Trigeminal neuralgia. Pathophysiology and treatment.

Trigeminal neuralgia is a very peculiar disease. The pain, also known as "tic douloureux", is paroxystic and very severe. It can be triggered by a light cutaneous stimulus on a very localized spot on the face (the so-called "trigger zone"). The patient can sometimes benefit from long remissions without any treatment. With the exception of multiple sclerosis and of uncommon cases of posterior fossa tumours or other lesions impinging on the trigeminal nerve, ganglion or root, trigeminal neuralgia is considered as "idiopathic". Some benign abnormality had for long been suspected. The current opinion is now in favour of a "neurovascular conflict": an artery, most often a loop of the superior or anteroinferior cerebellar artery, has an offending contact with the trigeminal nerve root, which results in localized demyelination and ectopic triggering of neuronal discharges. This hypothesis is in agreement with the relief provided by antiepileptic drugs and is supported by recent neuroimaging data. Therapeutic options are reviewed: very efficient drugs are available but fail to provide a significant relief and/or have important side effects in many cases. Surgical alternatives are available, for which guidelines are proposed.

[Chronic pain: introduction]. / La douleur chronique: introduction.

This paper is an introduction to a teaching session devoted to chronic pain. The results of a belgian epidemiological study illustrate the social and economical consequences of acute and chronic pain. Many studies have revealed that, if we want to understand the onset and the perpetuating mechanisms of chronic pain, we have to take into account a conjunction of biological, psychological and social factors. The general practitioner should be aware of this biopsychosocial model, the main points of which being summarised in this introduction. The teaching staff will deal with chronic headaches, psychoanalytical approach to chronic pain, and the so-called "invasive" techniques of pain control.

Comparative efficacy and safety of calcium carbasalate plus metoclopramide versus ergotamine tartrate plus caffeine in the treatment of acute migraine attacks.

This randomized, double-blind, double-dummy, multicenter, parallel-group study aimed at comparing the efficacy and safety of calcium carbasalate (equivalent to 900 mg aspirin) plus metoclopramide 10 mg (CM) with ergotamine tartrate 1 mg plus caffeine 100 mg (EC) administered in the treatment of 2 acute migraine attacks. A total of 296 patients fulfilling the International Headache Society diagnostic criteria for migraine were enrolled. In total, one or two migraine attacks were treated in 268 and 235 patients, respectively. The primary endpoint for the first treated attack was headache relief, with intensity decreasing from moderate or severe to mild or absent 2 h after drug intake. Usual secondary efficacy endpoints were assessed. A superiority of CM over EC was observed for both treated attacks for the main endpoint: success in 54 versus 36%, p = 0.003 for the first attack and 60 versus 44%, p = 0.02 for the second attack. CM was also significantly superior to EC during the first attack for complete headache relief (20 vs. 8%, p = 0.006), nausea (42 vs. 63%, p = 0. 007) and willingness to take the drug again (90 vs. 80%, p = 0.043). The global efficacy evaluation, rated by the investigators, was significantly more favorable to CM for both attacks (p = 0.001 for the first attack and p = 0.02 for the second). The patients' evaluation was significant for the first attack (p = 0.002). The global incidence of adverse events was 45% higher with EC, though not significant (32 vs. 22%, p = 0.075). They were most often unspecific and mild to moderate in intensity. Gastrointestinal side effects were significantly less frequent with CM than EC (7 vs. 21%, p = 0.001). Thus, CM is more effective and has a better gastrointestinal safety than EC in the acute treatment of migraine attacks.

[Correct use of serotonin agonists in migraine: oral or injectable form?]. / Du bon usage des agonistes de la sérotonine dans la migraine: forme orale ou injectable?

Sumatriptan and other selective serotonin agonists represent a major breakthrough in acute migraine treatment. These drugs are very efficacious and generally devoided of important side effects, but they are expensive and therefore have to be compared with other, more conventional drugs with established or assumed efficacy. We summarize the pharmacologic characteristics of Sumatriptan and give recommendations about its use in clinical practice.

Chronic intrathecal baclofen in severely disabling spasticity: selection, clinical assessment and long-term benefit.

