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Affection of the optic nerves play a central role in multiple sclerosis (MS) symptomatology. In reported autopsy series the prevalence of optic neuropathy has approached 100%. In the present study subclinical affection of the optic nerves was investigated by visual evoked response (VER), Farnworth-Munsell 100 Hue test (FM 100 Hue test) and Ishihara plates in 17 patients with normal visual acuity and without a history of acute optic neuritis. Optic neuropathy was demonstrated in 72% of the eyes. The occurrence of optic neuropathy was also investigated by the same methods in 16 patients with previous acute optic neuritis, which was bilateral in 5 patients. Affection of the optic nerves was demonstrated in 95% in this group. The affection of also the fellow eye in patients with previous monolateral optic neuritis is unexplained. It may be an analogue to the symmetry of plaques found in the brain and the spinal cord. The cause of this peculiar distribution of lesions is, like the ethiology of MS, unexplained at present. In compairing the different methods of demonstrating optic neuropathy, VER is recommended as the method of choice.

Axotomy of peripheral nerve stimulates events in multiple cell types that initiate a limited inflammatory response to axonal degeneration and simultaneous outgrowth of neurites into the distal segments after injury. We found that pharmacological blockade of RAGE impaired peripheral nerve regeneration in mice subjected to RAGE blockade and acute crush of the sciatic nerve. As our studies revealed that RAGE was expressed in axons and in infiltrating mononuclear phagocytes upon injury, we tested the role of RAGE in these distinct cell types on nerve regeneration. Transgenic mice expressing signal transduction-deficient RAGE in mononuclear phagocytes or peripheral neurons were generated and subjected to unilateral crush injury to the sciatic nerve. Transgenic mice displayed decreased functional and morphological recovery compared with littermate controls, as assessed by motor and sensory conduction velocities; and myelinated fiber density. In double transgenic mice expressing signal transduction deficient RAGE in both mononuclear phagocytes and peripheral neurons, regeneration was even further impaired, suggesting the critical interplay between RAGE-modulated inflammation and neurite outgrowth in nerve repair. These findings suggest that RAGE signaling in inflammatory cells and peripheral neurons plays an important role in plasticity of the peripheral nervous system.

A 34-week floppy preterm infant born to a mother with acute ulcerative colitis presented with a progressive reduction in spontaneous limb movements, severe generalized hypotonia, areflexia, autonomic dysfunction and respiratory failure. Electromyography revealed pronounced denervation activity and markedly slow nerve conduction velocity (3 m/s) with evidence of conduction block. These findings indicated demyelination with additional axonal features. The infant was diagnosed with congenital Guillain-Barré syndrome, was treated with intravenous immunoglobulin and showed clinical improvement within 48 hours of treatment. The relationship between inflammatory bowel syndrome and inflammatory demyelinating polyneuropathy is discussed.

In a prospective study twenty patients with benign intracranial hypertension, 15 females and five males with mean age 34 years (range 12–61 years), were followed up from 12 to 61 months (mean 22 months). Initially all patients showed marked papilledema, normal visual acuity, considerable enlargement of the blind spot area, and significantly delayed pattern reversal visual evoked potentials. During medical treatment eleven patients showed within 3–6 months a rapidly regression and normalization of papilledema, blind spot area, and visual evoked potentials. Eight patients continued in showing papilledema including disc gliosis, enlargement of blind spot area, and pathological visual evoked potentials. One patient developed optic nerve atrophy. The results indicated that repeated examinations of visual evoked potentials, when suspect of threatening visual loss has come up (papilledema, increased blind spot area, and field defects), might increase the change of diagnose of an optic nerve atrophy as early as possible.

Neuromuscular disorders are increasingly recognized in the critically ill but conventional electrodiagnostic techniques often provide non-specific results or are hampered by local conditions that prevent adequate disease classification. Muscle fiber inexcitability is a common phenomenon in critical illness myopathy possibly secondary to disordered sodium channel fast inactivation and associated with loss of myosin staining. Direct muscle stimulation techniques, measuring evoked response amplitudes and comparison of nerve and muscle stimulated responses, are recognized methods of demonstrating this phenomenon. Other measures studied in this population include increased compound motor action potential duration, motor unit number estimates and mean step area of individual motor unit potentials during motor unit number estimate studies. An electrophysiologic approach to the study of patients with critical illness associated weakness is proposed.

