|
Topical Treatment for
Arthritis.
Keller, B.C.
Clinical Study 2002 (unpublished).
Activity of pleconaril
against enteroviruses.
Pevear DC, Tull TM, Seipel ME, Groarke JM. ViroPharma
Incorporated, Exton, Pennsylvania 19341, USA.
dpevear@viropharma.com
Antimicrob Agents Chemother 1999 Sep;43(9):2109-15
The activity of pleconaril in cell culture against
prototypic enterovirus strains and 215 clinical isolates of
the most commonly isolated enterovirus serotypes was
examined. The latter viruses were isolated by the Centers
for Disease Control and Prevention during the 1970s and
1980s from clinically ill subjects. Pleconaril at a
concentration of </=0.03 microM inhibited the
replication of 50% of all clinical isolates tested. Ninety
percent of the isolates were inhibited at a drug
concentration of </=0.18 microM. The most sensitive
serotype, echovirus serotype 11, was also the most
prevalent enterovirus in the United States from 1970 to
1983. Pleconaril was further tested for oral activity in
three animal models of lethal enterovirus infection:
coxsackievirus serotype A9 infection in suckling mice,
coxsackievirus serotype A21 strain Kenny infection in
weanling mice, and coxsackievirus serotype B3 strain M
infection in adult mice. Treatment with pleconaril
increased the survival rate in all three models for both
prophylactic and therapeutic dosing regimens. Moreover,
pleconaril dramatically reduced virus levels in target
tissues of coxsackievirus serotype B3 strain M-infected
animals. Pleconaril represents a promising new drug
candidate for potential use in the treatment of human
enteroviral infections.
SUGGESTED
READING
Herpes simplex virus type
2: unique biological properties include neoplastic
potential mediated by the PK domain of the large subunit of
ribonucleotide reductase.
Aurelian L Department of Biochemistry, The Johns Hopkins
School of Public Health, 615 North Wolfe Street, Baltimore,
MD 21205, USA.
Front Biosci 1998 Feb 15;3:D237-49
The prevalence of herpes simplex virus type 2 (HSV-2)
infections in the US has increased approximately 30%. Like
HSV-1, which causes facial lesions, HSV-2 causes
symptomatic lesions (at genital sites) and establishes
latent infections of the sensory ganglia. However, the two
viruses are biologically distinct, suggesting that they
possess unique functions which are mediated by different
viral genes. Unlike HSV-1, HSV-2 is a tumor virus. It
causes neoplastic transformation of cultured human cells
and tumors in animals. The oncogene is at the 5'-terminal
of a chimeric gene that also codes for the large subunit of
viral ribonucleotide reductase (RR1). It was captured from
the cell and it codes for a novel growth factor receptor
serine-threonine protein kinase (PK) the minimal genetic
information of which can adapt to a relatively wide
functional diversity due to the flexibile use of additional
and alternate catalytic sites and protein interaction
motifs which are organized in an efficient, almost
superimposed fashion. By contrast to other growth factor
receptor serine-threonine kinases studied so far, the HSV-2
oncoprotein (RR1 PK) activates the RAS signaling pathway,
thereby providing a biological bridge to the tyrosine
growth factor receptor kinases. Expression of the oncogene
is required for neoplastic transformation and tumor growth
in vivo is inhibited by antisense inhibition of oncogene
expression. The virus conserved the captured oncogene
because it provides a biological advantage for its
survival. In cultured cells, RR1 PK is required for viral
IE gene transcription. In vivo, RR1 PK is likely to be
involved in latency reactivation.
Outbreaks of aseptic
meningitis associated with echoviruses 9 and 30 and
preliminary surveillance reports on enterovirus
activity--United States, 2003.
Centers for Disease Control and Prevention (CDC).
MMWR Morb Mortal Wkly Rep. 2003 Aug 15;52(32):761-4.
