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Background: Guillain-Barre syndrome (GBS) is an acute, immune-mediated flaccid paralysis frequently associated with Campylobacter infection. Of two predominant GBS subtypes, a demyelinating subtype (acute inflammatory demyelinative polyneuropathy [AIDP]) predominates in the United States and Europe, and axonal subtype (acute motor axonal neuropathy [AMAN]) is the predominant form in China. Previous clinical studies suggested that AMAN also occurs in Mexican children. The purpose of this study was to describe the subtypes of GBS in children from Mexico City. Methods: We prospectively studied 121 children admitted to two pediatric hospitals in Mexico City from 1996 to 2002. Clinical histories were obtained, electrophysiologic studies were performed to determine GBS subtype, and microbiologic studies were performed. Results: Of the 121 children, 46 had AMAN and 32 had AIDP. The male to female ratio was 1.3 for AMAN cases (mean age = 6.3) and 3.0 for AIDP cases (mean age = 7.0). There was a strong seasonal distribution of AMAN cases in July to September. Children with AMAN, but not AIDP, had worsening of illness during hospitalization as judged by peak severity scores. Vomiting was more likely in AIDP (28.1%) vs AMAN (6.5%) ( p = 0.012) and diarrhea was more common in AMAN (32.6%) than AIDP (12.5%) ( p = 0.06). IgG anti-GM1 antibody titers were higher in patients with AMAN vs AIDP ( p = 0.067). Anti-GD1a antibodies were equally present in both groups. Anti GQ1b titers were higher in AMAN vs AIDP ( p = 0.009). Campylobacter antibody responses were positive in 44.1% of patients with AMAN and 37.0% of patients with AIDP. Twenty patients (14 = AMAN, 6 = AIDP) had positive stool cultures for C jejuni . Two serotypes, HS:19 and HS:41, accounted for 6 of 10 Campylobacter isolates available for serotyping from these cases. Conclusions: This study confirms that acute motor axonal neuropathy is an important Guillain-Barre syndrome subtype in Mexican children, is associated with diarrhea, and occurs seasonally. GLOSSARY: AIDP = acute inflammatory demyelinative polyneuropathy; AMAN = acute motor axonal neuropathy; AMSAN = acute motor sensory axonal neuropathy; GBS = Guillain-Barre syndrome; HS = heat stable; INP = Instituto Nacional de Pediatria; HPL = Hospital Legaria.

The authors report significant worsening of a pre-existing neuropathy in six patients who received "non-toxic" dosages of known neurotoxic agents. Before treatment, baseline total neuropathy score (TNS) averaged 9.5 (range 0 to 19). After chemotherapy (Taxol [125 to 175 mg/m(2) x 4]; vincristine [2 to 5 mg]; cisplatin [40 mg/m(2) x 8]; and thalidomide [60 g]), the TNS averaged 22 (range 13 to 29). The authors conclude that functionally disabling toxic neuropathy can occur in patients with pre-existing neuropathy at standard doses.

To determine the prevalence of different forms of peripheral neuropathy in patients with restless legs syndrome (RLS) and correlate the findings with other clinical characteristics.RLS is characterized by a desire to move the extremities, often associated with paresthesias or dysesthesias, motor restlessness, worsening of symptoms with rest with relief by activity, and worsening of symptoms in the evening or night. The association between RLS and peripheral neuropathy remains controversial. The observation that many patients with small-fiber neuropathy also complain of RLS prompted this prospective case series.Twenty-two consecutive patients with RLS were evaluated for evidence of large-fiber neuropathy (LFN) and small sensory fiber loss (SSFL).In eight of the 22 (36%) patients, neuropathy was identified. Three patients had pure LFN; two had mixed LFN and SSFL; and three had isolated SSFL. The SSFL group had a later onset of RLS (p0.009), reported pain in their feet with RLS more frequently (p0.001), and tended to have no family history of RLS (p0.078). Patients with LFN did not have similar associations with age at onset, family history status, or presence of pain.The results suggest that two forms of RLS exist: one is triggered by painful dysesthesias associated with SSFL, has later onset, and no family history; and one without involvement of SSF, with an earlier onset age, positive family history for RLS, and no pain. The authors hypothesize that patients with the SSFL subtype of RLS will preferentially respond to neuropathic pain medications.

