Ghai Essential Pediatrics8th

1History, examination, investigations to ascertain cause

Fig. 18.6: Management of status epilepticus. Following initial assessment, patients need to be treated with anticonvulsants. If required, more than one agent may be administered sequentially. Patients should bemonitored forrespiratorydifficultyand mightneed assisted ventilation

lorazepam, midazolam or diazepam. If diazepam is used when treating SE, a long acting anticonvulsant such as phenytoin must be administered concurrently with diazepamtopreventrecurrentconvulsions. Seizurecontrol occurs within 5 min of benzodiazepine administration in

80% of patients. The usual IV dosage for diazepam is 0.1 to 0.3 mg/kg given at a rate of 1 mg/min. This dose can be repeated two times every 5 to 10 min if seizures persist up to a maximum dose of 10 mg. Lorazepam (0.05--0.1 mg/kg IV)isthepreferredfirstlineanticonvulsantasithasalonger duration of action (12-24 hr), less respiratory depression and repeated doses are less often required than with diazepam. A second long-acting anticonvulsantisalsonot requiredbecauseoflongerdurationofaction. Maintenance drugs should be added to control further seizures. If IV access cannot be immediately obtained, then other routes of administration (rectal, oral) should be considered.

Midazolam is animportant drug for the initial management of acute seizure. It can be used IMor intranasal if IV access is not available at a dose of 0.1 to 0.2 mg/kg.

Phenytoin is used for maintaining a prolonged antiseizure effect after rapid termination of seizures with a benzo­ diazepine. The loading dose is 20 mg/kg infused at a rate of 0.5-1 mg/kg/min(maximum50 mg/min).A therapeutic effect can be seen in 20 min. Saline solution should be used for dilution as phenytoin precipitates in dextrose. Side effects include hypotension, cardiac dysarrhythmia, phlebitisandtissue necrosis from extravasation, movement disorder and cerebellar ataxia.

Fosphenytoin is a water-soluble ester of phenytoin that is rapidly converted to phenytoin bysystemic phosphatases and can be administered intramuscularly. The dose of fosphenytoin is expressed in phenytoin equivalents (PE) and is 15-20 mg/kg, infused at a rate of no more than 3 mg/kg/min (maximum 150 mg/min). Phlebitis is less common with fosphenytoin but itsprimarydisadvantage is high cost.

If no response to benzodiazepines and phenytoin, phenobarbitone is administered at a loading dose of 10 to 20 mg/kg at a rate of 1 to 2 mg/kg/min. Potential side effects include hypotension, respiratory depression and sedation. Phenobarbitone is thedrug of choice in neonatal seizures, hypersensitivity to phenytoin and cardiac conduction abnormality.

In patients on oral phenytoin or phenobarbitone,

5-10 mg/kg of the drug should be given if drug with­ drawal is the likely cause of SE.

Paraldehyde is generally not available; can be administered per rectally or intramuscularly with a glass syringe.

If signs and symptoms of raised intracranial pressure are present, mannitol can be administered at a dose of

5 ml/kg (20%) IV over 10 min to decrease cerebral edema.

Maintenance therapy should be simultaneously started with appropriate AED.

Refractory Status Epilepticus

When the seizure do not respond to at least two doses of benzodiazepines, followed by phenytoin/valproate and phenobarbitone or midazolam infusion beyond 60 min after treatment has been started, it is labeled as refractory

SE and must be ideally managed in a tertiary health care

center with intensive care unit where facility for artificial ventilation is available. Treatment of refractorySE include barbiturate coma, midazolam infusion, lignocaine, intra­ venous valproate, propofol and inhalation anesthesia.

Inarecentmeta-analysis,midazolaminfusionwasfound tobeagoodchoiceforinitial treatment ofrefractorySE with fewer hemodynamic consequences and lesser need for invasive monitoring and mechanical ventilation. A bolus dose of 0.15 mg/kg of midazolam is followed by conti­ nuousinfusionatarateof1 µg/kg/minincreasingby 1µg/ kg/min every 15 min until a maximum of 18 µg/kg/min or seizure control. The optimum rate of infusion at which seizure control is achieved is maintained for a period of 48 hr. Subsequently the infusion rate is gradually decreased by 1 µg/kg/min every three hr with frequent EEG review. Anyseizureactivityduringtheweaningperiodrequiresan immediate resumption of the infusion to achieve again a seizure-free period of 48 hr.

Both pentobarbital and thiopental have been used for barbiturate coma. Patients requiring barbiturate coma must be intubated and mechanically ventilated with close hemodynamic and continuous EEG monitoring. Pento­ barbital is given in a loading dose of 5 mg/kg followed by an infusion of 0.5-3 mg/kg/hr. The patient is moni­ tored for a burst suppression pattern by EEG. The patient remains in barbiturate coma for 12 to 24 hr. The patient is then weaned and observed for recurrence of seizure activity. If seizure recurs, the patient is placed back into the barbiturate coma and weaning is again tried after another 24 hr. Barbiturate coma is advantageous over the use of general anesthesia. Continuous EEG is necessary to ensure that burst suppression has occurred.

