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Background: The place of health-related quality of life (HRQoL) instruments in clinical research trials and clinical practice as compared to more traditional clinical outcome measures such as headache intensity and frequency is unclear., Objectives: To review the current status of HRQoL measurement in migraine., Methods: A literature search was done for HRQoL and migraine. Selected articles dealing with migraine and commonly used HRQoL instruments and HRQoL measures used in recent clinical trials were reviewed., Results: Several general and migraine specific HRQoL instruments can detect changes over time in response to at least major changes in migraine therapy. Both also show a correlation with clinical headache features. However, their sensitivity to detect clinically significant changes over time is not clear., Conclusion: The SF-36, a general HRQoL measure and several migraine-specific HRQoL instruments are useful endpoints for migraine clinical trials. Their role in clinical practice is yet to be established.

Much has been added to our knowledge of effective physician-patient communication by the research of the past two decades. Good communication skills are especially important for the clinician dealing with a migraine patient, as neither laboratory tests nor diagnostic physical findings are available to assist the physician in diagnosis and treatment. It is important for clinicians to understand that effective communication skills can be taught and learned and that, once mastered, they have the potential to improve patient outcomes.

Objective: To compare sumatriptan responders and nonresponders in a migraine population with regard to a number of clinical, psychiatric and psychologic features., Methods: Patients were drawn from a referral headache clinic population, and classified as responders or nonresponders. Clinical features were assessed by a written questionnaire. The lifetime prevalence of several psychiatric disorders was determined by the National Institute of Mental Health diagnostic interview schedule and personality factors were measured by the 16 Personality Factors (16PF) Questionnaire., Results: Nonresponders indicated less influence on their migraine by menstrual factors, had a higher lifetime prevalence of generalized anxiety, and showed 16PF scores indicating greater shyness, self-sufficiency and perfectionism. Nonresponders were also more imaginative and less socially outgoing., Conclusion: Although they must be interpreted with caution due to small sample size and the multiple comparisons made, our results indicate that there may be differences between sumatriptan responders and nonresponders with regard to a number of clinical, psychiatric and psychologic factors. These results suggest that biological differences exist between the two patient groups which likely account for both the differences in their responses to sumatriptan and in the clinical features noted above.

Monocytes and macrophages are activated by various environmental challenges, including microorganisms, radiation, and pollutants. These cells release cytokines, such as interleukin (IL)-1 beta, that mediate physiological adaptations to stress. This study sought to define further the role of IL-1 beta in general adaptation to environmental stress by testing the hypothesis that high altitude (20,000 ft, 6,096 m) would stimulate IL-1 beta secretion from isolated human blood mononuclear cells. Cells from six young men (aged 22--26 yr) were divided into separate cultures incubated in either standard ambient conditions or in one of three test conditions, hypobaric hypoxia (simulating 20,000 ft), hypobaric normoxia (20,000 ft, O(2) supplemented), and normobaric hypoxia (10% O(2)). This design allowed differentiation between pressure-related vs. oxygen-related effects. Each subject made multiple blood donations in order that cells from all subjects were tested in all conditions. Contrary to the hypothesis, IL-1 beta secretion was not induced at simulated altitude in basal cell cultures. In lipopolysaccharide-stimulated cell cultures, exposure to altitude inhibited IL-1 beta secretion by approximately 40%, and the inhibition was due to the change in pressure (P = 0.039) rather than the change in oxygen. Secretion of other factors (IL-1 receptor antagonist and soluble IL-1 receptor type II) was not inhibited. Although these results are in opposition to the original hypothesis, they provide insight regarding adaptations necessary for hematopoiesis in response to high altitude and also provide a cellular rationale for the mountain sanatoriums of the 19th and early 20th centuries.

