John D. Stewart

Autoantibodies to Ganglionic Acetylcholine Receptors in Autoimmune Autonomic Neuropathies

BACKGROUND Idiopathic autonomic neuropathy is a severe, subacute disorder with a presumed autoimmune basis. It is indistinguishable from the subacute autonomic neuropathy that may accompany lung cancer or other tumors. Autoantibodies specific for nicotinic acetylcholine receptors in the autonomic ganglia are potentially pathogenic and may serve as serologic markers of various forms of autoimmune autonomic neuropathy. METHODS We tested serum from 157 patients with a variety of types of dysautonomia. Immunoprecipitation assays with iodine-125-labeled epibatidine and solubilized human neuroblastoma acetylcholine receptors were used to detect autoantibodies that bound to or blocked ganglionic receptors. RESULTS Ganglionic-receptor-binding antibodies were found in 19 of 46 patients with idiopathic or paraneoplastic autonomic neuropathy (41 percent), in 6 of 67 patients with postural tachycardia syndrome, idiopathic gastrointestinal dysmotility, or diabetic autonomic neuropathy (9 percent), and in none of 44 patients with other autonomic disorders. High levels of the binding antibodies correlated with more severe autonomic dysfunction (including the presence of tonic pupils). Levels of these antibodies decreased in patients who had clinical improvement. All seven patients with ganglionic-receptor-blocking antibodies had ganglionic-receptor-binding antibodies and had idiopathic or paraneoplastic autonomic neuropathy. CONCLUSIONS Seropositivity for antibodies that bind to or block ganglionic acetylcholine receptors identifies patients with various forms of autoimmune autonomic neuropathy and distinguishes these disorders from other types of dysautonomia. The positive correlation between high levels of ganglionic-receptor antibodies and the severity of autonomic dysfunction suggests that the antibodies have a pathogenic role in these types of neuropathy.

Chronic inflammatory demyelinating polyneuropathy (CIDP) in diabetics

Seven diabetic patients developed a progressive, moderately severe, motor rather than sensory neuropathy predominantly affecting the legs. This met clinical and electrophysiological criteria for chronic inflammatory demyelinating polyneuropathy (CIDP). Nerve biopsies showed a variety of abnormalities, none of which clearly distinguished between diabetic polyneuropathy and CIDP. The patients were treated with combinations of corticosteroids, azathioprine, plasmapheresis and intravenous immune globulin; all improved substantially. We believe that CIDP may masquerade as unusually severe and progressive diabetic distal symmetric polyneuropathy. It is important to recognize CIDP in diabetics because, unlike diabetic polyneuropathy, CIDP is treatable.

Peripheral neuropathy with IgM kappa monoclonal immunoglobulin directed against myelin‐associated glycoprotein

Three patients with a monoclonal IgM kappa paraproteinemia had a slowly progressive segmental demyelinating peripheral neuropathy. Sural nerve biopsies showed predominantly large fiber loss, with widening of the intraperiod line of myelin associated with active demyelination. Immunoblot analysis showed reactivity of IgM to myelin-associated glycoprotein (MAG) of human myelin. An enzyme-linked immunosorbent assay (ELISA) was developed to provide a simple quantitative technique for detection of antibodies to MAG. Treatment with corticosteroids, immunosup-pressive agents, and plasmapheresis produced no significant improvement.

Normal distributions of thermal and vibration sensory thresholds

The distributions of sensory thresholds were estimated in a healthy population while controlling for potential covariates. Using the method of levels and the two‐alternative forced choice, thermal and vibration thresholds respectively were measured in the hand and foot of 148 subjects. Age was uniformly distributed between 20 and 86 years. Independent effects of age, gender, height, and skin temperature were estimated using multiple linear regression. Parametric and nonparametric methods were used to estimate the distributions of interest. Significant age‐related increases were observed for all vibration thresholds (P < 0.0001), and for thermal thresholds in the foot (P < 0.0002). Percentiles were estimated for thermal thresholds in the hand and age‐adjusted continuous distributions were calculated for all other thresholds. Height was positively associated with vibration thresholds in the foot (P < 0.003), and appropriate corrections were made. Our results provide reference values for thermal and vibration sensory thresholds in a healthy population, allowing for the accurate diagnosis of disordered sensory function.

