Copyright # Munksgaard 2001 Acta Neurol Scand 2001: 104: 185–190 Printed in UK. All rights reserved ACTA NEUROLOGICA SCANDINAVICA ISSN 0001-6314 Case report Abulia and cognitive impairment in two patients with capsular genu infarct Pantoni L, Basile AM, Romanelli M, Piccini C, Sarti C, Nencini P, Inzitari D. Abulia and cognitive impairment in two patients with capsular genu infarct. Acta Neurol Scand 2001: 104: 185–190. # Munksgaard 2001. Background – An internal capsule genu infarct has been rarely reported to cause cognitive impairment and behavioral changes. This clinical picture can be explained on anatomical and functional basis because important subcortical–cortical pathways traverse the internal capsule genu. We report 2 previously non-demented patients who developed acute confusional state, abulia, and moderate cognitive decline after the occurrence of an infarct in the capsular genu. Methods – Clinical, neuropsychological, and MRI evaluation at baseline and 12-month follow-up. Results – Abulia and cognitive impairment were still present 1 year after stroke. In 1 patient there were associated multiple lacunar infarcts and leukoaraiosis. In the other an old small left frontal infarct was also present. In both moderate cortical atrophy co-existed. Conclusions – We hypothesize that co-existing lesions, possibly associated with a sub-clinical reduction of cognitive functions, facilitate the development of a persistent clinically evident mental deficit after the occurrence of an infarct in the capsular genu. The term vascular dementia encompasses a wide spectrum of clinical–pathological entities with different pathogenic mechanisms (1). Many vascular dementia cases occur in relation with stroke, but even the stroke-related forms of vascular dementia are heterogeneous from the clinical and pathogenic points of view (2). Different possibilities can explain why stroke patients are more prone to develop dementia (3). Single-strategic infarct dementia defines a clinical picture characterized by the abrupt onset of cognitive impairment and behavioral changes in relation to the occurrence of a single infarct in specific regions of the brain such as the thalamus, the caudate nucleus, and the angular gyrus (4). Cognitive alterations following unilateral infarcts of the genu of the internal capsule have been rarely described (5–9). The clinical picture is that of a frontal lobe syndrome with inattention, apathy, psychomotor retardation and has been interpreted as a thalamocortical disconnection syndrome (5). Madureira et al. (10) recently reported 4 patients with cognitive impairment and L. Pantoni, A. M. Basile, M. Romanelli, C. Piccini, C. Sarti, P. Nencini, D. Inzitari Department of Neurological and Psychiatric Sciences, University of Florence, Italy Key words: vascular dementia; strategic infarct dementia; dementia; stroke; internal capsule genu; frontal-subcortical circuits Leonardo Pantoni, Department of Neurological and Psychiatric Sciences, University of Florence, Viale Morgagni 85, 50134 Florence, Italy Tel.: 39 055 4277 995 Fax: 39 055 4298 461 e-mail: pantoni@neuro.unifi.it Accepted for publication March 2, 2001 an isolated inferior capsular genu infarction; their patients markedly improved within 12 months. We describe 2 patients with persistent abulia and cognitive impairment following an infarct of the left capsular genu, hypothesizing that in our cases the presence of concomitant cerebral lesions explains the persistence of the disturbance. Case reports Patient 1 was a 74-year-old retired, right-handed, man, with a 5-year education level, fully independent in activities of daily living and without any obvious cognitive impairment. He had a 40-year history of smoking (1 pack/day), and no history of diabetes mellitus, hypertension, or alcohol abuse. One day he suddenly became moderately confused and unable to carry out the activities he had planned for that day. On the following day, because of persisting mental confusion, the patient was admitted to the emergency room where the general 185 Pantoni et al. examination was unremarkable. A cranial CT showed multiple lacunar infarcts in the basal ganglia and thalami and diffuse hypodensity of the white matter. The genu of the left internal capsule showed mild initial hypodensity (Fig. 1). He was then admitted to the Neurology Unit. On admission, he was afebrile, alert and cooperative, oriented to place and person, but not to time. He did not show any obvious deficit in verbal expression or denomination but appeared abulic and with a tendency to