Objectives: To investigate whether opiate overuse might cause chronic daily headache in those with migraine, we studied patients who were taking codeine (or other opiates) for control of bowel motility after colectomy for ulcerative colitis., Background: Analgesic overuse is considered by many to be one factor which can result in the transformation of migraine into a chronic daily headache pattern. Most of the evidence for this comes from patients with migraine who are taking increasing amounts of analgesia for headache. Many of these patients revert to an intermittent migraine pattern once the analgesics are stopped., Methods: Women who were 1 year postcolectomy for ulcerative colitis were identified in several colorectal surgery practices in Calgary. They were sent a questionnaire designed to determine if they had a history of migraine prior to surgery, if they currently had chronic daily headache, what medications they were taking to control bowel motility, and what medications they were taking for headache., Results: Twenty-eight patients who met our inclusion criteria returned completed questionnaires. Eight of these exceeded the recommended limits for opiate use in patients with headache. Eight patients met diagnostic criteria for migraine. Two patients had chronic daily headache starting after surgery. Both used daily opiates beginning after their surgery, and both had a history of migraine. The other six patients who used opiates daily did not have a history of migraine and did not have chronic daily headache. All patients with migraine who used daily opiates to control bowel motility following surgery developed chronic daily headache after surgery., Conclusions: Patients with migraine who use daily opiates for any reason are at high risk of developing transformed migraine with chronic daily headache. This risk appears much lower in patients without a history of migraine who use opiates for nonpain indications.

The triptans represent a major advance in migraine therapy but their cost per dose greatly exceeds that of many older treatments. There is evidence that for a significant proportion of migraine patients these new drugs can show a positive cost benefit and also improve quality of life. Cost benefit would be expected to be greatest in patients with more severe migraine attacks.

Prophylactic drug therapy is a major component of overall migraine management. However, because we do not know how currently used prophylactic drugs exert their beneficial effects in migraine, their use is based primarily on clinical trials. In general, prophylactic drugs are indicated when patients have three or more attacks a month and symptomatic medication use alone is not satisfactory. The choice of drug must be individualized, and is influenced by contraindications, potential side effects, the need to treat associated symptoms like tension-type headache and insomnia, and drug cost. Whether an individual patient will respond to a given drug cannot be predicted, but there are varying degrees of scientific evidence supporting the use of each prophylactic drug in migraine. This evidence is best for metoprolol, divalproex, amitriptyline, atenolol, flunarizine and naproxen. Based on placebo-controlled crossover studies, it would appear that at least some prophylactic drugs exert the greater part of their prophylactic effects very quickly, and that these also disappear very quickly once the drug is stopped. This may not apply to all prophylactic drugs and more research is needed. More well designed clinical trials are needed to guide our use of migraine prophylactic drugs. Although clinical experience is useful, placebo responses and variations in the migraine tendency over time can make interpretation of this experience difficult. Major advances will likely only occur once the pathogenesis of migraine and the mode of action of the prophylactic drugs is better understood.

This multicentre, randomized, double-blind, placebo-controlled, parallel group dose-ranging study compared the efficacy and tolerability of four doses of sumatriptan nasal spray (2.5, 5, 10 and 20 mg) with a placebo, in the acute treatment of a single migraine attack. In total, 544 patients received the study medication as a single spray in one nostril, to treat a single migraine attack in the clinic. Efficacy assessments included the measurement of headache severity, clinical disability, and the presence/absence of associated symptoms. The incidence of headache recurrence was also assessed. The three highest doses of sumatriptan (5 mg 49%, 10 mg 46%, 20 mg 64%) were significantly better than the placebo (25%) at providing headache relief (moderate or severe headache improving to mild or none) 120 min after treatment (P

Objective: To study the clinical features and treatment given to episodic cluster headache patients in the Calgary region., Patients: Fifty-one (51) patients who responded to a media campaign, had previously been diagnosed by their family physicians, and who met International Headache Society (IHS) criteria for episodic cluster headache, formed the population for this study., Methods: The media campaign consisted of newspaper advertisements and radio publicity including physician interviews and talk shows. Patients were required to complete by 200-item questionnaire detailing clinical features and treatment of their cluster headache syndrome. Each patient was also interviewed by our research nurse for clarification and proper completion of questionnaire., Results: Fifty-one percent (51%) of our patients had short headache attacks lasting one hour or less. Almost one-half (45%) had three or four attacks per 24 hour period. Eighty-six percent (86%) had been referred to a neurologist. Sixty-nine percent (69%) had never used oxygen, but of those who had, one-half were still using it. Sumatriptan by injection had been tried by 26% of patients and of these, 93% considered it effective. Subcutaneous dihydroergotamine had been tried by 8%. For prophylaxis, 41% had tried methysergide, 31% prednisone, and 4% verapamil. Many patients had been prescribed migraine prophylactic drugs which are ineffective for cluster headache, and some had also undergone dental procedures or nasal and sinus surgeries., Conclusions: Many cluster headache patients had not, to their knowledge, been prescribed or used the best symptomatic and prophylactic treatments for cluster headache. This should be addressed through educational programs and through making up-to-date information on the treatment of cluster headache readily available to physicians and patients.

