Botulinum toxin for the treatment of spasticity in children: attainment of treatment goals

Forty patients (mean age 5 years) with a spastic disorder treated by botulinum injections (53 sessions) were evaluated for functional outcome in terms of achievement of their individual predetermined goals of treatment, rated on a modified Goal Attainment Scale from 1 (worsening function) to 4 (improved gross motor function). At the 2-week follow-up, 40% had a score of 1, 33% a score of 2, and 13% a score of 3; 12% showed no functional change. Botulinum treatments failed to significantly improve the gross motor function in this patient group. Treatment goals and expectations should clearly be established beforehand.     

Hereditary family signature of facial expression

Although facial expressions of emotion are universal, individual differences create a facial expression "signature" for each person; but, is there a unique family facial expression signature? Only a few family studies on the heredity of facial expressions have been performed, none of which compared the gestalt of movements in various emotional states; they compared only a few movements in one or two emotional states. No studies, to our knowledge, have compared movements of congenitally blind subjects with their relatives to our knowledge. Using two types of analyses, we show a correlation between movements of congenitally blind subjects with those of their relatives in think-concentrate, sadness, anger, disgust, joy, and surprise and provide evidence for a unique family facial expression signature. In the analysis "in-out family test," a particular movement was compared each time across subjects. Results show that the frequency of occurrence of a movement of a congenitally blind subject in his family is significantly higher than that outside of his family in think-concentrate, sadness, and anger. In the analysis "the classification test," in which congenitally blind subjects were classified to their families according to the gestalt of movements, results show 80% correct classification over the entire interview and 75% in anger. Analysis of the movements' frequencies in anger revealed a correlation between the movements' frequencies of congenitally blind individuals and those of their relatives. This study anticipates discovering genes that influence facial expressions, understanding their evolutionary significance, and elucidating repair mechanisms for syndromes lacking facial expression, such as autism.     

Brain correlates of discourse processing: an fMRI investigation of irony and conventional metaphor comprehension

Higher levels of discourse processing evoke patterns of cognition and brain activation that extend beyond the literal comprehension of sentences. We used fMRI to examine brain activation patterns while 16 healthy participants read brief three-sentence stories that concluded with either a literal, metaphoric, or ironic sentence. The fMRI images acquired during the reading of the critical sentence revealed a selective response of the brain to the two types of nonliteral utterances. Metaphoric utterances resulted in significantly higher levels of activation in the left inferior frontal gyrus and in bilateral inferior temporal cortex than the literal and ironic utterances. Ironic statements resulted in significantly higher activation levels than literal statements in the right superior and middle temporal gyri, with metaphoric statements resulting in intermediate levels in these regions. The findings show differential hemispheric sensitivity to these aspects of figurative language, and are relevant to models of the functional cortical architecture of language processing in connected discourse.     

Could steroids mask the diagnosis of cerebrotendinous xanthomatosis?

Cerebrotendinous xanthomatosis (CTX) is a rare autosomal recessive disorder of bile acid synthesis, caused by impaired hydroxylation of cholesterol side chains due to deficiency of the mitochondrial enzyme sterol 27-hydroxylase (CYP27A1), leading to accumulation of cholestanol and cholesterol in brain and other tissues. Elevated plasma cholestanol serves as a key marker for the clinical diagnosis of CTX. In the present report we describe a young man with CTX who was on high dose steroids for a misdiagnosed chronic inflammatory demyelinating polyneuropathy (CIDP) and had normal level of serum cholestanol. When steroids were discontinued, markedly elevated serum cholestanol was measured concomitant with marked clinical worsening. This observation may imply that steroids can lower plasma cholestanol, possibly by directly inducing residual CYP27A1 activity or by inducing alternative pathways for cholestanol elimination.     

