Brain (1993), 116, 1541-1548

Severe frontal syndrome associated with
infarcts of the left anterior cingulate gyrus and
the head of the right caudate nucleus
A clinico-pathological case
J.-D. Degos, N. da Fonseca, F. Gray and P. Cesaro

SUMMARY

The clinicopathological findings in a patient who presented a severe frontal syndrome
and who had ischaemic lesions in the left anterior cingulate gyrus and in the head of
the right caudate nucleus are reported. The clinical features included complex disorders
such as distractibility, docility, emotional unconcern, manual grasping, prehension and
utilization behaviour, perseverations and anterograde amnesia. They are closely similar
to those previously described in a patient with bilateral lesions involving the anterior
cyngulate gyri. These findings suggest that (i) in the presence of a lesion of the anterior
cingulate gyrus on one side, a lesion of the head of the contralateral caudate nucleus
may be equivalent to a lesion of the anterior cingulate gyrus, the anterior cingulate
gyrus - caudate complex working as a single functional unit; (ii) the anterior cingulate
gyri (and anterior cingulate gyrus - caudate complexes) play a crucial role in the expression
of frontal lobe functions; (iii) they are necessary for sustained goal-oriented responses
to (emotionally or not) discriminated stimuli.
INTRODUCTION

Severe deficits, such as decreased spontaneous speech and movements have been described
in association with bilateral ischaemic lesions of the anterior cingulate gyrus (Barris and
Schuman, 1953; Faris, 1969; Freemon, 1971; Buge et al., 1975). However, the lesions
extended beyond the anterior cingulate gyrus, making the signs difficult to interpret.
Amnesia and personality changes (Okawa et al., 1980; Alexander and Freedman, 1984),
such as apathy or lack of concern, following rupture of anterior communicating artery
aneurysms, appear related to lesions in areas including the anterior cingulate gyrus, but
may also involve other possibly relevant structures. Laplane et al. (1981) reported a case
of complex behavioural changes, including gross inattention, indifference, docility, prehension and utilization behaviour and a confabulatory amnestic syndrome, associated
with a bilateral infarct of anterior cingulate gyrus and fornices. We report the clinicopathologicalfindings in a patient with a clinicallysimilar disorder who had limited ischaemic
Correspondence to: Dr J.-D. Degos, Service de Neurologie, C.H.U. Henri Mondor, 94010 Creteil, France.

© Oxford University Press 1993

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Departement de Neurosciences, C.H. U. Henri Mondor, Creteil, France

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J.-D. DEGOS AND OTHERS

lesions in the left anterior cingulate gyrus and anterior cingulate bundle, and in the head
of the right caudate nucleus.
CASE REPORT

NEUROPA THOLOGICAL FINDINGS

Post-mortem examination was performed 18 h after death. It revealed a massive pulmonary
embolus.

