Neurological Nonlocalizing Soft Signs

The application of newer techniques of central nervous system (CNS) investigation, such as functional neuroimaging, has generated interest in finding meaningful connections between clinical observations and the underlying neuropathology of schizophrenia. A review of the literature on neurological signs (Heinrichs and Buchanan 1988) demonstrated a higher prevalence of such signs in schizophrenia than in nonpsychiatric and psychiatric control subjects, including some degree of temporal stability, a lack of medication effect (i.e., signs appear to be a stable trait), a trend toward increased neurological soft sign prevalence in males, and a modest influence of age and socioeconomic status. The majority of studies have found abnormalities in integrative sensory function, such as bilateral extinction, left-right confusion, impaired audiovisual integration, agraphes-thesia, and astereognosis. Other areas frequently found to show difficulties include motor coordination (e.g., balance, station and gait, and general coordination) and motor sequencing (e.g., performance of complex sequences of action, such as repetitive alternations of hand position). These findings indicate that basic mechanisms of sensory input and motor output are not disturbed, but rather that higher-order functional integration of sensory and motor responses is impaired.

Associations between the occurrence of neurological signs and thought disorder and cognitive impairment (including performance on mental status examination) appear to be fairly robust. Similar associations have been identified for negative symptoms and chronicity of illness; moreover, first-degree biological relatives of schizophrenic probands appear to have increased evidence of neurological signs.

One major difficulty in interpreting the literature on this subject has been the application of various nonstandardized examination techniques. To remedy this, Buchanan and Heinrichs (1989) developed the Neurological Evaluation Scale (NES), a structured examination rating scale with respectable reliability. Since the Heinrichs and Buchanan review, efforts to investigate the significance of neurological signs have produced a number of interesting findings. For example, Gupta et al. (1995) found that 23% of neuroleptic-nai've and 46% of medicated schizophrenic subjects had evidence of neurological signs, whereas others (Chen et al. 2000; Ismail et al. 1998a) have found high prevalences of neurological abnormalities in schizophrenic patients and their siblings. Wong et al. (1997) found additionally that neurological signs are associated with negative symptoms, poor psychosocial performance, and increased cognitive impairment. Interestingly, Flashman et al. (1996) suggested that neurological signs are not indicative of global cognitive impairment, but rather are a manifestation of a localizable behavioral deficit of the neural systems subserving motor speed, coordination, and sequencing, suggesting a frontal subcortical circuit disturbance in schizophrenia.

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