An elderly female patient with tardive oromandibular dystonia after prolonged use of the histamine analog betahistine.

Tardive oromandibular dystonia (OMD) is iatrogenic in origin and is characterised by orofacial and lingual stereotypes more frequently than the idiopathic form of OMD Tardive OMD is often associated with anti-dopaminergic treatment involving drugs such as anti-psychotics, anti-emetics, and anti-vertigo agents, although the syndrome can also be triggered by anti-epileptic or anti-depressant drugs that do not have anti-dopaminergic properties. We report an elderly female patient with OMD after prolonged, self-administered treatment with betahistine dihydrochloride, a histamine analogue.

Hypoglossal nucleus projections to the rat masseter muscle.

We investigated in the rat whether hypoglossal innervation extended to facial muscles other than the extrinsic musculature of the mystacial pad. Results showed that hypoglossal neurons also innervate the masseter muscle. Dil injected into the XII nucleus showed hypoglossal axons in the ipsilateral main trunk of the trigeminal nerve. After Gasser's ganglion crossing, the axons entered into the infraorbital division of the trigeminal nerve and targeted the extrinsic muscles of the mystacial pad. They also spread into the masseter branch of the trigeminal nerve to target the polar portions of the masseter muscle spindles. Retrograde double labelling, performed by injecting Dil into the pad and True Blue into the ipsilateral masseter muscle, showed labelled hypoglossal neurons in the medio-dorsal portion of the XII nucleus. The majority of these neurons were small (15-20 microm diameter), showed fluorescence for Dil and projected to the mystacial pad. Other medium-size neurons (25 microm diameter) were instead labelled with True Blue and projected to the masseter muscle. Finally, in the same area, other small hypoglossal neurons showed double labelling and projected to both structures. Functional hypotheses on the role of these hypoglossal projections have been discussed.

Hypoglossal nuclei participation in rat mystacial pad control.

Recently, we showed that extra-trigeminal axons, originating from the hypoglossal nucleus, travel with the infraorbital division of the trigeminal nerve (ION), which is known to innervate the rat mystacial pad. Dil was monolaterally injected into the rat XII nucleus to analyse the peripheral distribution of hypoglossal axons to the mystacial pad, to evaluate their involvement in facial sensory-motor control. Electromyographic responses of mystacial pad motor units to electrical stimulation of the ION were recorded, along with the evoked responses to electrical stimulation of the ipsilateral XII nucleus. The results showed that hypoglossal axon terminals target the ipsilateral extrinsic musculature of the mystacial pad, but they do not have any contact with the intrinsic muscles. ION electrical stimulation increased electromyographic activity in the ipsilateral pad extrinsic muscles, even following VII nerve transection. Hypoglossal nucleus electrical stimulation induced field potentials and monosynaptic responses in the same motor units that persisted even following VII nerve transection, these disappearing after cooling the ION. We suggest that the small hypoglossal neurons projecting to the extrinsic musculature of the mystacial pad are part of a hypoglossal-trigeminal loop that participates in the sensory-motor control of the rat vibrissae system.

Epileptic seizures after treatment with thiocolchicoside.

PURPOSE: To report the occurrence of epileptic seizures in humans, closely related to the use of the centrally acting muscle relaxant thiocolchicoside. METHODS: Description of three case histories. RESULTS: Two patients, affected with complex-partial seizures, sometimes secondarily generalized, receiving antiepileptic therapy, were seizure free for 7 and 9 years, respectively. They had the reappearance of tonic-clonic seizures few days after the continued use of thiocolchicoside, at a cumulative dose of the drug of 52 mg and 76 mg, respectively. The third patient was brain damaged and without a history of seizures. He had a sudden, convulsive seizure a few minutes after 4 mg intramuscular thiocolchicoside. CONCLUSIONS: Our case histories indicate that thiocolchicoside has a powerful epileptogenic activity. This drug should be avoided in patients with epilepsy or acute brain injury and possible disruption of the blood-brain barrier.

Epileptic discharge of cortical, subcortical and spinal neurons in penicillin induced experimental epilepsy.

