Safwan Jaradeh

Plasma exchange in polyneuropathy associated with monoclonal gammopathy of undetermined significance

BACKGROUND Polyneuropathy associated with monoclonal gammopathy of undetermined significance (MGUS) has been treated with plasma exchange, intravenous immune globulin, and chemotherapy, but the effectiveness of these treatments remains uncertain. METHODS We randomly assigned 39 patients with stable or worsening neuropathy and MGUS of the IgG, IgA, or IgM type to receive either plasma exchange twice weekly for three weeks or sham plasma exchange, in a double-blind trial. The patients who initially underwent sham plasma exchange subsequently underwent plasma exchange in an open trial. RESULTS In the double-blind trial, the average neuropathy disability score improved by 2 points from base line (from 62.5 to 60.5) in the sham-exchange group and by 12 points (from 58.3 to 46.3) in the plasma-exchange group (P = 0.06). A similar difference was observed in the weakness score, a component of the neuropathy disability score (improvement, 1 and 10 points, respectively; P = 0.07). After treatment the summed compound muscle action potentials of motor nerves were 1.2 mV lower (worse) than at base line in the sham-exchange group and 0.4 mV higher (better) in the plasma-exchange group (P = 0.07). The greater degree of improvement with plasma exchange was equal in magnitude to or greater than the difference between not being able to walk on the heels or toes and being able to perform these activities. Changes in the vibratory detection threshold, summed motor-nerve conduction velocity, and sensory-nerve action potentials did not differ significantly between the treatment groups. In the open trial, in which patients who initially underwent sham exchange were treated with plasma exchange, the neuropathy disability score (P = 0.04), weakness score (P = 0.07), and summed compound muscle action potentials (P = 0.07) improved more with plasma exchange than they had with sham exchange. In both the double-blind and the open trial, those with IgG or IgA gammopathy had a better response to plasma exchange than those with IgM gammopathy. CONCLUSIONS Plasma exchange appears to be efficacious in neuropathy associated with MGUS, especially of the IgG or IgA type.

Identification and characterization of cerebral cortical response to esophageal mucosal acid exposure and distention.

BACKGROUND & AIMS Esophageal acid exposure is a common occurrence in healthy individuals and patients with esophagitis. Clinically, perception of this exposure ranges from no perception to severe heartburn and chest pain. Cerebral cortical response to esophageal mucosal contact to acid has not been systematically studied. The aim of this study was to elucidate cerebral cortical response to esophageal acid exposure in normal individuals by functional magnetic resonance imaging (FMRI). METHODS We studied 10 normal healthy volunteers. Cortical FMRI response to 10 minutes of intraesophageal perfusion of 0.1N HCl (1 mL/min) was determined, and the results were compared with those of saline infusion and balloon distention. RESULTS Acid perfusion did not induce heartburn or chest pain but increased FMRI signal intensity by 6.7% +/- 2.0% over the preperfusion values. No increase was detected for saline infusion. FMRI signal intensity to balloon distention was similar to that of acid perfusion. Activation latency, activation to peak, and the deactivation periods for response to acid perfusion were significantly longer than those of balloon distention (P < 0.05). CONCLUSIONS Contact of esophageal mucosa with acid, before inducing heartburn, evokes a cerebral cortical response detectable by FMRI. Temporal characteristics of this response are significantly different from those induced by esophageal balloon distention.

The impact of a neurointensivist-led team on a semiclosed neurosciences intensive care unit*

Objective:To evaluate the impact of a newly appointed neurointensivist on neurosciences intensive care unit (NICU) patient outcomes and quality of care variables. Design:Observational cohort with historical controls. Setting:Ten-bed neurointensive care unit in tertiary university hospital. Patients:Mortality, length of stay (LOS), and discharge disposition of all patients admitted to the NICU were compared between two 19-month periods, before and after the appointment of a neurointensivist. Data regarding these patients were collected using the hospital database and the University Hospitals Consortium database. Individual patient medical records were reviewed for major complications and important prognostic variable documentation. Interventions:Appointment of a neurointensivist. Measurements and Main Results:We analyzed 1,087 patients before and 1,279 after the neurointensivist’s appointment. The unadjusted in-hospital mortality decreased from 10.1% in the before to 9.1% in the after period (95% confidence interval, −1.3 to 3%, relative mortality reduction of 9.9%), but this decrease was significantly different than the expected increase of 1.4% in University Hospitals Consortium mortality during the same period (p = .048). The unadjusted mortality in the NICU decreased from 8% to 6.3% (95% confidence interval, −0.5 to 4, relative mortality reduction 21%) and mean NICU LOS from 3.5 to 2.9 days (95% confidence interval, 0.2 to 0.9, relative NICU LOS reduction 17%). A significant 42% reduction of the risk of death during the first 3 days of NICU admission (p = .003) and a 12% greater risk for NICU discharge (p = .02) were found in the after period in multivariate proportional hazard models. Discharge home increased from 51.7% in the before to 59.7% in the after period (95% confidence interval, 4 to 12, relative increase of 15%) and discharge to a nursing home decreased from 8.1% to 6.8% (95% confidence interval, −1 to 4, relative decrease of 16%). Although a higher total number of complications occurred in the after period, fewer of them occurred in the NICU (odds ratio, 0.2; 95% confidence interval, 0.08 to 0.54, p = .001); this may possibly be due to the better documentation by the NICU team in the after period. Conclusions:The institution of a neurointensivist-led team model was associated with an independent positive impact on patient outcomes, including a lower intensive care unit mortality, LOS, and discharge to a skilled nursing facility and a higher discharge home.

