第35章神経系

Like Alzheimer’s disease, Parkinson’s disease is a neurodegenerative disease. It was first characterized by James Parkinson in 1817. Each year, 50,000-60,000 people in the United States are diagnosed with the disease. Parkinson’s disease causes the loss of dopamine neurons in the substantia nigra, a midbrain structure that regulates movement. Loss of these neurons causes many symptoms including tremor (shaking of fingers or a limb), slowed movement, speech changes, balance and posture problems, and rigid muscles. The combination of these symptoms often causes a characteristic slow hunched shuffling walk, illustrated in Figure 35.30. Patients with Parkinson’s disease can also exhibit psychological symptoms, such as dementia or emotional problems.

Although some patients have a form of the disease known to be caused by a single mutation, for most patients the exact causes of Parkinson’s disease remain unknown: the disease likely results from a combination of genetic and environmental factors (similar to Alzheimer’s disease). Post-mortem analysis of brains from Parkinson’s patients shows the presence of Lewy bodies—abnormal protein clumps—in dopaminergic neurons. The prevalence of these Lewy bodies often correlates with the severity of the disease.

There is no cure for Parkinson’s disease, and treatment is focused on easing symptoms. One of the most commonly prescribed drugs for Parkinson’s is L-DOPA, which is a chemical that is converted into dopamine by neurons in the brain. This conversion increases the overall level of dopamine neurotransmission and can help compensate for the loss of dopaminergic neurons in the substantia nigra. Other drugs work by inhibiting the enzyme that breaks down dopamine.

Neurodevelopmental disorders occur when the development of the nervous system is disturbed. There are several different classes of neurodevelopmental disorders. Some, like Down Syndrome, cause intellectual deficits. Others specifically affect communication, learning, or the motor system. Some disorders like autism spectrum disorder and attention deficit/hyperactivity disorder have complex symptoms.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder. Its severity differs from person to person. Estimates for the prevalence of the disorder have changed rapidly in the past few decades. Current estimates suggest that one in 88 children will develop the disorder. ASD is four times more prevalent in males than females.

A characteristic symptom of ASD is impaired social skills. Children with autism may have difficulty making and maintaining eye contact and reading social cues. They also may have problems feeling empathy for others. Other symptoms of ASD include repetitive motor behaviors (such as rocking back and forth), preoccupation with specific subjects, strict adherence to certain rituals, and unusual language use. Up to 30 percent of patients with ASD develop epilepsy, and patients with some forms of the disorder (like Fragile X) also have intellectual disability. Because it is a spectrum disorder, other ASD patients are very functional and have good-to-excellent language skills. Many of these patients do not feel that they suffer from a disorder and instead think that their brains just process information differently.

Except for some well-characterized, clearly genetic forms of autism (like Fragile X and Rett’s Syndrome), the causes of ASD are largely unknown. Variants of several genes correlate with the presence of ASD, but for any given patient, many different mutations in different genes may be required for the disease to develop. At a general level, ASD is thought to be a disease of “incorrect” wiring. Accordingly, brains of some ASD patients lack the same level of synaptic pruning that occurs in non-affected people. In the 1990s, a research paper linked autism to a common vaccine given to children. This paper was retracted when it was discovered that the author falsified data, and follow-up studies showed no connection between vaccines and autism.

Treatment for autism usually combines behavioral therapies and interventions, along with medications to treat other disorders common to people with autism (depression, anxiety, obsessive compulsive disorder). Although early interventions can help mitigate the effects of the disease, there is currently no cure for ASD.