Sensory phenotype and risk factors for painful diabetic neuropathy: a cross-sectional observational study.

Different sensory profiles in diabetic distal symmetrical sensory-motor polyneuropathy (DSPN) may be associated with pain and the responsiveness to analgesia. We aimed to characterize sensory phenotypes of patients with painful and painless diabetic neuropathy and to assess demographic, clinical, metabolic, and electrophysiological parameters related to the presence of neuropathic pain in a large cohort of well-defined DSPN subjects. This observational cross-sectional multi-center cohort study (performed as part of the ncRNAPain EU consortium) of 232 subjects with nonpainful (n = 74) and painful (n = 158) DSPN associated with diabetes mellitus of type 1 and 2 (median age 63 years, range 21-87 years; 92 women) comprised detailed history taking, laboratory tests, neurological examination, quantitative sensory testing, nerve conduction studies, and neuropathy severity scores. All parameters were analyzed with regard to the presence and severity of neuropathic pain. Neuropathic pain was positively correlated with the severity of neuropathy and thermal hyposensitivity (P < 0.001). A minority of patients with painful DSPN (14.6%) had a sensory profile, indicating thermal hypersensitivity that was associated with less severe neuropathy. Neuropathic pain was further linked to female sex and higher cognitive appraisal of pain as assessed by the pain catastrophizing scale (P < 0.001), while parameters related to diabetes showed no influence on neuropathic pain with the exception of laboratory signs of nephropathy. This study confirms the value of comprehensive DSPN phenotyping and underlines the importance of the severity of neuropathy for the presence of pain. Different sensory phenotypes might be useful for stratification of patients with painful DSPN for analgesic treatment and drug trials.

Spinal Cord MR Diffusion Properties in Patients with Degenerative Cervical Cord Compression.

BACKGROUND AND PURPOSE: Diffusion tensor imaging (DTI) has previously been used as a biomarker of myelopathy in patients with degenerative cervical cord compression (DCCC). However, many factors may affect the diffusion properties of the spinal cord. This prospective study seeks to identify sources of variability in spinal cord DTI parameters in both DCCC patients and healthy subjects. METHODS: The study group included 130 patients with DCCC confirmed by magnetic resonance imaging and 71 control subjects without signs of DCCC. DTI data of the cervical spine were acquired in all subjects. Fractional anisotropy (FA) and apparent diffusion coefficient (ADC) values were measured at different levels of the spinal cord (SCLs). Statistical data analysis was then used to determine diffusion parameters in terms of age, sex, SCL, and spinal cord compression. RESULTS: Significant variations in FA and ADC values emerged when several spinal cord levels were mutually compared in the control group. FA values correlated significantly with age in the DCCC group and sex had a significant influence on ADC values in both groups. The two diffusion parameters in the DCCC group differed significantly between patients with clinical signs of mild-to-moderate myelopathy compared with asymptomatic patients, and correlated with measurements of spinal canal morphology. CONCLUSIONS: Diffusion parameters of the cervical spinal cord were thus shown to respond significantly to spinal cord compression, but were subject to interaction with several other factors including sex, age, and SCL. These findings may be important to the interpretation of DTI measurements in individual patients.

Prevalence and Imaging Characteristics of Nonmyelopathic and Myelopathic Spondylotic Cervical Cord Compression.

