Case Report
Open Access
Case Report Of Chronic Meningo Encefalitis By
Coccidiodes Immitis
Gabriel Miranda Nava*
Head of Neurology of the Hospital Center of the Presidential General Staff. Av Constituyentes 240, Extension Daniel Garza, Daniel
Garza, 11840 Mexico City.
*Corresponding author: Gabriel Miranda Nava, Head of Neurology of the Hospital Center of the Presidential General Staff. Av Constituyentes 240, Extension Daniel Garza, Daniel Garza, 11840 Mexico City; E-mail:
chidozieagu@gmail.com,
cagu@phrinitiative.com
Received: July 19, 2018; Accepted: December 20, 2018; Published: December 22, 2018
Citation: Gabriel Miranda N (2018) Case Report Of Chronic Meningo Encefalitis By Coccidiodes Immitis. SOJ Immunol 6(3): 1-5.
Summary
Chronic meningoencephalitis is a syndrome that corresponds
to approximately 10% of meningeal symptoms. It is a disease with
various etiologies, which is a true diagnostic challenge. Among the
most frequent causes are: infectious, toxic, inflammatory, neoplastic,
autoimmune and idiopathic agents. This type of disorder demands a
very extensive and expensive study battery, in spite of this; it is not
always possible to establish the diagnosis. Cerebral and meningeal
biopsies play an important role in the study of these patients. A
detailed and careful clinical history is of the utmost importance,
together with the study of the CSF to guide the physician towards the
etiology of the problem. The different modalities of Neuroimaging
have become a useful tool in the search for diagnosis in these cases.
The treatment of chronic meningitis depends on the underlying cause.
Once a specific cause has been established, case-directed therapy
should be initiated. When the cause is unknown, a decision must be
made to employ empirical therapy, while the diagnostic evaluation is
ongoing. We present the case of the clinical-pathological session in
the Hospital Central Militar, about a male patient who was previously
healthy and who shows a clinical picture compatible with chronic
meningoencephalitis, with a progressive and unfavorable course,
in which despite the studies of image, laboratory and CSF, as well as
empirical treatment management, it becomes impossible to determine
etiology. Finally, postmortem diagnosis of neurococcidioidomycosis
is made by means of histopathological study of brain tissue sections.
Showing the diagnostic difficulty that these tables represent and the
importance of early diagnosis when conditions favor it.
Keywords: Chronic Meningoencephalitis, Coccidioides Immitis and
Neurococcidioidomycosis.
Abstract
Chronic meningoencephalitis is a syndrome that corresponds
to about 10% of meningeal tables. It is a condition with many
causes and therefore constitutes a real diagnostic challenge.
Among the most common causes include infectious agents, toxic,
inflammatory, neoplastic, autoimmune and idiophatic. These
disorders require a battery of extensive and expensive studies,
although it is not always possible to establish the diagnosis.
Cerebral and meningeal biopsies play an important role in
examining these patients.
A detailed and careful history and examination is required
along with CSF parameters to guide a clinician towards the
etiology of the problem. Neuroimaging modalities have become
a useful tool in the quest for a diagnosis in such cases. Treatment
of chronic meningitis depends on the underlying cause. Once
a specific cause has been established, appropriate targeted
therapy is initiated. When the cause is unknown, a decision
must be made whether to employ empiric therapy while the
diagnostic evaluation is ongoing. We presents a case commented
in clinical-pathologic session in Central Military Hospital, about
an inmucompetente male patient, previously healthy manifesting
clinical signs compatible with chronic meningoencephalitis,
with a progressive and unfavorable course, in which, despite the
imaging studies, laboratory and CSF, as well as empirical therapy
management is becomes impossible to determine etiology. Finally
neurococcidioidomicosis performed postmortem diagnosis by
means of histopathological examination of brain tissue sections.
Demonstrating the diagnostic difficulty that these paintings
represent and the importance of early diagnosis when conditions
favor it.
