NEUROLOGY III.pptx

NEUROLOGY III CNS INFECTIONS Dr Ugolee Jerry. INTRODUCTION • CNS infections are the commonest causes of non-traumatic coma in children. • They are among the most common causes of fever associated with neurologic signs and symptoms in children in the tropics. • Despite better anti-microbial agents...

NEUROLOGY III CNS INFECTIONS Dr Ugolee Jerry. INTRODUCTION • CNS infections are the commonest causes of non-traumatic coma in children. • They are among the most common causes of fever associated with neurologic signs and symptoms in children in the tropics. • Despite better anti-microbial agents and technologic advances, morbidity & mortality rates for children with acute bacterial meningitis remains significantly high in many developing countries. • The CNS is protected by the skull, dura (pachymeninx), the pia and arachnoid (leptomenings), surrounded by the blood-brain barrier comprising of the blood-csf, vasculo-endothelial & arachnoid barriers INTRODUCTION • Micro-organisms breaching the BBB, proliferate much faster than in plasma because of the lack of host defence mechanisms in the sub-arachnoid space including the absence of polymorphs& poor complements in CSF. • CNS infections maybe diffuse e.g meningitis &encephalitis or maybe focal e.g cerebrities, cerebral abscess. They follow direct invasion of the leptomeningis, sub-arachnoid space & superficial cortical structures and blood vessels by microbes. • May follow direct spread e.g penetrating head injuries or skull fractures or haematogenous spread e.g following otitis media& nasopharyngeal infections • CNS infections are a dare emergency especially in children in the tropic and may result in death within a few hours or leave severe neurologic squeale. EPIDERMIOLOGY • The exact incidence of CNS infections worldwide is not known. Estimates show that about 1.2million people contact bacterial meningitis each year and 11% die from it. • In children in developing countries, the risk of developing meningitis by 5years of age is between 1:400 – 1:20,000.Accounting for 1-6% of hospital admissions with a high M&M rate. • A geographical belt in sub-Saharan Africa has been recognised and referred to as the ‘meningitis belt’ spanning from far east Africa to west Africa including Ethiopia, Sudan, northern Nigeria, Niger, Benin &Chad. • Regions within the belt have a range of 300mm-1000mm of annual rainfall and experience epidemics of meningococcal meningitis every 5-10 years • In Nigeria epidemics occur from Jan- March(dry, hot, dusty season) and disappears at the start of the raining season. AIETIOLOGY • The inflammation of the CNS may directly result from invasion by microbes( bacterial, viral, fungal or protozoa) and can also be caused rarely by cancer, a drug reaction or by diseases of the immune system. • Bacterial (pyogenic) meningitis, including TB meningitis is more common in children. Causative organisms causing pyogenic meningitis in children are related to the age and immune status of the child. • In the neonatal period up to the 2nd month of life, are usually organisms colonizing the maternal birth canal or the are nasocromally transmitted. AIETIOLOGY • The major pathogens causing neonatal meningitis include Grampositive: group B streptococci, Staphylococcus aureus and Listeria monocytogenes and Gram-negatives: E coli, Pseudomonas aeruginosa, Proteus species, Aerobacter aerogenes and Klebsiella pneumonia. • In infants and older children, common infecting agents include Grampositive organisms like Streptococcus pneumonia, Staphylococcus, Pneumococcus, Listeria monocytogenes, Mycobacterium tuberculosis and Gram-negatives like Haemophilus influenza( type b),Neisseria Meningitides, Klebsiella pneumonia, E coli, Shigella, Pseudomonas and Proteus species. AIETIOLOGY • Viral causes of meningitis are most commonly Non-polio enterovirus