Longterm anticonvulsant drugs The decision for therapy is based on the underlying cause and predicted risk of seizure. When no etiology is identified and the EEG is normal, the recurrence risk is 24% at 2 yr. Patients with abnormal neuroimaging/EEG orfocal seizures have a 65% risk of recurrence and should receive longterm anti­ convulsant therapy.

Suggested Reading

Abend NS, Dlugos DJ. Treatment of refractory status epilepticus: literature review and a proposed protocol. Pediatr Neurol 2008;38: 377-90

Bleck TP. Intensive care unit management of patients with status epilepticus.Epilepsia 2007;48 Suppl 8:59-60

Brevoord JC, Joosten KF, Arts WF, et al. Status epilepticus: clinical analysis of a treatment protocol based on midazolam and phenytoin. J Child Neurol 2005;20:476--81

Prasad K, Al-Roomi K, Krishnan PR, Sequeira R. Anticonvulsant therapy for status epilepticus. Cochrane Database Syst Rev 2005; (4):CD003723

FEBRILE CONVULSIONS-------

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Febrileconvulsions are the commonestprovokedseizures affecting 3-5% children. They are defined as seizures

duringfever occurring between 6 months and 5 yr age in the absence of infection of the central nervous system in a neurologically normal child. Febrile seizures are frequently genetically determined. The convulsions are not related to the degree of temperature, but are frequent if temperature rises abruptly. Febrile convulsions may be

(i) simple, benign; or (ii) atypical, complex.

Simplefebrile convulsions. The seizure occurs within 24 hr of the onset of fever, last less than 15 min and are usually single per febrile episode. Convulsions are generalized. There is no postictal neurological deficit.

Atypical febrile seizures. Atypical or complex febrile convulsions should be distinguished from simple febrile convulsions. Presence of family historyof epilepsy, neuro­ developmental retardation and atypical episodes increase recurrence risk of febrile seizures and subsequent epilepsy.

Convulsions in developmentally challenged children may be precipitated by fever, as the cerebral threshold for seizures is reduced with the elevation of temperature.

These are distinct from febrile convulsions, which occur in a neurodevelopmentally normal child.

Differentiation from meningitis. Infections of the central nervous system such as meningitis or encephalitis, are importantcausesof convulsionsassociatedwith feverand can be easily confused with simple febrile convulsions. Lumbarpunctureshould be performed in the first episode of febrile seizure, in infants below 1 yr who are not immunized with Hib and pneumococcal vaccine, or if immunization status is not known and where meningitis is suspected. In all patients with febrile convulsions, a lumbar puncture is not required routinely. EEG and neuroimaging have no role in febrile seizures.

Treatment. Febrile convulsions are managed by prompt reduction of temperature with antipyretics or hydro­ therapy to comfort the patient. Maintenance of airway, breathing and circulation should be ensured. In case of prolonged febrile seizures, IV access should be established to maintain adequate hydration and to administer anticonvulsant medication. Possibility of meningitis should be excluded by a lumbar puncture if indicated. Injectionof midazolamordiazepam (0.2--0.3mg/kg/dose) is given for control of seizures.

Febrile Seizure Prophylaxis

Prophylaxis may be continuous or intermittent. Inter­ mittent prophylaxis of febrile convulsions is indicated if 3 or more febrile seizures in 6 months, or 6 or more in 1 yr, febrile seizures lastingmore than 15 min or requiring pharmacological therapy to control seizures.

Intermittent prophylaxis is currently prescribed during episodes of fever. A drug that attains druglevels quickly and prevents febrile convulsions should be used. Oral

clobazam (0.75-1 mg/kg/day) is aneffectiveprophylactic andisgivenfor 3 days duringfever episodes. Antipyretics, hydrotherapy and meticulous temperature recording should be advocated for all patients. Domiciliary care is recommended.

Continuous prophylaxis with antiepileptic drugs is advo­ cated in the event of failure of intermittent therapy, recurrent atypicalseizuresandin particular,whenparents are unable to promptly recognize the onset of fever. Only sodium valproate (10-20 mg/kg/day) or phenobarbitone (3-5 mg/kg/day) are effective for febrile seizure prophy­ laxis. Carbamazepine and phenytoin are ineffective. The duration of therapy should be for 1-2 yr or until 5 yr of age.

