Robert Darnell has pioneered the use of paraneoplastic antibodies to screen complementary DNA (cDNA) expression libraries for clones of DNA that encode the target onconeural antigens. The paraneoplastic neurologic disorder (PND) cDNAs have allowed new clinical studies, in which the disease and its pathophysiologic mechanisms have given fresh insights into tumor immunity and autoimmune brain disease. He reviews the molecular mechanisms underlying the major PNDs and associated antigens. Insights into potential therapies for the major PNDs and related cancers are outlined in this elegant and insightful review.
Lu and colleagues report the presence of parkinsonism in families with spinocerebellar ataxia type 2 (SCA2) in Taiwan. They found expanded CAG repeats of SCA2 in 7 patients from 4 parkinsonian families (about 10% of their familial parkinsonian series). Thus, SCA2 can manifest parkinsonism as a major feature and is associated with a lower abnormal range of CAG repeat length and with a late age at onset. Spinocerebellar ataxia type 2 should be considered as a genetic basis for familial parkinsonism. Editorial perspective is provided by Katrina Gwinn-Hardy, MD.
Linfante and colleagues studied 23 patients with extracranial carotid artery stenting (CAS) who were otherwise ineligible for surgery according to the criteria of the North America Symptomatic Carotid Endarterectomy Trial (NASCET). The latest generation self-expanding stents were used. Carotid artery stenting was successful in all cases, with an average residual stenosis of less than 20%. Thus, extracranial CAS using the latest generation self-expanding stents is a valid alternative treatment in high-risk or NASCET-ineligible patients.
Sandroni and colleagues compared patients who were seropositive and seronegative for ganglionic acetylcholine receptor (AChr) autoantibodies. The seropositive group had a subacute onset, with significant overrepresentation of abnormal pupillary responses, sicca complex, and lower gastrointestinal tract dysautonomia compared with the seronegative group. Their observations support the view that ganglionic AChR antibodies are diagnostically and pathophysiologically important.
Chinese patients with hereditary spastic paraplegia were studied for mutations in the spastin gene (SPG4) by Tang and colleagues in China. Three novel mutations were detected in 4 affected individuals, including 2 missense mutations (T1258A and A1293G) and 1 deletion mutation (1668-1670delCTA). This is the first report of SPG4 mutations in China.
The essential baseline characteristics of mild cognitive impairment (MCI) were defined by Grundman et al to differentiate patients with MCI from patients with Alzheimer disease (AD) and normal elderly controls. They found that patients with MCI are more impaired in memory tasks compared with normal controls, but they have less severe impairments in other cognitive domains. Patients with MCI had hippocampal volumes that were intermediate between normal controls and AD patients. They conclude that AD prevention trials with MCI patients appear to be a promising approach for detecting, intervening, and delaying clinical AD while the disease is still in a transitional clinical stage.
In the Cardiovascular Health Study, 622 elderly participants without a history of transient ischemic attack or stroke were studied by Longstreth et al for homocysteine levels and findings on brain magnetic resonance imaging (MRI). An association was seen for an MRI pattern combining infarcts and a high white matter grade. Their findings support the view that elevated total homocysteine levels may cause subcortical vascular encephalopathy with diffuse white matter lesions and lacunes.
Afunctional definition of cognitive reserve (CR) is the ability of an individual to cope with advancing brain disease so that he or she remains free of symptoms. Scarmeas and colleagues investigated CR-mediated differential brain activation in patients with Alzheimer disease (AD) compared with healthy elderly controls. Using H215O positron emission tomography, they imaged 12 AD patients and 17 healthy controls while the subjects performed a serial recognition memory task. Evidence is presented to support the concept that CR provides incremental abilities to delay or modify cognitive loss in AD.
The effect of vitamins C and E to reduce the risk of Alzheimer disease (AD) was studied by Zandi and colleagues. They found that the use of vitamin C and E supplements in combination was associated with reduced AD prevalence and incidence. Antioxidant supplements merit further study as agents for the primary prevention of AD.
Welter et al studied the effects of high-frequency subthalamic nucleus (STN) stimulation on the neuronal activity of STN neurons in patients with Parkinson disease (PD) as a means of defining the effectiveness of this therapeutic modality. They found that stimulation at a frequency greater than 40 Hz applied within the STN significantly decreased the firing frequency and increased the burst-like activity in the firing pattern of STN neurons. Their evidence supports the view that the beneficial effects of high stimulation result from a change in the firing pattern of cellular discharge and a blockade of the spontaneous overactivity of STN neurons.
Effects of subthalamic nucleus (STN) high-frequency stimulation on neuronal activity in the structure (140 Hz, 60 microseconds, 2 mA). A, High-frequency stimulation applied within the STN: mean firing rate of 21 cells before, during, and after stimulation (left); distribution of the firing pattern of these 21 cells before, during, and after stimulation (right). B, High-frequency stimulation applied above the STN: mean firing rate of 8 cells before, during, and after stimulation (left); distribution of the firing pattern of these 8 cells before, during, and after stimulation (right).
Total dopaminergic drug dose rather than the specific dopamine agonist used is the best predictor of daytime sleepiness in patients with Parkinson disease who are receiving dopamine agonist therapy as reported by Razmy and colleagues. Polysomnographic monitoring for impaired daytime sleep latency is of clinical diagnostic value in evaluating this adverse effect of therapy.
Guis and colleagues report a family with malignant hyperthermia (MH). Multiminicores on muscle biopsy were observed in MH-susceptible patients. These multiminicore lesions may be secondary to mutations in the ryanodine receptor gene. As a consequence, these patients must be distinguised from patients with multiminicore disease and from other MH-susceptible patients for whom multiminicores are not observed. Editorial perspective is provided by Katherine D. Mathews, MD.
This Month in Archives of Neurology. Arch Neurol. 2004;61(1):18-19. doi:10.1001/archneur.61.1.18