Thymectomy in Pemphigus Foliaceus: A Thirty-Year Observation.

Myasthenia gravis is an archetypal human autoimmune disease. Thymectomy is proven effective by controlled clinical trials, and is commonly part of the immunotherapeutic approach when myasthenia creates generalized weakness. Pemphigus foliaceus is also autoimmune but treated medically; and thymectomy is not part of therapy unless thymoma is discovered.

Identifying potential targets for prevention and treatment of amyotrophic lateral sclerosis based on a screen of medicare prescription drugs.

: Few well-established factors are associated with risk of amyotrophic lateral sclerosis (ALS). We comprehensively evaluate prescription drugs use in administrative health claims from U.S.

Relationship of statins and other cholesterol-lowering medications and risk of amyotrophic lateral sclerosis in the US elderly.

Objective: Statins are commonly prescribed drugs that have been inconsistently associated with amyotrophic lateral sclerosis (ALS) risk. We examined associations between ALS risk and overall statin use, statin categories based on lipophilicity and other cholesterol-lowering medications, in Medicare beneficiaries.

Methods: In this nation-wide population-based case-control study, 10,450 Medicare participants (ages 66-89 years) diagnosed with ALS, using Medicare Parts A and B claims, between 1 January 2008 and 31 December 2014, were frequency-matched to 104,500 controls on age, sex, and selection year.

Associations between cancer and Parkinson's disease in U.S. elderly adults.

Background: Several studies suggest that cancer is reduced before and after a Parkinson's disease (PD) diagnosis. However, determining relationships among diseases of ageing is challenging due to possible biases in ascertaining disease. This study evaluates the PD and cancer relationship, addressing potential biases.

Calbindin-D28K is increased in the ventral horn of spinal cord by neuroprotective factors for motor neurons.

Slow glutamate-mediated neuronal degeneration is implicated in the pathophysiology of motor neuron diseases such as amyotrophic lateral sclerosis (ALS). The calcium-binding proteins calbindin-D28K and parvalbumin have been reported to protect neurons against excitotoxic insults. Expression of calbindin-D28K is low in adult human motor neurons, and vulnerable motor neurons additionally may lack parvalbumin.

The risk of amyotrophic lateral sclerosis after cancer in U.S. elderly adults: a population-based prospective study.

Although epidemiologic studies have examined the risk of amyotrophic lateral sclerosis (ALS) in relation to cancer, none have been large population-based studies using incident ALS and adjusting for medical surveillance. Addressing those limitations, all first primary cancer cases from the Surveillance, Epidemiology and End Results (SEER) Program (1992-2005), linked to Medicare claims data were used. Cases were followed from cancer diagnosis until the earliest date of ALS diagnosis, a break in Medicare claims data, death, age 85 or December 31, 2005.

Vitamin E serum levels and controlled supplementation and risk of amyotrophic lateral sclerosis.

There are no observational studies or controlled trials of amyotrophic lateral sclerosis (ALS) and circulating α-tocopherol (vitamin E) for prevention of ALS. This study addresses that gap. The study population comprised 29,127 Finnish male smokers, aged 50-69 years, who participated in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study, which is both a prospective cohort and a randomized, double-blind, placebo-controlled trial of α-tocopherol (50 mg/day) and β-carotene (20 mg/day).

The association between cancer and amyotrophic lateral sclerosis.

Objective: Increasing evidence suggests that some neurodegenerative disorders, such as Parkinson's disease, are inversely related to cancer. Few epidemiologic studies have examined the relationship between cancer and amyotrophic lateral sclerosis (ALS), another major neurodegenerative disease. This study addresses that gap.

Etiology of limb girdle muscular dystrophy 1D/1E determined by laser capture microdissection proteomics.

Limb girdle muscular dystrophy 1D/1E (OMIM nomenclature LGMD1D, Human Gene Nomenclature Committee LGMD1E), a skeletal and cardiac myopathy, has previously been linked to chromosome 6q23. We used laser capture microdissection to isolate cytoplasmic inclusions from skeletal muscle from a patient with LGMD1D/1E, performed mass spectrometry-based proteomics on these minute inclusions, and identified through bioinformatics desmin as their major constituent. Sequencing in this patient and family members identified the genetic basis of the previously reported 6q23 linked LGMD1D/1E to be due to an intron splice donor site mutation (IVS3+3A>G) of the desmin gene located on chromosome 2q35.

Agents and mechanisms of toxic myopathy.

Purpose Of Review: Mechanistic-based research has made possible a more pathophysiologic approach to certain drug-induced muscle disorders, especially those caused by the lipid-lowering statin family of drugs, but also myopathies caused by antimicrotubule drugs, mitochondrial toxins, foods, and purported nutriceutical remedies. This is a critical review of those syndromes that are most well founded on evidence of challenge/de-challenge/re-challenge, case-controls, or experimental controls.

Recent Findings: Statins are well tolerated drugs with very high safety windows in skeletal muscle, and third-generation statins now under development offer the hope of even less risk of toxic myopathy.

Wernicke's encephalopathy: beyond alcoholism.

Background: A 17-year-old pregnant woman presented to hospital at 19 weeks' gestation with an 8-week history of hyperemesis gravidarum, 16.8 kg of weight loss, and new-onset weakness, dizziness and blurred vision. Examination of the patient showed confusion, papilledema, ophthalmoparesis, nystagmus, reduced hearing and truncal ataxia.

Amyotrophic lateral sclerosis mortality in 1.9 million US cancer survivors.

Background: Large cancer registries offer the opportunity to explore and generate hypotheses about the pathogenesis of cancer and other diseases, including neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS).

