Intrathecal immunoreactivity in people with or without previous infectious mononucleosis.

OBJECTIVES: The risk of developing multiple sclerosis (MS) increases (OR: 3.1) after infectious mononucleosis (IM). However, the nature of this link is obscure. We tested the hypothesis that IM might incur long-term sequelae, including low-key inflammatory activity, with characteristics of an MS endophenotype (or presymptomatic trait) and that assays of MS-relevant cyto-/chemokines in the cerebrospinal fluid (CSF) post-IM may show a trend in this direction. MATERIALS AND METHODS: We selected seven CSF cytokines (IL-1b, IL-6, YKL-40, TNF-alpha) or chemokines (IL-8, CCL2, IP-10), representing pro-inflammatory factors previously associated with MS. We assayed the CSF levels of these seven cyto-/chemokines in healthy individuals with a median follow-up time of 10 years after serologically confirmed IM (post-IM group, n = 22), and in healthy controls without a history of IM (n = 19). A group of MS patients (n = 23) were included as reference. RESULTS: The CSF levels of IP-10, YKL-40, and CCL-2 were higher in the post-IM group than in our IM unexposed controls (P = .021, .049, .028). Seven of seven cyto-/chemokine assays showed a trend in the predicted direction (P of binomial ratio = .008). However, this trend was non-significant in a multivariate test (P = .22). A power analysis indicated that similar studies including a larger cohort would be numerically realistic. CONCLUSIONS: These results do not reject the hypothesis that the established epidemiological association between IM and MS results from a stepwise inflammatory propagation from IM sequelae to an MS endophenotype (or presymptomatic trait) in a proportion of IM patients, pending confirmation with adequate power.

Neurological presentation of hemophagocytic lymphohistiocytosis.

Hemophagocytic lymphohistiocytosis (HLH) is an inflammatory disorder arising from defects in critical regulatory pathways responsible for termination of inflammatory response. We are presenting a case report of a 20-year-old male, admitted to the Department of Neurology because of left lower limb weakness and balance disturbances. After a few days of hospitalization, fever occurred. Laboratory tests revealed anemia, neutropenia, lymphopenia, and thrombocytopenia. The clinical course and laboratory tests results confirmed the diagnosis of HLH. In our opinion, the disorder in the presented case occurred due to severe chronic active Epstein-Barr virus infection syndrome. We are presenting the case of pure neurological onset of hemophagocytic lymphohistiocytosis in an adult patient. Hemophagocytic lymphohistiocytosis, initially presenting with neurological symptoms, can occur in adult patients with irrelevant family history. It is a life-threatening but potentially curable condition requiring proper diagnostic and treatment management.

Clinically severe Epstein-Barr virus encephalitis with mild cerebrospinal fluid abnormalities in an immunocompetent adolescent: a case report.

A 15-year-old boy developed Epstein-Barr virus (EBV) encephalitis, a rare complication of infectious mononucleosis. The severe clinical picture and the marked neuroimaging changes were in contrast with mild cerebrospinal fluid abnormalities: leukocyte count was normal and protein level was only slightly elevated. EBV DNA was detected in cerebrospinal fluid by polymerase chain reaction.

[Isolated palsy of the hypoglossal nerve complicating infectious mononucleosis]. / Paralysie isolée du nerf hypoglosse compliquant une mononucléose infectieuse.

INTRODUCTION: Neurological complications of infectious mononucleosis are rare. Various disorders have been described: meningitis, encephalitis, peripheral neuropathy. Isolated cranial nerve palsy has rarely been reported. OBSERVATION: A 16-year-old man was admitted for isolated and unilateral hypoglossal nerve palsy, four weeks after infectious mononucleosis. Cerebral MRI, cerebrospinal fluid study and electromyography were normal. IgM anti-VCA were positive. Two months later, without treatment, the tongue had almost fully recovered. CONCLUSION: To the best of our knowledge, only seven cases of isolated palsy of the hypoglossal nerve complicating infectious mononucleosis have been previously reported.

Epstein-Barr virus load in cerebrospinal fluid of patients with chronic active Epstein-Barr virus infection.

Chronic active Epstein-Barr virus (EBV) infection is a rare chronic mononucleosis syndrome involving clonally proliferating EBV-infected T-/NK-cells. EBV DNA was quantified in nonpleocytotic cerebrospinal fluid (CSF) of 9 patients. Three patients with neurologic and/or neuroimaging abnormalities showed high CSF copy numbers. In 1 patient, CSF copy number exceeded the peripheral blood value. CSF EBV-load may predict the central nervous system involvement of EBVT-/NK-cells.

