Childhood strokes, though perceived to be relatively rare, have an incidence approximately equal to pediatric brain tumors. Epidemiological studies have revealed an annual incidence of 2.5-2.7 pediatric strokes per 100,000 children.1 This figure comprises ischemic and hemorrhagic events, and excludes strokes from trauma or birth-related complications.
Cerebral emboli typically present acutely with a sudden loss of neurological function. Thrombi may also present in a subacute or stutterial fashion, with prodromal transient ischemic attacks. There may be considerable overlap, and it may not be possible to distinguish an embolic event from a thrombotic event by clinical criteria. The signs and symptoms depend on the location and size of the occluded vessel, as well as the patient's age. Anterior circulation strokes are much more common than posterior, and the left cerebral hemisphere is affected more often than the right.
Two-thirds of children will present with an acute hemiplegia. Seizures, lethargy, or coma may complicate presentation. Preceding self-limited episodes of hemiparesis are experienced in 25% in patients. Medical attention is often sought for these transient events and they usually are attributed to a musculoskeletal injury. The remainder present with a more indolent course noted over several weeks. Infants may have no clinical manifestations, or a profound motor weakness (initially flaccid and later becoming spastic). In infants, pathologic early hand preference is commonly a presenting complaint. In infant cases, it may be that the occlusion is gradual, allowing adequate arterial anastomotic channels to develop. In addition, the potential for recovery is so great that children may be seen without major deficit months or years after an ischemic event, despite large areas of brain infarction. A third reason for the delay of clinical presentation in infants is that identification of clinical signs may not occur until brain maturation reaches a stage allowing expression of the deficit.2
In adults, the common underlying risk factors for stroke include hypertension, diabetes mellitus, atherosclerosis, cardiac arrhythmias and valvular abnormalities. In childhood, however, the potential etiologies are many and the diagnostic challenge can be formidable.3
Congenital cyanotic heart disease is the most frequent cause of pediatric strokes. The incidence of stroke in pediatric cardiac patients is 4%, and 75% of the stokes occur within the first two years of life. Potential mechanisms of stroke include: hyperviscosity and diminished oxygenation of blood, paradoxical emboli from right-to-left shunting, and emboli from vegetations secondary to valvular disease. Other abnormal structural defects predisposing to emboli include: atrial myxoma, cardiac rhabdomyoma, cardiomyopathies, bacterial endocarditis, rheumatic heart disease, and prosthetic valves. Cardiac arrhythmias, particularly atrial fibrillation, as in adults, predispose to emboli.
In one third of thrombotic carotid artery occlusion, a preceding infection is noted, often in the pharynx or cervical area. Pharyngitis, cervical adenitis, tonsillitis, sinusitis, and retropharyngeal abscess have all been reported to be precursors of internal carotid artery thrombosis. The mechanism is likely to be local inflammation of the arterial wall. Cat-scratch fever, varicella, mycoplasma, and viral encephalitis have also been associated with cerebrovascular disease.
A variety of hematological causes will lead to arterial ischemic disease in children, though venous occlusion and hemorrhagic events may also occur in the same disease processes. Hyperviscosity syndromes (polycythemia, hyper-leukocytosis, and thrombocytosis) can lead to arterial occlusion. Hemoglobinopathies, the prototype of which is sickle cell disease, are often complicated by stroke. The incidence of stroke in sickle cell disease is between 5% and 10%, with the median age of the first stroke being seven years of age. Recurrence without treatment occurs in up to 90% of patients, most within three years.
There has been a recent recognition of the importance of hypercoagulable states. These may be genetically acquired, associated with autoimmune and other systemic disorders, or found independent of an underlying disease. Antithrombin III, protein C, and protein S are naturally occurring anticoagulants whose deficiencies are inherited as an autosomal recessive trait. These and various other mutations and deficiencies involving the coagulation cascade have been described in childhood stroke and continue to be an area of active research.
