Most central nervous system (CNS) pathogens infect the nervous system nonspecifically, and disease is the result of the brain's immune response. This is exemplified by viral and bacterial meningitis, which cause extensive inflammation of the brain or its coverings. However, some pathogens show neural tropism and specifically infect certain neurons, as illustrated by motor neuron infections underlying poliomyelitis, neurosyphilis, or infection of sensory neurons by herpes simplex. Similarly, infestation of the brain by larvae (cysticerci) from intestinal tapeworms nonspecifically causes neurological disease in millions of people in the developing world, whereas rare paralytic amoeba actively invade the brain through the nasal canal and feast on brain tissue. By far the most important neurological disease caused by a pathogen is neuro–acquired immunodeficiency syndrome (AIDS), the development of cognitive decline and dementia in the late stages of AIDS due to brain infection with human immunodeficiency virus. Given the magnitude of the global AIDS endemic, these cases will soon rival more traditional age-related dementia. Neuroscientists are unlikely to contribute to the development of more effective treatments, a task that rests on microbiologists and immunologists who to develop vaccines and antivirals. However, several neurotoxins (Botox) and neurotropic viruses (herpes simplex virus 1) are providing tools to treat neurological disease through targeted delivery of genes or paralytic therapeutics.
Epilepsy is one of the most common neurological syndromes and affects over 50 million people worldwide. It is characterized by the spontaneous recurrence of seizures, abnormal synchronous discharges of neuronal networks, which present with a range of behavioral abnormalities. The underlying causes vary and are frequently unknown. Seizure risks include congenital brain abnormalities, tumors, trauma, infections, vascular disease, and drug exposure. While epilepsy is pharmacologically curable in two-thirds of patients, the remaining patients suffer lifelong and often severe disabilities and poor quality of life. Advances in basic and clinical science have provided invaluable insights into possible causes of epilepsy, including mutations in ion channels and neurotransmitter receptors. These studies put forth the hypothesis that enhanced susceptibility to seizure is the result of changes in the normal balance between neuronal excitability and inhibition. Various animal models allow the genesis of epilepsy to be studied and the efficacy of new drugs to be tested. The apparent multigenetic nature of the disease suggests that patient-specific “personalized” treatment approaches may be considered in the future.
Often the first symptom of Parkinson disease is trembling or shaking (tremor) of a limb, especially when the body is at rest. Typically, the tremor begins on one side of the body, usually in one hand. Tremors can also affect the arms, legs, feet, and face. Other characteristic symptoms of Parkinson disease include rigidity or stiffness of the limbs and torso, slow movement (bradykinesia) or an inability to move (akinesia), and impaired balance and coordination (postural instability). These symptoms worsen slowly over time.
Over 50 million people worldwide live with the consequences of brain and spinal cord injury. Unfortunately, nervous system tissue is very fragile and its protection by the bones of skull and vertebral column is insufficient to withstand the forces encountered in motor vehicle accidents or during contact sports. Though our understanding of primary and secondary nervous system injury is excellent, effective therapeutics to enhance a patient’s recovery are largely absent. At best, rehabilitation and robotic assist devices make disease more manageable. The major hurdles are the inability of most neurons to replicate after injury, and the active, multipronged suppression of axonal regeneration by myelin-associated molecules and glial scars. Exciting progress has been made in overcoming these hurdles in preclinical studies, and clinical trials show promise with the implantation of autologous stem cells. Increased public awareness of the danger associated with repeated mild injuries in sporting activities is having positive effects on the use of protective measures in athletics.