mutism. He presented with slight right facial–brachial motor weakness. No sensory or cerebellar disturbances were present. Lasègue sign and rigor nucalis were absent. Blood gases analysis, routine blood tests, folic acid, vitamin B12, and thyroid hormones serum levels were within normal values. Blood tests for syphilis were negative. Electroencephalogram showed mildly altered vigilance and frontal–temporal theta component excess. A carotid and vertebral echo-color Doppler study revealed only intimal thickening of both internal carotid artery. A cranial MRI performed 2 days after admission showed moderate cortical atrophy, diffuse white matter alterations on the T2-weighted images, and one hyperintense lesion of the genu of the left internal capsule compatible with a recent lacunar infarct. During the following days the patient was somnolent and remained silent in the bed for Fig. 1. Patient 1. Cranial CT performed in the acute phase showing multiple lacunar infarcts in the basal ganglia and thalami and diffuse hypodensity of the white matter. The genu of the left internal capsule showed mild initial hypodensity (arrowhead). 186 most of the day-time. A thorough neuropsychological assessment (11–23) performed 8 days after admission showed slight mental deterioration with prevalent impairment of executive and memory functions; Mini-Mental State Examination (24) score was 20/30. The patient was disoriented to time, and uncertain in referring information on relevant facts of actuality. He showed an impairment of performances on tasks exploring abstraction, attention, verbal memory, and fluency. Moreover, he had difficulty in reading, writing, and calculation, while constructional praxis was normal (Table 1). In order to assess the pre-stroke cognitive status, we conducted an informant interview based on current criteria for dementia (25) and validated in a study assessing the incidence of dementia in a stroke registry (26). The interview was administered to the wife and excluded any intellectual deficit. Six months after the event, the patient had moderate memory impairment, a deterioration of emotional control, and an intellectual deficit so severe to heavily affect activities of daily living. This clinical picture was judged to be compatible with a diagnosis of dementia (25, 26). At the 12-month follow-up, the neuropsychological evaluation disclosed slightly worse scores in comparison with the previous one (Table 1). The patient continued to be disoriented to time and showed psychomotor retardation. He was still described by his relatives as hypokinetic and abulic, laying for most of his time on bed. Formally tested, he did not fit the DSM-IV criteria for major depression (27). A cranial MRI clearly showed the lacunar lesion of the genu of the left internal capsule (Fig. 2). Patient 2 was a 75-year-old retired, right-handed, man, with a 5-year education level, fully independent and without any obvious cognitive impairment. He had a history of hypertension and hypercholesterolemia. One day, while he was driving his tractor, he suddenly developed difficulties to continue the task and became moderately confused and hypoactive. Furthermore, he presented with right-side weakness, including facial paresis, and dysarthria. He was not hospitalized on this occasion. A cranial CT showed a mildly hypodense lesion of the left internal capsule genu; the exam also disclosed a small left frontal cortical hypodense lesion, with well defined limits, related to an old ischemic infarct. Two months later the patient came to our attention. On admission, he was alert and cooperative, but only partially oriented to place, time, and persons. He appeared abulic and with a tendency to mutism. He presented with slight dysarthria, right facial paresis and Babinski sign; he did not show any limb motor weakness nor sensory or cerebellar deficits. Routine blood tests, folic acid, Abulia and cognitive impairment in capsular genu infarct Table 1. Hospital and 12-month follow-up neuropsychological evaluations Patient 1 Neuropsychological tests Blessed’s IMCT (12) Weigl test (13) Visual search (14) Digit span forward (15) Corsi block test (16) RMT (17) Five words acquisition Five words 10-min recall Five words 24-h recall Associated words acquisition Associated words 10-min recall Associated words 24-h recall Babcock story (18) Immediate recall 10-min recall Token test (19) Set test (category fluency) (20) Letter fluency (21) CAS/ma (22) Copying drawings (23) Patient 2 Hospitalization assessment score* Follow-up assessment score* Hospitalization