Several inborn errors of metabolism are associated with cerebral infarction. Homocystinuria, due to defect of methionine metabolism, may present as a thrombotic syndrome. High levels of homocystine lead to endothelial damage and increased platelet aggregation. Young adults heterozygous for homocystinuria are also felt to be at increased risk. Stroke-like episodes in a nonvascular distribution are seen in mitochondrial encephalomyopathy with lactic acidemia and stroke-like episodes (MELAS). This recently described disorder is due to a mutation of mitochondrial DNA and may require muscle biopsy to confirm. Disorders of lipid metabolism continue to generate interest. Though hypercholesterolemia is emerging as a risk factor for adult cerebrovascular disease, its role in children is less certain. Progeria, familial hypoalphalipo-proteinemia, Tangier disease and several familial forms of hypercholesterolemia are conditions associated with stroke in children and young adults.
Autoimmune disorders may lead to cerebrovascular disease through a vasculitis or by inducing a hypercoagulable state. A hypercoagulable state is created by antiphospholipid antibodies, which includes the lupus anticoagulant and the anti-cardiolipin antibody. In systemic lupus erythematosus, neurologic involvement is seen in over 50% of patients. Polyarteritis nodosa, Wegener's granulomatosis, Henoch-Schonlein purpura, ulcerative colitis, Kawasaki disease and the dermatomyositis / polymyositis complex have had rare associations with childhood stroke.
Trauma to the neck may predispose to carotid thrombosis. This can be a blunt injury to the neck, intraoral trauma, i.e. falling with a pencil in the mouth, or trauma to the cervical spine, i.e. chiropractic manipulation. Carotid dissection should always be considered as a cause of stroke, and it may be spontaneous or follow a neck injury. In a dissection, a tear in the arterial wall leads to an expanding hematoma which obstructs blood flow. The patient may complain of neck pain or referred pain to the eye or forehead. A Horner's syndrome may be noted during the physical examination.
Various drugs, illicit and legally prescribed, have been linked to strokes. Cocaine, phencyclidine (PCP), and amphetamines predispose to vascular injury via hypertension, vasospasm and vasculitis. Phenylpropanolamine, present in many over-the-counter medications, may induce a similar pathological picture. Steroids may cause endothelial hyperplasia and increase platelet adhesiveness.
Even with the increase of knowledge, approximately a third of children with strokes, have no recognizable cause.1 Acute infantile hemiplegia refers to a young, previously health child with sudden hemiplegia, fever, coma and seizures. Alternating hemiplegia of childhood also affects primarily young children. It is characterized by repeated attacks of hemiplegia, autonomic disturbances, with gradual motor and mental deterioration. Moyamoya disease is characterized by an angiographic picture of progressive occlusion of the supraclinoid portion of the interval carotid arteries and the development of a fine web-like collection of abnormal anastomotic vessels at the base of the brain. The majority of cases are idiopathic, though there are several associated conditions, including neurofibromatosis, post-irradiation therapy and sickle cell disease. Migraine-related stroke has been reported.4 Diagnosis of migraine-related stroke is suggested by a family history of migraine, prior migraines in the patient, and exclusion of other etiologies by a thorough diagnostic evaluation.
The evaluation of a child with stroke has two components. The first is to recognize that a stroke has occurred and to distinguish this from similar processes. The differential diagnosis of an acute focal neurologic deficit is listed in Table 1. The second component, once a stroke is confirmed, is to identify the underlying cause.
Table 1. Differential Diagnosis of Acute Focal Neurological Deficit |
| Focal cerebral ischemia Intracranial hemorrhage Cerebral abscess Encephalitis (herpes simplex virus) Brain tumor Alternating hemiplegia of infancy Multiple sclerosis Malingering/conversion disorder Epilepsy: post-ictal Todd's paralysis or a focal inhibitory seizure Complicated migraine |
Identifying the underlying etiology in a child with a stroke may be a very simple process or a challenging task. In a child known to have a predisposing cause or systemic illness such as congenital heart disease, meningitis, or sickle cell disease, an extensive evaluation may not be necessary. If preliminary evaluation fails to reveal a definitive cause, further testing is mandatory. An aggressive approach is recommended to prevent further episodes. Table 2 provides a tiered approach to a rational diagnostic work-up.
