Quantitative sudomotor abnormalities in clinically isolated rapid eye movement sleep behavior disorder.

BACKGROUND: Post-ganglionic sudomotor abnormalities are common in Parkinson's disease (PD), however data in clinically isolated REM sleep behavior disorder (iRBD) are limited. OBJECTIVE: To determine the prevalence of sudomotor abnormalities in a cohort of patients with iRBD. METHODS: We performed a retrospective review of patients seen in our autonomic clinic who underwent testing with the quantitative sudomotor axon reflex test (QSART). We identified three groups for comparison: 1.) iRBD, 2.) PD with RBD (PDwRBD) 3.) PD without RBD (PDwoRBD). RESULTS: PDwRBD (n = 27) patients demonstrated the greatest sudomotor abnormalities (sudomotor CASS 1.44 ± 1.24), followed by PDwoRBD (n = 23, 0.57 ± 0.5) and iRBD (n = 20, 0.55 ± 0.94) (p = 0.015). Twenty percent of patients with iRBD had an abnormal result, compared to 67% PDwRBD and 35% PDwoRBD. DISCUSSION: Sudomotor abnormalities are common in patients with iRBD, supporting the concept that peripheral autonomic impairment occurs early in the course of disease.

Autonomic nerve function in adults with cyclic vomiting syndrome: a prospective study.

BACKGROUND: Cyclic vomiting syndrome (CVS) is a functional gastrointestinal disorder that is characterized by recurrent episodes of intense vomiting. There are several postulated mechanisms involved in its pathogenesis and one potential explanation for this disorder may be linked to autonomic dysfunction. The aim of our study was to evaluate autonomic nerve function in patients with CVS prospectively. METHODS: We tested the sympathetic nervous system through postural changes in heart rate (HR) and blood pressure and the thermoregulatory sweat test. The parasympathetic nervous system was tested through the HR response to deep breathing (R-R variability on EKG). KEY RESULTS: A total of 20 patients who met Rome III criteria for CVS, 14 (70%) women and 6 (30%) men, and 20 controls were enrolled in the study. A total of 17 (85%) CVS subjects and 2 (10%) controls had abnormalities on thermoregulatory sweat testing (P < 0.001). A total of 7 (35%) patients and one control subject had evidence of postural tachycardia (P = 0.04) with an increase in HR > 30 on standing. Of the subjects, 18 (90%) had either abnormal sudomotor function or postural tachycardia or both. The HR response to deep breathing was normal in 19 (95%) subjects with CVS and 18 (95%) controls. CONCLUSIONS & INFERENCES: The results of this study suggest that the majority of subjects (90%) with CVS have impairment of the sympathetic nervous system with postural tachycardia and/or sudomotor dysfunction while parasympathetic nerve function appears to be intact. These findings of dysautonomia in CVS have implications in both the diagnosis and treatment of these patients.

Gender differences in cortical representation of rectal distension in healthy humans.

Cerebral cortical processing of information relayed via visceral afferents is poorly understood. We determined and compared cortical activity caused by various levels of rectal distension in healthy male and female subjects. Twenty-eight healthy, young (20-44 yr) volunteer subjects (13 male, 15 female) were studied with a paradigm-driven functional magnetic resonance imaging (fMRI) technique during barostat-controlled rectal distension at perception threshold and 10 mmHg below and above perception threshold. Male subjects showed localized clusters of fMRI activity primarily in the sensory and parietooccipital regions, whereas female subjects also showed activity in the anterior cingulate and insular regions. A progressive increase in maximum percent fMRI signal change and total volume of cortical activity was associated with the intensity of rectal distension pressure in both genders. Regions of cortical activity for below-threshold stimuli showed less substantial signal intensity and volume than responses for threshold and above-threshold stimuli. Volume of cortical activity during rectal distension in women was significantly higher than that for men for all distensions. We conclude that 1) there are substantial differences in female cortical activation topography during rectal distension compared with males; 2) intensity and volume of registered cortical activity due to rectal stimulation are directly related to stimulus strength; and 3) rectal stimulation below perception level is registered in the cerebral cortex.

Swallow-related cerebral cortical activity maps are not specific to deglutition.

Cortical representation of swallow-related motor tasks has not been systematically investigated. In this study, we elucidated and compared these cortical representations to those of volitional swallow using block-trial and single-trial methods. Fourteen volunteers were studied by functional magnetic resonance imaging. Cortical activation during both swallowing and swallow-related motor tasks that can be performed independent of swallowing, such as jaw clenching, lip pursing, and tongue rolling, was found in four general areas: the anterior cingulate, motor/premotor cortex, insula, and occipital/parietal region corresponding to Brodmann's areas 7, 19, and 31. Regions of activity, volume of activated voxels, and increases in signal intensity were found to be similar between volitional swallow and swallow-related motor tasks. These findings, using both block-trial and single-trial techniques, suggest that cerebral cortical regions activated during swallowing may not be specific to deglutitive function.

Cerebral cortical representation of reflexive and volitional swallowing in humans.

