EPSTEIN-BARR VIRUS AND GUILLAIN-BARRE SYNDROME

Five patients with Guillain-Barré (G.B.) syndrome, aged from 18 months to 27 years, had very high levels of antibodies to Epstein-Barr (E.B.) virus. All five had higher titres of E.B.-virus antibody than age-matched control groups. Two of the five patients had infectious mononucleosis (I.M.) but three had neither clinical nor laboratory evidence of this disease. These findings strongly suggest an association of E.B. virus with G.B. syndrome even without the signs of I.M.     

Videofluoroscopic evaluation of patients with Guillain-Barré syndrome

We reviewed 14 patients with clinically confirmed Guillain-Barré syndrome for swallowing dysfunction. All had swallowing dysfunction varying from mild to severe. Six patients (43%) had equivalent impairment during oral and pharyngeal phases. Seven patients (50%) had more severe functional abnormalities during the pharyngeal phase than during the oral phase. One patient (7%) had moderate disorder during the oral phase and mild disorder during the pharyngeal phase. Thirty-six percent of the patients had moderate-to-severe dysfunction during the oral phase, and 71% had moderate-to-severe dysfunction during the pharyngeal phase. In 5 patients who had multiple sequential examinations, moderate or severe swallowing disorders improved to mildto-moderate disorders within 4–8 weeks after the onset of the symptoms. Residual swallowing disorders may be seen in those who had severe swallowing dysfunction during the later phases of their disease. Further investigations are needed to determine if swallowing abnormalities persist after complete recovery from Guillain-Barré syndrome.     

ISOLATION OF CYTOMEGALOVIRUS FROM THE BLOOD LEUCOCYTES OF A PATIENT WITH POST-TRANSFUSION MONONUCLEOSIS

Cytomegaloviæmia was demonstrated in an adult female patient who was suffering an episode of post-transfusion mononucleosis, as a consequence of the administration of a large volume of fresh blood. The primary nature of this infection was confirmed by demonstration of a complement-fixing antibody rise during the course of the illness to a final titre of 1 : 512. The virus was isolated from unpurified blood leucocytes, and again one week later from purified blood lymphocytes. Although a newly acquired infection with cytomegalovirus (CMV) has been demonstrated in this case, its ætiological role cannot be confidently assessed. The likely source of the virus is regarded as being one or more of the blood donors, and the possibility of a primary infection or a reactivation of a latent infection has been considered. Antibody titrations were carried out on eight sets of stored sera from patients with post-transfusion mononucleosis. Four of these showed a significant rise in antibody titre and only one set gave negative results. These results are consistent with the CMV infection having occurred in seven of these patients at the time of their episode of pest-transfusion mononucleosis. The suggestion is made that a revision of the criteria for the utilization of fresh blood for certain groups of patients may become necessary.     

Guillain-barré syndrome and tularemia pleuritis with high adenosine deaminase activity in pleural fluid

Summary A 56-year-old man suffered from prolonged fever, sore throat and cough, followed by pleural effusion and reversible progressive ascending muscle weakness. The condition fulfilled the diagnostic criteria of Guillain-Barré syndrome. Tuberculosis was initially suspected because of lymphocyte predominance and high adenosine deaminase activity in the pleural fluid. Later, an agglutination titer of 10,240 toFrancisella tularensis antigen was found and an infected hare exposure could be identified. Thus, the activity of adenosine deaminase may be high also in tularemia pleuritis.

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Guillain-Barré-Syndrom und Pleuritis mit hoher Adenosindesaminaseaktivität in der Pleuraflüssigkeit bei Tularämie

Zusammenfassung Ein 56 Jahre alter Mann litt an langanhaltenden Fieberzuständen, Halsschmerzen und Husten; in der Folge trat ein Pleuraexsudat auf und es entwickelte sich eine zunehmende aufsteigende Muskelschwäche, die sich als reversibel erwies. Der Zustand erfüllt die diagnostischen Kriterien für ein Guillain-Barré-Syndrom. Anfangs bestand Verdacht auf Tuberkulose, da sich in der Pleuraflüssigkeit vorwiegend Lymphozyten und eine hohe Adenosindesaminaseaktivität fanden. Später wurde ein Agglutinationstiter gegenFrancisella tularensis-Antigen von 10 240 entdeckt und Kontakt mit einem infizierten Hasen festgestellt. Hohe Adenosindesaminaseaktivität ist folglich auch bei der Tularämie-Pleuritis zu finden.

