Kinematics of fast wrist movements in manic-depressive illness chronically treated with lithium carbonate

Abstract

Lithium salts have been shown to impair kinematics of fast voluntary movements during acute intoxication. The aim of the present study was to determine whether lithium carbonate affected the kinematics of fast movements in patients chronically treated and who did not exhibit signs of neurotoxicity. We analysed fast wrist flexion movements in 6 healthy subjects, in 5 patients presenting a manic-depressive illness without treatment, and in 8 patients receiving lithium carbonate for a manic-depressive disease. The mean duration of treatment was 3.9±4.1 years, the mean daily dose 837±341 mg and the mean serum level 0.95±0. 15 mEq/l. Although mean movement amplitudes were similar in the 3 groups, the variability of fast movements was increased in patients receiving lithium salts. The ratio of maximum to average velocities (VmNaveJ was significantly higher in patients treated, and their movements were temporally asymmetrical, with a ratio ofacceleration duration divided by deceleration duration being lower than in the 2 other groups. These kinematic abnormalities show that a chronic treatment with lithium salts is associated with an impairment of the cerebellar control of fast single-joint movements. [Neural Res 1998; 20: 320-326]     

Motor skill learning in children with Developmental Coordination Disorder

Children with Developmental Coordination Disorder (DCD) are characterized as having motor difficulties and learning impairment that may last well into adolescence and adulthood. Although behavioral deficits have been identified in many domains such as visuo-spatial processing, kinesthetic perception, and cross-modal sensory integration, recent studies suggested that the functional impairment of certain brain areas, such as cerebellum and basal ganglia, are the underlying causes of DCD. This review focuses on the “motor learning deficits” in DCD and their possible neural correlates. It presents recent evidence from both behavioral and neuroimaging studies and discusses dominant neural hypotheses in DCD. Given the heterogeneity of this disorder, a successful intervention program should target the specific deficits on an individual basis. Future neuroimaging studies are critical steps in enhancing our understanding of learning deficits in DCD.     

Pilot study of fetal brain development and morphometry in prenatal opioid exposure and smoking on fetal MRI

PurposeThe purpose of this study was to assess for any differences in brain maturation, structure and morphometry in fetuses exposed to opioids in utero, compared to non-opioid exposed fetuses on fetal MRI.MethodsWe performed a prospective study in pregnant women using opioids and healthy pregnant women without prenatal opioid use. We evaluated brain maturation, structure, and morphometry on second or third trimester fetal MRI and assessed group differences.Results28 pregnant women were enrolled, 12 with opioid exposure (average gestational age 33.67, range 28–39 w), 9 of whom also smoked, and 16 without opioid exposure (average gestational age 32.53, range 27–38 w). There was a significant difference in the anteroposterior diameter of the fetal cerebellar vermis in the opioid exposed fetuses compared to non-opioid exposed fetuses (p = 0.004). There were no significant differences in brain biparietal diameter, fronto-occipital diameter, transverse cerebellar diameter and anteroposterior dimension of the pons in opioid exposed fetuses compared to non-opioid exposed fetuses. There were no abnormalities in brain maturation and no major brain structural abnormalities in the opioid exposed fetuses.ConclusionSmaller fetal anteroposterior cerebellar vermian dimension was associated with in utero opioid exposure. There were no abnormalities in brain maturation or major structural abnormalities in fetuses exposed to opioids.     

Role of tissue transglutaminase type 2 in calbindin-D28k interaction with ataxin-1

