Lambert-Eaton Myasthenia Research Articles

A Computational Quantum Chemical Approach for Surface Assimilation Effects of Well‐Known Voltage Sensitive Potassium Channel Blockers (4‐Aminopyridine and 3,4‐Diaminopyridine) over Carbon Nanotube

AbstractThe compound 3,4‐diaminopyridine (3,4‐AP), a derivative of 4‐aminopyridine (4‐AP), is used in the symptomatic treatment of fatigue in multiple sclerosis as well as Lambert–Eaton myasthenia syndrome whereas the parent compound 4‐AP is used as an acetylcholine‐releasing drug, in serum, saliva, and urine. 4‐AP is an experimental drug that may reduce symptoms in some people with multiple sclerosis, particularly those who are more sensitive to heat. The carbon nanotubes (CNTs) have inside cavity tethering on the surface upon functionalization and adsorption on the walls of CNTs, which provides extra ability to carry pharmaceutical agents through multiple ways. Due to these benefits, this communication will discuss the comparative changes in geometry, electronic properties, and shielding parameters of 4‐AP and 3,4‐AP absorbed C56H16. The DFT/B3LYP/6–31G (d, p) method is used for the first time to report electronic structure and interaction parameters on the CNT surface. The same level theory is used to discuss the thermodynamic stability of CNT‐4‐AP/3,4‐AP. The calculated UV spectra of CNT are compared with UV spectra of CNT‐4‐AP and 3,4‐AP by using the same level theory in a water solvent, which provides a better comprehension of CNT as a drug delivery system after absorption of the 4‐AP and 3,4‐AP in the human body. The nature and strength of interactions have been discussed with the help of AIM analysis, and the frontier orbital highest occupied molecular orbital–lowest unoccupied molecular orbital (HOMO–LUMO) gap, chemical softness, and chemical hardness have been calculated to understand its complete chemical properties. The characters of the frontier molecular orbitals are discussed and analyzed by comparing the DOS spectra of CNT with CNT‐4‐AP/3,4‐AP.

Therapeutic Plasma Exchange: For Cancer Patients.

Therapeutic plasma exchange is used as a trial method for the treatment of cancer patients. Therapeutic plasma exchange uses in vitro technology to remove pathogenic factors in the plasma, returning the replacement and remaining components to the patient to facilitate cure. In the effort to explore new methods of cancer treatment, the introduction of therapeutic plasma exchange brings new hope for cancer treatment; however, the current evidence supporting therapeutic plasma exchange is controversial, and most of the evidence comes from observational studies, lacking large prospective randomized trials. Therefore, this review attempts to focus on the main indications of therapeutic plasma exchange for the treatment of tumors and their complications, including hematological tumors (multiple myeloma cast nephropathy and hyperviscosity syndrome), nervous system tumors (myasthenia gravis associated with thymoma, paraneoplastic neurological syndrome, Lambert–Eaton myasthenia syndrome, and anti-N-methyl-D-aspartate receptor encephalitis), overdose of chemotherapy drugs. In addition, the issues of side-effects and safety in the use of therapeutic plasma exchange are also discussed. However, well-designed prospective trials are needed to better define the role of therapeutic plasma exchange in cancer.

