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Articles by M Synofzik
Total Records ( 2 ) for M Synofzik
  M Anheim , B Monga , M Fleury , P Charles , C Barbot , M Salih , J. P Delaunoy , M Fritsch , L Arning , M Synofzik , L Schols , J Sequeiros , C Goizet , C Marelli , I Le Ber , J Koht , J Gazulla , J De Bleecker , M Mukhtar , N Drouot , L Ali Pacha , T Benhassine , M Chbicheb , A M'Zahem , A Hamri , B Chabrol , J Pouget , R Murphy , M Watanabe , P Coutinho , M Tazir , A Durr , A Brice , C Tranchant and M. Koenig

Ataxia with oculomotor apraxia type 2 (AOA2) is an autosomal recessive disease due to mutations in the senataxin gene, causing progressive cerebellar ataxia with peripheral neuropathy, cerebellar atrophy, occasional oculomotor apraxia and elevated alpha-feto-protein (AFP) serum level. We compiled a series of 67 previously reported and 58 novel ataxic patients who underwent senataxin gene sequencing because of suspected AOA2. An AOA2 diagnosis was established for 90 patients, originating from 15 countries worldwide, and 25 new senataxin gene mutations were found. In patients with AOA2, median AFP serum level was 31.0 µg/l at diagnosis, which was higher than the median AFP level of AOA2 negative patients: 13.8 µg/l, P = 0.0004; itself higher than the normal level (3.4 µg/l, range from 0.5 to 17.2 µg/l) because elevated AFP was one of the possible selection criteria. Polyneuropathy was found in 97.5% of AOA2 patients, cerebellar atrophy in 96%, occasional oculomotor apraxia in 51%, pyramidal signs in 20.5%, head tremor in 14%, dystonia in 13.5%, strabismus in 12.3% and chorea in 9.5%. No patient was lacking both peripheral neuropathy and cerebellar atrophy. The age at onset and presence of occasional oculomotor apraxia were negatively correlated to the progression rate of the disease (P = 0.03 and P = 0.009, respectively), whereas strabismus was positively correlated to the progression rate (P = 0.03). An increased AFP level as well as cerebellar atrophy seem to be stable in the course of the disease and to occur mostly at or before the onset of the disease. One of the two patients with a normal AFP level at diagnosis had high AFP levels 4 years later, while the other had borderline levels. The probability of missing AOA2 diagnosis, in case of sequencing senataxin gene only in non-Friedreich ataxia non-ataxia-telangiectasia ataxic patients with AFP level ≥7 µg/l, is 0.23% and the probability for a non-Friedreich ataxia non-ataxia-telangiectasia ataxic patient to be affected with AOA2 with AFP levels ≥7 µg/l is 46%. Therefore, selection of patients with an AFP level above 7 µg/l for senataxin gene sequencing is a good strategy for AOA2 diagnosis. Pyramidal signs and dystonia were more frequent and disease was less severe with missense mutations in the helicase domain of senataxin gene than with missense mutations out of helicase domain and deletion and nonsense mutations (P = 0.001, P = 0.008 and P = 0.01, respectively). The lack of pyramidal signs in most patients may be explained by masking due to severe motor neuropathy.

  M Synofzik , P Thier , D. T Leube , P Schlotterbeck and A. Lindner

The experience of being the initiator of one's own actions seems to be infallible at first glance. Misattributions of agency of one's actions in certain neurological or psychiatric patients reveal, however, that the central mechanisms underlying this experience can go astray. In particular, delusions of influence in schizophrenia might result from deficits in an inferential mechanism that allows distinguishing whether or not a sensory event has been self-produced. This distinction is made by comparing the actual sensory information with the consequences of one's action as predicted on the basis of internal action-related signals such as efference copies. If this internal prediction matches the actual sensory event, an action is registered as self-caused; in case of a mismatch, the difference is interpreted as externally produced. We tested the hypothesis that delusions of influence are based on deficits in this comparator mechanism. In particular, we tested whether patients’ impairments in action attribution tasks are caused by imprecise predictions about the sensory consequences of self-action. Schizophrenia patients and matched controls performed pointing movements in a virtual-reality setup in which the visual consequences of movements could be rotated with respect to the actual movement. Experiment 1 revealed higher thresholds for detecting experimental feedback rotations in the patient group. The size of these thresholds correlated positively with patients’ delusions of influence. Experiment 2 required subjects to estimate their direction of pointing visually in the presence of constantly rotated visual feedback. When compared to controls, patients’ estimates were significantly better adapted to the feedback rotation and exhibited an increased variability. In interleaved trials without visual feedback, i.e. when pointing estimates relied solely on internal action-related signals, this variability was likewise increased and correlated with both delusions of influence and the size of patients’ detection thresholds as assessed in the first experiment. These findings support the notion that delusions of influence are based on imprecise internal predictions about the sensory consequences of one's actions. Moreover, we suggest that such imprecise predictions prompt patients to rely more strongly on (and thus adapt to) external agency cues, in this case vision. Such context-dependent weighted integration of imprecise internal predictions and alternative agency cues might thus reflect the common basis for the various misattributions of agency in schizophrenia patients.

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