Ghai Essential Pediatrics8th

usage. Latex agglutination and ELISA have sensitivity and specificity of almost 80%. Polymerase chain reaction is used for diagnosis of infection with herpes simplex, enteroviruses, meningococci and tuberculosis.

Differential Diagnosis

Meningism. This may occur in inflammatory cervical lesions, apical pneumonia and in toxemia due to typhoid, influenza. There are no neurological signs and the cerebrospinal fluid is normal.

Partially treated bacterialmeningitis. If the child has received prior antibiotics, the cerebrospinal fluid becomes sterile. Biochemistry may be altered and pleocytosis persists, though type of cellular response changes. It poses a difficult problem in the differential diagnosis from tuberculous meningitis and aseptic meningitis. The onset, clinical course, rapid diagnostic tests and other ancillary investigations may be useful.

Aseptic meningitis. The clinical and laboratory profile is similar to pyogenic meningitis. The CSF pressure is ele­ vated, shows mild pleocytosis and moderate increase in protein with near normal sugar. The CSF lactic acid is not elevated. No organisms are cultured.

Tuberculousmeningitis. The onset is insidious with lethargy, low-grade fever, irritability, vomiting and weight loss. Features of meningeal irritation are less prominent and course of the illness is prolonged. Neurological features include seizures, gradually progressive unconsciousness, cranial nerve deficits, motor deficits and visual involve­ ment. Features of hydrocephalus and decerebration are relatively common. Evidence of systemic tuberculosis and family contact should be looked for. Mantoux test may be positive and there may be evidence of tuberculosis else­ where. CSF shows 100-500 cells, with majority of lympho­ cytes; sugar is less reduced than in pyogenic meningitis and protein is elevated.

Cryptococcal meningitis. It usually occurs in an immuno­ compromised host. There is low-grade fever, mild cough and pulmonary infiltration. Meningeal involvement has a gradual onset with a protracted course. The clinical fea­ tures are not specific. The CSF shows the fungus as thick walled budding yeast cells, surrounded by a large gelatinous capsule in India ink preparation. The organism grows well on Sabouraud medium.

Viral encephalitis. Acute onset with early disturbances of sensorium, raised intracranial pressure and variable neurological deficit. The CSF is clear, mayshowmildpleo­ cytosis, mild elevation of protein and normal sugar. PCR for viral antigens and rising CSF antibody titers are useful diagnostic clues.

Subarac/moid hemorrhage. Sudden headache and sensorial alteration occur without preceding fever. The course of illness is rapid and signs of meningeal irritation are marked. CT scan is diagnostic. CSF reveals crenated RBCs.

Central Nervous System -

Lyme disease. It is an infection of central nervous system with Borrelia burgdorferi, a tick-borne spirochete. Patients develop encephalopathy, polyneuropathy, leukoence­ phalitis and hearing loss.

Treatment

Initial Empiric Therapy

Initial therapy recommended is a third generation cephalo­ sporin such as ceftriaxone or cefotaxime. A combination of ampicillin (200 mg/kg) and chloramphenicol (100 mg/ kg/24 hr) for 10-14 days is also effective as initial empiric choice. If fever or meningeal signs persist after 48 hr of therapy, a lumbar puncture should be repeated and the choice of antibiotics reviewed. All antibiotics are adminis­ tered intravenously.

Specific Antimicrobial Therapy

Meningococcal or pneumococcal meningitis. Penicillin 400500,000 units/kg/day q 4 hr. Cefotaxime (150-200 mg/ kg/day q 8 hr IV) or ceftriaxone (100-150 mg/kg/day q 12 hr IV) are also effective.

H. influenzae meningitis. Ceftriaxone or cefotaxime IV is used as a single agent. The combination of ampicillin (300 mg/kg/day IV q 6 hr) and chloramphenicol (100 mg/kg/ day) is less preferred.

Staphylococcal meningitis. Vancomycin is the treatment of choice if methicillin or penicillin resistance is suspected. Addition of rifampicin to the regime increases CSF penetrance and efficacy of these drugs.

Listeria. Ampicillin (300 mg/kg/day IV q 6 hr) and amino­ glycoside (gentamicin, amikacin or netilmicin) are preferred.

Gram-negativebacilli. Cefotaxime, ceftazidime or ceftriaxone, or a combination of ampicillin and aminoglycoside may be used.

Pseudomonas. A combination of ceftazidime and an aminoglycoside is used. Ceftazidime may also be replaced with ticarcillin. Meropenem or cefepime are effective agents, if the above drugs fail.

Duration of Therapy

Generally, patients with bacterial meningitis show quick improvement within days. The treatment is for 10-14 days. except for staphylococcal meningitis and Gram-negative infection, where it is extended to 3 weeks. Routine lumbar puncture at the end of therapy is not recommended. In delayed or partial clinical response, a repeat CSF examination is indicated. Therapy is stopped if child is afebrile, cerebrospinal fluid protein and sugar become normal, and the cell count in the cerebrospinal fluid is less than 30/mm3•

Steroid Therapy

Dexamethasone at a dose of 0.15 mg/kg IV q 6 hr for 2-4 daysisrecommended. Thefirst dose of corticosteroids is best given shortly before or simultaneously with the first dose of antibiotic. This helps to reduce the incidence of residual neurological complications, such as sensori­ neuraldeafness, hydrocephalusandbehavioraldisturbances. This is especially useful in Haemophilus meningitis. There is no role of dexamethasone in neonatal meningitis.

Symptomatic Therapy

Increased intracranial pressure. Lumbar puncture should be doneverycarefully in thepresenceofincreasedintracranial pressure. Osmotic diuresis with 0.5 g/kg of mannitol as a 20% solution is administered intravenously every 4-6 hr for a maximum of 6 doses.