WS3.7. Repetitive Nerve Stimulation Testing

Repetitive nerve stimulation (RNS) is the most frequently used electrodiagnostic test to diagnose neuromuscular junction disorders. Although seemingly simple, attention to technique is essential to avoid technical errors. Stimulation at low rates (2–5 Hz) (LF-RNS) depletes acetylcholine stores at diseased motor endplates, causing failure of neuromuscular transmission. A decrement of at least 10% to trains of 2-3 Hz stimulation at rest or immediately after a period of maximal muscle contraction (“activation”) is the usual criterion of abnormality; 5% can be used if technical artifacts can be excluded. Take care to deliver adequate stimulation and prevent movement of the tested muscle throughout nerve stimulation; peripheral muscles should be kept warm during testing. RNS is reportedly abnormal in up to 90% of generalized myasthenia gravis (MG) patients and in up to 60% of ocular myasthenia – sensitivity is strongly dependent on the muscles selected for testing. RNS is more often abnormal in proximal, facial and clinically weak muscles; even so, RNS is frequently normal in mild or purely ocular disease. For maximal diagnostic yield, test several muscles, including those that are weak. The characteristic findings in Lambert-Eaton myasthenia (LEM) are: small CMAPs at rest, a decrement to LF-RNS, and marked facilitation. In MG, activation for 30–60 seconds is used to unmask a mild decrement. In LEM, activation is used to demonstrate facilitation; the simplest procedure is to elicit a single CMAP from the rested muscle, have the patient contract the muscle for 10 seconds, then immediately elicit a single CMAP. Facilitation of at least 60% is evidence of a pre-synaptic disorder, but may not be seen in all muscles. A decrement in at least one hand muscle is the most frequent RNS abnormality in LEM and may be seen even when CMAPs are not small and diagnostic facilitation cannot be demonstrated. In MG the decrement is usually greatest in the 4th or 5th response and is less during subsequent responses, producing a so-called ‘‘U-shaped” pattern. A continually progressive decrement is usually seen in LEM. The pattern in MuSK MG resembles that in LEM.

Symposium 4: Neuromuscular junction and related disorders SY4.1. Myasthenia gravis and related disorders

Autoimmune myasthenia gravis (MG) results from autoantibodies that bind to the neuromuscular junction (NMJ). Incidence and prevalence vary worldwide; the estimated US prevalence is 20/100,000, or ∼60,000 patients. Women develop MG more often before age 40, men after 50. Drooping eyelids or double vision is the first symptom in 60%; weakness remains limited to periocular muscles in 10–15% – ocular myasthenia. The voice may be nasal or hoarse, especially after prolonged talking, and swallowed liquids may escape through the nose. Weakness typically worsens throughout the day. Spontaneous improvement may occur early on but is rarely permanent. The diagnosis depends on recognizing distinctive patterns of weakness and confirmation by serologic and electrodiagnostic tests. 80–85% of patients have circulating anti-AChR antibodies; repetitive nerve stimulation (RNS) demonstrates abnormal neuromuscular transmission (NMT) in up to 90% of generalized MG and 60% of ocular myasthenia. Increased jitter is found in almost all patients if appropriate muscles are examined. Approximately 10% of patients have antibodies to muscle specific tyrosine kinase (MuSK). Clinical findings resemble non-MuSK MG in some patients; many have predominant weakness in cranio-bulbar muscles with marked atrophy. Others have predominant neck, shoulder and respiratory weakness. With selected treatment most non-MuSK and MuSK-MG patients have only minimal long-term morbidity. Congenital myasthenic syndromes result from genetic defects of muscle endplate molecules involved in NMT; most have autosomal recessive inheritance. The diagnosis is suggested by clinical features and response to cholinesterase inhibitors, or electrodiagnostic findings. Identification of specific genetic or physiologic defects requires genetic studies or specialized morphological and electrophysiological studies. Lambert-Eaton myasthenia results from antibodies to voltage-gated calcium channels (VGCC) on presynaptic nerve terminals, which produces the classic triad of weakness, reduced muscle stretch reflexes and autonomic dysfunction. Approximately 50% have an underlying malignancy, usually small cell lung cancer. The diagnosis is confirmed by a decrementing pattern during low frequency RNS and low muscle responses that increase at least 60% after muscle activation. Antibodies to the VGCC are found in most cases. Treatment is initially directed against any underlying malignancy. Amifampridine produces symptomatic improvement in most patients; immunomodulatory therapy may provide modest benefit in some.

