Stage Of Paralysis Research Articles

Ефективність моделювання експериментального алергічного енцефаломієліту як експериментальної моделі розсіяного склерозу

The purpose of the study was the most adequate modeling of multiple sclerosis in the form of autoimmune allergic encephalomyelitis for further use in the study of experimental equivalents of neurodegenerative conditions. Materials and methods. The article highlights the results of the formation of experimental allergic encephalomyelitis, for the induction of which homologous brain homogenates were used, which in terms of encephalitogenicity ranks first among other drugs (homologous, heterogeneous brain and spinal cord homogenates). An encephalitogenic mixture was injected into the connective tissue of the base of the animal's tail at the rate of 0.1 ml per 100 g of body weight. Results and discussion. Experimental allergic encephalomyelitis reproducible by intradermal administration of a homogenate of the brain, spinal cord and peripheral nerves with a Freund's stimulator belongs to a true autoimmune disease of the nervous system and is an experimentally reproducible model of multiple sclerosis. According to the experimental data obtained, the state of the animals showed that the rats of the experimental group lost body weight, had a number of pathological neurological symptoms, which manifested on average from 10-12 days. The increase in symptoms continued for an average of 7 days and was not very stable. Experimental animals had paresis, manifestations of ataxia, walking disorders and urinary and fecal incontinence, lethargy, which corresponded to 1-2 degrees of the rating scale in 13 animals. In 7 rats, paresis of the hind limbs and loss of tail tone were expressed (grade 3). Most of the rats recovered spontaneously within 6-8 days after the onset of clinical manifestations (18-20 days after immunization). According to the requirements of the experiment, during the paralytic stage, the rats had free access to food and water. In addition, our experimental studies on the formation of experimental allergic encephalomyelitis were confirmed morphologically using electron microscopy. Conclusion. The use of this technique for the formation of experimental allergic encephalomyelitis made it possible to obtain a simulated pathological state of multiple sclerosis in the form of experimental allergic encephalomyelitis and can be used in further studies to identify the corresponding patterns, the degree and nature of changes in the immune and nervous systems of the body during the reproduction of an experimental pathological state. The data obtained can serve as a basis for further studies of drugs and their combinations in order to improve and rationalize the pharmacotherapy of multiple sclerosis

Upregulation of Cathepsins in Olfactory Bulbs Is Associated with Transient Olfactory Dysfunction in Mice with Experimental Autoimmune Encephalomyelitis.

Cathepsins are a family of lysosomal/endosomal proteolytic enzymes that include serine, aspartate, and cysteine proteases. The role of cathepsin in neurodegenerative diseases, including Alzheimer's disease and Parkinson's disease, remains elusive. We evaluated the expression level and localization of different cathepsins in the olfactory bulbs of mice with experimental autoimmune encephalomyelitis (EAE), a model of human multiple sclerosis. Quantitative real-time PCR results and Western blotting analyses revealed that serine, aspartate, and cysteine cathepsins are expressed at significantly higher levels in the olfactory bulbs of mice with EAE in the paralytic stage compared with those of control mice. Immunohistochemical analyses indicated that cathepsin A, D, and S were expressed in the glomerulus layer, external plexiform layer, and mitral cell layer. Furthermore, cathepsins were detected in astrocytes, microglia, inflammatory cells, and vascular cells in the olfactory bulb of EAE mice at the paralytic stage. Collectively, these results suggest that the upregulation of cathepsins in the olfactory bulb of mice with EAE is associated with transient olfactory dysfunction in autoimmune encephalomyelitis.

Upregulation of periostin in MOG-induced experimental autoimmune encephalomyelitis in mice

Periostin has dual roles as a multifunctional cytokine and an extracellular matrix protein that binds to several integrins on a variety of cells. This study evaluated whether the expression and cellular localization of periostin changes in the spinal cord of mice with experimental autoimmune encephalomyelitis (EAE), an animal model of human multiple sclerosis. Western blot analysis revealed that periostin was significantly upregulated in the spinal cord of EAE-induced mice in the effector stage, and did not significantly decrease in the recovery stage of EAE, compared with normal control. Periostin was constitutively detected in the neurons, ependymal cells, vascular endothelial cells, and astrocytes of normal mice. In the paralytic stage of EAE, periostin immunoreactivity was detected in some macrophages in the subarachnoid space (SAS), as well as in some microglial cells; in addition, periostin immunoreactivity was enhanced in astrocytes and vascular endothelial cells in EAE lesions. Collectively, these results suggest that periostin, either from monocyte-derived macrophages in SAS or glial cells in the parenchyma, partly facilitates the migration of inflammatory cells in the effector stage of EAE; moreover, periostin in the recovery stage of EAE appears to be involved in the plasticity of damaged central nervous system tissues.

