International Journal of Psychiatry in Clinical Practice, 2005; 9(4): 238 /243
ORIGINAL ARTICLE
Dyskinesia and soft neurological signs in schizophrenia: a comparative study
CIGDEM AYDEMIR, EROL GOKA, CEBRAIL KISA, AYDIN KURT & FATIH VOLKAN YUKSEL Psychiatry Department, Ankara Numune Hospital, Ankara, Turkey
Abstract Objective. Several neurological abnormalities can be found at a greater frequency in patients with schizophrenia, including neurological soft signs (NSS) and signs of the ‘‘pyramidal’’ and ‘‘extrapyramidal’’ systems. We aimed to explore the frequency of movement disorders in patients with antipsychotic naı¨ve schizophrenia and to compare and contrast with antipsychotic-treated patients and healthy controls. Methods. Twenty-two antipsychotic naive schizophrenic patients, 22 antipsychotic treated patients and 22 healthy control subjects were assessed by Neurological Evaluation (NES), Abnormal Involuntary Movements (AIMS), and Positive and Negative Syndrome (PANSS) Scales. Results. The NES scores of the never-medicated schizophrenic group were significantly higher than those of normal controls but did not differ significantly from the medicated group. Dyskinesia rates in the both schizophrenic groups were higher than in healthy controls. Medicated and non-medicated schizophrenic patient scores did not differ in AIMS with regard to facial and oral movements, but medicated patients scored higher than non-medicated subjects with respect to extremity movements. Conclusion. Our data suggest that: soft neurological signs and abnormal involuntary movements in the facial region are more prevalent in patients with schizophrenia, whether they are medicated or antipsychotic naı¨ve. On the contrary, abnormal involuntary movements in the trunk and the extremities seem to be associated with medication.
Key Words: Schizophrenia, dyskinesia, neurologic signs
Introduction Previous studies have suggested that neurological abnormalities may be present in patients with schizophrenia [1]. Neurological abnormalities have been revealed in the first episode of schizophrenia [2], and the presence of neurological abnormalities was usually regarded as a trait marker of schizophrenia. While neurological abnormalities assessed at the time of admission were found to increase during follow-up [3], Madsen et al reported a decline in neurological abnormalities in treated patients [4]. Neurological signs have been associated with some structural abnormalities, like larger ventricles and lower cortical volume, and suggested as having a prognostic value such that patients with neurological signs had poorer outcome and more negative symptoms [5/7]. Also, family history of psychosis was found to be associated with an increased prevalence of focal neurological abnormalities in patients with schizophrenia [8].
Neurological soft signs (NSS) are more prevalent in patients with schizophrenia than normal controls [9,10], and patients with mood disorders [11]. NSS scores are correlated positively with positive and negative symptoms [10], cognitive impairment [12], and associated with morphological alterations in the basal ganglia [13]. NSS were found to be higher in the deficit group [14]. It was also found that NSS scores varied during the clinical course of schizophrenia [13]. Spontaneous dyskinesia was found to be common in never-treated chronic patients with schizophrenia in the series of studies conducted by Mc Creadie et al [3,15,16], and also shown by Puri et al [17]. Some authors have indicated that spontaneous dyskinesia is of high prevalence among schizophrenia patients and family members, suggesting a potential role of environmental or genetic factors [7,18,19]. This study is based on the assumption that schizophrenic patients have biological tendency to involuntary movements. Our null hypothesis was ‘‘There would be no difference in the rates of
Correspondence: Cigdem Aydemir, Tunali Hilmi Caddesi 24/6, Kavaklidere, Ankara, Turkey 06660. Tel: / 90 542 647 1953. E-mail: [email protected]
(Received 14 March 2005; accepted 21 August 2005) ISSN 1365-1501 print/ISSN 1471-1788 online # 2005 Taylor & Francis DOI: 10.1080/13651500500329150
Dyskinesia and soft neurological signs in schizophrenia dyskinesia or neurological soft signs between the groups in Middle Eastern Caucasians’’. We aimed to estimate the frequency of dyskinetic movements and neurological soft signs in a sample of Middle Eastern Caucasian schizophrenic patients. Antipsychotic naive schizophrenic patients were compared with their counterparts on ongoing antipsychotic treatment, and healthy controls with regard to abnormal involuntary movements and soft neurological signs.
