MENINGEAL SYNDROME IN THE PRACTICE OF INFECTIOUS DISEASES SPECIALISTS

Central nervous system (CNS) infections are among the most dramatic medical conditions, not just because of their clinical presentations, possible ultimate consequences, but also because of the complexity of their diagnosis and treatment, and clinically they are manifested with meningeal syndrome, regardless of the type of causative agent. The aim of the study was to determine the correlation between certain clinical signs of meningeal syndrome and results of lumbar puncture which is used to diagnose the central nervous system infection. The study included a group of 54 patients who were treated at the Clinic for Infectious Diseases Clinical Centre Niš, with a clinical picture of bacterial meningitis. The diagnosis of the disease was based on a clinical picture, findings of lumbar puncture and isolation of the causative agent out of the cerebrospinal fluid. In all patients, there was pleocytosis in the cerebrospinal fluid with predomination of polymorphonuclears. There were 20 (37.0%) females and 34 (63.0%) males, with mean age 52.37 ± 18.10 years. The most dominant clinical symptoms in patients were headache in 74.1%, elevated temperature in 70.4%, stiff neck in 63.0% and Brudzinski's upper sign in 55.6%. Ethical verification from the cerebrospinal fluid was negative in 32 (59.3%) patients, Klebsiella, Pneumoccocus and Staphylococcus were found in 4 (7.4%) patients each. It was found that headaches with stiff neck, disturbance of consciousness and elevated temperature represent an absolute indication for lumbar puncture and are in direct correlation with the positive finding in the cerebrospinal fluid. Acta Medica Medianae 2017;56(2):32-37.


Introduction
A large number of infectious and other agents can get into the cerebrospinal fluid system by blood, lymphatic or neural route causing the inflammation process on meninges.Regardless of the causative agent, there comes to increased production of cerebrospinal fluid, which results in an increase of intracranial pressure.
Regardless of whether intracranial pressure has been increased due to increased production of cerebrospinal fluid or brain volume, there are always certain characteristic signs known as meningeal syndrome (1).CNS infections are among the most dramatic of medical conditions, not just because of their clinical presentations, possible ultimate consequences, but also because of the complexity of their diagnosis and treatment (1,2).
Acute bacterial meningitis belongs to the group of serious infectious diseases, caused by various types of bacteria, during which the pestilent exudate is created in the suabrahnoidal space and meninges.They are clinically manifested by the appearance of meningeal syndrome with characteristic meningeal signs (3).
Bacterial meningitis, despite the application of most modern antibiotic therapy, represents a huge problem to the healthcare system, since according to Gray's data morbidities in the US range from 2-6 per 100,000 inhabitants with a mortality of 3-33% (4).Regardless of the applied antibiotic therapy, mortality in the world ranges from 20-30%, while in almost 50% of cases, there are sequelae which appear in the form of hearing damage, neurological outbreaks, learning and behavior disorders, etc (5).
Mortality rate according to Van de Beku is 34%, and up to 50% of patients suffer from the long-term consequences (6).

Aim
Bearing in mind the fact that the clinical picture of meningeal syndrome can be very different and that in some cases, discretely expressed meningeal syndrome can be followed by very rich cerebrospinal fluid findings, we wanted to determine the clinical significance of certain meningeal signs.

Materials and methods
In our prospective analysis, we included 54 patients who were treated at the Clinic for Infectious Diseases, Clinical Centre Niš, with the diagnosis of meningitis bacterialis.Diagnosis is set on the basis of the clinical picture and the LP findings, where cerebrospinal fluid protein content, cerebrospinal fluid glucose content and pleocytosis were determined as parameters for the bacterial or viral etiology of the disease.
For the purpose of ethological verification of the causative agent, the cerebrospinal fluid was sent to the Public Health Institute in Niš, where Gram staining was done, and in cases with posi-tive findings, the antibiogram was done.Statistical data processing, descriptive and analytical statistics were used.The results are presented in tables and graphs.

Results
Out of 54 respondents, 20 (37%) were women and 34 (63%) were men, with mean age of 52.37 ± 18.10 years, of whom the youngest participant was 19 and the oldest was 85 years old.The most common diagnosis on admission was meningitis of unknown, origin set up in 48 (88.9%) patients, while the diagnoses of febrile state, bacterial meningitis, and coma were found in two (3.7%) patients each.(Table 2, 3) Almost half of the subjects, 24 (44.4%), were without comorbidity.Diabetes mellitus was diagnosed in 6 (11.1%) patients, cardiac insufficiency and brain tumor were found in four patients each (7.4%); two (3.7%) were alcoholics, had ear infections, glaucoma, hypertension, lupus nephritis, heart valve operation, head injury, and prostate tumor.(Table 4, 5) On average, patients were awaiting 4.70 ± 4.62 days until hospitalization.On admission, 38 (70.4%) patients were febrile, 14 (25.9%)afebrile, while 2 (3.7%) subjects were in hypothermia.The average temperature of the entire population was 37.77 ± 1.14 0C.(Table 6)  The values and parameters from the cerebrospinal fluid measured in patients on admission are shown in (Table 8).

