Rehabilitation for paraplegia caused by neuromyelitis optica: a case report.

STUDY DESIGN: Single case report. OBJECTIVE: We present a case of paraplegia due to neuromyelitis optica (NMO) with poor rehabilitation outcome. SETTING: University hospital, Japan. CASE REPORT: A 27-year-old woman with NMO presented with T5 paraplegia of ASIA impairment scale grade A. Spinal cord magnetic resonance imaging revealed a lesion spanning C3 to L1 level. After acute phase treatment, flaccid paraplegia below T5 and a T2-weighted hyperintense lesion from T6 to T10 level remained. Rehabilitation aimed at independence of activities of daily living with wheelchair assistance, including transfer activity, was provided for 19 months. However, flaccid paralysis of the trunk and limbs persisted, and safe independent transfer was not achieved. CONCLUSION: Spinal lesions spanning many vertebral segments, a characteristic of NMO, can cause extensive flaccid paralysis of the trunk and limbs. Rehabilitation may achieve poorer functional recovery than that for spinal cord injury.

Anti-annexin A5 antibodies in reproductive failures in relation to antiphospholipid antibodies and phosphatidylserine.

PROBLEM: The presence of IgG anti-annexin A5 (IgGalphaA5) and/or antiphospholipid antibodies (aPL) are risk factors associated with recurrent spontaneous abortion. Problems are whether IgA antiannexin A5 (IgAalphaA5) is pathogenic, and how IgGalphaA5 works. METHOD OF STUDY: Blood samples from 238 patients with early recurrent spontaneous abortion, 48 patients with recurrent in vitro fertilization-embryo transfer failure, 179 non-pregnant women and 120 pregnant controls were tested for IgAalphaA5 by enzyme-linked immunosorbent assay. We also determined if IgGalphaA5 appeared coincident with aPL. The antigenic epitope(s) recognized by IgGalphaA5 was investigated. RESULTS: We observed no difference between patients and controls for IgAalphaA5. The prevalence of IgGalphaA5 was not different statistically between patient samples with or without aPL. Patient IgGalphaA5 bound annexin A5 when the latter was free/unbound but not when annexin A5 was associated with phospholipid. CONCLUSIONS: The IgAalphaA5 does not appear to be pathogenic. IgGalphaA5 works to make a complex with annexin A5 without relation to aPLs, which may reduce annexin A5 available for binding to trophoblast.

Kininogen domain 3 contains regions recognized by antiphosphatidylethanolamine antibodies.

Antiphosphatidylethanolamine antibodies (APE) have been described in patients with thrombotic diseases and recurrent pregnancy loss (RPL). It has been reported that certain APE are not specific for phosphatidylethanolamine (PE) per se, but are directed to PE-binding plasma proteins, called kininogens. Our recent in vitro data suggest that APE may recognize the domain 3 (D3) region of kininogens. In this study, we have used synthetic peptides that span the D3 of kininogens in inhibition and direct binding studies to identify epitopes that are sites for binding APE. Our present data demonstrate that among 24 RPL patients who were positive for kininogen-dependent immunoglobulin (IgG) APE, 17 patients (70.8%) recognized the LDC27 peptide. We mapped the APE-binding region on D3 using plasma from a RPL patient (X) who had a high titer of IgG APE that recognized LDC27. APE of patient X recognized a 13-residue segment in LDC27, named CNA13. Leu331-Met357 (LDC27) and Cys333-Lys345 (CNA13) are located on the carboxyl-terminal portion of kininogen D3, which is known as the major kininogen heavy chain cell attachment site where it overlaps its cysteine protease inhibitory region. Because APE interferes with the balance of hemostasis in vitro, APE may therefore induce a similar condition in patients thereby causing thrombosis and RPL.

Presence of aldose reductase inhibitors in tea leaves.

Water extract from commercial English tea has a potent inhibitory activity against human placenta aldose reductase (NADPH oxidoreductase, E.C.1.1.1.21.). Inhibitory activity was separated into five major fractions by one-step chromatography with a C-18 reverse phase column. The most active fraction was further subjected to reverse phase column chromatography. As a result, a well-known flavone-glycoside, isoquercitrin, was isolated as the most potent chemical. The inhibitory character of isoquercitrin for aldose reductase was a mix of uncompetitive and noncompetitive inhibitions, and its IC50 was 1 x 10(-6) M. In rat sciatic nerve tissue preparations, sorbitol accumulation in the presence of high concentrations of glucose (30 mM) was inhibited by 38% at 5 x 10(-4) M of isoquercitrin. The flavone-glycoside isoquercitrin is the active inhibitor of aldose reductase inhibitor present in English tea. Given the ability of aldose reductase inhibitors to prevent diabetic complications, an epidemiological study of the effect of tea consumption on the pathogenesis and progression of diabetic complications would be interesting.

