682
Correspondence
BIOL PSYCHIATRY 1990;27:671-685
our laboratory, results were inconsistent. As the shipment had taken 6 days to reach New Orleans, rather than the usual 2 days required for frozen samples, we feared that sample warming may have biased the results. To check on this possibility, we allowed aliquots of our own serum samples that had previously yielded consistent results to warm to room temperature for 36 hr. After refreezing and thawing, they were tested and gave variable results similar to those of the New Zealand samples. We therefore considered the test inadequate and so informed Knight.
Basal Ganglia Calcification in Schizophrenia To the Editor: In a preliminary review of CT scans of 45 (DSMHI) schizophrenic patients, large bilateral calcifications of the globus pallidus were seen in 3 patients, whereas a fourth showed a small calcification in the right globus pallidus only. The frequency of this finding (6.6% if one "counts" the first 3 patients only, and 8.8% if all 4 are included) is far in excess of the rate of basal ganglia calcification observed in large prior series of CT scans that were unselected for diagnosis (Table 1). In these reports basal ganglia calcification was seen most frequently in patients over 60 years old, wherees the oldest of our schizophrenic patients with calcification was 53. Similarly, Stevens (1982) encountered mineralization of the globus pallidus in a neuropathological study of schizophrenia and commented that this "occurred in two schizophrenics under age 35 and no young control subjects."
Robert G. Heath Katherine L. Mc Carron Carol E. O'NeU
Tulane University Medical Center Department of Psychiatry and Neurology School of Medicine 1430 Tulane Ave. New Orleans, LA 70112-2699
Regarding possible etiologies for this timing: (1) None of these patients had abnormal serum calcium or inorganic phosphate levels (These tes!~, however, were done as routine chemistries before CT scan resuits were known, and not as part of a work-up for basal ganglia calcification. Thus, blood was not drawn under conditions of restricted dietary calcium; urine calcium and phosphate were not measured; and parathommne levels were not studied.) (2) One patient (who had the small, unilateral calcification) had hyperthyroidism that had been treated medically, but he had not had thyroid surgery. None of the remaining 3 patients had had thyroid disease or surgery. (3) None had had radiotherapy or chemotherapy. (4) None knew of having had childhood encephalitis or other infectious CNS disease in childhood. (5) None had histories of significant head trauma. (6) None knew whether or not they had had unusually difficult births. (7) None knew of exposure to high levels of carbon monoxide (i.e., suicide attempts with CO). We speculated that pcfinatal or childhood CNS
Table 1. Frequency of Basal Ganglia Calcification Noted in Large Series of CT Scans No. of CT SCanS
Reference
examined
Cohen et al. 1978 Keller et al. D79 Sachs et al. 1979 Goldscheider et al. 1980
5000 4219 3800 8000
Present report
45
No. of cases of basas ganglia calcification found 32 (25 in patients over 60 yrs.) 14 (7 in patients over 60 yrs.) 14 (7 in patients over 60 yrs.) 19 (12 in patients over 50 yrs., individual ages not given) 3-4
% 0.60% 0.32% 0.40% 0.24% 6.6%-8.8%
Diagnosis
P
Undifferentiated 1 Paranoid 2 Paranoid 3 Mean 4- SD: 3 patients with bilateral calcifications Mean 4- SD: patients without calcifications Chi-Squared (Discriminant).
Patient No.