Infiltrating monocytes trigger EAE progression, but do not contribute to the resident microglia pool

In multiple sclerosis and the experimental autoimmune encephalitis (EAE) mouse model, two pools of morphologically indistinguishable phagocytic cells, microglia and inflammatory macrophages, accrue from proliferating resident precursors and recruitment of blood-borne progenitors, respectively. Whether these cell types are functionally equivalent is hotly debated, but is challenging to address experimentally. Using a combination of parabiosis and myeloablation to replace circulating progenitors without affecting CNS-resident microglia, we found a strong correlation between monocyte infiltration and progression to the paralytic stage of EAE. Inhibition of chemokine receptor-dependent recruitment of monocytes to the CNS blocked EAE progression, suggesting that these infiltrating cells are essential for pathogenesis. Finally, we found that, although microglia can enter the cell cycle and return to quiescence following remission, recruited monocytes vanish, and therefore do not ultimately contribute to the resident microglial pool. In conclusion, we identified two distinct subsets of myelomonocytic cells with distinct roles in neuroinflammation and disease progression.

Glial cell line‐derived neurotrophic factor is expressed by inflammatory cells in the sciatic nerves of Lewis rats with experimental autoimmune neuritis

Neurotrophic factors, including glial cell line-derived neurotrophic factor (GDNF), have been known to play a role in neuroprotection in the injured peripheral nervous system (PNS). To evaluate the involvement of GDNF in experimental autoimmune neuritis (EAN) pathogenesis, the expression of GDNF in rat sciatic nerves with EAN was studied. Western blot analysis showed that the level of GDNF protein significantly increased 1.8-fold at the paralytic stage of EAN at day 12 post-immunization (PI) (p < 0.01), and its level further increased approximately 2.5-fold at day 21 PI (p < 0.001) in the sciatic nerves of EAN-affected rats compared with those of control rats, and then declined thereafter at day 28 PI. Immunohistochemical analysis showed that axons and Schwann cells constitutively contained GDNF in normal controls. In sciatic nerves with EAN at day 12 PI, GDNF was immunostained in infiltrating inflammatory cells including macrophages and T cells. Collectively, we postulate that GDNF plays a regulatory role in EAN paralysis. A paradoxical role of inflammatory cells to ameliorate PNS inflammation remains to be further studied in EAN, an animal model of human demyelinating disease.

Upregulation of erythropoietin in rat peripheral nervous system with experimental autoimmune neuritis

The glycoprotein erythropoietin (EPO) is a multifunctional cytokine involved in erythropoiesis. Recent data have suggested that EPO and EPO receptors are expressed in the central nervous system, where EPO exerts neuroprotective effects. However, peripheral nervous system (PNS) EPO and EPO receptor expression has not been widely studied. EPO and EPO receptor expression was examined in the PNS in an experimental autoimmune neuritis (EAN) rat model in the present study to elucidate EPO/EPO-receptor binding pathway involvement in injured PNS tissue. Western blot analysis demonstrated that EPO was significantly increased in the PNS at the paralytic stage on day 14 post-immunization (PI); levels were significantly decreased at day 30 PI. EPO was identified in PNS-derived vascular endothelial cells, Schwann cells, and axons in normal control rats. Most inflammatory cells in EAN lesions were EPO immunopositive at day 14 PI. In addition, the intensity of EPO immunoreactivity in both Schwann and vascular endothelial cells was greater than that of normal controls at this stage; intensity declined at day 30 PI. These findings suggest that EPO is transiently upregulated in EAN lesions and that the EPO/EPO-receptor binding pathway is associated with neuroprotection in EAN-affected PNS tissues.

