INFECTION OF THE CENTRAL NERVOUS SYSTEM

INFECTIONS OF THE CENTRAL NERVOUS SYSTEM Meningitis Pyogenic bacterial meningitis Viral meningitis Tubercular meningitis Fungal ( in immune-deficient) meningitis Aseptic meningitis Encephalitis Rabies Cerebral abscess Poliomyelitis 11/17/2018 Dr. Alka Stoelinga

Definition Meningitis An infection or inflammation of meninges (Connective tissue covering the central nervous system) 11/17/2018 Dr. Alka Stoelinga

11/17/2018 Dr. Alka Stoelinga

ACUTE PYOGENIC BACTERIAL MENINGITIS 11/17/2018 Dr. Alka Stoelinga

At all age groups- Strep. Pneumoniae Adolescents- N. meningitidis Causative organisms Neonate (E.coli) Children (Hemophilus influenzae, Nesierria meningitidis, Streptococcus pneumoniae) Adults (Nesierria meningitidis, Streptococcus pneumoniae) Routes of infection Hematogenous From adjacent structures (Sinusitis, CSOM, Head injuries) Iatrogenic ( Post LP, After neurosurgical procedures) NOTE At all age groups- Strep. Pneumoniae Adolescents- N. meningitidis Very young and very old- Listeria monocytogens After any neurosurgery- Staph HIV- Cryptococcus 11/17/2018 Dr. Alka Stoelinga

Pathology In acute bacterial meningitis: The pia-arachnoid is congested with polymorphs. A layer of pus forms. This may organize to form adhesions, causing cranial nerve palsies and hydrocephalus. In chronic infection (e.g. TB): The brain is covered in a viscous grey-green exudates with numerous meningeal tubercles. Adhesions are invariable. Cerebral oedema occurs in any bacterial meningitis. In viral meningitis : There is a predominantly lymphocytic inflammatory CSF without pus formation, polymorphs or adhesions; there is little or no cerebral edema unless encephalitis develops 11/17/2018 Dr. Alka Stoelinga

Clinical features: The classic clinical triad of meningitis is Nuchal rigidity ("stiff neck"). Sudden High Fever Altered mental status Other signs associated with meningitis are Headache Photophobia (intolerance to bright light) Phonophobia (intolerance to loud noises) Nausea, vomiting Alteration in mental status (confusion, delirium, lethargy, coma) Progressive drowsiness, cranial nerve palsy and focal neurological deficits indicate complications such as severe cerebral edema or hydrocephalus or think of alternative diagnosis such as cerebral abscess or encephalitis when these symptoms/ signs are seen Kernig's and Brudzinski's signs are classic signs of meningeal irritation. Seizures Rashes(meningococcemia) Signs of increased ICP ↓ level of consciousness, sluggish pupils, bradycardia, hypertension, irregular respiration 11/17/2018 Dr. Alka Stoelinga

Meningococcal meningitis Meningitis caused by the bacterium Neisseria meningitidis (known as "meningococcal meningitis“) It can be differentiated from meningitis with other causes by a rapidly spreading petechial rash which may precede other symptoms. The rash consists of numerous small, irregular purple or red spots ("petechiae") on the trunk, lower extremities, mucous membranes, conjunctiva, and (occasionally) the palms of the hands or soles of the feet. The rash is typically non-blanching: the redness does not disappear when pressed with a finger or a glass tumbler. 11/17/2018 Dr. Alka Stoelinga

Features of Meningococcal Septicemia: Meningitis Rash Shock DIC Renal failure Peripheral gangrene Arthritis(Septic/Reactive) Pericarditis(Septic/Reactive) 11/17/2018 Dr. Alka Stoelinga

Examination: Altered consciousness Hypotension/Hypertension Bradycardia Rash Neurological: Neck stiffness Jolt accentuation maneuver +ve Kernig’s sign +ve Brudzinski's sign +ve Hypertonia Increased DTR 11/17/2018 Dr. Alka Stoelinga

11/17/2018 Dr. Alka Stoelinga

Specific Examinations Kernig's sign It is assessed with the patient lying supine, with the hip and knee flexed to 90 degrees. In a patient with a positive Kernig's sign, pain limits passive extension of the knee. Brudzinski's sign It is said to be positive when flexion of the neck causes involuntary flexion of the knee and hip. Jolt accentuation maneuver Helps determine whether meningitis is present in patients reporting with fever and headache. The patient is told to rapidly rotate his or her head horizontally; if this does not make the headache worse, meningitis is unlikely 11/17/2018 Dr. Alka Stoelinga

