M.R AshrafiProfessor Of Pediatric Neurology

Children’s Medical CenterTehran university Of Medical Sciences

Neurologic Complications of Immunization

Adverse Events Following Immunization / AEFI

Vaccine Reaction

Program Error

Coincidental

Injection Reaction

Unknown

AEFI / Neurologic Complications Vaccine Reaction

Hypotonic-Hyporesponsive Episode

Persistent Crying Seizure Encephalopathy Paralytic poliomyelitisGuillaine-Barre Syndrome

Hypotonic-Hyporesponsive Episode

Worrisome uncommon shock-like reaction to DTP

Occurs within 24 hours with a mean interval of 12 hoursIncidence of 0.06 % of DPT-immunized infants

Approximately one-half of infants are febrile

The episode subsides in minutes to at most 4 hours

Leaving no apparent residua

AEFI / Neurologic Complications Vaccine Reaction

Persistent or high pitched crying of 1 hour or more was seen in 3.5 % of DPT-immunized infants .

Drowsiness was seen in approximately 32-62 % of DPT-immunized infants .

A transient increase in ICP , manifested by a bulging fontanel , has been encountered after DPT immunization .

AEFI / Neurologic Complications Vaccine Reaction

The use of whole-cell pertussis vaccine has been associated with febrile and afebrile seizures , which are generalized and typically occur within 72 hours after immunization .

FS occur in 1 : 1750 immunization

Acute Encephalopathy

Generalized febrile or nonfebrile convulsions , altered consciousness and serious neurologic or psychologic residua can occur within 72 hours of DPT immunization .

Incidence of 1 : 165000 immunization

The prognosis for survival is good

Major neurologic residua in 77 % of cases such as MR and epilepsy .

Acute EncephalopathyAcute encephalopathy can follow

immunization with measles or MMR vaccine .Occur between 2 – 15 days after

immunization , and peak onset of encephalopathy on days 8 or 9 .

Seizures , altered behavior or consciousness and ataxia .

Death or mental regression is common No cases of encephalopathy have been

identified after administration of monovalent mumps or rubella vaccines .

AEFI / Neurologic Complications Vaccine Reaction

Hypotonic-Hyporesponsive Episode

Persistent Crying Seizure Encephalopathy Paralytic poliomyelitisGuillaine-Barre Syndrome

Vaccine Associated Paralytic Poliomyelitis / VAPP

Any case of AFP with onset of paralysis 4-30 days following receipt of OPV and the presence of neurological sequelae compatible with poliomyelities 60 days following paralysis onset and isolation of vaccine-derived poliovirus from the stools .

Serotype 3 is most frequently isolated poliovirus from patients with VAPP (60-90%)

The following criteria must be fulfilled before diagnosis of VAPP

Paralysis should be clinically compatible with poliomyelitis (residual paralysis at 60 days )

Adequate stool negative for wild polioRuled out other illnesses Evaluation by expert committee

Contact VAPP

Known contact with a vaccinee that received OPV 7-70 days before onset of paralysis of

the patient and the contact between the patient and vaccinee should have occurred 4-30 days before paralysis onset.

Half of the cases of VAPP reported from America are among contacts of vaccinated children

VDPV (Vaccine-derived poliovirus )

Usually 1-15% differences from parent OPV strains

Classified as wild.Extensive period of virus excretion or

transmission.

AEFI / Neurologic Complications Vaccine Reaction

Hypotonic-Hyporesponsive Episode

Persistent Crying Seizure Encephalopathy Paralytic poliomyelitisGuillaine-Barre Syndrome

GBS study group diagnostic criteria

Required for diagnosis :

Progressive motor weakness involving

more than one extremity

Areflexia or marked hyporeflexia

GBS study group diagnostic criteriaStrongly supportive of diagnosis :

Initial absence of fever

Progressive over days to a few weeks

Onset of recovery 2-4 weeks after cessation

of progression

Relatively symmetric weakness

Mild sensory sign and symptoms

Cranial nerve palsies

Autonomic dysfunction

Elevation of CSF protein after one week of symptoms

Slowed NCV

GBS / Etiology

Two-thirds of patients report an antecedent , acute

infectious illness , most commonly a respiratory tract

infection or gastroenteritis .

The interval between the prodromal infection and the

onset of GBS symptoms varies between 1-3 weeks .

