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ALSUntangled reviews alternate and off-label treatments prompted by patient interest. Here, we review psilocybin, a chemical derived from mushrooms and belonging in the category of drugs known as psychedelics. Psilocybin has plausible mechanisms for slowing ALS progression because of its ability to cross the blood brain barrier and effect neurogenesis and inflammation. Currently, there are no pre-clinical ALS models, case reports, or trials for psilocybin and ALS in the context of disease modifying therapy. Depending on dosing, there can be a high risk of psychological side effects including hallucinations and physical harm. Based on the above information, we do not currently support the use of psilocybin as a means to slow ALS progression.

ALSUntangled reviews alternative and off-label treatments on behalf of people with ALS (PALS) who ask about them. Here, we review withania somnifera (WS) commonly known as ashwagandha or winter cherry. WS has plausible mechanisms for slowing ALS progression because of its effects on inflammation, oxidative stress, autophagy, mitochondrial function, and apoptosis. Preclinical trials demonstrate that WS slows disease progression in multiple different animal models of ALS. Of the five individuals we found who described using WS for their ALS, two individuals reported moderate benefit while none reported experiencing any significant side effects. There is currently one clinical trial using WS to treat PALS; the results are not yet published. There are no serious side effects associated with WS and the associated cost of this treatment is low. Based on the above information, WS appears to us to be a good candidate for future ALS trials.

The Wahls diet is a modified Paleolithic diet that emphasizes dark green leafy vegetables, colorful fruits, high-quality animal proteins, and omega-3 polyunsaturated fatty acids, while limiting grains, legumes, dairy products, sugar, and processed foods containing proinflammatory omega-6 fatty acids. The Wahls diet may reduce inflammation, oxidative stress, and mitochondrial dysfunction and has plausible mechanisms for slowing amyotrophic lateral sclerosis (ALS) progression. However, research on its dietary components in the ALS animal models has yielded conflicting results. Though multiple cohort studies suggest high carotenoids, omega-3 fatty acids and fruit intake are associated with reduced ALS risks, neither the diet nor its components has been demonstrated to slow down ALS progression in case studies or clinical trials. On the contrary, the Wahls diet, a restrictive, low-carbohydrate and low glycemic index diet, caused an average weight loss of 7.2% BMI in multiple sclerosis clinical trials, which is a significant concern for people living with amyotrophic lateral sclerosis (PALS) as weight loss is associated with faster ALS progression and shorter survival. Considering the above, we cannot endorse the Wahls diet for slowing ALS progression.

Spurred by patient interest, ALSUntangled herein examines the potential of the Portable Neuromodulation Stimulator (PoNS™) in treating amyotrophic lateral sclerosis (ALS). The PoNS™ device, FDA-approved for the treatment of gait deficits in adult patients with multiple sclerosis, utilizes translingual neurostimulation to stimulate trigeminal and facial nerves via the tongue, aiming to induce neuroplastic changes. While there are early, promising data for PoNS treatment to improve gait and balance in multiple sclerosis, stroke, and traumatic brain injury, no pre-clinical or clinical studies have been performed in ALS. Although reasonably safe, high costs and prescription requirements will limit PoNS accessibility. At this time, due to the lack of ALS-relevant data, we cannot endorse the use of PoNS as an ALS treatment.

Lion's Mane ( Hericium erinaceus) has historically been used as traditional medicine in Asia and Europe for its potential benefits in fighting infection and cancer. It has gained interest in the neurodegenerative disease field because of its mechanisms of action; these include anti-inflammation, neuroprotection, and promoting neurite growth demonstrated in various cell and animal models. A very small, double-blind, placebo-controlled trial in patients with mild cognitive impairment showed a temporary improvement in cognitive function; this finding has yet to be replicated. However, there have been no studies in ALS cell or animal models or in humans with ALS. Lion's Mane appears safe and inexpensive when consumed in powder or capsule, but one anaphylactic case was reported after a patient consumed fresh Lion's Mane mushroom. Currently, we do not have enough information to support the use of Lion's Mane for treating ALS. We support further research in ALS disease models and clinical trials to study its efficacy.

ALSUntangled reviews alternative and off-label treatments for people living with amyotrophic lateral sclerosis (PALS). Here we review insulin, which has at least one plausible mechanism for slowing ALS progression. However, pre-clinical studies are limited and there have been no trials in PALS yet. Insulin use in patients without a metabolic need may cause very serious and potentially lethal side effects. While further studies to evaluate potential benefits may be warranted, at this time we cannot endorse insulin treatment to slow ALS progression.

