Radiol Oncol 2002; 36(4): 297-303.
Cortico-basal ganglionic degeneration: radiological and functional features
Maja Ukmar1, Rita Moretti2, Paola Torre3, Rodolfo M. Antonello3, Renata Longo4, Antonio Bava2, Roberto Pozzi Mucelli1
1Department of Radiology, 2Department of Physiology and Pathology,
3Department of Internal Medicine and Clinical Neurology,
4Department of Physics, University of Trieste
Background. Cortico-basal ganglionic degeneration is a rare degenerative pathology that involves parietal areas and gradually determines frontal involvement. The aim of our work was to describe the main radiological findings in this pathology and to evaluate the cortical activation in these patients by f-MRI during simple and complex movements.
Patients and methods. We have evaluated eight patients with morphological and functional magnetic resonance by using a 1.5 T imager.
Results. Morphological evaluation: We found an asymmetric perirolandic cortical atrophy in seven patients, a mild hyperintensity in the perirolandic cortex in five patients, a mild atrophy of the basal ganglia in seven patients and, in one, a hypointensity in the lenticular nuclei. In one patient the morphological aspect was normal. Functional evaluation: The most important aspect was the hypoactivation of the parietal areas during the movement with the affected hand in all the patients. Conclusions. We consider f-MRI a helpful tool for the diagnosis and follow-up of this pathology.
Key words: basal ganglia diseases, cortico-basal degeneration; magnetic resonance imaging; fluorine radioisotopes, f-MRI; movement, apraxia, parietal lobe
Introduction
Cortico-basal ganglionic degeneration (CBGD) has become a more widely recognized entity: it has been considered as a degenerative movement disorder since its first
Received 25 October 2002 Accepted 4 November 2002
Correspondence to: Maja Ukmar, MD, Department of Radiology, University of Trieste, Trieste, Italy
description by Rebeiz thirty years ago.1 Since then, one hundred cases have been reported,2 but it remains a rare disease of unknown incidence and prevalence.3,4
CBGD usually presents after the fifth decade of life, with a varied combination of symptoms including stiffness, clumsiness, jerking, segmental dystonia, bradykinesia and usually ideomotor apraxia which can progress to the complete development of an »alien hand syndrome«. Other symptoms, such as action-induced and stimulus sensitive
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focal reflex myoclonus may precede or accompany the development of dystonic pos-tures.5 Invariably, it leads to a progressive disability (both motor and cognitive) which gradually leads to immobilization and institutionalisation.
Logistic regression analysis identified two models that contributed to distinguish these disorders and predicted the diagnosis of CBGD. The first one included asymmetric Parkinsonism as symptom onset and instability and falls at first clinic visit. The other one included cognitive disturbances, asymmetric parkinsonism within the first year of symptom onset and speech disturbances at the first clinic visit.6 A recent evaluation7 suggests that cognitive signs of disruption, which comprise a marked impairment of daily living functions, may be the commonest presentation of CBGD, rather than the better recognised perceptual-motor syndrome, described previously.
Radiological evaluation seems to be important as a diagnostic and clinical follow-up instrument. The most constant expression of the pathological features are: an important atrophy of the perirolandic gyri, particularly in the postrolandic cortex, associated with a mild atrophy of the basal ganglia,8-10 and an almost evident, though not constant hy-pointensity of the lenticular nuclei.8-10
The possibility of a direct and functional evaluation of cortical activation during hand motion, registered in CBGD patients, seems to us very interesting. This was the aim of our study: we discussed the results with an overview of literature.
Patients and methods
handed (average score at Briggs and Nebes Test: + 22.56).11
The past history of all the patients was completely mute for cerebrovascular disease, hypertension and metabolic disorders. No signs of addiction could be found. Their most common complain was the relatively recent development of an asymmetric akinetic syndrome (55% of cases), affecting in all the eight patients their left superior limb, ideomotor apraxia (43% of cases), bradykinesia (36% of cases), alien-limb syndrome (16% of cases), slurred speech (5% of cases) and gait difficulty (5% of cases). Only two of the subjects (35% of cases) showed action tremor and one of them (13% of cases) supranuclear gaze palsy affecting vertical and horizontal gazes (evidenced at oculomotor evaluation). All the patients underwent a complete oculomotor evaluation: a normal saccadic velocity (considering anti-saccades, reflexive saccades and voluntary saccades), with increased latency of saccades (especially of voluntary saccades) and preserved pursuit and optokinetic nystagmus were globally evidenced.
The mean duration of symptoms dated from 7.62 + 5.32 months prior to their admission.
