Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “DEMYELINATION”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 217 records · Page 12Linked to original sources
PubMed2006

Nodal, paranodal and juxtaparanodal axonal proteins during demyelination and remyelination in multiple sclerosis.

Saltatory conduction in myelinated fibres depends on the specific molecular organization of highly specialized axonal domains at the node of Ranvier, the paranodal and the juxtaparanodal regions. Voltage-gated sodium channels (Na(v)) have been shown to be deployed along the naked demyelinated axon in experimental models of CNS demyelination and in multiple sclerosis lesions. Little is known about aggregation of nodal, paranodal and juxtaparanodal constituents during the repair process. We analysed by immunohistochemistry on free-floating sections from multiple sclerosis brains the expression and distribution of nodal (Na(v) channels), paranodal (paranodin/Caspr) and juxtaparanodal (K(v) channels and Caspr2) molecules in demyelinated and remyelinated lesions. Whereas in demyelinated lesions, paranodal and juxtaparanodal proteins are diffusely distributed on denuded axons, the distribution of Na(v) channels is heterogeneous, with a diffuse immunoreactivity but also few broad Na(v) channel aggregates in all demyelinated lesions. In contrast to the demyelinated plaques, all remyelinated lesions are characterized by the detection of aggregates of Na(v) channels, paranodin/Caspr, K(v) channels and Caspr2. Our data suggest that these aggregates precede remyelination, and that Na(v) channel aggregation is the initial event, followed by aggregation of paranodal and then juxtaparanodal axonal proteins. Remyelination takes place in multiple sclerosis tissue but myelin repair is often incomplete, and the reasons for this remyelination deficit are many. We suggest that a defect of Na(v) channel aggregation might be involved in the remyelination failure in demyelinated lesions with spared axons and oligodendroglial cells.

Adult↗
PubMed2003

Subpial demyelination in the cerebral cortex of multiple sclerosis patients.

The extent and pattern of demyelination in the cerebral cortex was determined in 78 tissue blocks from the brains of 20 multiple sclerosis (MS) patients and 28 tissue blocks from 7 patients without neurological disease. Tissue blocks from 4 predetermined areas (cingulate gyrus, frontal, parietal, and temporal lobe) were studied, irrespective of macroscopically evident MS plaques. All tissue blocks contained cerebral cortex and periventricular and/or subcortical white matter. One hundred and nine demyelinating lesions were detected in the cerebral cortex, of which 92 (84.4%) were purely intracortical and 17 (15.6%) were lesions extending through both white and gray matter areas. In 5 of the 20 MS brains, subpial demyelination was extensive in the 4 widely spaced cortical areas studied, thus considered to represent a general cortical subpial demyelination. The percentage of demyelinated area was significantly higher in the cerebral cortex (mean 26.5%, median 14.1%) than in white matter (mean 6.5%, median 0%) (p = 0.001). Both gray and white matter demyelination was more prominent in the cingulate gyrus than in the other areas examined (p < 0.05). These results indicate that the cerebral cortex is likely to be a predilection site for MS lesions and identify general cortical subpial demyelination as a distinct pattern occurring in a significant subpopulation of MS patients.

Adult↗
PubMed1987

The distribution of sodium and potassium channels in single demyelinated axons of the frog.

1. Frog sciatic nerves were focally demyelinated by intraneural injection of lysolecithin. Fibres were examined 1-8 days later. At early times axons contained zones just a few micrometers long that were covered by myelin debris. These zones lengthened and the debris was cleared over the next several days. 2. The loose patch clamp technique was used to measure ionic currents in the demyelinated axolemma in both internodal and paranodal regions. 3. Transient inward currents that have been identified as Na+ currents on the basis of voltage dependence and sensitivity to tetrodotoxin were recorded at all stages tested. There was no significant increase in internodal peak Na+ current with time over the first 8 days after injection. 4. Peak inward currents varied relatively little with distance along the internode at 1 day post-injection. However, sharp gradients were detected at demyelinated paranodal and nodal membranes. 5. By combining the patch clamp with external stimulation proximal to the patch site it has been possible to record membrane current responses to propagating signals invading the demyelinated zone. With demyelination only in the distal heminode the extent of Na+ channel activation is similar to that predicted for normal nodes of Ranvier by Frankenhaeuser & Huxley (1964). 6. The ratio of K+ conductance to Na+ conductance is much higher in demyelinated internodes than in normal nodes of Ranvier. 7. It is concluded that Na+ channels are likely to be present in normal internodes. The total number of these internodal channels may be about 40 times the total number at nodes. Steep gradients of Na+ channel density remain at nodal regions at least up to 6 days following demyelination.