Methods Sample Study included 22 antipsychotic naive patients (13 women, nine men) with diagnosis of schizophrenia who were admitted consecutively to our in-patient service. All patients fulfilled the diagnostic criteria for schizophrenia according to DSM-IV [20]. Their ages ranged from 21 to 52 years (mean 34.689/9.22) and they had been ill for an average of 3.779/3.13 years (min. 1, max. 10). The comparison group included schizophrenia patients under treatment and also healthy controls. Patients under treatment were 22 subjects (13 women, nine men), with ages ranging from 20 to 57 years (mean 32.819/11.29), who had been ill for an average of 7.959/9.27 years (min. 1, max. 35). All patients fulfilled the diagnostic criteria for schizophrenia according to DSM-IV [20]. For each antipsychotic naı¨ve patient; the next admitted schizophrenic patient on ongoing antipsychotic medication and fitting the matching criteria was included. We applied one-to-one matching for gender and group matching for age and education. Patients who had been exposed to antipsychotics but were off medication at the time of screening were not included in order to exclude the possibility of withdrawal dyskinesia. To be in the first episode of schizophrenia was also an additional exclusion criterion for each group. Of the medicated patients, three patients were on olanzapine (two patients 10 mg/day and one patient 20 mg/day). Three patients were on quetiapine (one on 800 mg/day and the other two on 600 mg/day). Nine patients were on monthly zuclopenthixol decanoate injections. Two patients were on amisulpiride (one 800 mg/day and the other 900 mg/day). Four patients were on haloperidol (one patient 30 mg/day, two patients 20 mg/day and two patients 10 mg/day) One patient had monthly injections of fluphenazine decanoate. None of the patients on olanzapine, quetiapine or amisulpiride used biperiden. While all the patients, apart from the one on 30 mg haloperidol and one on parenteral zuclopenthixol decanoate, were on 2 /6 mg biperiden daily. The study also included a total of 22 healthy subjects, matched to naı¨ve schizophrenic patients for gender, and of similar age and education (one-to-
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one matching for gender and group matching for age and education). They were confirmed to be mentally healthy [20]. Past axis I disorder and exposure to antipsychotic medication were accepted to be exclusion criteria for healthy controls. None of the healthy controls had family history of any kind of psychotic disorder or bipolar disorder. The diagnosis was made through mental state examination and history obtained from patients and relatives and from the case records, if available. To be included in the study, all subjects were confirmed to be in good physical health, not to have a history of neurological disorders, such as seizures or major head trauma, substance abuse or mental retardation. Informed consent was received from all subjects’ families or legal guardians. Tools The patients’ mental state was assessed using the Turkish version of the Positive and Negative Syndrome Scale (PANSS) for schizophrenia [21,22]. Dyskinesia was measured by the Abnormal Involuntary Movements Scale (AIMS), examining seven areas of the body [23]. Dyskinesia was defined as present [24] if movements were ‘‘mild’’ in at least two areas, or ‘‘moderate’’ in at least one. Neurological soft signs were assessed by Neurological Evaluation Scale (NES) [25]. NES is a structured scale that presents scores in four subscales (sensory integration, motor coordination, sequencing of complex motor acts, and ‘‘others’’). In 26 items it captures a wide range of neurological signs. Each item is rated on a scale of 0/2. The motor coordination subscale includes tandem walk, rapid alternating movements, finger / thumb opposition and finger-to-nose test. The sensory integration subscale includes audio-visual integration, stereognosis, graphesthesia extinction and right/left confusion. Sequencing of motor acts includes the fist-ring test, the fist-edge /palm test, the Ozeretski test and rhythm tapping test B. ‘‘Others’’ includes adventitious overflow, the Romberg test, tremor, memory, mirror movements, rhythm tapping test A, synkinesis, convergence gaze, impersistence, glabellar reflex, snout reflex, grasp reflex, and suck reflex. Higher scores indicate greater neurological impairment. The total score and scores for each of the four subscales were used. Procedures On the first day of the hospitalization, patients underwent thorough physical examination and laboratory testing. The presence of any metabolic or cerebral disease potentially correlated with the psychotic symptoms was excluded. Afterwards, all patients were clinically assessed with the PANSS, AIMS, and NES.
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We are aware that differential diagnosis of movement disorders is a major problem. In order to achieve this, we made sure to include the consensus ratings, and all the authors are experienced psychiatrists trained in the assessment of both schizophrenia and movement disorders. Also, as expressed above, most of our medicated patients were on secondgeneration antipsychotics or additional anticholinergics to alleviate any possible side effects. Statistical analysis Statistical analyses included frequency and percent distributions. Study groups had small number of subjects and distribution of the variables were not normal. Therefore, non-parametric tests were used in comparison of groups. Comparative analyses of continuous variables were carried out using the Kruskal /Wallis test and the Mann /Whitney U- test, and of categorical variables, using the chi-squared test. Associations between variables were assessed by Spearman’s correlation coefficient. Two-tailed tests with a 5% level of significance were used throughout the analyses. All statistical analyses were performed using SPSS for Windows11.5.