Epstein-Barr virus acute encephalomyelitis in a 13-year-old boy.

The association of acute myelopathy and encephalopathy is reported in a 13-year-old boy. Signs and symptoms of infectious mononucleosis, presence of heterophile antibodies, anticapsid antibodies and Epstein-Barr virus DNA detected in cerebrospinal fluid, disclosed a primary or reactivated infection by Epstein-Barr virus. Outcome was rapid and benign with complete clinical recovery in 1 month, after pulse therapy with methylprednisolone. Epstein-Barr virus is a known agent related to acute disseminated encephalomyelitis, by immune mediated mechanisms. However, in this case, cortical involvement in magnetic resonance imaging, short time between infectious mononucleosis and central nervous system manifestations, and the presence of viral DNA in cerebrospinal fluid, raised the possibility of a direct action of the virus in central nervous system. Acute myelopathy associated to Epstein-Barr virus encephalitis has been rarely reported in children.

Valacyclovir treatment in Epstein-Barr virus subset chronic fatigue syndrome: thirty-six months follow-up.

BACKGROUND: We hypothesized that subset classification of Epstein-Barr virus (EBV) in chronic fatigue syndrome (CFS) is required. At first, a blinded-random placebo-controlled trial of valacyclovir in EBV CFS subset was performed (Group 1), and this EBV subset was followed for thirty-six months (Group 2). Patients were given valacyclovir at 14.3 mg/kg every 6 hours. The validated Energy Index (EI) point score assessing physical functional capacity, Holter monitor, multigated (radionuclide) MUGA rest/stress ventriculographic examination, EBV serum IgM viral capsid antibodies (VCA), and EBV early antigen diffuse (EA) were followed. After six-months, Group 1 CFS patients receiving valacyclovir experienced an increased mean least square EI point score +1.12 units (122 kcal/day), while the placebo cohort increased +0.42 EI units (65 kcal/day). EI point scores at Group 2 increased progressively. Sinus tachycardias decreased and abnormal cardiac wall motion improved. Serum antibody titers to EBV VCA IgM decreased. Patients resumed normal activities.

[Encephalitis after acute Epstein-Barr virus infection]. / Encefalitt etter akutt Epstein-Barr-virusinfeksjon.

BACKGROUND: Epstein-Barr virus (EBV) infection is known to cause severe neurological complications such as encephalitis. MATERIAL AND METHODS: We present the history of two men, aged 17 and 22, who developed encephalitis after acute primary EBV infection. One of them survived with cerebral complications, the other died. RESULTS: One of them had the classic presentation of infectious mononucleosis and EBV-specific findings in the cerebrospinal fluid. The other had neither signs of infectious mononucleosis nor specific findings in the cerebrospinal fluid such as EBV-PCR. Nevertheless, the clinical features of encephalitis were very similar. They were characterized by memory problems, personality changes, reduced consciousness, brainstem disorders and epileptic seizures. CT and MRI findings indicated involvement of basal ganglia and limbic structures. None of them responded to acyclovir. INTERPRETATION: We conclude that EBV infection can lead to severe cerebral complications without general symptoms of infectious mononucleosis and specific serologic findings in the cerebrospinal fluid.

[An acute meningo-encephalitis with a favourable prognosis and occasional severe electrical and clinical changes; infectious mononucleosis meningo-encephalitis (author's transl)]. / Une méningo-encéphalite aiguüe d'évolution favorable avec tableau électroclinique parfois gravissime: la méningo-encéphalite de la mononucléose infectieuse.

Four cases of severe meningo-encephalitis in patients with infectious mononucleosis (IMN) are reported. In three cases the clinical context suggested a mononucleosis. In the other case there was fever but only isolated neurological signs, which demonstrates the importance of serological diagnostic tests because of the benign prognosis of this affection. In fact, neurological complications of IMN are considered to be reversible even though deaths have occurred from respiratory failure, from polyradiculoneuritis, or bulbar involvement. In the cases reported, the onset of a deep coma with loss of reflexes and pauses in respiration required resuscitation therapy, which enabled vital functions to be restored and complete recovery to be obtained. Electro-encephalographic changes were marked by the severity of the initial changes in the tracings with very slow delta waves and prolonged electrical silences which were, however, reversible. The prognostic value of the EEG has to be stressed as improvement in the EEG always preceded clinical improvement.