THE EFFECTS OF LARGE INTRAVENOUS INFUSIONS ON BODY FLUID

Much consideration has been given to the changes which result in man and in experimental animals from administering by vein various quantities of fluids of different composition (1, 2, 3). Thus, the dislocation of body fluid and the urinary changes which follow rapid infusion of massive quantities of fluid in animals have been described (4, 5, 6). Shifts of water and salts between muscle and blood after infusion of isotonic fluids of varying pH have been studied in dogs by means of muscle biopsy and analysis (7). The circulatory effects of administering fluid by vein in various clinical conditions have been investigated, having in mind the primary importance of circulatory dynamics in determining response to intravenous fluid therapy (1, 8). Such studies have served to emphasize the fundamental conclusions of Gamble (9, 10, 11), Peters (12, 13), and others. In the work on which the present report is based it seemed desirable to determine the results of large amounts of isotonic glucose and NaCl solutions administered by constant intravenous drip over a period of several days. The physiological responses to sustained submaximal infusions were under inquiry rather than the reaction to a large or small intravenous injection of brief duration, for it seemed possible that compensatory mechanisms of a different nature might be brought into play as the infusions were continued.

Auditory Agnosia: Apperceptive or Associative Disorder?

Neuropsychological testing of a patient with auditory agnosia showed that certain difficulties in the initial analysis of sounds may be the cause of his inability to understand spoken words and other sounds. Abnormalities included a slow reaction time to brief auditory stimuli (but not to equally brief visual stimuli or to longer auditory stimuli) and the need for approximately 1/4 sec of silence between two tones before the patient was able to hear them as separate. He could identify words and word associations if he was able to view the object whose name or word associate he was hearing. The findings imply that this patients deficit in comprehending speech was probably apperceptive rather than associative in origin.

Common peroneal neuropathy A study of selective motor and sensory involvement

We performed a prospective clinical and electrophysiologic study of common peroneal (CP) neuropathy to evaluate the extent of involvement of the muscles and cutaneous areas supplied by this nerve. In 22 patients, seven had more weakness clinically in muscles innervated by the deep peroneal nerve than in those innervated by the superficial peroneal nerve; the reverse never occurred. Statistical paired comparisons confirmed the tendency in the entire group of patients for weakness to be greater in muscles supplied by the deep peroneal nerve. On EMG, denervation was more often present and of more marked degree in muscles supplied by the deep peroneal nerve. Motor nerve conduction studies indicated axonal damage and focal demyelination with similar frequency. Sensory deficits varied in the three areas supplied by the cutaneous branches of the CP nerve: five patients had involvement of all three areas, 11 of two areas, two of one area, and four had no sensory deficit. The most likely explanation for these findings is differing degrees of damage to individual fascicles within the CP nerve.

Pediatric meralgia paresthetica

Meralgia paresthetica is a focal peripheral neuropathy involving the lateral femoral cutaneous nerve and is rarely observed in pediatric practice. Previous reports have highlighted its occurrence within the context of a regional bony malignancy. We present here three patients less than 18 years of age with idiopathic meralgia paresthetica.

Distal sciatic nerve compression by a popliteal artery aneurysm

A 77-year-old man developed progressive sensory and motor symptoms in the right lower leg. Examination showed neurological deficits in the distribution of the right tibial and common peroneal nerves. Swellings in both popliteal fossae were palpated. Investigation showed these to be large thrombosed aneurysms. On surgical examination on the right, the aneurysm was found to be compressing the distal sciatic nerve.

Computed tomography in the evaluation of plexopathies and proximal neuropathies.

We describe nine patients with plexopathies or proximal mononeuropathies due to mass lesions. In four, computed tomography (CT) was the only radiological technique to show the cause of the neuropathy. In five patients, CT either unequivocally confirmed the presence of an abnormality or was superior to other imaging techniques in showing its full anatomical extent. CT scanning is a valuable aid in the assessment of lesions of the peripheral nervous system, particularly plexopathies and mononeuropathies caused by retroperitoneal, pelvic or superior pulmonary sulcus tumors.