never-medicated patients and healthy subjects with respect to extremity movements, and global judgment scores. Never-medicated schizophrenic patients and normal controls scored similar by means of extremity movements, but differed with regard to global judgment score. Medicated and non-medicated schizophrenic patients scored similar, but significantly higher than control subjects with regard to the total AIMS score. Three groups were similar regarding trunk movements (Table III). The never-medicated schizophrenic group had significantly higher NSS total scores than healthy controls but did not differ significantly from the medicated group. The medicated schizophrenic group also had significantly higher NSS total scores than normal controls. Medicated and non-medicated schizophrenic patients scored similar with respect to all NES subscales. Antipsychotic naı¨ve schizophrenia patients scored higher than healthy controls in all NES subscales except ‘‘sequencing of motor acts’’. Treated schizophrenia patients scored higher than healthy control subjects with respect to all NES subscales (Table IV). We did not find any correlations between any of variables including age, duration of illness PANSS, NES and AIMS subscales
Results Distribution of age and educational level were not statistically significantly different by study group (Table I). Antipsychotic treated patients had significantly longer length of illness (7.959/9.27 years) than the antipsychotic naı¨ve group (P /0.029), yet even the latter had a considerably long duration of illness (3.779/3.13 years) (Table II). Medicated schizophrenic patients, compared to never-medicated ones scored significantly higher in all subscales of PANSS, except for negative symptoms (Table II). Dyskinesia according to Schooler and Kane criteria [24], was present in five (22%) of the antipsychotic naı¨ve, and 10 (45%) of the medicated patients (P /0.203) but none in the healthy controls (P /0.048 and P /0.001, in comparison to naı¨ve and medicated patients, respectively). In AIMS subscales, medicated and non-medicated schizophrenic patient scores did not differ significantly with regard to facial and oral movements (Table III). Both groups scored higher than healthy controls. Medicated schizophrenic patients scored higher than
Discussion Our results indicate that treated schizophrenic patients had a longer duration of illness, and more positive symptoms. Their symptom severity was higher than untreated ones, which brought them to treatment opportunities earlier. Lower severity of positive symptoms, as in our untreated patients, enables symptoms to remain unnoticed, and/or considered as unimportant. Such patients remain untreated for long periods of time until an exacerbation leads the family or neighbours to bring the patient to a hospital. Some studies indicated the importance of age in movement disorders [15], such that movement disorders are more frequent in older age groups. Similar distribution of age in the two schizophrenic groups and the healthy control group enabled our comparison of groups with regard to other variables more meaningful. In recent years, studies have indicated that dyskinesia is a common phenomenon in patients with schizophrenia [15]. Mc Creadie et al [15] found
Table I. Distribution of age and educational status by study groups.
Age (years) Education level (years)
Antipsychotic naı¨ve
Antipsychotic treated
Control subjects
34.689/9.22 med /34 (21 /52) 8.549/3.83 med /8.5 (3 /15)
32.819/11.29 med /33 (20 /57) 8.319/4.37 med /7 (3 /17)
34.459/6.67 med /35 (23 /56) 8.729/4.3 med /7.5 (0 /17)
P value for Kruskal /Wallis test 0.608 0.152
Dyskinesia and soft neurological signs in schizophrenia
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Table II. Features of psychotic symptoms.
Length of illness PANSS-positive symptoms PANSS-negative symptoms PANSS general psychopathology PANSS total
Antipsychotic naı¨ve
Antipsychotic treated
3.779/3.13 med /2 (1 /10) 25.479/5.95 median /26 (13 /36) 21.149/7.72 med:19 (11 /41) 41.099/7.94 med:39 (30 /56) 87.239/14.03 med:85 (62 /121)
7.959/9.27 med /5 (1 /35) 31.319/5.89 med:32 (20 /42) 22.459/6.41 med:23 (11 /33) 46.909/8.32 med:48.5 (34 /59) 100.689/10.56 med: 99 (84 /117)
dyskinesia in 38% of antipsychotic naı¨ve elderly schizophrenic patients. Some studies from different settings and countries, on the other hand, found lower prevalence of dyskinesia in antipsychotic naı¨ve patients, ranging between 1,1 and 15% [2,26 /28]. In our study the prevalence of dyskinesia in the antipsychotic naı¨ve group was lower than that of Mc Creadie et al [3], but higher than those found by Fenn et al [26], Puri et al [27], and Fenton [28]. Many studies investigated dyskinesia in antipsychotic exposed patients, with frequencies of 6.7% [29], 11% [27], and 40.6% [30]. In our group, prevalence of dyskinesia in the antipsychotic exposed group was considerably high (45%); this may be a result of racial differences, given that two of abovementioned studies were conducted in Chinese and Malay patients and one in English patients. Our study participants were all Middle Eastern Caucasians. We found similar rates of dyskinesia in the two groups of schizophrenic patients. Both groups had higher rates of dyskinesia than healthy controls. This finding suggests that dyskinesia may be a part of neurobiological and one of the clinical manifestations of schizophrenia. Supporting Fenton’s finding, the frequency of orofacial dyskinetic movements was higher in our group of schizophrenic patients, either
Mann /Whitney U- test P value 0.029 0.002 0.263 0.022 0.002
treated or untreated. Medicated and non-medicated patients had higher mean scores of orofacial movements and total AIMS score than healthy controls. This was in accordance with the findings of Puri et al [27], supporting the idea that dyskinesia, in the orofacial region in particular, is a part of the clinical presentation of schizophrenia. Our results indicate that schizophrenic patients, regardless of treatment, had more neurological soft signs which are assessed by higher NES scores than healthy controls. We investigated a group of never medicated patients to exclude possible effects of antipsychotic drugs and found no difference between medicated and non medicated patients. This implies that NSS are not sequelae of the medication and replicates the previous findings of more soft neurological signs in patients with schizophrenia than in healthy subjects [31]. Furthermore, our results are concordant with the studies which reveal that NSS may be present at the onset of illness as a part of the disease process and may not be the result of antipsychotic medication [19,31,32]. We used the same scale with the aforementioned studies. However, total NES scores were lower than the results of Venkatasubramanian et al [32], but similar to those of Egan et al [19], and Sanders et al [31]. This may also be the result of racial differences, as we suggested for dyskinetic movements.
Table III. Comparison of AIMS subscales.