Prognosis. Recurrence risk of febrile convulsions varies from 30 to 50%. Risk factors that canpredictthe recurrence of simple and complex febrile seizures are early age of onset (<15 months), epilepsy or fevers in first-degree rela­ tives, frequent fevers and low temperature at the onset of the febrile seizure. About 1-2% of children with simple febrile convulsions and up to 5% of those with recurrent complex seizures are likely to develop epilepsy. Parents of the child should be reassured that the risk of epilepsy after simple febrile seizure is not significantly greater than the general population. The risk of developing epilepsy is higher if the seizures are atypical, electroencephalogram is persistently abnormal, if the child has abnormal neuro­ developmentora family history of epilepsy. Complex par­ tial seizures may manifest after several years of prolonged atypical febrile convulsions.

Suggested Reading

Capovilla G, Mastrangelo M, Romeo A, Vigevano F. Recommen­ dations for the management of febrile seizures. Ad hoc Task Force of LICE Guidelines Commission. Epilepsia 2009;50:2-{)

Dube CM, Brewster AL, Richichi C, Zha Q, Baram TZ. Fever, febrile seizures and epilepsy. Trends Neurosci 2007;30:490-{)

Febrile seizures: Guideline for the neurodiagnostic evaluation of child with a simple febrile seizure. Subcommittee on febrile seizures. Pediatrics 2011;127:389

EPILEPSY

Epilepsyischaracterizedbyrecurrent,episodic,paroxysmal, involuntary clinical events associated with abnormal electrical activity from the neurons. The patient may present with motor, sensory or psychomotor phenomena, often with alteration in sensorium.

Epidemiology and Classification

Five percent of children may experience one or more seizures in childhood, less than 1% have epilepsy. The incidence is highest in the preschool years. Intrafamilial recurrence of convulsions, especially simple febrile convulsions, is common.

Central Nervous System -

Epilepsy is classified by appraisal of (i) seizure type, (ii) etiology, and (iii) electroencephalographic data. If an underlyingetiologyisidentifiedit issymptomaticepilepsy otherwise it is called idiopathic. In cryptogenic epilepsy, a cause is presumed. A simplified modified version of the classification proposed by the International League Against Epilepsy (ILAE 1981) is given in Table 18.4.

Clinical Features

Epilepsy is described as generalized or partial (focal). Generalized seizures may be (i)tonic;clonicor tonic-clonic; (ii) absence (petit mal); (iii) atonic, and (iv) myoclonic.

Tonic-C/onic Seizures (Grand Mal Type)

Generalized tonic-clonic seizures are the most frequent form of childhood epilepsy. Classic form has four phases viz. (i) aura; (ii) tonic; (iii) clonic; and (iv) postictal phase.

Aura. A transitory premonitory symptom or aura heralds the onset of aseizure. Aura may be sensory, visceral, motor or autonomic. Only one-third of patients can describe the aura properly.

Tonic phase. During this phase, skeletal muscles go into a sustained spasm. The muscular rigidity is most marked

Table 18.4: Classification of epilepsy

Generalized

Generalized epilepsy may be (i) tonic-clonic (grand mal), (ii) tonic, (iii) clonic, (iv) absence, (v) atonic, (vi) myoclonic

Idiopathic: (i) benign neonatal convulsions, (ii) childhood absence, (iii)juvenileabsence, (iv)juvenilemyoclonicepilepsy,

(v) grand mal seizures on awakening, (vi) generalized idiopathic

Symptomatic/Cryptogenic: (i)Westsyndrome(infantilespasms), (ii)Lennox-Gastaut syndrome (childhood epileptic encephalo­ pathy), (iii) myoclonic astatic seizures, (iv) myoclonic absences

Partial

Simple partial (elementary symptoms, no impairment of consciousness) with (i) motor, (ii) sensory, (iii) autonomic, (iv) psychic

Complex partial (impaired consciousness): (i) simple partial followed by loss of consciousness; and (ii) with impaired consciousness at onset

Partial seizures evolving to secondary generalized seizures

Syndromes

Idiopathic: Benignchildhoodfocalepilepsy with centrotemporal spikes (Rolandic epilepsy); epilepsy with occipital paroxysms Symptomatic: (i) chronic progressive epilepsy; (ii) epilepsia partialis continua; (iii) progressive myoclonic epilepsy

Undetermined syndromes

Neonatal seizures

Severe myoclonic epilepsy of infancy, migratory partial seizures of infancy

Epilepsy with continuousspike waves duringslow wave sleep Acquired epileptic aphasia

in the antigravity muscles, such as flexors of arms and extensors of lower extremities. The child becomes uncon­ scious, falls, face appears pale, pupils are dilated and eyes are rolled and there is frothing from the mouth. Urine or stools may be passed involuntarily. This phase lasts for about thirty seconds.

Clonic phase. It is characterized by rhythmic alternating contractions of muscle groups. In many patients, epileptic phases overlap each other.

Postictal phase. The child may complain of headache, confusionandhas little recollection later. Rarely, the child develops a transient paresis, may lose bladder/bowel control or injurehimself. EEG shows generalized burst of spikes and irregular 4-6 Hz spike-wave complex.

