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Hereditary neuropathy with liability to pressure palsy (HNPP) is characterised by recurrent mononeuropathies following minor trauma. We describe a case of fulminant HNPP beginning on the first day of military physical training. Protracted weakness, muscle atrophy, hand contractures, and multifocal sensory loss developed during a further three weeks of basic training. Nerve conduction changes were typical of HNPP, but without segmental slowing. Electromyographically, there was prominent acute denervation in muscles of the hands and right shoulder. Sural nerve biopsy demonstrated tomaculae and remyelination. Genetic testing revealed PMP-22 gene deletion. This case report demonstrates that HNPP can present with rapidly progressive peripheral nerve dysfunction and electrophysiological evidence of focal axonal loss.

Most neuropathic pain conditions are caused by damage to peripheral nociceptive neurons known as 'small-fibers.' Examination of punch skin biopsies immunolabeled with pan-axonal markers has identified degeneration of distal nociceptive axons as a pathological hallmark of most neuralgias including numerous polyneuropathies, postherpetic neuralgia, and complex regional pain syndrome. Similar axonopathy is present in several rodent models of neuralgia (chronic constriction injury and spared nerve injury). Here we have measured the density of distal cutaneous small-fiber axons in rats with persistent mechanical allodynia caused by the sciatic inflammatory neuropathy (SIN), a model of painful neuritis. We have evaluated whether perineural immune activation sufficient to cause evoked-pain behaviors is also associated with loss of distal epidermal innervation. SIN was created in adult male Sprague-Dawley rats by perineural zymosan administration using established methods. Unoperated rats provided controls. Two weeks of sensory testing established the presence of static mechanical allodynia. Full-thickness punches were then collected from ipsilesional sural-innervated plantar hindpaw skin. These were immunolabeled against PGP9.5 using standard methods, and the density of epidermal neurites quantitated microscopically by a single examiner who was unaware of rats' experimental group. Neurite densities were similar in SIN and control samples (P = 0.96), suggesting that mechanical allodynia can occur from inflammation near a nerve, without distal small-fiber degeneration. [ABSTRACT FROM AUTHOR]

Inferior alveolar nerve blockade is one of the most common, yet technically difficult local procedures performed. Inadvertent injury to the inferior alveolar or lingual nerve, resulting in persistent anesthesia, paresthesias, loss of taste, or pain in the distribution of these nerves, is more common than once thought. We report on two cases of lingual nerve injury during routine inferior alveolar nerve blockade. These cases are consistent with the hypotheses that direct nerve trauma, whether by nerve-needle contact or compression by anesthetic bolus, and the neurotoxic effects of specific anesthetic preparations may produce long term nerve damage. When this damage occurs to the pain-sensing A-delta and C-fibers, symptoms may resemble those seen in complex regional pain syndrome. [ABSTRACT FROM AUTHOR]

Transaldolase (TALDO) deficiency has various clinical manifestations including liver dysfunction, hepatosplenomegaly, anemia, thrombocytopenia, and dysmorphic features. We report a case presenting prenatally with hyperechogenic bowel and intrauterine growth restriction. The infant was born small for gestational age, with cutis laxa and hypertrichosis. Postnatally, meconium plug was identified, complicated with intestinal obstruction necessitating laparotomy, partial resection of the intestine, and ileostomy. Liver biopsy revealed cholangiolar proliferation and portal fibrosis. He also suffered from persistent congenital thrombocytopenia requiring platelet transfusions and severe hypothyroidism with normal anatomical and structural gland responding only to the combination of T3 and T4 treatment. Neurologically, severe hypotonia and anisocoria were noted at the age of 2 months. Brain MRI was normal. Shortly after the abdominal surgery, a rapid liver failure ensued, which eventually led to his death. Specific metabolic tests ruled out glycosylation disorders, yet urine analysis using 1H NMR showed accumulation of sedoheptulose which was previously described in patients with transaldolase deficiency. Sequencing of the gene-encoding transaldolase (TALDO1) revealed a homozygous stop mutation c.669C>G; p.Tyr223*. In conclusion, we present an infant with a novel homozygous mutation in TALDO1, causing TALDO deficiency, and extend the clinical characteristics of this rare syndrome.

