The 4-kilodalton (39 to 43 amino acids) amyloid beta protein (beta AP), which is deposited as amyloid in the brains of patients with Alzheimer's diseases, is derived from a large protein, the amyloid beta protein precursor (beta APP). Human mononuclear leukemic (K562) cells expressing a beta AP-bearing, carboxyl-terminal beta APP derivative released significant amounts of a soluble 4-kilodalton beta APP derivative essentially identical to the beta AP deposited in Alzheimer's disease. Human neuroblastoma (M17) cells transfected with constructs expressing full-length beta APP and M17 cells expressing only endogenous beta APP also released soluble 4-kilodalton beta AP, and a similar, if not identical, fragment was readily detected in cerebrospinal fluid from individuals with Alzheimer's disease and normal individuals. Thus cells normally produce and release soluble 4-kilodalton beta AP that is essentially identical to the 4-kilodalton beta AP deposited as insoluble amyloid fibrils in Alzheimer's disease.

Tremor rating scales (TRSs) are used commonly in the clinical assessment of tremor, but the relationship of a TRS to actual tremor amplitude has never been quantified. Consequently, the resolution of these scales is unknown, and the clinical significance of a 1-point change in TRS is uncertain. We therefore sought to determine the change in tremor amplitude that corresponds to a 1-point change in a typical 5-point TRS. Data from five laboratories were analysed, and 928 patients with various types of hand tremor were studied. Hand tremor was quantified with a graphics tablet in three different labs, an accelerometer in three labs and a mechanical-linkage device in one lab. Tremor in writing, drawing, horizontal posture, rest and finger-nose testing was graded using a variety of TRSs. The relationship between TRS scores and tremor amplitude was computed for each task and laboratory. A logarithmic relationship between a 5-point (0-4) TRS and tremor amplitude (T, measured in centimetres) was found in all five labs, despite widely varying rating scales and transducer methodology. Thus, T2/T1 = 10(alpha(TRS2-TRS1)). The value of alpha ranged from 0.414 to 0.441 for writing, 0.355-0.574 for spiral drawing, 0.441 to 0.488 for rest tremor, 0.266-0.577 for postural tremor and 0.306 for finger-nose testing. For alpha = 0.3, 0.4, 0.5, 0.6 and 0.7, the ratios T2/T1 for a 1-point decrease in TRS are 0.501, 0.398, 0.316, 0.251 and 0.200. Therefore, a 1-point change in TRS represents a substantial change in tremor amplitude. Knowledge of the relationship between TRS and precise measures of tremor is useful in interpreting the clinical significance of changes in TRS produced by disease or therapy.

We completed a single site, double-blind, placebo-controlled, parallel design study of quetiapine for hallucinations in PD. Thirty-one subjects with PD and prominent visual hallucinations and Mini-Mental State Examination score >21 were randomly assigned in a 2:1 drug to placebo ratio, up to 200 mg daily of quetiapine or matching placebo given in two doses. They were seen at 3 weeks (100 mg/day) and 12 weeks (200 mg/day, with optional dose reduction). Evaluation included the Unified Parkinson's Disease Rating Scale (UPDRS), the Baylor PD Hallucination Questionnaire, and a battery of neuropsychological tests. The demographics between subjects randomized to drug (n = 21) vs. placebo (n = 10) were similar. The final dose of active drug was 200 (n = 11), 150 (n = 2), 100 (n = 3), and 75 (n = 1) mg per day. All placebo subjects were on the equivalent of 200 mg per day. The UPDRS Activities of Daily Living and Motor scores did not significantly change compared to placebo. Compared to placebo, there were no significant changes in our hallucination questionnaire, the Brief Psychiatric Rating Scale (BPRS), or question 12 (hallucination item) of the BPRS. There were no significant changes on any of the neuropsychological measures. Adverse events on drug included sedation (n = 9), but no drug-related adverse events precipitated discontinuation and none were rated as serious. Quetiapine, up to 200 mg daily, was well tolerated and did not worsen UPDRS scores; however, there was no significant improvement in psychosis rating scales compared to placebo. Larger doses of drug and greater sample sizes might be considered in future studies.

Objective To determine the reliability of a new scale for the clinical assessment of essential tremor. Background The Essential Tremor Rating Assessment Scale contains nine performance items that rate action tremor in the head, face, voice, limbs and trunk 0–4 in half-point intervals. Head and limb tremor ratings are defined by specific amplitude ranges in centimeters. Design/Methods Videos of 44 patients and 6 controls were rated by 10 specialists on two occasions, 1–2 months apart. Inter- and intra-rater reliabilities were assessed with a two-way random effects intraclass correlation, using an absolute agreement definition. Results The inter- and intra-rater intraclass correlations for head and upper limb tremor ranged from 0.86 to 0.96, and the intraclass correlations for the total score were 0.94 and 0.96. The intraclass correlations for voice, face, trunk and leg were less robust. Conclusions This scale is an exceptionally reliable tool for the clinical assessment of essential tremor.

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When primary torsion dystonia is caused by a GAG deletion in the TOR1A gene (DYT1 dystonia), it typically presents with an early-onset dystonia involving distal limbs, subsequently spreading to a generalized dystonia. We describe a large family with an unusually broad variability in the clinical features of their dystonia both with regard to severity and age of onset. The proband of this family succumbed in his second decade to malignant generalized dystonia, whereas other family members carrying the same mutation are either asymptomatic or display dystonia that may be focal, segmental, multifocal, or generalized in distribution. One family member had onset of her dystonia at age 64 years, probably the oldest reported in genetically confirmed DYT1 dystonia. We conclude that marked phenotypic heterogeneity characterizes some families with DYT1 dystonia, suggesting a role for genetic, environmental, or other modifiers. These findings have implications for genetic testing and counseling.

To compare autonomic effects of botulinum toxin (BTX), we randomized patients with cervical dystonia to receive either BTX-A or BTX-B in a double-blind manner. Efficacy and physiologic questionnaire measures of autonomic function were assessed at baseline and 2 weeks after injection. Patients treated with BTX-B had less saliva production (p < 0.01) and greater severity of constipation (p = 0.037) than those treated with BTX-A, but did not differ in other tests of autonomic functions.