From the cognitive perspective, intelligence performances were within normal ranges (111 + 2.34) as stated by the average score obtained in Raven Standard Progressive Matrices;12 the patients recognised right/left personal and extrapersonal hemispace, and no signs of tactile agnosia and of bucco-facial apraxia were found. Wechsler Adult Intelligence Scale (WAIS) average results demonstrated a mild general tendency to global deterioration (21.1% SD + 2.34%).13 All the patients could reproduce Koh’s Block quite well, by copy and by memory. Wechsler Memory Scale (WMS)14 put in evidence an MQ average score of 56.35 (SD + 5. 41), underlying a mild deterioration of logical, procedural and verbal memory strategies. All the subjects could not pantomime to
During the period between 1st January 1997 and 1st January 2002, eight patients (three males and five females) were included into our observation. Their mean age was 62.1 years old (SD + 6.9), all of them were right-Radiol Oncol 2002; 36(4): 297-303.
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verbal command of the examiner: all together showed signs of ideomotor apraxia with the left, affected hand. On the contrary, they did not show signs of ideational apraxia. All the patients showed moderate insight into their general situation, but principally into their motion disruption.
All the patients underwent brain-MRI, performed by a 1.5 T magnet. For the morphological evaluation an axial SE PD/T2 (TR/TE=2709/20-80) and a turbo-FLAIR (TR/TE/TI=9832/150/2000) sequences were performed.
In order to obtain a dynamic acquisition of cortical activation during complex and acquired motor process, we decided to study our patients with f-MRI. After training, subjects had to oppose the thumb to the other fingers in a sequential task, in a 2, 3, 4, 5 sequence and in a complex, alternating sequence, 1-2, 1-4, 1-3 and 1-5 sequence.
The total acquisition time was equally divided into three-motor task periods, alternated with a three-rest period. Seven images per period were collected; so, in each measurement, 42 images were acquired. The images were oriented transversally. The major parameters of the 2D gradient-echo MR pulse sequence were the following: TR=60 ms, TE=40ms, Flip Angle=25, FOV=160x144 mm2, Slice Thickness=4 mm, Scan Matrix=128x 128. The T1 contrast enhancement option
was activated.15
An MR angiography acquisition was performed per each T1-GRE f-MRI acquisition. The major parameters of the angiographic sequence were the following: TR=shortest, Flip Angle=20, FOV=the same of the T1-gre, Slice Thickness=1 mm, Scan Matrix=256x256, Slices=12, Slice Thickness=1 mm, Phase Contrast Technique.
The image analysis is performed by a program developed in IDL environment (Interactive Data Language, Research System Inc., USA). The basic analysis consists of the calculation of the correlation coefficient be-
tween the time-intensity behavior of each pixel and the square wave model function.
In order to exclude transient hemodynam-ic responses, 5 images per block (from the 3rd to the 7th of each block) are included in the analysis. A raw activation map was obtained by applying a correlation analysis (p<0.001) and a cluster filtering (at least 5 pixels). The raw map was affected by flow artefacts; to eliminate these artefacts, activation map and MR angiography were compared and activation clusters related to the vessels were rejected. Whole-head high-resolution T1-weighted images (TR/TE=500/15) were then acquired to be used as an anatomical reference for the transformations into the Talairach space.16
Results
In seven patients, the morphological examination showed an important, asymmetric perirolandic and postrolandic cortical atrophy (Figure 1) associated to a mild atrophy of the basal ganglia. Subtle MRI T2 hyperin-
Figure 1. Axial SE T2 image: Diffuse brain atrophy particularly marked at the level of the right perirolandic cortex.
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tense lesions in the primary motor cortex, compatible with underlying gliosis, were found in five patients (Figures 2a, 2b), hy-pointensity in the lenticular nuclei in one case only. In one patient the morphological aspect was normal.
During simple motor task carried out with the non-affected hand, we could observe a good activation of the contralateral rolandic cortex, associated with a discrete activation of the supplementary motor area (SMA) and of the parietal regions, as well as with a discrete activation of the right prefrontal region, but without significant difference from those in healthy population.
On the contrary, during a simple task of opposing the fingers executed with the affected hand, an evident hypo-activation of the homolateral and contralateral periro-landic cortex, associated with an evident hypo-activation of the contralateral SMA and with the affected parietal region, was observed. It was significantly different from the healthy control subjects.
During the complex sequence execution by the non-affected hand, an obvious bilateral activation of rolandic areas, of the parietal areas, of the SMA, and of the contralateral frontal region could be seen. These observations are similar to those in healthy controls.
When the complex sequence was executed by the affected hand, the observed activation was limited to the bilateral rolandic region, to SMA, and to a very modest activation of the parietal regions. Quantitatively, hypoactiva-tion was significantly different from that in healthy population.
Qualitatively, the movement of the affected hand was impaired and not fluent at all despite more training exercises. Moreover, it was obvious that the patients had to see the entire procedure when they were performing the exercise with the affected hand. Without receiving the visual input that controlled the motor act the movement was even more impaired.
