The development of goal-directed reaching in infants: hand trajectory formation and joint torque control

Nine young infants were followed longitudinally from 4 to 15 months of age. We recorded early spontaneous movements and reaching movements to a stationary target. Time-position data of the hand (endpoint), shoulder, and elbow were collected using an optoelectronic measurement system (ELITE). We analyzed the endpoint kinematics and the intersegmental dynamics of the shoulder and elbow joint to investigate how changes in proximal torque control determined the development of hand trajectory formation. Two developmental phases of hand trajectory formation were identified: a first phase of rapid improvements between 16 and 24 weeks of age, the time of reaching onset for all infants. During that time period the number of movement units per reach and movement time decreased dramatically. In a second phase (28–64 weeks), a period of fine-tuning of the sensorimotor system, we saw slower, more gradual changes in the endpoint kinematics. The analysis of the underlying intersegmental joint torques revealed the following results: first, the range of muscular and motiondependent torques (relative to body weight) did not change significantly with age. That is, early reaching was not confined by limitations in producing task-adequate levels of muscular torque. Second, improvements in the endpoint kinematics were not accomplished by minimizing amplitude of muscle and reactive torques. Third, the relative timing of muscular and motion-dependent torque peaks showed a systematic development toward an adult timing profile with increasing age. In conclusion, the development toward invariant characteristics of the hand trajectory is mirrored by concurrent changes in the control of joint forces. The acquisition of stable patterns of intersegmental coordination is not achieved by simply regulating force amplitude, but more so by modulating the correct timing of joint force production and by the system's use of reactive forces. Our findings support the view that development of reaching is a process of unsupervised learning with no external or innate teacher prescribing the desired kinematics or kinetics of the movement.     

GCH1 mutation in a patient with adult-onset oromandibular dystonia

The authors report a mutation in exon 5 of GCH1 in a patient with adult-onset oromandibular dystonia and no obvious family history of dystonia. The patient responded positively to treatment with L-dopa. These findings demonstrate that GCH1 mutations must be considered even in patients with dystonic symptoms not typical of dopa-responsive dystonia.     

UV-Sensitivity of Shiga Toxin-Converting Bacteriophage Virions Φ24B, 933W,P22, P27 and P32

Shiga toxin-converting bacteriophages (Stx phages) are present as prophages in Shiga toxin-producing Escherichia coli (STEC) strains. Theses phages can be transmitted to previously non-pathogenic E. coli cells making them potential producers of Shiga toxins, as they bear genes for these toxins in their genomes. Therefore, sensitivity of Stx phage virions to various conditions is important in both natural processes of spreading of these viruses and potential prophylactic control of appearance of novel pathogenic E. coli strains. In this report we provide evidence that virions of Stx phages are significantly more sensitive to UV irradiation than bacteriophage λ. Following UV irradiation of Stx virions at the dose of 50 J/m², their infectivity dropped by 1–3 log₁₀, depending on the kind of phage. Under these conditions, a considerable release of phage DNA from virions was observed, and electron microscopy analyses indicated a large proportion of partially damaged virions. Infection of E. coli cells with UV-irradiated Stx phages resulted in significantly decreased levels of expression of N and cro genes, crucial for lytic development. We conclude that inactivation of Stx virions caused by relatively low dose of UV light is due to damage of capsids that prevents effective infection of the host cells.     

Lack of mutations in the epsilon-sarcoglycan gene in patients with different subtypes of primary dystonias.

Primary dystonias represent a clinically and genetically heterogeneous group of movement disorders. Mutations in the epsilon-sarcoglycan (SGCE) gene have been found recently to cause myoclonus-dystonia (MD). Considerable clinical variation of SGCE mutation carriers leads to the hypothesis that mutations in the SGCE gene might also be relevant for other subtypes of dystonias. To determine the contribution of mutations in the SGCE gene in patients with different subtypes of dystonias, we analyzed the coding sequence of the SGCE gene in a group of 296 patients with a clinical phenotype of primary dystonia and in 2 patients with a clinical phenotype of myoclonus-dystonia. Patients with mutations in the DYT1 gene were excluded. We could not detect a mutation in the SGCE gene in any of the 298 patients. Our results suggest that mutations in the SGCE gene cannot be held responsible for other subtypes of primary dystonia.     

Aspirin non-responder status in patients with recurrent cerebral ischemic attacks