Convulsions. These are treated using diazepam 0.3 mg/kg (maximum 5 mg) IV, followed by phenytoin 15-20 mg/ kg as initial treatment and continued at a dose of 5 mg/ kg/day PO or IV. Antiepileptic drugs can be stopped after 3 months.

Fluid and electrolyte homeostasis. Maintenance fluids are given,hypotonicfluids shouldbe avoided. ADH secretion occurs in some patients. If unconscious, child may be fed through the nasogastric tube.

Hypotension. The patients are treated with intravenous fluids andvasopressorssuchas dopamineanddobutamine.

Nursing care. The oral cavity, eyes, bladder and bowel should be taken careof. Management of constipation pre­ vents atony of the rectum. Retention of theurine is mana­ ged by gentle suprapubic pressure or a hot water bottle. Bedsores are prevented by repeated change of posture in the bed and application of methylated spirit. Soft foam rubber mattress or air cushion is used to prevent pressure on the bony points.

Complications

Subdural empyema is managed by drainage of the subdural space along with intensive antibiotic therapy; subdural effusions generally resolve spontaneously.

Hydrocephalus may occur in the acute phase and generally regresses. Ventriculoatrial or ventriculoperitoneal shunt is rarely required.

Followup and Rehabilitation

Followup for early detection of residual neurological handicaps ensures appropriate rehabilitation. Auditory evaluation should be carried out at the time of discharge and 6 weeks later.

Suggested Reading

El Bashir H, Laundy M, Booy R. Diagnosis and treatment of bacterial meningitis. Arch Dis Child 2003;88:615-20

Maconochie I, Baumer H, Stewart MER. Fluid therapy for acute bacterial meningitis. Cochrane Database of Systematic Reviews 2008; 1:CD004786

Tunkel AR, Hartman BJ, Kaplan SL. Practice guidelines for the management of bacterial meningitis. Clinical Infectious Diseases 2004;39:1267-84

van de Beek D, de Gans J, McIntyre P, Prasad K. Corticosteroids for acute bacterial meningitis. Cochrane Database of Systematic Reviews 2007; CD004405

TUBERCULOUS MENINGITIS

Meningitis is a serious complication of childhood tuberculosis. It may occur at any age, but is most common between 6 and 24 months of age. There is usually a focus of primary infection or miliary tuberculosis. Mortality rate has reduced but serious disabling neurological sequelae may occur.

Pathogenesis

The tuberculous infection usually reaches the meninges by hematogenous route, less commonly through the lym­ phatics. Tubercle bacilli affect end arteries and form sub­ meningeal tubercular foci. The tubercle bacilli discharge intothesubarachnoidspace intermittently, proliferate and cause perivascular exudation followed by caseation, gliosis and giant cell formation. Tuberculous meningitis may occur as apart of the generalized miliary tuberculosis, with tubercles in the choroid plexus directly infecting the meninges.

Pathology

The meningeal surface and ependyma are inflamed, covered with yellowgrayish exudatesandtubercles. These are most severe at the base, in the region of the temporal lobes and along the course of the middle cerebral artery. The subarachnoid space and the arachnoid villi are obliterated resulting inpoorreabsorption of cerebrospinal fluid and dilation of the ventricles, resulting in hydro­ cephalus. Cerebral edema may be present.

The choroid plexus is congested, edematous and studded with tubercles. Theremaybe infarcts in the brain due to vascular occlusion. Necrotizing or hemorrhagic leukoencephalopathy may occur in some cases.

Clinical Manifestations

The clinical course of tuberculous meningitis is described in threestages.This differentiation is arbitrary as one-stage merges into the other.

Prodromal stage or stage ofinvasion. The onset is insidious and vague with low grade fever, loss of appetite and disturbed sleep. The child who was active and playful earlier becomes peevish, irritable and restless. Vomiting is frequent and the older children may complain of headache. Child may exhibit head banging and resents exposure to sunlight (photophobia).

Stage ofmeningitis. During this stage, neck rigidity may be present and Kernig sign may be positive. Fever may be remittent or intermittent, pulseisslowbut regular. Breath­ ing may be disturbed. The patient may be drowsy or deli­ rious. Muscle tone may be increased. As the disease progresses, convulsions and neurological deficits may occur; sphincter control is usually lost.

Stage of coma. This stage is characterized by loss of con­ sciousness, rise of temperature and altered respiratory pattern. Pupils aredilated, often unequal, withnystagmus and squint. Ptosisandophthalmoplegiaare frequent. With the progression of the disease, coma deepens; episodic decerebration is observed which progresses in severity. The respiration becomes Cheyne-Stokes or Biot type, bradycardia iscommon. Untreated illnessislethal in about four weeks.

Hemiplegia, quadriplegia, cranial nerve palsies and decerebrate rigidity are common findings. Some patients show monoplegia, hemiballismus, tremors, cerebellar sings and decorticate rigidity.

Diagnosis

Lumbarpuncture. Lumbarpunctureshouldalwaysbedone inchildrenwithlow gradepyrexia,unexplained recurrent vomiting, unusual irritability and lassitude. The cerebro­ spinal fluid pressure is elevated to 30-40 cm H20 (normal 3-4 cm H20). The CSF may be clear or xanthochromic. On standing, a pellicle or a cobweb coagulum is formed in the center of the tube. It is composed of cells and tubercle bacilli enmeshed in fibrin. CSF show lymphocytic pleocytosis (100-500 cells/mm3), elevated protein (more than 40 mg/dl), mild hypoglycorrhachia and lowchloride values (lessthan 600 mg/dl). Cerebrospinalfluid does not confirm the etiological diagnosis, but provides adequate evidenceforstartingantituberculartherapy.Demonstration of acid fast bacilli by direct smear and culture yields variable results.