Lambert-Eaton myasthenia syndrome: specified description of a response pattern to low-frequency repetitive nerve stimulation

ObjectiveWe aimed to specify and quantify the characteristics of the decrement in low-frequency repetitive nerve stimulation response in Lambert-Eaton myasthenia syndrome (LEMS) and compare it to those of myasthenia gravis (MG). Patients and MethodsWe retrospectively reviewed 18 patients with LEMS and 24 patients with MG. Ten consecutive stimulations were applied at 3 Hz to the abductor pollicis brevis. We determined the position of the smallest wave in the stimulation sequence, and we calculated the decrement and recovery. ResultsThe median sequential order of the minimum wave was 8 in the LEMS group and 5 in the MG group (p < 0.001). The median decrement in the LEMS group was 36.7%, while that in the MG group was 21.0% (p = 0.047). The recovery percentage was 1.4% in the LEMS group and 3.5% in the MG group (p = 0.001). The area under the curve for the sequential order of the minimum wave was 0.90, and the reciprocal optimum cut-off point was 6.5. ConclusionsWe elucidated a pattern with a delayed nadir and subsequent poor recovery, featuring a low-frequency decrement; furthermore, we determined the most likely sequential order of the minimum wave in patients with LEMS, and the indicator was useful for differentiation.

Validation of the triple timed up-and-go test in Lambert-Eaton myasthenia.

There are no validated, practical, and quantitative measures of disease severity in Lambert-Eaton myasthenia (LEM). Data from the Effectiveness of 3,4-Diaminopyridine in Lambert-Eaton Myasthenic Syndrome (DAPPER) trial were analyzed to assess triple timed up-and-go (3TUG) reproducibility and relationships between 3TUG times and other measures of LEM severity. The coverage probability technique showed ≥0.90 probability for an acceptable 3TUG difference of ≤0.2, indicating that it is reproducible in LEM patients. The correlation between 3TUG times and lower extremity function scores was significant in subjects who continued and in those who were withdrawn from 3,4-diaminopyridine free base. Worsening patient-reported Weakness Self-Assessment Scale and Investigator Assessment of Treatment Effect scores corresponded with prolongation of 3TUG times. The 3TUG is reproducible, demonstrates construct validity for assessment of lower extremity function in LEM patients, and correlates with changes in patient and physician assessments. These findings, along with prior reliability studies, indicate 3TUG is a valid measure of disease severity in LEM.

Clinical characteristics and long term follow-up of Lambert-Eaton myasthenia syndrome in patients with and without small cell lung cancer

In order to describe the clinical characteristics, treatment response and long-term follow up in Lambert–Eaton myasthenic syndrome (LEMS) patients with and without small cell lung cancer (SCLC) in East China, patients seen in Huashan Hospital from January 1997 to December 2017 were included. Clinical information was collected retrospectively and quantitative MG (QMG) score, manual muscle testing (MMT), activities of daily living (ADL) scale were evaluated when the patients were followed up. Of 50 patients, 23 (46%) were SCLC-LEMS and 20 (40%) were nontumor LEMS (NT-LEMS). The median onset age was 55.5 (18–86) years old and the gender ratio was about 1.8:1. It took less time to make the diagnosis (median time: 6 vs 22.5 months, p = 0.0003) and there were more patients with other paraneoplastic syndromes in SCLC-LEMS group than in NT-LEMS group (8/23 vs 0/20, p = 0.0042). Electrophysiologically, the peroneal compound motor action potential (CMAP) of rest showed difference between SCLC-LEMS and NT-LEMS (0.8 vs 1.6 mV, p = 0.0499). The median survival time of 19 SCLC-LEMS patients since the diagnosis of SCLC was 30 months. According to their survival time, SCLC patients with LEMS showed a more favorable prognosis than those without LEMS. In the time of follow-up, most NT-LEMS showed improvement or obtained status of CSR/PR/MM after immunosuppressive therapy and no significant difference in proportion of achieving CSR/PR/MM was found between SCLC-LEMS and NT-LEMS patients (0/5 vs 6/13, p = 0.114).

Lambert-Eaton Myasthenia With and Without Cancer: Clinical Characteristics and Long-term Survival (P6.444)

Lambert-Eaton Myasthenia With and Without Cancer: Clinical Characteristics and Long-term Survival (P6.444)

3,4-diaminopyridine base effectively treats the weakness of Lambert-Eaton myasthenia.