Objective and methods—Inclusion body myositis is said to have both myopathic and neurogenic features on electrophysiological tests. Twenty one studies from 20 patients with biopsy defined inclusion body myosis, 13 of whom had quantitative electromyography (qEMG), were reviewed to determine if this technique added diagnostic specificity (one patient had both needle EMG and a later study with qEMG before muscle biopsy). Results—Excessive numbers of polyphasic motor unit potentials (MUPs) (>12% per muscle) were seen in 11 of the 13 patients. In 10 of 13 patients, mean MUP duration was abnormally reduced (26% to 48%). In three patients, mean MUP duration was abnormally reduced only after polyphasic MUPs were excluded.In all 13 patients,the simple MUP duration was reduced. Myopathy was unequivocally diagnosed in all 13 studies that included qEMG; of the remaining eight patients, the conclusions of the electrophysiological studies without qEMG was myopathy (one), neurogenic (four) or non-diagnostic (three). Conclusions—There is no evidence of a neurogenic component in inclusion body myosis if qEMG is used. Quantitative EMG is often necessary to make an electrophysiological diagnosis of a myogenic disorder in patients with inclusion body myosis. (J Neurol Neurosurg Psychiatry 1997;63:776‐779)

Some have suggested that nonfamilial motor neuron disease (MND) may be autoimmune, and the neurological disorder may benefit from immunotherapy. There have been reports of over 30 cases of lymphoproliferative disease (lymphoma, multiple myeloma, Waldenstrom's macroglobulinemia) with MND, and these patients might he offered immunosuppressive therapy. Bone marrow examination might increase the sensitivity of the diagnostic workup for lymphoma and other lymphoproliferative disorders. We examined the bone marrow in our first evaluation of 161 patients with MND seen at Columbia-Presbyterian Medical Center during 1991-1994. Four of 161 patients (2.5%) had lymphoproliferative disease in the marrow; only 1 of these had a monoclonal paraprotein. Routine bone marrow examination of patients with MND increases the diagnostic yield of lymphoproliferative diseases. The frequency of these bone marrow abnormalities in comparison with a group of age-matched control subjects should be studied further.

We compared the binding of human antibodies from patients with neuropathy to the myelin-associated glycoprotein (MAG), to its cross-reactive glycolipid sulfoglucuronyl paragloboside (SGPG), and to sections of peripheral nerve. Titers were correlated with the clinical presentation and results of electrophysiological and pathological studies. Most patients had a predominantly sensory or sensorimotor demyelinating neuropathy and highly elevated antibodies to both MAG and SGPG, but 2 had highly elevated antibodies to MAG alone, and 1 to SGPG alone. Two patients had predominantly motor neuropathy and highly elevated antibodies to SGPG which reacted with MAG by Western blot but not by enzyme-linked immunosorbent assay. One patient had amyotrophic lateral sclerosis and antibodies to SGPG but not to MAG. These studies indicate that the neuropathic syndrome associated with anti-MAG or -SGPG antibodies are more heterogeneous than previously suspected, and that although most of the antibodies react with both MAG and SGPG, some may react with MAG or SGPG alone.

We measured residual latency (RL), motor conduction velocity (MCV), and terminal latency index (TLI) in 15 patients with neuropathy and anti-MAG or SGPG antibodies and compared these to values obtained in 103 patients with other types of polyneuropathy (PN) and to 57 normal subjects. Ten patients had anti-MAG antibody titers of 25,600 or higher, and 5 had titers between 800 and 12,600. Patients with the highest titers had longer RL, slower MCV and shorter TLI than those with lower titers, acute or chronic inflammatory demyelinating PN, hereditary neuropathy, and metabolic or axonal neuropathy. In contrast F-wave latencies did not contribute to the differentiation between the groups of demyelinating neuropathies. RL and TLI correlated best with anti-MAG antibody titers, whereas there was a poor correlation with anti-SGPG titers suggesting that MAG more than SGPG may be the antigen in PN, and that the distal nerves are affected more than their proximal segments. The RL rather than TLI turned out to be the best variable to classify the demyelinating type of anti-MAG neuropathy. Sural nerve biopsy in 5 of the patients with the highest titer of anti-MAG antibodies showed deposits of IgM and C3 on the myelin sheaths, pronounced demyelination and widening of the myelin lamellae. In 4 of the patients with lower titers demyelination was absent or less pronounced.

Summary We describe a method of power spectrum analysis of all-night sleep EEGs in 20 normal subjects aged 18–43 years. The analysis calculates the energy of the whole sleep period, the various frequency bands, and selected sleep stages automatically. The numerical value of the energies was directly comparable between subjects, presented in numbers (μV2s) and displayed as a color density spectral array with fixed power values for each color. A significant relationship between age and power spectra was found, in that total energy/minute was higher in younger subjects than in older. The energy in delta sleep/minute also showed an inverse relationship with age.