The sensitivity and electrophysiological patterns of paroxysmal activity induced in different brain structures by topical application of penicillin-G were evaluated in the rat. Recordings were carried out in five groups of animals, in telencephalon, diencephalon, mesencephalon, rombencephalon and spinal cords. The following analysis were carried out: frequency distribution histograms, latency and time course duration of paroxysmal activity, duration and amplitude of epileptic bursts. The results obtained showed that the nervous structures tested with penicillin-G had a different epileptogenic sensitivity and response pattern which significantly changed along the cerebral cortex-spinal cord axis. The highest epileptic sensitivity was observed in somatosensory cortex (SI) at 500-600 microns depth; in the other cortical layers, a significant lenghtening in latency was observed. Among the other structures, the spinal cord seemed to be the most sensitive target to the epileptogenic action of penicillin-G, whereas in the remaining structures, sensitivity significantly decreased in rostro-caudal direction. As far as the features of the paroxysmal activity are concerned, significant differences among tested structures were observed. In particular, within the SI cortex, the main differences were represented by the gradual increase in burst frequency and voltage from the surface to the IVth layer and by their subsequent decrease in deeper layers (V-VI). In the diencephalon, the paroxysmal activity was similar to that observed in more superficial and deeper cortical layers even though epileptic bursts showed a lower amplitude. Mesencephalon and rombencephalon displayed a paroxysmal activity with a distinctive feature, characterized by long lasting bursts of low amplitude, although bulbar outbursts showed a shorter duration than the mesencephalic ones. In the spinal cord, the epileptiform activity displayed a different paroxysmal pattern, characterized by the longest duration and the highest amplitude. The different sensitivities of the investigated brain structures to penicillin-G and the characteristics of the induced paroxysmal activity have been extensively discussed.

Tubulin isoforms are differently expressed in developing and mature neurons: a study on the cerebral cortex of newborn and adult rats.

Tubulin heterogeneity was observed in the rat brain, where these proteins can vary in different neurons suggesting multiple functions. In this paper, the different expression of tubulins in cerebral cortex between newborn and adult rats was analyzed by Western blot and immunocytochemical methods, using anti-tubulin antibodies. Our results showed that tubulins were present at higher levels in the newborn than in the adult cerebral cortex. In newborn rats, a marked staining of the perikarya and basal dendrites of pyramidal cells was noted. This significant expression of tubulins in the newborn cerebral cortex could be related to the major needs of tubulins in developing neurons. The higher amount in tyrosine-tubulin and class III beta-tubulin could be consistent with the state of "dynamic instability", typical of the microtubular network of neurons during brain development.

Co-variation of free amino acids in brain interstitial fluid during pentylenetetrazole-induced convulsive status epilepticus.

Effects of pentylenetetrazole (PTZ)-induced convulsive status epilepticus on free amino acids changes in venous blood, CSF and interstitial fluid (IF) of the brain were examined in dogs. A volume of brain IF sufficient for analysis was obtained by chronically implanted tissue cages. The onset of PTZ-induced convulsive seizures seemed mainly related to a marked increase of glutamate, aspartate, taurine, glycine and phosphoserine while, the maintenance and frequency of seizures seemed related to a marked increase of serine and glycine, in combination with a moderate rise of glutamate. L-alpha-Aminoadipate was recovered in moderate amount in epileptic brain IF, while, in controls, this compound was present in minimal amount. The observed complex temporal variation of the amino acidic pattern may play a role in PTZ-induced seizures and, possibly, in pharmacological kindling and brain structural alterations induced by PTZ.

Beta-endorphin and cortisol levels in plasma and CSF following acute experimental spinal traumas.

beta-endorphin and cortisol were measured in cerebrospinal fluid (CSF) and plasma by radioimmunological method (RIA) in two groups of rabbits with spinal cord traumatic injuries at cervical and lumbar levels, respectively with and without concomitant spinal shock and arterial hypotension, and in a group of sham operated animals as controls. The two groups with spinal lesions displayed a significant beta-endorphin increase in CSF, whereas the cortisol level remained unchanged both in the spinal traumatized rabbits and in controls. Both the opioid and the cortisol concentration rose significantly in plasma in all three groups and in particular resulted significantly higher in the cervical traumatized group where spinal trauma was associated with spinal shock and hypotension. However, no significant difference was found when beta-endorphin concentrations in plasma were compared between the sham operated animals and the spinal lumbar traumatized animals without concomitant spinal shock. The results seem to suggest that the beta-endorphin increase in CSF is related to the nervous tissue lesion, while its increase in plasma, like that of cortisol, is due to surgery or other stress factors inherent in the experiment. This independent behaviour of beta-endorphin in plasma and in CSF suggests its different origin in these two compartments.