assessment score* Follow-up assessment score* Normative value** mean scoretSD Global mental function Abstraction Attention Short-term verbal memory Short-term spatial memory 28/34 3 18 3 5 22/34 – – 3 4 22/34 – – 2.5 2.5 22/34 1 37 3 2.5 32.5 (1.8) 10.1 (3.1)# 46.7 (8.2)# 4.2 (1.2) 4 (1.2) Long-term verbal memory Long-term verbal memory Long-term verbal memory Long-term verbal memory Long-term verbal memory Long-term verbal memory 7 15 1 10 20 16 3 4 4 4 10 8 0 0 0 0 0 0 0 0 0 0 0 0 11.8 (1.9) 17.6 (1.9) 15.4 (5.0) 13.3 (2.5) 21.2 (2.8) 20.3 (3.1) Long-term verbal memory Long-term verbal memory Language Language and executive functions Language and executive functions Counting, writing, reading, alphabet Constructional praxis 3 3 30 32 8 8 15 1 2 28.5 38 13 8 15 3 0 22 26 6 8 10 3 0 24.5 27 10 10 10 9.1 (4.2) 11.2 (5.0) 33.1 (2.2) 38.5 (1.6) 26.0 (9.3) 10.2 (1.2) 13.2 (1.9) Cognitive functions * Adjusted for age and education. ** In a series of 146 subjects (11). #According to Spinnler & Tognoni (14). IMCT: Information-Memory-Concentration-Test (12). RMT: Randt Memory Test (17). CAS/ma: Clifton Assessment Schedule mental ability (22). vitamin B12, and thyroid hormones serum levels were within normal values. Blood tests for syphilis were negative. A carotid and vertebral echo-color Fig. 2. Patient 1. Cranial MRI performed 1 year after stroke showing a cavitate lesion of the inferior genu of the left internal capsule (arrowhead) on the FLAIR (Fluid Attenuated Inversion Recovery, TR: 6000; TE: 100) sequence compatible with an old lacunar infarct. Doppler study revealed an occlusion at the origin of the left internal carotid artery with activation of collateral circles. A cranial MRI T2-weighted study showed a lacunar infarct of the genu of the left internal capsule and confirmed the presence of a small left frontal hyperintense lesion compatible with a watershed infarct between the anterior and middle cerebral artery territories. Mild cortical atrophy was also described (Fig. 3). The neuropsychological assessment showed a moderate mental deterioration with prevalent impairment of attention, acquisition, and comprehension functions; Mini-Mental State Examination score was 20/30. The patient showed a prevalent impairment of performances on tasks exploring verbal memory and fluency. Moreover, he had difficulty in reading, writing, and calculation, while constructional praxis was only partially impaired (Table 1). A neuropsychological assessment performed 12 months after stroke was similar to the previous one and showed moderate mental deterioration with prevalent impairment of attention, shifting of attention, verbal memory, and fluency (Table 1). MiniMental State Examination score was 15/30. At this time, he was still described by his relatives as hypokinetic and abulic; however, he was reported to be able to carry out his usual activities of daily living. The informant interview excluded any obvious intellectual deficit before the event. 187 Pantoni et al. Fig. 3. Patient 2. Cranial MRI performed 2 months after stroke. T2-weighted images showed a hyperintense lesion of the genu of the left internal capsule (arrowhead) suggesting a lacunar infarct and the presence of a small left frontal hyperintense lesion compatible with a watershed infarct between anterior cerebral artery and middle cerebral artery territories. Twelve months after, he was reported to have moderate memory deficit that slightly affected everyday life activities. This clinical picture was judged to be compatible with mild cognitive impairment but not with a diagnosis of dementia (25, 26). He was not diagnosed as major depressive by the DSM-IV criteria. Discussion We reported 2 patients with persistent abulia and cognitive impairment mainly characterized by deficit in executive functions which occurred after a capsular genu infarct. Lesions localized in the genu of the internal capsule are usually associated with contralateral facial and lingual hemiparesis and dysarthria (28). In his seminal review, Fisher (29) described a patient affected by an internal capsule lacunar infarct presenting with confusion and impairment of attention and memory in addition to pure motor hemiparesis. Other rare instances of cognitive deficit resulting from a lacunar infarct localized in the genu of the internal capsule have been reported (5–10). Cognitive and behavioral alterations in the case of genu infarct can be explained on anatomical and functional bases. Important pathways traverse the internal capsule 188 genu; among these, are the thalamo-cortical