Dual-site murine antibody-based immunoassays are commonly used in clinical laboratories to quantitate the MB isoenzyme of creatine kinase (CK-MB). Because the serum level of CK-MB is a relatively specific and sensitive indicator of myocardial ischemic damage, accurate quantitation is essential for a correct diagnosis. Heterophile antibodies (eg, human anti-murine antibodies) can interfere with these assays, however, and produce erroneous results. A subpopulation of 19 surgical patients with colorectal carcinoma who had received injections of an 125I-labeled murine monoclonal antibody directed against a tumor-associated glycoprotein was studied. Serum specimens from eight patients (42%) showed a marked increase in the level of CK-MB and normal total CK concentrations. The increased concentrations of CK-MB, which were attributed to interference by human antimurine antibodies, were substantially reduced in these specimens after a heterophile blocking reagent was added. However, this reagent did not significantly alter the serum level of CK-MB in patients who had clinical evidence of acute myocardial ischemia.

Our objective was to determine if Chinook weather conditions in the Calgary area increase the probability of headache attacks in migraine sufferers. Environment Canada meteorologic summaries for January through June 1992 were analyzed and times of Chinook wind onset identified. Chinook weather conditions were defined as calendar days when Chinook winds were present and the calendar day immediately preceding Chinook wind onset. The diaries of 13 migraine patients were analyzed, and times of headache onset classified according to the existing weather conditions. The probability of migraine headache onset was greater on days with Chinook weather (17.26%) than on non-Chinook days (14.65%) (P = 0.042). Older patients appeared more weather sensitive than younger patients. For patients over age 50, the probability of migraine occurrence on Chinook weather days was much greater than on non-Chinook days (P = 0.007). Chinook weather conditions increase the probability of migraine headache occurrence. Older migraine sufferers appear particularly vulnerable to this effect.

Initiation of oral contraceptive (OC) therapy in migraine may worsen pre-existing migraine or change the pattern of the individual migraine attacks. Many women experience no change in their migraine and a few show improvement. Evidence is accumulating that migraine increases ischemic stroke risk and that this risk is higher in migraine with aura than in migraine without aura. OCs also increase stroke risk, and the increased stroke risk attributable to each of migraine and OC therapy may be additive. The risk of ischemic stroke in young women is very low and likely remains acceptably low in young women with migraine without aura and in those with a simple migraine aura when OCs are prescribed. However, the presence of a complex or prolonged migraine aura, or of additional stroke risk factors such as increased age, smoking, and hypertension likely increases the ischemic stroke risk further in patients with migraine when OCs are prescribed. Whether OCs can be prescribed safely for the patient with migraine depends upon many factors including patient age, type of migraine, and the presence or absence of other stroke risk factors.

Experiments were performed to compare the ability of normal subjects and patients with spinal spasticity to suppress antagonist H reflexes during isometric ankle contractions. Soleus H reflex suppression was examined during tonic pretibial muscle contractions in which the torque levels were constant and during dynamic pretibial muscle contractions in which the torque followed a predetermined ramp. As well, subjects were instructed to alternately contract ankle plantarflexors and dorsiflexors at various frequencies to examine patterns of EMG activity during rhythmically alternating isometric contractions in antagonist muscles. Patients with incomplete spinal cord injury demonstrated reduced ability to suppress soleus H reflexes during pretibial muscle contraction. At slow speeds of alternating contraction, spinal cord injured patients retained the ability to perform alternating isometric pretibial/soleus muscle contractions. The patients demonstrated abnormal coactivation in soleus muscle during faster alternating isometric ankle muscle contractions. Furthermore, the patients who demonstrated the greatest impairment in natural reciprocal inhibition, also displayed the largest amount of coactivation. In general, the results would suggest that impairment of natural reciprocal inhibition is correlated with an increase in the amount of antagonist muscle coactivation seen during alternating isometric muscle contractions.

