Novel findings in a Swedish primary familial brain calcification cohort.

Introduction: Brain calcifications are frequent findings on imaging. In a small proportion of cases, these calcifications are associated with pathogenic gene variants, hence termed primary familial brain calcification (PFBC). The clinical penetrance is incomplete and phenotypic variability is substantial.

Safety and efficacy of rituximab versus dimethyl fumarate in patients with relapsing-remitting multiple sclerosis or clinically isolated syndrome in Sweden: a rater-blinded, phase 3, randomised controlled trial.

Background: B-cell depleting therapies are highly efficacious in relapsing-remitting multiple sclerosis but one such therapy, rituximab, is not approved for multiple sclerosis and no phase 3 trial data are available. We therefore examined the safety and efficacy of rituximab compared with dimethyl fumarate in patients with relapsing-remitting multiple sclerosis to obtain data that might allow inclusion of rituximab in treatment guidelines.

Methods: RIFUND-MS was a multicentre, rater-blinded, active-comparator, phase 3, randomised controlled trial done at 17 Swedish university and community hospitals.

The unique rectus extraocular muscles of cetaceans: Homologies and possible functions.

Each rectus extraocular muscle in cetaceans divides into two portions: a massive palpebral belly that inserts into the deep surface of the eyelids and a smaller scleral belly that inserts onto the eyeball. While the cetacean palpebral insertions have long been recognized, their homologies and functions remain unclear. To compare cetacean rectus EOM insertions with the global and orbital rectus EOM insertions of other mammals we dissected orbital contents of 20 odontocete species, 2 mysticete species and 18 non-cetacean species, both aquatic and terrestrial.

The oblique extraocular muscles in cetaceans: Overall architecture and accessory insertions.

The oblique extraocular muscles (EOMs) were dissected in 19 cetacean species and 10 non-cetacean mammalian species. Both superior oblique (SO) and inferior oblique (IO) muscles in cetaceans are well developed in comparison to out-groups and have unique anatomical features likely related to cetacean orbital configurations, swimming mechanics, and visual behaviors. Cetacean oblique muscles originate at skeletal locations typical for mammals: SO, from a common tendinous cone surrounding the optic nerve and from the medially adjacent bone surface at the orbital apex; IO, from the maxilla adjacent to lacrimal and frontal bones.

Cetacean Orbital Muscles: Anatomy and Function of the Circular Layers.

Dissections of cetacean orbits identified two distinct circular muscle layers that are uniquely more elaborate than the orbitalis muscles described in numerous mammals. The circular orbital muscles in cetaceans form layers that lie both external and internal to the rectus extra ocular muscles (EOMs). A cone-shaped external circular muscle (ECM) that invests the external surface of the rectus EOMs was found in all cetacean specimens examined.

Hindbrain neurovascular anatomy of adult goldfish (Carassius auratus).

The goldfish hindbrain develops from a segmented (rhombomeric) neuroepithelial scaffold, similar to other vertebrates. Motor, reticular and other neuronal groups develop in specific segmental locations within this rhombomeric framework. Teleosts are unique in possessing a segmental series of unpaired, midline central arteries that extend from the basilar artery and penetrate the pial midline of each hindbrain rhombomere (r).

Rituximab treatment did not aggravate ongoing progressive multifocal leukoencephalopathy in a patient with multiple sclerosis.

A multiple sclerosis (MS) patient developed progressive multifocal leukoencephalopathy (PML) after 43 months of natalizumab treatment. New clinical and magnetic resonance imaging (MRI) findings were initially misinterpreted as breakthrough MS disease activity and natalizumab treatment was replaced by rituximab treatment. The patient had a single infusion of rituximab 1000 mg before a definite PML diagnosis was confirmed.

A hindbrain segmental scaffold specifying neuronal location in the adult goldfish, Carassius auratus.

The vertebrate hindbrain develops as a series of well-defined neuroepithelial segments or rhombomeres. While rhombomeres are visible in all vertebrate embryos, generally there is not any visible segmental anatomy in the brains of adults. Teleost fish are exceptional in retaining a rhombomeric pattern of reticulospinal neurons through embryonic, larval, and adult periods.

Ancestry of motor innervation to pectoral fin and forelimb.

Motor innervation to the tetrapod forelimb and fish pectoral fin is assumed to share a conserved spinal cord origin, despite major structural and functional innovations of the appendage during the vertebrate water-to-land transition. In this paper, we present anatomical and embryological evidence showing that pectoral motoneurons also originate in the hindbrain among ray-finned fish. New and previous data for lobe-finned fish, a group that includes tetrapods, and more basal cartilaginous fish showed pectoral innervation that was consistent with a hindbrain-spinal origin of motoneurons.

Amphioxus and the evolution of head segmentation.

Whether or not the vertebrate head is fundamentally segmented has been controversial for over 150 years. Beginning in the late 19th century, segmentalist theories proposed that the vertebrate head evolved from an amphioxus-like ancestor in which mesodermal somites extended the full length of the body with remnants of segmentation persisting as the mesodermal head cavities of sharks and lampreys. Antisegmentalists generally argued either that the vertebrate ancestors never had any mesodermal segmentation anteriorly or that they lost it before the origin of the vertebrates; in either case, the earliest vertebrates had an unsegmented head and the embryonic cranial mesoderm of vertebrates is at best pseudo-segmented, evolving independently of any pre-vertebrate segmental pattern.

Evolutionary origins for social vocalization in a vertebrate hindbrain-spinal compartment.