The nature of facilitation of leg muscle motor evoked potentials by knee flexion.

Knee flexion is a movement that initiates rising from a sitting position, which is a common therapeutic exercise for patients unable to ambulate. We investigated how voluntary isometric biceps femoris contraction affects motor evoked potential (MEP) amplitude following transcranial magnetic stimulation, background electromyographic (EMG) amplitude, and H-reflex amplitude in ipsilateral leg muscles. Subjects were seated on the edge of a bed with their hips and knees flexed at 90 degrees, and the soles of their feet on the floor. MEP and background EMG were recorded from the tibialis anterior (TA) and soleus (SOL), and H reflexes from SOL of 30 volunteers. Background EMG and MEP also were recorded while voluntarily contracting tested muscles. Biceps femoris contraction increased MEP and background EMG for TA and SOL (p < 0.01). Maximal background EMG and MEP increased with increasing voluntary contraction of tested muscles (p < 0.005). Regression slope differed little between TA and SOL. Biceps femoris contraction facilitated MEP comparably for TA and SOL, while SOL background EMG exceeded that of TA (p < 0.02). The relationship between MEP facilitation and background EMG changed to favor more efficient facilitation in TA (p < 0.05), but not SOL (p > 0.1). MEP recorded from TA and SOL with subthreshold stimuli using needle electrodes were more frequent with biceps femoris contraction (p < 0.04). H-reflex amplitude of SOL decreased during biceps femoris contraction (p < 0.001). We concluded that biceps femoris contraction affects leg muscle MEP, background EMG, and H reflexes differently.

Anti-paternal antibodies by flow cytometry in the management of alloimmunization on recurrent miscarriages.

PROBLEM: There is no reliable laboratory test available to diagnose immunologically mediated miscarriages. We investigated the clinical significance of maternal anti-paternal leukocyte antibodies by flow cytometry after alloimmunization. METHOD OF STUDY: The flow cytometry crossmatch (FCXM) was performed in 158 patients with a history of three or more unexplained first-trimester miscarriages without live birth. After negative FCXM patients were immunized, subsequent pregnancy outcomes and FCXM results were followed. RESULTS: Of 112 subsequent pregnancies, 83 of 100 (83.0%) FCXM-positive patients after immunotherapy had successful pregnancy outcomes, whereas seven of 10 (70.0%) FCXM-negative patients had miscarriages (P = 0.0001). The percent live birth ratio was 2.77 (CI, 1.07-7.16; P=0.0001) for FCXM-positive patients compared to FCXM-negative patients. The calculated predictive value showed that 75.6% of FCXM-negative patients would have subsequent miscarriages. CONCLUSIONS: Positive FCXM is closely associated with successful pregnancy outcome following immunotherapy. We propose that FCXM might be included in the routine laboratory tests for the management of recurrent miscarriages.

Memory rehabilitation of an amnesic patient following limbic encephalitis and a role of family members: a case report.

We describe problems in daily living that arose in a 46-year-old man with severe amnesia following limbic encephalitis. Amnesic symptoms changed from stage I (difficulty in memory retention) to stage II (loss of continuity of memory) and finally to stage III (paramnesia and confused sequence of events), significantly affecting his ability to function. Questionnaire response assessment, directly observed behavior, neuropsychological testing, and especially interviewing permitted qualitative assessment of clinical changes, promoted patient insight into the memory disturbance, and enhanced motivation to use a memory notebook. Additionally, the family gained a better understanding of the disorder, made appropriate environmental modifications, and provided other necessary assistance. Episodic memory improved, and the memory notebook served as an effective compensatory tool. However, disturbance in prospective memory did not improve, and was not compensated adequately by use of the notebook. Anxiety and significant impairment of everyday functioning resulted. Long-term supportive intervention at home was necessary. The patient's wife in particular needed to make environmental adjustments and aid him in use of the notebook.

Relationship between hypoxemia and fibrillation potential firing rate in denervated muscle.

The effects of hypoxia and ischemia on the firing rate of fibrillation potentials in denervated rat muscle were examined. We recorded electromyograms from the denervated left extensor digitorum longus muscle. Hypoxia was induced by low-oxygen ventilation. Ischemia was established by ligating the abdominal aorta and inferior vena cava, with or without extracorporeal hindlimb perfusion. The fibrillation potential firing rate correlated with the PaO2 (P < 0.0001) and temperature (P = 0.0001). Fibrillation potentials disappeared after the initiation of ischemia and reappeared after restitution of blood flow; they disappeared during ischemia with extracorporeal perfusion. The attenuation curves for the firing rate of fibrillation potentials during ischemia were well-described by exponential curves, but there was no significant difference in the attenuation constants for circulatory arrest and perfusion with a physiologic salt solution. We conclude that the fibrillation potential firing rate is proportional to oxygen supply, presumably because of the rate of aerobic metabolism.

