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Indian Pediatrics 2000;37: 159-171

Cerebrovascular Disease in Children

Subhash Kaul

 

From the Department of Neurology, Nizam Institute of Medical Sciences, Hyderabad 500 082, India.

Reprint requests: Dr. Subhash Kaul, Associate Professor, Department of Neurology, Nizam Institute of Medical Sciences, Hyderabad 500 082, India.

E-mail: subashkaul@hotmail.com

 


Stroke is defined as the abrupt or ictal onset of focal or global neurologic symptoms caused by ischemia or hemorrhage within or around the brain resulting from diseases of the cerebral blood vessels(1). Although, predominantly a disease of adults, its occurence in children (0-16 years) is not so rare as once thought due to the advent of more accurate diagnostic techniques(2). Also, the incidence of cerebro-vascular lesions has increased in recent years as more effective treatment for some underlying conditions causing stroke has allowed much longer life expectancy during which time they may have a stroke(3). Stroke in children differs from stroke in adults primarily because of predominance of congenital and genetic causes. There are also notable differences in incidence, etiology and clinical presentation. The present article presents an overview of stroke in children.

Epidemiology

Data about childhood stroke is rare due to non uniformity of definitions and criteria across the world(4). The reported annual incidence of cerebral infarction in children, all over the world, varies between 1.2 per 100,000(5) to 2.7 per 100,000(6). About 20-30% of all infants of less than 35 weeks gestational age have intra-ventricular or germinal matrix hemorrhage(7). For reasons not clear, a high prevalence of childhood stroke has been reported from France and Saudi Arabia(8,9). There is no population based published data about the incidence or prevalence of pediatric stroke in India. In the hospital based studies from India, pediatric strokes have constituted less than 1% of all pediatric admissions and 5-10% of all stroke in young (<40 years)(10,11).

Pathophysiology

The two primary pathophysiologic features of cerebrovascular disease are interruption of blood flow to part of the brain or rupture of blood vessels with bleeding into the cerebral parenchyma. The type and extent of damage produced by either of these events depends on the anatomy of the vascular system and the metabolic needs of the brain. Ischemic strokes in children are caused by impairment of arterial blood flow as a result of thrombosis and embolism. The destructive effects of decreased cerebral blood flow result from the high cerebral metabolic rate and the paucity of energy stores in the brain. Glucose storage in the brain allows survival of cerebral tissue for upto 90 minutes if adequate oxygen is supplied. The newborn can use lactate as a substrate for the production of energy, but this capacity is lost quickly(12). A localized region of metabolic acidosis occurs and produces dilatation of surrounding blood vessels. This increased vascularity is called luxury perfusion. Damage to neurons and glia and destruction of the blood brain barrier produce localized cerebral edema, which in turn can compress capillaries and cause further damage. Neuronal injury and death in hypoxic states is also the result of a chain of events initiated by the release of excessive quantities of the excitatory neurotransmitters L-glutamate and L-aspartate(13). This produces increased postsynaptic stimulation of N-methyl-D-aspartate receptors, causing entry of sodium and calcium into the neuron and cell death. Delayed cell death can be produced by calcium influx, which causes mitochondrial dysfunction with subsequent breakdown of cell components and free radical formation(14).

Occlusion of venous structures initiates a similar chain of events, but because of the increased venous pressure, there is a tendency for blood vessels to rupture, which produces bleeding. There is also a tendency for a marked increase in intracranial pressure to occur.

Hemorrhage results in a collection of blood that can be intraparenchymal or extracerebral and that acts as a mass lesion and can accentuate the rise in intracranial pressure. Severe damage to the blood brain barrier also promotes cerebral edema. The presence of blood and breakdown products of erythrocytes adds to the pre-existing damage and can sometimes result in hydro-cephalus.

Etiology

Even in the best centers of the world the underlying etiology of stroke remains unknown in one-third of the patients despite thorough evaluation(8,15). It is these stroke cases of unknown etiology to which the term "acute infantile hemiplegia" is applied. Among the known causes of childhood stroke, occlusive vascular disease is slightly more common (55%) than intracranial hemorrhage (45%)(16). The common causes of ischemic and hemorrhagic strokes are summarized in Tables I & II, respectively(1,3,4,15,17,18).

