots, in Biotechnology in Agriculture and Forestry, Vol 33, in Medicinal and Aromatic Plants VIII Edited by Bajaj YPS Berlin and Heidelberg, Germany, Springer-Verlag, 1995, pp 412–426 Furmanowa M, Skopinska-Rozewska E, Ragola E, et al: Rhodiola rosea in vitro culture: phytochemical analysis and antioxidant action Acta Societatis Botanicorum Poloniae 67:69– 73, 1998 Galletti P, De Rosa M, Cotticelli MG, et al: Biochemical rationale for the use of CDPcholine in traumatic brain injury: pharmacokinetics of the orally administered drug J Neurol Sci 103 (suppl):S19–25, 1991 Gillis JC, Benefield P, McTavish D: Idebenone: a review of its pharmacodynamic and pharmacokinetic properties, and therapeutic use in age-related cognitive disorders Drugs Aging 5:133–152, 1994 Gouliaev AH, Senning A: Piracetam and other structurally related nootropics Brain Res Brain Res Rev 19:180–222, 1994 Gutzmann H, Hadler D: Sustained efficacy and safety of idebenone in the treatment of Alzheimer’s disease: update on a 2-year double-blind multicentre study J Neural Transm Suppl 54:301–310, 1998 Hakkarainen H, Hakamies L: Piracetam in the treatment of post-concussional syndrome: a double-blind study Eur Neurol 17:50–55, 1978 Hassing L, Wahlin A, Winblad B, et al: Further evidence of the effects of vitamin B12 and folate levels on episodic memory functioning: a population-based study of healthy very old adults Biol Psychiatry 45:1472–1480, 1999 Hayes RL, Dixon CE: Neurochemical changes in mild head injury Semin Neurol 14:25–31, 1994 Herrmann WM, Kern U, Rohmel J: On the effects of pyritinol on functional deficits of patients with organic mental disorders Pharmacopsychiatry 19:378–385, 1986 Hindmarch I, Fuchs HH, Erzigkeit H: Efficacy and tolerance of vinpocetine in ambulant patients suffering from mild to moderate organic psychosyndromes Int Clin Psychopharmacol 6:31–43, 1991 Huber W, Willmes K, Poeck K, et al: Piracetam as an adjuvant to language therapy for aphasia: a randomized double-blind placebo-controlled pilot study Arch Phys Med Rehabil 78:245–250, 1997 Ishihara K, Katsuki H, Sugimura M, et al: Idebenone and vinpocetine augment long-term potentiation in hippocampal slices in the guinea pig Neuropharmacology 28:569–573, 1989 TEXTBOOK OF TRAUMATIC BRAIN INJURY Itil TM, Menon GN, Songar A, et al: CNS pharmacology and clinical therapeutic effects of oxiracetam Clin Neuropharmacol 9 (suppl 3):S70–72, 1986 Itil TM, Eralp E, Ahmed I, et al: The pharmacological effects of ginkgo biloba, a plant extract, on the brain of dementia patients in comparison with tacrine Psychopharmacol Bull 34:391–397, 1998 Kang SY, Kim SH, Schini VB, et al: Dietary ginsenosides improve endothelium-dependent relaxation in the thoracic aorta of hypercholesterolemic rabbit Gen Pharmacol 26:483–487, 1995 Kelly GS: L-Carnitine: therapeutic applications of a conditionally essential amino acid Altern Med Rev 3:345–360, 1998 Kessler J, Thiel A, Karbe H, et al: Piracetam improves activated blood flow and facilitates rehabilitation of poststroke aphasic patients Stroke 31:2112–2116, 2000 Kitamura K: Therapeutic effect of pyritinol on sequelae of head injuries J Int Med Res 9:215–221, 1981 Kitani K, Minami C, Maruyama W, et al: Common properties for propargylamines of enhancing superoxide dismutase and catalase activities in the dopaminergic system in the rat: implications for the life prolonging effect of (-)deprenyl J Neural Transm Suppl (60):139–156, 2000 Knezevic S, Mubrin Z, Risberg J, et al: Pyritinol treatment of SDAT patients: evaluation by psychiatric and neurological examination, psychometric testing and rCBF measurements Int Clin Psychopharmacol 4:25–38, 1989 Knoll J: Outlines of a drug strategy to slow brain aging Neuropsychopharmacologia Hungarica 11:151–170, 2000 Kurkin VA, Zapesochnaya GG: Khimicheskiy sostav i farmakologicheskiye svoystva rasteniy roda Rhodiola Obzor [Chemical composition and pharmacological properties of Rhodiola rosea] (Russian) Khim-Farm Zh [Chemical and Pharmaceutical Journal Moscow] 20:1231–1244, 1986 Le Bars PL, Katz MM, Berman N, et al: A placebo-controlled, double-blind, randomized trial of an extract of Ginkgo biloba for dementia North American EGb Study Group JAMA 278:1327–1332, 1997 Leon-Carrion J, Dominguez-Roldan JM, Murillo-Cabezas F, et al: The role of citicholine in neuropsychological training after traumatic brain injury NeuroRehabilitation 14:33– 40, 2000 Levin HS: Treatment of postconcussional symptoms with CDPcholine J Neurol Sci 103 (suppl):S39–42, 1991 Lolic MM, Fiskum G, Rosenthal RE: Neuroprotective effects of acetyl-L-carnitine after stroke in rats Ann Emerg Med 29:758–765, 1997 Long DA, Ghosh K, Moore AN, et al: Deferoxamine improves spatial memory performance following experimental brain injury in rats Brain Res 717:109–117, 1996 Lozano R: CDP-choline in the treatment of cranio-encephalic traumata J Neurol Sci 103 (suppl):S43–47, 1991 Lun A, Gruetzmann H, Wustmann C, et al: Effect of pyritinol on the dopaminergic system and behavioural outcome in an animal model of mild chronic postnatal hypoxia Biomed Biochim Acta 48:S237–242, 1989 PA R T V I I Prevention This page intentionally left blank 39 Pharmacotherapy of Prevention Saori Shimizu, M.D., Ph.D Carl T Fulp, M.S Nicolas C Royo, Ph.D Tracy K McIntosh, Ph.D NEUROPATHOLOGICAL INVESTIGATIONS HAVE classified traumatic brain injury (TBI) as either focal or diffuse (Graham et al 1995) Although focal injuries most often involve contusions and lacerations accompanied by hematoma (Gennarelli 1994), diffuse brain swelling, ischemic brain damage, and diffuse axonal injury are also considered to be major components of the diffuse injury profile (Adams et al 1989; Graham et al 1995; Maxwell et al 1997) All TBIs can be further stratified into primary injury (encompassing the immediate, nonreversible mechanical damage to the brain), and secondary or delayed injury, which represents a potentially reversible process with a time of onset ranging from hours to days after injury that progresses for weeks or months (Graham et al 1995) This secondary injury process is a complex and poorly understood cascade of interacting functional, structural, cellular, and molecular changes, including, but not limited to, impairment of energy metabolism, ionic dysregulation, breakdown of the blood–brain barrier (BBB), edema formation, activation and/or release of autodestructive neurochemicals and enzymes, changes in cerebral perfusion and intracranial pressure (ICP), inflammation, and pathologic/ protective changes in intracellular genes and proteins (Figure 39–1) Although these events may lead to delayed cell death and/or neurological dysfunction, the delayed onset and reversibility of secondary damage offer a unique opportunity for targeted therapeutic pharmacological intervention to attenuate cellular damage and functional recovery during the chronic phase of the injury (McIntosh et al 1998) It is now well established that several clinically relevant experimental TBI models mimic many aspects of behavioral impairment and histopathological damage reported after human brain injury (for review see Laurer et al 2000) Moreover, these experimental models provide us with the unique opportunity to both identify and investigate the pathophysiological changes triggered by TBI and target these pathways using new pharmacological strategies As the pathophysiological sequelae of TBI are multifactorial, the development and characterization of new compounds remains extremely challenging This chapter reviews some of the more promising neuroprotective strategies studied to date in clinical and preclinical settings Excitatory Amino Acid Antagonists Pathologic release of the excitatory amino acid (EAA) neurotransmitters glutamate and aspartate and subsequent activation of specific glutamate receptors result in increased neuronal influx of cations (sodium and calcium) into the cell (Figure 39–2) This ionic influx may damage or destroy cells (i.e., excitotoxicity) through direct or indirect pathways (Olney et al 1971) Both experimental and clinical brain injury induce an acute and potentially neurotoxic increase in extracellular glutamate concentrations (Faden et al 1989; Globus et al 1995; Katayama et 699 700 F I G U R E 3 9 – 1 Cascade of secondary damaging events in experimental traumatic brain injury al 1989, 1990; Nilsson et al 1990; Palmer et al 1993; Panter et al 1992) Although most experimental studies have suggested that the posttraumatic rise in extracellular glutamate is of short duration, clinical studies have reported that glutamate concentrations are significantly elevated in the cerebrospinal fluid (CSF) of brain-injured TEXTBOOK OF TRAUMATIC BRAIN INJURY patients for several days or perhaps weeks (Baker et al 1993; Palmer et al 1994) Regional distribution of both N-methyl-D-aspartate (NMDA) and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate/kainic acid (AMPA/KA) receptors has been directly related to the selective vulnerability of specific brain regions caused by CNS injury (for review see Choi 1990) Miller et al (1990) reported an acute decrease in NMDA but not AMPA/KA receptor binding in the hippocampal CA1 stratum radiatum, the molecular layer of the dentate gyrus, and the outer (1–3) and inner (5–6) layers of the neocortex within 3 hours after TBI in the rat The hippocampus, which plays a prominent role in learning and memory, possesses a high density of glutamate receptors (Monaghan and Cotman 1986) Cognitive dysfunction, including a suppression of long-term potentiation and deficits in learning and memory, has been reported after TBI (for review see Albensi 2001) Sun and Faden (1995b) demonstrated that pretreatment with antisense oligodeoxynucleotides directed against the NMDA-R1 receptor subunit enhances survival and neurological motor recovery after TBI in rats These studies un- FIGURE 39–2 Glutamate receptor subtypes: N-methyl-D-aspartate (NMDA) and α-amino-3-hydroxy-5methyl-4-isoxazolepropionate (AMPA)/kainate APV=2-amino-5-phosphovaleric acid; CPP=3-(2-carboxypiperizin-4yl)-propyl-1-phosphonic acid; I2CA=indole-2-carboxylic acid Pharmacotherapy of Prevention derscore the potentially important role of the NMDA receptor in mediating part of the pathological response to brain trauma (Table 39–1) Although competitive NMDA receptor antagonists are logical candidates for the treatment of traumatic CNS injury, most of the early-generation compounds such as 2-amino-5-phosphovaleric acid (APV) and 3-(2-carboxypiperizin-4yl)-propyl-1-phosphonic acid (CPP) were strongly lipophobic and possessed poor BBB permeability, resulting in the necessity for direct CNS administration Intracerebral administration of CPP was shown to improve neurological outcome (Faden et al 1989), and intracerebroventricular APV administration was reported to reverse hypermetabolism after TBI in rats (Kawamata et al 1992) In addition, CPP has recently been shown to increase apoptotic damage despite its ability to decrease excitotoxic cell damage in a model of TBI in the developing rat (Pohl et al 1999) More recently developed competitive NMDA antagonists such as Selfotel (CGS-19755 or cis-4-[phosphomethyl]-2-piperidine carboxylic acid), LY233053 ([1][2SR,4RS]-4-[1H-tetrazol-5-ylmethyl] piperidine-2-carboxylic acid), and CP101,606 ([1S, 29]-1-[4-hydroxyphenyl]-2-[hydroxy-4-phenylpiperidino]-1-propanol), an NR2B-selective NMDA receptor antagonist, have been shown