Autonomic dysfunction, vasomotor rhinitis, and extraesophageal manifestations of gastroesophageal reflux

OBJECTIVE: Several recent reports suggest there may be a relationship between chronic rhinitis and extraesophageal manifestations of gastroe-sophageal reflux (EER). It is hypothesized that this relationship is a result of autonomic nervous system (ANS) dysfunction. STUDY DESIGN: Patients with isolated vasomotor rhinitis (VR), both VR and EER, and a control group were studied by a battery of tests designed to objectively evaluate ANS function. In addition all 3 groups underwent barium esophagogram and 4-site (proximal pharynx, distal pharynx, proximal esophagus, and distal esophagus) ambulatory pH monitoring. Adult patients fulfilling diagnostic criteria for VR, and with both VR and EER underwent objective ANS testing in a recently developed ANS testing laboratory. The control group consisted of age- and sex-matched adults without diagnostic criteria for VR or EER. RESULTS: In patients with VR only (n = 9), 2 patients had a positive esophagogram, whereas a positive pharyngeal reflux probe was found in 1 and an abnormal composite autonomic scoring scale (CASS) was found in 8 (mean VR CASS = 1.750 vs control CASS 0.556, P = .02). The group with VR and EER (n = 12) had a positive esophagogram in 10 patients, positive pharyngeal reflux by probe in 9, and all 12 had an abnormal CASS (mean CASS VR/EER = 2.909 vs CASS control = 0.556, P = .001 and vs VR CASS = 1.750, P = .05). The control patients (n = 9) had normal transesopohageal gastroduo-denoscopy in 8, 1 had a positive pharyngeal probe study, and all 9 had a normal CASS. In addition ANS testing in patients with diagnostic criteria for both VR/EER revealed statistically significant evidence of an adrenergic deficit as compared with control patients on the basis of mean phase II blood pressure response to Valsalva maneuver (mean phase II VR/EER = −16.730 vs control = −7.780, P = .05). In the VR only group, the phase II blood pressure decrease was greater than in control patients, but did not reach statistical significance (mean phase II VR = −9.370 vs control = − 7.780, P = 0.672). CONCLUSION: Patients with VR and VR/EER have objective evidence of ANS dysfunction when compared with a group of age- and sex-matched control patients. Patients with both VR/EER demonstrate a significantly greater degree of ANS dysfunction than patients with isolated VR. The mechanism by which VR and EER interact is not entirely clear, but ANS dysfunction is objectively associated with both disorders. In addition, patients with VR/EER seem to demonstrate hypo-function of the adrenergic component of the ANS, in contrast to the generally held hypothesis that VR results from increased cholinergic activity. Further characterization of the type of ANS abnormality may allow the development of novel pharmacologic therapies for these disorders.

Möbius syndrome: evidence for a vascular etiology.

We report five infants with restricted lateral gaze, facial diplegia, feeding difficulty, and/or respiratory disorders without significant pulmonary disease. Viral studies were negative in all patients. Two children had radiologic findings that included brain-stem hypoplasia and symmetric calcification in the dorsal tectum at the junction of the midbrain and pons. Autopsy of one of these two children demonstrated capillary telangiectasia in the mesencephalon and pons. The other three children had normal computed tomographic (CT) scans. However, their autopsies revealed focal brain-stem necrosis with calcifications but without vascular malformation. We suggest that the capillary malformations in one of our patients directly resulted in a vascular-induced necrosis and the manifestation of Möbius sequence. The similarity of symmetric neuropathologic findings in the three other patients and the CT scan in the one surviving patient suggest focal hemodynamic changes restricted to the posterior circulation, indirectly supporting a vascular theory of embryopathogenesis. (J Child Neurol 1993;8:260-265).