     

Fatal Autonomic Dysfunction Due to Guillain-Barré Syndrome After Cardiac Surgery

Guillain-Barré syndrome, a rare peripheral neuropathy, appears to occur more often in patients who have recently undergone surgery than in the general population. However, the pathophysiologic relationship between surgery and Guillain-Barré syndrome is elusive. Few cases of Guillain-Barré syndrome after cardiac surgery have been reported. Autonomic dysfunction, a serious complication of Guillain-Barré syndrome, has not been previously reported after cardiac surgery.We describe the case of a 71-year-old woman in whom the acute motor axonal neuropathic subtype of Guillain-Barré syndrome developed after mitral valve replacement. Despite plasmapheresis and intravenous immunoglobulin therapy, she died of complications from severe autonomic dysfunction 25 days postoperatively. Recognizing the potential cardiovascular involvement of Guillain-Barré syndrome is important, because patients who undergo cardiac surgery can be vulnerable to autonomic dysfunction in the early postoperative period.     

Guillain-Barré syndrome in two patients with respiratory failure and a review of the Japanese literature

We described two patients with Guillain-Barré syndrome and respiratory failure with or without mechanical ventilation. Case 1 was a 44-year-old man who treated as pneumonia under mechanical ventilation for a month and transferred to our hospital with unsuccessful weaning trials because of phrenic nerve palsy. Case 2 was a 74-year-old man who presented with aspiration pneumonia because of bulbar palsy. The present two cases with review of the Japanese literature showed that antecedent infection with initial symptoms within the most recent 5 to 46 days is a clinical clue to the diagnosis even in patients with Guillain-Barré syndrome accompanied by respiratory failure.KEY WORDS : Guillain-Barré syndrome, respiratory failure, antecedent infection, initial symptoms     

Hepatitis in fatal infectious mononucleosis

A detailed clinicopathologic analysis of 30 patients with sporadic fatal infectious mononucleosis and 31 males with fatal infectious mononucleosis and the X-linked lymphoproliferative syndrome was performed to determine the extent of hepatic dysfunction in these cases. At death, the median age of patients with sporadic infectious mononucleosis was 10.7 yr vs. 2.4 yr for X-linked lymphoproliferative syndrome. The median survival time was 8 wk for sporadic infectious mononucleosis and only 4 wk for X-linked lymphoproliferative syndrome. The male to female ratio was 3:2 in sporadic infectious mononucleosis; all patients with X-linked lymphoproliferative syndrome were males. Fever, sore throat, lymphadenopathy, hepatomegaly, and splenomegaly were prominent findings. Hepatic dysfunction was uniformly present and caused death in 13 of 30 sporadic infectious mononucleosis cases and 18 of 31 X-linked lymphoproliferative syndrome cases. Diagnosis of infectious mononucleosis was confirmed by heterophile antibody titers or Monospot, Epstein-Barr virus antibody studies, viral culture, molecular hybridization studies, clinical and histologic findings, and pedigree analysis.     

GLUCOCORTICOID DEFICIENCY WITH ACHALASIA OF THE CARDIA AND LACK OF LACRIMATION

Four recent reports describe a multisystem disorder in which ACTH insensitivity is associated with achalasia and alacrima. We report studies on a male patient with this rare triad. The patient had alacrima from birth; isolated glucocorticoid deficiency had been diagnosed at 3.5 years of age and achalasia at age 6. The possibility that this syndrome could be due to a parasympathetic degeneration has already been proposed; the cause of the glucocorticoid deficiency, however, remains unclear. Parasympathetic function in other areas was investigated to determine whether there might be a more generalized abnormality. Specific cardiac tests of parasympathetic function showed that parasympathetic input to the heart was affected in the patient, while the same tests in an Addisonian child were normal. We show, then, a hitherto undetected parasympathetic abnormality in a patient with this syndrome, suggesting a generalized disturbance of this system. On this basis we may hypothesize that the glucocorticoid failure may be a consequence of the loss of parasympathetic input to the adrenal gland, although this remains to be demonstrated experimentally.     

