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[Clinico-pathogenetic variants of peripheral nervous system diseases of herpetic etiology].

Of 340 patients with various manifestations of herpetic disease, 261 showed predominant involvement of the peripheral nervous system. Apart from ganglioneuritis of the cranial and spinal nerves there occurred forms accompanied by inflammatory changes in the liquor, commissural processes in the meninges, involvement of the anterior roots and vegetative ganglions. The results of clinicovirological comparisons and differentiation of herpetic diseases as well as their initial manifestations are reported. Some aspects of the pathogenesis of herpetic diseases are discussed.

Adult↗

Immunofluorescent evidence of an FMRFamide-like peptide in the peripheral nervous system of the gastropod mollusc Helix aspersa.

An antiserum raised against the FMRFamide peptide revealed a highly developed peripheral nervous system in the mollusc Helix aspersa. Immunoreactive fibres associated with muscular fibres are observed in all organs. Cell bodies are frequently seen, for example in the digestive and genital tracts. The antiserum also revealed associations between immunoreactive fibres and non-reactive perikarya. In Helix aspersa an FMRFamide-like peptide is most likely a neurotransmitter/neuromodulator for muscular and peripheral nervous activity.

Animals↗

Proteolipid DM-20 predominates over PLP in peripheral nervous system.

The major central nervous system (CNS) myelin proteolipid (PLP) is also expressed in the peripheral nervous system (PNS). This paper gives evidence that DM-20, an isoform of PLP, also occurs in rat sciatic nerves, where, in contrast to what is seen in CNS myelin, it predominates over PLP. This conclusion was reached on the basis of results obtained by immunoblot analysis of a crude proteolipid extract from adult peripheral nerve with two site-specific anti-proteolipid (PLP and DM-20) antibodies. This finding was further corroborated by characterization of the products obtained by Polymerase Chain Reaction (PCR) amplification of cDNAs synthesized from total RNA of 14-day-old sciatic nerves. The significance of the occurrence of these proteolipids in PNS remains obscure.

Amino Acid Sequence↗

Some aspects of the peripheral nervous system in the human fetus as revealed by the acetylcholinesterase in toto staining method.

By means of the AChE in toto staining method (Baljet and Drukker 1975) the peripheral nervous system in several human fetuses has been investigated. Especially concerning the peripheral autonomic nervous system some striking results were found. In the human fetus there exists a large variability in number and diameter of the communicating rami. Many ganglia in the sympathetic trunks are fused. The major splanchnic nerve arises at various levels from the thoracic sympathetic trunks as well as many smaller thoracic sympathetic nerves. Furthermore various visceral nerves and nerve related elements are presented in this study.

Acetylcholinesterase↗

Axonal transport and targeting of the t-SNAREs SNAP-25 and syntaxin 1 in the peripheral nervous system.

Axonal transport and targeting of the t-SNAREs SNAP-25 and syntaxin 1 were investigated in the rat peripheral nervous system using a stop-flow (crush) technique. In crush-operated sciatic nerves, accumulations of SNAP-25 and syntaxin 1 immunoreactivities were detected as early as 1 h after operation, indicating fast axonal transport. The amounts increased on the proximal side of the crush with time after crushing. Distal accumulations of SNAP-25, representing recycling to the cell body, were less than 10% of the proximal accumulations, but 40% for syntaxin 1, 50% for synaptobrevin II and 70% for synaptophysin. Immunoelectron microscopic studies demonstrated that SNAP-25 and syntaxin 1 are present on pleiotropic membranes within a diameter of 50 to 100 nm in axons proximal to a crush. Distal to the crush, labeling for syntaxin 1 and SNAP-25 were sparse and barely detectable, respectively. In addition, the two proteins were found in the axolemma. In nerve terminals of the spinal cord, both proteins were concentrated around small synaptic vesicles (about 50 nm in diameter), whereas only very few gold particles were observed near the presynaptic membrane or the active zones.

Animals↗

Gene expression during reactivation of herpes simplex virus type 1 from latency in the peripheral nervous system is different from that during lytic infection of tissue cultures.

