The relation of infantile spasms, tubers, and intelligence in tuberous sclerosis complex.

BACKGROUND: The aetiology of the learning difficulty in tuberous sclerosis is debated. It may be related to the amount of tubers in the brain or caused by the infantile spasms that occur in early life. AIMS: To examine the relative contributions to final intelligence (IQ) made by both cerebral tubers and infantile spasms. METHODS: As part of an epidemiological study of tuberous sclerosis in the south of England, patients were recruited who were able to undergo magnetic resonance imaging (MRI) without the need for an anaesthetic. Epilepsy history was determined by interview and review of clinical records. IQ was assessed using either Wechsler intelligence scales or Raven's matrices. RESULTS: A total of 41 patients consented to have an MRI scan. IQ scores were normally distributed about a mean of 91. Twenty six patients had a positive history of epilepsy, and 11 had suffered from infantile spasms. There was a significant relation between the number of tubers and IQ. Infantile spasm status partly confounded the relation between tubers and IQ, but did not render the relation statistically insignificant. The relation between infantile spasms and learning difficulty remained strong even when controlling for the number of tubers.     

Cardiac tumour in a neonate with tuberous sclerosis: echocardiographic demonstration and magnetic resonance imaging

In a neonate with tuberous sclerosis, cardiac tumours were diagnosed by two-dimensional echocardiography and evaluated by electrocardiogram-gated magnetic resonance imaging (MRI). The tumour size, shape and mobility in the ventricular cavities were more precisely determined by two-dimensional echocardiography than electrocardiogramgated MRI, while the extent of tumour mass at the apex was more clearly delineated by MRI. As two-dimensional echocardiography provides real-time imaging of cardiac anatomy without sedation, it is useful for initial evaluation of cardiac masses in neonates with genetic predisposition to tuberous sclerosis.Abbreviation MRI magnetic resonance imaging     

Clinically silent seizures in a neonate with tuberous sclerosis

Although seizures during infancy in patients with tuberous sclerosis complex are common, seizures in neonates are infrequent. Here, we report the clinical course and electroencephalography (EEG) findings of a neonate with tuberous sclerosis complex associated with clinically silent seizures. The patient was a girl in whom cardiac tumors were detected on fetal ultrasonography. Brain magnetic resonance imaging during the neonatal period showed subependymal and cortical tubers. Routine EEG indicated unexpected ictal changes with no noticeable clinical symptoms. Ictal EEG was associated with a subtle increase in heart rate and a brief increase in chin electromyogram. These changes were difficult to identify clinically. The patient later developed focal seizures and epileptic spasms and had severe psychomotor delay. The present case suggests the occurrence of clinically silent seizures before the appearance of epileptic spasms in infants with tuberous sclerosis, and that EEG is an option for neonates with a prenatal diagnosis.     

结节性硬化症16例临床特征和诊断

目的 评价结节性硬化症的临床特征和ＣＴ,ＭＲＩ对其诊断价值。方法 对１６例结节性硬化症患者的临床资料进行分析。结果 １６例患儿的临床特征为起病年龄３岁以内１５例,占９３％,全部患儿均以癫痫发作为首发症状,有皮肤表现者１３例,占８１％,以色素脱失斑最多见。智力低下者３例,占１９％,全部患儿均有脑ＣＴ或ＭＲＩ改变,对３例不典型病列通过脑ＣＴ检查确诊。结论 癫痫,特殊的皮肤损害为本病的主要临床特征,脑Ｃ     