Action Potentials↗
PubMed1987

T lymphocyte-derived demyelinating activity in multiple sclerosis patients in relapse.

Supernatants of cultured T lymphocytes of multiple sclerosis patients were tested for a demyelinating activity in rat cerebellum explant cultures. Supernatants of unstimulated T lymphocytes in seven out of 10 multiple sclerosis patients in relapse produced demyelination when checked by phase contrast microscopy. Supernatants of unstimulated T lymphocytes from healthy subjects did not produce demyelination, but when T cells were stimulated by phytohaemagglutinin (PHA), 50% of tested supernatants produced demyelination, which was, however, never as advanced as in multiple sclerosis supernatant treated cerebellum cultures. The demyelinating activity proved to be heat labile. Gel filtration study revealed two fractions of the demyelinating activity 12.5-29.0 kD and 43.0-66.0 kD. The results suggest that lymphokines can be directly involved in the pathogenesis of demyelination in multiple sclerosis.

Adult↗
PubMed1998

Measurement of the retinal nerve fibre layer with scanning laser polarimetry in patients with previous demyelinating optic neuritis.

OBJECTIVES: Subjective visual deficits are common after demyelinating optic neuritis despite the frequent return of normal visual acuity. Visual and electrodiagnostic tests have demonstrated evidence of these persisting functional abnormalities, which are thought to be secondary to demyelination and variable axonal loss in the optic nerve. Scanning laser polarimetry (SLP) is a new image analysis technique which uses the polarising properties of the retinal nerve fibre layer (RNFL) to produce a quantitative measure of its thickness. This study was carried out to assess the prevalence, extent, and pattern of RNFL loss after demyelinating optic neuritis using SLP. METHODS: Twenty four patients with a history of previous demyelinating optic neuritis were re-examined. Examination included measurement of logmar visual acuity, Pelli-Robson contrast sensitivity, and the presence of a relative afferent pupil defect and optic atrophy. SLP was performed and a mean RNFL profile from a series of three images from each eye was constructed. This was compared with normative data from 20 age matched normal subjects. The lower 99.9% confidence limit of the normal data was calculated and used as the cut off criterion for abnormality. RESULTS: There were a total of 31 eyes with a history of demyelinating optic neuritis and SLP disclosed an abnormality in 29 (94%) of these. Twenty three eyes recovered an acuity of 0.0 or better, 21 of which had evidence of RNFL loss on polarimetry. Scanning laser polarimetry was the only abnormality found in nine of the 31 eyes (29%). The pattern and extent of RNFL loss was very variable and there was no significant difference in these indices between patients with multiple sclerosis compared with those with isolated demyelinating optic neuritis. CONCLUSION: Scanning laser polarimetry can provide a quantitative measure of RNFL loss after demyelinating optic neuritis, demonstrating its occurrence in a high percentage of patients recovering normal visual acuity.

Adult↗
PubMed2000

Glycosphingolipid antibodies and blood-nerve barrier in autoimmune demyelinative neuropathy.

OBJECTIVE: To evaluate morphologic changes in small endoneurial vessels in patients with autoimmune demyelinative neuropathy and antiglycosphyngolipid antibodies. BACKGROUND: Although a humoral immune cause has been postulated for various demyelinating neuropathies, the mechanism by which large molecules like immunoglobulins can traverse the blood-nerve barrier (BNB) to enter the endoneurium is not understood. METHODS: We examined histologic and ultrastructural changes in small endoneurial vessels in sural nerve biopsy specimens from autoimmune demyelinative neuropathy patients, with or without anti-glycosphingolipid (GSL) antibodies. Density of small endoneurial vessels, mean endothelial area, mean luminal area, and the percentage of endothelial cell junctions (that make up the BNB) that showed evidence of disruption were evaluated. RESULTS: Only junctional disruption showed a significant difference: autoimmune demyelinative neuropathy patients with anti-GSL antibodies showed more BNB disruption than autoimmune demyelinative neuropathy patients without antibodies or control patients with nonautoimmune neuropathies. The most commonly observed endoneurial change in antibody-positive autoimmune demyelinative neuropathy patients was the finding of continuous, patent spaces lacking tight junctions between endothelial cells. CONCLUSIONS: Brain endothelial cells and endoneurial endothelial cells share various GSL antigens, including GM1 and GD1b gangliosides, with peripheral nerve tissues. Circulating anti-GSL antibodies could damage cell-to-cell attachments in endoneurial endothelium. This barrier disruption may permit the large molecules like immunoglobulins to enter the endoneurial space, contributing to development of autoimmune demyelinative neuropathy.