The presence of an APOE epsilon4 allele may be a risk factor for neuropathy severity in diabetes. The authors assessed the frequency of APOE epsilon4 in patients presenting with sensory predominant neuropathy. APOE epsilon4 frequency among patients with early diabetic neuropathy and impaired glucose tolerance-associated neuropathy was 16 to 17%, and not different from patients with idiopathic neuropathy (17%) or published normative values (16%). APOE epsilon4 may not function as a susceptibility gene in sensory predominant neuropathy.

The authors report the use mycophenolate mofetil (MM) in the treatment of neuromuscular diseases. Thirty-eight patients (32 with MG, three with inflammatory myopathy, and three with chronic acquired demyelinating neuropathy) were treated with MM for an average duration of 12 months. All patients tolerated MM without major side effects. Twenty-four patients improved either in their functional status or in their ability to reduce corticosteroid dose. Mean time to improvement was 5 months.

Twenty-eight patients with sensory complaints of unknown etiology had repeated skin biopsies. Patients with large nerve fiber swellings on initial biopsy showed a decline in epidermal nerve fiber density on repeated biopsies (p < 0.05 within group; p < 0.05 vs those without swellings). Patients without nerve fiber swellings did not have changes in nerve fiber density between biopsies. Patients with large nerve fiber swellings were most likely to present clinically with paresthesias (p < 0.05).

Background: There are a number of distal and generalized small-fiber neuropathies. The neuropathologic basis is poorly understood as somatic and autonomic C fibers are not usually studied in the same region of the body. Objective: To evaluate prospective somatic and autonomic C-fiber function in 11 healthy control subjects and 38 patients with different clinical patterns of neuropathy. Methods: Distal small-fiber neuropathy (DSFN), peripheral neuropathy (PN), diabetic neuropathy (DN), neuropathic postural tachycardia syndrome (POTS), and idiopathic autonomic neuropathy (IAN) were evaluated. Intraepidermal nerve fiber density was used to evaluate distal somatic C fibers. Both quantitative sudomotor axon reflex test and skin norepinephrine content were measured for the biopsy site to assess distal autonomic C-fiber function. Postganglionic sudomotor, adrenergic, and cardiovagal functions were evaluated by autonomic reflex testing and quantified using a Composite Autonomic Severity Scale. Results: Skin norepinephrine concentration was significantly related to CASS. DN was associated with somatic and autonomic C-fiber impairment with good agreement. POTS was associated with selective distal autonomic deficit. DSFN had combined distal somatic and C-fiber impairment. IAN showed combined and selective distal and generalized autonomic C-fiber impairment. The somatic neuropathies had C-fiber impairment affecting both populations to varying degrees. Conclusion: Although a general agreement exists between the loss of somatic C fibers and autonomic deficits, selective involvement occurs for specific autonomic neuropathies.

Objective: To compare the neuropathy associated with impaired glucose tolerance (IGT) and diabetes mellitus (DM) determined by oral glucose tolerance testing (OGTT). Methods: Patients with peripheral neuropathy of unknown cause were prescribed OGTT. Duration of neuropathic symptoms, neuropathic pain, neuropathy classification, nerve conduction test results, and intraepidermal nerve fiber densities (IENFD) were compared between IGT and DM groups. Results: Seventy-three patients completed OGTT; 41 (56%) had abnormal results. Of these 41 patients, 26 had IGT and 15 had DM. Patients with IGT had less severe neuropathy than patients with diabetes, as measured by sural nerve amplitudes ( p = 0.056), sural nerve conduction velocities ( p = 0.03), and distal leg IENFD ( p = 0.01). Patients with IGT had predominantly small fiber neuropathy, compared to patients with DM ( p = 0.05), who had more involvement of large nerve fibers. Conclusions: The neuropathy associated with IGT is milder than the neuropathy associated with DM. Small nerve fibers are prominently affected and may be the earliest detectable sign of neuropathy in glucose dysmetabolism. OGTT is appropriate in patients with idiopathic neuropathy.