Coupling between spontaneous (resting state) fMRI fluctuations and human oculo-motor activity

The recent discovery of incessant spontaneous fluctuations in human brain activity (also termed resting state fMRI) has been a focus of intense research in brain imaging. The spontaneous BOLD activity shows organized anatomical specialization as well as disruption in a number of brain pathologies. The link between the spontaneous fMRI fluctuations and human behavior is therefore of acute interest and importance. Here we report that a highly significant correlation exists between spontaneous BOLD fluctuations and eye movements which occur subliminally and spontaneously in the absence of any visual stimulation. Of the various eye movement parameters tested, we found robust and anatomically consistent correlations with both the amplitude and velocity of spontaneous eye movements. Control experiments ruled out a contribution of spatial and visual attention as well as smooth pursuit eye movements to the effect. The consistent anatomical specificity of the correlation patterns and their tight temporal link at the proper hemodynamic delay argues against a non-neuronal explanation of the effect, such as cardiac or respiratory cycles. Our results thus demonstrate a link between resting state and spontaneously emerging subconscious oculo-motor behavior.     

Systematic autistic-like behavioral phenotyping of 4 mouse strains using a novel wheel-running assay

Three core symptoms of autistic spectrum disorders are stereotypic movements, resistance to change in routines and deficits in social interaction. In order to understand their neuronal mechanisms, there is a dire need for behavioral paradigms to assess those symptoms in rodents. Here we present a novel method which is based on positive reward in a customized wheel-running apparatus to assess these symptoms. As a proof of concept, 4 mouse strains were tested in the new behavioral paradigm; 2 control lines (C57BL/6 and ICR) and 2 mouse-models of autism (BTBR T+ tf/J and Nlgn3(tm1Sud)). We found that the C57BL/6, ICR and Nlgn3(tm1Sud) mice showed a significant reduction in stereotypical behavior in the presence of the running wheel, ability to forfeit the running habit when the running-wheel was jammed, and preference of interacting with a social stimulus over the jammed running-wheel. No difference was found between genotypes of the Nlgn3(tm1Sud) mice. On the other hand, the BTBR mice exhibited persistent, elevated levels of stereotypical behavior. In addition, they presented a deficit in their ability to adjust to a changing environment, as manifested in persistence to interact with the wheel even when it was jammed. Lastly, the BTBR mice exhibited no significant preference to interact with the stranger mouse over the jammed running-wheel. These results were validated by a set of commonly used behavioral tests. Overall, our novel behavioral paradigm detects multiple components of autistic-like phenotypes, including cognitive rigidity, stereotypic behavior and social deficiency.     

Vitamin D diminishes the high platelet aggregation of type 2 diabetes mellitus patients

Platelet activation is found in inflammatory conditions and implicated in the pathogenesis of chronic medical conditions, such as atherosclerosis, coronary vascular disease, cerebrovascular disease, and diabetes mellitus (DM). HbA1c is inversely related to vitamin D25 levels in individuals with and without DM. This study aimed to determine the relation between platelet aggregation, vitamin D and HbA1c among healthy individuals and those with Type 2 DM (T2DM). The direct effect of vitamin D1, 25 (calcitriol) on platelet aggregation was also investigated. The study included four groups: A. normoglycemic Control group: HbA1c<5.7%; B. Pre-diabetes (DM): 5.7% ≥ HbA1c ≤ 6.4%; C. DM on aspirin therapy: HbA1c>6.4%(+)Asp.; and D. DM not on aspirin therapy: HbA1c > 6.4%(?)Asp. Platelet aggregation was tested with and without calcitriol or saline pre-treatment, using collagen or adenosine diphosphate (ADP) as agonists. Platelet aggregation was higher in DM(?)Asp group compared to normoglycemic and DM(+)Asp, and higher, but not significant compared to pre-DM. The entire study population exhibited negative correlation between HbA1c and serum concentration of vitamin D25. Excluding DM(+)Asp, aggregation induced by collagen was significantly higher in patients with insufficient (<76 nmol/L) vitamin D25 compared to sufficient (≥76 nmol/L) vitamin D25. In this cohort, a negative correlation was found between serum concentrations of vitamin D25 and collagen-induced percent maximum (%max) aggregation and area under curve (AUC) aggregation. In the DM(?)Asp group, collagen-induced aggregation was reduced by approximately 25% after calcitriol treatment. Calcitriol decreased ADP-induced aggregation of control and DM(+)Asp groups to approximately 85% of saline treatment. We conclude that glycemic control is inversely associated with high platelet aggregation and low vitamin D25 levels. This elevated aggregation could be regulated by a novel, direct effect of calcitriol, indicating a beneficial effect of vitamin D on vascular complications related to diabetes. We offer a possible non-genomic mechanism for the vitamin D/Vitamin D receptor (VDR) pathway.