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A STUDY OF PRESENTING SIGN-SYMPTOMS AND MRI
CHARACTERISTICS IN CASES OF ACUTE MENINGOENCEPHALITIS IN
IMMUNOCOMPETENT ADULTS IN A TERTIARY CARE HOSPITAL OF
EASTERN INDIA
Dr. Sinjan Ghosh
Department Of Neurology, NRS Medical College And Hospital, West Bengal, India
Dr. Md. Hamid
Ali*
Department Of General Medicine, Murshidabad Medical College And Hospital, W.B,
India *Corresponding Author
Original Research Paper
General Medicine
INTRODUCTION:
The incidence of acute encephalitis in western countries is 7.4 cases
per100,000 population per year. In tropical countries, the incidence is
[3][4]
6.34 per 100,000 per year. Herpes simplex encephalitis has an
[5]
incidence of 2–4 per million population per year. . The common
pathogens; which are encountered in adult bacterial meningitis are
Streptococcus pneumonia (30-50%), Neisseria meningitides (10-
35%), St ap hyloc oc ci (5 -15%) , other Strept oc occus spec ie s,
Haemophilus influenzae (1-3%), Gram-negative bacilli (1-10%) and
[6]
Listeria monocytogenes . Prompt recognition, early diagnosis,
efficient decision making followed by rapid institution of therapy plays
a pivotal role in saving a large salvageable portion of the affected
population and thus reducing mortality. Tuberculous meningitis
(TBM) remains the most common presentation. In spite of advances in
diagnostic technology and effective therapeutic options, it continues to
po se s ig nifi ca nt m ana ge men t cha lle ng es. Des pi te a nti -T B
chemotherapy, 20-50% of the affected people die and many who
survive have significant neurological deficits. The case fatality noted
to be associated significantly with delay in diagnosis and treatment.
Tuberculous meningitis (TBM) generally occurs in course of a sub
acute or chronic case but TBM may have an acute presentation.
Diagnostic evaluation includes various microbiological, pathologic,
molecular, and biochemical investigations& imaging modalities.
Imaging helps in early diagnosis and helps in preventing morbidity and
[7]
mortality. Imaging is essential in showing complications in addition
[8]
to diagnosis.
The plethora of magnetic resonance sequences available with the
radiologist today provides a wealth of information; anatomical,
pathological, physiological, functional and molecular aspects of the
brain. It is most often; the procedure of choice and preferred over CT
scan, due to its multilane and multi parametric imaging, and to its
[9]
better contrast resolution. It may detect the possible predisposing
CSF leaks in par nasal sinuses, orbital cellulites, rhino sinusitis-the
factors that may culminate into meningoencephalitis.
AIMS AND OBJECTIVES OF THESE STUDIES:
is to study the morphological pattern of brain parenchymal lesions with
Magnetic resonance imaging (MRI) of brain in Acute Meningo
encephalitis.
MATERIALS AND METHODS:
a) Patients, who admitted in between January 2013—August 2014 in
the department of General Medicine of NRS Medical College and
Hospital from rural and urban catchment area, were included in this
study as simple random selection. 50 patients, aged>12years were
included in this prospective observational study with Fever and Signs
of Meningitis (Nuchal rigidity, vomiting, and headache) or Signs of
meningoencephalitis: Meningeal signs with altered sensorium, focal
neuro-deficits, and seizures. The following patients with Sepsis,
Me ta bol ic E nc eph al opa th y, Dy selec tr oly te mia , Poi son in g,
Cerebrovascular Accident, Intracranial SOL, Neuro cysticercosis,
Enteric Fever with meningism, Vascular Aneurysms producing local
compressive effect, Acute disseminated Encephalomyelitis (ADEM)
and C erebr al Malaria were excluded from the study. Clinical
Characteristics-Glasgow Coma Scale (GCS) Scoring ( 3 to 15) as a
marker of clinical severity on admission. According to the score
calculated on admission, patients divided into three groups- Gr. A
(GCS 3-5), Gr. B (GCS 6-9), Gr. C (GCS 10-15). : The macroscopic
appearance of the CSF recorded. A routine CSF total and differential
count; done by a haemocytometer by standard methods. The CSF
samples subjected to a cytospin by using Shandon cytospin MODEL
001/ 002. CSF(500 microlitres) was added to the spin cups, spun for 10
minutes at 800 rpm and the resultant smear was Gram stained and
examined microscopically. ZN staining, Bacterial culture, TB culture
(BACTEC) and Cryptococcal staining(INDIA INK STAIN) were also
done. Specific Viral analysis; done by CSF ELISA according to
relevance, availability and feasibility. All CSF samples; cultured on
Sh ee p b lo od a ga r, Cho co la te agar, M acConkey's a ga r and
Thioglycollate broth for specific diagnosis. MRI (Magnetic resonance
imaging) with contrast (1.5 tesla machine) with Axial, Coronal and
Saggital cuts were taken sometimes with Special Sequences like DWI
(diffusion-weighted imaging), T1 and T2 FLAIR (fluid attenuated
inversion recovery) an d GRE(Gradient Echo) [ As applicable-
according to discretion of Radiologist. Neuroimaging may precede
CSF study by lumbar puncture if there is any contraindication to the
procedure like history suggestive of presence of Intracranial SOL,
Papilloedema, focal neurodeficits, signs of increased intracranial
tension or new onset seizures. We used laboratory methods available in
the Hospital and NABL accredited private laboratory. It was a Simple
obs erv ati onal s tudy. History takin g and Meticul ous Cl ini cal
Ex am ina tion & H aem at o-P atho logi cal an d B ioc he mic al
Investigations: including complete blood count, Fasting and Post
Prandial Glucose, Blood Urea and Creatinine, Serum Sodium and
Potassium, Blood Culture study, HIV 1& 2, HbsAg and Anti HCV
Antibody, Malaria dual antigen, Dengue Ns1 antigen and Dengue
Meningoencephalitis is a life threatening illness that is prevalent worldwide and bacterial infection remains a major cause
[1]
of death and long term neurological disabilities and thus hampers the quality of life. . Patient is usually presented with
[2]
photophobia, headache, or stiff neck, restless, irritability, confusion, convulsion, coma & death. .. Study conducted to study the morphological
pattern of brain parenchymal lesions with Magnetic resonance imaging (MRI) of brain in Acute Meningoencephalitis. There are very few studies
in India, especially from the eastern part of the country regarding evaluation of MRI findings in acute meningoencephalitis. The morphological
features evident in MRI of brain in various etiological groups vary and an area that needs to be explored. Brain imaging in acute
meningoencephalitis along with clinical features & CSF study is truly essential to formulate a proper management. Along with revelations of
recent trends of infection responsible for meningoencephalitis, this study also shows that early confirmation of clinical suspicion with judgement
of severity & neuroimaging (MRI with contrast) with CSF study is of great significance. Prompt diagnosis provides physicians with an
opportunity to prevent undue mortality and morbidity.. Here lies the relevance of this study.
ABSTRACT
KEYWORDS : Acute Meningoencephalitis, Cerebrospinal Fluid, Mri Of Brain
INDIAN JOURNAL OF APPLIED RESEARCH
45
Dr. Nandini
Chatterjee
Department Of General Medicine, IPGMER, West Bengal, India
Dr. Udas Chandra
Ghosh
Department Of General Medicine, Murshidabad Medical College And Hospital, W.B
India
Volume-9 | Issue-12 | December - 2019 | . PRINT ISSN No 2249 - 555X | DOI : 10.36106/ijar
46
INDIAN JOURNAL OF APPLIED RESEARCH
specific IgG and IgM, Widal's Test, Leptospira specific IgM antibody.
CSF was analysed for a) Cytology-Cell type and Cell count, b)
Biochemistry- Glucose, Protein and Chloride and c) Microbiology-
Gram staining, ZN staining, Bacterial culture, TB culture(BACTEC)
and Cryptococcal staining (India Ink Stain) d) Specific Viral analysis
by CSF ELISA according to relevance, availability and feasibility.
Final Diagnosis Based on Set Criteria and Segregation of cases
according to e tiological groups from CSF an d MRI findings.
Descriptive statistical methods; used, utilizing the SPSS software for
data analysis.
