Victor De Pasqua

Occipital nerve stimulation for drug-resistant chronic cluster headache: a prospective pilot study.

BACKGROUND Drug-resistant chronic cluster headache (drCCH) is a devastating disorder for which various destructive procedures have been tried unsuccessfully. Occipital nerve stimulation (ONS) is a new, safe strategy for intractable headaches. We undertook a prospective pilot trial of ONS in drCCH to assess clinical efficacy and pain perception. METHODS Eight patients with drCCH had a suboccipital neurostimulator implanted on the side of the headache and were asked to record details of frequency, intensity, and symptomatic treatment for their attacks in a diary before and after continuous ONS. To detect changes in cephalic and extracephalic pain processing we measured electrical and pressure pain thresholds and the nociceptive blink reflex. FINDINGS Two patients were pain free after a follow-up of 16 and 22 months; one of them still had occasional autonomic attacks. Three patients had around a 90% reduction in attack frequency. Two patients, one of whom had had the implant for only 3 months, had improvement of around 40%. Mean follow-up was 15.1 months (SD 9.5, range 3-22). Intensity of attacks tends to decrease earlier than frequency during ONS and, on average, is improved by 50% in remaining attacks. All but one patient were able to substantially reduce their preventive drug treatment. Interruption of ONS by switching off the stimulator or because of an empty battery was followed within days by recurrence and increase of attacks in all improved patients. ONS did not significantly modify pain thresholds. The amplitude of the nociceptive blink reflex increased with longer durations of ONS. There were no serious adverse events. INTERPRETATION ONS could be an efficient treatment for drCCH and could be safer than deep hypothalamic stimulation. The delay of 2 months or more between implantation and significant clinical improvement suggests that the procedure acts via slow neuromodulatory processes at the level of upper brain stem or diencephalic centres.

Post-stroke reorganization of hand motor area: a 1-year prospective follow-up with focal transcranial magnetic stimulation

OBJECTIVE Focal transcranial magnetic stimulation was used to test prospectively corticospinal excitability changes and reorganization of first dorsal interosseous (FDI) motor cortical representation in 31 patients who experienced a first ischemic stroke in the middle cerebral artery territory. All had severe hand palsy at onset. METHODS Patients were assessed clinically with the Medical Research Council, Rankin, the National Institutes of Health stroke scales and Barthel Index at days 1, 8, 30, 90, 180 and 360 after stroke. The following parameters of FDI motor evoked potential (MEPS) to focal transcranial magnetic stimulation were measured at the same delays: motor threshold, MEP amplitude, excitable cortical area, hot spot and center of gravity of FDI motor maps on affected and unaffected hemispheres. Correlations were sought between clinical and electrophysiological parameters. RESULTS In patients whose affected motor cortex remained excitable at day 1, motor thresholds were not significantly different between sides and were similar to those of controls. Persistence of MEP on the affected side at day 1 was a strong predictor of good recovery. If present at day 1, MEPs recorded in affected FDI were significantly smaller than of the opposite side or in normals and progressively recovered up to day 360. In these patients, area of excitable cortex remained stable throughout the entire study. At day 1, amplitudes of MEPs obtained in unaffected FDI were significantly larger than later. Between days 1 and 360, we observed a significant displacement of center of gravity of motor maps towards more frontal regions on the affected side while no change was noted on the unaffected side. CONCLUSIONS Our data confirm the early prognosis value of transcranial magnetic stimulation in stroke. They indicate that the brain insult induces a transient hyperexcitability of the unaffected motor cortex. The evolution of FDI motor maps along the course of recovery mostly reflect corticospinal excitability changes but might also reveal some degree of brain plasticity. Most modifications observed occurred within 3 months of stroke onset.

Ipsilateral Motor Responses to Focal Transcranial Magnetic Stimulation in Healthy Subjects and Acute-Stroke Patients

Background and Purpose— Prevalence and characteristics of ipsilateral upper limb motor-evoked potentials (MEPs) elicited by focal transcranial magnetic stimulation (TMS) were compared in healthy subjects and patients with acute stroke. Methods— Sixteen healthy subjects and 25 patients with acute stroke underwent focal TMS at maximum stimulator output over motor and premotor cortices. If present, MEPs evoked in muscles ipsilateral to TMS were analyzed for latency, amplitude, shape, and center of gravity (ie, preferential coil location to elicit them). In stroke patients, possible relationships between early ipsilateral responses and functional outcome at 6 months were sought. Results— With relaxed or slightly contracting target muscle, maximal TMS over the motor cortex failed to elicit ipsilateral MEPs in the first dorsal interosseous (FDI) or biceps of any of 16 normal subjects. In 5 of 8 healthy subjects tested, ipsilateral MEPs with latencies longer than contralateral MEPs were evoked in FDI muscle (in biceps, 6 of 8 subjects) during strong (>50% maximum) contraction of the target muscle. In 15 of 25 stroke patients, ipsilateral MEPs in the unaffected relaxed FDI (in biceps, 6 of 25 stroke patients) were evoked by stimulation of premotor areas of the affected hemisphere. Their latencies were shorter than those that MEPs evoked in the same muscle by stimulation of the motor cortex of the contralateral unaffected hemisphere. Such responses were never obtained in normal subjects and were mostly observed in patients with subcortical infarcts. Patients harboring these responses had slightly better bimanual dexterity after 6 months. Conclusions— Ipsilateral MEPs obtained in healthy individuals and stroke patients have different characteristics and probably different origins. In the former, they are probably conveyed via corticoreticulospinal or corticopropriospinal pathways, whereas in the latter, early ipsilateral MEPs could originate in hyperexcitable premotor areas.