The reported (published and unpublished) etiology from India is varied. In one series, the underlying cause could not be identified in 23 out of 43 patients. In the remaining 20 patients, Moya-Moya disease was found in 6, arteritis in 5, mitral valve prolapse in 3, fibromuscular dysplasia in 2, scorpion sting in 2, small vessel occlusion in 1 and superior sagittal thrombosis in 1 patient(10). In another case series of 6 patients of pediatric stroke from India, 3 had Moya Moya disease, 2 had mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) and 1 had homocystinuria(11). Other published informa-tion on pediatric strokes has been in the form of case reports and has consisted of stroke associated with hyperlipidemia, antiphospho-lipid antibodies and myocarditis(19-21). In short, the documentation of childhood stroke in India exists in bits and pieces and there is not enough published information on this subject. One must therefore, consider all the established causes in pediatric strokes as this helps in management and prognostication.

Table I__Common Causes of Ischemic Stroke

Heart Diseases

Congential heart disease

Rheumatic heart disease

Infective endocarditis

Complication of surgery

Hematologic Disorders

Sickle cell anemia

Thrombocytosis

Polycythemia

Leukemia

Antithrombin 3, Protein C and Protein S deficiency

Antiphospholipid antibodies

Infective Vasculitis

Pyogenic

Tuberculous

Fungal

AIDS

Non Infective Vasculitis

Systemic lupus erythematosus

Polyarteritis nodosa

Takayasu arteritis

Non specific

Moya Moya Syndrome

Trauma

Blunt cervical arterial trauma

Arterial dissection

Oral foreign bodies injuring the carotid artery

Hereditary Metabolic

Homocystinuria

Mitochondrial myopathy, encephalopathy, lactic acidosis and stroke like episodes (MELAS)

Toxic

Phencyclidine

Methamhateminne

Phenylpropanolamine

Cocaine


Table II__ Common Causes of Hemorrhagic Stroke

Vascular Malformations

Arteriovenous malformation

Aneurysm

Angiomas

Hematological

Leukemia

Thrombocytopenia

Hemophilia

Coagulopathy secondary to liver disorders

Disseminated intravascular coagulation

Trauma

Falls

Shaken baby syndrome

Prematurity

Subependymal hemorrhage

 

Ischemic Strokes

Cardiac Disease

According to previous studies one third of all pediatric strokes have a cardiac source of  embolus(15). In an unpublished study from India, 13 of 14 childhood strokes had an underlying cardioembolic etiology (rheumatic heart disease 50%, congenital heart disease 30% and prosthetic valve endocarditis in 15%)(22). Children with cyanotic heart disease are most likely to develop cerebrovascular complications before 2 years of age. Cardiogenic emboli may break off from apical clots in poorly contractile ventricles due to myocarditis or cardio-myopathy. Rarely, fat emboli from long bone fractures or those arising from the deep venous thrombosis cross from right side of heart to the left side through a patent foraman ovale or atrial septal defect. Rhabdomyoma of the heart associated with tuberous sclerosis is a rare cause of cerebral emboli(23). Embolic stroke is a complication of cardiac surgery in the intra-operative and immediate postoperative periods. The usual sources of emboli are thrombi on damaged or prosthetic heart valves. Thrombo-embolic complications occur in 5% of patients undergoing valve replacement who are not anticoagulated(23). Complications of cardiac catheterization are relatively uncommon. The incidence of stroke during cardiac catheteriza-tion correlates with the efficacy of hepariniza-tion during the procedure(24).

Hematologic Disease

Many studies have shown that sickle cell anemia is the most common hemoglobinopathy associated with cerebrovascular disease. Approximately 25% of patients with sickle cell anemia develop cerebrovascular complication of whom 80% are under 15 years of age(25). The mean age of stroke is 7.7 years and the risk of recurrence is 67%(26). Sickle cell anemia promotes cerebral arterial thrombosis, sino-venous occlusion and subarachnoid hemorr-hage. Recently, it has been shown that trans-cranial doppler (TCD) can predict the patients at highest risk for cerebral infarction(27). Other hematologic causes are thrombocytopenia, thrombocythemia, protein C, S and anti-thrombin 3 deficiency. Of note, there have been recent reports suggesting a strong association between iron deficiency anemia and ischemic events in children between 6 and 18 months of age(28). Out of 43 pediatric strokes reported in a series, 12 had anemia(10). Coagulation factor deficiencies, such as hemophilia or thrombo-cytopenia, predispose children to intracranial hemorrhage after minor trauma. Every child with stroke should have a thorough hematologic screening so that the underlying defect can be corrected and the recurrence prevented.