Complex regional pain syndrome (CRPS) is the current consensus-derived name for a syndrome usually triggered by limb trauma. Required elements include prolonged, disproportionate distal-limb pain and microvascular dysregulation (e.g., edema or color changes) or altered sweating. CRPS-II (formerly "causalgia") describes patients with identified nerve injuries. CRPS-I (formerly "reflex sympathetic dystrophy") describes most patients who lack evidence of specific nerve injuries. Diagnosis is clinical and the pathophysiology involves combinations of small-fiber axonopathy, microvasculopathy, inflammation, and brain plasticity/sensitization. Females have much higher risk and workplace accidents are a well-recognized cause. Inflammation and dysimmunity, perhaps facilitated by injury to the blood-nerve barrier, may contribute. Most patients, particularly the young, recover gradually, but treatment can speed healing. Evidence of efficacy is strongest for rehabilitation therapies (e.g., graded-motor imagery), neuropathic pain medications, and electric stimulation of the spinal cord, injured nerve, or motor cortex. Investigational treatments include ketamine, botulinum toxin, immunoglobulins, and transcranial neuromodulation. Nonrecovering patients should be re-evaluated for neurosurgically treatable causal lesions (nerve entrapment, impingement, infections, or tumors) and treatable potentiating medical conditions, including polyneuropathy and circulatory insufficiency. Earlier impressions that CRPS represents malingering or psychosomatic illness have been replaced by evidence that CRPS is a rare complication of limb injury in biologically susceptible individuals., (© 2015 Elsevier B.V. All rights reserved.)

Oxylipins, a class of oxygenase-derived unsaturated fatty acids, are important signal molecules in many biological systems. Recent characterization of an Aspergillus flavus lipoxygenase gene, lox, revealed its importance in maintaining a density-dependent morphology switch from sclerotia to conidia as population density increased. Here, we present evidence for the involvement of four more oxylipin-generating dioxygenases (PpoA, PpoB, PpoC, and PpoD) in A. flavus density-dependent phenomena and the effects of loss of these genes on aflatoxin production and seed colonization. Although several single mutants showed alterations in the sclerotia-to-conidia switch, the major effect was observed in a strain downregulated for all five oxygenases (invert repeat transgene [IRT] strain IRT4 = ppoA, ppoB, ppoC, ppoD, and lox). In strain IRT4, sclerotia production was increased up to 500-fold whereas conidiation was decreased down to 100-fold and the strain was unable to switch into conidial production. Aflatoxin (AF) production for all mutant strains and the wild type was greatest at low population densities and absent in high populations except for strain IRT4, which consistently produced high levels of the mycotoxin. Growth on host seed by both IRT4 and IRT2 (downregulated in ppoA, ppoB, and ppoD) was marked by decreased conidial but increased AF production. We propose that A. flavus oxygenases and the oxylipins they produce act in a highly interdependent network with some redundancy of biological function. These studies provide substantial evidence for oxylipin-based mechanisms in governing fungus-seed interactions and in regulating a coordinated quorum-sensing mechanism in A. flavus.

Plant and fungal lipoxygenases (LOX) catalyze the oxidation of polyunsaturated fatty acids, creating fatty-acid hydroperoxides (oxylipins). Fungal oxylipins are required for normal fungal development and secondary metabolism, and plant host-derived oxylipins interfere with these processes in fungi, presumably by signal mimicry. The maize LOX gene ZmLOX3 has been implicated previously in seed-Aspergillus interactions, so we tested the interactions of a mutant maize line (lox3-4, in which ZmLOX3 is disrupted) with the mycotoxigenic seed-infecting fungi Aspergillus flavus and Aspergillus nidulans. The lox3-4 mutant was more susceptible than wild-type maize to both Aspergillus species. All strains of A. flavus and A. nidulans produced more conidia and aflatoxin (or the precursor sterigmatocystin) on lox3-4 kernels than on wild-type kernels, in vitro and under field conditions. Although oxylipins did not differ detectably between A. flavus-infected kernels of the lox3-4 and wild-type (WT) maize, oxylipin precursors (free fatty acids) and a downstream metabolite (jasmonic acid) accumulated to greater levels in lox3-4 than in WT kernels. The increased resistance of the lox3-4 mutant to other fungal pathogens (Fusarium, Colletotrichum, Cochliobolus, and Exserohilum spp.) is in sharp contrast to results described herein for Aspergillus spp., suggesting that outcomes of LOX-governed host-pathogen interactions are pathogen-specific.

