Assessment of transient ischemic dilation (TID) ratio in gated SPECT myocardial perfusion imaging (MPI) using regadenoson, a new agent for pharmacologic stress testing.

BACKGROUND: Abnormal values of the transient ischemic dilation (TID) ratio are associated with severe and extensive coronary artery disease (CAD). The objective of this study was to determine the relationship between TID, determined from stress and rest ventricular volumes during regadenoson gated single-photon emission computed tomography myocardial perfusion imaging (MPI) dual isotope studies, and the extent of CAD found during coronary angiography. METHODS: 195 patients who underwent dual isotope MPI with regadenoson and cardiac angiography between March 2009 and February 2010 were analyzed. TID was calculated using commercially available software, Emory Cardiac Toolbox. Mean TID values were compared across disease types. A threshold for abnormal TID was determined by adding two standard deviations (SDs) to the mean TID of the "non-obstructive CAD" subgroup. RESULTS: In the 195-patient group analyzed, the mean TID ratio for non-obstructive CAD (n = 104) was found to be 1.09 with a SD of 0.15. In a subgroup of patients whose angiogram was within 3 months of MPI (n = 155), the mean TIDs for non-obstructive disease (n = 81), single-vessel disease (n = 35), and multi-vessel disease (n = 39) were 1.09, 1.15, and 1.19 with SDs of 0.16, 0.19, and 0.26, respectively. Those with an abnormal TID had a crude and adjusted odds ratio of 3.4 for multi-vessel disease which was statistically significant. History of diabetes was not found to be a significant confounder, effect modifier, or mediator of the relationship between the TID and the vessel disease. CONCLUSION: The mean TID ratio in patients with multi-vessel disease was 1.19. The threshold for an abnormal TID was 1.39 with specificity of 95% and sensitivity of 15% for determining multi-vessel CAD status. We conclude that the level of TID in gated SPECT MPI using regadenoson is associated with the degree of CAD on angiography.

Phase II screening trial of lithium carbonate in amyotrophic lateral sclerosis: examining a more efficient trial design.

OBJECTIVE: To use a historical placebo control design to determine whether lithium carbonate slows progression of amyotrophic lateral sclerosis (ALS). METHODS: A phase II trial was conducted at 10 sites in the Western ALS Study Group using similar dosages (300-450 mg/day), target blood levels (0.3-0.8 mEq/L), outcome measures, and trial duration (13 months) as the positive trial. However, taking riluzole was not a requirement for study entry. Placebo outcomes in patients matched for baseline features from a large database of recent clinical trials, showing stable rates of decline over the past 9 years, were used as historical controls. RESULTS: The mean rate of decline of the ALS Functional Rating Scale-Revised was greater in 107 patients taking lithium carbonate (-1.20/month, 95% confidence interval [CI] -1.41 to -0.98) than that in 249 control patients (-1.01/month, 95% CI -1.11 to -0.92, p = 0.04). There were no differences in secondary outcome measures (forced vital capacity, time to failure, and quality of life), but there were more adverse events in the treated group. CONCLUSIONS: The lack of therapeutic benefit and safety concerns, taken together with similar results from 2 other recent trials, weighs against the use of lithium carbonate in patients with ALS. The absence of drift over time and the availability of a large database of patients for selecting a matched historical control group suggest that use of historical controls may result in more efficient phase II trials for screening putative ALS therapeutic agents. CLASSIFICATION OF EVIDENCE: This study provided Class IV evidence that lithium carbonate does not slow the rate of decline of function in patients with ALS over 13 months.

Practice parameter update: the care of the patient with amyotrophic lateral sclerosis: drug, nutritional, and respiratory therapies (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology.