Radiol Oncol 2002; 36(4): 297-303.
Figure 2a. Slight hyperintensity at the level of the right perirolandic cortex shown on the T2 weighted image.
Figure 2b. Slight hyperintensity at the level of the right perirolandic cortex better shown on the FLAIR image.
Discussion
The patients with progressive focal cortical syndromes are being recognized with increasing frequency. CBGD is a degenerative disor-
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301
der, involving primarily parietal areas, and gradually extending to frontal areas. The patients with CBGD revealed a mild to moderate global deficits including a frontal dysex-ecutive syndrome, explicit learning deficits without retention difficulties and displayed prominent deficits on the tests of sustained attention/mental control and verbal fluen-cy.17
Different neuroimaging studies have been conducted on CBGD, using conventional computed tomography (CT) and magnetic resonance imaging (MRI),4,18 and demonstrating an asymmetric pericentral cortical atrophy in approximately 50% of cases. On the contrary, another recent MRI study, comparing clinically diagnosed cases of CBGD with progressive supranuclear palsy (PSP), found that 87.5% patients with CBGD (but none of the PSP group) had asymmetric fronto-pari-etal atrophy while midbrain atrophy was seen in 6.3% and 89.3% of the same cases respec-tively.18
Another radiological observation4 revealed that pathologically proven PSP, frontal lobe dementia and AD with clinical features of CBGD had similar MRI cortical changes.
The only possible conclusion is that, due to the distribution of pathological changes, the static imaging simply correlates with the predominant clinical presentation and not with the specific underlying pathological substrate.
Functional imaging studies were done with positron emission tomography (PET), but results did not seem to be conclusive.18FDG-PET studies demonstrated a greater heterogeneity of the metabolic patterns including diffuse hypometabolism despite asymmetrical clinical features. F-Dopa PET demonstrated a severe asymmetric reduction in striatal F-Dopa uptake which tended to be equal in putamen and caudate consistent with widespread substantia nigra neuron loss.19 From these studies, the general suggestion is that (18F)-fluorodeoxyglucose (FDG) and (18F)-flu-
oro-dopa (F-Dopa)-PET must be utilized at the same time, in the same patient.19,20
Our study is the first one on f-MRI in CBGD: the most interesting part is the dynamic acquisition which gives information on how the cortex works when the affected arm is moving.
The results obtained from this selected group of eight patients confirmed the results, reported previously.21-25
Our f-MRI evaluation revealed, while the patients executed the simple task of opposing the fingers with the affected hand, a hypo-activation of the homolateral and contralateral perirolandic cortex, associated with an evident hypo-activation of the contralateral SMA and of the affected parietal region. During the complex motor skills with the affected hand, a drastic reduction of activation of premotor and motor areas (perirolandic region) of the contralateral cortex, associated with a very modest activation of the supplementary motor area of the same hemisphere were noted.
It is interesting to see a very modest activation of motor areas, associated with the reduced activity of the parietal area: the latter is largely preventable, but the former is rather unexpected.
The imaging studies on both monkeys and humans report of the activation in the region of the supplementary motor area, globus pal-lidus, and parietal cortex during the performance of sequential movements.26 Neurons of the globus pallidus also discharge during specific phases of a sequential performance.26 This does not involve uniquely motor speed and correct execution, but also attention, coordination and dynamic adjustment to the situation. The hypoactivity of the cortical areas we have reported does match with previous finding.
Nevertheless, there is an unresolved question: our patients indisputably presented with a parietal (postrolandic) atrophy: considering that the parietal damage is the cause, why should the pure motor areas should hy-Radiol Oncol 2002; 36(4): 297-303.
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poactivated? We maintain that the brisk stop due to the disconnection of the parietal cortex and the SMA because of degenerative alteration of parietal areas causes an interruption of the neural net to putamen and pallidus, ending in frontal and prefrontal areas.
Therefore, f-MRI, with its constant demonstration of hypoactivity of motor cortical areas, SMA and parietal areas, while affected arm is moving, might be a valid supportive tool for the diagnosis of CBGD: a positive correlation with hypoactivation of motor areas could be found even in modest, and initial stages of disease.
Having assessed that the accuracy of neurologists’ clinical diagnosis of CBGD is very low, even in specialized centers2 (at first visit mean sensitivity for CBGD 35%, specificity 99.6% and at the last visit mean sensitivity 48.3% while specificity remained stable), then MRI and f-MRI might be suggested as an ad-junctive tool of the diagnosis refinement.
References
1.   Rebeiz JJ, Kolodny EH, Richardson EP. Corticodentatonigral degeneration with neuronal achromasia. Arch Neurol 1968; 18: 20-33.