Adolescent↗
PubMed2003

Extracellular potentials of myelinated and demyelinated human motor nerve fibres.

The extracellular potentials of myelinated and demyelinated human motor nerve fibres in an unbounded volume conductor are studied. Using our previous double-cable models of normal and demyelinated human fibres, the spatial and temporal intracellular potentials are calculated in the cases of point polarization and adaptation of the fibres. The intracellular potentials are then used as input to a line source model that allows to calculate the corresponding spatial and temporal extracellular potentials at various radial distances in the surrounding volume conductor. Four fibre demyelinations (termed as internodal focal\systematic and paranodal focal\systematic demyelinations, respectively) are studied. In all investigated cases, the radial decline of the peak-to-peak amplitude of the extracellular potential depends on the radial distance of the field point and increases with the increase of the distance. The results are consistent with the interpretation that the considerably different spatial and temporal distributions of the extracellular potentials depend not only on the cable properties of the fibres, but on the methods of fibre stimulation. In the case of fibre adaptation, the temporal extracellular potentials in the normal and demyelinated cases correspond well with electromyograms (EMGs) from healthy subjects and patients with demyelinated disorders as reported in the literature. Simulation results indicate that the models used are rather promising tools in studying the main properties of compound action potentials in patients with demyelinated disorders which up till now have not been sufficiently well understood.

Electric Stimulation↗
PubMedDate not supplied

Excitability properties of normal and demyelinated human motor nerve axons.

The strength-duration time constants and rheobase currents, which provide an indirect indication of the axonal properties are calculated in two cases of stimulation, using our previous double cable models of normal and demyelinated human motor fibres. The time constants and rheobases are defined as nodal when the case of point fibre polarization (intracellular current application at the first node) is used for their calculations, whereas the time constants and rheobases are defined as internodal when the case of periodic kind of uniform fibre polarization (simultaneous intracellular current application at each axon segment) is used. Four fibre demyelinations (termed as paranodal focal 1 systematic and internodalfocal 1 systematic demyelinations) are studied. For both investigating cases of current application, the stimulus duration is increased in 0.025-ms steps from 0.025-ms to 1-ms and the strength-duration and charge-duration curves are plotted for the axons. The strength-duration time constants are calculatedfrom the curve-fitting equation for the resulting charge-duration curves. The results are consistent with the interpretation that the time constants depend not only on the types of the demyelinated axon, but on the methods of fibre stimulation. The strength-duration time constants (nodal 1 internodal) are almost the same for the normal axons and focally demyelinated axons, however, they are shorter for the paranodally systematically demyelinated axons, and longer for the internodally systematically demyelinated axons. For all investigated cases, the internodal time constants are greater than the nodal time constants and there is an inverse relationship between the time constants and rheobase currents.

Action Potentials↗
PubMed1986

Ultrastructural study of central nervous system demyelination in galactocerebroside sensitized rabbits.

