Neurocuse (1997) Vol. 3. pp.

137-149 Oxford University PresA 1997

Dramatic Neurobehavioral Disorder in Two Cases

Following Bilateral Anteromedial Frontal Lobe Injury:
Delayed Psychosis and Marked Change in Personality

Colin Harrington, Stephen Salloway and Paul Malloy

Department of Clinical Neurosciences and Psychiatry and Human Behavior, Brown University School of Medicine,
Providence, RI, USA

Abstract

This paper describes two cases of closed head injury causing bilateral frontal lobe contusions that resulted
in enduring changes in self-control, perception, mood and cognition. In the first case the primary feature was
delayed-onset psychosis. In the second case the patient developed mood lability, poor impulse control, a
dramatic change in personality and impaired cognition. Midline, anterior frontal regions were most severely
affected In both cases. The diagnostic evaluation and the clinical course are described. The neuropsychiatric
syndromes are discussed with reference to lesion location and the literature on the neurobehavioral sequelae
of closed head injury.

Introduction
There are more than two million cases of traumatic brain
injury (TBI) reported each year, with 70 000-90 000 of
these survivors suffering chronic neuropsychiatric sequelae
(Silver et al., 1992). The majority of these cases are the
result of motor vehicle accidents (MVA), but other
common causes include falls, assaults and recreation-
related injuries. The mechanisms of brain injury include
direct tissue destruction from penetrating injuries, contu-
sions, diffuse axonal injury, mass effect from hematomas,
hypoxia and free radical formation (Silver et al., 1992).
Contusions, including contrecoup injury, occur primarily in
the frontal and temporal lobes where brain parenchyma is
closely associated with the bony prominences at the base of
the skull. Diffuse axonal injury occurs in the context of
acceleration/deceleration injuries and results from the
twisting and shearing forces acting on axons. Neuro-
transmitter systems implicated in the neuropsychiatric
sequelae of TBI are reviewed extensively elsewhere (Silver
et al., 1991, 1992) and include norepinephrine, serotonin,
glutamate and dopamine. The neuropsychiatric sequelae of
TBI include cognitive deficits, most commonly in
concentration, processing speed, memory and executive
functions, affective disorders (both depression and mania),
anxiety disorders, psychosis, mood lability, aggression,
personality changes and epilepsy.
We describe two cases of TBI involving bilateral
contusions to the anteromedial frontal lobes. The clinical
manifestations of the two cases were quite different,
demonstrating the wide variability of neurobehavioral
dysfunction seen after orbitomedial frontal injury.
The orbitofrontal region is closely connected to
subcortico-thalamic limbic structures and plays a pivotal
role in the regulation of impulses and mood. Injury to this
region can result in dramatic personality change, im-
pulsivity, mood lability and impaired self-monitoring. In
case 1 we report on a 34-year-old man who sustained a
severe TBI at the age of 21 and went on to develop a
delayed-onset psychotic disorder and depression. The
patient had abnormalities on EEG and a positive response
to carbamazepine which raised the possibility of temporal
lobe epilepsy (TLE). The discussion of this case will
review the known patterns of regional brain dysfunction in
injury-induced psychosis. The diagnoses of psychosis and
epilepsy, and their relationship to brain injury, will be
reviewed as well. Case 2 involves a 57-year-old man who
slipped on the ice and struck the back of his head, leading to
contrecoup frontal injury. This minor accident caused a
change in personality, marked mood lability and impulsiv-
ity, and impairment in executive cognition. The discussion
of case 2 highlights the functions of the orbitofrontal cortex.

