Mixed carcinomatous neuropathy in patients with lung cancer and lymphoma

A clinical, electrophysiological and histological study of the peripheral nerve was performed on 62 patients with lung cancer and 30 patients with lymphoma. There was a mild peripheral neuropathy (MPN) in 17.7% of patients with lung cancer and in 10% of those with lymphoma. MPN was related to the degree of weight loss. Histological studies of 5 patients with MPN demonstrated a loss of large myelinated fibers in all patients, axonal degeneration in 2 and remyelination in 3 patients. Electromyographic and histological findings indicate a primary axonal neuropathy with remyelination, probably secondary to axonal damage. 2 patients with lymphoma developed a severe neuropathy that remitted in 1 patient. The main pathological abnormality was segmental demyelination in both cases. Immunofluorescence studies were negative in all cases with mild or severe neuropathy.     

4 cases of Guillain-Barré syndrome with axonal lesions

We report the neurological features observed in 4 patients who developed a clinically typical Guillain-Barré syndrome. Electrophysiological and histological data displayed an unusual number of axonal lesions, although these were always associated with demyelination. These cases must be distinguished from the rare cases of Guillain-Barré syndrome with pure axonal lesions. Three patients had a poor functional recovery. This confirms the more severe prognosis of Guillain-Barré syndrome with major axonal degenerative changes.     

Carcinomatous neuropathy: clinical and pathologic findings of sural nerve biopsy in 7 cases

Sural nerve biopsy was done 7 cases of cancer patients associated with peripheral neuropathy. There were 3 cases of lung carcinoma and one each of pancreas adenoma, seminoma, sigmoid carcinoma and chondrosarcoma of the femur. The neurological features manifested themselves with sensory pattern of neuropathy associated with ataxia in one case, sensorimotor neuropathy in 3 cases, and idiopathic polyneuropathy, peripheral neuropathy with proximal myopathy and neuropathy with paraneoplastic cerebellar syndrome each in one case, 6 patients showed neuropathy before malignancy was discovered and only one patient had neuropathy after the onset of carcinoma. Sural nerve biopsy studied in all the 7 patients with light and electron microscope revealed no infiltration of carcinomatous cells in the sural nerve fascicles. There was severe loss of myelinated fibers and severely axonal degeneration in one patient. Another patient showed segmental demyelination (5.03 x 10(3)/mm2). There was evidence of both axonal degeneration and demyelination associated with moderate reduction in the number of the myelinated fiber density ranging from 1.02 to 4.35 x 10(3)/mm2. In 6 cases, mononuclear cells were seen in nerve fascicles under the electron microscope. The characteristic pathological findings, their relation with the duration and onset of the cancer and some ideas regarding the pathogenesis are discussed.     

Chronic inorganic mercury induced peripheral neuropathy

We report the clinical features, electrophysiological studies, and morphometric analysis of sural nerve pathology in a patient with polyneuropathy due to inorganic mercury intoxication. He developed slowly progressive generalized paralysis of all limbs after 3 months ingestion of herb drugs which contained mercuric sulfate. Electrophysiologic studies revealed axonal polyneuropathy involving both motor and sensory fibers. Sural nerve biopsy demonstrated axonal degeneration with demyelination and a predominant loss of large myelinated fibers. His muscle strength showed only mild improvement after 2 years' follow-up. We concluded that inorganic mercury exposure may induce severe axonal sensorimotor polyneuropathy in humans and that neurological deficits may persist in severe cases.     

Pathology of the motor-sensory axonal Guillain-Barré syndrome

The concept of a severe motor-sensory neuropathy of acute onset caused by an immune attack on the axon (“axonal” Guillain-Barré syndrome) has been advanced primarily based on electrodiagnostic and limited pathological data, but remains controversial. At autopsy some cases demonstrate unusually severe inflammatory demyelinating neuropathy. There are conflicting data about whether antecedent Campylobacter jejuni infection is associated with “axonal” Guillain- Barré syndrome. We report 4 individuals from Hebei Province, China, who died 7, 7, 18, and 60 days after onset of a syndrome diagnosed clinically as Guillain-Barré syndrome. High titers of antibodies recognizing C. jejuni, consistent with recent infection, were found in the 2 patients tested. At autopsy the 3 with early disease had ongoing wallerian- like degeneration of fibers in the ventral and dorsal roots and in the peripheral nerves, with only minimal demyelination or lymphocytic infiltration. All 3 had numerous macrophages in the periaxonal space of myelinated internodes, and rare intraaxonal macrophages as well. Examination of the patient having the syndrome for 60 days confirmed the extensive loss of large fibers in the spinal roots and nerves, and the paucity of demyelination and remyelination. These observations confirm predictions that some patients with severe motor-sensory Guillain-Barré syndrome, as defined clinically, have predominantly axonal lesions of both motor and sensory fibers, even in the early stages of the disease, and that axonal Guillain-Barré syndrome can follow C. jejuni infection. The pathology supports the possibility that such cases of motor-sensory axonal Guillain-Barré syndrome represent the most severe end of a spectrum of immune attack directed toward epitopes on the axon.     