Introduction
Meningitis refers to an inflammatory process of leptomeninges
and CSF within the subarachnoid space. Meningoencephalitis
refers to the inflammation of the meninges and cerebral
parenchyma. [1] Chronic meningoencephalitis is a syndrome that
corresponds to approximately 10% of meningeal symptoms. They
share a clinic of insidious nature such as headache, behavioral
alterations, compromise of consciousness, signs of focal
neurological compromise and seizures, more encephalitically
than meningitically, associated with moderate CSF pleocytosis
composed of mononuclear cells or a mixture of polymorph
nuclear cells and cells. Mononuclear; the level of proteins is
high, often markedly, and the glucose content is usually reduced
or normal, the former in a picture that persists for at least 4
weeks. [2] The etiologies are diverse, both infectious (fungi,
parasites) and bacteria) as non-infectious (chemical exposure),
neoplastic, autoimmune and even idiopathic, so their syndromic
study merits a series of CSF tests, bounded when possible by
the clinic. In the absence of risk factors or clinically orienting in
the etiological, in a subacute or chronic meningoencephalitis,
evaluation of the CSF whose appearance is clear must include:
cytochemical examination, Chinese ink stain and fungal culture,
stain and culture for bacillus of koch, tests of cysticercosis, study
of syphilis, adenosine deaminase and search for neoplastic cells.
The lethality of these pictures will depend on the etiology, but it
reaches 30%,además tiene un alto índice de secuelas. En el caso
clínico que nos ocupa en esta ocasión, la clínica, laboratorio y
paraclínicos nos orientan hacia una meningoencefalitis de origen
micótico. En éstas, el cerebro suele estar afectado solo al final
de la enfermedad, donde existe una diseminación hematógena
del hongo, la mayor parte de las veces Candida albicans, Mucor,
Aspergillus fumigatus y Criptococcus neoformans. En las
zonas endémicas patógenos como Histoplasma capsulatum,
Coccidioides immitis y Blastomyces dermatidis pueden afectar
al SNC tras una infección primaria pulmonar o cutánea. [3] La
coccidioidomicosis (CM) es una micosis endémica en algunas
regiones de los Estados Unidos, en el Noroeste y Noreste de
México y en ciertas áreas en Centroamérica y Sudamérica. [4]
La CM extrapulmonar se presenta en 1 de cada 200 sujetos
infectados; los sitios más comúnmente afectados son meninges,
huesos, articulaciones, [5] piel y tejidos blandos. [6] La CM es
la más antigua de las micosis sistémicas,[7] fue descrita por
primera vez en un soldado argentino en 1892 reportándose el
caso como micosis fungoidea. [8] La meningitis es la complicación
más grave de esta infección, sin tratamiento específico el
100% de los pacientes mueren. [9] A continuación se presenta
el caso clínico de paciente inmunocompetente, previamente
sano, con manifestaciones de meningitis crónica, con cultivos
para bacterias y hongos negativos en LCR, en quien a pesar de
tratamiento a base de compuestos azólicos, fallece y posterior
a esto se realiza diagnóstico histopatológico que revela como
agente causal Coccidiodes immitis, poniendo de manifiesto la
dificultad diagnóstica y la importancia del diagnóstico temprano
cuando las condiciones lo favorecen.
It also has a high rate of sequelae. In the clinical case that
concerns us on this occasion, the clinical, laboratory and
paraclinical lead us to a meningoencephalitis of fungal origin. In
these, the brain is usually affected only at the end of the disease,
where there is a haematogenous spread of the fungus, most often
Candida albicans, Mucor, Aspergillus fumigatus and Cryptococcus
neoformans. In pathogenic endemic areas such as Histoplasma
capsulatum, Coccidioides immitis and Blastomyces dermatidis
can affect the CNS after a primary pulmonary or cutaneous
infection. [3] Coccidioidomycosis (CM) is an endemic mycosis in
some regions of the United States, in the Northwest and Northeast
of Mexico. Mexico and in certain areas in Central and South
America. [4] Extrapulmonary CM occurs in 1 of every 200 infected
subjects; the most commonly affected sites are meninges, bones,
joints, skin and soft tissues. [6] CM is the oldest systemic mycosis,
[7] was first described in an Argentine soldier in 1892, reporting
the case as mycosis fungoidea. [8] Meningitis is the most serious
complication of this infection, with no specific treatment 100% of
patients die. [9] The clinical case of immunocompetent patient,
previously healthy, with manifestations of chronic meningitis,
with cultures for bacteria and negative fungi is presented below
in CSF, who despite treatment with azo compounds, died and
after this histopathological diagnosis was made that reveals
Coccidiodes immitis as a causative agent, highlighting the
diagnostic difficulty and the importance of early diagnosis when
conditions favor it.
