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C Armon

Publications and source records attributed to C Armon.

At least 19 recordsLinked to original sources
PubMed2004

Assessment: transcranial Doppler ultrasonography: report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology.

OBJECTIVE: To review the use of transcranial Doppler ultrasonography (TCD) and transcranial color-coded sonography (TCCS) for diagnosis. METHODS: The authors searched the literature for evidence of 1) if TCD provides useful information in specific clinical settings; 2) if using this information improves clinical decision making, as reflected by improved patient outcomes; and 3) if TCD is preferable to other diagnostic tests in these clinical situations. RESULTS: TCD is of established value in the screening of children aged 2 to 16 years with sickle cell disease for stroke risk (Type A, Class I) and the detection and monitoring of angiographic vasospasm after spontaneous subarachnoid hemorrhage (Type A, Class I to II). TCD and TCCS provide important information and may have value for detection of intracranial steno-occlusive disease (Type B, Class II to III), vasomotor reactivity testing (Type B, Class II to III), detection of cerebral circulatory arrest/brain death (Type A, Class II), monitoring carotid endarterectomy (Type B, Class II to III), monitoring cerebral thrombolysis (Type B, Class II to III), and monitoring coronary artery bypass graft operations (Type B to C, Class II to III). Contrast-enhanced TCD/TCCS can also provide useful information in right-to-left cardiac/extracardiac shunts (Type A, Class II), intracranial occlusive disease (Type B, Class II to IV), and hemorrhagic cerebrovascular disease (Type B, Class II to IV), although other techniques may be preferable in these settings.

Adolescent↗
PubMed2003

Can we eliminate placebo in ALS clinical trials?

BACKGROUND: Previous studies concluded that the decline in strength in patients with amyotrophic lateral sclerosis (ALS) is a linear function. If so, a patient's natural history might serve as the control, instead of placebo, in a clinical trial. METHODS: A placebo-controlled ALS clinical trial included a natural history phase, followed by a 6-month treatment phase. Each patient's forced vital capacity (FVC) score and maximal voluntary isometric contraction (MVIC) raw scores were measured monthly, standardized, and averaged into megascores. For 138 patients, the arm, leg, FVC, arm+leg combination, and arm+leg+FVC combination megascore slopes during the natural history phase and during the placebo phase were compared. RESULTS: The mean slope of megascores during the natural history phase and the mean slope during the placebo phase were not different for the arm, leg, and arm+leg megascores, but were different for the FVC and arm+leg+FVC combination megascores. CONCLUSIONS: Natural history controls may be useful in ALS exploratory trials that use arm megascore slope as the primary outcome measure. However, there are distinct limitations to the use of natural history controls, so that Phase 3 ALS clinical trials require placebo controls.

Amyotrophic Lateral Sclerosis↗
PubMed2001

Environmental risk factors for amyotrophic lateral sclerosis.

In order to evaluate reported associations of environmental risk factors with amyotrophic lateral sclerosis (ALS), consideration is given first to robust clinical and epidemiologic observations. These are observations which have persisted in time, have been replicated consistently and likely reflect the reality of the disease. Sporadic, familial and Western Pacific ALS are considered. In contrast, other associations appear to have emerged due to chance, sometimes compounded by faulty study design, and have dissipated once greater attention was given to methodological rigor. Current data suggest that there are no robust environmental risk factors for sporadic ALS.

Environmental Pollution↗
PubMed2000

Linear estimates of disease progression predict survival in patients with amyotrophic lateral sclerosis.

We have shown that linear estimates of rates of disease progression (LEP), derived from isometric myometry [grip or foot dorsiflexion (FD) strength] and forced vital capacity (FVC%), are clinically and statistically significant predictors of survival of patients with amyotrophic lateral sclerosis (ALS) from date of disease onset and, except those based on grip strength, of survival from the date of measurement. We tested these results in 2 additional groups of patients: 1) those who participated in a previously reported Protropin (GH) study; and 2) those enrolled in two other clinical trials (group 2). The LEP were derived and tested as predictors of survival. In a Cox proportional hazards model, LEP based on all measures predicted survival from disease onset in both groups of patients. Using cutoff points determined within the original group to stratify patients in the validation groups into faster and slower progressing subgroups resulted in statistically significant separation of survival curves from disease onset in group 2 for all LEP and in group 1 (the GH group) for LEP derived from FD strength; and, for survival from date of measurement in group 2, when stratified by LEP based on FD strength or FVC%. LEP based on data generated by myometry or pulmonary function studies have now been shown to predict survival in 3 unrelated groups of patients with ALS entering clinical trials. Their precise use in clinical trial design needs to be explored further.

