Focal lesions area feature of chronic inflammatory demyelinating polyneuropathy (CIDP).

In a study designed to identify the neuropathological features typical of chronic inflammatory demyelinating polyneuropathy (CIDP), we reviewed the sural nerve biopsy findings in 105 patients with this disorder. The patients' mean age at biopsy was 49 years. In 65% of patients the disease had a progressive and in 35% a relapsing-remitting course. In 47% of cases the disorder was idiopathic; the remainder had various concurrent conditions. All sural nerve biopsy specimens showed varying amounts of active demyelination associated with onion bulbs (48% of cases), endoneurial edema (55%) and inflammatory infiltrates (25%). The immunopathological hallmarks were T cell infiltration with macrophagic activation and up-regulation of major histocompatibility complex (MHC) class II expression, without B cell infiltration or immunoglobulin deposition on myelin sheaths. In 30% of cases some myelin sheaths showed C3d deposition. Analysis of proinflammatory cytokine expression invariably showed interleukin-1 in perivascular and endoneurial ramified cells and tumor necrosis factor-alpha prevalently in epineurial macrophages, whereas it detected interferon-gamma only in samples with perivascular inflammatory cells. This immunological pattern suggests that the cellular components of immunity play the major role in CIDP. In 19% of cases the neuropathological changes had a focal distribution. This distinctive feature corresponded to more active demyelination, more frequent detection of inflammatory infiltrates and more prominent immunological activation, suggesting that focal involvement is a possible step in the course of the disease.

Role of HIV in the pathogenesis of distal symmetrical peripheral neuropathy.

We report the results of a clinical, electrophysiological and pathological study conducted in 18 AIDS patients presenting a distal symmetrical predominantly sensory polyneuropathy (DSPN) characterized by painful dysesthesias as main complaint. Onset of the neuropathy was at CDC (Center for Disease Control) stage II in 2 patients, at CDC stage III in 5 patients and at CDC stage IV in the remainder. Electrophysiological investigation confirmed the presence of an axonal alteration in the sensory nerves, but also revealed motor involvement in all cases. The neuropathological features of sensory nerves were fiber loss and axonal degeneration with macrophagic activation. The expression of monocyte-macrophage markers and of major histocompatibility complex class II antigens appeared up-regulated in endoneurial ramified cells, while expression of CR3, a complement receptor involved in the process of phagocytosis, was down-regulated. In six nerve biopsy samples and in two out of five DSPN dorsal root ganglia we found HIV-related mRNA and protein located in scattered cells of the endoneurium which we presume to be macrophages. These data suggest that: (a) DSPN may occur early in the course of the disease and is not limited to later stages; (b) DSPN is not a ganglionitis but is actually a sensory-motor neuropathy; (c) the virus enters the peripheral nervous system and induces changes in the immunocompetent cell population with activation of macrophages. Storage of the virus inside macrophages may act both as a reservoir for the virus and as a putative cause of nerve damage, probably through release of cytotoxins and/or interaction with trophic factors.

Clinical spectrum of the tomaculous neuropathies. Report of 60 cases and review of the literature.

Tomaculous neuropathy has a distinctive pathological pattern of myelin thickenings in a high proportion of internodes but no specific pattern of nerve degeneration. We have analyzed the variable clinical expression of this disorder in a large series of patients. Different phenotypes have been recognized: the majority of our patients (52 cases) had hereditary neuropathy with liability to pressure palsy (HNPP) showing wide variability of clinical progression and of severity of the single episodes. 3 patients suffered from familial recurrent brachial plexus neuropathy (FBPN); 5 patients had a symmetrical progressive sensorimotor involvement of the limbs (SSMN), predominantly in the distal portions and leading to permanent disability. The explanation for this clinical variability does not emerge from our data or from the literature. Segmental demyelination is the major change correlating with the episodes of nerve palsy; axonal degeneration might be rarely associated. The myelin sausages are the markers of a selective vulnerability of the nerve fibers either to mechanical injury or to some other unknown event.

Histopathological and ultrastructural study of a case of infantile metachromatic leukodystrophy.

The histopathological and ultrastructural findings on a nerve biopsy specimen and on a CNS necropsy specimen in a case of IML with a typical clinicaL course are reported. Nerve biopsy once again proved to be a sure diagnostic guide even at an early stage of the disease. Some differences in the fine structure of the cytosomes between the nerve biopsy and CNS necropsy material studied four years later may be due to the different rates of catabolism of the constituent lipids as well as to post mortem artefacts.

Congenital toxoplasmosis: histological and ultrastructural study.

