Acta Pzdiatr Scand 65: 119-124, 1976 CASE REPORT SPONTANEOUS CEREBRAL THROMBOSIS IN CHILDREN Report of Two Cases K. B. LILLQUIST and H. M. INGSTRUP From the Department of Paediatrics, Aulborg Hospital, Section North und the Department of Diagnostic Radiology, Aalhorg Hospital, Section South, Denmark I ABSTRACT. Lillquist, K. B. and Ingstrup, H. M. (Department of Paediatrics, Aalborg Hospital, Section North, and Department of Diagnostic Radiology, Aalborg Hospital, Section South, Denmark). Spontaneouscerebral thrombosis in children. Acta Paediatr &and, 65: 119, 1 9 6 . 4 e r e b r a l arterial occlusions are rare in children, but they are demonstrated with increasing frequency as angiographic examination of children with acute hemiplegia becomes a routine procedure. Two cases of idiopathic cerebral thrombosis in boys, aged 6 1and 5 years, involving the basilar artery and the middle cerebral artery, respectively, are presented. The clinical flndings supplemented by angiography confirmed the diagnosis. KEY WORDS: Cerebral thrombosis, acute hemiplegia, children Since the introduction of cerebral angiography in paediatric hospitals, arterial occlusions have been found increasingly often to be a cause of acute hemiplegia in children. In a large number of cases of acute cerebral occlusions in childhood the pathogenesis still remains unknown. Fortunately, the condition is only rarely fatal. CASE HISTORIES Case 1 A 64-year-old boy was admitted to hospital in December, 1973, with a tentative diagnosis of acute encephalitis. The maternal grandfather had senile diabetes, and died of coronary thrombosis. The mother had hypertension during pregnancy, was delivered at term by Caesarian section owing to contracted pelvis. Premorbid development of the patient normal. No head injuries. From late October to early November the patient had bilateral sinusitis. On December 3, 1973, the patient awoke with paraesthesia in one foot, and a few hours later he became increasingly dizzy. Vomiting, restlessness and unsteady gait. On admission, ataxia, speech disturbances and spastic increase in the tonus of the left arm were found. N o definite change in tonus in the legs. The deep reflexes were brisk, almost equal bilaterally. Bilateral, atypical Babinski’s sign. There was no fever. Blood pressure 115lSO mmHg. Ophthalmoscopy normal. The auscultation of the heart revealed a slight protosystolic murmur, grade 2 in the intercostal space 111-IV at the left sternal margin spreading to the pulmonary ostium. Coagulation status: Coagulation time: 8 min (5-1 1 min), recalcification time: 207 sec (<230 sec), partial thromboplastin time: 97 sec (about 65%). factor V: 60% (>about 65%). plasmathrombin time: 33 sec (about 30 sec), plasmathrombin+toluidine blue: 28 sec (about 30 sec), fibrinogen in plasma: 269 mgl100 ml (300-500 mg/100 ml), Behring PTT: 49 sec ( 4 2 sec), FDP negative, euglobulin-clot-lysis time: 90-105 min (60-240 min), antithrombin 111: (Method: Laurell, C.-B.) 90 arbitrary units (80-1 16 arbitrary units), platelets: 292X 109/1 (14O-340X 10s/l). The results of the following laboratory examinations were all normal: Sedimentation rate, leukocyte and differential counts, haemoglobin, haematocrit, blood glucose, serum carbamide, serum electrolytes, serum protein, serum lipid and lipoprotein pattern, thyroid parameters, amino-acid chromatography, alkaline phosphatases, rheumatoid-arthritis test, antinuclear factor, Rose-Waaler test, LE-cell test, antistreptolysin 0, antistreptococcushyaluronidase, streptococcus-agglutinating titre, blood cultures, cultures of pharyngeal and oral swabs, cerebrospinal fluid and agar-gel electrophoresis and microscopy of urine. Acru Pzdiorr Scond 65 120 K . 3. Lillquist and H . M . Ingstrup inward rotation of the left foot. The patient was mentally alert, but somewhat euphoric in his behaviour. At a follow-up examination after 12 months there was no longer any right-left confusion. The gait and balance had further improved Case 2 Fig. I . Complete occlusion of the basilar artery. Echo encephalography and electro-encephalography showed no abnormalities; brain scintigraphy did not reveal any abnormalities either. Electrocardiogram normal for the age. Chest radiography showed no abnormalities. A biopsy specimen of muscular and vascular tissue from the temporal region, examined by light microscopy, showed normal conditions. The following stains were used: haematoxylin-eosin, van Gieson-Hansen, toluidine and elastin (Weigert) (Neuro-pathological Laboratory, Aarhus Municipal Hospital). Under general anaesthesia, left-sided vertebral angiography and angiography of the carotid artery on both sides by the method of Seldinger were performed. The vertebral angiography revealed an occlusion of the basilar artery extending over 1-1.5 cm. (Figs. 1 and 2.) During the first few days, the patient was drowsy. with uncontrolled movements, but after 2 weeks he was