Adult↗
PubMed2000

Alzheimer's disease underlies some cases of complex partial status epilepticus.

Alzheimer's disease is a known risk factor for seizures, and age older than 60 years is a recognized risk factor for poor outcome from convulsive and nonconvulsive status epilepticus. The authors suspect that there may be a causal relationship between dementia pathology and the development and maintenance of refractory seizures. They report two selected patients with complex partial status epilepticus whose presentation and clinical course provide partial support for this hypothesis. Their methods include case reports with clinical, EEG, imaging, and pathologic correlations. The patients were 70 and 85 years of age. Both had central and peripheral brain atrophy on imaging studies (with some regions that were affected more than others), left temporal seizure foci corresponding to areas of greatest cortical atrophy, and early presentation with inhibitory epileptic symptoms (aphasia), with evolution to complex partial status epilepticus. Pathologic confirmation of Alzheimer's disease was obtained in one patient who had not been diagnosed previously. It involved maximally the cortex underlying the seizure focus. A diagnosis of probable Alzheimer's disease was established in the other patient. Alzheimer's disease may be causal in some cases of complex partial status epilepticus. Additional observations in support of this hypothesis are needed.

Aged↗
PubMed2000

Inhibitory simple partial (non-convulsive) status epilepticus after intracranial surgery.

OBJECTIVES: To report on five patients who developed, 2 to 4 days after an intracranial neurosurgical procedure, new, persistent, focal neurological deficits which were due to inhibitory simple partial (non-convulsive) status epilepticus, and resolved with anticonvulsant treatment. METHODS: The age range of the five patients was 15-74 years. The operations were: aneurysm clipping (three patients) and resections of an oligodendroglioma and a cavernous haemangioma (one patient each). The new focal deficits were: right hemiparesis and aphasia (two patients), aphasia alone (two patients), and left hemiparesis (one patient). The deficits were not explained by CT (obtained in all patients) or cerebral angiography (performed in two). RESULTS: Electroencephalography showed, in all patients, continuous or intermittent focal seizures arising from cortex regionally relevant to the clinical dysfunction. Subtle positive epileptic phenomena (jerking) occurred intermittently in three patients as a late concommitant. Administration of anticonvulsant drugs resulted in significant improvement within 24 hours in four patients, with parallel resolution of ictal EEG activity. The fifth patient improved more slowly. Two patients relapsed when anticonvulsant concentrations fell, and improved again when they were raised. CONCLUSIONS: It is suggested that inhibitory simple partial (non-convulsive) status epilepticus be considered in the differential diagnosis when a new unexplained neurological deficit develops after an intracranial neurosurgical procedure. An EEG may help to diagnose this condition, leading to definitive treatment.

Adolescent↗
PubMed1999

Motor unit number estimate-based rates of progression of ALS predict patient survival.

We have examined, as predictors of survival in patients with amyotrophic lateral sclerosis (ALS), linear estimates of rates of disease progression (LEP), based on motor unit number estimates (MUNE). Motor unit number estimates of thenar, hypothenar, and extensor digitorum brevis muscles (according to the manual method of McComas), isometric grip and foot dorsiflexion (FD) strength, and forced vital capacity (FVC) were available in 34 patients. Linear estimates of rates of disease progression were derived. Probability of survival was calculated using the Kaplan-Meier method. Motor unit number estimates, LEP based on MUNE, and demographic characteristics were tested as risk factors within the Cox Proportional Hazards Model, using regression techniques. Individually, all MUNE-based LEP were highly significant (P < 0.00005); bulbar onset attained modest significance (P = 0.044). Secondary analysis showed MUNE-based LEP were more significant than regionally concordant function-based LEP. Linear estimates of rates of disease progression based on MUNE may thus predict survival of patients with ALS better than LEP based on function.

Adult↗
PubMed1999

How can physicians and their patients with ALS decide to use the newly-available treatments to slow disease progression?

The 1990s decade has seen the testing of treatments to slow disease progression in patients with ALS. Two such treatments (riluzole and myotrophin) have shown minimal or modest efficacy. Of these, riluzole has been approved for marketing in the United States, in Europe and in other countries. Patients and physicians who are trying to decide whether to use these treatments require background information: (a) to place these treatments in the context of other treatments; (b) to understand the outcome measures used; and (c) to understand the significance of the efficacy these treatments have shown. For example, in some cases treatment efficacy has been shown by some measures, but not others. This paper attempts to assist in this process. In addition, we attempt to show how to integrate objective data with relative or subjective factors, such as patient values, economic considerations, and the role of hope.

Acetates↗
PubMed1998

Linear estimates of rates of disease progression as predictors of survival in patients with ALS entering clinical trials.