SUMMARY objective We wished, by means of power spectrum EEC analysis, to examine REM and delta sleep energy in adults with high and normal plasma growth hormone (GH) concentration design After a 3-day regular sleep/wake schedule, all-night polysomnographic recordings were performed on two consecutive nights before as well as one year after treatment for acromegaly by adenomectomy. The sleep energy was calculated by power spectrum analysis patients We studied nine patients aged 24–45 years with untreated active acromegaly. The same patients were reexamined one year after adenomectomy when plasma GH concentrations were normal measurements The acromegaly was verified biochemically by measuring basal plasma GH concentration and plasma GH during hyperglycaemia as well as Insulin-like growth factor. Cerebral computer tomography (CT) and magnetic resonance (MR) scans revealed an intrasellar adenoma in all patients. The resulting sleep records obtained before and after adenomectomy were subjected to power spectrum analysis and a manually blinded sleep scoring results The power spectrum analysis showed that when circulating GH was elevated the energy In the REM sleep per minute was significantly higher compared to the REM energy/mm after surgery when GH concentration had normalized. A similar relation was found for delta sleep (stage 3 + 4, deep sleep) where the energy per minute was higher before treatment than after conclusions The study demonstrates that plasma GH concentration was correlated to sleep energy. During high GH concentration the REM and delta sleep energy were high and normalization of plasma GH was followed by normalization of REM and delta sleep energy per time unlt

To examine the association between pressure pain sensitivity (PPS) at sternum and various well established physiological stress measures among opera singers during a performance as a measure for transitional stress, and resting values in out-clinic patients as a measure for persistent stress.Changes in PPS on the index finger and sternum, middle blood pressure (MAP), heart rate (HR), pressure-rate-product (PRP) and salivary cortisol (SCO) were recorded in 26 opera solo singers during a performance. Resting PPS, HR, MAP, PRP and presence of a noxious withdrawal reflex (NWR) were recorded in 181 out-clinic patients.During opera performance, the PPS on sternum changed concomitantly with MAP (correlation coefficient (r) r=0.42, p0.005), HR (r=0.55, p0.001), PRP (r=0.54, p0.001) and SCO (r=0.26, p=0.066). During rest, a significant correlation was found between PPS on sternum and HR, PRP and presence of noxious withdrawal reflex (all p0.01).The PPS measurement at sternum was associated with well established physiological stress measures and may represent a simple, objective and reliable measure of physiological stress used by both non-professional and professionals.

Daytime somnolence and fatigue are frequently ignored symptoms in acromegaly. To examine whether sleep apnea or other abnormalities in the sleep structure is the underlying cause, 9 young patients with active untreated acromegaly for 2-7 years were studied with all night polysomnography. It revealed a decrease in REM sleep time in all the acromegalics compared to age- and sex-matched normal subjects (p less than 0.001) and also a reduction in delta sleep (p less than 0.05). None had obstructive sleep apnea. At reexamination 12-15 months posttreatment the daytime sleepiness had disappeared in all patients. REM sleep time increased in all patients (p less than 0.001) to normal level; delta sleep time increased moderately (p less than 0.05). Thus sleepiness in patients with high fasting level of growth hormone (GH) is not related to sleep apnea but more likely to a reduced amount of REM sleep time. By normalizing the GH concentration, REM sleep time became normal and the daytime sleepiness disappeared in all patients.

OBJECTIVES To determine the number of motor units (MUNEs) in the anterior tibial muscle of normal subjects for comparison with those of severely paretic or paralytic muscles of critically ill patients in intensive care units. RESULTS The mean MUNE for 24 normal subjects (194 +/- 5; mean +/- standard deviation) was similar to that of the 22 patients with critical illness (184 +/- 10). However, both the mean amplitude of the evoked compound muscle action potential (CMAP) and of the single motor unit action potential (S-MUAP) among patients were approximately one third of those in normal subjects. CONCLUSION Critically ill patients in this study demonstrated normal MUNEs with reduced CMAP and S-MUAP amplitudes in the setting of severe clinical weakness, suggestive of predominantly myopathic injury. MUNE may provide a valuable tool for distinguishing between neuropathy and myopathy in critically ill patients.

Symptomatic polyneuropathy in human immunodeficiency virus (HIV) infection was studied in ten men with acquired immunodeficiency syndrome (AIDS) and in ten men without the immune deficiency. In both groups of patients electrophysiological signs of polyneuropathy of the axonal type were present in the sural, median and peroneal nerves. The AIDS patients had a greater reduction of the mean (SD) sural nerve action potential, 3.1 (2.7) microV, than in patients without AIDS, 10.2 (6.1) microV (p less than 0.01) and greater slowing of peroneal nerve conduction velocity, 42.6 (1.4) m/s in AIDS patients versus 52.6 (3.3) m/s in patients without AIDS (p less than 0.0001). These findings indicate that in most HIV infected patients the severity but not the type of neuropathy depends on whether an immune deficient state has developed. Seven patients with symptomatic polyneuropathy were treated with azidothymidine (AZT) for an average of 10 months and compared with a group of five untreated patients with similar symptoms. No effect of AZT treatment on sural or median nerve amplitude or conduction velocity or on the vibratory or temperature thresholds was observed.

