Positive neuropathic sensory symptoms as endpoints in diabetic neuropathy trials.
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Clinical Trials as Topic↗
Biomedical subjects
I A Grant
Publications and source records attributed to I A Grant.
Progress in clinical neurosciences: Charcot-Marie-Tooth disease and related inherited peripheral neuropathies.
The classification of Charcot-Marie-Tooth disease and related hereditary motor and sensory neuropathies has evolved to incorporate clinical, electrophysiological and burgeoning molecular genetic information that characterize the many disorders. For several inherited neuropathies, the gene product abnormality is known and for others, candidate genes have been identified. Genetic testing can pinpoint a specific inherited neuropathy for many patients. However, clinical and electrophysiological assessments continue to be essential tools for diagnosis and management of this disease group. This article reviews clinical, electrophysiological, pathological and molecular aspects of hereditary motor and sensory neuropathies.
Charcot-Marie-Tooth Disease↗
Autonomic neuropathy associated with sicca complex.
We retrospectively studied 52 patients with sicca complex who presented primarily with peripheral neuropathic symptoms to assess the degree of autonomic involvement and its relationship to somatic neuropathy, serological tests and extraglandular disease. One patient presented with severe panautonomic dysfunction, with another six patients reporting prominent autonomic symptoms, and a further 40 patients having mild or asymptomatic disease. Eighty-seven percent of patients showed abnormalities on an autonomic reflex screen (ARS). Fifty-eight percent of patients showed a mixed pattern of autonomic dysfunction with abnormalities in two or more ARS subgroups of sudomotor, cardiovagal and adrenergic function. Three patients had a cholinergic autonomic neuropathy with sparing of adrenergic function. Tonic pupils were present in 13 patients. Autonomic neuropathy occurred in patients with a variety of somatic neuropathy subtypes, without a clear relationship between the type of autonomic neuropathy and the type of somatic peripheral neuropathy. Extraglandular disease was uncommon, occurring in only four patients. Serological abnormalities (extractable nuclear antigen [ENA], SS-A, SS-B) occurred in 20% of patients. We conclude that: (1) A wide spectrum of autonomic dysfunction is seen in sicca complex. (2) Severe autonomic involvement is uncommon, with most patients showing mildly symptomatic or asymptomatic disease. (3) Overall, characteristic patterns of autonomic dysfunction did not predominate, and there were no clear relationships with the different types of somatic peripheral neuropathy. (4) Clinical and serological evidence of non-neurological extraglandular disease is uncommon in this group of patients.
Adult↗
Peripheral neuropathy associated with sicca complex.
Peripheral neuropathy occurs in Sjögren's syndrome, a disorder in which systemic immunologic phenomena, including vasculitis, are common. Neuropathy also occurs with isolated sicca complex (keratoconjunctivits sicca and xerostomia); whether this represents a distinct syndrome is unclear. We retrospectively studied 54 patients with sicca complex and peripheral neuropathy to determine mode of presentation, neuropathic patterns, frequency and pattern of serologic abnormalities, and frequency of systemic disease, including necrotizing vasculitis. Peripheral neuropathy was the presenting problem in 87%. Although sicca symptoms occurred in 93%, they were a presenting complaint in only 11% and were usually mild, reported only after specific inquiry. Minor salivary gland biopsy was positive in 73%. Sensory neuropathies strongly predominated; 61% of patients manifested either sensory polyneuropathy or polyganglionopathy. Less common patterns included sensorimotor polyneuropathy (17%) and polyradiculoneuropathy (11%). Vasculitic neuropathy was demonstrated in only two patients, but nonspecific epineurial inflammation was present in 70% of nerve biopsies. Clinical evidence of systemic disease was uncommon, particularly in the sensory polyganglionopathy group, in whom extraglandular features other than weight loss occurred in only 1 of 12 patients. Antibodies to extractable nuclear antigens, the most specific serologic marker of Sjögren's syndrome, were present in 10.4%. We conclude that peripheral neuropathy and isolated sicca complex form a distinctive syndrome in which neuropathy is the presenting feature and sicca is easily overlooked; sensory polyneuropathy and polyganglionopathy predominate; serology is confirmatory but very insensitive; and extraglandular disease, including vasculitis, is uncommon compared with typical Sjögren's syndrome. Tests of ocular or salivary involvement are needed for diagnosis, and demonstration of inflammation in biopsied nerve is supportive. Improved definition of this disorder should permit further studies of natural history and efficacy of immunotherapy.
Adult↗
Ten steps in characterizing and diagnosing patients with peripheral neuropathy.
Cost-effective approaches for arriving at correct diagnoses should be used. Herein, we compare three approaches for the differential diagnosis of a common neurologic syndrome, peripheral neuropathy. In the "shotgun" approach, a standard battery of hematologic, biochemical, serologic, antibody, enzyme, molecular genetic, and other tests are ordered after the presence of a neuropathy is established, without a detailed characterization of the neuropathy. In the "gestalt" approach, the specific variety of neuropathy is identified by recognition of a clinical pattern of symptoms, course, or disease associations. The "10-step" approach, encompassing components of the two other methods and adding others, evolved from our assessment of many patients with peripheral neuropathy. In the 10-step approach, the history and neurologic examination place the patient's disorder into one of perhaps 21 anatomic-pathologic patterns. Next, electrophysiologic and other tests confirm the correctness of this anatomic-pathologic patterns. Finally, a series of evaluations exclude or include an increasingly shorter list of diagnoses until only one likely one remains or the disorder remains undiagnosed. We advocate the 10-step over the shotgun or gestalt approach, because it emphasizes careful initial characterization of neuropathy and emphasizes use of a logical step-by-step inclusion or exclusion to arrive at a short list of diagnostic possibilities. The approach depends ultimately on the judgement of adequately trained and experienced physicians, not on the results of single tests. The 10-step approach is not a mindless algorithm, leading inevitably to the correct diagnosis, but depends on judgment based on extensive background and neurobiologic and clinical knowledge and training.
Humans↗