Antipsychotic naı¨ve (0) Antipsychotic treated (1) Healthy control (2)
0 versus 1 0 versus 2 1 versus 2 1
2 2 2
AIMS facial and oral movements
AIMS extremity movements
AIMS trunk movements
AIMS Global Judgment
AIMS Total
0.599/1.18 med:0 (0 /4) 0.599/0.73 med:0 (0 /2) 0.00 med:0 (0 /0) P /0.0031 P /0.358 P /0.009 P B/0.0001
0.0459/0.21 med:0 (0 /1) 0.639/0.58 med:1 (0 /2) 0.00 med:0 (0 /0) P B/0.00011 P B/0.0001 P /0.317 P B/0.0001
0.00 med:0 (0 /0) 0.00 med:0 (0 /0) 0.00 med:0 (0 /0) P /1.001 P /1.00 P /1.00 P /1.00
0.229/0.52 med:0 (0 /2) 0.779/0.75 med:1 (0 /2) 0.00 med:0 (0 /0) P B/0.00011 P /0.006 P /0.038 P B/0.0001
1.009/1.71 med:0 (0 /6) 2.049/1.86 med:2 (0 /6) 0.00 med:0 (0 /0) P B/0.00011 P /0.051 P /0.002 P /0.02
Kruskal /Wallis test P values are presented for each of the AIMS subtests, comparing three study groups. Mann /Whitney U- test P values were presented for AIMS subtests dual comparisons of study groups where, 0, 1 and 2 stand for antipsychotic naı¨ve, antipsychotic treated patients and healthy controls, respectively.
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Table IV. Comparison of NES subscales.
Antipsychotic naı¨ve (0) Antipsychotic treated (1) Healthy Control (2)
0 versus 1 0 versus 2 1 versus 2
2 2 2
NES total
Sensory integration
Motor coordination
5.409/6.49 med:4.5 (0 /30) 6.319/3.48 med:6.5 (1 /14) 0.779/1.1 med:0 (0 /3) P B/0.00011 P /0.164 P /0.001 P B/0.0001
0.509/1.01 med:0 (0 /4) 0.909/0.97 med:1 (0 /3) 0.009/0.00 med:0 (0 /0) P B/0.00011 P /0.078 P /0.009 P B/0.0001
2.779/2.94 med:2.5 (0 /12) 3.009/2.28 med:3 (0 /8) 0.459/0.67 med:0 (0 /2) P B/0.00011 P /0.536 P /0.003 P B/0.0001
Sequencing of motor complex acts
Others
0.409/1.00 med:0 (0 /4) 0.779/0.92 med:0 (0 /6) 0.209/0.52 med:0 (0 /2) P /0.0341 P /0.079 P /0.606 P /0.016
1.729/2.35 med:1.5 (0 /10) 2.459/1.89 med:2 (0 /6) 0.139/0.35 med:0 (0 /1) P B/0.00011 P /0.101 P /0.001 P B/0.0001
1
Kruskal /Wallis test P values are presented for each of the NES subtests, comparing three study groups. Mann /Whitney U- test P values were presented for NES subtests dual comparisons of study groups where, 0, 1 and 2 stand for antipsychotic naı¨ve, antipsychotic treated patients and healthy controls, respectively. 2
We did not find any correlations between any of variables; this may be due to the small number of subjects Our main limitation was small sample size. Also, it would be better if we applied the Simpson /Angus scale for parkinsonism. Although most of our medicated patients were on second-generation antipsychotics or additional anticholinergics, which would have confounded the assessment, we could have assessed spontaneous parkinsonism in the antipsychotic naive group. In conclusion, we found that both neurological soft signs and orofacial dyskinesia are more prevalent in schizophrenic patients compared to healthy subjects. These findings support the suggestion that some neurological signs may be a part of the disease or the developmental process rather than a medication effect. Particularly, dyskinesias in the orofacial region, which are mostly accepted as a late effect of antipsychotics and misconstrued as ‘‘tardive dyskinesia’’ can be part of the disease process, probably exacerbated by the effect of medications. Clinicians should be cautious in diagnosing tardive dyskinesia in all patients with dyskinetic movements. It should be kept in mind that both profacial and limb /truncal dyskinesia could be part of the disease process. This study stresses the importance of the assessment of all movement disorders before initiating antipsychotic treatment in order to avoid an over-diagnosis of all movement disorders as drug side effects.
Statement of interest The author has no conflict of interest with any commercial or other associations in connection with the submitted article.