CT scan. Computerizedtomographyisuseful in tubercular meningitis and may reveal basal exudates, inflammatory granulomas,hypodenselesionsorinfarcts, hydrocephalus both communicating and less commonly obstructive type (Fig. 18.7). X-ray of the chest may provide supportive evidencefor tuberculosis. NegativeMantoux test does not exclude the diagnosis.

Serological tests for thediagnosisof tuberculous meningitis are not very sensitive. Bactec and PCR for tuberculosis carry better sensitivity and specificity. Tests for HIV should be performed on all suspected subjects.

Differential Diagnosis

Purulent meningitis. The onset is acute with rapid progression. The cerebrospinal fluid is turbid or purulent with a significant increase in the number of polymorpho­ nuclear leukocytes in the CSF. CSF protein content is

Central Nervous System -

Fig. 18.7: Contrast enhanced CT of brain showing communicating hydrocephalus and periventricular ooze in a child with tubercular meningitis (Courtesy: Dr Atin Kumar, Deptt. of Radiodiagnosis, AIIMS, New Delhi)

elevated and sugar level is markedly decreased. The etiological agent is demonstrated by the examination of smear, culture or serology.

Partially treated purulent meningitis. The clinical features and cerebrospinal fluid changes are often indistin­ guishable from tuberculous meningitis. Rapid diagnostic tests to rule out specific bacterial antigens should be performed PCR and Bactec provide supportive evidence fortuberculosis.MRIbrain withgadoliniumcontrastoften provides clue to the underlying etiology.

Encephalitis. The onset is acute with fever, seizures, disturbances of sensorium, drowsinessand diffuseor focal neurological signs. The cerebrospinal fluid reveals mild pleocytosis, normal or mildly elevated proteins and normal sugar. MRI brain may be normal or may show signal changes in basi frontal and temporal lobes (Herpes encephalitis); thalamic and midbrain involvement occur in Japanese B encephalitis.

Typhoid encephalopathy. Typhoid presents with severe toxemia, drowsiness without meningeal signs. Cerebro­ spinalfluid is normal. Blood culture for S. typhi and Widal test is positive.

Brain abscess. Presents with irregular low grade fever, localized neurological symptoms and features of raised intracranial pressure. A prior history of congenital cyanotic heart disease or pyogenic lesions (suppurative otitis media, mastoiditis, lung abscess or osteomyelitis) should be asked for. The cerebrospinal fluid is normal except when the abscess communicates with the subara­ chnoid space; CT scan is diagnostic.

Brain tumor. The onset is slow with history of headache, recurrent vomiting, disturbances of vision and localizing neurological signs. The patients are usually afebrile. CT or MRI helps in diagnosis.

Chronic subdural hematoma. There may be a history of head injury or trivial trauma, headache, vomiting, localizing neurological signs and features of raised intracranial pressure. The fundusshowspapilledema or choked discs. The sutures may be separated. The cerebrospinal fluid is normal. CT scan or ultrasound is useful. The subdural tap shows fluid with high protein concentration.

Amebic meningoencephalitis. Free living amebae can cause meningoencephalitis. While Naegleria meningoence­ phalitis presents acutely, Acanthamoeba meningoence­ phalitis presents as chronic granulomatous encephalitis, chiefly in immunocompromised hosts. Nonresponse to antipyogenic or antitubercular therapy should arouse suspicion. Diagnosis is made by demonstration of motile amebae in fresh CSF preparation. Culture is confirmatory.

Prognosis

The prognosis is poorer in younger children. Early diagnosis, adequate and prolonged therapy improves the prognosis. Untreated cases die within 4 to 8 weeks.

Recovery is a rule in stage 1 disease. The mortality in stage 2 is 20-25% and of the survivors, 25% have neuro­ logical deficits. Stage 3 disease has 50% mortality and almostallsurvivorshaveneurologicalsequelae. Longterm complications include intellectual disability, seizures, motor and cranial nerve deficits, hydrocephalus, optic atrophy, arachnoiditis and spinal block.

Treatment

Antitubercular therapy. The treatment of tuberculous meningitis should be prompt, adequate and prolonged for at least 12 months. Short course chemotherapy is not recommended. At least 4 antitubercular drugs should be used for initial 2 months comprising (i) isoniazid (5 mg/ kg/day, maximum 300 mg per day); (ii) rifampicin (10 mg/kg/orally, once empty stomach in the morning, maximum dose 600 mg/day); (iii) ethambutol (15-20 mg/ kg/day); and (iv) pyrazinamide (30 mg/kg/day PO). Streptomycin (30-40 mg/kg/day IM)may be usedinitially for 2-3 weeks. The first two drugs are continued to com­ plete one year of therapy.

Steroids. Parenteral dexamethasone (0.15 mg/kg/dose q 6 hr) is preferred in acute phase of illness and switched over to oral prednisolone. Oral corticosteroids may be continued for 6 weeks and tapered over next two weeks. Steroids reduce the intensity of cerebral edema, risk of development of arachnoiditis, fibrosis and spinal block.

Symptomatic therapy of raised intracranial pressure, seizures, dyselectrolyternia should be done. The patient should be kept under observation for development of papilledema, optic atrophy or increasing head circum­ ference. Decerebration is common in advanced cases in the acute phase. Ventriculocaval shunt may be required

in cases with increasing hydrocephalus and persistent decerebration.

Suggested Reading

Shah GV. Central nervous system tuberculosis: imaging mani­ festations. Neuroimaging Clin N Am 2000;10:355-74

Thwaites GE, Nguyen DB, Nguyen HD, et al. Dexamethasone for the treatment of tuberculous meningitis in adolescents and adults. New Eng J Med 2004;351:1741-51

Tuberculosis: clinical diagnosis andmanagement oftuberculosis,and measures for its prevention and control. London: Royal College of Physicians, 2006

ENCEPHALITIS AND ENCEPHALOPATHIES----------

Encephalitis is defined as an inflammatory process of the brain parenchyma. The term encephalopathy implies cerebral dysfunction due to circulating toxins, poisons, abnormal metabolites or intrinsic biochemical disorders affecting neurons but without inflammatory response.