Increased phosphorylation of caveolin-1 in the sciatic nerves of Lewis rats with experimental autoimmune neuritis

The levels of phosphorylated caveolin-1 (p-caveolin-1) were analyzed in the sciatic nerves of Lewis rats with experimental autoimmune neuritis (EAN). Western blot analysis showed that the phosphorylation of caveolin-1 increased significantly in the sciatic nerves of EAN-affected rats at the paralytic stage of EAN on day 14 post-immunization (PI) ( P < 0.05) and declined slightly thereafter during the recovery stage. Immunohistochemistry showed intense p-caveolin-1 immunostaining in some inflammatory macrophages, as well as in T-cells in individual nerve fascicles at the peak stage of EAN, while p-caveolin-1 was weakly expressed in some of the vascular endothelial cells and Schwann cells of normal sciatic nerves. The inflammatory cells with intense p-caveolin-1 expression in the EAN-affected individual nerve fascicles were not positive for terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL), while the TUNEL-positive apoptotic cells in the perineurium, where infiltration initially occurred, were weakly positive for p-caveolin-1. Based on these findings, we postulate that caveolin-1 is phosphorylated in inflammatory cells soon after they infiltrate the sciatic nerve, as well as in the perineurium, and that p-caveolin-1 activates intracellular signaling in inflammatory cells, leading to cell death, which ultimately eliminates the infiltrating inflammatory cells from the sciatic nerves of animals with EAN.

Four Distinct Neurologic Syndromes in Marek's Disease: Effect of Viral Strain and Pathotype

A chronological study of central nervous system disorders induced by Marek's disease virus (MDV) has been conducted. Neurologic clinical signs were recorded daily for individual chickens of two genetic lines after inoculation of 13 serotype 1 MDV strains representing all three pathotypes. In addition to classical transient paralysis (TP) previously described by many workers, and acute TP, described in the companion paper, we have identified for the first time two other neurologic syndromes, persistent neurologic disease (PND) and late paralysis (LP). PND designates birds that showed a variety of neurologic signs (ataxia, torticollis, and nervous tics) after recovery from paralysis (12-15 days postin-oculation [DPI]) that either persisted through the observation period or presented a cyclic pattern. LP was a rare syndrome characterized by the late onset of the paralytic stage (about 20 DPI), perhaps indicating occasional failure of the initial intraabdominal inoculation to induce infection. Clinical signs and histopathologic alterations of the brain were also evaluated sequentially in chickens of two genetic lines after inoculation with two MDV strains (virulent MDV and very virulent plus MDV). Although clinical response differed greatly among treatment groups, types of lesions (endotheliosis, mononuclear perivascular cuffing, vasculitis, vacuolization, and increase in cellularity of the neuropil) were similar. However, early onset of lesions (by 6 days) appeared to be associated with a greater severity of clinical signs. We also found that neurologic response was greatly influenced by viral pathotype (virulence). This study thus confirms that the central nervous system is an important target organ for MDV resulting in several distinct clinical manifestations and suggests that neurologic responses in antibody-free chickens might be a useful criterion for virus pathotyping.

Serotonergic Neuronal Sprouting as a Potential Mechanism of Recovery in Multiple Sclerosis

Experimental allergic encephalomyelitis (EAE) is widely considered as an animal model of multiple sclerosis (MS). Damage to the bulbospinal serotonergic (5-HT) neurons occurs in the early paralytic stages of EAE in rats with the severity of neurologic signs corresponding to spinal serotonergic depletion. Neurologic recovery of EAE rats is associated with reestablish-ment of spinal 5-HT transmission possibly through sprouting of undamaged axons and nerve terminals. Damage to the bulbospinal serotonergic fibers also occurs in patients with MS (as reflected by reduced lumbar CSF 5-HIAA levels) and may contribute to several manifestations of the disease including autonomic dysregulation, sensory symptoms (i.e., paresthesias, pain) and motor symptoms (weakness, spasticity, clonus). Spinal serotonergic neuronal sprouting with regeneration of 5-HT nerve terminals may also occur in the early stages of MS and may be associated with spontaneous remission of MS symptoms following an acute relapse. Sprouting of serotonergic neurons may also explain the disparity in MS between the extent of demyelinating plaques and clinical signs of the disease. The chronic course of MS may be associated with progressive axonal degenerative changes with reduction of serotonergic nerve terminals and loss of their sprouting capability. It is proposed that the beneficial effects of treatment with AC pulsed electromagnetic fields on the symptoms and course of the disease in patients with chronic progressive MS may be related in part to renewed sprouting of serotonergic neurons.

