Combined hereditary neuropathy with liability to pressure palsy and non‐systemic vasculitic neuropathy

Dear Editor, Peripheral neuropathy is a common feature of many vasculitic syndromes and can be diagnosed by biopsy. Hereditary neuropathy with liability to pressure palsy (HNPP) presents as recurrent incidents of pressure palsy, usually in the second or third decade. Initially, the patient may sleep on a limb and the resulting palsy remains for days to weeks, instead of clearing in seconds to minutes. HNPP is accompanied by a chronic asymptomatic generalized polyneuropathy in many patients. In most families with HNPP, it is associated with a submicroscopic deletion on chromosome 17p11.2 involving the same 1.5-megabase interval that is duplicated in hereditary motor and sensory neuropathy type 1A (Chance et al., 1993; Li et al., 2004). We present electrophysiological, genetic, and pathology studies of a 38-year-old woman who had both HNPP and non-systemic necrotizing vasculitic neuropathy as a very unusual combination of neuropathies. The woman was referred because of numbness in the left ring and little fingers for 2 years, which developed gradually and did not extend to other fingers or limbs. She denied injury but had a history of several transient episodes of upper limb weakness in her second and third decades, which lasted for several days. She had no history of drug exposure, alcohol abuse, diabetes, or infection. She did not have any constitutional symptoms, including weight loss, anorexia, fatigue, arthralgia, myalgia, or fever. She had three brothers, one daughter, and one son without history of neuromuscular disorders. The patient’s neurological deficits were confined to motor weakness (MRC Grade 4/5), muscle atrophy, and mild sensory changes in the left ulnar nerve. The tendon reflexes were normal except for a bilaterally decreased triceps jerk. Results were normal, non-specific, or negative for the following laboratory tests: complete blood cell count; sedimentation rate; liver function; serum protein and immunoelectrophoresis; fasting blood sugar; glycosylated hemoglobin; C-reactive protein; hepatitis Bs antigen and antibody; cryoglobulin; thyroid function; vitamin B12; rheumatoid arthritis factor; anti-doublestranded DNA antibody; anti-HIV antibody; fluorescent anti-nuclear antibody; and anti-neutrophil cytoplasmic antibody. A cerebrospinal fluid examination disclosed normal protein concentration and no cellular reaction. Nerve conduction studies were consistent with an asymmetric multifocal polyneuropathy of the upper and lower limbs, which was more pronounced in sensory than in motor nerves. Neither a conduction block nor a temporal dispersion of action potentials was seen. Genetic analysis was carried out in the patient, her daughter, and her son. We used real-time quantitative polymerase chain reaction amplification using SYBR Green I on the ABI 7700 Sequence Detection System to detect the PMP22 gene deletion. The relative gene copy number was quantified using a comparative threshold cycle method and was found to be 0.42, 0.55, and 0.90 in the patient, her daughter, and her son, respectively. Normal control values in our patient population ranged from 0.85 to 1.26 (Kim et al., 2003). Despite the molecular diagnosis and nerve conduction studies, we considered that she did not have the typical symptoms and signs of HNPP. A biopsy of the sural nerve was performed to find other causes of polyneuropathy. The most striking finding was of dense inflammatory cell collections in the perivascular area of epineurial arterioles, sometimes within muscular leaflets of the vessel wall. Fibrinoid material was also noted by trichrome staining. No endoneurial vessels were affected. On plastic sections, the density of myelinated fibers was not significantly decreased (5,932/mm). Many regenerating clusters were noted in a few fascicles. Teased nerve fiber preparations showed sausage-shaped thickened fibers (4%) and very scanty axonal degeneration (2%), but segmental demyelination was not apparent. The patient was administered a moderate dose of prednisone (30 mg/day) for 8months. The numbness andweakness were much relieved, but atrophy was still apparent. Address correspondence to: Sang-Soo Lee, MD, Department of Neurology, Chungbuk National University, 62 Gaeshin-dong, Cheongju-si, Chungbuk 361-711, Korea. Tel: þ82-43-2696336; Fax: þ82-43-2757591; E-mail: sslee@chungbuk.ac. kr Journal of the Peripheral Nervous System 10:215–216 (2005)