Nuedexta is a combination of dextromethorphan hydrobromide and quinidine sulfate and was approved by the Food and Drug Administration (FDA) in 2010 to treat pseudobulbar affect (PBA). There have since been anecdotal case reports of bulbar function improvements after Nuedexta treatment. Here, we review the off-label use of Nuedexta for improving bulbar function in people with ALS. Nuedexta has plausible mechanisms for protecting brain stem motor neurons via its effects on S1R and glutamate excitotoxicity. Recent clinical trials support that Nuedexta can improve bulbar function in PALS, with or without PBA. Nuedexta causes mild to moderate side effects. Based on this information, we support considering Nuedexta treatment for bulbar dysfunction in ALS patients with or without PBA.

ALSUntangled reviews alternative and off-label treatments on behalf of people with ALS who ask about them. Here we review rituximab, a drug which specifically depletes B lymphocytes. We show a current lack of evidence for a role of these cells in ALS progression. The one patient we found who described using Rituximab for their ALS found no benefit. Given all this, and the known serious risks of rituximab, we advise against its use as an ALS treatment.

Several infections have been associated with motor neuron diseases resembling ALS, including species of viruses, bacteria, and parasites. Mycobacterium avium subspecies paratuberculosis (MAP), most known for its probable etiologic association with Crohn's disease, has been suggested as another possible infectious cause of motor neuron disease. Two published case reports describe the successful treatment of ALS-like symptoms with antimycobacterial antibiotics. Both cases had atypical features. Based on these, we believe it would be reasonable to begin performing chest imaging in PALS who have features of their history or exam that are atypical for ALS such as pain, fevers, or eye movement abnormalities. If the chest imaging is abnormal, more specific testing for mycobacteria may be indicated. Until there is more clear evidence of an association between mycobacteria and ALS, we cannot endorse the widespread use of potentially toxic antimycobacterial antibiotics for PALS.

ALSUntangled reviews alternative and off-label treatments for people living with amyotrophic lateral sclerosis (PALS). Here we review ozone therapy. Ozone therapy has possible mechanisms for slowing ALS progression based on its antioxidant, anti-inflammatory, and mitochondrial effects. A non-peer-reviewed report suggests that ozone treatment may slow progression in a mTDP-43 mouse model of ALS. One verified "ALS reversal" occurred on a cocktail of alternative treatments including ozone. There are no ALS trials using ozone to treat PALS. There can be potentially serious side effects associated with ozone therapy, depending on the dose. Based on the above information, we support an investigation of ozone therapy in ALS cell or animal models but cannot yet recommend it as a treatment in PALS.

ALSUntangled reviews alternative and off-label treatments for people living with amyotrophic lateral sclerosis (PALS). Here we review astaxanthin which has plausible mechanisms for slowing ALS progression including antioxidant, anti-inflammatory, and anti-apoptotic effects. While there are no ALS-specific pre-clinical studies, one verified "ALS reversal" occurred in a person using a combination of alternative therapies which included astaxanthin. There have been no trials of astaxanthin in people living with ALS. Natural astaxanthin appears to be safe and inexpensive. Based on the above information, we support further pre-clinical and/or clinical trials of astaxanthin in disease models and PALS, respectively, to further elucidate efficacy.

ALSUntangled reviews alternative and off-label treatments for people living with amyotrophic lateral sclerosis (PALS). Here, we review caffeine which has plausible mechanisms for slowing ALS progression. However, pre-clinical studies are contradictory, and a large case series showed no relationship between caffeine intake and ALS progression rate. While low doses of caffeine are safe and inexpensive, higher doses can cause serious side effects. At this time, we cannot endorse caffeine as a treatment to slow ALS progression.

ALSUntangled reviews alternative and off-label treatments for people with amyotrophic lateral sclerosis (PALS). Here we review glucocorticoids. Neuroinflammation plays a prominent role in amyotrophic lateral sclerosis (ALS) pathogenesis, so some hypothesize that glucocorticoids might be an effective ALS therapy through their immunosuppressive effects. In this paper, we review the available evidence for glucocorticoids in ALS, including one pre-clinical study with a genetic mouse model of ALS, nine case reports (ranging from 1 to 26 patients each), and four clinical trials. We also review the possible side effects (including steroid myopathy) and the costs of therapy. We graded the level of evidence as follows: Mechanism, D; Pre-Clinical, F; Cases, B; Trials, F; Risks, C. Our review of the current evidence concludes that glucocorticoids do not offer clinical benefit in ALS and confer serious risks. Thus, ALSUntangled does not recommend glucocorticoids as a treatment for ALS.