Cranial Infections

Stroke is a common sequel of severe meningitis in children, especially Haemophillus influenzae, pneumococcal and tuberculous meningitis. Purulent material about the basilar cistern and orbitofrontal area of the brain envelopes the circle of Willis, small arteries and veins leading to vasculitis and thrombus formation. Bacterial meningitis is the most common cause of intracranial arteritis in children. Young age (<12 yrs) and delayed institution of treatment are predictive of stroke. In one series 7.4% of children with tuberculous meningitis developed stroke. Fungal and syphilitic meningitis do the same(29). Strokes have been reported to occur in children within two months of primary Varicella infection(30). Children with AIDS have been reported to develop stroke at a rate of 1.3% per year, but about a fourth of autopsied patients have some type of cerebrovascular lesion. Both infarction and hemorrhage can occur(31). Carotid arteritis can occur in children with chronic tonsillitis and cervical adenitis, and retropharyngeal abscess. Unilateral and bilateral occlusions of the cervical portion of the internal carotid arteries may develop(23).

Non Specific Arteritis

Arteritis of unknown origin is an important cause of childhood stroke(32). Arteritis can be diagnosed only after arteriographic evidence but it must be undertaken by well trained and experienced angiographers.

Cancer and its Treatment

Children with leukemia and other forms of cancer have a 14% risk for stroke, usually within the first year after diagnosis. Vascular throm-bosis occurs with leukocytosis over 100,000 white blood cells per liter, neoplastic infiltration of the vessels, central nervous system infection, and secondary to chemotherapeutic drugs (L-asparaginase, cytosine arabinoside)(3). Secondary thrombocytopenia causes intra-parenchymal hemorrhage, and radiation therapy produces a progressive vasculopathy that results in large-vessel occlusion. Disseminated intra-vascular coagulation (DIC) is a complication of the acute leukemias, especially acute pro-myelocytic leukemia and infections. DIC may be associated with focal neurological features or generalized encephalo-pathy. Venous sinus occlusion occurs most commonly in the torcula in association with metastatic neuroblastoma, in which case radiation therapy may be beneficial. Other vascular complications include emboli from cardiac or pulmonary tumours, marantic endocarditis, and drug induced cardio-myopathy(23). Strokes have also been reported to occur after bone marrow transplantation(33).

Moya-Moya Syndrome

Moya Moya syndrome is a vasculopathy of the cranial arteries, usually the carotids, leading to progressive intracranial occlusion with distal collateral vessels. This is a very frequent cause of pediatric stroke in India(10,11). Children usually present with an acute focal deficit such as hemiplegia, whereas in later years sub-arachnoid hemorrhage is a common presenta-tion. Due to bilateral carotid involvement sometimes alternating hemiplegia is seen. The outcome varies widely without treatment. Moya Moya disease is usually idiopathic, although same radiographic pattern is seen in some patients with sickle cell disease, neuro-fibromatosis, postcranial irradiation and in various other conditions(15). There is no proven treatment of Moya Moya disease. Medical management involves use of aspirin but needs further testing. Surgical treatment involves cervical sympathectomy, intracranial graft of omentum or temporalis muscle and bypass of superficial temporal artery to the middle cerebral artery(34).

Table III__Evaluation of Stroke in Children

Standard evaluation

CT Scan (plain)

MRI scan (plain); if CT scan is normal

Ischemic Stroke

Electrocardiogram 

Carotid duplex studies

Echocardiography (TTE) 

Echocardiography (TEE) 

if TTE is normal 

Hematological studies

Complete blood count and platelet count Optional (pending initial assessment)

Electrolytes, BUN, and creatinine, Glucose 

Total protein, Uric acid 

Calcium, phosphate 

Cholesterol, triglycerides 

Optional(pending initial assessment)

Lumbar puncture

Imaging studies

Magnetic resonance angiography

Digital subtraction angiography

CT angiography

Tc-99m HMPO SPECT

Collagen vascular screen

Rheumatoid factor

Antinuclear antibody

Lupus anticoagulant

Serum protein electrophoresis

Coagulation profile

Protein C and protein S

Antithrombin 3

Other

VDRL/HIV

Blood cultures

Urinalysis

Lactate/pyruvate levels

 

Hemorrhagic Stroke

Hematological studies

Complete blood count platelet count Clotting factors

 Liver function tests

Optional (pending initial assessment) Imaging studies Magnetic resonance imaging        CT angiography

Digital subtraction angiography

Physical Agents

Strokes have been reported to occur following injury to the carotid artery. Focal neurologic signs occur suddenly or develop with a stuttering onset 2 to 24 hours following injury. The initial injury produces an intimal tear with formation of a dissecting aneurysm. The delayed neurologic symptoms are caused by thrombosis in the vessels with extension into cerebral vessels or embolization from the thrombosis in neck(35). In children intraoral trauma produced from falling on a stick held in the mouth is a common cause of this syndrome(36).

