Orthostatic hypotension is the leading feature; in those with the previously mentioned antibody, pupillary changes and difficulty with accommodation, dry mouth and dry eyes, and gastrointestinal paresis were the most common findings according to Sandroni and colleagues. Perhaps a subgroup is in some way related to Sjögren syndrome as sicca symptoms are prominent, but these later features could just as well be a component of the autonomic failure. There is not enough information to determine if all these cases are accounted for by one process or to judge the effects of various immune treatments.
The defining features of this unusual syndrome are searing and pulling sensations involving small cutaneous areas, that are evoked by extending or stretching the limb, as happens when reaching for an object, kneeling, or pointing with the foot (see Wartenberg). The pain is momentary but leaves in its wake a patch of circumscribed numbness. Cutaneous sensory nerves must be involved in some way and are irritated during such mechanical maneuvers. The areas involved are usually proximal to the most terminal sensory distribution of nerves encompassing, for example, a patch on the lateral side of the hand and the proximal fifth finger or a larger region over the patella (these were the sites affected in 3 of our patients). Recovery of the area of numbness takes several weeks, but it may persist if the symptoms are induced repeatedly. Except for these patches of cutaneous analgesia, the clinical examination is normal. Selected sensory nerves may show abnormalities in conduction, but nerve conduction studies are for the most part normal. Matthews and Esiri have listed the many areas that may be affected in a single patient and have described an increase in the endoneurial connective tissue in a biopsied sural nerve. The syndrome may come in episodes over many years, without symptoms between attacks. A spurious diagnosis of multiple sclerosis is often made. The pathology is not certain, but some form of fibrosis or inflammation of cutaneous nerves has been suggested, perhaps similar to the condition of perineuritis described below.
Under this title, Asbury and colleagues (1972) described a patchy, burning, painful, partially remitting distal cutaneous sensory neuropathy. The pathologic picture was one of inflammatory scarring restricted to the perineurium, with compression of the contained nerve fibers. As with the Wartenberg syndrome above, reflexes and motor function were unaffected. Digital nerves, as well as the medial and lateral branches of the superficial peroneal nerve, were the ones most often involved. Matthews and Squier have described a trigeminal and occipital distribution of painful sensory symptoms and 1 of the patients of Asbury and coworkers (1972) also had symptoms on the scalp. A Tinel sign is characteristically elicited by tapping the skin overlying the involved cutaneous nerves and is indicative of partial nerve damage and regeneration.
The differential diagnosis includes numerous other forms of painful sensory neuropathy, but the patchy and painful, and often burning, quality of symptoms distinguishes this process. The diagnosis can only be established with certainty by biopsy of a distal cutaneous branch of a sensory nerve. Perhaps some of the large group of patients with “burning” feet may have a small-fiber neuropathy that affects intradermal nerve fibers in a similar way (see further on).
Since the original report, the fibrosing perineurial pathologic changes that characterize perineuritis have been described in a number of polyneuropathies, mainly in diabetic patients but also in those with cryoglobulinemia, nutritional diseases, and malignancies (Sorenson et al). However, these patients displayed diverse clinical patterns of neuropathy, mainly mononeuritis multiplex and demyelinating neuropathy. Nonetheless, the pathologic feature of perineuritis may be less specific than initially thought but a perineuritis clinical syndrome is still a useful concept. A proportion of the idiopathic cases seem to respond to corticosteroids.