Etiopathology

Various causes of encephalitis and encephalopathies are listed in Table 18.7.

The pathological changes are nonspecific except in herpessimplexencephalitis andrabies.Gross examination of the brain usually shows diffuse edema, congestion and hemorrhages. Microscopically, there may be perivascular cuffing with lymphocytes and neutrophils. The neurons show necrosis and degeneration, associated with neuro­ nophagocytosis.

Clinical Manifestations

The clinical manifestations depend on: (i) severity of infection; (ii) susceptibility of the host; (iii) localization of the agent; and (iv)presence of raised intracranial pressure. Clinical spectrum may range from inapparent/abortive ilness to severe encephalomyelitis.

Onset. The onset of illness is generally sudden but may at times be gradual.

Initial symptoms. The initial symptoms are high fever, mentalconfusion, headache, vomiting, irritability, apathy or loss of consciousness, often associated with seizures. Raised intracranial pressure may result in decerebration, cardiorespiratory insufficiency, hyperventilation and autonomicdysfunction.Child may develop ocularpalsies, herniplegia, involuntary movements speech dysfunction and cerebellar symptoms. Extrapyramidal symptoms are common in Japanese B encephalitis and lateralization to one side with temporal or frontal involvement is common in herpes encephalitis.

Typical features. Include increased intracranial pressure and evidence of brainstem dysfunction. Unchecked brain swelling may lead to herniation at tentorial hiatus,

Table 18.7: Etiology of encephalitis and encephalopathies Encephalitis

RNA viruses (mumps, measles, rubella, enteroviruses)

DNA viruses (herpes simplex, cytomegalovirus, Epstein- Barr)

Arthropod borne viruses Oapanese B, West Nile, Russian spring summer, equine viruses)

HIV, rabies, lyrnphocytic choriomeningitis, dengue virus Slow virus infections, prion infections

Rickettsia; fungi (cryptococcus); protozoa (T. gondii) Bacteria (tuberculous meningitis, listeria)

Encephalopathies

Acute disseminated encephalomyelitis Postinfectious: Typhoid, shigella, Reye syndrome Hypoxic encephalopathy, heat hyperpyrexia

Metabolic: Diabetic acidosis, uremic coma, hepatic coma, neonatal hyperbilirubinernia, lactic acidosis, mitochondrial disorders, inborn errors of metabolism

Fluid and electrolyte disturbances. Water intoxication, hypernatremia, hyponatremia, alkalosis, acidosis

Toxic: Heavy metals (lead, mercury, arsenic), insecticides,

Cannabis indica, carbon monoxide Post-vaccination

compression of the midbrain causing deterioration in consciousness, pupillary abnormalities, ptosis,sixthnerve palsy,ophthalmoplegia, paralysis ofupwardgaze,Cheyne­ Stoke breathing, hyperventilation and bradycardia.

Prognosis

Recovery depends on the severity of illness. Mild illness usually has a complete recoveryand substantial morbidity occurs in severe forms. Metabolic encephalopathies may have an intermittent or progressive course despite treat­ ment. Inborn metabolic errors may have an intermittent course.

Diagnosis

Everyeffortshouldbemadetoarriveatapreciseetiological diagnosis by a careful history, systemic examination, account of recent illnesses or exposure to toxins. Lumbar puncture must always be done after excluding papill­ edema. CSFcytology, biochemistry, serologyandcultures are mandatory. Serum electrolytes, blood sugar, urea, blood ammonia, metabolic screening, ABC,serum lactate, urinaryketonesandurinalysisshould bedone. Toxicologic studies should be undertaken in suspected patients. One shouldexcludetreatablecausessuch asenteric encephalo­ pathy, malaria, shigella, toxins, poisoning, diabetes mellitus and renal disease. Serum lead levels should be estimated ifthereis a possible exposure ofthechild tolead contaminated environment.

Acute disseminated encephalomyelitis (ADEM). Acute demyelination of brain and spinal cord may occur with

Central Nervous System -

insults to oligodendroglia following an infection or vacci­ nation. Damageisperivenularinlocation,commonlyatthe gray-whitezone.Usuallyamonophasicillness,permanent deficits after the initial severe manifestation occasionally. Acutestageischaracterizedbyseizures,alteredsensorium, multifocalneurologicalsigns,raisedintracranial pressure, visual disturbances, etc. Cerebrospinal fluid may be normal,orshowsmildpleocytosis, mildlyelevatedprotein and normal glucose. MRI brain generally reveals multiple hyperintensities in white matter, which enhance with contrast. MRI may also show spinal cord, basal ganglia lesions in addition to white matter involvement. Therapy with pulse corticosteroids is useful.

Management

Treatment aims to save life, prevent neurological residua and relieve symptoms.

Emergency treatment. Airway should be kept patent and assisted respiration given if necessary. Hyperpyrexia should be managed with water sponging and anti-pyre­ tics. Shock is managed by infusion of appropriate fluid, or vasopressors. Dopamine or dobutamine are used to maintain blood pressure. Seizures are controlled by intravenous diazepam and phenytoin. Raisedintracranial pressure is managed by IV infusion of 20% mannitol solution and corticosteroids. The role of corticosteroids in most encephalitides is not proven except in acute disseminated encephalomyelitis and autoimmune ence­ phalitis.

