腓浅神经与腓骨短肌联合活体组织检查的诊断意义初探及15例临床病理报告

目的 开展单一切口下的腓浅神经与腓骨短肌联合活体组织检查,通过回顾相关病例的临床和病理资料,分析联合活体组织检查的诊断意义.方法 共15例患者,女性7例,男性8例,年龄14 ～72岁,其中亚急性6例、慢性9例,均患有周围神经病,3例临床上合并肌肉病.周围神经病的临床类型包括对称性感觉和运动性神经病7例、多发性单神经病5例、对称性感觉性神经病3例.在外踝前上方纵切口,取材腓浅神经与腓骨短肌.神经和肌肉病理结论的意义评价分为3级:(1)具有确诊意义;(2)对诊断有帮助:(3)对诊断无帮助.结果 活体组织检查病理结论有确诊意义者7例,包括血管炎5例、炎性脱髓鞘性周围神经病1例和淀粉样变性1例.有帮助者5例:病理改变分别为:慢性髓鞘性神经病伴洋葱球样肥大纤维;小血管病变伴轻度炎性反应;轻度间质炎性反应;脂褐素沉积等.无帮助者3例.最终12例通过活体组织检查得以确诊.结论 联合活体组织检查的诊断阳性率较高,血管炎周围神经病和淀粉样变性等适用联合活体组织检查.     

Physiologic-pathologic correlation in Guillain-Barré syndrome in children

OBJECTIVE: To correlate electrophysiologic patterns with sural nerve pathology in children with Guillain-Barré syndrome (GBS). BACKGROUND: Based on electrophysiologic and pathologic observations, GBS has been divided into demyelinating and axonal subtypes. The acute motor axonal neuropathy (AMAN) involves predominantly motor nerve fibers with a physiologic pattern suggesting axonal damage, whereas the acute inflammatory demyelinating polyneuropathy (AIDP) involves both motor and sensory nerve fibers with a physiologic pattern suggesting demyelination. In this study, we sought to confirm these observations by correlating sural nerve pathology with electrophysiologic findings in GBS patients. METHODS: Biopsies of sural nerve from 29 of 50 prospectively studied GBS patients were obtained. Nerves were examined by light and electron microscopy, and with immunocytochemistry for macrophages, lymphocytes, and complement activation products. RESULTS: Sural nerves from AMAN patients were normal or had only a few (0.1% to 0.7%) degenerating fibers without lymphocytic infiltration or complement activation. One patient with reduced sural sensory nerve action potential classified as acute motor sensory axonal neuropathy (AMSAN) had many degenerating fibers (2.3%) in the sural nerve. All three AIDP patients displayed active demyelination, and in two patients, lymphocytic infiltration and complement activation products were observed on the abaxonal Schwann cell surface. CONCLUSION: Classification of Guillain-Barré syndrome subtypes based on motor conduction studies correlates closely with pathologic changes seen in sural nerve. In acute motor axonal neuropathy cases, the sural nerve is almost completely spared pathologically. In acute inflammatory demyelinating polyneuropathy cases, macrophage-mediated demyelination and lymphocytic infiltration are common in the biopsies of sural nerves.     

Microvasculitis in non-diabetic lumbosacral radiculoplexus neuropathy (LSRPN): similarity to the diabetic variety (DLSRPN)

Diabetic lumbosacral radiculoplexus neuropathy (DLSRPN) has been shown to be due to ischemic injury from microvasculitis. The present study tests whether ischemic injury and microvasculitis are the pathologic cause of non-diabetic lumbosacral radiculoplexus neuropathy (LSRPN), and whether the pathologic alterations are different between LSRPN and DLSRPN. We studied distal cutaneous nerve biopsies of 47 patients with LSRPN and compared findings with those of 14 age-matched healthy controls and 33 DLSRPN patients. In both disease conditions, we found evidence of ischemic injury (multifocal fiber degeneration and loss, perineurial degeneration and scarring, characteristic fiber alterations, neovascularization, and injury neuroma) that we attribute to microvasculitis (mural and perivascular mononuclear inflammation of microvessels, inflammatory separation, fragmentation and destruction of mural smooth muscle, and previous microscopic bleeding [hemosiderin]). Teased nerve fibers in LSRPN showed significantly increased frequencies of axonal degeneration, segmental demyelination, and empty nerve strands. The segmental demyelination appeared to be clustered on fibers with axonal dystrophy. The nerves with abnormal frequencies of demyelination were significantly associated with nerves showing multifocal fiber loss. We reached the following conclusions: 1) LSRPN is a serious condition with much morbidity that mirrors DLSRPN. 2) Ischemic injury from microvasculitis appears to be the cause of LSRPN. 3) Axonal degeneration and segmental demyelination appear to be linked and due to ischemia. 4) The pathologic alterations in LSRPN and DLSRPN are indistinguishable, raising the question whether these 2 conditions have a common underlying mechanism, and whether diabetes mellitus contributes to the pathology or is a risk factor in DLSRPN. 5) Both LSRPN and DLSRPN are potentially treatable conditions.     

