Klinische Leitlinien zur Behandlung von Schulkindern mit einer Auf- merksamkeitsdefizit/ Hyperaktivitätsstörung (ADHS) Gekürzte Zusammenfassung von „Clinical Practice Guideline:Treatment of the School-Aged Child with ADHD“ der Ameri- can Academy of Pediatrics, PEDIATRICS Vol. 108 No 4, Oct. 2001, S 1033ff Dr. med. M. Ryffel Die vorliegenden Leitlinien sind für Erstversorger, d.h. in d
M.b5z.netNeuropsychiatric Sequelae of Traumatic Brain Injury The authors review the psychiatric disturbances associated with traumatic brain injury. Theyhighlight the close link between traumatic brain injury and psychiatry and provide an overviewof the epidemiology, risk factors, classification, and mechanisms of traumatic brain injury. Theydescribe various neuropsychiatric sequelae, and the respective treatments are outlined with em-phasis on a multidisciplinary approach. [Note: The following article is the fifth in a special neu- 500,000 will probably require hospitalization, and about ropsychiatry series edited by Dr. Constantine Lyketsos. The 80,000 will suffer from some level of chronic disability.1 Men first four articles appeared in the January–February 2000 are injured twice as frequently as women, with the risk of fatal head injury being four times greater. The incidence ofhead injury increases to peak from ages 15 to 25, thereafter TraumaisacommoncauseofbraininjuryintheUnited fallingoff,onlytoriseagaininlateryears.2Inpersonsunder States and is a significant public health problem.1 45 years of age, TBI is the leading cause of death and dis- Traumatic brain injury (TBI) can result in a variety of neu- ability, with an overall mortality rate of 25 per 100,000. Motor ropsychiatric disturbances ranging from subtle deficits to vehicle accidents are the most common cause of head injury, severe intellectual and emotional disturbances. In rare accounting for more than 50%, followed by falls (21%), vi- cases, it results in chronic vegetative states. The neuropsy- olence (12%), and injuries from sports or recreational activ- chiatric disturbances associated with TBI include cognitive ities (10%).3 Health costs from TBI are estimated to be on impairments, mood disorders, anxiety disorder, psychosis, This article will provide an overview of the common Risk Factors for Neuropsychiatric Disorders neuropsychiatric sequelae of TBI along with a guide to theassessment and treatment of these conditions. The primarygoal of this review is to demonstrate the link between psy- The major risk factors for neuropsychiatric distur- chiatry and TBI. We will summarize the epidemiology, risk bances after TBI include increasing age, arteriosclerosis, factors, classification, and mechanism of brain injury after and alcoholism. These all delay the reparative process TBI. Next, a description of the various neuropsychiatric within the central nervous system.5 Premorbid personality disorders associated with TBI will be provided. Finally, a also a plays a significant role in the process of rehabilita- brief discussion of pharmacological treatment in TBI will tion, as was pointed out by Symonds: “The response to be outlined, followed by concluding remarks.
head injury depends on the kind of head that was injured.”6 Received and accepted September 2, 1999. From the Neuropsychiatryand Memory Group, Department of Psychiatry and Behavioral Sciences, School of Medicine, The Johns Hopkins University, Baltimore, Maryland.
Address reprint requests to Dr. Rao, Osler 320, The Johns Hopkins Hos- The annual incidence of head trauma in the United States pital, Baltimore, MD 21287. email: [email protected] is approximately 2 million per year.1 Of these patients, Copyright ᭧ 2000 The Academy of Psychosomatic Medicine.
Similarly, factors such as marital discord, poor interper- oxia, anemia, metabolic abnormalities, hydrocephalus, in- sonal relationships, problems at work, or financial insta- tracranial hypertension, fat embolism, and subarachnoid bility are important contributors to the neuropsychiatric hemorrhage. Other delayed effects include release of ex- citatory amino acids, oxidative free-radical production, re-lease of arachidonic acid metabolites, and disruption of neurotransmitters like monoamines and serotonin.15–17 Head injury can be classified along several lines. The most common classification is based on physical trauma:open vs. closed head injury, depending on whether or notthe skull has been breached.