ALSUntangled reviews alternative and off-label treatments for people living with amyotrophic lateral sclerosis (PALS). Here we review butyrate and its different chemical forms (butyrates). Butyrates have plausible mechanisms for slowing ALS progression and positive pre-clinical studies. One trial suggests that sodium phenylbutyrate (NaPB) in combination with Tauroursodeoxycholic acid (TUDCA) can slow ALS progression and prolong survival, but the specific contribution of NaPB toward this effect is unclear. Butyrates appear reasonably safe for use in humans. Based on the above information, we support a trial of a butyrate in PALS, but we cannot yet recommend one as a treatment.

Vitamin C is one of the most common supplements taken by people with ALS. As an antioxidant, it has a plausible mechanism for slowing disease progression and there are some flawed pre-clinical studies and case reports suggesting benefit. However, a small human trial showed no benefit. Given this negative trial, we do not currently advise vitamin C as an ALS treatment.

ALSUntangled reviews alternative and off-label treatments for people with ALS. Here we review light therapy. We show that it has theoretically plausible mechanisms, three flawed pre-clinical data, studies, and one incompletely documented case report supporting its use. We explain why further studies are needed to determine whether any specific light therapy protocol can help people with ALS.

We investigated the Central Nervous System (CNS) and skeletal muscle tissue from A woman was clinically diagnosed with amyotrophic lateral sclerosis (ALS) at the age of 22. Neuropathologic evaluation showed upper and lower motor neuron loss, corticospinal tract degeneration and skeletal muscle denervation. Analysis of the patient's Deoxyribonucleic acid (DNA) revealed a AGT>GGT change resulting in an S375G substitution in the C-terminal region of TDP-43. This variant was previously reported as being benign. Considering the early onset and severity of the disease in this patient, we tested the effects of this genetic variant on TDP-43 localization, pre-mRNA splicing activity and toxicity, in parallel with the effects on known neighboring disease-associated mutations. In cell lines, expressed in culture, S375G TDP-43 appeared to be more significantly localized in the nucleus and to exert higher toxicity than wild-type TDP-43. Strikingly, a phosphomimic mutant at the same residue (S375E) showed a strong tendency to accumulate in the cytoplasm, especially under stress conditions, and molecular dynamics simulations suggest that phosphorylation of this residue can disrupt TDP-43 intermolecular interactions. The results of the current study highlight the importance of phosphorylation and regulation of TDP-43 nuclear-cytoplasmic shuttling/redistribution, in relation to the pathogenetic mechanisms involved in different forms of ALS., (© 2018 International Society of Neuropathology.)

Objective: Speech and swallowing impairments are highly prevalent in individuals with amyotrophic lateral sclerosis (ALS) and contribute to reduced quality of life, malnutrition, aspiration, pneumonia and death. Established practice parameters for bulbar dysfunction in ALS do not currently exist. The aim of this study was to identify current practice patterns for the evaluation of speech and swallowing function within participating Northeast ALS clinics in the United States., Methods and Results: A 15-item survey was emailed to all registered NEALS centres. Thirty-eight sites completed the survey. The majority (92%) offered Speech-Language Pathology, augmentative and alternative communication (71%), and dietician (92%) health care services. The ALS Functional Rating Scale-Revised and body weight represented the only parameters routinely collected in greater then 90% of responding sites. Referral for modified barium swallow study was routinely utilised in only 27% of sites and the use of percutaneous gastrostomy tubes in ALS patient care was found to vary considerably., Conclusions: This survey reveals significant variability and inconsistency in the management of bulbar dysfunction in ALS across NEALS sites. We conclude that a great need exists for the development of bulbar practice guidelines in ALS clinical care to accurately detect and monitor bulbar dysfunction.