8.3 4- 5.1 NS
35.4 --. 8.5 272.8 (50 years) 0.0001
12 4 4 6.7 4- 4.6
NS
10.1 4- 5.1
20 8 2 10.0 4- 9.2
Childhood Adolescence
Premorbid adjustment
53 48 51 50.7 ± 2.5
Age (years)
NS
3.4 4- 2.7
5 2 15 7.3 - 6.8
Soft signs
42.6 4- 10.4
39 38 28 35.0 ± 6.1
BPRS pretreatment
37.7 - 7.4
39 45 28 37.3 --. 8.6
BPRS posttreatment
6.24 ( - 2 0 % change) 0.013
- 4 . 8 4- 7.8
0 7 0 2.3 4- 4.0
Change with treatment
Table 2. Clinical Characteristics o f Schizophrenic Patients with Bilateral Globus Pallidus Calcification Versus Remainder o f Sample
t~
oo
O~
1
684
eIOL PSYCHIATRY
Correspondence
1990;27:671-685
Table 3. Radiologic Characteristics of CT Scans of Schizophrenic Patients with Bilateral Globus Pallidus Calcifications Versus the Remainder of the Sample
Patient No. 1 2 3 Mean _ so: 3 patients with bilateral calcifications Mean ~ sD: patients without calcifications Chi-squared (discriminant) p
Width 3rd ventricle (nun)
Frontal horn/brain diameter
2.90 1.75 3.00 2.55 -- 0.70
0.33 0.3 0.35 0.33 _ 0.03
0.0045 0.0045 0.0075 0.0055 .4- 0.0002
0.122 0.059 0.115 0.099 .4- 0,034
1.35 .4- 0.68
0.31 .4- 0.04
0.0037 .4- 0.0022
0.087 .4- 0.032
5.88 (1~35) 0.02
6.24 (0.31) 0.01
3.56 (0.0037) 0.06
injury might lead to abnormal premorbid adjustment and increased neurological soft signs. These and other clinical data for the 3 patients with large bilateral calcifications versus the remainder of the schizophrenic sample (without calcification) are shown in Table 2. Neither worse premorbid adjustment (Cannon-Spoor et al. 1982), nor soft signs (Quitkin et al. 1976) was more frequent in the group with calcification (in X2 analyses in which the discriminant "cutoff,' was the mean for the group without intracerebral calcification). On the other hand the patients with calcification were older (in a X2 analysis with a discriminator of 50 years) and were less neurolepticresponsive (in X2 analysis using the response discriminator of 20% BPRS decrement proposed by Kane et al. 1988). No patient with bilateral calcification improved after neuroleptics. We also examined other CT measures; these data are shown in Table 3. Patients with basal ganglia calcification had larger third ventricle widths than those without (X2 analysis using the mean of the noncalcified group as the"cm-off'). Two of the 3 patients with bilateral calcification (#1 and #3) had third ventricle widths more than 2 SD from the mean for the schizophrenic group as a whole. The linear frontal hem VBR (maximum linear measure across the tips of the fmutal horns/linear measure of the brain at the same location and slice) was also larger in the patients with calcifications (X2 analysis with the mean for the noncalcified group as the discriminant "cut-off'.'). Similar analysis showed a trend for the area of the third ventricle divided by the brain area of the same slice (as measured on a digitizer pad) to be larger in the group with bilateral calcification. The standard
Third ventricle area brain area
Area lateral ventricles/brain area
NS
(lateral ventricle) VBR, however, was not more fiequently enlarged in the calcified group. Patient #3 also had the largest sulci in the entire schizophrenic sample. Thus in this sample, patients with basal ganglia calcification tended to be older, less neuroleptic responsive, and to have more structural brain abnormalities. In the absence of any obvious etiology for the calcification and its increased occurrence in our patient group, we wonder if this finding is associated with schizophrenia per se, or part of the notorious heterogeneity of this disorder. Schizophrenia-like psychoses are stated to occur in up to 50% of patients with idiopathic calcification of the basal ganglia (Davidson 1987). Other diseases affecting the basal ganglia, such as postencephalitic parkinsonism and Huntington's disease, are also associated with a prevalence of schizophrenia-like psychoses that far exceeds that of the general population (Davison 1987). This relationship led Cummings et al. (1983) to suggest that "(t)he occurrence of schizophrenia-like psychoses in subcortical disorder may thus provide a heuristic link between the idiopathic and the symptomatic schizophrenias and present an important avenue for investigating the psychobiology of schizophrenic psychoses." We would be much interested to know if investigators who have studied CT scans in schizophrenia have observed similar findings. This study was supported by the Veterans Administration and was approved by the Subcommitteefor Human Subjects at the New York Veterans AdministrationMedical Center.