to have greater BBB permeability than earlier generations of similar compounds (Menniti et al 1995) Although Selfotel has shown no beneficial effects on behavioral outcome, administration of this antagonist has been reported to reduce trauma-induced extracellular glutamate release in rats (Panter and Faden 1992) On the basis of this and other published data from experimental models of ischemia, a multicenter trial of Selfotel was initiated in the United States and Europe but was prematurely terminated because of side effects associated with competitive NMDA antagonism (Bullock 1995) Administration of CP101,606 and its stereoisomers has been shown to attenuate both cognitive dysfunction and regional cerebral edema in TBI in the rat (Okiyama et al 1997, 1998) The CP101,606 compound is currently in Phase II trials in the United States and in Phase I trials in Japan for the potential treatment of brain injury and has been shown to be well tolerated and able to penetrate CSF and brain (Bullock et al 1999; Merchant et al 1999) In the initial pilot studies, mild to moderately head-injured patients did not exhibit differences in performance on the Neurobehavioral Rating Scale or Kurtzke Scoring (Merchant et al 1999), whereas severely head-injured patients who were treated with the CP101,606 compound presented with, on average, better Glasgow Outcome Scores (Bullock et al 1999) 701 Noncompetitive NMDA receptor antagonists also appear to have efficacy in the treatment of TBI Hayes et al (1988) first reported that pretreatment with the dissociative anesthetic and noncompetitive NMDA antagonist phencyclidine (PCP) attenuated neurological motor deficits after TBI in rats Similar results were obtained with prophylactic treatment using dizocilpine (MK-801) (McIntosh et al 1990) Treatment with MK-801 after TBI in rats also improved brain metabolic function and restored magnesium homeostasis (McIntosh et al 1990), and administration of higher doses improved neurological motor deficits and reduced regional cerebral edema (Shapira et al 1990) Pretreatment with MK-801 was found to attenuate the extracellular rise in glutamate associated with closed head injury followed by hypoxia in rats (Katoh et al 1997) and enhance the recovery of spatial memory performance in animals subjected to combined TBI and entorhinal cortical lesions (Phillips et al 1997) Administration of the noncompetitive NMDA antagonists dextrophan and dextromethorphan improved brain metabolic state, attenuated neurological motor deficits, and reduced the postinjury decline in brain magnesium concentrations observed after TBI in rats (Faden et al 1989) Golding and Vink (1995) reported that dextromethorphan improved brain bioenergetic state and restored brain magnesium homeostasis after TBI in rats Dextrophan also improved neurologic motor function and reduced edema after TBI in rats (Shohami et al 1993) The NMDA-associated channel blocker ketamine has also been shown to improve posttraumatic cognitive outcome (Smith et al 1993a), maintain both calcium and magnesium homeostasis (Shapira et al 1993), and reduce expression of several immediate early genes (IEGs) induced in cerebral cortex and hippocampal dentate gyrus after TBI in rats (Belluardo et al 1995) Gacyclidine, a more recently discovered phencyclidine derivative that acts as a noncompetitive NMDA antagonist (Hirbec et al 2000), reduced lesion volume and improved neuronal survival and motor function when administered intraparenchymally after TBI (Smith et al 2000) Although administration of the high-affinity, noncompetitive NMDA receptor antagonist CNS1102 (Aptiganel or Cerestat) was shown to attenuate contusion volume and hemispheric swelling after TBI in rats (Kroppenstedt et al 1998), a clinical trial of this drug was prematurely terminated because of high mortality rates in an associated stroke trial Although few studies have evaluated the potential neuroprotective effects of noncompetitive NMDA antagonists in models of brain trauma, Smith et al (1997) reported that the NMDA receptor-associated ionophore blocker remacemide (2-amino-N-[1-methyl1,2-diphenylethyl] acetamide hydrochloride) also signifi- 702 TABLE 39–1 TEXTBOOK OF TRAUMATIC BRAIN INJURY Excitatory amino acid antagonists and agonists classified according to binding site Compound Type of research Outcome References APV e ↓ glucose utilization Kawamata et al 1992 CPP e ↑ motor function, apoptotic damage; ↓ necrosis Faden et al 1989; Pohl et al 1999 Selfotel e,c ↑ bioenergetic state, Mg2+ homeostasis Bullock 1995; Juul et al 2000; Morris et al 1998; Panter et al 1992 CP101,606 e,c ↑ cognitive function; ↓ cell death, edema Bullock et al 1999; Merchant et al 1999; Okiyama et al 1997, 1998 Phencyclidine e ↑ motor function Hayes et al 1988 MK-801 e ↑ bioenergetic state, Mg homeostasis, motor/ cognitive function; ↓edema, glutamate release Dextrophan e ↑ bioenergetic state, motor Faden et al 1989 function, Mg2+ homeostasis; ↓ edema Dextromethorphan e ↑ bioenergetic state, motor function, Mg2+ homeostasis Faden et al 1989; Golding et al 1995 Ketamine e ↑ cognitive function, Mg2+,Ca2+ homeostasis; ↓ immediate early genes Belluardo et al 1995; Shapira et al 1993; Smith et al 1993a Gancyclidine e ↑ motor function; ↓ cell death, Hirbec et al 2001; Smith et al lesion volume 2000 Cerestat e,c ↓ edema, lesion volume; ↑ psychomotor side effect Kroppenstedt et al 1998; Muir et al 1995 Remacemide hydrochloride e ↓ lesion volume Smith et al 1997 NMDA glycine site I2CA e ↑ motor/cognitive function; ↓ edema Smith et al 1993b NMDA Mg2+ site MgCl2 e ↑ motor/cognitive function; ↓edema Bareyre et al 2000; Heath and Vink 1998; McIntosh et al 1989; Okiyama et al 1995; Saatman et al 2001; Smith et al 1993a MgSO4 e ↑ motor/cognitive function; ↓ edema Heath and Vink 1998; McIntosh et al 1988 e ↓ edema, BBB breakdown Okiyama et al 1998 Eliprodil e ↑ cognitive function; ↓ lesion volume Hogg et al 1998 ODC inhibitor DFMO e ↑ cognitive function; ↓ edema, Baskaya et al 1996 ODC mGluR1 antagonist AIDA e ↑ motor/cognitive function; ↓ cell death, lesion volume NMDA antagonist Competitive Noncompetitive NMDA polyamine site Ifenprodil 2+ Katoh et al 1997; McIntosh et al 1990; Phillips et al 1997; Shapira et al 1990 Faden et al 2001; Lyeth et al 2001 703 Pharmacotherapy of Prevention TABLE 39–1 Excitatory amino acid antagonists and agonists classified according to binding site (continued) Type of research Outcome References mGluR1/2 antagonist MCPG e ↓ cell death Gong et al 1995; Mukhin et al 1996 mGluR2 agonist LY354740 e ↑ motor function Allen et al 1999 DCG-IV e ↓ cell death Zwienenberg et al 2001 mGluR3 agonist CPPG e No effect Zwienenberg et al 2001 mGluR5 antagonist MPEP e ↑ motor/cognitive function; ↓ lesion volume Movsesyan et al 2001 Inhibition of Glu release Lamotrigine e,c ↓ glutamate release Miller et al 1986; Showalter and Kimmel 2000 BW1003C87 e ↓ edema Okiyama et al 1995 619C89 e,c ↑ motor/cognitive function; ↓ cell death, gliosis Sun et al 1995; Voddi et al 1995 Riluzole e ↑ motor/cognitive function; ↓ edema, lesion volume, glutamate release Bareyre et al 1997; McIntosh et al 1996; Stover et al 2000; Wahl et al 1997; Zhang et al 1998 e ↑ cognitive function; ↓ cell death, edema Hicks et al 1994; Smith et al 1993b CNQX e ↓ glucose utilization Kawamata et al 1990, 1992 NBQX e ↓ cell death Bernert and Turski 1996; Ikonomidou and Turski 1996; Ikonomodou et al 1996, 2000 GYKI-52466 e ↑ cognitive function; ↓ cell death Hylton et al 1995 Talampanel e ↓ cell death Belayev et al 2001 Compound AMPA/KA antagonist KYNA Competitive Noncompetitive Note BBB=blood–brain barrier; c=clinical trial; e=experimental study; NMDA = N-methyl-D-aspartate cantly reduced posttraumatic cortical lesion volume after TBI in rats The magnesium ion functions as a key endogenous modulator of the NMDA receptor, and its essential roles in many bioenergetic and cellular metabolic and genomic processes makes it an attractive candidate for use in the treatment of TBI The loss of intracellular magnesium concentrations after experimental TBI (Shohami et al 1993; Vink et al 1996) suggests that replacement therapy using this ionic salt may have therapeutic value Both preand postinjury treatment with magnesium salts (MgCl2 or MgSO4) has been demonstrated to improve neurological motor and cognitive deficits and decrease regional cerebral edema formation (Bareyre et al 2000; McIntosh et al 1988, 1989; Okiyama et al 1995; Saatman et al 2001; Shapira et al 1993; Smith et al 1993a) Because of this documented efficacy in experimental trauma models, a single-center National Institutes of Health–sponsored clinical trial in severely injured TBI patients has been initiated in the United States Other strategies to block NMDA-receptor associated neurotoxicity involve blockade or modulation of the NMDA receptor–associated glycine sites and/or polyamine binding sites One selective glycine site antagonist, indole-2-carboxylic acid (I2CA), has been shown to improve behavioral outcome and reduce edema after TBI in rats (Smith et al 1993b) Two broad-spectrum glutamate antagonists, kynurenate (KYNA) and 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), which antagonize both the glycine site and AMPA/KA receptors with varying affinity, have also been shown to be efficacious in reducing posttraumatic metabolic and neurobehavioral dysfunction in experimental TBI (Kawamata et al 1992; Smith et al 1993b) Postinjury administration of KYNA reduced the posttraumatic loss of hippocampal neurons after TBI in the rat (Hicks et al 1994) Inhibition of the ornithine decar- 755 Index nootropics, 679 pain, 419 personality disorders, 246 psychosis, 214 Delirium, 175–195 causes of, 180–181, 181t, 191 in continuum of consciousness, 176, 177f definitions of, 175–178, 179, 353, 354t differential diagnosis of, 339 duration of, 186 encephalography in, 187–189 environmental manipulations in, 191–192 functional neuroimaging in, 190–191 hyperactive, 178, 179 affecting outcome, 185 hypoactive, 178 affecting outcome, 185 medications in, 192–194 motoric agitation in, 179 neuropathophysiology of, 186f, 186–191 rating scales for, 182–184, 183t and recovery of cognitive abilities, 180, 181f reversibility in elderly patients, 185 risk factors for, 181–182, 182t severity and location of injury in, 184–185 signs and symptoms of, 178t, 178–180 structural neuroimaging in, 189–190 subclinical, 176–177 treatment of, 191–194 Delirium Rating Scale (DRS), 177, 183t, 184 Dementia in Alzheimer’s disease See Alzheimer’s disease awareness deficits in, 356 differential diagnosis of, 339 in elderly persons, cholinesterase inhibitors affecting, 504 PET scans in, 119 pugilistica, 456, 500 SPECT imaging in, 110, 111 Demoralization as dysphoric state, 339 Denial of illness, 354t organic, 246 and psychotherapy, 648–649, 652t in substance abuse, 518 L-Deprenyl, 681t–682t, 683t, 690, 691t in personality disorders, 254, 255t Depression, 201–205, 208 and aggressive behavior, 203, 264, 264t anxiety in, 203 apathy associated with, treatment of, 347 in children, 485 differential diagnosis of, 488 treatment of, 489 demographic variables in, 204t, 204–205, 205t diagnosis of, 203 differential diagnosis, 167, 203–204 as dysphoric state, 339 in elderly persons, 502–503 functional MRI in, 124 headache in, 389t medications in, 615–619 adverse effects of, 618–619 guidelines for, 610 in mild TBI, 290–292, 291t medications in, 298 PET