The rabbit eye model was used to investigate the role of delayed type hypersensitivity and of circulating antigalactocerebroside antibody in primary demyelination. Delayed type hypersensitivity reaction to tuberculin was induced within the retinal myelinated layers by injecting purified protein derivative into the vitreous of rabbits that were previously immunized with complete Freund's adjuvant (CFA) alone, or galactocerebroside (GC) in CFA. The morphological features of the myelinated zones were assessed 5 days after injection. All rabbits showed infiltration of mononuclear cells within the myelinated fiber bundles. Rabbits previously sensitized with CFA alone showed nonspecific destruction of nerve fibers in severe inflammatory lesions, but primary demyelination was rarely found. This suggests that myelin destruction induced by delayed type hypersensitivity reaction to interstitial antigens (purified protein derivative, so-called "bystander demyelination") by itself does not play a major role in inducing primary demyelination. On the other hand, primary demyelination was recognized in the vicinity of infiltrating mononuclear cells in rabbits previously immunized with GC in CFA and had elevated titers of serum anti-GC antibody. The destruction of the blood-brain barrier was suggested by the presence of fibrin exudates in demyelinative lesions where observation revealed selective myelin breakdown such as vesicular disruption and active stripping of myelin. This study indicates that the anti-GC antibody is an important factor in central nervous system demyelination of GC-sensitized rabbits.

Animals↗
PubMed1978

Antiserum-mediated demyelination in vivo: a sequential study using intraneural injection of experimental allergic neuritis serum.

Primary segmental demyelination accompanied by mononuclear phagocytes was induced by injection of antiserum into rat peripheral nerve, and the morphologic sequence of events was studied. Antisera were obtained from rabbits with experimental allergic neuritis (EAN) produced by the inoculation of emulsified bovine peripheral nerves in complete Freund's adjuvant. Sera were injected directly into rat sciatic nerve to circumvent the blood-nerve barrier. Recipient rats developed sensorimotor paralysis on the side injected with experimental allergic neuritis sera. Intense focal demyelinative lesions resulted from injection of experimental allergic neuritis sera. Control sera obtained from rabbits inoculated with bovine serum albumin in complete Freund's adjuvant did not produce paralysis or demyelination. The earliest change was damage to Schwann cells, seen 20 minutes after antiserum injection. Within a few hours lamellar splitting and vacuolation of myelin began to paranodal regions and Schmidt-Lanterman clefts and there were infiltrating polymorphonuclear cells. By 8 hours without the detectable presence of monocytes or macrophages, myelin vesiculation became advanced and widespread. By 15 hours, endoneurial edema had reached its maximum. Macrophages were found in association with myelinated nerve fibers. From that time through the next 5 days, demyelination progressed to complete denudation of axons by macrophage phagocytosis of myelin. Activated cytoplasm of Schwann cells reinvested demyelinated axons, often in concert with persisting phagocytic macrophages. Peripheral nerve demyelination thus transferred evolved rapidly, and myelin destruction occurred prior to the appearance of monocytes or macrophages. Demyelinating activity was lost after absorption by purified peripheral nerve myelin but not by liver or kidney and was heat-labile and complement dependent (T. Saida, K. Saida, D. H. Silberberg, and M. J. Brown: Nature 272: 639, 1978).

Animals↗
PubMed2000

Electrodiagnosis of demyelinating neuropathies.

The inflammatory demyelinating neuropathies constitute a significant proportion of the acquired polyneuropathies. Major progress in finding the causes and in the treatment of these neuropathies has been made over the last decade. Early recognition is of paramount importance, because timely and appropriate treatment can largely reduce morbidity and disability. Electrodiagnosis plays a key role in the detection and characterization of the inflammatory demyelinating neuropathies. Electrodiagnostic criteria for primary demyelination have therefore been developed. They are empirically based on changes of nerve conduction parameters in populations of patients with a confirmed clinical and laboratory diagnosis of inflammatory demyelinating neuropathy. The challenge consists of defining criteria sets that are highly specific but also as sensitive as possible. Most of the hereditary demyelinating neuropathies are part of Charcot-Marie-Tooth disease type 1. The pattern of nerve conduction abnormalities usually provides valuable clues for the distinction from chronic inflammatory demyelinating neuropathies.

Action Potentials↗
PubMed1988

Evoked potentials in chronic inflammatory demyelinating polyneuropathy.

Eighteen patients with chronic inflammatory demyelinating polyneuropathy were studied with evoked potentials to assess for evidence of central nervous system demyelination. Both visual and brain-stem auditory evoked responses were obtained, and the results were compared with magnetic resonance imaging (MRI). An evoked potential was abnormal in nine of 18 patients, five of whom had central nervous system evidence of demyelination by MRI. Evoked potentials identified four patients with probable anterior optic pathway involvement that was not demonstrable by MRI. These findings continue to support that chronic inflammatory demyelinating polyneuropathy is associated with a central demyelinating disorder and more importantly emphasize the possibility of a common pathogenic mechanism in central and peripheral nerve demyelination.