Methods: Using data from nine population-based cancer registries of the Surveillance, Epidemiology, and End Results (SEER) Program of the US National Cancer Institute (NCI) and death certificates, we followed 1.9 million cancer survivors who were diagnosed between 1973 and 2000 and who survived at least 1 year, through the year 2000.

Exocytotic "constipation" is a mechanism of tubulin/lysosomal interaction in colchicine myopathy.

Colchicine, a known microtubule disrupting agent, produces a human myopathy, characterized by accumulation of lysosomes. We have created a reliable animal model of colchicine myopathy that replicates the subacute myopathy seen in humans, reproducing the chronic proximal weakness and vacuolar changes in nonnecrotic myofibers. If a microtubule network plays a role in lysosomal function in muscle, disturbance of it could alter degradation of intrinsic membrane receptors, presumably at some intracellular processing site or at exocytosis.

Identification of the neuroprotective molecular region of pigment epithelium-derived factor and its binding sites on motor neurons.

Pigment epithelium-derived factor (PEDF), a member of the serine protease inhibitor (serpin) family, is a survival factor for various types of neurons. We studied the mechanisms by which human PEDF protects motor neurons from degeneration, with the goal of eventually conducting human clinical trials. We first searched for a molecular region of human PEDF essential to motor neuron protection.

Pigment epithelium-derived factor is elevated in CSF of patients with amyotrophic lateral sclerosis.

Pigment epithelium-derived factor (PEDF), a recently defined retinal trophic factor and anti-angiogenic factor for the eye, is also present in the CNS and is a motor neuron protectant. We asked whether PEDF levels in CSF are altered in patients with amyotrophic lateral sclerosis (ALS). Pigment epithelium-derived factor protein was detected by quantitative western blot analysis with a PEDF-specific antiserum.

Additivity and potentiation of IGF-I and GDNF in the complete rescue of postnatal motor neurons.

Background: Both growth and survival of motor neurons may depend on multiple neurotrophic factors. Individually, insulin-like growth factor I (IGF-I) and glial cell line-derived neurotrophic factor (GDNF) are potent neurotrophic/survival factors for postnatal motor neurons.

Methods: We used an organotypic spinal cord model of glutamatergic degeneration in ALS to investigate whether IGF-I and GDNF interact to enhance motor neuron survival, their trophic effect on choline acetyltransferase (ChAT) activity, and their effect on neurite outgrowth.

A deceptive case of amyloid myopathy: clinical and magnetic resonance imaging features.

Amyloid myopathy is a well-described, increasingly recognized clinical entity. Similar to inflammatory myopathies, amyloid myopathy presents with proximal muscle weakness and can be associated with elevated levels of muscle enzymes. We report the case of a 58-year-old woman who, at presentation to her physician with proximal muscle weakness and congestive heart failure, was antinuclear antibody positive and had muscle biopsy findings "consistent with inflammatory myopathy.

Delayed application of IGF-I and GDNF can rescue already injured postnatal motor neurons.

IGF-I, GDNF, and other neurotrophic factors, when applied at the time of injury, can protect postnatal motor neurons from slow glutamate injury in organotypic spinal cord. However, in human spinal cord diseases, motor neuron injury is already established when treatment could begin. We tested whether neurotrophic factors can protect already-injured motor neurons, and whether combinations of factors can further lengthen the therapeutic time window.

Preclinical testing of neuroprotective neurotrophic factors in a model of chronic motor neuron degeneration.

Many neurotrophic factors have been shown to enhance survival of embryonic motor neurons or affect their response to injury. Few studies have investigated the potential effects of neurotrophic factors on more mature motor neurons that might be relevant for neurodegenerative diseases. Using organotypic spinal cord cultures from postnatal rats, we have demonstrated that insulin-like growth factor-I (IGF-I) and glial-derived neurotrophic factor (GDNF) significantly increase choline acetyltransferase (ChAT) activity, but brain-derived neurotrophic factor (BDNF), neurotrophin-4 (NT-4/5), and neurotrophin-3 (NT-3) do not.

Occult presentation of myotonia congenita in a 15-year-old athlete.

A case of myotonia congenita in an adolescent athlete was presented. Although this is a rare condition unknown to many treating physicians, the key to diagnosis was provocation of the patient's symptoms of muscle "tightening" and "cramping" during sustained exercise. The diagnosis would have been missed in routine office examinations with the patient at rest.

Pigment epithelium-derived factor (PEDF) protects motor neurons from chronic glutamate-mediated neurodegeneration.

Although pigment epithelium-derived factor (PEDF) is a neurotrophic factor that may aid the development, differentiation, and survival of adjacent neural retinae, the wider distribution of PEDF mRNA in the central nervous system suggested to us that this factor could have pleiotropic neurotrophic and neuroprotective effects on nonretinal neurons. We examined the distribution of PEDF mRNA and its transcript in the spinal cord. By immunohistochemistry and western blot analysis using an antihuman PEDF antiserum of known specificity, we found that PEDF protein is present in spinal cord, cerebrospinal fluid, and skeletal muscle and that its mRNA appears concentrated in motor neurons of the human spinal cord.

Neuroprotective utility and neurotrophic action of neurturin in postnatal motor neurons: comparison with GDNF and persephin.

Neurturin and persephin are recently discovered homologs of glial cell line-derived neurotrophic factor (GDNF). Here, we report that neurturin, like GDNF, increases the choline acetyltransferase activity of normal postnatal motor neurons, induces neurite outgrowth in spinal cord, and potently protects motor neurons from chronic glutamate-mediated degeneration. Persephin, in contrast, does not appear to have neurotrophic or neurite-promoting effects on mature motor neurons and may instead worsen the glutamate injury of motor neurons.