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Key points . Dyskinesia, especially in the orofacial region in schizophrenia, is not necessarily drug-related and it may be a motor component of the disease . Abnormal involuntary movements in trunk and extremities are drug-related in schizophrenia . Soft neurological signs are found in patients with schizophrenia, regardless of medication effect
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Dyskinesia and soft neurological signs in schizophrenia [14] Tiryaki A, Yazici MK, Anil AE, et al. Reexamination of the characteristics of the deficit schizophrenia patients. Eur Arch Psychiatry Clin Neurosci 2003;253:221 /7. [15] Mc Creadie RG, Thara R, Kamath S, et al. Abnormal movements in never-medicated Indian patients with schizophrenia. Br J Psychiatry 1996;168:221 /6. [16] Mc Creadie RG, Padmavati R, Thara R, et al. Spontaneous dyskinesia and parkinsonism in never medicated chronically ill patients with schizophrenia: 18 month follow up. Br J Psychiatry 2002;181:135 /7. [17] Puri BK, Richardson AJ, Oatridge A, et al. Cerebral ventricular asymmetry in schizophrenia: A high resolution 3D magnetic resonance imaging study. Int J Psychophysiol 1999;34(3):207 /11. [18] Mc Creadie R, Rangaswamy T, Srinivasan TN, et al. Spontaneous dyskinesia in first-degree relatives of chronically ill, never treated people with schizophrenia. Br J Psychiatry 2003;183:45 /9. [19] Egan M, Hyde TM, Bonomo JB, et al. Relative risk of neurological signs in siblings of patients with schizophrenia. Am J Psychiatry 2001;158:1827 /34. [20] American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 4th ed. (DSM-IV). Washington, DC: American Psychiatric Association; 1994. [21] Kay SR, Fiszbein A, Opler LA. The positive and negative syndrome scale (PANSS) for schizophrenia. Schizophr Bull 1987;13:261 /76. [22] Kostakoglu AE, Batur S, Tiryaki A, et al. The validity and reliability of the Turkish version of the Positive and Negative Syndrome Scale (PANSS). Turk Psikol Derg 1999;14:23 / 32. /
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ORIGINAL ARTICLE
Dyskinesia and soft neurological signs in schizophrenia: a comparative study
CIGDEM AYDEMIR, EROL GOKA, CEBRAIL KISA, AYDIN KURT & FATIH VOLKAN YUKSEL Psychiatry Department, Ankara Numune Hospital, Ankara, Turkey
Abstract Objective. Several neurological abnormalities can be found at a greater frequency in patients with schizophrenia, including neurological soft signs (NSS) and signs of the ‘‘pyramidal’’ and ‘‘extrapyramidal’’ systems. We aimed to explore the frequency of movement disorders in patients with antipsychotic naı¨ve schizophrenia and to compare and contrast with antipsychotic-treated patients and healthy controls. Methods. Twenty-two antipsychotic naive schizophrenic patients, 22 antipsychotic treated patients and 22 healthy control subjects were assessed by Neurological Evaluation (NES), Abnormal Involuntary Movements (AIMS), and Positive and Negative Syndrome (PANSS) Scales. Results. The NES scores of the never-medicated schizophrenic group were significantly higher than those of normal controls but did not differ significantly from the medicated group. Dyskinesia rates in the both schizophrenic groups were higher than in healthy controls. Medicated and non-medicated schizophrenic patient scores did not differ in AIMS with regard to facial and oral movements, but medicated patients scored higher than non-medicated subjects with respect to extremity movements. Conclusion. Our data suggest that: soft neurological signs and abnormal involuntary movements in the facial region are more prevalent in patients with schizophrenia, whether they are medicated or antipsychotic naı¨ve. On the contrary, abnormal involuntary movements in the trunk and the extremities seem to be associated with medication.
Key Words: Schizophrenia, dyskinesia, neurologic signs
Introduction Previous studies have suggested that neurological abnormalities may be present in patients with schizophrenia [1]. Neurological abnormalities have been revealed in the first episode of schizophrenia [2], and the presence of neurological abnormalities was usually regarded as a trait marker of schizophrenia. While neurological abnormalities assessed at the time of admission were found to increase during follow-up [3], Madsen et al reported a decline in neurological abnormalities in treated patients [4]. Neurological signs have been associated with some structural abnormalities, like larger ventricles and lower cortical volume, and suggested as having a prognostic value such that patients with neurological signs had poorer outcome and more negative symptoms [5/7]. Also, family history of psychosis was found to be associated with an increased prevalence of focal neurological abnormalities in patients with schizophrenia [8].
Neurological soft signs (NSS) are more prevalent in patients with schizophrenia than normal controls [9,10], and patients with mood disorders [11]. NSS scores are correlated positively with positive and negative symptoms [10], cognitive impairment [12], and associated with morphological alterations in the basal ganglia [13]. NSS were found to be higher in the deficit group [14]. It was also found that NSS scores varied during the clinical course of schizophrenia [13]. Spontaneous dyskinesia was found to be common in never-treated chronic patients with schizophrenia in the series of studies conducted by Mc Creadie et al [3,15,16], and also shown by Puri et al [17]. Some authors have indicated that spontaneous dyskinesia is of high prevalence among schizophrenia patients and family members, suggesting a potential role of environmental or genetic factors [7,18,19]. This study is based on the assumption that schizophrenic patients have biological tendency to involuntary movements. Our null hypothesis was ‘‘There would be no difference in the rates of
Correspondence: Cigdem Aydemir, Tunali Hilmi Caddesi 24/6, Kavaklidere, Ankara, Turkey 06660. Tel: / 90 542 647 1953. E-mail: [email protected]
(Received 14 March 2005; accepted 21 August 2005) ISSN 1365-1501 print/ISSN 1471-1788 online # 2005 Taylor & Francis DOI: 10.1080/13651500500329150
Dyskinesia and soft neurological signs in schizophrenia dyskinesia or neurological soft signs between the groups in Middle Eastern Caucasians’’. We aimed to estimate the frequency of dyskinetic movements and neurological soft signs in a sample of Middle Eastern Caucasian schizophrenic patients. Antipsychotic naive schizophrenic patients were compared with their counterparts on ongoing antipsychotic treatment, and healthy controls with regard to abnormal involuntary movements and soft neurological signs.
