The cerebellar cortex is crucial for sensorimotor integration. Sensorimotor inputs converge on cerebellar Purkinje cells via two afferent pathways: the climbing fibre pathway triggering complex spikes, and the mossy fibre-parallel fibre pathway, modulating the simple spike activities of Purkinje cells. We used, for the first time, the mouse whisker system as a model system to study the encoding of somatosensory input by Purkinje cells. We show that most Purkinje cells in ipsilateral crus 1 and crus 2 of awake mice respond to whisker stimulation with complex spike and/or simple spike responses. Single-whisker stimulation in anaesthetised mice revealed that the receptive fields of complex spike and simple spike responses were strikingly different. Complex spike responses, which proved to be sensitive to the amplitude, speed and direction of whisker movement, were evoked by only one or a few whiskers. Simple spike responses, which were not affected by the direction of movement, could be evoked by many individual whiskers. The receptive fields of Purkinje cells were largely intermingled, and we suggest that this facilitates the rapid integration of sensory inputs from different sources. Furthermore, we describe that individual Purkinje cells, at least under anaesthesia, may be bound in two functional ensembles based on the receptive fields and the synchrony of the complex spike and simple spike responses. The 'complex spike ensembles' were oriented in the sagittal plane, following the anatomical organization of the climbing fibres, while the 'simple spike ensembles' were oriented in the transversal plane, as are the beams of parallel fibres.

OBJECT Patients with syndromic and complex craniosynostosis are characterized by the premature fusion of one or more cranial sutures. These patients are at risk for developing elevated intracranial pressure (ICP). There are several factors known to contribute to elevated ICP in these patients, including craniocerebral disproportion, hydrocephalus, venous hypertension, and obstructive sleep apnea. However, the causal mechanism is unknown, and patients develop elevated ICP even after skull surgery. In clinical practice, the occipitofrontal circumference (OFC) is used as an indirect measure for intracranial volume (ICV), to evaluate skull growth. However, it remains unknown whether OFC is a reliable predictor of ICV in patients with a severe skull deformity. Therefore, in this study the authors evaluated the relation between ICV and OFC. METHODS Eighty-four CT scans obtained in 69 patients with syndromic and complex craniosynostosis treated at the Erasmus University Medical Center-Sophia Children’s Hospital were included. The ICV was calculated based on CT scans by using autosegmentation with an HU threshold < 150. The OFC was collected from electronic patient files. The CT scans and OFC measurements were matched based on a maximum amount of the time that was allowed between these examinations, which was dependent on age. A Pearson correlation coefficient was calculated to evaluate the correlations between OFC and ICV. The predictive value of OFC, age, and sex on ICV was then further evaluated using a univariate linear mixed model. The significant factors in the univariate analysis were subsequently entered in a multivariate mixed model. RESULTS The correlations found between OFC and ICV were r = 0.908 for the total group (p < 0.001), r = 0.981 for Apert (p < 0.001), r = 0.867 for Crouzon-Pfeiffer (p < 0.001), r = 0.989 for Muenke (p < 0.001), r = 0.858 for Saethre- Chotzen syndrome (p = 0.001), and r = 0.917 for complex craniosynostosis (p < 0.001). Age and OFC were significant predictors of ICV in the univariate linear mixed model (p < 0.001 for both factors). The OFC was the only predictor that remained significant in the multivariate analysis (p < 0.001). CONCLUSIONS The OFC is a significant predictor of ICV in patients with syndromic and complex craniosynostosis. Therefore, measuring the OFC during clinical practice is very useful in determining which patients are at risk for impaired skull growth.

PurposeBrain abnormalities in patients with syndromic craniosynostosis can either be a direct result of the genetic defect or develop secondary to compression due to craniosynostosis, raised ICP or hydrocephalus. Today it is unknown whether children with syndromic craniosynostosis have normal brain volumes. The purpose of this study was to evaluate brain and ventricular volume measurements in patients with syndromic and complex craniosynostosis. This knowledge will improve our understanding of brain development and the origin of raised intracranial pressure in syndromic craniosynostosis.MethodsBrain and ventricular volumes were calculated from MRI scans of patients with craniosynostosis, 0.3 to 18.3 years of age. Brain volume was compared to age matched controls from the literature. All patient charts were reviewed to look for possible predictors of brain and ventricular volume.ResultsTotal brain volume in syndromic craniosynostosis equals that of normal controls, in the age range of 1 to 12 years. Brain growth occurred particularly in the first 5 years of age, after which it stabilized. Within the studied population, ventricular volume was significantly larger in Apert syndrome compared to all other syndromes and in patients with a Chiari I malformation.ConclusionsPatients with syndromic craniosynostosis have a normal total brain volume compared to normal controls. Increased ventricular volume is associated with Apert syndrome and Chiari I malformations, which is most commonly found in Crouzon syndrome. We advice screening of all patients with Apert and Crouzon syndrome for the development of enlarged ventricle volume and the presence of a Chiari I malformation.

Therapeutic, III.