Correspondence to: Stephen Salloway, Director of Neurology, Butler Hospital. 345 Blackstone Blvd, Providence, RI 02906, U S A
138 C. Harrington, S. Salloway and P. Malloy
Case 1
MF was a 34-year-old white male who had an unremark-
able medical history until the age of 21 when he sustained a
traumatic brain injury as an unrestrained passenger in a
MVA. He was found unconscious at the scene with reports
of systolic blood pressures as low as 60 mmHg. He was
intubated in the field. On initial examination he had no
spontaneous respiration, was unresponsive to verbal
commands, and had equal and reactive pupils. He had
roving eye movements, a right gaze preference, an upgoing
left toe, and intermittent spontaneous movements of the
right upper extremity only. Chest X-ray revealed multiple
rib fractures, and a chest tube was placed. Blunt abdominal
trauma required splenectomy. Initial CT scan of the head
demonstrated small midline ventricles, but no contusions or
extra-axial fluid collections. There was no mention of a
skull fracture. A ventriculostomy was placed for monitor-
ing of intracranial pressure and drainage. On the fourth
hospital day he was extubated, and the ventriculo-
stomy was removed. He remained unresponsive to verbal
commands until day 13 when he began to follow simple
commands. He was transferred to another hospital closer to
his home on hospital day 18. An EEG performed 3 months
after his injury demonstrated paroxysmal medium to high
amplitude slow wave activity with left anterior predomi-
nance. He was placed on prophylactic phenytoin. This was
discontinued 6 years after his head injury as he never
experienced a documented seizure.
The patient was a US serviceman at the time of the
accident, and received an honorable discharge for medical
reasons. He received extensive physical therapy and speech
therapy in rehabilitation. Residual neurological deficits
included moderate left hemiparesis, left foot drop, and a
neurogenic bladder. He appeared to make a good recovery
and went on to earn a BS degree in medical technology
within 7 years of the accident. However, he took 6 years to
complete the degree and required special accommodation
during examinations due to distractability.
Prior neuropsychiatric history was notable for excessive
weekend alcohol use, and brief experimentation with
hallucinogens and marijuana. He sustained a minor head
injury with a 1 h loss of consciousness at age 5 , secondary
to a bicycle accident. This reportedly resulted in ‘learning
difficulties’, and he repeated the first grade. Family
psychiatric history was notable for alcoholism in his
mother.
Eight years after the accident, at the age of 29, the
patient became preoccupied with the paranoid belief that he
was being pursued as a suspect in a widely publicized
murder in his home state. He believed that his telephone
was tapped and that he was being tailed by the police.
Hallucinations were denied. Mild depressive symptoms
were described, but were less prominent than his presenting
psychotic symptoms. The depth of his convictions to his
delusion was demonstrated when he made a suicide attempt
by overdose in an effort to avoid incarceration after he
became convinced that he would be arrested. While
hospitalized he made a second suicide attempt by wrist
slashing. Examination revealed stable neurological deficits
of moderate left hemiparesis, left foot drop, and expressive
dysprosody. Evaluation at that time included a CT scan of
the brain which demonstrated bilateral confluent frontal
white matter hypodense areas, left greater than right,
consistent with encephalomalacia, and mild bilateral
cortical volume loss, right fronto-parietal greater than left
(Fig. 1). EEG was normal. Serum chemistries, liver func-
tion testing, and thyroid function testing were normal.
Psychotic symptoms responded to low-dose haloperidol.
The patient was discharged to a highly structured out-
patient psychiatric program and did well for -8 months
while maintained on perphenazine. Amitriptyline was
added for symptoms of depression. Eight months after
the first hospitalization, the patient was re-admitted for
escalating suicidal ideation related to recurrent paranoid
concerns about his imagined implication in ‘terrible’
crimes, and fear that he would be arrested and incarcerated.
Medication non-compliance was suspected but not
confirmed. He responded well to hospital structure and
continuation of neuroleptics. Repeat CT scan of the head
was unchanged. Repeat EEG was normal.
He was discharged back to outpatient treatment and
maintained on amitriptyline and fluphenazine. Neuropsy-
chological testing was obtained in 1991, and revealed mild
deficits in sustained attention, mild to moderate deficits in
executive function and response inhibition on Go-No-Go
tasks, problems with retrieval and short-term memory,
anosognosia, and marked aprosody. Mild deficits in
construction and visuoperception were thought to be
secondary to poor organization and integration of informa-
tion (i.e. dysexecutive problems).
A trial of fluoxetine was substituted for aniitriptyiine in
an effort to minimize antidepressant side-effects, but
fluoxetine caused drooling, ataxia, sedation, hypophonia
and motor slowing, and had to be discontinued. The patient
remained well on fluphenazine alone. Fluphenazine was
empirically tapered and discontinued, and his psychiatric
symptoms remained mild for -3 months off medications.
Paranoid symptoms reappeared and responded to low-dose
thioridazine. Again, the patient remained well for - I I
months until he discontinued his medications and was
rehospitalized, after attempting to gain access to a tele-
vision camera at a professional sporting event to reveal
what he believed to be special information regarding the
0. J. Simpson trial.
On discharge from the hospital, at age 32, now 1 1 years
after his head injury, the patient was placed on fluphena-
zine decanoate to ensure compliance. Though he mini-
mized his cognitive and motor deficits and had limited
insight into his symptoms, he remained compliant with his
treatment. Fluphenazine decanoate was tapered to 6.25 mg
every 3 weeks with good symptom control. Despite
 Neurobehavioral disorder following bilateral anteromedial frontal lobe injury
minimal side-effects, the patient insisted upon a return to
oral thioridazine, misattributing many of his residual
neurologic symptoms to fluphenazine.
Routine neurological follow-up during this period of
stability included a screening EEG which demonstrated
bilateral temporal lobe slowing and bilateral posterior
temporal sharp waves suggestive of a diagnosis of temporal
lobe epilepsy. There was no interim history of seizures.
Prior neurologic follow-up had been unremarkable,
including normal EEGs. Carbamazepine was started and
titrated to 200 mg three times daily with good response.
The patient has tolerated this well, with levels in the mid-
therapeutic range. He is clinically stable, and remains o n
carbamazepine and thioridazine. Psychotic and affective
symptoms have been in remission for 2 years.
Discussion
MF suffered a severe closed head injury with hypotension,
hypoventilation, left hemiparesis, chest and abdominal
trauma, and deep depression of consciousness. Overall, he
made a good gradual recovery of function. The. main
finding in this case, and the most disabling symptom for
this patient, was the development of delayed-onset delu-
sions 8 years after the head injury. There was no significant
personal or family psychiatric history other than alcohol
abuse, and it seems reasonable to assume an etiological
relationship between head injury and psychosis in this
patient.
Psychotic symptoms occur frequently in patients
following head injury, with prevalence rates in the litera-
ture ranging from 0.7 to 20%. Davison and Bagley (1969)
conducted a large survey and reviewed eight studies which
examined the prevalence of psychosis secondary to brain
injury, and documented rates of psychosis ranging from 0.7
to 9.8%. Subsequent studies have likewise confirmed an
increased incidence of psychosis in patients with head
injury (Brown et al, 198 1 ; Thomsen, 1984; Violon and De
Mol, 1987). Severity of head injury is directly related to an
increased risk of post-traumatic psychosis. Hillbom ( 1960)
reviewed the records of 3552 Finnish soldiers who suffered
TBI during WWII and noted a correlation between severity
of head injury and psychosis, with frequencies of psychosis
ranging from 2.8% in those with mild TBI to 7.2% in the
moderate head injury group, and 14.8% in the severe head
injury group.
Studies have also shown an increase in head injury
among psychotic patients. Davison and Bagley (1969)
reviewed five studies which examined the frequency of
brain injury in identified psychotic populations, document-
ing brain injury histories in 1- 15% of the patients. More
recently, Wilcox and Nasrallah ( 1987) conducted retro-
spective chart reviews of 659 patients admitted to
university-based hospitals and compared frequencies of
head injury histories in 200 patients with schizophrenia,
122 with mania, 203 with depressive disorders, and 134
139
surgical controls. The frequency of documented childhood
brain injury in the schizophrenic population was 11%
compared to 4.9, 1.5 and 0.7% in the manic, depressed and
surgical control populations respectively.
The onset of psychotic symptoms in this case was 8 years
after TBI, reflecting the variable onset and course of
psychotic symptoms after brain injury. Late-onset psycho-
sis after TBI has been reported in other studies. Bamhill
and Gaultieri (1989) reported on two cases of late-onset
psychosis which presented more than 3 years after TBI.
Affective symptoms were prominent in both of these
patients. CT scans demonstrated diffuse atrophy and
ventricular enlargement, but no focal changes. EEG in
one patient demonstrated high-voltage slow wave activity
in the right hippocampal region, while EEGs in the other
case were repeatedly negative. There was no evidence in
either patient of frank epileptiform activity. Both patients,
who had done poorly despite multiple prior pharmacologic
trials, improved after the addition of carbamazepine to their
regimen. Filley and Jarvis (1987) also described a case of
delayed-onset psychosis occurring 3 years after TBI. Of
particular relevance to this case, the patient had bifrontal
and right hemisphere pathology as demonstrated by head
CT and neuropsychological testing. Levine and Finklestein
( 1 982) reported on eight patients who developed delayed-
onset psychosis after right temporoparietal stroke or
trauma. Onset of psychotic symptoms ranged from 1 month
to I 1 years after brain injury, and seven of eight patients
had seizures. In addition, in Thomsen’s (1984) review of 40
patients followed for 10-15 years after TBI, six of eight
patients who developed psychosis had a delayed onset of
symptoms.
CT scan (Fig. 1) done in 1991 shows clearly demarcated
hypodensities in the anteromedial frontal lobes bilaterally,
and mild cortical atrophy. Neurological examination
revealed persistent moderate left hemiparesis and dyspro-
sodic speech. Neuropsychological testing revealed promi-
nent deficits in executive and attentional functions. Taken
together, these findings suggest bifrontal and right hemi-
sphere pathology, and their combination may help to
explain the development of psychosis, depression, and
impulsive suicidal behavior in this patient. The literature
suggests temporal lobe involvement may be important in
the development of psychosis. In Hillbom’s (1960) sample,
40% of those patients with post-traumatic psychosis had
temporal lobe lesions. Davison and Bagley (1969) reported
left hemisphere and temporal lobe predominance of a wide
variety of CNS lesions in 150 patients with psychosis
related to focal disease. In contrast, Koufen and Hagel
(1987) reported bilateral abnormal EEG foci in 70 of 100
patients with post-traumatic psychotic disorders, with
unilateral left-sided findings in only 12 patients. They
did, however, note marked predominance of temporal lobe
foci.
Post-stroke studies suggest that patients with right
hemisphere lesions superimposed upon generalized atrophy
140 C. Harrington, S. Salloway and P. Malloy

Fig. 1. (a) Non-contrast axial CT scan from MF at the superior end of the body of the lateral ventricles 8 years after the accident dernonstrates WCII
developed hypodense areas in the anterio-medial frontal lobe, left greater than right. (b) Non-contrast CT scan from MF. the same study, near the
superior surface of the brain demonstrates mild, diffuse sulcal widening, right slightly greater than left.