occasionally following recently acquired flu’s. Other viral causes include mumps virus, influenza virus, measles virus and lymphocytic choriomeningitis virus. • Fungal causes of meningitis are rare and occur more commonly in children with weakened immune systems. Examples include Cryptococcus, Histoplasma, Coccidioides, and Blastomyces. • Parasite causes of meningitis is much less common and often associated with eosinophilia. Examples include Angiostrongylus cantonensis, Baylisascaris procyonis and Gnathosoma spinigerum. TYPES ACUTE BACTERIAL MENINGITIS: • ABM is one of the most challenging paediatric emergencies. Its importance worldwide derives principally from its ability to cause neurologic sequelae. While mortality from ABM especially in children ˃5years has decreased world-wide, following immunization, in the tropics , there is still a need to focus attention on strategies to reduce its persistently high case fatality and gross neurologic sequelae. • 0.9-5.1% of hospital admissions in Nigeria are due to ABM. • Risk factors include male sex, black race, age less than 2years, poor socioeconomic circumstances, attendance at day care, overcrowding, immuno- deficient states, VP shunts, Splenic dysfunction, neural tube defects, penetrating head injury, neurosurgical procedures, cribriform plate fracture. ACUTE BACTERIAL MENINGITIS PATHOLOGY/PATHOGENESIS: • ABM is usually spread haematogenously following systemic bacteraemia which commonly follows an URTI, otitis media or endocarditis, may also occur as a direct extension of infections in the CNS e.g penetrating head injuries, VP shunts. • Following bacteria invasion of CSF, there is proliferation of polymorphonuclear leukocytes& fibrin. • The leptomeninges (arachnoid&pia)of spinal cord& brain show signs of inflammation with swelling & are covered by fibropurulent exudate especially @the base of the brain. ACUTE BACTERIAL MENINGITIS PATHOLOGY/PATHOGENESIS: • Increased intracranial pressure follows cerebral oedema from the inflammatory process as well as the cytotoxic induced capillary vascular permeability, increased hydrostatic pressure causing interstitial oedema and possibly from obstruction of CSF reabsorption. • Pus may accumulate & become encapsulated to form an abscess, or may obstruct the foramina of the ventricles and sub-arachinoid cisterns leading to hydrocephalous. • Inflammation of the spinal nerve roots produces meningeal signs and CN embedded in the exudate at the base of the brain neuropathies. ACUTE BACTERIAL MENINGITIS CLINICAL FEATURES: • These are usually age dependent. In neonates up to 2months symptoms are largely non-specific. They include poor suck, excessive inconsolable crying, fever/hypothermia, irritability, vomiting. Signs may include a bulging anterior fontanel& convulsions, hypertonia and exaggerated DTR. Signs of meningeal irritation and neck stiffness are usually not present. • Infants and older children may present with headache, back pain, fever, projectile vomiting, seizures, irritability, neck stiffness, altered sensorium and may show signs of an upper motor neurone lesion including hypertonia, hypereflexia, sustained ankle clonus& an extensor plantar response. Kernigs & brudzinski signs are usually present. ACUTE BACTERIAL MENINGITIS CLINICAL FEATURES: • A triad of irregular breathing pattern, systolic hypertension and bradycardia (Cushing's triad) may indicate ↑ ICP. • Focal neurologic signs especially CN palsies of CN III(ptosis), IV & VI(opthalmoplegia) and VII(facial deviation) may be elicited. There may also be abnormal pupillary responses. • Cutaneous manifestations should be looked for, they include purpura and petechial haemorrhages(meningococcemia) ACUTE BACTERIAL MENINGITIS DIAGNOSIS: • A definitive diagnosis is made following a lumber puncture and an analysis of the obtained CSF ( biochemistry and m/c/s). • The