Herpes simplex encephalitis. Herpes simplex type I virus is the causative organism. Type II virus causes perinatal herpes infections. Clinicalfeatures includesfeverof sudden onset, mental confusion, vomiting, meningeal irritation, headache and papilledema. In localizing signs (focal seizures, focal neurological deficit and EEG changes), presence of red cells in the CSF and focal involvement of thetemporallobeon CTscanareimportantdiagnosticclues. Diagnosis can be established by CSF culture or PCR. The drug of choice is acyclovir (20mg/kg/dose every 8 hourly) for 21 days. Early therapy is crucial for recovery. Prognosis is variable; about half the patients recover after timely therapy.

Suggested Reading

Amin R, Ford Jones E, Richardson SE, et al. Acute childhood encephalitis and encephalopathy assoc iated with influenza: a prospective11-yr review. Pediatr Infect Dis J 2008;27:390-5

Bulakbasi N, Kocaoglu M. Central nervous system infections of herpes virus family. Neuroimaging Clin N Am 2008;18:53-84

Fitch MT, Abrahamian FM, Moran GJ, Talan DA. Emergency department management of meningitis and encephalitis. Infect Dis Clin North Am 2008;22:33-52

Reye Syndrome

The first description of this syndrome was probably made by Najib KhaninJamshedpur,in 1956 Oamshedpurfever).

Reye and colleagues described an entity with diffuse fatty infiltration of the liver, to a lesser extent of the kidney and cerebral edema with diffuse mitochondrial injury.

Pathogenesis

It is an acute self limiting metabolic insult of diverse etio­ logy resulting in generalized mitochondrial dysfunction. Drugs (salicylates), toxins (aflatoxins), viral infections (varicella, influenza) and certain inborn errors of meta­ bolism (single enzyme defects of -oxidation) can precipitate Reye syndrome. Neuroglucopenia andhyper­ ammonemiaresult frommitochondrialandsodiumpump failure. Encephalopathy is secondary to the liver damage.

Clinical Features

A mild prodromal illness is followed by acute onset of the disease. The child has vomiting for one or two days along with anorexia, listlessness, followed by altered sensorium, irregular breathing, decerebration, pupillary changes and rapidly developing coma. Seizures occur in more than 80% patients. There are few focal neurological or meningeal signs. Hepatomegaly is present in half the cases; jaundice is infrequent. The clinical features are described in four stages:

Stage I. Vomiting, anorexia, mild confusion, listlessness, apathy

Stage II. Delirium, restlessness, irritability, lack of orien­ tation, frightened, agitated states

Stage III. Coma, decorticate posture which later becomes decerebrate.

Stage IV. Flaccidity, areflexia, apnea, dilated pupils not reacting to light, severe hypotension

Laboratory Investigations

There may be some degree of hypoglycemia with low levels ofglucose in the cerebrospinalfluid. Serum ammo­ nialevels areelevated.Prothrombintime isprolonged and hepatic enzymes are increased. Liver biopsy shows fatty change and glycogen depletionbut no necrosis oftheliver cells. EEG shows generalized slow waves.

Prognosis

Prognosis is poor with 25-70% mortality. Survivors may have neurological sequelae.

Management

Hepatic failure needs appropriate management. The patient is given low protein diet with adequate calories. Intravenous infusion of mannitol (20% solution;0.5 g/kg/ IV q 6 hr) and dexamethasone are used to reduce the brain edema. Hypoglycemia should be corrected by IV 10-25% glucose. Acidosis, hypoxia and dyselectrolytemia should be corrected. Double volume exchange transfusion has

been used in stage III. Vitamin Kand fresh frozen plasma may be required. Surgical decompression of raised intracranial pressure may be required to save life.

Sug ges ted Reading

Casteels Van Daele M, Van Geet C, Wouters C, et al. Reye syndrome revisited: a descriptive term covering a group of heterogeneous disorders. Eur J Pediatr 2000;159:641-8

Glasgow JF, Middleton B. Reye syndrome-insights on causation and prognosis. Arch Dis Child 2001;85:351-3

Schriir K Aspirin and Reye syndrome: A review of the evidence. Paediatr Drugs 2007;9:195-204

INTRACRANIAL SPACE OCCUPYING LESIONS

Intracranialspaceoccupyinglesionsinclude brain tumors, masses of congenital origin and inflammatory disorders such as brainabscess,neurocysticercosis,tuberculomaand subdural fluid collection. Brain edema may also simulate space occupying lesions. Clinical features of space occupying lesion in brain are detailed below:

Increased lntra cranialTens oni (ICT)

Theintracranialspaceanditscontents (brain, CSFandblood) arein a state of delicate equilibrium. After closure of sutures and fontanel the adaptive mechanisms to raised pressure in the brain are through the displacement of CSF from the intracranial cavity and compensatory hemodynamic changes. Heart rate slows, respiratory rate is altered and blood pressure rises to maintain the cerebral circulation.

The signs of raised ICT appear early in infratentorial tumors and are relativelylateinsupratentorialneoplasms. Common clinical features of raised ICT include either one or a combination of the following clinical features.

Increased head size and/or papilledema. In infants, there is separation of the cranial sutures, wide fontanels and increased head circumference. The fontanel should be examined with the babyrelaxed andplaced in the upright position. A delayed fontanel closure or a tense and non­ pulsatile fontanel is significant. Separation of the sutures compensates for increase in the intracranial pressure.

TheMacEwenor crackpot sign indicatesraisedintracranial pressure aftersutureshave closed. Papilledemais unusual in infancy unless intracranial pressure is very high. The changes include loss of cupping of the disc, absent venous pulsations and raised disc margins. In severe cases, hemorrhages may be observed.

Vomiting. Unexplainedprojectile vomitingwith orwithout headache should arouse suspicion of raised pressure. It is attributed to direct pressure on the medullary centers.

Headache. Persistent headache in young children, prominent in early morning is highly suspicious.

Diplopia and sixth nerve palsy. Increasedpressure displaces the brainstem downwards, thus stretching the sixth nerve and resulting in paralysis of the lateral gaze and diplopia.