The spectrum of bent spine disorders Head ptosis (drop) results from weakness of the neck extensor, or increased tone of the flexor muscles. It is characterised by marked anterior curvature or angulation of the cervical spine and is associated with various neuromuscular (table 1) and extrapyramidal disorders.12–15 Camptocormia or the bent spine syndrome was first described in hysterical soldiers in 1915 by the French neurologist Souques.16 Typically there is marked anterior curvature of the thoracolumbar spine. In some patients the spine is angulated forward, the arms propped against the thigh for support. More cases, all among soldiers, were reported during the first and second world wars. These patients responded well to psychotherapy. Recently camptocormia arising as a result of weakness or abnormality in the tone of the paraspinal muscles has been described (table 2). In contrast with other skeletal disorders of the spine such as kyphosis, the deformity in head ptosis and camptocormia is not fixed and is corrected by passive extension or lying in the supine position. It is not possible to straighten the neck or back voluntarily. The evaluation of these disorders can indeed be challenging and often no definite diagnosis is made, as illustrated by four cases of head ptosis and camptocormia seen by us at the Johns Hopkins Hospital. View this table: Table 1 Neuromuscular causes for head ptosis View this table: Table 2 Causes of camptocormia An 80 year old man developed head ptosis insidiously over a period of few weeks. A week before this he had an upper respiratory tract infection and also experienced transient sharp pain over the left and then the right shoulder. He had no diplopia, dysarthria, dysphagia, limb weakness, or fatiguability. Examination showed severe neck extensor weakness, Medical Research Council (MRC) grade 2. Muscle strength was normal in all other cranial, proximal, and distal limb muscles. Serum …

To correlate electrophysiologic patterns with sural nerve pathology in children with Guillain-Barré syndrome (GBS).Based on electrophysiologic and pathologic observations, GBS has been divided into demyelinating and axonal subtypes. The acute motor axonal neuropathy (AMAN) involves predominantly motor nerve fibers with a physiologic pattern suggesting axonal damage, whereas the acute inflammatory demyelinating polyneuropathy (AIDP) involves both motor and sensory nerve fibers with a physiologic pattern suggesting demyelination. In this study, we sought to confirm these observations by correlating sural nerve pathology with electrophysiologic findings in GBS patients.Biopsies of sural nerve from 29 of 50 prospectively studied GBS patients were obtained. Nerves were examined by light and electron microscopy, and with immunocytochemistry for macrophages, lymphocytes, and complement activation products.Sural nerves from AMAN patients were normal or had only a few (0.1% to 0.7%) degenerating fibers without lymphocytic infiltration or complement activation. One patient with reduced sural sensory nerve action potential classified as acute motor sensory axonal neuropathy (AMSAN) had many degenerating fibers (2.3%) in the sural nerve. All three AIDP patients displayed active demyelination, and in two patients, lymphocytic infiltration and complement activation products were observed on the abaxonal Schwann cell surface.Classification of Guillain-Barré syndrome subtypes based on motor conduction studies correlates closely with pathologic changes seen in sural nerve. In acute motor axonal neuropathy cases, the sural nerve is almost completely spared pathologically. In acute inflammatory demyelinating polyneuropathy cases, macrophage-mediated demyelination and lymphocytic infiltration are common in the biopsies of sural nerves.

Oculodentodigital syndrome (O.D.) is an autosomal dominant disorder comprising facial anomalies, syndactyly, microcorneae, dental enamel hypoplasia, and leukodystrophy. We describe a four generation family with O.D. in which anomalies such as syndactyly appear congenitally, whereas neurological (i.e., leukodystrophic) signs and symptoms tend to be expressed in a more severe form and/or at an earlier age of onset in successive generations of the kindred. This pattern of phenotypic expression is consistent with the phenomenon of genetic anticipation, and we suggest that O.D. may be a trinucleotide repeat disorder.

The concept of a severe motor-sensory neuropathy of acute onset caused by an immune attack on the axon ("axonal" Guillain-Barré syndrome) has been advanced primarily based on electrodiagnostic and limited pathological data, but remains controversial. At autopsy some cases demonstrate unusually severe inflammatory demyelinating neuropathy. There are conflicting data about whether antecedent Campylobacter jejuni infection is associated with "axonal" Guillain-Barré syndrome. We report 4 individuals from Hebei Province, China, who died 7, 7, 18, and 60 days after onset of a syndrome diagnosed clinically as Guillain-Barré syndrome. High titers of antibodies recognizing C. jejuni, consistent with recent infection, were found in the 2 patients tested. At autopsy the 3 with early disease had ongoing wallerian-like degeneration of fibers in the ventral and dorsal roots and in the peripheral nerves, with only minimal demyelination or lymphocytic infiltration. All 3 had numerous macrophages in the periaxonal space of myelinated internodes, and rare intraaxonal macrophages as well. Examination of the patient having the syndrome for 60 days confirmed the extensive loss of large fibers in the spinal roots and nerves, and the paucity of demyelination and remyelination. These observations confirm predictions that some patients with severe motor-sensory Guillain-Barré syndrome, as defined clinically, have predominantly axonal lesions of both motor and sensory fibers, even in the early stages of the disease, and that axonal Guillain-Barré syndrome can follow C. jejuni infection. The pathology supports the possibility that such cases of motor-sensory axonal Guillain-Barré syndrome represent the most severe end of a spectrum of immune attack directed toward epitopes on the axon.