The cellular outcome of changes in nitrogen availability in the context of development and early stages of pathogenicity was studied by quantitative analysis of two-dimensional gel electrophoresis of Colletotrichum acutatum infecting strawberry. Significant alterations occurred in the abundance of proteins synthesized during appressorium formation under nitrogen-limiting conditions compared with a complete nutrient supply. Proteins that were up- or down-regulated were involved in energy metabolism, nitrogen and amino acid metabolism, protein synthesis and degradation, response to stress and reactive oxygen scavenging. Members belonging to the reactive oxygen species (ROS) scavenger machinery, superoxide dismutase and glutathione peroxidase, were up-regulated at the appressorium formation stage, as well as under nitrogen-limiting conditions relative to growth with a complete nutrient supply, whereas abundance of bifunctional catalase was up-regulated predominantly at the appressorium formation stage. Fungal ROS were detected within germinating conidia during host pre-penetration, penetration and colonization stages, accompanied by plant ROS, which were abundant in the apoplastic space. Application of exogenous antioxidants quenched ROS production and reduced the frequency of appressorium formation. Up-regulation in metabolic activity was detected during appressorium formation and nutrient deficiency compared with growth under complete nutrient supply. Enhanced levels of proteins related to the glyoxylate cycle and lipid metabolism (malate dehydrogenase, formate dehydrogenase and acetyl-CoA acetyltransferase) were observed at the appressorium formation stage, in contrast to down-regulation of isocitrate dehydrogenase. The present study demonstrates that appressoria formation processes, occurring under nutritional deprivation, are accompanied by metabolic shifts, and that ROS production is an early fungal response that may modulate initial stages of pathogen development.

Neuropathic pain is initiated or caused by damage or dysfunction of the peripheral or central nervous systems in various disorders, each having pain-related symptoms and signs thought secondary to common pain mechanisms. Ancillary testing may demonstrate associated nervous system abnormalities, however its specificity is inadequate at present, as it makes inferential conclusions from indirect data. Symptom assessment and physical findings remain paramount in the diagnosis of neuropathic pain.

Purpose of Review: Recent dramatic increases in the incidence and prevalence of diabetes make an understanding of chronic symmetric sensorimotor diabetic polyneuropathy, the most common and problematic of chronic diabetic complications, essential for a wide range of medical practitioners., Recent Findings: The demonstration of neuropathic dysfunction in patients with prediabetes or impaired glucose tolerance emphasizes the susceptibility of peripheral nerve fibers, especially small A delta fibers and C fibers, to relatively mild, short-duration hyperglycemia. New testing can reveal peripheral nerve dysfunction prior to clinical neuropathic symptoms and signs. In the absence of effective medications to halt or reverse nerve damage or promote nerve regeneration, early diagnosis of diabetic polyneuropathy, followed by tight glycemic control with diet and exercise, offers the best opportunity to prevent progressive symptoms of sensory loss, pain, autonomic dysfunction, ulcerations, and amputations. Some patients with impaired glucose tolerance have a reversal of neuropathic features with tight glycemic control. Nonpharmacologic therapies for neuropathic pain in diabetic polyneuropathy appear promising., Summary: Tight glycemic control, especially early in diabetes, is the best approach to minimizing the prevalence and severity of diabetic polyneuropathy and makes research into the deleterious effects of even mild hyperglycemia imperative.