GFAP mRNA fluctuates in synchrony with chronic relapsing EAE symptoms in SJL/J mice.

Activation of astrocytes and hypertrophy of their processes is a result of a number of pathological conditions in the central nervous system. Astrocytic gliosis is especially prominent in multiple sclerosis (MS), where astrocytic fibers form a dense matrix around demyelinated axons. Experimental allergic encephalomyelitis (EAE), a laboratory model for MS, is also accompanied by astrocytic hyperactivity. We have previously shown the formation of plaque-like structures which stain heavily for glial fibrillary acidic protein (GFAP) in the brains and spinal cords of SJL/J mice after several episodes of chronic relapsing EAE (Smith and Eng: J Neurosci Res 18:203, 1987). To further investigate the mechanisms of this phenomenon, we have measured the levels of mRNA for GFAP throughout the course of three episodes and recoveries of EAE in the SJL/J mouse. Mice were immunized with spinal cord homogenate and subsequently developed EAE. After recovery they were again immunized at appropriate intervals, resulting in successive episodes of EAE, with partial or complete recovery between the paralytic stages. At appropriate times in the course of the different stages of EAE, spinal cords were dissected and RNA was prepared from each spinal cord. RNA was analyzed by Northern blots to determine the levels of mRNA for GFAP and, as a control for the 70 kDa neurofilament (NF-L). With the onset of the first EAE episode GFAP mRNA in spinal cords from animals with mild symptoms increased to sixfold the control level (P < 0.02) and to 20-fold in those with paralysis (P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Studies on body sway of patients with unilateral peripheral vestibular disorder--with special reference to characteristic sway in various stages of spontaneous nystagmus

In order to investigate the influence of the status on body sway, 60 normal persons and 73 patients with unilateral peripheral vestibular disorder were examined by stabilometry. Results were analyzed, by signal processor 7T17 (NEC, SANEI), with respect to three basic components: extent, speed and direction of body sway.The affected side of the patient was decided by neurotological examinations and the status of the diseased labyrinth was diagnosed as or paralytic, by the direction of spontaneous nystagmus.From this investigation, the following results were obtained:1) The extent of body sway in patients with spontaneous nystagmus was greater than normal, and the speed of body sway towards the direction of spontaneous nystagmus was faster than that in the opposite direction.2) A characteristic difference in body sway between the patients showing irritative nystagmus and the patients showing paralytic nystagmus was observed in the direction component. In the irritative stage, divergence of body sway was observed and patients fluctuated to all directions. In contrast, patients in the paralytic stage fluctuated to the right and left sides, thus the characteristic sway in this stage was lateral.3) Patients without spontaneous nystagmus, in spite of showing labyrinthine preponderance by Contraves computerized rotary chair system, did not sway beyond the normal range. This discrepancy was thought to be caused by neurophysiological differences between the vestibuloocular reflex and the vestibulo-spinal reflex.

The presence of specific antigen-reactive cells during the induction, recovery, and resistance phases of experimental allergic encephalomyelitis

Experimental allergic encephalomyelitis (EAE) is an induced disorder in which an autoimmune response specific for myelin basic protein (BP) results in neural tissue destruction and acute paralysis. Lewis rats rapidly recover from induced paralysis and do not display any clinical manifestations of EAE following a second BP injection. The object of this study was to determine if immunologic recognition of encephalitogenic fragments of the BP molecule occurs during the induction, recovery, and resistance phases of EAE. Paralysis was induced in Lewis rats by a single injection of BP in complete Freund's adjuvant (CFA). The results indicate that macrophage migration inhibition in the presence of encephalitogenic BP fragments containing amino acid residues 43–88 and 68–88 is detectable during the paralytic stage of EAE, and also following recovery from clinical neurologic impairment. Although rats which had recovered were resistant to secondary BP-induced paralysis, macrophage migration inhibition in the presence of BP, or its encephalitogenic fragments, was detected after the second BP-CFA challenge. In order to assess humoral immunologic recognition, levels of serum antibody specific for the 43–88 BP fragment were determined. Specific antibody was not detected during the paralytic episode, but appeared upon recovery. Specific antibody was also detected following the secondary BP-CFA challenge. These data indicate that antigen-sensitive cells are present during the induction, recovery, and resistance phases of EAE in the Lewis rat. The mechanism which controls the activity of these cells in vivo has not been established.