Olfactory influence on tongue activity.

Recent findings have shown that olfactory stimulation by brief puffs of air odorized with amyl acetate induces several patterns of response in rabbit hypoglossal neurons. It has been argued that the functional role of the olfactory input may be the modulation of tongue muscular tone during the oral phase of digestion. In the present research, the peripheral effect of olfactory-hypoglossal modulation was analyzed. Both the spike traffic along the fibers of the hypoglossal nerve and the electromyographic activity of single tongue muscles (genioglossus, styloglossus, superior longitudinal and hyoglossus) were recorded before, during and after olfactory stimulation. Results showed that brief puffs of air odorized with amyl acetate induced a significant change in the efferent volleys along the hypoglossal nerve, as well as a substantial modulation of tongue muscle activity. Olfactory stimulation induced a significant increase in the spontaneous activity of both type I and type II genioglossal fibers; excitation followed by inhibition both in tonic and phasic styloglossal fibers; excitatory responses in tonic and phasic superior longitudinal fibers and short-lasting excitatory responses in the hyoglossal fibers. The diverse patterns of activation of the tested muscle and the significant differences between fibers, tonically or phasically controlled by the XIIth neurons, indicate that olfaction may be strongly involved in tongue reflex regulation. Different functional hypothesis are discussed about the role played by olfaction in the economy of tongue muscle activity.

Antiepileptic treatment and oculomotor neurons.

This report describes the changes of the spontaneous firing rate due to an acute non-toxic dose of phenytoin (PHT), a drug commonly used in antiepileptic therapy, in the pre-motor neurons involved in saccadic movement. The drug (500 mg/kg of a 10% PHT suspension in arabic gum) was orally administered, and plasma and brain levels were regularly evaluated (EMIT assay). Results show that PHT significantly modifies the spontaneous electrical activity of the pre-motor neurons localized in the paramedian pontine reticular formation by inducing excitation, inhibition, or a biphasic effect. PHT action was observed 10-15 min after drug administration, when plasma and brain concentrations were still very low. The oculomotor system neurons appear to be a more specific target to this drug in comparison to the cerebellum and the vestibular system. Since the PHT action was observed 1 hour after drug administration in the vestibular nuclei and the cerebellum, which are extensively connected with the oculomotor neurons, it is possible to hypothesize that PHT can affect the oculomotor neurons directly and, with longer latency, indirectly through the vestibular nuclei and the cerebellum.

Brain electrobiogenesis protection induced by nimodipine and MK-801 during acute hypoxia in hypertensive rats.

The protective effect of nimodipine, a calcium entry blocker, and MK-801, an excitatory amino acid antagonist, on the cortical electrobiogenesis of hypertensive SHR-Charles-River adult rats during a 90-s session of acute hypoxia, was tested either with a single treatment or with a therapeutic association. Pretreatment with nimodipine alone (0.1 mg kg-1, i.v.) was particularly effective in increasing the rat brain resistence to hypoxia when compared to the controls. MK-801 pretreatment alone (3 mg kg-1, subcutaneous), improved significantly the recovery of brain electrical activity from hypoxia, as it not only shortened the recovery time but also abolished the post-hypoxic burst activity. The combined pretreatment with both drugs, using the same doses, displayed a more powerful brain protective effect on the cortical electrobiogenesis than the single drug pretreatment, suggesting the existence of a synergy between nimodipine and MK-801.

Effect of fetal hypoxia on seizure susceptibility in rats.

In the present study, susceptibility to Pentylentetrazol (PTZ)-induced seizures was tested in 45 four-wk old rats born to mothers exposed to moderate asphyxia in the last week of pregnancy by breathing N2 99.9% for 6 min in two separate sessions, (Group I--experimental rats) and in 44 rats of the same age, born after a normal pregnancy (Group II--controls). The results showed that the experimental rats, following episodes of asphyxia in intrauterine life, had a higher susceptibility to PTZ-induced seizures than the controls, manifested by earlier onset of convulsions and a higher incidence of fetal epileptic status. This occurred despite normal development and the absence of neurological deficits in the experimental rats in the first 4 wk of extrauterine life.