The neuropsychiatric disturbances associated with TBI are Another important classification system depends on numerous. They are generally observed to be disorders of the severity of initial impairment, combining the initial mood, cognition, or behavior. Cognitive deficit has been Glasgow Coma Scale (GCS), the duration of loss of con- variously classified as delirium,14 dementia due to head sciousness (LOC), and the duration of posttraumatic am- trauma,2 amnestic disorder due to head trauma,2 or intel- nesia (PTA).9 A GCS of 13–15, LOC of less than 30 min- lectual impairment,18 depending on the variety of symp- utes, and/or PTA of less than 1 hour is classified as mild toms and their time of onset and resolution. The behavioral TBI. People with moderate TBI have a GCS of 9–12, LOC problems associated with TBI have been the most difficult of 1–24 hours, and/or PTA of 30 minutes to 24 hours. A to classify. The signs and symptoms of the frontal and tem- GCS of 8 or less, LOC of more 24 hours, and/or PTA of poral lobe damage have been variously classified as frontal more than 1 day is classified as severe TBI.9 Some studies and temporal lobe syndromes,9 aggressive disorders,19 and have used only the GCS to classify the severity,10 whereas others have used LOC and/or PTA.11 The prognosis of In our opinion, these terms are too restrictive to describe moderate and severe TBI is fairly well correlated with these the complex clinical manifestations of diffuse brain damage.
characteristics, but the relationship is not as clear with Organic Personality Syndrome or Personality Changes Due milder forms of TBI, which falls into a less well-defined to Head Trauma are also misnomers, as there are no pro- spective studies to document that these symptoms are an ex-aggeration of premorbid personality. The DSM-IV classifi- cation of the neuropsychiatric sequelae of TBI is alsoinadequate. Except for “dementia due to head trauma,” all TBI is the result of mechanical forces applied to the other disorders are classified as “disorder due to general- skull and transmitted to the brain. This may lead to focal medical condition.” The term post-concussion syndrome and/or diffuse brain damage. Focal lesions often result (PCS), frequently noted in the literature, is also vague and from a direct blow to the head and include brain laceration, nondescriptive. It is also a misnomer because it can be seen contusion, intracerebral hemorrhage, subarachnoid or sub- in anyone with TBI, with or without a “concussion.” dural hemorrhage, and ischemic infarct. Contusion occurs We propose a classification of the neuropsychiatric se- directly beneath or contralateral to the site of impact, com- quelae of TBI according to their phenomenology as de- monly referred to as coup and contre-coup injury.12 It is scribed in Table 1. We prefer the term “behavioral dyscon- most common in the orbital–frontal area and the temporal trol disorder, major variant” to describe a specific tips, where acceleration/deceleration forces cause the brain syndrome of mood, cognitive, and behavioral disturbances to impact on the bony protuberances of the skull.13 following head injury. The term “behavioral dyscontrol Diffuse brain injury also results from the differential disorder, minor variant” is preferred to describe what is motion of the brain within the skull, causing a shearing and known as “post-concussion syndrome.” We believe that stretching of the axons.3 This can produce a wide spectrum both these disorders have the same etiopathogenesis; that of injuries, ranging from brief physiological disruption to is, diffuse brain damage, with predominance of frontal and widespread axonal tearing, called diffuse axonal injury temporal lobe lesions, as they are more likely to be injured.
(DAI).14 In addition to brain damage occurring at the time The two disorders probably differ only in the severity of of the impact, secondary damage from several processes their symptoms—major variant being more severe. The may occur during the recovery period. These include hyp- major variant has predominantly behavior symptoms, com- pared with the minor variant, which has more somatic come depends on a number of factors, such as degree of symptoms. What follows is a discussion of these disorders.
diffuse axonal injury, duration of LOC and PTA, clinicalevidence of brain stem dysfunction at the time of injury, and presence and size of focal hemispheric injury.
Treatment is multidisciplinary and includes pharma- TBI is associated with a plethora of cognitive deficits, cotherapy, physical therapy, occupational therapy, recrea- some of which are more common than others. They include tion therapy, speech therapy, and vocational rehabilitation.
impairment of arousal, attention, concentration, memory, Cognitive rehabilitation is also important, especially during language, and executive function. Loss of memory may be the first 6 months after injury, and involves techniques to for both verbal and nonverbal skills. Disturbances of ex- retrain the patient in specific domains by providing a series ecutive functioning include poor planning, organizing, se- of mental stimuli, tests, and activities.22 Dopaminergics23 quencing, and set-shifting, with impaired judgment and im- or psychostimulants may improve deficits of arousal, poor attention, concentration, and memory. Numerous case re- Researchers have suggested that cognitive deficits can ports are available on the efficacy of dopaminergics in be divided into four groups according to when they occur treating cognitive symptoms.24–26 Cholinergic agents such in relation to the phases of the TBI.20,21 The first is the period as those developed to treat dementia are also showing of loss of consciousness or coma, which occurs soon after injury. The second phase is characterized by a mixture ofcognitive and behavioral abnormalities, such as agitation, confusion, disorientation, and alteration in psychomotor ac-tivity. This period is associated with inability to recall Mood disorders associated with TBI have been re- events, sequence time, and learn new information. The first ported in the medical literature for a number of years.
two phases, which last anywhere from a few days to 1 month Adolf Meyer, in 1904, referred to these symptoms as “trau- after injury, are a form of posttraumatic delirium.14 What matic insanities,” and proposed that there might be an as- follows is a 6–12 month period of rapid recovery of cog- sociation between these symptoms and brain lesions.29 De- nitive function, followed by plateauing of recovery over 12– pression and mania are common after TBI.