Absence Seizures

Absence seizures start abruptly in childhood; the peak prevalence is between 6-8 yr. Absence seizures are not preceded by aura. The patients have a brief abrupt lapse of awareness or consciousness, sudden discontinuation of the activity being performed with staring spell, eye fluttering, or rhythmic movements. The seizure lasts less than 30 seconds. There is no loss of posture, incontinence of urine/stools or breathing difficulty. Other neurological manifestations and postictal phenomena are absent and development is normal. Unaware of the nature of their illness, school teachers may consider them inattentive pupils.

Hyperventilation for3 min oftenprecipitatesthe attacks. Absence seizures may occur in multiples, everyday. Attacks following in close succession indicate petit ma/ status or pyknolepsy.

About half of patients become seizure free and the rest develop tonic-clonic fits. Learning disabilities and behavior disorders when present are probably related to associated conditions. EEG shows a characteristic 3 per second spike and slow wave pattern. Absence fits are distinguished from complex partial seizures by shorter duration (10 seconds), absence of aura and abrupt return of full consciousness.

Partial Seizures

Partial seizures account for 60% of seizures in childhood. Common causes include inflammatory granulomas, atrophic lesions, vascular insults, birth asphyxia, head trauma and neoplasms. In some geographic areas including India, neurocysticercosis has emerged as a commoncause. Neurocutaneoussyndrome, arteriovenous malformations and infarcts are less frequent. Magnetic resonance imaging may help to clarify the etiology more accurately than CT scanning.

Partial seizures are classified as

i.Simple partial without loss of consciousness, with motor, sensory, autonomic or mixed symptoms

ii.Complex partial withimpairment of consciousness and automatisms, psychomotor or limbic system symp­ toms

iii.Partial with secondary generalization

Simple partial seizures begin with a focal epileptiform discharge, howsoever brief. The symptoms may be motor or sensory, include tingling, pain, sensation of cold, burning. Sometimes visual, olfactory, auditory or taste hallucinations may be complained of. Consciousness is not impaired. When the simple seizure spreads uni­ laterally as per the motor cortex, it is called Jacksonian march.

Complex partial seizures. Originate from parietal or temporal lobe and may be associated with automatisms, or with loss of consciousness, even if seizures are not generalized.

Complex partial seizures originating from temporal lobe (psychomotor epilepsy). Symptoms are very protean and misdiagnosed for absenceseizures,behavior problems or malingering. Brief visceral, olfactory or visual aura are followed by peculiar posture, tonic jerks of the face and limbs, or one-sided dystonia. Patients may perform lip smacking,chewing orcomplexautomatisms or acts. There is no memory for the events and consciousness is impaired. Itmanifests, as memory disturbances like forced thinking or dreamy states, transitory fear, visual or other hallucinations. Vasomotor changes are often present. Tonic or clonic movements may follow in about 15%.

Benign childhood epilepsy with centrotempora/ spikes The syndrome is characterized by (i)onsetbetween 2 and 13 yr; (ii) no neurological or intellectual deficit; (iii) seizures generally occur in sleep, are partial and involve mouth area. Speech involvement, dysarthria and somatosensory symptoms are common; (iv) interictalEEG shows a spike focus over the centrotemporal or rolandic area; and (v) may be self limiting with spontaneous remission around adolescence. These comprise about one­ fourth childhood epilepsy and have autosomal dominant inheritance.

Neonatal Seizures

Incidence ranges from 1 to 2% to almost 20% in preterm infants. Poor myelinationandincompletedendriticarbori­ zation result in clinical manifestations that are different from older children.

Neonatal seizures present in decreasing order of frequency as (i) subtle; (ii) focal clonic; (iii) multifocal clonic; (iv) generalized tonic; and (v) myoclonic. Subtle seizures may manifest as eyelid blinking, fluttering or buccal-lingual movement. There may be pedaling or automatic movements because of subcortical neuronal discharges.

The common causes are hypoxic ischemic encephalo­ pathy (almost 50% cases), sepsis and bacterial meningitis.

Metabolic seizures due to hypoglycemia, hypocalcemia, dyselectrolytemia and hypomagnesemia account for almost one-fourth. Intracranial bleeding, developmental anomalies and inborn errors of metabolism need to be excluded. Malformations and dysgenetic states are importantcausesoftonicor myoclonictypeofjerks. About one-third are multifactorial and idiopathic.

Itisimportanttoestablishthe cause ofneonatalseizures; investigations for hypoglycemia, hypocalcemia, hypo­ magnesemia, hypoxia, sepsis should be performed. Lumbar puncture for the diagnosis of meningitis is advised. Hypoglycemia and hypocalcemia should be corrected before the administration of anticonvulsants.