Localizing Signs

These signs help to detect the anatomical site of the lesion.

Cranial nerve palsies. Multiple cranial nerve palsies occur in brainstemlesions along with involvement ofpyramidal tract and cerebellar pathways. Sixth nerve palsy usually hasnolocalizingvalue. Combinedsixth and seventh nerve involvement may suggest a pontine lesion. Pseudobulbar palsy may suggest lX and X cranial nerves involvement.

In supranuclear hypoglossal paralysis, tongue is tilted to contralateral side. Nasopharyngeal masses, rhabdo­ myosarcoma, lymphosarcoma and inflammatory masses may involve cranial nerves in their course.

Head tilt. Head tilt is seen in superior oblique paralysis, cerebellar lesions and posterior fossa tumors.

Ataxia. Ataxia occurs in cerebellar, spinocerebellar tract, frontal lobe or thalamic lesions.

Motor deficit. This may occur in cerebral, brainstem and spinal cord lesions.

Seizures. These indicate cortical or subcortical lesion. Intermittent decerebrate posturing may be due to infratentorial pathology.

Nystagmus. Both irritative and destructive lesions in any part of cerebellovestibular system may cause nystagmus with fast and slow components in opposite direction. Unilateral cerebellar lesion may produce bilateral manifestations because ofcompression across the midline. Brainstem lesions cause vertical nystagmus. The site of lesion is towards the side of the coarse nystagmus.

Vision. It is difficult to evaluate visual acuity and field of vision in children. Impaired vision with normal refraction should arouse suspicion of lesion near optic nerve, chiasma, optic radiations or cortical blindness. Bitemporal hemianopsia may indicate compression over chiasma.

Personality disturbances. Infants may become irritable, lethargic and show disturbances of behavior or speech. Loss of cortical sensation as described in supratentorial tumors of adults is difficult to interpret in children. There may be a decline in intellectual function.

Personality disturbances, inappropriate sphincter control and grasp response suggest localization of tumor near the frontal lobe. There may be optic atrophy in the fundus of the same side and papilledema in the opposite eye

Brain Tumors

Tumors arising from the brain are common in children. Certain genetic syndromes and familial factors increase risk of occurrence of brain tumors. Primary brain tumors may be malignant or benign. Benign tumors located near the vital areas of brain may be life-threatening.

Over two-thirds of brain tumors in children are

infratentorial. About one-third to half of these are medulla-

Central Nervous System -

Brain­ stem gliomas andependymomasaccountfor therest. Most of these tumors occur near the midline. Therefore they commonly obstruct CSF circulation and cause hydro­ cephalus early in disease. In adults, infratentorial tumors account for less than 10% of brain neoplasms. Common supratentorial tumors are astrocytomas, ependymomas, craniopharyngioma and malignant gliomas. Papillomas of choroid plexus and pineal body tumors are less common. Meningiomas, acoustic neuromas and pituitary adenomas are rare inchildhood. Ataxia telangiectasia and neurocutaneous syndromes are associated with a higher incidence of brain tumors. CT gives adequate information about ventricular size, tumor and surrounding edema. It is useful for followup. MRI provides better information regarding mass size, infratentorial and spinal cord extension and tumor detail.

Cerebellar Tumors

Medulloblastoma. These are midline cerebellar tumors and occur in infancy. They are fast growing and malignant. Craniospinal spread along neuraxis is common and death occurs early. Theycausetruncalataxia, early papilledema, unsteadiness in sitting position and a tendency to walk with a broad base. Radiation, chemotherapy and a ventriculoperitoneal shunt are generally required.

Astrocytoma. These are common in the cerebellar hemisphere. Ataxia and incoordination are common on the side of the lesion. Nystagmus is observed on lateral gaze of the child to the affected side. Areflexia and hypotonia are present. The head is tilted to the side of lesionto relievetheincreased intracranial pressure caused by herniation of tumor or cerebellar tonsils through the foramen magnum. Complete surgical excision of the tumor is often feasible. Chemotherapy with tomustin, vincristine and cisplatin is advised. Brachytherapy is now usedin a variety ofbraintumors tolimitradiationnecrosis and provide local irradiation to improve prognosis.

Bralnstem Tumors

Signs of increased intracranial tension are minimal, yet vomiting occurs due to infiltration of medullary vomiting center. Hemiparesis,cranial nerve deficits andpersonality changes are common; reflexes in the lower limbs are exaggerated. The pontine tumors affect the 6th and 7th cranial nerves.

Glioma ofthe brainstem causes bilateral involvement of the cranial nerves and long tracts. Cerebellar dysfunction is often present. The usual age of onset is in the later half of the first decade. Brainstem gliomas carry the worst prog­ nosis. Most children die within 18 months. Surgical exci­ sion is difficult and not very promising. Hyper­ fractionationradiotherapyisbeingevaluated. Chemotherapy does not have significant role.

Ependymoma of the fourth ventricle. It occurs in the first decade oflife. Theflow of cerebrospinal fluid is obstructed, causing an early rise in the intracranial pressure. These patientsmay present with subarachnoid hemorrhage. The tumors metastasize along the neuraxis. Surgical excision is rarely possible, patients may be treated with radio­ therapy. Survival of the child for a long period is unusual.

Supratentorial Tumors

Craniopharyngioma. These can present at anytime during childhood. The tumor is congenital and arises from squa­ mous epithelial cell rests of the embryonic Rathke pouch. The neoplasm is usually cystic and benign. Clinical features include: (i) growth failure; (ii) bitemporal hemi­ anopsia, asymmetric or unilateral visual field defects; (iii) signs of increased intracranial pressure; and (iv) endocrine abnormalities such as diabetes insipidus and delayed puberty (in less than 10% of cases). X-ray films mayshowcalcification. Cranial imagingrevealstheextent of mass and its nature. Bone age is retarded. Surgical excision is possible but difficult. The tumor cyst may be aspirated or malignantonesaretreatedwithradiotherapy or implants.