Purpose: To assess bronchiectasis depicted with computed tomography (CT) in patients with alpha 1-antitrypsin deficiency and to examine associated clinical correlates., Materials and Methods: CT scans in 14 patients with alpha 1-antitrypsin deficiency were evaluated by two thoracic radiologists for the presence and extent of bronchiectasis and emphysema. The findings were correlated with numeric infection scores on the basis of symptoms of sputum production and respiratory infection and with a history of conditions that may predispose to development of bronchiectasis., Results: Six (43%) of 14 patients had CT evidence of bronchiectasis. Patients with bronchiectasis had significantly higher infection scores than did patients without bronchiectasis (P < .005). Two patients had diffuse cystic bronchiectasis, and neither reported a history of illness that may have predisposed them to this condition., Conclusion: Bronchiectasis may be more common in patients with alpha 1-antitrypsin deficiency than has been previously recognized. The diagnosis of alpha 1-antitrypsin deficiency should be considered in patients with emphysema and diffuse cystic bronchiectasis.

The effectiveness of dihydroergotamine administered by home subcutaneous injection by the patient or family for severe headache attacks was assessed retrospectively in 51 patients. Average follow-up was 21 weeks. Twenty-one patients had intermittent migraine attacks, 27 had transformed migraine with chronic daily headache, and 3 had chronic tension-type headache. Of the 51 patients taught home injection, 35% had an excellent overall response, 18% had a good response, 12% had a poor response but continued to use dihydroergotamine, and 35% had discontinued dihydroergotamine use. Side effects were the main reason for stopping dihydroergotamine. These included nausea or vomiting or both, limb pain or numbness or both, chest or throat tightness or both, and soreness at the injection site. Thirty-three patients (65%) continued to use dihydroergotamine at the end of the follow-up period. In patients who previously required injections from medical personnel for headache crises and in whom home injection of dihydroergotamine was effective, a dramatic reduction occurred in hospital emergency room and physician office utilization. Dihydroergotamine use by home injection can be an effective treatment for a significant proportion of patients with severe migraine including patients with transformed migraine and medication overuse.

Background: Severe spasticity unresponsive to oral drugs may respond satisfactorily to baclofen delivered intrathecally., Methods: Intrathecal baclofen (IB) therapy delivered by means of implanted infusion pumps was used for nine patients with severe spasticity. Six patients had multiple sclerosis, two cervical spinal cord injury, and one head injury. All were non-ambulatory., Results: Patients showed improvement in many areas, including ability to transfer, seating, pain control, personal care, and liability to skin breakdown. Before IB therapy, only three of the nine patients were able to live at home in the community and six were institutionalized. At the end of our follow-up period, only one patient remained institutionalized, three lived in group homes and five lived at home in the community. In the year preceding pump implantation, the nine patients spent a total of 755 days in acute care hospitals. In the year following onset of IB therapy, they spent only 259 days in hospital., Conclusions: IB therapy can improve patient quality of life and can be cost-effective in carefully selected patients with severe spasticity and disability. The drug delivery catheter is that part of the therapeutic system most vulnerable to failure. Because of the varied expertise required to manage these patients effectively, and the potential for a variety of complications, it is essential that an IB program is supported by a well-organized multi-disciplinary medical team.

Background: Some patients with reflex sympathetic dystrophy (RD) develop intractable symptoms unresponsive to conventional therapy. Recently, intrathecal morphine therapy has been used with some success in such patients., Methods: The clinical course of two patients with intractable reflex sympathetic dystrophy (RSD) is described. Both patients developed intractable leg pain, swelling and autonomic changes after a leg injury. Numerous medical treatments and surgical sympathectomies failed to provide long term relief., Results: Relatively satisfactory symptom control was achieved only with the use of long term intrathecal morphine therapy delivered by subcutaneously implanted infusion pumps. Exacerbations of the RSD continued to occur, at times in association with further leg trauma, but these could be controlled by a temporary escalation of the intrathecal morphine dose. Complications of morphine therapy were relatively minor. A red rash appearing over the pump site was the first sign that a drug catheter break had occurred, necessitating surgical catheter revision., Conclusion: Long term intrathecal morphine therapy is a useful treatment option for patients with intractable severe RSD who have failed other therapies and remain markedly disabled.

The present study was designed with two intentions; Are the effects of angular velocity detectable in the cardiovascular responses during the hyper-G? Another is object to examine how the otolith signal could modify the cardiovascular responses provoked by the exposure to the hyper-G. NASA/KC-135 hyper-gravity flight was used to generate high gravito-inertial forces to exclude a possible effect of angular velocity. Six healthy subjects was indicated to make dorsal flexion of the neck to reduce the otolith input. An exposure to +l.8Gz stress resulted in a remarkable increase of systolic and diastolic blood pressure, thereby pulse pressure became a little bit narrower. R-R interval revealed a tachycardia during the hyper-G except one subject. The present experiment bore the similar cardiovascular responses as those observed in the previous studies with a short rotating radius, suggesting that almost no effect of angular velocity acts on their responses. A weaker otolith input could possibly work on them. However a systematical observation can not recognize among the subjects for the vestibular effect on the cardiovascular responses. This fact of vestibular qualification leads us to speculate that it would depend on the subjects or other factors.

