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Antiangiogenic therapy can rapidly reduce vascular permeability and cerebral edema but high doses of bevacizumab may induce selective pressure to promote resistance. This trial evaluated the efficacy of low dose bevacizumab in combination with lomustine (CCNU) compared to standard dose bevacizumab in patients with recurrent glioblastoma. Patients (N = 71) with recurrent glioblastoma who previously received radiation and temozolomide were randomly assigned 1:1 to receive bevacizumab monotherapy (10 mg/kg) or low dose bevacizumab (5 mg/kg) in combination with lomustine (90 mg/m(2)). The primary end point was progression-free survival (PFS) based on a blinded, independent radiographic assessment of post-contrast T1-weighted and non-contrast T2/FLAIR weighted magnetic resonance imaging (MRI) using RANO criteria. For 69 evaluable patients, median PFS was not significantly longer in the low dose bevacizumab + lomustine arm (4.34 months, CI 2.96-8.34) compared to the bevacizumab alone arm (4.11 months, CI 2.69-5.55, p = 0.19). In patients with first recurrence, there was a trend towards longer median PFS time in the low dose bevacizumab + lomustine arm (4.96 months, CI 4.17-13.44) compared to the bevacizumab alone arm (3.22 months CI 2.5-6.01, p = 0.08). The combination of low dose bevacizumab plus lomustine was not superior to standard dose bevacizumab in patients with recurrent glioblastoma. Although the study was not designed to exclusively evaluate patients at first recurrence, a strong trend towards improved PFS was seen in that subgroup for the combination of low dose bevacizumab plus lomustine. Further studies are needed to better identify such subgroups that may most benefit from the combination treatment.

Imaging has become a central part of the evaluation of lesions of the central nervous system. Despite patterns of the appearances of several types of central nervous system malignancies and improving resolution of imaging techniques, there are other processes that can display similar characteristics. Time and again, vascular, inflammatory, and vascular lesions will mimic a neoplastic process, requiring tissue diagnosis. With the introduction of advanced magnetic resonance imaging (MRI) and positron emission tomography (PET) imaging in the evaluation of the brain tumor, there has been improvement in determining whether a lesion is neoplastic, and further advances may lead to noninvasive pathological and molecular diagnoses.

Neuropathic pain, a form of chronic pain caused by injury to or disease of the peripheral or central nervous system, is a formidable therapeutic challenge to clinicians because it does not respond well to traditional pain therapies. Our knowledge about the pathogenesis of neuropathic pain has grown significantly over last 2 decades. Basic research with animal and human models of neuropathic pain has shown that a number of pathophysiological and biochemical changes take place in the nervous system as a result of an insult. This property of the nervous system to adapt morphologically and functionally to external stimuli is known as neuroplasticity and plays a crucial role in the onset and maintenance of pain symptoms. Many similarities between the pathophysiological phenomena observed in some epilepsy models and in neuropathic pain models justify the rational for use of anticonvulsant drugs in the symptomatic management of neuropathic pain disorders. Carbamazepine, the first anticonvulsant studied in clinical trials, probably alleviates pain by decreasing conductance in Na+ channels and inhibiting ectopic discharges. Results from clinical trials have been positive in the treatment of trigeminal neuralgia, painful diabetic neuropathy and postherpetic neuralgia. The availability of newer anticonvulsants tested in higher quality clinical trials has marked a new era in the treatment of neuropathic pain. Gabapentin has the most clearly demonstrated analgesic effect for the treatment of neuropathic pain, specifically for treatment of painful diabetic neuropathy and postherpetic neuralgia. Based on the positive results of these studies and its favourable adverse effect profile, gabapentin should be considered the first choice of therapy for neuropathic pain. Evidence for the efficacy of phenytoin as an antinociceptive agent is, at best, weak to modest. Lamotrigine has good potential to modulate and control neuropathic pain, as shown in 2 controlled clinical trials, although another randomised trial showed no effect. There is potential for phenobarbital, clonazepam, valproic acid, topiramate, pregabalin and tiagabine to have antihyperalgesic and antinociceptive activities based on result in animal models of neuropathic pain, but the efficacy of these drugs in the treatment of human neuropathic pain has not yet been fully determined in clinical trials. The role of anticonvulsant drugs in the treatment of neuropathic pain is evolving and has been clearly demonstrated with gabapentin and carbamazepine. Further advances in our understanding of the mechanisms underlying neuropathic pain syndromes and well-designed clinical trials should further the opportunities to establish the role of anticonvulsants in the treatment of neuropathic pain.

This study estimated the frequency of nine primitive reflexes (PR) and assessed their possible clinical value in a group of patients with acquired immunodeficiency syndrome. We studied 78 patients with human inmunodeficiency type 1 (HIV-1) infection in WHO clinical stage 3 or 4 and 81 matched seronegative controls. All participants were examined using a standardized neurological examination and the Mini-Mental State Examination. Cognitive impairment and PR was found in 36% of patients but in none of the controls (P < 0.0001; logistic regression odds ratio: 14.7). Overall, PR were 2–36 times more frequent in patients with HIV-1 infection. This association was stronger for the glabellar, snout, Rossolimo, and digital signs. At least two PR were observed in 92% of patients vs. 8% of controls (P < 0.0001; 95% confidence interval: 68%–100%; logistic regression odds ratio: 10.8). These data support the association of PR with cognitive decline in patients with advanced HIV-1 infection without overt neurological disease. Larger follow-up studies with multivariate techniques are needed to identify which PRs are useful as indicators of HIV-1-associated cognitive/motor complex and minor neurocognitive disorders.