Methods Sample Study included 22 antipsychotic naive patients (13 women, nine men) with diagnosis of schizophrenia who were admitted consecutively to our in-patient service. All patients fulfilled the diagnostic criteria for schizophrenia according to DSM-IV [20]. Their ages ranged from 21 to 52 years (mean 34.689/9.22) and they had been ill for an average of 3.779/3.13 years (min. 1, max. 10). The comparison group included schizophrenia patients under treatment and also healthy controls. Patients under treatment were 22 subjects (13 women, nine men), with ages ranging from 20 to 57 years (mean 32.819/11.29), who had been ill for an average of 7.959/9.27 years (min. 1, max. 35). All patients fulfilled the diagnostic criteria for schizophrenia according to DSM-IV [20]. For each antipsychotic naı¨ve patient; the next admitted schizophrenic patient on ongoing antipsychotic medication and fitting the matching criteria was included. We applied one-to-one matching for gender and group matching for age and education. Patients who had been exposed to antipsychotics but were off medication at the time of screening were not included in order to exclude the possibility of withdrawal dyskinesia. To be in the first episode of schizophrenia was also an additional exclusion criterion for each group. Of the medicated patients, three patients were on olanzapine (two patients 10 mg/day and one patient 20 mg/day). Three patients were on quetiapine (one on 800 mg/day and the other two on 600 mg/day). Nine patients were on monthly zuclopenthixol decanoate injections. Two patients were on amisulpiride (one 800 mg/day and the other 900 mg/day). Four patients were on haloperidol (one patient 30 mg/day, two patients 20 mg/day and two patients 10 mg/day) One patient had monthly injections of fluphenazine decanoate. None of the patients on olanzapine, quetiapine or amisulpiride used biperiden. While all the patients, apart from the one on 30 mg haloperidol and one on parenteral zuclopenthixol decanoate, were on 2 /6 mg biperiden daily. The study also included a total of 22 healthy subjects, matched to naı¨ve schizophrenic patients for gender, and of similar age and education (one-to-
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one matching for gender and group matching for age and education). They were confirmed to be mentally healthy [20]. Past axis I disorder and exposure to antipsychotic medication were accepted to be exclusion criteria for healthy controls. None of the healthy controls had family history of any kind of psychotic disorder or bipolar disorder. The diagnosis was made through mental state examination and history obtained from patients and relatives and from the case records, if available. To be included in the study, all subjects were confirmed to be in good physical health, not to have a history of neurological disorders, such as seizures or major head trauma, substance abuse or mental retardation. Informed consent was received from all subjects’ families or legal guardians. Tools The patients’ mental state was assessed using the Turkish version of the Positive and Negative Syndrome Scale (PANSS) for schizophrenia [21,22]. Dyskinesia was measured by the Abnormal Involuntary Movements Scale (AIMS), examining seven areas of the body [23]. Dyskinesia was defined as present [24] if movements were ‘‘mild’’ in at least two areas, or ‘‘moderate’’ in at least one. Neurological soft signs were assessed by Neurological Evaluation Scale (NES) [25]. NES is a structured scale that presents scores in four subscales (sensory integration, motor coordination, sequencing of complex motor acts, and ‘‘others’’). In 26 items it captures a wide range of neurological signs. Each item is rated on a scale of 0/2. The motor coordination subscale includes tandem walk, rapid alternating movements, finger / thumb opposition and finger-to-nose test. The sensory integration subscale includes audio-visual integration, stereognosis, graphesthesia extinction and right/left confusion. Sequencing of motor acts includes the fist-ring test, the fist-edge /palm test, the Ozeretski test and rhythm tapping test B. ‘‘Others’’ includes adventitious overflow, the Romberg test, tremor, memory, mirror movements, rhythm tapping test A, synkinesis, convergence gaze, impersistence, glabellar reflex, snout reflex, grasp reflex, and suck reflex. Higher scores indicate greater neurological impairment. The total score and scores for each of the four subscales were used. Procedures On the first day of the hospitalization, patients underwent thorough physical examination and laboratory testing. The presence of any metabolic or cerebral disease potentially correlated with the psychotic symptoms was excluded. Afterwards, all patients were clinically assessed with the PANSS, AIMS, and NES.
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We are aware that differential diagnosis of movement disorders is a major problem. In order to achieve this, we made sure to include the consensus ratings, and all the authors are experienced psychiatrists trained in the assessment of both schizophrenia and movement disorders. Also, as expressed above, most of our medicated patients were on secondgeneration antipsychotics or additional anticholinergics to alleviate any possible side effects. Statistical analysis Statistical analyses included frequency and percent distributions. Study groups had small number of subjects and distribution of the variables were not normal. Therefore, non-parametric tests were used in comparison of groups. Comparative analyses of continuous variables were carried out using the Kruskal /Wallis test and the Mann /Whitney U- test, and of categorical variables, using the chi-squared test. Associations between variables were assessed by Spearman’s correlation coefficient. Two-tailed tests with a 5% level of significance were used throughout the analyses. All statistical analyses were performed using SPSS for Windows11.5.