Nerve growth factor receptor, expressed in Schwann cells during early development of the PNS, is rarely found in the normal mature PNS. Following nerve transection nerve growth factor receptor is re-expressed at high levels in the Schwann cells of the denervated nerve fibres. In this study we asked if demyelination caused by an immune-mediated process or by physical destruction of myelin is associated with expression of nerve growth factor receptor, and if so, what cells are positive. We examined spinal roots and sciatic nerves from rats with experimental autoimmune neuritis and sciatic nerves from rats with focal demyelination produced by local application of lysolecithin. Both in 1 micron serial cryosections and in immunostained teased nerve fibres we found that the Schwann cells that were associated with demyelinated internodes expressed nerve growth factor receptor. Immunoreactivity for nerve growth factor receptor appeared first in a perinuclear ring, probably corresponding to the Golgi complex. In completely demyelinated internodes the postmitotic Schwann cells ensheathing the axons expressed nerve growth factor receptor on their plasmalemma. Neighbouring Schwann cells with intact myelin sheaths remained nerve growth factor receptor negative. In contrast, Schwann cells of neighbouring unmyelinated fibres expressed prominent nerve growth factor receptor immunoreactivity. These data further indicate that expression of nerve growth factor receptor by Schwann cells does not require axonal degeneration, but can be stimulated by some factor associated with acute demyelination.

Maximal voluntary eccentric (ECC) and concentric (CON) capacity of knee and elbow muscle groups was investigated in healthy untrained men (N = 40) and women (N = 50), 21-67 yr of age. Purposes of the study were to describe torque-velocity and ECC-CON relationships, and to compare these relationships among muscle groups and between genders. Average torque was measured at angular velocities of 30 degrees and 120 degrees.s-1 from knee flexor (KF), knee extensor (KE), and elbow flexor (EF) muscle groups unilaterally, using an isokinetic protocol including gravity compensation. Data were analyzed using ANOVA procedures, and a significance level of 0.01 was used for all hypothesis testing. Torque-velocity relationships were similar for each muscle group and gender; i.e., ECC average torque did not change as a function of velocity and CONC torque decreased as angular velocity increased. Women generated greater ECC relative to CONC torque than men in upper and lower extremity muscle groups. Muscle groups differed in ECC relative to CONC capacity in both men and women, with ECC/CONC ratios being greater for KE and EF than KF. In all muscle groups, the magnitude of ECC-CONC differences increased as angular velocity increased. Genders differed in relative strength balance between muscle groups, with men exhibiting greater KF/KE and EF/KF torque ratios than women for both ECC and CONC actions. Results of this study contribute to the body of women.(ABSTRACT TRUNCATED AT 250 WORDS)

Thirteen patients, 11 women and 2 men, developed sensory and autonomic neuronopathies in association with features of primary Sjögren's syndrome. In 11, Sjögren's syndrome had not been previously diagnosed at the time of neurological presentation. All had prominent loss of kinesthesia and proprioception. Pain and thermal sensibility were less severely affected. Most had evidence of autonomic insufficiency. In some this was severe, with Adie's pupils, fixed tachycardia, and orthostatic hypotension. The course ranged from an abrupt, devastating onset to indolent progression over years. Stabilization or functional improvement occurred in 6 patients, 2 of whom received no drug therapy. Sensory nerve conduction studies and examination of nerve biopsy specimens demonstrated a wide spectrum in the severity of loss of large myelinated fibers. The cutaneous nerves of 6 patients had perivascular mononuclear infiltrates without necrotizing arteritis. Examination of biopsy specimens of dorsal root ganglia in 3 patients revealed lymphocytic (T-cell) infiltration in the dorsal roots and ganglia, with focal clusters around neurons. In the more mildly affected ganglia, individual sensory neurons were undergoing degeneration. In the most advanced case, very few neurons remained. The possibility of Sjögren's syndrome should be considered in patients, especially women, who develop acute, subacute, or chronic sensory and autonomic neuropathies, with ataxia and kinesthetic loss.

