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\begin{document}

\title{A fatal acute bacterial meningoencephalitis with the highest
cerebrospinal fluid white blood cell count ever reported in literature}



\author[1]{Hend Alhodaif}%
\author[2]{Sultan Alotaibi}%
\author[1]{Salih  Bin Sailh}%
\author[1]{Makki  Almuntashri}%
\author[1]{Nassir Alotaibi}%
\author[1]{Ismail  Khatri}%
\affil[1]{King Abdulaziz Medical City}%
\affil[2]{King Saud bin Abdulaziz University for Health Sciences}%


\vspace{-1em}



  
  \date{June 15, 2024}


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\selectlanguage{english}
\begin{abstract}
We present a case of a man who had chronic otitis media caused acute
bacterial meningitis due to Streptococcus pneumoniae. The neuroimaging
indicated thick exudates in the CSF spaces. Our patient's CSF consisted
of frank pus. The CSF white blood cell count was highly elevated, not
reported in prior literature.%
\end{abstract}%



\sloppy


\textbf{Abstract}

Bacterial meningitis is one of the most life-threatening neurological
emergencies. Delayed diagnosis and management results in high morbidity
and mortality. Although most cases of bacterial meningitis do not have a
precise mechanism, local spread from adjacent structures, such as the
ear, nose, and throat is not uncommon. Many bacterial species cause
bacterial meningitis; however, \emph{Streptococcus pneumoniae} is the
most frequent lethal pathogen. The cerebrospinal fluid (CSF) is often
turbid with an elevated white blood count and proteins. We present a
case of a middle-aged man who had chronic otitis media that caused acute
fulminant bacterial meningitis due to \emph{Streptococcus
pneumoniae.}The CSF consisted of frank pus and neuroimaging indicated
extensive parenchymal damage with thick exudates in the CSF spaces.
There was also radiological evidence of cerebral venous thrombosis. Our
case is a rare case of the CSF changing to a frank pus-like appearance.
The CSF white blood cell count was highly elevated, not reported in
prior literature. The radiological findings reported in this case are
unique and highly educational.

\textbf{Introduction} : The estimated global incidence of bacterial
meningitis is more than 1.2 million cases per year
(1).\emph{Streptococcus pneumoniae} ~is the most frequent pathogen
causing bacterial meningitis in adults, with a frequency ranging from
9.6\% to 75.2\% (2,3). Recurrent community-acquired bacterial meningitis
accounts for approximately 6\% of meningitis cases,
with~\emph{Streptococcus~pneumoniae} responsible for the majority of the
cases (4). In developing countries, the estimated mortality rate of
bacterial meningitis was 22.1\%, with 17.1\% of the mortality attributed
to \emph{Streptococcus pneumoniae} (5). Although a high white blood cell
count in the cerebrospinal fluid (CSF) is a hallmark of pyogenic
meningitis, the frank pus-like appearance of CSF is extremely rare. We
report a case of pyogenic meningitis with an exceptionally high CSF WBC
count, with the CSF looking like frank pus. We propose that the pus-like
appearance of CSF be termed pyorrhachia.

\textbf{Case report:~} A 58-year-old man presented at the emergency room
with a two-day history of headache, sore throat, cough, and fever. He
had a past medical history of uncontrolled diabetes mellitus,
hypertension, bronchial asthma, and chronic otitis media. He required an
otomastoidectomy for the chronic otitis media, complicated by a tegmen
tympani defect and secondary pseudomeningocele formation communicating
with the left temporal horn (Figure 1). He had bacterial meningitis six
years ago, complicated by hydrocephalus that required a temporary
external ventricular shunt placement.

