Copyright 2001 American Medical Association. All Rights Reserved. Applicable FARS/DFARS Restrictions Apply to Government Use.2001
Galvin and colleagues describe a new set of molecular pathologies involving α-, β-, and γ-synuclein proteins and neurodegenerative diseases. Efforts to elucidate the pathobiology of synuclein proteins will lead to improved strategies for diagnosis and future therapies for this diverse group of emerging neurodegenerative diseases.
Tan and Ashizawa bring us up to date with a genomic classification of the inherited ataxias. Diagnosing by genotype and not phenotype is reinforced once more.
Barbot and colleagues describe the diagnostic clinical criteria of Portuguese patients affected with ataxia and ocular apraxia as an autosomal recessive disorder. Ataxia with occular apraxia is more common than previously suggested. Critical editorial comment is provided by David Dawson, MD.
Goetz and colleagues have studied dopamine receptor gene polymorphisms in Parkinson disease (PD) patients with and without hallucinations. There was no clear correlation between dopamine receptor gene polymorphism type and PD with hallucinations. The DRD3 allele 2 showed a borderline increased frequency among cases compared with controls. Further study is required.
Ondo and colleagues have studied patients with PD and essential tremor with unilateral or bilateral deep brain stimulation. Bilateral thalamic deep brain stimulation was more effective than unilateral stimulation at controlling bilateral appendicular and midline tremors in patients with essential tremor and PD. Overall functional disability improved only in patients with essential tremor. Bilateral deep brain stimulation should be considered if unilateral stimulation does not offer a satisfactory benefit.
Honnorat and colleagues find evidence suggesting a link between high levels of glutamic acid decarboxylase antibodies and cerebellar ataxia, particularly in women with insulin-dependent diabetes mellitus. Glutamic acid decarboxylase antibodies are emerging as an important diagnostic marker for sporadic cerebellar ataxia and may provide insight into the biology of this serious disorder.
Askmark and colleagues describe a series of patients with parkinsonism with neck extensor weakness resulting in head drop. Electrophysiologic studies suggest that the process is a myopathy, and several patients in this study had an autonomic disorder as well, suggesting that the spectrum may include multiple system atrophy (MSA).
Friess and colleagues describe patients with PD and MSA and their differential response to growth hormone released by apomorphine. They found that after a low dose of apomorphine, the increase in the plasma growth hormone concentration was significantly greater in patients with PD than in those with MSA or control subjects. Apomorphine appears to be a useful tool in identifying PD vs MSA, and also a differential specific deficit of central dopamine synthesis and release in the two patient groups.
Rascol and colleagues have compared the use of a selective D1-receptor agonist with levodopa in their study of patients with PD. Their data provide evidence that, in patients with PD, a D1 agonist induces the same antiparkinsonian and dyskinetic effects as levodopa.
Müller et al studied differences in the evolution of dysarthria and dysphagia in autopsy-confirmed parkinsonian disorders. The latency periods until onset of dysarthria and dysphagia clearly differentiated PD from atypical parkinsonian disorder, but failed to differentiate the various atypical parkinsonian disorders; survival after onset of dysphagia was similarly poor across all parkinsonian disorders. This study helps to define important clinical features in relation to specific pathologic processes. These findings will be useful in planning practical patient management.
Kluin and colleagues have correlated the types of dysarthria with neuropathologic features in patients with progressive supranuclear palsy. They find that the hypokinetic dysarthria of progressive supranuclear palsy results from degenerative changes in the substantia nigra and not in other basal ganglia structures.
Kirkwood et al have delineated the progression of symptoms in patients with Huntington disease (HD) in the early and middle stages of disease. In order to evaluate the efficacy of future therapeutic agents designed to delay or prevent HD progression, measures sensitive to cognitive function and behavioral abnormalities specific to HD are necessary. This detailed study is useful in that regard.
Schmitt and colleagues find that subjects with Williams syndrome have cerebral and cerebellar shapes significantly different from those of normal controls. Decreased volume of the corpus callosum may be associated with a decreased size of the splenium. Clinical and morphological evidence of myopathy in this syndrome, giving rise to hypotonia in infancy, delayed walking, joint contractures, scoliosis, and increased exhaustion on exertion, has been reported in some patients. Thus, patients may have a motor syndrome associated with a movement disorder. More commonly, patients have enhanced language ability and enhanced auditory memory as well as considerable social use of language in the presence of mental retardation. Abilities in playing musical instruments, loquaciousness, and engaging personality characteristics are well known. Thus, the finding of major changes in brain shape in this syndrome with behaviorial and motor alterations makes the structural brain observations provided by Schmitt and colleagues most interesting and insightful.
Denier and colleagues describe the Glu 1757 Lys missense mutation associated with episodic ataxia type 2 (EA2) in a family. Most mutations in the α1A subunit of CACNA1A in EA2 patients are caused by a truncated protein, whereas missense mutations have been associated with familial hemiplegic migraine. Here we find a missense mutation associated with EA2. These data strongly suggest that additional work is needed to fully establish the phenotype-genotype correlations for CACNA1A mutations. Jen and Geschwind provide critical editorial comment .
Gwinn-Hardy and colleagues describe parkinsonism in a large African American pedigree with autosomal dominant neurologic disease, members of which were shown to possess pathogenic CAG expansions in the MJD/SCA3 gene. Autosomal dominant parkinsonism should be evaluated for this mutation.
Soong et al studied patients with spinocerebellar ataxia type 6 using fluorine-18–labeled deoxyglucose and found significant hypometabolism in the cortex and basal ganglia as well as the cerebellar hemispheres and brainstem in patients with expanded CAG repeats in the spinocerebellar ataxia type 6 gene. These studies extend observations concerning altered glucose metabolism in this dominant ataxia.
This Month in Archives of Neurology. Arch Neurol. 2001;58(2):169-170. doi:10.1001/archneur.58.2.169