Classification and prediction of clinical Alzheimer's diagnosis based on plasma signaling proteins.

A molecular test for Alzheimer's disease could lead to better treatment and therapies. We found 18 signaling proteins in blood plasma that can be used to classify blinded samples from Alzheimer's and control subjects with close to 90% accuracy and to identify patients who had mild cognitive impairment that progressed to Alzheimer's disease 2-6 years later. Biological analysis of the 18 proteins points to systemic dysregulation of hematopoiesis, immune responses, apoptosis and neuronal support in presymptomatic Alzheimer's disease.

Progressive cerebral injury in the setting of chronic HIV infection and antiretroviral therapy.

Emerging evidence suggests that CNS injury and neurocognitive impairment persist in the setting of chronic HIV infection and combination antiretroviral therapy (CART). Yet, whether neurological injury can progress in this setting remains uncertain. Magnetic resonance spectroscopy and neurocognitive and clinical assessments were performed over 2 years in 226 HIV-infected individuals on stable CART, including 138 individuals who were neurocognitively asymptomatic (NA). Concentrations of N-acetylaspartate (NAA), creatine (Cr), choline (Cho), myoinositol, and glutamate/glutamine (Glx) were measured in the midfrontal cortex (MFC), frontal white matter (FWM), and basal ganglia (BG). Longitudinal changes in metabolite levels were determined using linear mixed effect models, as were metabolite changes in relation to global neurocognitive function. HIV-infected subjects showed significant annual decreases in brain metabolite levels in all regions examined, including NAA (2.95 %) and Cho (2.61 %) in the FWM; NAA (1.89 %), Cr (1.84 %), Cho (2.19 %), and Glx (6.05 %) in the MFC; and Glx (2.80 %) in the BG. Similar metabolite decreases were observed in the NA and subclinically impaired subgroups, including subjects with virologic suppression in plasma and CSF. Neurocognitive decline was associated with longitudinal decreases in Glx in the FWM and the BG, and in NAA in the BG. Widespread progressive changes in the brain, including neuronal injury, occur in chronically HIV-infected persons despite stable antiretroviral treatment and virologic suppression and can lead to neurocognitive declines. The basis for these findings is poorly understood and warrants further study.

Analysis of continuous diaphragm electromyographic signal: results from a patient with amyotrophic lateral sclerosis.

INTRODUCTION: Analysis of continuous diaphragm electromyography (dEMG) has not been well studied. We describe a system of analyzing continuous dEMG using implanted electrodes. METHODS: dEMG signal was acquired via two pairs of electrodes near the diaphragm motor points. Raw bursts of dEMG signal were compared to externally captured electrocardiogram (ECG) using adaptive filtering in order to remove cardiac contamination. Differential energy levels were used to identify each dEMG burst, and average amplitude and area values from both hemidiaphragms were aggregated and averaged for the duration of the recording. RESULTS: A 64-year-old patient with amyotrophic lateral sclerosis underwent three serial dEMG studies every 6 months. An average of three tracings were collected per visit, and all had excellent intertest reliability (κ > 0.8). Average dEMG area correlated with forced vital capacity and mean inspiratory pressure (r(2) > 0.9). CONCLUSIONS: The approach described represents a comprehensive method for capturing and analyzing continuous diaphragm EMG signal.

Utility of electrodiagnostic testing in evaluating patients with lumbosacral radiculopathy: An evidence-based review.

This is an evidence-based review of electrodiagnostic (EDX) testing of patients with suspected lumbosacral radiculopathy to determine its utility in diagnosis and prognosis. Literature searches were performed to identify articles applying EDX techniques to patients with suspected lumbosacral radiculopathy. From the 355 articles initially discovered, 119 articles describing nerve conduction studies, electromyography (EMG), or evoked potentials in adequate detail were reviewed further. Fifty-three studies met inclusion criteria and were graded using predetermined criteria for classification of evidence for diagnostic studies. Two class II, 7 class III, and 34 class IV studies described the diagnostic use of EDX. One class II and three class III articles described H-reflexes with acceptable statistical significance for use in the diagnosis and confirmation of suspected S1 lumbosacral radiculopathy. Two class II and two class III studies demonstrated a range of sensitivities for use of muscle paraspinal mapping. Two class II studies demonstrated the utility of peripheral myotomal limb electromyography in radiculopathies.

