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Mieke Hulens,1 Frans Bruyninckx,2 Dietmar Rudolf Thal,3,4 Ricky Rasschaert,5 Chris Bervoets,6– 8 Wim Dankaerts1 1Department of Rehabilitation Sciences, Musculoskeletal Rehabilitation Research Unit, Faculty of Kinesiology and Rehabilitation Sciences, KU Leuven, Leuven, Belgium; 2Department of Physical Medicine & Rehabilitation, EMG-Laboratory, University Hospitals of Leuven, Leuven, Belgium; 3Department of Imaging and Pathology, Laboratory of Neuropathology, and Leuven Brain Institute, KU Leuven, Leuven, Belgium; 4Department of Pathology, University Hospitals of Leuven, Leuven, Belgium; 5Department of Neurosurgery, AZ Rivierenland, Bornem, Belgium; 6Department of Neurosciences, Adult Psychiatry, KU Leuven, Leuven, Belgium; 7Department of Ophthalmology, University Hospitals of Leuven, Leuven, Belgium; 8Department Adult Psychiatry, University Psychiatric Center of KU Leuven, Leuven, BelgiumCorrespondence: Mieke Hulens,Department of Rehabilitation Sciences, Musculoskeletal Rehabilitation Research Unit, Faculty of Kinesiology and Rehabilitation Sciences, University of Leuven, Tervuursevest 101, Leuven, Belgium, Tel +32 478 338003, Fax +32 16 32 91 97, Email miekehulens@gmail.comPurpose: Tarlov cysts (TCs) are dilated nerve root sheaths originating from increased cerebrospinal pressure. Patients with TCs often complain of neuropathic pain and paresthesia. The aim of this study was to retrospectively review intraepidermal nerve fiber density (IENFD) and electrodiagnostic (EDX) data from TC patients.Patients and Methods: Lower leg skin biopsy results and EDX data from the L2–S4 myotomes of patients with lumbar or sacral TCs ≥ 8 mm were retrieved from a database of a physical medicine clinic. Patients with compressive pathology, diabetes mellitus and chemotherapy were excluded.Results: IENFD data from 17 patients and EDX data from 24 patients with TCs ≥ 8 mm were available. The mean age was 47 ± 10y, and 83% were women. In 82% of patients, the IENFD was below the 5th percentile by age and sex. EDX showed increased Hoffmann reflex latencies in 25%, increased anal reflex latencies in 95%, and a patchy distribution of neurogenic motor unit potentials in 100%. More than 50% of needle EMG abnormalities appeared in myotomes unrelated to the location of the TCs.Conclusion: Small- and/or large-fiber neuropathy was documented in a significant proportion of patients with TCs. The novel findings may add to the understanding of the mechanisms involved in symptomatic TCs. We propose that pathologically elevated cerebrospinal fluid pressure not only dilates some of the nerve root sheaths to form TCs but also potentially damages axons in nondilated nerve root sheaths and neurons in the dorsal root ganglia.Keywords: perineural cysts, skin biopsies, radicular pain, anal reflex, nerve conduction studies, fibromyalgia