BIOL PSYCHIATRY
Correspondence
1990;27:671-685
Antonio Fernandez-Bouzas ~ Burr Angrist 2 Paula Hemdal 2 Lenard A. Adler 2 John Rotrosen 2
'Department of Neurology Hospital 20 de Novemb~, l SSSTE Mexico City, Mexico 2Psychiatry Service II6A VA Medical Center First Avenue and East 24th Street New York, NY 10010
References Cannon-Spoo: HE, Potkin $G, Wyatt RJ (1982): Measurement of premorbid adjustment in chronic schizophrenia: Schizophrenia Bull 8:470-474. Cohen CR, Duchesneau PM, Weinstein MA (1978): Calcification of the basal ganglia as visualized by computed tomography. Radiology 134:97-99. Cummings JL, Gosenfeld LF, Houl.:,han JP, McCaffrey T (1983): Neuropsychiatric disturbances associated with ide~oathic calcification of the basal ganglia. Biol Psyche,airy 18:591-601.
685
Davison K (1987): Organic and toxic concomitants of schizophrenia: association or chance. In Helmchen H, Henn F (eds)~Biological Perspectives of Schizophrenia. Chichester, New York, Brisbane, Toronto, Singapore: John Wiley and Sons, Ltd., pp. 139-160. Gold.~heider HG, Lischewski R, Claus D, Streibl W, WaibEnger G 0.980): Klnische, endokrinologische, und computertomorgraphische ~-.,te~sachungen zur symmetrischen st.~n~ngangieveraUmng(M. Fahr). Arch Psychiat Nervenl~o 228:53-65. Kane J, Honigfeld G, Singer J, Meltzer H, and the Clozaril Collaborative Study Group (1988): Clozapine for the ~eaunent-resistant scb~zopb_renic.Arch Gen Psychiatry 45:789-796. Koller WC, Cochran ~1~',Klawans HL (1979): Calcification of the basal ganglia: computerized tomography and clinical correlation. Neurology 29:328-333. Quitkin F, Rifkin A, Klein DF (1976): Neumlogic soft signs in schizophrenia and character disorders, orgs.,ficity in schizophrenia with premorbid asociality and emotionally unstablecharacterdisorders. Arch Gen Psychiatry 33:845853. Sachs C, Ericson K, Erasmie U, Bergstrom M (1979): Incidence of basal ganglia calcifications on computed tomography. J Comput Assist 7omogr 3:339-344. Stevens JR (1982): Neuropathology of schizophrenia. Arch Gen Psychiatry 39:1131-1139.
Correspondence
BIOL PSYCHIATRY 1990;27:671-685
our laboratory, results were inconsistent. As the shipment had taken 6 days to reach New Orleans, rather than the usual 2 days required for frozen samples, we feared that sample warming may have biased the results. To check on this possibility, we allowed aliquots of our own serum samples that had previously yielded consistent results to warm to room temperature for 36 hr. After refreezing and thawing, they were tested and gave variable results similar to those of the New Zealand samples. We therefore considered the test inadequate and so informed Knight.
Basal Ganglia Calcification in Schizophrenia To the Editor: In a preliminary review of CT scans of 45 (DSMHI) schizophrenic patients, large bilateral calcifications of the globus pallidus were seen in 3 patients, whereas a fourth showed a small calcification in the right globus pallidus only. The frequency of this finding (6.6% if one "counts" the first 3 patients only, and 8.8% if all 4 are included) is far in excess of the rate of basal ganglia calcification observed in large prior series of CT scans that were unselected for diagnosis (Table 1). In these reports basal ganglia calcification was seen most frequently in patients over 60 years old, wherees the oldest of our schizophrenic patients with calcification was 53. Similarly, Stevens (1982) encountered mineralization of the globus pallidus in a neuropathological study of schizophrenia and commented that this "occurred in two schizophrenics under age 35 and no young control subjects."
