The document discusses the long term effects of bacterial meningitis and sepsis in children. It finds that 50% of children develop new psychopathology like depressive and anxiety disorders following meningococcal disease, with 25% still experiencing issues after a year. Children with more severe illness are at higher risk. It also notes long term physical effects in survivors like scarring, neurological impairments, and reduced cognitive function and academic performance, with meningitis and sepsis having particularly detrimental impacts. Survivors are also at risk for hearing loss, motor deficits, and mental health disorders into adolescence and adulthood.

1. After effects of bacterial meningitis
and meningococcal disease: how and
why?
Dr Nelly Ninis

2. What happens in invasive bacterial
infections
- Meningitis
- Septicaemia
- And afterwards

3. The Bacteria
 Meningococcus
 Pneumococcus
 GAS
 Pseudomonas / staphylococcus

4. Infection – the start
 Viruses
 Common colds
 Flu
 C’Pox

6. Toxins
 Cause inflammatory explosion of immune system
 More toxins in blood = worse disease
 Antibiotics kill bacteria not toxins
 Once toxins detonate the immune system –
antibiotics, supportive care and time

7. Prodrome
Cardiovascular failure
MD – disease
development
Rash comes
at some point

8. Meningitis

9. Complications
 Brain swelling
 Vessel ( vascular ) complications- stroke
 Effusions
 Obstruction of flow of CSF

10. Intracranial pressure

11. Septicaemia
 Inflammation in the blood vessels throughout the
body
 Rapid onset multi-organ failure

12. Blood vessels are targetted

13. The Rash

16. Infection
Microbial Products
(exotoxin/endotoxin)
Cellular Responses
Oxidases
Platelet
Activation
Kinins
Complement
Coagulopathy/DIC
Vascular/Organ System Injury
Multi-Organ Failure
Death
Coagulation
Activation
Cytokines
TNF, IL-1, IL-6
Pathogenesis of Severe Sepsis:
Inflammation/Coagulation are Linked

18. Treatment

19. © Imperial College London
Treatment

20. Management of meningococcal disease
1940–1980s: Penicillin and pray
Recognition of rash
Penicillin
Counsel parents
Hope and prayer
© Imperial College London

22. Purpura Fulminans
 Topical treatments
 Fasciotomies
 Anti-toxins
 Anti- clotting
 NOTHING WORKS

23. After Effects

24. Psychiatric assessment of children 3–16 years admitted
with meningococcal disease, London
 Cohort study of children aged 3-16 years with MD admitted to 3 PICUs and
22 general paediatric wards in the London area
 Parents and children seen 2-5 days following hospital admission, and followed
up following discharge at 3 months (postal questionnaire) and 12 months
(interview)
 Psychiatric risk assessed in children (SDQ), parents (GHQ) and both (IES)
 Sample
 70/78 (89%) (36 boys; 34 girls) consecutive admissions for meningococcal disease
 52 PICU
 18 Non-PICU
 Median age at follow-up: 6.8 years
 (IQR: 4–12 years)

25. Psychological after effects in children and their
parents
Outcomes in children and parents, 3 months and 12 months post discharge
Children < 6y Children >6y Parents
3 months
post
discharge
12% had PTSD
Psychological symptoms linked to: PICU admission, illness severity,
similar symptoms in parents and pre-morbid psychological symptoms
MD associated with emotional and hyperactivity symptoms
~50% mothers and
~25% fathers had
PTSD symptoms
12 months
post
discharge
11% children at risk for PTSD
Psychological symptoms linked to illness-related changes in parenting
23% mothers and
11% fathers at high
risk for PTSD
Maternal PTSD
linked to paternal
PTSD
1 child developed PTSD
22% scored above cut-off for
psychiatric disorder
Problems: tantrums, difficult to
manage, sleep problems,
fears and feeding problems
50% at least one disorder
15% major depression
10% minor depression
7% adjustment disorder
10% oppositional defiant disorder
5% phobic disorder
2% panic disorder
2% transient psychotic disorder
Summary: 50% of children develop mostly new psychopathology following MD
(primarily depressive and anxiety-related disorders). In 25% this persisted at one year.
Garralda ME, et al. Pediatr Crit Care Med. 2009;10(6):675-80; Shears D, et al. J Am Acad Child Adolesc Psychiatry, 2007;46(1):76-82; Shears D, et al.
Pediatr Crit Care Med. 2005;6:39-43.