Bone abnormalities of the cervical spine or trauma to the cervical spine caused by sudden twisting or jerking of the head can injure the carotid or vertebral arteries. Lacerations of the carotid artery at the foramen lacerum, a complication of basilar skull fracture is associated with active bleeding from mouth and ipsilateral ear(37).

Metabolic

Primary venous or sinus thrombosis can occur in infants with fever and dehydration(32). A variety of extremely rare but well described vascular syndromes occur in genetically determined metabolic disorders in children. These have been extensively reviewed by Natowicz and Kelley(17). Homocystinuria occurs from a deficiency of cystathione beta synthetase and is associated with arterial and venous thrombosis. Recent reports have suggested that a heterozygote for homocystin-uria may also be at risk for premature cerebrovascular disease although this is controversial(38). A spectrum of disorders of organic acid metabolism recently has been found to be associated with stroke like presentations and pathologies. These disorders include methyl-malonic, propionic, isovaleric and glutaric type 1 acidemias and Leigh's disease(39). The mitochondrial encephalo-pathies especially, MELAS Syndrome, frequently present with stroke(40). At first the patients with MELAS are developmentally and neurologically normal. Then as children or adolescents, they develop episodic vomiting, headache, epileptic seizures, proximal muscle weakness, or focal neurological deficits. Some authors believe that strokes in MELAS are caused by mitochondrial angiopathy. Osler-Weber- Rendu Syndrome characterized by telengectasia of brain, viscera, mucous membranes and skin may present with Moya- Moya Syndrome or with hemorrhagic strokes. Rarely, tuberous sclerosis and Down's Syndrome may be associated with stroke. Rarely, vasculopathy can occur in patients with neurofibromatosis(32).

Sinovenous Occlusions

Occlusion of cortical veins and dural sinuses are probably underdiagnosed. It should be suspected in a child with features of focal deficit, raised intracranial pressure and seizures in the setting of chronic otitis, sinusitis or orbital cellulitis. It is also seen in children with hemoglobinopathy, congestive heart failure, polycythemia and dehydration(15).

Intracerebral Hemorrhage

Preterm Infants

Subependymal hemorrhage and intra-ventricular hemorrhage are the most common forms of cerebrovascular disease in the preterm infant(41). Bleeding initially occurs in the highly vascular subependymal germinal matrix and can then rupture into lateral ventricles. Hemorrhagic infarction of the periventricular white matter is present in 15% of infants with intraventricular hemorrhage. Several factors are involved in the pathogenesis of this lesion, including intravascular factors such as fluctuat-ing cerebral blood flow, increase in cerebral venous pressure, and abnormal platelet and coagulation function; vascular factors such as immature capillaries in the germinal matrix; and the extravascular factors such as deficient vascular support and fibrinolytic activity. The risk of subependymal hemorrhage and intraventricular hemorrhage increases with low apgar scores, vaginal delivery, prolonged labor, intrapartum hemorrhage, blood pressure fluctuation in the neonate, and rapid infusion of colloid.

Two clinical syndromes after subependymal hemorrhage and intraventricular hemorrhage have been described. The catastrophic syn-drome has a sudden onset and a rapid evolution to coma. Respiratory abnormalities, extensor posturing, seizures, and abnormalities in brain-stem reflexes are present. Severe derangements of metabolic homeostasis occur and mortality is high(32). The saltatory syndrome manifests with an altered level of consciousness, decreased spontaneous movements, lessened responsiveness to external stimuli, and oculo-motor abnormalities. These signs evolve slowly, and a period of stabilization followed by a second episode of deterioration often occurs. Mortality is lower than with the catastrophic syndrome(32).

Term Infants

Intracranial hemorrhage in term newborns is caused most frequently by birth trauma, usually associated with forceps and breech deliveries, but can sometimes occur without evidence of any complicated delivery. The infant is usually in poor general condition at birth, and resuscitation may be difficult. Clinical features include apathy or restlessness, seizures or tremors, high-pitched cry, and irregular respirations(32).

