Hall 1

Supplemental Data E- Appendix 1

Case reports

Patient III-1. She noticed a change in her spelling and handwriting at the age of 41. Over the next year, she had problems with intermittent confusion, personality change, and clumsiness of the hands. Her neurologic exam was remarkable for disorientation, unintelligible speech, and a blunted affect. She was diagnosed with “organic psychosis” and died at the age of 50.

Patient IV-2. She was a “good-natured” woman who had personality changes in her early 30s. She then had gradual onset of cognitive deficits, including memory loss, problems with calculations, and word finding difficulties. She became impulsive and would spend money recklessly. She frequently became lost while driving and she had her driver’s license revoked when she almost ran over her son. Poor judgment became a prominent feature of her disease and was illustrated by her killing her neighbors’ dog when it would not stop barking. She was placed in a nursing home and was described in her late thirties as perseverative, with decreased spontaneous speech and a tendency to spend long periods of time moving around items in her room. She died at the age of 41.

Patient IV-4. Personality change and memory problems began at the age of 33. He had difficulty with telephone conversations, acted hostile, and was described as “strange” by members of his squadron in the army after 15 years of duty. On examination, he had poor short term memory with confabulation and decreased attention. He had difficulty following complex commands, but had a good knowledge of current events. His affect was restricted and labile. He frequently perseverated and had psychomotor slowing. He had slight dysarthria and an unsteady tandem gait. He also had poor motor coordination. He was diagnosed with an “acute brain syndrome,” possibly related to alcoholism. He died at the age of 47.

Patient V-1. At the age of 30, she had the onset of short term memory loss and difficulty walking. She became hostile with erratic behavior. Neurologic exam at age 41 showed perseverative speech with stuttering and problems with memory. She had increased tone in all extremities with brisk reflexes and downgoing toes. A snout reflex was present. She had repetitive “busy” movements of her hands, frequent scratching the tops of her hands, and pulling of her hair. She had dystonic posturing of the hands and fisting when she walked. In her mid-forties, she developed hallucinations and refractory generalized seizures.

Patient V-3. She had normal development and good health, but was held back a year in grade school before dropping out of school in the 10th grade. She overdosed on aspirin during a suicide attempt in her 20s. At age 30, she began to have cognitive difficulties. On examination at the age of 38, she had subtle athetotic hand movements, but no dysmetria. Reflexes were normal, but a snout reflex was present. Examination at the age of 52 found her to be nonverbal. She recognized some family members and responded to her name, but did not follow any commands. She was easily agitated and would cry out if touched or moved. She had increased tone in all four extremities without cogwheel rigidity and would move all extremities spontaneously. Her reflexes were 3+ in all of her extremities with downgoing toes. Glabellar, snout, and palmomental reflexes were present. She was unable to walk. She is now 53 years old and living in a nursing facility.

Patient V-4. He was noted to have neurological problems from the time of birth. He had delayed development of both language and motor skills and attended special education classes. He dropped out of school in the 6th grade and was able to hold a series of odd jobs for local farmers. Throughout his adolescence, he had a preoccupation with fire. In his late teens and early 20s, he had worsening cognitive impairment. At age 23, he was no longer able to hold down a job and was granted social security disability. He moved in with his aunt until the age of 33, when he required total care and was transferred into a nursing home. His first neurological examination was at the age of 35. He was disoriented and had moderate difficulty with short-term memory. He was impulsive and perseverative, with displayed deficits in auditory comprehension. His speech was remarkable for dysarthria and stuttering, and he had trouble swallowing liquids without choking. He had repetitive “unusual” hand movements throughout the examination. He had both truncal and gait ataxia, frequently falling forward. Over the next few years, he became increasingly aggressive and combative in the nursing home. His ataxia steadily worsened and he developed marked dysphagia. He died at the age of 42 from pneumonia.

Patient V.5. She dropped out of high school to have children and did well until she was 44, when she began having memory problems and clumsiness. Neurological examination at age 48 showed a Mini Mental Status Exam5 score of 25/30 with deficits in orientation, memory, repetition, and auditory comprehension. An “expressive” aphasia with dysarthria was present. She had repetitive movements, such as hand wringing and brisk reflexes. Her gait was wide-based and ataxic. She is currently cared for by her stepmother.

Patient V-7. At the age of 25, he was fired from his job due to a decline in his performance. He was able to do odd jobs until he started having short term memory problems, a change in his handwriting, and inability to do simple calculations. Examination at the age of 32 showed decreased short term memory, poor judgment, and no ability to interpret proverbs. He was inattentive during the interview. He had decreased fine motor movements, and was hyperreflexic. Tone was normal. He had decreased arm swing on the right. His ataxia continued to worsen, he could only follow simple commands, and his speech is unintelligible. He now lives in a nursing home at the age of 45.

Patient VI-3. He had problems in childhood with dyslexia, pyromania, and poor school performance. Accepted into the Navy, he served and was discharged at age 24, when he was noted by his family to have personality changes. He was frequently in trouble with the law for pedophilia, buying alcohol for minors, and loitering. He was convicted for attacking a girl with a knife and put on probation. In his late 20s, he became homeless and jobless and was diagnosed as paranoid schizophrenic. He was later treated for post-traumatic stress disorder (PTSD) from his military service. On examination at age 27, he was impulsive with poor judgment. He had masked facies, decreased blinking, and normal saccades. His tone was normal but he had decreased arm swing bilaterally. He had some hand fisting when walking. Testing showed his full scale IQ was 70. He is currently in an assisted living facility.

Patient VI-4. She had onset of symptoms at the age of 31 with abnormalities in her behavior and memory. She had had a gradual decrease in her cognition and speech over two years before being evaluated. She had frequent word finding difficulties and her husband reported a decrease in her ability to write and perform calculations. She is now unable to help her elementary school children with their homework. Her short term memory has deteriorated and she frequently forgets conversations. She has occasional episodes of confusion, especially when driving, causing her to lose direction and resulting in at least one motor vehicle accident. She is unable to grocery shop, cross-stitch, and follow recipes, and she will inadvertently leave on stove burners. She has had a change in personality and depression with suicidal ideation. On examination, she had difficulty following complex commands and odd posturing. Her Mini Mental Status Exam5 score was 19/30 with decreased orientation and tasks of attention. She had poor abstraction and judgment. She was found to have motor perseveration and bilateral grasp responses. She had weakness in the hands and mild past-pointing bilaterally. Reflexes were normal. She walked pigeon-toed, had decreased arm swing, and was unable to tandem.

Patient VI-5. He began stealing when he was in elementary school, not understanding the concept of money. This persisted into his adolescence and 20s, when he served three years in prison for robbery. After release at the age of 26, he was noted to have poor short term memory, word finding difficulties, and poor judgment. He was put in a care facility after he set a fire in his bedroom and was found watching the fire, mesmerized.