Motor neuron diseases, manifest as weakness and atrophy of skeletal muscles, occur in infancy, childhood, and adult life. Some forms of this disease are inherited. Motor neurons are selectively affected and exhibit cytoskeletal pathology, primarily enlargements of proximal axons by accumulations of transported neurofilaments. A motor neuron disease, hereditary canine spinal muscular atrophy, has been discovered in Brittany spaniels. The disease is inherited as an autosomal dominant characteristic and shows striking clinical and pathological features in common with human motor neuron disease. The availability of this excellent animal model of the human condition has allowed neurobiological investigations of the dynamics of structural and chemical pathologies of vulnerable neurons.

Background The sensitivity of neuron-specific antibodies permit the identification of the small unmyelinated nerve fibers within the skin. Objectives To develop a reference range of epidermal nerve fiber density in humans, and to evaluate their diagnostic efficiency for sensory neuropathies. Methods Ninety-eight normal controls (age range, 13-82 years) were examined with both directed neurologic examinations and quantitative sensory testing. The diagnostic utility was examined in 20 patients with sensory neuropathies. Each subject had 2 punch biopsies performed at each site in the thigh and distal part of the leg (total of 392 biopsies). After formalin fixation, 50-µm-thick free-floating sections were stained with a polyclonal antibody to neuron-specific ubiquitin hydrolase, anti–protein gene product 9.5. We enumerated intraepidermal nerve fibers per millimeter to derive a "linear density." The linear density technique was validated against a stereological technique that used the fractionator to measure the total length of intraepidermal nerve fibers per 3-mm punch. Results The biopsy technique was well tolerated, with no notable complications. The linear density quantitation was rapid and had high intraobserver and interobserver reliability. We determined that the density of intraepidermal fibers in normal controls was 21.1±10.4 per millimeter (mean±SD) in the thigh (fifth percentile, 5.2 per millimeter), and was 13.8±6.7 per millimeter at the distal part of the leg (fifth percentile, 3.8 per millimeter). Significantly higher intraepidermal fiber densities were seen in the youngest group ( P =.004), and we observed no significant effect of race, sex, height, or weight. The density at the thigh was significantly correlated with that at the distal part of the leg ( P =.01) and was consistently higher by about 60%, a reflection of the normal proximal-distal gradient. The results obtained with stereology and the linear density correlated significantly ( P =.001), providing internal validation for the technique. Epidermal nerve fiber density was significantly reduced ( P =.001) in patients with sensory neuropathies. With a cutoff derived from the fifth percentile of the normative range for the distal part of the leg, the technique had a positive predictive value of 75%, a negative predictive value of 90%, and a diagnostic efficiency of 88%. Conclusions We have established a reference range for intraepidermal nerve fiber density in normal humans by means of a simple quantitation method based on enumeration of individual intraepidermal nerve fibers on vertical sections of punch skin biopsy specimens stained with the sensitive panaxonal marker anti–protein gene product 9.5. The utility of the density measurement was confirmed for sensory neuropathy with a diagnostic efficiency of 88%. Skin biopsies may be useful to assess the spatial distribution of involvement in peripheral nerve disease and the response to neurotrophic and other restorative therapies.

Two human retroviruses, HIV-1 and HTLV-I, have been associated with myelopathies in addition to other neurologic disorders. We report an American dually infected with HIV-1 and HTLV-I who developed steroid-responsive myeloneuropathy. This 28-year-old bisexual man developed interstitial pneumonitis and a transient midthoracic sensory level followed by the evolution of a slowly progressive spastic paraparesis and sensorimotor neuropathy. Serologic studies demonstrated coinfection with both HIV-1 and HTLV-I. Peripheral blood absolute CD4 count was persistently within the normal range. Cranial MRI was normal and spinal MRI showed T3-T10 atrophy. Serial CSF analyses demonstrated marked intrathecal synthesis of anti-HTLV-I IgG, lymphocytic pleocytosis, elevated protein and immunoglobulin G, and oligoclonal bands. HIV-1 was isolated from CSF but not from peripheral nerve. Lymphoproliferative studies confirmed spontaneous proliferation in both blood and CSF. Soluble interleukin 2 receptor and soluble CD8 were greatly elevated in blood and CSF when compared with patients with HIV-related vacuolar myelopathy and seronegative patients with other causes of myelopathy. Nerve biopsy showed epi- and endoneurial CD8+ lymphocytic infiltration without vasculitis; muscle biopsy showed features of acute and chronic denervation. A 6-week course of prednisone produced sustained improvement in leg strength and walking times. We speculate that the myeloneuropathy was caused by HTLV-I in the setting of coinfection with HIV-1.