Effects of dantrolene sodium on fibrillation potentials in denervated rat muscles.

To examine whether a decrease in cytosolic Ca2+ affects fibrillation potentials, we studied effects of dantolene on these potentials in denervated rat muscle. Administered intraperitoneally, dantrolene sodium (12-22 mg/kg) abolished fibrillation potentials and subthreshold oscillating potentials over 2.5-6 h without affecting excitability of the muscle to electrical stimulation. Fibrillation potentials reappeared 36-96 h after administration of dantrolene. We suggest that cytosolic Ca2+ has a specific role in generating fibrillations.

An individual patient comparison of response to a memory training program--psychogenic V organic amnesia: brief report.

Psychogenic amnesia ("dissociative amnesia" in DSM-IV) has received relatively little attention in the literature. We compared neuropsychological and behavioral findings between a patient with psychogenic amnesia and one with organic amnesia from their early stages in a rehabilitation program. A 52-yr-old man developed anterograde and retrograde amnesia and short-term memory disturbance 1 mo after an operation for esophageal carcinoma, with no loss of personal identity and information. No apparent organic causes were identified, but because the patient and his wife rejected psychiatric treatment and memory deficit characteristics were compatible with that of an organic origin, the patient was referred to a physiatrist. A 46-yr-old man with anterograde amnesia was diagnosed with limbic encephalitis based on findings of magnetic resonance imaging and single-photon emission computed tomography, which showed lesions in both medial temporal lobes. Both patients underwent "memory book" training because they showed preserved performance in motor learning tasks. The first patient's responses to training contrasted with the other's and were indicative of psychogenic amnesia, with cancer representing a precipitating stress. Counseled by the physiatrist, the patient and his wife accepted suggestions to undergo psychiatric treatment. We propose that it is important to consider behavioral responses to memory rehabilitation as well as neuropsychological findings in differentiating psychogenic amnesia from an organic one and that physiatrists may be pivotal in diagnosing and initiating treatment in such psychiatric disorders.

Solubilization and characterization of the rat pituitary gonadotrophin-releasing hormone receptor.

Specific receptors for gonadotrophin-releasing hormone (GnRH) were extracted from the rat pituitary gland with several detergents and characterized by binding studies with the potent GnRH antagonist [Ac-D-pCl-Phe1.2, D-Trp3, D-Lys6, D-Ala10]-GnRH (GnRHant). The particulate GnRH receptors were most effectively solubilized with 5 mM 3-[(3-cholamidopropyl)-dimethylammonio]-1-propanesulphonate (CHAPS), which extracted 63% of the original membrane binding activity when assayed with 125I-labelled GnRHant. The binding affinities of particulate and CHAPS-solubilized receptors analysed with 125I-labelled GnRHant were 1.5 +/- 0.4 x 10(9) M-1 and 1.2 +/- 0.2 x 10(9) M-1 respectively. Gel filtration of the CHAPS-solubilized receptor revealed a major peak of specific binding activity with Mr of about 700,000. A hormone-receptor complex of similar Mr was observed when CHAPS-solubilized receptors were labelled with photoreactive radioiodinated [D-Lys6]-des-Gly10-GnRH-N-ethyl-amide and then analysed by gel chromatography. However, when pituitary particles were photolabelled and solubilized in 2% Triton X-100 before analysis on Sephacryl S-300, the Mr of the receptor was approximately 250,000, similar to the value obtained by sucrose density gradient centrifugation of the CHAPS-solubilized receptor. After solubilization in sodium dodecyl sulphate (SDS) the photolabelled receptor was eluted from Sephacryl S-300 as a 60 kDa peak which on SDS-gel electrophoresis contained a 52 kDa component, corresponding to the major binding subunit extracted directly from photolabelled pituitary membranes. The difference in higher molecular weight forms observed under non-denaturing and denaturing conditions could reflect the need for additional membrane components to maintain the active conformation of the GnRH receptor site. Whereas the minimum Mr of the solubilized receptor is about 250,000 under non-denaturing conditions, analysis of the photolabelled GnRH-receptor complex by SDS chromatography and electrophoresis indicates that a binding subunit with Mr of 50,000-60,000 is present in the GnRH holoreceptor.