Bleeding Diathesis

Intracerebral hemorrhage is a serious complication of leukemia, idiopathic thrombo-cytopenia (ITP) or hemophilia. In some instances, the trauma may be trivial. In ITP, the platelet count is usually below 20,000 per mm3 at the time of intracranial hemorrhage(42).

Arteriovenous Malformations (AVM)

Arteriovenous malformations are the third most common cause of intracranial hemorrhage in children after trauma and coagulopathies. The presentation of an AVM varies with age. Symptomatic neonates usually present with unexplained high-output cardiac failure. Occasional neonates suffer a hemorrhage or hydrocephalus but more typically hydro-cephalus occurs a bit later during infancy, particularly in infants with a posterior fossa AVM with secondary aneurysmal dilatation of the vein of Galen. An AVM in an older child or adolescent on the other hand presents much like an adult patient with either seizure or intraparenchymal hemorrhage(42).

Subarachnoid Hemorrhage

Subarachnoid hemorrhage in a child may present with unexplained irritability, vomiting, photophobia or seizures. Trauma is the most frequent cause. Other causes include coagulo-pathies, sickle cell disease, AVM and aneurysms. Saccular aneurysms are rarely symptomatic in childhood and are considerably less frequent than AVMs. Congenital aneu-rysms are sometimes associated with coarctation of the aorta and polycystic kidneys. Probably the main difference in saccular aneurysm in children versus adults is their anatomic location. Children tend to have more aneurysms in the 

posterior circulation and the intracranial internal carotid arteries than the adults. Massive extracerebral hemorrhage, either subdural or subarachnoid may occur in the "shaken baby syndrome". Sudden acceleration or deceleration of the infant's head may rupture bridging veins leading to extracerebral collection of blood(15).

Clinical Presentation

In general, the clinical features in older children resemble those in adults, consisting of hemiplegia, hemisensory loss, aphasia and other neurological deficits appropriate to the vascular territory affected. However, the findings in younger children tend to be more subtle and variable. Infants most frequently present with seizures; motor signs are few until the child begins to develop skilled motor acts. Some-times, the only evidence of a childhood stroke is an early hand preference(32). The clinician therefore needs to be very careful in assessing a child for suspected stroke.

Conditions Which Mimic Stroke

The conditions which mimic hemiplegia due to stroke include four major entities, namely, transient postictal hemiparesis (Todd's paralysis), hemiplegic migraine, syndrome of alternating hemiplegia and intracranial space occupying lesion. Transient postictal hemi-paresis usually lasts less than 24 hours and is never permanent. An electroencephalogram may disclose epileptiform activity in postictal hemiparesis and slow wave activity in cases of stroke. In contrast to stroke, imaging studies in postictal hemiparesis do not show edema, mass effect or infarction. Patients with complicated migraine may develop symptoms and signs referable to a vascular territory but differs from stroke in several respects. First, hemiplegic migraine is preceded by severe headache. Second, the neurological deficits are transient, generally lasting more than 60 minutes but less than a week. Third, neuroimaging studies are generally normal. In unusual circumstances, complicated migraine may be associated with cerebral infarction, but the prognosis for complete or near-complete recovery is good. Alternating hemiplegia is an unusual syndrome of young children (onset <18 months) characterized by frequent episodes of hemi-plegia involving both sides of the body, pro-gressive developmental delay, and oculomotor and autonomic disturbances(43). Although, the children frequently have seizure disorders, the attacks of hemiplegia are not associated with epileptogenic discharges. Cerebral blood flow studies with single photon emission commputed tomography (SPECT) have not demonstrated cerebral ischemia. Similarly, the normal lactate and pyruvate levels in children with alternating hemiplegia differentiate this disorder from the syndrome of MELAS (mitochondrial ence-phalopathy, lactic acidosis, and stroke like episodes). Intracranial space occupying lesions like brain abscess, brain tumor and even a granuloma can occasionally present like a stroke and can be mistaken for a vascular lesion. Diagnostic evaluation should be complete enough to eliminate nonvascular conditions and once a cerebrovascular lesion has been identified, attempt should be made to find the underlying etiology for the stroke.