Giant Axonal Neuropathy Locus Refinement To A < 590 KB Critical Interval

Diabetic lumbosacral radiculoplexus neuropathy (DLSRPN) has been shown to be due to ischemic injury from microvasculitis. The present study tests whether ischemic injury and microvasculitis are the pathologic cause of non-diabetic lumbosacral radiculoplexus neuropathy (LSRPN), and whether the pathologic alterations are different between LSRPN and DLSRPN. We studied distal cutaneous nerve biopsies of 47 patients with LSRPN and compared findings with those of 14 age-matched healthy controls and 33 DLSRPN patients. In both disease conditions, we found evidence of ischemic injury (multifocal fiber degeneration and loss, perineurial degeneration and scarring, characteristic fiber alterations, neovascularization, and injury neuroma) that we attribute to microvasculitis (mural and perivascular mononuclear inflammation of microvessels, inflammatory separation, fragmentation and destruction of mural smooth muscle, and previous microscopic bleeding [hemosiderin]). Teased nerve fibers in LSRPN showed significantly increased frequencies of axonal degeneration, segmental demyelination, and empty nerve strands. The segmental demyelination appeared to be clustered on fibers with axonal dystrophy. The nerves with abnormal frequencies of demyelination were significantly associated with nerves showing multifocal fiber loss. We reached the following conclusions: 1) LSRPN is a serious condition with much morbidity that mirrors DLSRPN. 2) Ischemic injury from microvasculitis appears to be the cause of LSRPN. 3) Axonal degeneration and segmental demyelination appear to be linked and due to ischemia. 4) The pathologic alterations in LSRPN and DLSRPN are indistinguishable, raising the question whether these 2 conditions have a common underlying mechanism, and whether diabetes mellitus contributes to the pathology or is a risk factor in DLSRPN. 5) Both LSRPN and DLSRPN are potentially treatable conditions.     

Chronic relapsing axonal neuropathy: A first case report

A relapsing and remitting axonal polyneuropathy developed in a woman at age 47. Serial electrophysiological studies showed that the amplitudes of compound muscle action potentials and sensory action potentials were reduced but conduction velocities were only midly slowed. F wave latencies were normal and there was no evidence of conduction block. Two sural nerve biopsy specimens showed changes supportive of axonal neuropathy. Repeated responses to prednisolone alone and later prednisolone and azathioprine suggested that inflammatory, possibly autoimmune, processes were important in this case of chronic relapsing axonal neuropathy.     

Superficial peroneal nerve/peroneus brevis muscle biopsy in vasculitic neuropathy

OBJECTIVE: To determine the sensitivity and specificity of superficial peroneal nerve (SPN)/peroneus brevis muscle (PBM) biopsy in a cohort of patients with suspected peripheral nerve vasculitis. BACKGROUND: In patients with suspected vasculitic neuropathy, combined nerve and muscle biopsies have been advocated as a way to increase the diagnostic yield, but the sensitivity and specificity of this approach have not been evaluated. Pathologic predictors of biopsy-proven peripheral nerve vasculitis have also not been analyzed in a systematic fashion. METHODS: The clinical, laboratory, and pathologic data for all patients undergoing SPN/PBM biopsy for possible vasculitis from 1986 through 1996 were analyzed. Biopsies were classified as positive, negative, or suspicious for vasculitis. Patients were then divided into vasculitis and nonvasculitis cohorts by final clinical diagnosis. RESULTS: Of 70 SPN/PBM biopsies, 22 (30%) showed definite vasculitis; nerve was diagnostic in 90% (n = 20) and muscle in 50% (n = 11). Nerve biopsy had a higher yield than muscle in patients with nonsystemic vasculitic neuropathy (p = 0. 0047) but not in those with systemic vasculitis. The estimated sensitivity of a positive SPN/PBM biopsy for vasculitis was 60%. Considering biopsies either positive or suspicious for vasculitis increased the sensitivity to 86% with a corresponding specificity of 85%. Pathologic features associated with necrotizing vasculitis were muscle fiber necrosis/regeneration (relative risk 18.1; 95% CI 3.4 to 96.1), predominant axonal nerve pathology (>8.8; >1.0 to 77.4), Wallerian-like degeneration (5.6; 1.4 to 21.9), and asymmetric nerve fiber loss (4.6; 1.4 to 15.9). CONCLUSIONS: These findings establish the yield, sensitivity, and specificity of SPN/PBM biopsy for diagnosing vasculitic neuropathy and validate the use of suggestive pathologic features for diagnosing cases lacking definite necrotizing vascular changes.     