24 months subsequent to the injury. The fourth phase is Major depression occurs in approximately 25% of pa- characterized by permanent cognitive sequelae, and includes tients with TBI.30,31 Feelings of loss, demoralization, and dis- problems with speed of information-processing, attention couragement seen soon after injury are often followed by and vigilance, short- and long-term memory deficits, verbal symptoms of persistent dysphoria. Fatigue, irritability, sui- and nonverbal deficits, and problems with executive func- cidal thoughts, anhedonia, disinterest, and insomnia are seen tions and mental inflexibility. This phase has also been de- in a substantial number of patients 6–24 months or even scribed as “dementia due to head trauma.” longer after TBI.32,33 Psychological impairments in excess of The cognitive deficits are caused by the cumulative the severity of injury and poor cooperation with rehabilitation effects of focal and diffuse brain damage.14 Cognitive out- are strong indicators of a persistent depressive disorder.9Clinical and research studies have also shown that poor pre-morbid level of functioning and past history of psychiatric Neuropsychiatric sequelae of traumatic brain
illness are major risk factors for depression.30 The mechanismof depression following head injury is probably due to dis- ruption of biogenic amine-containing neurons as they pass through the basal ganglia or frontal-subcortical white mat- ter.34 The presence of left dorsolateral frontal and left basal ganglia lesions is associated with an increased probability of The treatment of depression secondary to TBI is very similar to the treatment of major depressive disorder. It includes antidepressants, psychostimulants, and electro- convulsive therapy (ECT). The choice of medications must be influenced by their side-effect profile. Agents such as serotonin-specific reuptake inhibitors (SSRIs) are safe and tant as pharmacotherapy in the treatment of anxiety dis- well tolerated.35 Drugs with anticholinergic effects in gen- eral should be avoided. Psychostimulants36,37 and even thedopaminergics can be helpful in these cases, as they have an antidepressant effect. ECT is a highly effective mode oftreatment for TBI patients refractory to antidepressants.38It is important to remember that in TBI patients, mood Psychotic symptoms are not uncommon in TBI pa- disorders are commonly accompanied by problems in the tients. A review of the literature by Davison and Bagley51 other categories—cognitive, behavioral, and somatic.
revealed that 0.7%–9.8 % of patients with TBI develop Treatment should attempt to address as many areas as pos- schizophrenia-like psychosis. Most of these patients do not sible, and at the least, not worsen any specific area.
have a family history of schizophrenia. Other studies have Mania after TBI is less common than depression but shown that the incidence of head injury pre-dating psy- much more common than in the general population. It is chotic symptoms in a population of patients with schizo- seen in about 9% of patients.39 Changes in mood, sleep, phrenia is about 15%.52 Psychotic symptoms following and activation may manifest as irritability, euphoria, in- TBI often manifest as frank delusions, hallucinations, and somnia, agitation, aggression, impulsivity, and even violent illogical thinking. They may also be associated with symp- behavior.40 Positive family history of affective disorder and toms of agitation, ideas of reference, grimacing, silly gig- subcortical atrophy prior to TBI are added risk factors.41 gling, expression of odd ideas, regression, and impulsive Mania is often seen in patients with right-hemispheric lim- aggressiveness.53,54 The psychotic features may be acute or chronic, transient or persistent, and may or may not be Treatment with anticonvulsants such as carbamaze- pine or valproate may be more effective than lithium, Both right55 and left hemispheres56 have been impli- which is not specific to the neuropathology of TBI and may cated in the genesis of psychotic symptoms. It is important worsen cognitive impairment.9 Other than this, there is lit- to remember that psychosis is a symptom, not a diagnosis tle empirical knowledge about the treatment of mania fol- A rational approach based on our knowledge of the neuropathology of TBI must be applied when choosingtreatment options. For instance, when there is a suggestion of left-temporal involvement, there may be benefit fromthe use of an anticonvulsant. Delusional-type symptoms Anxiety disorders are common in patients with TBI that seem more related to cognitive and behavioral impair- and range in frequency from 11%–70%.42,43 All variants ments from frontal lobe dysfunction can benefit from do- of anxiety disorders are seen, including generalized anxiety paminergics. Neuroleptics, if administered, should be disorder, panic disorder, phobic disorders, posttraumatic given in low doses, as animal studies have shown impaired stress disorder, and obsessive–compulsive disorder. TBI patients often experience generalized “free-floating” anxi-ety associated with persistent worry, tension, and fearful- ness.44 Increased activity of the aminergic system and de-creased activity of the GABA inhibitory network is theproposed mechanism for the clinical manifestation of anxi- Ten percent of patients tend to have apathy without ety.45 Right-hemispheric lesions are more often associated depression, and 60% have some degree of apathy and de- with anxiety disorder than left-sided lesions.46 pression following TBI.58 Apathy refers to a syndrome of Anecdotal evidence suggests that antidepressants such disinterest, disengagement, inertia, lack of motivation, and as SSRIs, opioid antagonists such as naltrexone,47 and bus- absence of emotional responsivity. The negative affect and pirone48 are promising in the treatment of anxiety disor- cognitive deficits seen in patients with depression are not ders. Benzodiazipines49 and antipsychotics50 should be seen in patients with apathy. Apathy may be secondary to avoided because they cause memory impairment, disinhi- damage of the mesial frontal lobe.59 It often responds well bition, and delayed neuronal recovery.