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Mrs P., a 78-year-old right-handed woman, described by her family as an active housewife and an independentminded, self-sufficient person, was admitted immediately after the abrupt onset of left hemiparesis with loss
of consciousness. Hypertension was the only significant previous disorder. On admission, Mrs P. was alert
but unable to obey commands or answer questions. The left hemiparesis had recovered and neurological
examination was normal except for bilateral Babinski signs and grasp reflexes. Clinical and ECG signs of
atrial fibrillation were noted.
During the following days, the patient could be persuaded to walk and talk only by vigorous encouragement.
When left to herself, she remained silent and motionless for hours, with episodic motor agitation. When
fed or nursed, she seemed remarkably Indifferent to both the nurses and the situation. On examination, bilateral
extensor plantar responses and grasp reflex persisted; an obvious prehension and utilization behaviour was
observed: silent tactile and/or visual presentation of objects compelled the patient to grasp them (she could
end up with many objects in her hands), and use them (e.g. having grasped a pen and a sheet, she started
writing, but without order); this behaviour occurred even if the patient was told a few seconds before not
to grasp. Her attention shifted constantly to any external stimulus. Formal neuropsychological assessment
was impossible because of this distractibilityby irrelevant stimuli and inabilityto sustain goal-oriented behaviour.
Mrs P., of Portuguese parents, was born in France and was bilingual; however, whether a question was
put in French or Portuguese, she regularly answered in French. Her speech was unaltered but her responses
were usually limited to a single word. She was able to state her name, age, birth date and address, and,
occasionally, she gave coherent responses about past events in her life. She could even repeat long sentences
correctly, and her digit span was 6. She could state the year and the month, but not the precise day. She
could not recognize the members of the medical staff and was unable to recall a single word 2 min after
learning it. Neither confabulation nor false recognition was noted. Objects and pictures (photographs) were
correctly named, but serial presentations resulted in perseverations. Alternate motor and graphic Luria's tasks
were not carried out. Ideational (e.g. candle lighting) and ideomotor (pantomime, symbolic gesture, imitation
of manual or finger postures) apraxia tests were correctly performed. Drawing tasks elicited gross perseverations
and disclosed a constructive disability.
Two weeks after her admission, Mrs P. began to feed, wash and dress herself but only if she was specifically
and repeatedly asked to do so. Unless someone regularly took the precaution of reminding her to visit the
toilet, she urinated and defecated wherever she happened to be. Although the reduction in spontaneous speech
persisted, provoked responses seemed more readily obtainable. Sometimes she merely answered with a nod
or a gesture. She showed little initiative and was very docile. For example, she used to stay motionless at
the nurses' office until someone accompanied her back to her room. Her mood seemed rather euphoric in
that she used to smile and laugh in imitation of those around her. However, underneath this surface appearance,
her lack of emotional concern was startling. Not even the most tragic event or situation seemed to trouble
her. She hardly reacted when she was told that her husband to whom she was devoted had fallen ill. One
week later, when she was informed of his death, an astonished expression fleetingly crossed her face, but
almost immediately her attention was drawn to noise outside her room and it was easy to make her laugh.
Questioned about the effect his death had on her, she replied with a smile: 'It's not really great fun.' The
prehension and utilization behaviour gradually diminished during this period although the bilateral grasp reflex
persisted. Mrs P. knew that she was in a hospital, but not the reason why. She was unable to recall a single
word from three she had learned 3 min before, or to recognize more than one in a multiple choice test.
Motor and graphic alternate serial tasks continued to be impossible to carry out, and perseverations still
interfered with the quality of her writing and drawing.
Her condition remained stable for 1 month before she died suddenly 6 weeks after the onset of the neurological
signs.

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1543

Gross examination of the brain (1280 g) on coronal sections of the hemispheres and
sections of the brainstem and cerebellum perpendicular to their axis, showed several,
often haemorrhagic, infarcts, all in the anterior cerebral artery territories (Fig. 1). The

basilar part of the right anterior cerebral artery was occluded by an old embolus. The
anterior communicating artery, the right pericallosal artery and the left anterior cerebral
artery were neither stenosed nor occluded. The remaining intracerebral arteries and
the cervical arteries of the carotid-vertebral system were devoid of atherosclerosis or
occlusion.
All the hemispheric slices containing the lesions were embedded in celloidin, serially
cut at 15 /lm, and stained with haematoxylin and eosin and Loyez's stain for myelin.
Every 10 mm on the left and 3 mm on the right a section stained for myelin was drawn
with a camera lucida to give a precise topography of the lesions.
Light microscopy confirmed several infarcts of various ages. Two of them (in the
territories of left and right anterior cerebral arteries) were old ones, containing numerous
lipid laden macrophages and occasional siderophages. More recent lesions with necrosis,
slight inflammatory reaction and extravasation of blood cells were also present in the

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FIG. 1. A, coronal section of the left cerebral hemisphere at the level of the anterior part of the putamen and head of
caudate nucleus, Loyez stain for myelin. A partly haemorrhagic infarct involving the cortical territory of the left anterior
cerebral artery including the superior frontal gyrus and the cingulate gyrus can be seen. B, coronal section of the right
cerebral hemisphere at the same level as A, Loyez stain for myelin. A pale infarct in the territory of the medial striate
artery (recurrent artery of Heubner) involving the head of the caudate nucleus and adjacent part of the putamen can be
seen. More recent subcortical ischaemic lesions are also present in the inferior frontal gyrus.