Glue sniffer's neuropathy.

Progressive sensorimotor neuropathy developed in two patients exposed to prolonged (chronic) inhalation of n-hexane (glue sniffing). Sural nerve biopsies showed loss of axons; remaining axons were either normal or showed accumulation of filaments of 90 to 100 A thick, widened nodes of Ranvier, and focal enlargements. The muscle biopsy revealed neurogenic atrophy. Intramuscular nerve twigs and end-plates, studied in one patient, showed loss of axons and nerve terminals. Unmyelinated axons also showed accululation of 60 to 100 A thick filaments. The similarities between the pathologic findings in the peripheral nerve of these patients and those with acrylamide neuropathy suggest that the n-hexane inhalation produces a dying back neuropathy.     

Sarcoid neuropathy: clinico-pathological study of 4 new cases and review of the literature

There are several reviews devoted to neurosarcoidosis and a few reports restricted to sarcoid neuropathy. Since 1989, we have investigated 4 new cases of sarcoid neuropathy, 1 with chronic sensory motor neuropathy (CSMN), another with painful neuropathy and 2 with atypical chronic inflammatory demyelinating polyneuropathy (CIDP). In each case, biopsy specimens from the superficial peroneal nerve and peroneus brevis muscle were taken by the same cutaneous incision and studied on paraffin sections, semi-thin sections and under electron microscope. We compared neuropathological findings from our 4 cases with those from 34 well-studied nerve biopsies previously reported in the literature, and which concerned 16 cases of CSMN, 13 cases ofmononeuropathy multiplex, 2 cases of painful neuropathy and three cases of CIDP. In all of these 38 cases of sarcoid neuropathy, the characteristic noncaseiting granulomas (NCG) were observed on the nerve in 11 cases, on the muscle alone in 5, on both muscle and nerve in 10, and in the nerve and another parenchyma in 4. In the 8 remaining cases, NCG were observed in another parenchyma, mainly lung or lymph nodes. Moreover, necrotizing vasculitis was present in nerve biopsies from 8 cases and microvasculitis without obvious necrosis in 2 others. Nerve fiber lesions, which are mainly axonal, are probably related to mechanical compression by NCG and/or to an ischemic process due to vasculitis. Cytokines and immune factors may also play a role, especially in certain cases with a clinical presentation of CIDP.     

Cerebrotendinous xanthomatosis. Controversies about nerve and muscle: observations in ten patients

Neuromuscular characteristics were documented in ten patients with biochemically and genetically confirmed cerebrotendinous xanthomatosis. An array of genotypes was found in these patients. Only one patient complained of muscle weakness, while clinical signs of peripheral neuropathy were present in six patients. Electromyogram showed predominantly axonal neuropathy in seven patients. Neurogenic changes were seen in muscle biopsies of nine patients. Sural nerve biopsies of three patients showed features of axonal neuropathy. In addition, in one patient, extensive onion bulb formation was seen, which is indicative of a primarily demyelinating process. Five patients had normal mitochondrial respiratory chain enzyme activity. It is concluded that myopathy is not a feature of cerebrotendinous xanthomatosis and that the most prominent neuromuscular abnormality is sensorimotor axonal polyneuropathy.     

