John C.M. Brust

Selective proprioceptive loss from a thalamic lacunar stroke

In an elderly woman a small thalamic infarct, documented by computed tomography and nuclear magnetic resonance imaging, caused proprioceptive loss contralaterally without impairment of other sensory modalities. This patient, the first so reported, demonstrates the anatomic separation of spinothalamic and dorsal column/medial lemniscus sensory modalities in the human thalamus.

Embolic stroke after smoking "crack" cocaine.

A 39-year-old woman had an embolic upper division middle cerebral artery branch occlusion 3 hours after smoking the free base of cocaine (crack). Radionuclide ventriculography demonstrated cardiomyopathy, and echocardiography documented a left atrial thrombus. This case demonstrates that embolism is one mechanism of ischemic stroke after cocaine use, and that cardiomyopathy, possibly cocaine induced, may be the source of embolus. A cardiac source of embolus should be sought in patients with cocaine-associated cerebral infarction.

Editorial Comment—Over-the-Counter Cold Remedies and Stroke

For decades a number of sympathomimetic drugs have been marketed as over-the-counter diet pills, decongestants, or both. During the 1980s and 1990s one of these, phenylpropanolamine (PPA), accounted for an estimated 5 billion doses annually in the United States. In humans PPA produces arousal; unlike amphetamine it does not produce euphoria. It is a recognized street drug, however, sometimes misrepresented as amphetamine (“look-alike pills”), and by mail order it has been available as a “legal stimulant.”1nnComplications of PPA include acute hypertension, psychosis, seizures, and stroke, especially hemorrhagic. More than 30 case reports describe intracerebral or subarachnoid hemorrhage following either recommended or excessive dosage. Proposed mechanisms include surges of hypertension, cerebral vasospasm (sometimes evident at angiography), and vasculitis (in one case evident at leptomeningeal biopsy).2 In 2000 Kernan and coworkers reported results of a multicenter case-control study addressing the association of …

A pilot study of the end point verification system in the asymptomatic carotid atherosclerosis study

Ipsilateral transient ischemic attack (TIA) and cerebral infarction (CI) are primary end points of the Asymptomatic Carotid Atherosclerosis Study (ACAS), an ongoing multicenter, prospective, randomized trial designed to assess the effectiveness of carotid endarterectomy for patients with asymptomatic, hemodynamically significant stenosis of the internal or common carotid artery. The evanescent nature and absence of residual physical findings in TIAs pose special difficulties that contribute to interobserver disagreement. A standardized definition was established to be applied accurately and uniformly at the participating centers, including a questionnaire on six cardinal neurological symptoms, a computerized algorithm for characterization of events, and a verification system involving the independent evaluations of three reviewers. Modifications to the end point verification protocol after pilot testing in 115 patients with one or more symptoms enabled the algorithm to distinguish vascular from nonvascular events with a sensitivity of 83%, a specificity of 69%, positive predictive value of 71%, and negative predictive value of 82%. ACAS has developed a system for detecting and diagnosing end points. Using the algorithm as a guideline, consensus between two institutional physicians and a blinded independent reviewer must be made for an end point to be declared. If no consensus can be reached, a panel of two blinded external reviewers confers to arrive at an adjudication of the case. All potential end points are reviewed retrospectively by an end points committee for final adjudication.

Chapter 59 – Acute Intoxications

Publisher Summary nThis chapter presents a discussion on acute intoxications. The chapter mentions that any patient with unexplained nonfocal neurological symptoms may suffer from an acute intoxication. A high proportion of head injury victims are intoxicated, usually with ethanol and illicit drugs. A history of drug abuse, a psychiatric disorder, or a recent adverse life event can precede intentional overdose. Circumstantial evidence may point to drug overdose. Most toxic substances lead to obtundation or coma when taken in high doses. Other neurological and computed tomography (CT) signs can narrow the differential diagnosis. Acute death after intoxication is most often caused by apnea, pulmonary edema, heart failure, or severe cardiac arrhythmia. The initial treatment of the poison victim aims at the stabilization of cardiopulmonary function and on the prevention of irreversible organ failure. The vulnerability of the brain to even short interruptions of energy metabolism must always be considered. The discussion on practical management of specific intoxications includes analgesics—such as— acetaminophen and salicylates, anticonvulsants, antidepressants, sedative-hypnotics, drugs of abuse, and others.

Chapter 51 – Seizures and Commonly Prescribed Drugs

Publisher Summary This chapter presents various aspects of seizures and commonly prescribed drugs. Various combinations of seizures, myoclonus, psychosis, and delirium have been reported with a number of cephalosporins, including cephaloridine, cephalothin, cephazolin, cefonicid, cephalexin, cefmetazole, cephacetrile, cefotaxime, cephoroxime, and latamoxef. Myoclonus, seizures, and altered mentation have also been associated with imipenem/cilastatin, in both animals and humans. The neurotoxicity of the beta-lactam agents is dose-related and correlates with high blood concentrations and increased permeability of the blood-brain barrier (BBB). It is suggested that cerebrospinal fluid drug concentrations may not reflect actual brain concentrations and these drugs enter the brain directly from the blood. The pathogenesis of beta-lactam neurotoxicity may be related to γ-aminobutyric acid (GABA) receptors. Penicillins bind to benzodiazepine receptors, and penicillins, cephalosporins, and imipenem/cilastatin inhibit GABA binding. Status epilepticus can be refractory to treatment with phenytoin or barbiturates. Isoniazids convulsant properties, like its ability to cause peripheral neuropathy, might be related to decreased tissue and serum levels of pyridoxine resulting from the formation of rapidly excreted isoniazidpyridoxine hydrazones. It is observed that benzodiazepines can produce physical dependence, with barbiturate-like withdrawal symptoms, including seizures.

Chapter 54 – Seizures, Ethanol, and Recreationally Abused Drugs

Publisher Summary This chapter focuses on seizures in nonepileptic substance abusers with no underlying cerebral pathology or additional risk factors. Among those with unprovoked seizures, the risk of seizures increased with increasing ethanol use. It is found that seizures were not clearly associated temporally with abstinence. They occurred more than 2 weeks after the last drink in 16% of patients, and during or within 1 h of drinking in 19%. Ethanol affects a number of neurotransmitter systems, including gamma-aminobutyric acid (GABA), but probably indirectly, a secondary consequence of nonspecific fluidizing actions on neuronal membranes. Barbiturates not only potentiate GABA but also have direct actions on chloride channels, and they antagonize glutamate excitatory neurotransmission. These different actions probably account for the ability of some barbiturates such as phenobarbital to prevent seizures without producing anesthesia. It is found that a number of nonbarbiturate, nonbenzodiazepine sedatives such as chloral hydrate or meprobamate also produce physical dependence and withrawal seizures. It is observed that seizures and myoclonus are acute neurotoxic side effects of meperidine, a consequence of its metabolite, normeperidine, which also causes delirium and hallucinations.