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.     

Axonal damage in Guillain-Barré syndrome

In Guillain-Barré syndrome patients, severe axonal degeneration occasionally occurs, often resulting in permanent functional deficit. In order to assess the development of axonal degeneration, we followed a consecutive series of 42 patients longitudinally using clinical and neurophysiological methods. Eight patients were considered to have severe axonal degeneration: in these patients denervation potentials were eventually found and at least 1 nerve proved inexcitable, and clinical recovery was slow and incomplete. Five of these 8 patients initially showed a pronounced generalized conduction block, the physiological hallmark of demyelination, before signs of axonal degeneration developed. In the remaining three patients, the first evaluation revealed low amplitudes with only modest conduction block; this is consistent with predominantly distal demyelination, but might, alternatively, be explained by primary axonal degeneration. Caution is necessary in using distal CMAP parameters for prognostic purposes, because the distal CMAP may be relatively spared in the early phase of the disease despite severe axonal degeneration later.     

Peripheral neuropathy associated with mitochondrial disorders: 8 cases and review of the literature

Forty-three cases of peripheral neuropathy (PN) have been reported in the literature with a proven mitochondria (mt) DNA mutation, and 21 had a peripheral nerve biopsy (PNB). We studied 8 patients, 1 of whom had severe sensory PN, 3 mild PN, and 4 subclinical PN. Nerve biopsy was performed in every case; all patients showed axonal degeneration and 4 showed features of primary myelin damage. In addition, there were 2 crystalline-like inclusions in the Schwann cell cytoplasm of a patient with MERRF, and 1 in a patient with multiple deletions on the mtDNA. There are 11 cases of PNB in the literature with axonal lesions, 5 with demyelination, and 4 with mixed lesions. One PNB was not modified. A few crystalline-like inclusions were seen in 1 case of MERRF. Such inclusions were first reported in the Schwann cell cytoplasm of unmyelinated fibers in a patient with Refsum disease and were considered to be modified mitochondria. However, their mitochondrial origin remains debatable.     

Two families of Charcot-Marie-Tooth disease with Adie's pupil, axonal neuropahy and the Thr124Met mutation in the peripheral myelin protein zero gene]

We reported two families of Charcot-Marie-Tooth disease (CMT) with Thr124Met mutation in the peripheral myelin protein zero (MPZ). The clinical features of the proband patients of both families showed Adie's pupil, severe sensory dominant neuropathy in lower extremities, and axonal changes in sural nerve biopsies and nerve conduction studies. Muscle atrophy and weakness was mild in the lower legs, while sensory impairment was marked. The proband patient of family 1 had four symptomatic siblings and one of them showed Adie's pupil. The elderly daughter of the proband of family 2 showed Adie's pupil and younger daughter showed photophobia. The biopsied sural nerves of both proband patients revealed prominent axonal sprouting, and sub-perineurial edema and mild fascicular enlargement. Segmental demyelination was not frequent in teased fiber assessment. The present two family cases strongly suggest that this MPZ gene mutation (Thr124Met) could be present among the patients with CMT type 2, axonal form. Furthermore, the patients showing sensory neuropathy and Adie's pupil may need to be reexamined with this mutation. It is also necessary to reassess genotype-phenotype correlation in CMT patients particularly in reference to type 1 and type 2.     

Axonal Guillain–Barré syndrome

The issue of “axonal” Guillain–Barré syndrome (GBS) remains controversial. Supportive evidence comes from pathological examination of peripheral nerves in 4 extreme cases of GBS 17–29 days after onset which showed severe axonal degeneration without inflammatory-demyelination. It has been suggested that inflammatory-demyelination may have been missed. This is difficult to disprove but it seems unlikely, given the known correlation between the severity of axonal degeneration and inflammation/demyelination in the experimental model of GBS, experimental allergic neuritis (EAN). Electrically inexcitable nerves in GBS may reflect axonal degeneration, terminal demyelination or both. This finding proved to be a sign of poor prognosis in 19 of 27 (70%) patients, although a good outcome occurred in some cases. © 1994 John Wiley & Sons, Inc.     