to either psychostimulants, dextroamphetamine, amanta- Behavioral therapy and psychotherapy are as impor- ing longer than 1 year.68,69 The underlying pathogenesis isthought to be diffuse axonal injury from acceleration and deceleration forces. Interestingly, however, in some pa- nitive, and behavioral manifestations is seen in a number tients, the neurologic exam, neuropsychological testing, of patients after TBI.61 This occurs in both the acute and and neuroimaging studies have all been normal. Case re- chronic stages after TBI and in patients with mild, mod- ports of positron emission tomography (PET ) and single- erate, and severe injury. Its prevalence is about 5%–70%.19 photon emission computerized tomography (SPECT) stud- Because the major feature of the syndrome is dyscontrol ies are available that have shown focal abnormalities of of emotion, behavior, and cognition, we prefer the term glucose uptake and regional cerebral blood flow, respec- behavior dyscontrol disorder, major variant to define the tively.70,71 As far as we know, case-controlled studies of large series of patients are not available. Functional mag- Behavior dyscontrol disorder may be due to the effects netic resonance imaging (fMRI) studies might be able to of both focal and diffuse brain injury that results in a dis- shed light on this controversial syndrome. The perplexing ruption of neuronal network, creating lapses in cognitive question is whether PCS is really a separate entity with functioning and coarsening of behavior. Focal damage to specific features or is merely a milder version of the be- the orbital–frontal area causes disinhibition, and injury to the dorsal convexity of the frontal lobe causes dysexecutive The management of this disorder should be practical symptoms.59 Damage to the temporal lobes causes emo- and holistic. Education and support of patients and family members should be associated with supportive and behav- A multidisciplinary approach should be maintained in ioral psychotherapy, occupational and vocational interven- treating these patients. They would benefit from a combi- tion, and social skills training. If the patient is experiencing nation of environmental modification strategies;62 behav- significant cognitive or emotional difficulties, he or she ioral therapy, including positive and negative reinforce- should be evaluated for an affective or anxiety disorder and ment; vocational training;63 supportive psychotherapy; and family therapy.64 Pharmacotherapy for behavior dyscontroldisorder would include use of dopaminergic agents, psy-chostimulants, opioid antagonists, SSRIs, high-dose beta- blockers, buspirone, trazodone, and anticonvulsants.60,65 Behavior dyscontrol disorder, minor var- TBI patients may present with a variety of other symp- iant, or post-concussion syndrome (PCS), is the most com- toms, such as sleep disturbances or headaches. Careful monly diagnosed entity following TBI. The syndrome is evaluation of these patients should be done to ascertain if poorly defined and has been a source of controversy for a they are just isolated symptoms or if they are part of a number of years. It refers to a cluster of signs and symp- syndrome. Treatment should be aimed at a specific disorder toms that often follows mild TBI but can occur with injury of any severity.66 LOC is not necessary for its develop-ment.9 The symptoms of PCS can be broadly divided into Behavior dyscontrol disorder, minor variant
somatic, cognitive, and mood symptoms (Table 3).9 Cognition
Most patients recover within 3–6 months after injury.67 However, about 15% of patients will have symptoms last- Behavior dyscontrol disorder, major variant
injury.17 The frontal lobes are especially rich in dopamine, and their frequent involvement in TBI is associated withdecreased dopamine activity. Amantadine, bromocriptine, Treatment of neuropsychiatric sequelae of TBI is compli- and levodopa are commonly used dopaminergic agents.
