MRI and skin biopsy findings in sensory ganglionopathies

Objective. To support the clinical diagnosis of sensory ganglionopathy by (1) high signal intensity in the posterior columns on T2-weighted magnetic resonance imaging (MRI), and identifying (2) a distinct pattern of epidermal denervation in the leg on skin biopsy. Background. Ganglionopathies should be distinguished from sensory axonal neuropathies because of the different pathogenesis. Evidence of both central and peripheral sensory pathway degeneration in a fashion that is not length-dependent localizes the disease to sensory neurons of dorsal root ganglia (DRG). The early gait and limb ataxia and the distribution of positive symptoms at proximal areas of the body suggest that both large and small class sensory fibers degenerate in a fashion that is not length-dependent. Methods. Forty-two patients with predominantly sensory disturbances underwent cervical spine MRI and 3 of them also thoracic and lumbar MRI scanning. In 32 patients, skin biopsies were taken at the proximal thigh and the distal leg. In 4 of them further specimens were obtained from C5 dermatome and the hand. Fifteen healthy subjects also underwent skin biopsies in the lower limb. In 3 sections from each biopsy, immunostained with PGP9.5, linear density of intraepidermal nerve fibers (IENF) was quantified and compared by analysis of variance (ANOVA). Results. Neurological features. In 26 patients, sensory ganglionopathy was suspected. Limb and gait ataxia and proprioceptive sensory loss dominated the clinical picture, while positive sensory symptoms frequently involved face, trunk, and limbs in a patchy or asymmetrical fashion. Five patients had autonomic dysfunctions and 3 patients showed nystagmus. Disease was idiopathic in 7 cases, paraneoplastic in 6 cases, and associated with Sjögren, AIDS, and autoimmune chronic active hepatitis in 3 cases. One patient had a hereditary sensory autonomic neuropathy. Six patients developed sensory and cerebellar dysfunction in childhood: 4 of them had vitamin E deficiency and 2 a spinocerebellar syndrome. In 15 patients, sensory axonal neuropathy was diagnosed. Disease was related to diabetes, alcoholism, AIDS on antiretroviral treatment, and monoclonal gammopathy of undetermined significance. MRI findings. All ganglionopathy patients showed high signal intensity in the posterior columns on cervical T2-weighted MRI scanning. Signal abnormality was found at the dorsal and lumbar levels as well. Conversely, MRI was negative in all axonal neuropathy patients. Skin biopsy findings. Healthy subjects showed the distinct proximal:distal decreasing gradient of IENF density in the leg. All 16 neuropathy patients had significantly lower IENF density on the distal leg than on the proximal thigh, sup- porting a dying-back process. In 10 of 16 patients with a mixed sensory ganglionopathy, we did not find any change in IENF density with respect to the proximal:distal orientation in the leg. Similarly, in the arm, neuropathies had a lengthdependent loss of IENF while ganglionopathies did not show differences between the proximal and distal site. Epidermal innervation was normal in the remaining 6 ataxic patients. Discussion. Unlike peripheral motor disorders, sensory disturbances are less frequently diagnosed by the probable site of pathology. Ganglionopathy should be suspected when gait and limb ataxia and cutaneous sensory symptoms involving the proximal regions of the body dominate the clinical picture. These features reflect the impairment of sensory axons from muscle spindles and skin in a fashion that is not length-dependent. Particularly, this pattern of small class fiber loss was confirmed by skin biopsy. All ganglionopathy patients showed a clear-cut T2-weighted hyperintensity in the posterior columns, reflecting the degeneration of central sensory projection. These findings definitively localized the pathological process to T-shaped sensory neurons and strongly supported the clinical diagnosis of ganglionopathy.