Intracranial vascular abnormalities in patients with Alagille syndrome

OBJECTIVES: To define the spectrum of intracranial events and cerebrovascular lesions in patients with Alagille syndrome using magnetic resonance imaging with angiography of the head and medical histories and to correlate the presence of lesions with the clinical outcome of bleeding or ischemic intracranial events. METHODS: 26 patients with Alagille syndrome underwent magnetic resonance imaging with angiography of the head; 22 had no symptoms and underwent study for screening purposes and 4 were symptomatic with neurologic changes. The results of studies and the history of ischemic intracranial events were reviewed. RESULTS: Cerebrovascular abnormalities were detected in 10 of 26 (38%) patients (9 by head magnetic resonance imaging with angiography and 1 by necropsy). The findings included stenoses of the internal carotid arteries unilaterally (n = 5) or bilaterally (n = 3), basilar artery aneurysm (n = 1) and middle cerebral artery aneurysm (n = 1). Among the 9 patients with cerebrovascular abnormalities detected by magnetic resonance imaging with angiography, 5 had no symptoms (23%, 5 of 22) and 4 were symptomatic. Thus, 100% of symptomatic patients had detected abnormalities and 23% of screened, asymptomatic patients had detected anomalies. Screening magnetic resonance imaging with angiography failed to detect vascular anomalies in 2 asymptomatic patients who had fatal ischemic intracranial events years later. There was evidence of progression of vascular abnormalities in 4 patients. Ischemic intracranial events occurred in 10 of 26 (38%) patients and were associated with cerebrovascular abnormalities in 6 of 10 patients. CONCLUSION: The cerebral vasculopathy of Alagille syndrome predominantly involves the internal carotid arteries. It is more prevalent than would be suggested by the number of symptomatic individuals, appears to be progressive and shares many similarities with moyamoya. Magnetic resonance imaging with angiography is useful to detect these lesions and may have a valuable role in screening for treatable lesions such as aneurysms.     

Magnetic resonance imaging and dexamethasone therapy for bacterial meningitis

We conducted a third placebo-controlled, double-blind study of dexamethasone as adjunctive therapy for bacterial meningitis. Thirty-one patients received cefuroxime sodium (300 mg/kg per day in 3 doses) and dexamethasone phosphate (0.6 mg/kg per day in 4 doses for 4 days), and 29 received cefuroxime and placebo. The groups were comparable at the beginning of therapy. Magnetic resonance imaging performed between days 2 and 5 of therapy was used to assess brain water content indirectly. There were no differences between the 2 treatment groups with respect to the T1- or T2-weighted images. Fifty-two patients (88%) had normal magnetic resonance images; 5 patients had parietal or bifrontal extra-axial fluid collections, and 2 children had areas of abnormal signal intensity in the brain on T2-weighted images. Abnormal findings on magnetic resonance imaging did not alter clinical management, and there was no correlation between the results of magnetic resonance imaging and the outcome of meningitis. The number of patients in this study was too small to determine any statistically significant differences in rates of hearing impairment; however, the cerebrospinal fluid findings and clinical outcome in dexamethasone-treated patients further support the previously reported beneficial effect of corticosteroid treatment in patients with bacterial meningitis.     

Diagnosis of cerebrovascular disease in sickle cell anemia by magnetic resonance angiography

The study of blood flow by means of magnetic resonance techniques has led to a noninvasive magnetic resonance angiography (MRA) technique for imaging large cerebral vessels. Ten children with sickle cell hemoglobinopathy and a history of acute neurologic syndromes were studied with combined parenchymal magnetic resonance imaging (MRI) and MRA. Six had abnormal MRI findings and MRA-defined luminal lesions in the vascular distribution of these parenchymal infarctions. The three children with previous intraarterial angiography had MRA abnormalities that corresponded with vascular lesions on conventional angiograms. Four had normal MRI and MRA findings. We conclude that a combination of MRI and MRA provides a noninvasive screening test for large-vessel disease in this population.     

Familial bilateral periventricular nodular heterotopia mimics tuberous sclerosis.

A mother and daughter with an initial diagnosis of tuberous sclerosis are described. The daughter presented with partial seizures at the age of 8 months. Computed tomography showed uncalcified periventricular nodules which on magnetic resonance imaging were ovoid, almost contiguous, of grey matter density, and did not enhance with gadolinium. Brain imaging of her asymptomatic mother was similar. Absence of severe mental retardation, extracranial hamartomas, and depigmented patches distinguishes familial bilateral periventricular nodular heterotopia (FNH) from tuberous sclerosis. FNH is probably inherited as an X linked dominant with lethality in males.     