26. Admission to Paediatric Intensive Care
 Major stressful event for child and their family
 Families experience overwhelming shock and disbelief,
accompanied by feelings of helplessness
 Parents faced with worries about outcome of treatment
and acute life-threatening illness in their child
 PICU experience is intense—sights and sounds in the
environment, and seeing other children undergo painful,
distressing procedures or even death
 PICU admission imposes an immense burden on
critically ill children, their siblings, parents and other
family members, potentially increasing risk of adverse
psychological outcomes

27. Clinical evidence of neuropsychological effects
 Prospective observational case-control study of 88 children aged 5-16y
admitted to ICUs between 2007-2010 c.f. 100 healthy controls
 Follow-up 3-6 months after PICU admission
 Demographic and critical illness details were obtained, and children were assessed
using tests of intellectual function, memory, and attention
 Questionnaires addressing academic performance were returned by teachers
 Measurement tools
 IQ:
 Wechsler Abbreviated Scale of Intelligence (WASI; The Psychological Corporation,
1999) – 6 yrs and older
 Wide Range Intelligence Test (WRIT; Glutting et al) – 5 yr olds
 Verbal memory and learning:
 Children’s Memory Scale (CMS; Cohen, 1997)
 Visual memory, learning and attention:
 Cambridge Neuropsychological Test Automated
 Battery (CANTAB; Cambridge Cognition, 2006)

28. Neuropsychologic function after PICU admission
Psychiatric risk
70
60
50
40
30
20
10
0
PTSD risk
% at risk for PTSD
Septic Illness M-Encephalitis
Patient Ctr
Cognitive function
• Summary: Meningoencephalitis and sepsis particularly associated with reduced
neuropsychological function
Als LC, et al. Crit Care Med. 2013;41(4):1094-1103.

29. Deteriorating academic performance in
school post PICU (Sepsis worst performance)
Number of days off since
returning to school
11.50 ME 9.00 Sepsis 6.00 Patient Contr
Als LC, et al. Crit Care Med. 2013;41(4):1094-1103.

30. Conclusions from this study
Als LC, et al. Crit Care Med. 2013;41(4):1094-1103.
 In children with sepsis, meningo-encephalitis and other
disorders admitted to PICU:
 PICU admission was followed by an increase in child psychopathology
persisting at 12 months
 Children with more severe illness, those with septic shock and those
with impairing pre-morbid emotional and behavioural problems have the
highest risk
 Changes in parenting and maternal mental health may contribute to the
persistence of the psychological morbidities and may be potentially
treatable

31. What is known about the outcomes of
meningitis?
 CNS infections acquired in childhood lead to impairment in
motor and cognitive functions (Carter et al. 2003)
 12-year follow-up of children with bacterial meningitis found
general performance and executive function impairments in
comparison to controls (Anderson et al. 2004)
 Academic limitations identified in 32% children 4–10 years
following bacterial meningitis (Koomen et al. 2005)
 Teenagers from national incidence study of infantile meningitis
in England & Wales passed significantly fewer 16+ exams
compared with controls (De Louvois et al. 2007)