The latency and amplitude of the first negative peak of visual evoked potentials (VEP) were evaluated in 52 term infants, investigated within 48 h after birth. Sixteen were light-for-gestational-age (LGA), 16 were appropriate-for-gestational-age (AGA) and 20 were infants of diabetic mothers (IDM). The VEP latency was shorter in LGA infants compared to AGA infants, and it was closely related to the birth weight deviation. The VEP latency was inversely related to gestational age and positively related to head circumference. When corrected for gestational age and head circumference, the VEP latency was not significantly different between the subgroups, nor related to the birth weight deviation, ponderal index or skinfold thickness. Thus, it could be argued that the high conduction velocity in LGA infants is due to stress maturation or alternatively due to the smaller head circumference. The VEP amplitude was higher in LGA infants when compared with AGA infants, and inversely related to the birth weight deviation. No differences were found in VEP latency or VEP amplitude between IDM and AGA infants.

Axotomy of peripheral nerve triggers events that coordinate a limited inflammatory response to axonal degeneration and initiation of neurite outgrowth. Inflammatory and neurite outgrowth-promoting roles for the receptor for advanced glycation end products (RAGE) have been suggested, so we tested its role in peripheral nerve regeneration. Analysis of immunohistochemical localization of RAGE by confocal microscopy revealed that RAGE was expressed in axons and infiltrating mononuclear phagocytes upon unilateral sciatic nerve crush in mice. Administration of soluble RAGE, the extracellular ligand binding domain of RAGE, or blocking F(ab')2 fragments of antibodies raised to either RAGE or its ligands, S100/calgranulins or amphoterin, reduced functional recovery as assessed by motor and sensory nerve conduction velocities and sciatic functional index and reduced regeneration, as assessed by myelinated fiber density after acute crush of the sciatic nerve. In parallel, in mice subjected to RAGE blockade, decreased numbers of mononuclear phagocytes infiltrated the distal nerve segments after crush. These findings provide the first evidence of an innate function of the ligand/RAGE axis and suggest that RAGE plays an important role in regeneration of the peripheral nervous system.

Objective To describe the clinical and electrophysiologic features of patients with inclusion body myositis that was misinterpreted as motor neuron disease. Patients and Methods We retrospectively retrieved the medical records of 70 patients with a pathologic diagnosis of inclusion body myositis. From this group, we selected those who had been first diagnosed as having motor neuron disease or amyotrophic lateral sclerosis. We reviewed the clinical, electrophysiologic, laboratory, and morphologic studies. Results Nine (13%) of 70 patients with inclusion body myositis had been diagnosed as having motor neuron disease. Six of the 9 patients had asymmetric weakness; in 4 the distal arm muscles were affected. Eight patients had finger flexor weakness. Tendon reflexes were preserved in weak limbs in 6, hyperactive in 2, and absent in 1. Four patients had dysphagia. Fasciculation was seen in 2 patients. None had definite upper motor neuron signs or muscle cramps. Routine electromyographic studies showed fibrillation potentials and positive sharp waves in all 9. Fasciculation potentials were seen in 7 and long-duration polyphasic motor unit potentials were seen in 8. There was no evidence of a myogenic disorder in these 9 patients. Muscle biopsy was done because of slow progression or prominent weakness of the finger flexors and was diagnostic of inclusion body myositis. A quantitative electromyogram was myopathic in 4 of the 5 patients studied. Conclusions Inclusion body myositis may mimic motor neuron disease. Muscle biopsy and quantitative electromyographic analysis are indicated in patients with atypical motor neuron disease, especially those with slow progression or early and disproportionate weakness of the finger flexors.

Objective : Unexplained weakness in critically ill patients is recognized with increasing frequency. However, it is debated whether the condition is a peripheral neuropathy or a myopathy. Diagnostic difficulties can arise from multiple sources that are not generally a factor in other neuromuscular conditions. Conventional electrodiagnostic techniques may provide only non-specific data, clinical examination is often hampered, and muscle biopsy is not a practical screening tool. Method : To improve diagnostic yield, we studied 22 consecutive patients with critical illness associated weakness with additional electrodiagnostic techniques, including direct muscle stimulation, quantitative electromyography, and motor unit number estimation. Results : The applied techniques supported an underlying myopathy in all the patients examined. The diagnosis was confirmed by muscle biopsy in 9 patients. Additional lesser features of neuropathy were concomitantly present in one patient who also underwent sural nerve biopsy. Conclusions : The study suggests that myopathy is much more common than polyneuropathy in critical illness. Suspicion of this entity should be high in this setting even without exposure to corticosteroids or non-depolarizing blocking agents.