never-medicated patients and healthy subjects with respect to extremity movements, and global judgment scores. Never-medicated schizophrenic patients and normal controls scored similar by means of extremity movements, but differed with regard to global judgment score. Medicated and non-medicated schizophrenic patients scored similar, but significantly higher than control subjects with regard to the total AIMS score. Three groups were similar regarding trunk movements (Table III). The never-medicated schizophrenic group had significantly higher NSS total scores than healthy controls but did not differ significantly from the medicated group. The medicated schizophrenic group also had significantly higher NSS total scores than normal controls. Medicated and non-medicated schizophrenic patients scored similar with respect to all NES subscales. Antipsychotic naı¨ve schizophrenia patients scored higher than healthy controls in all NES subscales except ‘‘sequencing of motor acts’’. Treated schizophrenia patients scored higher than healthy control subjects with respect to all NES subscales (Table IV). We did not find any correlations between any of variables including age, duration of illness PANSS, NES and AIMS subscales
Results Distribution of age and educational level were not statistically significantly different by study group (Table I). Antipsychotic treated patients had significantly longer length of illness (7.959/9.27 years) than the antipsychotic naı¨ve group (P /0.029), yet even the latter had a considerably long duration of illness (3.779/3.13 years) (Table II). Medicated schizophrenic patients, compared to never-medicated ones scored significantly higher in all subscales of PANSS, except for negative symptoms (Table II). Dyskinesia according to Schooler and Kane criteria [24], was present in five (22%) of the antipsychotic naı¨ve, and 10 (45%) of the medicated patients (P /0.203) but none in the healthy controls (P /0.048 and P /0.001, in comparison to naı¨ve and medicated patients, respectively). In AIMS subscales, medicated and non-medicated schizophrenic patient scores did not differ significantly with regard to facial and oral movements (Table III). Both groups scored higher than healthy controls. Medicated schizophrenic patients scored higher than
Discussion Our results indicate that treated schizophrenic patients had a longer duration of illness, and more positive symptoms. Their symptom severity was higher than untreated ones, which brought them to treatment opportunities earlier. Lower severity of positive symptoms, as in our untreated patients, enables symptoms to remain unnoticed, and/or considered as unimportant. Such patients remain untreated for long periods of time until an exacerbation leads the family or neighbours to bring the patient to a hospital. Some studies indicated the importance of age in movement disorders [15], such that movement disorders are more frequent in older age groups. Similar distribution of age in the two schizophrenic groups and the healthy control group enabled our comparison of groups with regard to other variables more meaningful. In recent years, studies have indicated that dyskinesia is a common phenomenon in patients with schizophrenia [15]. Mc Creadie et al [15] found
Table I. Distribution of age and educational status by study groups.
Age (years) Education level (years)
Antipsychotic naı¨ve
Antipsychotic treated
Control subjects
34.689/9.22 med /34 (21 /52) 8.549/3.83 med /8.5 (3 /15)
32.819/11.29 med /33 (20 /57) 8.319/4.37 med /7 (3 /17)
34.459/6.67 med /35 (23 /56) 8.729/4.3 med /7.5 (0 /17)
P value for Kruskal /Wallis test 0.608 0.152
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Table II. Features of psychotic symptoms.
Length of illness PANSS-positive symptoms PANSS-negative symptoms PANSS general psychopathology PANSS total
Antipsychotic naı¨ve
Antipsychotic treated
3.779/3.13 med /2 (1 /10) 25.479/5.95 median /26 (13 /36) 21.149/7.72 med:19 (11 /41) 41.099/7.94 med:39 (30 /56) 87.239/14.03 med:85 (62 /121)
7.959/9.27 med /5 (1 /35) 31.319/5.89 med:32 (20 /42) 22.459/6.41 med:23 (11 /33) 46.909/8.32 med:48.5 (34 /59) 100.689/10.56 med: 99 (84 /117)
dyskinesia in 38% of antipsychotic naı¨ve elderly schizophrenic patients. Some studies from different settings and countries, on the other hand, found lower prevalence of dyskinesia in antipsychotic naı¨ve patients, ranging between 1,1 and 15% [2,26 /28]. In our study the prevalence of dyskinesia in the antipsychotic naı¨ve group was lower than that of Mc Creadie et al [3], but higher than those found by Fenn et al [26], Puri et al [27], and Fenton [28]. Many studies investigated dyskinesia in antipsychotic exposed patients, with frequencies of 6.7% [29], 11% [27], and 40.6% [30]. In our group, prevalence of dyskinesia in the antipsychotic exposed group was considerably high (45%); this may be a result of racial differences, given that two of abovementioned studies were conducted in Chinese and Malay patients and one in English patients. Our study participants were all Middle Eastern Caucasians. We found similar rates of dyskinesia in the two groups of schizophrenic patients. Both groups had higher rates of dyskinesia than healthy controls. This finding suggests that dyskinesia may be a part of neurobiological and one of the clinical manifestations of schizophrenia. Supporting Fenton’s finding, the frequency of orofacial dyskinetic movements was higher in our group of schizophrenic patients, either
Mann /Whitney U- test P value 0.029 0.002 0.263 0.022 0.002
treated or untreated. Medicated and non-medicated patients had higher mean scores of orofacial movements and total AIMS score than healthy controls. This was in accordance with the findings of Puri et al [27], supporting the idea that dyskinesia, in the orofacial region in particular, is a part of the clinical presentation of schizophrenia. Our results indicate that schizophrenic patients, regardless of treatment, had more neurological soft signs which are assessed by higher NES scores than healthy controls. We investigated a group of never medicated patients to exclude possible effects of antipsychotic drugs and found no difference between medicated and non medicated patients. This implies that NSS are not sequelae of the medication and replicates the previous findings of more soft neurological signs in patients with schizophrenia than in healthy subjects [31]. Furthermore, our results are concordant with the studies which reveal that NSS may be present at the onset of illness as a part of the disease process and may not be the result of antipsychotic medication [19,31,32]. We used the same scale with the aforementioned studies. However, total NES scores were lower than the results of Venkatasubramanian et al [32], but similar to those of Egan et al [19], and Sanders et al [31]. This may also be the result of racial differences, as we suggested for dyskinetic movements.