OBJECTIVE: To systematically review evidence bearing on the management of patients with amyotrophic lateral sclerosis (ALS). METHODS: The authors analyzed studies from 1998 to 2007 to update the 1999 practice parameter. Topics covered in this section include slowing disease progression, nutrition, and respiratory management for patients with ALS. RESULTS: The authors identified 8 Class I studies, 5 Class II studies, and 43 Class III studies in ALS. Important treatments are available for patients with ALS that are underutilized. Noninvasive ventilation (NIV), percutaneous endoscopic gastrostomy (PEG), and riluzole are particularly important and have the best evidence. More studies are needed to examine the best tests of respiratory function in ALS, as well as the optimal time for starting PEG, the impact of PEG on quality of life and survival, and the effect of vitamins and supplements on ALS. RECOMMENDATIONS: Riluzole should be offered to slow disease progression (Level A). PEG should be considered to stabilize weight and to prolong survival in patients with ALS (Level B). NIV should be considered to treat respiratory insufficiency in order to lengthen survival (Level B) and to slow the decline of forced vital capacity (Level B). NIV may be considered to improve quality of life (Level C) [corrected].Early initiation of NIV may increase compliance (Level C), and insufflation/exsufflation may be considered to help clear secretions (Level C).

Practice parameter update: the care of the patient with amyotrophic lateral sclerosis: multidisciplinary care, symptom management, and cognitive/behavioral impairment (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology.

OBJECTIVE: To systematically review evidence bearing on the management of patients with amyotrophic lateral sclerosis (ALS). METHODS: The authors analyzed studies from 1998 to 2007 to update the 1999 practice parameter. Topics covered in this section include breaking the news, multidisciplinary clinics, symptom management, cognitive and behavioral impairment, communication, and palliative care for patients with ALS. RESULTS: The authors identified 2 Class I studies, 8 Class II studies, and 30 Class III studies in ALS, but many important areas have been little studied. More high-quality, controlled studies of symptomatic therapies and palliative care are needed to guide management and assess outcomes in patients with ALS. RECOMMENDATIONS: Multidisciplinary clinic referral should be considered for managing patients with ALS to optimize health care delivery and prolong survival (Level B) and may be considered to enhance quality of life (Level C). For the treatment of refractory sialorrhea, botulinum toxin B should be considered (Level B) and low-dose radiation therapy to the salivary glands may be considered (Level C). For treatment of pseudobulbar affect, dextromethorphan and quinidine should be considered if approved by the US Food and Drug Administration (Level B). For patients who develop fatigue while taking riluzole, withholding the drug may be considered (Level C). Because many patients with ALS demonstrate cognitive impairment, which in some cases meets criteria for dementia, screening for cognitive and behavioral impairment should be considered in patients with ALS (Level B). Other management strategies all lack strong evidence.

Bilateral isolated phrenic neuropathy causing painless bilateral diaphragmatic paralysis.

The authors report four patients with a syndrome of painless bilateral isolated phrenic neuropathy. Electrophysiologic testing demonstrated active denervation restricted to the diaphragm. Long-term recovery was poor. The authors conclude that bilateral isolated phrenic neuropathy is a cause of painless diaphragmatic paralysis distinguishable from immune brachial plexus neuropathy and other neuromuscular disorders with similar clinical presentation.

Myopathy with skeletal asymmetry and hemidiaphragm elevation is caused by myotubularin mutations.

The authors report two families with a myopathy phenotype affecting only women, marked by asymmetric weakness, skeletal asymmetry, and an elevated hemidiaphragm. One family had a mutation in a stop codon in exon 9 of the myotubularin gene, and the other had a splice site mutation in exon 13. Both families had manifesting and nonmanifesting carriers. Skewed X-inactivation appeared to explain the clinical manifestations in only one of the two families.

Axonal multifocal motor neuropathy without conduction block or other features of demyelination.

BACKGROUND: Conduction block is considered an essential finding for the distinction between motor neuropathies and lower motor neuron disorders. Only a small number of reports describe patients with multifocal motor neuropathies who lack overt conduction block, although in these cases other features of demyelination still suggest the presence of a demyelinating disorder. In contrast, a purely axonal multifocal motor neuropathy has not been described. METHODS: This report describes nine patients with slowly or nonprogressive multifocal motor neuropathies who had purely axonal electrodiagnostic features. RESULTS: GM1 antibodies titers were normal in all nine cases. Six patients were treated with either prednisone or IV immunoglobulin and three showed convincing improvement. CONCLUSIONS: These findings suggest an immune-mediated motor neuropathy with axonal electrophysiologic features that appears to be distinct from both multifocal motor neuropathy and established motor neuron disorders.

Malnutrition-induced myopathy following Roux-en-Y gastric bypass.