Diagnostic Approach

The diagnostic evaluation has two purposes: one to confirm the presence of a cerebrovascular lesion and exclude other types of neurological dysfunction. Second, to find the etiology of the stroke. This is important as the recurrence rate is largely determined by the underlying cause and whether it is treatable.

There are many causes of cerebrovascular disease in children, but it is usually unnecessary to investigate for all of them in every child. While it is theoretically possible for a child to have more than one risk factor, it is not necessary to pursue all the rare disorders once a likely cause has been established. The general approach to diagnostic evaluation is summarized in Table III. although in practice the direction of the workup has to be individualized.

The evaluation should begin with a computed tomography (CT) scan, without contrast administration. This will differentiate between hemorrhage and infarction and rule out other diagnosis. Contrast agent should be administered only if there is a doubt of space occupying lesion on plain CT scan. CT scan may fail to reveal the lesion, if it is located in brainstem or if the infarction is less than 48 hours old. In this situation Magnetic resonance imaging (MRI) should be performed(44). MRI scan, however, is more expensive, less readily available and more time consuming. Tc-99m-HMPAO SPECT is another sensitive diagnostic measure in the early detection and localization of regional cerebral blood flow (rCBF) changes in cases of stroke. It does not, however, have any place in the routine evaluation of a childhood stroke at present and its use is restricted to research purposes. Another imaging modality which can be performed bedside and is useful in babies with open anterior fontanel is cranial ultrasonography. This can detect the presence of an infarction, hemorrhage or even a vascular malformation. However, it is less reliable than either CT or MRI scans and cannot be done in older children.

Having confirmed the existence of an infarct or hemorrhage, one should go ahead to determine the etiology of stroke. All stroke patients should undergo the evaluation of arteries, blood and cardiac system and can be remembered by the mnemonic, A,B,C. To begin with, complete blood count should be obtained which provides clues to a wide array of conditions such as polycythemia, hemo- globinopathy, infections or isoimmune throm-bocytopenic purpura. Peripheral blood smear for sickle cells and hemoglobin electrophoresis should be done on patients at risk for hemoglobinopathy. All children with stroke should have a sedimentation rate, prothrombin time (PT) and partial thrombo-plastin time (PTT) done.

Next, children with stroke should have a thorough cardiac examination, chest X-ray, electrocardiogram, and echocardiogram. If transthoracic echocardiogram is noncontri-butory and the suspicion of cardiac source of embolism is high, then the patient should be subjected to transesophageal echocardiography (TEE). Ambulatory cardiac monitoring is sometimes helpful.

Carotid doppler studies should be done on all patients with childhood stroke to evaluate extracranial carotid arteries. Intracranial vascular disease should be screened by transcranial doppler, when available. If any stenosis or occlusion is demonstrated anywhere, it should be confirmed by Magnetic Resonance Angiography (MRA) or Spiral CT angiography. Both these investigations are non invasive, and obviate the need for invasive cerebral angiography in majority of patients.

Cerebrospinal fluid analysis is mandatory in a stroke patients with unexplained fever or signs of central nervous system infection. Chronic meningitis or early tuberculous meningitis can present with stroke. Syphilis serology should be done in adolescents with infarction; recent reports also link human immunodeficiency virus to cerebrovascular dysfunction. Mild sub-archnoid hemorrhage, not apparent on CT scan can be demonstrated via lumbar puncture.

If the evaluation does not uncover one of the more common causes of pediatric stroke, then the investigation should be extended to test for unusual risk factors such as homocystinuria, MELAS, or deficiencies of Protein C, Protein S, or antithrombin 3.

Finally, four vessel digital subtraction angiogram may be required in some patients. It should be done only if no explanation for the cerebrovascular lesion has been found with the preliminary tests. One must consider the risk to the patient should a diagnosis be missed. A youngster with a small intracerebral or subarachnoid hemorrhage, for example, should almost always undergo angiography unless there is an obvious diagnosis, because the risk of rebleeding from a missed small AVM or aneurym is far higher than that of an angiogram. But angiography should be performed only by an experienced radiographer(15).

Treatment

Medical Management

The treatment is largely supportive. Every child with a suspected stroke should be under strict observation in a pediatric intensive care unit. General principles of management as regards attention to airway, breathing and blood pressure are same as in any other pediat- ric emergency. Blood gas analysis and bio-chemical examination particularly for sugar should be performed and appropriate action taken.