Findings in the CSF of Patients with Meniere's Diseases

Cerebral Spinal Fluid (CSF) of 22 patients with Meniere's disease was examined regarding pressure, number of cells, protein, glucose, and IgA, G, M and E. Almost of all values were within normal limits.There were no differences of each mean value and SD between the irritative and paralytic stage and also between Meniere's diseases and labyrinth related syphilis. Regarding the osmolarity of CSF, 5 of 22 patients showed normal values.Other peripheral vestibular lesions (vestibular neuritis, inner ear vertigo due to unknown causes, Ramsey-Hunt's syndrome and Vogt-Koyanagi-Harada's disease) were considered to be due to viral infections and immunological disorders.Thus causes of Meniere's disease may not be revealed in the CSF, and the inner ear fluid should be examined.

Biochemical study of certain enzymes and metabolites of the carbohydrate metabolism in the skeletal muscle of the dengue virus-infected mice.

Changes in enzymes and metabolites of the carbohydrate metabolism in skeletal muscles were studied in mice after intracerebral inoculation of dengue type 2 virus. It was noted that lactic dehydrogenase, aldolase, phosphoglucoisomerase, phosphoglucomutase, GO-T and GP-T activity were enhanced initially by two- to three-fold, reaching a peak on day 5. As the illness appeared in mice, all the enzyme activities were lowered and were about three times less in the paralytic stage on the 8th day as compared to controls. Fructose-1,6-diphosphatase activity was increased on the 4th and 5th days but decreased later. Acid phosphatase increased abruptly from the 6th day while alkaline phosphatase activity was irregular. Creatine increased on the 4th and 5th days but diminished later. Glycogen decreased from the beginning and was lowest on the 5th day, but the levels increased later and were maximum in paralysed muscles. On the other hand, lactic acid began accumulating in the muscles and was maximum on the 5th day, then declined. Dengue virus was detected in the muscles from the 2nd day but higher titres were seen from the 6th day. Changes similar to the preparalytic stage of mice may occur in human beings, causing myalgia.

Optimal parameters of electrical defibrillation of the atria

A severe form of chronic intoxication was caused in guinea pigs by a single intracutaneous inoculation of triorthocresyl phosphate (TOCP); the intensity of acetate-2(14)C incorporation into the brain stem and spinal cord phospholipids and cholesterol was investigated in vivo. In paralytic stage of the disease incorporation of 14C into phospholipids and cholesterol was found to be markedly depressed; the inhibition of the synthesis of these lipids was observed not only in the most vulnerable lumbo-sacral region of the spinal cord, but also in the brain stem. This finding is in favour of the systemic character of lipid metabolism disorder in the central nervous system and indicates alteration of oligodendrocyte metabolism caused by TOCP.

Effect of triorthocresyl phosphate poisoning on intensity of incorporation of [2-14C]acetate into phospholipids and cholesterol of the guinea pig brain and spinal cord

A severe form of chronic triorthocresyl phosphate poisoning was induced in guinea pigs by a single intradermal injection of this compound and the intensity of incorporation of [2-14C]acetate into lipids of the spinal cord and brain stem was investigated in vivo. In the paralytic stage of the disease incorporation of the label into phospholipids and cholesterol was clearly reduced; inhibition of synthesis of these lipids was observed not only in the most vulnerable lumbosacral region of the spinal cord, but also in the brain stem, evidence of the systemic character of the disturbance of lipid metabolism in the CNS and of changes in the metabolism of the oligodendroglia.

Role of acetylcholine in organophosphate-induced release of adipokinetic hormone in the locust Schistocerca gregaria

The release of adipokinetic hormone at the paralytic stage of poisoning is probably a result of the excitant effects of insecticides on the central nervous system. When poisoned with organophosphorus compounds, the synaptic buildup of acetylcholine acts as a transmitter for the release of hormone. Muscarinic and nicotinic antagonists prevent organophosphate-induced release of this hormone.

Insecticide-induced release of hyperglycaemic and adipokinetic hormones of Schistocerca gregaria

Poisoning of adult Schistocerca gregaria leads to the release of the hyperglycaemic and adipokinetic factors from the corpus cardiacum. The mode of action appears to involve the liberation of hormones at the paralytic stage of poisoning in amounts greater than that released normally. Behavioural changes and disturbances in metabolism resulting from insecticide-induced hormone release possibly contribute to the eventual death of treated insects.

