Neuroanatomical correlates of neurological soft signs in antipsychotic-naive schizophrenia

Recent imaging studies suggest that the so-called “soft” neurological signs in schizophrenia might have neuroanatomical validity. We examined gray matter volume correlates of neurological soft signs (NSS) in antipsychotic-naive schizophrenia patients using an automated image analysis technique. NSS were assessed using a modified neurological evaluation scale with good inter-rater reliability. Magnetic resonance images of 30 schizophrenia patients and 27 age-, sex-, education- and handedness-matched healthy controls were processed using optimized voxel-based morphometry (VBM). Logistic regression analysis showed that only the Motor Sequencing Signs (MSS) sub-score was a significant predictor of subject's status among the NSS sub-scores. Optimized VBM analysis showed that the MSS sub-score had a significant negative correlation with total and regional gray matter volumes (prefrontal, posterior cingulate, temporal cortices, putamen, and cerebellum) in schizophrenia patients but not in controls. Prefrontal and temporal cortices, putamen and cerebellum had significant volume deficits in patients. Cortical and cerebellar correlates of the sub-score MSS support the concept of “cognitive dysmetria” in schizophrenia.     

Development of a brief ataxia rating scale (BARS) based on a modified form of the ICARS

To develop a brief ataxia rating scale (BARS) for use by movement disorder specialists and general neurologists. Current ataxia rating scales are cumbersome and not designed for clinical practice. We first modified the International Cooperative Ataxia Rating Scale (ICARS) by adding seven ataxia tests (modified ICARS, or MICARS), and observed only minimally increased scores. We then used the statistics package R to find a five‐test subset in MICARS that would correlate best with the total MICARS score. This was accomplished first without constraints and then with the clinical constraint requiring one test each of Gait, Kinetic Function‐Arm, Kinetic Function‐Leg, Speech, and Eye Movements. We validated these clinical constraints by factor analysis. We then validated the results in a second cohort of patients; evaluated inter‐rater reliability in a third cohort; and used the same data set to compare BARS with the Scale for the Assessment and Rating of Ataxia (SARA). Correlation of ICARS with the seven additional tests that when added to ICARS form MICARS was 0.88. There were 31,481 five‐test subtests (48% of possible combinations) that had a correlation with total MICARS score of ≥0.90. The strongest correlation of an unconstrained five‐test subset was 0.963. The clinically constrained subtest validated by factor analysis, BARS, had a correlation with MICARS‐minus‐BARS of 0.952. Cronbach alpha for BARS and SARA was 0.90 and 0.92 respectively; and inter‐rater reliability (intraclass correlation coefficient) was 0.91 and 0.93 respectively. BARS is valid, reliable, and sufficiently fast and accurate for clinical purposes. © 2009 Movement Disorder Society     

Gaze shifts evoked by electrical stimulation of the superior colliculus in the head-unrestrained cat. II. Effect of muscimol inactivation of the caudal fastigial nucleus

The medioposterior cerebellum [vermian lobules VI and VII and caudal fastigial nucleus (cFN)] is known to play a major role in the control of saccadic gaze shifts toward a visual target. To determine the relative contribution of the cFN efferent pathways to the brainstem reticular formation and to the superior colliculus (SC), we recorded in the head-unrestrained cat the effects of cFN unilateral inactivation on gaze shifts evoked by electrical microstimulation of the deeper SC layers. Gaze shifts evoked after muscimol injection still exhibited the typical qualitative features of normal saccadic gaze shifts. Nevertheless, consistent modifications in amplitude and latency were observed. For ipsiversive movements (evoked by the SC contralateral to the inactivated cFN), these changes depended on the locus of stimulation on the motor map: for the anterior 2/3 of the SC, amplitude increased and latency tended to decrease; for the posterior 1/3 of the SC, amplitude decreased and latency increased. For the contraversive direction, amplitude moderately decreased and latency tended to increase for all but the caudal-most stimulated SC site. These modifications of SC-evoked gaze shifts during cFN inactivation differed from the ipsiversive hypermetria/contraversive hypometria pattern observed for visually triggered gaze shifts recorded during the same recording sessions. We conclude that (i) the topographical organization of gaze shift amplitude in the deeper SC layers is influenced by the cerebellum and is either severely distorted or demonstrates an amplitude reduction during inactivation of the contralateral or ipsilateral cFN, respectively; (ii) gaze shifts evoked by SC microstimulation and visually triggered gaze shifts either rely on distinct cerebellar-dependent control processes or differ by the location of the caudal-most active SC population. We present a functional scheme providing several predictions regarding the modulatory influence of the cerebellum on SC neuronal activities and on the topographical organization of fastigial-SC projections.     

Cognition and resting-state functional connectivity in schizophrenia

Individuals with schizophrenia consistently display deficits in a multitude of cognitive domains, but the neurobiological source of these cognitive impairments remains unclear. By analyzing the functional connectivity of resting-state functional magnetic resonance imaging (rs-fcMRI) data in clinical populations like schizophrenia, research groups have begun elucidating abnormalities in the intrinsic communication between specific brain regions, and assessing relationships between these abnormalities and cognitive performance in schizophrenia. Here we review studies that have reported analysis of these brain–behavior relationships. Through this systematic review we found that patients with schizophrenia display abnormalities within and between regions comprising (1) the cortico-cerebellar-striatal-thalamic loop and (2) task-positive and task-negative cortical networks. Importantly, we did not observe unique relationships between specific functional connectivity abnormalities and distinct cognitive domains, suggesting that the observed functional systems may underlie mechanisms that are shared across cognitive abilities, the disturbance of which could contribute to the “generalized” cognitive deficit found in schizophrenia. We also note several areas of methodological change that we believe will strengthen this literature.     

