Phenotypic spectrum of dynamin 2 mutations in Charcot-Marie-Tooth neuropathy.

Dominant intermediate Charcot-Marie-Tooth neuropathy type B is caused by mutations in dynamin 2. We studied the clinical, haematological, electrophysiological and sural nerve biopsy findings in 34 patients belonging to six unrelated dominant intermediate Charcot-Marie-Tooth neuropathy type B families in whom a dynamin 2 mutation had been identified: Gly358Arg (Spain); Asp551_Glu553del; Lys550fs (North America); Lys558del (Belgium); Lys558Glu (Australia, the Netherlands) and Thr855_Ile856del (Belgium). The Gly358Arg and Thr855_Ile856del mutations were novel, and in contrast to the other Charcot-Marie-Tooth-related mutations in dynamin 2, which are all located in the pleckstrin homology domain, they were situated in the middle domain and proline-rich domain of dynamin 2, respectively. We report the first disease-causing mutation in the proline-rich domain of dynamin 2. Patients with a dynamin 2 mutation presented with a classical Charcot-Marie-Tooth phenotype, which was mild to moderately severe since only 3% of the patients were wheelchair-bound. The mean age at onset was 16 years with a large variability ranging from 2 to 50 years. Interestingly, in the Australian and Belgian families, which carry two different mutations affecting the same amino acid (Lys558), Charcot-Marie-Tooth cosegregated with neutropaenia. In addition, early onset cataracts were observed in one of the Charcot-Marie-Tooth families. Our electrophysiological data indicate intermediate or axonal motor median nerve conduction velocities (NCV) ranging from 26 m/s to normal values in four families, and less pronounced reduction of motor median NCV (41-46 m/s) with normal amplitudes in two families. Sural nerve biopsy in a Dutch patient with Lys558Glu mutation showed diffuse loss of large myelinated fibres, presence of many clusters of regenerating myelinated axons and fibres with focal myelin thickenings--findings very similar to those previously reported in the Australian family. We conclude that dynamin 2 mutations should be screened in the autosomal dominant Charcot-Marie-Tooth neuropathy families with intermediate or axonal NCV, and in patients with a classical mild to moderately severe Charcot-Marie-Tooth phenotype, especially when Charcot-Marie-Tooth is associated with neutropaenia or cataracts.

Quantitative gait analysis in patients with dementia with Lewy bodies and Alzheimer's disease.

Gait disorders in people with dementia have been documented in a number of studies. There is some preliminary evidence suggesting there may be a relationship between dementia type and gait abnormality. Quantitative gait analysis has not previously been reported for people diagnosed with dementia with Lewy bodies (DLB). Therefore, this study aimed to quantify gait patterns of people with DLB and compare them with those of people with Alzheimer's disease (AD) and control subjects. Two groups of 10 subjects divided according to a diagnosis of DLB and AD, and 10 control subjects underwent gait analysis using an electronic walkway. Participants were required to walk at self-selected slow, preferred and fast speeds. There were no differences between the DLB and AD patient groups for any of the measured gait variables. Velocity and stride length values were significantly reduced in both patient groups compared to the control group at all speeds and percentage of time spent in double limb support was significantly increased in both patient groups compared to the control group at all walking speeds. Significant correlations were found between gait speeds and gait outcome variables. Spatiotemporal gait characteristics of people with AD and DLB are similar, but significantly different from the normal population.

Physiological falls risk assessment in older people with Alzheimer's disease.

BACKGROUND: Falls are common in people with Alzheimer's disease (AD). There is some evidence that deficits in vision, peripheral sensation, strength, reaction time and balance may be partly responsible for this increased risk. AIMS: To determine the feasibility and test-retest reliability of a physiological test battery designed to assess falls risk [the Physiological Profile Assessment (PPA)] in people with AD, and to compare their PPA scores to age- and sex-matched controls. METHODS: Twenty-one community-dwelling people with probable, mild to moderate AD aged 63-91 years, and 21 age- and sex-matched controls underwent the PPA tests and the Mini-Mental State Examination. All tests were then repeated in the AD group to determine test-retest reliability. RESULTS: Most of the PPA tests could be successfully administered to participants with AD. The AD group had a significantly higher overall falls risk score (t(40) = -2.41, p < 0.02), slower hand (t(40) = -4.86, p < 0.01) and foot reaction time (t(40) = -2.26, p < 0.05) and worse coordinated stability (t(40) = -2.40, p < 0.05) than the controls. CONCLUSION: Physiological falls risk assessment is feasible in older people with mild to moderate AD. Older people with AD demonstrate significant impairments in several physiological domains, particularly reaction time, compared to controls.

Gait variability in community dwelling adults with Alzheimer disease.

Studies have shown that measures of gait variability are associated with falling in older adults. However, few studies have measured gait variability in people with Alzheimer disease, despite the high incidence of falls in Alzheimer disease. The purpose of this study was to compare gait variability of community-dwelling older adults with Alzheimer disease and control subjects at various walking speeds. Ten subjects with mild-moderate Alzheimer disease and ten matched control subjects underwent gait analysis using an electronic walkway. Participants were required to walk at self-selected slow, preferred, and fast speeds. Stride length and step width variability were determined using the coefficient of variation. Results showed that stride length variability was significantly greater in the Alzheimer disease group compared with the control group at all speeds. In both groups, increases in walking speed were significantly correlated with decreases in stride length variability. Step width variability was significantly reduced in the Alzheimer disease group compared with the control group at slow speed only. In conclusion, there is an increase in stride length variability in Alzheimer disease at all walking speeds that may contribute to the increased incidence of falls in Alzheimer disease.