Case Report
It is a male patient, 33 years old, active military, originating
and resident of the city of Oaxaca, Oaxaca, in Mexico. He began
his illness in November 2009, one month before his admission
to the Regional Military Hospital of Puebla (HMRP), with a
clinical picture characterized by: intense headache, oppressive,
predominantly frontal, which does not yield to the administration
of analgesics, accompanied by nausea without reaching vomiting,
disturbances of thinking with fluctuations in the course of the
day, reduced ability to maintain or direct attention, disorganized
thinking, even led to disciplinary problems.
He entered the HMRP on December 23 of the same year
where he was approached by the Neurology and Psychiatry
services. On admission with few data since indirect interrogation
is performed, pathological and non-pathological personal history
is unknown, the physical examination reveals: Glasgow 12/15,
neck stiffness, kerning and brudzinski (+), fever of 38ºC, acute
confessional state with Incoherent verbal responses, alteration
of critical judgment and reasoning, at 24 hrs generalized tonicclonic
seizures are added.
Table 1.0: Hematic Biometry: Leukocytes 14,690 x103, with neutrophilia,
platelets 187,000.
Characteristics |
24.12.09 |
31.12.09 |
05.01.10 |
Appearance |
Rock wáter |
cloudy |
Thick |
Colour |
Colorless |
Xanthochromic |
Xanthochromic |
Pressure |
|
|
|
Glucose |
16 mg/dl |
27 mg/dl |
50 mg/dl |
Proteins |
158 mg/dl |
190.4 mg/dl |
|
Chlorides |
|
115 mEq/L |
|
Leukocytes |
25 |
686 |
34 |
Polymorphonuclear |
60% |
85% |
60% |
Mononuclear |
40% |
15% |
|
LDH |
|
105 UI/L |
200 UI/L |
Serology studies with V.I.H and V.D.R.L negative. Lumbar
puncture: Colorless, appearance in rock water, Glucose 16 mg /
dl, protein 158mg / dl, leukocytes 25, PMN 60%, mononuclear
40%, negative bacterial cultures. (Table 1.0) Hematic Biometry:
Leukocytes 14,690 x103, with neutrophilia, platelets 187,000.
(Table 2.0) Blood chemistry: Glucose 120 mg / dl (Table 3.0).
Chest x-ray, EGO and Uroculture without alterations. Cabinet:
Skull CAT scan in simple and contrasted phase.
Table 2.0:Blood chemistry: Glucose 120 mg / dl
HEMATIC BIOMETRY |
Parametro |
24.12.09 |
31.12.09 |
Leucocits |
14,690 X103 |
15,789x103 |
Neutrofilos |
83.90% |
95% |
Lymphocytes |
3.90% |
3.40% |
Platelets |
187,000 |
92,000 |
Table 3.0:Chest x-ray, EGO and Uroculture without alterations
BLOOD CHEMISTRY |
Parameter |
24.12.09 |
31.12.09 |
Glucose |
120 mg/dl |
127 |
Creatinin |
0.6 mg/dl |
|
Urea |
29 mg/dl |
|
Sodium |
134 mEq/L |
155 |
Potassium |
4.2 mEq/L |
4.22 |
(Figure 1) Computed tomography of the skull. A. Simple phase
is observed apparently normal. B and C. Phase contrasted with
meningeal reinforcement.
Empirical treatment is started with: Meropenem, cefotaxime,
rifampin plus isoniazid, acyclovir, dexamethasone, B complex,
parenteral fluids. It persists with fever, neurological deterioration
and a psychiatric problem is ruled out, so on December 31, 2009,
it moves to the 3rd level of care at the Central Military Hospital.
It enters with the following clinical data: Disorientation, intense
headache, throbbing, holocranana, accompanied by nausea and
vomiting, fever of 38 °, confusional state with psychomotor
agitation, vague, irrelevant and incoherent language, neck
stiffness without finding other meningeal data. The CSF study
gives the following data: xanthochromic appearance, thick,
glucose 27 mg / dl, proteins 190.4 mg / dl, chlorides 115 mEq /
L, leukocytes 686 with 85% PMN. BAAR, GRAM, KOH, Chinese ink
and culture for fungi in Sabouraud negative medium. (Table 1.0)
Antifungal treatment is modified by initiating RIFATER,
Vancomycin and Acyclovir are added. EEG shows generalized
epileptiform discharges, which is why Valpróico Acid is started.
January 2, 2010, fluconazole 400mg is added every 12 hrs
intravenously. January 5 MRI showed changes compatible with
meningoencephalitis, cerebral edema and hydrocephalus
non-communicating, acute ischemic events in ganglia of the
base and left side mesencephalon.