Aseptic or viral meningitis is the most common type of
meningitis and is associated with an estimated
26,000--42,000 hospitalizations each year in the United
States. Enteroviruses are the most common cause of aseptic
meningitis. Echovirus 9 (E9) and echovirus 30 (E30) have
been associated frequently with outbreaks of aseptic
meningitis. During March 2003, several state public health
departments noted increased reports of aseptic meningitis
and, as of August 7, seven states (Arizona, California,
Georgia, Idaho, Oregon, South Carolina, and Texas) had
reported outbreaks associated with either E9 or E30. This
report summarizes the epidemiologic features of the aseptic
meningitis outbreaks in five states (Arizona, California,
Georgia, Idaho, and South Carolina) and provides an
overview of enterovirus activity in the United States
during January 1--August 7. Enteroviruses, E9 and E30 in
particular, should be considered in the differential
diagnosis of persons with aseptic meningitis.
[Herpetic meningitis in
the child] [Article in French]
Dupuis C, Despert V, Vigneron P. Departement de medecine
de l'enfant et de l'adolescent, hopital Sud, CHU de Rennes,
16, boulevard de Bulgarie, BP 56129, 35056 Rennes,
France.
Arch Pediatr. 2002 Nov;9(11):1153-5.
In children, viral meningitis is usually caused by
Enteroviruses. Herpes simplex viruses (HSV) are known to be
a cause of meningo-encephalitis. HSV-2 has been reported to
cause recurrent meningitis (Mollaret's meningitis) in
adults.
CASE REPORT: We report the case of a three-year-old girl
with HSV-1 meningitis, whose evolution with treatment by
aciclovir was good.
CONCLUSION: HSV-1 has rarely been reported as a cause of
isolated aseptic meningitis in children. Primary phase of
herpes simplex virus infection is not usually associated
with neurologic complications.
Epstein-Barr virus
infections of the central nervous system.
Fujimoto H, Asaoka K, Imaizumi T, Ayabe M, Shoji H, Kaji
M. First Department of Internal Medicine, Kurume University
School of Medicine, Kurume 830-0011.
Intern Med. 2003 Jan;42(1):33-40.
OBJECTIVE: Epstein-Barr virus (EBV), a lymphotropic
herpes virus causing infectious mononucleosis (IM), also
causes various central nervous system (CNS) infections. In
the present study, EBV CNS infections were
investigated.
PATIENTS AND METHODS: For adult inpatients in our
hospital and related hospitals between 1984-2002, CNS
syndromes with IM symptoms were examined, and serologic
positives were assessed according to established criteria.
Polymerase chain reaction (PCR) was performed for
cerebrospinal fluid (CSF) from seven patients.
RESULTS: Ten patients with EBV-related CNS infections
were found; their mean age was 36 years (20-79 years). The
neurologic forms were as follows: acute encephalitis (4
patients), acute cerebellar ataxia (1), acute disseminated
encephalomyelitis (ADEM) (2), myelitis (1), and meningitis
(2). The PCR from CSF was positive in two patients with
meningitis, one patient with ADEM, and one patient with
encephalitis-associated chronic EVB infection. One case of
encephalitis and another of relapsing ADEM were attributed
to chronic EBV infection.
CONCLUSION: Our study identified a variety of
EBV-related CNS infections. EBV CNS infections are divided
into two groups: 1) CNS syndromes associated with primary
EBV or reactivated infection, and 2) those associated with
chronic EBV infection; it is notable that in the former,
diverse CNS syndromes including ADEM can occur, whereas in
the latter, chronic or recurrent CNS syndromes are
produced.
Optic neuritis
complicating west nile virus meningitis in a young
adult.
Gilad R, Lampl Y, Sadeh M, Paul M, Dan M. Dept of
Neurology, Wolfson Medical Center, Holon, Israel.
Infection. 2003 Jan;31(1):55-6.
A case of West Nile virus (WNV) infection with
meningitis and optic neuritis in a 28-year-old man is
presented. The patient had a number of unusual clinical and
laboratory findings that broadened the differential
diagnosis. The emergence of WNV infection in southern
Europe and North America calls for increased awareness of
physicians to this clinical entity.
Mollaret's meningitis: a
case with increased circulating natural killer
cells.
Goldstein R, Guberman A, Izaguirre CA, Karsh J
Ann Neurol 1986 Sep;20(3):359-61
A patient with longstanding Mollaret's meningitis had an
increased number of circulating natural killer cells during
an acute attack, as evidenced by 73% large granular
lymphocytes and 80% Leu-11a-positive peripheral mononuclear
cells. Numbers of large granular lymphocytes and
Leu-11a-positive cells returned to normal by three months
after the attack. Similarity of the morphological features
of the Mollaret's cell to those of large granular
lymphocytes is noted.