The patient was initially managed as a case of upper respiratory tract
infection and discharged on the same day with a course of oral
antibiotics. He returned to the emergency room one day later because of
worsening headache and vomiting associated with altered sensorium. The
patient was well built but sick-looking. His systolic blood pressure was
160/75mm Hg, heart rate 110 beats per minute, respiratory rate 27 per
minute, the temperature 38 degrees Celsius, and oxygen saturation 96\%
at room air. His initial neurological examination revealed no
eye-opening to pain, and he produced sounds only as a verbal response.
His pupils' size was 4 mm and reactive to light, and he blinked to a
threat in both eyes. With the fundus examination, there was bilateral
papilledema. He had a normal vestibulo-ocular reflex, positive corneal
reflex, no facial asymmetry, the gag reflex was preserved, and in
response to painful stimulus on the sternum, he showed withdrawal
response bilaterally. He had nuchal rigidity with positive Brudzinski
and Kernig signs. His arterial blood gas results showed a pH of 7.512,
pCO2 of 30.8, pO2 of 80.2, and an HCO3 of 24.1. The laboratory results
were significant with the white blood count (WBC) of 13,000 cells per
microliter, the lactic acid was 2.49 mmol/L (0.5 to 2.2 mmol/L), and the
potassium was 2.7 mmol/L (3.6 to 5.2 mmol/L). The other laboratory
parameters including hemoglobin, platelets, renal function, liver
function, coagulation profile and cardiac enzymes were within normal
limits. A brain computerized tomography (CT) scan showed no significant
structural abnormality. Following the brain CT, a lumbar puncture was
performed. The appearance of the CSF was a thick yellow liquid
resembling pus (Figure 2). The CSF WBC count was
\textbf{158,000}cells/\selectlanguage{greek}µ\selectlanguage{english}L (0-5 cells/\selectlanguage{greek}µ\selectlanguage{english}L), the CSF protein \textbf{18.67}
mg/mL (0.15 to 0.6 mg/mL), the CSF lactic acid 42.37 mmol/liter (0-3
mmol/liter), the CSF glucose \textbf{0.1} mg/100 mL (50 to 80 mg/100
mL), the CSF RBCs were less than 1 RBC/mm3 (\textless{}1 RBC/mm3) and
the CSF culture indicated~\emph{Streptococcus pneumoniae} (see note). He
was started on a regimen with ceftriaxone, vancomycin, ampicillin,
metronidazole, and dexamethasone. Due to respiratory failure, he was
intubated with an endotracheal tube and transferred to an intensive care
unit. On the second day of admission, his level of consciousness
deteriorated, and his Glasgow coma scale (GCS) was 3 out of 15. A
repeated brain CT scan and brain venogram revealed multiple filling
defects in the superior sagittal sinus (Figure 1). The brain magnetic
resonance imaging (MRI) showed extensive gyrifrom diffusion restriction
abnormality involving the frontal, anterior temporal lobes, insular
cortices, and bilateral deep gray nuclei and brainstem suggestive of
meningoencephalitis with gyrifrom hemorrhagic foci in the insula and
frontal lobes (Figure 1). Multiple small collections were also noted
along the leptomeningeal surface of the brain stem and cerebellar
convexities representing exudates (Figure 1). Unfortunately, on the
fifth day of admission, his physical examination continued to show GCS
of 3 out of 15, and brainstem reflexes were absent. A brain perfusion
scan showed no brain perfusion, and he was declared brain dead.

\textbf{Discussion:} Our patient's history of chronic otitis media with
mastoiditis was possibly the most important factor of the recurrent
severe bacterial meningitis. Otitis media have many serious
complications, including mastoiditis, labyrinthitis, seventh cranial
nerve palsy, meningoencephalitis, brain abscess, and cerebral venous
thrombosis (6). Acute bacterial meningitis is a devastating complication
of otitis media with a reported mortality rate of 41\% and chronic
otitis media was the cause in 74\% of the morality cases (7). Our
patient had a significantly elevated CSF WBC count of 158,000 cells/\selectlanguage{greek}µ\selectlanguage{english}L
as a result of severe bacterial meningoencephalitis, with no
radiological evidence of abscess formation. However, the
meningoencephalitis was severe enough to form brainstem and cerebellar
convexity exudates observed on the brain MRI. The mean white cell count
in the CSF investigated in children with bacterial meningitis was 4839
cells/\selectlanguage{greek}μ\selectlanguage{english}L, which is a significantly lower count than in our patient (8).
There is no report in literature with a CSF WBC level as high as in our
patient. We found one report of a 55-year-old woman with acute bacterial
meningitis who had a high level of white cell count in the CSF of
104,000 cells/mm3, but unlike our patient the CSF appearance was turbid.
Similar to our patient, the meningitis was due to \emph{Streptococcus
pneumoniae} bacteria; with no evidence of an intracranial abscess on
brain imaging (9). Of the many factors contributing to our patient's
mortality is his initial symptomatology of cough, sore throat, and
headache that misled emergency physicians not to recognize
meningoencephalitis early and administer the appropriate antibiotics. A
delayed presentation to hospital, decreased level of consciousness on
presentation, \emph{Streptococcus pneumoniae} infection, abnormal brain
imaging, and the use of intracranial measuring devices are some of the
factors that predict a poor prognosis and mortality in an adult with
fulminant bacterial meningitis (10). A history of prior complicated
bacterial meningitis and complicated chronic otitis media are essential
factors to be considered in any patient presenting with fever and
headache, regardless of other symptomatology to rule out central nervous
system (CNS) infection.

