Observational, open-label, non-randomized study on the efficacy of onabotulinumtoxinA in the treatment of nummular headache: The pre-numabot study

Background Nummular headache is a primary headache characterised by superficial, coin-shaped pain. Superficial sensory fibre dysfunction might be involved in its pathophysiology. Considering the mechanism of action of onabotulinumtoxinA, it could be a reasonable option in treatment of nummular headache. The aim of the study was to evaluate the efficacy and tolerability of onabotulinumtoxinA in a series of nummular headache patients. Patients and methods This was an observational, prospective, non-randomized and open-label study. Nummular headache patients with at least 10 headache days in three preceding months were included. They were administered 25 units of onabotulinumtoxinA. The primary endpoint was the decrease of headache days per month, evaluated between weeks 20 to 24, compared with baseline. The secondary endpoints included reduction of intense headache days and acute treatment days evaluated between weeks 20–24 and weeks 8–12, compared with baseline. The 30%, 50% and 75% responder rates were determined, and tolerability described. Results We included 53 patients, 67.9% females, with a median age of 54 years. Preventive treatment had been used previously in 60.4% of patients. The median diameter of the nummular headache was 5 cm. At baseline, the number of headache days per month was 24.5 (7.3); the number of intense headache days was 12.5 (10.1), and the number of acute treatment days was 12.8 (7.8). After onabotulinumtoxinA, the mean number of headache days per month decreased to 6.9 (9.3) between weeks 20 and 24 ( p < 0.001). Secondary endpoints concerning intense headache days per month and acute treatment days per month were also statistically significant ( p < 0.001). The 50% responder rate, evaluated between weeks 20 and 24, was 77.4% and the 75% responder rate was 52.8%. Concerning tolerability, 26 patients (49.1%) experienced an adverse event (AE), the commonest being injection-site pain in 12 cases (22.6%). There were no moderate or severe AEs. Conclusion It was found that after injecting onabotulinumtoxinA, the number of headache days per month was reduced in nummular headache patients. The number of intense headache days per month and acute treatment days were also lowered. No serious adverse events occurred during treatment.

Sensory Ganglionopathy and the Blink Reflex: Electrophysiological Features

Background: Sensory ganglionopathy (SG) is characterised by asymmetrical sensory fibre degeneration, with the primary pathology occurring at the level of the dorsal root ganglion. It is seen in the context of autoimmune, paraneoplastic, and degenerative disorders. There is limited literature examining the electrophysiological correlate of the trigeminal ganglion and associated pathways, the blink reflex (BR), in cases of SG. Previous work has suggested that the BR is preserved in cases of SG associated with paraneoplasia. Methods: The local clinical neurophysiology database was searched for patients diagnosed with SG from peripheral nerve conduction studies in whom the BR was performed. Twenty-six patients were included in the final analysis. Results: Sjögren’s syndrome constituted the most common SG aetiology (8/26), followed by idiopathic cases (7/26) and paraneoplasia (5/26). BR abnormalities were seen in 9 of the 26 patients (34.6%) across all aetiologies. No patients reported sensory disturbance in the distribution of the trigeminal nerve, indicating that the changes noted are subclinical. Three patients showed abnormality of the R1 response; in the remaining six patients, only R2 responses were affected. Conclusions: Subclinical abnormalities of both R1 and R2 can be seen in the context of SG of varying aetiologies, including paraneoplasia. Performing the BR in patients with suspected of having SG may be helpful in providing additional evidence of patchy sensory fibre involvement that is characteristic of the disease.

The non-impulsive stretch-receptor complex of the crab: a study of depolarization-release coupling at a tonic sensorimotor synapse

A new preparation for the study of synaptic transmission is described from the thoracic ganglion of the crab Callinectes sapidus . The central anatomy of the nonimpulsive stretch-receptor neurons of the thoracic-coxal joint and that of the promotor motoneurons with which they form synaptic junctions was studied with intracellular cobalt staining and light and electron microscopy. Attention was centred on the interaction of the stretch-receptor T-fibre and the four large motoneurons supplying the promotor muscle which have their cell-bodies on the dorsal surface of the ganglion. The presynaptic terminal region of the T-fibre appeared to be a simple cylinder in form with a diameter of 40-60 μm and containing large stores of synaptic vesicles at its periphery, opposite the complex of motoneuron dendrites. The transmission characteristics of the junctions between receptor cell and motoneurons were studied by transmembrane current injection into the isolated T-fibre by means of a sucrose gap and simultaneous intracellular recording with microelectrodes from the presynaptic terminal and the somata of postsynaptic cells. It was shown that depolarization-release coupling in the T-fibre has similar properties to those that have been demonstrated in the squid giant synapse, with the same values for ‘threshold’, peak release and ‘suppression potential’. The crab synapses differ from that of the squid in that they normally transmit prolonged, graded depolarizations (i.e. receptor potentials) which are decrementally conducted from the periphery. Consistent with this role, the junctions were found to be capable of continuous tonic transmission over many seconds without the strong depletion seen in more phasic synapses. In a study of the relation between the synaptic properties and the stretch reflex it was shown that some of the time- and amplitude-dependent behaviour of the overall reflex can be encoded at the level of the synaptic transmission, largely through the parameter of transmitter availability. Conduction of electrical signals in the proximal and presynaptic part of the sensory fibre was also investigated. Transient responses to step depolarizing currents in the fibre indicate the existence of a mechanism for the partial compensation of capacitative distortion in the decrementally conducted receptor potential. This is the first example of intracellular recording from presynaptic terminals of nonimpulsive neurons with simultaneous monitoring of postsynaptic potential changes, allowing for a direct analysis of depolarization-release coupling characteristics. The use of the preparation for further study of synaptic physiology and sensorimotor systems is discussed.