Distinctive pathologic findings in proximal diabetic neuropathy (diabetic amyotrophy)

OBJECTIVE: To investigate the pathogenesis of proximal diabetic neuropathy (PDN) with nerve and muscle biopsies. BACKGROUND: Recent evidence suggests that nerve ischemia secondary to immune-mediated vasculopathy rather than diabetic microangiopathy may be responsible for PDN.Method:- Fifteen patients with PDN and two diabetic controls underwent nerve and muscle biopsy and clinical, electrophysiologic, and laboratory evaluation. There were eight men and seven women between 49 and 79 years of age with type II diabetes. All had progressive, painful, asymmetric, proximal weakness with duration of 5 weeks to 12 months. None had evidence of systemic autoimmune disorder. RESULTS: Four patients showed the distinctive findings of polymorphonuclear small-vessel vasculitis affecting epineurial vessels with transmural infiltration of postcapillary venules with polymorphonuclear leukocytes. Immunoglobulin M (IgM) deposits were found along the endothelium and intramurally in affected vessels. IgM staining was seen in the subperineurial space and in the endoneurium. Activated complement deposition was seen along endothelium of small vessels. Three of these four patients were evaluated within 6 seeks of onset of PDN, and the fourth patient during acute flare of PDN 6 months after the initial onset. Six patients showed "perivasculitis" with mononuclear cell infiltrates around small epineurial vessels without vasculitis (fibrinoid necrosis or transmural inflammation). One patient showed recanalized vessels with transmural lymphocytes without fibrinoid necrosis, possibly suggesting healed vasculitis. CONCLUSION: These distinctive pathologic findings support that proximal diabetic neuropathy has an immune-mediated inflammatory basis and suggest that polymorphonuclear vasculitis with immune complex and complement deposition may be the primary event in the acute phase of proximal diabetic neuropathy.     

Skin denervation in vasculitic neuropathy

BACKGROUND: Skin denervation in vasculitic neuropathy has rarely been documented despite frequent manifestations of small-fiber neuropathy including reduced sensitivity and neuropathic pain. Recently, skin biopsy has been established as a new approach to diagnose small-fiber sensory neuropathy. OBJECTIVES: To investigate the pathologic features of cutaneous nerves and to evaluate inflammatory vasculopathy in the skin of patients with vasculitis. DESIGN: Case series. SETTING: National Taiwan University Hospital, Taipei.Patients Six patients with vasculitic neuropathy. INTERVENTIONS: Patients had 3-mm punch biopsy specimens taken from the distal part of the leg (without active vasculitic lesions) and a sural nerve biopsy specimen was taken in addition to detailed neurologic examinations, laboratory investigations, and nerve conduction studies. MAIN OUTCOME MEASURES: Results of nerve conduction studies, epidermal nerve fiber density studies, and immunohistochemistry. RESULTS: All 6 patients had combined large- and small-nerve-fiber involvement on the neurologic examinations. Nerve conduction studies showed a pattern of axonal neuropathy or mononeuropathy multiplex. Epidermal nerve fiber densities were significantly reduced in the skin of all patients, consistent with concomitant small-fiber neuropathies. Perivascular infiltration by T cells and macrophages was demonstrated by immunohistochemistry. All patients experienced neurologic improvement in muscle strength and alleviation of sensory symptoms after immunotherapy with corticosteroids, plasma exchange, or cyclophosphamide. CONCLUSIONS: Small-diameter sensory nerves are affected in vasculitis in addition to the well-known effect of vasculitis on large-diameter nerves. Significant inflammatory vasculopathy is present in the skin despite the absence of clinically active vasculitic lesions.     

Immune-mediated neuropathy and myopathy in post-streptococcal disease: electron-microscopical, morphometrical and immunohistochemical studies.

A 22-year-old man suffered from a complete flaccid tetraparesis and an immune complex-mediated rapid progressive glomerulonephritis after group A streptococcal infection. Serum creatine kinase was excessively elevated and myoglobinuria occurred. Nerve conduction studies revealed evidence of axonal neuropathy. Recovery was satisfactory within 18 months. Sural nerve and peroneus muscle biopsies were performed in the 4th and 14th week of the disease. Light microscopy of the sural nerve showed an incipient axonal type of neuropathy in the first biopsy. Ultrastructurally, Wallerian degeneration and endoneurial inflammatory cells were present. In the muscle biopsy, few atrophic fibers and altered blood vessels without further anomalies were found. In the second sural nerve biopsy, macrophages were numerous, some of which were immunoreactive for HLA-DR, and only a few myelinated and some unmyelinated nerve fibers remained. Muscle fibers in the second biopsy showed high-grade atrophy and myofibrillar abnormalities. Immunohistochemistry revealed diffuse endoneurial immunoglobulin deposition in the first sample, while in the later biopsy specimen, deposits of IgG, and kappa and lambda light chains were visible in circumscribed endoneurial areas. Immune-mediated neuropathy and myopathy are not well-known complications of streptococcal disease. This is, to our knowledge, the first detailed report on morphological findings in muscle and nerve in such a disorder.     

