Handbook of clinical neurology
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Review Case Reports
Natural history of cerebral cavernous malformations.
Cerebral cavernous malformations (CCM) are vascular abnormalities of the central nervous system with an incidence of 0.4-0.5% and an annual rate of hemorrhage ranging from 0.7% to 1%. Most lesions are located in the cerebral hemisphere but some occur in deeper locations such as the basal ganglia and pons. The most common symptoms during presentation are headache, seizures, and focal neurologic deficits. ⋯ This finding, however, is not consistent in all natural history studies evaluated. During follow-up, the most important and consistent risk factor for rebleed was a prior hemorrhage. Here, we provide an indepth but concise review of the literature regarding the natural history of CCMs.
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The human prion diseases comprise Creutzfeldt-Jakob disease, variably protease-sensitive prionopathy, Gerstmann-Sträussler-Scheinker disease, fatal familial insomnia, and kuru. Each is a uniformly fatal rare neurodegenerative disease in which conformational changes in the prion protein are thought to be the central pathophysiologic event. The majority of cases of human prion diseases occur worldwide in the form of sporadic Creutzfeldt-Jakob disease and a minority of around 10-15% are associated with mutations of the prion protein gene, termed PRNP, in the forms of genetic Creutzfeldt-Jakob disease, Gerstmann-Sträussler-Scheinker disease, and fatal familial insomnia. ⋯ Despite having a high public profile, human prion diseases are both rare and heterogeneous in their clinicopathologic phenotype, sometimes making a diagnosis challenging. A combined clinical, genetic, neuropathologic, and biochemical approach to diagnosis is therefore essential. The intensive study of these diseases continues to inform on neurodegenerative mechanisms and the role of protein misfolding in more common neurodegenerative diseases such as Parkinson disease and Alzheimer disease.
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A neurocatastrophe or severe brain injury (SBI) is a central nervous system insult associated with a high likelihood of death or severe disability. While many etiologic processes may lead to SBI, the most common and best-studied clinical paradigms are traumatic brain injury and anoxic-ischemic encephalopathy following cardiac arrest. Clinical phenotypes following SBI include acute and chronic disorders of consciousness as well as a range of cognitive and behavioral impairments. ⋯ Yet existing scores fail to classify outcomes with the accuracy that would support individual patient-level decision making. Improved prognostication will likely depend on the use of molecular and imaging data that capture unique biologic features in individual patients with SBI. The integration of these additional layers of information will require iterative computational approaches.
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Delirium is common in critically ill patients and associated with increased length of stay in the intensive care unit (ICU) and long-term cognitive impairment. The pathophysiology of delirium has been explained by neuroinflammation, an aberrant stress response, neurotransmitter imbalances, and neuronal network alterations. Delirium develops mostly in vulnerable patients (e.g., elderly and cognitively impaired) in the throes of a critical illness. ⋯ Nonpharmacologic strategies with early mobilization, reducing causes for sleep deprivation, and reorientation measures may be effective in the prevention of delirium. Antipsychotics are effective in treating hallucinations and agitation, but do not reduce the duration of delirium. Combined pain, agitation, and delirium protocols seem to improve the outcome of critically ill patients and may reduce delirium incidence.
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Epilepsy is one of the most common neurologic disorders, affecting about 50 million people worldwide. The disease is characterized by recurrent seizures, which are due to aberrant neuronal networks resulting in synchronous discharges. The term epilepsy encompasses a large spectrum of syndromes and diseases with different etiopathogenesis. ⋯ Access of this clinically well-characterized neurosurgical material has provided neuropathologists with the opportunity to study a variety of structural brain abnormalities associated with epilepsy, by combining traditional routine histopathologic methods with molecular genetics and functional analysis of the resected tissue. This approach has contributed greatly to a better diagnosis and classification of these structural lesions, and has provided important new insights into their pathogenesis and epileptogenesis. The present chapter provides a detailed description of the large spectrum of histopathologic findings encountered in epilepsy surgery patients, addressing in particular the nonneoplastic pathologies, including hippocampal sclerosis, malformations of cortical development, Sturge-Weber syndrome, and Rasmussen encephalitis, and reviews current knowledge regarding the underlying molecular pathomechanisms and cellular mechanisms mediating hyperexcitability.