LETTERS

Frontal Lobe Syndrome in a

Patient without Structural
Brain Abnormalities
To the Editor: The frontal lobe plays
an important role in guiding and
supervising complex behavior. Depending on the location of the injury, manifestations of frontal lobe
dysfunction range from cognitive
(executive) decits to akinesia and
mutism to changes in personality.1
Here we present a case with neuropsychiatric symptoms mimicking a
frontal lobe syndrome in the absence of structural brain abnormalities.
Case Report
A 27-year-old man was admitted to
our hospital because of depressed
mood, severe insomnia, and suicidal ideations. Since early childhood the patient showed poor
speech and language and symptoms of psychomotor and intellectual slowing. He nished secondary
school at the age of 17 (usually 15
16 years) and was then employed in
simple jobs. He suffered from auditory hallucinations, delusions, and
illusionary misinterpretations for
about 4 years. A rst episode of catatonic stupor with waxy exibility
and catalepsy occurred 1 month
prior to admission and further episodes were observed during his
stay in our clinic, each of them associated with extreme anxiety and
motor anosognosia. There was no
indication of a head trauma, meningitis, or encephalitis in the patients
medical history.
We observed a patient with impaired speech initiation, slowness
and poverty of speech, verbal perseverations, and difculties with
the grammar but preserved language comprehension. Interestingly,
the patient spoke only to very few
individuals in the hospital who be-

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came familiar to him and trustworthy, which is consistent with a selective mutism, a behavioral trait
reported to have existed since his
rst schooldays. However, his nonverbal social behavior was normal
and there was no indication for
symptoms of the autistic spectrum
disorder. During his psychotic episode, our patient had even less
drive than before, his motion was
markedly slowed down and he was
unable to recognize his personal situation; he was totally unconcerned
in this respect. He was also indifferent to consequences of important
decisions he made. Routine laboratory parameter testing, including
drug screening, was normal, as
were physical status and neurological examination. EEG, MRI, and
[18F]uorodeoxyglucose positron
emission tomography (FDG-PET)
did not show any brain abnormalities. Cognitive functions were rst
assessed 10 weeks after admission
when acute psychosis, catatonia,
and depressive mood had remitted,
and 19 weeks later with standardized neuropsychological testing
procedures.2 Medication consisted
of risperidone (8 mg/day) and venlafaxine (300 mg/day). Cognitive
performance was severely impaired
in visual processing speed, alertness, selective and divided attention, verbal and visual working
memory, verbal learning, and word
uency. In contrast, concept formation and reasoning were normal.
The neuropsychological decit pattern was similar 19 weeks later indicating that cognitive decits were
state- and not trait-dependent. Consistently, subscales (especially anergia) of the Brief Psychiatric Rating
Scale (BPRS)3 that cover motivation
and initiation did not change over
this period but were still the most
affected items even 29 weeks after
admission. In contrast, scores in the
subscale for anxiety/depression of
the BPRS (18 points) and in the

Hamilton Depression Rating Scale

(HAM-D) (30 points)4 were clearly
pathological at admission. These
scores continuously dropped and
remained stable ongoing from week
10 (BRPS45; HAM-D24
points).
Comment
This case demonstrates a complex
neuropsychiatric pattern of cognitive decits and psychopathological
features that suggests a kind of
frontal lobe symptom cluster which
can be explained by regional prefrontal subsyndromes. The main
cognitive and psychopathological
symptoms can be explained by assuming supramodal executive dysfunction, which is characteristic for
the dysexecutive (dorsal convexity system) and apathetic (mesial
frontal system) types of regional
prefrontal syndrome.1 Positive
symptoms such as delusions and
hallucinations can be attributed to
prefrontal and medial temporal
dysfunction.5,6 Following Northoff,7
catatonic symptoms as shown by
the patient may be due to impaired
connectivity from orbitofrontal to
premotor/motor cortex resulting in
dysregulation of the motor loop
during emotional stimulation, visible as akinesia. In addition, the difculty in initiating actions may be
attributed to a disorder of the socalled willed action system that
includes the dorsolateral prefrontal
cortex, the anterior cingulated cortex, the anterior supplementary motor area and fronto-striatal circuits.
Alterations of the orbitofrontal cortex may result in D2-receptor downregulation of the caudate nucleus
and may thus cause waxy exibility. Motor anosognosia is thought
to be a result of the dysfunction of
ventrolateral prefrontal cortex and
subsequent network disturbances
between the right ventrolateral prefrontal cortex, right dorsolateral
prefrontal cortex, and right poste-

