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This Month in Archives of Neurology
Arch Neurol. 2002;59:681-683.
 Neurotherapeutics 2002
This issue of the ARCHIVES is a theme issue on "Neurotherapeutics 2002."
It is our objective to emphasize new and emerging therapies for neurologic
disease. Editorials that emphasize new developments in neurotherapeutics are
included from Ira Shoulson, MD; David Pleasure, MD, and colleagues; Christopher
G. Goetz, MD, and Vanessa K. Hinson, MD, PhD; Louis R. Caplan, MD; John J.
Redington, MD, and Kenneth L. Tyler, MD; Hassan M. Fathallah-Shaykh, MD; Khurram
Bashir, MD, MPH, and John N. Whitaker, MD; Paul C. Van Ness, MD; and J. Ned
Pruitt II, MD, and Thomas R. Swift, MD.
Friedreich Ataxia: A Molecular Success Story
David R. Lynch and colleagues (SEE ARTICLE) provide a splendid clinical and molecular review of recent exciting developments
in the etiology of Friedreich ataxia. This is one of the major molecular genetic
success stories of this decade.
Intravenous Immunotherapy for Diabetic Neuropathy
Sharma and colleagues (SEE ARTICLE) describe their experience in treating diabetic demyelinating polyneuropathy
with intravenous immunoglobulin therapy. The result is of one of significant
clinical improvement in most patients in this study. It is an important article
from a therapeutic and conceptual point of view.
Demyelinating Neuropathy in Diabetes Mellitus
Sharma et al (SEE ARTICLE) describe
their experience with patients with diabetes mellitus who seem to have a predisposition
to develop chronic inflammatory demyelinating polyneuropathy. Their criteria
for this spectrum of demyelinating disease are unique and offer new thoughts
regarding the use of immunotherapy for diabetic demyelinating polyneuropathy.
Migrating Mononuclear Cells in Multiple Sclerosis
Gelati et al (SEE ARTICLE) , using
an in vitro model, have considered how intravenous methylprednisolone treatment
in patients with multiple sclerosis (MS) could influence transmigration of
mononuclear cells. They find that the absolute number of transmigrated mononuclear
cells from methylprednisolone-treated patients with MS significantly decreased
at 3 hours and increased again at 24 hours. Thus, their results indicate that
methylprednisolone does affect transmigration of mononuclear cells across
the blood-brain barrier and in so doing may affect activity and length of
disease. These observations may play a pivotal role in appreciating more fully
the pathogenesis of MS.
Bone Loss Due to Antiepileptic Drugs
Andress et al (SEE ARTICLE) have considered
the issue of bone loss in patients receiving long-term antiepileptic drug
(AED) therapy. Femoral neck bone mineral density by dual energy x-ray absorptiometry
(DEXA) was examined in patients receiving AEDs. Clearly, AED therapy does
cause significant bone loss at the hip in the absence of vitamin D deficiency,
and this loss can be measured using DEXA scanning. The syndrome is reversible
with calcium and vitamin D replacement therapy. Clinicians need to know of
this adverse effect of AEDs and of the means to easily monitor patients.
Homocysteine and Alzheimer Disease
Hogervorst and colleagues (SEE ARTICLE) find that higher homocysteine levels are an independent risk factor for moderate
to severe white matter changes in the cerebral hemispheres in patients with
Alzheimer disease (AD). Logistic regression shows that leukoaraiosis was more
prevalent in AD cases than in control subjects and that at an older age, higher
levels of total homocysteine were independently associated with an increased
risk of leukoaraiosis. Therapeutic lowering of elevated homocysteine levels
with folic acid is achievable and should be rigorously studied as a means
of affecting the level and extent of white matter changes associated with
AD.
DNA Damage, Antioxidants, and Alzheimer Disease
Mecocci and colleagues (SEE ARTICLE) measured lymphocyte DNA 8-hydroxy-2-deoxyguanosine (8-OHdG) content in patients
with Alzheimer disease (AD) compared with age-matched controls. Lymphocyte
DNA OhdG content was significantly higher and plasma levels of antioxidants
were significantly lower in patients with AD compared with controls. Their
findings support the view that lymphocyte 8 (OHdG) in patients with AD reflects
a condition of increased oxidative stress related to low antioxidant status.