STUDY DESIGN: Cross-sectional population-based observational study. OBJECTIVE: To estimate the prevalence of nonmyelopathic spondylotic cervical cord compression (NMSCCC) and cervical spondylotic myelopathy (CSM) in a population older than 40 years and to evaluate the magnetic resonance imaging (MRI) characteristics of these conditions. SUMMARY OF BACKGROUND DATA: The prevalence of neither NMSCCC nor CSM is known and there exists no commonly accepted quantitative MRI definition of cervical cord compression. METHODS: A group of 183 randomly recruited volunteers, 93 women, median age 66 years, range 40-80 years, underwent MRI examination of the cervical spine and spinal cord on a 1.5 T device using conventional sequences from disc levels C2/C3 to C6/C7. The imaging criterion for cervical cord compression was defined as a change in spinal cord contour at the level of an intervertebral disc on axial or sagittal MRI scan. RESULTS: MRI signs of cervical cord compression were found in 108 individuals (59.0%; 95% CI: 51.5%-66.2%); their numbers increased with age from 31.6% in the fifth decade to 66.8% in the eighth. Clinical signs of symptomatic CSM were found in two cases (1.1%), and 75 cases (41.0%) were without compression. An anteroposterior cervical canal diameter at the level of intervertebral disc (CDdisc) of less than 9.9 mm was associated with the highest probability of NMSCCC-odds ratio (OR) = 32.5, followed by a compression ratio of ≤0.5: OR = 11.1. CONCLUSION: The prevalence of NMSCCC in a population older than 40 years is higher than previously reported and increases with age. CDdisc and compression ratio had the highest capacity to discriminate between subjects with and without asymptomatic compression, and their cut-off values could be used to objectify criteria for cervical cord compression. LEVEL OF EVIDENCE: 2.

Broadening the spectrum of controls for skin biopsy in painful neuropathies: spondylotic cervical myelopathy patients with painful feet.

PURPOSE: Intraepidermal nerve fiber density (IENFD) is useful in the evaluation of small-fiber neuropathy (SFN). Recent guidelines recommend extending the spectrum of controls for IENFD assessment by evaluation of patients whose clinical picture mimics that of SFN. The aim of this study was to broaden the spectrum of IENFD controls by the assessment of patients with cervical spondylotic myelopathy (CSM) and painful feet. METHODS: Evaluation of IENFD from skin biopsy samples and quantitative sensory testing (QST) were performed in a cohort of 14 CSM patients (eight men, median age: 58; range: 46-63 years), with painful feet, exhibiting no clinical or electrophysiological signs of large-fiber polyneuropathy, and no risk factors for peripheral neuropathies. RESULTS: Quantitative sensory testing abnormalities were found in all but two of the CSM patients (86%), while the IENFD values were within reference range. The mean IENFD value (6.87 ± 2.78 fibers/mm) did not differ from that of an age- and sex-matched cohort of healthy volunteers (7.97 ± 2.21 fibers/mm, P > 0.05). CONCLUSIONS: The study confirmed normal skin biopsy findings in patients with CSM as one of the clinical conditions mimicking SFN and provided further support for the use of IENFD assessment in case of suspicion of SFN.

Does lumbar spinal stenosis increase the risk of spondylotic cervical spinal cord compression?

PURPOSE: The aim of this prospective cross-sectional observational comparative study was to determine the prevalence of spondylotic cervical cord compression (SCCC) and symptomatic cervical spondylotic myelopathy (CSM) in patients with symptomatic lumbar spinal stenosis (LSS) in comparison with a general population sample and to seek to identify predictors for the development of CSM. METHODS: A group of 78 patients with LSS (48 men, median age 66 years) was compared with a randomly selected age- and sex-matched group of 78 volunteers (38 men, median age 66 years). We evaluated magnetic resonance imaging findings from the cervical spine and neurological examination. RESULTS: The presence of SCCC was demonstrated in 84.6% of patients with LSS, but also in 57.7% of a sample of volunteers randomly recruited from the general population. Clinically symptomatic CSM was found in 16.7% of LSS patients in comparison with 1.3% of volunteers (p = 0.001). Multivariable logistic regression proposed the Oswestry Disability Index of 43% or more as the only independent predictor of symptomatic CSM in LSS patients (OR 9.41, p = 0.008). CONCLUSIONS: The presence of symptomatic LSS increases the risk of SCCC; the prevalence of SCCC is higher in patients with symptomatic LSS in comparison with the general population, with an evident predominance of more serious types of MRI-detected compression and a clinically symptomatic form (CSM). Symptomatic CSM is more likely in LSS patients with higher disability as assessed by the Oswestry Disability Index.