scans in, 119 with posttraumatic stress disorder, 237 prevalence of, 201–203, 202f in seizures after brain injury, 314 SPECT imaging in, 110, 113 in substance abuse, treatment of, 520–521 suicide risk in, 737 treatment of, 208–209–210 Derogatis Interview of Sexual Function, 441 Desensitization in pain management, 430, 430t Desferal, neuroprotection with, 706t, 707 Design Fluency Test, 161t Desipramine in cognitive impairment, 623 in depression, 209, 298, 617 in pain relief, 425t Dexamethasone in pain relief, 425t Dexanabinol, neuroprotection with, 706t, 711 Dextroamphetamine adverse effects of, 624 in affective lability, 621 in attention-deficit/hyperactivity disorder, 489 in cognitive dysfunction, 328, 622t, 622–623 in fatigue, 379, 627 interaction with haloperidol, 631 in motivational loss, 348, 348t in personality disorders, 254, 254t Dextromethorphan as NMDA receptor antagonist, 701, 702t psychiatric side effects of, 611t Dextrophan as NMDA receptor antagonist, 701, 702t DFMO compound as NMDA receptor antagonist, 702t, 704 Diabetes insipidus after TBI, 66, 66t Diacylglycerol formation in brain injury, 705 Diathermy in pain relief, 427 Diazepam adverse effects of, 629 in delirium, 194 Differential diagnosis of TBI, 166–170 Differential reinforcement of other behaviors (DRO), 669–670, 670t Diffuse injuries, 28, 28t, 34–38, 699 axonal, 34–38, 34f, 35f, 34t, 35t experimental models of, 44 hypoxic-ischemic damage in, 37–38 multifocal vascular injury in, 38 secondary insults in, 38 Diffusion-tensor imaging, 94f, 94–95, 95f Difluoromethylornithine (DFMO) as NMDA receptor antagonist, 702t, 704 Digit Span Test, 161t, 163 Digit Symbol Test, 161t, 163 Digitalis, psychiatric side effects of, 611t, 612t Dihydroergotamine in headache, 390 Diminished capacity concept, 593 Disabilities after mild TBI, 293 determined in civil litigation, 599 estimated new numbers of, 20–22, 22f Disability insurance, 576–577 Disability Rating Scale (DRS), 81 Disorientation in delirium, 180 Distractibility, testing of, 163 Divalproex sodium for elderly persons, 504 Dix-Hallpike maneuver, 400 Dizocilpine (MK-801) as NMDA receptor antagonist, 701, 702t Dizziness and balance problems, 393–403, 413 in benign positional paroxysmal vertigo, 400 common complaints in, 394–395, 395t diagnostic procedures in, 394–399 drug-induced, 395, 397t emotional factors in, 402–403 history of patient in, 394–395 laboratory tests in, 398–399, 399t medications in, 401, 401t in Ménière’s disease, 400 outcomes in, 403 in perilymphatic fistula, 400 physical examination in, 395–398, 398t physiology in, 394 prevalence of, 393–394 vestibular dysfunction in central, 400–401 peripheral, 400 vestibular rehabilitation in, 402 Dizziness Handicap Inventory, 395, 396f 756 Do-not-resuscitate (DNR) orders, 587 Donepezil affecting memory in mild TBI, 299 and cognition in elderly persons, 504 in cognitive dysfunction, 326t, 327–328, 622t, 625–626 in delirium, 194 in mood disorders, 209 in motivational loss, 347, 348f Dopamine systems activity in delirium, 186 in aggression, 263 in aging brain, 499, 499t agonists affecting cognition in elderly persons, 504 affecting memory, 299 in fatigue, 379 in motivational loss, 347–348 in personality disorders, 254–255, 255t in diminished motivation, 343 dysfunction after brain injury, 41, 613–614 and personality attributes, 248 Dopaminergic agents adverse effects of, 624 in apathy, 627 in cognitive impairment, 622t, 622–624 Doxepin adverse effects of, 618 affecting sexual function, 440t Droperidol in delirium, 193 Drug abuse See Substance abuse Drug interactions with antidepressants, 619 Drug therapy See Medications DSM-III diagnoses, depression after mild TBI, 291 DSM-III-R diagnoses, delirium, 177 DSM-IV diagnoses delirium, 177 insomnia, 372 DSM-IV-TR diagnoses, 64, 64t alcoholism and drug addiction, 511, 512t concussion, 280 delirium, 178, 179t depression, 201, 203 in forensic psychiatric evaluation, 597 learning disorders, 169 manic syndromes, 205 pain disorder with psychological factors, 419 personality changes in medical conditions, 214t, 249t, 261t psychotic disorders, 214 Durable power of attorney, 587–588 Dynamic Gait Index, 398 TEXTBOOK OF TRAUMATIC BRAIN INJURY Dynorphin activity after brain injury, 41 Dysarthria, 326 Eagle syndrome, 387, 387t, 390 Ear, anatomy of, 394 Edinburgh Rehabilitation Status Scale, and postconcussive symptoms, 286 Education See also Psychoeducation for pain management, 429t programs for disabled children, 560, 565 and school problems after brain injury, 68, 478–479, 488 and school relationship with parents, 549–550 Eldepryl, 690 Elderly persons, 495–504 age affecting outcomes after injury, 495–498, 497t agitation and psychosis in, 503–504 Alzheimer’s disease in See Alzheimer’s disease apoE ε4 allele linked to poor outcomes, 500 assessment of, 501–502 clinical features of injuries in, 501 cognitive dysfunction in, treatment of, 504 cognitive outcome after injury, 497, 501–502 delirium reversibility in, 185 depression in, 502–503 falls in, 495, 496t, 733 families of, 502 functional outcome after injury, 496–497, 501–502, 501f medications affecting, 502, 503t neurobiology of aging in, 498 neurochemical changes in, 498–499, 499t neuroimaging, 501 population of, 495, 496t treatment of, 502–504 Electrical injuries, brain damage in, 74, 75t Electroconvulsive therapy in agitated delirium, 194 in depression, 618 in mania, 620 in mood disorders, 209 Electroencephalography, 142–144 burst-suppression ratio in, 144 in delirium, 187–189 in headache after trauma, 388 in mild TBI, 296 normal and trauma-related findings in, 142t, 142–144 outcome predictions in, 144–145 quantitative (QEEG), 144–147 in delirium after brain injury, 188–189 discriminant function scores in, 145–147 in mild TBI, 296–297 in seizures, 311 silence ratio in, 144 Electronystagmography, 398–399, 399t Electrophysiology, 135–153 abnormal rhythms in, 137 alpha rhythm in, 136, 137f, 137t basic principles of, 136–137 beta activity in, 136, 137f, 137t brain electrical activity mapping in (BEAM), 139, 141f delta activity in, 136, 137f, 137t dipoles in radially oriented, 138, 138f tangentially oriented, 138, 138f electrode placement in, 138, 139f electroencephalography see Electroencephalography event-related potentials in, 147, 149–152 evoked potentials in, 147–152 See also Evoked potentials idling in, 136, 137 intermixed slowing in, 137 limitations of recordings in, 140 magnetoencephalography, 152–153 recording methods, 140–141 in mild TBI, 296–297 misinterpretation of data in, 139 montages in, 138, 140f normal rhythms in, 136–137 quantitative analyses in, 139 reactivity diminished in, 137 recording methods in, 137–141 sharp waves in, 137 slow waves in, 137 spikes in, 137 thalamic pacemaker neurons in, 136 theta activity in, 136, 137f, 137t Eletriptan in headaches, 390 Eliprodil as NMDA receptor antagonist, 702t, 704 Emergency department workup in severe TBI, 51 Emotional disorders, 61t in addicted persons with brain damage, 527 in children with brain injuries, 479 dizziness and balance problems in, 402–403 environmental interventions in, 671 medications in, 615–621 Emotional incontinence, 620 Employment after brain injury, 574–576, 575f and vocational rehabilitation, 577–578 Encephalopathy in boxers, 456 Endocannabinoid system activity in brain injury, 711 757 Index Endocrine symptoms, 66, 66t Environmental interventions in aggression, 671 in delirium, 191–192 for elderly persons, 502 in emotional reactions to injury, 671 Epidemiology, 3–25 case definitions and inclusion criteria, 3–6, 4t–5t estimated annual injuries, 10f estimation of new disabilities, 20–22, 22f exposures associated with injuries, 12f, 12–13, 13f fatality rates, 6, 8f, 16–17, 18f in elderly patients, 496 high-risk groups, 8–12 hospital discharges, 14–15 by diagnoses, 8, 9t, 14, 16f, 24 sex- and age-specific, 15f, 24 hospitalization rates, 7–8, 10f incidence studies, 6–8, 7f mild TBI, 281t, 281–282 seizures, 309–311 severity distribution of injuries, 13–14, 14f types of lesions, 15–16, 17f Epilepsy See Seizures Epinephrine activity after brain injury, 40–41 Epworth Sleepiness Scale, 375, 376t Equestrian sports, injuries in, 460 Erectile dysfunction, treatment of, 446–447 Eriksonian stages and childish behavior after brain injury, 250, 250t clinical use of, 254 Estrogen, 439, 440t, 445t therapy affecting sexual function, 440t Ethical issues, 583 See also Legal issues in sexual dysfunction, 447–448 Ethnicity or race and family reactions to disabilities, 554–555 and risk of brain injury, 9 Ethosuximide in seizures with behavioral symptoms, 315t Evaluation of patient See Assessment procedures Evaluative model of behavioral therapy, 663, 663t Event-related potentials, 147, 149–152 middle-latency, 149–150 in mild TBI, 297 N200 latency in, 151–152 P300 latency in, 151–152 in sensation-seeking behavior, 247 Evoked potentials, 147–152 auditory mismatch negativity in (MMN), 151 contingent negative variation in (CNV), 151 latency of, 147 long-latency, 150 middle-latency, 149–150 in mild TBI, 297 multimodal, 148 N100 waveform in, 147, 147f P30 and P50 waveforms in, 147, 147f polarity of, 147 postinjury P50 response to paired auditory stimuli, 149–150, 150f short-latency, 147–149 somatosensory, in posttraumatic amnesia, 187–188 Executive functions in addicted persons with brain damage, 526–527 changes related to clinical rating of MR scans, 95–97, 97f impairment of, 324t, 324–325 in personality disorders, 252, 252t testing of, 161t, 164 Exercise in pain relief, 428 Experimental models diffuse brain injury, 44 focal brain injury, 43–44 mild brain injury, 282–283, 461 seizures, 312 Expert Consensus Panel for Agitation in Dementia, 630 Extinction techniques in aggression, 670, 670t Eye problems See Vision problems Eysenck Personality Questionnaire, 535 Falls causing brain injuries, 12, 12f prevention of, 733 risk in elderly persons, 495, 496t Families, 533–555 as advocates of patients, 578 of children with psychiatric disorders, 482, 490 community relationships of, 545, 547–548 cultural backgrounds of, 554–555 differing perceptions in, 536 of elderly persons, 502 formal therapy for, 546 guardianship arrangements, 588–589 homeostasis and involvement in, 533–534 impact of TBI, 534–555 on children, 537, 541 clinical observations of, 538–539 on extended family, 541–542 on parents, 540–541 phase I in, 534 phase II in, 534 phase III in, 534–535 phase IV in, 535–538 research on, 534–538, 535t on siblings, 541 on spouses, 539–540 individuality of, 555 information and education for, 545–546 instruction in behavior management skills, 673–674 interventions for, 538, 543–549, 544t acute care in, 546 community reintegration in, 547–548 concentric circles of, 544f, 544–545 levels of, 545f, 545–546 long-term issues in, 548–549 rehabilitation in, 546–547 stages of, 546–548, 547f involvement in patient’s treatment, 533–534, 651–652 issues in mild TBI, 549 legal issues in, 553–554 long-term outcome in, 536 Natural-Setting Behavior Management Program for, 538 of patients with awareness deficits, 363 of patients with motivational deficits, 349 proxy decision making, 589–590 psychiatric symptoms in, 68, 68t relationship with school system, 549–550 sexual problems affecting, 447 stages of adjustment in, 534, 542t, 542–543 structural and role changes in, 539–542 support, problem-solving, and restructuring for, 546 translators for, 545 unrealistic expectations of, 