Tuberous sclerosis complex (TSC) is an autosomal dominant neurocutaneous syndrome with variable penetrance; the estimated frequency is approximately one in 6,000 newborns [1,2]. Although a wide variety of central nervous system abnormalities are associated with TSC, intracerebral hemorrhage is rare [3-9].

A 2-year-old boy presented with history of sudden onset repeated vomiting, loss of consciousness, recurrent attacks of generalized tonic-clonic seizures, and left-sided hemiparesis. There was no history of trauma or antecedent surgery, congenital cyanotic heart disease, dehydration, tuberculosis or bleeding disorders. Child was previously admitted to a local hospital where he was treated with phenytoin and aspirin. Past history revealed that he was suffering from recurrent focal seizures since six months of age for which he was prescribed sodium valproate, but the drug compliance was poor for the last three months. He was born out of a non-consanguineous marriage and had two siblings. His elder brother was also suffering from similar kind of focal seizures since early infancy, and had profound mental disability.

At presentation, he was afebrile but comatose with Glasgow Coma Scale of E2V2M3 with stable vital signs, including blood pressure. On examination, he had spasticity and weakness in the left upper and lower limb, positive Babinski sign and exaggerated deep tendon reflexes on the left side. Ophthalmological examination showed mid-dilated pupils with sluggish reaction to light and bilateral papilledema. Child had no signs of meningeal irritation or any cranial nerve involvement. Multiple hypopigmented macules were noted over the face, abdomen and trunk of the child. Other systemic examination was unremarkable.

Routine hematological and biochemical investi-gations were normal. A non-enhanced computed tomography (CT) scan of brain showed massive acute intracranial hemorrhage with perilesional edema located in the right fronto-parietal region with multiple periventricular subependymal calcified nodules (Fig. 1a). MR angiography did not detect any vascular abnormality except intracerebral hemorrhage (Fig. 1b).

Fig. 1 (a) Non-enhanced CT scan showing large intracranial hemorrhage with perilesional edema located in the right fronto-parietal region as well as multiple periventricular subependymal calcified nodules; (b) MR angiography showing intracranial hemorrhage in the right fronto-parietal region without any abnormality in the major cerebral vessels.

Protein C and protein S level, blood lactate levels, Carotid doppler study, and abdominal ultrasound were non-contributory. Ophthalmological examination did not reveal any retinal abnormality. 2D Echocardiography showed two masses, one in left ventricle of size 16×14 mm, attached to the intraventricular septum, and another (10×10 mm) in the right ventricle suggestive of rhabdomyoma. In view of history, clinical examination and investigations, including neuroimaging, the child was diagnosed as a case of tuberous sclerosis. Other family members were assessed; except mother, all had TSC but the clinical presentations were varied. Child improved gradually on medical management and discharged with the advice to continue sodium valproate and physiotherapy. CT scan repeated at 3 month of follow-up visit showed resolution of hemorrhage.

Tuber is the characteristic brain lesion of TSC, and may rarely differentiate into a malignant subependymal giant cell astrocytoma. The most common neurologic manifestations are seizures, cognitive impairment, and behavioral abnormalities, including autism [1].

In TSC, intracerebral hemorrhage – with or without intraventricular component – is rare. In most of the reported cases, it was associated with either underlying cerebrovascular malformation, like ectasia, aneurysm and arteriovenous malformation or hemorrhage into the subependymal giant cell astrocytoma [3-9]. The underlying pathophysiologic mechanism of intratumoral hemorrhage remains unclear; increased venous pressure secondary to an increased intracranial pressure is the most accepted pathogenesis leading to necrosis and hemorrhage [6].

In the present case, neither vascular anomaly nor intratumor hemorrhage was detected. Other possible etiologies like hypertension, primary or metastatic central nervous system malignancy, leukemia, coagulopathy, use of drugs like warfarin, amphetamines, cocaine, phenypropanolamine, history of head trauma or antecedent intracranial surgery were excluded. Although the etiology remains unexplained in the index case, possibility of early hemorrhagic transformation of an underlying embolic ischemic infarction could not be ruled out as the probable pathophysiologic mechanism where cardiac tumours were the potential source of emboli [10].

Contributors: RP: diagnosed, worked up the case and wrote the manuscript; SB and BR: managed the case and reviewed the literature; RP and RB: prepared the final manuscript and followed up the case.

Funding: None; Competing interests: None stated.

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