A 42-year-old man developed a myopathy in the setting of malnutrition following Roux-en-Y gastric bypass for the treatment of morbid obesity. No specific vitamin or electrolyte deficiency was identified. Muscle biopsy revealed type II fiber atrophy. He recovered after the initiation of continuous enteral feeding. We suggest that malnutrition was the underlying cause of his myopathy.

Dying in long-term care facilities: support needs of other residents, relatives, and staff.

This paper explores the support needs of residents, relatives, and care staff when someone dies in a facility for older people. The authors draw on the qualitative findings from an English study, which investigated the case for applying the principles and practices of palliative care to people dying in these settings. Relatives need practical as well as emotional support, which is often not met adequately by nursing home staff. Managers varied in the extent to which they recognized other residents' emotional needs or supported relatives. Care staff members acknowledged needing practical and emotional support, but management was often unable to deliver it. Lack of training in recognizing and addressing needs in addition to financial and staffing constraints were factors that prevented managers from providing support for staff, residents, and relatives.

Physical and occupational therapy undergraduates' stereotypes of one another.

Literature suggests that increased interaction between physical therapy and occupational therapy students may improve their understanding of each other's profession. This cross-sectional study examined positive and negative stereotypes in an educational setting in which physical and occupational therapy students take over 25% of their curricular courses together. The aim of the study was to assess whether interaction between these students in and out of the classroom positively affected their views of each other, as compared with physical and occupational therapy students in previous studies who did not take classes together. Senior students, 25 physical therapy and 28 occupational therapy, completed two copies of the Health Team Stereotype Scale questionnaire exploring attitudes concerning their own chosen profession and the other participants' profession. They also completed an extracurricular activities survey to indicate how much they participated in activities outside of the classroom with students from the other profession. On the stereotype scale, physical therapy students' self-assessment compared with their assessment of occupational therapy students yielded 28 significantly (p<.05) different adjective pairs; occupational therapy students' self-assessment compared with their assessment of physical therapy students yielded 26 significantly (p<.05) different adjective pairs. The students rarely or never participated in extracurricular activities with each other. When comparing present results with those of previous studies, present subjects selected significantly fewer negative adjective pairs to describe the other profession. The results indicate a more positive view of each other's profession than in the previous studies. The interdisciplinary education model examined in our institution may have fostered positive attitudes among students in these programs.

Clinical spectrum of chronic acquired demyelinating polyneuropathies.

A number of presentations of chronic demyelinating polyneuropathy have been identified, each distinguished by its phenotypic pattern. In addition to classic chronic inflammatory demyelinating polyneuropathy (CIDP), which is characterized clinically by symmetric proximal and distal weakness and sensory loss, several regional variants can be recognized: multifocal motor neuropathy (MMN: asymmetric and pure motor), multifocal acquired demyelinating sensory and motor (MADSAM) neuropathy (asymmetric, sensory, and motor), and distal acquired demyelinating symmetric (DADS) neuropathy (symmetric, distal, sensory, and motor). There are also temporal, pathological, and disease-associated variants. This review describes a clinical scheme for approaching the chronic acquired demyelinating polyneuropathies that leads to a rational use of supportive laboratory studies and treatment options. In addition, we propose new diagnostic criteria for CIDP that more accurately reflect current clinical practice.

Cervicobrachial involvement in diabetic radiculoplexopathy.

Diabetic radiculoplexopathy is commonly viewed as a condition affecting the lower extremities. However, other regions may also be affected and the presence of upper extremity involvement has rarely been emphasized. Our goal was to illustrate the clinical features of arm involvement in this condition. Of 60 patients with diabetic lumbosacral radiculoplexopathy, we identified 9 who also had upper extremity involvement. The study included 8 men and 1 woman, ranging in age from 36 to 71 years. Upper limb involvement developed simultaneously with the onset of lower limb disorder in 1 patient, preceded it by 2 months in another patient, and occurred between 3 weeks and 15 months later in the remaining 7. In 5 cases, arm involvement developed after symptoms in the legs began to improve. The upper extremity weakness affected the hands and forearms most severely. It was unilateral in 5 patients and bilateral but asymmetric in 4. Pain was often present, but it was not a prominent feature. In most patients, neurologic deficits in the arms improved spontaneously after 2-9 months. We conclude that diabetic radiculoplexopathy may involve the cervical region before, after, or simultaneously with the lumbosacral syndrome. The upper limb process is similar to that in the legs, with subacutely progressive weakness and pain followed by spontaneous recovery.