CMV is the most common viral trigger of GBS .

C.Jejuni is recognized as the most frequent antecedent

pathogen for GBS .

Preceding Events

Infection

Campylobacter Jejuni

Cytomegalovirus

EBV / HIV / VZV / Lyme Disease

Vaccination

Rabies / Swine Flu / Tetanus / OPV / Meningococcus

Neoplasia

Lymphoma / Hodgkin Disease

Drug

Captopril / Danazole / Penicillamine /Amitriptyline

Heavy metals / Nitrofurantoin / Hydralazine

Adverse Events Following Immunization / AEFI

Vaccine Reaction

Program Error

Coincidental

Injection Reaction

Unknown

AEFI / Neurologic Complications injection Reaction / Faint

Syncope is defined as a sudden loss of consciousness and postural tone , because of transient cerebral hypoperfusion , followed by spontaneous recovery .

Syncope is rare in childhood and more common in adolescence particularly in girls .

Syncope is seen in about 15 % of individuals under the age of 18 years.

30 to 50 % of children have at least one episode of syncope by adolescence .

Vasovagal (75 % )ReflexDecreased venous returnCardiac

Syncope & Faint Vasovagal ( Neurocardiogenic Syncope ) Triggered by pain & emotional upset .

Reflex Hyperventilation , violent coughing , hot bath , defecation and micturition .

Reduced venous return Valsalva maneuver

Cardiac syncope Cardiac asystole ( Stokes-Adams Syndrome)ArrhythmiaLeft ventricular outflow obstructionAnemiaProlonged QT interval : Romano-Ward syndrome ( AD) Jervell-Lange-Nielsen Syndrome ( AR )

Syncope & Faint Prodromal phase or presyncope

Light-headedness , blurred vision , epigastric discomfort , nausea , pallor , diaphoresis .

Loss of consciousness

Is usually brief ( few seconds to 1-2 minutes ) followed by rapid spontaneous recovery without persistent neurologic deficits .In 40 % of cases syncopal attacks are accompanied by a convulsion. ( usually tonic spasm , less often clonic or TC )

Postictal period

May be accompanied by nausea , pallor and diaphoresis .

Adverse Events By DPT Vaccine

Event Conclusion Evidence indicates causation Anaphylaxis prolonged crying Febrile SeizureEvidence consistent with causation Acute

encephalopathy HHEEvidence does not indicate causation Afebrile Seizure Infantile Spasm SIDS Reye Syndrome

Adverse Events By DPT Vaccine

Event Conclusion Insufficient evidence to Aseptic meningitis draw a conclusion Chronic neurological

damage

Epilepsy GBS Peripheral mononeuropathy Hemolytic anemia Thrombocytopenia Juvenile Diabetes Learning or attention

disorders Erythema multiform

No evidence available either way Autism

AEFI / Neurologic Complications Sudden Infant Death Syndrome

SIDS is defined as the sudden death of an infant that is unexpected by history and unexplained by a thorough postmortem examination , which include a complete autopsy , investigation of the scene of death , and review of the medical history .

Infants are at greatest risk of SIDS at 2-4 months of age , with most deaths having occurred by 6 months .

Male infants are 30-50 % more likely to be affected than females .

The actual risk for SIDS in individual infants is determined by complex interactions between genetic and environmental risk factors .

AEFI / Neurologic Complications Sudden Infant Death Syndrome

AEFI / Neurologic Complications Sudden Infant Death Syndrome

No association between

immunization and SIDS

has been found .

Diazepam IV / PR / IO IV : 0.1 to 0.3 mg/kg /dose every 10-15 min

PR : 0.2 to 0.5 mg/kg/dose

Maximum dose of DZP is 10 -20 mg/dose .

DZP should be administered at a rate of 1-2 mg/min .

DZP stops seizure within 5 to 10 min in 80 % of status .

Median time to stop seizure : 2 min

Peak effect : 1 to 5 min

Duration of action : 20 to 30 min

A longer acting AED should be given if DZP

successfully stops the status .

Rectal DiazepamRectal diazepam is an effective and safe treatment for

prolonged seizures outside the hospital .

It achieves blood levels adequate for seizure treatment

more rapidly than any route except for IV one .

It has FDA approval for acute repetitive seizures

but not for Status .

Reports mention its successful use in status .

•Buccal and intranasal midazolam are other treatment options .