We performed quantitative immunohistochemical studies of sural nerve biopsy specimens from 20 patients to determine whether endoneurial and epineurial lymphocytic infiltration occurs in diabetic nerves. The diabetic nerves contained a mean of 129 CD3+ cells per tissue section compared to 19 cells in patients with chronic neuropathy matched for the histologic severity of disease, and 0–5 cells in normal control nerves. The T-cell infiltrates in the diabetic nerves were predominantly of the CD8+ cell type. Activated endoneurial lymphocytes expressed immunoreactive cytokines and major histocompatibility class II antigens. Microvasculitis was found in 12 (60%) patients. Infiltrative T cells may contribute to the pathogenesis of diabetic neuropathy through a variety of effector mechanisms. © 1996 John Wiley & Sons, Inc.

Fritz Buchthal was born in Witten, Germany, the son of merchant S. Buchthal and his wife Hedwig—both of Jewish descent from the Netherlands, who had emigrated to Nordrhein-Westphalen in Germany. By the time he was 11 years old, Buchthal began to show fascination with physics and biology—interests that would form his lifelong ambitions. In 1925, he started medical school at the University in Freiburg im Breisgau. A year later, he fled to California in protest of the rising of the “Deutsche Nationalismus.” His father did not support him financially while he was in California, but did offer him a return ticket to Germany. To support himself, he worked as a shoemaker’s aide and a college cleaning assistant at night. He also taught students at Stanford University how to write applications in German. In 1927, Buchthal passed the entrance examination to Stanford where he studied anatomy, genetics, biology, and physiology. Under the tutelage …

Immune mechanisms have been implicated in the pathogenesis of motor neuropathy with conduction blocks and of acute axonal neuropathy, and GM1 ganglioside has been identified as a potential target antigen. In these experiments, the B subunit of cholera toxin (CT-B), which binds to GM1, was used to target an antibody response to GM1 in peripheral nerve. CT-B was injected into the sciatic nerves of rats, in which anti-CT antibodies were previously induced by immunization, so that the circulating anti-CT-B antibodies bound to the CT-B-GM1 complex in the nerve. Electrophysiological studies revealed the presence of conduction block, and in pathological studies there was axonal degeneration with little demyelination. Control animals, in which keyhole limpet hemocyanin was substituted for CT, did not develop conduction block or axonal degeneration. These studies indicate that antibodies directed at GM1 sites in peripheral nerve could cause an axonal neuropathy with conduction block.

Article abstract-Antibodies to myelin-associated glycoprotein (MAG) are found in patients with both monoclonal gammopathy and sensorimotor peripheral neuropathy but almost never in patients with amyotrophic lateral sclerosis (ALS). Ninety percent of patients with anti-MAG activity also have antibodies to sulfated glucuronic acid paragloboside (SGPG). We studied a patient with autopsy-proven ALS who had high titers of anti-SGPG but normal anti-MAG--one more unexplained immunologic abnormality in ALS. NEUROLOGY 1995;45: 827-829

We studied the effect of acupuncture in 49 patients with angina pectoris with focus on its relationship to psycho-social factors and changes in skin temperature, pain thresholds, and pain tolerance thresholds. No significant influence from patient expectation, social stress (strain) or profiles of the Minnesota Multiphasic Personality Inventory (MMPI) was found (all p > 0.1). Acupuncture slightly increased exercise tolerance (median 7%), the difference in Systolic Blood Pressure-Heart Rate Product between rest and maximal exercise (delta PRP) (median 3%), and the time to onset of pain (median 10%); decreased nitroglycerin consumption (median 58%) and anginal attack rate (median 38%). Improvement in exercise tolerance was significantly correlated to an improvement in delta PRP (correlation coefficient = 0.7; p < 0.0001) but not to time of myocardial ischemia (correlation coefficient = 0.1; p = 0.1). Compared with 28 patients with a less pronounced anti-anginal effect, the 21 patients with a pronounced effect had a significant increase in local skin temperature, but had no significant change in distant skin temperature and pain thresholds. It is concluded that acupuncture, due to hemodynamic alterations, might have a specific effect on angina pectoris in addition to drug treatments.

We review clinical, neurophysiological, immunological, and experimental data concerning multifocal motor neuropathy (MMN), a newly recognized disorder that mimics MND. It is separated from MND by the presence of multifocal conduction block (CB) demonstrated electrophysiologically, and in some instances by the association of high titers of GM1 antibodies. The possible immunopathogenetic effect of GM1 antibodies is discussed. However, 70% of patients with MMNCB do not have elevated titers of GM1 antibodies, but may respond nevertheless to immunosuppressive treatment. Thus, so far unrecognized antibodies may react against some other epitopes in the paranodal region than those attacked by GM1 antibodies to cause CB.