Brain Stem↗
PubMed2000

Chronic inflammatory demyelinating polyradiculoneuropathy: a study of proposed electrodiagnostic and histologic criteria.

OBJECTIVE: To examine the sensitivity of the 3 proposed electrodiagnostic (EDX) criteria for demyelination, the sensitivity and specificity of the proposed Ad Hoc Subcommittee of the American Academy of Neurology AIDS [Acquired Immunodeficiency Syndrome] Task Force histologic criteria (AAN criteria), the degree of agreement among these criteria, and the diagnostic value of sural nerve histologic criteria in patients with idiopathic chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). DESIGN AND METHODS: A retrospective analysis of 24 patients with idiopathic CIDP and 12 patients with diabetic polyneuropathy (DP) who underwent comparable testing of clinical, histologic, and EDX features. RESULTS: We found 42%, 50%, and 79% sensitivity of the proposed EDX, AAN teased fiber, and AAN electron microscopic (EM) criteria, respectively, for demyelination in CIDP. The specificity of the proposed AAN teased fiber and EM criteria for demyelination was greater than 80% when tested against patients with DP. There was lack of agreement between the EDX and histologic criteria. Almost two thirds of patients with CIDP who met the EM criteria but none of the EDX criteria for demyelination showed a favorable response to immunomodulatory therapy. CONCLUSIONS: Sural nerve histologic criteria offer unique sensitivity and acceptable specificity toward the diagnosis of CIDP. Sural nerve biopsy should be considered when a clinical suspicion of CIDP remains in patients who do not meet the proposed EDX criteria for demyelination.

Adult↗
PubMed2003

Chronic acquired demyelinating symmetric polyneuropathy classified by pattern of weakness.

OBJECTIVES: To study a representative group of patients with chronic acquired symmetric demyelinating polyneuropathies, and to evaluate classification by pattern of weakness and by presence of immunoglobulin monoclonal protein (M protein). METHODS: In Vest-Agder County, Norway, an unselected population of patients with chronic symmetric polyneuropathies who fulfill electrodiagnostic criteria for demyelination are registered in a database and followed up prospectively. Data were taken from the database on April 2, 2001. Patients with proximal as well as distal weakness were classified as having chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), and patients with only distal symptoms as having distal acquired demyelinating symmetric polyneuropathy (DADS). RESULTS: A total of 29 patients had chronic acquired symmetric demyelinating polyneuropathy; 15 had CIDP and 14 had DADS. The 2 categories differed regarding spinal protein level (mean +/- SD, 0.102 +/- 0.060 g/dL in CIDP vs 0.065 +/- 0.029 g/dL in DADS; P =.05); clinical course (remitting in 6 of 13 patients with CIDP vs 0 of 14 with DADS; P =.02); disability score at diagnosis (mean +/- SD, 3.3 +/- 1.0 in CIDP vs 1.9 +/- 0.6 in DADS; P<.001) and at peak of symptoms (mean +/- SD, 3.6 +/- 1.1 in CIDP vs 2.3 +/- 0.6 in DADS; P<.001); and response to immunosuppressive treatment (11 of 12 patients with CIDP vs 2 of 7 with DADS; P =.01). An M protein was detected in 8 patients (3 with CIDP and 5 with DADS). Patients with polyneuropathy with and without M protein were similar in clinical features, course, disability, and treatment response. CONCLUSION: Classification by presence or absence of proximal weakness separates patients with chronic acquired symmetric demyelinating polyneuropathy into groups that are different in clinical course, disability, and treatment response.

Adult↗
PubMed1996

Increased vulnerability to demyelination in streptozotocin diabetic rats.