ABSTRACT Introduction: 3,4‐diaminopyridine has been used to treat Lambert‐Eaton myasthenia (LEM) for 30 years despite the lack of conclusive evidence of efficacy. Methods: We conducted a randomized double‐blind placebo‐controlled withdrawal study in patients with LEM who had been on stable regimens of 3,4‐diaminopyridine base (3,4‐DAP) for ≥ 3 months. The primary efficacy endpoint was >30% deterioration in triple timed up‐and‐go (3TUG) times during tapered drug withdrawal. The secondary endpoint was self‐assessment of LEM–related weakness (W‐SAS). Results: Thirty‐two participants were randomized to continuous 3,4‐DAP or placebo groups. None of the 14 participants who received continuous 3,4‐DAP had > 30% deterioration in 3TUG time versus 72% of the 18 who tapered to placebo (P < 0.0001). W‐SAS similarly demonstrated an advantage for continuous treatment over placebo (P < 0.0001). Requirement for rescue and adverse events were more common in the placebo group. Discussion: This trial provides significant evidence of efficacy of 3,4‐DAP in the maintenance of strength in LEM. Muscle Nerve 57: 561–568, 2018

Reliability of the triple-timed up-and-go test.

We report the reliability of a new measure, the triple-timed up-and-go (3TUG) test, for assessing clinical function in patients with Lambert-Eaton myasthenia (LEM). Intrarater reproducibility and interrater agreement of the 3TUG test were assessed in 25 control participants, 24 patients with non-LEM neuromuscular disease, and 12 patients with LEM. The coverage probability (CP) method was the primary measure of reproducibility and agreement. The a priori acceptable range was < 20% difference in 3TUG test times and a CP ≥0.90 confirmed agreement. CP values > 0.90 for intrarater and interrater tests confirmed acceptable reproducibility and agreement for all groups. The 3TUG test is a quick, noninvasive, and reproducible measure that is easy to perform, measures clinically important weakness in LEM patients, and requires little training. Additional evaluation in a larger number of LEM patients is in progress to validate the 3TUG test as a clinical measure in LEM. Muscle Nerve 57: 136-139, 2017.

Single-fiber EMG with concentric electrodes in lambert-eaton myasthenia.

We analyzed jitter recordings made with concentric needle electrode (CNE) single-fiber electromyography (SFEMG) in Lambert-Eaton myasthenia (LEM). Fifteen subjects diagnosed with LEM were studied using CNE-SFEMG in the extensor digitorum (ED) and tibialis anterior (TA) muscles. CNE-SFEMG in the ED and TA was also used to evaluate 12 and 10 healthy controls (HCs), respectively. Ten men and 5 women were diagnosed with LEM based on an increase of 100% in compound muscle action potential amplitude during 50 Hz repetitive nerve stimulation. All patients exhibited markedly greater jitter in the ED (88.8 ± 23.2 µs) and TA (92.2 ± 30.2 µs) than HCs (28.3 ± 3.4 µs and 30.9 ± 5.1 µs, respectively). CNE-SFEMG is sensitive for discovering abnormalities in neuromuscular transmission in LEM. Muscle Nerve 56: 253-257, 2017.

Paraneoplastic cerebellar degeneration and lambert‐eaton myasthenia in a patient with merkel cell carcinoma and voltage‐gated calcium channel antibodies

Merkel cell carcinoma is a rare cutaneous, aggressive tumor. Although it shares many neuroendocrine features with small cell lung carcinoma, it has only occasionally been reported with paraneoplastic neurological syndromes. A healthy 67-year-old man developed acute ataxia, vertigo, and nausea. Subsequently he also developed dysarthria, diplopia, xerostomia, fatigability and progressive anorexia. He underwent a full diagnostic workup and was found to have a high titer of voltage-gated calcium channel antibodies in serum and cerebrospinal fluid, neurophysiological findings compatible with Lambert-Eaton myasthenia and neurological signs compatible with cerebellar degeneration. A positron emission tomography study revealed a hypermetabolic lesion in the axilla, subsequently biopsied and consistent with Merkel cell carcinoma. In most previous reports, neurological symptoms preceded the Merkel cell carcinoma diagnosis, and the primary localization was in lymph nodes. This tumor should be considered in patients with paraneoplastic syndrome, and particularly Lambert-Eaton myasthenia after exclusion of small cell lung carcinoma. Muscle Nerve 56: 998-1000, 2017.