projection fibers that originate from the ventral-anterior and medial-dorsal nuclei of the thalamus and terminate in the frontal lobe. These white matter tracts are part of a complex system of cortical-subcortical-frontal circuits through which the flow of information from the entire cortex, after relay in the basal ganglia and thalami, reaches the frontal cortex (30). According to the review performed by Cummings, executive function deficits occur with lesions of the dorsolateral prefrontal circuit; disinhibition and changes in personality with lesions of the orbitofrontal circuit; and, apathy in cases of injury to the anterior cingulate circuit (31). Despite that in our patients cerebral blood flow could not be evaluated, previous studies have confirmed that in the case of capsular genu infarct the disruption of the thalamic projection fibers determines a functional deactivation of the ipsilateral frontal cortex (thalamocortical disconnection syndrome) (5, 8). To explain the occurrence of cognitive deterioration in cases of capsular genu infarct at least two hypotheses can be put forward: 1) only capsular genu infarcts that, because of their inferior location or bigger size, affect the inferior and anterior thalamic peduncles (thalamo-frontal connection) result in cognitive deficits; 2) co-existing lesions interact with the capsular genu infarct in determining the clinical picture. In both our patients the infarct was placed in the lower portion of the genu and both had associated lesions. In our first patient, the lesion was obviously located in the genu of the internal capsule. In patient 2 the lesion was bigger and partially involved the anterior thalamus. As far as associated lesions are considered, patient 1 showed diffuse white matter alterations (leukoaraiosis) and multiple lacunar infarcts. Leukoaraiosis has been described in association with subtle cognitive deficits, in particular in frontal lobe tasks (32), but it remains to be definitely established its net contribution to cognition particularly in respect of the role of concomitant lesions such as lacunar infarcts. In this regard, it should be underlined that leukoaraiosis has been shown to be an independent predictor of post-stroke dementia in hospital-based series (33, 34). Although not formally tested before the occurrence of the capsular genu infarct, we are confident that patient 1 could not be defined as overtly demented at that time; the family emphasized that before the stroke he was able to properly and independently carry out all his usual activities. This was formally verified by means of a structured informant interview (26). Thus, the occurrence of the capsular genu infarct seems to be relevant in relation to the post-stroke cognitive profile of this patient. In patient 2, a small Abulia and cognitive impairment in capsular genu infarct cortical infarct was also detected by MRI evaluation. This lesion appeared to have remained silent until the time of the stroke. This is in agreement with Godefroy et al.’s (35) observation that small frontal lesions are frequently associated and may contribute to the clinical picture of patients with subcortical infarcts. We hypothesize that in our patients the presence of pre-existing lesions was associated with a subclinical reduction of residual cognitive functions and that the occurrence of a strategically seated infarct led the subjects to develop a clinically evident mental deficit. The presence of associated lesions could also explain why our patients, differently from those described by Madureira et al. (10), did not recover at follow-up. We suggest that in cases of strategic-infarct dementia the coexistence of other cerebral lesions should be carefully sought in order to assess a possible synergist effect. Along with vascular lesions, both our patients showed cortical atrophy on MRI, a sign that might suggest the presence of neurodegenerative changes in their brains. Thus, also these alterations could have contributed to the clinical picture. The hypothesis that the strategic infarct could have disclosed a subtle cognitive impairment related to Alzheimer’s type changes is in line with recent data (36). Finally, another issue of interest deriving from the observation of our 2 patients is their behavior change after stroke. A considerable number of patients develop depression after stroke (37). This could obviously be linked with the functional deficit resulting from stroke (38, 39). On the other hand, Alexopoulos et al. 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