cated. It includes pharmacological therapy and rehabilita- Amantadine was first used in the 1960s for treatment tive interventions, which are equally important. Rehabili- of influenza and was later found to have antiparkinsonian tation should begin on the day of the injury and continue actions.73 It enhances release of dopamine, inhibits reup- until the patient is stable or has reached his or her pre- take, and increases activity at the postsynaptic receptors.74 injury baseline. Rehabilitation is multifaceted. It includes Also, it is an N-methyl-D-aspartate (NMDA) glutamate re- cognitive rehabilitation, behavioral treatment, social skills ceptor antagonist, and this property might protect neuronal training, vocational training, individual therapy, group cells against excitotoxicity.74 Side effects of amantadine therapy, and family therapy. In this review, we will not be include confusion, hallucinations, edema, and hypotension.
discussing the extensive array of different rehabilitative Optimal doses are found to be between 50 mg/day and 400 measures; we will focus our attention only on the discus- mg/day. Case reports have shown that amantadine is useful sion of psychopharmacology in TBI patients. The overview in the treatment of mutism, impulsivity, and aggression, certainly does not encompass all the drugs used in brain- and helpful for information-processing, apathy, and inat- injured patients, but includes only the most commonly ad- tention.74 Gualtieri60 studied the effects of amantadine in 30 severely impaired TBI patients 2–144 months after in- The literature review reveals that there have been very jury. Sixty-three percent were noted to have improvement few randomized controlled studies of neuropsychiatric se- in symptoms of agitation, distractibility, emotional lability, quelae of TBI. Most reports in literature are either anecdotal reports or uncontrolled small-series case studies. In general, Levadopa and bromocriptine are both dopamine ago- TBI patients are very sensitive to medications; hence, treat- nists. They have been studied in small, uncontrolled case ment should be initiated at low doses with gradual increase.
studies and have been found to be effective in the treatment Careful and close monitoring of patients during treatment is of mood, cognition, and behavior.75,76 Lal et al.75 studied mandatory. The commonly used medications in brain-in- the effect of L-dopa/carbidopa in 12 moderate or severe jured patients are psychostimulants, dopaminergic agents, TBI patients and found functional cognitive and behavioral and antidepressants, and other drugs, such as opioid antag- improvement. Common side effects of these medications onists, beta-blockers, and anticonvulsants.
include nausea, psychosis, and sedation. The dose of L- dopa/carbidopa varies from 10/100 mg to 25/100 mg qid.
Bromocriptine is initiated at 2.5 mg/day and gradually in- Methylphenidate and dextroamphetamine are the com- monly used psychostimulants. They act by increasing cat-echolamine activity by blocking the reuptake of norepi- nephrine and dopamine.65 Side effects include paranoia,dysphoria, agitation, and irritability. Methylphenidate is SSRIs are useful in the treatment of depression, mood usually initiated at 5 mg bid and dextroamphetamine at 2.5 lability, and impulsivity.9 However, no placebo-controlled, mg bid. The maximum dose of both drugs is 60 mg/day.
double-blind case series is available to demonstrate the ef- Anecdotal reports have demonstrated the efficacy of ficacy of these medications. Tricyclics and monoamine ox- psychostimulants in the treatment of inattention, distracti- idase inhibitors are generally not preferred in the treatment bility, disorganization, hyperactivity, impulsivity, hypo- of TBI patients because of their anticholinergic side effects arousal, apathy, and hypersomnia.24,37,72 One double-blind, and drug–food interactions, respectively. Saran77 con- placebo-controlled cross-over study of methylphenidate in ducted a cross-over study of phenelzine and amitriptyline 15 TBI patients showed improvement in mood and cog- in patients with minor brain injury and found no response.
Studies have shown that trazodone is useful for agitationand sleep.78 For information about and dosage of these drugs, the reader is advised to refer to the psychopharma- TBI is frequently associated with disturbances of do- cology chapter in Neuropsychiatry of Traumatic Brain In- pamine transmission, which persists for many years after treating self-injurious behavior.82 A study on three bulimicTBI patients83 reported its efficacy.