Driving with polyneuropathy.

Polyneuropathy may result in pain, numbness, and weakness, which may in turn affect driving ability. Medications used to treat neuropathic pain may alter cognition, which may further affect driving. Although such impairments have engendered questions about the driving safety in this group of patients, the rate of motor vehicle accidents (MVAs) in patients with neuropathy has not been studied rigorously. We surveyed patients with neuropathy from three medical centers for reported accident rate, and we analyzed variables related to increased risk for accidents compared to National Highway Traffic Safety Administration data. Surveys from 260 subjects demonstrated that 40.6% were involved in traffic accidents (0.11 accidents/year). Their accident rate was 10.8 MVAs per million vehicle miles traveled (MVA/MVMT), compared to 3.71 MVA/MVMT in 55-59-year-old drivers and 3.72 in 60-64-year-olds (National Highway Traffic Safety Administration data). In all, 72.4% cited their neuropathy and 55.2% cited their medications as playing a role in their accidents, and 51.6% changed their driving habits after developing neuropathy. Independently, elevated levels of pain, motor weakness, and ambulation difficulty met statistical significance for increased MVA frequency. We conclude that accident frequency and discomfort with driving are higher in neuropathy patients compared to age-matched national statistics. However, most patients seem to change habits according to their ability to drive; as such, driving issues should be addressed with caution and on a case-by-case basis.

Chemotherapy-related polyneuropathy may deteriorate quality of life in patients with B-cell lymphoma.

PURPOSE: This prospective study was performed to evaluate the effect of chemotherapy-related neurotoxicity on quality of life (QOL) of patients with lymphoma. METHODS: Thirty-two patients with diffuse large B-cell or follicular lymphoma without prior evidence of neuropathy were enrolled. Patients underwent the evaluations based on neuropathy symptom and disability score, nerve conduction studies, and SF-36 questionnaire for QOL assessment. They received six cycles of chemotherapy every three weeks, and all evaluations were repeated during and after the completion of 6th cycle. RESULTS: Sensory neuropathy-associated symptoms were observed in 27 patients (84.4%), and polyneuropathy was confirmed by nerve conduction study in 14 patients (43.8%). These patients with polyneuropathy showed worse QOL in domains mainly associated with physical health status including "physical function" compared to patients without polyneuropathy. There was a significant association of neuropathy symptom and disability scores with "bodily pain" and "vitality" of QOL domains. The serial evaluations of patients with neuropathy showed a worsening of QOL and neuropathy symptom scores during chemotherapy, then improvement of these values after chemotherapy. Thus, the final nerve conduction study confirmed the decrease in polyneuropathy compared to the 2nd evaluation (P = 0.032). CONCLUSION: Chemotherapy-related polyneuropathy may deteriorate QOL of patients with lymphoma, mainly physical health-associated QOL.

Hexane exposure and persistent peripheral neuropathy in automotive technicians.

Automotive technicians are commonly exposed to organic and chlorinated solvents, particularly through use of cleaning products. Mainly during the period 1989-2002, n-hexane was a component of some of these products. In other occupational contexts, n-hexane has been shown to be a cause of peripheral neuropathy. The purpose of the present study was to investigate whether previous exposures to low concentrations of n-hexane were a cause of persistent peripheral neuropathy in automotive technicians. Enrolled in the study were 830 San Francisco Bay Area automotive technicians. Each participant underwent a battery of tests to investigate peripheral nervous system impairment. Test results regressed against estimated hexane and total solvent exposures showed only limited evidence of association with solvent exposures. Exposures to both hexane and general solvents were well below their occupational exposure limits. Generally, our results provide reassurance about persistent peripheral neuropathic effects in automotive technicians who previously used hexane-containing automotive cleaning products. This may reflect repair processes, since the exposures occurred some years previous to the study. However, we cannot exclude the possibility that the absence of observed effect in this study may be attributable to low exposures, exposure misclassification and/or the healthy worker survivor effect.

Ambient geothermal hydrogen sulfide exposure and peripheral neuropathy.