550–553 Family history of TBI patients, 67 and posttraumatic psychosis, 219, 221, 226 Fatality rates, 6, 8f, 16–17, 18f in elderly patients, 496 Fatigue and sleep problems, 369–382 abnormal sleep-wake cycle in, 376–377 apnea in sleep, 375 circadian rhythm sleep disorder, 376–377 clinical features of, 371–377 in fatigue, 371–372 in sleep disorders, 372–377 evaluation of, 371–378 in brain injury, 377t, 377–378 hypersomnia, 375–376 insomnia, 372–375 medications in, 379–380, 627, 630 narcolepsy, 375–376 parasomnias, 377 758 Fatigue and sleep problems—continued pathophysiology in, 370–371 relation to brain injury, 371, 371f SPECT imaging in, 111, 113 treatment of, 378t, 378–382, 379t in fatigue, 379–380 in sleep disorders, 380–382 Fatigue Impact Scale (FIS), 372, 373f–374f Fatigue Severity Scale (FSS), 372 Females sexual dysfunction in, 442 diagnostic testing in, 444, 445t sports injuries in, 455 Fentanyl in pain relief, 426t Fibroblast growth factor (FGF), 707t, 712f, 713t, 713–714 activity after brain injury, 42 Finger Tapping Test, 161t Firearms causing brain injuries, 12, 12f prevention of, 736 Flecainide in pain relief, 425t Fluoride-18 in PET scans, 117, 121t Fluoxetine in affective lability, 620–621 in aggression, 272 in depression, 615–616 in childhood, 489 in pain relief, 425t seizures from, 616, 618 Fluphenazine in anxiety, 241 Flurazepam in withdrawal from alcohol or drugs, 514t Focal brain injuries, 28, 28t, 29–34, 699 blood vessels in, 33 cranial nerves in, 33 experimental models of, 43–44 hemorrhagic lesions in, 33–34 hypothalamus and pituitary in, 33 intracranial hematomas in, 30–33 intracranial pressure in, 33 pontomedullary junction tears in, 33 scalp, skull, and dura lesions in, 29 surface contusions and lacerations in, 29–30, 30f, 30t Follicle-stimulating hormone, 439, 440t, 445t Football, injuries in, 457, 472 prevention of, 734–735 Forensic psychiatric evaluations, 579, 591, 596–599 brain injury mimics in, 598–599 collateral sources of information in, 597–598, 598t and disability determinations, 599 factors affecting test findings in, 598, 599t index of suspicion for malingering in, 597, 598t medications affecting, 599 mental status examination in, 598 no confidentiality in, 597 TEXTBOOK OF TRAUMATIC BRAIN INJURY no doctor-patient relationship in, 597 standard diagnostic schema in, 597 team approach in, 597 Fractures See Skull fractures Freedox, neuroprotection with, 706t, 708 Fregoli syndrome, 220 Frontal lobe “bedside” evaluation of function, 69t executive function impairments, 324t, 324–325 syndromes, 247 aggression in, 261, 262 symptoms in, 64 Frovatriptan in headaches, 390 Functional Independence Measure (FIM), 81 Functional Self-Assessment Scale, 358t g-force calculations of injury severity, 471 G-stop task, functional MRI in, 124 Gabapentin in aggression, 271 in anxiety disorders, 241 in headache, 389t in mania, 620 in pain relief, 425t in seizures with behavioral symptoms, 314, 315t Gacyclidine as NMDA receptor antagonist, 701, 702t Gage, Phineas, 246 Galantamine, 680, 681t–682t, 683, 683t, 691t in motivational loss, 347, 348f Galveston Orientation and Amnesia Test (GOAT), 63, 70, 161, 162f in delirium study, 177 in posttraumatic amnesia, 180, 182, 183t Gender and mild brain injuries, 281, 281t and posttraumatic psychosis, 219 and risk of brain injury, 9, 11f, 15f, 24 General Rehabilitation Assessment Sexuality Profile, 443, 443t, 444t Generalization of behaviors in process model of behavioral therapy, 664, 666–669 Genetic vulnerability to anxiety disorders, 238 and bipolar illness after TBI, 292 and posttraumatic psychosis, 219, 221, 226 and response to neurotrauma, 299–300 Geniculate body, lateral, 408, 408f Geriatric Evaluation by Relative’s Rating Instrument (GERRI) scores affected by ginkgo biloba, 689 Ginkgo biloba, 681t–682t, 683t, 689–690, 691t Ginseng, 681t–682t, 683t, 690, 691t Glasgow Coma Scale, 5t, 5–6, 24–25, 60t, 70, 477 and assessment of older patients, 496, 501 and benefits of citicholine, 686 in mild TBI, 51, 279, 280t, 281 and postconcussive symptoms, 286 in posttraumatic amnesia, 182, 183t relation to CT findings, 80, 82f and return to work, 575, 576 and seizure development, 312, 312t in severe TBI, 51 substance abuse affecting, 516 Glasgow Outcome Scale, 17 and postconcussive symptoms, 286 Glial-derived neurotrophic factor (GDNF), 707t, 712f, 713, 713t Glucose levels, and diminished capacity concept, 593, 595 Glutamate activity after brain injury, 41–42 cerebrospinal fluid levels in, 206 Glutethimide in withdrawal from alcohol or drugs, 514t Glycerol in withdrawal from alcohol or drugs, 514t Goal-directed behavior in awareness deficits, 362, 363 diminished motivation in, 338 Golden root, 681t–682t, 683t, 688–689 Gonadotropin-releasing hormone, 439, 440t Grooved Pegboard Test, 161t Group therapy in awareness impairment, 363, 363t in substance abuse, 518–519 Growth factors activity after brain injury, 42, 706t–707t, 711–715 receptors for, 712f Growth hormone, impaired release after TBI, 66 Guanfacine in mild TBI, 299 Guardianship, 588–589 Guilt experienced by patients, 649–650, 652t Guilty but mentally ill, 593–594 Gunshot injuries, 12, 12f prevention of, 736 GYKI-52466 compound as AMPA/KA receptor antagonist, 703t, 704 Habit reversal in pain management, 429t Haddon Matrix, 729 Hair cells in ear, 394 Halazepam in withdrawal from alcohol or drugs, 514t Hallpike-Dix maneuver, 400 Haloperidol affecting sexual function, 440t in aggression, 269–270 759 Index in anxiety, 241 in delirium, 192–193, 194 interaction with dextroamphetamine, 631 Halstead-Reitan Neuropsychological Test Battery (HRNB), 160 in sports injuries, 467 Hamilton Rating Scale for Depression after mild TBI, 291 Hasegawa Dementia Scale, Huperzine affecting, 684 Head Injury Behaviour Scale, 358t Headache, posttraumatic, 385–390 assessment of, 386–388 causes of, 386–387, 387t cluster, 390 complications of, 388 definitions of, 385 in life-threatening conditions, 386, 387t natural history of, 388 pathophysiology in, 385–386 PET scans in, 119 prevalence of, 385 SPECT imaging in, 111, 112 tension-type, 385–386, 386t treatment of, 388–390, 389t Headache Disability Rating, 422t Health care proxy, 587–588, 603–605 Health insurance policies, 567 Hearing problems, screening for, 397 Helmet use bicycle, 459–460, 733–734 in equestrian events, 460 football, 472, 734 motorcycle, 732 skateboarding, 741 Hematoma burst lobe in, 29, 32, 32f, 33 epidural, 31, 31f, 31t in infancy and childhood, 39 in severe TBI, 54–55, 55f xenon-enhanced computed tomography in, 129f intracerebellar, 32–33 intracerebral, 32–33 swelling of brain with, 38 intracranial, 21f, 29–33, 31t, 32f, 32t in skull fractures, 29 types and frequency of, 30t intradural, 31–33 subarachnoid, 31–32 subdural, 29, 32, 32f in infancy and childhood, 39 in severe TBI, 55f, 55–56, 56f swelling of brain with, 38–39, 39f Hemianopia, 411 awareness deficit with, 355 Hemiplegia, awareness deficit with, 355 Hemorrhage in diffuse axonal injury, , 34, 34f, 34t Hendler Chronic Pain Screening Test, 422t Hennebert sign in perilymphatic fistula, 400 Herbal alternative treatments, 688–690 in sleep disorders, 381 Herniations, intracranial, 33 Hexamethylpropyleneamine oxime labeled with technetium-99m in SPECT imaging, 112t Hinckley, John, Jr., 592 Hippocampus in stress response, 237–238 History of patient, 59–60, 60t, 66–69 in dizziness and balance problems, 394–395 in prisoners on death row, 260 sexual history, 443–444 Hockey, prevention of injuries in, 735–736 Homeless people, posttraumatic psychosis in, 223 Homeopathy, 691–692 Hooper Visual Organization Test, 161t Hopkins Verbal Learning Test, 161t, 163 in sports injuries, 467 Horseback riding, injuries in, 460 Hospitalization discharges and diagnoses, 14–15, 15f, 16f length of stay in, substance abuse affecting, 515 rates for brain injuries, 7–8, 9t, 10f stresses in, 248, 249t Huperzine, 681t–682t, 683t, 683–684, 691t Hydrocodone in pain relief, 426t Hydrogen-1 in magnetic resonance spectroscopy, 125, 125t Hydromorphone in pain relief, 426t Hydrotherapy in pain relief, 427 Hydroxyzine in headaches, 390 Hyperphagia, 66, 66t Hypersexuality in Klüver-Bucy syndrome, 438, 446 treatment of, 446 Hypersomnia, 375–376 Hypertension headache in, 389t intracranial See Intracranial pressure Hypnosis in pain management, 429t Hypnotics, psychiatric side effects of, 612t Hypoglycemia as defense to criminal charge, 595 Hypomania in children, 485 Hyposexuality, treatment of, 446 Hypothalamus, 66, 66t in aggression, 262, 262t dysregulation of, opiate antagonists in, 255, 255t in focal brain injury, 33 in sexual function, 438 Hypoxic-ischemic brain damage, 37–38, 73 evoked potentials in, 148 in infants and children, 40 Ibuprofen as COX inhibitor, 705 psychiatric side effects of, 611t Idebenone, 681t–682t, 683t, 688, 691t Ifenprodil as NMDA receptor antagonist, 702t, 704 Illness, denial of See Denial of illness Illness Behavior Questionnaire, 422t Imagery and hypnosis, in pain management, 429t Imaginary Processes Inventory, Sexual Imagery subscale of, 442 Imaging techniques See also specific techniques computed tomography, 79–84 xenon-enhanced, 127, 127f, 128f–129f for elderly persons, 501 functional, 107–129 in delirium and posttraumatic amnesia, 190–191 frontal lobe in, 247 in mild TBI, 294t, 295, 296 magnetic resonance imaging, 84–92 functional, 108t, 123–125 magnetic resonance spectroscopy (MRS), 108t, 125–126 magnetoencephalography, 126–127 in mild TBI, 293–296, 294t positron emission tomography (PET), 117–123 in posttraumatic stress disorder, 238–239 single-photon emission computed tomography (SPECT), 108–117 structural, 79–104 in delirium and posttraumatic amnesia, 189–190 Imipramine adverse effects of, 618 in affective lability, 621 in premature ejaculation, 446 Immediate Post-Concussion Assessment and Cognitive Testing (ImPACT), 468 Immunohistochemistry in diffuse axonal injuries, 35f, 36 Immunosuppressants, neuroprotection with, 706t, 710 Impulse disorders, and insanity defense, 593 Inappropriate behavior after brain injury, 251 Incidence of brain injuries, 6–8, 7f, 24, 727–728, 728f mild injuries in, 281, 281t 760 Incompetency, 586–587 definition of, 584, 588–589 Individuals With Disabilities Education Act, 565 Indole-2-carboxylic acid (I2CA) as NMDA receptor antagonist, 702t, 703 Indomethacin as COX inhibitor, 705, 706t psychiatric side effects of, 611t, 612t Infancy, brain injuries in, 39–40 Infarction of brain tissue, 33 Informed consent, 584–586, 585t options available for, 586, 586t Injury control theory, 728–729 Insanity defense, legal issues in, 592–593 Insight deficiency, 354t in brain injury and in psychotic disorders, 222 Insomnia, 372–375 Insulinlike growth factor-1, 707t, 712f, 713t, 714 Insurance coverage for care of patients, 566–568 disability, 576–577 Integrative model of behavioral therapy, 663, 663t Intelligence quotient (IQ), and posttraumatic psychosis, 219 Intelligence tests, 161 Interactive staff training (IST), 673 Interleukins activity in brain injury, 709–710 IL-1, 41 IL-6, 41 neuroprotection with IL-1ra, 706t, 709 IL-10, 706t, 710 International Classification of Diseases (ICD), 8, 9t, 14, 16 Intoxication as defense to criminal charge, 594 Intracranial pressure increased brain damage from, 33 in hypoxia-ischemia, 37 in children, 477 monitoring in severe TBI, 53, 54t normal values, 33 Iodine-123–N-isopropyl-piodoamphetamine in SPECT imaging, 112t Ion changes