Massimo Leandri

Migraine with Aura and Right-to-Left Shunt on Transcranial Doppler: A Case-Control Study

Right-to-left shunt (RLS), usually due to patent foramen ovale, is a well-established risk factor for ischemic stroke in young patients, while the role of migraine as an independent factor is still debated. We evaluated 44 patients suffering from migraine with aura, and compared them with 73 patients younger than 50 with focal cerebral ischemia, and 50 controls, asymptomatic for cerebrovascular disease, and without a history of migraine. All the subjects underwent bilateral transcranial Doppler with injection of contrast medium in an antecubital vein. The test was performed during normal ventilation and during Valsalva maneuver, recording both the middle cerebral arteries and the basilar artery. Criteria for diagnosing RLS was the presence of at least 3 microbubbles within 15 s from injection. Eighteen out of 44 migraine patients (41%) showed RLS, as opposed to 8 of 50 controls (16%) (p < 0.005). Twenty-six out of 73 patients with cerebral ischemia had RLS (35%). We conclude that the prevalence of RLS in patients with migraine with aura is significantly higher than in normal controls, and is similar to the prevalence of RLS in young patients with stroke. These findings could be helpful in understanding the relationship between migraine and stroke.

Clinical effectiveness of lamotrigine and plasma levels in essential and symptomatic trigeminal neuralgia.

This paper reports on the effectiveness of oral lamotrigine in 15 patients suffering from “essential” trigeminal neuralgia and in five patients suffering symptomatic trigeminal neuralgia concomitant with multiple sclerosis. We recorded objective and subjective pain ratings and correlated them to daily dosage (400 mg maximum) and plasma levels of the drug. We detected pain relief proportional to daily dosage and to drug plasma levels. Eleven of the cases affected by the “essential” form of neuralgia showed complete pain relief on reaching their maximum daily dosage. All cases affected by the symptomatic form had complete pain relief. We could detect no changes from these results by the end of the follow-up period (3 to 8 months after the study ended).

Low-Dose Gabapentin Combined with either Lamotrigine or Carbamazepine Can Be Useful Therapies for Trigeminal Neuralgia in Multiple Sclerosis

Paroxysmal symptoms occur frequently in multiple sclerosis (MS). Usually they are treated with carbamazepine (CBZ) and phenytoin, although these medications are often interrupted due to adverse effects. We report 11 MS patients with trigeminal neuralgia (TN): 6 intolerant to a therapeutic dosage of CBZ, showing serious adverse effects and subsequently treated with a combination of low-dose CBZ and gabapentin (GBP) (group 1); 5 treated with lamotrigine (LMT), showing adverse effects and subsequently treated with GBP (group 2). Subjective pain level and impairment in performing daily activities were rated utilizing a 3-point scale at time 0 and at optimal dosage time (T1). GBP was initiated at 300 mg daily and titrated, until pain control was achieved without new adverse effects, to a maximum dose of 1,200 mg daily. CBZ or LMT were reduced to a level which no longer produced adverse effects, although resulting in a lack of efficacy in relieving pain. Pain control was obtained in all patients but 1, with no side effects. The plasma level analysis, performed in 5 patients, resulted in normal values. The mean dosages at T1 were: group 1 CBZ 400 mg and GBP 850 mg daily; group 2 LMT 150 mg and GBP 780 mg daily. Combining drugs with complementary modes of action may provide a rational pharmacological approach to the management of TN in MS.

Persistence of High-Dose Oxaliplatin-Induced Neuropathy at Long-Term Follow-Up

Oxaliplatin (L-OHP) has become a standard treatment for advanced colorectal cancer and a valid option for patients in the adjuvant setting. Compared with cisplatin, L-OHP has no renal toxicity, only mild hematological and gastrointestinal toxicity, while neurotoxicity is the limiting toxicity. This side effect has been described as a transient distal dysesthesia, enhanced by exposure to cold, and as a dose-related cumulative mild sensitive neuropathy. We studied two groups of patients (18 and 13) with advanced colorectal cancer, treated with median cumulative doses of L-OHP 862 mg/m2 and 1,033.5 mg/m2. All the patients had been evaluated previously, during treatment, after discontinuation and after a long follow-up of 5 years to verify the incidence and the characteristics of the neuropathy induced by this antineoplastic agent. The clinical and neurophysiological examinations showed an acute and transient neurotoxicity and a cumulative dose-related sensory neuropathy in nearly all the patients. The reversibility of these effects was studied. Five patients continue to manifest symptoms and signs of neurotoxicity after a long follow-up, indicating persistence of this peculiar type of neuropathy.

Recovery of nerve conduction following microvascular decompression for trigeminal neuralgia

Objective: To assess the function of trigeminal nerve before and after microvascular decompression for trigeminal neuralgia. Background: To date there is no direct evidence that microvascular decompression of the trigeminal root restores normal conduction in the nerve. Methods: The authors examined 10 patients with trigeminal neuralgia in whom preoperative MRI and MR angiography demonstrated neurovascular contact. During microvascular decompression, the trigeminal nerve was monitored by recording early scalp trigeminal evoked potentials immediately before, during, and after decompression. Direct recordings from the root entry zone were also performed. Results: In all patients preoperative scalp evoked potentials showed impaired conduction of the trigeminal root. Microvascular decompression was associated with immediate recovery of conduction in seven patients, demonstrated by both scalp evoked potentials and direct root recordings. All 10 patients were pain free postoperatively. Conclusions: Improvement in trigeminal neuralgia following microvascular decompression is often associated with normalization of neurophysiologic data, suggesting recovery of nerve function. Rapid electrophysiologic recovery and pain relief following microvascular decompression argue that neither phenomenon is linked to remyelination. It is possible that the trigeminal evoked potentials might predict an effective microvascular decompression.