Peripheral neuropathy in the hypereosinophilic syndrome: a case report

We observed a patient with the hypereosinophilic syndrome that showed as a prominent clinical feature peripheral nerve dysfunction. The neuropathy evolved over 4 months and affected sensory and motor functions. Nerve conduction studies and EMG were compatible with axonal neuropathy. Nerve and muscle biopsies revealed severe axonal degeneration with neurogenic atrophy of muscle. Morphometry of peroneal nerve showed marked axonal loss, more prominent in large myelinated fibers. There was no evidence of vasculitis process. Neuropathy is produced by eosinophil-released substances exerting a neurotoxic effect through direct altered vascular endothelial permeability and local mast cell histamine release.     

Multifocal neuropathy with vasculitis in hypereosinophilic syndrome

Summary A 56-year-old male with a 2-year history of bronchial asthma, together with pulmonary infiltration and marked eosinophilia, developed a subacute multifocal sensorimotor neuropathy. Electrodiagnostic studies demonstrated both multifocal and generalized nerve involvement. Sural nerve and muscle biopsies revealed axonal degeneration with almost complete loss of myelinated fibres, lymphomononuclear vasculitis of interstitial vasa nervorum without eosinophils, and neurogenic atrophy of muscle without angiitis. Although eosinophilia decreased drastically with corticosteroid treatment, neuropathy rapidly progressed to total disability. The patient died from pulmonary embolism 4 months after the onset of neurological signs. Autopsy disclosed vasculitis of epineurial vessels of peripheral nerves and severe axonal neuropathy, particularly of the lower limbs, without vasculitis or other inflammatory lesions in any other organ system, including the lungs. Retrospective analysis revealed that the onset of pulmonary infiltration and eosinophilia coincided with the administration of cromolyn sodium (Intal), which is known to produce PIE syndrome (pulmonary infiltration and eosinophilia), vasculitis and allergic granulomatosis, while multifocal neuropathy with vasculitis appears not to have been reported in connection with this substance.     

The heterogeneity of distal arthrogryposis

A study of distal arthrogryposis is described including neurology, electromyography, cerebral and muscular CT-scanning, and muscle and nerve biopsies. In four cases presenting with congenital distal contractures, various neuromuscular disorders were diagnosed. They were respectively, congenital myopathy with core-like structures, congenital hypertrophic neuropathy, axonal neuropathy and anterior horn cell disease. The role of cerebral disorders in the pathogenesis of distal contractures is also considered. The significance of abnormal dermatoglyphics in the determination of the prenatal time of onset of congenital myopathies and arthrogryposis is discussed. Our findings provide evidence for the hypothesis that distal arthrogryposis may not be a distinct clinical entity with an autosomal dominant inheritance pattern, but a symptom, indicating various cerebral, neuromuscular and connective tissue disorders, present in numerous congenital syndromes with different modes of inheritance. In addition the value of electromyography, nerve conduction velocity studies, muscle and cerebral CT-scanning, and histology of muscle and nerve biopsies in the differential diagnosis of (distal) arthrogryposis is stressed.     

Alcoholic neuropathy: Clinical,electrophysiological, and biopsy findings

Nerve conduction and biopsy findings from the sural nerve in 37 patients with alcohokic neuropathy were compared with findings in 6 patients who had neuropathy associated with postgastrectomy malnutrition. Half the patients with alcoholic neuropathy had both muscle weakness and sensory loss, half had only sensory impairment, but all had electromyographic signs of denervation. Only half the patients, with or without muscle weakness, had signs of malnutrition. In alcoholics, sural nerve conduction velocity was slowed to at most 60% of normal, correlating with loss of large fibers. These findings, together with a marked reduction in amplitude of the sensory potentials, are consistent with axonal loss. Myelinated fiber counts showed loss of small and large fibers in most nerves, retaining a bimodal distribution. Signs of regeneration were rare. Segmental demyelination was found in only 0.3% of teased fibers. Electron microscopy confirmed axonal degeneration of myelinated and unmyelinated fibers. Neuropathy after gastrectomy malnutrition was clinically similar to alcoholic neuropathy. Conduction velocities were slower than expected from the diameter of the largest myelinated fibers, however, and teased fibers showed segmental demyelination. The findings are against alcoholic neuropathy being due to malnutrition and suggest a toxic action on peripheral nerve.     