The mechanism of toxicity of hydrogen sulfide (H2S) gas is thought mainly to operate through effects on the nervous system. The gas has high acute toxicity, but whether chronic exposure causes effects, including peripheral neuropathy, is yet unclear. The city of Rotorua, New Zealand, sits on an active geothermal field and the population has some of the highest measured ambient H2S exposures. A previous study in Rotorua provided evidence that H2S is associated with peripheral neuropathy. Using clinical methods, the present study sought to investigate and possibly confirm this association in the Rotorua population. The study population comprised 1635 adult residents of Rotorua, aged 18-65. Collected data relevant to the peripheral neuropathy investigation included symptoms, ankle stretch reflex, vibration sensitivity, as measured by the timed-tuning fork test and a Bio-Thesiometer (Bio-Medical Instrument Co., Ohio), and light touch sensitivity measured by monofilaments. An exposure metric, estimating time-weighted H2S exposure across the last 30 years was used. Principal components analysis was used to combine data across the various indicators of possible peripheral neuropathy. The main data analysis used linear regression to examine associations between the peripheral nerve function indicators and H2S exposure. None of the peripheral nerve function indicators were associated with H2S exposure, providing no evidence that H2S exposure at levels found in Rotorua is a cause of peripheral neuropathy. The earlier association between H2S exposure and peripheral neuropathy diagnoses may be attributable to the ecological study design used. The possibility that H2S exposure misclassification could account for the lack of association found cannot be entirely excluded.

Action at a distance: a lumbar spine tumor presenting as trigeminal neuralgia.

Trigeminal neuralgia (TN) is often secondary to an underlying structural cause, frequently compression of the fifth nerve root by an ectatic artery. Here we describe a case of a 36-year-old woman with symptoms of TN who was found to have severe communicating hydrocephalus. Further investigation revealed a lumbar myxopapillary ependymoma, which in turn was responsible for the communicating hydrocephalus. An argument connecting these seemingly disparate findings is made. This unusual set of circumstances is an example of "action at a distance" in the nervous system, and reminds clinicians to think broadly about the various pathophysiologic mechanisms that can potentially underlie common disorders.

Practice guideline update summary: Botulinum neurotoxin for the treatment of blepharospasm, cervical dystonia, adult spasticity, and headache: Report of the Guideline Development Subcommittee of the American Academy of Neurology.

OBJECTIVE: To update the 2008 American Academy of Neurology (AAN) guidelines regarding botulinum neurotoxin for blepharospasm, cervical dystonia (CD), headache, and adult spasticity. METHODS: We searched the literature for relevant articles and classified them using 2004 AAN criteria. RESULTS AND RECOMMENDATIONS: Blepharospasm: OnabotulinumtoxinA (onaBoNT-A) and incobotulinumtoxinA (incoBoNT-A) are probably effective and should be considered (Level B). AbobotulinumtoxinA (aboBoNT-A) is possibly effective and may be considered (Level C). CD: AboBoNT-A and rimabotulinumtoxinB (rimaBoNT-B) are established as effective and should be offered (Level A), and onaBoNT-A and incoBoNT-A are probably effective and should be considered (Level B). Adult spasticity: AboBoNT-A, incoBoNT-A, and onaBoNT-A are established as effective and should be offered (Level A), and rimaBoNT-B is probably effective and should be considered (Level B), for upper limb spasticity. AboBoNT-A and onaBoNT-A are established as effective and should be offered (Level A) for lower-limb spasticity. Headache: OnaBoNT-A is established as effective and should be offered to increase headache-free days (Level A) and is probably effective and should be considered to improve health-related quality of life (Level B) in chronic migraine. OnaBoNT-A is established as ineffective and should not be offered for episodic migraine (Level A) and is probably ineffective for chronic tension-type headaches (Level B).

Effects of noninvasive ventilation on sleep outcomes in amyotrophic lateral sclerosis.

