Handbook of clinical neurology
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Patients with hemophilia and other congenital bleeding disorders are at risk for development of central nervous system (CNS) hemorrhage and can present with acute or chronic neurologic symptoms. These disorders are generally caused by qualitative or quantitative deficiency of components of hemostasis such as coagulation proteins, von Willebrand factor, or platelets. ⋯ Since hemophilia is the most common bleeding disorder encountered in clinical practice, more emphasis is placed on management of hemophilia. Additionally, neurologic manifestations related to the bleeding diathesis in patients with hemophilia are elaborated.
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Complex multiorgan failure may require simultaneous transplantation of several organs, including heart-lung, kidney-pancreas, or multivisceral transplantation. Solid organ transplantation can also be combined with hematopoietic stem cell transplantation to modulate immunologic response to a solid organ allograft. Combined multiorgan transplantation may offer a lower rate of allograft rejection and lower immunosuppression needs. ⋯ Heart-lung allograft recipients have very similar clinical course and spectrum of neurologic complications to lung transplant recipients. At this time there are no reports of an increased risk of graft-versus-host disease with combined transplantation of solid organ allograft and hematopoietic stem cells. Chronic immunosuppression and complex toxic-metabolic disturbances after multiorgan transplantation create a permissive environment for development of a wide spectrum of neurologic complications which largely resemble complications after transplantations of individual components of complex multiorgan allografts.
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Cardiac transplantation remains the best treatment option for patients with end-stage, NYHA class IV heart failure who have failed conventional therapy. However, transplant rates have remained static largely due to limited organ donor supplies. Therefore, appropriate allocation of this precious resource is critical to maximize benefit, both at a patient level and at a societal level. ⋯ These include: (1) drug toxicities, such as lowering of seizure thresholds; (2) encephalopathy, such as posterior reversible encephalopathy syndrome (PRES); (3) infections; (4) malignancies, such as post-transplant lymphoproliferative disorder (PTLD). Many of the same considerations discussed in adult heart transplant recipients apply to pediatric heart transplant recipients as well. In children, seizures are the most common neurologic complication, although other neurologic complication rates are comparable.
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Neuropathies related to diabetes mellitus can affect 60-70% of patients with diabetes. These can include peripheral polyneuropathies, mononeuropathies, and autonomic neuropathies. ⋯ Besides control of the above listed risk factors, we do not have effective medications to treat the pathophysiologic mechanisms of diabetic neuropathies. Treatment is limited to ameliorating pain and correcting the end organ consequences of the neuropathic processes.
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Alcoholism, more generically drug addiction, can be defined as a chronically relapsing disorder characterized by: (1) compulsion to seek and take the drug (alcohol); (2) loss of control in limiting (alcohol) intake; and (3) emergence of a negative emotional state (e.g., dysphoria, anxiety, irritability), reflecting a motivational withdrawal syndrome, when access to the drug (alcohol) is prevented (defined here as dependence). The compulsive drug seeking associated with alcoholism can be derived from multiple neuroadaptations, but the thesis argued here, derived largely from animal models, is that a key component involves decreased brain reward function, increased brain stress function, and compromised executive function, all of which contribute to the construct of negative reinforcement. Negative reinforcement is defined as drug taking that alleviates a negative emotional state. ⋯ A brain stress response system is hypothesized to be activated by acute excessive drug intake, to be sensitized during repeated withdrawal, to persist into protracted abstinence, and to contribute to the compulsivity of alcoholism. Other components of brain stress systems in the extended amygdala that interact with CRF and may contribute to the negative motivational state of withdrawal include increases in norepinephrine function, increases in dynorphin activity, and decreases in neuropeptide Y. The combination of impairment of function in reward circuitry and recruitment of brain stress system circuitry provides a powerful neurochemical basis for the negative emotional states that are responsible for the negative reinforcement that drives the compulsivity of alcoholism.