are at particular risk for developing psychosis. Rabins et al.
( 1991 ) reported on five patients who developed an atypical
schizophreniform psychosis following right hemisphere
stroke and compared them to controls matched for lesion
size and location who did not develop a psychiatric dis-
order. Those patients who developed a psychotic disorder
had larger frontal horn and third ventricle ratios on CT scan
than did the control subjects, leading the authors to
conclude that premorbid subcortical atrophy and a new
right hemisphere lesion are risk factors for developing
psychosis after stroke. These findings are consistent with
those of Levine and Grek (1984) who studied nine patients
with delusions after right hemisphere stroke, comparing
them to 16 control patients with right hemisphere lesions of
similar size and location but without delusions, and
concluded that new right hemisphere lesions and pre-
existent diffuse atrophy are the primary risk factors for
developing psychosis following stroke. Age, location and
size of lesion had no major effect on the development of
psychosis. Though the patients studied in the post-stroke
literature are significantly older than the typically younger
victims of TBI, the combination of right hemisphere and
bifrontal pathology in this case is similar to the damage in
post-stroke patients.
The role of the right hemisphere and frontal lobe lesions
in the development of psychosis is more compelling when
the nature of the psychotic disorder is limited to mono-
symptomatic or content-specific delusions (CSD) (Malloy
et al., 1992). Content-specific delusions relate to a specific
content or theme. Patients with CSD often fail to exhibit
the formal thought disorder or deficit symptoms of other
psychotic patients. Primary cases of Capgras, such as seen
in schizophrenia, tended to have negative diagnostic work-
ups and gradual onset of symptoms, while secondary cases
had acute onset of symptoms, and positive findings o n
EEG, brain imaging, neurological exam and cognitive
testing. Malloy and Richardson (1994) studied cases of
Capgras syndrome, Fregoli syndrome, erotomania, Othello
syndrome, reduplicative paramnesia and others, and con-
cluded that lesions of the frontal lobes and right hemisphere
are critical to the development of content-specific delu-
sions. Although the psychotic disorder in this case does not
fit the definition of a CSD, the CT findings and neuro-
psychological data are consistent with those found in
secondary CSDs.
Neuropsychological mechanisms have been proposed to
account for the role of frontal and right hemisphere injury
in the development of delusions, and may be relevant to
 Neurobehavioral disorder following bilateral anteromedial frontal lobe injury
the case presented here. In the case of reduplicative
paramnesia, it is hypothesized that right posterior temporo-
parietal lesions may lead to visuospatial deficits that result
in a sense of unfamiliarity for place (Benson et al., 1976).
Benson et al. (1976). Staton et af. (1982), Hakim et al.
(1988), Kapur et al. (1988), Ruff and Volpe (1981) and
Forstl et al. (1991)invoke additional frontal lobe deficits in
self-monitoring and working memory which result in
ongoing misinterpretation of events, inability to integrate
new information with past experience, and indifference and
unconcern when confronted with conflicting information,
which leads to the formation of a delusion.
Feinberg and Shapiro (1989) stress the importance of
right temporal lobe dysfunction in the production of these
delusional disorders. They cite the occurrence of dt5jA-vu
phenomena in patients with temporal lobe epilepsy and in
subjects from Penfield’s electrical stimulation studies of
the non-dominant temporal lobe cortex, and suggest that
abnormal right temporal lobe activity may result in the
experiences of over-familiarity of Fregoli syndrome, while
right temporal lobe destructive lesions may result in the
experience of unfamiliarity of Capgras syndrome. Using
depth electrodes, Bancaud et al. ( I 994) clearly associated
disturbances of familiarity with seizure discharges in the
non-dominant mesial temporal lobe and superior temporal
gyrus in patients with refractory epilepsy. As in the case of
reduplicative paramnesia, additional deficits in frontal lobe
functions of self-monitoring and self-correction, and frontal
lobe indifference, theoretically lead to ongoing mispercep-
tion and confabulation when patients are presented with
conflicting information (Malloy and Richardson, 1994).
Seizures und psychosis
This patient has not had a documented seizure, and it is not
clear that he has epilepsy. A recent EEG demonstrated
bilateral temporal lobe slowing and bilateral temporal lobe
sharp waves. These abnormalities are non-specific but
could represent a tendency toward partial seizures or could
be caused by prior temporal lobe injury or psychotropic
medication. Prior EEGs were normal. None the less,
seizures and their complications are common sequelae of
TBI, and could account for the development of psychotic
symptoms in this patient. The temporal lobes are often
damaged in CHI without the development of a clear seizure
disorder. His frontal lobe injury, combined with a more
subtle secondary temporal lobe dysfunction without
obvious structural damage on CT scan, could also account
for the evolution of psychosis in this patient.
Annegers et al. (1 980) studied a cohort of 2747 patients
with head injury and documented rates of post-traumatic
seizure of 11.5% for severe injury, 1.6% for moderate
injury and 0.6% for mild injury at 5 years. Factors most
strongly associated with an increased risk of post-traumatic
seizures included depressed skull fracture, dural compro-
mise and penetrating brain injury, none of which was
documented in this case. The relationship between epilepsy
141
and psychosis is complex, especially when one considers
the frequent co-occurrence of TBI, post-traumatic epilepsy
and psychosis, and the difficulty distinguishing between
psychosis resulting directly from the tissue damage of the
head injury versus that resulting indirectly from post-
traumatic epilepsy.
McKenna et af. (1985) found a 7% prevalence of
psychosis in epileptic patients in large-scale community
studies of psychosis in epileptic populations from Norway
and Iceland. The relationship between psychosis and
temporal lobe epilepsy is even more compelling (McKenna
et al., 1985). Pritchard et al. (1980) documented an
incidence of overt psychosis in 1 I % of 56 patients with
temporal lobe epilepsy, noting a particular association
between psychosis and left temporal lobe foci on EEG.
These studies documented an incidence of psychotic
symptoms that was four to 12 times greater in the temporal
lobe epilepsy population than in those with generalized
epilepsy. The presence of bilateral temporal lobe foci was
most highly associated with psychosis.
Four major psychiatric syndromes associated with
epilepsy have been described in the literature, including
ictal and postictal confusional psychoses, late-onset schizo-
phreniform psychoses, atypical episodic psychosis, and an
enduring interictal personality syndrome. Psychosis com-
monly occurs during ictal and postictal states, and is often
associated with confusion or a clouding of consciousness.
This change in the level of consciousness helps distinguish
the psychotic behavior from other psychotic syndromes
associated with temporal lobe epilepsy that occur with a
clear sensorium. In cases of ictal psychosis, the EEG