Mononucleosis syndrome and acute monocytic leukemia

The association of infectious mononucleosis and an immunocompromised host such as occurs in acute leukemia is reported. The most common cause of infectious mononucleosis is Epstein-Barr virus (EBV) and cytomegalovirus (CMV). Patients with mononucleosis syndrome caused by other agents are rare. We report a case of acute monocytic leukemia (AMoL) who developed varicella zoster virus (VZV) mononucleosis syndrome in the bone marrow recovery phase after myelosuppression due to high-dose cytarabine. Mononuclear leukocytes appearing during the mononucleosis syndrome were very similar to the initial leukemic cells. Varicella zoster virus mononucleosis syndrome was confirmed by delayed herpes zoster rash with dermatomal distribution.     

Serum levels of lymphokines and soluble cellular receptors in primary Epstein-Barr virus infection and in patients with chronic fatigue syndrome.

The immunopathology in primary Epstein-Barr virus (EBV) infections and in chronic fatigue syndrome was studied by examining serum levels of interleukins (IL) and of soluble T cell receptors in serum samples. Serum samples were from patients during and 6 months after primary EBV-induced infectious mononucleosis and from patients with chronic fatigue syndrome and serologic evidence of EBV reactivation. Markers for T lymphocyte activation (soluble IL-2 and CD8) and for monocyte activation (neopterin) were significantly elevated during acute infectious mononucleosis but not in patients with chronic fatigue syndrome. Interferon-alpha, IL-1 beta, and IL-6 levels were not significantly increased in any patient group but inferferon-gamma levels were significantly increased during the acute phase of infectious mononucleosis. The levels of IL-1 alpha were significantly higher than in controls both in patients with infectious mononucleosis and in those with chronic fatigue syndrome. In the latter, the lack of most markers for lymphocyte activation found in patients with infectious mononucleosis makes it less likely that EBV reactivation causes symptoms.     

THE INVOLVEMENT OF THE PENTOSE SHUNT IN THYROID METABOLISM AFTER STIMULATION WITH TSH OR WITH IMMUNOGLOBULINS FROM PATIENTS WITH THYROID DISEASE. 1. THE GENERATION OF NADPH IN RELATION TO STIMULATION OF THYROID GROWTH

It has been shown previously that both thyrotrophin (TSH), and also immunoglobulins (Ig) derived from patients with goitrous Graves’disease, stimulate DNA-synthesis in guinea-pig thyroid tissue maintained in vitro. Here we describe the use of the same in vitro system and methods of quantitative cytochemistry to test the effect of these substances on the generation of NADPH, which is another indicator of the potential for growth. As could be predicted by its trophic action, TSH stimulated the generation of NADPH by glucose 6-phosphate dehydrogenase. The Ig-fraction from normal subjects depressed this activity. The Ig-fraction from Graves’disease patients with goitres stimulated the generation of NADPH, whereas the Ig from patients with Graves’disease but with minimal enlargement of the thyroid gland behaved like normal Ig. A similar lack of stimulation was found with Ig from patients with Pendred's syndrome, other dyshormonogenetic goitres, and autonomous single adenomas. In all specimens tested, there was good correlation between the amount of DNA-synthesis, measured by Feulgen cytophotometry, and the activity of glucose 6-phosphate dehydrogenase activity that generated NADPH. These results support the concept that there is a distinct type of autoantibody that influences thyroid growth.     

EXPERIENCE WITH TRILOSTANE IN THE TREATMENT OF CUSHING'S SYNDROME

Five patients with pituitary dependent Cushing's syndrome and two with adrenal carcinoma were treated with increasing doses of trilostane (up to 1440 mg daily). There was no consistent fall in serum cortisol levels. In addition there was no rise in the levels of precursors immediately preceding the proposed site of action of trilostane. These results suggest that trilostane does not effectively block the enzyme 3β-hydroxysteroid dehydrogenase Δ4,Δ5 isomerase in patients with Cushing's syndrome and that it should no longer be recommended for their treatment.     