Spinocerebellar ataxia-1 (SCA1) is caused by the expansion of a polyglutamine repeats within the disease protein, ataxin-1. The mutant ataxin-1 precipitates as large intranuclear aggregates in the affected neurons. These aggregates may protect neurons from mutant protein and/or trigger neuronal degeneration by encouraging recruitment of other essential proteins. Our previous studies have shown that calcium binding protein calbindin-D28k (CaB) associated with SCAl pathogenesis is recruited to ataxin-l aggregates in Purkinje cells of SCAl mice. Since our recent findings suggest that tissue transglutaminase 2 (TG2) may be involved in crosslinking and aggregation of ataxin-l, the present study was initiated to determine if TG2 has any role in CaB-ataxin-l interaction. The guinea pig TG2 covalently crosslinked purified rat brain CaB. Time dependent progressive increase in aggregation produced large multimers, which stayed on top of the gel. CaB interaction with ataxin-l was studied using HeLa cell lysates expressing GFP and GFP tagged ataxin-l with normal and expanded polyglutamine repeats (Q2, Q30 and Q82). The reaction products were analyzed by Western blots using anti-polyglutamine, CaB or GFP antibodies. CaB interacted with ataxin-1 independent of TG2 as the protein-protein crosslinker DSS stabilized CaB-ataxin-l complex. TG2 crosslinked CaB preferentially with Q82 ataxin-1. The crosslinking was inhibited with EGTA or TG2 inhibitor cystamine. The present data indicate that CaB may be a TG2 substrate. In addition, aggregates of mutant ataxin-l may recruit CaB via TG2 mediated covalent crosslinking, further supporting the argument that ataxin-l aggregates may be toxic to neurons.     

Neurotoxic effects of homocysteine on cerebellar Purkinje neurons in vitro

Whilst a plethora of studies that describe the toxicity of homocysteine to CNS neurons have been published, the effects of homocysteine on the Purkinje neurons of the cerebellum that play a vital role in motor function remain wholly unexplored. We have therefore established cultures of embryonic cerebellar Purkinje neurons and exposed them to a range of concentrations of homocysteine and determined its effects on their survival. The experiments revealed that all concentrations of homocysteine studied, from 50 to 500microM, caused a significant decrease in cerebellar Purkinje neuron number. This loss could be counteracted by the pan-caspase inhibitor z-VAD-fmk in the first 24h following homocysteine exposure, revealing that the initial loss was apoptotic. However, z-VAD-fmk could not prevent homocysteine-mediated loss of cerebellar Purkinje neurons in the longer term, after 6 days in vitro. In addition to its effects on Purkinje neuron survival, homocysteine markedly reduced both the overall magnitude and the complexity of the neurite arbor extended by the cerebellar Purkinje neurons, following 6 days incubation with this agent in vitro. Taken together our data reveal that homocysteine is toxic to cerebellar Purkinje neurons in vitro, inhibiting both their survival and the outgrowth of neurites.     

Impaired predictive motor timing in patients with cerebellar disorders

The ability to precisely time events is essential for both perception and action. There is evidence that the cerebellum is important for the neural representation of time in a variety of behaviors including time perception, the tapping of specific time intervals, and eye-blink conditioning. It has been difficult to assess the contribution of the cerebellum to timing during more dynamic motor behavior because the component movements themselves may be abnormal or any motor deficit may be due to an inability to combine the component movements into a complete action rather than timing per se. Here we investigated the performance of subjects with cerebellar disease in predictive motor timing using a task that involved mediated interception of a moving target, and we tested the effect of movement type (acceleration, deceleration, constant), speed (slow, medium, fast), and angle (0°, 15° and 30°) on performance. The subjects with cerebellar damage were significantly worse at interception than healthy controls even when we controlled for basic motor impairments such as response time. Our data suggest that subjects with damage to the cerebellum have a fundamental problem with predictive motor timing and indicate that the cerebellum plays an essential role in integrating incoming visual information with motor output when making predictions about upcoming actions. The findings demonstrate that the cerebellum may have properties that would facilitate the processing or storage of internal models of motor behavior.     