reveals generalized changes and frank epileptiform dis-
charges, whereas in postictal confusional psychosis, the
EEG typically demonstrates diffuse slowing.
Persistent schizophrenia-like psychosis can develop on
average 14 years after the onset of temporal lobe epilepsy
(Levine and Finklestein, 1982). Psychotic symptoms in
such cases occur with a clear sensorium and are indepen-
dent of clearly defined ictal behavior. The psychosis is
typically characterized by a predominance of visual and
auditory hallucinations, odd and delusional belief systems
and mystical states, but demonstrates a striking absence of
deficit symptoms, with well preserved affect, personalities
and social relatedness (McKenna et al., 1985).
Brief psychotic episodes in temporal lobe epilepsy that
are neither paroxysmal and confusional nor chronic and
enduring have been described (Dongier, 1959; Waxman
and Geschwind, 1975; Tucker et al., 1986). In many of
these episodes there was no report of confusion, nor any
evidence of generalized EEG changes. Episodes varied in
duration from days to weeks, included prominent psychotic
and affective symptoms, and some culminated in a seizure.
Perceptual changes and psychotic symptoms were of very
brief duration, often lasting minutes to hours, whereas
affective symptoms were more likely to last hours to days.
Interepisodic function was often described as normal. In
142 C. Harrington, S. Salloway and P. Malloy
Tucker er al.’s study (1986) the psychotic and depressive
symptoms responded well to treatment with anticonvulsant
medications.
In the case of MF there is no mention of mental status
change, clouding of consciousness, delirium or typical
ictal behavior to suggest that psychotic symptoms resulted
directly from a seizure or during a postictal state. The
psychotic symptoms described here were episodic and
therefore not consistent with the chronic and enduring
schizophrenia-like psychoses described by Levine and
Finklestein (1982). However, the episodic nature of MF’s
psychosis appears related to his degree of compliance with
neuroleptic and other psychotropic medications. Despite
good interepisodic function there does appear to be an
underlying psychosis that is controlled by antipsychotic
medication. There is no evidence of the classically
described interictal personality in this patient (Bear and
Fedio, 1977). Affective symptoms were significantly less
prominent than psychotic symptoms, making a diagnosis of
psychotic depression less likely. While not entirely
consistent with the syndrome of brief psychotic episodes
described by Dongier ( 1959) and Tucker et al. ( 1986), this
patient did have an episodic illness, relatively good inter-
episodic functioning and atypical affective symptoms. In
addition, his psychotic and affective symptoms responded
well to carbamazepine. Carbamazepine may therefore be
both acting as a mood stabilizer and providing protection
against recurrent psychotic symptoms.
Brain injury and depression
Though delusions were the primary and most troublesome
symptoms in this patient, there were frequent references in
the record to affective symptoms, and treatment trials with
both tricyclic antidepressants and serotonin reuptake
inhibitors were attempted. The combination of depression,
mood-congruent delusions of guilt and frontal dyscontrol
may very well have led to the impulsive suicidal behavior
noted in this patient. It is interesting to note that despite
bilateral anteromedial frontal injury, MF did not develop
the persistent disinhibition seen in case 2. His impulsive
and bizarre behavior was more episodic and organized into
dramatic delusional thinking.
Depression is common after brain injury, including
stroke and TBI. Depression after TBI, with rates in the
literature ranging from 6 to 77%, can occur early and
transiently or can occur later and be chronic (Robinson and
Jorge, 1994). Post-stroke depression is often associated
with lesions in the left frontal cortex, left basal ganglia and
right parietal lobe (Robinson and Starkstein, 1990).
Robinson and Jorge (1994) and Robinson and Szetela
( I98 1 ) found a similar relationship between left anterior
cortical and left basal ganglia lesions and depression in
their series of TBI patients. Using PET scanning, Mayberg
( 1994) has demonstrated orbitofrontal and anterior
temporal hypometabolism in secondary depression. These
findings are particularly relevant to this case where, despite
bifrontal and bihemispheric findings, the largest CT
abnormality is located in the left anteromedial frontal lobe.
Fedoroff et al. ( 1992) reported an increased frequency of
post-traumatic depression in subjects with a personal
history of psychiatric disease. Of particular relevance to
this case, the difference in rates of depression between the
groups with and without prior psychiatric histories was lost
when alcohol and substance abuse histories were excluded.
Starkstein et al. (1989) also demonstrated that post-stroke
depression occurred more frequently in patients with a
personal or family history of psychiatric disease. Though
there was not a strong personal or family history of
psychiatric illness, both MF and his mother had a history of
alcohol abuse. In addition, MF had a history of prior head
injury and ‘learning difficulties’ as a child. His previous
brain injury and personal and family history of alcohol
abuse could have resulted in an increased susceptibility to
depression and psychosis in MF.
Case 2
AZ was a 59-year-old man with mixed motor dominance,
who was in good mental and physical health until February
1994 when he slipped and fell on the ice, striking the back
of his head. He was confused and agitated at the scene but
there was no definite loss of consciousness. He spent
10 days in the general hospital and during that time he was
intermittently agitated and confused. CT scan of the brain
showed bifrontal hemorrhagic contusions, greater on the
right than the left, with subfalcine herniation from right to
left and downward mass effect with blood in the right
lateral ventricle (Fig. 2). A right frontal subdural hematorna
and a small area of old lacunar infarction in the head of the
left caudate nucleus/anterior limb of the internal capsule
were also present. He then spent 6 weeks on a neuro-
rehabilitation unit.
On arrival at the rehabilitation unit he was noted to have
problems with memory and attention. He was not oriented
to-date, he had trouble recalling personal information such
as his address, and responses were delayed. His affect was
flat and his behavior was intermittently agitated. Neuro-
leptics, benzodiazepines and physical restraints were
sometimes required. He was placed on phenytoin prophyi-
actically but no seizures were noted. A repeat CT scan
6 weeks after the accident showed a gradual reduction in
hemorrhage and edema but persistence of the midline
anterior frontal contusions, right greater than left.
During the course of his stay there was some improve-
ment in attention, concentration and problem-solving
skills. His persistence in activities of daily living fluctuated
due to fatigue and easy frustration. He did fairly well in
tasks requiring well-developed skills but performance
deteriorated markedly with more complex demands.
Initiation was poor and he relied on his wife for guidance.
His insight into his deficits was limited. Irritability and
obstinate behavior began to develop toward the end of his
 Neurobehavioral disorder following bilateral anteromedial frontal lobe injury 143