Table 2. Diagnostic Evaluation in a Child with Cerebrovascular Disease |
||
| FIRST LINE: Performed within first 48 hours of admission |
SECOND LINE: Performed within
first week as indicated |
THIRD LINE: Performed electively as indicated |
| CT scan of
brain MRI of brain Complete blood count PT/PTT Electrolytes, Ca, Mg, Phos, glucose Liver function test Chest x-ray ESR ANA Urinalysis BUN, creatinine Urine drug screen 12-lead EKG |
Echocardiogram
(transthoracic) with saline contrast Holter monitor Transcranial and/or carotid dopplers MR angiogram EEG Hypercoaguable evaluation (Hematology consultation)
Rheumatoid factor |
HIV Lyme titers Mycoplasma titers Cat-scratch titers Cardiac MRI Echocardiogram (transesophageal) Muscle Biopsy DNA testing for MELAS Cerebral angiogram (transfemoral) Leptomeningeal biopsy Serum homocystine after methionine load |
As in all of medicine, nothing can replace a detailed history, including past medical, social and family histories and examination. Emphasis on the family history should include premature coronary and cerebrovascular disease, unexplained thrombotic events and migraines. Social history should include inquires regarding drug and alcohol abuse, and HIV risk-factors. Other potentially important historical items which might be overlooked include recent head or neck trauma (even mild), mental retardation or learning disabilities, recent viral infection, and systemic signs such as rashes, arthalgias, fevers, and weight loss. A careful general examination should include the skin (looking for rashes which might suggest an autoimmune disorder, stigmata of neurocutaneous syndromes, and evidence of systemic emboli) and particularly the cardiovascular system. The head and neck should be carefully ausculated for bruits. A detailed neurological examination should always be performed.
The acute treatment of cerebral ischemia is largely supportive and requires an intensive care unit setting. Attention to oxygenation, fluid and electrolyte status, seizures, and infections are critical. Treatment should be directed to the underlying cause if it is identifiable.5
Cerebral edema is maximal over the first 72 hours. Initially, edema is cytotoxic, although a vasogenic component occurs after two to three days. Edema is usually effectively managed with hyperventilation and fluid restriction. In general, the use of steroids and osmotic agents are not indicated. However in case of progressive deterioration, mannitol and decadron may be used.
The use of anticoagulation in pediatric ischemic stroke is controversial, although it is often used in the presence of a definable and recurrent source of emboli or evolving thrombotic stroke. Anticoagulation is contraindicated in hemorrhagic infarct and uncontrolled hypertension. Long-term anticoagulation with warfarin is indicated in deficiency of protein C, S, antithrombin III and in the presence of anti-phospholipid antibodies. Low-dose aspirin is a consideration though controlled studies in children have not been performed. In patients with sickle cell disease, strokes should be initially treated with an exchange transfusion and then a hypertransfusion protocol. Use of early thombolytic therapy with intravenous tissue plasminogen activator (tPA) has not been reported in children. Rehabilitation through aggressive physical, occupational, and speech therapy is essential for all patients. Behavioral problems and learning disabilities may become apparent upon returning to school, and children may need neurocognitive testing and special educational classes.
The prognosis for childhood strokes is variable and most
dependent upon underlying etiology. The experience from the Mayo
Clinic from 1965 to 19741 showed that 80% of children
survived 10 years after an ischemic stroke, although most had
residual hemiparesis. Solomon6 highlighted the
poor prognosis of strokes that presented with seizures during
infancy, and with an angiographic pattern of moyamoya disease.
Abram7 studied 42 children with idiopathic ischemic
stroke exclusively and found a poor outcome in 43% of patients at
an average of 7.4 years following the stroke. Recurrent stroke
occurred in 7 children. In the children who did well, an early
recovery was observed. Risk factors for poor outcome included
persistence of hemiparesis one month after the stroke, cortical
location, and a moyamoya pattern on angiography.
REFERENCES
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