Familial bilateral periventricular nodular heterotopia mimics tuberous sclerosis

A mother and daughter with an initial diagnosis of tuberous sclerosis are described. The daughter presented with partial seizures at the age of 8 months. Computed tomography showed uncalcified periventricular nodules which on magnetic resonance imaging were ovoid, almost contiguous, of grey matter density, and did not enhance with gadolinium. Brain imaging of her asymptomatic mother was similar. Absence of severe mental retardation, extracranial hamartomas, and depigmented patches distinguishes familial bilateral periventricular nodular heterotopia (FNH) from tuberous sclerosis. FNH is probably inherited as an X linked dominant with lethality in males.     

Ischaemic and haemorrhagic brain lesions in newborns with seizures and normal Apgar scores.

Serial ultrasound scans and conventional and diffusion weighted magnetic resonance imaging (MRI) were performed on 16 neonates who presented with seizures. The Apgar scores were normal and subsequently no metabolic or infective cause could be found. The aim of the study was to evaluate the extent to which early sequential imaging can elucidate the cause of seizures in apparently neurologically normal infants. Fourteen of the infants had haemorrhagic or ischaemic lesions on MRI and these were detected by ultrasound scanning in 11. Early ultrasound scanning detected the haemorrhagic lesions but the ischaemic lesions were often not seen until the end of the first week of life. Early MRI, however, was able to detect all the ischaemic lesions. The evolution of the insult could be timed by using serial ultrasound scans and a combination of diffusion weighted and conventional MRI during the first week of life, confirming a perinatal insult even in the absence of fetal distress. Although the aetiology of these lesions remains obscure, serial ultrasound scans will detect the presence of cerebral lesions in neonates presenting with isolated seizures but additional MRI sequences will give better definition on type, site, and extent of the pathology.     

Neuroimaging in tuberous sclerosis: A clinicoradiological evaluation in pediatric patients

CT, MRI and neurological features of 27 children with tuberous sclerosis were prospectively compared. Imaging studies were positive in 92.5% of cases. CT was more useful in detecting subependymal nodules, while MRI showed the number and location of cerebral cortical and subcortical lesions more accurately. Cortical lesions in the cerebellar hemispheres were present in 26% of patients. Gadolinium-DTPA used in 10 patients showed slight enhancement of the subependymal lesions in 80% of cases, probably representing active lesions with alteration of the blood-brain barrier. None of the cortical and subcortical lesions enhanced. Giant-cell astrocytomas were detected in 5 patients, the postcontrast CT and MRI studies improving their assessment. Unlike subependymal nodules, all tumors showed marked enhancement regardless of their size. Seizures were present in 96% of patients, mostly beginning before 1 year of age. There was no clear relationship between the radiological features and the neurological evolution of these patients. There-fore, it is not possible to establish a clinical prognosis based on the radiological findings. MRI is the procedure of choice in the diagnosis of tuberous sclerosis. When pre and postcontrast MRI are negative, CT is used to exclude small calcified subependymal nodules. MRI followup is required only when tumoral development is clinically suspected.     

Neuroimaging correlation with neurological severity in tuberous sclerosis complex.

OBJECTIVE: To delineate the relationship between neurological severity and neuroimage of lesion load including specific topography of supratentorial cortical tubers and white matter lesions in tuberous sclerosis complex (TSC). METHODS: Twenty-five TSC patients more than 2 years of age who underwent conventional and fluid-attenuated inversion recovery sequence (FLAIR) magnetic resonance imaging (MRI) were retrospectively studied. Neurological severity score was designated for three items: seizure, developmental delay and/or mental retardation, and autism. A neuroimaging scoring system was designed to evaluate the load of the cerebrum lesions with respect to location and size of cortical tubers and white matter lesions based on FLAIR MRI. RESULTS: A linear trend was observed between MRI lesion score and neurological severity score (r=0.511; p=0.009). The lesion score in the left temporal lobe has positive correlation to neurological severity score (r=0.609; p=0.001). CONCLUSIONS: The brain lesion load was positively correlated with neurological prognosis in TSC patients. Patients with larger lesion load in the left temporal lobe may be correlated with increased neurological severity in right-handed patients with TSC.     