Maximal voluntary isometric grip and foot dorsiflexion (FD) strength and forced vital capacity (FVC) were obtained in 62 patients with ALS at or close to enrollment into two clinical trials. The agents tested did not slow disease progression. Isometric strength data were standardized, and the worse side was taken. FVC was expressed as a percentage of the predicted value (FVC%). We derived linear estimates of rates of disease progression based on the isometric myometry and FVC measures and on disease duration. Forty one patients were known to have died or to have undergone tracheostomy for ventilatory support. Probability of tracheostomy-free survival was calculated using the Kaplan-Meier method. The measured values, the linear estimates for rates of decline of these values, gender, age at onset, bulbar vs. spinal onset, height and weight were tested as risk factors within the Cox proportional hazards model, using regression techniques. When tested individually, estimates of rates of decline based on all three measures (FD, grip and FVC%) were the only statistically significant risk factors (P<0.005). Multivariate analysis resulted in a 3-variable model (chi-square=75.3, P<0.00001) in which estimated rates of decline of FD strength and of FVC%, and bulbar onset were independently significant (P<0.0001, P<0.0007 and P<0.05, respectively). We conclude that linear estimates of the rate of disease progression till enrollment into a clinical trial may be better predictors of patient survival than demographic data or discrete biologic measures.

Adult↗
PubMed1998

Toward earlier diagnosis of amyotrophic lateral sclerosis: revised criteria. rhCNTF ALS Study Group.

We modified the World Federation of Neurology (WFN) diagnostic criteria for ALS to facilitate early diagnosis and used these criteria for enrollment of ALS patients in a clinical trial. The criteria developed required lower motor neuron (LMN) involvement in at least two limbs and upper motor neuron involvement in at least one region (bulbar, cervical, or lumbosacral). The EMG finding of fibrillation potentials was required for evidence of LMN involvement. Electrodiagnostic studies, neuroimaging, and laboratory studies were also used to exclude disorders that might mimic ALS. Using these criteria, the diagnosis of ALS was made at a mean time of 9.7 months from onset of symptoms, which compares favorably with the 12-month period cited in the literature. Using clinical assessment at completion of the trial, the diagnosis of ALS was believed to be accurate in those patients entered in the trial. However, pathologic confirmation of the diagnosis of ALS was not obtained. Based on our preliminary experience, we propose that these ALS diagnostic criteria will facilitate early diagnosis of ALS. Future studies should prospectively compare these criteria with the WFN criteria currently in use.

Amyotrophic Lateral Sclerosis↗
PubMed1998

Seizure onset from periventricular nodular heterotopias: depth-electrode study.

The association between gray matter heterotopias and seizures is well established; whether seizures originate from these lesions is not known. We evaluated three patients with intractable complex partial seizures and periventricular nodular heterotopias (PNHs) with video-EEG monitoring with multiple depth electrodes, including placement in the PNH, to determine whether seizures originate from the PNH. In two of the three patients, all seizures arose from the PNH as low-voltage beta activity. In the third patient, 80% arose from the hippocampi and 20% from the heterotopia. PNHs may serve as an epileptogenic focus in patients with intractable epilepsy.

Adult↗
PubMed1997

Reliability of maximal voluntary isometric contraction testing in a multicenter study of patients with amyotrophic lateral sclerosis. Syntex/Synergen Neuroscience Joint Venture rhCNTF ALS Study Group.

Maximal voluntary isometric contraction (MVIC) is becoming widely used for monitoring disease progression in amyotrophic lateral sclerosis (ALS). We evaluated the variability of MVIC in a large multicenter (29 sites) drug trial in ALS. Intra- and interrater variability were assessed twice during the 19-month study. Intrarater reliability increased from the first to the second test, approaching the reliability reported for a single experienced clinical evaluator, but interrater reliability did not. Multiple clinical evaluators in a single site increased the variability of MVIC measurements. Rigorous quality assurance standards and monitoring of clinical evaluators should be incorporated into the design of multicenter studies using MVIC, since low variability is necessary to detect a modest treatment effect.

Adult↗
PubMed1997

A brief quality-of-life measure for ALS clinical trials based on a subset of items from the sickness impact profile. The Syntex-Synergen ALS/CNTF Study Group.

We previously demonstrated a significant relationship (P<0.0001) between maximum voluntary isometric contraction (MVC) plus pulmonary function scores (the Tufts Quantitative Neuromuscular Exam Combination Megascore (TQNE CM)), and the Sickness Impact Profile (SIP) in a cohort of 524 ALS patients. Because the 136-item SIP questionnaire can be difficult to administer in this population, we examined SIP subscales and clinically derived item sets in relation to the TQNE CM in an effort to define a briefer measure of quality of life for use in clinical trials. Two 'Mini-SIP' indices performed as well as the overall SIP in reflecting the impact of muscle weakness on ALS patients' quality of life: a combination of two SIP subscales ('SIP-33'), and a 19-item set of questions independently chosen by a panel of ALS specialists ('SIP/ALS-19'). Either index potentially could be useful in ALS clinical trials. The SIP/ALS-19 is currently being used in a National ALS data base, providing an opportunity to evaluate its utility prospectively against other QOL measures in ALS patients.

