Long-term effect of prednisolone on functional blink recovery after transient peripheral facial motor paralysis.

Objective: To determine the functional recovery in patients with severe transient peripheral facial motor paralysis (Bell palsy).

Study Design: Prospective controlled trial.

Setting: Academic medical center.

Anti-malaria drug mefloquine induces motor learning deficits in humans.

Mefloquine (a marketed anti-malaria drug) prophylaxis has a high risk of causing adverse events. Interestingly, animal studies have shown that mefloquine imposes a major deficit in motor learning skills by affecting the connexin 36 gap junctions of the inferior olive. We were therefore interested in assessing whether mefloquine might induce similar effects in humans.

Long-term changes in cerebellar activation during functional recovery from transient peripheral motor paralysis.

Localized altered cerebellar cortical activity can be associated with short-term changes in motor learning that take place in the course of hours, but it is unknown whether it can be correlated to long-term recovery from transient peripheral motor diseases, and if so, whether it occurs concomitantly in related brain regions. Here we show in a longitudinal fMRI study of patients with unilateral Bell's palsy that increases in ipsilateral cerebellar activity follow the recovery course of facial motor functions over at least one and a half years. These findings hold true for changes in brain activity related to both oral and peri-orbital activation, even though these processes are differentially mediated by unilateral and bilateral brain connectivities, respectively.

Savings and extinction of conditioned eyeblink responses in fragile X syndrome.

The fragile X syndrome (FRAXA) is the most widespread heritable form of mental retardation caused by the lack of expression of the fragile X mental retardation protein (FMRP). This lack has been related to deficits in cerebellum-mediated acquisition of conditioned eyelid responses in individuals with FRAXA. In the present behavioral study, long-term effects of deficiency of FMRP were investigated by examining the acquisition, savings and extinction of delay eyeblink conditioning in male individuals with FRAXA.

Are locus coeruleus neurons involved in blinking?

To investigate the involvement of the noradrenergic locus coeruleus (LC) in the reflex blink circuit, c-Fos and neuronal tracer experiments were performed in the rat. LC neurons involved in reflex blink were localized by analyzing c-Fos protein expression after electrical stimulation of the supraorbital nerve. Subsequently, neuronal tracers were injected in two different nuclei which are part of the reflex blink circuit.

Exceptional good cognitive and phenotypic profile in a male carrying a mosaic mutation in the FMR1 gene.

Fragile X (FRAX) syndrome is a commonly inherited form of mental retardation resulting from the lack of expression of the fragile X mental retardation protein (FMRP). It is caused by a stretch of CGG repeats within the fragile X gene, which can be unstable in length as it is transmitted from generation to generation. Once the repeat exceeds a threshold length, the FMR1 gene is methylated and no protein is produced resulting in the fragile X phenotype.

Blink recovery in patients with Bell's palsy: a neurophysiological and behavioral longitudinal study.

Purpose: To examine the recovery process of blinking in a longitudinal study of nine patients severely affected by Bell's palsy.

Methods: Kinematics of bilateral eyelid and eye movements and concomitant orbicularis oculi activity during voluntary blinking and air-puff- and acoustic-click-induced reflex blinking were determined by using the magnetic search coil technique and electromyographic recording of the orbicularis oculi muscle (OO-EMG).

Results: In the first 3 months of absence of OO-EMG activity, reduced eyelid and eye movement of the palsied eyelid were observed during all types of blinking.

Reticulo-collicular and spino-collicular projections involved in eye and eyelid movements during the blink reflex.

Reflex blinking provides a useful experimental tool for various functional studies on the peripheral and central nervous system, yet the neuronal circuitry underlying this reflex is not precisely known. In the present study, we investigated as to whether neurons in the reticular formation and rostral cervical spinal cord (C1) may be involved in the blink reflex in rats. To this end we investigated c-Fos expression in these areas following supraorbital nerve stimulation combined with retrograde tracing of gold conjugated horse radish peroxidase (Gold-HRP) from the superior colliculus.

Eyelid movements during blinking in patients with Parkinson's disease.

We examined eyelid movements during spontaneous, voluntary, and trigeminal reflex blinks in 16 patients with mild to moderate Parkinson's disease (PD) off medication and 14 controls. Voluntary and reflex blink amplitudes tended to be smaller than normal for PD patients, whereas eyelid kinematics (amplitude-maximum velocity relationship) for all three blink types were normal. Spontaneous blink rate was less than normal for 10 patients and abnormally high for 6 patients.

Deletion of FMR1 in Purkinje cells enhances parallel fiber LTD, enlarges spines, and attenuates cerebellar eyelid conditioning in Fragile X syndrome.

Absence of functional FMRP causes Fragile X syndrome. Abnormalities in synaptic processes in the cerebral cortex and hippocampus contribute to cognitive deficits in Fragile X patients. So far, the potential roles of cerebellar deficits have not been investigated.

Reticulo-collicular projections: a neuronal tracing study in the rat.

