Neuropsyhoiogra, Vol. 30, No. Prmted I” Great Bntam 2, pp. 109-121. 1992. IT 0028&3932;92 65 OO+O.CJJ 1992 Pergamon Press plc RIGHT MOTOR NEGLECT ASSOCIATED WITH DYNAMIC APHASIA, LOSS OF DRIVE AND AMNESIA: CASE REPORT AND CEREBRAL BLOOD FLOW STUDY V. DE LA SAYETTE,*~F. LE DOZE,* G. BOUVARD,~ I. MORIN,* F. EUSTACHE,* M. FIORELLI,~ F. VIADER* and P.MORIN* *Services de Neurologie Vastel et Dejerine; IService de Mtdecine nuclbaire, CHU CBte de Nacre, Caen, France; and f&ServiceHospitalier Frbdtric Joliot, CEA, Dtpartement de Biologie, Orsay, France (Received 29 October Abstract-A 30-year-old drive following bilateral 1990: accepted 21 September 1991) right-handed man had right motor neglect, amnesia, aphasia thalamic and subthalamic infarctions. Serial resting cerebral and loss of blood flow (CBF) measurements with either Xenon 133 inhalation or positron emission tomography at 1,8 and IO months post-onset showed a widespread and long-lasting low CBF in the cortex. An additional CBF measurement, during motor tasks, showed a marked interhemispheric asymmetry in the pattern of activation: whereas left hand movement resulted in a CBF increase in contralateral superior rolandic and prerolandic areas, no significant regional CBF changes were seen during right hand movement, despite recovery from motor neglect. This loss ofCBF increase in cortical motor and premotor areas during voluntary movement of the previously neglected side points to a disruption of cortico-subcortical pathways subserving motor activation. The pathophysiology of aphasia, loss of drive and amnesia as well as their relationships to motor neglect, may also be discussed on the basis of thalamo-cortical disconnections. INTRODUCTION MOTOR NEGLECT (MN) was initially described by CRITCHLEY (1953) [14] as a lack of spontaneity affecting motor function, following expanding lesion within the parietal lobe. This manifestation was further specified by CASTAICNE et al. (1970,1972) [l 1, 121 so that the main features of MN include: (1) unilateral and spontaneous reduction of the motricity without motor deficit; (2) decreased withdrawal motor reaction to pain; (3) inappropriate position of the limbs left in uncomfortable position; (4) reversibility of these symptoms after verbal stimulation. This syndrome is more often than not part of the non-dominant hemisphere syndrome [2,6,7,59,60] but may occur rarely as a pure condition without other deficits suggestive of spatial or sensory neglect. These isolated cases, along with experimental studies in non-human primates [SS], have allowed to hypothesize a primary defect of programming and planning movement [25] independent of sensory and spatial neglect [54]. The lesions underlying unilateral MN have been ascribed to various topographic sites, most in the right cerebral hemisphere: parieto-temporal cortex [lo, 251, frontal cortex [ll, 251, anterior limb of the internal capsule [45, 561, internal capsule and lenticulostriate structures [54], thalamus [S, 24,471 and ventrolateral nucleus of the thalamus [63]. All these structures tAddress for reprints: CC-dex. France. Dr V. de la Sayette, Service de Neurologie 109 Vastel, CHU C6te de Nacre, F14033 Caen are thought to be concerned in the planning, programming and organizing of movement [25] and thus would comfort the hypotheses described above. Here, we report a clinical case of right MN caused by left thalamic lesions, without sensory or spatial neglect, but associated with profuse neuropsychological deficits. As neuropsychological symptoms following thalamic lesions are thought to reflect cortical dysfunction [7, 16,601, each deficit could be interpreted in terms of specific thalamocortical dysconnections. The measurement of CBF in the present case has shown a diffuse and remote cortical low flow reflecting a probable hypometabolism. Such hypometabolism, following thalamic lesions, has been previously demonstrated [4, 361 and interpreted in terms of interruption of neural connections, reminiscent of the concept of diaschisis [ 17, 371. An additional regional CBF measurement, during left and right sensorimotor activation tasks, showed a marked interhemispheric asymmetry in the pattern of activation. CASE PRESENTATION A right-handed 30.year-old man born in Turkey suddenly had a diffuse and severe headache and then became comatose for 24 hr. After that time, when the patient was again completely conscious, he was found to have a lack of spontaneous movement of the right limbs. His gait was severely disturbed by constant deviation to the right; hc dragged the right leg and did not swing the right arm; he fell often. Moreover, he frequently hit objects with his right side but no attempt was made to avoid them. Spontaneously, when he was sitting he left his right arm limp next to the body, and when he was lying the leg and the arm were left in uncomfortable positions