REVIEW OF LITERATURE:
Nearly one in four adults with acute bacterial meningitis will die, and
many survivors sustain neurological deficits. The outcome has not
changed since the early 1960s despite the introduction of potent
antibiotics and specialised intensive care units. The prognosis is worse
[10]
with a delay in management. Bacterial meningitis in adults (those
aged over 15 years) is a serious condition. The principles of prevention
and treatment are easy to state but, unlike recommendations in
guidelines for other conditions, the evidence base for many of our
recommendations is lacking or a subject of controversy. Despite the
existence of antibiotic therapies against acute bacterial meningitis,
patients with the disease continue to suffer significant morbidity and
[11]
mortality in both high and low-income countries. Dilemmas exist for
emergency medicine and primary- care providers who need to
accurately diagnose patients with bacterial meningitis and then rapidly
administer antibiotics and adjunctive therapies for this life-threatening
[7]
disease.
Marjolein J. Lucas,Matthijs C. Brouwer, et al in their study; published
in 2014, assessed the incidence, clinical characteristics, and outcome
of patients with bacterial meningitis presenting with a minimal score
on the Glasgow Coma Scale from a nationwide cohort study of adults
with community-acquired bacterial meningitis in the Netherlands
from 2006 to 2012. Thirty of 1,083 patients (3%) presented with a
score of 3 on the Glasgow Coma Scale. In 22 of 30 patients (73%), the
minimal Glasgow Coma Scale score; explained by use of sedative
medication or complications resulting from meningitis such as
seizures, cerebral edema, and hydrocephalus. Systemic (86%) and
neurologic (47%) complications occurred frequently, leading to a high
proportion of patients with un-favourable outcome (77%). However,
12 of 30 patients (40%) survived and 7 patients (23%) had a good
functional outcome, defined as a score of 5 on the Glasgow Outcome
Scale. They concluded that patients with community-acquired
bacterial meningitis rarely present with a minimal score on the
Glasgow Coma Scale, but this condition is associated with high rates of
morbidity and mortality. However, 1 out of 5 of these severely ill
patients will make a full recovery, stressing the continued need for
[12]
aggressive supportive care in these patients.
Schutte CM and van der Meyden CH in their study: found that, 88% of
patients with a GCS value of > 12 had a good neurological outcome,
while 88% of those with a GCS value of < or = 8 had a poor outcome.
They found good correlation between both the GCS and CSF-protein
level at admission and the outcome of patients with meningitis with the
GCS value. GCS value was a better prognostic indicator than high
[13]
CSF protein levels . Mani R, Pradhan S et al in their study conducted
[20]
in South India (NIMHANS) in 2007 observed that, as compared to
Western studies, the relative incidence of meningitis caused by H.
influenzae, N. meningitides and Listeria is less in South-East Asia. On
the contrary, gram negative bacilli such as Klebsiella pneumonia and
Pseudomonas aeruginosa are increasingly being recognised as
important pathogens of community-acquired as well as nosocomial
meningitis. It is especially seen among the elderly and in patients with
ch ron ic d ebi lit at ing di sea se s li ke c irr ho sis , diab ete s and
[14]
malignancies. As life expectancy is increasing, it may not be
uncommon to see an increased incidence of community acquired acute
bacterial meningitis in the elderly in the coming years. I. Steiner, H.
Budka et a l i n their rev iew o f d ia gn osis and m anageme nt
recommendations in Viral ence phal itis sta tes that analys is of
cerebrospinal fluid for protein and glucose contents, cellular analysis
and identification of the pathogen by polymerase chain reaction (PCR)
amplificatio n ( re c o m m e n d a t i o n l e v e l A) an d s e r o l o g y
(recommendation level B). Neuroimaging, preferably by magnetic
re son a nc e ima gin g , is a n es sen t ia l asp e ct of ev alu a ti on
(recommendation level B). Lumbar puncture can follow neuroimaging
when immediately available, but if this cannot be obtained at the
shortest span of time it should be delayed only in the presence of strict
contraindications. Brain biopsy should be reserved only for unusual
and diagnostically difficult cases. All encephalitis cases must be
[15]
hospitalized with an access to intensive care units.
Oliver Kastrup, Isabel Wanke, and Matthias MaschkeIn in their study
[16]
Neuroimaging of Infections states that cases of uncomplicated
meningitis, cranial computed tomography (CT) appears to be
sufficient for clinical management to exclude acute brainedema,
hydrocephalus, and pathology of the base of skull. Magnetic resonance
imaging (MRI) is superior in depicting complications like sub-
/epidural empyema and vasculitic complications notably on FLAIR
(fluid-attenuated inversion recovery)-weighted images. The newer
techniq ue of diffusion-wei ghted i maging (DWI) shows early
parenchymal complications of meningitis earlier and with more clarity
and is of help in differentiation of pyogenic abscess (PA) from ring
enhancing lesions of other aetiology. Pfister HW, Feiden W, Einhäupl
KM studied 86 patients with bacterial meningitis having central
ne rvo us syst em c omp lic ati ons , in clu din g br ain s we l li n g,
hydrocephalus, brain abscess, subdural empyema, or subdural effusion
(using computed tomography) and cerebrovascular involvement
(using cerebral angiography), systemic complications, including
septic shock, disseminated intravascular coagulation, adult respiratory
[17]
distress syndrome, or septic or reactive arthritis.
Acute bacterial meningitis diagnosis is based on clinical and
microbiological findings with neuroimaging in the form of MRI
reserved for those with specific adverse clinical features or when an
underlying cause such as mastoiditis is suspected. MRI is extremely
[11]
useful for detecting and monitoring the complications of meningitis.
A study named - Viral aetiology and clinico-epidemiological features
of acute encephalitis syndrome in eastern India conducted by Rathore
SK, Dwibedi B et al during April 2011 to July 2012. Blood and CSF
samples of 526 AES cases; investigated by serology and/or PCR. Viral
aetiology was identified in 91 (17·2%) cases. Herpes simplex virus
(HSV; types I or II) was most common (16·1%), followed by measles
(2·6%), Japanese encephalitis virus (1·5%), dengue virus (0·57%),
va ri ce ll a zos te r vir us (0·38%) an d ent er ov ir us es ( 0· 19 %) .
Simultaneous infection of HSV-I with measles; observed in seven
cases. This report provides the first evidence on viral aetiology of
Acute encephalitis syndrome viruses from eastern India showing
dominance of HSV that will be useful in informing the public health
[18]
system.
[19]
Panagariya A, Jain RS et al in a study conducted in North West India
with Herpes simplex encephalitis cases included patients admitted
with provisional diagnosis of an encephalitic illness over a period of 30
months. Special investigations included CSF analysis, EEG, CT scan
and MRI. Herpes simplex virus (HSV) antibody estimation in CSF and
blood; done simultaneously using ELISA. 28 patients showed
electroencephalographic, serologic and/or neuroradiological evidence
of herpes simplex encephalitis. Males affected more than females. Age
ranged from 4 years to 65 years. HSV encephalitis occurring
[20]
worldwide, contributing to 10-20% cases of viral encephalitis. Exact
incidence of this disease (HSE) is the most difficult to estimate,
because only few patients with common cause of fatal sporadic acute
encephalitis with severe disease report to hospital whereas mild and
self limiting cases usually go unrecognised. In India, HSE appears to
be under diagnosed, probably due to lack of awareness and diagnostic
facilities. Curiously, till 1992 only occasional case reports were
[21]
available. CT scan showed asymmetric fronto-temporal lesions with
or without haemorrhage in 18 (64%) cases. MRI was characteristic
with bilateral asymmetric fronto-temporal lesions in all the 16 patients,
in whom it was done. Magnetic resonance imaging appears to be the
most sensitive and specific neuroimaging method for HSE. It shows
hyper intense signals on T2WI in medial temporal and inferior frontal
[22]
areas bilaterally. These characteristic MRI findings seen in their
patients were similar to MR lesions seen in PCR confirmed HSE
[40]
patients of another series. MRI showed bilateral asymmetrical
fronto-temporal lesions in 12 cases, while bilateral isolated temporal
lesions were seen in 4 patients. All the four patients were below the age
of 19 years. Demonstration of virus in the brain biopsy is 100%
confirmatory test. However, brain biopsy is now rarely undertaken,
[23]
because of risk of haemorrhage and other complications.