不同类型吉兰-巴雷综合征患者的临床表现及预后

目的:分析不同类型的吉兰-巴雷综合征(GBS)患者的临床表现及预后。方法:以电生理方法将63例患者分为脱髓鞘型、轴索型和未分类型。比较脱髓鞘型和轴索型患者的临床表现、疾病高峰期及出院时的神经功能残疾评分。结果:轴索型和脱髓鞘型患者疾病高峰期神经功能残疾评分分别为(4.0±1.05)分和(2.8±0.98)分,出院时分别为(2.6±1.84)分和(1.3±0.75)分,两组间评分差异有统计学意义(均P<0.01)。轴索型患者有较高比例的前趋期腹泻和呼吸肌麻痹症状发生,但感觉异常少见。结论:轴索型GBS患者易有前躯期腹泻和呼吸肌麻痹的临床表现,其病情重、预后差。     

Spinal and cranial hypertrophic neuropathy in multiple sclerosis

Two patients with multiple sclerosis developed symptomatic chronic inflammatory demyelinating polyneuropathy with massive spinal or cranial nerve hypertrophy revealed by neuroimaging. Sural nerve biopsy in one showed only moderate demyelination, axonal loss, and onion-bulb formation, illustrating dichotomy between severe proximal and milder distal nerve involvement. Patients with coexistent central and peripheral demyelination usually are symptomatic from dysfunction at one site or the other, but not from both. Our patients showed minimal response to steroids, intravenous immunoglobulin, or azathioprine. These cases suggest that the mechanism of disease in symptomatic central and peripheral demyelination may differ from that of disease in only one region, and that optimal therapy in this situation must be explored further.     

INTRAMYELINIC EDEMA: AN ELEMENTARY PATHOLOGICAL LESION IN CIDP

Pathological abnormalities of sural nerve biopsies from patients affected by chronic inflammatory demyelinating polyneuropathy (CIDP) include segmental demyelination, inflammatory infiltrates, axonal degeneration, subperineurial edema and Schwann cell proliferation. There are few reports in the literature (Waddy '89, Sabatelli '96) describing edema of the myelin sheath as an additional pathological feature of CIDP. This peculiar abnormality is a prominent finding in several experimental toxic and compression neuropathies. In 1993 Tatum described Intramyelinic Edema in experimental allergic neuritis induced by systemic passive transfer of human IgM anti‐myelin‐associated glycoprotein, and suggested that this change may play a role in the pathogenesis of demyelination. In order to establish whether intramyelinic edema may represent an elementary pathological lesion in human peripheral neuropathies, we reviewed morphological data of sural nerve biopsies from 46 CIDP patients admitted to our Institute from 1988 to 2001 and we compared them with findings from patients affected by other neuropathies. IE was observed in 6 patients with CIDP, but in none of the 500 patients affected by neuropathies of different etiology. In two out of the six patients the neuropathy was associated with IgM‐paraprotein, without anti‐MAG activity. IE was a prominent feature in only one patient while in the remaining patients it was confined to sporadic fibers. In one patient with a mild form of CIDP, IE was the only pathological finding. In the remaining patients it was associated with segmental demyelination and axonal loss. Our findings show that although IE is observed in only a minority of CIDP patients (13% of our series), this pathological finding may be considered a specific abnormality of inflammatory demyelinating neuropathies. We suggest that axonal shrinkage, which is invariably associated with IE, may represent a mechanism of loss of function in CIDP, in addition to segmental demyelination and axonal loss.     

Chronic relapsing idiopathic polyneuropathy with primary axonal lesions.

Idiopathic polyradiculoneuropathy with primary axonal lesions is rarely encountered. Two cases are reported with a chronic relapsing course and a fatal outcome. Neuropathological examination of biopsied peripheral nerve in the two patients and in a necropsy case showed loss of myelinated fibres, but neither active demyelination nor inflammatory cells were observed. Acute and chronic relapsing axonal polyradiculoneuropathies appear to be two clinical forms of a peculiar entity different from GBS.     

Sensorimotor and autonomic neuropathy associated with systemic lupus erythematosus

In this article, one described 7 patients with systemic lupus erythematosus (SLE) and the pathological findings of their sural nerves. In 4 of the 7 cases the criteria for diagnosis of SLE were satisfied and in 3 cases there was serological evidence of an undifferentiated connective tissue disease, most likely to be SLE. The peripheral neuropathy was of a chronic sensorimotor type with predominantly sensory features and gradual onset. In 2 cases the presentation was asymmetrical. One patient had autonomic dysfunction. There was ischemic neuropathy in 2 cases, segmental demyelination in 2 cases, and axonal degeneration with demyelination in 3 cases. In 6 cases there was increased expression of Ia antigen within the nerve fascicle, perineurium and endothelial cells.     