The macroevolutionary events leading to neural innovations for social communication, such as vocalization, are essentially unexplored. Many fish vocalize during female courtship and territorial defense, as do amphibians, birds, and mammals. Here, we map the neural circuitry for vocalization in larval fish and show that the vocal network develops in a segment-like region across the most caudal hindbrain and rostral spinal cord.

Preservation of segmental hindbrain organization in adult frogs.

To test for possible retention of early segmental patterning throughout development, the cranial nerve efferent nuclei in adult ranid frogs were quantitatively mapped and compared with the segmental organization of these nuclei in larvae. Cranial nerve roots IV-X were labeled in larvae with fluorescent dextran amines. Each cranial nerve efferent nucleus resided in a characteristic segmental position within the clearly visible larval hindbrain rhombomeres (r).

Evolutionary patterns of cranial nerve efferent nuclei in vertebrates.

All vertebrates have a similar series of rhombomeric hindbrain segments within which cranial nerve efferent nuclei are distributed in a similar rostrocaudal sequence. The registration between these two morphological patterns is reviewed here to highlight the conserved vs. variable aspects of hindbrain organization contributing to diversification of efferent sub-nuclei.

Myelin tetraspan family proteins but no non-tetraspan family proteins are present in the ascidian (Ciona intestinalis) genome.

Several of the proteins used to form and maintain myelin sheaths in the central nervous system (CNS) and the peripheral nervous system (PNS) are shared among different vertebrate classes. These proteins include one-to-several alternatively spliced myelin basic protein (MBP) isoforms in all sheaths, proteolipid protein (PLP) and DM20 (except in amphibians) in tetrapod CNS sheaths, and one or two protein zero (P0) isoforms in fish CNS and in all vertebrate PNS sheaths. Several other proteins, including 2', 3'-cyclic nucleotide 3'-phosphodiesterase (CNP), myelin and lymphocyte protein (MAL), plasmolipin, and peripheral myelin protein 22 (PMP22; prominent in PNS myelin), are localized to myelin and myelin-associated membranes, though class distributions are less well studied.

Quantifying the ontogeny of optokinetic and vestibuloocular behaviors in zebrafish, medaka, and goldfish.

We quantitatively studied the ontogeny of oculomotor behavior in larval fish as a foundation for studies linking oculomotor structure and function with genetics. Horizontal optokinetic and vestibuloocular reflexes (OKR and VOR, respectively) were measured in three different species (goldfish, zebrafish, and medaka) during the first month after hatching. For all sizes of medaka, and most zebrafish, Bode plots of OKR (0.

Differential spatial organization of otolith signals in frog vestibular nuclei.

Activation maps of pre- and postsynaptic field potential components evoked by separate electrical stimulation of utricular, lagenar, and saccular nerve branches in the isolated frog hindbrain were recorded within a stereotactic outline of the vestibular nuclei. Utricular and lagenar nerve-evoked activation maps overlapped strongly in the lateral and descending vestibular nuclei, whereas lagenar amplitudes were greater in the superior vestibular nucleus. In contrast, the saccular nerve-evoked activation map coincided largely with the dorsal nucleus and the adjacent dorsal part of the lateral vestibular nucleus, corroborating a major auditory and lesser vestibular function of the frog saccule.

Efficacy and tolerability of levetiracetam during 1-year follow-up in patients with refractory epilepsy.

Problem: Levetiracetam (LEV) is a new antiepileptic drug shown to be effective for the treatment of partial seizures in pivotal clinical trials. We investigated the long-term efficacy and tolerability of LEV as add-on therapy, regardless of seizure type, especially in persons who would not be eligible for clinical trials due to factors such as mental retardation and concomitant psychiatric disorders.

Methods: Ninety-eight patients participated and were followed for 1 year.

The frog as a unique vertebrate model for studying the rhombomeric organization of functionally identified hindbrain neurons.

The segmental organization of cranial nerve efferent, vestibular, and precerebellar neurons of larval ranid frogs is essentially retained in adult frogs, indicating the absence of any substantial postembryonic longitudinal migration of hindbrain neurons in this group. Comparison of the rhombomeric organization of vestibulomotor and branchiomotor pathways across different species suggests that the frog hindbrain blueprint is common to most vertebrates. The unique segmental stability seen in frogs can be used to create a quantitative stereotactic map of the adult brain that mirrors the embryonic and larval rhombomeric framework.

Cerebral hypoxia-ischemia in immature rats: involvement of mitochondrial permeability transition?

The aim of this study was to evaluate the involvement of mitochondrial membrane permeability transition (MPT) after hypoxia-ischemia (HI) in 7-day-old rats. [14C]2-deoxyglucose (DOG) was administered to controls, and at various time points after HI. MPT in the cerebral cortex was measured as entrapment of DOG-6-P in mitochondria.

Rhombomeric organization of vestibular pathways in larval frogs.

Rhombencephalic subnuclei and projection pathways related to vestibular function were mapped in larval ranid frogs. The retention of overt postembryonic rhombomeres (r) allowed direct visualization of the locations of neurons retrogradely labeled with fluorescent dextran amines from the midbrain oculomotor complex, cerebellum, vestibular nuclei, and spinal cord. Oculomotor projecting vestibular neurons were mainly located in bilateral r1/2, ipsilateral r3, and contralateral r5-8, and spinal projecting vestibular neurons mainly in ipsilateral r4 and contralateral r5.

Bacterial endotoxin sensitizes the immature brain to hypoxic--ischaemic injury.

Epidemiological studies show a markedly increased risk of cerebral palsy following the combined exposure of infection and birth asphyxia. However, the underlying mechanisms of this increased vulnerability remain unclear. We have examined the effects of a low dose of bacterial endotoxin on hypoxic--ischaemic injury in the immature brain of rats.