A randomized, double-masked, crossover comparison of the efficacy and safety of botulinum toxin type A produced from the original bulk toxin source and current bulk toxin source for the treatment of cervical dystonia.

In 1997, the US FDA approved a new bulk toxin source (now referred to as current) for the manufacture of botulinum toxin type A (BTX-A). The current BTX-A preparation has a lower neurotoxin complex protein load than the original BTX-A preparation, which may reduce antigenic potential. The present double-masked, multicenter study compared the efficacy and safety of BTX-A (BOTOX) produced from both original and current bulk toxin sources for the treatment of cervical dystonia. Patients (N = 133) were injected with BTX-A produced from original and current bulk toxin sources using a crossover design. Adverse events were assessed at each visit. Efficacy was assessed at 2 and 6 weeks post-injection using the severity and pain-disability subscales of the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS). Mean BTX-A doses were comparable (original: 155 U, current: 156 U). Both BTX-A preparations produced similar, statistically significant reductions in TWSTRS severity and pain-disability scores at weeks 2 and 6 post-injection. The original and current BTX-A preparations showed no significant differences in adverse events, including both treatment-related (34%, 31%) and treatment-unrelated (27%, 32%), respectively. BTX-A produced from the original and current bulk toxin sources showed comparable efficacy and safety in the treatment of cervical dystonia; both significantly reduced dystonia severity and pain.

Aphasia and infarction of the posterior cerebral artery territory.

Spoken language disorders are rarely mentioned in superficial infarction of the posterior cerebral (PCA) territory. Two clinical types have been reported: transcortical sensory and amnesic aphasia. Between 1979 and 1990, we studied retrospectively 76 patients suffering from an occipitotemporal infarction located in the superficial territory of the posterior cerebral artery, all well documented by CT. Aphasia was one of the first and prominent signs in 18 cases. Middle cerebral artery concomitant infarction could have been the cause of language impairment in 10. In 8 patients aphasia was only explained by a PCA territory infarct. Three patients showed features of transcortical sensory aphasia. CT localization showed internal lobe and thalamic involvement of the dominant hemisphere. Five patients exhibited word finding impairment with various degrees of amnestic syndrome. The dominant internal temporal lobe was always affected. Dominant thalamus involvement was found in one case only. Some correlations between clinical features and anatomical support (vascular supply and anatomical structure) might be suggested in our 8 cases of aphasic disorders due to PCA infarcts. They are discussed and compared with data in the literature.

Late flexion reflex in paraplegic patients. Evidence for a spinal stepping generator.

We demonstrated previously that electrical stimulation of the Flexor Reflex Afferents (FRA) induces a late flexion reflex with a central conduction time longer than 100 msec. Its latency is prolonged by increasing the intensity or the duration of the stimulation. This late reflex is therefore similar to the late flexion reflex observed in acute spinal cat with DOPA. Some findings suggest that in man the late flexion reflex could be inhibited at a premotoneuronal level by contralateral FRA stimulation. In relation to the late flexion reflex, a late contralateral facilitation of soleus monosynaptic reflex (MSR) was observed. Rhythmical activity was observed in only one patient who had an exceptional form of spinal myoclonus. This myoclonus could be modulated by FRA stimulation. These facts show that the reflex organization in paraplegic patients is similar to the one described in acute spinal cat with DOPA and therefore suggest that a spinal stepping generator could exist in humans.

Locomotion in rats transplanted with noradrenergic neurons.

It is known that catecholaminergic drugs can induce both locomotion and a late flexion reflex in spinalized animals. We studied spinal reflexes and locomotor activity in five adult spinal rats which had received a suspension of fetal noradrenergic (NA) neurons below the transection and in three control spinal rats. A rhythmical activity similar to the one of locomotion was regularly observed in three of the grafted rats held above a moving belt. In two of them, the step frequency was increased when the velocity of the moving belt was increased. This was not observed in control rats. A late flexion reflex was obtained in grafted rats that displayed locomotor activity, as well as in two controls. In the two rats which exhibited locomotor activity, analysis showed numerous immunoreactivite (against NA) cells and processes with terminals concentrated around the perikarya of motoneurones.

Evidence for a spinal stepping generator in man. Electrophysiological study.

We present some evidence favouring the presence of a spinal stepping generator in humans. Electrophysiological studies have shown that the spinal cord even deprived of supraspinal influence can generate rhythmic activity, and that some elements of the spinal circuitry on which the generation of stepping rhythmic relies in lower vertebrates exist in man. Moreover, comparison of the variations of the polysynaptic spinal flexor reflex in normal subjects and paraplegic patients brought about some evidence that normal subjects use a spinal locomotor center. Nevertheless, these studies do not absolutely prove the existence of a central pattern generator in man.

Recovery of locomotor activity in the adult chronic spinal rat after sublesional transplantation of embryonic nervous cells: specific role of serotonergic neurons.