Mollaret's meningitis
associated with acute Epstein-Barr virus
mononucleosis.
Graman PS
Department of Medicine, University of Rochester, School
of Medicine and Dentistry, NY 14642.
Arch Neurol 1987 Nov;44(11):1204-5
A 19-year-old man developed recurrent aseptic meningitis
(Mollaret's meningitis) during the course of acute
Epstein-Barr virus infectious mononucleosis. Serum
contained heterophil antibody and Epstein-Barr
virus-specific antibodies characteristic of acute
infection. Seven brief episodes of aseptic meningitis were
documented over the following one-year period, in each case
with a polymorphonuclear pleocytosis in the cerebrospinal
fluid. Acute infection with Epstein-Barr virus, or
subsequent reactivation of virus, may account for some
cases of Mollaret's meningitis.
Recurrent herpes
simplex virus type 2 meningitis: a case report of
Mollaret's meningitis.
Kojima Y, Hashiguchi H, Hashimoto T, Tsuji S, Shoji H,
Kazuyama Y. Department of Neurology, University of
Occupational and Environmental Health, School of Medicine,
Kitakyushu 870-8555, Japan.
Jpn J Infect Dis. 2002 Jun;55(3):85-8.
It is well known that herpes simplex virus (HSV) type 2
produces acute meningitis, while HSV type 2 rarely causes
recurrent meningitis (Mollaret's meningitis). We report the
history of a 40-year-old patient with recurrent HSV type 2
meningitis (Mollaret's meningitis). The patient had seven
episodes of meningeal symptoms within a 7-year period. In
the seventh episode, HSV type 2 DNA was confirmed by nested
polymerase chain reaction (PCR) with the cerebrospinal
fluid (CSF). A real-time quantitative PCR study of the
first CSF sample detected 2,000 copies of the HSV genome,
which rapidly disappeared following treatment with
acyclovir. The present case may be the first case of HSV
type 2 Mollaret's meningitis to be documented in Japan. In
our case, HSV serum antibody titers were at low levels
during the whole course of the disease. The possible
pathophysiology of this case is discussed.
Mollaret's meningitis:
a case report and literature review.
Lee CT, Chao CH, Yu KW, Liu CY
Department of Medicine, National Defense Medical Center,
Taipei, Taiwan, R.O.C.
Chung Hua I Hsueh Tsa Chih (Taipei) 1992
Apr;49(4):289-93
Mollaret's meningitis is a rare syndrome with
characteristic features. We present a case with interesting
clinical course and cerebrospinal fluid studies. The
patient was admitted to Veterans General Hospital-Taipei 6
times between May, 1984 and May, 1991 because of recurrent
meningitis (Mollaret's meningitis). No causative etiology
was identified although a series of investigations were
performed, including studies of the blood and CSF,
roentgenogram and nuclear scintinographs. To date, there
has been no standard therapeutic modality for this disease.
We use aspirin for his symptomatic control with
satisfactory result though colchicine has been reported as
being effective also.
Mollaret's meningitis:
an unusual disease with a characteristic
presentation.
Mascia RA, Smith CW Jr
Am J Med Sci 1984 Jan-Feb;287(1):52-3
Mollaret's meningitis (benign recurrent aseptic
meningitis) is a rare syndrome with characteristic
features. Patients present with recurrent attacks of
meningismus which are sudden in onset and last from one to
seven days. During the attacks the spinal fluid shows
pleocytosis with lymphocyte predominance. Large endothelial
cells with indistinct cytoplasm (Mollaret's cells) are
typically present in the CSF. The attacks resolve
spontaneously and without sequellae. Symptom-free intervals
can be as brief as a few days or as long as several years.
Though specific treatment is not available, Colchicine has
been reported to decrease the severity and frequency of
attacks. While acute episodes may cause significant
symptoms, the long-term prognosis is excellent.
[Lactoferrin and its
role in the pathogenesis of tick-borne
encephalitis] [Article in Russian]
Merzeniuk ZA, Lykova OF, Konysheva TV.
Klin Lab Diagn. 2003 Apr;(4):18-9.