Herpes simplex virus (HSV) replicates in peripheral tissues and forms latent infections in neurons of the peripheral nervous system. It can be reactivated from latency by various stimuli to cause recurrent disease. During lytic infection in tissue culture cells, there is a well-described temporal pattern of (i) immediate-early, (ii) early, and (iii) late gene expression. However, latency is characterized by little if any expression of genes of the lytic cycle of infection. During reactivation, the pattern of gene expression is presumed to be similar to that during the lytic cycle in tissue culture, though recent work of W. P. Halford et al. (J. Virol. 70:5051-5060, 1996) and P. F. Nichol et al. (J. Virol. 70:5476-5486, 1996) suggests that it is modified in neuronal cell cultures. We have used the mouse trigeminal ganglion explant model and reverse transcription-PCR to determine the pattern of viral and cellular gene expression during reactivation. Surprisingly, the pattern of viral gene expression during lytic infection of cell cultures is not seen during reactivation. During reactivation, early viral transcripts were detected before immediate-early transcripts. The possibility that a cellular factor upregulates early genes during the initial reactivation stimulus is discussed.

Animals↗

Distribution of protein kinase C (alpha, beta, gamma subtypes) in normal nerve fibers and in regenerating growth cones of the rat peripheral nervous system.

The distribution of protein kinase C (alpha, beta, gamma subtypes) was studied using immunocytochemical techniques in normal nerve fibers and in regenerating sprouts (growth cones) from the nodes of Ranvier following crush injuries to the rat peripheral nervous system. In normal nerves, for each protein kinase C subtype, immunoreactivity was present in both myelinated and unmyelinated axons. In myelinated axons, immunoreactivity for all three subtypes was patchy in the axoplasm and diffuse in the subaxolemmal peripheral zones. No immunoreactivity was found in the microtubule and neurofilament (cytoskeletal) domain. In contrast, in unmyelinated axons, immunoreactivity was distributed diffusely in the axoplasm. Schwann cells of myelinated fibers exhibited protein kinase C immunoreactivity, but those of unmyelinated fibers did not. In regenerating nerves, early sprouts and growth cones extending through the crushed site along Schwann cell basal laminae exhibited intense immunoreactivity for all three subtypes. Immunoreactivity was distributed diffusely throughout the axoplasm of the regenerating sprouts (growth cones), in which microtubules and neurofilaments were very rare. Thus, the subcellular localization of the protein kinase C immunoreactivity in growth cones of early regenerating nerves differed from that of normal parent axons. These findings suggest that protein kinase C (alpha, beta and gamma subtypes), whose subcellular distribution becomes more extensive in regenerating axons, may have important functional roles in axonal sprouting and in the regulation of growth cone activity in the peripheral nervous system.

Animals↗

Functional implications of the localization and activity of acid-sensitive channels in rat peripheral nervous system.

Acid-sensitive ion channels (ASIC) are proton-gated ion channels expressed in neurons of the mammalian central and peripheral nervous systems. The functional role of these channels is still uncertain, but they have been proposed to constitute mechanoreceptors and/or nociceptors. We have raised specific antibodies for ASIC1, ASIC2, ASIC3, and ASIC4 to examine the distribution of these proteins in neurons from dorsal root ganglia (DRG) and to determine their subcellular localization. Western blot analysis demonstrates that all four ASIC proteins are expressed in DRG and sciatic nerve. Immunohistochemical experiments and functional measurements of unitary currents from the ASICs with the patch-clamp technique indicate that ASIC1 localizes to the plasma membrane of small-, medium-, and large-diameter cells, whereas ASIC2 and ASIC3 are preferentially in medium to large cells. Neurons coexpressing ASIC2 and ASIC3 form predominantly heteromeric ASIC2-3 channels. Two spliced forms, ASIC2a and ASIC2b, colocalize in the same population of DRG neurons. Within cells, the ASICs are present mainly on the plasma membrane of the soma and cellular processes. Functional studies indicate that the pH sensitivity for inactivation of ASIC1 is much higher than the one for activation; hence, increases in proton concentration will inactivate the channel. These functional properties and localization in DRG have profound implications for the putative functional roles of ASICs in the nervous system.

Acid Sensing Ion Channels↗

State of the peripheral nervous system in patients with hypothalamic insufficiency.

