Search

Background Emergence of a malignant tumor at the site of an operation is a rare event and most often arises in association with retained foreign material. Case Description We describe a patient who 1 year after a left carotid endarterectomy for typical atheromatous lesions presented with several transient ischemic attacks with stepwise worsening of the deficit and rapid death. A few weeks before, a tumor of the neck had appeared at the site of the previous endarterectomy. At postmortem examination, we found a malignant histiocytofibroma occluding the left carotid artery, with several recent ischemic foci in the corresponding cerebral hemisphere without metastasis or tumor emboli. Conclusions This observation is unusual owing to the histological type of the neoplasm and to the circumstance of emergence of the neoplasm.

CD4+ T-cell lymphocytopenia without HIV infection was reported as a specific syndrome at the Ninth International AIDS Conference in Amsterdam (July 1992). It is a rare condition, and extensive studies have confirmed immunodeficiency without evidence of HIV-1, HIV-2, HTLV-I, or HTLV-II infection [1,2]. Epidemiologic studies have not identified a transmissible agent [2]. Opportunistic infections may appear in these patients, whereas other patients are asymptomatic and a few develop either autoimmune diseases or cancer [3-5]. Case report. A 55-year-old heterosexual man presented with paresthesias of both hands in April 1992 and extension to the lower limbs in June. These symptoms slowly worsened, and in August weakness developed in the legs. The patient had no serious illness in the past but had visited …

The present communication described changes on nerve biopsies from 16 diabetics without neuropathy, except the fact that the ankle jerks were often decreased bilaterally, as it is often encountered in diabetes mellitus. 16 non-diabetic patients with various peripheral neuropathies were also studied; the glucose tolerance tests were always normal in this group and none had any vascular or collagen disease. The three series included patients between 45 to 75 years old. Obervations made on nerve biopsies from these three groups have been compared. The basement membranes of endoneurial capillaries were measured. These measurements have been made on the thinnest part of the basement membranes and pericyte processes were not included. At least 5 capillaries per 1 patient have been studied. Averaging with a computer has permitted demonstration of significant thickenings of basement membranes in diabetic patients without neuropathy; such an observation was not made in non-diabetic patients with various peripheral neuropathies, while the thickenings were the most important in patients with diabetic neuropathy. It must be said that individual variations were encountered in each group. Nerve parenchyma has been carefully studied. In diabetic patients without neuropathy, 14 cases displayed a typical but usually moderate proliferation of Schwann cells. Axon lesions were mild and unfrequent. The exact relationships between thickening of basement membranes of vasa nervorum and lesions of nerve parenchyma need some further informations.

We report the ultrastructural findings in superficial peroneal nerve biopsies in two patients, one with idiopathic sensory neuropathy and the other with the Guillain-Barré syndrome and Hodgkin's disease. In addition to demyelination, there was an intense proliferation of microfilaments within numerous vesicles of the endoplasmic reticulum of a great number of myelinated Schwann cells. This abnormality does not appear to have been previously reported in the literature. The mechanisms responsible for this finding are unknown.

Quantitative, immunopathological, light and electron microscopic studies of superficial peroneal nerve biopsies from 31 patients with IgM monoclonal gammopathy were carried out. Six patients had Waldenström's macroglobulinemia and 25 had IgM monoclonal gammopathy of undetermined significance. Serum samples from 28 of these patients were assayed for anti-myelin-associated glycoprotein (anti-MAG) activity. Anti-MAG activity was found in 25 of the samples. There was a relationship between the widening of some myelin lamellae observed on ultrastructural examination and the serum anti-MAG activity (23 cases). Immunopathological examination showed IgM binding to myelin sheaths in 17 cases.

One hundred and ninety-two cases of supratentorial astrocytic tumors are classified in 4 groups according to the presence or absence in the pathological material of simple morphological criteria: abnormal cellular density, nuclear pleomorphism, neovascularization, necrosis. Each one of these criteria is strongly correlated with prognosis. Nevertheless only a simple classification in low and high grade lesions has a definite predictive value. A multivariate analysis utilizing Cox's hazard function confronts these histological findings with a number of clinical and etiological possible factors of prognosis. Age and performance status at the time of diagnosis are the best predictors of survival time. The clinical use of a predictive model derived from Cox's function analysis is discussed.