Allograft inflammatory factor-1: a pathogenetic factor for vasculitic neuropathy

Allograft inflammatory factor-1 (AIF-1) is a cytokine that plays a major role in the immune response and proliferative vasculopathy that occur during chronic allograft rejection. The purpose of this study was to characterize the cellular expression pattern and pathogenetic role of AIF-1 in nerve biopsies from patients with vasculitic neuropathy. We performed immunohistochemistry in human nerve biopsies of 10 patients with vasculitic neuropathies (VASs), 6 with chronic inflammatory demyelinating polyneuropathies (CIDPs), 5 with noninflammatory axonal neuropathies (NIANs), and 3 control nerves (CNs). In the CIDP and VAS nerves, AIF-1 expression was higher than in CN and NIAN nerves (P < 0.05). AIF-1 was increased in the arterial walls of VAS compared with CIDP nerves (P < 0.05). Vascular smooth muscle cells in vasculitic nerve express AIF-1 at a higher level compared with CIDP and NIAN. AIF-1 plays a role in inflammatory nerve disease and vascular smooth muscle cell proliferation and may be a new molecular target for treatment.     

Sensory CIDP presenting as cryptogenic sensory polyneuropathy

The objective of this study was to report that patients with chronic inflammatory demyelinating polyneuropathy (CIDP) can present with a clinical picture of cryptogenic sensory neuropathy. Patients with distal sensory neuropathy and electrodiagnostic studies that are minimally abnormal or consistent with an axonal pathology are usually diagnosed as having cryptogenic sensory neuropathy if no cause for neuropathy can be found. Some of these patients, however, may have sensory CIDP. We reviewed the records of eight patients with CIDP, diagnosed by sural nerve biopsy, who presented with sensory neuropathy and electrodiagnostic studies that were minimally abnormal or revealed changes consistent with axonal neuropathy. All patients reported distal numbness and paresthesias and, on examination, had predominantly large fiber distal sensory loss and normal muscle strength. In most patients, deep tendon reflexes were reduced or absent. Sural nerve biopsies in all patients were consistent with chronic myelinopathy, with quantitative teased fiber analysis revealing segmental remyelination in 13-40% of the fibers. The four patients who received IVIg therapy had improved sensation and gait. Of the remaining four patients, one is being followed, one had spontaneous remission, one was lost to follow-up, and one, with contraindications to therapy, reported disease progression. Sensory CIDP may present as cryptogenic sensory polyneuropathy with normal or axonal electrophysiologic features. Sural nerve biopsy should be considered in patients with progressive, predominantly large fiber sensory neuropathy of otherwise unknown etiology, as they may have sensory CIDP that responds to therapy.     

Clinical phenotype of Charcot-Marie-Tooth disease (CMT) and familial amyloid polyneuropathy (FAP)]

A nationwide study of CMT and FAP has been performed. In FAP TTR Met30 families with late onset, neuropathy showed male preponderance, low penetrance, little relationship to endemic foci, sensorimotor symptoms beginning distally in the lower extremities with disturbance of both superficial and deep sensation, and relatively mild autonomic symptoms, consistent with pathological findings. In contrast, families with early onset showed higher penetrance, concentration in endemic foci, predominant loss of superficial sensation, severe autonomic dysfunction. Demyelinating versus axonal phenotypes are major issues in CMT. CMT1A duplication caused mainly demyelinating phenotype, while axonal features were variably present. In CMT1B, two distinctive phenotypic subgroups were present: one showed exclusively axonal features; and another was exclusively demyelinating. CMTX showed intermediate slowing of MCV, predominantly axonal features, and relatively mild demyelinating pathology. Differing from CMT1B, these axonal and demyelinating features were concomitantly present in individual patients in variable extent. Median nerve MCVs were well maintained independently of age, disease duration, and severity of clinical and pathologic abnormalities. Amplitude of CMAPs was correlated significantly with distal muscle strength, indicating that clinical weakness results from reduced numbers of functional large axons, not from demyelination. CMT patients with demyelinating and/or axonal features, together with FAP patients with axonal feature and scattered distribution, are supposed to increase according to the development of genetic diagnosis for hereditary neuropathy that verifies late-onset, de novo and asymptomatic patients.