Modulatory effects of 1 Hz rTMS over the cerebellum on motor cortex excitability

Clinical observations and data from animal experiments point to a physiological facilitatory influence of the deep cerebellar structures on the motor system through the cerebello-thalamo-cortical pathways. The aim of the present study was to explore the long-term effects of low-frequency (1 Hz) repetitive transcranial magnetic stimulation (rTMS) over the cerebellum on short intracortical inhibition (SICI) and facilitation (ICF) of the motor cortex in normal subjects. Eight healthy subjects (mean age 26.9 ± 3.1) underwent 1 Hz frequency rTMS delivered on the right cerebellar hemisphere. Before and after cerebellar rTMS, SICI and ICF were assessed in the motor cortex contralateral to the stimulated cerebellar hemisphere by means of a paired pulse paradigm with a conditioning subthreshold stimulus set to 80% of the motor threshold (MT) followed by a testing stimulus at 120% of MT intensity. Five different interstimulus intervals (ISIs) were used to assess SICI (2 and 4 ms) and ICF (7, 10 and 15 ms). Amplitude of the responses was expressed as the percentage of motor evoked potential (MEP) to test stimulus alone. Results showed a significant decrease of ICF at 10 ms ISI that persisted up to 20 min after cerebellar rTMS. This was the only significant modulatory effect of cerebellar stimulation on intracortical motor excitability A suppressive effect of the low-frequency TMS on Purkinje cells could be supposed, even if, the lack of effects on other facilitatory ISIs, stands for more complex modulatory effects of rTMS over cerebellum. The study is a further demonstration that rTMS over the cerebellum induces a long-lasting modulatory effect on the excitability of the interconnected motor area.     

胎儿小脑表面叶裂的产前超声研究

目的研究正常胎儿小脑表面叶裂随孕周的变化规律并建立孕16~32周正常胎儿小脑叶裂数目参考值。 方法选取2019年6月至2020年12月在南方医科大学附属深圳妇幼保健院行产前超声检查无结构异常的644名妊娠12~32周的单胎孕妇,按孕周分为2个时间段观察：孕12~15周为阶段1,孕16~32周为阶段2,在二维图像上观察原裂、水平裂的显示情况并计数孕16~32周小脑原裂之前、原裂与水平裂之间、水平裂之后的叶裂数目及总数目,并分析其形态变化。随机抽取40名阶段2胎儿行叶裂数目两测量者间的组内相关系数（ICC）分析;建立阶段2胎儿小脑叶裂数目的参考值范围,采用Spearman相关行叶裂数目与孕周的相关性分析并建立拟合方程。 结果叶裂数目的计数两观察者之间的重复性检验一致性较好（ICC=0.969,P＜0.001）。各散点图显示正常胎儿小脑原裂之前、原裂与水平裂之间、水平裂之后叶裂数目及总数目与孕周呈正相关（r=0.863、0.698、0.831、0.932,P均＜0.001）。建立了各区域叶裂数目及总数目与孕周的二次多项式回归方程,原裂之前、原裂与水平裂之间、水平裂之后叶裂数以及总数目与孕周的回归方程分别为：Y=0.974X-0.014X ² -12.65,Y=0.362X-0.005X ² -4.843,Y=-0.125X+0.006X ² +0.285,Y=1.800X-0.024X ² -22.904。 结论利用产前超声可以较好地观察胎儿小脑表面叶裂并对其发育情况作出初步评估。胎儿小脑表面叶裂数目的正常参考值以及形态变化规律能为产前超声评估小脑皮质发育作出参考。     

Brainstem arteriovenous malformation presenting with dyspraxic handwriting in a young girl

We report the case of a 11-year-old girl who developed an isolated hand-writing disorder with dysgraphia at the beginning of the school year in the sixth grade. A brain magnetic resonance angiography showed a round arteriovenous malformation sited in the left side of the midbrain extending to the ipsilateral medio-basal thalamus. Child neurologists should never neglect a thorough neurological evaluation in case of isolated worsening of handwriting, to rule out possible underlying organic causes.     

Different patterns of cerebellar abnormality and hypomyelination between POLR3A and POLR3B mutations

Background

Mutations of POLR3A and POLR3B have been reported to cause several allelic hypomyelinating disorders, including hypomyelination with hypogonadotropic hypogonadism and hypodontia (4H syndrome). Patients and methods: To clarify the difference in MRI between the two genotypes, we reviewed MRI in three patients with POLR3B mutations, and three with POLR3A mutations. Results: Though small cerebellar hemispheres and vermis are common MRI findings with both types of mutations, MRI in patients with POLR3B mutations revealed smaller cerebellar structures, especially vermis, than those in POLR3A mutations. MRI also showed milder hypomyelination in patients with POLR3B mutations than those with POLR3A mutations, which might explain milder clinical manifestations. Conclusions: MRI findings are distinct between patients with POLR3A and 3B mutations, and can provide important clues for the diagnosis, as these patients sometimes have no clinical symptoms suggesting 4H syndrome.