As a community, physicians with expertise in child development and an appreciation of school-related challenges are uniquely positioned to enhance the well-being of children with specific learning disabilities. Efforts in such areas as differential diagnosis, enhancing communication between home and school and among parents and related service providers, accountability for effective and timely intervention, advocacy, and the application of scientific approaches to instruction and progress monitoring are among the ways in which the medical community can support children with special learning needs.

Gene mutations within the P/Q type neuronal calcium channel in familial hemiplegic migraine (FHM) suggest a therapeutic role for calcium-channel blockade. The authors have previously reported abortive therapy of FHM with IV verapamil. Here the authors describe four cases of sporadic hemiplegic migraine (SHM) responsive to verapamil, administered either orally or IV. The findings indicate that verapamil is effective therapy for both SHM and FHM.

F-wave abnormalities, in the presence of normal distal motor nerve conduction, most often are the first indicators of proximal peripheral nerve dysfunction in demyelinating polyradiculoneuropathies. However, a 15-year-old female-who developed lumbosacral spinal cord infarction with paraplegia, sensory loss, and incontinence beginning 15 hours after a fall-studied electrophysiologically at 2 days postparaplegia manifested absent lower-extremity f-waves and H-reflexes and normal compound muscle action potentials and distal motor and sensory conduction velocities. Subsequent evaluations demonstrated permanent loss of compound muscle action potentials, f-waves, and H-reflexes and prominent acute denervation in paralyzed lower-extremity muscles. Thus early f-wave and H-reflex loss can also occur in spinal cord disease, thereby representing the first evidence of motoneuron destruction.

Background: The National Institute of Neurological Disorders and Stroke (NINDS) rt-PA Stroke Study showed a similar percentage of intracranial hemorrhage and good outcome in patients 3 months after stroke treatment given 0 to 90 minutes and 91 to 180 minutes after stroke onset. At 24 hours after stroke onset more patients treated 0 to 90 compared to 91 to 180 minutes after stroke onset had improved by four or more points on the NIH Stroke Scale (NIHSS). The authors performed further analyses to characterize the relationship of onset-to-treatment time (OTT) to outcome at 3 months, early improvement at 24 hours, and intracranial hemorrhage within 36 hours., Methods: Univariate analyses identified potentially confounding variables associated with OTT that could mask an OTT-treatment interaction. Tests for OTT-treatment interactions adjusting for potential masking confounders were performed. An OTT-treatment interaction was considered significant if p < or = 0.10, implying that treatment effectiveness was related to OTT., Results: For 24-hour improvement, there were no masking confounders identified and there was an OTT-treatment interaction (p = 0.08). For 3-month favorable outcome, the NIHSS met criteria for a masking confounder. After adjusting for NIHSS as a covariate, an OTT-treatment interaction was detected (p = 0.09): the adjusted OR (95% CI) for a favorable 3-month outcome associated with recombinant tissue-type plasminogen activator (rt-PA) was 2.11 (1.33 to 3.35) in the 0 to 90 minute stratum and 1.69 (1.09 to 2.62) in the 91 to 180 minute stratum. In the group treated with rt-PA, after adjusting for baseline NIHSS, an effect of OTT on the occurrence of intracranial hemorrhage was not detected., Conclusions: If the NINDS rt-PA Stroke Trial treatment protocol is followed, this analysis suggests that patients treated 0 to 90 minutes from stroke onset with rt-PA have an increased odds of improvement at 24 hours and favorable 3-month outcome compared to patients treated later than 90 minutes. No effect of OTT on intracranial hemorrhage was detected within the group treated with rt-PA, possibly due to low power.

We are investigating the genetics of a large family with an autosomal dominant form of hereditary distal myopathy. This slowly progressive myopathy begins during early adulthood in the distal leg muscles, producing a gait disturbance. Cardiomyopathy is also present in most affected family members, manifesting itself as conduction block or congestive heart failure. Histologically, an accumulation of the protein, desmin, occurs in the subsarcolemmal spaces of myofibers. We have performed linkage analyses of this family, and have mapped the location of the gene causing the myopathy to human chromosome 2q33. The gene is within a 17-cM segment of chromosome 2q bounded by the DNA markers D2S2248 and D2S401. The best candidate gene for this myopathy is desmin., (Copyright 2000 S. Karger AG, Basel.)

