Neurology
Question 109 of 300
A 16 year old boy presents to the Emergency Department complaining of a headache with neck stiffness and photophobia. On examination you note a non-blanching purpuric rash on his shins. Which of the following pathogens is the most likely infectious cause?
Answer:
Neisseria meningitidis capsular group B (MenB) is the most common cause of meningococcal disease in people aged under 25 years. In children and young people aged 3 months or older, the most frequent causes of bacterial meningitis include Neisseria meningitidis (meningococcus), Streptococcus pneumoniae (pneumococcus) and Haemophilus influenzae type b (Hib).Paediatric Meningococcal Disease
Neurology
Last Updated: 12th February 2021
Meningococcal disease may present with a clinical spectrum ranging from acute bacterial meningitis to rapidly progressive meningococcal septicaemia. Although bacterial meningitis can affect all ages, incidence of bacterial meningitis and meningococcal disease is highest in children aged under 2 years and declines during childhood.
Definitions
- Meningococcal disease is infection with Neisseria meningitidis.
- Meningococcal meningitis is inflammation of the pia and arachnoid mater of the brain and spinal cord resulting from infection with Neisseria meningitidis.
- Meningococcal septicaemia is infection of the bloodstream by Neisseria meningitidis with subsequent bacterial endotoxin release, and rapid progression to shock and circulatory collapse.
Transmission
- Neisseria meningitidis is a gram-negative, aerobic, encapsulated diplococcus.
- Neisseria meningitidis is transmitted by aerosol, droplets, or direct contact with secretions from the upper respiratory tract.
- Neisseria meningitidis is usually commensal. Prevalence increases through childhood from around 5% in infants to a peak of 24% in 19 year olds, decreasing in adulthood to around 8%.
- The incubation period is usually 3–5 days.
- Neisseria meningitidis capsular group B (MenB) is the most common cause of meningococcal disease in people aged under 25 years.
Clinical features
Consider bacterial meningitis and meningococcal septicaemia in children and young people who present with the symptoms and signs below. Be aware that:
- some children and young people will present with mostly non-specific symptoms or signs, and the conditions may be difficult to distinguish from other less important (viral) infections presenting in this way.
- children and young people with the more specific symptoms and signs are more likely to have bacterial meningitis or meningococcal septicaemia, and the symptoms and signs may become more severe and more specific over time.
Be alert to the possibility of bacterial meningitis or meningococcal septicaemia when assessing children or young people with acute febrile illness.
| Non-specific features | More specific features |
|---|---|
|
|
Signs of shock:
- Capillary refill time more than 2 seconds
- Unusual skin colour
- Tachycardia and/or hypotension
- Respiratory symptoms or breathing difficulty
- Leg pain
- Cold hands/feet
- Toxic/moribund state
- Altered mental state/decreased conscious level
- Poor urine output
Differential diagnosis
The diagnosis of acute bacterial meningitis can be challenging, as it can present with common, non-specific clinical features. Differential diagnoses include:
- Bacterial meningitis of another cause
- In children and young people aged 3 months or older, the most frequent causes of bacterial meningitis include Neisseria meningitidis (meningococcus), Streptococcus pneumoniae (pneumococcus) and Haemophilus influenzae type b (Hib).
- In neonates (children younger than 28 days), the most common causative organisms are Streptococcus agalactiae (Group B streptococcus), Escherichia coli, S pneumoniae and Listeria monocytogenes.
- Viral meningitis
- Enteroviruses (for example Coxsackie A and B viruses, and echoviruses) are the most common cause in children.
- Fungal meningitis
- Cryptococcus is the most common cause of fungal meningitis in immunocompromised people.
- Tuberculous meningitis
- Encephalitis
- Sepsis
- Pneumonia
- Malignancy
- Central nervous system abscess
- HIV infection
- Subarachnoid haemorrhage
- Other non-infective causes of meningitis e.g. autoimmune disorders such as SLE and Behcet's syndrome, drug-induced meningitis (such as nonsteroidal anti-inflammatory drug, trimethoprim/sulfamethoxazole, amoxicillin, ranitidine)
Investigation and initial management of petechial rash
- Perform a very careful examination for signs of meningitis or septicaemia in children and young people presenting with petechial rashes.