after brain injury, 42 Iron chelators, neuroprotection with, 706t, 707 Irritability in personality disorders, 251 Ischemia, cerebral See Hypoxicischemic brain damage N-Isopropyl-p-iodoamphetamine labeled with iodine-123 in SPECT imaging, 112t TEXTBOOK OF TRAUMATIC BRAIN INJURY Jargon aphasia, 355–356 Judgment in addicted persons with brain damage, 526 impairment after brain injury, 251 Judgment of Line Orientation Test, 161t Julia Farr Centre PTA scale, 183, 183t Kallikrein-kinin system in brain injury, 711 Ketamine as NMDA receptor antagonist, 701, 702t psychiatric side effects of, 611t, 612t Ketorolac in pain relief, 426 Klüver-Bucy syndrome hypersexuality in, 438, 446 violent behavior in, 590 Kynurenate (KYNA) as AMPA/KA receptor antagonist, 703, 703t Lacerations, 29–30, 30t brain swelling with, 38, 39f Lactate labeled with hydrogen-1 in magnetic resonance spectroscopy, 125t Lamotrigine in anxiety disorders, 241 in cognitive dysfunction, 326t, 330, 623 in mania, 620 as NMDA receptor antagonist, 703t, 704 in pain relief, 425t in seizures with behavioral symptoms, 314, 315t Language impairment, 65, 250, 250t, 252–253, 325t, 325–326 in addicted persons with brain damage, 526 testing of, 161t, 164–165 Laughing, pathological, 204 medications in, 620–621 Learning disorders, 323t, 323–324 differential diagnosis of, 169–170 testing in, 161t Lecithin, and cognition in elderly persons, 504 Leeds scale in depression after mild TBI, 291 Legal issues, 287–289, 287t, 583–605 advance directives, 587–588 civil litigation, 595–596 disability determinations in, 599 expert testimony in, 595 forensic experts in, 596 See also Forensic psychiatric evaluations treating clinician in, 595–596 competency concept in, 583–584 and competency to stand trial, 591 criminal proceedings, 590–595 diminished capacity concept, 593 do-not-resuscitate (DNR) orders, 587 exculpatory and mitigating disorders, 594–595 in family matters, 553–554 guardianship, 588–589 guilty but mentally ill, 593–594 health care decision making, 584–590, 603–605 incompetent patients, 586–587 informed consent, 584–586, 585t insanity defense, 592–593 litigation problems, 578–579 in mild TBI, 300 and public policy decisions, 571–574 in sexual dysfunction, 447–448 substituted judgment in proxy decision making, 589–590 Leukocyte adherence inhibitors, neuroprotection with, 706t, 709 Levetiracetam in pain relief, 425t Levodopa affecting sexual function, 440t in affective lability, 621 in cognitive dysfunction, 326t, 329, 622t, 623 in fatigue, 379 in mild TBI, 299 in motivational loss, 348t in personality disorders, 254, 255t psychiatric side effects of, 611t, 612t LF-16-0687Ms compounds, neuroprotection with, 706t, 711 Lidocaine in pain relief, 425t in premature ejaculation, 446 Lifestyle adjustments in headache, 389 and fatigue, 380 and sleep disorders, 381 Lifetime supported living services in care system, 565 Limbic system in aggression, 262, 262t in motivational circuitry, 341 Lipid peroxidation after brain injury, 42–43 Lithium in affective lability, 621 in aggression, 271–272, 630t for elderly persons, 504 in mania, 209–210, 619 Litigation problems, 578–579 Living wills, 587 Location of brain lesions and mood disorders, 207 and psychosis, 218, 222–223 Loneliness of patients, 650–651, 652t Lorazepam in delirium, 194 in insomnia, 380 761 Index Loss of consciousness (LOC) in mild brain injury, 279, 280t, 281 relation to CT findings, 80, 82f and severity of concussion, 464t, 464–465, 465t Lubeluzole as glutamate inhibitor, 206 Luria’s Memory Words—Revised, and benefits of citicholine, 686 Luteinizing hormone, 439, 440t, 445t LY341122 compound, neuroprotection with, 706t, 707 LY354740 compound as NMDA receptor antagonist, 703t, 704 Magnesium ion changes after brain injury, 42 salts as NMDA receptor antagonists, 702t, 703 Magnetic resonance imaging, 84–92 anatomic specificity of, 84, 84f clinical rating of scans in, 95, 96f related to behavioral and cognitive function, 96–97, 97f in corpus callosum atrophy, 86f, 90 degenerative changes tracked in, 85, 86f in delirium after brain injury, 189 diffusion-tensor imaging in, 94f, 94–95, 95f in dizziness and balance problems, 398, 399t findings related to outcome, 90–92, 91f in focal brain injury, 33–34 in follow-up of baseline CT images, 87, 89f functional, 108t, 123–125 abnormal findings in, 124 blood oxygen level dependent (BOLD), 296 in brain injury, 124 indications for, 123 limitations to, 123 in mild TBI, 194t, 295, 296 practical considerations in, 123 in psychiatric disorders, 124 recommendations for, 124–125 image sequences in, 88, 88t diffusion-weighted (DW), 88, 88f fluid-attentuated inversion recovery (FLAIR), 88, 88f, 189 gradient recalled echo (GRE), 88, 88f proton density (PD), 88, 88f T1 and T2, 88, 88f indications for, 85–87 in mild TBI, 294t, 294–295 quantitative image analysis in, 84, 89–90, 103–104 small but critical lesions in, 83f, 86f, 89f, 92 SPECT imaging with, 92, 93f, 113, 114f, 116f superiority of, 92, 93f typical lesions in, 87–89 contusion, 88, 89f focal atrophy, 89, 89f shear, 86f, 88 white matter abnormalities, 89, 89f, 189 ventricle to brain ratio (VBR) in, 85f, 90, 91f in ventriculomegaly, 84, 85f voxel-based morphometry in, 87f Magnetic resonance spectroscopy (MRS), 108t, 125–126 in brain injury, 126 indications for, 125 limitations of, 126 in mild TBI, 294t proton, in delirium after brain injury, 189–190 in psychiatric disorders, 126 recommendations for, 126 tracers used in, 125, 125t Magnetic source imaging in brain injuries, 152–153, 294t Magnetoencephalography, 126–127, 152–153 abnormal low-frequency magnetic activity in (ALFMA), 152–153 recording methods in, 140–141 Malingering detection of, 579 in litigation, 597, 598t postconcussive symptoms in, 287–289 testing for, 165–166 Mania after mild TBI, 291t, 292 in children, 485 differential diagnosis of, 205–206 in elderly persons, 504 medications in, 619–620 in seizures after brain injury, 314 treatment of, 209–210 Mannitol in intracranial hypertension, 53, 54t Maprotiline, seizures from, 618–619 Matrix Reasoning Test, 161t Maximum Abbreviated Injury Scale (MAIS), 20, 25 MCPG compound as NMDA receptor antagonist, 703t, 704 Mechanisms of brain damage after injury, 27–28, 28t Meclizine in dizziness and balance problems, 401, 401t Meclofenoxate See Centrophenoxine Medicaid, 565, 567–568 waiver programs in states, 574, 574t Medical disorders apathy in, 343t personality changes in, 214t, 249, 249t, 261, 261t psychotic disorders in, 214, 214t Medical history of TBI patients, 67 Medicare, 567 Medications affecting elderly persons, 502, 503t affecting neuropsychological test results, 599 affecting sexual function, 439, 440t–441t, 446–447 aggression associated with, 265, 265t in anxiety, 240–241 apathy from, 343t, 344 in attention-deficit/hyperactivity disorder, 489 in cognitive dysfunction, 326t, 326–338 in delirium, 192–194 in depression, 615–619 in children, 489 in dizziness and balance problems, 401, 401t drugs interacting with antidepressants, 619 in fatigue and sleep problems, 379–380, 627, 630 in history of TBI patients, 67 interactions of, 610, 613 in mild TBI, 298–300 in motivational loss, 347–349 neuroleptics, 628–629 See also Neuroleptic medications overuse causing headaches, 387, 388 for pain, 424–427, 425t, 426t issues involved with, 421, 423–424 in personality disorders, 254t, 254–255, 255t psychiatric side effects of, 611t–612t psychopharmacology, 609–632 See also Psychopharmacology psychotropic agents effects in brain injury patients, 208–209 in mild TBI, 298 in substance abuse, 520–521 Medroxyprogesterone affecting sexual function, 441t Melatonin in sleep disorders, 381 Memory in addicted persons with brain damage, 526 declarative, 323, 323t and delayed recall, 163 dysfunction of, 323t, 323–324 episodic, 323, 323t functional MRI studies of, 124 immediate, 163 implicit, 323, 323t 762 Memory—continued metamemory deficits, 323 in mild TBI, cholinergic and catecholaminergic agents affecting, 298–299 in personality disorders, 252 in posttraumatic stress disorder, 168 prospective, 323 recent, 163 studies in posttraumatic amnesia, 180 testing of, 161t, 163–164 working, 323, 323t dysfunction of, 323 Ménière disease, 400 Mens rea, 590 Menstrual disorders after TBI, 66, 66t Mental health services in care system, 565–566 Mental status examination, 69, 69t Meperidine in pain relief, 426t Meprobamate in withdrawal from alcohol or drugs, 514t Metabolic disorders, and diminished capacity concept, 593, 595 Methadone in opiate withdrawal, 514 Methandrostenolone affecting sexual function, 440t Methaqualone in withdrawal from alcohol or drugs, 514t N-Methyl-D-aspartate (NMDA), 699–700, 700f receptor antagonists and agonists, 700–704, 702t–703t Methyldopa affecting sexual function, 440t Methylphenidate adverse effects of, 624 affecting memory after mild TBI, 298–299 in affective lability, 621 in attention-deficit/hyperactivity disorder, 489 and cognition in elderly persons, 504 in cognitive dysfunction, 328, 622t, 622–623 in depression, 617 for elderly persons, 503 in fatigue, 379, 627 in motivational loss, 348, 348t in personality disorders, 254, 254t psychiatric side effects of, 611t Methysergide in headache, 390 psychiatric side effects of, 611t Metoclopramide in headache, 390 psychiatric side effects of, 611t Mexiletine in pain relief, 425t Michigan Alcoholism Screening Test (MAST), 512 Migraine PET scans in, 119 TEXTBOOK OF TRAUMATIC BRAIN INJURY SPECT imaging in, 112 treatment of, 390 Mild brain injury, 6 amnesia in, 279, 280t, 281 and anxiety disorders, 291f, 292–293 behavioral sequelae in, 285–293 cognitive sequelae in, 283–285 definitions of, 279–281, 280t depression in, 290–292, 291t diffuse cerebral swelling in, 283 disability in, 293 electrophysiological studies in, 296–297 epidemiology of, 281t, 281–282 evaluation of, 297–298 experimental studies, 461 family issues in, 549 Glasgow Coma Scale in, 51, 60t, 279, 281, 477 indicators of, 280t loss of consciousness in, 279, 280t, 281 and mania, 291t, 292 medical-legal issues in, 300 medications in, 298–300 neuroimaging in, 293–296, 294t pathophysiology of, 282–283 postconcussive symptoms in, 285–290, 300–301 and posttraumatic stress disorder, 236–237, 291t, 292–293 psychoeducation in, 300 psychotherapy in, 646–647 and psychotic disorders, 290, 291t second impact syndrome in, 283, 462–463 in sports, 453–472 treatment of, 297–300 Millon Behavioral Health Inventory, 422t Mini-Mental State Examination (MMSE), 69, 166 in delirium, 184 Ginkgo biloba affecting, 689 Huperzine affecting, 684 vinpocetine affecting, 688 Minnesota Multiphasic Personality Inventory (MMPI), 248, 423t Minocycline, neuroprotection with, 706t, 709 Mirtazapine affecting sexual function, 441t in depression, 616 Mitral valve prolapse, headache in, 389t MK-801 compound as NMDA receptor antagonist, 701, 702t Moclobemide in depression, 617–618 Modafinil in cognitive impairment, 622t in fatigue, 379–380, 627 in motivational loss, 348, 348t in narcolepsy, 381 in personality disorders, 254t Moderate brain injury, Glasgow Coma Scale in, 60t, 477 Monoamine oxidase in aging brain, 499 inhibitors of in depression, 617–618 in motivational loss, 347 Mood disorders after TBI, 201–210 affecting patient outcome, 207–208 depression, 201–205 mania, 205–206 physiological correlations in, 206–207 treatment of, 208–210 Morphine in pain relief, 426t Mortality rates, 6, 8f, 16–17, 18f in elderly