The role of anticonvulsants in the treatment of neu- Buspirone, a selective serotonin antagonist is useful in ropsychiatric sequelae of TBI are multiple. They are used the treatment of anxiety disorders and aggression in doses to treat seizure disorder, mood lability, mania, impulsivity, aggression, and rage.79,80 Carbamazepine and valproic acid Similarly, beta-blockers, such as propranolol, have are most commonly used and found to be equally benefi- also been used to treat aggression and violent behavior.85 cial. No large-scale controlled studies are available to dem-onstrate the efficacy of these drugs. Phenytoin and barbi- Patients with traumatic brain injury are often referred to as performance81 and, hence, are not recommended. For in- “the walking wounded,” because a number of them have formation about and dosage of these drugs, the reader is persistent neuropsychiatric sequelae. Even though they ap- advised to refer to the psychopharmacology chapter in pear physically “normal,” they are disabled personally, so- Neuropsychiatry of Traumatic Brain Injury.65 cially, and occupationally. Ideally, treatment of these pa-tient should involve a multidisciplinary approach, with the neuropsychiatrist working in close collaboration with thepatient, family, neurologist/neurosurgeon, physiatrist, so- Studies have shown that naltrexone, an opioid antag- cial worker, and the staff of community groups such as the onist, in doses of 50 mg–100 mg/day may be useful in local chapter of the brain injury association.
1. Frankowski RF: Descriptive epidemiologic studies of head injury 13. Gennarelli TA: Cerebral concussion and diffuse brain injuries, in in the United States: 1974–1984. Adv Psychosom Med 1986; Head Injury, Vol 2. Edited by Cooper PK. Baltimore, MD, Williams 2. Capruso DX, Levin HS: Neuropsychiatric aspects of head trauma, 14. Kwentus JA, Hart RP, Peck ET, et al: Psychiatric complications of in Comprehensive Textbook of Psychiatry, Vol 1. Edited by Kaplan closed head trauma. Psychosomatics 1985; 26:8–15 HI, Saddock BJ. Baltimore, MD, Williams & Wilkins, 1995, pp 15. Palmer AM, Marion DW, Botscheller ML, et al: Traumatic brain injury-induced excitotoxicity assessed in a controlled cortical im- 3. McAllister TW: Neuropsychiatric sequelae of head injuries. Psy- pact model. J Neurochem 1993; 61:2015–2024 16. Hammill RW, Woolf PD, McDonald JV, et al: Catecholamines pre- 4. Max W, Mackenzie E, Rice D: Head injuries: cost and conse- dict outcome in traumatic brain injury. Ann Neurol 1987; 21:438– quences. J Head Trauma Rehabil 1991; 6:76–91 5. Lishman WA: Physiogenesis and psychogenesis in the post- 17. Vecht CJ, van Woekom TCAM, Teelken AW, et al: Homovanillic concussional syndrome. Br J Psychiatry 1988; 153:460–469 acid and 5-hydroxyindole acetic acid cerebrospinal fluid levels.
6. Symonds CP: Mental disorder following head injury. Proceedings of the Royal Society of Medicine 1937; 30:1081–1092 18. Lishman WA: The psychiatric sequelae of head injury: a review.
7. Whitlock FA, Stoll JK, Rekhdahl RJ: Crisis, life events, and acci- dents. Aust N Z J Psychiatry 1977; 11:127–132 19. Silver JM, Yudofsky SC: Aggressive disorder, in Neuropsychiatry 8. Selzer ML, Rogers JE, Kern S: Fatal accidents: the role of psycho- of Traumatic Brain Injury. Edited by Silver JM, Yudofsky SC, pathology social stress, and acute disturbances. Am J Psychiatry Hales RE. Washington, DC, American Psychiatric Press, 1994, pp 9. Kraus MF: Neuropsychiatric sequelae: assessment and pharmaco- 20. Levin HS: Neurobehavioral sequelae of head injury, in Head Injury, logic intervention, in Traumatic Brain Injury, Vol 14. Edited by 2nd Edition. Edited by Cooper PR. Baltimore, MD, Williams & Marion DW. New York, Thieme Medicine Publishers, 1999, pp 21. Cripe LI: The neuropsychological assessment