(Figure 2) Magnetic resonance image. A is observed. Axial
slice in T2 sequence. Sagittal section in T1 sequence. C. Coronal
section in T2 sequence. January 7, the Glasgow falls to 8/15,
January 10 was damaged by neurological deterioration and severe
respiratory distress and enters intensive therapy, on January
11, ventriculostomy is performed to improve hydrocephalus,
however, it occurs with increased pressure intracranial and
neurological deterioration, with lethargy and stupor. January
15 falls into cardiorespiratory arrest without success in the
resuscitation maneuvers. On January 16, a histopathological
study was performed, which reports: Meningitis with basal
arachnoiditis, secondary hydrocephalus, vasculitis, multiple
infarctions, parenchymal granulomas and thrombosis of the
cavernous sinus.
Figure 1: Computed tomography of the skull
Figure 2: Magnetic resonance image
BIOMETRIA HEMATICA |
PARAMETRO |
24.12.09 |
31.12.09 |
LEUCOCITOS |
14,690 X 103 |
15, 789 x103 |
NEUTROFILOS |
83.90% |
95% |
LINFOCITOS |
3.90% |
3.40% |
PLAQUETAS |
187,000 |
92,000 |
QUIMICA SANGUINEA |
PARAMETRO |
24.12.09 |
31.12.09 |
GLUCOSA |
120 mg/dl |
127 |
CREATININA |
0.6 mg/dl |
|
UREA |
29 mg/dl |
|
SODIO |
134 mEq/L |
155 |
POTASIO |
4.2 mEq/L |
4.22 |
Discussion
Coccidioidomycosis or San Joaquin Valley fever is a systemic
mycosis caused by the dimorphic fungi Coccidioides immitis
or C. Posadassi, which despite being highly contagious, is not
transmitted from person to person and its true incidence and
prevalence is unknown because it is not among the pathologies
of mandatory reporting. Epidemiology It is an endemic mycosis
in some regions of the United States (California, Arizona, New
Mexico and Texas), in the Northwest and Northeast of Mexico and
in certain areas in Central and South America, 4 this dimorphic
fungus that grows in layers of topsoil in semi-arid zones [10]
where a warm climate prevails, low altitude and little rain.
Pathophysiological En el hábitat mencionado se desarrolla como
un micelio ( forma saprófita), éstas células miceliales alternantes
sufren un proceso de autolisis y adelgazamiento de sus paredes
celulares, las células restantes (artroconidias) desarrollan una
capa externa hidrofóbica lo que les confiere la capacidad para
mantenerse viables durante periodos largos de tiempo y sus
frágiles fijaciones se tornan propensas a la separation by physical
rupture or even by some turbulence of air, consequently, they are
transmitted by the air in a form apt to be deposited in the lungs
if they are inhaled. In the lungs the arthroconidia are remodeled
into spherical cells (parasitic form) and lose their hydrophobic
outer wall, divide, multiply and as they mature, they break to
release viable endospores, which produce a chemotactic effect
in neutrophils. The most common route of dissemination to the
CNS is hematogenous, and it can also occur by contiguity in cases
of cranial or vertebral osteomyelitis.Clinical course The clinical
picture is characterized by: Headache, neurological alterations,
data of meningeal irritation, signs and constitutional symptoms.
The disease can affect individuals at any stage of life and often
has an unfavorable evolution. However, males become infected
more frequently, probably because of the relationship with
occupational exposure to contaminated dust; however, they
also have a greater tendency to spread, suggesting a genetic or
hormonal component [11]. Laboratory and Cabinet The red
and white series do not usually undergo changes, however, in
some cases leukocytosis with eosinophilia has been reported.
Examination of cerebrospinal fluid usually reveals mononuclear
pleocytosis, hypoglucorrhakia, and protein elevation. In some
cases, elevated CSF pressure has been reported. Approximately in
33% of the cases it is not possible to identify this agent despite the
exhaustive analysis of the CSF and other possible causes outside
the CNS. Some microorganisms that cause chronic meningitis
take several weeks to grow in culture. Because extra pulmonary
coccidioidomycosis is always secondary to dissemination from a
primary pulmonary focus, chest x-rays should be performed, in
which it is possible to find a frequently unilateral infiltrate with
involvement of the upper lobes [12].