Myoclonic Epilepsies

West syndrome (infantile spasms). The onset is usually between 3-8 months of life. It is characterized by a combinationof salaamspells(suddendroppingofthehead and flexion of arms), developmental retardation and hypsarrhythmia on EEG. Common causes of infantile spasms are: (i) hypoxic ischemic encephalopathy; (ii) neurocutaneous syndromes specially tuberous sclerosis; (iii) perinatal infections; (iv) hemorrhage;

(v) injury; (vi) metabolic disorders; and (vii) localized structuralmalformations;and(viii)idiopathic.Thespasms occur in clusters usually on waking. Prognosis for normal mental development is poor. ACTH and corticosteroids frequently help, the course varies from 2-12 weeks, dependinguponresponse.Vigabatrinisthedrugofchoice, especially in tuberous sclerosis.

Lennox-Gastaut syndrome. Onset is usually in late infancy or childhood, is characterizedbymixedseizures,including myoclonic, atypical absence, generalized tonic-clonic or partial seizures. Intellectual regression is invariable. Very slow background and generalized slow and spike wave discharges (2.5 per second) are observed on EEG. This diffuse form of encephalopathy may result from factors such as headinjury, anoxia, cardiopulmonary arrest, post­ vaccinal encephalopathy/neurogenetic disorder and neurlogical infections. Drugs of choice are valproic acid, benzodiazepines and ACTH. Prognosis is often unsatis­ factory. Newer antiepileptic drugs, lamotrigine, topira­ mate and zonisarnide are promising.

Common Errors in Diagnosing Epilepsy

A wronglabel of epilepsymaybe givento 20-30% children reporting to epilepsy clinics. A variety of paroxysmal disorders, which mimic seizures, should be excluded. These include syncope, breath holding spells, acute psychiatric states,migraine variants, abnormal movement disorders, paroxysmal disturbances of sleep like night terrors, narcolepsy andlastlyhysteria.Carefulhistory and EEG are useful to rule out these conditions. Treatment should be deferred until the diagnosis becomes obvious on followup of the natural course of the disease.

Central Nervous System -

Management of Epilepsy

Epilepsy management includes drugs, psychosocial and lifestylemanagement.Epilepsy requires management for a period 1 to 4 yr.

Drug Therapy

The first line antiepileptic drugs (AED)include phenytoin, phenobarbitone, sodium valproate and carbamazepine. The indications, dose and side-effects of commonly used drugs is depictedin Table 18.5. Age, sex, economic factors and seizure type determine choice of AED.

Tonic-clonic seizures. Carbamazepine is an effective drug for partial and generalized tonic-clonic seizures. It has the advantage of very few side-effects. Phenobarbitone is the drug of choice in the first year of life. Almost 20% develop hyperactivebehaviorand learning disabilitiesafter first year of life. Phenytoin is often used as initial choice if economic constraints exist. Therapy should be initiated with lowest anticonvulsant doses. The drug dose should be increased gradually. If seizures control is inadequate or toxicity appears, an alternate antiepileptic drugshouldbetriedand theinitialdrugtapered. Polytherapy should be discouraged unless monotherapy fails.

Antiepileptic drug level monitoring is not required routinely. It helps in better and safer control of therapy:

(i) if high doses are being used; (ii) in mixed seizure disorders; (iii)polytherapy; (iv)to assessdrugcompliance; and (v) to determine plasma level before discontinuing a major drug.

Complex-partial seizures. The drug of choice is carbamaze­ pine or oxcarbazepine, 10-30 mg/kg/day in 2-3 divided doses. It has a positive psychotropic effect. Slow release preparations may have advantage. Newer drugs and surgery should be restricted for selected patients.

Absence seizures. Effective agents include ethosuximide, sodium valproate, lamotrigine and benzodiazepines

Myoclonic and atonic seizures. Sodium valproate, levetir­ acetam,benzodiazepines such as clonazepam, nitrazepam or clobazam may be used.

Infantile spasms. In West syndrome, intramuscular ACTH 40 to 60 unit per day may be given 4-6 weeks and then tapered off. On the other hand oral prednisolone at 2 mg/ kg/day in 2 divided doses may also be used. These agents abolish spasms and may result in resolution of hyps­ arrhythrnia.

Newer antiepileptic drugs. Lamotrigineand topiramate have wide spectrum and areusefuladjunctafterprimaryfailure inpartialandgeneralizedepilepsies.Familiarizationofdrug use and side effects is essential. Oxcarbazinemay be useful for partial epilepsies; and vigabatrine for infantile spasms.

Surgical Treatment

Medically resistant cases of epilepsy may be treated surgically after a careful selection and work up. Possible

extremities (3), extension response to painful stimuli (2), no movement (1).

V. Best verbal response. Well oriented (5), confused conversation (4), inappropriate words are spoken (3), incomprehensible sounds (2), no vocal response (1).

Diagnosis of Coma

The airway, breathing and circulatory status should be documentedby respiration, blood pressure, capillaryrefill time recording and any compromise should be imme­ diately attended. Intravenous access should be obtained. A detailed neurologic examination should be carried out to rule out involvement of cranial nerves, motor deficits andbladder/bowel dysfunction. If respiratory depression or circulatory collapse is present, appropriate therapy is necessary.