Inflammatory demyelinating polyradiculoneuropathies exhibit well-known ultrastructural lesions of the peripheral nerve, both in acute cases, i.e., Guillain-Barré syndrome, and in relapsing, sub-acute and chronic cases. We present a case of relapsing inflammatory demyelinating polyradiculoneuropathy in a diabetic patient with a biopsy exhibiting these lesions, as well as a widening of the outermost myelin lamellae in some fibers. Such associated lesions are classic in experimental inflammatory demyelinating polyradiculoneuropathies, but have not been reported in human pathology.

Four cases of early infantile polyneuropathy with defective myelination are reported. The peripheral nerve was studied by light and electron microscopy; different morphological characteristics have been noticed in these patients. Case 1 presented aspects of defective myelination with atypical "onion bulb" formation composed of multiple layers of basement membrane. In case 2, defective myelination and atypical "onion bulb" formation were associated with aberrant hypermyelination. Cases 3 and 4 were brothers, who presented axonal damage and atypical "onion bulb" formation.

Peripheral nerve biopsies from two patients with chronic sensorimotor neuropathy were studied. The first case was a non-Hodgkin malignant lymphoma and did not show any dysglobulinemia. The second case had a benign monoclonal gammopathy IgG, Lambda type. Direct immunofluorescence showed no deposits in the first case and slight deposits of anti IgG sera on a few myelinated fibers in the second case. There were numerous fibers showing uncompacted myelin lamellae, 7% in the first case and 4% in the second case. Some of these fibers had axons containing more tubules than filaments. The very few cases reported on neuropathies showing that uncompacted myelin lamellae were frequently associated with dysglobulinemic neuropathy. However, this ultrastructural abnormality of the myelin sheath can be observed without any dysglobulinemia.

Nuclear inclusions in striated muscle from patients with oculopharyngeal dystrophy have been detected recently. We carried out ultrastructural examinations of biopsy specimens on 5 patients with oculopharyngeal dystrophy and we also reexamined a former case. In these 6 cases we found filamentous inclusions in a few nuclei. These inclusions seem to be characteristic of this disease as they have never been seen elsewhere.

Essential mixed cryoglobulinemia, which can cause hypersensitivity vasculitis, was observed in five patients with peripheral neuropathy. Three cases presented with multifocal neuropathies and two cases with symmetrical polyneuropathy. One had cryoglobulinemia with IgM monoclonal gammopathy and IgG polyclonal gammopathy, and the other four had cryoglobulinemia with polyclonal gammopathy. Biopsies showed perivascular infiltration by mononuclaer cells around medium, and mainly small-sized blood vessels. This was observed in the epineurium (five cases) and muscular fragments (three cases). At ultrastructural examination two cases showed severe damage of most myelinated fibers, which presented acute stages of Wallerian-like degeneration, and the three other cases showed a less widespread destruction of myelinated fibers. Most endoneurial capillaries showed swollen endoneurial cells. Myelino-axonal degeneration of myelinated fibers is probably due mainly to the vasculitis always present in the epineurium. This damage was probably worsened by the modifications of endoneurial capillaries. These lesions and their mechanisms are quite different from those observed in cases of cryoglobulinemia with an isolated monoclonal gammopathy.

A 48-year-old patient presented for the past 4 years an amyotrophy of the quadriceps and moderate involvement of the truncal and pelvic girdle muscles. The CK level was elevated (10 times the normal rate) and the EMG revealed a fibrillation pattern on relaxation, myotonic bursts on needle insertion and reduced activity during contraction. The histological study of the muscle biopsy showed nuclear cytoplasmic inclusion bodies and pseudo-myelinic membranes. The case was classified in the inclusion body myositis group. Analysis of the other published cases underlines the variety of the clinical, biological and electromyographical aspects and abnormalities.

A variety of lesions of varying complexity were noted during pathological examinations of the brain in 30 cases of acute severe traumatic coma, of whom 27 survived for less than 10 days. "Diffuse brain damage" were present in all cases and contusions were frequently noted (83 p. 100). The lesions appear immediately after, and are directly related to the injury. Ischemic lesions were present in 66 p. 100 of cases and their mechanisms of production are various and interwoven. The frequency of respiratory difficulties associated with brain injuries is stressed. Two thirds of the cases with brain stem lesions (80 p. 100) were secondary to phenomena related to trans-tentorial herniation. Clinical examinations of these patients with acute severe coma demonstrates the difficulties encountered in assessing prognosis based on clinical findings within the first 48 hours.

