110 Journal ofNeurology, Neurosurgery, and Psychiatry 1991;54:110-115 J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.54.2.110 on 1 February 1991. Downloaded from SPECT, MRI and cognitive functions in multiple sclerosis Carlo Pozzilli, Domenico Passafiume, Silvia Bemardi, Patrizia Pantano, Chiara Incoccia, Stefano Bastianello, Luigi Bozzao, Gian Luigi Lenzi, Cesare Fieschi Abstract in the study of cognitive deficit associated Seventeen patients with relapsing remit- with Alzheimer's dementia.2"22 ting multiple sclerosis (MS) and mild The aim of this study was to examine the physical disability had neuropsycho- regional distribution of 99mTc HMPAO in logical testing, magnetic resonance the brain, the extent of cerebral lesions by imaging (MRI) and single photon MRI and their relationship to neuropsycho- emission computerised tomography logical findings in MS. Our study specifically (SPECT) using technetium 99m (99mTc) addresses the relapsing-remitting MS type hexamethyl-propyleneamine oxime with relatively mild physical and cognitive (HMPAO). Performance in verbal disturbance. fluency, naming and memory testing appeared to be impaired in MS patients compared with 17 age-sex and education Materials and methods matched normal controls. Patients Weighted periventricular and con- Seventeen right handed MS patients (12 fluent lesion scores and the width of the women and five men), mean (SD) age 31 (10) third ventricle, proved to be the most years and educational level 14 (3 5) years were sensitive MRI measures in differentiat- selected from those admitted to our MS out- ing more cognitively impaired patients patient clinic. The patients were evaluated from those who were relatively unim- according to the Schumacher criteria as paired. having clinically definite MS.23 The diagnosis Ratios of regional to whole brain was further supported by evoked potentials activity, measured by SPECT, showed and CSF studies. All patients had a relapsing- significant reduction in the frontal lobes remitting form of MS24 and they were studied and in the left temporal lobe of MS during a stationary phase. At least three patients. A relationship was found be- months elapsed between the occurrence of an tween left temporal abnormality in exacerbation or the termination of therapy 99mTc-HMPAO uptake and deficit in (steroids/corticotropin) and testing. verbal fluency and verbal memory. Excluded from the study were any patients http://jnnp.bmj.com/ Finally, asymmetrical lobar activity who did not meet the criteria of definite MS University of Rome, or Department of indicated a predominant left rather than whose disease course was chronic-progres- Neurological Science right temporo-parietal involvement. sive. Patients with EDSS score >4 or those C Pozzilli with Mini Mental State Examination S Bernardi P Pantano (MMSE) lower than 23 were also excluded. S Bastianello A substantial proportion of patients with mul- Mean (SD) clinical disease duration was L Bozzao tiple sclerosis (MS) show disturbance of eight (five) years, mean degree of impairment G Lenzi higher cognitive functions.'` Cognitive as estimated by the Kurtzke Expanded Dis- on September 29, 2021 by guest. Protected copyright. C Fieschi decline is more frequent at the more advanced ability Status Scale (EDSS)2" was 1-7 (1 0) Department of stage of the disease6 and in Psychology chronic progres- and mean MMSE was 28-5 (1-7). C Incoccia sive MS.7 It may, however, also be present in University of the early phase89 and in patients with mild Neuropsychological assessment L'Aquila, Rome, Italy physical disability.'°0 The extent of cognitive The neuropsychological test battery26 consis- Department of impairment is related to cerebral ventricular ted of measures Environmental of general intelligence, lan- Science size"2 corpus callosum atrophy'3 14 and degree guage, memory, attention and visuospatial D Passafiume of cerebral lesions quantified by magnetic abilities lasting approximately two hours. The Presented as an abstract at resonance imaging (MRI).1'58 battery was composed of the following tests: the 14th International Previous work using positron emission General intelligence Coloured Symposium on Cerebral Progressive Blood Flow and Metabolism, tomography (PET) has demonstrated a Matrices. This test was administered follow- "Brain 89", Bologna, 28th generalised coupled reduction in both cerebral ing the standard procedure to provide an May-Ist June 1989 oxygen utilisation and blood flow in MS estimate of non verbal general Correspondence to: intelligence. Dr Pozzilli, Department of patients. The reduction was found in both Abstract/conceptual reasoning Wisconsin Neurological Science, white and grey matter and correlated with University of Rome, Viale Sorting Card Test. This was administered dell'Universita 30, 00185 cognitive impairment, rather than with following the standard procedure. The Rome, Italy. locomotor disability or clinical disease number of perseverative errors were recorded Received 11 December 1989 duration.'9 Recently, single photon emission as a and in revised form measure of abstracting ability. 