Neuropathy, Encephalopathy, Lambert-Eaton Myasthenic Syndrome and Myasthenia Gravis in a Non-Small Cell Neuroendocrine Tumor of the Lung - An Interesting Paraneoplastic Syndrome: Case Report and Review of Literature. (NELM Syndrome) (P04.094)

Objective: To report a case of Neuropathy, Encephalopathy, Myasthenia Gravis and Lambert Eaton Myasthenic Syndrome in a patient with neuroendocrine lung cancer. Background Case reports of combined Myasthenia Gravis(MG) and Lambert-Eaton Myasthenic Syndrome(LEMS) have been reported with small cell lung cancer but never been reported in Large Cell NeuroEndocrine Cancer(LCNEC) in English literature. We describe the first case of MG, LEMS and demyelinating neuropathy in a patient with LCNEC of lung and response to intravenous immunoglobulin (IVIG) treatment. Design/Methods: case report and review of literature. Results: A 64-year-female with LCNEC(stage-1A) status post wedge resection presented with one week history of encephalopathy, diplopia, generalized weakness and paresthesia. She had autonomic instability reflected by wide fluctuation in her blood pressure. Examination showed external ophthalmoplegia, facial diplegia and proximal 2/5, distal 4/5 strength with areflexia. She was intubated secondary to neuromuscular weakness. EEG showed moderate encephalopathy. MRI of brain and cerebrospinal fluid analysis were unremarkable. Electrophysiological studies revealed severe sensorimotor demyelinating polyneuropathy. Repetitive nerve stimulation showed decremental response of > 20%. She also had positive acetylcholine receptor binding antibody and voltage gated calcium channel antibody. An extensive paraneoplastic panel was negative. Anti-Gq1b antibody was negative. Immunoperoxidase staining of lung biopsy was positive for CD-15, TTF-1, CK-7 and CAM 6.2. Patient received 2 courses of IVIG 2 gm/ kg with rapid recovery. Follow- up showed mild right upper extremity weakness and ataxia. She did not have any recurrence of symptoms in a 2 year follow- up. Conclusions: This is an unusual paraneoplastic manifestation of LCNEC lung cancer where patient presented with features of MG, LEMS and demyelinating neuropathy at the same time with very good response to IVIG. A combination of encephalopathy, ophthalmoplegia, areflexia and demyelinating neuropathy also suggests Bickerstaff Encephalitis(BE) despite negative anti-Gq1b antibody(32% negative anti-Gq1b antibody in BE). Multiple antibodies targeting different receptors may underlie pathology. Disclosure: Dr. Neelam has nothing to disclose. Dr. Lim has nothing to disclose. Dr. Singh has nothing to disclose.

Stability studies of ionised and non-ionised 3,4-diaminopyridine: Hypothesis of degradation pathways and chemical structure of degradation products