and management of 10. Kraus JF, Black MA, Hessol N, et al: The incidence of acute brain closed head injury: general guidelines. Cognitive Rehabilitation injury and serious impairment in a defined population. Am J Epi- 22. Wilson BA: Cognitive rehabilitation: how it is and how it might 11. Annegers JF, Grabow JD, Kurland CT, et al: The incidence, causes, be. J Int Neuropsychol Soc 1997; 3:487–496 and secular trends in head injury in Olmstead County, Minnesota: 23. Karli DC, Burke TD, Kim HJ, et al: Effects of dopaminergic com- 1965–1974. Neurology 1980; 30:912–919 bination therapy for frontal lobe dysfunction in traumatic brain in- 12. Auerbach SH: The pathophysiology of traumatic brain injury, in jury rehabilitation. Brain Inj 1999; 13:63–68 Physical Medicine and Rehabilitation: State of the Art Review, 24. Van Reekum R, Bayley M, Garner S, et al: N-of-1 study: amanta- Traumatic Brain Injury, Vol 3. Edited by Horn IJ, Cope DN. Phila- dine for the amotivational syndrome in a patient with TBI. Brain delphia, PA, Hanley and Belfas, 1989, pp 1–11 25. Bleiberg J, Garmoe W, Cederquist J, et al: Effects of dexedrine on 49. Preston GC, Ward CE, Broks P, et al: Effects of lorazepam on performance consistency following brain injury. Brain Inj 1993; memory attention and sedation in attention by Ro15-1788. Psycho- 26. Kraus MF, Maki P: The combined use of amantadine and L-dopa/ 50. Feeney DM, Gonzalez A, Law WA: Amphetamine, haloperidol, carbidopa in the treatment of chronic brain injury. Brain Inj 1997; and experience interact to affect rate of recovery after motor cortex 27. Taverni JP, Seligei G, Lichtman SW: Donepezil-mediated memory 51. Davison K, Bagley CK: Schizophrenia-like psychosis associated improvement in traumatic brain injury during post-acute rehabili- with organic disorder of the CNS. Br J Psychiatry 1969; 28. Goldberg E, Gerstman LJ, Mattis S, et al: Effects of cholinergic 52. Nasrallah HA, Fowler RC, Judd LL: Schizophrenia-like illness fol- treatment on posttraumatic anterograde amnesia. Arch Neurol lowing head injury. Psychosomatics 1981; 22:359–361 53. Brown G, Chadwick O, Shaffer D, et al: A prospective study of 29. Meyer A: The anatomical facts and clinical varieties of traumatic children with head injuries: psychiatric sequelae. Psychol Med insanity. Am J Insanity 1904; 60:373–441 30. Fedoroff JP, Starkstein SE, Forrester AW, et al: Depression in pa- 54. Thompsen C: Late outcome of very severe blunt head trauma: a tients with traumatic brain injury. Am J Psychiatry 1992; 149:918– 10–15-year follow-up. J Neurol Neurosurg Psychiatry 1984; 31. Jorge RE, Robinson RG, Arndt SV, et al: Comparison between 55. Levine DN, Finkelstein S: Delayed psychosis after right temporal– acute and delayed-onset depression following traumatic brain in- parietal stroke or trauma: relation to epilepsy. Neurology 1982; 32. Hinkeldy NS, Corrigan JD: The structure of head-injured patients’ 56. Lishman WA: Brain damage in relation to psychiatric disability neurobehavioral complaints: preliminary studies. Brain Inj 1990; after head injury. Br J Psychiatry 1968; 114:373–410 57. Feeney DM, Sutton RL: Pharmacotherapy for recovery of function 33. Van Zomeran AH, van den Burg W: Residual complaints of patients after brain injury. Crit Rev Neurobiol 1997; 3:135–197 two years after severe head injury. J Neurol Neurosurg Psychiatry 58. Kant R, Duffy JD, Pivovarnik A: The prevalence of apathy follow- ing head injury. Brain Inj 1988; 12:87–92 34. Starksein SE, Robinson RG, Price TR: Comparison of cortical and 59. Duffy JD, Campbell JJ: The regional prefrontal syndromes: a theo- subcortical lesions in the production of poststroke mood disorders.
retical and clinical overview. J Neuropsychiatry Clin Neurosci 35. Bessette RF, Peterson LG: Fluoxetine and organic mood syndrome.