History. A detailed history of events preceding coma, background illnesses, exposure to drugs and toxins provides useful information. The onset, presence of fever, history of trauma and possible bacterial, viral, or parasitic infestations is important. Immunocompromised states or malignancy may suggest opportunistic infections; and history may suggest tuberculosis, malaria or dengue. Headache, vomiting and diplopia suggest raised intra­ cranial pressure. Failure to thrive, vomiting, peculiar skin and urinary odor suggest a metabolic cause. Endocrine dysfunction, dyselectrolytemia, hypo or hyperglycemic states, uremia and hyperammonemiasuggest a metabolic cause. History of preceding seizure may indicate postictal coma.

Onset. Sudden onset may be due to trauma, poisoning, intracranial vascular episodes, postictal phase, acute hypoxia or hydrocephalus due to obstruction of cerebro­ spinal pathway in cases of brain tumor.

Systemic examination. This includes measurement of vital signs, pupil size and reactivity, coma scale, airway patency, pattern and adequacy of respiration. Skin and mucosa are inspected for bleeding diathesis, exanthem or systemic disease. Organ failure is suggested by associated jaundice, anemia, etc.

Respiration. Periodic or Cheyne-Stokes breathing indicates bilateral damage to the cerebral cortex with an intact brainstem. It occursin transtentorial herniation, congestive cardiac failure and some metabolic disorders. It is attributedtoanabnormally increased ventilatory response to CO2 followed by apnea.

Hyperventilation. Occurs in metabolic coma with acidosis and in brainstem lesions. Prolonged inspirationfollowed by expiratorypauseindicates pontine lesions. Irregular or ataxic breathing indicates involvement of respiratory center in the medulla.

Depth ofunconsciousness. Presence of yawning, swallowing or licking movements of the lips, is an evidence of intact

functioning of the brainstem and deep coma is unlikely However, flexion and extension movements may be seen in comatose patients as they are mediated at lower spinal reflex level.

Involuntary movements. Repetitive, multifocal, myoclonic jerks or seizures are seen in anoxic, metabolic, toxic encephalopathies or CNS infections.

Pupillary signs. Pupils are generally small, equal and reactive in toxic, metabolic cause of coma. Pupils are moderately dilated in midbrain damage; they do not react to light but fluctuate slightly. Pinpoint pupils indicate pontinelesion or morphine poisoning. Bilateralfixed dilated pupils are seen in terminal states or severe ischemic brain damage, atropine or belladonna poisoning. Unilateral unreactive dilated pupils indicate third nerve damage, often associated with transtentorial herniation ofthetemporal lobe or traction of third cranial nerve against posterior cerebral artery.

Eye movements. Stimulation of cortical center for gaze, results in conjugate eye movements to the contralateral side, whereas ablation produces conjugate deviation of the eyes to the ipsilateral side.

Doll's eye response. If the head is suddenly turned to one side, there is a conjugate deviation of eye in the opposite direction indicating that brainstem is intact. Doll's eye movement is not seen in normal conscious infants and is absent when brainstem centers for eye movements are damaged.

Oculovestibular response. If the external auditory canal is irrigated with cold water, the eyes normally deviate towards the stimulated side. This response is lost in pontine lesions, labyrinthitis andcoma due to drugs such as sedatives and phenytoin.

The hallmark of metabolic encephalopathy consists of loss of oculocephalic and oculovestibular reflexes with preservation of the pupillary light reflex.

Motor responses. Structural lesions involving cortical or subcortical motor areas lead to contralateral hemiparesis, hemifacial weakness, partial seizures or tone changes.

Flexion of upper extremities with or without extension of the legs (decorticate posture) denotes a cerebral cortical and subcortical disturbance with preservation of brainstem structures. Decerebrate posturing (extension of all extremities) is observed in bilateral cerebral cortical disease extending to upper pons. Decerebrate rigidity can resultfromincreased ICP originating in theposteriorfossa, metabolic disease, cerebral hypoxia, hypoglycemia and liver dysfunction.

Flaccidity occurs when a lesion has abolished cortical and brainstem function.

Investigaton s

Laboratory studies should be carried out to exclude hypo or hyperglycemia, uremia, hepatic dysfunction, dys-

electrolytemia and other metabolic abnormalities. Blood ammonia, lactate, acid-base disturbances, toxins and poi­ soning should be investigated on suspicion by preserving appropriate samples. Ferric chloride test shows purple color with ketones and aspirin poisoning. It gives green color with phenothiazine and isoniazid intoxication. Inflammatory causes of the CNS should be excluded by a lumbar puncture and blood/CSF culture and a sepsis screen. In febrile coma, peripheral smear should be examinedformalarialparasite. Computerized tomography helps to identify intracranial bleeds, infarct, raised ICP, meningeal enhancement and hydrocephalus.