HSE is the only form of sporadic encephalitis which has a specific
antiviral therapy i.e. acyclovir. HSE is not very uncommon and carries
a very high mortality and morbidity in absence of treatment. Acyclovir
is quite innocuous as well as effective, if used early in the course, a
Volume-9 | Issue-12 | December - 2019 | . PRINT ISSN No 2249 - 555X | DOI : 10.36106/ijar
INDIAN JOURNAL OF APPLIED RESEARCH
47
clinical criteria of diagnosis by exclusion and relevant supportive
evidences with EEG, neuroradiology and CSF examination may prove
to be practical in initiating treatment in most of the centres in Indian
conditions.
.
[25]
S.K. Handiquea, R.R. Das et al conducted a study named- Temporal
Lobe Invol vem ent in Jap ane se Encephalitis: Problems i n
Differential Diagnosis. In this study they selected sixty-two patients
with JE who underwent CT or MR imaging or both. On MR imaging
and CT, Japanese encephalitis (JE) shows lesions in the thalami,
substantia nigra, basal ganglia, cerebral cortex, cerebellum, brain
stem , an d wh ite matter, w hereas temporal lobe involvement;
characteristicall y seen in Herpes simplex enceph alitis (HSE).
Tempora l l obe in vo lv em ent in JE m ay c au se problem s i n
differentiating it from HSE. They undertook this study to show the
temporal lobe involvement pattern in JE and highlight differentiating
features from temporal lobe involvement in HSE. Eleven (17.7%)
patients showed temporal lobe involvement with abnormal MR
imaging in all. They concluded that the temporal lobe involvement
pattern is characteristic and mostly involves the hippocampus, usually
sparing the rest of the temporal lobe. This and the concurrent
involvement of the thalami, substantia nigra (SN), and basal ganglia
allow differentiation from HSE. If the temporal lobe involvement is
more severe, laboratory tests may be the only way to differentiate it
from HSE
Suyash Mohan, Krishan K. Jain Et al describes in their study- Imaging
of Meningitis and Ventriculitis describes how imaging helps in non-
invasive differentiation of infective from the non-infective conditions
and helps in better clinical decision-making. In acute meningitis;
meningeal enhancement is located over the cerebral convexity,
whereas in chronic meningitis it is most prominent in the basal cisterns.
The role of neuroimaging is to confirm suspected meningitis, rule out
meningitis mimics, evaluate for complications, and rule out increased
[26]
intracranial pressure before lumbar puncture. Magnetic resonance
imaging is critical in evaluating complications of meningitis (eg.
ven tr iculi tis, extra- axial co ll ectio ns, cere br itis and absce ss,
herniations, cranial neuropathy, and vasculopathy). A study aimed at
evaluating the clinical and radiological outcome of tuberculous
meningitis (TBM) patients with pulmonary miliary tuberculosis was
done by Kalita and Misra in which MRI was abnormal in 7 out of 8
patients(revealed hydrocephalus, granuloma, exudates and infarction)
and 3 of these patients had normal CT scan. This study shows the
Superiority of MRI over CT Scan in detecting Brain pathology of
[27]
Tuberculous aetiology. During the last two decades, the clinical
presentation of TBM has changed, Atypical presentations include
acu te me nin gi tis synd rome simu latin g p yo gen ic me ningi tis,
progressive dementia, status epilepticus, psychosis, stroke syndrome,
locked-in-state, trigeminal neuralgia, infantile spasm and movement
[28]
disorder
P Kamra, R Azad et al performed a study- Infectious meningitis:
prospective evaluation with magnetization transfer MRI. The
study was performed in lucknow (India) with the aim of prospectively
characterizing infectious meningitis of different aetiology using
magnetization transfer (MT) MRI. Spin-echo (SE) T1, T2 and pre- and
pos t-contra st T1 weig hte d M T imag es in 100 pati ents w ith
aetiologically proven meningitis were evaluated for the visibility and
enhancement of the meninges on pre- and post-contrast T1 weighted
MT images, respectively. The MT ratio (MTR); calculated from the
thickened meninges in tuberculous meningitis. In addition, the
percentage difference in the mean signal intensity (SI) of the meninges
and adjacent brain parenchyma was calculated and compared between
different groups. Visibility of the meninges on pre-contrast T1
weighted MT images may be considered highly suggestive of
[30]
tuberculous meningitis.
Wakai M1, Hayashi M et al report a case of acute onset of tuberculous
meningoencephalitis presenting with symmetric linear lesions in the
bilateral thalamus. It shows at the severest stage of the disease, a brain
MRI revealing symmetric, linear lesions without the effect of Gd-
enhancement in the bilateral thalamus, which thereafter disappeared
along with the healing of the illness. They conclude with the remarks
with; Thalamic and other parenchymal lesions must be kept in mind in
[31]
dealing with acute tuberculous meningo-encephalitis . Ete T,
Mondal S, Sinha D, Siddhanta S et al reported; in their case of Miliary
tuberculosis and tuberculoma of brain presenting like meningitis in
[32]
immunocompetent patient . Deepak Patkar, JayantNarang Et al in
their study- Central Nervous System Tuberculosis Patho-physiology
and Imaging Findings outlines that Imaging, particularly magnetic
resonance imaging, is a cornerstone in the diagnosis as well as follow-
up of central nervous system (CNS) tuberculosis. Imaging appearance
of CNS TB is becoming more and more complex and atypical with the
onset of multidrug-resistant tuberculosis. Early, accurate diagnosis can
help in preventing morbidity and mortality. Newer imaging techniques
li ke m agn et ic re s ona nc e spe ct ros copy he l p to im p r ove
[33]
characterization and thus aid in diagnosis of atypical CNS TB.
It is concluded that MRI could have an important role in the early
screening for infectious meningitis, provided a gadolinium-enhanced
FLAIR sequence is used.
RESULTS AND ANALYSIS
All immune-competent patients aged 12yrs or more were selected
randomly over a period of 19 months for this observational study as per
the clini cal in clu sio n c rit eria.18 cases(3 6%) we re male and
32cases(64%) were female. Patients ranging from ages 12 yrs to 77
yrs: selected and divided into age groups. Maximum number of
patients (26%) belonged to 12-20 yrs age group. (See figure 7)
The patients were clinically examined and classified into three groups
according to the Glasgow coma scale.15 cases (30%) belonged to
group A (GCS 3 to 5), 22 cases (44%) Belonged to Gr. B (GCS 6 to 9)
while 13 cases (26%) belonged to Gr. C (GCS 10 to 15) on admission,
30% patients had a very poor clinical condition (GCS 3 to 5) during
admission as evident from the GCS category distribution while
majority of patients belonged to group B. Patients were subjected to
MRI of brain with contrast (appropriate sequences were used)
followed by CSF examination. CSF culture and VIRAL ELISA:
performed as applicable and as per feasibility and availability. In some
cases, CSF study: done prior to MRI of brain for the sake of the patient
before initiating therapy. After obtaining the investigation results, the
cases: segregated into etiological groups and Re classified according
to the GCS groups and gender. Majority of cases had a viral aetiology
(56%) followed by tuberculous (28%) and bacterial aetiology (16%).
Pyogenic meningitis cases had a Male predilection (62.5%) while
tuberculous and viral meningitis had female predilection in incidence,
57.14% and 75% respectively. (See Figure-8)
Majority of pyogenic meningitis cases (37.5%) belonged to 31-40yrs
age group while maximum number of tuberculous meningitis cases
(35.71%) and viral Meningoencephalitis cases (28.57%) belonged to
12-20 yrs age group. Out of 50 cases 8 cases(16%) were diagnosed as
pyogenic meningitis[ 5males(62.5%) and 3 females(37.5%)] 1case
was in gr A(GCS 3 to 5), 5 cases in gr B(GCS 6 to 9) and 2 cases were in
gr C(GCS 10 to 15). So, 12.5% cases presented in a clinically severe
state (GCS 3 to 5) during admission. 14 cases (28%): diagnosed as
tuberculous meningitis [6males (42.86%) and 8 females (57.14%)].
Among them, 6cases were in gr A (GCS 3 to 5), 6 cases in gr B (GCS 6
to 9) and 2 cases were in gr C (GCS 10 to 15). 42.86% cases presented
in a clinically poor condition (GCS 3 to 5) on admission, 28
cases(56%) were diag nosed as viral meningoenceph ali tis [
7males(25%) and 21females (75%)] 8 cases were in gr A(GCS 3 to 5),
11 cases in gr B(GCS 6 to 9) and 9 cases were in gr C(GCS 10 to
15).28.57% cases presented in a clinically poor state(GCS 3 to 5) on
admission. After comparative analysis of three etiological groups and
their GCS categories it was found that tuberculous meningitis
cases(42.8%) presented in a more severe state followed by cases of
viral meningoencephalitis(28.57%) and pyogenic meningitis(12.5%).