patients, 496 Motivation brain circuitry in, 339–342, 340f description of, 337 impairment of, 337–349 See also Apathy assessment of, 343–345 behavioral interventions in, 346 clinical pathogenesis of, 342 differential diagnosis of, 339 disorders in, 338–339 environmental interventions in, 346 medications in, 347–349 neurobehavioral mechanisms in, 342–343 neurochemical mechanisms in, 343 psychological prosthesis in, 346–347 rating methods in, 344–345 recognition of, 338–339 treatment of, 345–349 in test performance, 289 testing of, 165 Motor processes in disabled intention system, 359 dysfunction of, 65, 65t agitation in, 179 testing of, 161 Motor vehicles car seats for children, 740 injuries in, 12, 510 prevention of, 730–732, 739 insurance policy types, 567 Motorcycle accidents, injuries in, 13, 13f prevention of, 731–732, 739 MPEP compound as NMDA receptor antagonist, 703t, 704 Multiaxial Pain Inventory, 422t Multilingual Aphasia Examination, 161t Multiple sclerosis association with TBI, 65 fatigue in, treatment of, 379, 380 763 Index Multiple Sleep Latency Test (MSLT), 378 Mutism, akinetic, 338 conditions associated with, 343t treatment of, 345–346 Nadolol in aggression, 272, 273 Naproxen affecting sexual function, 440t Naratriptan in headache, 390 Narcolepsy, 375–376 modafinil in, 381 Narcotics addiction to See Substance abuse psychiatric side effects of, 611t Narcotics Anonymous (NA), 517, 517t National Center for Catastrophic Sports Injury Research, 455 National Head Injury Foundation, 571, 572 National Health Interview Survey (NHIS), 5t, 6, 7 National Highway Safety Administration, 731 National Hospital Ambulatory Medical Care Survey (NHAMCS), 5t, 6, 7 National Hospital Discharge Survey (NHDS), 5t, 6, 7, 14, 15, 16 National Institutes of Health, 560 research and conference on traumatic brain injury, 572–573, 573t Stroke Scale scores affected by citicholine, 685 National Rehabilitation Association, 577 Natural-Setting Behavior Management Program for families, 538 NBQX compound as AMPA/KA receptor antagonist, 703t, 704 Nefazodone in depression, 616 Neglect, unilateral, 355 Neocortex in aggression, 262–263 Nerve growth factor, 706t, 711–712, 712f activity after brain injury, 42 in aging brain, 498 Neuralgia syndromes, headache in, 387t treatment of, 390 Neuroanatomy in aggression, 261–263, 262t in dizziness and balance problems, 394 in pain, 420 in personality change, 246–247 in sexual functioning, 437–439, 438t Neurobehavioral Cognitive Status Examination (NCSE), 70, 72f, 166 Neurobehavioral Rating Scale, 609 in personality changes, 249 in posttraumatic amnesia, 183, 183t Neurobehavioral Rating Scale—Revised (NRS-R), 70 Neurobehavioral treatment in care system, 564 Neurobiology in aging, 498 in anxiety disorders, 237–238 Neurochemical changes See also Neurotransmitter changes after brain injury in aging, 498, 499t posttraumatic, 40–43 acetylcholine levels, 40 amino acids, excitatory, 41–42 arachidonic acid cascade, 40 catecholamine and monoamine neurotransmitters, 40–41 cytokines, 41 growth factors, 42 ions, 41 opioid peptides, endogenous, 41 oxygen-free radicals and lipid peroxidation, 42–43 Neuroendocrine disorders in sexual dysfunction, 445–446, 445t treatment of, 446 Neuroimaging See Imaging techniques Neuroleptic malignant syndrome, 629 Neuroleptic medications, 628–629 in aggression, 269–270 in delirium, 192–193 in posttraumatic psychosis, 225 in seizures with behavioral symptoms, 315 Neurological disorders apathy in, 343t, 344 and posttraumatic psychosis, 219 symptoms in TBI, 65t, 65–66 Neuron-specific enolase in cerebrospinal fluid, after brain injury, 41 Neuropathology, 27–44 brain swelling, 38–39, 39f cellular changes, 43 classification of damage in, 27, 28t in fatal blunt head injury, 29–40 in focal injury, 29–34 in infancy and childhood, 39–40 mechanisms of damage in, 27–28, 28t neurochemical changes in, 40–43 Neurophysiology in balance problems and dizziness, 394 in concussion, 460–464 in delirium, 186f, 186–191 Neuropsychiatric assessment, 59–75 after coronary artery bypass graft, 74 in anoxia/hypoxia, 73–74 behavioral assessment in, 69–70 behavioral disorders in, 61t biopsychosocial approach, 59–71 classification of injury in, 60t cognitive disorders in, 61t in cognitive rehabilitation, 657–658 collateral history in, 60–62, 61t current behavioral symptoms in, 62, 62t of elderly persons, 501–502 in electrical injuries, 74, 75t emotional disorders in, 61t endocrine symptoms in, 66 history of patient in, 59–60, 60t family history, 67 medical history, 67 medications used, 67 preinjury disorders, 66–67 psychiatric disorders, 66 social functioning, 67–69 substance abuse, 67 mental status examination in, 69, 69t neurological symptoms in, 65t, 65–66 in nontraumatic brain injuries, 71–74 and PET scan results, 122 physical examination in, 69 physical symptoms in, 61t, 66 psychiatric disorders in, 64t, 64–65 preinjury disorders, 66 Rancho Los Amigos Cognitive Scale in, 62, 63t results related to SPECT findings, 116–117 in severe TBI, 62–63 in sports injuries, 467–468 symptom checklist in, 60, 61t symptoms after TBI, 63–66 DSM-IV-TR disorders in, 64, 64t in traumatic brain injuries, 59–71 Web-based protocol in, 468 Neuropsychiatric disorders care systems in, 559–568 in children, 479–490 in elderly persons, management of, 502–504 Neuropsychiatric Inventory, 344, 609 Neurosis, compensation, 579 Neurosurgical interventions, 51–58 See also Severe brain injury Neurotransmitter changes after brain injury, 613–615 See also Neurochemical changes acetylcholine, 615 in aggression, 263–264 catecholamines, 613–614 serotonin, 614–615 Neurotrophic factors, brain injury affecting, 42, 711–715 New York University Head Injury Family Interview, 537–538, 538t Newtonian formulas in mechanics of injury, 471–472 Nimesulide as COX-2 inhibitor, 706t, 707 Nitric oxide synthase (NOS) in brain injury, 705 inhibitors of, neuroprotection with, 706t, 708 Nitrogen-13 in PET scans, 121t 764 NMDA receptors, 699–700, 700f antagonists and agonists of, 700–704, 702t–703t Nonfatal brain injuries, 6–8, 9t Nonsteroidal anti-inflammatory drugs in headaches, 389 Nootropics, 690 definition of, 679 Norepinephrine activity after brain injury, 40–41, 613–614 cerebrospinal fluid levels, 207 serum levels in aggression, 263 in aging brain, 498–499, 499t North American Adult Reading Test, 167 Nortriptyline affecting sexual function, 440t in affective lability, 621 in depression, 209, 617 in pain relief, 425t Novelty seeking, apathy affecting, 342 Nucleus accumbens in motivational circuitry, 340f, 341 Nurses’ Observation Scale for Geriatric Patients (NOSGER), idebenone affecting, 688 Nursing homes, neurobehavioral programs in, 566 Nutrients as alternative treatments, 686–688 Nutrition in fatigue, 380 in sleep disorders, 381 Nystagmus, 394, 395–396, 407t Obsessive-compulsive disorder, 235, 235t in children, 485 differential diagnosis of, 168 PET scans in, 119 SPECT imaging in, 111, 113 Occupational functioning of TBI patients, 68–69 Oculomotor problems, 410 Olanzapine affecting sexual function, 440t in aggression, 270 in anxiety, 241 in delirium, 193, 194 for elderly persons, 504 in posttraumatic psychosis, 225–226 Olfactory disorders, 253 screening for, 397 Ophthalmology, 407 Opiates in pain relief, 426t patient agreement for use of, 427, 435–436 withdrawal from, 514 Opioid peptides activity after brain injury, 41 TEXTBOOK OF TRAUMATIC BRAIN INJURY antagonists in personality disorders, 255, 255t Oppositional defiant disorder in children, 479, 484 differential diagnosis of, 487 Optic tract, 408, 408f Optometry, 407 Orientation disorders in delirium, 180 testing of, 160–161 Orientation Log (O-Log), 70, 71f Otoliths, 394 Outcomes of brain injuries See Consequences of brain injuries Outpatient therapy services, 564 Ovarian hormones in sexual function, 439, 440t, 445t Overcorrection in aggression, 670, 670t Overt Aggression Scale (OAS), 259, 266, 267f, 609 Overt Agitation Severity Scale, 183t, 266, 268f and selection of antipsychotic drugs, 194 Oxazepam in withdrawal from alcohol or drugs, 514t Oxcarbazepine in aggression, 271 in mania, 620 in pain relief, 425t Oxford PTA scale, 183, 183t Oxiracetam as alternative treatment, 690 Oxybutynin affecting sexual function, 440t Oxycodone in pain relief, 426t Oxygen-15 in PET scans, 117, 121t Oxygen reactive species formed after brain injury, 705 P30 and P50 evoked potentials, 147, 147f P50 nonsuppression in responses, 626 Paced Auditory Serial Addition Task (PASAT), 161t, 163, 322 in sports injuries, 467 Pain assessment of, 421, 422t–423t during examinations, 421, 424t behavioral therapy in, 428, 429t chronic, 419–430 cognitive dysfunction in, 420–421 definition of, 419 desensitization model for interventions in, 430, 430t in headaches See Headache and insomnia, 375 medications in, 424–427, 425t, 426t issues involved with, 421, 423–424 and “narcotics agreement” for patients, 427, 435–436 neuroanatomy of, 420 PET scans in, 119 physical agents for therapy in, 427–428 SPECT imaging in, 111, 112–113 Panic disorder, 235, 235t dizziness and balance problems in, 402 Paranoid symptoms in children, treatment of, 489 Parasomnias, 377 Parenchymal lesions in severe TBI, 56, 57f Parkinson disease, SPECT imaging in, 111 Paroxetine adverse effects of, 618 in affective lability, 621 in depression, 209 in pain relief, 425t Patient Competency Rating Scale, 358t Patient education in pain management, 429t Patient Self-Determination Act, 587 PBN compound, neuroprotection with, 706t, 707 PC-SOD enzyme, neuroprotection with, 706t, 708 Pediatric injuries, 39–40, 477–490 adjustment disorder in, 488 attention-deficit/hyperactivity disorder in, 479, 483–484 differential diagnosis of, 487–488 treatment of, 489 on bicycles, 13, 13t, 459–460 prevention of, 733–734 in child abuse, 740 depression in differential diagnosis of, 488 treatment of, 489 educational services for, 565 epidemiology of, 477 etiology and pathophysiology, 477–478 falls in, 733 and family functioning, 482, 537 neurological sequelae of, 478 oppositional defiant disorder in, 479, 484 differential diagnosis of, 487–488 and parental relationship with school system, 549–550 personality change in, 479, 482–483 differential diagnosis of, 487–488 treatment of, 488–489 personality style changes in, 487 postconcussion syndrome in, differential diagnosis of, 488 posttraumatic stress disorder in, 484–485 prevention of, 490 765 Index prevention of brain trauma in, 740–741 psychiatric disorders in, 479–490 adaptive function after, 486 affecting family function, 482 cognitive outcome in, 486 differential diagnosis of, 486–488 frequency of, 483t postinjury status in, 480 predictors of, 480–482, 482t preinjury status in, 480 studies of, 480, 481t treatment of, 488–489 psychosis after, 216–217, 224 psychosocial treatments in, 489–490 and schizophrenia development, 220 school failure in, 488 school programs in, 560 school sequelae of, 478–479 PEG-SOD enzyme, neuroprotection with, 706t, 708 Pemoline in fatigue, 379 in personality disorders, 254 Penetrating injuries, and posttraumatic psychosis, 219 Penis biothesiometry of, 444 innervation of, 439 Pentazocine, psychiatric side effects of, 612t Pentobarbital in withdrawal from alcohol or drugs, 514t Pentoxifylline, neuroprotection with, 706t, 710 Perceived Stress Scale (PSS), 423t Perception problems in personality disorders, 253 Performance in process model of behavioral therapy, 664, 