The purpose of this study was to compare cerebral cortical representation of experimentally induced reflexive swallow with that of volitional swallow. Eight asymptomatic adults (24-27 yr) were studied by a single-trial functional magnetic resonance imaging technique. Reflexive swallowing showed bilateral activity concentrated to the primary sensory/motor regions. Volitional swallowing was represented bilaterally in the insula, prefrontal, cingulate, and parietooccipital regions in addition to the primary sensory/motor cortex. Intrasubject comparison showed that the total volume of activity during volitional swallowing was significantly larger than that activated during reflexive swallows in either hemisphere (P < 0.001). For volitional swallowing, the primary sensory/motor region contained the largest and the insular region the smallest volumes of activation in both hemispheres, and the total activated volume in the right hemisphere was significantly larger compared with the left (P < 0.05). Intersubject comparison showed significant variability in the volume of activity in each of the four volitional swallowing cortical regions. We conclude that reflexive swallow is represented in the primary sensory/motor cortex and that volitional swallow is represented in multiple regions, including the primary sensory/motor cortex, insular, prefrontal/cingulate gyrus, and cuneus and precuneus region. Non-sensory/motor regions activated during volitional swallow may represent swallow-related intent and planning and possibly urge.

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. METHODS: It has been suspected that vasomotor rhinitis is due either to a hyperactive parasympathetic nervous system or an imbalance between it and the sympathetic nervous system. The exact relation has not been determined. Recently neurological laboratories have been developed in which a battery of tests can be performed to determine reactivity of the autonomic nervous system. RESULTS: Autonomic nervous system testing was performed on 19 patients with symptoms fulfilling the diagnostic criteria for vasomotor rhinitis and the results were compared with 75 sex- and age-matched control subjects. Patients with vasomotor rhinitis had significant abnormalities of their sudomotor, cardiovagal, and adrenergic subscores. Their composite autonomic scale score was significantly impaired at 2.43, as compared with 0.11 for controls (P < .005). CONCLUSION: Autonomic nervous system dysfunction is significant in patients with vasomotor rhinitis. Possible factors that trigger this dysfunction including nasal trauma and extraesophageal manifestations of gastroesophageal reflux are discussed.

Spin-lock magnetic resonance imaging of muscle in patients with autosomal recessive limb girdle muscular dystrophy.

Spin-lock imaging is a new magnetic resonance imaging (MRI) technique used to reflect the microstructural integrity of muscle. The purpose of this study was to characterize spin-lock contrast (SLC) of calf muscles in limb girdle muscular dystrophy (LGMD). The calf muscles of 5 patients with LGMD and 10 healthy volunteers were imaged with an off-resonance magnetic resonance (MR) spin-lock suppression pulse. Spin-lock suppression ratios were calculated for anterior tibialis, posterior tibialis, soleus, and gastrocnemius muscles. Clinical assessments of muscle strength were compared to the spin-lock suppression ratios in the LGMD group. Strong SLC was observed in healthy muscles, with mean (+/- SD) suppression ratios ranging from 51.2% (+/- 3.6%) to 56.3% (+/- 1.3%). In diseased muscle, spin-lock signal suppression was reduced by 8%-70%, demonstrating an inverse correlation between symptom duration and suppression ratios. Spin-lock contrast in the patients with LGMD, as a reflection of tissue integrity, was best preserved in posterior tibialis, anterior tibialis, soleus, and gastrocnemius muscles in descending order. Clinical assessments did a poorer job of differentiating than SLC did and were in poor agreement with spin-lock suppression ratios. Spin-lock MRI can quantify microstructural changes in LGMD and appears to provide information not obtainable from clinical evaluations. This suggests that this noninvasive technique may be useful in evaluating the extent, progression, and response to therapy of LGMD.

Electromyographic recording of the cricopharyngeus muscle in humans.

Electromyography of the cricopharyngeus muscle is helpful in the study of normal swallowing and in the evaluation of various conditions leading to dysphagia. This article describes the technical aspects of the studies and the findings in normal controls and in various disease states.

Progressive polyradiculoneuropathy in diabetes: correlation of variables and clinical outcome after immunotherapy.

OBJECTIVE: To quantify the progression of diabetic polyradiculoneuropathy-a condition in which immune factors have been implicated-after immunotherapy. METHODS: The study evaluated 15 consecutive patients with this condition. All patients were older than 40. Four had type I diabetes and six were women. The duration of pre-existing diabetes varied from 2 to 20 years. The clinical presentation was dominated by painful progressive motor weakness, with or without exacerbation of sensory symptoms. The weakness involved all limbs, but was often asymmetric. RESULTS: Electrophysiological testing showed a predominantly axonal polyneuropathy, with more recent denervating polyradiculopathy. Analysis of CSF showed increased protein in 14 and oligoclonal bands in five. Quantitative autonomic tests showed abnormalities in all patients. Sural nerve biopsy was performed in 14 patients; all showed fibre loss and segmental demyelination, four had occasional onion bulbs, and 10 showed various inflammatory infiltrates. After immunomodulating therapy, there was no further deterioration and clinical improvement occurred in all patients. Sweat responses, cardiovascular reflexes, and sural nerve fibre density correlated best with functional outcome. There was no significant difference between plasmapheresis and intravenous gammaglobulin. CONCLUSION: Immunotherapy may improve this condition, but only certain variables correlate with rapid therapeutic response.