THE SIGNIFICANCE OF ELEVATED LEVELS OF GASTRIN IN PATIENTS WITH PITUITARY ADENOMA

Six patients were studied with pituitary adenomas and elevated concentrations of gastrin similar to those found in cases of benign antral gastrinoma syndrome. Chromatography of the serum using Sephadex-G50 revealed different molecular forms of gastrin according to the type of adenomas. In those cases of acromegaly and gonadotrophinoma, gastrin-34 and unsulphated gastrins constitute the predominant forms. In contrast, in cases of Cushing's disease, gastrin-17, sulphated as well as non-sulphated were the predominant types; the chromatographic pattern was similar to that observed in two patients with antral gastrinoma syndrome who acted as controls. These findings demonstrate that pituitary adenomas might secrete gastrin. Taking into account that gastrin-34 and unsulphated gastrins were the predominant forms in cases of acromegaly, gonadotrophinoma and non-functioning adenoma, it is assumed that those molecular forms are mainly produced in the anterior lobe of the hypophysis. Conversely, gastrin-17 was the principal molecular form in cases of Cushing's disease confirming the close relationship of the synthesis of gastrin and corticotrophin peptides. The cases with Cushing's disease exhibited a serum gastrin pattern similar to that observed in the two cases with antral syndrome in which the predominant immunoreactive form of gastrin in gastrin-17 exhibiting a degree of sulphation corresponding to that of antral gastrin. It is concluded that the circulating excess of gastrin originated in the pituitary tumour tissue and the molecular form varied with the type of pituitary adenoma.     

A rare clinical presentation of Ebstein-Barr virus

In this letter we report a case of Guillain-Barré syndrome associated with infectious mononucleosis. A 20-year-old woman presented to our hospital with weakness of legs and arms. She had felt weakness in her legs for three days and in arms for one day. She had one week history of pharyingitis, muscle pain, and fever. Serological data confirmed infectious mononucleosis. Electrophysiological findings and cerebrospinal fluid examinations confirmed Guillain-Barré syndrome. She was treated with immunoglobulin, methylprednisolone and acyclovir. Paresis improved five days after the end of immunoglobulin therapy. Ebstein-Barr virus infection and infectious mononucleosis must be considered among patients with Guillain-Barré syndrome.     

POST-TRANSFUSION MONONUCLEOSIS

Thirty-two patients with circulating atypical mononuclear cells appearing after blood transfusions are described. The term “post-transfusion mononucleosis” is introduced to describe this finding. In all but one of these cases, the transfused blood was known to have been freshly donated before the transfusion. Serial blood films from most of these patients have been reviewed, and the atypical mononuclear cells are described. They resemble the transformed lymphocytes which develop in tissue culture from small lymphocytes under the influence of phytohæmagglutinin. Splenomegaly, fever and lymphocytosis are common features of post-transfusion mononucleosis, but the neutrophil count has usually been normal or reduced. Eosinophilia, lymphadenopatny and anæmia have rarely been found. Elevated titres of sheep cell agglutinin have been found in several cases, but in only one case did the type of agglutinin constitute a positive Paul Bunnell test. Post-transfusion mononucleosis may mimic infectious mononucleosis and acute or subacute bacterial endocarditis, and the criteria for the differentiation of these diseases are discussed. The ætiology of the syndrome is unknown, and the hypothesis is made that it may be a graft rejection response directed against viable transfused foreign lymphocytes contained in freshly donated blood.     

Hépatite E aiguë associée à un syndrome de Guillain-Barré chez un patient immunocompétent

Introduction

Hepatitis E virus (HEV) infection is now recognized to be an emerging autochthonous disease in several countries. There have been several reports of neurological manifestations associated with HEV infections. Immunocompromised patients seem to be particularly vulnerable.

Case report

We report a 73-year-old man who presented with an acute polyradiculopathy and an acute hepatitis. HEV RNA was positive in serum and cerebrospinal fluid. Serum antiganglioside antibodies were also detected. Liver function tests returned to normal rapidly and HEV RNA was undetectable 4 weeks after initial testing. The neurological features improved gradually with the use of intravenous immunoglobulins.

Conclusion

We report a case of Guillain-Barré syndrome related to acute hepatitis E in an immunocompetent patient. The outcome was favorable after intravenous immunoglobulins administration. HEV screening should be systematic in patients who present with an acute polyradiculopathy and abnormal liver function tests.     

Persistent transfusion-associated infectious mononucleosis with transient acquired immunodeficiency

Trauma and blood transfusion led to profound, persistent infectious mononucleosis in a 21 year old man. Splenectomy and trauma had apparently produced transient immune deficiency which was complicated by osteomyelitis of a fractured tibia. The transfused blood probably contained Epstein-Barr virus (EBV). Infectious mononucleosis had ensued 25 days after a blood transfusion was given, antibodies to EBV appeared in his serum, and the infectious mononucleosis persisted for nearly two years. His immunity returned gradually to normal, but because of nonunion of the fracture site, which was infected by Staphylococcus aureus, above-knee amputation was required. The acquired, transient immune deficiency to EBV and profound infectious mononucleosis seen in this patient is analogous to inherited, permanent immune deficiency to this virus in the X-linked lymphoproliferative syndrome.     