CSF Findings
CYTOLOGY:
In cases that were later diagnosed as pyogenic meningitis, the cell
counts ranged from 120 to 5900 cells/cumm with a mean count of
950.5± 3748.84 cells/cumm and neutrophil predominance. In cases
with a final diagnosis of tuberculous meningitis, the cell counts
ranged fr om 60 t o 4 60 cells/cumm w it h a mean c ou nt of
225.86±217.22 cells/cumm, with lymphocyte predominance. In cases
categorized as viral meningoencephalitis, the cell counts ranged from
30 to 510 cells/cumm with a mean count of 128.607±276.86cells
/cumm and a predominantly lymphocytic picture.
BIOCHEMISTRY & ADA LEVELS:
Pyogenic meningitis cases reve aled a mean CSF glucose of
19±18.9mg/dl, mean protein levels of 62.375±48.52mg/dl, mean
chloride levels of 112.88± 12.48 meq/Lt with mean ADA level of
Volume-9 | Issue-12 | December - 2019 | . PRINT ISSN No 2249 - 555X | DOI : 10.36106/ijar
8.025±24.14. This picture was consistent with hypoglycorrhachias
expected in pyogenic meningitis.
Tuberculous meningitis cases revealed a mean CSF glucose of
35.79±22.9 mg/dl, mean protein levels of 268.86±368.12 mg/dl, mean
chloride levels of 112.714±12.54 mEq/Lt with mean ADA level of
16.29±16.14 U/L. Protein levels: markedly increased with ADA levels
also higher than normal range along with low glucose levels consistent
with the diagnosis.
Viral meningoencephalitis cases revealed a mean CSF glucose of
60.11± 32.28 mg/dl, mean protein levels of 96.96±91.98 mg/dl, mean
chloride levels of 113.45±14.32 mEq/Lt with mean ADA level of
3.76±4.38U/L. The protein levels were higher with normal glucose
levels.
CSF CULTURE, STAINING AND VIRAL PCR:
According to affordability of the patient and availability of appropriate
facilities in Eastern India CSF culture and staining, CSF viral antibody
detection by ELISA(when suspected) were sent with the routine
samples. Some cases were diagnosed accurately from CSF culture and
ELISA that were corroborating with the clinical assumptions and
radiological imaging findings.
PYOGENIC MENINGITIS ETIOLOGIES:- (N=8)
CSF gram staining and culture revealed Streptococcus pneumoniae in
4( 5 0% ) cas es, N eis s er ia m eni n gi tid es in 1(1 2.5 % ) ca se ,
Staphylococcus aureus in 1(12.5%) case and culture negative in
2(25%) cases. This shows that majority of the culture positive cases
were positive for Streptococcus pneumonia followed by equal
incidence of Neisseria meningitides and Staphylococcus aureus. 25 %
cases that were culture negative had classical symptoms which
resolved with empiric antibiotics.
TUBERCULOUS MENINGITIS:- (N= 14)
All the cases suspicious of tuberculous aetiology were ZN smear
negative. CSF culture was negative in 10 cases (71.4%) while culture
could not be done in 4 cases(28.6%). Diagnosis had to established on
clinical features, CSF cytology, CSF biochemistry, brain imaging and
therapeutic response to antitubercular drugs.
VIRAL MENINGOENCEPHALITIS:- (N=28)
Patients with CSF cytology indicating a viral infection revealed the
following viral etiologies in CSF Elisa( IgG). 10 cases(35.72 %) were
positive for Herpes simplex, 3 cases(10.72%) were positive for
Varicella zoster,4 cases(14.28%) were positive for Japanese B while 11
cases (39.28%) were negative or indeterminate.
.
MRI FINDINGS:
(With contrast and appropriate sequences as relevant and applicable.)
The MRI findings as observed and analysed with the expert opinion of
the radiologists not only strengthened our diagnosis but revealed
different patterns of lesions varying with MRI sequences (T1, T2,
FLAIR and DWI with gadolinium contrast) and involving certain
anatomical regions of brain and the meninges. They not only revealed
the morphological spectra of the primary pathology but also the
sequelae, complications and associated features. The pattern of
involvement in MRI Brain has been described below. They are
classified into groups which were in some cases coexistent and had a
considerable overlap in different cases in varying combinations.
Cases diagnosed as Pyogenic Meningitis revealed.
PATTERN OF LESION:
Cerebritis with hypo-intensities on T1 and hyper-intensities on T2
Flair sequences seen in 4 cases(50%). Meningeal enhancement on T2
weighted images in 4 cases(50%), Ventriculitis with intra-ventricular
fluid collections in 3 cases(37.5%), Lacunar infarcts evident on DWI
sequence in 2 cases(25%), Middle cerebellar peduncle involved with
patchy signal intensities and mild restricted diffusion along with
patchy enhancement of right cavernous sinus (suggestive of cavernous
sinus thrombo-phlebitis) in 1 case(12.5%). Maxillary sinusitis was
found in 1 case(12.5%) and 2 cases(25%) had a normal MRI.
ANATOMICAL AREAS INVOLVED
4(50%) cases showed meningeal involvement, 2(25%) cases involved
the peri-ventricular area, 1case(12.5%) showed basal ganglia lacunar
infarct, 1(12.5%) case revealed patchy altered signal intensities
involving the middle cerebellar peduncle with mild restricted diffusion
and 1(12.5%) case involved centrum semiovale region.
CASES WITH A FINAL DIAGNOSIS OF TUBERCULOUS
MENINGITIS REVEALED—
PATTERN OF LESION :
Mildly dilated ventricles or hydrocephalus in 9 cases(64.29%).
Meningeal enhancement on T2 weighted images in 7 cases (50%).
Ring enhancing or nodular lesions scattered in various parts of brain in
6 cases(42.86%). Perifocal or peri-lesional edema in 5 cases(
35.71%), Infarcts in different areas of brain in 4 cases(28.57%),
Granulomatous lesions in 3 cases(21.43%) and normal MRI in 1 case
ANATOMICAL AREAS INVOLVED :
Ventricles dilated in 9 cases(64.29%), Meningeal enhancement in 7
cases (50%), Basal ganglia in 6 cases(42.86%), Thalamic involvement
in 5cases(35.71%), Parietal area in 5 cases(35.71%), Brainstem in 3
cases(21.43%), Cerebellum in 3 cases(21.43%),Occipital region
involved in 2 cases
CASES CATEGORIZED AS VIRAL MENINGOENCEPHALITIS
AFTER DIAGNOSIS REVEALED—
T2 hyper intensities in Temporal region in 7 cases(25%) ,Thalamic
involvement in 7 cases(25%), Periventricular area in 6 cases (21.43%)
with lacunar infarct in periventricular and basal ganglia region in 1case
out of the 6 cases. Hypo intense on T1 weighted images with Hyper
intensities on T2 FLAIR images were seen in Parietal area in 5 cases
(17.86%)and Basal ganglia or Midbrain involvement seen in 4 cases
eac h(14. 29% ). Front al area al ong with parie tal or te mpora l
in vol vem ent (h ae mor rha gic co mp one nt) were f o un d i n 2
cases(7.14%). Cerebellar hyper intensities with effaced folia seen in 1
case (3.57%) and Corpus callosal (splenium) hyperintensity seen in 1
case (3.57%). 11 cases( 39.29%) had a normal MRI. 10cases(35.72%)
were established as Herpes simplex encephalitis as confirmed on CSF
ELISA and they had similar MRI findings. Hypo to iso intense on T1
weighted images while hyper intensities on T2 FLAIR images were
observed in temporal areas with fronto-parietal or temporo-parietal
spread along with basal ganglia, thalamus and midbrain involvement
in varying combinations in different cases. 4 cases (14.28%) with
positive clinical suspicion were diagnosed as cases of Japanese B
encephalitis on CSF serology (positive IgG for Jap B). They had
similar MRI findings when analysed after obtaining the serology
results. 75% of the four cases had bilateral thalamic hyper intensities
along with midbrain involvement in 2cases and basal ganglia with
periventricular involvement in 1case. While 25% of the 4 cases had
MRI simulating Herpes virus encephalitis. The MRI revealed hyper
intensities on T2 Flair images in bilateral temporo-parietal region,
basal ganglia, thalamic and paraventricular area. 3(10.72%)cases with
history of varicella zoster virus infection shared similar MRI feature of
periventricular T2 hyper intensities in all and lacunar infarcts in
2(7.14%) out of the 3 cases. 11(39.28%)cases were etiologically
inconclusive due to negative CSF ELISA. The MRI revealed bilateral
thalamic involvement with corpus callosal hyper intensities in 1case
(3.57 %) , 1 ca se (3.57%) had cerebe ll ar hy per i ntens it ies, 1
case(3.57%) had periventricular T2 enhancement and another case
showed bilateral thalamic, basal ganglia and midbrain involvement.