Magnetization transfer imaging of skeletal muscle in autosomal recessive limb girdle muscular dystrophy.

PURPOSE: The purpose of this work was to characterize magnetization transfer (MT) contrast of skeletal muscles in limb girdle muscular dystrophy (LGMD). METHOD: The calf muscles of five LGMD patients and 10 normal volunteers were imaged with an off-resonance MT suppression pulse applied to T1-weighted images. MT suppression ratios were calculated for anterior tibialis, posterior tibialis, soleus, and gastrocnemius muscles in the LGMD and control groups. The relationship between MT of individual muscles and the duration of LGMD symptoms was determined. RESULTS: Strong MT contrast was observed in normal calf muscles, with mean (+/-SD) suppression ratios ranging from 37.9% (+/-3.0) to 41.1% (+/-2.1). In diseased muscle, MT signal suppression ranged from 11 to 38%, demonstrating an inverse relationship between symptom duration and suppression ratios. MT contrast in the LGMD patients, as a reflection of muscle tissue integrity, was preserved in posterior or anterior tibialis, soleus, and gastrocnemius muscles, respectively. Suppression ratios were dramatically reduced in muscles with gross fatty infiltration but also were reduced in muscle tissues without visual evidence of fatty infiltration. CONCLUSION: MT imaging provides a quantitative measure of pathologic changes occurring within the skeletal muscles of patients with LGMD relative to normal and may be useful in evaluating disease extent, progression, and response to new therapies as they become available.

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.

Single-voxel proton MR spectroscopy of nonneoplastic brain lesions suggestive of a neoplasm.

BACKGROUND AND PURPOSE: MR spectroscopy is used to characterize biochemical components of normal and abnormal brain tissue. We sought to evaluate common histologic findings in a diverse group of nonneoplastic diseases in patients with in vivo MR spectroscopic profiles suggestive of a CNS neoplasm. METHODS: During a 2-year period, 241 patients with suspected neoplastic CNS lesions detected on MR images were studied with MR spectroscopy. Of these, five patients with a nonneoplastic diagnosis were identified retrospectively; a sixth patient without tissue diagnosis was added. MR spectroscopic findings consistent with a neoplasm included elevated choline and decreased N-acetylaspartate and creatine, with or without detectable mobile lipid and lactate peaks. RESULTS: The histologic specimens in all five patients for whom tissue diagnoses were available showed significant WBC infiltrates, with both interstitial and perivascular accumulations of lymphocytes, macrophages, histiocytes, and (in one case) plasma cells. Reactive astrogliosis was also prominent in most tissue samples. This cellular immune response was an integral component of the underlying disorder in these patients, including fulminant demyelination in two patients, human herpesvirus 6 encephalitis in one patient, organizing hematoma from a small arteriovenous malformation in one patient, and inflammatory pseudotumor in one patient. Although no histologic data were available in the sixth patient, neoplasm was considered unlikely on the basis of ongoing clinical and neuroradiologic improvement without specific therapy. CONCLUSION: Nonneoplastic disease processes in the CNS may elicit a reactive proliferation of cellular elements of the immune system and of glial tissue that is associated with MR spectroscopic profiles indistinguishable from CNS neoplasms with current in vivo MR spectroscopic techniques. Such false-positive findings substantiate the need for histologic examination of tissue as the standard of reference for the diagnosis of intracranial mass lesions.

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.

Mobius syndrome: electrophysiologic studies in seven cases.

Mobius syndrome is characterized by congenital facial diplegia, frequent impairment of gaze, variable involvement of other cranial muscles, and various musculoskeletal anomalies. The site of dysfunction remains debatable. We performed detailed electrophysiologic studies in 5 children and 2 adults with Mobius syndrome to better delineate the pathophysiology of this disorder. Sensory and motor conduction studies were normal in the extremities. Facial compound muscle action potential amplitudes were reduced in all patients. The blink reflex R1 responses were unobtainable unilaterally in 2 patients and unobtainable bilaterally in 3 patients. Otherwise, R1 and R2 latencies were variably prolonged. The jaw jerk and masseter silent periods, tested in 2 patients, were normal. Detailed electromyographic studies of facial muscles revealed multifocal, chronic neurogenic changes. The findings indicate a brain stem process predominantly affecting the facial nuclei and their internuclear connections rather than a supranuclear or muscular site of involvement.

Isolated sensory impairment of the thumb due to an intraneural ganglion cyst in the median nerve.

We describe an unusual case of digital neuropathy of the thumb due to compression of the median nerve in the distal forearm by an extruded ganglion cyst originating from the radio-scaphoid joint of the wrist. Electrophysiologically, both conduction slowing and block of median motor and sensory axons were present across the cyst. These changes improved after surgery.

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.