Locomotor movements are programmed in a specialised neuronal network that is localised in the central nervous system and referred to as the central pattern generator (CPG) for locomotion. This CPG can be activated by pharmacological agents such as monoamines. The aim of the present study was to try to activate the CPGs by using cells that are supposed to release serotonin locally. Adult chronic spinal rats were injected with embryonic brainstem neurons within the spinal cord under a thoracic transection. This procedure resulted in a monoaminergic reinnervation of the lumbar enlargement. With the help of a specific neurotoxin for noradrenergic neurons (6-hydroxydopamine), it was possible to isolate the serotonergic system. After such transplantation of monoaminergic neurons and even with serotonergic neurons alone, a bilateral, alternating, rhythmic locomotor-like activity recovered in hindlimbs. Furthermore, this locomotor-like activity was clearly facilitated when the re-uptake of serotonin was blocked by zimelidine. Therefore, we conclude that transplanted embryonic serotonergic neurons are able to activate the CPG for locomotion.

Myoclonus in a patient with spinal cord transection. Possible involvement of the spinal stepping generator.

A patient with clinically complete cervical spinal cord transection developed rhythmic myoclonic movements of the trunk and lower limbs, demonstrating that, in man, such movements can be generated within the spinal cord itself when deprived of supraspinal control. Electromyographic (EMG) recordings used to define the features of the myoclonus, which had a frequency of 0.3-0.6 Hz, was bilaterally symmetric, and involved extensor muscles. The EMG bursts always appeared in phase in all muscles involved. Peripheral stimulation of flexor reflex afferents (FRA) could induce, slow or interrupt the rhythmic activity. When FRA stimulation induced a flexion reflex, it occurred between extensor EMG bursts and induced alternating flexion-extension activity which could be sustained for several cycles. Soleus and quadriceps monosynaptic reflexes were depressed during the silent period of the rhythmic activity. Several arguments, mainly the great sensitivity of the myoclonus to flexor reflex afferent stimulation, suggest that the myoclonus observed in this patient was due to partial release of a spinal stepping generator.

Intrathecal catheter with subcutaneous port for clonidine test bolus injection. A new route and type of treatment for detrusor hyperreflexia in spinal cord-injured patients.

INTRODUCTION AND OBJECTIVES: The objective of this study was to assess the feasibitity, technical data and use of intrathecal catheter implantation with subcutaneous port for clonidine test injections and individual evaluation. METHODS: According to approval of the local ethics committee, 9 consecutive SCI patients (6 men, 3 women) had catheter and port implantation between January 1998 and May 1999. All did not respond to systemic drug therapy in combination to self-clean intermittent catheterisation (SCIC). Implantation was done under general anesthesia. Needle and catheter were Medtronic Infusion Synchromed Intraspinal catheter (Induratrade mark, 8703W). Clonidine test injections were allowed at D5. RESULTS: There were no complications during operation. Follow-up was 8.2 months (0.5-17). After clonidine bolus injection test and validation, 6 patients decided to have permanent pump implantation, 2 chose other therapies and one did not tolerate clonidine intrathecal injections for blood arterial pressure side effects. CONCLUSIONS: Intrathecal clonidine may represent a useful conservative treatment of both severe bladder hyperreflexia and spinal spasticity. Its short-term effects can be individually evaluated through bolus injection in subcutaneous port before definitive pump implantation.

Neurological correlations of ejaculation and testicular size in men with a complete spinal cord section.

This study was of 135 patients with a complete spinal cord section suffered from loss of ejaculation. The spinal cord injuries were classified following the upper and the lower limits of the lesion. The volume of the testes of the patients and of 13 normal control subjects were measured. Physostigmine allowed 75 patients to ejaculate and 15 of them procreated. The possibility of ejaculation after physostigmine mainly depended on the integrity of the T12-L2 metamers. The testicular volume was significantly smaller in patients with a lesion including the T12 metamer than in patients with a lesion sparing the T12 metamer. Six patients with a lesion including the T12 metamer had testicular atrophy. This suggests that T12 segment plays a role in testicular function in paraplegic patients.

Fictive motor activities in adult chronic spinal rats transplanted with embryonic brainstem neurons.

The present study was designed to examine the effects of an intraspinal transplantation of embryonic brainstem neurons on fictive motor patterns which can develop in hindlimb nerves of adult chronic spinal rats. Seventeen adult rats were spinalized at T8-9 level and, 8 days later, a suspension of embryonic cells obtained either from the raphe region (RR, n = 8) or from the locus coeruleus (LC, n = 9) was injected caudally (T12-13) to the cord transection. Eight control animals (control rats) were spinalized and injected with vehicle under the same conditions. One to three months later, the animals were decorticated and fictive motor patterns were recorded in representative hindlimb nerves. The data revealed that both control and grafted spinal rats could exhibit two distinctly different fictive motor patterns, one which could be associated with stepping and the other with hindlimb paw shaking. They further showed that following transplantation of embryonic RR or LC neurons the excitability of the spinal stepping generator was increased, whereas that of the spinal neural circuits which generate hindlimb paw shaking was not significantly affected. A histological analysis performed on the spinal cord segments below the transection revealed complete absence of serotonin and noradrenaline immunoreactivity in control spinal animals and, in both types of grafted rats, an extensive monoaminergic reinnervation with synaptic contacts between monoaminergic transplanted neurons and host interneurons and/or motoneurons. The possible mechanisms by which grafted monoaminergic neurons can influence the spinal motor networks are discussed.