An investigation was carried out by non-invasive techniques of the state of the peripheral nervous system in patients with a constitutional-acquired form of hypothalamic insufficiency. Ten healthy individuals were included in the control group. The presence of subclinical parasympathetic vegetative insufficiency was identified by cardiovascular tests. It was more marked in patients with an early onset of the neuroendocrine disturbances and longer course of the disease. In the opinion of the authors, this suggests the constitutional-acquired character of the vegetative disturbances. In addition, a slowing of the speed of conduction through the sudomotor preganglionic sympathetic fibers in the upper and lower extremities and the predominance of these disturbances in the group of patients with pronounced dysraphic status were identified. The latter suggests a defect of the laying down of these peripheral vegetative fibers. This investigation makes it possible to hypothesize that subclinical peripheral insufficiency is one of the factors governing the occurrence of both permanent (tachycardia, elevations of AP, hyperhidrosis) and paroxysmal vegetative disturbances (panic attacks, migraine) in hypothalamic insufficiency.

Adult↗

[The use of deoxypeganin hydrochloride in the combined treatment of patients with diseases of the peripheral nervous system].

A study is presented of the efficacy of 1% deoxypeganin hydrochloride solution in muscle lesions due to involvement of the peripheral nervous system in 19 patients in whom the drug was administered into the motor points of the involved muscles. In 13 similar patients the drug was given intramuscularly. Clinical and electromyographic studies indicate that local use proved more effective than traditional.

Adult↗

Light and electron microscopic analysis of the central and peripheral nervous systems of acid sphingomyelinase-deficient mice resulting from gene targeting.

The acid sphingomyelinase (aSmase)-deficient mouse line recently generated by gene targeting (Otterbach and Stoffel, 1995) develops a lethal storage disease which is phenotypically comparable to the neurovisceral form of the human sphingomyelinosis, Niemann-Pick disease type A (NPA). This report describes the progressive accumulation of uncatabolized lipid substrates at the cellular and ultrastructural level in different regions of the nervous system of homozygous aSmase-/- mice, including cerebrum, cerebellum, spinal cord, optic nerve and peripheral nerves. We saw a cytoplasmic accumulation of pleomorphic lysosomal structures in cells of all regions under study, most extensively in macrophages, vascular endothelial cells, and also in neuronal perikarya. The complete and early degeneration of Purkinje cells was particularly striking. Moreover, we found a storage material in the cytoplasm of Schwann cells and to a minor extent in oligodendrocytes. In most advanced stages of the disorder, we detected an axonal dystrophy in both the central nervous system (CNS) and peripheral nervous system (PNS), without signs of dysmyelination or demyelination. The morphological changes of the central and peripheral nervous systems in the homozygous aSmase-/- mouse line closely resemble those in human NPA.

Animals↗

HveC (nectin-1) is expressed at high levels in sensory neurons, but not in motor neurons, of the rat peripheral nervous system.

The entry of herpes simplex virus (HSV)-1 into cells is a complex process mediated in part by the binding of the HSV glycoprotein D (gD) to a specific cellular receptor identified as HveC, or nectin-1. We examined the distribution of HveC in sensory and motor neurons of the peripheral nervous system (PNS) by immunocytochemistry. HveC is expressed at high levels in sensory neurons of dorsal root ganglion and their peripheral axons, at lower levels in motor neurons of spinal cord, and without detectable expression in motor nerve terminals at the neuromuscular junction. These results have implications regarding the tropism of HSV to specific neuronal populations, and for the construction of HSV-based vectors for the peripheral nervous system.

Animals↗

The peripheral nervous system complications of HTLV-1 myelopathy (HAM/TSP) syndromes.

Human T-cell lymphotropic virus type I (HTLV-1) is a human retrovirus and the etiologic agent for a progressive neurological disease called HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). With its primary site of involvement occurring at the thoracic spinal cord level, HAM/TSP is characterized by muscle weakness, hyperreflexia, lower extremity spasticity, and urinary disturbance. However, HAM/TSP has also been associated with other autoimmune disorders as well as widespread dysfunction within the nervous system that results in less frequent symptoms of cerebral, cerebellar, and cranial nerve involvement. Although masked by the more prominent myelopathy, involvement of the peripheral nervous system also occurs. Syndromes of anterior horn cell, peripheral nerve, and muscle dysfunction have been reported.