Fig. 2. Non-contrast CT scan from AZ at the level of the upper brainstem (left) and thalamus (right) on the day of the accident demonstrates large areas
of antero-medial frontal hemorrhagic contusion, larger on the right than left. with downward mass effect on the right frontal horn, and blood in the
ventricles. A small subdural hematoma is present adjacent to the right side of the frontal pole. A small hypodense area is present in the left anterior limb
of the internal capsule representing an old lacunar infarction in this region.

6-week stay on the rehabilitation unit. Prominent mood
lability developed and phenytoin was switched to carba-
mazepine. Carbamazepine had to be discontinued because
of a rash.
He was unable to work from the time of the accident. He
tried to resume employment but found that he was too
confused to follow the complex multiple steps required for
engine repair and that prolonged periods of concentration
made him dizzy and unsteady. His major symptoms after
the accident involved a marked change in personality
characterized by disinhibited behavior, dramatic mood
swings, delusional jealousy, temper outbursts, impulsivity,
foul language, decreased hygiene and self-care and
decreased interest in his usual activities. He was easily
fatigued and very impatient.
AZ was born in Israel, completed high school, and
served for a number of years as a senior mechanic in the
Israeli Armed Forces. He emigrated to the United States in
1975 and became a naturalized citizen in 1992. Hebrew
was his native language but he spoke English well. He
successfully operated his own auto repair business for
7 years prior to the accident. He has three children and four
grandchildren from a prior marriage in Israel. He is married
to his second wife and they apparently had a stable
relationship prior to the accident. She has been very
devoted to him and has helped him manage his affairs so
that he can remain living in the community.
His wife states that before his fall AZ was very
independent, energetic, good-humored and affectionate.
Since the accident he has been very dependent, lethargic,
dull, and much less affectionate. In the past he would spring
up from the dinner table and help with the clearing up. Now
he sits listlessly after dinner and does not offer to help even
though h e recognizes that it would be a good thing to do. At
times he confabulates dramatic stories of events that have
happened to him, or plans that he has.
He has also experienced a marked decrease in libido.
Since the accident he has been very suspicious of his wife
and has accused her of being unfaithful despite the lack of
any concrete evidence. On one occasion he went to her
school in order to catch his wife and her imagined lover
together and physically put an end to their illicit
relationship. He has threatened her many times but has
never been physically aggressive.
There is a past history of upper GI bleeding secondary to
peptic ulcer disease. He has been a heavy drinker at times in
the past. There was no evidence of alcohol use at the time of
the accident or that alcohol abuse had impaired his
144 C. Harrington, S. Salloway and P. Malloy
functioning prior to the accident. He has a history of
untreated hypertension. He smoked one pack of cigarettes
per day until 3 years ago. He had no prior history of psychi-
atric treatment. A younger brother committed suicide.
On examination 16 months after the accident he was
unkempt and had not shaven for a few days. There was an
odor to his socks when he removed his shoes. His blood
pressure was 130180 and pulse was 78 and regular. Thyroid
and carotid exams were normal. Mental status exam
revealed that he was alert and oriented to name but not to
time and place. He was markedly disinhibited and had very
poor insight and judgment. He had poor regulation of his
impulses. He made a small scene in the waiting room as he
insisted on waiting in the main passageway that patients
travel through. He threatened to become violent without
showing any intention of acting on it. He was afraid that
people would hurt him. At times he was quite whimsical
and told jokes which were inappropriate. After the exam
was over he tried to touch the examiner and use the medical
instruments in the examiner’s coat pocket. He stated that he
wanted to give the examiner a hug.
He had difficulty stating the months of the year
backwards. Overall his vigilance was decreased. He was
able to name and repeat correctly in English. He had
difficulty doing arithmetic problems and was not able to put
much cognitive effort into problem-solving. Figure copying
was mildly impaired. Smell was decreased and there was a
mild left facial asymmetry. Strength was 5 out of 5 , reflexes
were 2+, toes were downgoing. Finger tapping was
normal. Coordination was normal. He was missing a finger
on his right hand. There was a mild limp of the right leg.
He underwent neuropsychological assessment on 4/94,
8/94, 2/95, 9/95 and 9/96. He appeared to have hazy recall
for a 2-month period following the accident. He recalled
falling, had a scant memory of his acute hospitalization and
remembered being confused and disoriented on the
rehabilitation unit. ‘1 didn’t even know my wife until the
last 2 weeks on Rehab.’ AZ had difficulty tolerating the
cognitive evaluation on each occasion due to impatience,
easy frustration, irritability and mood lability. His English
ability was quite good and language ability did not interfere
significantly with testing. His premorbid intelligence was
estimated to be in the above-average range.
On 4/94 he was disoriented to time and place. Attention
and concentration were impaired. He had difficulty
sustaining attention on tasks lasting more than I minute
and he was highly distractible. Short-term memory was
impaired. Cueing and recognition failed to improve recall.
He had poor organization and planning of constructions.
Executive function was severely impaired. He had diffi-
culty maintaining set and perseverated. He had trouble
performing multi-step commands. Verbal IQ was 8 1,
Performance IQ was 76 and Full-Scale IQ was 78, clearly
below his premorbid level.
On examination on 2/95 he was oriented to place and
person. He was easily irritated, socially inappropriate and
lost his temper on a number of occasions. He often gave
up on tasks prematurely. Attention remained impaired.
Processing speed was slow. However, he could carry out
some tasks well for brief periods - for example, digit span
was at the 25th percentile and visual span was at the 37th
percentile. Verbal and visual recall were severely impaired.
Visuoperceptual skills were impaired. Wisconsin Card Sort
Testing was not completed due to low frustration tolerance.
Performance IQ was 87, a mild improvement from 4/94.
On 9/95 AZ was tested at a site out of state. He arrived
an hour late for his appointment. His hygiene was poor. He
was pleasant but made sexual innuendoes to female staff.
His responses to self-rating scales were rapid, impulsive
and unreliable. He threw the paper at the tester when
frustrated. On the second day of testing he failed to appear
as scheduled. The examiner went to his hotel room and
found him having breakfast in the dining room. He was
penniless, having been robbed the night before. He was
animated and agitated and could not settle down to
complete the cognitive testing. The estimated Verbal IQ
was 72, Performance IQ was 84 and Full-Scale IQ was 77.
Cognitive testing on 9/96 was generally consistent with
prior evaluations. During the evaluation he alternated
between being affable and irritated, and made inappropri-
ate, intrusive comments to another patient in the hall. He
had difficulty attaining and maintaining set on several
tasks, and sometimes abandoned tasks that he found
difficult. As a result, testing was incomplete. He often
expressed frustration and disappointment about the quality
of his performance.
AZ was only partially oriented to place (‘Hospital’), and
missed the day of week and date (‘1959’). Sustained and
directed attention were moderately impaired on tasks
requiring cognitive manipulation of information such as
alphabet recitation, serial addition and counting backward.
His performance on tests of frontal lobe functions was
moderately to severely impaired. He was moderately to
severely impaired on controlled word fluency. His perform-
ance was remarkable for repetition of the examples
provided by the examiner, production of socially inappro-
priate words, termination of the task prematurely, and loss
of set demonstrated by intrusions. He was unable to
perform Luria’s complex motor programming. He was able
adequately to perform one of the Luria alternating figures
tasks in the presence of the model. His performance on the
second task was incomplete and demonstrated over-
simplification. He refused to attempt the figures i n the
absence of the model. Trails A was moderately impaired.
He was unable to complete Trails B. Language abilities
were intact except for naming. Assessment of reading and
comprehension of written paragraphs were terminated due
to frustration on the longer passages.
On a drawing task, he demonstrated good selt-
monitoring and was able to copy a square and a triangle,
but was unable to reproduce more complex shapes
correctly. He perseverated during clock reading, drawing
 Neurobehavioral disorder following bilateral anteromedial frontal lobe injury 145

Fig. 3. Non-contrast CT scan at the same level from AZ 2 years after the accident demonstrates bilateral anteromedial encephalomalacia in the frontal
lobes, right larger than left. Blood products have been resorbed. Note dilatation of the frontal horns of the lateral ventricles.

hands from the previous clock-drawing task. He refused to
complete other visuospatial tasks.
Memory was also severely impaired. He improved from
three to only four of 12 words on a list across five learning
trials. He displayed poor free recall of the list after brief
and 20-min delays, and cueing did not further improve
performance. Recognition recall was significantly better
( I 1/12), but still lower than expected based on normative
comparisons.
Follow-up CT scan of the brain revealed evidence of old
injury to the anteroinferomedial frontal lobes, right greater
than left (Fig. 3). MRI scan of the brain demonstrated
marked encephalomalacia of the right orbitofrontal and
anteromedial prefrontal cortex (Fig. 4).

