Epidermal nerve fiber density, axonal swellings and QST as predictors of HIV distal sensory neuropathy

We investigated the associations of baseline epidermal nerve fiber (ENF) densities and morphology (percent ENF swellings) and quantitative sensory testing (QST) with clinically defined human immunodeficiency virus (HIV)‐associated distal polyneuropathy (DSP) and whether these measures are predictive of development of symptomatic DSP over time. Fifty‐seven HIV‐infected subjects with and without DSP and 19 controls participated. Mean ENF densities were lower at the distal leg and proximal thigh in asymptomatic or symptomatic DSP than in controls. Mean ENF densities did not differ significantly among the HIV groups. Percent ENF swellings was higher in patients with symptomatic DSP than controls at the distal leg, and was also greater at the proximal thigh in patients with asymptomatic or symptomatic DSP than in controls. The percent ENF swellings at the distal leg correlated with the thresholds for both minimal (HP 0.5) and intermediate (HP 5.0) heat pain (HP) intensity. A higher percent ENF swellings in the distal leg [hazard ratio (HR) 1.16, 95% CI 1.02–1.31] and HP 0.5 thresholds (HR 1.03, 95% CI 1.01–1.05) were the only two measures associated with a shorter time to development of symptomatic DSP. Quantitation of ENF swellings and heat pain thresholds deserve further study as predictors of symptomatic neuropathy. Muscle Nerve 29: 420–427, 2004

[1]  D. Cornblath,et al.  Predominantly sensory neuropathy in patients with AIDS and AIDS‐related complex , 1988, Neurology.

[2]  G. Fuller,et al.  Subclinical peripheral nerve involvement in AIDS: an electrophysiological and pathological study. , 1991, Journal of neurology, neurosurgery, and psychiatry.

[3]  A study of neuropathy in HIV infection. , 1992, The Quarterly journal of medicine.

[4]  P C O'Brien,et al.  Cool, warm, and heat‐pain detection thresholds , 1993, Neurology.

[5]  P C O'Brien,et al.  A 4, 2, and 1 stepping algorithm for quick and accurate estimation of cutaneous sensation threshold , 1993, Neurology.

[6]  G. Wendelschafer‐Crabb,et al.  The innervation of human epidermis , 1993, Journal of the Neurological Sciences.

[7]  S. Wesselingh,et al.  Unifying hypothesis for the pathogenesis of HIV-associated dementia complex, vacuolar myelopathy, and sensory neuropathy. , 1995, Journal of acquired immune deficiency syndromes and human retrovirology : official publication of the International Retrovirology Association.

[8]  G. Wendelschafer‐Crabb,et al.  Quantitation of epidermal nerves in diabetic neuropathy , 1996, Neurology.

[9]  L. Wilkins Clinical confirmation of the American Academy of Neurology algorithm for HIV-1-associated cognitive/motor disorder , 1996, Neurology.

[10]  J. McArthur,et al.  Intraepidermal nerve fiber density in patients with painful sensory neuropathy , 1997, Neurology.

[11]  J. McArthur,et al.  Epidermal nerve fiber density: normative reference range and diagnostic efficiency. , 1998, Archives of neurology.

[12]  T. Crawford,et al.  Small‐fiber sensory neuropathies: Clinical course and neuropathology of idiopathic cases , 1998, Annals of neurology.

[13]  J. McArthur,et al.  Epidermal innervation: changes with aging, topographic location, and in sensory neuropathy , 1999, Journal of the Neurological Sciences.

[14]  P. Dyck,et al.  Quantitative sensation testing in epidemiological and therapeutic studies of peripheral neuropathy , 1999, Muscle & nerve.

[15]  J. McArthur,et al.  Epidermal nerve fiber density and sural nerve morphometry in peripheral neuropathies , 1999, Neurology.

[16]  T. Larson,et al.  Patterns of quantitative sensation testing of hypoesthesia and hyperalgesia are predictive of diabetic polyneuropathy: a study of three cohorts. Nerve growth factor study group. , 2000, Diabetes care.

[17]  D. Katzenstein,et al.  A phase II trial of nerve growth factor for sensory neuropathy associated with HIV infection , 2000, Neurology.

[18]  J. McArthur,et al.  Subclinical sensory neuropathy in late-onset restless legs syndrome , 2000, Neurology.

[19]  D. Pareyson,et al.  Epidermal nerve fiber density in sensory ganglionopathies: Clinical and neurophysiologic correlations , 2001, Muscle & nerve.

[20]  K. Marder,et al.  Incidence of and risk factors for HIV-associated distal sensory polyneuropathy , 2002, Neurology.

[21]  J. Dötsch,et al.  Spontaneous Nocturnal Leptin Secretion in Children with Myelomeningocele and Growth Hormone Deficiency , 2002, Hormone Research in Paediatrics.

[22]  D. Katzenstein,et al.  Reduced intraepidermal nerve fiber density in HIV-associated sensory neuropathy , 2002, Neurology.

[23]  D. Herrmann,et al.  Epidermal reinnervation concomitant with symptomatic improvement in a sensory neuropathy , 2003, Muscle & nerve.

[24]  A. Hoke,et al.  Incidence of and risk factors for HIV-associated distal sensory polyneuropathy , 2003, Neurology.

[25]  D. Pareyson,et al.  Axonal swellings predict the degeneration of epidermal nerve fibers in painful neuropathies , 2003, Neurology.