able to stand and walk, although the balance was still poor. At discharge, after 14 months of physical therapy, there was good, almost equal muscular power in the extremities. The gait was unsteady and still uncoordinated. At a follow-up examination 9 months later a slight right-left confusion was found. When walking, the patient dragged his left foot; and there was a slight drop-foot with a 5-year-old boy was admitted to hospital on January 3 , 1974, in a somnolent condition. No predisposition to cardiac or vascular diseases. Perfectly natural development. No head injuries. From late November to midDecember, 1973, the patient had had chickenpox. During the period December 24-31, 1973, he had run a temperature of 39°C with a red rash on the right lower leg. The last 3 days prior to admission the patient was alert and without fever. Suddenly on the day of admission, right-sided hemiparesis developed, accompanied by slight affection of the facial nerve in right oral region, expressive aphasia, a tendency to fall to the right, and enuresis. There was increased tonus on the right side. Babinski's sign was positive on the right side. Apart from a rise in temperature to 38.4"C on the third day in hospital, the patient had no fever during the entire stay. Blood pressure 120/70 mmHg. Ophthalmoscopy normal. The auscultation of the heart revealed a cardiac murmur over the base of the heart, grade 2-3. Sedimentation rate 25 mmlh, there was a slight leukocytosis, 15.7= 109/1with a rapid fall to normal values. Coagulation sfatus: Coagulation time: 8 min (5-1 I min) recalcification time: 195 sec ( 4 3 0 sec), partial thromboplasin time: 100 sec ( < I 10 sec), prothrombin (Quick): 17 sec (<16 sec), prothrombin-proconvertin: 60 7% (>about 6 5 % ) , factor V: 60% (>about 6 5 % ) , plasmathrombin time: 34 sec (about 30 sec), fibrinogen in plasma: 214 mg/100 ml(300-500 mg/100 ml), Behring PTT: 47 sec (<52 sec), FDP: negative, euglobulin-clot-lysis time: 200-215 min (60-240 min), antithrombin 111: (Method: Laurell, C.-B.) 103 arbitrary units (80-1 16 arbitrary units), platelets: 2 0 6 109/1 ~ (140-MOX10911). The results of the following laboratory tests were all normal: haemoglobin, haematocrit, blood glucose, serum carbamide, serum electrolytes, serum protein, serum lipid, lipoprotein pattern, thyroid parameters, amino-acid chromatography, alkaline phosphatases, antistreptolysin 0, antistreptococcus-hyaluronidase, rheumatoid-arthritis test, antinuclear factor, Rose-Waaler test, LE-cell test, blood cultures, cultures of pharyngeal swabs, cerebrospinal fluid including agar-gel electrophoresis and microscopy of urine. The EEG showed foci in the occipitotemporal region. The electrocardiogram revealed sinus rhythm, with normal conduction time, a transient rsr' pattern, a pronounced U wave and inverted T waves in leads I , I1 and 111 and in V,-V,. Chest radiography normal. A biopsy specimen of muscular and vascular tissue from the temporal region, stained and examined as in the first case, showed normal conditions. Under general anaesthesia, left-sided angiogrdphy of the common carotid artery was carried out, with direct puncture of the common carotid artery on the neck. There was a thrombus in the middle cerebral artery extending over about 1 cm, localized about 2 cm peripheral to the bifurcation of the internal carotid artery. Filling of one Spontaneous cerebral thrombosis in children 12 1 Fig. 2. Retrograde filling of basilar artery proximally. middle branch occurred, peripheral to the thrombus. Otherwise, the vessels were, of normal calibre (Figs. 3 . 4 and 5 ) . The clinical picture improved rapidly, and after a week the patient was able to utter a few words and to walk with an acceptable gait when slightly supported. At discharge after well over 1 month in hospital the hemiparesis had almost completely disappeared. At a follow-up examination 6 months later, slight right-sided hemiplegia was present. The gait was normal and steady. At the second follow-up examination after 10 months there was a distinct spastic increase of the tonus in the right arm, and the patient preferred to use his left hand. No mental abnormalities were observed. DISCUSSION Fig. 3. Incomplete occlusion of the left middle cerebral artery. In cerebral thrombosis in children it is possible in most cases to demonstrate an aetiological cause (12, 14, 15, 16) of the thrombus formation-secondary thrombosis, though occasionally thrombosis of unknown aetiology occurs-a primary, idiopathic or spontaneous thrombosis (8). The site of arterial thrombosis with cerebral manifestations may either be extracranial in the cervical part of the internal Ac.fcr Pzdiorr Sc.