Soleus H-reflexes were recorded in 10 normal subjects and seven patients with spasticity caused by incomplete spinal cord injury while they pedalled on a stationary bicycle which had been modified to trigger electrical stimuli to the tibial nerve at eight precise points in the pedal cycle. Stimulus strength was adjusted to yield M-waves of constant amplitude at each pedal position. During active pedalling, all normal subjects showed modulation of the H-reflex with the amplitude being increased during the downstroke portion of the pedal cycle and the reflex suppressed or absent during the upstroke. This modulation was not present during passive pedalling, with the experimenter cranking the pedals by hand, or when the pedals were locked at each of the eight positions. In five of the seven patients with spasticity, there was reduced or absent modulation of the H-reflex during active pedalling and the reflex remained large during pedal upstroke. It is concluded that descending motor commands that produce patterned voluntary activity during pedalling normally cause cyclical gating of spinal reflexes by either presynaptic or postsynaptic inhibitory mechanisms. Loss of supraspinal control over these spinal inhibitory systems could result in failure to produce appropriate suppression of reflexes during patterned voluntary movements such as pedalling or walking, and may be an important factor contributing to the functional disability in spasticity.

Performance on an eye-hand tracking task and a multi-joint reaching movement to a visual target was studied in a patient with stable cerebellar ataxia and in control subjects. The patient subsequently died and a full neuropathological examination was performed. The neuropathological findings were similar to those seen in patients with paraneoplastic cerebellar degeneration, but no tumor was found at autopsy eight years after onset of the patient's cerebellar syndrome. A severe cerebellar cortical degeneration with complete Purkinje cell loss was demonstrated, whereas cerebellar nuclei and brainstem structures showed no neuronal loss. Tracking performance by the patient was characterized by abnormally large numbers of high velocity movements and hand direction reversals, and by excessive lagging of the hand behind the target in time. In the multi-joint reaching movement, the patient showed a delay in movement onset at the elbow joint compared to movement onset at the shoulder joint. The velocity profile of the movement at the shoulder joint was abnormal. The duration of the acceleration phase was poorly correlated with both peak angular velocity and the duration of the deceleration phase. One of the most striking findings was the inability of the patient to consistently produce the same movement direction from trial to trial while reaching to the same target. Our data suggests that the cerebellar cortex is involved in multiple aspects of motor control including visuomotor integration mechanisms.

Clinical and neurophysiologic studies were done on a patient with action myoclonus secondary to Ramsay Hunt syndrome (dyssynergia cerebellaris myoclonica). Myoclonic jerks in the arms were much more common during movements directed to a target than in other movements. They appeared to be triggered primarily by external sensory inputs relevant to the movement rather than by the motor activity itself. Both somatosensory and visual inputs appeared able to trigger the myoclonic jerks. Myoclonic jerks in the deltoid muscle followed finger contact with a target by approximately 100 msec. Electrical stimuli delivered to the fingers during a reaching movement also triggered myoclonic jerks with a similar latency and also evoked giant cortical potentials which preceded the myoclonic jerks in deltoid by 15-20 msec. Our results suggest that during sensory guided movements, sensory inputs relevant to successful completion of the movement may have access to motor systems controlling the muscles involved. In our patient, who likely has lesions involving the cerebellar nuclei and/or cerebellar cortex, these sensory inputs appeared to result in an excessive motor response, possibly through mechanisms involving cerebellar-motor cortex connections.

