Table 1. Follow-up studies of neurological soft signs in patients with first-episode schizophrenia.
| Studies | Patients sample | Follow-up Period | Healthy controls | NSS Examination | Main Findings | Limitations |
|---|---|---|---|---|---|---|
| Madsen et al., 1999 | Thirty-four patients with first-episode schizophrenia and 29 patients with other psychotic disorders were recruited. | Only 18 patients were followed up at 5 years later. | Twenty healthy controls were recruited but only 10 being followed up. | SNE | Patients showed significantly higher prevalence of NSS than healthy controls at baseline assessment. Such a difference increased 5 years later, especially for signs capturing frontal, cortiospoinal and temporo-parietal functions. | The SNE is not a standardized and well-validated scale for the evaluation of NSS in schizophrenia population.The patients and controls samples were very small though the follow-up period was 5 years. There was only 2 time-point assessment that could not reflect general longitudinal changes of NSS in patients with schizophrenia. The association between NSS and negative symptoms was not examined |
| Whitty et al., 2003 | Ninety-seven patients with first-episode schizophrenia and schizophreniform disorders were recruited. | Patients were followed up at 6 months. | Seventy-three healthy controls were recruited and followed up. | NES | Patients showed significant reduction in NSS at the follow-up assessment suggesting that NSS manifested state-like characteristics that varied with clinical course. | The CNE was not a well-validated scale for NSS assessment. The items included in the NES consist of both “hard” and “soft” signs. Despite a reasonable large sample for both patients with first-episode schizophrenia and healthy controls, the follow-up period was limited to a 2 time points at 6-month interval. The association between NSS and negative symptoms was not examined. |
| Bachmann et al., 2005 | Thirty-nine patients with first-episode schizophrenia spectrum disorders | Patients were followed up at 14 months | Twenty-two healthy controls were recruited and followed up at 14 months. | Heidelberg Scale | Patients demonstrated significantly higher NSS prevalence than controls at baseline and follow-up. However, the prevalence of NSS remained stable in patients over the two time points. | The items included in the Heidelberg scale consist of both “hard” and “soft” signs. Relative small samples for both patients and controls and the follow-up period was limited to a 2 time points. The association between NSS and negative symptoms was not examined. |
| Chen et al., 2005 | One hundred and thirty-eight patients with first-episode schizophrenia, and schizophreniform, and schizoaffective disorder were recruited. | Only 93 patients were followed up at 3 years | Sixty-eight healthy controls were assessed at baseline. | Only motor coordination subscale of the CNI | Patients with medication-naïve schizophrenia demonstrated significantly higher prevalence of NSS than healthy controls, and the prevalence of NSS persisted over the 3 years since onset of schizophrenia. The association between NSS and negative symptoms increased gradually from the first year after the initial episode. | The findings were limited to the motor coordination signs. The changes of other signs such as sensory integration and disinhibition were not clear. No additional neurocognitive function assessment was obtained from this study. |
| Prikryl et al., 2007 | Ninety-two male patients with first-episode schizophrenia were recruited. | Patients were followed up at 1 year. | None | NES | Patients with remission demonstrated significantly lower NSS prevalence than those without remission. The remitters showed a significant reduction in NSS subscores except sensory integration, whereas the non-remitters reported a significant reduction of the overall NES score. | The findings were limited to male patients and might not be able to generalize to female patients. Relatively small sample for the follow-up of NSS at only 2 time points. The association between NSS and negative symptoms was not examined. |
| Mayoral et al., 2008 | Twenty-four patients with first-episode schizophrenia were recruited. | Patients were followed up over a 2-year period. | Thirty healthy controls were recruited and followed up 2 years later. | NES | Patients demonstrated significantly more NSS than controls at baseline assessment, and showed a significant decrease in the sensory integration, others and total NES score over the follow up period, whereas the controls only demonstrated a significant decrease in the total NES score. | Small sample size followed up only at 2 time points. The association between NSS and negative symptoms was not examined. No additional neurocognitive function assessment was obtained from this study. |
| Cuesta et al., 2012 | One hundred patients with medication naïve psychotic disorders | Only 77 patients were followed at baseline, 1 month and 6 months. | Twenty-eight healthy controls | NES | Patients receiving atypical antipsychotics showed significant improvement on the total NES score and most NES subscales except for frontal signs. Clinically meaningful changes on the NES score ranged from 25% to 50%. | The study was mainly a drug trial study testing the efficacy of risperidone, olanzapine, mixed antipsychotics or no medication. The sample was mixed with psychotic disorders other than schizophrenia. The relationship between NSS and negative symptoms was not examined. No additional neurocognitive function was obtained from the study. |
| Prikryl et al., 2012 | Sixty-eight male patients with first-episode schizophrenia were recruited. | Patients were followed up 4 years later. | None | NES | The patients with remission (57% of the original sample) demonstrated a decrease in the sensory integration and sequencing of complex motor acts. For the patients without remission (43%), they showed increase in the total NES score and other item of the NES. A relationship between NSS and negative symptoms was also found. | The findings were limited to male patients and might not be able to generalize to female patients. Relatively small sample for the follow-up of NSS at only 2 time points. |
| Mayoral M et al., 2012 | One hundred first-episode psychosis patients | Fifty-nine patients were followed up 2 years later. | Ninety-eight healthy controls were recruited and only 80 of them were followed up 2 years later. | NES | Patients showed more NSS than controls both at baseline and the 2-year follow-up . However, the patients demonstrated a significant greater reduction of NSS than the healthy controls at follow-up. No significant differences were demonstrated among different diagnostic groups of schizophrenia, bipolar disorders and other psychoses. | No association of NSS and negative symptoms was evaluated. . No additional neurocognitive function assessment was obtained from this study. |
NES: Neurological Evaluation Scale (Buchanan & Heinrichs, 1989); SNE: Standard Neurological Examination (Madsen et al., 1999); Heidelberg Scale (Schroder et al., 1992).