Robert G. Heath Katherine L. Mc Carron Carol E. O'NeU
Tulane University Medical Center Department of Psychiatry and Neurology School of Medicine 1430 Tulane Ave. New Orleans, LA 70112-2699
Regarding possible etiologies for this timing: (1) None of these patients had abnormal serum calcium or inorganic phosphate levels (These tes!~, however, were done as routine chemistries before CT scan resuits were known, and not as part of a work-up for basal ganglia calcification. Thus, blood was not drawn under conditions of restricted dietary calcium; urine calcium and phosphate were not measured; and parathommne levels were not studied.) (2) One patient (who had the small, unilateral calcification) had hyperthyroidism that had been treated medically, but he had not had thyroid surgery. None of the remaining 3 patients had had thyroid disease or surgery. (3) None had had radiotherapy or chemotherapy. (4) None knew of having had childhood encephalitis or other infectious CNS disease in childhood. (5) None had histories of significant head trauma. (6) None knew whether or not they had had unusually difficult births. (7) None knew of exposure to high levels of carbon monoxide (i.e., suicide attempts with CO). We speculated that pcfinatal or childhood CNS
Table 1. Frequency of Basal Ganglia Calcification Noted in Large Series of CT Scans No. of CT SCanS
Reference
examined
Cohen et al. 1978 Keller et al. D79 Sachs et al. 1979 Goldscheider et al. 1980
5000 4219 3800 8000
Present report
45
No. of cases of basas ganglia calcification found 32 (25 in patients over 60 yrs.) 14 (7 in patients over 60 yrs.) 14 (7 in patients over 60 yrs.) 19 (12 in patients over 50 yrs., individual ages not given) 3-4
% 0.60% 0.32% 0.40% 0.24% 6.6%-8.8%
Diagnosis
P
Undifferentiated 1 Paranoid 2 Paranoid 3 Mean 4- SD: 3 patients with bilateral calcifications Mean 4- SD: patients without calcifications Chi-Squared (Discriminant).
Patient No.
8.3 4- 5.1 NS
35.4 --. 8.5 272.8 (50 years) 0.0001
12 4 4 6.7 4- 4.6
NS
10.1 4- 5.1
20 8 2 10.0 4- 9.2
Childhood Adolescence
Premorbid adjustment
53 48 51 50.7 ± 2.5
Age (years)
NS
3.4 4- 2.7
5 2 15 7.3 - 6.8
Soft signs
42.6 4- 10.4
39 38 28 35.0 ± 6.1
BPRS pretreatment
37.7 - 7.4
39 45 28 37.3 --. 8.6
BPRS posttreatment
6.24 ( - 2 0 % change) 0.013
- 4 . 8 4- 7.8
0 7 0 2.3 4- 4.0
Change with treatment
Table 2. Clinical Characteristics o f Schizophrenic Patients with Bilateral Globus Pallidus Calcification Versus Remainder o f Sample
t~
oo
O~
1
684
eIOL PSYCHIATRY
Correspondence
1990;27:671-685
Table 3. Radiologic Characteristics of CT Scans of Schizophrenic Patients with Bilateral Globus Pallidus Calcifications Versus the Remainder of the Sample
Patient No. 1 2 3 Mean _ so: 3 patients with bilateral calcifications Mean ~ sD: patients without calcifications Chi-squared (discriminant) p
Width 3rd ventricle (nun)
Frontal horn/brain diameter
2.90 1.75 3.00 2.55 -- 0.70
0.33 0.3 0.35 0.33 _ 0.03
0.0045 0.0045 0.0075 0.0055 .4- 0.0002
0.122 0.059 0.115 0.099 .4- 0,034
1.35 .4- 0.68
0.31 .4- 0.04
0.0037 .4- 0.0022
0.087 .4- 0.032
5.88 (1~35) 0.02
6.24 (0.31) 0.01
3.56 (0.0037) 0.06
injury might lead to abnormal premorbid adjustment and increased neurological soft signs. These and other clinical data for the 3 patients with large bilateral calcifications versus the remainder of the schizophrenic sample (without calcification) are shown in Table 2. Neither worse premorbid adjustment (Cannon-Spoor et al. 1982), nor soft signs (Quitkin et al. 1976) was more frequent in the group with calcification (in X2 analyses in which the discriminant "cutoff,' was the mean for the group without intracerebral calcification). On the other hand the patients with calcification were older (in a X2 analysis with a discriminator of 50 years) and were less neurolepticresponsive (in X2 analysis using the response discriminator of 20% BPRS decrement proposed by Kane et al. 1988). No patient with bilateral calcification improved after neuroleptics. We also examined other CT measures; these data are shown in Table 3. Patients with basal ganglia calcification had larger third ventricle widths than those without (X2 analysis using the mean of the noncalcified group as the"cm-off'). Two of the 3 patients with bilateral calcification (#1 and #3) had third ventricle widths more than 2 SD from the mean for the schizophrenic group as a whole. The linear frontal hem VBR (maximum linear measure across the tips of the fmutal horns/linear measure of the brain at the same location and slice) was also larger in the patients with calcifications (X2 analysis with the mean for the noncalcified group as the discriminant "cut-off'.'). Similar analysis showed a trend for the area of the third ventricle divided by the brain area of the same slice (as measured on a digitizer pad) to be larger in the group with bilateral calcification. The standard