The contribution of the cerebellar cortex to coordination of a multi-joint throwing movement was studied by measuring various movement and EMG parameters while normal control subjects and patients with cerebellar cortical atrophy threw a ball at a target. Although patients did not throw as accurately as controls, several coordination measurements were normal in the patients. These included parameters used by us to assess elbow-wrist coordination and the coordination of hand opening with activation of more proximal arm muscles. Postural support for the movement at the shoulder was also normal in that the shoulder was not pushed backwards by the reaction forces resulting from the rapid forward acceleration of the forearm and hand. In contrast, however, patients were unable to coordinate the muscles so as to produce the same hand direction from trial to trial when throwing at the same target. In addition, EMG onset times were abnormal in the antagonist muscles relative to agonist EMG bursts and kinematic parameters of the movement. In conclusion, our patients with cerebellar cortical atrophy showed abnormalities in visual-motor coordination, in that they were unable to consistently produce the appropriate hand direction in response to a visual target. Agonist-antagonist relationships were also impaired. Other aspects of coordination, such as the relative timing of EMG onsets of agonist muscles, even when these were active at different joints, were normal.

Manual tracking performance was studied in five patients with cerebellar incoordination due to unilateral cerebellar hemisphere lesions. The subjects were required to track a target on an oscilloscope screen by moving a cursor controlled by flexion-extension movements of the wrist. In comparison to normal subjects, the cerebellar patients, using their clinically affected arm, demonstrated irregular tracking patterns with inappropriate accelerations and decelerations, numerous high velocity peaks of movement, and an increased time lag between the cursor and the target. The addition of a viscous load provided by feeding back wrist velocity to a torque motor coupled to the apparatus resulted in significant improvement in tracking performance and suppression of the high velocity peaks. Increasing elastic stiffness by feeding back wrist position or inertial load by adding weights to the hand did not improve performance on this task. It is proposed that a hypotonic cerebellar limb behaves like an underdamped mechanical system. The addition of viscous loads helps restore more normal damping during voluntary movements of the arm.

To investigate how motor programs can be modified by sensory inputs we recorded kinematic and EMG patterns from normal human subjects performing well-practised wrist flexion movements in response to an auditory tone. On random trials unexpected wrist perturbations were introduced at varying times after the signal to move had been given. Extension perturbations delivered before agonist EMG onset resulted in an increased maximum velocity (MV) during the wrist flexion movement and in an increased target overshoot even though the wrist was further from the target than expected by the subject at the onset of the movement. The first agonist EMG burst and the antagonist burst were both increased in magnitude in these perturbed trials. Flexion perturbations delivered before the agonist EMG onset moved the hand nearer to the target just prior to movement onset. These resulted in a reduced MV, but the expected increased target overshoot did not occur. The first agonist burst was reduced in magnitude, and the antagonist burst was increased in magnitude. Perturbations delivered after agonist EMG onset produced less change in the first agonist and antagonist EMG burst, and less compensation for the perturbation was evident in wrist position and velocity recordings. These results indicate that, at least in some situations, motor programs for rapid voluntary movements can be modified by afferent inputs. This interaction between central motor commands and sensory feedback might occur at the cortical or spinal level, depending on when perturbations occur relative to onset of EMG and movement. The timing of the EMG changes suggest that both reflex mechanisms and longer latency 'voluntary' adjustments contribute to the compensatory changes in movement trajectory.

Sixteen tractor operators made a total of 64 runs through a tractor driving course designed to measure operator performance in a simulated field operation. The number of tasks the operator was required to perform was held constant while speed was varied and 12.9 km/h (2 and 8 mile/h). However, the psychological load was greater at the row end. The number of steering errors highly correlated with the speed, [Formula: see text] , [Formula: see text] . The steering error rate was not evenly distributed thorughout the course, but was significantly higher at the end of the rows as the tractor entered or exited. This research on speed-load theory as it applied to complex tractor-machinery operation indicates that the number of steering errors an operator makes is directly related to speed and psychological load.

Three children, age 2, 7, and 12, developed Fisher syndrome: inability to walk because of ataxia, complete areflexia, and ophthalmoplegia. Ptosis was prominent in all the children, but the pupillary response to light was affected only in one child. Limb weakness was never present, and sensation normal. One patient was obtunded for several days. Two had prodromal upper respiratory tract illnesses, and the third patient was bitten by an insect 2 days before her symptoms began. Cerebrospinal fluid (CSF) protein content was moderately increased in all patients, but only one child's CSF had a pleocytosis. CSF gamma globulin levels were normal. In the acute phase, F waves and H responses were absent in two cases but returned to normal with clinical recovery. All three patients had marked electroencephalographic (EEG) abnormalities that later improved. The EEG pattern suggested a brainstem disorder. These findings plus the obtundation, gaze paralysis, and ataxia indicate that in Fisher syndrome there is parenchymal involvement of the central nervous system with or without nerve root involvement.