The content of lactoferrin (LF) was studied in the
liquor and blood of patients with tick-borne encephalitis
(TBE) of the meningeal and focal types; additionally, the
information density of the discussed parameter was assessed
for evaluating the severity and degree of the inflammation
process in the central nervous system (CNS). The LF level
was determined in liquor of 37 samples obtained from TBE
patients (main group) and of 10 persons with
osteochondrosis (controls); it was also determined in the
serum taken from 21 TBE patients and from 40 healthy donors
by using the immune-enzyme analysis. The LF concentration
in TBE patients was found to exceed the normal value by
1.5-3 times during the whole observation period. As for the
liquor, it was high, by the onset of the disease, by more
than 20 times, however, after the 7th day it was higher
6-fold. A direct dependence of a concentration of the
studied protein on a form and severity of the disease was
established. The LF level in the liquor of TBE patients
alongside with clinical signs can be an objective indicator
of a severity and activity of the inflammation process in
the CNS; it can also be a criteria of how much the
conducted therapy effective is.
Case reports of viral
meningitis/encephalitis.
Norwood C, Naponick JJ, Burton S, Varoqua S, Morris J,
Kuizon D. Louisiana State University Family Medicine
Residency, Alexandria, USA.
J La State Med Soc. 2003 May-Jun;155(3):154-7.
The purpose of this paper is to present three case
reports of patients who presented to a local hospital in
Northern Louisiana with symptoms of viral meningitis and
encephalitis. It also updates physicians on the signs and
symptoms of persons infected with West Nile virus (WNV), a
new and emerging infection in the Western Hemisphere.
Beginning in June 2002, persons in Louisiana, particularly
the southern part of the state, started presenting to
health facilities with symptoms of infection with the WNV.
By August 2002, persons in the northern part of the state
were also experiencing symptoms that include neurologic
presentations of the disease. After completing recommended
diagnostic measures for possible infection with
flaviviruses, the three cases presented here were positive
for viral meningitis/encephalitis. Beginning in June 2002,
the state experienced an outbreak of WNV of epidemic
proportions. Consequently, clinicians need to be mindful of
the symptoms, diagnostic measures, treatment, prevention,
and reporting of meningitis/encephalitis.
[Enteroviral meningitis
in adults, underestimated illness: description of 30
observations from 1999 to 2000, and evolution of clinical
practices during 2001] [Article in French]
Peigue-Lafeuille H, Archimbaud C, De Champs C, Croquez
N, Laurichesse H, Clavelou P, Aumaitre O, Schmidt J,
Henquell C, Bailly JL, Chambon M. Laboratoire de virologie
du CHRU, faculte de medecine, 28, Place Henri-Dunant, 63001
Cedex, Clermont-Ferrand, France.
Helene.Lafeuille@u-clarmont1.fr
Pathol Biol (Paris). 2002 Nov;50(9):516-24.
Enteroviral meningitis is well documented in children
but underestimated in adults. The analysis of 30 cases of
adult meningitis prospectively diagnosed by enterovirus
genome detection (RT-PCR) in cerebrospinal fluid (CSF)
between 1999 and 2000 in routine practice showed diagnosis
to be problematic. Characteristic symptoms were inconstant
(the association of fever/headache/stiff neck absent in
41%) and sometimes misleading (the presence of peribuccal
lesions). CSF data showed a predominance of lymphocytes in
only 44% of patients. The most reliable criterion was
normal constant CSF glucose levels. Thirty three per cent
of patients were admitted during cold months. Management of
patients varied markedly between departments, and included
computed tomography (33%), and the prescription of
aciclovir (20%) or antibiotics (53%). A report of positive
enterovirus RT-PCR had only low impact on management
because it took 6 days to obtain the results (versus 3 days
in children during the same period). These findings were
communicated to all hospital physicians concerned and as a
result, the number of RT-PCR in adults increased
significantly during 2001. Again, enteroviral meningitis
was diagnosed in adults despite a much lower incidence of
the illness in 2001 compared to 2000. Thus this pathology
should not be underestimated in adults. Considerable
medical expenditure might be avoided (cumulative numbers of
172 days in hospital and 82 days of antibiotics in this
study), if rapid and accurate diagnostic techniques were
available.