In some myopathies of distal onset, the intermediate filament desmin is abnormally accumulated in skeletal and cardiac muscle. We report the first point mutation in desmin cosegregating with an autosomal dominant form of desmin-related myopathy. The L345P desmin missense mutation occurs in a large, six generation Ashkenazi Jewish family. The mutation is located in an evolutionarily highly conserved position of the desmin coiled-coil rod domain important for dimer formation. L345P desmin is incapable of forming filamentous networks in transfected HeLa and SW13 cells. We conclude that the L345P desmin missense mutation causes myopathy by interfering in a dominant-negative manner with the dimerization-polymerization process of intermediate filament assembly.

Health effects from chronic, low-level exposure to organophosphate pesticides have not been studied extensively and are not well-established. This report follows up a study in New York State in which a cohort of 90 male pesticide applicators were found to have increased vibration sensitivity thresholds, compared with a matched sample drawn from the general population. This investigation examined the nature and extent of peripheral nerve abnormalities in a small subgroup of the original cohort. Of the nine subjects studied, four had clinical evidence of peripheral neuropathic dysfunction, and one who was normal physiologically showed electrophysiological abnormalities. The remaining four showed no clinical, electrophysiologic, or quantitative signs or other abnormalities. This study adds to the growing evidence that organophosphates are toxic to the peripheral nervous system at levels of exposure that do not induce acute or subacute symptomatology.

Based on a review of the literature and the clinical research experience of the authors and reviewers, the AAEM proposes 17 criteria which should be used to construct and evaluate diagnostic and/or therapeutic outcome studies for patients with symptoms and signs of neuromuscular diseases. Neuromuscular diseases are defined as diseases that cause pathology and/or dysfunction of the sensory, motor, and/or autonomic nerve offers and/or muscles.

I examined 11 patients with upper-extremity causalgia secondary to peripheral nerve injury occurring during routine venipuncture. The nerves affected were the medial (n = 5) and lateral (n = 2) antebrachial cutaneous in the antecubital fossa, the superficial radial at the wrist (n = 2), and the dorsal sensory branches in the hand (n = 2). Anatomically, nerves lie on a plane just beneath and in close proximity to veins, making them vulnerable to injury during the procedure.

A large family is described with an autosomal dominant distal myopathy, the nature of which prompts the reevaluation of current classifications of these disorders. The disease begins in early to middle adulthood with gait disturbance due to distal leg weakness, and progresses over 5-10 years to involve all extremities, as well as bulbar, respiratory, and facial muscles. There is frequent cardiac involvement, manifest by arrhythmias, conduction blocks, and congestive failure, resulting in premature demise. On electromyography there is prominent spontaneous activity, short duration motor unit potentials, and polyphasia. Muscle biopsies from multiple family members at different stages of the disease are characterized by desmin storage and autophagocytosis. This distal myopathy differs from other phenotypically similar disorders in its rapidity of progression, fatal course and pathologic features. The role and specificity of excessive desmin accumulation in this and other myopathic and cardiac disorders are unknown.

The neuropathy associated with diabetes mellitus is arguably the most common peripheral neuropathy in the developed world. It can be classified into symmetrical and asymmetrical forms. The symmetrical form is predominantly sensory and autonomic, whereas the asymmetrical form can be sensory, or motor, or both, and can affect individual cranial or peripheral nerves. Pathologic and electrophysiologic studies indicate that the symmetrical polyneuropathy is characterized by a distally accentuated loss of myelinated and unmyelinated axons. The multifocal nature of the axonal degeneration and its association with vascular disease in the same pathologic specimens strongly suggest an ischemic cause involving the endoneurial microvascular circulation. The underlying biochemical abnormality appears to be the production of advanced glycosylated end products (AGEPs), in the presence of chronic hyperglycemia, which accumulate on endothelial proteins, causing basement membrane thickening and endothelial cell change. This produces multifocal vascular disease that, in turn, reduces nerve blood flow, causing endoneurial hypoxia and generating oxygen free radicals. Multifocal ischemic neuronal damage results. Currently, there is no accepted treatment, although long-term control of hyperglycemia is beneficial. Symptomatic relief of the burning pain is the most vexing therapeutic problem; tricyclic antidepressants and anticonvulsants have been used alone and together with varying success.