RUPTURE OF THE SPLEEN IN INFECTIOUS MONONUCLEOSIS: A CLINICOPATHOLOGIC REPORT OF SEVEN CASES

1. Seven cases of ruptured spleen as a complication of infectious mononucleosisare described and reference made to the 3 cases previously recorded in the literature.

2. It proved possible to make an objective histologic diagnosis of infectiousmononucleosis from well prepared sections of the spleens. The diagnosis wasbased on: (a) a blurred architectural pattern due chiefly to large numbers of atypical lymphocytes diffused throughout the pulp and clumped in the blood sinuses;(b) small, poorly defined follicles, usually without germinal centers, in less thanusual numbers per unit area; (c) cellular "infiltrates," composed largely of normaland atypical lymphocytes, in the capsule and trabeculae, in the adventitia ofsmall intratrabecular arteries, and in the subintimal zone of collecting venoussinuses and intratrabecular veins; (d) swelling of the lining or attached cells ofthe blood sinuses.

3. "Infiltration" of the capsule and trabeculae reached considerable proportions, occasionally to the point of complete dissolution of these structures, andserved as a predisposing cause of rupture. The same changes were noted in intactspleens from fatal cases of infectious mononucleosis.

4. The spleen in infectious mononucleosis was 3 to 4 times normal size andruptured during the third or fourth week of the disease.

5. The importance of trivial injury as the exciting cause of so-called "spontaneous" rupture of the spleen has been emphasized. It is recommended thatextreme caution be employed during attempted palpation of the spleen in a suspected case of the disease. When the diagnosis is obvious, splenic palpation maywell be omitted.

     

THE INDUCTION OF AN EROSIVE ARTHROPATHY IN THE GUINEA PIG WITH COPPER II BISGLYCINATE AND ITS TREATMENT WITH ANTIRHEUMATIC DRUGS

Single intra-articular injections of copper II bisglycinate[Cu(II)gly] (30–300µg) into guinea-pig knee jointsinduce progressive joint degradation which first appears afterabout 2 weeks and peaks about 12 weeks after injection. Thestable complex, copper II bishistidinate (300µg) was withouteffect. The Cu(II)gly induced syndrome has features more incommon with osteoarthritis than rheumatoid arthritis in thaterosion occurs in the absence of persistent synovial inflammation.The possibility that the damage may be caused by Cu(II)gly inducingfree radical formation within the joint, leading to a self-perpetuatingchain reaction is discussed. D-Penicillamine and other drugswere tested for their effects on the histological changes induced4 weeks after the intra-articular injections of 100 µgCu(II)gly. Few significant effects were observed and these wererestricted to D-penicillamine, which caused inconsistent protection,sodium aurothiomalate which protected at a dose causing weightloss and prednisolone which exacerbated joint damage. It isconcluded that the variability of the control response willneed to be reduced before the model can be used for routinedrug evaluation but it may be of value in the study of chronicdegradative joint disease. KEY WORDS: Copper, Disease model, Rheumatoid arthritis, Penicillamine     

Epstein-Barr virus infections in males with the X-linked lymphoproliferative syndrome

A registry of persons with the X-linked lymphoproliferative syndrome, which is characterized by marked susceptibility to diseases induced by the Epstein-Barr virus, has enrolled 161 patients within 44 kindreds. Fifty-seven percent of the males died of infectious mononucleosis, 29% developed acquired hypogammaglobulinemia, and 24% had malignant lymphoma. The mortality rate was 80%; 70% died by 10 years of age and 100% by 40 years. Thirty-two boys survive, most with malignant lymphoma, acquired hypogammaglobulinemia, or both. We hypothesized that the defective lymphoproliferative control locus on the X chromosome results in unregulated cytotoxic lymphocytic responses to the Epstein-Barr virus; hence, severe hepatitis and virus-associated hemophagocytic syndrome occur with the infectious mononucleosis phenotype. T-cell suppression of immunoglobulin secretion by B cells is responsible for acquired hypogammaglobulinemia. A sustained polyclonal B-cell proliferation probably converts to a monoclonal B-cell malignancy as a result of molecular alterations.