Treatment
Currently, triazole antifungals are the main drugs administered
for the treatment of many cases of coccidiomycosis. Fluconazole
has been shown to penetrate into the CSF, making it the azole
compound most indicated for the treatment of coccidioidal
meningitis, this should be used with the minimum adult oral dose
of 400mg / day that offers a response around the 70% This is an
important difference with the standard treatment of intrathecal
Amphotericin B, which was still common until a few years ago [13].
Currently, two new products of this category are posaconazole
and voriconazole. However, given the scarce clinical data, the high
cost and (especially in the case of voriconazole) the possible toxic
effects, the drugs in question are reserved for cases that remain
recalcitrant after treatment with fluconazole or itraconazole. The
administration of triazoles in high doses can be teratogenic, so we
can think of amphotericin B to treat coccidiomycosis in pregnant
women [14]. In addition to antifungal therapy to control meningeal
inflammation, interventions for other manifestations are needed.
Hydrocephalus usually does not respond to antifungal therapy
and requires a CSF bypass procedure. Ventriculoperitoneal shunts
become a conduit for C. immitis from the cerebrospinal space to
the peritoneum, but usually do not produce clinically evident
abdominal complications. Although the infection predominantly
affects the basal meninges, intracerebral abscesses sometimes
develop [15]. These lesions may require drainage or resection in
addition to systemic mycotic treatment.
Conclusions
The fact that coccidioidomycosis is now a newly emerging
disease can be attributed to changes in both demography
and contemporary medicine. First, the populations at risk of
exposure are very expanded. The regions in which C. Immitis
is endemic, which were previously sparsely populated, now
comprise major metropolitan centers. With this growth, tourism
and the movement of people towards infected areas and from
them have increased a lot. Second, an important stratum of the
population has emerged with compromise of cellular immunity
due to underlying diseases or immunosuppressive treatments to
control other diseases [16]. However, due to its low frequency in
immunocompetent patients, this diagnostic possibility may go
unnoticed, and should be considered in endemic areas.
- Robbins & Cotran Pathologic Basis of Disease 7aedition. pp1375-1376
- Tratado de Neurología Clínica, Jorge Nogales GAETE 2005, pp 345-350.
- Chonic meningitis, Shiraz E Medical Journal, vol. 1, No. 1, October 2009, Borhan Haghighi A.
- Mandell GL, Bennet JE, Dolin R,editores Stevens DA. Coccidioides immitis. En:. Principles and practice of infectious diseases, 4a ed. New York: Churchill-Livingstone.1995; pp. 2365-2375
- Zeppa M, Laorr A, Greenspan A, McGahan J, Steinbach L. Skeletal coccidioidomycosis: imaging findings in 19 patients. Skeletal Radiol 1996; 25(4): 337-343.
- Crum NF, Lederman ER, Stafford CM, et al. Coccidioidomycosis: a descriptive survey of a reemerging disease: clinical characteristics and current controversies. Medicine. 2004;83(3):149-175.
- Einstein HE, Jonhson RH. Coccidioidomycosis: new aspects of epidemiology and therapy. Clin Infec Dis 1993;16(3): 349-354
- Posada A. Un Nuevo caso de micosis fungoidea con psorospemias. Ann Círculo Médico Argentino 1892; 15: 585-598.
- Pappagianis D. coccidioides immitis. In: ajello L, Hay RJ. Microbiology and microbial infections vol 4.9th. Edic. Nueva York: Oxford University Press 2001: 357-72.
- A Coccidioidomycosis Outbreak Following the Northridge, Calif, Earthquake. Eileen Schneider at cols. 1997; 277:904.
- (Crum NF, Lederman ER, Stafford CM, Parrish JS, Wallace MR. Coccidioidomycosis: a descriptive survey of a reemerging disease. Clinical characteristics and current controversies. Medicine 2004;83:149-175.)
- (Galgiani JN. Coccidioidomycosis. West J Med 1993;159:153-171.)
- (Labadie EL, Hamilton RH. Survival improvement in coccidioidal meningitis by high-dose intrathecal amphotericin B. Arch Intern Med. 1986;146:2013-1018.)
- (Harrison 1248-1249 tomo 2.)
- (BaZuelos AF, Williams PL, Jonhson RH, et al. Central nervous system abscess due to coccidioides species. Clin Infect Dis. 1996; 22:240-250).
- (Rutala PJ, Smith JW. Coccidioidomycosis in potentially compromised host: The effect of immunosuppressive therapy in dissenation. Am J Med Sci. 1978;275.