Viral meningitis and
encephalitis: traditional and emerging viral
agents.
Romero JR, Newland JG. Combined Division of Pediatric
Infectious Diseases, Associate Professor of Pediatrics,
Pathology and Microbiology, University of Nebraska Medical
Center, Omaha, NE 68178, USA. jrromero@unmc.edu
Semin Pediatr Infect Dis. 2003 Apr;14(2):72-82.
In the United States, the annual number of central
nervous system (CNS) infections that occur as a result of
viral agents far exceeds that of infections caused by
bacteria, yeast, molds, and protozoa combined. The recent
incursion of West Nile virus (WNV) into North America has
led to a dramatic change in the incidence and epidemiology
of summer-associated viral CNS disease. As a result of
increased testing for WNV, lesser known viral causes of CNS
infection have been identified. Even the epidemiology of
such traditional viral neuropathogens as rabies has changed
in recent years. This review provides an overview of
viruses traditionally associated with meningitis and
encephalitis (enteroviruses, La Crosse virus, St. Louis
encephalitis virus, eastern and western equine viruses,
varicella-zoster virus), as well as several of the less
common (Powassan virus, lymphocytic choriomeningitis virus,
Colorado tick fever virus, rabies virus, influenza viruses,
etc.) and emerging (West Nile virus) viral pathogens.
Copyright 2003 Elsevier Inc. All rights reserved.
[A case of recurrent
meningitis with association of human herpes virus-6
hepatitis] [Article in Japanese]
Satoh A, Niwa K, Kawaguchi C, Takeoka T, Shinohara Y.
Department of Neurology, Tokai University School of
Medicine.
Rinsho Shinkeigaku. 2003 May;43(5):281-3.
A 27-year-old man presenting with recurrent meningitis
associated with the activation of hepatitis was reported.
Although he showed headache only, he was diagnosed as viral
meningitis with high transaminase activities on admission.
Human herpes virus-6 (HHV-6) DNA was revealed in the liver
tissue by the polymerase chain reaction. This case was
considered viral meningitis with HHV-6 associated
hepatitis. It is suggested that the importance of viral
evaluations not only herpes virus type 1 x 2, cytomegaro
virus and EB virus, but also HHV-6 infection in a case of
recurrent meningitis with hepatitis simultaneously.
The future of
meningitis vaccines.
Segal S, Pollard AJ. Department of Paediatrics, John
Radcliffe Hospital, Oxford OX3 9DU.
Hosp Med. 2003 Mar;64(3):161-7.
Without effective vaccines meningitis remains a
substantial worldwide threat with major health-care
implications. A number of advances have been made in
vaccine design and implementation over the last decade,
with new vaccine initiatives providing substantial promise
for the future reduction of global disease burden.
[Meningitis and
encephalitis in Poland in 2000] [Article in
Polish]
Stefanoff P, Zielinski A. Zaklad Epidemiologii
Panstwowego Zakladu Higieny ul. Chocimska 24, 00-791
Warszawa. pstefanoff@pzh.gov.pl
Przegl Epidemiol. 2002;56(2):265-73.
A total of 2,033 cases of meningitis and 570 of
encephalitis were reported in Poland in 2000. Among cases
of meningitis 1,051 (51.7%) were classified as viral and
982 (48.3%) as bacterial. Etiological factors were
determined in 36.7% (360/982) cases of bacterial
meningitis. Neisseria meningitidis, Haemophilus influenzae,
and Streptococcus pneumoniae were found in 10.3% (101/982),
8.7% (85/982), and 7.5% (74/982) cases, respectively. As in
previous years, N. meningitidis typed B was strongly
predominating. Out of 570 cases of encephalitis, 170
(29.8%) were tick borne, of which most were reported from
endemic areas of north-eastern part of the country.
Mollaret's meningitis:
CSF-immunocytological examinations.
Stoppe G, Stark E, Patzold U
J Neurol 1987 Feb;234(2):103-6
Mollaret's meningitis is a rare clinical entity
consisting of recurrent attacks of meningeal irritation,
which, after a sudden onset, last for a few days. The
prognosis appears to be excellent, although the aetiology
has not been established. In the CSF so-called endothelial
cells are a typical finding, but their classification is
not yet clear. In the present case immunocytological
examination of CSF cells revealed that the so-called
Mollaret cells are monocytes. The time course of changes in
helper/suppressor ratio is similar to that in other
infectious diseases of the central nervous system.