(rnd 65 122 K . B . Lillquist and H . M . Ingstrup Fig. 4. Incomplete occlusion of the left middle cerebral artery. Filling peripheral to a few middle branches. carotid artery or intracranial. The localization of the intracranial thrombosis is predominantly the terminal portion of the internal carotid artery and its branches, especially the middle cerebral artery. In extremely rare cases, the thrombus may occur in other intracranial arteries, especially the vertebral artery and the basilar artery ( 3 , 8). Isler (8) reported that in about 80% of the cases, the thrombosis led to apoplectiform hemiplegia and in about 10% the hemiplegia was accompanied by an initial epileptic seizure. In some patients, the seizure was preceded by headache, fatigue and vomiting for from a few hours to several days before the acute thrombosis, and in one case mental changes were observed 6 weeks before the acute thrombosis (13). The neurological sequeale of a cerebral arterial thrombosis depend on two critical factors : 1. The establishment at an early stage of an effective collateral circulation. 2 . The perservation of the lenticulostriate arteries ( 5 ) . The development of epilepsy as a late complication occurs in about 30% of the patients. In 50%, a severe organic psychosyndrome (dementia, memorizing difficulties, etc.) is developed in from 1 to 9 years (8). In our 2 patients, the disease began with an apoplectiform hemiplegia. In both cases, it was impossible to demonstrate any definite cause of the cerebral thrombosis. The first patient had symptoms of an infection 3 weeks earlier, but was perfectly well immediately before the acute attack. The second patient had, 3 or 4 days before the acute thrombosis, a feverish episode, but normal results of the laboratory tests, including negative blood cultures, speak against a septic thrombus or embolus as an aetiological factor. There was no blood eosinophilia and the histological examinations Spontaneous cerebral thrombosis in children 123 Fig. 5. Lateral view o f incomplete occlusion of the left middle cerebral artery. of the blood vessels did not reveal any signs of an allergic vasculitis. Traumatic, hypoxic and toxic factors have also been excluded. Both patients had slight, atypical cardiac murmurs, but the results of the cardiological examination rendered it unlikely that the patients had or had had any cardiac disease which could explain the vascular attack. It has not been possible to demonstrate any changes in the composition of the blood which might give rise to cerebral thrombosis in our 2 patients. In none of them did the coagulation analyses reveal any signs of hypercoagulability . Normal euglobulin-clot-lysis times militate against an increased level of fibrinolytic inhibitors. A decreased level of antithrombin 111 has been shown to predispose to thrombotic disease but our patients had normal levels of antithrombin 111. The occurrence in patients with an otherwise intact cardiovascular system of localized reversible vascular constrictions-vasospasms-is definitely possible (4, 6 , 7, 9). It is also a well-known fact that vasospasms may occur in connection with a poor technique of cerebral angiography. It is reasonable to assume that ischemic symptoms caused by vasospasms are reversible in most cases, at least in children, (8), and in our cases we find that it is beyond doubt that the angiographic manifestations were caused by thrombosis-not by vasospasms. The therapeutic possibilities at our disposal in the treatment of cerebral thrombosis are few and the therapy is often limited to symptomatic supportive treatment. Dahlmann et al. ( 1 ) described a case of cerebral thrombosis occurring in a 3 1-year-old man in which good effect of streptokinase therapy was apparently obtained. No case of cerebral thrombosis in children has been treated with streptokinase, and it is generally believed that thrombolytic therapy with streptase of fresh intracranial k r o Pzdintr Si.linil65 124 K . B . Lillquist and H . M . Zngstrup vascular occlusions should be abandoned as the risk of secondary haemorrhage involved in this therapy leads to a death rate which is higher than the primary mortality (10). Davie et al. (2) reported a .case in which they successfully performed thrombectomy within 48 hours in a 2-year-old child with hemiplegia caused by para-infectious thrombosis of the internal carotid artery close to the bifurcation. The purpose with the presentation of these case histories is to call attention to the occurrence of cerebral arterial thrombosis in children. Although they are rare, particularly in the basilar region, such cases should be borne in mind, and angiography will be indicated in selected patients. . REFERENCES I . 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London 1962. 15. Shillito, J. Jr: Carotid arteritis: a cause of hemiplegia in childhood. J Neurosurg, 21: 540, 1964. 16. Taveras, J. M.: Multiple progressive intracranial arterial occlusions: a syndrome of children and young adults. A m J Roentgenol Radium Ther Nucl Med, 106: 235, 1969. Submitted Jan. 4, 1975 Accepted June 20, 1975 (K. L.) Lindenborgvej 892 I V 9200 Skalborg Denmark