The goal of this randomized, blinded, crossover clinical trial was to determine whether Nuedexta (dextromethorphan and quinidine) enhanced speech, swallowing, and salivation in patients with ALS. Sixty patients with amyotrophic lateral sclerosis (ALS) received either Nuedexta or placebo for 28 to 30 days, followed by a 10 to 15-day washout period. Subsequently, patients were switched to the opposite treatment arm for the remaining days of the trial. The primary endpoint was a reduction in the self-report Center for Neurologic Study Bulbar Function Scale (CNS-BFS) score. The rater-administered ALS Functional Rating Scale Revised was the principal secondary endpoint. The CNS-BFS score improved with active treatment, decreasing from a mean of 59.3 in the placebo arm of the trial to 53.5 during the drug-treatment arm (p < 0.001). Each of the individual domains of bulbar function interrogated by the CNS-BFS responded to treatment with Nuedexta as follows: salivation: 15.8 versus 14.3 (p = 0.004); speech: 24.6 versus 22.2 (p = 0.003); swallowing: 18.9 versus 17.1 (p = 0.009). Similarly, the bulbar component of the ALS Functional Rating Scale Revised improved with active treatment (p = 0.003), although the drug did not affect the motor and respiratory components of this scale. This study is unique for several reasons. Firstly, it was driven by patient reports of improved speech and swallowing while taking Nuedexta for control of emotional lability. Secondly, the study was conducted over a short duration (70 days), and thirdly, a self-report scale was selected as the principle outcome measure. Considering the importance of bulbar functions, these results, if confirmed, point to an additional use of Nuedexta as an adjunct to the management of ALS.

To promote clinical and patient oriented research, as part of the Second International ALS Conference in Tarrytown, NY, USA, seven pairs of clinicians and scientists were asked to lead discussions with meeting attendees on six major topics (one of which was discussed by two groups); each one the focus of a 90-min Breakout Session. Approximately 25 meeting attendees participated in each session. The Breakout Sessions considered six major themes: 1) Approaches to encourage clinicians to engage in more clinical research to discover the pathogenesis and cause of ALS; 2) Exploring avenues to build more effective partnerships between basic scientists and ALS physicians; 3) Increasing patient interest and commitment to participating in non-trial clinical research; 4) Brainstorming about factors that are most critical to the discovery of the pathogenesis and cause of ALS; 5) Finding ways to incorporate clinical research projects into clinical trials; and 6) Developing state-of-the-art epidemiological studies to solve the mystery of ALS. In this paper, we present the reports from each of the Breakout Sessions; and we provide a wrap-up of the entire conference.

Purpose: The goal of this study was to determine if talkers with ALS are limited in their ability to increase lower lip and jaw speed at an early stage of the disease when their speaking rate and intelligibility are only minimally or not affected., Method: A novel metronome paced fixed-target task was used to assess movement speed capacities during lower lip and jaw oscillations in seven talkers with ALS and seven age and gender matched controls., Results: Lower lip peak speeds were significantly lower in talkers with mild ALS than in healthy talkers suggesting a lower lip speed constraint in talkers with mild ALS. Jaw peak speeds tended to be lower, but jaw displacements tended to be larger in talkers with mild ALS than in healthy talkers. Because greater speeds are typically expected for larger displacements, outcomes also suggest a jaw speed constraint in talkers with mild ALS., Conclusions: Lower lip and jaw peak speeds may be sensitive measures to identify bulbar motor performance decline at an early stage of the disease when speaking rate and intelligibility are only minimally affected., Learning Outcomes: The reader will be able to explain two different articulatory strategies to increase speaking rate and understand why fast speech tasks and diadochokinetic pseudo-speech tasks are not suited to assess articulatory speed capacity in healthy and impaired talkers. The reader will also be able to explain how orofacial movement speed capacity can be tested using a fixed-target task and how ALS affects lower lip and jaw speed capacities during the early stages of the disease., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Improved methods for assessing bulbar impairment are necessary for expediting diagnosis of bulbar dysfunction in ALS, for predicting disease progression across speech subsystems, and for addressing the critical need for sensitive outcome measures for ongoing experimental treatment trials. To address this need, we are obtaining longitudinal profiles of bulbar impairment in 100 individuals based on a comprehensive instrumentation-based assessment that yield objective measures. Using instrumental approaches to quantify speech-related behaviors is very important in a field that has primarily relied on subjective, auditory-perceptual forms of speech assessment(1). Our assessment protocol measures performance across all of the speech subsystems, which include respiratory, phonatory (laryngeal), resonatory (velopharyngeal), and articulatory. The articulatory subsystem is divided into the facial components (jaw and lip), and the tongue. Prior research has suggested that each speech subsystem responds differently to neurological diseases such as ALS. The current protocol is designed to test the performance of each speech subsystem as independently from other subsystems as possible. The speech subsystems are evaluated in the context of more global changes to speech performance. These speech system level variables include speaking rate and intelligibility of speech. The protocol requires specialized instrumentation, and commercial and custom software. The respiratory, phonatory, and resonatory subsystems are evaluated using pressure-flow (aerodynamic) and acoustic methods. The articulatory subsystem is assessed using 3D motion tracking techniques. The objective measures that are used to quantify bulbar impairment have been well established in the speech literature and show sensitivity to changes in bulbar function with disease progression. The result of the assessment is a comprehensive, across-subsystem performance profile for each participant. The profile, when compared to the same measures obtained from healthy controls, is used for diagnostic purposes. Currently, we are testing the sensitivity and specificity of these measures for diagnosis of ALS and for predicting the rate of disease progression. In the long term, the more refined endophenotype of bulbar ALS derived from this work is expected to strengthen future efforts to identify the genetic loci of ALS and improve diagnostic and treatment specificity of the disease as a whole. The objective assessment that is demonstrated in this video may be used to assess a broad range of speech motor impairments, including those related to stroke, traumatic brain injury, multiple sclerosis, and Parkinson disease.