Herpes simplex virus
infection as a cause of benign recurrent lymphocytic
meningitis.
Tedder DG, Ashley R, Tyler KL, Levin MJ University of
Colorado Health Sciences Center, Children's Hospital,
Denver.
Ann Intern Med 1994 Sep 1;121(5):334-8
OBJECTIVE: To identify the role of herpes simplex virus
(HSV) in causing benign recurrent lymphocytic
meningitis.
DESIGN: Prospective cohort study.
SETTING: Tertiary referral center.
PATIENTS: 20 consecutive patients with a provisional
diagnosis of benign recurrent lymphocytic meningitis had
cerebrospinal fluid specimens submitted between 1990 and
1993 to the diagnostic virology laboratory. Thirteen
patients met our criteria for benign recurrent lymphocytic
meningitis.
MEASUREMENTS: Herpes simplex virus DNA was detected in
cerebrospinal fluid specimens using the polymerase chain
reaction, followed by hybridization with a HSV-specific DNA
probe. Herpes simplex virus type 1 and type 2 DNA products
were distinguished by digestion with restriction enzymes
and analysis by gel electrophoresis. Anti-HSV antibodies in
cerebrospinal fluid were detected by immunoblot.
RESULTS: The patients had 3 to 9 attacks (mean, 4.6
attacks) of benign recurrent lymphocytic meningitis during
periods ranging from 2 to 21 years (mean, 8.4 years). Three
of 13 patients had known recurrent genital herpes.
Cerebrospinal fluid analysis showed 48 to 1600
cells/microL, glucose levels of more than 2.22 mmol/L (40
mg/dL), and protein levels of 41 to 240 mg/dL (0.41 to 2.4
g/L). Herpes simplex virus DNA and anti-HSV antibodies were
detected in cerebrospinal fluid samples in 11 of 13
patients (84.6%; 95% CI, 55% to 98%). Ten of these 11
patients had HSV type 2 DNA and HSV type 2 antibodies. One
patient had HSV type 1 DNA and HSV type 1 antibodies in the
cerebrospinal fluid. The remaining two patients had only
anti-HSV type 2 antibodies.
CONCLUSIONS: Herpes simplex virus, predominantly HSV
type 2, was the major agent causing benign recurrent
lymphocytic meningitis that met our specified diagnostic
criteria.
Herpes simplex virus
type 1 DNA in cerebrospinal fluid of a patient with
Mollaret's meningitis.
Yamamoto LJ, Tedder DG, Ashley R, Levin MJ Department of
Internal Medicine, St. Joseph's Hospital, Denver, CO.
N Engl J Med 1991 Oct 10;325(15):1082-5
No abstract.
[The thyroid function
in children with viral meningitis] [Article in
Polish]
Szychowska Z, Kucharska W. Klinika Chorob Zakaznych
Wieku Dzieciecego AM we Wroclawiu.
Endokrynol Diabetol Chor Przemiany Materii Wieku Rozw.
1998;4(1):13-7.
Thyroid function was investigated in children affected
with viral meningitis caused by Mumpsvirus or
enteroviruses. Serum or plasma levels of
thyroid-stimulating hormone (TSH), triiodothyronine (T3),
free triiodothyronine (FT3), thyroxine (T4) and free
thyroxine (FT4) were measured twice in course of the
disease: at admission and at recovery (day 10-14 from the
onset of illness). The levels of hormones were measured by
radioimmunoassay (RIA) or by enzyme linked fluorescent
assay (ELFA). A decrease in serum or plasma concentrations
of TSH, T3, FT3 and T4 (T4 - only when measured by RIA) was
found at the beginning of illness as compared to the
controls, which indicates the low-T3 syndrome in children
with viral meningitis. These disturbances were present also
at recovery. When comparing thyroid function in children
suffering from bacterial and viral meningitis, a more
significant decrease in the levels of thyroid hormones
(especially T3 and FT3) was found at the beginning of
bacterial than viral meningitis. Un resolved questions are
the causes and the importance of low-T3 syndrome in
children with viral meningitis.
|