- Give intravenous ceftriaxone immediately to children and young people with a petechial rash if any of the following occur at any point during the assessment (these children are at high risk of having meningococcal disease):
- petechiae start to spread
- the rash becomes purpuric
- there are signs of bacterial meningitis
- there are signs of meningococcal septicaemia
- the child or young person appears ill to a healthcare professional
- If a child or young person has an unexplained petechial rash and fever (or history of fever) carry out the following investigations:
- full blood count
- C-reactive protein (CRP)
- coagulation screen
- blood culture
- whole-blood polymerase chain reaction (PCR) for N meningitidis
- blood glucose
- blood gas
- In a child or young person with an unexplained petechial rash and fever (or history of fever) but none of the high-risk clinical manifestations:
- Treat with intravenous ceftriaxone immediately if the CRP and/or white blood cell count (especially neutrophil count) is raised, as this indicates an increased risk of having meningococcal disease.
- Be aware that while a normal CRP and normal white blood cell count mean meningococcal disease is less likely, they do not rule it out. The CRP may be normal and the white blood cell count normal or low even in severe meningococcal disease.
- If the child or young person is assessed as being at low risk of meningococcal disease and is discharged after initial observation, advise parents or carers to return to hospital if the child or young person appears ill to them.
Investigation and initial management of suspected bacterial meningitis
- In children and young people with suspected bacterial meningitis, perform a CRP and white blood cell count:
- If the CRP and/or white blood cell count is raised and there is a non‑specifically abnormal cerebrospinal fluid (CSF) (for example consistent with viral meningitis), treat as bacterial meningitis.
- Be aware that a normal CRP and white blood cell count does not rule out bacterial meningitis.
- Regardless of the CRP and white blood cell count, if no CSF is available for examination or if the CSF findings are uninterpretable, manage as if the diagnosis of meningitis is confirmed.
- Polymerase chain reaction (PCR) tests for bacterial meningitis and meningococcal disease
- Perform whole blood real-time PCR testing for N meningitidis to confirm a diagnosis of meningococcal disease. The PCR blood sample should be taken as soon as possible because early samples are more likely to be positive. Be aware that a negative blood PCR test result for N meningitidis does not rule out meningococcal disease.
- Submit CSF to the laboratory to hold for PCR testing for N meningitidis and S pneumoniae, but only perform the PCR testing if the CSF culture is negative.
- Lumbar puncture
- Perform a lumbar puncture as a primary investigation unless this is contraindicated.
- Do not allow lumbar puncture to delay the administration of parenteral antibiotics.
- CSF examination should include white blood cell count and examination, total protein and glucose concentrations, Gram stain and microbiological culture. A corresponding laboratory-determined blood glucose concentration should be measured.
- In children and young people with suspected meningitis or suspected meningococcal disease, perform a lumbar puncture unless any of the following contraindications are present:
- signs suggesting raised intracranial pressure
- reduced or fluctuating level of consciousness (Glasgow Coma Scale score less than 9 or a drop of 3 or more)
- relative bradycardia and hypertension
- focal neurological signs
- abnormal posture or posturing
- unequal, dilated or poorly responsive pupils
- papilloedema
- abnormal 'doll's eye' movements
- shock
- extensive or spreading purpura
- after convulsions until stabilised
- coagulation abnormalities
- coagulation results (if obtained) outside the normal range
- platelet count below 100 x 109/litre
- receiving anticoagulant therapy
- local superficial infection at the lumbar puncture site
- respiratory insufficiency (lumbar puncture is considered to have a high risk of precipitating respiratory failure in the presence of respiratory insufficiency).