Fig. 4. Non-contrast T-1 weighted sagittal MRI scan near the midline 2 years after the accident in patient AZ demonstrates a large area of
encephalomalacia in the frontal pole in the right hemisphere in the image on the left, extension of the low-density signal inferiorly into the orbitofrontal
region in the center image, and involvement of frontal pole and inferior orbilofrontal cortex in the left hemisphere in the image on the right.
146 C. Harrington, S. Salloway and P. Malloy
A number of psychotropic medications have been pres-
cribed to help control his mood lability and agitation, but
his compliance has been poor. Valproic acid was taken
briefly and irregularly. Paroxetine has also been prescribed.
He does take small doses of diazepam once or twice daily,
which has a calming effect. He was not compliant with
respiridone.
Alcohol use has been a problem at times but has been
only a minor problem recently. He has resisted any
recommendation for treatment on the behavioral neurology
inpatient unit. If not for the devoted care and supervision
provided by his wife he would be forced to live in a
supervised setting.
Discussion
The patient in case 2 experienced a dramatic frontal lobe
syndrome from a relatively minor fall. However, the CT
scans and follow-up MRI show that there was a major
bilateral hemorrhagic contusion to the prefrontal cortex
which was much more pronounced in the right hemisphere.
He experienced a variety of neurobehavioral symptoms
following the injury but was most disabled by his severe
mood lability, impulsivity, and decline in attention and
executive function. These findings are consistent with the
severity of the injury to his orbitofrontal cortex.
The prefrontal lobes are connected to the subcortex and
the thalamus in three distinct neurobehavioral circuits
(Alexander et d., 1986; Mega and Cummings, 1994). The
dorsolateral prefrontal circuit is involved in maintaining
cognitive flexibility, in forming cognitive plans and carry-
ing out working memory functions. Injury to this region
results in cognitive disorganization, impaired memory
search strategies, perseveration, decreased insight and
abstraction, and impaired attention. The inability to main-
tain set and to carry out tasks sequentially, functions that
are mediated in large part by the dorsolaterdl prefrontal
region, contributed to his inability to return to work as an
auto mechanic.
The orbitofrontal region is pivotal for regulation of
impulses and mood (Salloway, 1994; Duffy and Campbell,
1994). Injury to this region can result in a dramatic change
in personality characterized by impulsivity and disin-
hibited, inappropriate behavior. Individuals frequently
have marked mood lability and may demonstrate utilization
behavior (Lehrmitte, 1986a,b). Bilateral damage to the
orbitofrontal cortex (OFC) probably carries a greater risk
for behavioral dyscontrol than unilateral OFC injury, which
is similar to the increased likelihood of developing akinetic
mutism after bilateral injury to the anterior cingulate gyrus.
The anterior cingulate circuit is involved with main-
tenance of drive and motivation. Injury to this region may
result in apathy, psychomotor retardation and abulia.
Akinetic niutism can occur after bilateral lesions to this
region. It is not uncommon for an individual to experience
deficits in all three prefrontal domains after head injury. A
patient may be irritable and labile at one moment and listless
and apathetic at another time, as was true in this case. The
presence of an old lacunar infarction in the head of the left
caudate nucleus and anterior limb of the left internal capsule
caused by cerebrovascular disease may have increased his
susceptibility to the sequelae of his prefrontal injury.
AZ was most disabled by his orbitofrontal symptoms.
The OFC receives highly processed sensory information
from all sensory modalities. The composition of the OFC is
characterized by a gradual transition from dysgranular
allocortex in the medial posterior OFC to granular iso-
cortex in the anterior and lateral OFC. More highly
differentiated sensory input projects to granular cortex
and information from more primitive sensory association
areas projects to dysgranular regions (Zalcl and Kim.
1996a). The OFC contains cortical association areas for
olfaction and taste. Cells in the lateral OFC respond to one
or two specific odors, while cells in the medial OFC tend to
give a more generalized response to olfactory stimuli. Loss
of smell and taste is commonly seen after injury to this
region, as in case AZ (Fig. 5 ) .
The dysgranular allocortex seen in the medial posterior
orbital region receives direct limbic input from the
amygdala and insula and indirect limbic input from the
dorsomedial nucleus of the thalamus. The amygdala helps
attach emotional and behavioral significance to stimuli.
The amygdala also has rich autonomic connections with
the brainstem and hypothalamus. The OFC sends strong
projections to the lateral hypothalamic nucleus, which may
help mediate visceral responses to stimuli (Zald and Kim,
1996b).
The more granular areas of the lateral orbital region have
close connections with higher order association cortices in
other lobes and in other areas of prefrontal cortex. Thus, the
paralimbic orbitofrontal cortex sits at the crossroads
between limbic and higher order heteromodal sensory
cortex (Mesulam, 1986). These regions are rich in the
monoaminergic neurotransmitters serotonin, dopamine and
norepinephrine. The OFC channels drive and emotion into
appropriate targets in the environment. The OFC partici-
pates in the development of associations between stimulus
and reward and is sensitive to changes in reward con-
tingencies. For example, a cell in the OFC that responds
briskly to a stimulus may alter its response when the same
stimulus is associated with an aversive or neutral outcome.
Because of its limbic and autonomic connections the OFC
may mediate ‘the gut feeling’ people experience in
response to stimuli. Animal experiments have demon-
strated that the medial OFC is important for extinction of
behavior and the lateral OFC is essential for modulating
behavior when more than one choice is reinforced (Zald
and Kim, 1996b). It is this differential responding to the
behavioral relevance of stimuli that Mesulam ( 1986) has
proposed is the foundation of human autonomy.
The posteromedial OFC receives autonomic inputs and
helps regulate emotion. Individuals with OFC injury do not
 Neurobehavioral disorder following bilateral anteromedial frontal lobe injury
Fig. 5. Anatomic specimen highlighting the location of the anterior cingulate gyrus. orbitofrontal region. frontal pole and superior frontal gyrus in the
medial sagittal view in the figure on the left. The anatomy of the orbitofrontal region is highlighted in the basal view of the hrain in the figure on
the right.
lose the capacity for emotion but lose the ability to
modulate or regulate affect in response to environmental
demands. Mood lability is often the hallmark symptom of
OFC injury. Individuals with injury to this region may also
lose the ability to respond to social cues and may show
undue familiarity, as was seen in the case of AZ. Dramatic
confabulation may be seen as an example of disinhibited,
unfiltered speech.
The OFC also plays an important role in cognition. A
large part of OFC and surrounding prefrontal cortex is
made up of granular heteromodal isocortex. Injury to
heteromodal sensory areas usually results in general
inattentiveness (Levin and Kraus, 1994). Reciprocal
connections exist between the dysgranular caudal OFC
and the entorhinal cortex. The entorhinal cortex is closely
connected to the hippocampus, and injury to the OFC may
affect working memory processing, particularly for
feature-oriented information. Ablation of areas in the
lateral OFC in monkeys causes perseverative responses
and difficulty with responding to tasks of non-matching to
sample after a delay. Goldman-Rakic ( 1 YY4) has reported
deficits in working memory involved with object
recognition with lesions in the dorsolateral aspects of the
OFC.
Damage to the OFC causes difficulty in acquiring new
information. Reciprocal connections exist between the
granular OFC and the dorsolateral prefrontal cortex and
between the OFC and the cingulate gyrus. Disruption of the
dorsolateral connections may cause perseverative respond-
ing or difficulty in learning task rules. The disruption of
the connections to the cingulate may cause loss of the
147
motivational significance of stimuli. AZ injured the
anterior aspects of the superior frontal gyri along the
medial frontal pole as well as the OFC. The memory
deficits in this case were most likely due to impaired