Hospital records of thirty patients with methanol poisoning were studied. Neurologic manifestations at presentation including coma, seizures and decreased visual acuity were seen in nineteen patients. The mean blood pH at presentation was significantly lower in the patients with these neurologic signs and symptoms than in the eleven patients without them (p less than 0.05). Methanol levels at presentation tended to be higher in patients with neurologic manifestations at presentation and these patients tended to present later after methanol ingestion than those patients without neurologic manifestations. Fifteen patients with methanol poisoning developed serious neurologic sequelae or died. The mean blood pH was significantly lower in this patient group than in those who survived without neurologic sequelae (p less than 0.05). Methanol levels at presentation were not different in the patients who developed neurologic sequelae or died as compared to those who did not. The time from ingestion of methanol to presentation at the hospital was however significantly longer in those patients who developed neurologic sequelae or died (p less than 0.05). Initiation of treatment within eight hours of ingestion of methanol was associated with a better clinical outcome.

Two patients with recurrent aseptic meningitis are reported. Intracranial epidermoid tumors were eventually found in both patients. CSF changes in our first case with an epidermoid tumor were similar to those reported in Mollaret's meningitis, with an initial polymorphonuclear pleocytosis early in each attack, followed by a lymphocytic predominance several days later. Large cells which proved to be macrophages were also seen in the CSF of this patient. Both patients had meningitis attacks for several years before the underlying epidermoid tumor was found. Mollaret's meningitis remains a diagnosis of exclusion. These patients should remain tumor suspects for many years and deserve careful and repeated investigation.

The skin of both temples was examined ultrastructurally in six patients with cluster headaches and in three controls. An increased number of mast cells were present in the patients irrespective of whether they were in a cluster period or in a quiescent phase. The mast cells were found perivascularly and in the vicinity of cutaneous nerves in the patients, whereas they were predominantly found in perivascular areas in controls. Mast cell degranulation was not more prominent on the side of the pain and occasional degranulated mast cells were found in controls. These findings are consistent with the hypothesis that cluster headache is due to an axonal reflex in the trigeminal system, initiated perhaps by latent viral infection of IgE activation of mast cells.

To investigate the peripheral afferent mechanisms which mediate the short latency (M1) and long latency (M2) components of the stretch reflex, we have recorded EMG responses to extension perturbations at the wrist before and following inflation of a blood pressure cuff around the upper arm. After approximately 30 min of ischemia, the reflexes had almost completely disappeared, although subjects were still able to activate the forearm muscles voluntarily. As the ischemic block developed, the M2 component began to decrease in amplitude sooner than M1, and up to the time of complete loss of reflex activity, the suppression of M2 was relatively greater than that of M1. These results suggest that M2 may be mediated by a population of afferent fibers different from the Ia afferents which are believed to generate the M1 response.

A battery of colour vision tests was employed to evaluate visual function in patients with multiple sclerosis (M.S.). Colour deficits were found in 45% of patients tested with the Ishihara plates and 42.5% of patients tested with the FM 100-Hue test. 65% of M.S. patients failed at least one of the tests. The colour vision deficits were not restricted to patients with optic neuritis or with visual evoked potential (VEP) abnormalities and there was no significant correlation between an abnormal VEP latency and a colour vision deficit. Colour vision testing may be a useful option to consider in the investigation of M.S. patients, even if there is no other evidence of visual system involvement.

We report the experience at a large teaching hospital over a 10 year period with Miller Fisher Syndrome, facial diplegia, and multiple cranial nerve palsies. In these patients, absence of drowsiness on examination, normal cranial CT scans, albumino-cytological dissociation on CSF examination and slowing of nerve conduction, all suggest that a peripheral nerve dysfunction is the underlying mechanism. Pertinent literature is reviewed, in an attempt to separate these probable variants of Guillain-Barré Syndrome from brainstem encephalitis, with which they may be confused.