- signs suggesting raised intracranial pressure
- Start antibiotic treatment for bacterial meningitis if the CSF white blood cell count is abnormal:
- in neonates at least 20 cells/microlitre (be aware that even if fewer than 20 cells/microlitre, bacterial meningitis should still be considered if other symptoms and signs are present)
- in older children and young people more than 5 cells/microlitre or more than 1 neutrophil/microlitre, regardless of other CSF variables.
- In children and young people with suspected bacterial meningitis, consider alternative diagnoses if the child or young person is significantly ill and has CSF variables within the accepted normal ranges. Consider herpes simplex encephalitis as an alternative diagnosis.
- If CSF white cell count is increased and there is a history suggesting a risk of tuberculous meningitis, evaluate for the diagnosis of tuberculous meningitis
- Cranial computed tomography in suspected bacterial meningitis
- Use clinical assessment and not cranial computed tomography (CT), to decide whether it is safe to perform a lumbar puncture. CT is unreliable for identifying raised intracranial pressure.
- If a CT scan has been performed, do not perform a lumbar puncture if the CT scan shows radiological evidence of raised intracranial pressure.
- In children and young people with a reduced or fluctuating level of consciousness (Glasgow Coma Scale score less than 9 or a drop of 3 or more) or with focal neurological signs, perform a CT scan to detect alternative intracranial pathology.
Management
- Empirical antibiotics for suspected bacterial meningitis or meningococcal disease
- Treat children and young people aged 3 months or older with suspected bacterial meningitis without delay using intravenous ceftriaxone.
- Treat children younger than 3 months with suspected bacterial meningitis without delay using intravenous cefotaxime plus either amoxicillin or ampicillin.
- Treat suspected meningococcal disease without delay using intravenous ceftriaxone.
- Treat children and young people with suspected bacterial meningitis who have recently travelled outside the UK or have had prolonged or multiple exposure to antibiotics (within the past 3 months) with vancomycin in addition to the above antibiotics.
- If tuberculous meningitis is part of the differential diagnosis use antibiotic treatment appropriate for tuberculous meningitis.
- If herpes simplex meningoencephalitis is part of the differential diagnosis give appropriate antiviral treatment.
- Treatment for confirmed specific infections
- Meningococcal disease
- In children and young people with confirmed meningococcal disease, treat with intravenous ceftriaxone for 7 days in total unless directed otherwise by the results of antibiotic sensitivities.
- In children and young people with unconfirmed but clinically suspected meningococcal disease, treat with intravenous ceftriaxone for 7 days in total.
- Children > 3 months
- Treat H influenzae type b meningitis with intravenous ceftriaxone for 10 days in total unless directed otherwise by the results of antibiotic sensitivities.
- Treat S pneumoniae meningitis with intravenous ceftriaxone for 14 days in total unless directed otherwise by the results of antibiotic sensitivities.
- In children and young people aged 3 months or older with unconfirmed, uncomplicated but clinically suspected bacterial meningitis, treat with intravenous ceftriaxone for at least 10 days depending on symptoms and signs and course of the illness.
- Children < 3 months
- Treat Group B streptococcal meningitis with intravenous cefotaxime for at least 14 days. If the clinical course is complicated consider extending the duration of treatment and consulting an expert in paediatric infectious diseases.
- Treat bacterial meningitis due to L monocytogenes with intravenous amoxicillin or ampicillin for 21 days in total, plus gentamicin for at least the first 7 days.
- Treat bacterial meningitis due to Gram-negative bacilli with intravenous cefotaxime for at least 21 days unless directed otherwise by the results of antibiotic sensitivities. If the clinical course is complicated consider extending the duration of treatment and consulting an expert in paediatric infectious diseases.
- In children younger than 3 months with unconfirmed but clinically suspected bacterial meningitis, treat with cefotaxime plus either ampicillin or amoxicillin for at least 14 days. If the clinical course is complicated, consider extending the duration of treatment and consulting an expert in paediatric infectious diseases.