Kernig’s sign 11/17/2018 Dr. Alka Stoelinga

Brudzinski’s sign 11/17/2018 Dr. Alka Stoelinga

Investigations : Single most important investigation is Examination of CSF. Always examine optic fundi before LP Typical CSF picture Increased Cells (Poly-morpho-nuclear leukocytosis >100) Decreased Sugar (CSF: Blood ratio <0.4) Increased protein (Above 0.5 gm/l) Increased pressure (>18cm of CSF) Positive cultures or Gram’s stain Other investigations: CT scan/ MRI head to r/o any mass lesions/ raised ICP in brain Blood: TC,DC, Culture and sensitivity, CRP 11/17/2018 Dr. Alka Stoelinga

Typical CSF changes in meningitis NORMAL VIRAL PYOGENIC TUBERCULOSIS Appearance/ Color Crystal-clear Clear/ Sometimes turbid Turbid/purulent Turbid/viscous Pressure 50-180mm of H2O N/ Lower N/ Increased Mononuclear cells < 5 mm3 10-100 mm3 < 50 mm3 100-300 mm3 Polymorph cells Nil 200-300/mm3 0-200/mm3 Protein 0.2-0.4 g/L (< 50mg/ l) 0.4-0.8 g/L 0.5-2.0 g/L 0.5-4.0 g/L (Markedly Increased) Glucose ⅔ > ½ blood glucose (40-80 mg/dl) > ½ blood glucose/ Normal < ½ blood glucose/ Absent < ½ blood glucose 11/17/2018 Dr. Alka Stoelinga

Management: Recognition and immediate treatment of acute bacterial meningitis is vital. Minutes save lives. Bacterial meningitis is lethal. Even with optimal care, mortality is around 15%. 1. Supportive measures: Airway, Breathing, Circulation Electrolyte balance 2. Antimicrobial therapy High dose parenteral antibiotics 3. Management of complications 11/17/2018 Dr. Alka Stoelinga

Empirical Treatment Empirical treatment with 3rd generation cephalosporin Ceftriaxone 2gm 12 hourly /Cefotaxime 2gm 6 hourly for 10-14 days Alternative: Benzyl Penicillin 3 lakh unit/Kg/Day in 6 divided doses Organisms are isolated: N. meningitidis : Benzyl penicillin 2.4 gm IV 4 hourly for 5-7 days or Ceftriaxone/Cefotaxime or Chloramphenicol for 5-7 days For contacts: Ciprofloxacin 500mg single dose or Rifampicin 600mg bid for 2 days or Ceftriaxone 250 mg IM single dose 11/17/2018 Dr. Alka Stoelinga

Strep pneumomiae resistant to cephalosporin : Strep. Pneumoniae : Cefotaxime 2 gm IV 6 hourly or Ceftriaxone 2gm 12 hourly for10-14 days Strep pneumomiae resistant to cephalosporin : Add vancomycin or rifampicin H.influenzae : cefotaxime or ceftriaxone or chloramphenicol Listeria monocytogenous : Ampicillin +Gentamicin 11/17/2018 Dr. Alka Stoelinga

Antibiotics and acute bacterial meningitis Organism Antibiotic Alternative(e.g. allergy) Unknown Pyogenic Cefotaxime Benzylpenicillin and chloramphenicol Meningococcus Benzylpenicillin Cefotaxime/ Ceftriaxone S.Pneumococcus Add Vancomycin or Rifampicin if resistant to B-lactam Haemophilus Chloramphenicol Listeria Ampicillin+ Gentamycin, COTRIMOXAZOLE Gran negative bacilli Ceftriaxone/ Cefotaxime Ampicillin + Gentamycin 11/17/2018 Dr. Alka Stoelinga

Steroid (Dexamethasone) Steroid are used in initial few days of the treatment in cases of S.pneumoniae and H. influenzae meningitis. It should be started before antibiotics and should be tapered 2 days there after. It lowers the rate of meningeal adhesion and thus decreasing the long term complications Control of seizures Control of raised intracranial pressure Management of Raised intracranial pressure: Head end elevation to 15-30 ̊ Hyperventilation Osmotic agent: 20%Mannitol 125ml every 8hourly Dexamethasone 4mg IV 6 hourly Furesomide IV Glycerol 11/17/2018 Dr. Alka Stoelinga

3 to 7% in meningitis caused by H. influenzae and N. Meningitides Prognosis: Mortality is : 3 to 7% in meningitis caused by H. influenzae and N. Meningitides 15% in that due to L. monocytogenes and 20% in S. pneumoniae Residual neurological deficit occurs in about 25 % of the patients 11/17/2018 Dr. Alka Stoelinga