House Cricket Acetylcholinesterase: Histochemical Localization and in Situ Inhibition by O,O-Dimethyl S-Aryl Phosphorothioates1,2

The distribution of acetylcholinesterase (AChE) in the central nervous system of the house cricket, Acheta domesticus L., was investigated by histochemical localization. Abundant enzyme activity was evident in the head in the frontal ganglion, cerebrum, subesophageal ganglion, and optical lobes; and in the thorax in the ganglia and interganglionic connectives. AChE was concentrated in areas of complex synapses but was also present in the cell body region and in interganglionic connectives. The patterns of in situ inhibition of AChE by O,O -dimethyl S -aryl phosphorothioates were investigated. At the hyperactive state of poisoning AChE was reduced throughout the brain and in the peripheral areas of the thoracic ganglia and interganglionic connectives. In the paralytic stage, enzyme activity was still further decreased, and a few hours after knockdown, the enzyme activity had virtually disappeared. However, some spontaneous reactivation of AChE in dead animals was observed after 48 hours.

The Histopathology of Transient Paralysis of the Fowl

The histopathology of transient paralysis in the fowl is described. The basic lesion consisted of a vasculitis affecting the vessels of the brain, spinal cord and nerves, especially close to their spinal origins. During the acute paralytic stage there was extensive thickening of the vessel walls in the white matter of the cerebellar folia due to endothelial proliferation and mononuclear cell infiltration. Small cyst-like structures were occasionally seen in the walls of affected blood vessels. During the next 14 days following recovery from clinical symptoms the lesions regressed but lymphoid infiltration into a few randomly scattered blood vessels in the brain and spinal cord was pronounced between two and eleven weeks after recovery from clinical symptoms. On décrit l’histopathologie de cette paralysie transitoire chez la poule. La lésion de base consiste en une vasculite affectant les vaisseaux du cerveau, de la moelle épinière et des nerfs, principalement près de leurs origines spinales. Pendant le stade de paralysie aigüe il y avait un épaississement très grand des parois vasculaires dans la substance blanche des feuillets cérébelleux du à une prolifération endothéliale et une infiltration des mononucléaires. On voyait à l’occasion des structures ressemblant à des kystes dans les parois des vaisseaux affectés. Pendant les 14 jours qui suivaient la guérison des symptômes cliniques les lésions régressaient mais l’infiltration lymphoïde dans quelques vaisseaux sanguins répartis au hasard du ceveau et de la moelle épinière était encore prononcée de deux à sept semaines après guérison des symptômes cliniques. Beschreibung die Histopathologie der zeitweiligen Paralyse beim Geflügel. Die zugrundeliegende Erkrankung besteht in einer Entzündung, die Gehirngefässe, das Rückenmark und die Nerven befällt: von den letzteren besonders die, welche einen spinalen Ursprung haben. Während des akuten paralytischen Stadiums zeigte sich starke Verdickung der Gefässwände in der weissen Substanz der zerebellaren Folia infolge endothelialer Proliferation und Infiltration von mononuklearen Zellen. Gelegentlich fanden sich kleine zystenartige Strukturen in den Wänden der betroffenen Blutgefässe. In den zwei Wochen nach Abklingen der klinischen Symptome gingen diese Erscheinungen zurück aber nach zweienelf Wochen später fand sich ausgesprochene lymphoide Infiltration in manchen Gefässen des Gehirns und Rückenmarks. Se describe a continuación la histopatología de la parálisis transitoria de las aves de corral. La lesión fundamental consiste en una vasculitis que afecta a los vasos cerebrales, de la médula espinal y de los nervios, especialmente en los vasos cercanos a su origen espinal. Durante la fase aguda de parálisis se observó un engrosamiento extenso de la pared vascular en la substancia blanca de la hoja cerebelar debido a una proliferación endotelial y a una infiltración de células mononucleares. Ocasionalmente se vieron pequeñas estructuras de aspecto cistoideo en las paredes de los vasos afectados. Durante los siguientes 14 días después de la recuperación de los síntomas clínicos se observó una regresión de las lesiones aunque todavía permaneció una infiltración linfoide en unos cuantos vasos sanguíneos del cerebro y la médula, lesión que se mostró más pronunciada entre la segunda y undécima semana después de la recuperación de los síntomas clínicos.