Humans↗

Determination of RNA expression for cholecystokinin/gastrin receptors (CCKA, CCKB and CCKC) in human tumors of the central and peripheral nervous system.

Gastrin (G17) belongs to the cholecystokinin (CCK) peptide family widely distributed in the brain, and we were the first to show that it significantly modulates the growth and migration features of tumor astyrocytes. Conflictual data have been published as to whether CCKA, CCKB and CCKC receptors are, or are not, present in tumors of the central and peripheral nervous system (CPNS) in general, and in gliomas in particular. In the present study we employed polymerase chain reaction (PCR) on a series of 29 CNPS tumors, including 20 gliomas (17 astrocytic and 3 oligodendroglial tumors), 4 schwannomas and 5 meningiomas to investigate whether RNAs were present or absent in the case of these CCKA, CCKB and CCKC receptors. The presence of the three CCK receptor subtypes was also assayed on three experimental models, i.e. the U373 human glioma, the C6 rat glioma and the 9L rat gliosarcoma. The data show that 9/20 (45%) of the gliomas exhibited RNAs for the CCKB receptor as did the C6 rat glioma, 13/20 (65%) RNAs for the CCKC receptor as did the U373 human glioma and the 9L rat gliosarcoma. Of the 20 gliomas, 17 (85%) expressed RNAs for either the CCKB or the CCKC receptor (or both), a feature which was also observed in the experimental models. One schwannoma and one meningioma exhibited RNAs for the CCKB receptor, while 4/4 schwannomas and 4/5 meningiomas showed RNAs for the CCKC receptor. None of the gliomas, schwannomas or meningiomas exhibited RNAs for the CCKA receptor, which were found in the 9L rat gliosarcoma model only. These data emphasize that 85% of the gliomas under study and 86% (25/29) of the tumors of the central and peripheral nervous system exhibited CCKB and/or CCKC receptors. This therefore suggests an important role for gastrin in the biological development of these tumors.

Animals↗

Effects of hyperthermia on the peripheral nervous system: a review.

The present paper overviews the current knowledge about effects of hyperthermia at temperatures used in clinical oncology on the peripheral nervous system. From the experimental studies it may be concluded that the heat sensitivity of the nerve is determined by the sensitivity of the nerve vasculature. These studies show that in order to avoid induction of severe neuropathy, application of heat to the peripheral nerves should not be in excess of doses of 30 min at 44 degrees C or equivalent. Using modern equipment for application of loco-regional hyperthermia the incidence of even mild neurological complications is very low. In hyperthermic isolated limb perfusion (HILP) neurotoxicity is an often-mentioned side effect, this is in spite of the fact that in all studies a relatively mild hyperthermic temperature is used that, based on the experimental studies, should be well tolerated by the nerves and other normal tissues in the limbs. It seems that the neurotoxicity observed after HILP results from thermal enhancement of drug toxicity, very probably combined with effects of a high tourniquet pressure that is used to isolate the blood flow in the leg. Whole body hyperthermia (WBH), using anesthesia and appropriate monitoring to avoid cardiovascular stress is at present considered a safe procedure. Still in the recent past cases of neuropathy after treatment have been described. When chemotherapy, and notably cisplatin, is administered before or during hyperthermia there are several clinical and experimental observations that indicate a limited tolerance of the peripheral nervous tissue in such case. Also previous radiotherapy may limit the tolerance of nerves to hyperthermia, notably when radiation is applied with a large field size. Experimental studies show that combined treatment with radiation and heat leads to enhancement of effects of radiation (enhancement ratio approximately 1.5 at 60 min at 44 degrees C). A clear contraindication for the application of hyperthermia in patients is the presence of a neurodegenerative disease, such as multiple sclerosis. Vigilance is also required in the treatment of diabetic patients with hyperthermia, this based on experimental animal studies, but so far no clear clinical data are available.

Animals↗

Effects on the peripheral nervous system of tunnel workers exposed to acrylamide and N-methylolacrylamide.