3,4-Diaminopyridine is used to treat some symptoms met in Lambert–Eaton myasthenia syndrome. It was shown efficient to reduce a form of variable muscle weakness and fatigability typical of the disease and correlated to a block of acetylcholine release. In France, 3,4-diaminopyridine is nowadays given to patients under capsules form and the status of hospital preparation. Whatever the diluant used in the formulation, the stability period could not exceed 12 months. Preliminary studies were made on a salt form in order to test the influence of various stress factors and determine if there is interaction between them. From this study, the most influent stress condition, presence of hydrogen peroxide, was selected and a comparative study was performed to compare the stability of molecular and salt species. Solutions of each species were exposed to 5 or 15% of hydrogen peroxide and analyzed at 8, 24, 72 and 216 h of degradation by HPLC-UV. Fractions of detected impurities were purified and collected by semi-preparative HPLC-UV and analyzed by HPLC-UV–ESI–MS and IR spectroscopy in order to determine their structure hypotheses. Theses experiments demonstrate that the salt species were more stable under oxidative stress condition than molecular species. The two main degradation products were collected and identified as 4-amino, 3-nitropyridine and 3,4-diaminopyridine-N-oxide when the molecular form was degraded whereas only 4-amino, 3-nitropyridine was found in less quantity in the salt solutions. Nitrogen pyridine and pyridine amine could not easily be oxidized by hydrogen peroxide in salt comparatively to molecular species due to the lone pair of electron engaged in a bound with hydrogen in the first case and by resonance change of the pyridine in the second case. This modification of structure promoted different pathways of degradation for the salt form which are more dependent of energy. Owing to the better stability of the salt species, a new pharmaceutical form containing it was developed to assess its stability under ICH standard conditions allowing an industrial manufacture of this drug.

Manifestations rhumatologiques paranéoplasiques en dehors de l'ostéoarthropathie hypertrophiante

Paraneoplastic rheumatic syndromes (PRS), as any paraneoplastic syndrome, induce signs or symptoms related to a known or an unrecognized tumour, cancer, or haemopathy, often malignant but not always. The chronologic relationship between the neoplastic process and the symptomatology is essential. PRS is not due to a tumour-induced compression or a synovial or bone peri-articular metastatic invasion. They differ from pre-neoplastic systemic rheumatic conditions. They disappear when the patient may benefit from a radical treatment. The best rheumatologic example is the hypertrophic pneumogenic osteoarthropathy described elsewhere in this work. Here we review the other PRS conditions: the palmar fasciitis syndrome; the ovary (but not exclusively) polyarthritis and cancer; the paraneoplastic muscular syndromes induced by a dermatomyositis, polymyositis, Lambert-Eaton myasthenia syndrome, and stiff man syndrome; inflammatory rheumatisms (polyarthritis, pseudo Still's disease, benign oedematous acute polyarthritis of the elderly, rhizomelic pseudoarthritis) in their rare paraneoplastic presentations; the vascular lesions (erythromelalgia, Raynaud's disease, digital necrosis, vascularitis) in their paraneoplastic presentations; other potentially paraneoplastic systemic rheumatic conditions (atrophic polychondritis, multicentric reticuloendotheliosis, panniculitis-arthritis syndrome, and amyloid arthropathy); paraneoplastic hypercalcemias, in particular those related to the parathormone-related peptide; and oncogenous osteomalacia. Clinical and paraclinical orientations are considered, according to these different situations, particularly for the presented tumoural and haematological diseases.

Feasibility of Integrated Human Performance Testing in a Patient with Lambert-Eaton Myasthenia Gravis Syndrome (LEMS)

2099 PURPOSE: LEMS is a rare autoimmune neurological disorder of the neuromuscular junction. To the best of our knowledge, integrated human performance testing has not been previously reported in patients with LEMS. METHODS: Body composition and bone density (BMD) were measured by DEXA. Pulmonary function (PFT), maximal inspiratory muscle strength (MIPS); isokinetic strength testing (elbow and knee fiexors and extensors); and a maximal cardiorespoiratory exercise test (CPET) were performed before and after ingestion of 20mg 3–4 diaminopyridine (current medication standard) in a 48yr old male (69.9kg, 177.8cm, BMI 22.1(kg/cm2), diagnosed with LEMS 13 years ago. RESULTS: The patent tolerated all procedures well and did not complain of pain or undue fatigue. Body Composition: percent fat 35.6%; and lean body mass 41.9kg. Femoral BMD: 0633g/cm2, Z-score −2.3. Results are listed as pre and post medication respectively. PFT: FVC and FEV1 were reduced 73 and 75% predicted; PEF: 66 and 69% predicted; but PImax was 82 and 93% predicted. CPET Peak Values – WR: 21 and 28% predicted; VO2 (L/min): 29 and 32% predicted; HR: 95 and 100% predicted. CONCLUSIONS: Impaired exercise performance, as expected, was observed. Lung function was mildly reduced save for highly respiratory muscle dependent PEF results which were markedly reduced. BMD demonstrated osteoporosis. Although, BMI was relatively low, high fat percentage with decreased lean body mass was observed. Medications led to minor changes in strength and PFT's. Integrated human performance testing is feasible in patients with LEMS and may prove useful for staging the degree of impairment and for documenting the effect of medications. Multi-center studies are needed to create human performance data base for this rare disease. Supported by the National GCRC Applied Physiology and Human Performance Consortium