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.

A 75 years old man had a chronic lymphoid leukemia for 5 years. Within a period of three months he developed a polyneuritis. The biopsy of a peripheral nerve showed a large cellular infiltration by lymphocytes. The ultrastructural study shows in some Schwann cells disruption of the myelin. Their cytoplasm is invaded by a lymphocyte process as in Guillain-Barre. But in this case some of these invading lymphocytes show polygonal structures in their cytoplasm; that is sometimes seen in the proliferating cells of the chronic lymphoid leukemia.

Peripheral nerve biopsies of 22 patients who were seen with a peripheral neuropathy were studied. On each occasion an ultrastructural study was performed and on 12 occasions an immunopathologic study was done. Ten patients had Waldenstrom's macroglobulinemia and 12 had multiple myeloma. Cellular infiltrates were observed in three cases of Waldenstrom's macroglobulinemia by light microscopy. A widening of the myelin sheath, corresponding to an accumulation of macroglobulin, was found in three cases of Waldenstrom's macroglobulinemia. The presence of abundant deposits of amyloid was noted in one case of multiple myeloma. These diverse features show the various possible mechanisms that can produce peripheral nerve damage during the course of malignant dysglobulinemias. The segmental demyelination is probably of immunologic origin. The axonal lesions cannot be explained satisfactorily except in those rare cases where amyloid deposits are present in the endoneurium.

Summary In two cases with recurrent palsies, the results of electrophysiological studies led to nerve biopsy showing typical tomacula. The first case was an inherited neuropathy with liability to pressure palsies. The second case was an apparently sporadic painless recurrent brachial neuropathy. Electrophysiological alterations were diffuse and sensory fibres of the median nerve between index and wrist were the most involved. Conduction blocks were observed without palsy in narrow anatomical passageways where nerve compressions are frequent (ulnar nerve at the elbow, peroneal nerve at the fibula). A compression by a neighbouring anatomical structure could make the prognosis worse and justify nerve decompression. The nerves with slowest conduction have the most important risk of palsy and the patients should be given advice to avoid their compression.

Summary The authors review present day methods for the diagnosis of herpes encephalitis, and review 35 cases of this affection. A morphological study was carried out in 29 cases, and ultramicroscopic examination of biopsy or autopsy specimens demonstrated the presence of herpes virus in 24 cases. The virological methods used are described.

A case of amyloid neuropathy associated with a multiple myeloma IgG light chain is reported. Under light microscopy the peripheral nerve exhibited several amyloid deposits. Electron microscopy revealed numerous amyloid deposits; at their periphery, macropha-gic histiocytes were observed, containing a few tufts of parallel fibrils in their cytoplasm. A few plasma cells were scattered in the endoneurium and did not exhibit such a relationship. These findings resemble those recently observed in stem-cell cultures of IgG lambda chain human myeloma.

Angiotropic lymphoma can present as a vascular disease in the central nervous system. The patient described in this report had a sudden pain in the region of the right superficial peroneal nerve and a nerve biopsy showed tumoral cells in the lumen of most small blood vessels. This pathology, first described in the skin as malignant angioendotheliomatosis, can be compared with the occurrence of multiple emboli in the vasa nervorum. In recent cases, tumoral markers have evidenced a lymphomatous origin, generally of the B type.

• A chronic sensory neuropathy was the initial symptom in a case of Waldenstrom's macroglobulinemia in a 53-year-old woman. Ultrastructural analysis of a biopsied peripheral nerve revealed a modification of the lamellar structure of the myelin sheath. Immunofluorescent microscopy showed IgM-positive deposits on the myelin sheath. The monoclonal globulin (M component) present in the myelin appears to be a causative factor in the neuropathy.

We report a case of congenital neuropathy taking a rapidly fatal clinical course. Ultrastructural features of the peripheral nerve were unusual with sparsity of myelinated fibres, lack of “onion bulb” formation and presence of axonal damage. This case is compared with previously reported cases of early infantile neuropathy.

