Chronic immune sensory polyradiculopathy

Background: Chronic inflammatory neuropathies can present with a sensory ataxia due to involvement of dorsal root ganglia (DRG) or sensory nerves. Selective inflammatory involvement of sensory nerve roots proximal to the DRG has been postulated. Methods: The authors identified 15 patients with a sensory syndrome and normal nerve conduction studies. Sensory nerve root involvement was suggested by either somatosensory evoked potential (SSEP) or imaging abnormalities. CNS disease was excluded. Results: All patients had gait ataxia, large fiber sensory loss, and paresthesias, and nine had frequent falls. The disease course was chronic and progressive (median duration 5 years, range 3 months to 18 years). Sural sensory nerve action potential amplitudes were preserved and SSEP abnormalities were consistent with sensory nerve root involvement. Five patients had enlargement of lumbar nerve roots on MRI with enhancement in three. The CSF protein was elevated in 13 of 14 patients tested. Three patients had lumbar sensory rootlet biopsies that showed thickened rootlets, decreased density of large myelinated fibers, segmental demyelination, onion-bulb formation, and endoneurial inflammation. Six patients who required aids to walk were treated with immune modulating therapy and all had marked improvement with four returning to normal ambulation. Conclusion: Based on the described clinical features, normal nerve conduction studies, characteristic somatosensory evoked potential (SSEP) abnormality, enlarged nerve roots, elevated CSF protein, and inflammatory hypertrophic changes of sensory nerve rootlet tissue, we suggest the term chronic immune sensory polyradiculopathy (CISP) for this syndrome. This condition preferentially affects large myelinated fibers of the posterior roots, may respond favorably to treatment, and may be a restricted form of chronic inflammatory demyelinating polyradiculoneuropathy. NEUROLOGY 2004;63:1662–1669 A number of disorders can present with chronic sensory ataxia: vitamin deficiencies or excesses,1,2 inherited conditions (including spinocerebellar ataxias),3 infectious diseases (syphilis),4 lymphoand myeloproliferative disorders,5 toxic exposures,6-10 paraneoplastic diseases,11,12 metabolic conditions,13 and inflammatory demyelinating neuropathies (acute inflammatory demyelinating polyradiculoneuropathy [AIDP] and chronic inflammatory demyelinating polyradiculoneuropathy [CIDP]) as well as other immune disorders (sensory polyganglionopathy or Sjögren’s syndrome).14-16 Sensory ataxia theoretically may be due to involvement of dorsal columns, dorsal root entry zone, dorsal root, dorsal root ganglia (DRG), and sensory nerves. Inflammatory neuropathy with predominant involvement of the dorsal roots has been hypothesized in isolated cases as the cause of sensory ataxia.17-19 Here we provide clinical, electrophysiologic, radiologic, and pathologic description in a series of patients, suggesting that chronic immune sensory polyradiculopathy (CISP) is a definable, under-recognized, and possibly treatable clinical entity. Methods. We identified patients with a sensory polyradiculopathy by conducting a retrospective chart review from 1990 to 2002 of the Mayo Clinic, Rochester, MN, database. Medical records of 981 patients coded as having CIDP, polyganglionopathy, or ataxia were reviewed. Also reviewed were electrophysiologic studies with normal nerve conductions and EMG and abnormal somatosensory evoked potential (SSEP). Patients gave consent to have their records reviewed as monitored by our Institutional Review Board. We selected patients with localized neuropathy of the posterior roots based on the following criteria: 1) presence of a sensory syndrome without weakness; 2) essentially normal nerve conduction and EMG studies; 3) imaging studies that excluded brain, cerebellum, spinal cord, or compressive nerve root lesions; and 4) either SSEP or imaging abnormalities consistent with nerve root involvement. Electrophysiologic and quantitative sensory testing methods. Nerve conduction studies, EMG, and SSEP tests were performed using Nicolet Viking IV or Viking Select systems. Quantitative sensory testing was performed on the dorsal great toe or foot using CASE IV.20,21 Histologic methods. Three dorsal nerve rootlet biopsies were performed at Mayo Clinic, Rochester, MN. The pathologic alterations of three biopsied dorsal lumbar rootlets and of three age– range matched postmortem control specimens were evaluated in our laboratory, one of the control cases having been published previously.22 Standard histologic stains and immunohistochemistry (CD45, CD68) were prepared on paraffin sections. Semithin epoxy sections were stained with methylene blue and p-phenylenediamine. Electron microscopy was performed to better demonstrate ultrastructural changes. Teased fibers were prepared From the Peripheral Neuropathy Research Laboratory, Department of Neurology, Mayo Clinic and Mayo Foundation, Rochester, MN. Supported in part by grants obtained from the National Institute of Neurological Diseases and Stroke (NINDS 36797) and Mayo Foundation. Received September 25, 2003. Accepted in final form June 23, 2004. Address correspondence and reprint requests to Dr. P. James B. Dyck, Mayo Clinic, 200 First Street SW, Rochester, MN 55905; e-mail: [email protected] 1662 Copyright © 2004 by AAN Enterprises, Inc. and graded by previously defined pathologic criteria.23 Morphometric analysis was performed using our Imaging System for Nerve Morphometry.24 Results. Case presentation. A 66-year-old previously healthy woman with corrected hypothyroidism presented with marked sensory ataxia (Patient 1, tables 1 and 2). Ten years earlier, she noted onset of paresthesias in both lower extremities and loss of feeling in the left foot. The symptoms gradually worsened and spread proximally to become symmetric below the hips, and she progressively had difficulty walking. At presentation, she was using a wheelchair for long distances and two canes at home. She had started to experience prickling in her hands, and she had lack of feeling in her lower limbs without pain. Clinical examination revealed normal strength throughout. She was hyporeflexic in upper limbs and areflexic in lower limbs. Sensory examination was normal in upper limbs but showed absent vibration and joint position and motion sense with preserved pinprick in lower limbs. Motor and sensory nerve conduction studies of upper and lower limb nerves as well as needle EMG studies of distal and proximal lower limb and lumbar paraspinal muscles were normal for all parameters. Tibial SSEPs showed delayed scalp responses with absent cervical and lumbar responses. Median SSEPs were normal. The CSF was acellular with elevated protein (103 mg/dL). Brain and spinal cord imaging was normal. The following tests were normal or negative: vitamin B12, folate, vitamin E, lipid profile, serum protein immunofixation, rheumatologic antibodies, paraneoplastic antibodies and anti-gliadin antibodies, VDRL, HIV-I, II and HTLV I, II serologies, and spinocerebellar ataxia panel (SCA 1, 2, 3, 6, 7). MRI of the cauda equina showed hypertrophic nerve roots with enhancement post gadolinium (figure 1). A dorsal lumbar rootlet nerve biopsy was obtained. The myelinated fiber density was normal, but the fiber size distribution was altered with a marked reduction of large myelinated fibers (figure 2). There were scattered endoneurial lymphocytes (CD45), and endoneurial macrophages (CD68) were prominent despite absence of visible degenerating fiber profiles. Electron micrographs showed features of myelin remodeling with frequent onion-bulbs