Incontinence and troublesome behaviors predict institutionalization in dementia.

Factors predicting the early institutionalization of demented patients were studied in 143 outpatients using univariate and multivariate life-table methods. Four types of factors were evaluated for prognostic value: severity of functional impairment, behavioral disorders, individual patient characteristics, and type of caregiver. After follow-up of 19 +/- 12 months, 51 patients had been institutionalized.

Potassium channel blockers potentiate impulse inhibition by local anesthetics.

The ability of local anesthetics to reduce the amplitude of compound action potentials (CAP) of frog sciatic nerve was examined in the absence and presence of agents that selectively block K+ channels. In the presence of lidocaine concentrations that inhibit the CAP by about 20% at low frequencies of stimulation (1 per min, "tonic inhibition"), the addition of the K(+)-channel blocker tetraethylammonium ion (TEA, 12 mM) increased this inhibition by another 15%. Furthermore, the use-dependent inhibition induced by lidocaine at higher stimulation frequencies (5-20 Hz, "phasic inhibition") was markedly enhanced by TEA: at 20 Hz it increased from 35% with lidocaine alone to 63% with lidocaine plus TEA.

Primary progressive aphasia with focal neuronal achromasia.

We describe the clinical, radiologic, neuropsychological, and neuropathologic features of a 69-year-old man with a 3-year history of progressive transcortical expressive aphasia. Neuropsychological testing showed progressive dysfunction of expressive language. Neuropathologic examination demonstrated focal cortical degeneration involving the left superior frontal gyrus, with swollen achromasic neurons and no evidence of Alzheimer's disease, Pick's disease, Creutzfeldt-Jakob disease, Lewybody disease, or other dementing disorders.

Expression of heat shock proteins in Alzheimer's disease.

In an investigation of heat shock proteins (HSPs) in the brains of Alzheimer's disease (AD) patients and cognitively intact control subjects, we found that 2 HSPs, termed "HSP72" and "GRP78," underwent major changes in expression in AD. HSP72, which was present at very low levels in control brains, increased dramatically in AD patients, and was localized exclusively in neuritic plaques and neurofibrillary tangles. We hypothesize that HSP72 is induced as an early response to the formation of abnormal proteins, perhaps targeting them for proteolysis.

Suppression of immune responses to acetylcholine receptor by interleukin 2-fusion toxin: in vivo and in vitro studies.

The pathogenesis of the autoimmune disease, myasthenia gravis (MG), involves an antibody-mediated attack against acetylcholine receptors (AChRs). Since the relevant antibody response is T cell dependent, a therapeutic strategy aimed at T lymphocytes actively participating in the immune reaction to AChR should result in relatively selective suppression of AChR antibody. During an active immune response, T cells express receptors for interleukin 2 (IL2).

T-cell vaccination in experimental myasthenia gravis: a double-edged sword.

Immunization with antigen-specific T cells has been used successfully in the treatment of several T cell-mediated experimental autoimmune diseases, including experimental allergic encephalomyelitis, thyroiditis, and adjuvant arthritis. The aim of this study was to determine whether T-cell vaccination could be used to down-regulate specifically the antibody response to AChR in experimental autoimmune myasthenia gravis (EAMG), an antibody-mediated disorder. We produced T cells specific for the acetylcholine receptor (AChR) by immunizing Lewis rats with torpedo AChR, harvesting the regional lymph node cells, and restimulating them in vitro with AChR.

Heteroplasmy in chronic external ophthalmoplegia: clinical and molecular observations.

Chronic progressive external ophthalmoplegia (CPEO) describes a recognizable clinical syndrome frequently associated with variable dysfunction in other organ systems. Histochemical and biochemical studies suggested primary dysfunction of oxidative phosphorylation. This has recently been confirmed by demonstration of partially deleted as well as normal mitochondrial DNA--heteroplasmy--in some of these patients, most of them sporadic.

The indusium griseum: is it involved in Alzheimer's disease?

The histopathology of the indusium griseum (IG), a displaced hippocampal anlage, was studied in five patients with Alzheimer's disease (AD) and five controls. In the AD group, the IG had occasional neurons with granulovacuolar change (GVD) and rare Hirano bodies (HB), but no senile plaques (SP), neurofibrillary tangles (NFT), or neurons staining for phosphorylated neurofilament antigen. There was a slight but not statistically significant diminution of neurons within the IG.

Total lymphoid irradiation and antigen-specific tolerance: future therapy for experimental myasthenia gravis?

Total lymphoid irradiation (TLI) is effective in the immunosuppressive treatment of human and experimental autoimmune disorders, including experimental autoimmune myasthenia gravis (EAMG). Under certain circumstances. TLI may facilitate the induction of specific tolerance to antigens present during or shortly after the TLI treatment.

The prognosis in Alzheimer's disease. 'How far' rather than 'how fast' best predicts the course.

Clinical features at the initial examination of 42 patients with probable Alzheimer's disease were tested for prognostic value at subsequent follow-up of 54 +/- 25 months. These potential prognostic features were of three types: degree of severity features (eg, IQ scores); variable clinical features (eg, extrapyramidal signs); and individual distinguishing features (eg, gender, education, and age). The power of these potential prognostic features to predict prognosis was assessed using the Kaplan-Meier life-tables method and the Cox proportional hazards model.