Flexor and extensor spasms associated with severe spasticity frequently cause pain and suffering in neurologically impaired patients, and greatly interfere with comfort and activities. When high doses of oral medications are necessary to keep the symptoms under control and are poorly tolerated, the long-term spinal-selective intrathecal infusion of baclofen by means of implanted drug pump and catheter is a safe, efficient and reversible alternative to destructive surgical procedures. Between September 1991 and March 1995, intrathecal baclofen was infused in 18 selected patients out of a series of 42 severely disabled spastic cases. We report here our preliminary experience with the criteria of selection, the initial intrathecal bolus test and the long-term benefit of the selected patients. Our results confirm the dramatic immediate and long-term benefit reported in other series. After a period of treatment of 1 to 42 months, 13 patients had a complete disappearance of their spastic symptoms without any oral treatment, one patient kept unchanged clonus despite the use of low-dose oral treatment and another one a severe, not improved dysuria although in both of them hypertonia and spasms were abolished. Finally, 2 patients had important joint stiffness slightly impairing the benefit from the treatment. None of the 18 patients had central side-effects related to baclofen. With time, a slight increase in daily dose (inferior to 10%) was necessary in most patients.

Self-treatment of acute migraine with subcutaneous sumatriptan using an auto-injector device: comparison with customary treatment in an open, longitudinal study.

In a multicenter open longitudinal clinical trial where 479 patients suffering from migraine with or without aura were recruited, patients treated at home one to three migraine attacks with their customary treatment, and subsequently, over a 3-month period, one to three migraine attacks with 6 mg sumatriptan sc using an autoinjector. The headache response to customary treatment was 19% at 1 h and 30.5% at 2 h, and was not significantly different when only attacks treated "adequately" according to accepted treatment recommendations were considered: 16% at 1 h and 35% at 2 h. In contrast, 69% and 82% of patients treated with 6 mg sumatriptan sc had mild headache or no headache at 1 and 2 h respectively, regardless of migraine type or duration of symptoms prior to treatment. Other migraine symptoms (nausea, vomiting, photo- and phonophobia) were effectively treated with sumatriptan. Recurrence of migraine was observed in 31% of patients and was well controlled by a second injection of sumatriptan. It is concluded that 6 mg sumatriptan sc, self-administered using an autoinjector, is well tolerated and more effective than most currently used acute treatments for migraine in a population of severely affected patients consulting a neurologist.

[Neurotoxicity of formyl leurosine. An experimental and clinical study (author's transl)]. / Neurotoxicité de la formyl leurosine. Etude expérimentale et clinique.

Leg paralysis and wallerian degeneration of sciatic nerve fibres have been produced in rats by intraneural injection of 0.5, 1 or 5 microgram of vincristine (VCR) or formyl leurosine (FLR) dissolved in 5 microliter of saline. Nerve lesions were dose-related, and were similar for equal concentrations of the two drugs. Six patients received one to three 5-day courses of FLR. The total dose of FLR administered ranged from 15 to 131 mg (mean 83 mg). Clinical signs of peripheral neuropathy were absent in four patients, and limited to orthostatic hypotension in one case and transient depression of reflexes in another. Motor conduction velocities measured in four peripheral nerves, and muscle evoked potentials remained unchanged throughout the treatment in all patients.

[Neurotoxicity of formyl leurosine. An experimental and clinical study (author's transl)]. / Neurotoxicité de la formyl leurosine. Etude expérimentale et clinique.

Leg paralysis and wallerian degeneration of sciatic nerve fibres have been produced in rats by intraneural injection of 0.5, 1 or 5 micrograms of vincristine (VCR) or formyl leurosine (FLR) dissolved in 5 microliters of saline. Nerve lesions were dose-related, and were similar for equal concentrations of the two drugs. Six patients received one to three 5-day courses of FLR. The total dose of FLR administered ranged from 15 to 131 mg (mean 83 mg). Clinical signs of peripheral neuropathy were absent in four patients, and limited to orthostatic hypotension in one case and transient depression of reflexes in another. Motor conduction velocities measured in four peripheral nerves, and muscle evoked potentials remained unchanged throughout the treatment in all patients.

Central mechanisms of tremor in some feline and primate models.

For several years our interest has been in a postural Parkinson-like tremor at 4-6/sec. which can be produced in the monkey by lesions of the central nervous system. We have also studied the effects of harmaline, a drug which evokes or intensifies the Parkinson-like tremor in lesioned animals and which also induces a fine, generalized tremor at 7-12/sec. in normal animals. The results obtained so far indicate that these two types of tremor are generated by two independent central mechanisms which do not require the integrity of peripheral feedback loops. The experimental Parkinson-like tremor is generated by a thalamo-cortical mechanism while the olivo-cerebellar system is responsible for the faster "physiological" tremor. Similar tremor mechanisms may be involved in some movement disorders in man.