Help seeking behavior and onset-to-alarm time in patients with acute stroke: sub-study of the preventive antibiotics in stroke study.

BACKGROUND: Patients with acute stroke often do not seek immediate medical help, which is assumed to be driven by lack of knowledge of stroke symptoms. We explored the process of help seeking behavior in patients with acute stroke, evaluating knowledge about stroke symptoms, socio-demographic and clinical characteristics, and onset-to-alarm time (OAT). METHODS: In a sub-study of the Preventive Antibiotics in Stroke Study (PASS), 161 acute stroke patients were prospectively included in 3 Dutch hospitals. A semi-structured questionnaire was used to assess knowledge, recognition and interpretation of stroke symptoms. With in-depth interviews, response actions and reasons were explored. OAT was recorded and associations with socio-demographic, clinical parameters were assessed. RESULTS: Knowledge about stroke symptoms does not always result in correct recognition of own stroke symptoms, neither into correct interpretation of the situation and subsequent action. In our study population of 161 patients with acute stroke, median OAT was 30 min (interquartile range [IQR] 10-150 min). Recognition of one-sided weakness and/or sensory loss (p = 0.046) and adequate interpretation of the stroke situation (p = 0.003), stroke at daytime (p = 0.002), severe stroke (p = 0.003), calling the emergency telephone number (p = 0.004), and transport by ambulance (p = 0.040) were associated with shorter OAT. CONCLUSION: Help seeking behavior after acute stroke is a complex process. A shorter OAT after stroke is associated with correct recognition of one-sided weakness and/or sensory loss, adequate interpretation of the stroke situation by the patient and stroke characteristics and logistics of stroke care, but not by knowledge of stroke symptoms.

Organic syndromes diagnosed as conversion disorder: identification and frequency in a study of 85 patients.

BACKGROUND: The percentage of patients initially diagnosed with a conversion disorder and later identified as having an organic disorder has been decreasing in recent studies. METHOD: Consecutive patients with a diagnosis of conversion disorder were referred for psychiatric diagnosis and treatment. Research questions were: (1) What incidence of neurological disorder is revealed by neurological reassessment and by which diagnostic technique is the final diagnosis established? (2) What differences can be observed between true-positive and the false-positive results? RESULTS: Ten (11.8%) of the 85 patients examined appeared to suffer from a neurological disorder. In this sample, variables discriminating between the true positives and false positives were: (1) prior suspicion of neurological disorder; (2) older age at referral; (3) older age at onset of symptoms; (4) longer duration of symptoms; and (5) use of medication. Three variables contributed significantly to the prediction of organic disorder: prior suspicion of neurological disorder; age at onset of symptoms; and duration of symptoms. CONCLUSIONS: Although our results are in line with those of other recent studies, the percentage of false positives was still high. The data further emphasize the dangers of making a diagnosis of conversion disorder in the absence of positive evidence. It is important to continue to provide follow up for patients with a diagnosis of conversion disorder. Unfortunately, unreliable psychiatric indications, like certain behavioral characteristics, are still used in the diagnostic process. The results show that a general neurological examination is still a valuable diagnostic instrument in addition to modern diagnostic techniques.

Significant reduction in post-lumbar puncture headache using an atraumatic needle. A double-blind, controlled clinical trial.

A characteristic headache occurs in about 36-55% of patients after lumbar puncture, and many of these patients need bed rest for one or more days to get relief. In a double-blind randomized trial we compared a new 22-gauge atraumatic puncture needle with the most widely used 20-gauge "conventional" needle. In 49 patients randomized to the atraumatic needle, post-lumbar puncture headache occurred in 6%, whereas in the 50 patients randomized to the conventional needle this occurred in 32% (p = 0.001). On the basis of these results we recommend use of the atraumatic needle in order to diminish the frequency of post-lumbar puncture headache.

Liver function disturbances in Guillain-Barré syndrome: a prospective longitudinal study in 100 patients. Dutch Guillain-Barré Study Group.

