Repetitive transcranial magnetic stimulation for patients with functional paralysis: a randomized controlled study.

BACKGROUND AND PURPOSE: Repetitive transcranial magnetic stimulation (rTMS) has been proposed to treat functional neurological disorders. Here, the aim was to assess the efficacy of rTMS to treat functional paralysis in a controlled randomized trial. METHODS: Patients received two sessions of active or sham 0.25 Hz rTMS (60 stimuli each), with a 1-day interval, applied over the motor cortex contralateral to the paralysis. The primary outcome was the number of patients with an increase in motor score between baseline and after the second rTMS session, rated by two investigators blinded to the treatment allocation. Secondary outcomes were changes in global and fine motor scores between groups after rTMS, and the occurrence of adverse events. RESULTS: Sixty-two patients (46 female; mean [SD] age, 35.2 [13.9] years) were enrolled and randomized. Thirteen out of 32 (41%) and 11/30 (37%) patients had increased motor strength after active or sham rTMS, respectively (p = 0.80). Changes in both global and fine motor scores after rTMS relative to baseline were also not significantly different between treatment groups (median difference in the global motor score 0.62 [0.83] and 0.37 [0.61], and in the fine motor scores 0.12 [0.18] and 0.08 [0.11], in active and sham rTMS groups, respectively; p = 0.14). Six serious adverse events, consisting of three cephalalgia in the active group and two cephalalgia and one asthenia in the sham group, were observed. CONCLUSIONS: Two sessions of sham or active low frequency rTMS were effective to improve functional paralysis, suggesting a placebo effect of this non-invasive brain stimulation technique.

High-Frequency Neuronavigated rTMS in Auditory Verbal Hallucinations: A Pilot Double-Blind Controlled Study in Patients With Schizophrenia.

INTRODUCTION: Despite extensive testing, the efficacy of low-frequency (1 Hz) repetitive transcranial magnetic stimulation (rTMS) of temporo-parietal targets for the treatment of auditory verbal hallucinations (AVH) in patients with schizophrenia is still controversial, but promising results have been reported with both high-frequency and neuronavigated rTMS. Here, we report a double-blind sham-controlled study to assess the efficacy of high-frequency (20 Hz) rTMS applied over a precise anatomical site in the left temporal region using neuronavigation. METHODS: Fifty-nine of 74 randomized patients with schizophrenia or schizoaffective disorders (DSM-IV R) were treated with rTMS or sham treatment and fully evaluated over 4 weeks. The rTMS target was determined by morphological MRI at the crossing between the projection of the ascending branch of the left lateral sulcus and the superior temporal sulcus (STS). RESULTS: The primary outcome was response to treatment, defined as a 30% decrease of the Auditory Hallucinations Rating Scale (AHRS) frequency item, observed at 2 successive evaluations. While there was no difference in primary outcome between the treatment groups, the percentages of patients showing a decrease of more than 30% of AHRS score (secondary outcome) did differ between the active (34.6%) and sham groups (9.1%) (P = .016) at day 14. DISCUSSION: This controlled study reports negative results on the primary outcome but demonstrates a transient effect of 20 Hz rTMS guided by neuronavigation and targeted on an accurate anatomical site for the treatment of AVHs in schizophrenia patients.

The effects of familiarity and emotional expression on face processing examined by ERPs in patients with schizophrenia.

BACKGROUND: The main objective of the study was to determine whether patients with schizophrenia are deficient relative to controls in the processing of faces at different levels of familiarity and types of emotion and the stage where such differences may occur. METHODS: ERPs based on 18 patients with schizophrenia and 18 controls were compared in a face identification task at three levels of familiarity (unknown, familiar, subject's own) and for three types of emotion (disgust, smiling, neutral). RESULTS: The schizophrenic group was less accurate than controls in the face processing, especially for unknown faces and those expressing negative emotions such as disgust. P1 and N170 amplitudes were lower and P1, N170, P250 amplitudes were of slower onset in patients with schizophrenia. N170 and P250 amplitudes were modulated by familiarity and face expression in a different manner in patients than controls. CONCLUSIONS: Schizophrenia is associated with a genelarized defect of face processing, both in terms of familiarity and emotional expression, attributable to deficient processing at sensory (P1) and perceptual (N170) stages. These patients appear to have difficulty in encoding the structure of a face and thereby do not evaluate correctly familiarity and emotion.

A concordance study of three electrophysiological measures in schizophrenia.

OBJECTIVE: The authors evaluated concordance rates among three electrophysiological measures in patients with schizophrenia, nonschizophrenic first-degree relatives of schizophrenia patients, and healthy comparison subjects. The purpose of the study was to provide data for defining a common endophenotype for genetic studies of schizophrenia and for improving the criteria for diagnosis. METHOD: P50 event-related potential inhibition, antisaccade, and smooth pursuit eye tracking paradigms were measured. Data for all three paradigms were available for 81 patients with schizophrenia, 25 parents of patients with schizophrenia, and 60 healthy comparison subjects. RESULTS: The schizophrenia patients and the patients' parents showed a high rate of inhibitory deficits measured by the P50 inhibition and antisaccade paradigms. Both groups had a high prevalence of eye tracking dysfunction. Smooth pursuit gain and the error rate in the antisaccade paradigm were significantly correlated in the schizophrenia patients and the parents, whereas P50 inhibition showed no correlation with smooth pursuit gain or antisaccade paradigm measurements. CONCLUSIONS: Despite superficial similarities, two paradigms designed to measure central inhibition processes (antisaccade and P50 inhibition) do not appear to reflect the same neurobiological substrates. In contrast, the convergence in performance data for the antisaccade and eye tracking paradigms suggests that the neural circuitry underlying these tasks may overlap. P50 inhibition and antisaccade errors were the optimal paradigms for discrimination between comparison subjects, patients with schizophrenia, and the parents of patients with schizophrenia.

PRODH mutations and hyperprolinemia in a subset of schizophrenic patients.

The increased prevalence of schizophrenia among patients with the 22q11 interstitial deletion associated with DiGeorge syndrome has suggested the existence of a susceptibility gene for schizophrenia within the DiGeorge syndrome chromosomal region (DGCR) on 22q11. Screening for genomic rearrangements of 23 genes within or at the boundaries of the DGCR in 63 unrelated schizophrenic patients and 68 unaffected controls, using quantitative multiplex PCR of short fluorescent fragments (QMPSF), led us to identify, in a family including two schizophrenic subjects, a heterozygous deletion of the entire PRODH gene encoding proline dehydrogenase. This deletion was associated with hyperprolinemia in the schizophrenic patients. In addition, two heterozygous PRODH missense mutations (L441P and L289M), detected in 3 of 63 schizophrenic patients but in none among 68 controls, were also associated with increased plasma proline levels. Segregation analysis within the two families harboring respectively the PRODH deletion and the L441P mutation showed that the presence of a second PRODH nucleotide variation resulted in higher levels of prolinemia. In two unrelated patients suffering from severe type I hyperprolinemia with neurological manifestations, we identified a homozygous L441P PRODH mutation, associated with a heterozygous R453C substitution in one patient. These observations demonstrate that type I hyperprolinemia is present in a subset of schizophrenic patients, and suggest that the genetic determinism of type I hyperprolinemia is complex, the severity of hyperprolinemia depending on the nature and number of hits affecting the PRODH locus.