Discussion
Bacterial meningitis is the most significant and most severe manifestation of central nervous system infections.They can have very rapid and unfavorable clinical evolution, and despite the use of antibiotics and the most modern methods of treatment, a relatively high mortality rate is still present.Their frequency ranges from 0.2 to 6 cases per 100,000 inhabitants in the United States according to Gray and mortality of 3-33% for untreated and inadequately treated cases of bacterial meningitisis (4).Vikse states that 1.2 million people in the world get ill annually, with 135,000 deaths (7).Petra observes that the world's mortality rate is 20-30%, regardless of the treatment applied (5), Miyazaki found 10-40% (8) and Bamberger 21% in developed countries (9), De Jong 5% (10), Thigpen 14,3% (11).
Out of 54 respondents in our study, 63% were male and 37% female.Egidia Miftode, on a sample of 127 adults and 77 children with TB meningitis, found that in the child group, 61% were male and 39% female.In adults, this ratio was 58% versus 42% in favor of the male sex (12).
The timely diagnosis is in direct correlation with the outcome of the disease and is based on the clinical picture, LP and the etiological verification of the causative agent.Early recognition of meningeal signs is decisive for raising the suspicion of the presence of meningeal syndrome.
Bamberger states the following representation of meningeal signs (9).
In 95% of cases, two of the following were present: temperature, stiff neck, headache, mental state disorder.The most common symptom was headache: 87%, neck stiffness 83%, temperature above 38°C, and loss of consciousness 69%.
We found difficult mobility of the neck in 20% less cases, which may be due to different assessment criteria.Also, our respondents had a 13% less headache, which can be a result of the state of consciousness of patients on admission, since a patient with a consciousness disorder cannot give information about the existence of a headache.The diagnosis of meningitis can only be made by lumbar puncture, and it is very interesting that 70.4% of cerebrospinal fluid samples were clear and only 29.6% were blurred.All authors state that in the first lumbar puncture the appearance of the cerebrospinal fluid can range from slightly turbid resembling "cigarette smoke" to the purulent content that cannot pass through a needle for lumbar puncture (14,15).By a cytologic examination, pleocytosis with the prevalence of polymorphonuclears was found, which is in line with other authors.Garlicki (15) states that pleocytosis is over 1,000 cells in mm 3 , with over 80% predominance of polymorphonuclears.Machado (14) states that polymorphonuclears are the evidence of the presence of bac-terial antigens and that they exceed 90% of cell elements.In our respondents, expressed cerebrospinal fluid protein content and reduced cerebrospinal fluid glucose content were observed.Garlicki (15) also finds that protein values are elevated from 1-5gr/l and glucose levels are reduced to even undetectable values.
Thirty-six (66.7%) patients received treatment following the guideline, 4 (7.4%) received antibiotics after obtaining isolates from the cerebrospinal fluid (in which Klebsiella was identi-fied), while 6 patients (11.1%) had no response to therapy that had to be chaged ex juvantibus by including more potent carbapenem antibiotics and colistin.
Duszynska states that developed countries recommend cefotaxime or ceftriaxone as empirical treatment, often with vancomycin, to microbiological confirmation and antibiograms (16).

Conclusion
Clinical picture with the presence of meningeal syndrome and characteristic meningeal signs, headache, elevated temperature, stiffness of the neck were the most significant in raising suspicion of CNS infection.The diagnosis is made exclusively by the LP and there is no wrongly done LP, because sometimes clinical symptomatology can be very discrete, especially in elderly people.
All our respondents had pleocytosis with polynucleosis, which, with chemical findings of the cerebrospinal fluid, high cerebrospinal fluid protein content and low cerebrospinal fluid glucose content, indicated the bacterial etiology of the disease and prompted the clinician to start antibiotic therapy in time.A high percentage of 59.3% of the cerebrospinal fluid samples, from which there were no isolates, were the result of the previous use of antibiotics and irregular transport of cerebrospinal fluid.

Chart 2 .
Outcome of the disease Chart 3. Therapy

Table 1 .
Socio-demographic characteristics of the population surveyed Chart 1. Age of respondents by gender

Table 2 .
Diagnosis on admission

Table 3 .
Diagnosis on discharge

Table 5 .
Characteristics of patients on admission

Table 8 .
Values of the parameters from the cerebrospinal fluid on admission n(%), ±SD