In 100 consecutive patients with Guillain-Barré syndrome, we assessed liver function on admission and at fixed intervals after either intravenous immunoglobulin (IgIV) or plasma-exchange (PE) treatment. On admission, 38% showed a plasma alanine aminotransferase elevation, gamma glutamyl transferase elevation, or both or more than 1.5 times the upper limit of normal. Ten of these patients had serologic evidence of recent cytomegalovirus infection. The remaining 28 patients were negative for other known causes of liver damage, including infection with Epstein-Barr virus or hepatitis A, B, and C; alcohol abuse; hepatotoxic drugs; recent surgery; and concurrent liver disease. In a hospital control group of 100 consecutive patients with subarachnoid hemorrhage, only 5 had unexplained liver function disturbances on admission (p < 0.0001). In the IgIV-treated group, the percentage of patients with elevated liver function tests increased from 35% before to 69% shortly after treatment at 2 weeks postadmission (p < 0.005). In the PE-treated group, this percentage decreased somewhat from 41% to 36% (not significant). There was also a significant rise in median plasma activity of the various liver enzymes in the IgIV group. At 1 month, however, significant difference had disappeared. At 3 and 6 months, the percentage of patients with liver function disturbances reached a significantly lower level in both treatment groups compared with the time of admission. We concluded that many patients with Guillain-Barré syndrome had mild liver function disturbances without obvious cause. In addition, IgIV treatment was associated with mild transient liver function disturbances through an unknown mechanism.

Guillain-Barré syndrome without sensory loss (acute motor neuropathy). A subgroup with specific clinical, electrodiagnostic and laboratory features. Dutch Guillain-Barré Study Group.

We analysed data obtained from 27 out of a group of 147 patients with Guillain-Barré syndrome, who did not have sensory loss during a follow-up period of 6 months (motor Guillain-Barré syndrome). These patients had a distinctive clinical pattern compared with the other 120 Guillain-Barré syndrome patients. The clinical course was marked by a more rapid onset of weakness (3.9 versus 6.1 days, P = 0.002), an earlier nadir (6.3 versus 9.1 days, P < 0.001), an initially predominant distal weakness (67% versus 27%, P < 0.001), sparing of the cranial nerves (26% versus 68%, P < 0.001) and the disease was more often preceded by a gastro-intestinal illness (41% versus 13%, P = 0.001) often caused by a Campylobacter jejuni infection (67% versus 28% in the other Guillain-Barré syndrome patients, P < 0.001). High titres of anti-GM1 antibodies were also significantly more common in motor Guillain-Barré syndrome patients (42% versus 5%, P < 0.001). Electromyographic data of the motor Guillain-Barré syndrome patients at nadir revealed little or no evidence for demyelination. Abundant denervation activity was present in half of the patients. The response to immune globulin treatment was good but with plasma exchange significantly fewer motor Guillain-Barré syndrome patients reached the stage of independent locomotion after a follow-up period of 6 months especially if the acute motor neuropathy occurred after a C.jejuni infection.(ABSTRACT TRUNCATED AT 250 WORDS)

[Less headache following lumbar puncture with the use of an atraumatic needle; double-blind randomized study]. / Minder hoofdpijn na lumbale punctie bij gebruik van een atraumatische naald; dubbelblind gerandomiseerd onderzoek.

OBJECTIVE: To investigate the difference in frequency of headache after lumbar puncture with a standard needle or an atraumatic needle. DESIGN: Prospective, randomised double blind study. SETTING: Department of Neurology, Merwedeziekenhuis, Dordrecht. METHOD: One hundred sequential patients were randomised to lumbar puncture with a 'standard needle' (20 gauge) or an 'atraumatic needle' (pencil point, 22 gauge). The patients were interviewed one week later. Patient and interviewer were unaware of the needle used. RESULTS: After puncture with the standard needle 32% of the patients suffered from postlumbar puncture headache, after use of the atraumatic needle 6% (p < 0.001; 95% confidence interval of the difference: 0.11-0.40). Postpuncture complaints appeared to be less severe after puncture with the atraumatic needle. CONCLUSION: In comparison with a standard needle, there is significantly less postpuncture headache after lumbar puncture with an atraumatic needle.

