Neuroimaging of toxic and metabolic disorders.

Imaging of the brain, magnetic resonance imaging (MRI) in particular, is a key adjunctive tool in the diagnosis and management of toxic-metabolic disorders such as alcoholism, mitochondrial encephalopathies, disorders of iron or copper metabolism, exposure to carbon monoxide, radiotherapy, immunosuppressive agents, toluene, and recreational drugs. In this article, we review the neuroimaging findings of common toxic and metabolic disorders focusing on the role of conventional MRI. We also consider advanced imaging methods, such as magnetic resonance spectroscopy, diffusion MRI, and positron emission tomography. We hope this article will prove useful to trainees and practitioners in the clinical and imaging fields of the neurosciences.

The allegory of a mountain: an environmental introduction to neurotoxicology.

Overall, the area of human neurotoxicity offers significant difficulties as well as challenges in our attempts to maintain or enhance human well being. Many of the substances to which humans are being exposed are relatively new to the environment, i.e., the products of a sophisticated industrial development. As a result humans are exposed to volatile organic compounds not previously present in our environment in significant amounts. It is important to maintain our industrial complex and the economic growth of our society. The use of volatile organic compounds is often important to the success of the industry. However, it is also important for us to determine what concentration of a given substance may produce short-term effects or chronic long-term effects. Human exposure to these potentially toxic levels could then be prevented. This is especially true because once irreversible damage occurs there is no medical treatment that can lead to improvement. Therefore, prevention of neurotoxic injury is essential.

Carbon monoxide intoxication: an updated review.

Carbon monoxide (CO), a highly toxic gas produced by incomplete combustion of hydrocarbons, is a relatively common cause of human injury. Human toxicity is often overlooked because CO is tasteless and odorless and its clinical symptoms and signs are non specific. The brain and the heart may be severely affected after CO exposure with carboxyhemoglobin (COHb) levels exceeding 20%. Damage occurs because the affinity of hemoglobin for CO is 210 times higher than for O(2). Hypoxic brain damage predominates in the cerebral cortex, cerebral white matter and basal ganglia, especially in the globus pallidus. Diagnosis requires clinical acumen and a high index of suspicion, combined with epidemiological data, clinical examination, analysis of ambient air CO and patient COHb levels; also required are cardiology evaluation including ECG as well as neurological evaluation including brain imaging (CT and/or MRI, MR spectroscopy), and neuropsychological testing. Although immediate O(2) breathing is sometimes an adequate treatment, hyperbaric oxygen therapy (HBO) is favored. Subsequently, only symptomatic therapy is available for the long-term sequelae of CO poisoning.

Weapons of mass destruction: Overview of the CBRNEs (Chemical, Biological, Radiological, Nuclear, and Explosives).

The events of September 11, 2001, made citizens of the world acutely aware of disasters consequent to present-day terrorism. This is a war being waged for reasons obscure to many of its potential victims. The term "NBCs" was coined in reference to terrorist weapons of mass destruction, i.e., nuclear, biological and chemical. The currently accepted acronym is "CBRNE" which includes Chemical, Biological, Radiological, Nuclear, and Explosive weapons. Non-nuclear explosives are the most common terrorist weapon now in use. Nuclear and radiological weapons are beyond the scope of this publication, which focuses on the "CBEs", i.e. chemical, biological and explosive weapons. Although neurologists will not be the first responders to CBEs, they must know about the neurological effects in order to provide diagnosis and treatment to survivors. Neurological complications of chemical, biological and explosive weapons which have or may be used by terrorists are reviewed by international experts in this publication. Management and treatment profiles are outlined.

Carbon monoxide brain toxicity: clinical, magnetic resonance imaging, magnetic resonance spectroscopy, and neuropsychological effects in 9 people.