STUDY OBJECTIVES: The objective was to study the effects on noninvasive ventilation on sleep outcomes in patient with ALS, specifically oxygenation and overall sleep quality. METHODS: Patients with ALS who met criteria for initiation of NIV were studied with a series of 2 home PSG studies, one without NIV and a follow-up study while using NIV. Primary outcome was a change in the maximum overnight oxygen saturation; secondary outcomes included change in mean overnight oxygen saturation, apnea and hypopnea indexes, sleep latency, sleep efficiency, sleep arousals, and sleep architecture. RESULTS: A total of 94 patients with ALS were screened for eligibility; 15 were enrolled; and 12 completed study procedures. Maximum overnight oxygen saturation improved by 7.0% (p = 0.01) and by 6.7% during REM sleep (p = 0.02) with NIV. Time spent below 90% oxygen saturation was also significant-ly better with NIV (30% vs 19%, p < 0.01), and there was trend for improvement in mean overnight saturation (1.5%, p = 0.06). Apnea index (3.7 to 0.7), hypopnea index (6.2 to 5.7), and apnea hypopnea index (9.8 to 6.3) did not significantly improve after introducing NIV. NIV had no effect on sleep efficiency (mean change 10%), arousal index (7 to 12), or sleep stage distribution (Friedman chi-squared = 0.40). CONCLUSIONS: NIV improved oxygenation but showed no significant effects on sleep efficiency, sleep arousals, restful sleep, or sleep architecture. The net impact of these changes for patients deserves further study in a larger group of ALS patients.

Immune-mediated neuropathies.

PURPOSE OF REVIEW: The immune-mediated neuropathies are an important group of treatable neuropathies that often lead to severe neurologic disability. This review guides clinicians in the recognition and treatment of these disorders. RECENT FINDINGS: Advances include new insights in classification and new treatment paradigms in many of these disorders. SUMMARY: Proper diagnosis and treatment require recognition of the characteristic clinical and laboratory findings and the use of appropriate electrophysiologic or pathologic examination. With proper treatment, partial or complete remission is possible, even in patients who are severely affected.

Cost comparison between the atraumatic and cutting lumbar puncture needles.

OBJECTIVE: The aim of this study was to determine which type of spinal needle is preferred from a cost perspective, taking into account costs of the spinal needle and treatment of postlumbar puncture headache. METHODS: A decision-analytic model was created to determine the cost of diagnostic lumbar punctures using atraumatic and cutting needles. We assumed a health care system perspective and based the analysis on the treatment of a patient facing event probabilities derived from prior studies. The economic outcome measure was the difference in estimated costs between the 2 needles. One-way and probabilistic sensitivity analyses tested the robustness of the model. RESULTS: Lumbar puncture performed with the atraumatic needle is associated with an average cost savings of $26.07 per patient. Average total health care costs are $166.08 with the atraumatic needle, compared to $192.15 with the cutting needle. There is 94% certainty that the atraumatic needle is cost-saving compared to the cutting needle based on probabilistic sensitivity analysis. Use of the atraumatic needle over the cutting needle by neurologists alone may result in $10.4 million in cost savings to the US health care system per year. CONCLUSION: The atraumatic spinal needle is associated with an overall cost savings to the US health care system. The balance of costs and benefits favors the use of the atraumatic needle over the cutting needle for diagnostic lumbar puncture.

Assessment: symptomatic treatment for muscle cramps (an evidence-based review): report of the therapeutics and technology assessment subcommittee of the American academy of neurology.

BACKGROUND: A Food and Drug Administration advisory in 2006 warned against the off-label use of quinine sulfate and its derivatives in the treatment of muscle cramps. Physicians are faced with a difficult scenario in choosing a treatment regimen for patients with muscle cramps. This American Academy of Neurology assessment systematically reviews the available evidence on the symptomatic treatment of muscle cramps. METHODS: A total of 563 potential articles were reviewed, of which 24 met the inclusion criteria of prospective trials evaluating the efficacy of a particular treatment on muscle cramps as a primary or secondary outcome. RESULTS: There are Class I studies showing the efficacy of quinine derivatives for treatment of muscle cramps. However, the benefit is modest and there are adverse effects from published prospective trials as well as case reports. There is one Class II study each to support the use of Naftidrofuryl, vitamin B complex, lidocaine, and diltiazem in the treatment of muscle cramps. RECOMMENDATIONS: Although likely effective (Level A), quinine derivatives should be avoided for routine use in the management of muscle cramps because of the potential of toxicity, but in select patients they can be considered for an individual therapeutic trial once potential side effects are taken into account. Vitamin B complex, Naftidrofuryl, and calcium channel blockers such as diltiazem are possibly effective and may be considered in the management of muscle cramps (Level C). Further studies are needed to identify agents that are effective and safe for the treatment of muscle cramps.