Acute sensory neuropathy: a sensory form of Guillain-Barré syndrome?

A 62-year-old man presented with an acute onset of symmetric upper and lower extremity paresthesias. Neurological examination showed normal motor strength throughout with areflexia and reduced vibratory and proprioceptive sense in all four extremities. A lumbar puncture performed 6 weeks after onset demonstrated elevated cerebrospinal fluid protein with no cells. Electrodiagnostic testing 7 weeks after onset revealed a primarily sensory neuropathy with normal motor conduction and needle electromyographic studies Symptoms stabilized within 3 weeks of onset and improvement began within 2 months. Except for the absence of motor disturbance, this case appears to resemble Guillain-Barré syndrome.

Stimulus repetition effects on texture-based visual search by pigeons.

Four experiments investigated the effects of within-session stimulus repetition on texture discrimination. Six pigeons (Columba livia) searched for a contrasting target region (color or shape) randomly embedded within a larger distractor region for food reinforcement. Experiment 1 found that repeating features of the distractors, but not those of the target, across trials increased the accuracy of target localization relative to baseline. Experiment 2 found that subsequently switching the identity of a repeated distractor feature to the target decreased accuracy. Experiment 3 found that the effects of repeating a distractor feature influenced search performance for at least 60 trials after this learning. Experiment 4 found that differential stimulus-outcome relations can produce control by repeated target features. The results are discussed in terms of the factors and strategies involved in the control of avian visual search behavior.

Distal acquired demyelinating symmetric neuropathy.

OBJECTIVE: To characterize an acquired, symmetric, demyelinating neuropathic variant with distal sensory or sensorimotor features. BACKGROUND: Classic chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) patients have prominent proximal and distal weakness. However, chronic demyelinating neuropathies may present with different phenotypes. An approach that distinguishes these disorders primarily according to the pattern of weakness may be useful to the clinician. METHODS: A total of 53 patients with acquired symmetric demyelinating polyneuropathies were classified primarily according to the pattern of the neuropathy and secondarily according to the presence and type of monoclonal protein (M-protein) in this retrospective review. The authors distinguished between patients with distal sensory or sensorimotor involvement, designated as distal acquired demyelinating symmetric (DADS) neuropathy, from those with proximal and distal weakness, who were designated as CIDP. RESULTS: M-proteins were present in 22% of patients with CIDP. There were no features that distinguished clearly between CIDP patients with or without an M-protein, and nearly all of these patients responded to immunomodulating therapy. In contrast, nearly two-thirds of the patients with DADS neuropathy had immunoglobulin M (IgM) kappa monoclonal gammopathies, and this specific combination predicted a poor response to immunomodulating therapy. Antimyelin-associated glycoprotein (anti-MAG) antibodies were present in 67% of these patients. CONCLUSION: Distinguishing acquired demyelinating neuropathies by phenotype can often predict the presence of IgM kappa M-proteins, anti-MAG antibodies, and responses to immunomodulating therapy.

Brachial amyotrophic diplegia: a slowly progressive motor neuron disorder.

OBJECTIVE: To describe a sporadic motor neuron disorder that remains largely restricted to the upper limbs over time. BACKGROUND: Progressive amyotrophy that is isolated to the upper limbs in an adult often suggests ALS. The fact that weakness can remain largely confined to the arms for long periods of time in individuals presenting with this phenotype has not been emphasized. METHODS: We reviewed the records of patients who had a neurogenic "man-in-the-barrel" phenotype documented by examination at least 18 months after onset. These patients had severe bilateral upper-extremity neurogenic atrophy that spared lower-extremity, respiratory, and bulbar musculature. RESULTS: Nine of 10 patients meeting these criteria had a purely lower motor neuron disorder. During follow-up periods ranging from 3 to 11 years from onset, only three patients developed lower-extremity weakness, and none developed respiratory or bulbar dysfunction or lost the ability to ambulate. CONCLUSION: Patients presenting with severe weakness that is fully isolated to the upper limbs, without pyramidal signs, may have a relatively stable variant of motor neuron disease.

Power laws and athletic performance.