Cerebellar and mesencephalic influence on bulbar penicillin-G epileptogenesis in rats.

The influence of the cerebellum and mesencephalon on epileptic bulbar discharge induced by topical application of penicillin-G on the floor of the IVth ventricle was analyzed in rats. Bulbar multiunit activity was recorded at different depths. The animals were divided into two main groups: totally cerebellectomized rats (Group I) and lobus anterior cerebellectomized rats (Group II). Each main group was further subdivided into two subgroups: animals with intact mesencephalon and animals with transected mesencephalon. In Group I: the total cerebellectomy, in intact mesencephalic rats (first subgroup) induced a sudden disappearance of bulbar epileptic discharge. The mid-collicular transection (second subgroup) produced the immediate disappearance of bulbar paroxysms and the total cerebellectomy, subsequently performed, further decreased the spontaneous firing rate. In Group II: (first subgroup) the lobus anterior ablation in rats with intact mesencephalon, significantly enhanced the paroxysmal discharge. In the second subgroup, where the midcollicular transection had provoked the disappearance of bulbar paroxysms, the lobus anterior ablation induced the immediate reappearance of the paroxysmal activity. The penicillin-G epileptogenic activity showed a different intensity at different depths in the bulb with a maximum intensity at the level of the vestibular nuclei. In conclusion, the present study shows that both the mesencephalon and the cerebellum have a facilitating influence on bulbar epileptic discharge induced by the topical application of the GABA antagonist. However, not all the cerebellum has a facilitating effect, because the anterior lobus was found to have an inhibitory influence on bulbar discharge.(ABSTRACT TRUNCATED AT 250 WORDS)

Visual and vestibular projections to tongue motoneurons.

The rabbit hypoglossal neurons, localized in the mediocaudal part of the XIIth nucleus, receive visual and vestibular inputs able to induce reflex responses functionally driven both to prepare the oral cavity for food reception and to ensure a correct postural arrangement of the tongue. The aim of the present research was to show a possible convergence of visual input on the hypoglossal neurons modulated by the vestibular system and, thus, demonstrate that visual input plays a part in the control of the tongue posture. It was found that 78% of tested neurons responded to both photic stimulation of the retinae, performed by a conventional strobe unit, and electrical stimulation of the labyrinth, with different patterns of response. Moreover, visual input significantly modified both the hypoglossal neuron response and the electromyographic genioglossal response to caloric stimulation of the labyrinth. Because a significant visual influence on the hypoglossal nucleus response and the genioglossal muscle response to labyrinthine stimulation was observed, it can be concluded that vision does integrate the spatial information of the labyrinth to modulate the postural tone of the tongue muscles.

The brainstem cardioarrhythmogenic triggers and their possible role in sudden epileptic death.

The cardiovascular effects of simultaneous activation of hypothalamic and mesencephalic cardioarrhythmogenic triggers were studied in hemispherectomized rats. Paroxysmal activity of hypothalamic neurons (HEF), elicited by topical application of penicillin G on the thalamus, triggered short-lasting bradyarrhythmic episodes, up to a maximum of 6 s, and alterations in repolarization. In the hypothalamic neurons, an additional penicillin G epileptic focus at mesencephalic level (MEF) induced the enhancement of paroxysmal activity by a recruitment of new units and potentiation of their background activity. HEF+MEF triggered second-degree 2:1-8:1 atrioventricular (A-V) blocks, impairment of the A-V conduction, alterations in the recovery phase and bundle branch blocks. After HEF, the arterial blood pressure decreased by 4-6%. HEF+MEF induced a further reduction of 17% in systolic pressure only. It is possible that the enhancement of the HEF following MEF could depend on MEF spreading upward. The HEF, in turn, by spreading downward could influence the MEF and so activate, between HEF and MEF, a circuitry with reciprocal co-excitation that could explain the more serious cardiovascular alterations observed during HEF+MEF compared with those observed during HEF only or during MEF only. However, this cardiovascular impairment, which must be neurogenic in origin as it was observed in animals with normal acid-base and blood parameter values, did not induce heart death. Thus, additional concomitances must be considered, such as metabolic derangement which can occur during seizures, to explain sudden death in epileptic patients. Some aspects of metabolic complications in cardiac activity during epilepsy are also discussed.