Autonomic Nervous System Evaluation of Patients With Vasomotor Rhinitis

Objective To demonstrate the utility of quantitative neurological laboratory testing of autonomic nervous system dysfunction and to apply this methodology to further study the relation of chronic vasomotor (nonallergic) rhinitis to the autonomic nervous system.

Evaluation of the autonomic nervous system

This article has reviewed the laboratory evaluation of autonomic disorders. Autonomic testing can be divided into the assessment of three functional domains: sudomotor (assessed best by the thermoregulatory sweat test or QSART), cardiovagal (assessed by the Valsalva ratio and heart rate response to deep breathing or standing up), and adrenergic (assessed by the blood pressure response to the Valsalva maneuver or head-upright tilt). Tables 2 and 3 summarize the test findings in a variety of clinical disorders affecting autonomic nervous system function.

Neurophysiology of swallowing in the aged

The neurophysiology of normal swallowing and its alterations related to age are reviewed. Clinical implications in health and disease are discussed.

Rapid Gastric Emptying Is More Common than Gastroparesis in Patients With Autonomic Dysfunction

OBJECTIVES:Autonomic dysfunction is associated with a wide variety of gastrointestinal symptoms. It is unclear how many patients with autonomic dysfunction have slow or rapid gastric emptying. The aim of this study was to determine the prevalence of rapid and delayed solid phase gastric emptying in patients with autonomic dysfunction referred for evaluation of gastrointestinal symptoms and the association of emptying rate with clinical symptoms.METHODS:Retrospective review of all patients with autonomic dysfunction who had a gastric emptying test from January, 1996 to March, 2005. Demographic data, clinical symptoms, composite autonomic scoring scale (CASS) score, and gastric emptying parameters were analyzed.RESULTS:Sixty-one subjects (women 49, age 42 [16–74] yr) with autonomic dysfunction were reviewed. Patients had mild-to-moderate (mean CASS score 3) autonomic dysfunction. Twenty-seven, 17, and 17 patients had rapid, normal, and delayed gastric emptying t1/2, respectively. In addition, 10 patients had initially rapid emptying in phase 1, with subsequent slowing in phase 2 to produce an overall normal or delayed t1/2. There was no difference in demographic data or CASS score among the three groups. More patients with initial or overall rapid emptying had diarrhea (70%) compared to patients with normal (33%) or delayed (33%) emptying (P = 0.018).CONCLUSIONS:Unexpectedly, more patients with autonomic dysfunction have rapid rather than delayed gastric emptying. The presence of diarrhea in patients with autonomic symptoms should prompt consideration for the presence of rapid gastric emptying. Conversely, the finding of rapid gastric emptying in patients with gastrointestinal symptoms should prompt consideration for the presence of underlying autonomic dysfunction.

Pharyngoglottal closure reflex: identification and characterization in a feline model

Earlier studies in humans have shown that pharyngeal stimulation by water at a threshold volume induces a brief vocal cord adduction, i. e., pharyngoglottal closure reflex. The present study was undertaken to 1) develop a suitable animal model for physiological studies of this reflex and 2) delineate its neural pathway and effector organs. Studies were done in cats by concurrent videoendoscopy and manometry followed by electromyographic studies. At a threshold volume (0.3 +/- 0.06 ml), injection of water into the pharynx resulted in a brief closure of the vocal folds, closing the introitus to the trachea. Duration of this closure averaged 1.1 +/- 0.1 s. Bilateral transection of the glossopharyngeal nerve completely abolished this reflex but not swallows induced by pharyngeal water stimulation. The pharyngoglottal closure reflex is present in the cats. The glossopharyngeal nerve is the afferent pathway of this reflex, and the interarytenoid and lateral cricoarytenoid muscles are among its target organs.Earlier studies in humans have shown that pharyngeal stimulation by water at a threshold volume induces a brief vocal cord adduction, i.e., pharyngoglottal closure reflex. The present study was undertaken to 1) develop a suitable animal model for physiological studies of this reflex and 2) delineate its neural pathway and effector organs. Studies were done in cats by concurrent videoendoscopy and manometry followed by electromyographic studies. At a threshold volume (0.3 ± 0.06 ml), injection of water into the pharynx resulted in a brief closure of the vocal folds, closing the introitus to the trachea. Duration of this closure averaged 1.1 ± 0.1 s. Bilateral transection of the glossopharyngeal nerve completely abolished this reflex but not swallows induced by pharyngeal water stimulation. The pharyngoglottal closure reflex is present in the cats. The glossopharyngeal nerve is the afferent pathway of this reflex, and the interarytenoid and lateral cricoarytenoid muscles are among its target organs.