behind the body or hanging out of the bed. Surprisingly, spontaneous ‘placing rcactions’such as putting the hand on the footboard of the bed. on the vvall, or crossing the legs, were sometimes but rarely executed perfectly. in contrast to the paucity ofmovement of the right limbs. In usual bimanual motor activities such as eating, or dressing, he failed totally to use the right hand or merely made the beginning of the gesture. Painful stimuli to the right hemibody caused no. or a very light, withdrawal reaction. whereas pain was normally felt. Following verbal stimulation, when the patient was asked with insistence to contract his limbs, the motor strength was symmetrical and without segmental deficit. Deep tendon reflexes were symmetrical and the plantar reflcxcs flexor. A comment from theexaminer to indicate an inappropriate or uncomfortable position of the arm and leg was usually sufficient to lead the patient to rectify it. On the other hand, improvement of gait and gestures needed continuous and sustained encouragements and, even so, there was not full disappearance of the neglect. When the patient was asked to put his right index-fnger to his nose or ear. a detinite dysmetria was noted as he fell behind or beside the target. Examinations performed at different periods never showed sensory deficit or extinction. Somatosensory evoked potentials after stimulation of the median nerves wcrc asymmetrical since the latest parietal wave (42 msec) was not recorded on the left side. There was no hemianopsia or visual extinction. No visuo-spatial neglect was found on the following tasks: complex image description, placement ofcities on the map ofTurkey, tridimensional constructive praxia (Benton), clock and room drawing. The Rey ligure revealed a mild constructive apraxia. Verbal dichotic listening gave normal results. The patient’s behaviour was remarkable: he was extremely inert. spending much time doing nothing but watching telev,ision. He showed a total lack ofconcern regarding his presence in hospital and seemed unaware of his own illness. This impassive state was easily abolished by external stimulation: for instance, he would perform neuropsychological tasks with reasonably sustained attention. No frontal signs were detected in the Porteus maze test and the Raven progressive matrices: hc performed normally the sequence of three consecutive hand movements and had no grasping or imitation syndrome. A dynamic aphasia was present including loss of initiation of speech, reduced but coherent narration, with some word-finding dithculties and profoundly reduced verbal fluency: he said three words in I min in the verbal fucncy subtest of the French version of the Boston diagnostic aphasia examination (BDAE). A moderate anemia was definitely present since 55/105 was the score he obtained at the confrontation naming test of the BDAE. Although these abnormalitiesexisted in French and Turkish alike, the interpretation of the French language disorders must be tempered. Reading aloud seemed fluent in Turkish; the patient was French-illiterate. Comprehension and rcpelition were unimpaired, We ncvcr observed agrammatism. phonemic paraphasia, perseveration or articuiatory disturbances. Fmally, this patient exhibited marked memory impairment consisting in anterogradc amnesia wtth total disorientation both for place and time, loss of learning ability and retrograde amnesia as. for instance, he could not remember his own job or his present address. The remote memory was also severely impaired since he could not recall either the date of his immigration to France 7 years before or his birthday. The Wechsler memory scale 7. ’&..sub&t 3: 0, subteat 4: I. showed an MQ of40 and the scores of the different subtests were: subtest I : 4, subtest _. subtest 5: I. subtest 6: 2, subtest 7: 0. The long-term memory for visual material (visual reproduction = 2) as well as verbal material (logic memory = I ) was disturbed. The score of the digit span was 4. MOTOR NEGLECT, APHASIA, LOSS OF DRIVE, AMNESIA; CBF STUDY 111 Erolution Motor neglect began to improve approx. 4 weeks post-onset. Two months later, clinical examination still revealed dragging of the right leg, imbalance of the arm and slight deviation of gait but normal bimanual motor activity. Repeated motor examinations performed during the next 8 months showed the full disappearance ofmotor neglect although the patient still complained of a heavy and lazy right hand and clumsiness. Behavioural abnormalities remained severe and his performances in language and memory tests remained unchanged. Ten months after the onset of his disease, a marked decrease in spontaneous activity and poor affect were still present. He had to be stimulated by his wife into day-to-day actions, to wake up, wash and dress, eat and even to switch on the television. Obsessive-compulsive behaviour was