Clinical assessment of thyroid related orbitopathy: a review.

This review follows the process of evaluation of thyroid related orbitopathy (TRO) patients from diagnosis to treatment decision. We will attempt to define the criteria for referring TRO patients to the ophthalmologist and establish a common basis for orbital examination and TRO patient assessment. This should help classify TRO patients and achieve the best treatment regime. Thyroid related orbitopathy (TRO) is an endocrine disorder with orbital manifestations. Though most patients are first seen by an endocrinologist because of thyroid function disturbance symptoms, approximately 10% will first be seen by an ophthalmologist due to orbitopathy symptoms and signs (1). In the majority of cases the time interval between the appearance of dysthyroid symptomatology and orbital signs is less than a year. Among patients with thyroid endocrine dysfunction, 25% to 50% will gradually develop TRO. Most will have mild orbital manifestations, 28% will develop moderate to severe signs and only 3-5% will have the severe form (2). In this review we will follow the TRO patient through his first steps in the orbital clinic and emphasize the importance of clinical assessment as a crucial phase in determining the appropriate therapeutic approach.

Blood-brain barrier disruption in post-traumatic epilepsy.

BACKGROUND: Traumatic brain injury (TBI) is an important cause of focal epilepsy. Animal experiments indicate that disruption of the blood-brain barrier (BBB) plays a critical role in the pathogenesis of post-traumatic epilepsy (PTE). OBJECTIVE: To investigate the frequency, extent and functional correlates of increased BBB permeability in patient with PTE. METHODS: 32 head trauma patients were included in the study, with 17 suffering from PTE. Patients underwent brain MRI (bMRI) and were evaluated for BBB disruption, using a novel semi-quantitative technique. Cortical dysfunction was measured using electroencephalography (EEG), and localised using standardised low-resolution brain electromagnetic tomography (sLORETA). RESULTS: Spectral EEG analyses revealed significant slowing in patients with TBI, with no significant differences between patients with epilepsy and those without. Although bMRI revealed that patients with PTE were more likely to present with intracortical lesions (p = 0.02), no differences in the size of the lesion were found between the groups (p = 0.19). Increased BBB permeability was found in 76.9% of patients with PTE compared with 33.3% of patients without epilepsy (p = 0.047), and could be observed years following the trauma. Cerebral cortex volume with BBB disruption was larger in patients with PTE (p = 0.001). In 70% of patients, slow (delta band) activity was co-localised, by sLORETA, with regions showing BBB disruption. CONCLUSIONS: Lasting BBB pathology is common in patients with mild TBI, with increased frequency and extent being observed in patients with PTE. A correlation between disrupted BBB and abnormal neuronal activity is suggested.

Blood-brain barrier disruption results in delayed functional and structural alterations in the rat neocortex.

Disruption of the blood-brain barrier (BBB) is a characteristic finding in common neurological disorders. Human data suggest BBB disruption may underlie cerebral dysfunction. Animal experiments show the development of epileptiform activity following BBB breakdown. In the present study we investigated the neurophysiological, structural and functional consequences of BBB disruption. Adult rats underwent focal BBB disruption in the rat sensory-motor cortex using the bile salt sodium deoxycholate (DOC). Magnetic resonance imaging in-vivo showed an early BBB disruption with delayed reduction in cortical volume. This was associated with a reduced number of neurons and an increased number of astrocytes. In-vitro experiments showed that the threshold for spreading depression and the propagation velocity of the evoked epileptic potentials were increased 1 month after treatment. Furthermore, animals' motor functions deteriorated during the first few weeks following BBB disruption. Treatment with serum albumin resulted in a similar cell loss confirming that the effect of DOC was due to opening of the BBB. Our findings suggest that delayed neurodegeneration and functional impairment occur following the development of the epileptic focus in the BBB-permeable cerebral cortex.

Opening of the blood-brain barrier preceding cortical edema in a severe attack of FHM type II.

The authors report a patient with familial hemiplegic migraine type II who developed a long-lasting attack including fever, right-sided hemiplegia, aphasia, and coma. Quantitative analysis of early gadolinium-enhanced MRI revealed a mild but significant left-hemispheric blood-brain barrier (BBB) opening limited to the cortex and preceding cortical edema. The findings suggest that the delayed cortical edema was vasogenic in the severe migraine aura variant of this ATP1A2 mutation carrier.

Frequent blood-brain barrier disruption in the human cerebral cortex.

1. The blood-brain barrier (BBB) protects the brain from circulating xenobiotic agents. The pathophysiology, time span, spatial pattern, and pathophysiological consequences of BBB disruptions are not known. 2. Here, we report the quantification of BBB disruption by measuring enhancement levels in computerized tomography brain images. 3. Pathological diffuse enhancement associated with elevated albumin levels in the cerebrospinal fluid (CSF) was observed in the cerebral cortex of 28 out of 43 patients, but not in controls. Four patients displayed weeks-long focal BBB impairment. In 19 other patients, BBB disruption was significantly associated with elevated blood pressure, body temperature, serum cortisol, and stress-associated CSF 'readthrough" acetylcholinesterase. Multielectrode electroencephalography revealed enhanced slow-wave activities in areas of focal BBB disruption. Thus, quantification of BBB disruption using minimally invasive procedures, demonstrated correlations with molecular, clinical, and physiological stress-associated indices. 4. These sequelae accompany a wide range of neurological disorders, suggesting that persistent, detrimental BBB disruption is considerably more frequent than previously assumed.