18 April 1990. computed tomography (SPECT) has given Language Boston Naming Test.27 In this test Accepted 15 May 1990 information similar to that provided by PET of confrontational naming ability, subjects SPECT, MRI and cognitivefunctions in multiple sclerosis illl were shown line drawings, one at a time, of 60 radiologist (LB) blind to the clinical and J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.54.2.110 on 1 February 1991. Downloaded from objects that varied in familiarity. The total neuropsychological findings. number of correct responses serves as the Lesions were divided into two categories: score. single lesions and confluent lesions. Single Set test. This is a verbal fluency test, based lesions were defined as rounded areas of on the number of components in a given abnormal high signal intensity. Confluent category that the subject can denominate in lesions have an appearance of more than one 120s. We adopted the categories "furniture" rounded single lesion having come together to and "birds". Scoring is the mean of names form an irregularly shaped "lump" or thick produced in the two categories. (> 5 mm) linear area abnormality.28 Visuospatial abilities Street Completion Weighted lesion scores were developed Test. This is a test of "speed of closure". We based on the number and size of lesions. We adopted the 11 items version. Each item is assigned the following weights according to composed by an incomplete black figure of lesion size: 1 = < 8 mm; 2 = 8-20 mm; a common object that has to be identified. 3 = >20 mm. Scoring is on pass/fail basis. Lesions which were periventricular in part Elithorn's Perceptual Maze Test. This is and extended out into the brain parenchyma composed of an 18 lattice type maze and the were considered "periventricular", while subject has to trace a line from bottom to top lesions which were apparently separate from of the maze, through the maximum number of the ventricles were designated "discrete" black points randomly placed on the net cerebral lesions.29 This latter group included figure. The scoring is on time and number of both "pure" white matter lesions and those black point basis. located just beneath the cortical surface (grey- Verbal memory Digit Span. We administered white matter junctions). and scored this subtest of WAIS following The evaluation of the corpus callosum (CC) standard instructions. was carried out on sagittal TI weighted Rey Auditory Verbal Learning. A list of 15 images. To obtain area measurements of CC stimulus-name of common objects is read five and cerebral hemisphere, the outlines of these times by the examiner to the subject. After structures were traced on a monitor screen each presentation the subject has to repeat as with a cursor and their areas were then cal- many words as he/she can recall. We assigned culated by a means of a computerised graphic two different scores. Short term memory table. The CC/brain area ratio was calculated scores: number of words recalled after the and then analysed."' first presentation; Long term memory scores: Finally, linear measurements were recorded the words correctly reported after a 15 min- including: (1) Frontal Horn Index, the ratio utes delay. of the maximal distance between the lateral Visuospatial memory Corsi Tapping Test. border of the frontal horns and the maximal The subject is presented with nine blocks width of the outer skull table at the same level; impartially arranged on a board. The exam- (2) Cella Media Index, the ratio of the mini- iner taps the blocks, and the subject is mal width of the lateral ventricles at the cella required to tap the same blocks in exactly the media level to outer skull table at the same same pattern. Scoring is the longest sequence level; (3) Third Ventricular Index, the ratio of of blocks correctly tapped. the maximal width of the third ventricle and http://jnnp.bmj.com/ Rey Osterreith Complex Figure. The width of outer skull at the same level. subject is presented with a complex geo- metrical drawing that he/she has to reproduce SPECT first by copying and after 15 minutes from SPECT brain imaging was performed with a memory. Scores are the number of element rotating gamma camera (GE 400 T) connected correctly reproduced and placed. to a dedicated computer (HP 1000, Eurobit). Seventeen normal controls (NC) matched Twenty mCi of 99mTc HMPAO was injec- on September 29, 2021 by guest. Protected copyright. one to one with the patients in terms of age, ted into an antecubital vein with the patient sex and education level, were recruited from sitting quietly in a softly lit room. After 10 the community. Normal controls were people minutes, patients were placed supine using a from the hospital staff without a history of head holder to minimise motion. Acquisitions central nervous system disease or alcohol were made recording 64 angular views using a abuse. Normal controls were evaluated using 64 x 64 matrix format. In 30 minutes four the same neuropsychological procedures as million total counts were collected.