Abnormal excitatory amino acid metabolism in amyotrophic lateral sclerosis.

Recently, the excitatory amino acid neurotransmitter glutamate was implicated in the pathogenesis of a variety of chronic degenerative neurological diseases in humans and animals. This report describes abnormalities in excitatory amino acids in the central nervous system of 18 patients with amyotrophic lateral sclerosis (ALS). The concentration of the excitatory amino acids glutamate and aspartate in the cerebrospinal fluid were increased significantly (p less than 0.

A sensitive rosetting assay for detection of acetylcholine receptor antibodies using BC3H-1 cells: positive results in 'antibody-negative' myasthenia gravis.

Antibodies to acetylcholine receptor (AChR) were measured in a group of patients with myasthenia gravis (MG), some of whom had previously been classified as 'antibody negative' using the standard anti-AChR radioimmunoassay (RIA). AChR antibodies were measured using the rosetting assay, a new detection method which utilizes protein A-coated red blood cells and live BC3H-1 cells, a murine cell line which expresses muscle nicotinic AChR. The results of the rosetting assay were compared with those obtained in the anti-AChR RIA.

Antigen-specific suppressor macrophages induced by culture with cyclosporine A plus acetylcholine receptor.

Suppressor cells specific for the acetylcholine receptor (AChR) can readily be induced by culturing spleen cells from rats with experimental autoimmune myasthenia gravis in medium containing cyclosporine A plus AChR. We describe here the purification and characterization of novel antigen-specific suppressor cells, which appear to be macrophages, from these cultures. The cells were adherent to plastic, very large, and of low buoyant density.

Molecular mimicry and myasthenia gravis. An autoantigenic site of the acetylcholine receptor alpha-subunit that has biologic activity and reacts immunochemically with herpes simplex virus.

The large majority of patients with the autoimmune disease myasthenia gravis characteristically have detectable antibodies against the acetylcholine receptor (AChR). We used synthetic peptides to identify antibodies in sera of myasthenia gravis patients reactive with the human acetylcholine receptor (HuAChR) alpha-subunit, residues 160-167. Affinity purification of these antibodies, using the HuAChR alpha-subunit 157-170 peptide immobilized on thiopropyl-Sepharose, yielded IgG antibodies that bound to the native AChR and inhibited the binding of alpha-bungarotoxin to the receptor.

Novel drug delivery systems: opportunities and caveats.

Programmed infusion pumps, polymers and neural transplants provide the capability of delivering a variety of agents to specific locations in the central nervous system. If a necessary or therapeutically useful substance cannot otherwise penetrate the blood-brain barrier, or must be delivered to a precise location in the CNS, these strategies may be of value in neurologic disease. The possibility of transplanting functioning tissue into the brain raises the hope of providing "new parts for old.

Ocular pseudomyasthenia or ocular myasthenia 'plus': a warning to clinicians.

Myasthenia gravis (MG) commonly presents with weakness and fatigability of the lids and extraocular muscles, which respond to treatment with anticholinesterase medication. However, certain intracranial mass lesions may mimic these features of MG; alternatively, MG may mask the signs of a coexistent intracranial mass. We describe 8 patients originally diagnosed as having MG by knowledgeable clinicians, in whom an intracranial lesion instead of, or in addition to, MG was later identified.

Amyotrophic lateral sclerosis: an unconventional autoimmune disease?

The possibility of an autoimmune mechanism of pathogenesis in amyotrophic lateral sclerosis has long been considered, but the evidence to support a conventional autoimmune process, reviewed here, is inconclusive. However, antibodies that react in vitro with gangliosides have recently been found in sera of a large majority of patients with classical amyotrophic lateral sclerosis and other motor neuron syndromes. A working hypothesis is proposed, suggesting how antibodies might be related to the disease process.

Neurotransmission regulates stability of acetylcholine receptors at the neuromuscular junction.

The majority of acetylcholine receptors (AChRs) at normally innervated neuromuscular junctions are stable, with a half-life averaging about 12 d in most rodent muscles. Following denervation, the AChRs turn over much more rapidly after a lag period. The mechanism by which motor nerves normally maintain stabilization of junctional AChRs is not yet known.

Neural regulation of mRNA for the alpha-subunit of acetylcholine receptors: role of neuromuscular transmission.

Levels of mRNA for acetylcholine receptor (AChR) subunits are relatively low in innervated skeletal muscles. Following denervation they rise rapidly, leading to increased AChR synthesis. The mechanism by which motor nerves normally regulate these mRNA levels is not yet known.

Differential effects of prednisone and cyclophosphamide on autoantibodies in human neuromuscular disorders.

We compared the effects of treatment of patients with prednisone or cyclophosphamide on a series of different types of autoantibodies. Levels of antiacetylcholine receptor (anti-AChR) antibodies and of antibodies to GM1 and GD1a gangliosides were measured in patients with a variety of neuromuscular disorders before and after treatment. Most patients had several autoantibodies present.