Neurodegeneration in amyotrophic lateral sclerosis (ALS) is characterized by the specific loss of central and peripheral motor neurons. While this pattern of neuronal demise gives rise to a distinct clinical syndrome, at the cellular and molecular level ALS pathology is similar to that seen in other neurodegenerative diseases. In particular, mitochondrial dysfunction in ALS is reminiscent of that observed in Alzheimer's and Parkinson's diseases. Mitochondria in persons with ALS demonstrate impaired electron transport, increased free radical generation, and an inability to adequately buffer cytosolic calcium shifts. These abnormalities are probably systemic and potentially due to mutation of mitochondrial DNA.

Mitochondria are abnormal in persons with amyotrophic lateral sclerosis (ALS) for unknown reasons. We explored whether aberration of mitochondrial DNA (mtDNA) could play a role in this by transferring mitochondrial DNA (mtDNA) from ALS subjects to mtDNA-depleted human neuroblastoma cells. Resulting ALS cytoplasmic hybrids (cybrids) exhibited abnormal electron transport chain functioning, increases in free radical scavenging enzyme activities, perturbed calcium homeostasis, and altered mitochondrial ultrastructure. Recapitulation of defects previously observed in ALS subjects and ALS transgenic mice by expression of ALS mtDNA support a pathophysiologic role for mtDNA mutation in some persons with this disease., (Copyright 1998 Academic Press.)

For the last 20 years, the authors' institution has treated displaced femoral neck fractures in the elderly with femoral head prosthetic replacement. The procedure has been accomplished utilizing a posterolateral approach, sectioning of the short external rotators, suction fitting of the acetabulum, and capsular repair. The post-operative management has been progressive ambulation and full weight bearing. The authors review the operative procedure, perioperative complications, and functional long-term follow-up in 173 elderly patients who had prosthetic replacement for femoral neck fractures. These were all done as primary procedures. One hundred pressfit Austin Moore procedures were performed in 97 patients from 1977 to 1981. Eighty bipolar proximal femoral replacements were performed in 76 patients from 1985 to 1987. These were each consecutive groups of patients and excluded were patients with pathologic fractures. There were four patients with spasticity in the Austin Moore group and four patients with spasticity in the bipolar group. Medical complications were similar in both groups. There were no deep infections in either group. Two of the three dislocations in the Austin Moore group were in patients with spasticity. Seven patients (7%) died within 3 months in the Austin Moore group and nine patients (11%) died within 3 months in the bipolar group. At 2-year follow-up, 24 patients (24%) died within 2 years in the Austin Moore group and 16 patients (20%) died in the bipolar group. At follow-up (mean, 26 months), there did not appear to be any statistically significant difference in the patients' Harris hip scores. The average hip score ranged from 55 to 92, with a mean of 76 in both groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Thirty-one patients with arthroscopically documented partial thickness rotator cuff tears treated by arthroscopic debridement of the lesion were retrospectively reviewed. The patients had had symptoms for an average of 20.5 months prior to surgery. Twenty-two of these 31 shoulders also had bursoscopy, with 18 having arthroscopic subacromial decompression. The results were graded by both the UCLA Shoulder Rating Scale and Neer's criteria. Twenty-six (84%) of the patients had satisfactory results with the remaining 5 (16%) patients having unsatisfactory results. A classification system for the size and location of partial thickness rotator cuff tears is presented. The lesion size did not affect the result. Repeat arthroscopy in three patients demonstrated no further deterioration of their rotator cuff. The results with and without subacromial decompression were similar. The need for subacromial decompression is best determined by the arthroscopic finding of a bursal side tear.

