Memantine as adjunctive therapy in children diagnosed with autistic spectrum disorders: an observation of initial clinical response and maintenance tolerability.

Autism and Pervasive Developmental Disorder Not Otherwise Specified are common developmental problems often seen by child neurologists. There are currently no cures for these lifelong and socially impairing conditions that affect core domains of human behavior such as language, social interaction, and social awareness. The etiology may be multifactorial and may include autoimmune, genetic, neuroanatomic, and possibly excessive glutaminergic mechanisms. Because memantine is a moderate affinity antagonist of the N-methylD-aspartic acid (NMDA) glutamate receptor, this drug was hypothesized to potentially modulate learning, block excessive glutamate effects that can include neuroinflammatory activity, and influence neuroglial activity in autism and Pervasive Developmental Disorder Not Otherwise Specified. Open-label add-on therapy was offered to 151 patients with prior diagnoses of autism or Pervasive Developmental Disorder Not Otherwise Specified over a 21-month period. To generate a clinician-derived Clinical Global Impression Improvement score for language, behavior, and self-stimulatory behaviors, the primary author observed the subjects and questioned their caretakers within 4 to 8 weeks of the initiation of therapy. Chronic maintenance therapy with the drug was continued if there were no negative side effects. Results showed significant improvements in open-label use for language function, social behavior, and self-stimulatory behaviors, although self-stimulatory behaviors comparatively improved to a lesser degree. Chronic use so far appears to have no serious side effects.

Elevation of tumor necrosis factor-alpha in cerebrospinal fluid of autistic children.

Recent reports implicating elevated cytokines in the central nervous system in a small number of patients studied with autism have reported clinical regression. These studies have not focused on tumor necrosis factor-alpha as a possible marker for inflammatory damage. A series of 10 children with autism had clinical evaluation of their serum and spinal fluid for inflammatory changes and possible metabolic disease as part of their neurological evaluation. Elevation of cerebrospinal fluid levels of tumor necrosis factor-alpha was significantly higher (mean = 104.10 pg/mL) than concurrent serum levels (mean = 2.78 pg/mL) in all of the patients studied. The ratio of the cerebrospinal fluid levels to serum levels averaged 53.7:1. This ratio is significantly higher than the elevations reported for other pathological states for which cerebrospinal fluid and serum tumor necrosis factor-alpha levels have been simultaneously measured. This observation may offer a unique insight into central nervous system inflammatory mechanisms that may contribute to the onset of autism and may serve as a potential clinical marker. More controlled study of this potentially important observation may prove valuable.

Curcumin inhibits dose-dependently and time-dependently neuroglial cell proliferation and growth.

OBJECTIVES: Curcumin (CUR), the active chemical of the Asian spice turmeric, has strong anti-oxidant and anti-inflammatory properties. CUR inhibits proliferation and growth of several cell types, e.g. cancer cells. While CUR inhibitory effects on microglial cells are demonstrated, little is known of its effects on neuroglia, astrocytes (AST) and oligodendrocytes (OLG). Our work focuses on CUR's effects on neuroglial proliferation and growth in vitro, utilizing C-6 rat glioma 2B-clone cells, a mixed colony of both neuroglial cells, in 6 day trials. METHODS: The doses studied included 4, 5, 10, 15, and 20 microM - concentrations slightly smaller than those shown to stimulate protein expression in ASTs. Automated particle counter was used to determine proliferation, and marker enzyme assays were used to determine AST and OLG activity. RESULTS: CUR inhibited neuroglial proliferation, with the degree of inhibition correlated directly with the CUR concentration. Proliferative inhibition was observed after a concentration as low as 5 microM by day 6, while inhibition of 20 microM doses occurred by day 2 of culture. Proliferative inhibition is associated with morphological changes, e.g. cell elongation and neurite prolongation, and increased activity of a marker enzyme corresponding to differentiation of OLG and with a reduced activity of the marker enzyme for AST. CONCLUSIONS: Our data suggests CUR acts continuously over a period of time, with low doses being as effective as higher doses given a longer period of treatment. It has been suggested that CUR's anti-inflammatory and anti-oxidant actions may be useful in the prevention-treatment of neurodegenerative diseases, e.g. Alzheimer's and Parkinson's Diseases. Given neuroglial involvement in these diseases, and CUR's observed actions on neuroglia, the data presented here may provide further explanations of CUR's preventative-therapeutic role in these diseases.

Quality of life assessment in interventional radiology.

The aim of this review was to describe quality of life (QoL) questionnaires relevant to interventional radiology. Interventional radiologists perform a large number of palliative procedures. The effect of these therapies on QoL is important. This is particularly true for cancer therapies where procedures with marginal survival benefits may result in tremendous QoL benefits. Image-guided minimally invasive procedures should be compared to invasive procedures, with respect to QoL, as part of comparative effectiveness assessment. A large number of questionnaires have been validated for measurement of overall and disease-specific quality of life. Use of applicable QoL assessments can aid in evaluating clinical outcomes and help to further substantiate the need for minimally invasive image-guided procedures.