Glioma of the cerebral hemispheres. These usually occur during the first and second decade of the life. The patient presents with seizures and hemiparesis. Rarely, involve­ ment of frontopontine cerebellar fibers may cause ataxia. Vomiting, headache and papilledema are relatively late features of supratentorial tumors. Incidence of gliomas is higher in children with neurocutaneous syndromes. The histological types include astrocytoma, oligodendro­ glioma and glioblastoma.

Hypothalamic glioma. Theserare tumorscause diencephalic syndrome in infants. The children fail to thrive, the sub­ cutaneous fat islost and have sleep and respiratory distur­ bances. Older children may present with precocious puberty. Histological types observed are glioma, pinealoma, teratomas and hamartomas.

Glioma ofoptic nerve. Visualdisturbances,squint,proptosis, exophthalmos and optic atrophy are the usual presenting features. MRI of the orbit is diagnostic. Progression of tumor is relatively slow. Surgery is possible if the lesion is limited to one side.

Inflammatory Granulomas

Inflammatorygranulomasare animportantcause ofraised intracranial pressure and partial seizures in childhood. These may be tubercular, parasitic, fungal or bacterial in origin. Neurocysticercosis and tuberculomas are the commonest granulomas.

Neurocysticercosis

It is caused by larval stage of Taenia solium.

Pathogenesis. Evolution occurs from a nonattenuating cyst, to a ring with perilesional edema, to a disc lesion; which may disappear, persist or even calcify. Neurocysticercosis canbeclassifiedasparenchymal, intraventricular,meningeal, spinal or ocular depending on the site of involvement.

Clinicalfeatures. Parenchymal neurocysticercosis -seizures are the commonest manifestations (80%), followed by raised intracranial pressure, focal deficits and rarely meningeal signs.Seizuresmaybegeneralizedorpartial. Intraventricular neurocysticercosis may present with features of raised intracranial pressure, focal neurological deficits and hydrocephalus. Visualsymptomsorblindness results from cysts within the eye. Spinal neurocysticercosis presents with features of spinal cord compression or transverse myelitis.

Diagnosis. Neurocysticercosis is the most common cause of a cranial ring enhancing lesion (Fig. 18.8). The lesion is disc or ring like image with a hypodense center. Lesion may be single or multiple. A scolex is often present within the ring. There is often considerable edema surrounding the lesion. The midline shift is not significant. Lesion is usually supratentorialbutmayoccur in infratentorial regions.MRI is more useful than a CT scan in doubtful cases.

ELISA for cysticercosis is positive in almost half the patients with single lesion. Cerebrospinal fluid may be examined for cells, cysticercal antigens and PCR, though its diagnostic utility is variable.

Therapy. Cysticidal therapy is not necessary for inactive and calcified lesions. There may be benefit to treat single active and multiple lesions. Cysticidal drugs commonly used include albendazole and praziquantel. Albendazole is the preferred drug because of efficacy, and is less expensive. The dose (15 mg/kg/day) may be given for varying periods from 5 to 28 days. Corticosteroids

Fig. 18.8: Contrast enhanced CT of brain showing a degenerating ring enhancing cyst with eccentric scolex and perilesional edema in right frontal lobe (Courtesy, DrAtin Kumar, Deptt. of Radiodiagnosis, AIIMS, New Delhi)

(prednisolone 1-2 mg/kg/day) are started 2-3 days before initiating therapy and continued for a total of 5 days during cysticidal therapy. Symptomatic treatment includes anticonvulsantsfor6---9months or until resolution of the lesions. Calcified lesions require anticonvulsant therapy for 2-3 yr.

Tuberculoma

The clinical presentation is similar to neurocysticercosis. On CT scan, there is a single or multiple ring enhancing lesions. Tuberculoma rings are usually larger. The lesion often has a thick ( 20 mm) irregular wall and may be associated with a midline shift and severe perilesional edema (Fig. 18.9). Focal deficits are more frequent in tuberculomas. Presence of basal exudates should arouse suspicion of tuberculoma. The diagnosis is often suspected based on family history of contact, positive tuberculin reaction, other evidences of tuberculosis and subacute course of the illness.

Antituberculous therapy is recommended for 1 yr (2 HRZE + 10 HR) as for tubercular meningitis along with corticosteroids for initial 6-8 weeks.

Brain Abscess

Brain abscess is animportant differential diagnosis among children with unexplained fever, altered sensorium, elevated intracranial pressure, localized neurological findings and headache.

Predisposing/actorsinclude cyanotic heart disease, immuno­ suppressed status, otitis media, sinusitis, mastoiditis, systemic sepsis and post-traumatic.

Fig. 18.9: Contrast enhanced MRI (sagittal view) of brain showing

enhancing irregular ring like multiple tuberculomas (Courtesy, Dr Atin Kumar, Deptt. of Radiodiagnosis, AIIMS, New Delhi)

Central Nervous System -

Etiology. Anaerobic organisms, streptococci, Staphylococcus aureus, pneumococci, Proteus and Haemophilus influenzae are common infecting organisms. The abscesses are observed more often in the cerebrum compared to infratentorial compartment.

Clinical features of brain abscess may be described under 4 broad headings: (i) features of raised intracranial pressure; (ii) manifestations of intracranial suppuration such as irritability, drowsiness, stupor and meningeal irritation; (iii)features suggesting toxemia, e.g. fever, chills and leukocytosis; and (iv) focal neurological signs such as focal convulsions, cranial nerve palsies, aphasia, ataxia, visual field defects and neurological deficit.

Diagnosis is established by CT scan or MRI. Lumbar puncture is avoided as the procedure may precipitate herniation of the brainstem.