Synovial chondromatosis involving the acromioclavicular joint occurred in a 20-year-old woman. Synovectomy including removal of loose bodies and resection of the distal end of the clavicle relieved symptoms. Synovial chondromatosis is a relatively rare disorder and seems not to have been reported in the acromioclavicular joint.

Both operative and nonoperative methods have been advocated for the treatment of ACL tears. However, the optimum management of this injury remains controversial. In the present study, patients treated nonoperatively were evaluated retrospectively 4 to 10 years after ACL tears were documented by arthroscopy and by mild to moderate pivot shifts under anesthesia. Forty-nine patients who underwent arthroscopic evaluation of the knee between 1976 and 1982 were found to have complete tears of the ACL. A mild to moderate pivot shift was present under anesthesia. One or both menisci were torn in two-thirds of the knees, requiring partial meniscectomies. The average age of the patients was 27 years (range, 16 to 46 years). Because of persistent disabling instability, 9 patients (18%) underwent late ACL reconstruction. The remaining 40 patients were evaluated at an average of 5.6 years after documentation of the tear (range, 4 to 10 years). At followup, 25 (62%) of the 40 patients had satisfactory subjective results. Eight of the patients (20%) had returned to their preinjury level of athletic activities without restrictions, and 10 (25%) functioned at the same level but with symptoms, some patients requiring bracing. Seventeen patients (43%) had diminished their level of sports activities, while 5 patients (12%) had given up all sports. Only 2 patients required late meniscectomies. On physical examination, 27 patients (87%) had pivot shifts. Instrumented laxity testing revealed an injured to normal difference of 3.1 mm with a 20 pound force. Radiographic studies were interpreted as normal in 35% of the knees, whereas 65% demonstrated mild degenerative changes.(ABSTRACT TRUNCATED AT 250 WORDS)

High-resolution real-time sonography has been reported as a non-invasive means of evaluating the integrity of the rotator cuff. Fifty-two patients underwent both sonographic and arthroscopic evaluation of the rotator cuff. There were 42 men and 10 women with an average age of 47 years (range 28-71 years). The duration of shoulder pain averaged 24 months (range 3 months to 9 years). Thirty-five rotator cuff tears were noted arthroscopically. Twenty-seven of the tears were diagnosed by sonography for a sensitivity rate of 77%. Eleven of the 17 intact rotator cuffs were normal by sonography for a specificity rate 65%. The overall accuracy of sonography was 73% and the predictive value of a positive sonogram was 82%. Sonography appears to be a good initial screening examination in evaluating the integrity of the rotator cuff. It is noninvasive and relatively inexpensive. Technical limitations of this technique as well as the experience of the radiologist in performing and interpreting the examination play a major role in the accuracy of this test. As instrumentation improves and as experience in using this technique increases, we expect the accuracy of sonography in detecting tears of the rotator cuff to continue to improve.

Anterior and posterior marginal fractures of the distal end of the radius associated with dislocation of the carpus are rare injuries. The results of 20 patients with 12 anterior and eight posterior marginal fracture-dislocations of the distal radius were reviewed. Eleven patients had closed reduction and plaster cast immobilization, including three with external fixation, while nine patients required surgery and internal fixation. At a mean of 3.2 years, 40% were rated as excellent, 45% as good, 5% as fair, and 10% as poor. There was roentgenographic evidence of posttraumatic arthritis in 13 patients (65%). Major factors affecting the clinical results were accurate articular realignment and the presence of ipsilateral carpal injuries. There were no significant differences in results between anterior and posterior marginal fractures or between closed or operative methods of treatment when the radiocarpal articular surface was restored to less than 1 mm residual displacement. Restoration of articular congruency is the primary goal of management of these fractures.

A model of the 40 Hz auditory event-related potential (40 Hz AERP) was developed and evaluated in a group of normal subjects and two patient groups. The model views the 40 Hz AERP as a combination of the brain-stem auditory evoked potential (BAEP) and a sinusoidal component presumed to arise from structures rostral to the brain-stem. Fourier analysis techniques were used to quantify changes in the sinusoidal component. The results obtained demonstrated that the phase of the sinusoidal component was quite stable in normal subjects, but was predictably altered as a consequence of thalamic or midbrain lesions. Lesions of the temporal lobe did not alter the phase of the sinusoidal component. These results were interpreted as being consistent with the model developed and suggesting a midbrain or thalamic origin for the 40 Hz sinusoid.