End-stage cardiac disease as an initial presentation of systemic myopathies: case series and literature review.

Life-threatening cardiomyopathy is associated with certain systemic myopathies and usually presents as an end-stage progression of the disease. However, cardiac symptoms can sometimes precede muscle weakness. The authors reviewed medical records from 2003 to 2008 on patients attending their neuromuscular clinic and identified patients who initially presented with an end-stage cardiomyopathy and were later diagnosed with a specific muscle disease through muscle biopsy. They report 5 cases of children who initially presented with cardiomyopathies without neuromuscular symptoms. The cardiac symptoms were so severe that 4 of them required cardiac transplantation and 1 died prior to transplantation. Review of muscle pathology confirmed the diagnoses of Becker muscular dystrophy, myofibrillar myopathy, mitochondrial myopathy with cytochrome oxidase deficiency, Danon disease, and glycogen storage disease. The authors conclude that cardiomyopathy can be the initial presentation of a wide spectrum of systemic myopathies. Careful evaluation of neuromuscular systems should be carried out in patients presenting with end-stage cardiomyopathies.

Utility of the cutaneous silent period in patients with diabetes mellitus.

We performed this study to evaluate whether or not the cutaneous silent period (CSP) is a useful metric to identify small-fiber neuropathy in diabetic patients. The CSP was measured from the abductor pollicis brevis muscle in 30 healthy controls and 110 diabetic patients, who in turn were divided into 3 subgroups (patients with large-fiber neuropathy, patients with small-fiber neuropathy, and asymptomatic patients). The measured CSP and clinical characteristics were compared among the groups. The power of the CSP in discriminating patients from controls and any correlation with other clinical variables were analyzed. Each patient subgroup had a significantly delayed CSP latency compared to the controls. The latency of patients with large-fiber neuropathy was also significantly prolonged compared to the other subgroups of patients. The CSP latency was the only variable to discriminate patients. The latency showed a significant correlation with the late responses in nerve conduction studies. Thus, the CSP latency may be a useful tool in evaluating small neural fiber function in diabetic patients.

Disorders of the trigeminal system.

The management of patients with trigeminal system dysfunction requires an understanding of the system's complex anatomy, which extends from peripheral nerve endings, through the skull base, cavernous sinus (V1, V2 only), and trigeminal ganglion, to the intraaxial nuclei, tracts, and cerebral cortex. The differential diagnosis is broad. Seemingly minor facial sensory loss may indicate an underlying malignancy (as in numb-chin syndrome). Painful syndromes of the trigeminal nerve are numerous and require careful categorization. Understanding trigeminal system anatomy and the appropriate use of imaging and electrodiagnostics should aid in the diagnosis and treatment of these disorders.

Practice Advisory: utility of surgical decompression for treatment of diabetic neuropathy: report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology.

Surgical decompression at the site of anatomic narrowing has been promoted as an alternative treatment for patients with symptomatic diabetic neuropathy. Systematic review of the literature revealed only Class IV studies concerning the utility of this therapeutic approach. Given the current evidence available, this treatment alternative should be considered unproven (Level U). Prospective randomized controlled trials with standard definitions and outcome measures are necessary to determine the value of this therapeutic intervention.

High-dose cyclophosphamide in refractory myasthenia gravis with MuSK antibodies.

We describe a 48-year-old woman with seronegative myasthenia gravis (MG) and high-titer of anti-MuSK antibody. She had severe bulbar and respiratory weakness with minimal limb weakness for 2 years. Her disease responded poorly to all the conventional immunosuppressive regimens. Treatment with immunoablative dose of cyclophosphamide led to dramatic and sustained remission of her symptoms. High-dose cyclophosphamide is an effective alternative in patients with unusually refractory disease.