OBJECTIVES: This study evaluates the possible toxic effects on the peripheral nervous system of tunnel workers exposed to acrylamide and N-methylolacrylamide during grouting work. METHODS: Symptoms and nerve conduction velocities (NCV) were recorded for 24 tunnel workers 4 and 16 months after the cessation of exposure during grouting operations. Fifty tunnel workers not involved in grouting operations served as referents. Exposure was assessed by questionnaires, qualitative exposure indices, and measurements of hemoglobin adducts after the cessation of exposure. RESULTS: The exposed workers reported a higher prevalence of symptoms during grouting work than they did in an examination 16 months later. A statistically significant reduction in the mean sensory NCV of the ulnar nerve was observed 4 months postexposure when compared with the values of the reference group (52.3 versus 58.9 m/s, P = 0.001), and the mean ulnar distal delay was prolonged (3.1 versus 2.5 ms, P = 0.001). Both measures were significantly improved when measured 1 year later. Exposure-related improvements were observed from 4 to 16 months postexposure for both the median (motor and sensory NCV and F-response) and ulnar (sensory NCV, F-response) nerves. A significant reversible reduction in the mean sensory amplitude of the median nerve was also observed, while the mean sensory amplitude of the sural nerve was significantly reduced after 16 months. CONCLUSIONS: The results indicate demyelinating and axonal changes in peripheral nerves of tunnel workers in relation to exposure to N-methylolacrylamide and acrylamide during grouting operations. The changes were slight, mostly subclinical, and most of the effects were reversible, with normalization after 1 year.

Acrylamide↗

[F-wave amplitude in peripheral nervous system lesions].

BACKGROUND AND PURPOSE: F-wave is a late response recorded from muscle elicited by electric impulse conveyed antidromically to alpha-motor neurons of the spinal cord. F-wave latency and frequency are assessed in routine electroneurography providing information of conduction in the proximal segment of the nerves. F-wave amplitude is rarely analyzed, while it could add valuable information on excitability of motor neurons in different disease states. This study was conducted to determine whether F-wave amplitude is indicative of the level of the peripheral nervous system lesion. MATERIAL AND METHODS: EMG recordings of 204 consecutive patients suspected of peripheral nerves system lesion were retrospectively analyzed. Based on the clinical diagnosis three groups were defined: neuropathy (N=100), myopathy (N=33), ALS (N=18), reference (musculoskeletal pain syndromes: N=53). F-wave amplitude and F/CMAP-ratio (CMAP-compound motor action potential) and their relation to parameters of impulse conduction in motor nerve fibers was analyzed. RESULTS: Mean F/CMAP ratio was 11.1% in ALS, 5% in myopathy (p=0.008), 7.1% in neuropathies and 5.6% in the reference group. Giant F-wave (more than 10% of CMAP) was observed in 30% of nerves in ALS, 15% in neuropathy and 10% in myopathy (p=0.036). F-wave amplitude correlated significantly with CMAP amplitude in all groups, while F/CMAP ratio was inversely related to CMAP amplitude in ALS (r=-0.43, p<0.01) and neuropathy (r=-0.37, p<0.0001). F-wave frequency was similar in all groups and correlated with CMAP amplitude. CONCLUSIONS: F-wave amplitude is not indicative of the level of peripheral nervous system lesions. Giant F-wave is observed in neurogenic processes. It reflects an increase of motor unit size in the reinnervation process, but possibly also a change of excitability of motor neuron and its axon.

Adult↗

Gangliosides and glycosphingolipids of peripheral nervous system myelins--a minireview.

A summary is provided of the available data on the composition of gangliosides and glycosphingolipids in the peripheral nervous system (PNS) including myelins and their antigenic properties. The composition of gangliosides and glycosphingolipids in the PNS is very different from that in the central nervous system (CNS), both quantitatively and qualitatively. One major difference is the abundance of neolacto-series gangliosides in the PNS, with the backbone structure Gal beta 1-4GlcNAc beta1-3Gal beta 1-4Glc1-1'Cer. Their abundance contrasts with the abundance of ganglio-series gangliosides in the CNS. The neolacto-series gangliosides are localized mainly in the myelins of the PNS. In addition to gangliosides, other acidic and neutral glycosphingolipids in the neolactoseries are also characteristic of the myelins of the PNS. The ceramide (fatty acid and sphingosine base) compositions of gangliosides in the PNS are different from those in the CNS gangliosides, having greater percentages of long-chain fatty acids and dehydrosphingosines than found in the CNS gangliosides.

Animals↗