Tuberous sclerosis complex: a review of neurological aspects.

Tuberous sclerosis complex is characterized by hamartomatous lesions involving skin, brain, kidneys, eyes and heart. Pathologically, tuberous sclerosis is a disorder of cell migration, proliferation and differentiation. Cell lineage and cell migration disorders in the developing cortex of tuberous sclerosis complex patients might produce very different neurological phenotypes including epilepsy, cognitive impairment and autism. Cortical tubers constitute the hallmark of the disease and are pathognomonic of cerebral tuberous sclerosis. Epilepsy is the most common neurological feature, occurring in 96% of patients. Seizures often begin in the first months of life and are frequently severe and intractable. The treatment of seizures has recently benefited from the advent of the new anti-epileptic drugs. Selected drug-resistant patients with tuberous sclerosis complex could be considered for surgical treatment. Clear localization of the most active epileptogenic focus and the zone of the cortical abnormality may lead to tuberectomy and improved seizure control in selective drug-resistant patients. The finding of multiple areas of cerebral involvement should not automatically preclude epilepsy surgery in a child with intractable seizures and a well defined seizure origin.     

新生儿脑梗死的临床特征及其与预后关系的研究

目的分析新生儿脑梗死的临床特征与预后的关系,并通过早期诊断和干预,以改善本病的远期预后。方法总结6例确诊病例的临床特征,进行围产期因素和其它可能病因分析,并对存活患儿进行6～8个月的随访。结果1年内发现6例新生儿脑梗死,占同期住院患儿0．6％(6／969)。6例中3例经MRA确诊为脑血管畸形,1例为严重脑室内出血,1例与早产、母亲患重度妊娠高血压综合征及继发于支气管肺发育不良的呼吸衰竭等综合因素有关,1例原因不明。本组4例(4／6)出现各种形式惊厥,占同期新生儿惊厥的20％(4／20),是引起新生儿惊厥的第二位原因;6例在早期均无定位体征,仅有部分患儿表现为肌张力异常。头颅B超示6例中5例有阳性发现;弥散加权核磁共振成像(DW-MRI)能够做到早期准确诊断。1例随访至1岁未发现异常,其余5例均有不同程度不良预后。结论新生儿脑梗死并不少见,而且是新生惊厥的重要原因之一,影像检查是本病主要确诊方法,未能早期诊治和累及范围较广者预后不良。     

Oligosymptomatic variant of tuberous sclerosis with subependymal giant cell astrocytoma

We report on a 9-year-old boy who developed subependymal giant-cell astrocytoma associated with tuberous sclerosis. Remarkably, the boy was not mentally retarded and never had suffered from seizures. Apart from white skin patches symptoms of increased intracranial pressure were the presenting symptoms. The boy's mother, who was present at the boy's admission, presented with skin lesions typical of tuberous sclerosis. The importance of thorough examination of apparently asymptomatic relatives of patients with tuberous sclerosis is emphasized.     

Magnetic resonance imaging of the brain in infants and children before and after cardiac surgery. A prospective study

We assessed the morphologic findings of the brain prospectively before and after cardiac surgery using magnetic resonance imaging. There were 12 patients with acyanotic and 6 with cyanotic heart disease. There were 2 deaths, and 1 patient did not have to undergo postoperative magnetic resonance imaging. The study group consisted of 15 patients completing both the preoperative and postoperative magnetic resonance imagings. All patients in the study group underwent moderate hypothermic cardiopulmonary bypass using a nonpulsatile membrane oxygenator. The mean (+/- SD) cardiopulmonary bypass time was 100 +/- 55 minutes. Ten of the preoperative studies were interpreted as normal. One third (5 of 15) of the patients showed ventriculomegaly and dilatation of the subarachnoid spaces on preoperative magnetic resonance images. Measurements of the preoperative and postoperative magnetic resonance images showed a postoperative increase in the bicaudate and third ventricular diameters. Four patients in the study group developed postoperative subdural hematomas. The subdural hematomas were small and caused no demonstrable mass effect on magnetic resonance imaging. One patient had a preoperative white matter infarction. There was 1 patient with a postoperative infarction.     