absent. This abuha was still associated with dynamic aphasia and memory impairment although a slight improvement was observed. Mild disturbances were observed in the BDAE confrontation naming test (score 751105) but he totally failed twice at 2-monthly intervals in the verbal fluency subtest. The memory score on Wechsler’s scale was 61. Disorientation for place and time had disappeared. He was able to remember his last visit to hospital and to recognize the medical staff. Magnetic resonmcr imaying and angiography The magnetic resonance imaging (MRI) was performed 2 months after the onset of symptoms. Tl (TR = 600 msec; TE = 9 msec) and T2 (TR = 3273 msec; TE = 80 msec) weighted sequences were used in coronal and axial planes (parallel to orbito-meatal line); only Tl weighted sequences were used in the sagittal plane. Sequential slices (5 mm) were scanned in the thalamic region. We attempted to localize the MRI abnormalities, above all in the sagittal plane, using a three-dimensional atlas of the human brain [52]. Small size lesions exhibiting hypointense signals on Tl weighted images and hyperintense signal on T2 weighted images, consistent with infarctions, were seen in the left thalamic and subthalamic regions. The largest, a paramedian lesion, extended medially from the inferior and external part of the dorsomedial nucleus (DM) to the internal part of the ventrolateral nucleus (VL) laterally. Between these limits, the intralaminar nuclei were probably involved and included the parafascicular and the centromedian nuclei, but the anterior pole of the thalamus was preserved (Figs 1,2,5 and 7). A second lesion, located in the posterior and lateral thalamus, involved the pulvinar (Figs 3,6 and 7). Subthalamic lesions were noted in the vicinity of the substantia nigra and subthalamic nucleus (Fig. 2). On the right side, numerous dotted lesions were observed in the medial part of the thalamus and subthalamic region. At least two of them were probably located in the DM (Figs 4 and 5). The precise localization of the others proved difficult. Cerebral angiography revealed a total occlusion of the distal portion of the basilar artery. Measurements of’ cerebral blood J?OW (CBF) CBF was measured 4 weeks, 8 months and 10 months post-onset, under resting condition: the patient lay with eyes closed and ears plugged. The first and third measurements were carried out using the Xenon 133 (‘33Xe) inhalation technique, the third measurement also included activation trials (see protocol). The second investigation included a combined measurement ofCBF and cerebral oxygen consumption, and was carried out at 8 months postonset using positron emission tomography (PET). Xenon 133 procedure. The CBF measurement with the Xenon 133 ( ‘33Xe) inhalation technique 133,401 employed a device with 32 detectors positioned over both hemispheres (Novocerebrograph). CBF was measured from the washout curves by estimation of the initial slope index (ISI) 1401. The procedures of measurement during the resting state and activation trials, were identical to those previously reported in a similar case [45]. The positioning of the scanning probes is illustrated on Fig. 8. Protocol of’ the ucticution paradigm. The patient was submitted to three CBF measurements with the ‘33Xe inhalation technique: rest, left hand activation, right hand activation, with a I hr interval between each study. The activation measurements were made over an 11 min period by having the patient feel different objects with the same hand, each for 30 set, for a total number of 22 objects. Adequate palpation of the objects was ascertained by direct observation of the patient during the examination and adequate object identification by having the patient enumerate some of the objects felt after the measurement had been completed, despite his memory disturbance. Seven healthy, right-handed control subjects, five men and two women aged from 37 to 80 years (average age, 62.4 years) underwent the same protocol for comparison. The patient and control subjects performed identically. Statistic-al analysis. For the patient, as asymmetry indices observed previously between homologous probes in 11 control subjects in rest condition (average age, 31.2 years) were 5.16% + 3.5%, interhemispheric IS1 differences, comparing each probe to its contralateral homologous probe were considered significant PcO.05 if above 13% (mean + 2 SD). An index of immediate reproductibility (second CBF/first CBF x 100) has been previously calculated in 12 control subjects (average age, 33.4 years). The values were 102.2 + 2.2% and 103.5 + 4.9% for mean IS1 and regional ISI, respectively. So mean IS1 differences between baseline and activation were considered significant PcO.05 if above 6.9% and regional IS1 differences between baseline and activation were considered significant PcO.05 if above 14.5% and P