Feasibility of Integrated Human Performance Testing in a Patient with Lambert-Eaton Myasthenia Gravis Syndrome (LEMS)

2099 PURPOSE: LEMS is a rare autoimmune neurological disorder of the neuromuscular junction. To the best of our knowledge, integrated human performance testing has not been previously reported in patients with LEMS. METHODS: Body composition and bone density (BMD) were measured by DEXA. Pulmonary function (PFT), maximal inspiratory muscle strength (MIPS); isokinetic strength testing (elbow and knee fiexors and extensors); and a maximal cardiorespoiratory exercise test (CPET) were performed before and after ingestion of 20mg 3–4 diaminopyridine (current medication standard) in a 48yr old male (69.9kg, 177.8cm, BMI 22.1(kg/cm2), diagnosed with LEMS 13 years ago. RESULTS: The patent tolerated all procedures well and did not complain of pain or undue fatigue. Body Composition: percent fat 35.6%; and lean body mass 41.9kg. Femoral BMD: 0633g/cm2, Z-score −2.3. Results are listed as pre and post medication respectively. PFT: FVC and FEV1 were reduced 73 and 75% predicted; PEF: 66 and 69% predicted; but PImax was 82 and 93% predicted. CPET Peak Values – WR: 21 and 28% predicted; VO2 (L/min): 29 and 32% predicted; HR: 95 and 100% predicted. CONCLUSIONS: Impaired exercise performance, as expected, was observed. Lung function was mildly reduced save for highly respiratory muscle dependent PEF results which were markedly reduced. BMD demonstrated osteoporosis. Although, BMI was relatively low, high fat percentage with decreased lean body mass was observed. Medications led to minor changes in strength and PFT's. Integrated human performance testing is feasible in patients with LEMS and may prove useful for staging the degree of impairment and for documenting the effect of medications. Multi-center studies are needed to create human performance data base for this rare disease. Supported by the National GCRC Applied Physiology and Human Performance Consortium

Preparation of 3,4-diaminopyridine microparticles by solvent-evaporation methods.

The present study compares two methods of preparation of microparticles of 3,4-diaminopyridine (3,4-DAP) for the treatment for multiple sclerosis and Lambert-Eaton myasthenia syndrome. Poly( epsilon -caprolactone) microparticles were prepared with a solvent-evaporation W/O method. The 3,4-DAP was dispersed in dichloromethane, leading to a suspension. The dispersion and the solidification of the dichloromethane droplets in an aqueous phase have led to microparticles of 55.3+/-34.7 microm. The incorporation of the drug by milligram of powder was very low (1.91 micrograms/mg) and the scanning electron microscopy (SEM) did not show any crystal but marks of dissolved crystals were observed on the polymeric surface. EudragitRS microspheres containing 3,4-DAP were prepared by a solvent-evaporation technique using light mineral oil as continuous phase. The drug and the polymer were completely dissolved in an acetone solution, used as discontinuous phase. This formulation have led to a higher incorporation of the drug (88.25 micrograms/mg). The particle size was 91.8+/-44.3 microm. The observation, by SEM, shows many crystals on the surface and inside the microparticles. A slow-release of the drug in a phosphate buffer pH 7.4 was observed (50% in 60 min and about 70% in 4 h).