63.64% of these cases had a normal MRI of brain. 2 (7.14%) cases had
a positive history of measles in recent past and 3(10.72%) cases were
suffering from dengue along with meningoencephalitis. All 5 cases
had a normal MRI of brain. Now whether the measles or dengue
infection culminated into meningoencephalitis in those cases or they
were distinctly coexistent and totally unrelated to each other, could not
be exactly infer.
CO MPA RI SON OF MRI FIND INGS IN D IF FERE NT
ETIOLOGICAL GROUPS
Analysing the MRI findings of different etiological groups following
findings were noticed.
In pyogenic meningitis cases meningeal involvement was seen in 50%
cases while brain parenchymal involvement were relatively less as
compared to other etiological groups. Ventriculitis was seen in 37.5%
cases and infarcts seen in 25% cases could be attributed to a sequelae of
cerebritis and cerebral vasculitis.
In tuberculous meningitis cases, various anatomical areas were
48
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aff ected wi th pa ttern of br ain p arenc hymal an d v en tricu lar
involvement consistent with the diagnosis. The MRI's played a pivotal
role in confirmation of diagnosis with identification of the sequelae and
complications of tubercular infection. Majority of cases (64.29%)
revealed hydrocephalus. Ring enhancing lesions (42.86%) and
granulomas (21.43%) confirmed by MR Spectroscopy (in situations of
diagnostic dilemma). Meningeal enhancement was marked in 50%
cases. Infarcts were noted in 28.57% probably due to cerebral arteritis
and ischemia because of tubercular infection. The MRI findings on
retrospective analysis corroborated with the maximum clinically
severe cases (as per GCS category) during presentation in this
etiological group.
Viral meningoencephalitis cases showed cerebral hyper intensities (on
T2W, Flair images) in majority of cases (60.71%), attributable to the
seizure episode at or before presentation. Most of those cases which
turned out to be inconclusive in CSF ELISA, had a normal MRI
(39.29%) and belonged to Group C (GCS 10 – 15) during admission.
Thus, it was marked that patients who were relatively better clinically
and had negative viral ELISA had normal brain imaging or minimal
findings in MRI.
DISCUSSION
PYOGENIC MENINGITIS
Acute bacterial meningitis is more common in resource-poor than
resource-rich settings. Survival is dependent on rapid diagnosis and
early treatment, both of which are difficult to achieve when laboratory
support and antibiotics are scarce.
SyamalModi and Amit Kumar Anand in their study Phenotypic
Characterization and Antibiogram of CSF Isolates in Acute
Bacterial Meningitis done in a tertiary care hospital Patna (India)
found that 62.3% patients were males and 37.7% were females. The
gender distribution and male preponderance in disease incidence was
also marked (62.5 % males and 37.5% females) in our study done in
Eastern India. In our study sample, size was smaller in comparison to
[33]
theirs. This male predilection reported in several previous studies .
Similar to the study by Marjolein J. Lucas, Matthijs C. Brouwer et al
[12]
(2014) . patients using immunosuppressive drugs and those with
as pl eni a, d ia be tes mel li tu s, a lc oho li sm , or i nf ect io n with
immunodeficiency vir us: conside red immunocompromised and
excluded from our study.
The Glasgow coma scale (GCS) is an objective measurement of a
patient's level of consciousness and has prognostic implications in
traumatic head injuries. Morbidity and mortality of patients with
meningitis have related amongst others to level of consciousness,
hypoglycorrhachia, extremes of age, and high CSF protein values.
Schutte CM, van der Meyden CH in their study found patients with a
GCS value of > 12 had a good neurological outcome, while those with
a GCS value of ≤ 8 had a poor outcome. They concluded that the GCS
[13]
value was a better prognostic indicator than high CSF protein levels .
In our study we adapted GCS as the criteria for clinical severity. Group
A (GCS 3 to 5) considered as most severe clinical category. Pyogenic
meningitis accurately and rapidly diagnosed by gram staining. Some
studies have reported: sensitivities- 60-90% and specificities >97% of
[34]
CSF on gram staining in diagnosis of ABM . .In our study 50%
cas es we re di agnos ed as St repto co ccus pneumo nia indu ce d
meningitis, followed by equal incidence of Neisseria meningitides and
Staphylococcus aureus cases (12.5% each) on CSF gram staining and
culture 25percentage cases did not reveal any organism on CSF
culture. Negative CSF cultures are estimated to occur in 11%–20% of
[3 5]
patie nt s w it h bacter ia l m en in gitis Howeve r, the cl in ical .
presentation of patients with culture-positive bacterial meningitis and
patients with culture- negative bacterial meningitis was reported to be
similar. R Mani, S Pradhan et al in their study conducted in South India
(NIMHANS): found that streptococcus pneumoniae was the most
common etiological agent of community acquired meningitis in all age
groups accounting for 238 (61.8%) cases in their study, reflecting a
similar trend reported in an earlier study from their institute (1978-
[36]
1988). Most Indian studies have also reported a high incidence of
[37]
pneumococcal meningitis In our study also Streptococcu s .
pneumonia was the most common organism isolated from CSF
culture(50% cases). Analysis of the CSF is essential, and simple
techn iques can enhance the yield of diag nostic microbiology.
Penicillin-resistant and chloramphenicol-resistant bacteria are a
considerable threat in resource-poor settings that go undetected if CSF
and blood cannot be cultured.
Magnetic resonance imaging (MRI) is not routinely required in cases
of uncomplicated bacterial meningitis. It helps to visualize meningeal
enhancement more clearly. Potential sources of infection include
fractures of the paranasal sinus or petrous bone as well as inner ear
infection and mastoiditis. Pyogenic ventriculitis is an uncommon but
very severe intracranial infection requiring rapid diagnosis and
therapy because of its high mortality. Neuroimaging is the only tool to
reliably diagnose this life-threatening condition. MRI is more sensitive
and shows periventricular high signal on FLAIR images, ependymal
[16 ]
Enh anc ement Pyo gen ic and asepti c me ningitis may cau se .
leptomeningeal enhancement. Meningitis also may cause venous
thrombosis with hyper-densities on the surface of the brain or along
venous sinuses on brain MRI. Magnetic resonance venography (MRV)
: used to confirm venous thrombosis.
In our study a case showed cavernous sinus thrombophlebitis in MRI
and was considered a complication and consequence of the bacterial
meningitis. 50% cases showed meningeal involvement, 25% cases
involved the periventricular area, 12.5% showed basal ganglia lacunar
infarct,12.5% case revealed patchy altered signal intensities involving
the middle cerebellar peduncle with mild restricted diffusion and
12.5% case involved centrum semiovale region. Infarcts: considered, a
sequelae of cerebritis and vasculitis. MRI of patients suffering from
pyogenic meningitis were somewhat nonspecific in some cases and did
not contribute much to the confirmation of diagnosis. The future rests
with the provision of eff ective conjugate vac cines again st S
pneumoniae, Haemophilus influenzae, and Neisseria meningitides to
[39]
children in the poorest regions of the world.
VIRAL MENINGOENCEPHALITIS
Cranial MRI is superior to CT in early detection of signs of this
necrotizing encephalitis, which can be demonstrated within the first 48
h on T2-weighted (T2WI) or FLAIR images.39 In infants and
neonates, DWI appears to be more sensitive than T2WI or FLAIR
imaging in early detection of the cytotoxic cortical edema.[40]
A study named - Viral aetiology and clinico- epidemiological features
of acute encephalitis syndrome in eastern India conducted by Rathore
[18]
SK, Dwibedi B et al during April 2011 to July 2012. Blood and CSF
samples of 526 AES cases were investigated by serology and/or PCR.
