Painful small-fiber neuropathy in Sjogren syndrome.

Of 20 consecutive patients with Sjögren neuropathy, 16 (80%) presented with burning feet and 12 (60%) with non-length-dependent sensory symptoms. Leg and thigh skin biopsies, performed in 13 patients, including 7 with normal electrophysiology, showed either reduced epidermal nerve fiber (ENF) density or abnormal morphology. ENF loss was frequently non length dependent, suggesting that patients with this disorder commonly have a small-fiber sensory neuronopathy rather than a "dying-back" axonopathy.

Plantar nerve AP and skin biopsy in sensory neuropathies with normal routine conduction studies.

OBJECTIVE: To assess the medial plantar nerve action potential (NAP) and skin biopsy in the evaluation of suspected distal sensory neuropathies (SN) with normal routine nerve conduction studies (NCS). METHODS: A total of 110 consecutive patients with suspected distal SN and normal routine NCS underwent medial plantar NAP testing and punch skin biopsy. Patients were clinically stratified as having pure small fiber sensory neuropathy (SFSN), or distal SN with large fiber involvement (SN-LFI). RESULTS: A total of 56 patients were classified as SN-LFI and 54 SFSN. The medial plantar NAP, a measure of large fiber function, was abnormal in 31.8% of patients, more frequently in SN-LFI than SFSN. Distal leg epidermal nerve fiber (ENF) density, a measure of small fibers, was reduced in 47.3% of biopsies, with isolated ENF morphologic changes in 29.1% and normal findings in 23.6%. Biopsy abnormalities were more severe and prevalent in SN-LFI than in SFSN. In patients with a normal medial plantar NAP, distal leg biopsy showed reduced ENF density in 34.7%, and isolated morphologic changes in a further 37% of cases. CONCLUSIONS: The medial plantar nerve action potential and skin biopsy are complementary in evaluation of distal SN with normal routine NCS. Small sensory nerve fibers are affected early in SN, and more severely so when large fiber involvement is apparent clinically.

Distal myasthenia gravis with a decrement, an increment, and denervation.

We present two patients with distal myasthenia gravis poorly responsive to immunomodulatory therapy. In addition to a typical decrement on slow repetitive nerve stimulation, both had borderline to low compound muscle action potential (CMAP) amplitudes, a large increment in CMAP amplitude and area after exercise, and active denervation in distal muscles. Both had elevated acetylcholine receptor antibody (AChR Ab) levels, but normal voltage-gated calcium channel antibody levels. We hypothesize that these electrophysiological findings represent a more severe form of myasthenia gravis.

Acute and delayed cerebral infarction after wasp sting anaphylaxis.

A 52-year-old man developed a severe anaphylactic reaction after a wasp sting. Slurred speech and left hemiparesis were noted a few hours later. Three-and-one-half weeks later, he became acutely obtunded and quadriparetic. Angiographic studies demonstrated complete and near-complete occlusions of the right and left internal carotid arteries, respectively. A mechanism is suggested for delayed ischemic stroke after wasp sting anaphylaxis that involves cerebrovascular sympathetic innervation.

Ultrastructural immunohistochemical localization of poliovirus during virulent infection of mice.

Ultrastructural immunohistochemistry was used to localize type 2 human poliovirus (HPV 2) during virulent infection of mice caused by the Lansing strain. In the spinal cord, immune-reaction product was exclusively localized within neurons and their processes. The absence of viral antigen in glial, endothelial and inflammatory cells further supports the strict neuronotropicity of HPV. In addition, viral antigen and virus-like particles were localized in synaptic complexes and axons, including preterminal axons. This clear demonstration of HPV in neuronal cell bodies, their axons, and synaptic elements strongly supports the hypothesis of HPV dissemination in the central nervous system via axonal transport.

Antibody to myelin-associated glycoprotein reacts with plasma cells in mice.

A recent study on the relative disappearance of MAG versus MBP in primary and recurrent lesions of Theiler's infection had shown that numerous mononuclear cells in meninges and perivascular spaces specifically bound anti-MAG antibody. The present study was undertaken to clarify the nature of these cells. Immunocytochemistry and electron microscopy were done on serial sections of affected spinal cords. In addition sequential immunofluorescence and HRP immunocytochemistry were performed on single sections of spinal cords and spleens from normal mice and mice with Theiler's infection and EAE. Results indicate that cells binding anti-MAG antibody are plasma cells and that they are present in both normal and diseased animals.