A case of congenital toxoplasmosis is reported in which the patient died at 32 days following seizures, coma and respiratory disturbances. Neuropathological examination showed numerous foci of softening throughout the brain. Histological examination disclosed widespread areas of inflammatory necrosis. Circumscribed areas of granulomatous inflammation were also found. Cysts containing a variable number of microorganisms and toxoplasmas free in the damaged areas were frequently observed. Small calcifications were scattered in the cerebral cortex and basal ganglia. Electron microscopy of postmortem brain specimens demonstrated toxoplasmas at various stages of development. The microorganism is enveloped by a two-layered membrane, the pellicle. Replication occurs in a vacuole inside the host cell. Following replication the newly formed parasites, the trophozoites, are released. Several replications without release may also occur with consequent cyst formation. The motile form of the toxoplasma, the tachyzoite, is fusiform with truncated cone shape of the anterior ending which is the presenting surface modified for host cell penetration. The modality of transplacental transmission and the clinical syndromes associated with toxoplasma infection are discussed. EM even of post mortem material contributes to knowledge of the structure of the parasite and of its life cycles.

Friedreich's ataxia. A light- and electron microscopic study of peripheral nerve biopsies.

Sural or superficial peroneal nerve biopsies of patients with clinical diagnosis of Friedreich's ataxia were studied. Patients were divided in two groups, typical and abortive forms: loss of fibers accompanied by axonal atrophy and segmental demyelination are the basic changes in both groups, although the decrease in number of myelinated fibers was most severe in typical FA. In the cases with slower progression there is a tendency to form onion bulb complexes.

Toxic polyneuropathies in Italy due to leather cement poisoning in shoe industries. A light- and electron-microscopic study.

The peripheral nerve biopsy specimens of 4 cases of toxic polyneruopathies induced by exposure to leather cement in shoe industries were studied. Analysis of the cements used in the manufacturing process proved them to contain n-hexane as a volatile substance. Light- and electron-microscopic examination of nerve biopsies showed segmental swelling of axons due to the accumulation of packed filaments and thinning of the overlying myelin sheath. Neither active nerve fibre degeneration nor regeneration were frequently seen. It has been suggested that features of so-called giant axonal neuropathy are the most common pattern of peripheral nerve degeneration in chronic n-hexane intoxication.

[Infantile neuro-axonal dystrophy: anatomo clinical study of one case (author's transl)]. / La distrofia neuro-assonale infantile. Studio anatomo-clinico di un case

A case of Seitelberger's infantile neuroaxonal dystrophy (a rare familial neurologic disease of childhood) is described. The clinical picture is characterized by a progressive deterioration of psychomotor functions leading to flaccid paraplegia with hypotonia of axial muscles, complete involution of language, and total loss of communication with the external world; death due to recurrent unassociated disease occurred at the age of 4 years. Histology showed numerous axonal spheroids mainly in the gray matter of the C.N.S. and plurisystemic degenerations of the motor and sensory systems, of the cerebellum, of the basal ganglia, and of specific sensory system such as the optic and (reported here for the first time) of the olfactory and acoustic systems. In particular, the main histopathological findings included: 1) a characteristic distribution of axonal swellings prevailing in the posterior horn of the spinal cord and in the dorsolateral portions of the medulla oblongata, mainly at the level of the sensory nuclei; 2) demyelinization of the pyramidal tracts and of the ascendings pathways of the sensory system with fibrillar gliosis and myelin breakdown products in some areas (internal capsule, pes pedunculi, VPL thalamic nuclei); 3) severe cerebellar atrophy with almost complete loss of granule and Purkinje cells and marked fibrillary gliosis; 4) presence of enormous amount of sudanophilic lipids in the striatum and pallidum; 5) optic, acoustic and olfactory system degeneration with demyelinization and gliosis at all levels examined and, in particular, sudanophilic lipid deposition in the optic radiations, trigone, and olfactory striae. The discussion emphasized the dying-back type of evolution of the degenerative process insofar as a) the spheroids represent a peculiar alteration of presynaptic endings (as demonstrated by electron microscopy) prevailing at the first sensory neuron, and b) in all systems involved, the degeneration is most marked at distal levels. The striato-pallidal lipophanerosis suggests that the sudanophilic lipids are, here as in other systems, parenchymal degeneration products. On the other hand, there are still many unresolved problems in this rare and complex disease, such as a) the predilection of the lesions for the sensory systems which in our case involved all three special senses; b) the extreme cerebellar atrophy; and c) the etiopathogenetic substrate of the process. All biochemical and histochemical studies have not yielded any results up to the present.