There is not much published experience about the use of anticoagulants in ischemic stroke in children. Therefore use of heparin should be restricted to children thought to have a high risk of recurrence and minimum risk of secondary hemorrhage. For example, a child with congenital heart disease and evidence of systemic emboli who has a non hemorrhagic cerebral infarction would probably be anticoagulated. There is enough evidence to show that patients with sinovenous occlusion benefit from heparinization even if they have a hemorrhagic infarction(45). On the other hand patients with no definite source of embolus or patients with bacterial endocarditis who have a chance of harboring mycotic aneurysms are not good candidates for anticoagulation. On a long term basis, oral anticoagulation, may play a role in preventing cardiogenic embolization. One problem in chronically anticoagulating toddlers is the danger of cerebral hemorrhage due to frequent falls. In these circumstances treatment with platelet antagonists may be the most judicious course.

Transfusion

Patients with sickle cell disease who have a stroke have a 50% chance of having a recurrence which can be greatly reduced by repeated transfusions to suppress the production of sickle hemoglobin below 30%. The sickle hemoglobin does not have to be reduced acutely. One red cell transfusion can be given acutely followed by monthly transfusions. Cohen et al. introduced a modified transfusion program in 15 sickle cell patients without recurrent stroke for at least 4 years while on a transfusion program(46). Maintaining the hemoglobin S near 50% (instead of 30%) required an average of 31% less transfused blood, and no infarctions occurred.

Thrombolytic Agents

Unlike adults, there is little information about the use of thrombolytic agents in children. At some centers direct Urokinase infusion has been used to open thrombosed dural sinuses. Use of routine intravenous thrombolytics needs further study in children.

Neuroprotective Agents

These agents limit neuronal damage following an injury. Although several such drugs have been proposed, there is little information about the use of these drugs in children. Some agents such as phenobarbitol and Vitamin E have been tried in neonates at risk for intraventricular hemorrhage but are not very effective(15).

Antiplatelet Agents

There is little information about the use of aspirin or other antiplatelet agents in children specifically. Daily aspirin in low doses seems to be fairly safe in spite of the theoretical risk of Reye's Syndrome. Many pediatric neuro-logists have used aspirin without any obvious complications. Whether aspirin works in children and how much aspirin to use are difficult questions for which there are currently no answers. Again the dose of aspirin has been arbitrarily based on age: 0-3 years (60 mg/day), 4-8 years (150 mg/day), and 9-14 years (300 mg/day). It remains to be seen whether aspirin or ticlopidine have any role in pediatric cerebrovascular disease(15).

Increased Intracranial Pressure

Most of the children with stroke generally do not produce enough mass effect to require treatment. However large hemispherical lesions and many cerebellar lesions (both, hemorrhages and infarcts) can produce a rapid rise of pressue which may need intraventricular shunt placement or even surgical evacuation for which neurosurgical consultation should be taken. Rapid reduction of the PaCO2 by hyper-ventilation is the quickest way to lower the pressure.

Course and Prognosis

Mortality after stroke in children ranges from 20% to 30%, depending on the location and the underlying cause. Hemorrhagic stroke has a higher mortality than ischemic stroke. Residual neurological dysfunction is present in more than 50% of survivors and is more common after ischemic stroke. The prognosis is poor for infants whose initial features are seizures and hemiplegia. Most continue to have seizures, motor dysfunction, or cognitive impairment. In contrast, the risk of later epilepsy in children who do not have seizures at onset is only 20%. When seizures develop it is usually within 1 year of the stroke. Most children with residual hemiparesis will walk. The onset of hemiplegia during the first year is usually not associated with permanant facial weakness. Persistent mirror movements and atrophy of the involved limbs may be seen after strokes in young children. Chorea, dystonia, and other movement disorders are also seen. The plasticity of the immature nervous system has its greatest impact on the development of higher cognitive functions. Recovery of language is the rule in children with unilateral stroke below age 8 years, although some abnormalities persist when the left hemisphere is affected. The overall intelligence quotient (IQ) of children with proven unilateral strokes is measurably reduced. Children with left hemispheric lesions acquired after the first year have lower verbal than performance IQs, whereas children with right hemisphere lesions have lower performance IQs. Attentional problems, changes in dichotic listening performance, and academic difficulties in organizational skills (right-sided lesions) and in reading and writing (left sided lesions) are also seen. Unlike adults, these lesions in children seldom result from chronic hyper-tension but rather from small emboli, vasculitis or often without an identifiable risk factor. Provided there is only one such lesion, a good return of function is likely(47).

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