2.   Litvan I, Agid Y, Goetz C, Jankovic J, Wenning GK, Brandel JP, et al. Accuracy of the clinical diagnosis of corticobasal degeneration: a clinico-pathologic study. Neurology 1997; 48: 119-25.
3.   Lippa CF, Smith TW, Fontneau N. Corticonigral degeneration with neuronal achromasia. J Neurol Sci 1990; 98: 301-10.
4.   Lang A. Cortico-basal ganglionic degeneration. San Diego: American Academy of Neurology; 2000.
5.   Thompson PD, Day BL, Rothwell JC, Brown P, Britton TC, Marsden CD. The myoclonus in corti-cobasal degeneration. Evidence for two forms of cortical reflex myoclonus. Brain 1994; 117: 1197-207.
6.   Litvan I, Grimes DA, Lang AE, Jankovic J, McKee A, Verny M, et al. Clinical features differentiating patients with postmortem confirmed progressive supranuclear palsy and corticobasal degeneration. J Neurol 1999; 246(Suppl 2): 1-5.
7.   Grimes DA, Lang AE, Bergeron C. Dementia is the most common presentation of cortical-basal gan-glionic degeneration. Neurology 1998; 50(Suppl 4): a96.
8.   Hauser R., Murtaugh F, Akhter K, Gold M, Olahow C. Magnetic resonance imaging of corti-cobasal degeneration. J Neuroimaging 1996; 6(4): 222-6.
9.   Otsuki M, Sama Y, Yoshimuro N, Tsuji S. Slowly progressive limb-kinetic apraxia. Eur Neurol 1997; 37(2): 100-3.
10. Tokumaru AM, O’uchi T, Kuru Y, Maki T, Murayama S, Horichi Y. Corticobasal degeneration: MR with histopathologic comparison. ASNR 1996; 17(10): 1849-52.
11. Briggs GC, Nebes RD. Patterns of hand preference in a student population. Cortex 1975; 11: 230-8.
12. Raven JC. Standard progressive matrices. London: Lewis; 1938.
13. Wechsler D. Wechsler adult intelligence scale manual. New York: Grune & Stratton; 1976.
14. Wechsler D. A standardized memory scale for clinical use. J Psychol 1945; 19: 87-97.
15. Sobol WT, Gauntt DM. On the stationary states in gradient echo imaging. J Magn Reson Imaging 1996; 6: 384-98.
16. Talairach J, Tornoux P. Co-planar stereotaxic atlas of the human brain. Thieme: Stuttgart; 1988.
17. Kertesz A, Munoz DG. Clinical and pathological overlap between frontal dementia, progressive aphasia and corticobasal degeneration - the Pick complex. Neurology 1997; 48: 293-300.
18. Gimenez-Roldan S, Mateo D, Benito C, Grandas F, Perez-Gilabert Y. Progressive supranuclear palsy and corticobasal ganglionic degeneration: differentiation by clinical features and neuroimaging techniques. J Neural Transm 1994; 98(Suppl 42): 79-90.
19. Brooks DJ. Pet studies on the early and differential diagnosis of Parkinson’s disease. Neurology 1993; 43(Suppl 6): S6-16.
20. Eidelberg D. Differential diagnosis of parkinson-ism with (18-f)fluorodeoxyglucose FDG and PET. [abstract]. Mov Disord 1996; 11: 349.
21. Moretti R, Ukmar M, Torre P, Antonello RM, Longo R, Nasuelli D, et al. Cortical-basal ganglion-ic degeneration: a clinical, functional and cognitive evaluation (1-year follow-up). J Neurolog Sci 2000; 182: 29-35.
Radiol Oncol 2002; 36(4): 297-303.
Ukmar M et al / Cortical-basal ganglionic degeneration
22. Moretti R, Torre P, Antonello RM, Ukmar M, Cazzato G, Bava A. Valutazione con risonanza magnetica funzionale dell’attivazione corticale durante compiti motori fini in soggetti con degenerazione cortico-basale. Nuova Rivista di Neurologia 2001; 11(3): 73-9.
23. Moretti R, Torre P, Antonello RM, Bava A. Deterioramento cognitivo nella sindrome cortico-basale. Dementia Update 2002; 11: 49-52.
24. Moretti R, Torre P, Antonello RM, Ukmar M, Longo R, Cazzato G, et al. Complex distal movement in cortico-basal ganglionic degeneration. A functional evaluation. Funct Neurol 2002; 17(2): 71-6.
25. Jeannerod M, Arbib MA, Rizzolatti G, Sakata H. Grasping objects: the cortical mechanisms of vi-suomotor transformation. A review. Trends Neurosci 1995; 18: 314-20.
26. Lu MT, Preston JB, Strick PL. Interconnections between the prefrontal cortex and the premotor areas in the frontal lobe J Comp Neurol 1994; 341: 375-92.
Radiol Oncol 2002; 36(4): 297-303.