We studied 169 patients with motor neuron disease. Seventeen showed abnormal amplitude reduction of the compound muscle action potential. Ten had focal loss of both amplitude and area across a specific segment (conduction block). Eight of the 10 had slowing of conduction across that segment. Nine were men and had prominent hand involvement. Six had probable or definite upper motor neuron signs. Five of the 10 showed immunologic abnormalities (elevated GM1 antibody titers or paraproteinemia), and eight had had symptoms for more than 4 years. Seven of the 17 patients showed loss of amplitude without corresponding loss of area and focal slowing of conduction (temporal dispersion). Five of the seven were men, five had prominent hand involvement, and five had definite or probable upper motor neuron signs. Two had immunologic abnormalities, and only one had had symptoms for longer than 4 years. Among 152 patients with no abnormality of conduction, 64% were men, hands were dominantly involved in 34%, upper motor neuron signs were definite or probable in 72%, and 3% had immunologic abnormalities. None had symptoms for more than 4 years. Because there were so many exceptions, we could not define a unique syndrome by criteria involving conduction block, GM1 antibodies, or lack of upper motor neuron signs. The clinical syndrome associated with multifocal conduction block seemed uniform, however, and patients with conduction block had slower progression if there were no upper motor neuron signs.

Antibodies to GM1 or Gal(beta 1-3)GalNAc are associated with motor or sensorimotor neuropathy and with motor neuron disease. To investigate the role of these antibodies in the neurological disorder, rabbits were immunized with GM1 or with Gal(beta 1-3)GalNAc-BSA, and studied serologically, electrophysiologically and pathologically. Development of antibodies to the immunizing antigens was associated with a fall in the ratio of the amplitudes of the compound muscle action potential evoked by proximal versus distal stimulation of the sciatic nerve. Pathological studies revealed mild axonal degeneration and immunoglobulin deposits at the nodes of Ranvier in peripheral nerve, resembling those reported in a patient with motor neuropathy, motor conduction block and anti-GM1 antibodies. These studies provide evidence that anti-GM1 or anti-Gal(beta 1-3)GalNAc antibodies cause conduction abnormalities and indicate that the antibodies may exert their effect, in part, by binding at the nodes of Ranvier in peripheral nerve.

We compared anti-GM1 IgM antibody titers in patients with various neurologic diseases and in normal subjects. We found increased titers in patients with lower motor neuron disease, sensorimotor neuropathy, or motor neuropathy with or without multifocal conduction block. In patients with other diseases, titers are similar to those in normal individuals, suggesting that anti-GM1 antibody levels are not increased nonspecifically after neural injury or inflammatory diseases. Anti-GM1 antibodies in many of the patients occur as monoclonal gammopathies, predominantly of lambda light-chain type, but the antibodies are sometimes polyclonal with normal or increased serum IgM concentrations. Most of the anti-GM1 antibodies appear to react with the Gal(beta 1-3)GalNAc epitope which is shared with asialo-GM1 and GD1b, but in some patients the antibodies are more specific for GM1 and associated with motor neuropathy. Patients with motor or sensorimotor peripheral neuropathy or lower motor neuron disease should be tested for anti-GM1 antibodies or anti-Gal(beta 1-3)GalNAc antibodies, as therapeutic reduction in antibody concentrations was reported to result in clinical improvement in some patients.

The clinical significance of myelopathy associated with HIV infection is poorly understood. Recently, a prospective electrophysiological follow-up study of spinal-evoked potentials in HIV-seropositive men without AIDS revealed a 32% prolongation of the latency from the gluteal crease to the 12th thoracic vertebra (T12) following tibial nerve stimulation at the ankle performed after an interval of 2 years. In AIDS patients this transmission delay did not increase further. Instead, the latency prolongation took place proximal to T12. We assume that myelopathy is an integral part of HIV infection that it is asymptomatic in the early disease phase, spreads from the lumbar part the spinal cord in a rostral direction and leads to the development of leg weakness and ataxia during the later stages of the disease.

Objective To describe a patient with multifocal motor neuropathy with conduction block who had annual clinical and physiological examinations for 18 years but declined treatment for personal reasons. Design Case report. Setting Collaboration between 2 academic tertiary care hospitals. Patient One patient with multifocal motor neuropathy with conduction block. Results At age 44 years, there was weakness and wasting of the left biceps with conduction block in the left musculocutaneous and right ulnar nerves. The left median nerve was inexcitable. The right median, ulnar, and left peroneal nerves developed axonal change (loss of distal compound muscle action potential amplitude) at years 5, 12, and 13. By 2005, new weakness had appeared in 20 muscles (16 in the arms); he could not use a keyboard, button buttons, or write his name. Nerves that initially showed conduction block became inexcitable over the course of the illness. Conclusions Multifocal motor neuropathy with conduction block is a disease that may be “only” slowly progressive but is not always benign. Nerves showing conduction block may develop axonal change. Better markers for this disease are needed.

