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This Month in Archives of Neurology
December 2003

This Month in The Archives of Neurology

Arch Neurol. 2003;60(12):1675-1677. doi:10.1001/archneur.60.12.1675
Treating Parkinson Disease Circa 2003

Shults provides a superb discussion related to pertinent issues in treatment for Parkinson disease (PD). Is there a treatment that slows the progression of PD? Which medication(s) should be used first in the treatment of PD? What should be done for patients who have begun to have motor fluctuations and/or dyskinesia? What is the role of surgery in PD, and which surgical treatment is best? What can be done for patients with cognitive compromise and/or hallucinations? Are there new treatments on the horizon for PD? He has provided clear and compelling replies to each of these questions.

Metal Chelation Therapy for Alzheimer Disease

Ritchie and colleagues used metal chelation therapy for patients with Alzheimer disease (AD). They show that treatment with clioquinol, a metal-protein attenuating compound that inhibits zinc and redox-active copper ions from binding to β-amyloid (Aβ), results in promoting Aβ dissolution and diminishing its toxic properties, slowing the rate of cognitive loss in a severely affected group of AD patients. Plasma Aβ42 levels declined and plasma zinc levels rose in the clioquinol-treated group. These findings offer an innovative strategy for slowing cognitive loss in patients with AD. Editorial perspective is provided by Roger N. Rosenberg, MD.

Mean ± SE change from baseline in cognitive abilities (as assessed with the cognitive score of the Alzheimer's Disease Assessment Scale [ADAS-cog]). Stratification by severity within the treatment arms is shown (less severely affected, ADAS-cog score of <25; more severely affected, ADAS-cog score of ≥25). Asterisk indicates P= .01; dagger, P= .02.

Mean ± SE change from baseline in cognitive abilities (as assessed with the cognitive score of the Alzheimer's Disease Assessment Scale [ADAS-cog]). Stratification by severity within the treatment arms is shown (less severely affected, ADAS-cog score of <25; more severely affected, ADAS-cog score of ≥25). Asterisk indicates P= .01; dagger, P= .02.

Cerebrospinal Fluid Levels of Tau and β-Amyloid as Biomarkers in Alzheimer Disease

Clark and colleagues correlated cerebrospinal fluid (CSF) tau and β-amyloid (Aβ) levels with final dementia diagnosis. They found that elevated CSF tau levels are associated with the pathologic changes in AD and can be used to distinguish AD from other forms of dementia, including frontal dementia and dementia with Lewy bodies.

Stroke and Risk of Alzheimer Disease

Honig and colleagues studied the association between a clinical history of stroke and subsequent risk of Alzheimer disease (AD). In a large cohort of individuals without dementia, they determined the incidence rates for AD among those with and without stroke. The annual incidence rate for AD was 5.2% among individuals with stroke vs 4% for those without stroke. The hazards ratio for AD among those with a history of stroke was 1.6 compared with those without stroke. Of interest is the finding that of the vascular risk factors, hypertension, diabetes, and heart disease, only diabetes related to risk of AD in the absence of stroke.

Intracranial Hypotension

Schievink describes the diagnostic difficulties and diagnostic delay associated with spontaneous intracranial hypotension. Ninety-four percent of patients in this cohort were initially diagnosed incorrectly, and many had a significant diagnostic delay before intracranial hypotension was identified. Increasing the awareness of spontaneous intracranial hypotension is emphasized, and important clinical and diagnostic issues are carefully reviewed.

Rotigotine Patch for Parkinson Disease

The Parkinson Study Group assessed the efficacy and safety of rotigotine (D2 dopamine receptor agonist) patches (silicone-based transdermal system) for treating patients with Parkinson disease. Rotigotine-treated patients showed significant dose-related improvement in scores on the motor and activities of daily living subscales of the Unified Parkinson's Disease Rating Scale compared with controls. This study confirms previous findings that a dopamine agonist can be effectively and safely delivered via transdermal administration.

Diffusion-Weighted Imaging and Acute Stroke

Kang and colleagues describe the different topographic patterns in acute ischemic stroke. Lesion patterns on diffusion-weighted imaging (DWI) were classified into single lesions, scattered lesions in 1 vascular territory, and multiple lesions in multiple vascular territories. They found that early DWI lesion patterns are associated with specific causes of stroke. These patterns provide early clues to the cause of stroke. Their findings are of great interest and provide useful information for patient management.