665–666 Pergolide in cognitive dysfunction, 326t, 329 in motivational loss, 348t in personality disorders, 255, 255t Personality assessment after brain injury, 248–249 changes in, 206 affecting families, 535, 535t in children, 479, 482–483 differential diagnosis of, 487–488 treatment of, 488–489 compared with changes in personality style, 487 in medical conditions, 249, 249t, 261, 261t functional neuroimaging studies, 247 localization in brain, 246–248 neurochemical basis of, 248 premorbid, and reactions to brain injury, 248 Personality disorders, 245–255 abstract thought in, 252 affective instability in, 251 aggression and irritability in, 251 assessment of, 253–254 attention in, 251 childish behavior in, 250–251 clinical features of, 249–253 definition of, 246 inappropriate behavior in, 251 language deficits in, 250, 250t, 252–253 medications in, 254t, 254–255, 255t memory in, 252 perceptual problems in, 253 psychotherapy in, 255 in seizures, 314t treatment of, 253–255 Pharmacotherapy See Medications Phencyclidine as NMDA receptor antagonist, 701, 702t Phenelzine in depression, 616–617 psychiatric side effects of, 612t Phenobarbital in aggression, 271 in seizures with behavioral symptoms, 315t in withdrawal from alcohol or drugs, 514t Phenoxybenzamine affecting sexual function, 441t in premature ejaculation, 446–447 Phentolamine in erectile dysfunction, 446 Phenytoin affecting sexual function, 440t in aggression, 271 cognitive effects of, 631, 632 early posttrauma use of, 310 in pain relief, 425t Phobias, 235t Phospholipases, activation of, 705 Phosphorus-31 in magnetic resonance spectroscopy, 125, 125t Photosensitivity, 411–412 Phototherapy in circadian rhythm sleep disorder, 381–382 Physical modalities in pain relief, 427–428 Physical symptoms in TBI, 61t, 66 Physostigmine affecting memory in mild TBI, 299 in cognitive dysfunction, 326t, 327, 625 in elderly persons, 504 in delirium, 194 Picamilon, 681t–682t, 683t, 687 Pindolol in aggression, 272, 273 Piperidinedione in withdrawal from alcohol or drugs, 514t Piracetam, 691t as alternative treatment, 690 Pittsburgh Sleep Quality Index, 375 Pituitary gland in TBI, 66, 66t in focal brain injury, 33 Pituitary hormones in sexual function, 439, 445t Playground injuries, prevention of, 733, 740–741 Polysomnography, 378 Portland Digit Recognition Test, 165 Positron emission tomography (PET), 108t, 117–123 in activation studies, 122–123 in behavioral disorders, 122 capabilities of, 118, 120f, 121f compared to CT or MRI, 120–122 in headache after trauma, 386, 388 improvements in, 119f in mild TBI, 294t, 295–296 in neuropsychological assessments, 122 normal adult brain in, 120f procedure in, 117, 118f in psychiatric disorders, 118–119 recommendations for, 123 tracers in, 117–118, 121t, 123 in traumatic brain injury, 119–120, 190–191 Postconcussion symptoms, 285–290, 388 checklist for, 60, 61t See also Symptomatologies in children, differential diagnosis of, 488 headache in, 385 in immediate postinjury period, 285–286 in mild TBI, 300–301 medications in, 298–299 persistence of, 286–287 role of compensation and litigation in, 287–289, 287t Posterior fossa lesions in severe TBI, 56 Posttraumatic stress disorder, 235–239 after brain injury with amnesia, 235–236 after mild TBI, 291t, 292–293 in children, 484–485 cognition in, 237 depression with, 237 differential diagnosis of, 168, 204 incidence of, 235–236 medications in, 629–630 neurobiology in, 237–238 neuroimaging in, 238–239 relation to acute stress disorder, 236–237 relation to posttraumatic amnesia, 180 Posturography, 399, 399t Potassium ion changes after brain injury, 42 766 Prader-Willi syndrome, opiate antagonists in, 255, 255t Pramipexole in cognitive dysfunction, 326t, 329 in motivational loss, 348 in personality disorders, 255, 255t Pramiracetam as alternative treatment, 690 Prazepam in withdrawal from alcohol or drugs, 514t Prednisone in pain relief, 425t Prehospital management in severe TBI, 52 Prevention, 727–741 antagonists of excitatory amino acids in, 699–705, 702t–703t anti-inflammatory agents in, 706t, 708–711 in bicycle riding, 733–734 in boxing, 734 in children, 740–741 comprehensive approach to, 729–741 in falling, 733 in football, 734–735 Haddon Matrix in, 729 in hockey, 735–736 and injury control theory, 728–729 lipid peroxidation inhibition in, 705–708 in motor vehicles, 730–732 neurotrophic factors in, 706t–707t, 711–715 passive versus active strategies in, 729 pharmacotherapy in, 699–715 in soccer, 735 in sports and recreational injury, 733–736 in substance abuse, 737–740 and suicide risk in depression, 737 violent injuries, 736–737 Primary injuries, 27, 28t, 699 Primidone in seizures with behavioral symptoms, 315t Prisoners on death row history of TBI in, 260 posttraumatic psychosis in, 223 Process model of behavioral therapy, 663t, 663–669 Prochlorperazine in dizziness and balance problems, 401, 401t Progesterone, 439, 440t Prolactin, 439, 440t, 445t serum levels in seizures, 311 Promethazine in dizziness and balance problems, 401, 401t Propranolol in aggression, 272–273, 273t, 630t in agitation, 194 in headache, 390 psychiatric side effects of, 611t, 612t Prosodic dysfunction, 252–253 TEXTBOOK OF TRAUMATIC BRAIN INJURY Prostacyclin, neuroprotection with, 706t, 709 Protein kinase C formation in brain injury, 705 Protriptyline adverse effects of, 618 in cognitive impairment, 623 in motivational loss, 348t Proxy decision making for patients, 589–590 Pseudobulbar affect, 620 Pseudodepression, 247 Psychiatric disorders in brain injury, 64t, 64–65 mimicking brain injury, 598–599 in substance abuse, 515 Psychiatrists in civil litigation procedures, 595–596 Psychoeducation after mild TBI, 300 in awareness impairment, 362, 363t in fatigue, 380 in motivational loss, 349 Psychogenic conditions balance disorders, 399 PET scans in, 119 SPECT imaging in, 113 Psychological factors in pain disorders, 419 Psychological prosthesis in motivational loss, 346–347 Psychomotor retardation, differential diagnosis of, 339 Psychopharmacology, 609–632 concerns about medications in, 630–632 in emotional disorders, 615–621 evaluation of patients in, 609–610 general principles of, 610, 612t, 613 medications recommended, 615–630 in aggression and agitation, 630, 630t in anxiety and posttraumatic stress, 629–630 in apathy, 626–627 in cognitive impairment, 621–626, 622t in coldness, 627–628 in depression, 615–619 in emotional disorders, 615–621 in fatigue, 627 in mania, 619–620 in psychosis, 628–629 in sleep disorders, 630 and neurotransmitter dysfunction after brain injury, 613–615 and psychiatric side effects of neurological drugs, 611t–612t Psychosexual Assessment Questionnaire, 441 Psychosocial therapy in pediatric brain injuries, 489–490 Psychostimulants See Stimulants Psychotherapy, 641–653 in anxiety, 239–240 avoidance of childish responses in, 250–251 catastrophic conditions in, 649, 652t denial in, 648–649, 652t in depression after brain injury, 209 for elderly persons, 502 family involved in, 651–652 in fatigue, 380 flexibility needed in, 642–644 goal-directed activities in, 644, 645t group experiences in, 651 guilt, shame, and punishment in, 649–650, 652t historical perspective in, 642 loneliness in, 650–651, 652t in mild brain injury, 646–647 outcome measures in, 644–646 in personality disorders, 255 risk-taking encouraged in, 653 in sleep disorders, 382 starting point in, 642 and stigmatization of patients, 650, 652t suggested tactics in, 5t, 644 transference and countertransference issues in, 647–648, 652t Psychotic disorders associated with epilepsy, 206, 219–220, 314t in children, 485–486 definition of, 214 in elderly persons, 503–504 in medical conditions, 214, 214t medications in, 225–226, 628–629 posttraumatic, 213–226 after mild TBI, 290, 291t atypical versus typical symptoms in, 220–221 in children and teens, 216–217, 224, 485–486 cognition in, 221 in death row prisoners, 223 diagnosis of, 214–215 follow-up studies, 215–216 gender affecting, 219 in homeless people, 223 and inherent vulnerability to psychoses, 219, 221 IQ/cognition affecting, 219, 221 location of injury in, 218, 222–223 presence of, versus absence of, in brain-injured patients, 217–218 prevention of, 226 and prior neurological disorder, 219 767 Index in schizophrenia patients, 220 severity of injury in, 218 socioeconomic status in, 219 and substance abuse, 219 treatment of, 225–226 type of injury in, 218–219 in vulnerable populations, 223–224 schizophrenia development after childhood trauma, 220 See also Schizophrenia in seizures after brain injury, 314t Psychotropic agents See also Neuroleptic medications effects in brain injury patients, 208–209 in mild TBI, 298 Public policy and legislation on traumatic brain injury, 571–574 state programs in, 571–572, 572t Pudendal nerve, 439 Punch-drunk syndrome, 456, 500 Punishment experienced by patients, 649–650, 652t Pursuit deficits, ocular, 407t, 410 Pyritinol, 681t–682t, 683t, 687–688, 691t Pyrrolidones, 681t–682t, 683t, 690 Quetiapine affecting sexual function, 440t in aggression, 270 in anxiety, 241 in delirium, 193 for elderly persons, 504 in posttraumatic psychosis, 225–226 Quinazolines in withdrawal from alcohol or drugs, 514t Race or ethnicity and family reactions to disabilities, 554–555 and risk of brain injury, 9 Racetams, 681t–682t, 683t, 690, 691t Raclopride in PET scans, 123 Radicals, oxygen-free, activity after brain injury, 42–43 Radiotracers in magnetic resonance spectroscopy, 125, 125t in PET imaging, 117–118, 121t in SPECT SCANS, 109, 112T Railway spine, 579 Rancho Los Amigos Cognitive Scale in delirium study, 177, 185 in posttraumatic amnesia, 182–183, 183t in recovery phase, 564 Ranitidine affecting sexual function, 440t Raynaud phenomenon, headache in, 389t Reaction times, slowing of, 322 Reading skills after brain injury in children, 478–479 Reasoning and judgment in addicted persons with brain damage, 526 Recovery process in behavioral therapy, 663, 663t Recreation, brain injuries in, 12, 12f prevention of, 733–736 Recurrent TBI, 10–11 Refraction, ocular, after brain injury, 410–411 Rehabilitation acute, inpatient, 563 awareness impairment affecting, 361–363, 363t cognitive, 655–660, 664 See also Cognitive rehabilitation family focus in, 546 subacute, 563–564 systems of care in, 559–568 See also Care systems vestibular, 402 vocational, 577–578 Rehabilitation Act of 1973, 577, 578 Reinforcers in behavioral therapy, 665–666 and differential reinforcement of other behaviors (DRO), 669–670, 670t Relaxation techniques in headache, 389 in pain management, 429t Remacemide hydrochloride as NMDA receptor antagonist, 701–702, 702t Repeatable Battery for the Assessment of Neuropsychological Status, 166 Residential treatment in care system, 564 Restraints used in aggression, 670t, 671 Ret receptor family in central nervous system, 713, 713t Rewards in behavioral therapy, 665–666 Rey 15-Item Memory Test, 165 Rey Auditory-Verbal Learning Test, 161t, 163 in sports injuries, 467 Rey-Osterrieth Complex Figure Test, 161t, 163 Rhodiola rosea, 681t–682t, 683t, 688–689, 691t Riluzole as glutamate inhibitor, 206 as NMDA receptor antagonist, 703t, 705 Risk factors age in, 8–9, 10f, 14–15, 15f, 24 for delirium, 181–182, 182t ethnicity or race in, 9 for falls, 495, 496 gender in, 9, 11f, 15f, 24 in high-risk groups, 8–12 socioeconomic status in, 11–12 substance abuse in, 9–10, 67 for suicide, 737 Risk-taking encouraged in psychotherapy, 