Reply from the Authors: We thank Dr. Steck et al. for discussing our paper. [1] We agree with them in two essentials: (1) Almost all patients with high titers of antibodies to SGPG also have antibodies to MAG; (2) Almost all patients with high titers of anti-MAG and anti-SGPG have a sensorimotor peripheral neuropathy. [2] They cite as a patient who had a ``motor neuropathy'' (not motor neuron disease) who had two siblings with full-blown ALS. Was that merely a coincidence? Were there really two entirely different and unrelated diseases of the lower motor neuron in the same sibship? Or is that family another reminder that peripheral nerves may be affected in some patients with motor neuron …

We reviewed the clinical and electrophysiologic features of 36 patients with increased titers of IgM anti-GM1 antibodies. Mildly elevated titers of up to 3,200 were not associated with any particular clinical syndrome or disease. Clinically, 14 of 16 patients with highly elevated titers of 6,400 or higher had progressive weakness with lower motor neuron signs; six had active tendon reflexes and eight had absent reflexes, but none had definite upper motor neuron signs. Electrophysiologic studies showed spontaneous activity in all 14 patients, one or more motor conduction blocks in nine, slowed motor conductions in one, and normal conductions in four patients. None had abnormal sensory conductions. These patients presented with a syndrome that has features of, but is distinct from, both motor neuron disease and demyelinating neuropathy.

From 1984 to 1988, 11 of 120 patients (9%) with motor neuron disease (MND) had paraproteins detected by serum immunofixation electrophoresis (IFE), compared with 4 (3%) by cellulose acetate gels: 1 patient had progressive spinal muscular atrophy, 5 patients had amyotrophic lateral sclerosis (ALS), and 5 patients had ALS with probable upper motor neuron signs. Four of 5 patients (80%) with cerebrospinal fluid (CSF) protein content above 75 mg/dl had paraproteins, as did 6 of 30 with values above 50 mg/dl. Four of 14 patients with cerebrospinal oligoclonal bands (OCB) also had paraproteins. Two patients with ALS, CSF protein content above 75 mg/dl, and paraproteinemia had lymphoma. We conclude the following about patients with MND: high CSF protein content (especially above 75 mg/dl) or CSF OCB makes paraproteinemia more likely; some of these patients may have lymphoma; there is an inordinately high occurrence of paraproteinemia in MND; and IFE on agarose is more sensitive than electrophoresis on cellulose acetate in detecting paraproteins. Syndromes of paraproteinemia and high CSF protein are not restricted to the lower motor neuron but qualify as “ALS” with coexisting upper motor neuron signs.

Pattern reversal visual evoked potentials in 13 patients with pseudotumor cerebri were significantly delayed (99 +/- 7.3 ms [mean +/- SD]) compared with the findings in 20 normal subjects (94 +/- 2.7 ms), although only four patients had latencies outside the normal range. There was, however, a significant correlation between the intracranial pressure and the latency of visual evoked potentials. After medical treatment of the intracranial hypertension, visual evoked potential latencies decreased in patients who recovered and in whom the papilledema disappeared. In one patient with progressive visual failure, the visual evoked potentials were abnormal before disturbances of visual fields and visual acuity were evident. Repeated examinations of visual evoked potentials might be of value in patients with pseudotumor cerebri to ensure neurosurgical intervention in due time to prevent visual loss in patients with impending optic nerve atrophy.

The effect of anticholinesterase drugs on the clinical and electrophysiological features in a canine congenital myasthenic syndrome is compared with findings in acquired myasthenia gravis in dogs. Anticholinesterase treatment had no effect on muscle weakness or electrophysiological parameters in the congenital myasthenic syndrome in contrast to its effect on clinical signs and electrophysiological parameters in acquired myasthenia gravis. The lack of effect of anticholinesterase in congenital myasthenia suggests a presynaptic defect as the aetiological factor. No antibodies to acetylcholine receptors were found in the Danish dog breed Gammel Dansk Hønsehund with the myasthenic syndrome. This classifies the disease in the group of canine and human congenital myasthenic diseases.

Two estimations of global cerebral blood flow (CBF) using 133-Xenon clearance were done with an interval of about one hour in 16 mechanically ventilated, newborn infants, of less than 33 weeks gestational age. In eight infants CBF was estimated just before a change in ventilator settings, and again when the PaCO2 was stable. In the remaining eight infants small spontaneous changes in PaCO2 occurred. The CBF-CO2 reactivity was similar in the two groups (+67%/kPa (95% confidence interval 13-146) and 52%/kPa (24-86)) and considerably higher than the CBF-CO2 reactivity estimated from the interindividual variation of flow and PaCO2 (+19%/kPa (4-36)). There were no significant relations between CBF and arterial blood pressure. Flash evoked potentials (VEP) were recorded during the 133-Xenon clearances in 8 of the infants. VEP showed no relation to changes in CBF, even when the blood flow rose from the lowest levels. CBF and VEP were obtained once in 9 other infants. Among the 17 infants, the latency of the first negative wave of the VEP was not related to the CBF level. Mean CBF in the 25 infants was 12.3 ml/100 g/min (range 4.3 to 18.9), mean PaCO2 was 4.2 kPa (range 2.3 to 6.4). Thus, CBF-CO2 reactivity appeared to be normal in these clinically stable, mechanically ventilated, preterm infants, suggesting that their low cerebral blood flow was well regulated. The absence of a relation of CBF with VEP suggested that cerebral blood flow was not critically decreased.