J.-D. DEGaS AND OTHERS

1544

B

FIG. 2. A, schema representing the topography of ischaemic lesions on the left side. Every 10 mm a section stained for
myelin was drawn with a camera lucida. B, schema representing the topography of ischaemic lesions on the right side.
Every 3 mm a section stained for myelin was drawn with a camera lucida. The squared areas correspond with the lesions
responsible for the symptomatology; the hatched ones correspond with more recent lesions. Cc = corpus callosum;
CG = cingulate gyrus; CN = caudate nucleus; GR = gyrus rectus; IFG = inferior frontal gyrus; Ins = insula;
MFG = middle frontal gyrus; OG = orbital gyrus; PrCG = precentral gyrus; Put = putamen; SFG = superior frontal
gyrus.

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rightfrontal cortex. Some embolic arteriolar occlusions were seen in the leptomeninges
responsible for limited ischaemic changes.
The topography of all the cerebral lesions is represented in Fig. 2A, B. On the left
side, the infarct was old, haemorragic and restricted to the superficial territory of the
anterior cerebral artery. It destroyed the anterior part of the cingulate gyrus from its anterior
pole to a vertical plane through the mamillary body. The cingulum was involved at its
anterior part around the rostrum of the corpus callosum. The infarct also extended to
the internal part of the superior frontal gyrus. The corpus callosum, medial frontal gyrus
and precentral gyrus were spared. On the right side, a pale ischaemic lesion was present
in the territory of the medial striate artery (recurrent artery of Heubner). It destroyed
the anteromedial part of the head of the caudate nucleus and adjacent part of the putamen;
the internal capsule, the pillars of fornices and the septal nuclei were unaffected. Limited
and more recent cortico-subcortical haemorrhagic infarcts were observed on both sides
of the inferior frontal gyrus. The superior frontal gyrus, cingulate gyrus, cingulum, corpus
callosum and precentral gyrus were spared.

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1545

DISCUSSION

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The clinical features of this case included several complex disorders: distractibility, docility,
emotional unconcern, manual grasping, prehension and utilizationbehaviour, perseverations
and anterograde amnesia. They are closely similar to those described by Laplane et al.
(1981) in a patient with bilateral lesions involving the anterior cyngulate gyri, the rostral
cingulum bundle and the pillars of the fornices. The clinical similarity was so striking,
particularly regarding the dramatic emotional unconcern, that the diagnosis of a bilateral
lesion of the anterior cingulate area was immediately suspected.
The anatomical examination of the brain showed bilateral embolic infarcts in the territory
of the anterior cerebral arteries: on the left, the anterior parts of the cingulate gyrus and
of the cingulum and the adjacent internal part of the superior frontal gyrus were destroyed;
on the right the lesion was limited to the anteromedial part of the head of the caudate
nucleus and the adjacent part of the putamen, sparing the cingulate gyrus. These infarcts
are the same age, and probably responsible for the symptomatology. A few small infarcts
were also found in the right frontal cortex; however, these lesions were more recent (less
than days), and are likely to have occurred after the clinical onset. As they did not result
in any modification of the symptomatology, they can be considered not responsible for it.
These findings suggest that, in the presence of a lesion of the anterior cingulate gyrus
on one side, a lesion of the head of the contralateral caudate nucleus may be equivalent
to a lesion of the anterior cingulate gyrus. Anatomically, frontal cortico-caudate projections
originate from the supra- and infragranular layers of the cortex. This distinguishes them
from other cortico-fugal pathways to subcortical structures which arise from infragranular
layers only, and makes them similar to inter-cortical connections (Royce, 1982; Arikuni
and Kubota, 1986). Thus the function of the caudate nuclei may be intimately related
to the function of the corresponding cerebral cortex, and anterior cingulate gyrus-caudate
complex can be seen as a single functional unit.
Of interest in our case is the small size of the lesions contrasting with their devastating
neuro-behavioural effect. Most elements of the so-called frontal lobe syndrome were
present, suggesting that the anterior cingulate gyrus - caudate complex constitutes a crucial
pathway in the expression of frontal lobe functions. Small subcortical lesions are able
to produce some components of the frontal lobe syndrome (Castaigne et al., 1966; Richfield et al., 1987; Mendez et al., 1989; Caplan et al., 1990; Pedrazzi et al., 1990; Trillet
et al., 1990; Sandson et al., 1991). However, in our patient, as in the patient of Laplane
et ale (1981), the frontal lobe syndrome was strikingly complete and severe.
Prehension and utilization behaviour, which was present in these two cases, has been
described by Lhermitte (1983) who ascribed it to lesions of the orbital surface of the
frontal lobe, and possibly, of the head of the caudate nucleus. In fact, his pathological
case had ischaemic lesions in the territory of Heubner's arteries involving the head of
the caudate nucleus bilaterally. Furthermore, the coronal sections of the frontal lobes
displayed bilateral demyelination of the white matter reflecting the disconnection of large
areas of frontal cortex. The four other patients had large frontal lesions involving the
medial aspect of one cerebral hemisphere on CT scan; similar features were found in
the case described by Shallice et ale (1989). Therefore it seems likely that, in these cases,
the prehension and utilization behaviour resulted from a lesion of the anterior cingulate
gyrus-caudate complex.