The pyramidal tract of the hedgehog (Erinaceus europaeus) and its relationship with the olfactory bulb.

The pyramidal tract of the hedgehog has been investigated. The motor cerebral cortex was first located electrophysiologically and subsequently ablated. Ablation of the motor cortex did not apparently cause motor deficits. The cerebral hemisphere of the operated side, brain stem and spinal cord were removed for histological examination. The Nauta-Gygax and the horseradish peroxidase methods were employed to study the course and origin of the above mentioned tract. The pyramidal tract runs ipsilaterally in the cerebral peduncle, and does not go beyond the first cervical segments of the spinal cord (C3-C4); moreover, their fibers do not cross at spinal level. The close relation between this anatomical pathway and the olfactory bulb of the same side is also reported.

Propofol anticonvulsant activity in experimental epileptic status.

We have examined the anticonvulsant properties of propofol in high doses in two experimental models of status epilepticus: generalized pentylenetetrazol (PTZ)-induced seizures and partial, cortically applied penicillin G-induced seizures. Propofol was administered either as a single bolus injection or as a bolus injection followed by an infusion for 1 h. When administered as a single bolus injection, propofol 12 mg kg-1 suppressed electrical and clinical seizures in PTZ generalized epileptic status, and an infusion of 50 mg kg-1 h-1 prevented the reappearance of electrical and clinical signs. In focal epileptic status, the single dose stopped paroxysmal activity and the associated clonic jerks for a few seconds. When the bolus dose was followed by an infusion, the firing bursts were replaced by isolated spikes, and contralateral jerks became sporadic and feeble. The greater efficacy of propofol against PTZ convulsions may be a reflection of the opposite action of the two drugs on neural membrane conductance: PTZ induces paroxysmal neural discharge by enhancing membrane conductance while propofol appears to decrease membrane conductance, thus suppressing paroxysmal discharge. There was no close relationship between blood concentration of the anaesthetic and its clinical effects, at least after a short-term infusion, as used in the present experiments. We suggest that propofol may be a potentially useful drug in status epilepticus in patients in whom benzodiazepines, barbiturates and phenytoin have failed.

Penicillin-induced paroxysmal activity in brainstem neurons.

The spontaneous electrical activity of single mesencephalic and bulbar neurons was recorded in hemispherectomized rats, following topical application of the GABA-antagonist penicillin-G on the mesencephalon or on the rhombencephalon, to investigate whether these structures could develop a specific penicillin paroxysmal activity independently of the upper structures. Twenty minutes following penicillin-G, the mesencephalic neurons developed paroxysmal activity characterized by a significant increase in the spontaneous electrical activity, the appearance of multiunit activity and, frequently, phasic activity with rhythmical outbursts. The paroxysmal activity at bulbar level appeared later than that observed in the mesencephalon and was characterized by a significant increase of the spontaneous firing rate of the neurons, single short bursts and sometimes rhythmical outbursts. The bulbar outbursts always discharged at lower frequency than those at the mesencephalic level. Following a midcollicular transection the paroxysmal bulbar activity abruptly disappeared. This phenomenon might be explained by a loss of facilitation from superior structures on the bulbar neurons which in roditors show a poor GABA-receptor distribution. In other words, penicillin alone, due to the scarcity of GABA receptors, might not be sufficient to induce paroxysmal activity in bulbar neurons but the simultaneous presence of both the superior facilitation and the drug might enhance neuronal excitability to a critical level. However, the diffusion of the drug upwards to the mesencephalon, with consequent activation of a system allowing the downward propagation of paroxysmal activity, cannot be excluded. In conclusion, while the mesencephalic neurons demonstrate a proper ability to develop penicillin paroxysmal discharge, the bulbar neurons must be sustained by intact connections with upper structures to be able to do so.

[Nonodontogenic facial pain of dental significance]. / Le principali algie facciali non odontogene di interesse odontoiatrico.

The authors review the main facial pain syndromes, which put often important diagnostic problems to the chephalic district specialists. The syndromes are discussed with modern nosographic criteria. Epidemiologic data and pain peculiarities, both essentials for a correct diagnosis, are stressed for each of the reported syndromes.