Phosphorylated and nonphosphorylated epitopes of neurofdament (NF) proteins are distributed in different regions of individual neurons. Immunocyto-chemical methods, with monoclonal antibodies directed against phosphorylated and nonphosphorylated NF, demonstrated nonphosphorylated NF in perikarya and proximal axonal segments of neurons in dorsal root ganglia, while phosphorylated NF proteins were present in axons of these cells. The distribution of these epitopes of NF were examined at various times following injury of axons in the rat sciatic nerve. Between one and 2 I days after crush of the proximal nerve, phosphorylated NF were present in neuronal perikarya. We have compared patterns of perikaryal immuno-reactivity at one time point (three weeks) following a more distal crush or complete transection of the sciatic nerve. At this time period, following transection/ligation, phosphorylated NF immunoreactivity was not present in perikarya, but abnormal staining was observed after nerve crush. These altered distributions of phosphorylated epitopes of NF are of interest because several recent reports have indicated that similar, but not identical, abnormal staining patterns occur in human neurological diseases, including Alzheimer's disease and Parkinson's disease. In accord with previous studies, this investigation indicates that one response of neurons to injury, or to disease, is an abnormal distribution of phosphorylated epitopes of NF proteins.

The role of neurofilaments, the intermediate filaments of nerve cells, has been conjectural. Previous morphological studies have suggested a close relationship between neurofilament content and axonal caliber. In this study, the regenerating neuron was used as a model system for testing the hypotheses that neurofilaments are intrinsic determinants of axonal caliber, and that neurofilament content is controlled by the axonal transport of neurofilaments. This system was chosen because previous studies had shown that, after axotomy, axonal caliber was reduced within the proximal stump of the regenerating nerve and, because the relative amount of neurofilament protein undergoing axonal transport in regenerating axons was selectively reduced. The relationship between axonal caliber and neurofilament number was examined in a systematic fashion in both regenerating and control motor axons in rat L5 ventral root. Reconstruction of the spatial and temporal sequences of axonal atrophy in the proximal stump after axotomy showed that reductions in axonal caliber were first detected in the most proximal region of the root and subsequently progressed in a proximal-to-distal direction at a rate of 1.7 mm/day, which is identical to the rate of neurofilament transport in these neurons. Quantitative ultrastructural studies showed that these reductions in caliber correlated with a proportional decrease in the number of axonal neurofilaments but not microtubules. These results support the hypotheses that neurofilament content is a major intrinsic determinant of axonal caliber and that neurofilament content is controlled by the axonal transport of neurofilaments. On this basis, we suggest a role for neurofilaments in the control of axonal volume.

The effect of prolonged daily electrical stimulation (ES) on quadriceps strength in 22 patients during the 6 weeks following anterior cruciate reconstruction was investigated. Patients were randomly assigned to re ceive either a combination of ES and exercise or exer cise alone. Isometric quadriceps strength was meas ured at the 7th, 8th, and 9th postoperative weeks. No significant difference in strength existed between the groups as a result of ES. A significant difference in strength did exist between competitive and recreational athletes regardless of treatment. Further research is needed to determine if the addition of ES to isometric exercise during immobilization can significantly retard strength loss after anterior cruciate reconstructive sur gery.

A right-sided colon lesion appearing as a typical adenocarcinoma was biopsied and revealed squamous cell carcinoma. The etiologic possibilities include metastatic disease to the gastrointestinal tract (most likely from the lung in this case) and the very uncommon primary squamous cell carcinoma of the colon. The described features of both lesions are reviewed.