child is hyperflexed inwards if lying down with both knees to the abdominal wall and chin to chest or made lean forward if sitting with head tucked in, an imaginary line drawn across both illac crest, cutting thru the 5th & 6th ICS forms the usual landmark(L4-L5 vertebra). • Contraindications to this procedure may be relative or absolute. • Relative contraindications include an infection at the site of LP, thrombocytopenia, DIC, septic shock, seizures occurring less than 2hrs prior. • Absolute contraindications are signs of raised ICP and cardiorespiratory instability. ACUTE BACTERIAL MENINGITIS DIAGNOSIS: • The opening pressure at which CSF is expelled should be measured and CSF should be examined macro/microscopically. Turbid CSF suggests AMB as normal CSF is clear & colourless and is normally devoid of polymorphonuclear cells. • CSF protein, cell count and glucose estimation should be done. A concomitant plasma RBS done as CSF glucose is measured relative to it. • Gram staining and culture of the CSF completes the analysis. Characteristics of normal CSF characteristics neonates Older infants,children&adult appearance Clear,colourless Clear,colourless Opening pressure(LP) 50-180mmH20 70-180(average 125mmH20) Lymphocytes/ul 0-30 0-4 Polymorphs/ul 0-3 0 Red blood cells/ul 20-50 0 Protein,mg/dl Upto 150(full term),upto 170(preterm) 15-40 glucose >50% of blood glucose >66% blood glucose Cells:total &type condition Pressure( mmH2O) Leukocyte Protein(m s(mm3) g/dl) Glucose( mg/dl) normal 50-80 <5,>75% 20-45 >50(or 75% serum glucose) Partially treated bacterial meningiti s Normal or elevated 510,000;P MNs usually predomin ate but mononucl ear cells may if pretreate d for extended period of time Usually 100-500 Normal or Organi decreased sms may be seen on gram stain pretre atmen t may render CSF sterile. ABM Usually elevated( 100-300) 100-1000 Usually or>,usuall 100-500 y 3002,000,PM Ns Decrease d usually<4 0(<50% serum comm ents Organi sms usually seen on ACUTE BACTERIAL MENINGITIS DIAGNOSIS: • Blood culture may be positive in up to 80% of patient if no prior antibiotics have been used. • FBC,C-reactive protein, ESR are ancillary investigations that maybe useful. Cranial MRI/ CT maybe indicated to rule out differentials and complications. • More currently, counter-current immunoelectrophoresis(CIE), Latex agglutination test(LAT) and Enzyme linked immunosorbent assay(ELISA) are rapid ways of detecting bacterial antigen in CSF. ACUTE BACTERIAL MENINGITIS DIFFRENTIAL DIAGNOSIS: • Viral Encephalitis • Tuberculous Meningitis • Fungal Meningitis • Brain Tumour • Brain Abscess • Sub-arachnoid Haemorrhage • Leukemic infiltrates of CNS ACUTE BACTERIAL MENINGITIS TREATMENT: • Aim’s to sterilize the CSF with Abiotics and reduce CNS damage& sequlae. • Treatment is supportive and the judicious use of appropriate Abiotics for an adequate duration. • Supportive therapy includes good nursing care, anticonvulsants for seizures(phenobarbitone, diazepam), Dexamethsone(2-4mg/kg) to limit cerebral irritation and reduce the incidence of deafness& blindness, Mannitol(1g/kg bolus) to reduce ICP, fluid restriction to reduce incidence of SIADH. ACUTE BACTERIAL MENINGITIS TREATMENT: • Antibiotics of choice for neonates up to 2months include IV Amipicillin(1st line) 100mg-200mg/kg/day n 3DD to cover for E coli, Group B strep & Listeria monocytogen + IV Genticin (5mg/kg/day) or IV Kanamycin for E. coli, Pseudomonas Spp, Proteus&Kebsella for 7-10days. • IV Ceftazidime (100-150mg/kg/day) or IV Ceftrixione (100mg/kg/day) + IV Genticin as 2nd line. • In infants and older children, IV Cyrstalline Penicillin (0.4mu/kg/day) to cover for N meningitides, Pneumococcous +IV Chloramphenicol (100-150mg/kg) for H. influenza & E.coli as 1st line for10-14days. • IV Ceftrixaione,Vancomycim and Meropenem are 2nd line alternatives. ACUTE BACTERIAL