Demyelination is a prominent feature in nerve biopsies of patients with diabetic neuropathy. The mechanism is unknown because diabetic rodents, unlike humans, do not consistently develop segmental demyelination. We examined how diabetes influences toxicant-induced demyelination, remyelination, Schwann cell nerve growth factor receptor (p75) expression, and endoneurial macrophage apolipoprotein E (apo E) synthesis in diabetic rats. Postnatal day 17 (P17) rats were given 110 mg/kg streptozotocin intraperitoneally and then fed a diet containing metallic tellurium (Te) from P20 to P27 to induce demyelination. Transverse electron micrographs and immunostained longitudinal cryosections were prepared from sciatic nerve during demyelination and remyelination. Diabetic rats had a mean serum glucose concentration of 490 mg/dl and consumed equivalent doses of peroral Te. The number of demyelinated fibers in electron micrographs was increased significantly by 17% (P < .0011). Endoneurial density of p75-stained Schwann cells was increased in diabetic rats in proportion to the increased number of injured internodes. Density of apo E- and ED1-positive macrophages also was significantly increased in diabetes. There was no delay in macrophage myelin clearance. and remyelination was not compromised. Increased Schwann cell vulnerability to stress, by increasing the turnover rate of myelinated units, may explain why myelin defects accumulate after long-standing diabetes.

Animals↗
PubMed1999

Demyelinating X-linked Charcot-Marie-Tooth disease: unusual electrophysiological findings.

X-linked Charcot-Marie-Tooth disease (CMT-X) is caused by mutations of connexin-32 (Cx-32), which encodes a gap-junction protein. Whether the neuropathy is primarily demyelinative or axonal remains to be established. We report findings of prominent demyelination in a 71-year-old woman with late-onset disease. Electrophysiological studies revealed a nonuniform slowing of motor conduction velocities and dispersion of compound action potentials indicative of a demyelinating process which was confirmed by nerve biopsy. Such electrophysiological features are unusual in hereditary neuropathies and are more commonly found with acquired chronic demyelinating neuropathies. A systematic search confirmed the molecular genomic diagnosis of CMT-X, illustrating the value of such tests in sporadic cases. Severity of clinical symptoms and signs may vary with age and sex of the patient. The pathology of CMT-X in other reported cases has been variably interpreted as axonal, demyelinating, or showing both features. Our observations emphasize the demyelinative nature.

Action Potentials↗
PubMed1982

In vivo demyelinating activity of sera from patients with Guillain-Barré syndrome.

The in vivo demyelinating capacity of sera from 27 patients with Guillain-Barré syndrome (GBS) and 47 other individuals was studied by intraneural injection into rat sciatic nerves. The morphological features of the nerves in cross section taken just proximal to the site of needle insertion was assessed 48 hours after injection and the extent of demyelination was quantitated. All 27 GBS serum samples were obtained in the first three weeks of clinical disease. Of these, 11 (41%) produced demyelination. Demyelinative activity of GBS sera correlated only with severity of clinical disease (p less than 0.01). The extent of demyelination after intraneural injection of human sera was less intense on average than that produced by sera from animals with experimental allergic neuritis. Three of 40 (7.5%) sera obtained from normal subjects and patients with other neurological diseases also caused in vivo demyelination, although the activity was weaker and occurred less often than with GBS serum.

Adult↗
PubMed1985

Axonal attenuation and secondary segmental demyelination in myeloma neuropathies.

The sural nerves of 5 patients with osteosclerotic myeloma and polyneuropathy, of 3 patients with multiple myeloma and polyneuropathy, and of 6 healthy subjects were studied by neuropathological, morphometric, and teased-fiber approaches to assess cellular (Schwann cell or axon) vulnerability and to explore the mechanism of segmental demyelination. As compared with controls, the nerves of both types of myeloma neuropathy demonstrated a statistically significant and marked loss of myelinated fibers and increased frequencies of axonal degeneration among teased fibers at statistically significant levels. The peaks of diameter histograms of myelinated fibers of osteosclerotic myeloma/polyneuropathy nerves were displaced to smaller diameter categories, suggesting fiber atrophy. Segmental demyelination and remyelination was clustered, as found in secondary demyelination. Large- and intermediate-diameter myelinated fibers of osteosclerotic myeloma/polyneuropathy nerves had significantly smaller axon calibers relative to myelin spiral length seen in electron micrographs. The loss of myelinated fiber axons, the shift of the peaks of diameter histograms to smaller sizes, the lack of noticeable increased numbers of demyelinated axons, the clustered distribution of segmental demyelination, and the axonal attenuation suggest a special axonal or neuronal vulnerability and appear to provide an explanation for the observed segmental demyelination. Whether axonal attenuation has a perikaryeal or proximal axonal genesis now needs to be determined.

Adult↗