Fifty patients, ages 54-79, with ischemic hemispheric strokes productive of hemiparesis, at a minimum, underwent standardized neurological evaluations, computed tomographic scanning and cerebral angiography (N = 38) or carotid ultrasound (N = 12) within 5 h of onset. A second scan was performed at 5-7 days. Clinical scores were not associated with a history of, or the presence of: hypertension, smoking or cardiac disease, including atrial fibrillation, nor with severe internal carotid artery stenosis or occlusion. Clinical scores were adversely affected by early scan abnormalities (especially mass effect), lesion size, intracranial arterial occlusions, elevated serum glucose levels and the subsequent development of hemorrhagic infarction. Glucose levels correlated with infarct size and the development of hemorrhagic infarction. Delayed intracranial arterial filling and collateral flow were associated with reduced infarct size but did not confer clinical protection. We believe that combining the initial glucose level and scan results has prognostic significance, and early angiography is valuable in characterizing infarct etiology and assessing clinical severity.

Conduction along the sural nerve was studied in 64 normal subjects using near-nerve electrodes. Conduction velocities over the same nerve segments were calculated: (1) from the latency recorded from a site of stimulation to a site of recording (1R-method); and (2) from the difference in latency between 2 recording sites, the site of stimulation being situated elsewhere along the nerve (2R-method). Consistently faster velocities were seen with the 2R-method and could best be explained by a fixed delay of about 0.15 ms at the stimulus site (latency of activation, utilization time). This delay was markedly prolonged when a ramp rather than a rectangular stimulus was applied, though fast fibers were excited with both types of stimuli. The delay is thought to be dependent on the relationship between the density of current at the stimulus site and the threshold of responding fibers.

The sural nerve was studied orthodromically using the near-nerve technique in 273 normal subjects (155 females, 118 males) aged 5 to 90 years. The sensory action potential (SAP), evoked at the dorsum of the foot, was recorded at the lateral malleolus and midcalf, and at the midcalf when evoked at the lateral malleolus. In addition, the SAP was recorded at intermediate distal sites and at proximal sites at the popliteal fossa, the gluteal fold, and the S-1 root. The amplitude of the SAP recorded at midcalf was 32% higher in females than in males. This was probably due to volume-conduction properties, as differences between genders were less noticeable at more distal recording sites. The amplitude decreased steeply and exponentially with age. Conduction distance had a strong influence on the amplitude of the SAP, which decreased with increasing distance following a power relationship with an exponent of 1.4 to 1.7. This decrease was due to temporal dispersion with decreased summation and increased phase cancellation. The conduction velocity was slightly lower along the very distal course of the nerve than along more proximal segments.

Background and Purpose: Modern management of acute stroke necessitates early diagnosis. To this end, we sought to delineate the radiographic features of focal hemispheric infarction within 5 hours of ictus., Methods: Fifty patients, ages 54-79, with ischemic strokes productive of at least hemiparesis underwent computed tomographic scanning and cerebral angiography (n = 38) or carotid ultrasound (n = 12). Radiographic lesions were characterized for location, size, and pathophysiology., Results: Acute abnormalities, hypodensity, and mass effect were seen in 56% of scans and confirmed on a second scan 5-7 days later. Intracranial angiographic abnormalities occurred in 61% of patients: arterial occlusions in 45% and delayed arterial filling in 16%. Hemorrhagic infarctions occurred in 26% of second scans and were associated with mass effect (100%) and arterial occlusions (89%). Infarcts with hemorrhagic transformation were larger on both scans than those without (p = 0.001). Of four patients with infarctions in watershed territories on the scans, two had middle cerebral artery occlusions on angiography, thereby questioning the specificity of such scan lesions to low-flow states., Conclusions: We conclude that cerebral infarctions are often visible on early scans, but their locations may not be etiologically determinative. The infarcts associated with intracranial arterial occlusions (45%) were of thromboembolic origin, but, given current controversies as to the pathophysiology of lacunar and watershed infarctions, we cannot ascertain the etiology in the remainder. These findings are relevant to the new stroke therapies that require administration in the first hours after infarction.