Forty patients with MS initially tested in our laboratory were recalled for repeat PSVEP testing approximately two years later. Twelve normal controls were tested in a similar manner approximately two years apart. The PSVEP positive peak latency changed little in the 24 control eyes (mean 1.4 msec, range 0-6) over the study interval. Most MS patient eyes also showed little change in PSVEP latency over the two year study interval. Fifty-eight eyes changed 8 msec or less. Eighteen eyes showed a PSVEP latency increase of 10 msec or more. Six of these eighteen eyes were symptomatic (attack of clinical optic neuritis), twelve asymptomatic during the study interval. Symptomatic eyes tended to have greater latency increases during the study interval than asymptomatic eyes. Significant latency increases occurred with equal frequency in previously normal eyes (normal PSVEP on first test) and abnormal eyes (abnormal PSVEP on first test or previous clinical optic neuritis). Significant latency increases occurred with greater frequency in patients with a mixed or progressive course than in patients with a remitting-relapsing course, and in patients with greater disability rating (Kurtzke 3-7) than in patients with lower disability ratings (Kurtzke 0-2). Bilateral latency increases occurred during the study interval more frequently than expected by chance. Patient age and disease duration did not significantly influence the number of PSVEP latency increases seen during the study interval. Four eyes decreased in latency by 10 msec or more during the study interval. All these eyes had had an episode of acute optic neuritis which began in the 5 weeks immediately preceding the 1st PSVEP test.(ABSTRACT TRUNCATED AT 250 WORDS)

We report a patient with chronic, untreated idiopathic hypoparathyroidism who presented with papilledema and progressive deterioration of visual function. The papilledema resolved with treatment of the hypocalcemia. Visual acuity progressively improved as the serum calcium rose during treatment with vitamin D and calcium supplements. Lumbar puncture may also have contributed to the normalization of cerebrospinal fluid pressure and recovery of vision in this patient. The association of hypoparathyroidism and pseudotumor cerebri is rare, and a retrospective review of 41 patients with hypoparathyroidism admitted to two local general hospitals revealed no other cases.

Cells, originally called "endothelial" cells, have been described in the cerebrospinal fluid (CSF) of patients developing recurrent aseptic meningitis (Mollaret's meningitis). In an attempt at better establishing their nature, a 6-year-old child was followed for a period of 3 1/2 years. A cytological light microscopic and ultrastructural study was performed on samples of the CSF obtained during 17 attacks. The findings are presented, and the relationship of Mollaret's meningitis to intracranial epidermoid cysts is discussed.

Changes in EMG activity in the wrist flexor muscles were studied in response to electrical stimulation of digital nerves and to sudden extension perturbations at the wrist produced by a torque motor in human subjects with unilateral cerebral hemisphere lesions. With the subjects maintaining a steady voluntary contraction against a constant load, digital nerve stimulation produced a series of excitatory and inhibitory changes in tonic EMG activity from the wrist flexors in both the normal and paretic arm. The most consistent response was a period of EMG inhibition beginning approximately 38 msec after the stimulus and lasting approximately 35 msec. With relatively weak electrical stimuli, there was less EMG inhibition in the paretic arm than in the normal arm; with stronger stimuli, the inhibitory response was similar in the two arms. The electrical stimuli and mechanical perturbations were then delivered together, with the interval between them adjusted so that the expected period of inhibition following electrical stimulation coincided with either the early (M1) or the long latency (M2) components of the stretch reflex. In the normal arm electrical stimulation produced more inhibition of the M2 component than of the M1 component. In the paretic arm, inhibition during the M2 component was less marked and similar in degree to that which occurred during M1. These results are compatible with the view that M1 and M2 are normally mediated by separate neural pathways. The long latency EMG activity evoked by muscle stretch in the paretic arm of hemiplegic patients may be generated by pathways or mechanisms different from those in the intact arm.

1. Changes in electromyographic (e.m.g.) activity in the wrist flexors of normal human subjects were studied in response to electrical stimulation of digital nerves and to sudden extension perturbations at the wrist produced by a torque motor. 2. With the subjects maintaining a steady voluntary contraction, stimulation of the digital nerves produced a series of excitatory and inhibitory changes in the tonic e.m.g. activity from the wrist flexors. The most prominent and consistent response was a period of e.m.g. inhibition beginning 39 ms after the stimulus and lasting for approximately 36 ms. 3. The stretch reflex evoked by extension perturbations of the wrist consisted of an early response (M1) with an onset latency of approximately 30 ms, and a late response (M2) with an onset latency of approximately 60 ms. 4. The electrical stimuli and the mechanical perturbations were then delivered together, varying the interval between them so that the period of inhibition resulting from the electrical stimuli occurred at the same time as the M1 or M2 components of the stretch reflex, or during the later voluntary response. 5. The amount of e.m.g. inhibition during the M2 component was significantly greater than that during M1 (P less than 0.02). This result is compatible with the view that M1 and M2 are mediated by separate neural pathways.