Viral aetiology was identified in 91 (17·2%) cases. Herpes simplex
virus (HSV; types I or II) was most common (16·1%). Simultaneous
infection of HSV I with measles was observed in seven cases. This
repor t provides the first evid ence on viral aetiology of acute
encephalitis syndrome viruses from eastern India showing dominance
of HSV that will be useful in informing the public health system. In
our study, there were majority of HSV cases. In CSF Elisa (IgG). 10
cases(35.72 %) were positive for Herpes simplex, 3 cases(10.72%)
were positive for Varicella zoster,4 cases(14.28%) were positive for
Japanese B while 11 cases(39.28%)were negative or indeterminate.
Therefore, there is a similarity and etiological preponderance of HSV
in both western and eastern India.
In our study MRI brain in cases with herpes simplex encephalitis
revealed predominan t temporal lobe and in ferior frontal lobe
involvement along with T2 hyper intensities in parietal lobes too. This
neuroimaging finding is characteristic of herpes simplex encephalitis
as described in various literatures and other studies.
Japanese encephalitis (JE) is the leading cause of encephalitis in
Southeast Asia, where 30,000–50,000 cases are recorded annually
[41]
(Tsai, 1997). The World Health Organisation estimated nearly
14,000 deaths due to JE in the year 2002. Of these, 8,500 occurred in
Southeast Asia, 3,000 in the western Pacific region and about 2,000 in
the eastern Mediterranean region. Typical MRI features consist of
either mixed intensity or hypo intense lesions on T1WI and hyper
intense or mixed intensity lesions on T2WI predominantly in the
thalami, but also in the basal ganglia, brainstem, cerebellum, and
[16]
cortical areas This was also congruous to our neuroimaging findings .
that guided our investigations to reach an early diagnosis. 14.28%
cases were positive for Japanese B in our study.
During analysis of the study a solitary case h ad concu rrent
involvement of temporal lobes with bilateral thalamus and basal
ganglia, simulating herpes encephalitis. It was confirmed as Japanese
B encephalitis (JE) on CSF serology. As cited by S.K. Handique, R.R.
Das in their study, this pattern of involvement although not that
common, may be seen in JE creating a diagnostic dilemma with herpes
INDIAN JOURNAL OF APPLIED RESEARCH
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Volume-9 | Issue-12 | December - 2019 | . PRINT ISSN No 2249 - 555X | DOI : 10.36106/ijar
encephalitis. So an early MRI of brain with characteristic findings may
provide an important clue to the diagnosis in situations where antibody
estimation for JE is not readily available.
The incidence of neurologic complications associated with varicella is
[42]
estimated to be 1–3 per 10,000 cases . The central nervous system
(CNS) manifestations that occur most frequently with varicella are
[42]
cere bell ar ataxi a and encephalitis . The most ser ious CNS
complication of varicella, has an incidence of 1–2 episodes per 10,000
[43]
varicella cases, with the highest incidence in adults and infants. The
CSF findings are usually abnormal with elevated opening pressure, a
mild-to-moderate lymphocytic pleocytosis (usually <100 cells/μL),
mildly elevated protein (50–100 mg/dL), and normal glucose levels.
CNS imaging studies may show edema and areas of low attenuation
[44]
consistent with demyelination . In our study 10.72% cases with
history of varicella zoster had positive CSF Elisa. Their neuroimaging
revealed periventricular hyper intensities and focal white matter signal
changes similar to that seen in demyelination. So in this context it may
be taken into consideration that in developing countries like India,
MRI may prove to be an important noninvasive diagnostic tool in cases
of meningoencephalitis.
Dengue encephalopathy is a well-recognized and common entity, the
[45]
incidence ranging from 0.5 to 6.2 %. Dengue is not classically a
neurotropic virus, although there is recent evidence of direct neuronal
injury. Dengue encephalitis must be thought of in differentials of
encephalopathy, in patients with dengue. In such cases, neuroimaging
and CSF analysis should be done whenever possible. The virus or
antibody can be isolated from the serum, but the CSF samples may be
negative. The dengue encephalitis is thought to be benign, but can be
[46]
fatal at times.
We found 3 such cases in our study with feature of encephalopathy who
were diagnosed cases of IgM positive dengue with CSF analysis
indicating a viral aetiology and a normal MRI . Dengue specific IgM
antibody (ELISA) was negative in 2 and could not be done in 1 case. In
light of our knowledge regarding dengue encephalopathy, a negative
CS F ant ib ody canno t ref ut e it s presen ce . So whe the r t he
ence phalopa thy was due to some other vir al p athogen or as
consequence of dengue could not be confirmed. All 3 patients survived
without any residual neuro deficit or CNS complications.
Infection of the CNS with the measles virus (MV) may result in 1)
acute post-infectious encephalitis, 2) acute progressive encephalitis,
and 3) SSPE. Data about imaging find ings in acute measles
encephalitis are sparse. T2WI may reveal cortical edema and bilateral
symmetric hyper-intense lesions within the putamen and caudate
[47]
nuclei as well as within the centrum semiovale. Sometimes patients
also present bilateral thalamic lesions and signal abnormalities within
the corpus callosum. We found 2 cases with a recent history of measles
who subsequently developed features of encephalopathy. The disease
was self limiting and their MRI were normal.
We would sum up in accordance to I. Steiner, H. Budka et al and their
review of diagnosis and management recommendations in Viral
[21]
encephalitis. A holistic approach to diagnosis should be based on
medical history, examination followed by analysis of cerebrospinal
fluid fo r protein and gluco se contents , cellular analysis and
identification of the pathogen by polymerase chain reaction (PCR)
am p l i fic a t i on ( rec omm enda tion leve l A) a nd se ro logy
(recommendation level B). Neuroimaging, preferably by magnetic
resonance imaging, is an essential aspect of evaluation (recommen
dation level B).
Lumbar puncture can follow neuroimaging when immediately
available, but if this can not be obtained at the shortest span of time
it s h ould be de la y e d o n l y i n t h e p rese nc e o f s tr i ct
contraindications. All encephalitis cases must be hospitalized with an
access to intensive care units. Supportive therapy is an important basis
of management. Sp ecific, eviden ce- bas ed, anti-viral t her apy ,
acyclovir, is available for herpes encephalitis (recommendation
level A). Acyclovir might also be effective for varicella-zoster virus
encephalitis, gancyclovir an d foscarnet f or cyto meg alovirus
encephalitis
TUBERCULOUS MENINGITIS
J Kalita, UK Misra in their study evaluated the clinical and radiological
outcome of tuberculous meningitis (TBM) patients. In this study, most
of the pat ients were females who were anemic.MRI revealed
hydrocephalus, exudates, infarction and multiple granuloma and the
majority of the patients improved following antitubercular therapy. In
our study there was a female predilection (57.14%). Under nutrition
and anaemia may be a result or risk factor for development of
tuberculous meningitis. We came across a wide range of clinical
spectra and various morphological patterns of brain involvement with
complications as evident on brain MRI. Adults with tuberculous
meningitis (TBM) can often present with the classic meningitis
symptoms of fever, headache and stiff neck along with focal
neu rologica l d efic its, b ehavi ora l c hanges, and alte rat ions in
[48]
consc iousness . A history of tuberculosis is elicited in onl y
[48]
approximately 10% of patients The presence of active pulmonary .
tuberculosis on chest X- ray ranges from 30 to 50%. TBM may have an
acute presentation. The duration of presenting symptoms may vary
from 1 day to 9 months, although several cases may present with
symptoms of less than 2 weeks duration. In our cases patients had a
history of less than 2 weeks duration prior to admission.
Cerebrovascular complications of tuberculous meningitis that occur
typically as multiple or bilateral lesions in the territories of the middle
cere bral artery perforating ves sels are ter med as tuberc ulous
vasculopathy. Vessel pathology appears to be a consequence of its
immersion in the local inflammatory exudate. Infiltrative, proliferative
and necrotising vessel pathologies have been described, leading to
luminal thrombosis. There is some evidence that vasospasm may
mediate strokes early in the course of the disease and proliferative
[49]
intimal disease later strokes In this study we encountered 28.57% .
cases with cerebral infarcts.
Contrast enhanced MRI, generally considered as the modality of
choice. It is useful for assessment of the location of lesions and their
margins, as well as ventriculitis, meningitis and spinal involvement
[50]
(sensitivity 86%, specificity 90%) A large lipid, lactate peak has .
been used to specifically identify tuberculomas by magnetic resonance
[93]
spectroscopy In TBM, MRI shows diffuse, thick, meningeal .