attention and concentration and poor retrieval strategies.
Given the extensive frontal injury, there may have been
additional temporal lobe injury causing impairment of
limbic memory circuits as well.
Neuropsychological tests of the OFC may not be very
informative (Eslinger and Damasio, 1985j. Responses may
be variable and the results are dependent on the patient’s
behavioral state at the time of the examination. Further,
results may be normal. Smell should be tested (Varney,
1988). Malloy and others (1985) have demonstrated that
patients often fail Go-No-Go tasks. Patients may also be
impaired on the Wisconsin Card Sorting Test. Behavioral
assessments that evaluate the patient’s deportment and
mood, their ability to attend to tasks and monitor their
performance, and assessments of their problem-solving
strategies are very useful. Judgment, insight and reasoning
should be assessed. However, it should be noted that
patients may perform well in a highly structured office
setting, yet fail miserably in less structured situations.
Caution should be used in evaluating insight and problem-
solving because the patient may know a practical solution
lo a problem but have trouble enacting that solution in a
real-life situation. Questioning reliable informants about
the patient’s level of functioning in home, occupational and
social settings is essential. The examiner should observe
for signs of confabulation. Patient reports may need to be
verified with family informants.
148 C. Harrington, S. Salloway and P. Malloy
Like the first case, AZ also demonstrated delusional
symptoms. He developed delusional jealousy and at times
this symptom caused him to become threatening to his
wife. As we discussed in the first case, this symptom was
probably caused by the combination of the predominance
of right hemispheric and frontal injury. Other cases of
delusional jealousy have been reported following right
hemispheric lesions (Richardson et al., 1991). Delusional
jealousy has also been related to alcohol abuse, which was
a factor in this case (Shepard, 1961).
Treatment is extremely difficult for patients with
orbitofrontal injury (Campbell et al., 1994). Patients have
limited insight and motivation and often benefit little
From cognitive or psychodynamic interventions. Consistent
behavioral treatments can be helpful. Support and educa-
tion for the family are essential. It is important to settle
litigation resulting from the injury in a timely fashion. The
most important goals are to keep the patient and family safe
and ensure that the patient’s basic needs are met. It is also
important to monitor for the presence of seizures.
Psychotropic medications can sometimes be helpful but
compliance and medication side-effects are often proble-
matic, as in both of these cases. Mood lability often
responds to mood-stabilizing agents such as lithium or
valproic acid. Low-dose neuroleptics with a low potential
for extrapyramidal side-effects can often help with
psychotic symptoms and agitation. Antidepressant medica-
tion should be used if depression becomes a major
problem. A number of agents such as trazadone, buspirone
and benzodiazepines can be tried for the treatment of
agitation or anxiety. Stimulant medication such as methyl-
phenidate may treat apathetic symptoms.
Summary
Bilateral injury to the anteromedial frontal lobes can
produce dramatic changes in behavior and cognition. The
hallmark symptoms are inattention, mood lability, impuls-
ivity and impaired self-monitoring; however, delusions and
other impairments of learning and memory may also occur.
These two cases demonstrate the variability in clinical
symptoms seen following orbitofrontal injury. Careful
examination of individuals with focal frontal lesions, in
combination with advances in neuroanatomical and neuro-
imaging techniques, is expanding our knowledge of the
functional systems subserved by this important brain region.
References
Alexander GE, Delong MR, Strick PL. Parallel organization of
functionally segregated circuits linking basal ganglia and cortex.
Annual Review of Neurosciences 1986; 9: 357-81.
Annegers JF, Grabow JD. Groover RV. Laws ER, Elveback LR,
Kurland LT. Seizures after head trauma: a population study.
Neurology 1980; 30: 683-9.
Bancaud J , Brunet-Bourgin F, Chauvel P, Halgren E. Anatomical origin
of dc3u vu and vivid ‘memories’ in human temporal lobe epilepsy.
Brain 1994; I 17: 7 1 -90.
Barnhill LJ, Gaultieri CT. Two cases of late-onset psychosis after closed
head injury. Neuropsychiatry, Neuropsychology, and Behavioral
Neurology 1989; 2: 211-17.
Bear D, Fedio P. Quantitative analysis of interictal behavior in temporal
lobe epilepsy. Archives of Neurology 1977; 34: 454-67.
Benson DF, Gardner H, Meadows JC. Reduplicative paramnesia.
Neurology 1976; 26: 147-61.
Brown G. Chadwick 0, Shaffer D, Rutter M, Traub M. A prospectivc
study of children with head injuries, 111: psychiatric sequelac.
Psychological Medicine 1981; I I : 63-78.
Campbell JJ, Duffy JD. Salloway SP. Treatment strategies for patients
with dysexecutive syndromes. Journal of Neuropsychiatry and Clinical
Neurosciences 1994; 6: 41 1 - 18.
Davison K, Bagley CR. Schizophrenia-like psychoses associated with
organic disorders of the central nervous system: a review o f the
literature. In: Herrington RN, editor. Current problems in neuro-
psychiatry: schizophrenia, epilepsy, the temporal lobe. British Journal
of Psychiatry (Special Publication no 4 ) 1969: 113-X4.
Dongier S. Statistical study of clinical and electroencephalographic.
manifestations of 536 psychotic episodes occumng i n 5 I6 epileptics
between clinical seizures. Epilepsia 1959; I : 117-42.
Duffy JD, Campbell JJ. The regional prefrontal syndronies: a theoretical
and clinical overview. Journal of Neuropsychiatiy and Clinical
Neurosciences 1994; 6: 379-87.
Eslinger PJ, Damasio AR. Severe disturbance of higher cognition alter
bilateral frontal lobe ablation: patient EVR. Neurology Ic)8S; 3 5 :
I73 1-41.
Fedorotf JP, Starkstein SE, Forrester AW er al. Depression in patients
with acute traumatic brain injury. American Journal o f Psychiatry
1992; 149: 918-23.
Feinberg TE. Shapiro RM. Misidentification-reduplication and the right
hemisphere. Neuropsychiatry, Neuropsychology, and Behavioral
Neurology 1989; 2: 39-48.
Filley CM, Jarvis PE. Delayed reduplicative paramnesia. Neurology
1987; 37: 701-3.
Forstl H, Almeida OP, Owen AM, Burns A, Howard R. Psychiatric.
neurological and medical aspects of misidentification syndromes: a
review of 260 cases. Psychological Medicine 1991; 21: 905-10,
Goldman-Rakic PS. Working memory dysfunction i n schizophrenia.
Journal of Neuropsychiatry and Clinical Neurosciences 1994; 6 :
348-57.
Hakim H, Verna NP, Greiffenstein MF. Pathogenesis of reduplicative
paramnesia. Journal of Neurology. Neurosurgery, and Psychiatry
1988; 51: 839-41.
Hillbom E. After-effects of brain injuries. Acta Psychiatrica e l Neuro-
logica Scandinavica 1960; 142(Suppl): I - 195.
Kapur N, Turner A. King C. Reduplicative paramnesia: possible anatom-
ical and neuropsychological mechanisms. Journal of Neurology.
Neurosurgery, and Psychiatry 1988; 5 I : 579-8 I .
Koufen P, Hagel KH. Systematic EEG follow-up study of traumatic
psychosis. European Archives of Psychiatry and Neurologicnl
Sciences 1987; 237: 2-7.
Levin H, Kraus MF. The frontal lobes and traumatic brain injury. Journal
of Neuropsychiatry and Clinical Neurosciences 1994: 6: 443-54.
Levine DN, Finklestein S. Delayed psychosis after right temporoparietal
stroke or trauma: relation to epilepsy. Neurology 1982; 32: 267-73.
Levine DN, Grek A. The anatomic basis of delusions after right cerebral
infarction. Neurology 1984; 34: 577-82.
Lhermitte F, Pillon B, Serdaru M. Human autonomy and the frontal
lobes. Part I: Imitation and utilization behavior: a neuropsychological
study of 75 patients. Annals of Neurology 198ha; 19: 326-34.
Lhermitte F. Human autonomy and the frontal lobes. Part II: Patient
behavior in complex and social situations: the ‘environmental depend-
ency syndrome’. Annals of Neurology 1986b; 19: 335-43.
Malloy PF, Richardson ED. Assessment of frontal lobe functions. Journal
of Neuropsychiatry and Clinical Neurosciences I994a; 6: 399-4 10.
Malloy PF, Richardson ED. The frontal lobes and content-spccilic
delusions. Journal of Neuropsychiatry 1994b; 6: 455-66.
Malloy PF, Webster JS, Russell W. Tests of Luria’s frontal lobc
syndromes. International Journal of Clinical Neuropsychology 19x5:
7: 88-95.
Malloy PF, Cimino C, Westlake R. Differential diagnosis of primary and
secondary Capgras delusions. Neuropsychiatry, Neuropsychology. and
Behavioral Neurology 1992; 5 : 83-96.
 Neurobehavioral disorder following bilateral anteromedial frontal lobe injury 149