653 Risperidone affecting sexual function, 440t in aggression, 270 in anxiety, 241 in delirium, 193 for elderly persons, 504 in personality change in children, 489 in psychosis, 225–226, 628 Rivastigmine in motivational loss, 347, 348f Rivermead PTA Protocol, 183t, 183–184 Rizatriptan in headaches, 390 Romberg testing, 397–398 Ropinirole in cognitive dysfunction, 326t, 329 in personality disorders, 255, 255t Roseroot, 681t–682t, 683t, 688–689 Rotatory (Barany) chair testing, 399, 399t S-100 protein in cerebrospinal fluid after brain injury, 41 S-PBN compound, neuroprotection with, 706t, 707 Saccades after brain injury, 407t, 410 Sandoz Clinical Assessment—Geriatric scale, vinpocetine affecting, 688 SC 58125 as COX-2 inhibitor, 706t, 707 Schedule for the Assessment of Negative Symptoms (SANS), 344 Schizophrenia awareness deficits in, 356 in childhood, 220, 485–486 cognitive features in common with brain injury, 222 differential diagnosis of, 168–169 functional MRI in, 124 genetic vulnerability for, 219, 221 magnetic resonance spectroscopy in, 126 PET scans in, 119 SPECT imaging in, 111, 113 Schizophrenia-like psychosis (SLP), 169 School problems after brain injury, 68, 478–479, 488 programs for children with brain injuries, 560, 565 relationship with parents, 549–550 Scopolamine affecting sexual function, 440t in dizziness and balance problems, 401, 401t Seat belts and air bags, 730–731 768 Secobarbital in withdrawal from alcohol or drugs, 514t Second impact syndrome, 283, 462–463 in football, 735 Secondary injuries, 27, 28t, 38, 51, 52t, 699, 700f Sedatives in aggression, 270 in insomnia, 380–381 vestibular, 401 Seizures, 309–316 aggression in, 265t, 265–266 from antidepressants, 618–619 from antipsychotic medications, 629 in children, 478 consequences of, 313, 313t diagnosis of, 311 electroencephalography in, 143–144 emotional impact of, 315–316 epidemiology of, 309–311 functional MRI in, 124 headache in, 389t magnetoencephalography in, 126 pathogenesis of, 311–312, 312t PET scans in, 118 posttraumatic, 65t, 66 and posttraumatic psychosis, 219–220 prognosis of, 312–313 prolactin levels in, 311 psychopathology in, 313–314, 314t treatment of, 314–316 psychosis associated with, 206 in severe TBI, 53–54 temporal lobe as defense to criminal charge, 594–595 sexual problems in, 442, 446 Selegiline, 690 in cognitive dysfunction, 326t, 329 in motivational loss, 348t Self, innate sense of, loss after brain injury, 249–250 Self-Awareness of Deficits Interview, 358t Self-concept, brain injury affecting, 356–357 Self-controlled time-out in aggression, 670, 670t Self-injurious behavior, opiate antagonists in, 255, 255t Self/Other Rating Form, 358t Selfotel as NMDA receptor antagonist, 701, 702t Semicircular canals, 394 Sensory disorders, 65, 65t Sensory gating, impairment of, 626 Serotonin activity after brain injury, 41, 614–615 activity in aggression, 263 in aging brain, 499, 499t TEXTBOOK OF TRAUMATIC BRAIN INJURY cerebrospinal fluid levels after brain injury, 207 and personality attributes, 248 selective reuptake inhibitors adverse effects of, 618 affecting sexual function, 441t, 446 in aggression, 272 in anxiety, 240–241 in cognitive dysfunction, 326t, 330 in depression, 209, 615–616 in motivational loss, 347 in personality change in children, 489 Sertraline in aggression, 272 in depression, 209, 298, 616 in motivational loss, 347 Severe TBI, 51–58 computed tomography in, 52 decompressive craniectomy in, 57 depressed skull fractures in, 56–57 emergency department workup in, 52 epidural hematoma in, 54–55, 55f Glasgow Coma Scale in, 51, 60t, 477 in-hospital management of, 52–54 intracranial pressure monitoring in, 53, 54t management guidelines, 51 affecting patient outcome, 57–58, 58t parenchymal lesions in, 56, 57f posterior fossa lesions in, 56 prehospital care, 52 primary survey in, 53t prognosis of, 51, 57 recovery stages in, 62–63 resuscitation in, 53t secondary survey in, 53t seizures in, 53–54 subdural hematoma in, 55f, 55–56, 56f surgery in, 54–57 Severity of injuries distribution of, 13–14, 14f and posttraumatic psychosis, 218 Sexual abuse, recognition of, 448 Sexual dysfunction, 66, 66t, 419–431 clinical evaluation in, 443–444, 444t counseling issues in, 447–448 diagnostic testing in, 444, 445t family issues in, 448 genital, 446–447 neuroanatomy in, 437–439, 438t neuroendocrine dysfunction in, 445–446, 445t treatment of, 446 neurophysiology in, 439, 440t nongenital, 446 physical examination in, 444 research literature, 439–443 sexual history in, 443–444 treatment of, 444–448 in women, 442 diagnostic testing in, 444, 445t Shaken baby syndrome, 39–40 Shame experienced by patients, 649–650, 652t Shearing injury diffuse white matter, 34 MRI image of, 86f, 88 triad of, 34 Shipley Institute of Living Scale, 166 Sickness Impact Profile, 422t Sildenafil in erectile dysfunction, 446 Sinemet in cognitive impairment, 622t, 623 Single-photon emission computed tomography (SPECT), 108t, 108–117 in activation studies, 117 in behavioral problems, 115–116 in brain injury, 110 capabilities of, 109, 111f, 112f combined with structural imaging, 113–115 computed tomography with, 113, 114f in headache after trauma, 386, 388 improvements in, 109, 110f indications for, 110 limitations of, 110 in mild TBI, 294t, 295 MRI integrated with, 92, 93f, 113, 114f, 116f in neuropsychological testing, 116–117 normal adult brain in, 111f practical considerations in, 109–110 procedure in, 109, 109f in psychiatric disorders, 110–113 recommendations for, 117 tracers in, 109, 112t in traumatic brain injury, 190 in various patient populations, 117 619C89 compound as NMDA receptor antagonist, 703t, 704 Skateboarding, injuries in, 741 Skiing, injuries in, 459 Skills training in behavioral therapy, 664–665 in pain management, 429t Skull fractures in children, 477 depressed, management of, 56–57 and seizure development, 312t types of, 29t SLAM model for concussion assessment, 457, 467, 471 Sleep disorders in See Fatigue and sleep problems normal cycle in, 370, 370t 769 Index rapid eye movement in, 370, 370t stages with nonrapid eye movement, 370, 371t Sleep-wake cycle abnormalities, 376–377 Smell sense disorders of, 253 posttraumatic, 65, 65t Snowboarding, injuries in, 459 Sobriety checkpoints, breath testing in, 739–740 Soccer, injuries in, 457–459 prevention of, 735 Social extinction in aggression, 670, 670t Social functioning of patients, 67–69 aggressive behavior in, 266 apathy in, 343t examination of, 207 unawareness in, 251, 360 Social issues, 571–580 care systems, 559–568 disability insurance, 576–577 employment studies, 574–576, 575f ethical and legal issues, 583–600 family system, 533–555 litigation problems, 578–579 Medicaid waiver services, 574, 574t public policy and legislation, 571–574 in sexual dysfunction, 447–448 vocational rehabilitation, 577–578 Social Security Disability Insurance (SSD), 576–577 Socioeconomic status and posttraumatic psychosis, 219 and risk of brain injury, 11–12 SOD enzyme, neuroprotection with, 706t, 708 Somatosensory testing, 397 evoked potentials in See Evoked potentials Spatial Span Test, 161t, 163 SPECT imaging See Single-photon emission computed tomography (SPECT) Spectroscopy, magnetic resonance See Magnetic resonance spectroscopy (MRS) Speech disorders, 325t, 325–326 in addicted persons with brain damage, 526 posttraumatic, 65 testing of, 161t, 164–165 “speed gel” in pain relief, 425t, 426 Spelling skills after brain injury in children, 478–479 Spine, railway, 579 Sports injuries, 12, 12f, 453–472 and apoE ε4 allele linked to poor outcome, 456, 463–464 in boxing, 455–457, 500 case studies of, 468–471, 469t in cycling, 13, 13t, 459–460 in equestrian events, 460 in football, 457, 472 helmet use affecting, 459–460, 472 and neurophysiology of concussion, 460–464 and Newtonian formulas in mechanics of injury, 471–472 prevention of, 470–471, 733–736 return-to-play criteria in, 465–467, 466t second impact syndrome in, 283, 462–463, 735 severity measurements in, 464t, 464–465, 465t sideline assessment in, 467–468 in skiing, 459 in snowboarding, 459 in soccer, 457–459 Staff in rehabilitation programs interactive training of, 673 management issues, 672–673 Standardized Assessment of Concussion (SAC), 465, 467 State programs relating to traumatic brain injury, 571–572, 572t, 574, 574t State-Trait Anger Expression Inventory2, 423t Stigmatization of patients, 650, 652t Stimulants adverse effects of, 624 in aggression, 272 in attention-deficit/hyperactivity disorder, 489 in cognitive dysfunction, 326t, 328, 622t, 622–624 in depression, 209 in fatigue, 379, 627 in mild TBI, 299 in motivational loss, 347–348, 348t in personality disorders, 254, 254t withdrawal from, 514 Stress acute stress disorder, 236–237 in hospitalization, 248, 249t posttraumatic See Posttraumatic stress disorder Stress inoculation training (SIT) in emotional reactions to injury, 671–672 Strokes PET scan in, 118 SPECT imaging in, 118 Stroop Color and Word Test, 161t, 163 Stupor, differential diagnosis of, 339 Substance abuse, 509–529 abstinence in, 518 aggression in, 264–265, 265t agitation in, 515–516 anxiety in, 520–521 apathy in, 343t before brain injury, 67 and breath testing at sobriety checkpoints, 739–740 cognition in, 516 complications of, 515–516 denial in, 518 depression in, 520–521 diagnosis of, 511–513 criteria for, 511, 512t screening tests in, 512–513, 513t economic effects of, 516 effects of, compared with effects of brain injury, 517, 517t functional MRI in, 124 group therapy in, 518–519 interventions in acute state, 510–511 and intoxication as defense to criminal charge, 594 and length of stay in hospital, 515 and letter to AA sponsor of member with brain injury, 525–527 medications in, 520–521 mood disorders in, differential diagnosis of, 205–206 and motorcycle accidents, 732 neural basis of, 513 neuropathological effects of, 516 and posttraumatic psychosis, 219 prevalence of, 509–510 prevention of injuries in, 737–740 psychiatric sequelae of, 511t psychiatric symptoms in, 515 and risk of brain injury, 9–10, 67 and sexual dysfunction, 444 SPECT imaging in, 111, 113 treatment of, 517–521 for depression or anxiety, 520–521 duration of, 519–520 resources for, 517, 517t settings for, 519 techniques applied to brain injuries, 517, 517t treatment of withdrawal in, 513–515 and twelve steps of AA, 528 rewritten for TBI patients, 529 Substance Abuse Subtle Screening Inventory (SASSI), 513 Substituted judgment in proxy decision making, 589–590 Suicide after brain injury, 208 risk in depression, 737 Sulindac, psychiatric side effects of, 612t Sumatriptan in headaches, 390 Superoxide activity after brain injury, 42–43 radicals in injured brains, 705 Superoxide dismutase, neuroprotection with, 706t, 708 Supplemental Security Income (SSI), program, 576–577 ... LY233053 ([1][2SR,4RS ]-4 -[ 1H-tetrazol-5-ylmethyl] piperidine-2-carboxylic acid), and CP101,606 ([1S, 29 ]-1 -[ 4-hydroxyphenyl ]-2 -[ hydroxy-4-phenylpiperidino ]-1 -propanol), an NR2B-selective NMDA receptor... α-amino-3-hydroxy-5methyl-4-isoxazolepropionate (AMPA)/kainate APV=2-amino-5-phosphovaleric acid; CPP= 3-( 2-carboxypiperizin-4yl)-propyl-1-phosphonic acid; I2CA=indole-2-carboxylic acid Pharmacotherapy of. .. distribution of both N-methyl-D-aspartate (NMDA) and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate/kainic acid (AMPA/KA) receptors has been directly related to the selective vulnerability of specific brain