- Meningococcal disease
- Corticosteroids
- Bacterial meningitis
- Do not use corticosteroids in children younger than 3 months with suspected or confirmed bacterial meningitis.
- Give dexamethasone (0.15 mg/kg to a maximum dose of 10 mg, four times daily for 4 days) for suspected or confirmed bacterial meningitis as soon as possible if lumbar puncture reveals any of the following:
- frankly purulent CSF
- CSF white blood cell count greater than 1000/microlitre
- raised CSF white blood cell count with protein concentration greater than 1 g/litre
- bacteria on Gram stain.
- If dexamethasone was not given before or with the first dose of antibiotics, but was indicated, try to administer the first dose within 4 hours of starting antibiotics, but do not start dexamethasone more than 12 hours after starting antibiotics.
- After the first dose of dexamethasone discuss the decision to continue dexamethasone with a senior paediatrician.
- Meningococcal septicaemia
- Do not treat with high-dose corticosteroids (defined as dexamethasone 0.6 mg/kg/day or an equivalent dose of other corticosteroids).
- In children and young people with shock that is unresponsive to vasoactive agents, steroid replacement therapy using low-dose corticosteroids (hydrocortisone 25 mg/m2 four times daily) should be used only when directed by a paediatric intensivist.
- Bacterial meningitis
- Other aspects of management
- Metabolic disturbances
- Anticipate, monitor and correct metabolic disturbances including hypoglycaemia, acidosis, hypokalaemia, hypocalcaemia, hypomagnesaemia, anaemia, coagulopathy.
- Seizures
- Use local or national protocols for management of seizures in children and young people with suspected bacterial meningitis or meningococcal septicaemia.
- Raised intracranial pressure
- Use local or national protocols to treat raised intracranial pressure.
- Fluid management
- Assess for signs of shock, raised intracranial pressure and signs of dehydration.
- If present, correct dehydration using enteral fluids or feeds, or intravenous isotonic fluids (for example, sodium chloride 0.9% with glucose 5% or sodium chloride 0.9% with dextrose 5%).
- If intravenous maintenance fluid is required, use isotonic fluids (for example, sodium chloride 0.9% with glucose 5% or sodium chloride 0.9% with dextrose 5%). In neonates, use glucose 10% and added sodium chloride for maintenance.
- Monitor fluid administration and urine output to ensure adequate hydration and avoid overhydration. Monitor electrolytes and blood glucose regularly (at least daily while the child or young person is receiving intravenous fluids).
- Intravenous fluid resuscitation in meningococcal septicaemia
- If there are signs of shock, give an immediate fluid bolus of 20 ml/kg sodium chloride 0.9% over 5–10 minutes. Give the fluid intravenously or via an intraosseous route and reassess the child or young person immediately afterwards.
- If the signs of shock persist, immediately give a second bolus of 20 ml/kg of intravenous or intraosseous sodium chloride 0.9% or human albumin 4.5% solution over 5–10 minutes.
- If the signs of shock still persist after the first 40 ml/kg:
- immediately give a third bolus of 20 ml/kg of intravenous or intraosseous sodium chloride 0.9% or human albumin 4.5% solution over 5–10 minutes
- call for anaesthetic assistance for urgent tracheal intubation and mechanical ventilation
- start treatment with vasoactive drugs
- be aware that some children and young people may require large volumes of fluid over a short period of time to restore their circulating volume
- consider giving further fluid boluses at 20 ml/kg of intravenous or intraosseous sodium chloride 0.9% or human albumin 4.5% solution over 5–10 minutes based on clinical signs and appropriate laboratory investigations including urea and electrolytes
- Vasoactive therapy for shock in meningococcal septicaemia
- If shock persists despite fluid resuscitation (more than 40 ml/kg) and treatment with either intravenous adrenaline or intravenous noradrenaline, or both, consider potential reasons (such as persistent acidosis, incorrect dilution, extravasation) and discuss further management options with a paediatric intensivist.