J Neuropsychiatry Clin Neurosci 20:2, Spring 2008

LETTERS
rior parietal cortex. Orbitofrontal
cortex dysfunction during negative
emotional processing with subsequent hyperactivity of the anterior
cingulated cortex and medial prefrontal cortex may mediate catatonic stupor and akinetic mutism.
Similarly, selective mutism, a form
of social phobia/social anxiety disorder, can be regarded as a motivational disorder suggesting an
involvement of the dorsolateral prefrontal cortex as an essential part of
the willed action system. Indeed,
Tillfors et al.8 found an activation of
the amygdala, dorsolateral prefrontal cortex and inferior temporal cortex when subjects with social anxiety disorder were exposed to a
public speaking task to provoke
anxiety-related symptoms.
Although the etiology remains
unclear, patients speech and language disturbance ts in a congenital form of Brocas type or nonuent aphasia (left inferior frontal
cortex). Cognitive decits occurred
mainly in the executive domain
(sustaining and dividing attention,
verbal learning strategy, working
memory, and cognitive exibility),
while verbal memory, concept formation, and reasoning were spared.
According to Stuss et al.,9 these executive decits can be attributed to
dorsolateral and medial prefrontal
dysfunction.
In conclusion, anatomic regions
suggested to be affected in our patient include prefrontal association
cortex regions that have often been
associated with neuropsychiatric
disorders (dorsolateral, ventrolateral and medial prefrontal cortex,
orbitofrontal cortex, and anterior
cingulated cortex), but also parts of
the motor cortex including the left
inferior frontal lobe and the supplementary motor area. Because cortical/subcortical structural damage in
the MRI scan as well as signs of
hypofrontality in the PET study
were absent in our patient, it re-

mains open whether impaired connectivity between different brain regions might have caused both
functional hyperactivity of some regions (e.g., dorsolateral prefrontal
cortex in selective mutism) and hypoactivity of others (e.g., orbitofrontal cortex and supplementary motor
area in executive dysfunction), respectively. Thus, regional frontal
lobe syndromes, including neuropsychiatric symptoms, may be present without any signs of structural
abnormalities. In contrast to the
case reported by Ferrara et al.,10
structural and functional neuroimaging was not a helpful tool for diagnosis in our patient, but detailed
neuropsychological and psychopathological examinations were.
We thank Anna Wendl for her professional assistance in neuropsychological testing.
Johannes M.H. Hennings, M.D.
Thomas C. Wetter, M.D.
Max Planck Institute of Psychiatry, Munich, Germany
Josef Zihl, Ph.D.
Max Planck Institute of Psychiatry, Munich, Germany
Department of Psychology,
University of Munich,
Germany
References

1. Duffy JD, Campbell JJ: Regional prefrontal syndromes: a theoretical and

clinical overview, in Principles of Frontal Lobe Function. Edited by Stuss DT,
Knight RT. Oxford, England, Oxford
University Press, 2002, pp 113123
2. Lezak MD, Howieson DB, Loring DW:
Neuropsychological Assessment, 4th
ed. Oxford, England, Oxford University Press, 2004
3. Overall JE, Gorham DR: The brief psychiatric rating scale, in ECDEU Assessment Manual for Psychopharmacology,
Revised. Edited by Guy W. National
Institutes of Mental Health, Rockville,
Md., 1976, pp 157169
4. Hamilton M: A rating scale for depression. J Neurol Neurosurg Psychiatry
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J Neuropsychiatry Clin Neurosci 20:2, Spring 2008

5. Liddle PF: Schizophrenic syndromes,

cognitive performance and neurological dysfunction. Psychol Med 1987;
17:4957
6. Weinberger DR: Implications of normal
brain-development for the pathogenesis of schizophrenia. Arch Gen Psychiatry 1987; 44:660669
7. Northoff G: What catatonia can tell us
about top-down modulation: a neuropsychiatric hypothesis. Behav Brain
Sci 2002; 25:555577
8. Tillfors M, Furmark T, Marteinsdottir I,
et al: Cerebral blood ow during anticipation of public speaking in social
phobia: a PET study. Biol Psychiatry
2002; 52:11131119
9. Stuss DT, Alexander MP, Floden D, et
al: Fractionation and localization of
distinct frontal lobe processes: evidence
from focal lesions in humans, in Principles of Frontal Lobe Function. Edited
by Stuss DT, Knight RT. Oxford, England, Oxford University Press, 2002,
pp 392407
10. Ferrara M, Freda F, Massa R, et al:
Frontal lobe syndrome or adolescentonset schizophrenia? A case report.
Acta Psychiatr Scand 2006; 114:375377

Neuroimaging Correlates of
Chronic Delusional Jealousy
after Right Cerebral
Infarction
To the Editor: Although there have
been accounts of delusional jealousy occurring in patients with
structural brain damage, the phenomenon has rarely been reported
following right cerebrovascular infarction. In this new case we will
endeavor to describe the possible
pathogenic role of right hemisphere
localization.
During hospitalization for a transient left-sided hemiplegia after a
right middle cerebral artery infarct,
a 77-year-old man became convinced that members of the medical
staff wanted to steal his house. Although he was rapidly discharged
(5 days later), he subsequently declared that his wife had had a love
affair with a school master many

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