Brain lesion studies

The stimulation method could not address the role of the elaboration areas and the study of brain damaged patients or lesion studies of animals is hampered by the lack of temporal resolution. What is needed for another wave of reverse engineering, then, is the ability to stimulate the brain while it is doing something, or to be able to reversibly disrupt its functioning to give the lesion method a temporal dimension. The story of how we are able to achieve both of these takes us back to Faraday.. . . ... 

Surgery followed by whole-brain radiotherapy (WBRT) is best indicated for patients with an accessible single brain lesion and controlled or limited systemic MM.62 Two randomized studies reported improved survival in patients treated with combination surgery and WBRT compared with WBRT alone.62,63 For those patients with multiple metastatic brain... 

NIOSH (1976) reviewed and summarized animal studies prior to 1976. Many of those studies are deficient in descriptions of exposure and analytical techniques as well as exposure concentrations and durations. Considerations of most of those pre-1976 studies are not reviewed here. Several of those earlier studies describe brain lesions in exposed animals. Histopathological examinations were performed in only a few of the studies conducted after 1976. 

Before this topic is left behind, it should be noted that statistical significance is by no means the only consideration in interpretation of toxicity test results. If, in our particular case, the pathologist were to inform us that the brain lesion observed was extremely unusual or rare, we should certainly hesitate to dismiss our concerns because of lack of statistical significance. The toxicologist needs equally to understand biological significance, and, in this case, would almost certainly pursue other lines of investigation (perhaps an ADME study to determine if the pesticide reaches the brain, or a toxicity test in other species) to determine whether the effect was truly caused by the chemical. 

Multiple sclerosis (MS) is a devastating disease of the CNS that produces demyelination and inflammation. It is believed that its pathogenesis involves an immune reaction against various components of the myelin sheath. In a study by Lock et al. (2002), the gene expression patterns of brain lesions obtained during autopsies of MS patients were examined by microarray cluster analysis. A total of 1080 genes (from 7026 represented... 

Speciai risk Seizures, irrespective of drug relationship, occurred in 0.5% of patients during study therapy plus 14-day follow-up period. These experiences have occurred most commonly in patients with CNS disorders (eg, brain lesions or history of seizures) or compromised renal function. 

N.J. McDannold, N.l. Vykhodtseva, K. Hynynen, Microbubble contrast agent with focused ultrasound to create brain lesion at low power levels MR imaging and histologic study in rabbits, Radiology 241 (2006) 95-106. 

The recent addition of interferon-P-la and interferon-pib to the therapeutic arsenal for the treatment of MS aims to shut down inflammation at the blood-brain barrier and thereby reduce the rate of relapse and decrease frequency and severity of MS disease symptoms.Both P-interferons have demonstrated benefits in the treatment of patients with established MS, including slowing the progression of physical disability, reducing the rate of clinical relapses, and reducing the development of brain lesions, as assessed by MRI. Several trials have found that interferon-pib (Betaseron) reduced the frequency of relapse by approximately 30% [3-5]. These studies also suggested a trend toward a delay in the progression of disability. Interferon-pia (Avonex) was subsequently found to reduce the frequency of relapse [6-8]. 

Brain lesions that produce depression can be divided into structural and biochemical types. Any disease that produces a mass lesion or deficit in the frontal lobes can cause a depressive syndrome. Typically, occurrence and severity are correlated with proximity to the tip of the frontal lobe rather than to the extent of motor function loss. The most extensively studied lesions are strokes, but tumors and plaques related to multiple sclerosis can both produce similar results. 

A CT scan or MRI of the brain following a strokelike episode reveals a lucency (an area of luminosity) that is consistent with infarction. Later, cerebral atrophy and calcifications may be observed on brain imaging studies. The vascular territories of focal brain lesions and the prior medical history of these patients differ substantially from those of typical patients with stroke. Serial MRI studies often demonstrate lesion resolution, differentiating these lesions from typical ischemic strokes. An electroencephalogram is often performed when seizures are a concern. This is especially necessary in MELAS since patients occasionally have intractable status epilepticus as a terminal condition. Mental deterioration usually progresses after repeated episodic attacks. Psychiatric abnormalities (e.g., altered mental status, schizophrenia) may accompany the strokelike episodes. The encephalopathy may progress to... 

A systematic review of observational studies of post-stroke depression produced an estimated overall prevalence of 33% among all stroke survivors (Hackett et al. 2005). Predictors of depression include severity of stroke and cognitive impairment (Hackett and Andersen 2005). It has been postulated that left-sided brain lesions are more likely to cause depression, but this remains unproven (Bhogal et al. 2004). Mood disorder may impede rehabilitation and contribute to disability and handicap but usually improves with time. Treatment includes support and counseling and antidepressants. 

Prior to the era of in vivo brain functional imaging, this was based on human and animal lesion studies, with remarkable foresight. Spatial orientation deficits (Teuber and Proctor, 1964) are thought to reflect deficits of the posterior cortices and set-shifting impairment has been thought to reflect mostly frontal functions (Taylor et al., 1986). 

---