Intellectual abilities in tuberous sclerosis complex: risk factors and correlates from the Tuberous Sclerosis 2000 Study.

BACKGROUND: Tuberous sclerosis complex (TSC) is associated with intellectual disability, but the risk pathways are poorly understood. METHOD: The Tuberous Sclerosis 2000 Study is a prospective longitudinal study of the natural history of TSC. One hundred and twenty-five UK children age 0-16 years with TSC and born between January 2001 and December 2006 were studied. Intelligence was assessed using standardized measures at ≥2 years of age. The age of onset of epilepsy, the type of seizure disorder, the frequency and duration of seizures, as well as the response to treatment was assessed at interview and by review of medical records. The severity of epilepsy in the early years was estimated using the E-Chess score. Genetic studies identified the mutations and the number of cortical tubers was determined from brain scans. RESULTS: TSC2 mutations were associated with significantly higher cortical tuber count than TSC1 mutations. The extent of brain involvement, as indexed by cortical tuber count, was associated with an earlier age of onset and severity of epilepsy. In turn, the severity of epilepsy was strongly associated with the degree of intellectual impairment. Structural equation modelling supported a causal pathway from genetic abnormality to cortical tuber count to epilepsy severity to intellectual outcome. Infantile spasms and status epilepticus were important contributors to seizure severity. CONCLUSIONS: The findings support the proposition that severe, early onset epilepsy may impair intellectual development in TSC and highlight the potential importance of early, prompt and effective treatment or prevention of epilepsy in tuberous sclerosis.

Intractable headache after excision of an acoustic neuroma treated by stent revascularisation of the sigmoid sinus.

A 47 year old man developed severe headaches after resection of an acoustic neuroma ipsilateral to non dominant venous drainage. CSF pressures were normal but imaging studies showed acquired, severe narrowing of the sigmoid sinus where it traversed the surgical defect. Stenting the sinus gave a lasting clinical improvement.

Diffusion tensor imaging of benign intracranial hypertension: absence of cerebral oedema.

Cerebral oedema, it has been suggested, may have a role in the pathophysiology of benign intracranial hypertension (BIH). We applied diffusion tensor MR imaging (DTI), a technique able to detect cerebral oedema, to the study of patients with BIH. A quantitative regional analysis of diffusion parameters (trace and relative anisotropy) was conducted by comparing five BIH patients and six healthy controls. A small but significant increase in anisotropy accompanied by a small but significant decrease in trace was found in the putamen and head of the caudate nucleus. No significant changes were demonstrated in the thalamus, cerebral white matter or cortical regions. Our findings support other recent work that suggests cerebral oedema is not a factor in the pathogenesis of BIH.

Transverse sinus stenoses in benign intracranial hypertension demonstrated on CT venography.

Catheter studies show that patients with benign intracranial hypertension (BIH) frequently have high pressures in the intracranial venous sinuses proximal to stenotic lesions in the transverse sinuses. These lesions have now been demonstrated on MR venography. This study investigated whether they would be visible on CT. CT venography was performed on 10 patients with BIH and compared with 10 controls, matched for age and sex, undergoing CT angiography for subarachnoid haemorrhage. All controls were confirmed to have had ruptured intracranial aneurysms at craniotomy. Using a semi-automated technique to develop a profile of the cross-sectional areas along the lateral sinuses and to minimize observer bias, the narrowest point on each side was identified and summated in every subject. All patients with BIH exhibited a region of marked narrowing in both transverse sinuses, usually near the junction with the sigmoid sinus, rarely seen in our control group. Measured cross-sectional areas in these venous outflow tracts were substantially different between patients with BIH and controls (p<0.001). CT venography frequently demonstrates transverse sinus narrowing in BIH.

Two stage management of petrositis with associated mycotic aneurysm of the intrapetrous carotid artery.

Mycotic aneurysm of the petrous temporal bone is extremely rare, with only 12 cases previously reported. We review the literature to date and present a case of petrositis complicated by a mycotic aneurysm of the internal carotid artery, which was managed by endovascular balloon occlusion and subsequent total petrosectomy. We can find no other case in the literature where balloon occlusion has been used to treat a mycotic aneurysm of the intrapetrous carotid artery prior to total petrosectomy to treat petrositis.

MR venography in idiopathic intracranial hypertension: unappreciated and misunderstood.

BACKGROUND: Venous sinus disease must be excluded before diagnosing idiopathic intracranial hypertension but is found only rarely in typical cases. Magnetic resonance venography (MRV) is the technique of choice for investigating this, and provides images that are diagnostic and easy to interpret. However, recent work using more invasive techniques has documented pressure gradients and stenoses in the lateral venous sinuses in many cases of idiopathic intracranial hypertension. OBJECTIVE: To examine the reason for this discrepancy and to establish whether there are characteristic appearances on MRV in idiopathic intracranial hypertension that are routinely overlooked in clinical practice. METHODS: MRVs from 20 patients with idiopathic intracranial hypertension were reviewed, unblinded, by two neuroradiologists, and their appearances rated for focal narrowings and signal gaps. A control group of 40 asymptomatic volunteers, matched for age and sex with the patient group, was recruited prospectively for MRV, and their scans rated in the same way. RESULTS: The lateral sinuses presented a range of appearances with quite different distributions in the two groups (p<0.001). Bilateral lateral sinus flow gaps were seen in 13 of 20 patients with idiopathic intracranial hypertension and in none of 40 controls. CONCLUSIONS: A historical failure to use normal healthy controls to establish the boundaries between imaging artefact, normal anatomical variant, and disease means that the pathological significance of the different appearances of the lateral sinuses on MRV has not so far been appreciated.

Idiopathic intracranial hypertension: 12 cases treated by venous sinus stenting.

BACKGROUND: The high pressures documented in the intracranial venous sinuses in idiopathic intracranial hypertension (IIH) could be the result of focal stenotic lesions in the lateral sinuses obstructing cranial venous outflow. OBJECTIVE: To explore the relation between venous sinus disease and IIH. METHODS: 12 patients with refractory IIH had dilatation and stenting of the venous sinuses after venography and manometry had shown intracranial venous hypertension proximal to stenoses in the lateral sinuses. Intrasinus pressures were recorded before and after the procedure and correlated with clinical outcome. RESULTS: Intrasinus pressures were variably reduced by stenting. Five patients were rendered asymptomatic, two were improved, and five were unchanged. CONCLUSIONS: The importance of venous sinus disease in the aetiology of IIH is probably underestimated. Lateral sinus stenting shows promise as an alternative treatment to neurosurgical intervention in intractable cases.

Tuberous sclerosis presenting in late adult life.

A 59 year old woman presented with a three year history of left sided weakness. Magnetic resonance imaging of the brain showed a large high signal lesion occupying most of the right temporal lobe with mass effect. A probable diagnosis of low grade glioma led to temporal lobectomy. Histology revealed dysplastic cortical morphology typical of tuberous sclerosis. There were no clinical signs or family history of the disease. Ultrasound showed multiple bilateral renal angiomyolipomas, confirming the diagnosis of tuberous sclerosis. Molecular genetic analysis of peripheral white blood cells identified a novel mis-sense mutation R1409W in exon 33 of the TSC2 gene.