Mayberg HS. Frontal lobe dysfunction in secondary depression. Journal

of Neuropsychiatry and Clinical Neurosciences 1994; 6: 428-42.
McKenna PJ, Kane JM, Panish K. Psychotic syndromes in epilepsy.
Neurobehavioral disorder following
American Journal of Psychiatry 1985; 142: 895-904. bilateral anteromedial frontal
Mega MS. Cummings JL. Frontal-subcortical circuits and neuropsychia-
tric disorders. Journal of Neuropsychiatry and Clinical Neurosciences lobe injury
1994; 6: 358-70.
Mesulam M. Frontal cortex and behavior. Annals of Neurology 1986; 19:
320-5. C. Harrington, S. Salloway and P. Malloy
Pritchard PB. Lombroso CT. Mclntyre I. Psychological complications of
temporal lobe epilepsy. Neurology 1980; 30: 227-32. Abstract
Rabins PV. Starkstein SE, Robinson RG. Risk factors for developing This article describes two cases of closed head injury causing bilateral
atypical (schizophreniform) psychosis following stroke. Journal of frontal lobe contusions that resulted in enduring changes in self-control,
Neuropsychiatry 1991; 3: 6-9. perception, mood and cognition. In the first case the primary feature was
Richardson E, Malloy P, Grace J . Othello syndrome secondary to right delayed-onset psychosis. In the second case the patient developed mood
cerebrovascular infarction. Journal of Geriatric Psychiatry and lability, poor impulse control, a dramatic change in personality and
Neurology 1991; 4: 160-5. impaired cognition. Midline, anterior frontal regions were most severely
Robinson RG. Jorge R. Mood disorders. In: Silver JA er al., editors. affected in both cases. The diagnostic evaluation and the clinical course
Neuropsychiatry of traumatic brain injury. Washington, DC: APA are described. The neuropsychiatric syndromes are discussed with
Press, 1994. reference to lesion location and the literature on the neurobehavioral
Robinson RG, Starkstein SE. Current research in affective disorders sequelae of closed head injury.
following stroke. Journal of Neuropsychiatry and Clinical Neuro-
sciences 1990; 2: 1-14. Journal
Robinson RG, Szetela B. Mood change following left hemisphere brain Neurocase 1997; 3: 137-49
injury. Annals of Neurology 1981; 9: 447-53.
Ruff RL, Volpe BT. Environmental reduplication associated with right
Neurocase Reference Number:
0 71
frontal and parietal lobe injury. Journal of Neurology, Neurosurgery,
and Psychiatry 1981; 44: 382-6. Primary diagnosis of interest
Salloway SP. Diagnosis and treatment of patients with ‘frontal lobe’ Closed head injury
syndromes. Journal of Neuropsychiatry and Clinical Neurosciences
1994; 6: 388-98. Author’s designation of case
Shepard M. Morbid jealousy: some clinical and social aspects of a MF; AZ
psychiatric symptom. Journal of Mental Science 1961; 107: 687-753.
Silver JM, Yudofsky SC, Hales RE. Depression in traumatic brain injury. Key theoretical issue
Neuropsychiatry, Neuropsychology, and Behavioral Neurology I99 I : 0 Closed head injury can be associated with delayed-onset psychoses
4: 12-23. and mood lability.
Silver JM, Hales RE, Yudofsky SC. Neuropsychiatric aspects of Key words: closed head injury; frontal lobe deficits; psychosis; mood
traumatic brain injury. In: Yudofsky SC, Hales RE, editors. The lability
APA textbook of neuropsychiatry. 3rd ed. Philadelphia, PA: APA
Press, 1992. Scan, EEG and related measures
Starkstein SE, Robinson RG, Honig MA, Parikh RM, Joselyn J, Price TR. MT: CT; EEG
Mood changes after right hemisphere lesions. British Journal of AZ: CT; MRI
Psychiatry 1989; 155: 79-85.
Staton RD, Brumback RA, Wilson H. Reduplicative paramnesia: a Standardized assessment
disconnection syndrome of memory. Cortex 1982; 18: 23-36. MF: Unspecified neuropsychological assessment, including unspecified
Thomsen IV. Late outcome of very severe blunt head trauma: a 10-15 Go-No-Go tasks.
year second follow-up. Journal of Neurology, Neurosurgery, and AZ: Unspecified neuropsychological and intellectual assessment:
Psychiatry 1984; 47: 260-8. Wisconsin Card Sorting Test; Trails A and B.
Tucker GJ, Price TR, Johnson VB, McAllister T. Phenomenology of
temporal lobe dysfunction: a link to atypical psychosis - a series of Other assessment
cases. The Journal of Nervous and Mental Disease 1986; 174: 348-56. MF: Mental State Examination
Varney N. Prognostic significance of anosmia in patients with closed- AZ: Mental State Examination
head trauma. Journal of Clinical and Experimental Neuropsychology Lesion location
1988; 10: 250-4. 0 MF: Bilateral front white matter hypodensity, left greater than right.
Violon A, De Mol J. Psychological sequelae after head trauma in adults. Mild bilateral cortical volume loss, right frontal-parietal greater than
Acta Neurochirurgica (Wien) 1987; 85: 96- 102. left.
Waxman SG. Geschwind N. The interictal behavior syndrome of 0 AZ: Bifrontal haemorrhagic contusions, right greater than left; sub-
temporal lobe epilepsy. Archives of General Psychiatry 1975; 32: falcine herniation from right to left and downward mass effect; right
1580-6. frontal subdural haematoma. Old lacunar infarction in head of left
Wilcox JA, Nasrallah HA. Childhood head trauma and psychosis. caudate nucleus.
Psychiatry Research 1987; 2 1: 303-6.
Zald DH, Kim SW. Anatomy and function of the orbital frontal cortex, I: Lesion type
Anatomy, neurocircuitry, and obsessive-compulsive disorder. Journal MF: Encaphalomalacia
of Neuropsychiatry and Clinical Neurosciences I996a; 8: 125-38. AZ: Haernorrhagic contusions; herniation; lacunar infarction
Zald DH, Kim SW. Anatomy and function of the orbital frontal cortex,
11: Function and relevance to obsessive-compulsive disorder. Journal Language
of Neuropsychiatry and Clinical Neurosciences 1996b; 8: 249-61. English