Some cases of peripheral neuropathy associated with benign IgM monoclonal gammopathy, or Waldenstrom's macroglobulinemia, are probably of autoimmune origin; in some cases, anti-IgM serum reacts with the myelin sheaths of peripheral nerves. However, mechanisms may differ in other cases. In one case of neuropathy with macroglobulinemia, we found deposits of IgM immunoglobulin in the endoneurium. On ultrastructural examination, the deposits had erased the basement membrane of some nerve fibers that showed damage of both myelin and axon.

As has been shown during the course of experimental allergic neuritis, in the Guillain-Barre syndrome there is an invasion of the myelin sheath in certain fibres by a mononuclear cell, with an intact axon. In a series of 45 cases we have been able to show this feature in 31 cases. In certain cases the cytoplasm prolongation of the invading cell was seen in the myelin sheath, forcing apart two neighbouring layers.

A diabetic woman underwent an incision of the right big toe for an abscess and developed a typical Guillain-Barre syndrome 48 h later. A biopsy of a peripheral nerve, performed 10 days later, showed modifications usually seen in diabetic patients, as well as the characteristic ultrastructural modifications of the Guillain-Barre syndrome (GBS). Moreover, 22% of myelinated fibers exhibited vesicular disruption of the myelin sheaths. This lesion is rarely encountered on the biopsies of peripheral nerve in GBS and concerns only a few myelinated fibers. Such a prominence of myelinic vesicular disruption and its occurrence in a diabetic patient are discussed.

The peripheral nerve was taken from 25 diabetic patients with arteritis just before or after amputation of a leg. The ultrastructural study of myelinated fibers showed several alterations. Loss of fibers varied greatly from case to case. This was accompanied in some cases by hypertrophy of the Schwann cells around demyelinated fibers as has been observed in some ordinary diabetic neuropathies. Unusual abnormalities consisted of particular axonal degeneration and evidence of aberrant remyelination. This axonal injury was peculiar because of the accumulation of organelles which tended to transform some of the fibers into enlarged axons. Such a lesion might correspond to a hypoxic axonopathy.

A 28 year old woman presented a syndrome of slow spinal compression evolving over four and a half years at the level C1--C2 vertebrae due to a solitary osteochondroma of the posterior arch of the atlas which was excised by laminectomy. Radiographys of the skeleton did not show the presence of other osteogenic tumours. This is the fifth case of solitary osteochondroma to be published. Elsewhere, in six cases out of 14, the vertebral lesion formed part of generalised exostoses.

Recently it has been reported that the C57BL mice can be used as a model of benign monoclonal gammopathy (MG). Since experimental models have until now failed to reproduce specific lesions of human dysglobulinemic polyneuropathies, we decided to investigate the peripheral nerve of these mice. The sciatic nerve and the serum from 14 C57BL mice were examined: 9 of these animals were found to have an IgG, kappa light chain MG, while in the other 5 no abnormalities were detected in the serum. In the 14 mice, features of demyelination were found in certain fibers, as well as onion-bulb formations around other myelinated fibers. Features of active demyelination were found in 10 animals and it must be underlined that three of these had no serum abnormalities. The decrease of the conduction velocities and the temperature coefficients Q10 of the C57BL mice suggest a good correlation between morphological and functional parameters. This strongly suggests that this strain of mice provides a suitable model for inflammatory demyelinating polyneuropathy (IDPN).

Two cases of sarcoid neuropathy were diagnosed by histological examination of muscle and peripheral nerve biopsies. The epineurium of the first patient showed a few sarcoid granulomas surrounding and invading the wall of an arteriole, and in some arterioles there were sites of fibrinoid necrosis. Sarcoid granulomas encroached on the walls of arterioles in the epineurium of the second patient. Ultrastructural examination showed severe alteration of nerve fibres in the first case and only a few altered fibres in the second. Damage to nerve fibres in these cases depended mainly on the degree of arteriolar wall involvement.

A 59-year-old man developed a sensorimotor neuropathy of the upper and lower limbs, associated with a biclonal gammopathy, within the space of a few months. Each of two paraproteins was coupled with a distinct IgM kappa IgG lambda light chain. Examination of a nerve biopsy specimen by electron microscopy revealed a demyelinative process with a widening of the interlaminar space in the myelin sheath, as well as deposits of amyloid substance between nerve fibers. Direct immunofluorescence revealed the presence of IgM and of the kappa light chain in certain Schwann cells, while the lambda IgG was fixed to the amyloid deposits. Immunoperoxidase histochemistry showed a positive reaction in normal human nerve tissue to the immune serum IgM and kappa light chain. The findings suggest that the widening of the interlaminar space of the diseased myelin corresponds to an active fixation of immunoglobulin on the sheath of the Schwann cell. The presence of two light chains in this patient's gammopathy caused a dual pathology: the kappa chain, a demyelinative neuropathy, and the lambda chain, a primary amyloidosis, with deposits in the peripheral nerve and in the kidney.

