This Month in Archives of Neurology

There has been enormous progress in recent years in understanding the biochemical and molecular basis of lysosomal storage diseases. A cmprehensive updated review is provided by Wenger and colleagues, who have pioneered this field. In their detailed assessment, they emphasize an early diagnosis and possible hematopoietic stem cell transplantation or enzyme replacement therapy for selected disorders.

Cardiac QT dispersion is increased in the first 24 hours in patients with acute stroke with no cardiovascular disease compared with control subjects as reported by Afsar et al. The increase in QT dispersion seems to be more prominent in the early periods of stroke and to be related to humoral effects of the acute insult. Of note and concern, the increased QT dispersion could represent a substrate for arrhythmias, and close electrocardiographic monitoring of stroke patients during the acute phase is warranted.

Russmann et alreport that lenticular infarction mainly induces hemiparesis but no movement disorder. Associated sensory deficits, aphasia, and hemineglect clinically underline the function of the lenticular nucleus in connection with the prefrontal, temporal, and parietal cortices. These results contrast with previous reports, in which the most prominent clinical feature due to lenticular lesions was dystonia.

Few longitudinal studies of dementia in Parkinson disease (PD) have been reported. This study by Aarsland and colleaguesexamined the 8-year prevalence, characteristics, and risk factors for dementia with PD, involving 224 patients. Of note, more than three quarters of this representative PD cohort had developed dementia during the 8-year study period. Early hallucinations and akinetic-dominant parkinsonism were associated with increased risk for dementia.

For both Alzheimer disease (AD) and Parkinson disease (PD), the greatest neuronal loss was found in the locus coeruleus. Zarow et alreport that in AD, neuronal loss was most severe and best correlated with duration of illness in the locus coeruleus rather than in the nucleus basalis as traditionally expected. Correlations between neuronal loss in the locus coeruleus and nucleus basalis but not in the substantia nigra, in both PD and AD, suggest that the former 2 nuclei may share common pathogenetic susceptibilities. Given the prominent loss of neurons in the locus coeruleus, detection and treatment of noradrenergic deficiencies warrant attention in both AD and PD. Editorial comment is provided by David Rye, MD, PhD, and Mahlon R. DeLong, MD.

At any given level of clinical severity, the pathologic change in Alzheimer disease (AD) is more severe in those with more engagement in life's activities, even when education and IQ are taken into account, as reported by Scarmeas and colleagues. These findings suggest that interindividual differences in lifestyle may affect cognitive reserve by partially mediating the relationship between pathologic change in the brain and the clinical features of AD. Theater, travel, cooking, walking, dancing, and exercise, among other activities, are all of benefit to the patient with AD. The contribution of life experiences, styles, and activities to the ability to cope with the disease suggests the possibility of interventions that appear to delay the onset of clinical symptoms of dementia.

Caspase gene expression has been noted to be involved in the pathologic cellular functioning in Alzheimer disease (AD). Little is known about the temporal pattern of caspase gene expression relative to the onset and clinical progression of the disease. A regular pattern of proapoptotic gene activation followed by apoptotic gene expression is at play in disease progression as described by Pompl and colleagues. Specific caspases are activated as a function of clinical dementia in AD, with increasing neuropathologic burden, especially neurofibrillary tangles. These data provide compelling evidence that caspases are a major factor in the progression of AD and provide relevance for the development of caspase inhibitors as a form of potential therapy.

Brewer and colleaguesshow that tetrathiomolybdate in doses varying from 120 to 410 mg/d for 8 weeks in an open-label study of 55 patients with Wilson disease yielded an excellent response. Only 2 (3.6%) of 55 patients showed neurologic deterioration compared with an estimated 50% of patients treated with penicillamine. With rapid escalation of the dose, adverse effects from bone marrow suppression or transaminase elevations can occur. A dose of 120 mg/d for initial therapy in Wilson disease is recommended to minimize adverse effects. The stabilization of the clinical state during the initial period, while copper toxicity is controlled, then allows very good recovery of much neurologic function during the succeeding year or 2.

Imaging and postmortem studies suggest that frontal lobe white matter (FLWM) volume expands until about age 44 years and then declines. Bartzokis and colleaguesused magnetic resonance imaging to assess the integrity of FLWM and to index brain aging and its relationship to Alzheimer disease (AD). Two hundred fifty-two normal adults aged 19 to 82 years and 34 patients with AD aged 59 to 85 years were studied. In normal persons, FLWM increased until age 38 years and then declined markedly with age. Patients with AD had lower values than age- and sex-matched control subjects. Thus, FLWM volume may serve as a reliable index for the rate of brain aging and the rate of development of AD.

Five cases of myoclonus resulting from lithium treatment were studied by Caviness et al. In 2 cases, lithium treatment was discontinued and the myoclonus resolved. These patients had myoclonus, short-duration (<50-millisecond) myoclonus electromyogram discharges, and cortical action myoclonus without the presence of epileptiform abnormalities on routine electroencephalogram.

Cohen et alevaluated 64 patients with essential tremor (ET), 12 of whom also had rest tremor. When compared with the 52 patients with ET without rest tremor, these 12 had disease of longer duration and greater severity. Also, their ET was more widely disseminated as evidenced by a larger proportion with head tremor. The 5 patients with rest tremor who underwent electrophysiologic study had features that were consistent with parkinsonism (eg, slow spiral speed, increased decrement of spiral speed with radius). The basis of rest tremor could be basal ganglia involvement, raising the possibility that the pathologic process that is causal for ET may extend to these structures.