The electrodiagnostic findings in peripheral neuropathy associated with monoclonal gammopathy

The electrodiagnostic findings in 51 patients with monoclonal serum proteins of different etiologies and peripheral neuropathies are analyzed and the findings in an additional 10 patients with multiple myeloma are discussed. The nine patients with monoclonal gammopathy of undetermined significance had electrodiagnostic patterns consistent with either predominant axonal degeneration or demyelination. Almost all 15 patients with osteosclerotic myeloma had evidence of a demyelinating neuropathy. The 27 patients with primary systemic amyloidosis almost always displayed evidence of an axonal neuropathy with superimposed carpal tunnel syndrome in some cases. The 10 patients with multiple myeloma had heterogeneous findings. Electrodiagnostic studies can aid in classifying these patients and suggest the likelihood of a specific etiology.     

Malignant infiltration of peripheral nerves in the course of acute myelomonoblastic leukaemia: neuropathological study of two cases

Two patients suffering from acute myelomonoblastic leukaemia developed clinical evidence of peripheral nerve involvement. In both cases, a peripheral nerve biopsy revealed endoneurial cellular infiltrates which were identified as leukaemic cells by immunocytochemistry. Ultrastructural studies showed mainly axonal damage. Moreover, in one patient, a few features of active demyelination were also observed.     

Neuropathy caused by cisplatin. Clinical, electrophysiological and morphological study

Seven patients with cancer presented a sensory peripheral neuropathy induced by cisplatinum. This drug was used alone in 1 case and, in 6 other cases it was associated with drugs without any toxicity for the peripheral nervous system. Every patient had an electromyogram and motor and sensory nerve conduction studies. A sural nerve biopsy was performed in 5 cases for light and electron microscopic studies as well as for teasing and quantitative studies. Electromyograms and motor nerve conductions were normal. Sensory nerve conductions were slowed with very low amplitude sensory action potentials. Such results suggested axonal changes. Nerve biopsies showed typical axonopathic changes with secondary demyelination. Morphometric studies confirmed a loss of myelinated fibers affecting the large fibers in all cases, according to the slowed sensory nerve conductions. This study confirmed that the cisplatinum-induced neuropathy is a new form of toxic distal axonal neuropathy. The hypothesis of a primary demyelination of peripheral nerves, which has been proposed, could not be retained.     

The spectrum of changes on 20 nerve biopsies in patients with HIV infection

Nerve and muscle biopsies were performed on 20 patients with HIV infection and peripheral neuropathy. Nine patients had distal symmetrical peripheral neuropathy (DSPN) (six ARC and three AIDS), six had inflammatory demyelinating polyneuropathy (IDP) (three ARC, one AIDS, and two otherwise asymptomatic patients), one had mononeuropathy multiplex (MM) (AIDS), 1 had mononeuropathy (ARC), one had meningoradiculitis (AIDS), and two had areflexia-associated lymphocytic meningitides (ARC), DSPN exhibited axonal degeneration in four of nine cases and was associated with segmental demyelination in five of nine cases. IDP exhibited segmental demyelination associated with axonal degeneration in four of six cases. Demyelination was more frequent in asymptomatic patients (2 of 2 cases) and in ARC (7 of 12 cases), whereas axonal degeneration was predominant in AIDS (6 of 6 cases). Mononuclear cell infiltration was seen in 1 of 2 asymptomatic patients and in 11 of 12 ARC patients but was exceptionally found in AIDS (1 of 6 cases). Involvement of the walls of small vessels, mostly venules ("subacute microvasculitis"), was found in 1 of 2 asymptomatic patients, in 8 of 12 ARC patients, and never in AIDS. The polyclonal mononuclear cell population was composed mainly of Leu 2 (T8) positive cells in seven cases of ARC. No virions were seen in electron microscopy. HIV was isolated in two cases from the CSF or the nerve biopsy.     

Axonal degeneration in association with carpal tunnel syndrome

Median nerve entrapment in the palm to wrist segment is known as carpal tunnel syndrome (CTS). Electromyography is the best evaluation test to confirm the disease, as it shows a median reduced conduction velocity and/or conduction block; however, the usual CTS electrodiagnostic tests do not separate segmental demyelination alone from segmental demyelination plus secondary axonal degeneration. We studied 100 hands from CTS patients (classified as mild, moderate, and severe), and 50 hands from normal subjects. The median palmar sensory nerve action potential (SNAP) amplitude was measured and compared between the two groups. It would be expected that SNAP was normal if no axonal degeneration had occurred. The results showed that in mild CTS group and part of moderate CTS group SNAP amplitude was normal, whereas in severe CTS group, and part of moderate group SNAP amplitude was reduced, proving that axonal degeneration was involved. As it is well stated that axonal lesions have worse prognosis than segmental demyelinating ones, this simple test may help to preditic the CTS outcome and treatment.