MENINGITIS COMPLICATIONS: • May be immediate, intermediate or long term. • Immediate complications include CN palsies, ↑ ICP, hypoglycaemia, CVA, hemiplegia, transient visual/ hearing loss, cortical blindness subdural effusion. • Intermediate complications may include SIADH, Waterhouse friderichsen syndrome • Long term complications include cerebral palsy, learning disability, seizure disorders, hydrocephalous, blindness, sensoneural deafness, mental retardation. TUBERCULOUS MENINGITIS INTRODUCTION: • TBM IS A FORM OF EXTRAPULMONARY TUBERCULOSIS THAT AFFECT THE BRAIN AND THE MENINGES • CONSIDERED THE MOST SERIOUS COMPLICATION OF TUBERCULOSIS IN CHILDREN • FATAL WITHOUT PROMPT AND APPROPRIATE TREATMENT • TBM COMPLICATES ABOUT 0.3% OF UNTREATED TUBERCULOUSIS INFECTION IN CHILDREN • MOST COMMON IN CHILDREN AGED BETWEEN 6MONTHS-4YRS • OCCURS USUALLY BETWEEN 2 – 12 MONTHS FROM TIME OF PRIMARY INFECTION TUBERCULOUS MENINGITIS PATHOGENESIS: • Haematogenous spread of tubercle bacilli results in its seeding on the cerebral cortex and meninges giving rise to caseous lesions. • These lesions gradually increase in size and seed further bacilli into the subarachnoid space where it stimulates an inflammatory reaction with exudate formation. • Exudates infiltrate the cortico-meningeal vessels causing infarctions in the cerebral cortex, obstruction of the foramina and hydrocephalous. • Combination of vasculitis, cerebral oedema, infarction and obstructive hydrocephalous lead to severe brain damage that is often insidious. Microbacterium Tuberculosis (Light Microscopy) TUBERCULOUS MENINGITIS CLINICAL FEATURES: • SIMILAR TO OTHER FORMS OF MENINGITIS,EXCEPT THAT SYMPTOMS ARE INSIDIOUS • SYMPTOMS ARE CLASSIFIED INTO 3 STAGES: • STAGE 1(LAST,1-2WKS): • PRODROMAL PHASE-CHARACTERISED BY NON SPECIFIC SYMPTOMSLOW GRADE FEVER, HEADACHE, IRRITABILTY, MALAISE, WEIGHT LOSS, RESTLESSNESS. FOCAL NEUROLOGICAL SIGNS ARE OFTEN ABSENT, BUT SOME INFANTS MAY HAVE STAGNATED OR LOSS OF DEVELOPMENTAL MILESTONES.. TUBERCULOUS MENINGITIS CLINICAL FEATURES: • STAGE 2(LAST,2-3WKS): • MORE ABRUPT, CHARACTERISED BY NEUROLOGICAL SIGNS AND STMPTOMS; LETHARGY, NECK STIFFNESS, SEIZURES,POSITIVE KERNING AND BRUDZINSKI SIGN, HYPERTONIA, VOMITING, SIGNS OF BRAINSTEM INVOLVEMENT, CRANIAL NERVE PALSIES, RAISED ICPAND DISORIENTATION. • STAGE 3(3-4WKS): • STUPOR OR COMA, HEMIPLEGIA, DECEREBRATE RIGIDITY, OPISTHOTONIC POSITION, IRREGULAR BREATHING, CONSTRICTED OR DILATED PUPILS. FUNDOSCOPY SHOWS PAPILLOEDEMA AND CHOROIDAL TUBERCLES (PATHOGNOMONIC OF TBM WHEN ASSOCIATED WITH COMA AND CONVULSIONS) TUBERCULOUS MENINGITIS DIAGNOSIS: • DIAGNOSIS OF TBM IS OFTEN CHALLENGING AND REQUIRES A HIGH INDEX OF SUSPICION ON THE PART OF THE PHYSICIAN. • IDENTIFICATION OF ADULT WITH ACTIVE/INFECTIOUS DISEASE IN CONTACT WITH A CHILD. • MANTOUX TEST MAY BE POSITIVE IN 50% OF CASES,NEGATIVE RESULT DOES NOT EXCLUDE TBM. TUBERCULOUS MENINGITIS DIAGNOSIS: • MOST IMPORTANT INVESTIGATION AVAILABLE IN THIS PART OF THE WORLD IS LUMBAR PUNCTURE: CSF FOR MCS AND BIOCHEMICAL ANALYSIS-----CFS IS OFTEN CLEAR,BUT MAYBE XANTHOCROMIC AND FORMS PELLICLE IF LEFT TO STAND FOR FEW HOURS. • CSF CELL COUNT 10 - 500CELLS/CMM WITH PREDORMINANCE OF LYMPHOCYTES IN THE LATE PHASE. • ELEVATED PROTEIN (100 - 300mg/dl) EARLY PHASE AND UP TO 1000mg/dl in LATE PHASE. • LOW CSF GLUCOSE<40mg/dl TUBERCULOUS MENINGITIS DIAGNOSIS: • SMEARS OF CSF STAINED WITH ZIEHL-NEELSEN STAIN REVEAL AFB IN 30% OF CASES. • CULTURE IN LOWENSTEIN JENSEN MEDIUM IS POSITIVE IN 40-60% OF CASES.OFTEN THE GOLD STANDARD FOR CONFIRMING DIAGNOSIS, BUT RESULT IS DELAYED (ABOUT 6-8WKS). • NEWER DIAGNOSTIC TEST IS POLYMERASE CHAIN REACTION(PCR)FOR RAPID DETECTION OF MYCOBACTERIAL ANTIGEN. IT HAS REPORTED 70-90% SENSITIVITY AND 95-100% SPECIFICITY, WITH RESULTS AVAILABLE WITHIN 24HRS. • OTHER INVESTIGATIONS INCLUDE: FBC, ESR, E/U/CR, HIV