Oxidative stress continues to emerge as a significant issue in the pathogenesis
of AD and emphasizes the need for more effective antioxidant therapies.
Budipine in Treating Parkinson Disease
Przuntek et al (SEE ARTICLE) have
conducted a clinical trial of budipine as an additional form of therapy to
a stable, optimally titrated level of the levodopa/dopadecarboxylase inhibitor,
bromocriptine, and selegiline in patients with idiopathic Parkinson disease.
Budipine provided further therapeutic benefit in these patients. This pharmacologic
approach may be of value in selected patients requiring additional therapy.
Testosterone for Parkinson Disease
Okun and colleagues (SEE ARTICLE) have found in their Parkinson disease (PD) registry that 35% of patients had
plasma evidence of testosterone deficiency. Five patients with PD were treated
with testosterone, with significant improvements in their refractory nonmotor
symptoms. It is an area of evaluation that needs more emphasis to provide
our patients with a fuller life.
Cognitive Impairment in Patients With Human Immunodeficiency Virus
De Ronchi and colleagues (SEE ARTICLE) find that low education, low CD4+ cell count, and homosexual/bisexual and
heterosexual risk behaviors are risk factors for cognitive impairment in persons
with seropositive human immunodeficiency virus 1. Antiretroviral therapy exerts
a beneficial effect in these patients and should be implemented early in the
disease course.
Interleukin 4 Gene in Panencephalitis
Inoue and colleagues (SEE ARTICLE) investigated the association of polymorphisms in cytokine, interferon, and
interleukin (IL) genes in patients with subacute sclerosing panencephalitis
(SSPE) in Japan. Their study found a distinct possibility that the IL-4 promoter gene –589T polymorphism with increased IL-4 synthesis
in combination with interferon regulatory factor-1 allele does confer increased
host genetic susceptibility to SSPE in this Japanese population. These markers
may be of considerable value in identifying at-risk persons in susceptible
populations.
Spectroscopic Imaging in Alzheimer Disease
Block and colleagues (SEE ARTICLE) have used fast-proton spectroscopic imaging of the hippocampus and the laterotemporal
and occipital lobes in patients with Alzheimer disease (AD) to detect regional
metabolic changes that resemble the expected pattern of neuronal loss in AD.
They find that N-acetylaspartate–total creatine
(phosphocreatine and creatine) ratios were significantly reduced in the left
and right hippocampus in patients with AD. Thus, neuronal function can be
measured quantitatively using this metabolic mapping technique as a diagnostic
means for AD, progression of disease, and potential response to new therapies.
Magnetic Resonance Imaging in Multiple System Atrophy and Parkinson
Disease
Bhattacharya and colleagues (SEE ARTICLE) have provided a comprehensive magnetic resonance imaging (MRI) assessment
of patients with multiple system atrophy with predominant parkinsonism (MSA-P)
and Parkinson disease (PD). The authors present detailed and clinically useful
MRI criteria to differentiate the clinical forms of MSA and PD and provide
a simple diagnostic algorithm for diagnosing this difficult spectrum of patients.
Crossed Cerebellar Atrophy
Teixeira and colleagues (SEE ARTICLE) have thoroughly analyzed the frequency and pathogenetic factors of crossed
cerebellar atrophy (CCA) in patients with epilepsy secondary to destructive
brain insults of early development. Specific clinical phenotypes are presented
and the results of varying levels of risk for CCA are given. This is a unique
and valuable clinical and neuropathologic correlation study that offers clear
insight into the basis of CCA.
Familial Parkinson Disease
Payami and colleagues (SEE ARTICLE) show that Parkinson disease (PD) has a significant familial component. They
find that compared with relatives of controls, age-specific risk of PD was
increased by 7.76-fold in the relatives of patients with early-onset disease
(P<.001) and by 2.95-fold in relatives of patients
with late-onset disease (P = .02). Parkinson disease
is both a genetic and environmentally induced disorder.
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