Treatment

Airway should be keptpatent and tongue preventedfrom falling back. Dyselectrolytemia and fluid imbalance should be corrected. Hyper and hypothermia should be managed. Bladder/bowel care and care of the eyes and back to avoid bed sores is imperative. Raised intracranial pressure should be treated.

Fever with acute onset coma of uncertain origin with no evidence of meningitis merits treatment as cerebral malaria in endemic areas.

Specific treatment should be given for hypoglycemia (IV glucose), diabetic coma, inflammatory disease of brain or meninges, metabolic causes or organ failure. Raised intracranial pressure is treated with IV infusion of manni­ tol, at a dose of 0.5 g/kg every 6-8 hr for 6 doses. Hyper­ tonic saline also may be used. In some cases especially TBM, dexamethasone (0.15 mg /kg every 6 hr) may be used. Specific therapy is instituted for hepatic coma. Exchange transfusion, plasmapheresis and peritoneal dia­ lysis are indicated in specific situations. Corticosteroids have been used in certain metabolicencephalopathies and postviral encephalopathies, they are contraindicated in cerebral malaria. Metaboliccoma due toinborn metabolic errors requires specific treatment.

suggested Reading

Halley MK, Silva PD, Foley J, Rodarte A.Loss of consciousness: when to perform computed tomography? Pediatr Crit Care Med 2004;5: 230-3

Kirkham FJ. Nontraumatic coma in children. Arch Dis Child 2001; 85:303-12

Ranjit 5. Emergency and intensive care management of a comatose patient with intracranial hypertension, current concepts. Indian Pediatr 2006;43:409-15

ACUTE BACTERIAL MENINGITIS

Acutebacterialmeningitis,a majorcause ofmorbidityand mortality in young children, occurs both in epidemic and sporadic pattern.

Epidemiology

Age. Acute bacterial meningitis is commoner in neonates and infants than in older children because of poorer

Central Nervous System -

immunity and phagocytic functions. The common orga­ nisms in neonates are Escherichia coli, Streptococcus pneu­ moniae, Salmonella species, Pseudomonas aeruginosa, Streptococcus fecalis and Staphylococcus aureus. Three months to 3 yr, the infection is most often due to Haemo­ philus influenzae, S. pneumoniaeand meningococci (Neisseria meningitidis). Beyond 3 yr, the two most common orga­ nisms are S. pneumoniae and N. meningitidis.

Host. Patients with diminished host resistance (comple­ ment, immunoglobulin or neutrophil function defects), malignancies, on immunosuppressive drugs are more susceptible to develop meningitis, by fungi, Listeria and

Mycoplasma.

Pathogenesis

The infection spreads hematogenously to meninges from distant foci, e.g. pneumonia, empyema, pyoderma and osteomyelitis. Purulent meningitis may follow head injury. Rarely, the infection may extend from contiguous septic foci, e.g. infected paranasal sinuses, mastoiditis, osteomyelitis and fracture of the base of skull.

Recurrent meningitis may be associated with pilonidal sinus, CSF rhinorrhea, traumatic lesions of the cribriform plate and ethmoidal sinus or congenital fistulae, besides immune deficiency disorders.

Pathology

Theleptomeningesareinfiltratedwithinflammatorycells. The cortex of the brain shows edema, exudate and pro­ liferation ofmicroglia.Ependymalcells are destroyed and purulent exudate collects at the base of the brain, most marked in interpeduncular and chiasmatic cisterns. Exudates may block theforamina of Luschka and Magen­ dieresulting ininternalhydrocephalus. Thrombophlebitis of the cerebral vessels may occur leading to infarction and neurological sequelae. In cases of meningococcal meningitis, the illness maybefulminating and death may occur within a few hours because of endotoxic shock.

Subcellularpathogeneticmechanisms. Bacterialpathogens on destruction liberate cell wall and membrane active components (teichoicacids, endotoxinsandpeptidoglycans). In response the host cells and capillary endotheliaproduce tumor necrosis factor, cytokines and platelet activating factors. Their interaction with the blood brain barrier and neuronsresultsinextensive hostdamage. Cerebraledema (vasogenic) results due to endothelial cell injury or cyto­ toxins, leukocyte products and toxic radicals. The role of dexamethasone in reducing host damage due to blockage of the above mechanisms has been demonstrated in both experimental and clinical settings.

Clinical Features

The onset is usually acute and febrile. The child becomes irritable, resentslight, hasburstingheadache either diffuse or in thefrontalregion, spreading to the neck and eyeballs.

The infant may have projectile vomiting, shrill cry and a bulging fontanel.