Amyotrophic Lateral Sclerosis↗
PubMed1996

A placebo-controlled trial of recombinant human ciliary neurotrophic (rhCNTF) factor in amyotrophic lateral sclerosis. rhCNTF ALS Study Group.

Preclinical investigations indicated that recombinant human ciliary neurotrophic factor (rhCNTF) may have potential as therapy for amyotrophic lateral sclerosis (ALS). We evaluated the safety and efficacy of rhCNTF in a prospective, double-blind, placebo-controlled trial in 570 patients with ALS. Patients were randomized to receive 0.5, 2, or 5 micrograms/kg/day rhCNTF, or placebo, for 6 months. The primary efficacy end point was the change from baseline to the last on-treatment value of a combination megascore for limb strength (maximum voluntary isometric contraction) and pulmonary function. Secondary end points included individual arm and leg megascores, pulmonary function tests, an activities-of-daily-living outcome measure, and survival. The four treatment groups were similar at baseline with respect to age, sex, disease duration, and muscle strength values. At all doses tested, rhCNTF had no beneficial effect on the primary or secondary end points. Certain adverse events, as follows, appeared to be dose related: injection site reactions, cough, asthenia, nausea, anorexia, weight loss, and increased salivation. There was an increased number of deaths at the highest dose level. rhCNTF had no beneficial effect on any measure of ALS progression. There were increased adverse events in the 5 micrograms/kg group and increased deaths.

Adult↗
PubMed1996

Subacute encephalomyelitis presenting as stiff-person syndrome: clinical, polygraphic, and pathologic correlations.

A 60-year-old woman presented with stiff-person syndrome (SPS). Treatment with diazepam controlled her painful spasms initially. Two and one-half years after the onset of SPS, new spells of paroxysmal leg jerking and apnea developed. A spell was recorded with simultaneous video and polygraphic techniques that revealed simultaneous firing of motor unit potentials in several muscles (paraspinal, internal hamstring, and abdominal muscles). Apnea was associated with arterial oxygen desaturation. An increase in the dose of diazepam decreased the number and severity of these episodes. Seventeen months later, the patient began to taper the diazepam dose. Shortly thereafter, she had a cardiorespiratory arrest and subsequently died. Autopsy showed small chronic inflammatory foci in the pancreas (some associated with islets) and findings of diffuse encephalomyelitis characterized by perivascular cuffing in the spinal cord, brainstem, thalamus, hippocampus, and amygdala and a dense mononuclear infiltrate in the anterior horns of the lumbar and cervical cord, with relative preservation of axons and myelin. Cell typing showed this infiltrate was polyclonal and reactive. There have been rare cases of SPS associated with encephalomyelitis reported previously. Although the prolonged course in our patient suggested that SPS may have preceded encephalomyelitis, the more likely explanation is that the patient had an unusually long course of encephalomyelitis alone.

Brain↗
PubMed1996

Predictors of outcome of epilepsy surgery: multivariate analysis with validation.

PURPOSE: To identify predictors of outcome of epilepsy surgery, using the Duke experience, applying multivariate analysis and validation techniques. To compare the results of different modeling algorithms. Few previous studies have reported multivariate analysis, or validated their results. METHODS: Records of 116 patients with focal resections for intractable epilepsy from January 1, 1980 through June 30, 1989 were analyzed. Primary outcome variable was patient's condition in second postoperative year: seizure free (except auras), or not. Three predictors of biologic interest were specified a priori for confirmatory analysis. Additional predictors were considered within exploratory analysis. Logistic regression techniques were applied to assess relations with pre- and postoperative predictors. Internal validity was assessed by repeated random selection of training and validation samples, used in conjunction with bootstrap techniques. RESULTS: By using multivariate analysis, percentage of epileptic EEG activity arising from the site of resection and either imaging localization or lack of use of invasive monitoring were the only statistically significant preoperative predictors for good outcome at 2 years. Presence of seizures within 2 months of surgery was a significant postoperative predictor for a poor outcome. Adding more variables did not result in significantly improved models. Use of validation techniques reduced the degree of optimism in the predictive value of the models. CONCLUSIONS: Pooling of data from multiple institutions is needed to attain the large sample sizes needed for multivariate analysis with validation.

Adolescent↗