Neuroanatomical tract-tracing methods were used to study the topography of the reticulocollicular projections. Injections of gold-HRP or BDA tracers into the medial and/or central portions of the superior colliculus resulted in labelled neurones mainly in the medial reticular formation, whereas injections into the lateral portion of the superior colliculus showed labelling in the medial and lateral reticular formation. When tracer was injected into the lateral portion of the caudal superior colliculus, extensive lateral labelling was observed in the contralateral parvocellular reticular nucleus and the contralateral dorsal medullary reticular nucleus, two areas involved in reflex blinking.

Connections between the lacrimal gland and sensory trigeminal neurons: a WGA/HRP study in the cynomolgous monkey.

The sensory innervation of the lacrimal gland (LG) in the cynomolgous monkey was studied using the retrograde wheat germ agglutinin/horsereadish peroxidase (WGA/HRP) tracer technique. A small solidified piece of WGA/HRP was implanted in the LG. Labelled sensory first-order neurons were found in the ipsilateral trigeminal ganglion (TG) and in the ipsilateral mesencephalic trigeminal nucleus (MTN).

Projections from the superior colliculus to the trigeminal system and facial nucleus in the rat.

To determine the influence of the superior colliculus (SC) in orienting behaviors, we examined SC projections to the sensory trigeminal complex, the juxtatrigeminal region, and the facial motor nucleus in rats. Anterograde tracer experiments in the SC demonstrated predominantly contralateral colliculotrigeminal projections. Microinjections in the deep layers of the lateral portion showed labeled nerve fibers and terminals in the ventromedial parts of the caudal principal nucleus and of the rostral oral subnucleus and in the medial part of the interpolar subnucleus.

Eyelid movements: behavioral studies of blinking in humans under different stimulus conditions.

The kinematics and neurophysiological aspects of eyelid movements were examined during spontaneous, voluntary, air puff, and electrically induced blinking in healthy human subjects, using the direct magnetic search coil technique simultaneously with electromyographic recording of the orbicularis oculi muscles (OO-EMG). For OO-EMG recordings, surface electrodes were attached to the lower eyelids. To measure the vertical lid displacement, a search coil with a diameter of 3 mm was placed 1 mm from the rim on the upper eyelid on a marked position.

Organization of trigeminocollicular connections and their relations to the sensory innervation of the eyelids in the rat.

Relationships between the trigeminal component of blinking and the superior colliculus (SC) were studied in rats. To localize primary afferent eyelid projections in the sensory trigeminal complex, neuronal tracing experiments were performed as well as analysis of c-Fos protein expression after supraorbital (SO) nerve stimulation. Labelled nerve fibers were found to enter ventrally within the ipsilateral sensory trigeminal complex.

Lack of blood-brain barrier properties in microvessels of the prelaminar optic nerve head.

Purpose: To define the blood-brain barrier (BBB) characteristics of microvessels in the optic nerve head (ONH).

Methods: Immunohistochemical staining of different regions of the ONH, retro-laminar optic nerve, and retina of human and monkey eyes was carried out, using antibodies against BBB markers (glucose transporter 1, transferrin receptor, and P-glycoprotein), the non-BBB marker PAL-E, and against plasma proteins fibrinogen and IgG, which serve as endogenous markers of nonspecific microvascular permeability. In the ONH of monkey eyes, the number of transport-related endothelial pinocytotic vesicles and their cellular distribution within the microvessels were determined by electron microscopy.

Connections between the trigeminal mesencephalic nucleus and the superior colliculus in the rat.

Retrograde tracing methods are employed here to demonstrate that neurons in the trigeminal mesencephalic nucleus (5me) project to the superior colliculus (SC) in the rat. These neurons, mainly of small size, are situated bilaterally in the caudal part of the nucleus. Anterograde tracing studies demonstrated the existence of SC projections to neurons in 5me.

Retrograde tracing studies of subdivisions of the orbicularis oculi muscle in the rhesus monkey.

Functionally and anatomically, the orbicularis oculi (OO) muscle can be subdivided in a pretarsal, a preseptal, and an orbital portion. In the rhesus monkey, fluorescent and neuronal retrograde tracing experiments were performed in the pretarsal or the orbital portion of the OO muscle, or both, using fast blue, diamidino yellow, and wheat germ agglutinin-horseradish peroxidase as tracers. The preseptal portion was not investigated because of close anatomical relationships to the other portions.

Sensory innervation of conjunctival lymph follicles in cynomolgus monkeys.

Purpose: The importance of neuroregulation of immunoresponsiveness is recognized, but little is known of the innervation of conjunctival follicles. The access and distribution of nerves in follicles of the palpebral conjunctiva were therefore studied and those of trigeminal nerve origin distinguished.

Methods: Serial sections of follicles were prepared for light and selected sections for electron microscopy.

A retrograde double fluorescent tracing study of the levator palpebrae superioris muscle in the cynomolgus monkey.

In the cynomolgus monkey, motoneurons innervating the levator palpebrae superioris muscle form a nucleus within the oculomotor nuclei called the central caudal nucleus. After double fluorescent neuronal retrograde tracing experiments, using fast blue and diamidino yellow as tracers in the levator palpebrae superior muscles, labelled motoneurons (30%) were found in an unpaired central caudal nucleus. Approximately 2% of the labelled motoneurons were double-labelled.