Abstract
Hereditary sensory and autonomic neuropathy type III (HSAN III, Riley–Day syndrome, Familial Dysautomia) is characterised by elevated thermal thresholds and an indifference to pain. Using microelectrode recordings we recently showed that these patients possess no functional stretch-sensitive mechanoreceptors in their muscles (muscle spindles), a feature that may explain their lack of stretch reflexes and ataxic gait, yet patients have apparently normal low-threshold cutaneous mechanoreceptors. The density of C-fibres in the skin is markedly reduced in patients with HSAN III, but it is not known whether the C-tactile afferents, a distinct type of low-threshold C fibre present in hairy skin that is sensitive to gentle stroking and has been implicated in the coding of pleasant touch are specifically affected in HSAN III patients. We addressed the relationship between C-tactile afferent function and pleasant touch perception in 15 patients with HSAN III and 15 age-matched control subjects. A soft make-up brush was used to apply stroking stimuli to the forearm and lateral aspect of the leg at five velocities: 0.3, 1, 3, 10 and 30cm/s. As demonstrated previously, the control subjects rated the slowest and highest velocities as less pleasant than those applied at 1–10cm/s, which fits with the optimal velocities for exciting C-tactile afferents. Conversely, for the patients, ratings of pleasantness did not fit the profile for C-tactile afferents. Patients either rated the higher velocities as more pleasant than the slow velocities, with the slowest velocities being rated unpleasant, or rated all velocities equally pleasant. We interpret this to reflect absent or reduced C-tactile afferent density in the skin of patients with HSAN III, who are likely using tactile cues (i.e. myelinated afferents) to rate pleasantness of stroking or are attributing pleasantness to this type of stimulus irrespective of velocity.
Highlights
The hereditary sensory and autonomic neuropathies (HSAN) are a group of rare neurological disorders with sensory and, to a varying degree, autonomic deficits that can be classified into five types, depending on mode of inheritance, neuropathology and clinical symptoms (Dyck et al, 1983)
ELP1 protein (Slaugenhaupt et al, 2001). Depletion of this protein results in reduced transcriptional elongation of target genes required for cell motility, suggesting that defective cellular motility may underlie much of the developmental neuropathology of HSAN III (Close et al, 2006; Cohen-Kupiec et al, 2011)
Experiments were performed on 15 patients (10 female, 5 male; 14– 48 years, mean ± SE 27.0 ± 2.8 years) with hereditary sensory and autonomic neuropathy type III (HSAN III); molecular confirmation of diagnosis was available for all patients
Summary
The hereditary sensory and autonomic neuropathies (HSAN) are a group of rare neurological disorders with sensory and, to a varying degree, autonomic deficits that can be classified into five types, depending on mode of inheritance, neuropathology and clinical symptoms (Dyck et al, 1983). In childhood and adolescence affected individuals present with very labile blood pressures, with orthostatic hypotension and greatly elevated blood pressures during episodes of anxiety; these may precipitate into autonomic crises and vomiting (Riley et al, 1949, Norcliffe-Kaufmann et al, 2010, 2013; Macefield et al, 2013a) They exhibit elevated temperature thresholds (Hilz and Axelrod, 2000; Hilz et al, 2004), an indifference to pain (Riley et al, 1949; Dyck et al, 1983; Axelrod, 2002; Hilz et al, 2004), and absent tendon and H-reflexes (Aguayo et al, 1971; Macefield et al, 2011)
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