[51]
enhancement. Cerebral infarcts can be seen in nearly 30% of cases A
.
study f ro m S ou th Afric a rep or te d t ha t t he combination of
hydrocephalus, basal enhancement and infarction was 100% specific
and 41% sensitive for the diagnosis of TBM, although the authors
suggested pre-contrast hyper density in the basal cisterns as the best
[52]
predictor of TBM. Our cases had classical findings indicating TBM.
Ring enhancing lesions, perifocaledema, granulomatous lesions and
infarcts (due to vasculopathy or vasospasm as described above) in
var iou s a natomica l loca tio ns. Hydroce pha lus an d m eningeal
enhancement were also seen in the MRI's of our cases.
SUMMARY
This observational study was done in a tertiary care hospital of Eastern
India. 50 consecutive hospital admitted patients (>12 yrs) fulfilling the
inclusion criteria were randomly selected over a period of 19 months. A
male preponderance was marked in Pyogenic meningitis cases while a
female preponderance was noted in tuberculous meningitis and viral
meningoencephalitis cases.
An increased propensity of disease occurrence was seen in age groups
31-40 yrs in pyogenic meningitis and younger age groups ( 12- 30 yrs )
were more affected in tuberculous and viral meningoencephalitis.
Individual patients assessed by clinical status on admission and
divided into three GCS groups. 15 cases(30%) belonged to group
A(GCS 3 to 5), 22 cases(44%) belonged to gr B(GCS 6 to 9) while 13
cases( 26%) belonged to gr C( GCS 10 to 15) on admission. 18
cases(36%) were male and 32 cases(64%) were female. Patients ages
ranging from 12 yrs to 77 yrs were selected and divided into age
groups. CSF study and MRI brain was done and etiologically the cases
were reclassified.
Out of 50 cases 8 cases (16%) were diagnosed as pyogenic meningitis [
5 males (62.5%) and 3 females (37.5%)], 14 cases (28%) were
diagnosed as tuberculous meningitis [6males (42.86%) and 8 females
(5 7.1 4%) ] and 28 ca ses (5 6% ) wer e dia gno s ed a s v ir al
meningoencephalitis [7males (25%) and 21females (75%)]. CSF
study revealed neutrophilic picture with hypoglycorrhachia in
bacterial meningitis with CSF culture studies revealing Streptococcus
pneumoniae as the most commonly isolated pathogen (50% cases).
Tuberculous meningitis revealed CSF lymphocytic pleocytosis with
significantly increased protein and ADA levels. CSF ZN staining in all
cases were negative, CSF culture for tuberculosis was negative
50
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in71.4% cases and could not be done in 28.6% cases although the
diagnosis was established on other parameters and imaging evidence.
The CSF samples of viral meningoencephalitis revealed lymphocytic
picture and increased protein with majority of cases being positive for
Herpes simplex antibody (in CSF by ELISA method) in 35.72%.
14.28% cases were positive for Japanese B antibody. 10.72% cases
were diagnosed as Varicella zoster cases. Serological confirmation of
diagnosis was not possible in other cases due to non-availability of the
specific test (Viral PCR) or a negative serology in 39.28%.
MRI Brain was done with gadolinium contrast, using appropriate
sequences( T1W, T2W, FLAIR, GRE, DWI, Spectroscopy).The
morphological patterns as evident on MRI Brain were studied in each
patient. Cases with suspicion of pyogenic meningitis had features of
cerebritis, patchy hyper intensities of middle cerebellar peduncle
(12.5%),T2 hyper intensities of meninges and ventriculitis. Maxillary
sinusitis was noted in 12.5%, lacunar infarcts were noted in 25% cases
as se quelae. One case was complicated w ith cavernous sinus
thrombophlebitis (patchy enhancement) clinically presenting with
ophthalmoplegia.25% cases had a normal MRI.
The pattern of lesions identified in brain MRI in tuberculous
meningi ti s cases we re - H yd ro ce phalus(64 .2 9% ), me ni ng ea l
enhancement(50%), ring enhancing or nodular lesions(42.86%),
granulomatous lesion(21.43%) with perifocaledema(35.71%). The
pattern of radiological abnormalities identified in different anatomical
regions of brain and found in varying combinations. Apart from one
case out of 14 cases in this group, all the MRI's were abnormal and
helped immensely in confirmation of diagnosis.
In viral meningoencephalitis cases T2 hyper intensities were seen in
inferior frontal and temporal lobes (extension into parietal lobes in
some cases) with or without haemorrhagic component, consistent with
the diagnosis of Herpes Simplex encephalitis. Bilateral thalamic T2
hyper intensities (25%cases) with enhancement of basal ganglia
region: consistent with the diagnosis of Japanese B encephalitis. 1 case
had concurrent involvement of temporal lobes with bilateral thalamus
and basal ganglia, simulating herpes encephalitis. It was confirmed as
Japanese B encephalitis (JE) on CSF serology. This pattern of
involvement although not that common may be seen in JE creating a
diagnostic di lem ma with her pes encephalitis. P eri ven tri cular
hyperintensities(21.43% cases) and lacunar infarct(7.14%) were seen
in MRI's. Definite serological confirmation was not possible inm these
cases but periventricular hyperintensities suggest a possibility of CMV
encephalitis.
Lacunar infarcts and haemorrhages may be seen as asequelae of
secondary CNS vasculitis and focal white matter signal changes
(si mi lar to demyel inati ng le sions ) c onsiste nt with varice ll a
encephalitis. 39.28% cases had a normal MRI out of which 2
cases(7.14%) had a history of measles immediately prior to the
development of neurological symptoms and 3 cases (10.72%) were
suffering from Dengue during the episode of encephalopathy. 35.72%
cases were etiologically inconclusive without any suggestive history
of possible viral pathogen.
In pyogenic meningitis cases brain parenchymal involvement was
relatively less as compared to other etiological groups. In tuberculous
meningitis ca ses the MRI fi ndi ngs on ret ros pec tiv e analysis
corroborated with the maximum clinically severe cases (as per GCS
category) during presentation. Viral meningoencephalitis cases
showed cerebral hyper intensities (on T2W, Flair images) in majority
of cases (60.71%), attributable to the seizure episode at or before
presentation. Thus, it was marked that patients who were relatively
better clinically and had negative viral ELISA also had normal brain
imaging or minimal findings in MRI. The MRI has played a pivotal
role in confirmation of diagnosis with identification of the sequelae and
complication.
LIMITATIONS OF THE STUDY
Sample size is small (N= 50). This study was done over a certain
catchment area, hence not a multicentric study. As the study was done
in a tertiary care hospital, the mean values may not properly reflect the
actual population mean. Empiric therapy had to be started in most of
the cases prior to confirmation of diagnosis, for the sake of the patients.
Some of the patients who fulfilled the inclusion criteria, had to be
excluded due to economic constraints.
CONCLUSION
In this Eastern India based study viral aetiologies' were more
frequently detected (56%) followed by tub ercu lar (28%) and
pyogenic(16%) causes of disease. There was an overall female
preponderance (64%) with maximum number of patients belonging to
younger age groups. Male predilection in pyogenic meningitis
(62.5%) and a female predilection (57.14%) in tuberculous meningitis
was noted, which was similar to several other studies done in other
parts of the world. Most of the tuberculous meningitis cases (42.8%)
were clinically more severe according to the GCS category during
admission followed by viral meningoencephalitis (28.57%) and
pyogenic meningitis (12.5%). CSF cytology revealed neutrophillic
picture in pyogenic and lymphocytic pleocytosis in tuberculous and
vir al m e n i ngo en c e phal it i s. CSF bi oc hem is t r y r evea le d
hypoglycorrhachia in pyogenic and tuberculous meningitis and high
protein levels in viral and grossly high protein content in tuberculous
meningitis cas es. ADA levels were also high in tub erculous
meningitis. CSF gram staining, culture and serology results showed
Streptococcus pneumoniae as the most common pathogen causing
pyogenic meningitis(50%) and Herpes simplex as most common viral
pathogen(35.72%) causing meningoencephalitis. MRI findings were
highly informative, reliably contributed in diagnosis and helped in
retrospective analysis of symptom complex and sequelae. Brain
parenchymal involvement was more marked in viral meningitis in the
form of T2 hyperintensities in various anatomical sites, predominantly
in the temporal lobe in herpes simplex encephalitis and bilateral
thalamic involvement with basal ganglia involvement in Japanese B
encephalitis. Infarcts were noted in Varicella zoster encephalitis. Brain
Imaging(MRI) of tuberculous meningitis cases unveiled a wide
spectrum of parenchymal affection in the form of ring enhancing
lesions, cerebral granulomas, infarcts and edema al ong with
hydrocephalus. These two etiological groups comprised of more
number of cases presenting with seizures and altered sensorium as
compared to pyogenic meningitis cases. MRI of patients suffering
from pyogenic meningitis were somewhat nonspecific in some cases
and did not contribute much to the confirmation of diagnosis. This is a
potential area of research and rightfully demands attention in the near
future. India being a resource poor nation, improvisation of the specific
diagnostic modalities and implementation with regard to affordability
should be prioritised. Especially in this part of the world, there is a
dearth of multi centric prospective studies on meningoencephalitis.