Table III. Comparison of AIMS subscales.
Antipsychotic naı¨ve (0) Antipsychotic treated (1) Healthy control (2)
0 versus 1 0 versus 2 1 versus 2 1
2 2 2
AIMS facial and oral movements
AIMS extremity movements
AIMS trunk movements
AIMS Global Judgment
AIMS Total
0.599/1.18 med:0 (0 /4) 0.599/0.73 med:0 (0 /2) 0.00 med:0 (0 /0) P /0.0031 P /0.358 P /0.009 P B/0.0001
0.0459/0.21 med:0 (0 /1) 0.639/0.58 med:1 (0 /2) 0.00 med:0 (0 /0) P B/0.00011 P B/0.0001 P /0.317 P B/0.0001
0.00 med:0 (0 /0) 0.00 med:0 (0 /0) 0.00 med:0 (0 /0) P /1.001 P /1.00 P /1.00 P /1.00
0.229/0.52 med:0 (0 /2) 0.779/0.75 med:1 (0 /2) 0.00 med:0 (0 /0) P B/0.00011 P /0.006 P /0.038 P B/0.0001
1.009/1.71 med:0 (0 /6) 2.049/1.86 med:2 (0 /6) 0.00 med:0 (0 /0) P B/0.00011 P /0.051 P /0.002 P /0.02
Kruskal /Wallis test P values are presented for each of the AIMS subtests, comparing three study groups. Mann /Whitney U- test P values were presented for AIMS subtests dual comparisons of study groups where, 0, 1 and 2 stand for antipsychotic naı¨ve, antipsychotic treated patients and healthy controls, respectively.
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Table IV. Comparison of NES subscales.
Antipsychotic naı¨ve (0) Antipsychotic treated (1) Healthy Control (2)
0 versus 1 0 versus 2 1 versus 2
2 2 2
NES total
Sensory integration
Motor coordination
5.409/6.49 med:4.5 (0 /30) 6.319/3.48 med:6.5 (1 /14) 0.779/1.1 med:0 (0 /3) P B/0.00011 P /0.164 P /0.001 P B/0.0001
0.509/1.01 med:0 (0 /4) 0.909/0.97 med:1 (0 /3) 0.009/0.00 med:0 (0 /0) P B/0.00011 P /0.078 P /0.009 P B/0.0001
2.779/2.94 med:2.5 (0 /12) 3.009/2.28 med:3 (0 /8) 0.459/0.67 med:0 (0 /2) P B/0.00011 P /0.536 P /0.003 P B/0.0001
Sequencing of motor complex acts
Others
0.409/1.00 med:0 (0 /4) 0.779/0.92 med:0 (0 /6) 0.209/0.52 med:0 (0 /2) P /0.0341 P /0.079 P /0.606 P /0.016
1.729/2.35 med:1.5 (0 /10) 2.459/1.89 med:2 (0 /6) 0.139/0.35 med:0 (0 /1) P B/0.00011 P /0.101 P /0.001 P B/0.0001
1
Kruskal /Wallis test P values are presented for each of the NES subtests, comparing three study groups. Mann /Whitney U- test P values were presented for NES subtests dual comparisons of study groups where, 0, 1 and 2 stand for antipsychotic naı¨ve, antipsychotic treated patients and healthy controls, respectively. 2
We did not find any correlations between any of variables; this may be due to the small number of subjects Our main limitation was small sample size. Also, it would be better if we applied the Simpson /Angus scale for parkinsonism. Although most of our medicated patients were on second-generation antipsychotics or additional anticholinergics, which would have confounded the assessment, we could have assessed spontaneous parkinsonism in the antipsychotic naive group. In conclusion, we found that both neurological soft signs and orofacial dyskinesia are more prevalent in schizophrenic patients compared to healthy subjects. These findings support the suggestion that some neurological signs may be a part of the disease or the developmental process rather than a medication effect. Particularly, dyskinesias in the orofacial region, which are mostly accepted as a late effect of antipsychotics and misconstrued as ‘‘tardive dyskinesia’’ can be part of the disease process, probably exacerbated by the effect of medications. Clinicians should be cautious in diagnosing tardive dyskinesia in all patients with dyskinetic movements. It should be kept in mind that both profacial and limb /truncal dyskinesia could be part of the disease process. This study stresses the importance of the assessment of all movement disorders before initiating antipsychotic treatment in order to avoid an over-diagnosis of all movement disorders as drug side effects.
Statement of interest The author has no conflict of interest with any commercial or other associations in connection with the submitted article.
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Key points . Dyskinesia, especially in the orofacial region in schizophrenia, is not necessarily drug-related and it may be a motor component of the disease . Abnormal involuntary movements in trunk and extremities are drug-related in schizophrenia . Soft neurological signs are found in patients with schizophrenia, regardless of medication effect
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