In a previous study, we showed that the 1992 men's world record running times in the 100 m to 200 km could be represented accurately by the equation T = cDn, where T is the calculated record time for distance D, and c and n are positive constants. Here, we extend that to cover the years 1925-65 at 10-year intervals and 1970-95 in 5-year intervals for distances of 100 m to 10 km. Values of n for all years lie along a straight line with a small negative slope. A regression analysis yields an equation for values of n covering the period 1925-95. Values of c from 1925 to 1995 were fitted by a quadratic equation. These two equations define a surface in three-dimensional space (log(T), log(D), data) for all men's world record runs over the 70-year period for distances of 100 m to 10 km. We also demonstrated previously that event times, t, do not scatter randomly with respect to the values of T but form a consistent pattern about the straight lines in log(T) versus log(D) plots. In this study, we show that the pattern of (t-T)/t as a function of date has remained constant for the past 70 years.

Chronic cryptogenic sensory polyneuropathy: clinical and laboratory characteristics.

BACKGROUND: Chronic sensory-predominant polyneuropathy (PN) is a common clinical problem confronting neurologists. Even with modern diagnostic approaches, many of these PNs remain unclassified. OBJECTIVE: To better define the clinical and laboratory characteristics of a large group of patients with cryptogenic sensory polyneuropathy (CSPN) evaluated in 2 university-based neuromuscular clinics. DESIGN: Medical record review of patients evaluated for PN during a 2-year period. We defined CSPN on the basis of pain, numbness, and tingling in the distal extremities without symptoms of weakness. Sensory symptoms and signs had to evolve for at least 3 months in a roughly symmetrical pattern. Identifiable causes of PN were excluded by history, physical examination findings, and results of laboratory studies. We analyzed clinical and laboratory data from patients with CSPN and compared findings in patients with and without pain. RESULTS: Of 402 patients with PN, 93 (23.1%) had CSPN and stable to slowly progressive PN syndrome. These patients presented with a mean age of 63.2 years and a mean duration of symptoms of 62.9 months. Symptoms almost always started in the feet and included distal numbness or tingling in 86% of patients and pain in 72% of patients. Despite the absence of motor symptoms at presentation, results of motor nerve conduction studies were abnormal in 60% of patients, and electromyographic evidence of denervation was observed in 70% of patients. Results of laboratory studies were consistent with axonal degeneration. Patients with and without pain were similar regarding physical findings and laboratory test abnormalities. Only a few patients (<5%) had no evidence of large-fiber dysfunction on physical examination or electrophysiologic studies. All 66 patients who had follow-up examinations (mean, 12.5 months) remained ambulatory. CONCLUSIONS: Cryptogenic sensory polyneuropathy is a common, slowly progressive neuropathy that begins in late adulthood and causes limited motor impairment. Isolated small-fiber involvement is uncommon in this group of patients. Management should focus on rational pharmacotherapy of neuropathic pain combined with reassurance of CSPN's benign clinical course.

Multifocal acquired demyelinating sensory and motor neuropathy: the Lewis-Sumner syndrome.

We report 11 patients with multifocal acquired demyelinating sensory and motor (MADSAM) neuropathy, defined clinically by a multifocal pattern of motor and sensory loss, with nerve conduction studies showing conduction block and other features of demyelination. The clinical, laboratory, and histological features of these patients were contrasted with those of 16 patients with multifocal motor neuropathy (MMN). Eighty-two percent of MADSAM neuropathy patients had elevated protein concentrations in the cerebrospinal fluid, compared with 9% of the MMN patients (P < 0.001). No MADSAM neuropathy patient had elevated anti-GM1 antibody titers, compared with 56% of MMN patients (P < 0.01). In contrast to the subtle abnormalities described for MMN, MADSAM neuropathy patients had prominent demyelination on sensory nerve biopsies. Response to intravenous immunoglobulin treatment was similar in both groups (P = 1.0). Multifocal motor neuropathy patients typically do not respond to prednisone, but 3 of 6 MADSAM neuropathy patients improved with prednisone. MADSAM neuropathy more closely resembles chronic inflammatory demyelinating polyneuropathy and probably represents an asymmetrical variant. Given their different clinical patterns and responses to treatment, it is important to distinguish between MADSAM neuropathy and MMN.