Characteristics of Blood- Brain Barrier Permeability in Neurological Patients
Characteristics of Blood- Brain Barrier Permeability in Neurological Patients
The main goal of the present study is to challenge the hypothesis that blood- brain barrier
 disruption following brain injury increases the risk for long-term disability, development of
 brain dysfunction, epileptic seizures and neuroanatomical alterations.
Traumatic brain injury (TBI) is one of the most common traumatic events, occurring in
 approximately 200 per 100,000, and is a known risk factor for later development of epileptic
 seizures. This occurs in up to 17% of TBI patients, and accounts for approximately 20% of
 symptomatic epilepsies (Annegers, JF. et al, 1998). Typically, post-traumatic epilepsy (PTE)
 develops or several weeks but even years after the event. PTE is often chronic and poorly
 controlled pharmacologically. Although several factors have been attributed to an increased
 risk of developing PTE (e.g. severity of trauma, type of brain injury, time to the appearance
 of first seizure), the mechanisms underlying it remain unknown. Similar to TBI, ischemic
 injuries, most frequently occurring in the elderly population are the main cause of new onset
 epilepsy in this age group. It is still not known what are the risk factors and mechanisms
 underlying post-ischemic epilepsy.

 Under normal conditions the central nervous system is protected by the operation of the
 blood- brain barrier (BBB). Following brain injury (either traumatic or ischemic) the BBB is
 known to disrupt, leading to focal edema and altered extracellular composition. We have
 recently established methods for quantitative evaluation of the integrity of the BBB using
 magnetic resonance imaging (MRI) brain scans. Using these methods we are able to identify BBB
 disruption in patients suffering from various pathologies (Tomkins, O. et al. 2001; Avivi, E.
 et al. 2004). Such altered permeability may last up to years following the acute event and
 was found to correlate to areas of abnormal neurological function (Korn, A. et al. 2005)

 In recent work using an animal model, we have shown that following focal disruption of the
 BBB a focus of epileptiform activity is generated within several days. Such pathological
 activity remains for several weeks, long after the BBB has retained its former function
 (Seiffert, E. et al. 2004; Iven, S. et al. 2006). Furthermore, this condition may later lead
 to anatomical alterations as seen by brain MRI scans, as well as in histological sections.
 Such animals further suffer from functional deterioration and neuronal degeneration in the
 disrupted region (Tomkins, O. et al. 2006).

 In this work we will test the hypothesis that BBB disruption following brain injury increases
 the risk for long-term disability, development of brain dysfunction, epileptic seizures and
 neuroanatomical alterations. For that we will combine a prospective and retrospective study
 in patients following cerebral cortical injury (traumatic, hemorrhagic or ischemic).
 Clinical, functional and anatomical measures will be obtained in addition to BBB permeability
 measures.
Inclusion Criteria:

 -  One week following:

 -  Traumatic Brain Injury

 -  Cerebro- Vascular Accident

 -  Subsequent brain CT showed cerebral cortex injury.

 Exclusion Criteria:

 -  A known ailment of the central nervous system.

 -  Use of medications or illicit drugs that significantly affect the central nervous
 system.

 -  tourist or temporary residents not available for follow-up.

 -  For MRI examinations: heart pacemaker, metal implants, or metal shrapnel.