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Single photon emission computed tomography in Huntington's chorea
Psychiatry Research, 29 : 3 3 7-339 Elsevier
337
Single Photon Emission Computed Tomography in Huntington's Chorea F . Leblhuber, K . Hoell, F . Reisecker, B . Gebetsberger, W . Puehringer, E . Trenkler, and E . Deisenhammer
Huntington's chorea (HC) is a common autosomal dominant neurodegenerativc disorder with typical symptoms including involuntary movements and psychiatric disorders with progressive dementia and deterioration . Positron emission tomography (PET) studies have already shown reduced glucose metabolism in the caudate nuclei of symptomatic HC patients and similar, less severe reduction in glucose metabolism of caudates in some subjects at risk for the disease (Mazziotta et al ., 1987) . Since changes in the cerebral blood flow pattern may precede structural loss shown by conventional X-ray computed tomography (CT) scan, single photon emission computed tomography (SPECT) studies may he a sensitive marker of functional decline of the caudates in HC patients and at-risk subjects . Ten clinically affected patients (6 men, 4 women, aged 33-60 years) who met criteria for definitive HC (family history of at least one other member affected with typical symptoms of HC, dementia, impairment of voluntary movements, and chorea) and nine at-risk subjects (3 men, 6 women, aged 14-37 years) with a positive family history were studied . All patients had detailed neurological examinations and were staged according to the Functional Capacity Scale (Shoulson and Fahn, 1979) (Table 1) . Ten age-matched subjects served as a control group . SPECT was performed an a dual-head Rota camera (Siemens ZLC 37) . N-isopropyl-( 123 1)p-iodoamphetamine (IMP) was used as tracer (5 mCi) . After scatter correction, prereconstructional noise suppression, and attenuation correction, reconstruction resulted in eight final 12 .5-mm-thick axial slices . For semiquantitative estimation of tracer uptake, the count rate in each pixel was divided by the mean count rate of the contralateral gray matter . Focal decrease of tracer uptake was operationally declared as abnormal it exceeded 2 SD compared to the reference (corresponding ipsilateral or contralateral compartment) (Deisenhammer and Hoell, 1988) . X-ray CT was performed on a Siemens DRH system . Diffuse cerebral atrophy and bilateral atrophy of the caudate were found with CT in seven of the clinically affected patients . Normal findings without any structural loss of the caudate were seen in three of the clinically less severely affected patients (#6, #8, and #9 in Table 1) as well as in all at-risk subjects (see Fig . I) . Clearly reduced tracer uptake of caudate nuclei or no uptake at all was seen in all of the clinically affected patients, including the three cases with normal CT findings, and in two of the at-risk subjects (see Fig . 1) . In addition, clinically affected patients showed
Reprint requests to: Friedrich Lehlhuber, M .D., Dept, of Neurophysiology, Wagner-Jauregg-Krankenhaus, A-4020 l .inz, Austria. 0165-1781/89/$03 .50 0 1989 Elsevier Scientific Publishers Ireland Ltd .
338 Table 1 . Clinical information for patients with Huntington's disease Duration of Functional Case Age Sex symptoms capacity (0-13) 1
60
M
10
7
2
40
M
5
2
3
37
M
5
8
4
42
M
10
0
5
55
M
3
9
6 7
39
M F
4 4
10 6
8
42 35
F F
5 3
11
9 10
45
F
5
3
33
9
Fig . 1 . SPECT scans in Huntington's disease
Slices are 12 .5 mm thick at a level approximately 40 mm above the canthomeatal line and display the main parts of basal ganglia: (a) control subject has caudate and thalamus clearly visible ; (b) subject at risk (age 14, female) has similar although less severe reduction in caudate tracer uptake than that seen in symptomatic Huntington s patent (c) patient 5 in Table 1 shows caudate still visible . CT shows mild atrophic changes with increased intercaudate distance .
339
a focal pattern of SPECT abnormalities analogous to atrophic changes seen on CT . In clinically affected HC patients, CT abnormalities including atrophy of the caudate, are described, but normal CT findings may be seen in clinically affected patients as well, especially in the earlier course of the disease . PET imaging in symptomatic HC patients demonstrated alterations of glucose metabolism preceding gross structural loss of the basal ganglia (Kuhl et al ., 1982), and subjects at risk for HC were described as having similar though less severe reductions in caudate glucose metabolism (Mazziotta et al ., 1987), but these observations were questioned by others (Young et al ., 1987) . Similar to these PET findings, SPECT studies have also shown brain functional loss without any measurable morphologic abnormalities (Ell et al ., 1987 ; Jagust et al ., 1987). In our IMP-SPECT studies, there was visually apparent reduced tracer uptake in the caudate nuclei in all symptomatic subjects as compared to controls, even in cases with normal CT measures ; a similar pattern of reduced tracer uptake was seen in two of our individuals at risk, suggesting an additional marker in identifying potential carriers of the HC gene (Leblhuber et al ., 1987), but these preliminary findings should be interpreted cautiously ; since the caudate nucleus is a fairly small structure, further investigations and followup studies are needed .