A 49-year-old woman presented with isolated aphasia followed by dementia and ataxia with a duration of 4 years. Histopathologically there was panencephalic involvement, status spongiosus, and kuru-type plaques. Molecular analysis showed heterozygosity at codon 129 in the prion protein (PrP) gene, and type 2 protease-resistant PrP. The comparison between this case and those previously reported suggests that the panencephalopathic variant of Creutzfeldt-Jakob disease (CJD) is an aspecific end-stage condition displayed by most if not all CJD variants in individual patients with an unusually prolonged course.

The possibility that neuronal loss in prion diseases occurs through an apoptotic process has been postulated and is consistent with the lack of inflammation in these disorders. In order to test this hypothesis in FFI, in which neuronal loss is the predominant neuropathological feature, we examined samples of thalamus, basal ganglia, cerebral cortex, cerebellum and medulla from 10 subjects with FFI. All the patients had the characteristic 178 N mutation of the PrP gene. Eight subjects were homozygous methionine/methionine at codon 129 and 2 were heterozygous methionine/valine. Apoptotic neurons were identified by in situ end labelling in all the FFI cases and in none of the controls. They were mostly found in damaged regions and their presence and abundance seemed to correlate closely with the neuronal loss. They were particularly abundant in the thalamus and medullary olives. In heterozygous cases who had a longer disease duration and more widespread cerebral changes, apoptotic neurons were also found in the neocortex and striatum. The abundance of apoptotic neurons also correlated well with microglial activation as demonstrated by the expression of major histocompatibility complex class II antigens. PrP(res) immunostaining was almost invariably negative, consistent with previous data showing the lack of obvious correlation between neuronal loss and PrP(res) deposits in prion diseases.

Fatal familial insomnia (FFI) and a subtype of familial Creutzfeldt-Jakob disease (CJD), two clinically and pathologically distinct diseases, are linked to the same mutation at codon 178 (Asn178) of the prion protein gene. The possibility that a second genetic component modified the phenotypic expression of the Asn178 mutation was investigated. FFI and the familial CJD subtype segregated with different genotypes determined by the Asn178 mutation and the methionine-valine polymorphism at codon 129. The Met129, Asn178 allele segregated with FFI in all 15 affected members of five kindreds whereas the Val129, Asn178 allele segregated with the familial CJD subtype in all 15 affected members of six kindreds. Thus, two distinct disease phenotypes linked to a single pathogenic mutation can be determined by a common polymorphism.

Phenotypic heterogeneity in sporadic Creutzfeldt-Jakob disease (sCJD) is well documented, but there is not yet a systematic classification of the disease variants. In a previous study, we showed that the polymorphic codon 129 of the prion protein gene (PRNP), and two types of protease-resistant prion protein (PrP(Sc)) with distinct physicochemical properties, are major determinants of these variants. To define the full spectrum of variants, we have examined a series of 300 sCJD patients. Clinical features, PRNP genotype, and PrP(Sc) properties were determined in all subjects. In 187, we also studied neuropathological features and immunohistochemical pattern of PrP(Sc) deposition. Seventy percent of subjects showed the classic CJD phenotype, PrP(Sc) type 1, and at least one methionine allele at codon 129; 25% of cases displayed the ataxic and kuru-plaque variants, associated to PrP(Sc) type 2, and valine homozygosity or heterozygosity at codon 129, respectively. Two additional variants, which included a thalamic form of CJD and a phenotype characterized by prominent dementia and cortical pathology, were linked to PrP(Sc) type 2 and methionine homozygosity. Finally, a rare phenotype characterized by progressive dementia was linked to PrP(Sc) type 1 and valine homozygosity. The present data demonstrate the existence of six phenotypic variants of sCJD. The physicochemical properties of PrP(Sc) in conjunction with the PRNP codon 129 genotype largely determine this phenotypic variability, and allow a molecular classification of the disease variants.