The purposes of this study were to compare the value of isokinetic testing and manual muscle testing (MMT) in longitudinal measurements of muscle strength in patients with neuromuscular disease and to identify any consistent pattern demonstrated by the isokinetic testing of patients with specific diagnoses. We measured knee extensor muscle strength at periodic intervals in patients, using MMT and isokinetic testing at angular limb velocities of 30 and 180 degrees/sec. An isokinetic fatigability test also was conducted. The results indicated that in patients who were graded 9 to 10 (ie, within normal limits) by MMT methods, sequential isokinetic strength tests revealed improvement not indicated by MMT. In patients, however, having weakness detectable by MMT and whose course was deteriorating, isokinetic testing did not seem to add clinically significant information for long-term management. Some patients with myotonia demonstrated an increase in peak torque during the fatigability test; this response was unique among the diagnoses we tested. Isokinetic testing may provide, in some patients with neuromuscular disease, valuable information when used in conjunction with MMT for sequential monitoring of strength. Continued research is needed to investigate the value of isokinetic testing in the diagnosis and management of patients with neuromuscular disease.

The neurofibrillary changes produced by IDPN are the consequence of the ability of the agent to impair the slow axonal transport of neurofilaments. The susceptibility of various neurons to this effect depends upon their neurofilament content; neurofilament-rich large caliber axons are severely affected. In motor neurons the half-velocities of neurofilament proteins are reduced 2-10 fold, while tubulin and other slow component constituents are only mildly altered. Optic nerve fibers are intermediate in vulnerability, and small neurofilament-poor fibers have little change in slow transport. The agent acts directly on the axon, and the transport defect is expressed all along the course of susceptible axons. Similar alterations in neurofilament transport have recently been found with 3,4-dimethyl-2,5-hexanedione, indicating that similar pathogenetic mechanisms can occur with toxic agents other than IDPN.

The time course of recovery in the Guillain-Barré syndrome is known to vary widely, but factors associated with differences have not been previously defined. In this study we used multivariate analysis to identify such factors and to determine whether the presence or absence of specific factors would influence treatment decisions, particularly the use of plasmapheresis. Data from 245 patients randomized into conventional and plasmapheresis arms were used to assess the time to walk independently (Grade 2), the time to improve one grade, and the percentage improved at 4 weeks. Individually, many factors were associated with outcome. In the multivariate analysis, four factors correlate with poorer outcomes: mean amplitude of compound muscle action potential on stimulating distally of 20% of normal or less, older age, time from onset of disease of 7 days or less, and need for ventilatory support. The most powerful predictor of outcome was the abnormal mean amplitude of compound muscle action potential on stimulating distally. Plasmapheresis, the only variable the physician can influence, has a beneficial effect over and above any or all of these factors. The plasmapheresis patients on continuous flow machines had better outcomes than those on intermittent flow machines. From these data, tables of expected outcome probabilities have been developed.

A progressive neurologic disease was identified in a family of closely related Britanny Spaniel dogs. The disease developed in dogs less than 1 year old and characteristically resulted in paraspinal and proximal pelvic limb muscular atrophy. Neurologic examination, electrodiagnostic testing, and histologic studies indicated that the disease results from motor horn cell degeneration. A colony of affected dogs was established, and breeding studies incriminated an inherited basis for the disease.

To determine whether antibodies to acidic glycolipids of nervous tissue are present in patients with Guillain-Barré syndrome (GBS), sera from patients with GBS and appropriate control subjects were tested by a thin-layer chromatogram overlay technique. Chromatograms on which the whole ganglioside fractions from peripheral nerve and brain had been separated were overlaid with appropriate dilutions of the patients' sera (1:100 or greater), and antibody binding was revealed with a radiolabeled or peroxidase-labeled second antibody. Antibodies to ganglioside antigens were detected in 5 of 26 patients with GBS. IgG antibodies in 1 patient reacted strongly with LM1 (sialosyl paragloboside), the major ganglioside of human peripheral nervous system myelin, and its hexaose analog (sialosyl lactosaminyl paragloboside), a minor ganglioside of human peripheral nervous system myelin. The antibody titer in this patient fell 8-fold over 6 weeks coincident with clinical improvement. IgG from 2 other patients with GBS reacted with GD1b ganglioside, and the antibody titers in these patients also decreased substantially with clinical improvement. IgM antibodies in the sera from 2 other patients reacted with GD1a and GT1b gangliosides, which have a shared terminal carbohydrate sequence. Antibodies to gangliosides were not detected in the sera from 19 patients with other neurological diseases or from 10 normal subjects, and the frequency with which antiganglioside antibodies occurred in the patients with GBS was significantly greater than that in the combined control subjects (p less than 0.01). The results demonstrate relatively high levels of antibodies to gangliosides in some GBS patients.