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J.-D. DEGaS AND OTHERS

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It has been proposed that cingulate gyrus is a part of a network for the distribution
of directed attention (Mesulam, 1990). This statement is clinically based on the location
of the lesions responsible for neglect in both humans and monkeys, namely the dorsolateral
posterior parietal cortex, the dorsolateral premotor-prefrontal cortex and the cingulate
gyrus. However, as far as the anterior cingulate gyrus is concerned, it is not in accordance
with the present and previous clinico-pathological data (Laplane et al., 1981) where neglect
was absent. We propose another functional diagram after having surveyed the few available
data on anterior cingulate gyri.
Bilateral surgical lesions of the anterior cingulate gyrus and/or anterior cingulate bundles
in mentally disabled patients do not result in gross persistent neurological impairment
(Le Beau, 1954). However, detailed analysis of performance reveals specific deficits of
attention (Janer and Pardo, 1991). On the other hand, the major deficits described after
spontaneous bilateral cingulate injury are inconclusive because the lesions were not confined
to anterior cingulate gyri (Barris and Schuman, 1953; Faris, 1969; Freemon, 1971; Buge
et al., 1975).
Some informative results related to the function of the anterior cingulate gyrus arose
from its electrical stimulation in conscious man (Talairach et al., 1973; Bancaud et ale ,
1976; Halgren, 1982) which produced complex motor responses involving the face or
the hands in association with attention and mood modifications. When these responses
appeared, no spreading of the after-discharge to other structures was noticed. It seems
therefore that elaborated motor activity, mood and arousal changes represent specific effects
of anterior cingulate gyrus activation.
Recent PET studies have established a relationship between the anterior cingulate gyrus
and the attention required for generating action as opposed to attention to relevant sensory
stimuli (Posner et al., 1988; Pardo et al., 1991): selecting language (or other forms of
information) for action, requiring the inhibition of the habitual response and the selection
of the task-oriented response resulted in an increase of blood flow in areas of the medial
frontal lobe (Posner et al., 1988; Petersen et al., 1989; Pardo et al., 1990).
Anatomically, the anterior cingulate gyrus is interconnected with the frontal (prefrontal,
orbital, premotor) cortex (Selemon and Goldman-Rakic, 1985), the supplementary motor
area structure (Goldberg, 1985) and with the thalamus (mainly intralaminar and mediodorsal nucleus), mesencephalic reticular formation and amygdala. Powerful reciprocal
projections link the anterior cingulate gyrus to area 7 (Baleydier and Mauguiere, 1980),
which is known to be involved in the detection and spatial localization of behaviourally
relevant visual stimuli, and to drive movements directed towards them (Lynch, 1980);
it furnishes the only sensory input to the anterior cingulate gyrus. The efferent subcortical
projections of the anterior cingulate gyrus run to the striatum where they are intimately
mingled with other associative cortex projections (Percheron et al., 1984).
From these different data, the anterior cingulate gyrus can be considered the efferent
limb of a network of neocortical (frontal and parietal association areas), limbic and reticular
interconnections, on which converge influences from cognitive, emotional and arousal
systems. Thus it can reasonably be postulated that the specific function of the anterior
cingulate gyrus may be triggering appropriate, sustained goal-oriented responses to
discriminated stimuli. When the anterior cingulate gyri (or the anterior cingulate gyrus
on one side and the head of the caudate nucleus on the other side as in our patient) are
damaged, their efferent areas may be disconnected from the cortical and limbic influences
necessary for producing selective responses which no longer occur.

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1547

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Received March 15, 1993. Revised June 4, 1993. Accepted July 2, 1993