A multivariate statistical analysis of levels of serum acetylcholine receptor antibody (AChR Ab) obtained from 197 patients with various clinical forms of myasthenia gravis (MG) was performed. Elevated AChR Ab levels are specific for MG, but normal AChR Ab levels do not rule out MG. Patients in remission or with purely ocular MG had the lowest incidence of elevation of serum AChR Ab levels, while patients with generalized, severe MG, particularly in the presence of thymoma, tended to have the greatest antibody elevations. Corticosteroids depressed AChR Ab levels, but thymectomy did not exert a consistent effect on antibody levels within a 24- to 30-month postoperative period. The relatively low 55% positivity of antibody elevations in all 197 patients probably reflects the use of heterologous (rat) AChR.

Eleven patients had causalgia that resulted from surgical procedures or improperly placed injections. It is the intense, unremitting, burning quality of the pain that distinguishes causalgia from other nerve injury sequelae. The mode of injury, as well as the symptoms and signs and their duration, suggests that the recent tendency to divide causalgia into "major" and "minor" forms on the basis of its occurrence during war or peace, with or without autonomic dysfunction, is improper. Most of these patients have sought legal redress. All cases for which the legal issues are complete have been settled in favor of the plaintiffs.

Two hundred and fifty consecutive patients were evaluated for myasthenia gravis with repetitive supramaximal stimulation of peripheral nerves and regional curare administration when necessary. Among patients with definite generalized myasthenia gravis, 72 percent had abnormal responses to repetitive supramaximal stimulation alone and another 17 percent had abnormal responses after regional curare administration. Among those with possible generalized myasthenia gravis, 15 percent had abnormal responses to repetitive supramaximal stimulation and another 12 percent had abnormal responses after regional curare administration. Of those with only ocular symptoms, 46 percent had abnormal responses to repetitive supramaximal stimulation before or after regional curare administration, suggesting generalized involvement. Myasthenia gravis has not developed subsequently in any of the equivocal patients with negative electric tests. We have found these electric procedures to be simple, safe, and at least as effective as other methods in diagnosing myasthenia gravis.

Recognition of the idiopathic polyradiculoneuropathies began with Graves, Landry and Dumenil who, respectively, suggested, implied and established the peripheral nervous system as a site of disease. Over the ensuing decades other neurologists separated the idiopathic disorders from neuropathies of known cause, poliomyelitis and myelopathies. Guillain, Barré and Strohl described the acute benign syndrome and its cerebrospinal fluid abnormalities. Haymaker & Kernohan solidified the features of the acute disorder as did Dyck et al and Prineas & McLeod for the relapsing and chronic conditions. Currently the idiopathic polyradiculoneuropathies are regarded as autoimmune in nature, clinically generalized with some cases having focal involvement, and of varying severity with only occasional fatalities. Neurologists are divided as to whether the acute and chronic disorders represent 2 different conditions or whether they are 2 forms in the spectrum of a single disorder. This author favors the concept of a single disorder with multifarious manifestations.

In two patients, one with clinical hemifacial spasm (HFS) and one with clinical facial myokymia, the spontaneous electromyographic findings consisted of regular burst activity: each burst composed of high frequency repetitive motor unit potentials. These bursts fired synchronously in multiple ipsilateral facial muscles in both patients and from a contralateral facial muscle in the patient with HFS. In addition, the patient with HFS exhibited crossed evoked responses on the affected side with stimulation of the facial and supraorbital nerves on the unaffected side. It is concluded that the current electrophysiological distinctions between HFS and facial myokymia may be unsupportable and that facial nuclear hyperactivity with activation of bilateral facial nuclear connections plays a role in the pathophysiology of HFS.