Third ventricle area brain area
Area lateral ventricles/brain area
NS
(lateral ventricle) VBR, however, was not more fiequently enlarged in the calcified group. Patient #3 also had the largest sulci in the entire schizophrenic sample. Thus in this sample, patients with basal ganglia calcification tended to be older, less neuroleptic responsive, and to have more structural brain abnormalities. In the absence of any obvious etiology for the calcification and its increased occurrence in our patient group, we wonder if this finding is associated with schizophrenia per se, or part of the notorious heterogeneity of this disorder. Schizophrenia-like psychoses are stated to occur in up to 50% of patients with idiopathic calcification of the basal ganglia (Davidson 1987). Other diseases affecting the basal ganglia, such as postencephalitic parkinsonism and Huntington's disease, are also associated with a prevalence of schizophrenia-like psychoses that far exceeds that of the general population (Davison 1987). This relationship led Cummings et al. (1983) to suggest that "(t)he occurrence of schizophrenia-like psychoses in subcortical disorder may thus provide a heuristic link between the idiopathic and the symptomatic schizophrenias and present an important avenue for investigating the psychobiology of schizophrenic psychoses." We would be much interested to know if investigators who have studied CT scans in schizophrenia have observed similar findings. This study was supported by the Veterans Administration and was approved by the Subcommitteefor Human Subjects at the New York Veterans AdministrationMedical Center.
BIOL PSYCHIATRY
Correspondence
1990;27:671-685
Antonio Fernandez-Bouzas ~ Burr Angrist 2 Paula Hemdal 2 Lenard A. Adler 2 John Rotrosen 2
'Department of Neurology Hospital 20 de Novemb~, l SSSTE Mexico City, Mexico 2Psychiatry Service II6A VA Medical Center First Avenue and East 24th Street New York, NY 10010
References Cannon-Spoo: HE, Potkin $G, Wyatt RJ (1982): Measurement of premorbid adjustment in chronic schizophrenia: Schizophrenia Bull 8:470-474. Cohen CR, Duchesneau PM, Weinstein MA (1978): Calcification of the basal ganglia as visualized by computed tomography. Radiology 134:97-99. Cummings JL, Gosenfeld LF, Houl.:,han JP, McCaffrey T (1983): Neuropsychiatric disturbances associated with ide~oathic calcification of the basal ganglia. Biol Psyche,airy 18:591-601.
685
Davison K (1987): Organic and toxic concomitants of schizophrenia: association or chance. In Helmchen H, Henn F (eds)~Biological Perspectives of Schizophrenia. Chichester, New York, Brisbane, Toronto, Singapore: John Wiley and Sons, Ltd., pp. 139-160. Gold.~heider HG, Lischewski R, Claus D, Streibl W, WaibEnger G 0.980): Klnische, endokrinologische, und computertomorgraphische ~-.,te~sachungen zur symmetrischen st.~n~ngangieveraUmng(M. Fahr). Arch Psychiat Nervenl~o 228:53-65. Kane J, Honigfeld G, Singer J, Meltzer H, and the Clozaril Collaborative Study Group (1988): Clozapine for the ~eaunent-resistant scb~zopb_renic.Arch Gen Psychiatry 45:789-796. Koller WC, Cochran ~1~',Klawans HL (1979): Calcification of the basal ganglia: computerized tomography and clinical correlation. Neurology 29:328-333. Quitkin F, Rifkin A, Klein DF (1976): Neumlogic soft signs in schizophrenia and character disorders, orgs.,ficity in schizophrenia with premorbid asociality and emotionally unstablecharacterdisorders. Arch Gen Psychiatry 33:845853. Sachs C, Ericson K, Erasmie U, Bergstrom M (1979): Incidence of basal ganglia calcifications on computed tomography. J Comput Assist 7omogr 3:339-344. Stevens JR (1982): Neuropathology of schizophrenia. Arch Gen Psychiatry 39:1131-1139.