References Dcisenhammer, E ., and Hoell, K . Die dreidimensionale Szinligraphie des Gehirns : SinglePhoton-Emission-Computer-Tomographie (SPECT) . Wiener Klinische Wochenschrift,
100 :392, 1988 . Ell, P .J . ; Costa, D .C . ; and Harrison, M . Imaging cerebral damage in HIV infection, laneet .
569, 1987. Jagust, W .J . ; Budinger, T .F. ; and Reed, B .R . The diagnosis of dementia with single photon emission computed tomography. Archives of Neurology, 44 :258, 1987 . Kuhl, D .E . ; Phelps, M .E . ; Markham, C .H . ; Metter, E .J . ; Riege, W .H . ; and Winter, J . Cerebral metabolism and atrophy in Huntington's disease determined by '8FDG and computed tomographic scan . Annals of Neurology, 12 :425, 1982 . Leblhuber, F . ; Hoell, K . ; Gebetsberger, B.; Puehringer, W, ; and Deisenhammer, F . Long latency responses (I,LRs) and IMP-SPECT findings in early detection of Huntington's chorea (HC). Electroencephography and Clinical Neurophysiology, 66 :59, 1987 . Mazziotta, J .C . ; Phelps, M .E . ; Pahl, JJ . ; Huang, S .-C . ; Baxter, L .R . ; Riege, W .H . ; Hoffman, J .M . ; Kuhl, D .E . ; Lanto, A .B . ; Wapenski, J .A . ; and Markham, C .H . Reduced cerebral glucose metabolism in asymptomatic subjects at risk for Huntington's disease . New
England Journal of Medicine, 316 :357, 1987 . Shoulson L, and Fahn S . Huntington disease : Clinical care and evaluation . Neurology,
29 :1, 1979 . Young, A .B . ; Penney, J .B . ; Starosta-Rubinstein, S . ; Merkel, D . ; Berent, S . ; Rothley, J . ; Betley, A . ; and Hichwa, R . Normal caudate glucose metabolism in persons at risk for Huntington's disease . Archives of Neurology, 44 :254, 1987 .
337
Single Photon Emission Computed Tomography in Huntington's Chorea F . Leblhuber, K . Hoell, F . Reisecker, B . Gebetsberger, W . Puehringer, E . Trenkler, and E . Deisenhammer
Huntington's chorea (HC) is a common autosomal dominant neurodegenerativc disorder with typical symptoms including involuntary movements and psychiatric disorders with progressive dementia and deterioration . Positron emission tomography (PET) studies have already shown reduced glucose metabolism in the caudate nuclei of symptomatic HC patients and similar, less severe reduction in glucose metabolism of caudates in some subjects at risk for the disease (Mazziotta et al ., 1987) . Since changes in the cerebral blood flow pattern may precede structural loss shown by conventional X-ray computed tomography (CT) scan, single photon emission computed tomography (SPECT) studies may he a sensitive marker of functional decline of the caudates in HC patients and at-risk subjects . Ten clinically affected patients (6 men, 4 women, aged 33-60 years) who met criteria for definitive HC (family history of at least one other member affected with typical symptoms of HC, dementia, impairment of voluntary movements, and chorea) and nine at-risk subjects (3 men, 6 women, aged 14-37 years) with a positive family history were studied . All patients had detailed neurological examinations and were staged according to the Functional Capacity Scale (Shoulson and Fahn, 1979) (Table 1) . Ten age-matched subjects served as a control group . SPECT was performed an a dual-head Rota camera (Siemens ZLC 37) . N-isopropyl-( 123 1)p-iodoamphetamine (IMP) was used as tracer (5 mCi) . After scatter correction, prereconstructional noise suppression, and attenuation correction, reconstruction resulted in eight final 12 .5-mm-thick axial slices . For semiquantitative estimation of tracer uptake, the count rate in each pixel was divided by the mean count rate of the contralateral gray matter . Focal decrease of tracer uptake was operationally declared as abnormal it exceeded 2 SD compared to the reference (corresponding ipsilateral or contralateral compartment) (Deisenhammer and Hoell, 1988) . X-ray CT was performed on a Siemens DRH system . Diffuse cerebral atrophy and bilateral atrophy of the caudate were found with CT in seven of the clinically affected patients . Normal findings without any structural loss of the caudate were seen in three of the clinically less severely affected patients (#6, #8, and #9 in Table 1) as well as in all at-risk subjects (see Fig . I) . Clearly reduced tracer uptake of caudate nuclei or no uptake at all was seen in all of the clinically affected patients, including the three cases with normal CT findings, and in two of the at-risk subjects (see Fig . 1) . In addition, clinically affected patients showed
Reprint requests to: Friedrich Lehlhuber, M .D., Dept, of Neurophysiology, Wagner-Jauregg-Krankenhaus, A-4020 l .inz, Austria. 0165-1781/89/$03 .50 0 1989 Elsevier Scientific Publishers Ireland Ltd .