Immunocytochemical localization of MAG, MBP and P0 protein in acute and relapsing demyelinating lesions of Theiler's virus infection.

Acute demyelinating and relapsing demyelinating lesions from spinal cords of mice infected with the WW strain of Theiler's encephalomyelitis virus (TMEV) were studied immunocytochemically with antisera to various myelin constituents. Acute lesions were studied for differences in the distribution of myelin basic protein (MBP) and myelin associated glycoprotein (MAG). Relapsing lesions, characterized by demyelination of areas previously remyelinated by Schwann cells, were studied for differences in the distribution of P0 and MAG. In both instances the earliest lesions were characterized by preferential disappearance of MBP and P0 respectively when compared to MAG. In well-developed lesions, MAG, MBP and P0 were absent in essentially equal proportion. These observations are in agreement with previous findings suggesting a primary loss of myelin rather than a direct attack on oligodendrocytes as the main pathogenetic mechanism of demyelination in this viral model.

Serum and cells from Theiler's virus-infected mice fail to injure myelinating cultures or to produce in vivo transfer of disease. The pathogenesis of Theiler's virus-induced demyelination appears to differ from that of EAE.

Intracerebral inoculation of SJL mice with Theiler's Murine Encephalomyelitis virus (TMEV) results in a biphasic disease characterized by early grey matter involvement followed by late, chronic white matter inflammation and demyelination. Morphological parameters of TMEV-induced demyelination are essentially identical to those of experimental allergic encephalomyelitis (EAE) and immunosuppression has been shown to prevent demyelination. To test whether the pathogenesis of demyelination in TMEV infection is based on an autoimmune attack on myelin as in EAE, we tested sera and cells from infected animals for their ability to produce in vitro demyelination and cells for their ability to transfer disease in vivo. Isogeneic organotypic cultures were exposed to either serum or splenocytes from diseased animals. Neither serum nor splenocytes demyelinated or prevented myelination in these cultures. Splenocytes from diseased animals were also incubated with basic protein or whole spinal cord and assayed for their proliferative response or their ability to transfer disease to naive recipients. Neither proliferation nor transfer of disease was observed. These results show that the immunopathology of demyelination in the Theiler's model differs from that of EAE in a number of important parameters and support the contention that demyelination in this viral infection is produced by immunological mechanisms different from those operating in EAE.

Remyelination during remission in Theiler's virus infection.

Inoculation of the cell-adapted WW strain of Theiler's virus into mice produces a chronic demyelinating infection of the central nervous system (CNS) characterized by a remitting relapsing course. During remission, extensive remyelination of spinal cord white matter is observed. Remyelination is carried out by both Schwann cells and oligodendrocytes. This paper examines the possible mechanisms of entry of Schwann cells into the CNS, their possible source in different regions of the white matter, their relations with various CNS elements, and the relative activity of these cells versus that of oligodendrocytes. Observations suggest that Schwann cells, originating from peripheral roots and from perivascular areas, migrate into white matter through gaps in the glial limiting membrane ( GLM ), probably caused by active mononuclear inflammatory cells. Schwann cell invasion and axonal contact appear to be facilitated by the presence of collagen matrix along their pathway of migration. No alterations of astrocytes in the immediate vicinity of Schwann cells were observed, and free contact between Schwann cells and different neuroglial elements was present in the initial stages of Schwann cell migration. While Schwann cells were the predominant myelinating cells in the outer white matter, oligodendrocytes were numerous and very active in the inner portions of the spinal cord column. Although oligodendrocytes produced thinner myelin than normal, in most areas essentially complete remyelination by these cells was observed. These results contrast with those of previous studies of DA infected mice in which remyelination is sporadic in the presence of unabated inflammation which continues without remission for many months after infection. It is suggested that oligodendroglial cells are quite capable of extensive remyelinating activity in this infection, provided the noxa responsible for myelin injury subsides. The host inflammatory response appears to be the most likely noxa impeding remyelination in this model.