The value of cervical magnetic resonance imaging in the evaluation of the obtunded or comatose patient with cervical trauma, no other abnormal neurological findings, and a normal cervical computed tomography.

BACKGROUND: The value of magnetic resonance imaging (MRI) in the evaluation of the obtunded or comatose patient with a potential neck injury is a controversial subject. Some authors have suggested that MRI of the cervical spine adds no value in the evaluation of patients with a normal computed tomography (CT) of the neck. However, others have suggested that MRI is the gold standard for clearing the cervical spine in a clinically suspicious or unevaluatable blunt trauma patient. The purpose of this study is to evaluate our data in regard to these conflicting hypotheses. METHODS: Five consecutive years of data from 17,000 patients seen at our Level I trauma center yielded 512 individuals who underwent both CT and MRI of the cervical spine. Of the latter group, 150 individuals met three strict inclusion criteria for this study: (1) obtundation (Glasgow Coma Scale ≤13, with 94 of this group comatose [Glasgow Coma Scale ≤8]); (2) no obvious neurologic deficits; and (3) a normal cervical CT. The effect of MRI on the clinical management of these patients was evaluated. RESULTS: Among the 150 obtunded or comatose patients with a negative CT, the majority (51%) had a normal MRI. Among the patients with a positive MRI, the most common MRI-positive findings were ligamentous and soft tissue injury (81%). However, no MRI findings were deemed unstable, and no surgical intervention or change in the clinical management aside from collar immobilization of these individuals occurred after MRI. CONCLUSIONS: The addition of a cervical MRI to the evaluation protocol of obtunded or comatose patients with an otherwise normal neurologic examination and a normal cervical CT did not provide any additional useful information to change the management of these patients.

Multidisciplinary management of blunt pelvic trauma.

Pelvic fractures account for ∼3% of all fractures and usually occur in patients with polytrauma. Pelvic fractures usually indicate high energy transfer and a significant mechanism of injury, and they can involve massive hemorrhage. For this reason, mortality from pelvic trauma is high, ranging from 40% to 60% among patients in shock, and up to 90% in patients considered to be in extremis. Multidisciplinary approaches in the treatment of patients with pelvic fractures have resulted in improved outcomes for these complex and challenging injuries. In this article, we describe a case of a pediatric patient who suffered severe pelvic fracture with massive hemorrhage, requiring a multidisciplinary approach for control of hemorrhage and definitive repair of injuries.

Bullet embolization: multidisciplinary approach by interventional radiology and surgery.

Bullet embolization after penetrating trauma is an infrequent but important phenomenon. It presents an unexpected sequelae to the otherwise predictable injury pattern of penetrating missile injury mechanism and poses a challenging diagnostic and therapeutic dilemma. Bullets from penetrating wounds can gain access to the vasculature and migrate to nearly every large vascular bed. Patients can be asymptomatic, but the potential complications can be devastating including limb-threatening ischemia, sepsis, endocarditis, cardiac valvular incompetence, pulmonary embolism, stroke, and even death. The exact incidence of bullet embolization is unknown, but it was estimated to be 0.3% during the Vietnam War and 1.1% in the recent conflict in Afghanistan and Iraq. The scarcity of the condition and the lack of concentrated experience at any single institution contribute to the controversies pertaining to the management approach. Traditionally, surgical extraction of embolized bullets may involve difficult and invasive surgical exposures. Recent advancement in endovascular techniques provides an additional option in this treatment algorithm. In this article, we describe a case of venous bullet embolization from the left iliac vein treated by a combined endovascular and surgical approach.

Transcatheter treatment of liver laceration from blunt trauma.

Blunt hepatic trauma is a fairly common pathology seen in trauma centers. We describe a pediatric patient who suffered blunt hepatic trauma that was managed successfully with a combination of exploratory laparotomy and liver packing, followed by hepatic artery embolization by interventional radiology (IR) after he continued to have significant arterial extravasation. Also discussed are trends in overall blunt hepatic trauma management and the technique of IR management.

Computed tomography and magnetic resonance imaging of a basilar artery herniation into the sphenoid sinus.

We report a rare case of herniation of a basilar artery into the sphenoid sinus after a traumatic skull base fracture. Computed tomographic angiography, magnetic resonance imaging, and cerebral angiogram demonstrated patency of the basilar artery through the fractured clivus at the time of injury, a very rare occurrence. The following day, the patient developed pontine and cerebellar infarcts. In a patient with clival fracture, we advocate fast assessment of vertebrobasilar system with CTA and early anticoagulation treatment in those with vascular entrapment.