Poor prognostic factors Decreased level of consciousness on admission Onset of seizures within 24h of admission Signs of raised intra cranial pressure. Young age (infancy) and age >50 11/17/2018 Dr. Alka Stoelinga

Complications: ACUTE: Shock Status epilepticus Brainstem herniation Multisystem failure-Septicemia, DIC, Shock CHRONIC: Hydrocephalus Neurological deficit: Hemiplegia/Quadriplegia/Cranial nerve palsy, Deafness, Blindness Decreased cognitive function 11/17/2018 Dr. Alka Stoelinga

Differential Diagnosis: Viral meningitis Tuberculous meningitis Encephalitis Brain abscess Subarachnoid hemorrhage Cerebral malaria Brain tumor Meningism 11/17/2018 Dr. Alka Stoelinga

Viral meningitis Most common of all meningitis This is almost always a benign, self-limiting condition lasting 4- 10 days. Causes: Mumps, influenza, herpes, polio, Epstein-Barr, HIV are the usual pathogens. Clinical course is less severe compared to bacterial meningitis. Headache may follow for some months. There are no serious sequel In viral meningitis there is a predominantly lymphocytic inflammatory CSF reaction without pus formation, polymorphs or adhesions, with normal glucose and protein. There is little or no cerebral edema unless encephalitis develops Complete recovery occurs without any specific treatment. 11/17/2018 Dr. Alka Stoelinga

Case A 45 year old man is brought to ER (Emergency Department) with one day of fever, headache, nausea and vomiting. On physical examination he is found to have neck stiffness and photophobia. How will you diagnose and manage the case? 11/17/2018 Dr. Alka Stoelinga

CHRONIC MENINGITIS 11/17/2018 Dr. Alka Stoelinga

Tubercular meningitis Fungal meningitis Tuberculous meningitis (TBM) and cryptococcal meningitis commence typically with vague headache, lassitude, anorexia and vomiting. Acute meningitis can occur but is unusual. Meningitic signs usually take some weeks to develop. Drowsiness, focal signs (e.g. Diplopia, Papilloedema, Hemiparesis) and seizures are common. Syphilis, Sarcoidosis and Behcet's syndrome [Triad of recurring crops of mouth ulcers (aphthous ulcers), genital ulcers, and inflammation of a specialized area around the pupil of the eye (the uvea)] also cause chronic meningitis. In some chronic meningitis organisms are never identified. 11/17/2018 Dr. Alka Stoelinga

Tuberculous meningitis Severe form of tuberculosis More in immunocompromised patients,AIDS patients Hematogenous spread secondary to primary or post primary tuberculosis Occurs soon after a primary infection or as a part of milliary tuberculosis 11/17/2018 Dr. Alka Stoelinga

Clinical features: Early stage: Nonspecific symptoms: Headache, low grade fever, vomiting, loss of appetite, lassitude , irritability, depression and confusion are the presenting symptoms Over 1-2 weeks: Neck stiffness Occulomotor palsy Papilloedema Decreased conscious level Seizure Sometimes Focal neurological deficits Coma 11/17/2018 Dr. Alka Stoelinga

Signs: Occulomotor palsies Papilloedema Depression of conscious level Absence of Meningism during the onset of disease 11/17/2018 Dr. Alka Stoelinga

Investigations: 1. CSF analysis: Examination of CSF shows elevated cells,100-500 (predominant lymphocytes) Markedly increased protein (spider web formation) and Reduced sugar AFB stain positive 2. Imaging: CT scan head CT may show basal meningeal enhancement due to exudates CXR Imaging of lungs may show the primary site 3. Sputum for AFB 4. Mantoux test 11/17/2018 Dr. Alka Stoelinga

TREATMENT: Treatment should be initiated when CSF report is available with : 1. ATT : 2HRZE/S +7HR (9-12 months) 2. Steroid Should be given for 4-8 weeks Decrease neurological deficit 3. Sometimes surgical intervention is necessary. 4. Treatment of cerebral edema 5. Control of seizure 6. Treatment of Hydrocephalus if present 7. Physiotherapy Despite effective treatment some patients are left with permanent neurological deficit. 11/17/2018 Dr. Alka Stoelinga

Complications: ACUTE: Status epilepticus Cerebral edema Coma LATE: Focal neurological deficit Cognitive defects Hydrocephalus Seizure Cranial nerve palsies 11/17/2018 Dr. Alka Stoelinga