- Use local or national protocols for the administration of vasoactive agents in children and young people with suspected or confirmed bacterial meningitis or meningococcal septicaemia.
- Respiratory support
- In self-ventilating children and young people with signs of respiratory distress, administer 15-litre face mask oxygen via a reservoir rebreathing mask.
- If there is a threatened loss of airway patency, implement airway-opening manoeuvres, and start bag–valve mask ventilation in preparation for tracheal intubation.
- Use local or national protocols for intubation.
- Metabolic disturbances
Prophylaxis
- Be aware that bacterial meningitis and meningococcal disease are notifiable diseases.
- Seek advice regarding the management of close contacts of a case of bacterial meningitis or meningococcal disease from the regional health protection unit.
- Inform close contacts that the risk to a contact is low with meningococcal disease. The risk is highest in the first 7 days after a case is diagnosed and falls sharply thereafter.
- Prophylaxis against meningococcal disease should be considered for the following close contacts, regardless of meningococcal vaccination status:
- People who have had prolonged close contact with the case in a household-type setting during the 7 days before onset of illness (for example, people who are living or sleeping in the same household, pupils in the same dormitory, boy/girlfriends, or university students sharing a kitchen in a hall of residence).
- People who have had transient close contact with a case only if they have been directly exposed to large particle droplets/secretions from the respiratory tract of a case around the time of admission to hospital.
- Antibiotic prophylaxis should be given as soon as possible (ideally within 24 hours) after the diagnosis of the index case.
Complications
- Neurological complications
- Hearing loss
- Seizures
- Cognitive impairment
- Motor deficits
- Visual impairment
- Physical complications
- Amputations
- Skin scarring
- Other complications
- Hydrocephalus
- Learning difficulties
- Emotional and behavioural difficulties
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- Biochemistry
- Blood Gases
- Haematology
| Biochemistry | Normal Value |
|---|---|
| Sodium | 135 – 145 mmol/l |
| Potassium | 3.0 – 4.5 mmol/l |
| Urea | 2.5 – 7.5 mmol/l |
| Glucose | 3.5 – 5.0 mmol/l |
| Creatinine | 35 – 135 μmol/l |
| Alanine Aminotransferase (ALT) | 5 – 35 U/l |
| Gamma-glutamyl Transferase (GGT) | < 65 U/l |
| Alkaline Phosphatase (ALP) | 30 – 135 U/l |
| Aspartate Aminotransferase (AST) | < 40 U/l |
| Total Protein | 60 – 80 g/l |
| Albumin | 35 – 50 g/l |
| Globulin | 2.4 – 3.5 g/dl |
| Amylase | < 70 U/l |
| Total Bilirubin | 3 – 17 μmol/l |
| Calcium | 2.1 – 2.5 mmol/l |
| Chloride | 95 – 105 mmol/l |
| Phosphate | 0.8 – 1.4 mmol/l |
| Haematology | Normal Value |
|---|---|
| Haemoglobin | 11.5 – 16.6 g/dl |
| White Blood Cells | 4.0 – 11.0 x 109/l |
| Platelets | 150 – 450 x 109/l |
| MCV | 80 – 96 fl |
| MCHC | 32 – 36 g/dl |
| Neutrophils | 2.0 – 7.5 x 109/l |
| Lymphocytes | 1.5 – 4.0 x 109/l |
| Monocytes | 0.3 – 1.0 x 109/l |
| Eosinophils | 0.1 – 0.5 x 109/l |
| Basophils | < 0.2 x 109/l |
| Reticulocytes | < 2% |
| Haematocrit | 0.35 – 0.49 |
| Red Cell Distribution Width | 11 – 15% |
| Blood Gases | Normal Value |
|---|---|
| pH | 7.35 – 7.45 |
| pO2 | 11 – 14 kPa |
| pCO2 | 4.5 – 6.0 kPa |
| Base Excess | -2 – +2 mmol/l |
| Bicarbonate | 24 – 30 mmol/l |
| Lactate | < 2 mmol/l |