\textbf{Conclusions} : Turbid CSF with a high WBC count is often present
in bacterial meningitis; however, frank pus-like CSF with a WBC level of
158000 cells/\selectlanguage{greek}µ\selectlanguage{english}L is rare. The range of the white cells count at which the
CSF turns from a turbid to a pus-like appearance is unknown. We propose
that CSF resembling pus should be called pyorrhachia. More reports in
future may support our understanding of this extremely rare phenomenon.

Note:

Our laboratory is College of American Pathologists accredited. CSF WBC
count was done manually using a hemocytometer with 1/20 and 1/50 sample
dilutions with saline. The differential count was performed by adding
two drops of 5\% bovine albumin solution to one mL of diluted CSF
samples; 1/20 and 1/50 dilution in saline. Samples were centrifuged at
750 RPM for 5 minutes, and then the slides were stained with Wright's
Giemsa stain.

\textbf{References} :

\begin{enumerate}
\tightlist
\item
  World Health Organization.~Control of epidemic meningococcal disease:
  WHO practical guidelines, 2nd ed.~World Health Organization.1998
\item
  Van de Beek D, Cabellos C, Dzupova O, et al. ESCMID guideline:
  diagnosis and treatment of acute bacterial meningitis. \emph{Clin
  Microbiol Infect} 2016;3:S37-62.
\item
  Oordt-Speets AM, Bolijn R, van Hoorn RC, et al. Global etiology of
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\item
  Tebruegge M, Curtis N. Epidemiology, etiology, pathogenesis, and
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\item
  Rabbani MA, Khan AA, Ali SS, et al. Spectrum of complications and
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\item
  Wu JF, Jin Z, Yang JM, Liu YH, et al. Extracranial and intracranial
  complications of otitis media: 22-year clinical experience and
  analysis. \emph{Acta Otolaryngol} 2012;132:261-5.
\item
  Geyik MF, Kokoglu OF, Hosoglu S, et al. Acute bacterial meningitis as
  a complication of otitis media and related mortality
  factors.\emph{Yonsei Med J} 2002;43:573-8.
\item
  \selectlanguage{ngerman}Águeda S, Campos T, Maia A. Prediction of bacterial meningitis based
  on cerebrospinal fluid pleocytosis in children. \emph{Braz J Infect
  Dis} 2013;17:401-4.
\item
  Menaker J, Martin IB, Hirshon JM. Marked elevation of cerebrospinal
  fluid white blood cell count: an unusual case of Streptococcus
  pneumoniae meningitis, differential diagnosis, and a brief review of
  current epidemiology and treatment recommendations. \emph{J Emerg
  Med}2005;29:37-41.
\item
  Muralidharan R, Mateen FJ, Rabinstein AA. Outcome of fulminant
  bacterial meningitis in adult patients. \emph{Eur J
  Neurol}2014;21:447-53.
\end{enumerate}\selectlanguage{english}
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\includegraphics[width=0.70\columnwidth]{figures/FIGURE-1-no-legend/FIGURE-1-no-legend}

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\includegraphics[width=0.70\columnwidth]{figures/CSF-figure-2/CSF-figure-2}

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