60. Gualtieri CT: Neuropsychiatry and Behavioral Pharmacology. New 36. Kraus MF: Neuropsychiatric sequelae of stroke and traumatic brain 61. Gerring JP: Psychiatric sequelae of severe closed head injury. Pe- injury: the role of psychostimulants. Int J Psychiatry Med 1995; 62. Campbell JJ, Duffy JD, Salloway SP: Treatment strategies for pa- 37. Gualtieri CT, Evans RW: Stimulant treatment for the neurobehav- tients with dysexecutive syndromes. J Neuropsychiatry Clin Neu- ioral sequelae of TBI. Brain Inj 1988; 2:273–290 38. Ruedrich SL, Chu CC, Moore SL: ECT for major depression in a 63. Sohlberg KM, Mateer CA: Training use of compensatory memory patient with acute brain trauma. Am J Psychiatry 1983; 140:928– books: a three-stage behavioral approach. J Clin Exp Neuropsychol 39. Jorge RE, Robinson RG, Starksein SE, et al: Secondary mania fol- 64. Epstein NB, Bishop DS: Problem-centered systems therapy of the lowing traumatic brain injury. Am J Psychiatry 1993; 150:916–921 family, in Handbook of Family Therapy. Edited by Gurman A, 40. Stuart JW, Hemsath RN: Bipolar illness following TBI treatment Kniskern D. New York, Brunner/Mazel, 1981, pp 444–482 with lithium and carbamazepine. J Clin Psychiatry 1988; 49:74–75 65. Silver JM, Yudofsky SC: Psychopharmacology, in Neuropsychiatry 41. Robinson RG, Boston JD, Starkstein SE, et al: Comparison of ma- of Traumatic Brain Injury. Edited by Silver JM, Yudofsky SC, nia and depression after brain injury: causal factors. Am J Psychi- Hales RE. Washington, DC, American Psychiatric Press, 1994, pp 42. Klonoff H: Head injuries in children: predisposing factors, accident 66. Evans RW: The post-concussion syndrome and the sequelae of mild conditions, accident proneness, and sequelae. Am J Public Health head injury. Neurol Clin 1992; 10:815–847 67. Levin HS, Mattis S, Ruff RM, et al: Neurobehavioral outcome fol- 43. Lewis A: Discussion on differential diagnosis and treatment of lowing minor head injury: a three-center study. J Neurosurg 1987; post-concussional states. Proceedings of the Royal Society of Med- 68. Rutherford WH, Merrett JD, McDonald JR: Symptoms at one year 44. Lewis L, Rosenberg SJ: Psychoanalytic psychotherapy with brain- following concussion from minor head injuries. Brain Inj 1978; injured adult psychiatric patients. J Nerv Ment Dis 1990; 178:69– 69. McLean A, Temkin NR, Dikmen S, et al: The behavioral sequelae 45. Paul SM: Anxiety and depression: a common neurobiological sub- of head injury. J Clin Neuropsychol 1983; 5:361–376 strate. J Clin Psychiatry 1988; 49(suppl):13–16 70. Langfitt TW, Obrist WD, Alavi A, et al: Computerized tomography 46. Jorge RE, Robinson RG, Starkstein SE, et al: Depression and anxi- magnetic resonance imaging and positron emission tomography in ety following TBI. J Neuropsychiatry Clin Neurosci 1993; 5:369– the study of brain tumor. J Neurosurg 1988; 64:760–767 71. Gray BG, Ichise M, Chung DG, et al: Technitium 99m HMPAO 47. Tennant FS: Naltrexone treatment for PCS. Am J Psychiatry 1987; SPECT in evaluation of a patient with a remote history of TBI: a comparison with x-ray computed tomography. J Nucl Med 1992; 48. Gualiteri CT: Buspirone: neuropsychiatric effects. J Head Trauma 72. Evans RW, Gualtieri CT, Patterson DR: Treatment of chronic closed head injury with psychostimulant drugs: a controlled case study of 79. Mattes JA: Comparative effectiveness of carbamazepine and pro- an appropriate evaluation procedure. J Nerv Ment Dis 1987; pranolol for rage outburst. J Neuropsychiatry Clin Neurosci 1990; 73. Schwab RS, England AC, Postkanza DC, et al: Amantadine in the 80. Giakas WJ, Seibyl JP, Mazure CM: Valproate in the treatment of treatment of Parkinson’s disease. JAMA 1969; 208:1168–1170 temper outburst (letter). J Clin Psychiatry 1990; 51:525 74. Nickels JL, Schneider WN, Dombovy ML, et al: Clinical use of 81. Timble MR: Anticonvulsant drug and cognitive function: a review amantadine in brain injury rehabilitation. Brain Inj 1994; 8:709– of literature. Epilepsia 1987; 28:S37–S45 82. Sokol MS, Campbell M: Novel psychoactive agents in the treat- 75. Lal S, Merbitz CP, Gripp JC: Modification of function in a head ment of developmental disorders, in Psychopharmacology of the injury patient with Sinemet. Brain Inj 1988; 2:225–233 Developmental Disabilities. Edited by Aman MG, Sigh NN. New 76. Dobkin BH, Hanlan R: Dopamine against treatment of anterograde York, Springer-Verlag, 1988, pp 147–167 amnesia from a mediobasal forebrain injury. Ann Neurol 1993; 83. Childs A: Naltrexone in organic bulimia: a preliminary report.
77. Saran AS: Depression after minor closed head injury: role of dexa- 84. Levine AM: Buspirone and agitation in head injury. Brain Inj 1988; methasone suppression test and antidepressants. J Clin Psychiatry 85. Yudofsky SC, Silver JM, Schneider SE: Pharmacological treatment 78. Nirenberg AA, Addler LA, Peselow E, et al: Trazodone for anti- of aggression. Psychiatric Annals 1987; 17:397–407 depressant and related insomnia. Am J Psychiatry 1994; 151:1069–1072
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