Subclinical cerebellar impairment in the common types of migraine: A three-dimensional analysis of reaching movements

Mutations in the CACNA1A gene can cause familial hemiplegic migraine (FHM) and/or cerebellar ataxia. CACNA1A codes for the α1 subunit of P/Q‐Ca2+ channels and is highly expressed in the cerebellum. Using a pointing paradigm and infrared optoelectronic tracking system, we found subclinical hypermetria and other subtle cerebellar signs in the common forms of migraine. These were more pronounced in migraine with than without aura. Whether this reflects involvement of Ca2+ channel genes in the common types of migraine needs to be investigated by genetic analyses.

Multiple Clinical and Paraclinical Analyses of Chronic Tension-Type Headache Associated or Unassociated With Disorder of Pericranial Muscles

Thirty-two female patients fulfilling the diagnostic criteria of chronic tension-type headache underwent multiple clinical (severity index before and after biofeedback therapy; anxiety score) and paraclinical (pericranial EMG levels and pressure-pain thresholds, temporalis exteroceptive silent period) assessments. Twenty-three patients (72%) had at least one increased EMG level and/or at least one decreased pain threshold and qualified for the subgroup “associated with disorder of pericranial muscles” (code 2.2.1). Nine patients (28%) were within the normal range for both investigations and would have been classified in the subgroup “unassociated with such disorder” (code 2.2.2). No significant differences were found between these two groups of patients for headache severity, anxiety, response to biofeedback therapy or duration of temporalis second exteroceptive silent period. The various clinical and paraclinical parameters were not significantly correlated to each other. It is therefore suggested that the subdivision of chronic tension-type headache in two subgroups based on pericranial EMG levels and/or pain sensitivity might be artificial. Since both of the latter and temporalis silent periods vary independently, they appear complementary in the study of tension-type headache patients and probably represent peripheral abnormalities, which are induced to varying intensities by a common central nervous system dysfunction.

Nociceptive blink reflex and visual evoked potential habituations are correlated in migraine

Background.—Lack of habituation, as reported in migraine patients between attacks for evoked cortical responses, was also recently found for the nociceptive blink reflex (nBR) mediated by brainstem neurons. It is not known if both brain stem and cortical habituation deficits are correlated in the same patient, which would favor a common underlying mechanism.

Reduced gating of middle-latency auditory evoked potentials (P50) in migraine patients: another indication of abnormal sensory processing?

Habituation of cortical evoked responses to repetitive stimuli is reduced in migraine between attacks. To explore another aspect of information processing, we measured auditory sensory gating. The amplitude of the P50 response to the second of two homologous stimuli was significantly less reduced in migraineurs than in healthy volunteers. This lack of auditory sensory gating may be due to a hypofunction of monoaminergic subcortico-cortical pathways, which is also supposed to cause the interictal deficit of cortical habituation to repetitive stimuli.

Motor cortex inhibition is not impaired in patients with Alzheimer's disease: evidence from paired transcranial magnetic stimulation

Motor cortex excitability was studied by transcranial magnetic stimulation (TMS) in 17 patients with Alzheimers disease (AD). Resting and active thresholds for TMS were significantly reduced in AD patients compared to young and aged healthy subjects. The maximum amplitude of the motor response evoked by TMS was also significantly increased in AD patients. We have tested if these changes are related to a modification of the short-lasting intracortical inhibition of the motor cortex by paired conditioning-test TMS. We found no significant differences between AD patients and aged healthy subjects even if there is a slight but significant difference between aged and young normal subjects. We conclude that the modification of excitability of the motor cortex does not result from an impaired intracortical inhibition.

Age-related changes in fastest and slowest conducting axons of thenar motor units

Single thenar motor unit F waves (FMUPs) were collected from 23 healthy volunteers (age range 21–91 years, mean 46 ± 20 SD). In each subject, 10 distinct FMUPs were recorded, using surface stimulating and recording electrodes, and the conduction velocity (CV) of each motor unit was calculated. The distribution of CVs (overall range 42–66 m/s; individual FMUP CV dispersion range 6–27% of the maximal FMUP CV) was close to those previously reported whatever the technique used. With age, a progressive CV reduction was observed, and maximal FMUP CV was significantly correlated with age (r = −0.58, P < 0.01), whereas no statistically significant correlation was found between minimal FMUP CV and age (r = −0.27, ns). Individual FMUP CV dispersion presented a statistically significant decrease with age (r = −0.46, P < 0.05). Furthermore, thenar motor unit number (MUNE), estimated by the adapted multiple point stimulation method, decreased progressively with age and was statistically correlated with maximal FMUP CV (r = 0.59, P < 0.01), whereas there was no correlation with minimal FMUP CV (r = 0.34, ns). Thus, we propose that motor unit loss is progressive with age throughout life, affecting particularly the largest and fastest conducting motor units. Preferential involvement of these fibers could be responsible for the age‐related changes in motor nerve CV.

Emg Activity in Pericranial Muscles During Postural Variation and Mental Activity in Healthy Volunteers and Patients with Chronic Tension Type Headache

SYNOPSIS