精神分裂症神经系统软体征与认知功能相关性研究进展

既往众多研究发现,健康人群及包含精神分裂症、情感障碍、强迫障碍、注意多动障碍在内的多种精神疾病患者都伴有认知功能的损害及神经系统软体征（NeurologicalSoftSigns,NSS）。两者常同时在精神疾患的临床表现中可见,现对两者之间是否存在关联及关联为何进行综述。     

Movement disturbances in the differential diagnosis of Creutzfeldt‐Jakob disease

Movement disturbances are common in dementia disorders and are a central feature of the clinical classification criteria of Creutzfeldt‐Jakob disease (CJD). Polymorphism at codon 129 of the prion protein gene is known to determine the clinical picture of CJD. The frequency and characteristics of movement disturbances in other dementing disorders, such as Alzheimer's disease (AD), is barely known and leads to misdiagnoses. We investigated the occurrence and characteristics of movement disturbances in 143 patients neuropathologically confirmed with CJD (n = 100), AD (n = 29), dementia with Lewy bodies (DLB) (n = 7), or other diagnoses (n = 7). All patients had been referred with the differential diagnosis of prion disease. Ataxia and dysmetria were significantly more frequent in CJD than in AD or DLB patients, whereas hypokinesia was up to five times more frequent in AD or DLB (P < 0.05). Using an ordered logistic regression to identify constellations of movement disturbances, the diagnosis of CJD was likely in patients presenting ataxia but not hypokinesia. The reverse situation was statistically associated with AD. Ataxia and cogwheel rigidity were associated with valine‐homozygosity and akinesia with methionine‐homozygosity in the CJD patients. Our results indicate that the careful assessment of movement disturbances may be helpful in the differential diagnosis of Creutzfeldt‐Jakob disease. © 2008 Movement Disorder Society     

Relationship Between Basilar-Type Migraine and Migrainous Vertigo

Objective.— This study compared clinical manifestations and audiovestibular function tests among subjects of basilar-type migraine (BtM), definite and probable migrainous vertigo (dMV and pMV), in order to investigate the relationship between them.
Background.— Various diagnostic criteria such as BtM, dMV, and pMV have been proposed. However, a comparison between these diagnostic groups has not been conducted before.
Methods.— This study enrolled 77 subjects, including BtM in 15, dMV in 30, and pMV in 32 patients. All patients received structured interview of clinical presentations and underwent a battery of audiovestibular function tests.
Results.— Demographic features were similar between 3 groups, including age, gender, precipitating factors, and family preponderance. When considering the clinical manifestations, for example motion sickness, migrainous symptoms, and sequential relationship between headache and vertigo, BtM and dMV groups shared similar features, but differed from pMV group. As regards to differentiate between BtM and dMV patients, the former revealed higher occurrence rates than the latter in relation to the frequency of vertigo attacks, neurological symptoms, and saccadic dysmetria.
Conclusion.— The relationship between BtM, dMV, and pMV refers to a distribution of severity across the disease spectrum of migraine-related vertigo. Of them, BtM group presents the most severe form in clinical manifestation and brainstem involvement, followed by dMV, and pMV is the mildest form.     

Psychiatric misdiagnoses in Dandy–Walker variant

Cases of intellectual impairment and aberrant behavior in patients with cerebellar diseases have been described since the early nineteenth century. Here, we report on a patient suffering from Dandy–Walker variant who presented with symptoms of obsessive compulsive disorder and delusional disorder. The current findings emphasize the potential relevance of focal cerebellar lesions as organic correlates of these disorders.     

Saccadic lateropulsion in Wallenberg's syndrome may be caused by a functional lesion of the fastigial nucleus

One of the clinical oculomotor hallmarks of lateral medullary infarction (Wallenberg's syndrome) is the so-called saccadic lateropulsion. In man and in animals, cerebellar lesions lead to dysmetric saccades and underline the importance of cerebellar control on saccadic accuracy. In order to study the lesion site responsible for saccadic lateropulsion we prospectively examined 12 patients with Wallenberg's syndrome who did not show a cerebellar lesion on CT or MRI. All patients consistently showed hypermetric saccades to the ipsilateral side and hypometric contralateral saccades comparable with the effects of cerebellar lesions in monkeys on saccadic accuracy. Based on the most recent experiments involving recordings from saccade-related neurons in the deep cerebellar nuclei of monkeys (oculomotor region of fastigial nucleus), we hypothesize that saccadic lateropulsion in lateral medullary infarction is essentially identical with cerebellar saccadic dysmetria and results from a disruption of afferent olivocerebellar climbing fibres that gives rise to functional disinhibition of the cerebellar cortex and to increased inhibition of the deep cerebellar nuclei.