Carbon monoxide (CO) exposure is a common cause of toxic brain damage, whereby effects range from transient neurological dysfunction to coma and death. A spectrum of severity of magnetic resonance imaging (MRI) findings after CO brain toxicity, including globus pallidus and white matter lesions, is well documented. Reports of MR spectroscopy (MRS) findings re main sparse. This article reports 9 people exposed to CO because of an apartment house's faulty gas heater. Four, with transient loss of consciousness after chronic moderate level CO exposure, suffered intellectual impairment without MRI abnormalities. The MRS of 1 individual demonstrated decreased n-acetyl aspartase in the basal ganglia, bilaterally. Of 5 exposed to high levels for about 12 hours, 1 died prior to clinical and/or MRI evaluation. One who suffered coma recovered but was lost to evaluation. Three, who were unconscious for hours to days, exhibited T2 MRI white matter signal abnormalities. MRS showed decreased basal ganglia n-acetyl aspartase in 2. One of these suffers a Parkinsonian syndrome. All 3 are intellectually impaired. This study demonstrates that although MRI and MRS are useful markers of CO-induced brain damage, they are not always sensitive to resultant intellectual dysfunction.

The therapeutic effects of epidural intercellular adhesion molecule-1 monoclonal antibody in a rabbit model: involvement of the intercellular adhesion molecule-1 pathway in spinal cord ischemia.

The pathophysiology of ischemia/reperfusion injury involves extravascular migration of leukocytes from the bloodstream to the site of injury. Leukocyte adhesion and intercellular adhesion molecule-1 (ICAM-1) play an important role in the recruitment of leukocytes to the site of injury. In this study, we evaluated the role of the ICAM-1 in spinal cord ischemia and the therapeutic effects of epidural ICAM-1 monoclonal antibody (Mab). The descending aorta was occluded below the renal artery with an aneurysm clip in rabbits anesthetized with halothane. The following variables were evaluated, in addition to ICAM-1 expression in the lumbar spinal cord, in animals receiving saline or ICAM-1 Mab via the epidural route: (1) leukocyte recruitment in the lumen of capillary vessels of the lumbar spinal cord (L6-7) at 8 h after 30 min of aortic occlusion and (2) neurological evaluation at 20 h after aortic occlusion of 10, 15, 17.5, 20, or 25 min. Paraplegia was graded with the following scale: Grade 0, no deficit; Grade 1, partial deficit; and Grade 2, complete paraplegia. Spinal cord ischemia increased the expression of ICAM-1 in the endothelium of spinal cord capillaries and led to capillary leukocyte recruitment and extravascular migration into the lumbar spinal cord parenchyma, which was ablated with epidural ICAM-1 Mab. Epidural ICAM-1 Mab reduced neurological deficits and offered neuroprotection. These findings demonstrate the involvement of the ICAM-1 pathway in spinal cord ischemia and the neuroprotective effects of epidural ICAM-1 Mab. Strategies to ameliorate spinal cord ischemia may entail the administration of leukocyte antiadhesion molecules into the neuraxial space.

Acute experimental allergic encephalomyelitis increases lumbar spinal cord incorporation of epidurally administered [(3)H]-D-mannitol and [(14)C]-carboxyl-inulin in rabbits.

UNLABELLED: We sought to determine whether acute experimental allergic encephalomyelitis (EAE) alters the incorporation of epidurally administered [(3)H]-D-mannitol and [(14)C]-carboxyl-inulin into the lumbar spinal cord in rabbits. Acute EAE is an experimental model for demyelinating spinal cord diseases such as multiple sclerosis. It was induced in rabbits by footpad inoculation with rabbit spinal cord homogenate, resulting in hind limb paresis or paralysis. Animals were classified into four study groups: Control, Paraparesis, 1-Day Paraplegia, and 5-Day Paraplegia. Ten microCi each of [(3)H]-D-mannitol and [(14)C]-carboxyl-inulin were administered epidurally for 90 min. After infusion, animals were perfused with saline. The lumbar cord was dissected and divided into 11 segments. Compared with other groups, animals in the 5-Day Paraplegia group had greater incorporation of [(3)H]-D-mannitol and [(14)C]-carboxyl-inulin in lumbar segment 8, corresponding to the location of the epidural catheter tip. Compared with the Control group, EAE animals had increased [(3)H]-D-mannitol incorporation in various lumbar segments. Increases in the spinal cord incorporation of epidural drugs with EAE suggest that demyelination may render the spinal cord susceptible to larger amounts of substances administered in the epidural space. These findings may have implications regarding neurotoxicity in association with demyelinating spinal cord disease. IMPLICATIONS: Acute experimental allergic encephalomyelitis, a disease model for multiple sclerosis, increased spinal cord incorporation of radioactive drugs administered in the epidural space. We conclude that demyelinating disease processes may expose the spinal cord to larger amounts of substances administered neuraxially.