Seizures are a common symptom and may occur at the onset or during the course of the illness.Varyinggrades of alterations in sensorium may occur. Photophobia is marked.Thereisgeneralizedhypertoniaandmarkedneck rigidity.Flexion of the neck is painful and limited. Kernig sign is present, i.e. extension of knee is limited to less than 135 degrees. In Brudzinski sign, the knees show flexion as neck of the child is passively flexed. The fundus is either normalorshowscongestionandpapilledema.Ifskinofthe abdomen is lightly scratched, flushing may be seen (tache cerebrale). The muscle power in the limbs is preserved. Reflexes are normal, diminished or exaggerated. Neuro­ logical deficits like hemiparesis, cranial nerve palsies and hemianopsia may develop. Respiration may become periodicorCheyne-Stokestypeoftenwith shockin thelate stages of illness.

Meningitis in neonates and young infants. Neck rigidity and Kernig sign are seldom prominent. Symptoms and signs, which arouse suspicion of bacterial meningitis are: (i) sepsis; (ii) vacant stare; (iii) alternating irritability and drowsiness;(iv)persistent vomitingwithfever; (v)refusal tosuck; (vi)poortone; (vii)poorcry; (viii)shock,circulatory collapse; (ix) fever or hypothermia; (x) tremor or convul­ sions; and (xi) neurological deficits of varying types.

The following are risk factors for neonatal meningitis: Prematurity, low birthweight, complicated labor, pro­ longedrupture of membranes,maternalsepsis and babies given artificial respiration or intensive care.

Special Features

Meningococcal meningitis. Epidemics of meningococcal meningitis are generally caused by serotype A and less commonly by type C. Type B generally cause sporadic disease. Children living in overcrowded houses are spe­ cially predisposed. Carrier state is common in children.

Besides features of meningitis, children show petechial hemorrhages on the skin or mucosa. Meningococcemia may be associated with acute fulminant illness with adrenal insufficiency, hypotension, shock and coma.This

is called Waterhouse Friderichsen syndrome and occurs due to hemorrhage and necrosis in the adrenal glands.

Chronic meningococcemia may occur with intermittent fever, chills, joint pains and maculopapular hemorrhagic rashlasting for several days. Meningococci are very fragile organisms and are destroyed very easily if there is delay in CSF culture.

Pneumococcal meningitis. While pneumococcal meningitis occurs at all ages, it is uncommon in the first few months of life. Usually follows otitis media, sinusitis, pneumonia or head injury. Exudates are common on the cortex and subdural effusion is a usual complication.

Staphylococcal meningitis. Neonatal staphylococcal meningitis is often associated with umbilical sepsis,

pyoderma or septicemia. In older children it follows otitis media,mastoiditis,sinusthrombosis,pneumonia,arthritis and septic lesions of the scalp or skin.

Haemophilus influenzae type B meningitis. Is frequent between the ages of 3 and 12 months. Subdural effusion shouldbe suspected in infants in whom focal neurological signs and fever persist even after the CSF clears biochemically and microbiologically. Convulsions are common. Residual auditory deficit is a common complication.HiB vaccine is recommended to reduce the community prevalence of this infection.

Complications

CNS complicationsincludesubduraleffusionorempyema, ventriculitis,arachnoiditis,brainabscessandhydrocephalus. CNS complications should be suspected if infants and children fail to respond to treatment, or if fever, focal neurological signs and constitutional symptoms recur after a lapse of few days. Longterm neurological deficits include hemiplegia, aphasia, ocular palsies, hemianopsia, blindness, deafness, sensorineural auditory impairment (deafness)andmentalretardation.Systemiccomplications include shock, myocarditis, status epilepticus and syndrome of inappropriate ADH secretion (SIADH).

Diagnosis

Acute bacterialmeningitisshouldbe suspectedin children presenting with a brief history of fever, irritability, photo­ phobia, headache, vomiting, convulsions and altered sensorium. Diagnosis should be substantiated by exami­ nation of the cerebrospinal fluid. The CSF should be examined promptly for cellular response and sent for culture for bacteria and stained to identify morphology. The CSF has elevated pressure, is turbid with an elevated cell count, often >1,000/mm3 with mostly polymorpho­ nuclear leukocytes. Proteins are elevated above 100 mg/ dl andsugarisreducedbelow50% ofbloodsugaror below 40 mg/dl. Microscopic examination of the sediment stained with gram stain helps to identify organisms. Collect the CSF for culture on a transport medium.

In partially treated meningitis, CSF may be clear with predominant lymphocytes; culture is usually sterile. Biochemistry may be variably altered.

CT scan is not necessary for diagnosis, but is useful to exclude the presence of subdural effusion, brain abscess, hydrocephalus, exudates and vascular complications. It is also useful to distinguish partially treated pyogenic meningitis from tuberculous meningitis.

Rapid diagnostic tests may be used to distinguish between viral, bacterial and tuberculous meningitis based on

antigen or antibody demonstration, e.g. countercurrent immunoelectrophoresis, latex particle agglutination, coagglutination, ELISA and other techniques. Besides being rapid, they are unaltered by previous antibiotic