Acute Atrophy in Active Multiple Sclerosis

Hardmeier and colleagues tested whether atrophy can be detected over short intervals and correlated these findings in relationship to the degree of activity of patients with multiple sclerosis (MS). They found that the brain parenchymal fraction showed significant brain atrophy over short intervals in patients with active disease. These findings will be of value in determining the therapeutic effectiveness of drug interventions in patients with active relapsing remitting MS.

Platelet Amyloid Precursor Protein in Mild Cognitive Impairment

Borroni et al evaluated the potential role of platelet amyloid precursor protein (APP) forms ratio (APPr) in predicting progression from mild cognitive impairment (MCI) to Alzheimer disease (AD). They found that within 2 years, patients who progressed to AD from MCI showed a significant decrease in baseline APPr values compared with stable MCI subjects and patients who developed other types of dementia. These findings confirm and extend their previous observations that the platelet APPr biomarker is a useful predictor of disease progression.

Cholinergic Function in Parkinson and Alzheimer Dementia

Bohnen and colleagues studied in vivo cortical acetylcholinesterase (AChE) activity in patients with Alzheimer disease (AD), Parkinson disease (PD) with dementia, PD without dementia, and normal controls using AChE positron emission tomography. Compared with controls, mean cortical AChE activity was lowest in patients with PD with dementia, followed by patients with PD without dementia. The mean cortical AChE activity was relatively preserved in AD except for a regionally selective involvement of the lateral temporal cortex. Thus, their findings support the view that reduced cortical AChE activity is more characteristic of dementia associated with PD than early AD. Further, these data support the view that dementia with PD and dementia with Lewy bodies lie on a common disease spectrum with respect to cholinergic deficits.

Genetics of Spinocerebellar Ataxia Type 14

Yabe and colleagues describe their clinical and genetic analyses of spinocerebellar ataxia type 14 (SCA14) in a Japanese family. The locus of mutation was mapped to chromosome 19q13.4-qter. A novel missense mutation, Gln127Arg, was identified in all affected members of this family in the protein kinase C gamma gene. These findings define and extend the molecular and genetic basis of this type of SCA.

Electricity and Diagnosing Chronic Inflammatory Demyelinating Polyneuropathy

Magda and colleagues analyzed current electrodiagnostic criteria for chronic inflammatory demyelinating polyneuropathy (CIDP) and found them insensitive and inadequate to diagnose this condition in a substantial number of patients. More definite inclusive criteria for CIDP that allow identification of patients in routine clinical practice are needed.

Japanese Encephalitis

Kalita et al compared a series of children and adults with Japanese encephalitis (JE). They found that children with JE are more likely to have dystonia and a poor outcome compared with adults at 6 months. The reasons and factors involved in differences in outcomes for children and adults are discussed.

Motor Neuron Disease Genes

Mutations in the ALS2 gene were studied by Hand and colleagues in families with motor neuron disease and in sporadic cases. Twenty-three novel sequence variants were detected in the ALS2 gene, but none were disease associated. Mutations in the ALS2 gene are not a common cause of motor neuron disease, and caution is indicated in interpreting the significance of ALS2 polymorphisms.

Treating Spasticity in Multiple Sclerosis

Hawker and colleagues studied levetiracetam, a second-generation antieplieptic drug, for its value in treating spasticity in patients with multiple sclerosis. It is effective in reducing phasic but not tonic spasticity. Large, well-controlled clinical trials are now needed to confirm these important pilot study findings.

Testing Memory

Tang-Wai et al tested and compared the Mini-Mental State Examination (MMSE) with the Short Test of Mental Status (STMS) in patients to detect or predict mild cognitive impairment (MCI). Of interest, compared with the MMSE, the STMC was better able to document MCI and was more sensitive in detecting deficits in cognition in individuals who were normal but then later declined. The STMS is a new component that is highly valuable for diagnosing MCI, but as the authors state, clinical judgment and detailed cognitive testing are integral in the final analysis to make a diagnosis of MCI.