Curr Psychiatry Rep (2015) 17:32 DOI 10.1007/s11920-015-0570-4


Neurology Issues in Schizophrenia Katharina Hüfner & Beatrice Frajo-Apor & Alex Hofer

# Springer Science+Business Media New York 2015

Abstract Schizophrenia ranks among the leading causes of disability worldwide. The presence of neurological signs cooccurring with the psychiatric symptoms is indicative of an organic brain pathology. In the present article, we review the current literature on neurology issues in schizophrenia. Firstly, common neurological signs found in patients with schizophrenia (neurological soft signs and smell abnormalities) and their association with imaging findings are reviewed. Secondly, the significant association of schizophrenia with epilepsy and stroke is described as well as the absent association with other organic brain diseases such as multiple sclerosis. Thirdly, we discuss the potential role of NMDA receptor antibodies in schizophrenia. Fourthly, neurological side effects of antipsychotic drugs and their treatment are reviewed; and lastly, we discuss neurocognitive deficits in patients with schizophrenia and their treatment. The focus of the review remains on articles with relevance to the clinician.

growing understanding of the pathophysiological mechanisms leading up to the phenotype of schizophrenia, many questions still remain unsolved. Indisputably, schizophrenia is a highly heritable disease [4]. Since the genes responsible for the phenotype of schizophrenia are expressed not only in the brain but also in several tissues and cellular types [4], schizophrenia can be considered a systemic disease. It is thus associated with a high rate of somatic comorbidities. Therefore, the clinical management of schizophrenia patients requires expertise beyond primary psychiatric issues. This current review aims to highlight some important aspects concerning neurological soft signs in schizophrenia, the association of neurological diseases with schizophrenia, and medication issues. The emphasis is on clinically relevant topics and studies published in the last 3 years have been taken into account, without aiming to achieve a complete coverage.

Keywords Schizophrenia . Neurological soft signs . Neurologic comorbidities . Neurological side effects . Neurocognition

Neurological Soft Signs

Introduction Growing evidence points towards the presence of an organic brain pathology in first-episode untreated schizophrenia [1] and neurological signs co-occurring with the psychiatric pathology are thus regarded a trait feature of schizophrenia [2, 3•]. Despite This article is part of the Topical Collection on Schizophrenia and Other Psychotic Disorders K. Hüfner (*) : B. Frajo-Apor : A. Hofer Department of Psychiatry & Psychotherapy, Medical University of Innsbruck, Anichstrasse 35, 6020 Innsbruck, Austria e-mail: [email protected]

Findings of Neurological Soft Signs From Structural and Functional Imaging Studies So-called neurological soft signs (NSS) have conventionally been defined as subtle findings in the neurological examination with no definite localizing feature [5•]. Typically, they are classified into signs relating to motor coordination, sequencing of complex motor tasks, sensory-motor integration, and disinhibition [6]. So far, a number of scales have been developed to measure such signs, e.g., the NSS Neurological Evaluation Scale (NES) [6] and the Cambridge Neurological Inventory (CNI) [7]. From a neurological point of view, this terminology seems misleading since the neurological deficits might be Bsubtle,^ but neither are those findings Balmost insignificant^ nor Bindicative of a harmless disease,^ two possible implications of the term Bsoft.^ Also the Bnon-localizing^


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feature of the so called NSS is challenged in recent imaging studies in which substrates of morphofunctional alterations are associated with distinct pathologies commonly classified as Bsoft signs.^ In a meta-analysis of structural magnetic resonance imaging (MRI) studies, which included not only patients with schizophrenia but also those with related psychotic disorders, NSS were associated with bilateral atrophy of the precentral gyrus, the left postcentral gyrus, the left inferior frontal gyrus, the right temporal lobe, the left inferior parietal lobule, the thalamus, and the cerebellum. In this context, both gray and white matter abnormalities were detected (Fig. 1). In the same study, a meta-analysis of functional MRI studies (using different variations of a go/no go paradigm frequently

used to measure response inhibition) was also performed, which showed that NSS-related tasks were significantly associated with altered brain activation in the right inferior frontal gyrus, the left superior temporal gyrus, the globus pallidus and putamen, and the cerebellum [5•]. The authors concluded that these data support the concept of NSS as a manifestation of the cerebello-thalamo-prefontal brain network dysfunction in schizophrenia and related psychotic disorders [5•]. While the reported meta-analysis helps to specify the vague concept of NSS by identifying specific brain regions involved, a major limitation is that, in addition to patients with schizophrenia, those with Brelated psychotic disorders,^ such as bipolar disorder, borderline personality disorder, and obsessive-


a Inferior frontal gyrus


Inferior frontal gyrus


c Prefrontal gyrus


d y=-5

Left hemisphere

Right hemisphere

y=-56 1.6

Postcentral gyrus

Middle temporal gyrus 1.5





y=-68 NSS

Fig. 1 (a) Activation likelihood estimation (ALE) of structural magnetic resonance imaging studies in patients with neurological soft signs, adapted from Zhao et al. [5•]. Red labels are the ALE meta-analysis results of the gray matter foci negatively correlated with neurological soft signs (NSS) scores. Blue labels are the ALE meta-analysis results of the white matter foci negatively correlated with the NSS scores (P

Neurology issues in schizophrenia.

Schizophrenia ranks among the leading causes of disability worldwide. The presence of neurological signs co-occurring with the psychiatric symptoms is...
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