Background: Antiplatelet agents such as acetylsalicylic acid (aspirin) reduce the relative risk for cerebrovascular events in patients with cardiovascular or cerebrovascular disorders by approximately 23 %. Recent observations raise the possibility that aspirin resistance may contribute to the failure of aspirin treatment in a significant proportion of patients (aspirin non-responders). To evaluate the clinical relevance of aspirin non-responder status, we analysed platelet functions in symptomatic and asymptomatic patients treated with aspirin for secondary prevention of cardiovascular and cerebrovascular events. Methods: A total of 53 patients on 100 mg aspirin daily for secondary prevention (mean treatment duration > 60 months) were included. Patients were categorized as asymptomatic if they were free of cerebrovascular incidents for at least 24 months (n = 18). Symptomatic patients had suffered ischemic strokes or transient ischemic attacks within the previous 3 days (n = 35). Platelet function was assessed using the PFA–100 system that allows for quantitative assessment of platelet function, reporting platelet aggregatability as the time required to close a small aperture in a biologically active membrane. Results: Collagen/epinephrine closure times were significantly shorter in symptomatic patients than in asymptomatic patients (p < 0.01). Individual closing times were normal in 12 of 35 symptomatic patients (34 % non-responders) whereas all asymptomatic patients had prolonged closure times. Conclusions: Aspirin non-responder status may contribute to failure of aspirin therapy in the secondary prevention of cerebrovascular incidents in as much as 30–40 % of patients. Quantitative assessment of platelet functions may provide a means to predict aspirin treatment failure in individual patients and to re-direct therapeutic strategies. Received: 7 May 2002, Received in revised form: 28 August 2002, Accepted: 2 September 2002 Correspondence to Priv.-Doz. Dr. Helge Topka     

Do CTG expansions at the SCA8 locus cause ataxia?

To evaluate the significance of expanded CTG repeats at the SCA8 locus, we analyzed the allele distribution in 1,262 German ataxia patients. We found intermediate and expanded CTG repeats with similar frequencies in ataxia patients with and without established genetic diseases. One family linked to the SCA8 locus showed incomplete penetrance and an association of smaller CTG repeats with more severe disease. Our data question the disease-causing character of CTG expansions for SCA8 and advise great caution in genetic testing.     

Reversible segmental cerebral vasoconstriction (Call-Fleming syndrome): are calcium channel inhibitors a potential treatment option?

The Call-Fleming syndrome is characterized by sudden onset of thunderclap-like headache and focal neurological deficits. The pathophysiological correlate is a reversible segmental cerebral vasoconstriction frequently associated with focal cerebral ischaemia. The syndrome has been described in a variety of clinical conditions, and recently an association between the syndrome and exposure to vasoactive drugs was observed. Effective treatment options are not known. A 63-year-old female developed sudden 'worst ever' headache. Initial neurological examination, laboratory blood tests, CSF examination and brain magnetic resonance imaging (MRI) were normal. Previous medical history was unremarkable and she did not take vasoactive drugs. Eleven days after the onset of headache she developed visual field impairment and a right-sided hemiparesis. Brain MRI revealed bilateral posterior and left parietal ischaemic strokes. Cerebral catheter angiography showed segmental arterial vasoconstriction. A vasodilative therapy with calcium channel inhibitors was started and serial transcranial Doppler ultrasonography demonstrated resolution of cerebral arterial vasoconstriction. The present case illustrates that calcium channel inhibitors may be an effective therapy for segmental cerebral arterial vasoconstriction. However, more clinical data are needed to prove this observation.     

Task-specific plasticity of somatosensory cortex in patients with writer's cramp

Focal dystonias such as writer's cramp are characterized by muscular cramps that accompany the execution of specific motor tasks. Until now, the pathophysiology of focal dystonia remains incompletely understood. Recent studies suggest that the development of writer's cramp is related to abnormal organization of primary somatosensory cortex (SI), which in turn leads to impaired motor function. To explore contributions of SI on mechanisms of task specificity in focal dystonia, we investigated dynamic alterations in the functional organization of SI as well as sensory-motor gating for rest, left- and right-handed writing and brushing in writer's cramp patients and healthy controls. The functional organization of somatosensory cortex was assessed by neuromagnetic source imaging (151 channel whole-head MEG). In accordance with previous reports, distances between cortical representations of thumb and little finger of the affected hand were smaller in patients compared to healthy subjects. However, similar to healthy controls, patients showed normal modulation of the functional organization of SI as induced by the execution of different motor tasks. Both in the control subjects and patients, cortical distances between representations of thumb and little finger increased when writing and brushing compared to the resting condition. Although, cramps only occured during writing, no differences in the organization of SI were seen among motor tasks. Our data suggest that despite alterations in the organization of primary somatosensory cortex in writer's cramp, the capability of SI to adapt dynamically to different tasks is not impaired.     

Prevalence of THAP1 sequence variants in German patients with primary dystonia

Primary dystonias are a clinically and genetically heterogeneous group of movement disorders, but only for two of them, i.e., dystonia 1 and dystonia 6, the disease causing gene has been identified. Dystonia 1 is characterized by an early onset and is caused by a mutation in the TOR1A gene. Only recently, mutations in THAP1 have been shown to be the cause of DYT6 dystonia. We analyzed 610 patients with various forms of dystonia for sequence variants in the THAP1 gene by means of high resolution melting to delineate the prevalence of sequence variants and phenotypic variability. We identified seven sequence variants in patients and one sequence variant in a control. The sequence variants were not detected in 537 healthy controls. Four patients present with generalized dystonia with speech involvement of early onset, another three patients suffered exclusively from cervical dystonia of adult onset. These findings suggest that THAP1 sequence variations seem to be associated with different ages of onset and distribution of symptoms. Consequently, the phenotypic spectrum might be broader than previously assumed. © 2010 Movement Disorder Society