MR and CT imaging patterns in post-varicella encephalitis

The aim of the investigation was to determine the patterns of cerebral involvement on computed tomography (CT) and magnetic resonance (MR) imaging in post-varicella encephalitis. Four children between the ages of 2 and 11 years presented over a 5-year period with a diagnosis of post-varicella encephalitis. Their imaging studies and clinical data were reviewed retro-spectively. The medical histories of all four children were noncontributory except for recent bouts of chickenpox 1 week to 3 months prior to hospitalization. Three children presented with parkinsonian manifestations. Bilateral, symmetric hypodense, nonenhancing basal ganglia lesions were found on CT. These areas showed nonenhancing low signal intensity on T1-weighted images and high signal intensity on T2-weighted images on MR. One child presented with diffuse, multiple gray and white matter lesions of similar imaging characteristics; some lesions, however, did enhance. This child had no gait disturbances. Post-varicella encephalitis can produce two patterns of dramatic CT and MR findings. With an appropriate history and clinical findings, varicella as a cause of bilateral basal ganglia or diffuse cerebral lesions can be differentiated from other possible etiologies which include trauma, anoxia, metabolic disorders and demyelinating diseases.     

磁共振成像和计算机X线断层照像术对婴儿痉挛病因和预后判断的意义

目的　探讨头颅磁共振成像 (MRI)和计算机X线断层照像术 (CT)对婴儿痉挛 (IS)的病因和预后判断的意义。方法　采用螺旋CT平扫和MRI扫描T1和T2加权相、反转恢复序列和磁共振血管成像等技术对4 2例IS颅脑病变进行检测和分析。结果　CT检查 14例发现异常 ,对脑萎缩、出血、粗大畸形和钙化显示较好 ;2 4例MRI扫描阳性 ,对脑白质软化或髓鞘化延迟、海马和脑干萎缩、缺氧缺血性脑病 (HIE)和核黄疸、结节性硬化、灰质异位及胼胝体和脑血管畸形等病变都具有良好诊断价值 ;MRI对IS预后判断应结合临床和年龄。结论　MRI和CT对探寻IS等癫潜在病因、评估预后和指导治疗具有重要意义 ,前者对脑白质软化与髓鞘化、HIE、海马萎缩、局限性脑发育不全和灰质异位等病变检测尤敏感。     

Muscle-eye-brain disease: clinical features, visual evoked potentials and brain imaging in 20 patients.

Clinical features, magnetic resonance imaging and visual evoked potentials were analysed and correlated in 20 Finnish patients with muscle-eye-brain disease. Significantly enhanced visual evoked potentials were found in 15 patients (giant in 14 of them). Magnetic resonance images were available in 17 cases. The images of 12 patients with giant visual evoked potentials showed typical brain malformation pachygyria with a nodular cortical surface i.e. cobblestone cortex, midline defect and hypoplastic pons but no significant abnormalities in the grey-white matter. One male had typical structural changes but flat visual evoked potentials. His extreme hydrocephalus with optic nerve compression may explain the findings. No structural changes on magnetic resonance images were found in the remaining four patients; however, in two of them marked alterations in the white matter were found. Three of these patients showed normal and one flat visual evoked potentials. Only one patient with giant visual evoked potentials and typical structural findings on magnetic resonance imaging had changes in a large area in the white matter (several attacks of status epilepticus might have caused the alterations in the white matter). Thus, the combination of giant visual evoked potentials and typical structural changes on magnetic resonance imaging with normal intensities of white matter and deep grey matter seems to be a good marker for patients with muscle-eye-brain disease.