Management includes investigation for source of infection, treatment of precipitating cause, management of raised intracranial pressure and symptoms. Empirical therapy should begin with a third generation cephalosporin, vancomycin and metronidazole and continued for 4-8 weeks. Surgical drainage or excision of the abscess should be done in case of abscesses of >2.5 cm, located in posterior fossa, fungal abscess or if gas is identified inside the abscess.

Suggested Reading

Foerster BR, Thurnher MM, Malani PN, et al. lntracrarual infections: clinical and imaging characteristics. Acta Radio! 2007;48:875-93

Kraft R.Cysticercosis: an emerging parasitic disease. Am Fam Physician 2007;76:91-6

Leotta N, Chaseling R, Duncan G, Isaacs D. lntracrarual suppuration. J Paediatr Child Health 2005;41:508-12

Mazumdar M, Pandharipande P, Poduri A. Does albendazole affect seizure remission and computed tomography response in children with neurocysticercosis? A Systematic review and meta-analysis. J Child Neurol 2007;22:135-42

SUBDURAL EFFUSION

Subdural effusion may be acute or chronic. In infancy, subdural effusions are often associated with bacterial meningitis. These are generally acute, small and regress spontaneously. Rarely a large effusion may result in increased intracranial pressure and focal neurological signs. Chronic subdural effusion presents as raised intracranial pressure. The protein content of this fluid is high and vascular membrane forms around the subdural effusion. This may require surgical intervention.

Clinical features are nonspecific. Convulsions, vomiting, irritability and drowsiness are present. There is persistent fever, anterior fontanel bulges and head size increases. In the newborn period, the skull may show increased transillumination. CT/MRl or subdural tap establishes the diagnosis.

Treatment. Small collections are absorbed spontaneously. Large effusions may need to be aspirated every 24 to 48 hr until these become small. Surgical irrigation with indwel­ ling drains may be considered if the effusion persists for more than 2 weeks. Surgical excision of the subdural membrane is difficult and results are not encouraging.

HYDROCEPHALUS

The CSF is secreted by the choroid plexus within the ventricles by ultrafiltration and active secretion. It passes from thelateralventriclesto the third andfourth ventricles and exits from foramen of Luschka and Magendie into the basal cisterns and then the cerebral and spinal sub­ arachnoid spaces where it is absorbed via the arachnoid villi (granulations) into the venous channels and sinuses. About 20 ml of CSF is secreted in an hour and its turnover is 3 or 4 times in a day.

Etiology Hydrocephalus results from an imbalance between productionandabsorption of cerebrospinal fluid. It may be communicating or noncommunicating.

Communicating hydrocephalus. There is no blockage in the CSF pathway but reabsorption may be affected. Excess CSF may be produced in papilloma of choroid plexus.

Obstructive or noncommunicating hydrocephalus. The block is at any level in the ventricular system, commonly at the level of aqueduct or foramina of Luschka and Magendie (Fig. 18.10).

In obstructive hydrocephalus, the ventricles are dilated above the block. In cerebral atrophy, ventricles are dilated

Fig. 18.10: Arnold-Chiari II malformation: MRI T1W sagittal view showing obstructive hydrocephalus stretched brainstem and tonsillar herniation (patient also had a meningomyelocele) (Courtesy: Dr Atin Kumar, Deptt. of Radiodiagnosis, AIIMS, New Delhi)

but pressure is not raised (hydrocephalus ex vacuo). Presence of periventricular ooze on CT or MR imaging helps to identify the former. Hydrocephalus may be congenital or acquired (Table 18.8).

Table 18.8: Causes of hydrocephalus Congenital hydrocephalus

Intrauterine infections: Rubella, cytomegalovirus, toxo­ plasmosis, intracranial bleeds, intraventricular hemorrhage Congenital malformations: Aqueduct stenosis, Dandy-Walker syndrome (posterior fossa cyst continuous with fourth ventricle), Arnold-Chiari syndrome (portions of cerebellum and brainstem herniating into cervical spinal canal, blocking the flow of CSF to the posterior fossa)

Midline tumors obstructing CSF flow

Acquired hydrocephalus

Tuberculosis, chronic and pyogenic meningitis Post-intraventricular hemorrhage

Posterior fossa tumors: Medulloblastoma, astrocytoma, ependymoma

Arteriovenous malformation, intracranial hemorrhage, ruptured aneurysm

Hydrocephalus ex vacuo

Pathology Ventricles are dilated, at times unevenly. Ependymal lining of ventricles is disrupted resulting in periventricular ooze and hence periventricular white matter is compressed. Cortex is generally preserved until late but cortical atrophy may occur. The process may be reversible if the treatment is initiated early.

Clinical features Hydrocephalus may manifest with enlarging head size, delayed closure of fontanel and sutures. Associated symptoms includeheadache, nausea, vomiting, personality and behavior disturbances such as irritability, head banging, apathy and drowsiness.

Papilledema, pyramidal tract signs and cranial nerve palsies may occur. Skull contour becomes abnormal and forehead isprominent. Scalp veins become prominent and dilated. A sunset sign is seen in the eyes, i.e. sclera above the cornea becomes visible. Upward gaze is impaired. Limbs become spastic because of stretching of cortical fibers. Distortion ofthebrainstem maylead to bradycardia, systemic hypertension and altered respiration rate.

Congenital hydrocephalus starts in fetal life and may manifest or even develop subsequently. The large head size at birthcausesdifficultyin deliveryof the head during labor. There may be associated congenital malformations. Diagnosis Accurate serial recording of the head circum­ ference is essential for early diagnosis of hydrocephalus and should be supported by serial USG. An increase in the head circumferencein the first 3 months of life >1 cm every fortnight should arouse suspicion of hydrocephalus. Brain grows very rapidly in the first few weeks of life and thereforesagittaland coronalsutures may be separatedup