Subcortical and cortical responses following infraorbital nerve stimulation in man

Scalp responses following stimulation of the infraorbital nerve have been recorded in awake and anaesthetized subjects from non-cephalic (NCR) and vertex (VR) reference derivations. In awake subjects, after 3 very early potentials (W1, W2 and W3), 4 small components (P4, N5, P6 and N7) with widespread distribution have been constantly recorded from NCR derivations. Sometimes a further component, named N10, could be recorded in VR derivations on the scalp contralateral to the stimulus in the absence of earlier events. Large and inconstant waves were recorded following N7 in NCR and N10 in VR derivations. The muscular origin of these waves was demonstrated by simultaneous records taken from scalp and muscles. Records from NCR derivations in anaesthetized subjects showed that wave N7 was followed by a further event (N10) localized on the scalp contralateral to the stimulus and by a few slow waves. Wave N10 could also be recorded, in the absence of earlier events, from the VR derivation contralateral to the stimulus. All the responses recorded in these patients could be considered of neurogenic origin because curarization abolished any reflex activation of muscles. All the waves following W3 are of postsynaptic nature and, on the basis of their distribution and latency, we suggest that P4, N5, P6, N7 and N10 have their respective origins in the trigeminal nucleus, trigeminal lemniscus, thalamus, thalamic radiation and cortical projection of the stimulated area. It was also demonstrated that stimulation of lips and gums fails to evoke any neural event recordable from the scalp.

New subcortical components of the cerebral somatosensory evoked potential in man

Two new components of the human SEP upon stimulation of the contralateral median nerve at the wrist have been identified. Such components have been called N16 and N17, according to their polarity and latency. N16 and N17, as well as the N14‐P15 complex, are generated by separate subcortical dipoles. Particularly, they are supposed to be far‐field reflections of the activity of the dorsal columns nuclei or the medial lemniscus (N14‐P15), the thalamus (N16) and the thalamo‐cortical radiation (N17). Moreover, it has been established that N14 is the very first intracranial component of the human SEP, the main peak of S wave and the preceding ones being extracranial in origin.

Early evoked potentials detected from the scalp of man following infraorbital nerve stimulation

Stimulation of the infraorbital nerve evoked a short latency scalp response characterized by a large amplitude triphasic potential (W1), followed by two smaller negative deflections (W2 and W3). All these waves were presynaptic in origin (as shown by double pulse stimulation), but appeared to be generated by separate dipoles. Short distance bipolar recording showed that W1 travelled from the zygoma to the mastoid. This wave was thought to be generated in a nearby neural structure, presumably the proximal part of the maxillary nerve, the gasserian ganglion and possibly even the trigeminal root. W2 and W3 components were probably generated by the trigeminal root fibres running through the brain-stem. Their origin from slowly conducting trigeminal fibres was ruled out by their absence in short distance bipolar records along the line from the zygomatic bone to the mastoid process, and by studies on their thresholds, which were shown to be identical to those of W1. Control experiments with concurrent facial muscle recording excluded any possible contamination of the scalp response to infraorbital nerve stimulation by electromyographic activity, and demonstrated gross muscular artefacts, picked up as far-field activity by scalp electrodes, following electrical stimulation of the upper lip.

Early scalp responses evoked by stimulation of the mental nerve in humans

In 20 subjects, we stimulated the mental nerve through needle electrodes inserted into the homonymous foramen; recording electrodes were placed on the scalp and along the jaw. Within the 1st 5 msec after the stimulus we recorded 4 constant waves, thought to reflect the afferent activity from the mandibular nerve up to the trigeminal nuclei. These waves have similar characteristics and the same high degree of reliability as those obtained after stimulation of the infraorbital and supraorbital nerves; therefore, they should be a useful complement for a complete exploration of trigeminal nerve function.

Cutaneous innervation of the human face as assessed by skin biopsy

The morphology of cutaneous sensory and autonomic innervation in human trigeminal territory is still unknown. The aim of this study is to describe facial cutaneous innervation using skin biopsy. This new tool could be useful in understanding the mechanisms underlying several facial pain conditions. In 30 healthy subjects, we quantified epidermal nerve fibers (ENFs) and dermal myelinated fibers (MFs) in V1, V2 and V3, using indirect immunofluorescence and confocal microscopy applied to 2‐mm punch skin biopsies from areas adjacent to the eyebrow, upper and lower lip. Using selective markers, we also evaluated the distribution of peptidergic, cholinergic and noradrenergic fibers. Facial skin appeared abundantly innervated and rich in annexes. The ENF density decreased and the MF density increased, moving from the supraorbital to the perioral skin. Noradrenergic sudomotor fibers were particularly and constantly expressed compared with other body sites. Distribution of vasoactive intestinal peptide‐immunoreactive (VIP‐ir) fibers appeared peculiar for their constant presence in the subepidermal neural plexus – in close contact, but without colocalization with calcitonin gene related peptide (CGRP) and substance P (Sub‐P)‐ir fibers. Finally, in perioral skin samples, we observed striated muscle fibers with their motor nerves and motor endplates. Our work provides the first morphological study of human facial cutaneous innervation, highlighting some unique features of this territory. Quantification of unmyelinated and myelinated fibers on 2‐mm punch biopsies appeared to be feasible and reliable. Facial skin biopsy may be a new approach with which to study and to better characterize facial pain syndromes.