More studies to be conducted based on correlation of clinical aspects
with brain imaging; prognostication and taking into account the long-
term outcomes.
Figure 1 Figure 2 Figure 3 Figure 4 Figure 5
FIG 1& FIG 2: Bilateral temporal and inferior frontal hyper intensities
on T2 Flair images. Suggestive of Herpes simplex encephalitis. FIG 3
& 4- Viral haemorrhagic encephalitis suggestive of herpes simplex
enc ephal itis. FI G 5 - H erpes En cepha litis sh owing te mpora l
enhancements
Figure 6. Figure 7. Figure 8. Figure 9. Figure 10
FIG 6 & FIG 7- Bitemporal T2 Hyperintensities favouring Herpes
encephalitis. FIG 8- Showing meningeal enhancement post contrast in
the same patient. FIG 9 & 10- Right periventricular infarct in T2 Flair
image as a sequelae of pyogenic meningitis.
Figure 11. Figure 12. Figure 13. Figure 14. Figure 15
INDIAN JOURNAL OF APPLIED RESEARCH
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Volume-9 | Issue-12 | December - 2019 | . PRINT ISSN No 2249 - 555X | DOI : 10.36106/ijar
FIG 11, 12,13,14- Bilateral thalamic T2 hyperintensities in a case of
Japanese B encephalitis. FIG 15- Extensive rim enhancing nodular
focal lesions of various sizes with mild perilesional edema scattered in
both cerebral hemispheres (Tuberculomas). A case of TB Meningitis.
Figure 16. Figure 17. Figure 18. Figure 19. Figure 20.
Figure 21. Figure 22. Figure 23. Figure 24. Figure 25
FIG 16 & 17: Ring enhancing and granulomatous lesion suggestive of
TB Meningitis.
FIG 18 & 19: Right cerebral infarct with periventricular ischaemia and
hydrocephalus conspicuous in post contrast T2 Flair image. A case of
TB Meningitis. FIG 20: Hydrocephalus in a case of TB Meningitis.
FIG 21 & 22: Brainstem hyperintensities with ring enhancing lesion in
a ca se of TB Meningitis. F IG 2 3: Left parieto oc cip ital T2
Hyperintensities in a case of viral meningoencephalitis. FIG 24& 25-
Shows patchy altered signal intensities in right cerebellar peduncle
with eviden ce of mi ld re stric te d d iffus io n. Patch y contra st
enhancement of right sided cavernous sinus. (Right cavernous sinus
thrombo phlebitis).
CHARTS
Chart 1: Pattern of lesion in Pyogenic Meningitis
Chart 2: Anatomical areas involved in Pyogenic Meningitis
Chart 3: Tuberculous Meningitis: Pattern of lesion
Chart 4: Tuberculous Meningitis: Anatomical areas involved:
Chart 5: Viral Meningoencephalitis: Anatomical areas involved
Chart 6: Viral Meningoencephalitis: Pattern of lesion:
FIGURES
Figure 1
Pyogenic Meningitis-pattern of involvement in
MRI brain
No. of
Cases
Cerebritis
4
Infarcts
2
Cerebellar peduncle
1
Cavernous sinus thrombophlebitis
1
Ventriculitis with
intraventricular fluid collection
3
Meningeal enhancement
4
Maxillary sinusitis
1
Normal
2
52
INDIAN JOURNAL OF APPLIED RESEARCH
Volume-9 | Issue-12 | December - 2019 | . PRINT ISSN No 2249 - 555X | DOI : 10.36106/ijar
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Figure 2
Anatomical areas involved in MRI brain of pyogenic
meningitis
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Pricular area
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Figure 3
Tuberculous Meningitis- pattern of involvement in
MRI
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7
Hydrocephalus
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Ring enhancing and nodular lesions
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Normal
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Figure 4
Anatomical area of Brain involved in MRI in
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Ventricles
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Figure 5
Anatomical areas involved in MRI brain in Viral
meningoencephalitis
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Frontal area
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Mid Brain
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Cerebellum
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Corpus callosum
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Figure-6
VIRAL MENINGOENCEPHALITIS CASES-
PATTERN OF INVOLVEMENT
IN MRI BRAIN(CONTRAST)
No. of case
T2w And Flair Hyperintensities
17
Infarcts
2
Haemorrhagic Component
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Edema
5
Normal
11
DISTRIBUTION ACCORDING TO AGE GROUPS figure-7
AGE GROUPS ( IN YEARS)
NUMBER OF PATIENTS (N=50)
12 to 20
13
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12
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12
41 to 50
07
51 to 60
05
61 to 70
0
>71
01
VIRAL
MENINGOENC
EPHALITIS
28
7
21
MALES- 25
FEMALES- 75
Figure 8
ETIOLOGY
TOTAL
NUMBR
MALES
(N=18)
FEMALES
(N=32)
PERCENTAGE
(%)
PYOGENIC
MENINGITIS
8
5
3
MALES- 62.5
FEMALES- 37.5
TUBERCULOUS
MENINGITIS
14
6
8
MALES- 42.86
FEMALES-57.14
Figure-9 CLASSIFICATION ACCORDING TO GCS IN DIFFERENT
ETIOLOGICAL GROUPS
Clinical Groups
(Glasgow Coma
Scale/ Gcs)
Number Of
Patients
According
To Clinical
Severity On
Admission
Pyogenic
Meningitis
( N= 8)
Tuberculous
Meningitis
( N= 14)
Viral
Meningoencephlitis
(N = 28)
Group - A
(Gcs: 3 To 5)
15
1
6
8
Group - B
(Gcs: 6 To 9)
22
5
6
11
Group – C
(Gcs: 10 To 15)
13
2
2
9
Aetiological group
CSF - total cell
count( mean)
Neutrophils
( mean)
Lymphocytes
(mean)
Pyogenic meningitis
950.5 ± 3748.84
85.88 ± 25.18
14.13 ± 25.18
Tuberculous
meningitis
225.86 ± 217.22
13.14 ± 32.8
86.86 ± 32.8
Viral
meningoencephalitis
128.61 ± 276.86
14.93 ± 25.14
85.07 ± 25.14
Figure10 ORGANISMS ISOLATED IN CSF CULTURE OF
PYOGENIC MENINGITIS CASES
Sl.N
o.
Organisms isolated in CSF culture
in Pyogenic Meningitis
Number of
case ( N= 8)
Percentage
( %)
1.
Streptococcus pneumoniae
4
50
2.
Neisseria meningitidis
1
12.5
3.
Staphylococcus aureus
1
12.5
4.
Undetermined /Negative
2
25
Figure 11: CSF BIOCHEMISTRY AND ADA LEVELS IN
DIFFERENT ETIOLGICAL GROUPS
Etiological Group
CSF
Glucose
(Mean)
CSF
Protein
(Mean)
CSF
Chloride
(Mean)
CSF ADA
Levels
(Mean)
Pyogenic Meningitis
19 ± 18.9
62.375 ±
48.52
112.88 ±
12.48
8.03 ± 24.14
Tuberculous
Meningitis
35.79 ±
22.9
268.86 ±
368.12
112.71 ±
12.54
16.29 ± 16.14
Viral
Meningoencephalitis
60.11 ±
32.28
96.96 ±
91.98
113.45 ±
14.32
3.76 ± 4.38
Figure-12
Etiology confirmed on CSF
ELISA
Number of
patients (N=28)
Percentage(%)
HERPES SIMPLEX
10
35.72
JAPANESE B
04
14.28
VARICELLA ZOSTER
03
10.72
NEGATIVE/INDETERMINATE
11
39.28
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