Treatment of duodenal ulcer with the histamine H2-receptor antagonist, ranitidine, was assessed in a double-blind, randomized, multicenter trial in which patients were treated for two consecutive 4-week periods with ranitidine 150 mg b.i.d. or a placebo. All patients were allowed to take antacids as necessary for symptoms. Three hundred eighty-two patients were entered and 355 completed the first 4-week trial period. Ranitidine significantly improved healing at 2 weeks (37 versus 19%, p less than 0.01) and at 4 weeks (73 versus 45%, p less than 0.01), with better relief of pain and lower use of antacids. In the second 4-week trial period, 124 unhealed patients from the first 4 weeks were re-randomized. Ranitidine treatment resulted in a greater healing rate regardless of previous treatment (p less than 0.05). In this trial, side effects were uncommon and not different between placebo and the tested drug. One case of hepatitis in the ranitidine treated group was presumed on the evidence to be non-A non-B. Ranitidine is effective and appears to be safe in the treatment of duodenal ulcer and its symptoms.

The neurotoxicity of hexacarbon solvents has become apparent only recently, but an extensive literature has already developed as a result of the clinical and epidemiological implications of the human disease, and the advantages of small animal models of hexacarbon neurotoxicity in investigation of experimental neuropathies. This review selectively summarizes the literature, focusing on clinical manifestations and pathological alterations in the peripheral nerves. The clinical manifestations are dominated by a distal, symmetrical, sensorimotor polyneuropathy. Pathological changes include distal axonal degeneration and formation of neurofilament-filled axonal swellings in early or moderately severe exposure. A late manifestation in severely affected experimental animals is recurrent demyelination and remyelination.

The North American study of plasmapheresis in Guillain-Barré syndrome (GBS) included early, standardized electrodiagnostic testing in 210 of the 245 patients. To determine the types of abnormalities and the relation to outcome, we analyzed the prospectively collected motor conduction data obtained during the first 30 days of illness. For each parameter of motor conduction data, means were computed based on institutional normal data. Mean distal motor and F wave latencies commonly were abnormal in these early studies. In univariate analysis, mean compound muscle action potential (CMAP) amplitude from distal and proximal stimulation and mean motor conduction velocity were found to be related to the four predetermined outcome measures. In multivariate analysis of the motor conduction parameters, mean distal CMAP amplitude was the single best predictor of prognosis; other measures did not add to its predictive value. In further multivariate analysis of all factors relating to outcome, mean distal CMAP amplitude was determined to be the most powerful predictor of outcome, followed by plasmapheresis. These two factors were always statistically significant over and above all other variables. Our results indicate that prognostic information can be obtained from motor conduction studies even when performed early in the course of GBS; a mean distal CMAP amplitude of 0 to 20% of the lower limit of normal is associated with a markedly increased probability of a poor outcome. Nevertheless, even in patients with a low mean distal CMAP amplitude, the predicted outcome is improved with plasmapheresis therapy.

A 27-year old man with a long history of ulcerative colitis developed a nephrotic syndrome. Renal biopsy revealed a minimal change lesion and further evaluation revealed that the patient had colonic carcinoma. Total colectomy and a course of prednisone were followed by a complete and lasting remission of the nephrotic syndrome. To our knowledge this is the first recorded case of minimal change nephrotic syndrome occurring in a patient with ulcerative colitis and colonic carcinoma.

Our patient, who was known to have multiple myeloma, presented with weight loss, rectal bleeding, and a barium enema study suggestive of a colitis with a mass lesion. Colonoscopy with biopsy revealed the mass to be large mucosal folds infiltrated with amyloidosis. Amyloidosis has been reported to mimick malignancy, mainly by tumorous deposits in the stomach and less commonly in the small and large bowels. Gastrointestinal surgery in patients with amyloidosis potentially may have undesirable consequences due to failure of anastomotic suture lines and subsequent sepsis (6, 11, 17, 18). The knowledge that amyloidosis may be associated with multiple myeloma and an appreciation of the wide range of gastrointestinal roentgenographic findings in patients with amyloidosis should prompt the clinician to obtain endoscopic and biopsy evaluation of these patients.