SCREENING, CT SCAN AND MRI Tuberculin skin test (Mantoux test) TUBERCULOUS MENINGITIS TREATMENT: • RECOMMENDED TREATMENT REGIMEN FOR TBM INCLUDES: 4 ANTI TB DRUGS AND CORTICOSTERIODS • INTENSIVE PHASE(1ST 2MONTHS): TAB ISONIAZID 20MG/KG/DAY, CAP RIFAMPICIN15MG/KG/DAY, TAB PYRAZINAMIDE 30MG/KG/DAY, IM STREPTOMYCIN 20MG/KG/DAY. • CONTINUATION PHASE(10MONTHS), ISONIAZID AND RIFAMPICIN • CORTICOSTERIODS; REDUCES INFLAMMATION, CEREBRAL OEDEMA AND POSSIBLE ADHESIONS. TAB PREDNISOLONE 1MG/KG/DAY FOR 4WKS AND THEN TAPERED OVER 2-4WKS. • SUPPORTIVE CARE . TUBERCULOUS MENINGITIS COMPLICATIONS: • EARLY COMPLICATIONS: CEREBRAL OEDEMA,SIADH, RAISED ICP, RESPIRATORY FAILURE , NON COMMUNICATING HYDROCEPHALOUS & CRANIAL NERVE DEFICITS(CN 3,6&7). • LATE COMPLICATIONS: OBSTRUCTIVE HYDROCEPHALOUS, CORTICAL BLINDNESS, SENSORINEURAL DEAFNESS, SPEECH DEFICIT, MENTAL RETARDATION & SEIZURE DISORDERS. ENCEPHALITIS INTRODUCTION: • An acute Inflammation of the brain tissue caused mainly by viruses. • Usually diffuse and generalized but may affect certain parts of the brain more than others and is described with terms reflecting the affected areas e.g Meningoencephalitis, meningoencephalomyeloradiculitis(Guillan-barre syndrome), acute cerebella ataxia. • May also follow autoimmune bases with the immune system mistakenly attacking the brain. • Mostly a disease of children and older adult and immuno-compromised individuals. • Rarely life-threatening. ENCEPHALITIS CAUSES: • May be described as primary or secondary encephalitis. • Primary follows direct infection of the brain by viruses, 3categories of viruses have been implicated in its aetiology- common viruses, childhood viruses and arboviruses. • Examples of causative common viruses include the herpes simplex virus and Epstein-barr virus, childhood viruses include the measles and mumps viruses. Arboviruses are spread by mosquitoes ad ticks , they include the Japanese encephalitis virus, West Nile virus& tick-borne encephalitis virus. • 50% of cases of encephalitis are idiopathic. ENCEPHALITIS CAUSES: • Secondary encephalitis, sometimes described as post-infectious encephalitis follows a faulty immune response in which the immune system attacks the brain tissue mistaking it for antigens of viruses that may have infected the individual 2-3weeks earlier. • Usually follows flu-like illness with fever and nasal discharge. ENCEPHALITIS CLINICAL FEATURES: • In infants and younger children may present with poor feeding, vomiting, incessant crying, irritability, stiffness of the body and a bulging fontanel. • Older children typically complain of fever, headache and photophobia. There may be neck stiffness, muscle and joint aches, nausea, vomiting, slow movements, clumsiness, disorientation, memory loss, aggressiveness, hallucinations and coma. ENCEPHALITIS DIAGNOSIS: • A definitive diagnosis is only made by examining a slice of the brain tissue under the microscope. • Lumbar puncture and CSF analysis is usually done but the findings are often inconclusive and may resemble the picture of a partially treated ABM. • Cranial MRI / CT would show soft tissue changes typical of encephalitis. • EEG may show sharp waves in the temporal region especially in HSV encephalitis. ENCEPHALITIS TREATMENT: • Commonly symptomatic to alleviate symptoms. • Bed rest • Plenty fluid intake • Anticonvulsants • Corticosteroids (reduce inflammation) • Ayclovir and Adenine arabinoside have been shown to be helpful in HSV encephalitis. ENCEPHALITIS COMPLICATIONS: • Epilepsy • Memory loss • Personality changes • Aphasia and speech impairments • Hearing /Visual deficits • Paralysis ENCEPHALITIS PREVENTION: • Vaccination • Good hygiene practices • Protective clothing. FURTHER READING • Localized pyogenic CNS infections ( cerebral abscess, subdural effusion) • Congenital infections of the CNS( Rubella, Toxoplasmosis, Syphilis)