32. Long-term outcomes
Survivors of meningococcal septic shock that required PICU treatment
Long-term skin scarring &
orthopaedic sequelae
n=170, 4-16 years after discharge
Long-term overall outcome
and health-related QoL
n=120, 3-18 years after discharge
Long-term health status
n=120, 10 years after discharge
48% scarring
61% (73 of 120) had 1 of 4 major
adverse outcome variables
35% one or more neurological
impairment
8% amputations
26 of 73 had >1 major adverse
outcome
3% severe mental retardation
6% lower limb length discrepancy
47 of 73 had 1 major adverse
outcome
• 13 major physical
• 19 mild neurological
• 7 problem behaviour
• 8 IQ<85
3% epilepsy
All had higher severity of illness
scores
Longer LOS and higher severity
score predicted worse outcome
2% hearing loss
6% focal neurology (i.e. paresis)
Buysse CMP, et al. Arch Dis Child
2009;94:381–386.
Buysse CMP, et al. Crit Care
2010;14:R124.
Buysse CMP, et al. Arch Pediatr
Adolesc Med 2008;162(11):1036-1041.

33. Lancet Neurol 2012;11:774–783.
 245 survivors of group B meningococcal disease (3 years after
disease)
 Age and sex matched healthy controls
 2% profound bilateral SNHL
 5% moderate bilateral SNHL
 6% any SNHL (control < 1%)
 4% speech/communication difficulty
 IQ, memory and executive function significantly worse
 Significantly higher risk of mental health disorder
(26% vs 10% in controls)

34. Outcomes in adolescents

35. Outcomes from MD - 2003
Cohort of 101 case-control pairs
 Short and long term memory and attention
deficits
 Deficit in cognitive flexibility
 Higher rates of depression in MCD sufferers
 This should be attended to in follow up

36. 18 , 36 month follow up of cohort
 57% of survivors had physical disability- much
higher than studies with younger children
- Serogroup C disease, septicaemia had worse physical
outcome
 Adolescents who were younger at time of MD-greater
degree of cognitive deficit at follow up
- Development of “social brain” in adolescence

37. QoL worse than peers
• Mental Health – twice as many survivors had
depressive score in clinical range
• Social support – lower social support scores
• Educational outcomes- fewer passes at GCSE, 2x
more likely to have failed exam in past year

38. Wide range of significant sequelae from
Invasive Meningococcal Disease
Subacute and Chronic Sequelae of IMD
 Hearing loss/deafness
 Ossification of the inner ear
 Blindness
 Brain abscess
 Seizure disorders/epilepsy
 Cranial nerve palsies
 Hemiparesis or quadriparesis
 Obstructive hydrocephalus
 Neuropsychiatric disorders
 Post-traumatic stress disorder
 Learning deficits
 Motor deficits/ataxia
 Neurodevelopment deficits
 Cerebral infarction/stroke
 Cerebral arterial or venous thrombosis
 Subdural effusion
 Limb loss
 Digit amputation
 Growth plate damage
 Skin grafts/scar repair
 Necrotic skin loss
 Arthritis
 Renal impairment
 Chronic organ damage
 Adrenal failure
 Cognitive impairment
 Nonsuppurative complications—eg, immune
complex disorders, vasculitis, arthritis
 Empyema
 Endocrinopathies
Some sequelae do not become evident until years after the illness, long after
1. Singhi PD, et al. In: Helfaer MA, et al, eds. Rogers’ Handbook of Pediatric Intensive Care. Philadelphia, PA: Lippincott, Williams & Wilkins; 2009:
500-519; 2. Brandtzaeg P. In: Frosch M, et al, eds. routine Handbook of follow-Meningococcal up Disease: has Infection ceased.
Biology, Vaccination, Clinical Management. Weinheim,
Germany: Wiley-VCH Verlag GmbH & Co. KGaA; 2006:427-479; 3. Granoff DM, et al. In: Kleigman RM, et al, eds. Nelson Textbook of Pediatrics, 19th ed.
Philadelphia, PA: Saunders Elsevier; 2011;929-935; 4. Judge D, et al. Intensive Care Med. 2002;28:648-650; 5. Anderson V, et al. J Pediatr Psychol.
2004;29:67-81; 6. Bedford H, et al. BMJ. 2001;323:533-536.

39. In Conclusion
 Surviving sepsis and meningitis is difficult business
 Patients are very inspiring and capable and able
 Education about after effects very important
Thank you