In four patients with facial palsy following block dissection of the neck and total parotidectomy for malignant tumor, there was spontaneous recovery of facial motion ten months to 31/2 years later. Muscle twitching occurred around the corner of the mouth and nose on the involved side during masticatory action. The clinical findings were confirmed by electromyography before and after local anesthesia of the unaffected facial nerve. When stimulating the masticator nerve, responses were evoked in the orbicularis oris and triangularis muscles on the affected side, but not when stimulating the facial nerve. The findings suggest that reinnervation of facial muscles is due to misdirection of regenerating axons from a masticator nerve injured at the time of operation into the nearby facial muscles.

In 116 diabetic eyes scheduled for vitreous surgery, the visual evoked potential (VEP) after flash stimulation was recorded prior to surgery. Latencies of the flash evoked potentials show a distribution suggestive of a Gaussian curve with an abnormal extension. Dividing the material into two groups based on a latency shorter or longer than 100 milliseconds revealed a highly significant difference in the visual improvement following surgery between patients with a short and patients with a long latency (P less than 0.001). With a latency longer than 100 millisec. most patients showed no visual change after operation, and among the few who did the change, consisted more often in visual reduction than improvement. Additional investigations in the study reveal that it is likely that the prolonged latency of the flash VEP is due to pathology of the retina or visual pathways.

In the years 1977 to 1984, 10 of 206 patients (4.8%) with motor neuron disease (MND) had M proteins; 4 had IgM and 6 had IgG. Among 100 control patients with other neurologic diseases, only 1 had an M protein. We later added six cases of MND and M proteins, as well as three with polyclonal IgM elevations and two with Bence-Jones proteins. Including other reports, there are now 37 known cases of MND with monoclonal and 5 with polyclonal gammopathy. There is evidence that plasma cell dyscrasia is often undetected; the actual incidence of serum immunoglobulin abnormality in patients with MND may be greater than our figure.

A 76-year-old female with ocular ethambutol toxicity prompted two investigations. Firstly, she was followed electrophysiologically, with multichannel recorded pattern reversal visual evoked potential techniques using full-field, half-field, central-field and peripheral field stimulation, plus flash VEP and ERG. The examinations performed 2, 5 and 7 months after ethambutol withdrawal indicated damage to the papillomacular bundle, while a late follow-up after recovery showed potentials of near normal configuration. Secondly an epidemiological survey was attempted based on the 37 ethambutol toxicity cases registered to the Danish Board on Adverse Reactions 1972-81, making up 1% of those receiving antituberculous therapy. They showed a significant preponderance of elderly (24/37 greater than 65 years) and of females (29/37). There was only one foreigner in the series. A detailed analysis of visual function in a subsample of 22 cases (those registered 1977-81) showed that visual impairment lasted several months, and that usually recovery was not complete. Using the visual demands for driver's license as criterium, 20 fulfilled the demands prior to therapy, but only 12 after recovery.

The visual and somatosensory evoked potentials were delayed in two cases of the adult form of metachromatic leukodystrophy. Brainstem auditory evoked potentials were normal. The conduction velocity along peripheral nerves was 50% slowed in one case and near normal in the other. The findings are compatible with demyelination in the central and peripheral nervous systems. The diagnosis of metachromatic leukodystrophy should be considered in cases of early dementia, with or without psychosis or other neurologic deficits, in which evoked potentials are delayed and peripheral nerve conduction is slowed.

Delay of visual evoked potential (VEP) latencies can be an early indicator of compressive lesions of the visual pathways (Halliday et al. 1976). The purpose of the present study was to examine whether ventricular enlargement or increased intracranial pressure causes changes in VEP in patients with hydrocephalus or intracranial hypertension.

To determine whether or not the electrophysiological status of the eye can give information as to the result of vitreous surgery, the visual evoked potential to flash stimulation was measured prior to vitreous surgery. Seventy-four eyes were submitted to surgery. Latencies of flash evoked potentials showed a distribution suggestive of a Gaussian curve with an abnormal extension. Dividing the material into 2 groups based on a latency longer or shorter than 100 millisec revealed a highly significant difference in visual improvement after surgery between patients with long latency and patients with short latency (P less than 0.001). With a latency longer than 100 millisec the patient has an almost equal chance of visual improvement or visual reduction by surgery. The frequency of operative complications was twice as high in patients with latency longer than 100 millisec compared to patients with a latency shorter than 100 millisec.