338 Table 1 . Clinical information for patients with Huntington's disease Duration of Functional Case Age Sex symptoms capacity (0-13) 1
60
M
10
7
2
40
M
5
2
3
37
M
5
8
4
42
M
10
0
5
55
M
3
9
6 7
39
M F
4 4
10 6
8
42 35
F F
5 3
11
9 10
45
F
5
3
33
9
Fig . 1 . SPECT scans in Huntington's disease
Slices are 12 .5 mm thick at a level approximately 40 mm above the canthomeatal line and display the main parts of basal ganglia: (a) control subject has caudate and thalamus clearly visible ; (b) subject at risk (age 14, female) has similar although less severe reduction in caudate tracer uptake than that seen in symptomatic Huntington s patent (c) patient 5 in Table 1 shows caudate still visible . CT shows mild atrophic changes with increased intercaudate distance .
339
a focal pattern of SPECT abnormalities analogous to atrophic changes seen on CT . In clinically affected HC patients, CT abnormalities including atrophy of the caudate, are described, but normal CT findings may be seen in clinically affected patients as well, especially in the earlier course of the disease . PET imaging in symptomatic HC patients demonstrated alterations of glucose metabolism preceding gross structural loss of the basal ganglia (Kuhl et al ., 1982), and subjects at risk for HC were described as having similar though less severe reductions in caudate glucose metabolism (Mazziotta et al ., 1987), but these observations were questioned by others (Young et al ., 1987) . Similar to these PET findings, SPECT studies have also shown brain functional loss without any measurable morphologic abnormalities (Ell et al ., 1987 ; Jagust et al ., 1987). In our IMP-SPECT studies, there was visually apparent reduced tracer uptake in the caudate nuclei in all symptomatic subjects as compared to controls, even in cases with normal CT measures ; a similar pattern of reduced tracer uptake was seen in two of our individuals at risk, suggesting an additional marker in identifying potential carriers of the HC gene (Leblhuber et al ., 1987), but these preliminary findings should be interpreted cautiously ; since the caudate nucleus is a fairly small structure, further investigations and followup studies are needed .
References Dcisenhammer, E ., and Hoell, K . Die dreidimensionale Szinligraphie des Gehirns : SinglePhoton-Emission-Computer-Tomographie (SPECT) . Wiener Klinische Wochenschrift,
100 :392, 1988 . Ell, P .J . ; Costa, D .C . ; and Harrison, M . Imaging cerebral damage in HIV infection, laneet .
569, 1987. Jagust, W .J . ; Budinger, T .F. ; and Reed, B .R . The diagnosis of dementia with single photon emission computed tomography. Archives of Neurology, 44 :258, 1987 . Kuhl, D .E . ; Phelps, M .E . ; Markham, C .H . ; Metter, E .J . ; Riege, W .H . ; and Winter, J . Cerebral metabolism and atrophy in Huntington's disease determined by '8FDG and computed tomographic scan . Annals of Neurology, 12 :425, 1982 . Leblhuber, F . ; Hoell, K . ; Gebetsberger, B.; Puehringer, W, ; and Deisenhammer, F . Long latency responses (I,LRs) and IMP-SPECT findings in early detection of Huntington's chorea (HC). Electroencephography and Clinical Neurophysiology, 66 :59, 1987 . Mazziotta, J .C . ; Phelps, M .E . ; Pahl, JJ . ; Huang, S .-C . ; Baxter, L .R . ; Riege, W .H . ; Hoffman, J .M . ; Kuhl, D .E . ; Lanto, A .B . ; Wapenski, J .A . ; and Markham, C .H . Reduced cerebral glucose metabolism in asymptomatic subjects at risk for Huntington's disease . New
England Journal of Medicine, 316 :357, 1987 . Shoulson L, and Fahn S . Huntington disease : Clinical care and evaluation . Neurology,
29 :1, 1979 . Young, A .B . ; Penney, J .B . ; Starosta-Rubinstein, S . ; Merkel, D . ; Berent, S . ; Rothley, J . ; Betley, A . ; and Hichwa, R . Normal caudate glucose metabolism in persons at risk for Huntington's disease . Archives of Neurology, 44 :254, 1987 .