Prognostic value of electrodiagnosis in the Dutch Guillain-Barré study.

In the Dutch Guillain-Barré trial, three EMGs were performed according to a rigid protocol at early stages of the disease in 147 Guillain-Barré patients who were unable to walk independently. Independent locomotion 8 weeks and 6 months after entry were considered to be the outcome measures of most clinical value. Electrodiagnostic data obtained 1 week after entry were concluded to be most important for studying prognostic value. This has been attributed to the fact that 87% of the patients were in the nadir of their disease at that moment In univariate analysis, CMAP amplitudes of thenar and hypothenar muscles obtained after distal and proximal stimulation, as well as the recruitment pattern on maximal voluntary effort in these tested muscles, were significant predictors for outcome 8 weeks and 6 months after entry to the study. Motor nerve conduction velocity and distal motor latencies of ulnar and median nerves were weak predictors for outcome at 8 weeks after entry. In multivariate analysis the hypothenar CMAP amplitude on distal stimulation and recruitment pattern of abductor digiti minimi muscle both had an independent predictive value for independent locomotion 8 weeks after entry.

Prognosis in the Guillain-Barré syndrome

We studied 147 patients participating in the multicenter Dutch study for comparasion of the effectiveness of high doses of human immunoglobulin with the effectiveness of plasmapheresis in the Guillain-Barré syndrome in order to determine the influence of the following on the prognosis of the syndrome: age, duration of the disease (ó7 days), artificial respiration, compound muscle action potential (CMAP) < 3mV (20 per cent) - identified as prognostic factors in previous studies - and functional grading, grading by the summation of the Medical Research Council (MRC) scale, anti-GM1 antibodies and positive serology for Campylobacter jejuni - investigated in the present study. The main prognostic criterion was defined as improvement of at least one grade on the scale by the end of the 4th week. The secondary prognostic criterion was defined as the time needed for improvement of one grade and time needed to acquire independent locomotion (F = 2). Functional evaluation was also done in a more subtle manner by measuring muscle strength in 6 individual muscle groups on both sides of the body using the MRC. The factors influencing prognosis are listed below. A change in grading for the better if 1F or more by the end of the fourth week: age, intravenous human immunoglobulin, anti-GM1 antibodies and positive serology for Campylobacter. Time needed for grading to improve for the better by 1F or more: age, CMAP, GM1, summation by the MRC scale. Time needed to reach improvement of 2F: age, GM1, summation by the MRC scale. We are still investigating how the factors determined can be used to predict the time course of each patient individually. At present, we can state that if a patient is less than 50 years old, if no anti-GM1 antibodies are detected and the summation on the MRC scale is above 40, there is a probality of 90 per cent or more that he will succeed in walking unaided before a period of 6 months (functional grade 2). If these 3 factors differ from what has been described above, the probability falls to 30 per cent

High dose immunoglobulins and plasma exchange in the Guillain-Barré Syndrome

The background, design and preliminary results of the Dutch Guillain-Barré trial comparing high-dose immunoglobulins (IgIV) with plasma-exchange (PE) are described. This randomized trial was conservative in that the main aim was to show equal effect of both treatments within certain predefined limits. This approach was appropriate since IgIV is quickly and easily applicable, whereas PE is much more combersome leading to treatment delays and a considerable dropout rate. Moreover PE is not available in all hospitals. For these reasons IgIV would be preferable if the two treatments have a similar effect. We originally estimated that 200 patients would be needed to demonstrate a comparable effect of IgIV and PE (type I error = 0.05 and type II error = o.2). At the interim analysis after 150 patients the stopping criterion has been met. Four weeks after randomization 52.7 per cent in the IgIV group was functionally improved and 34.2 per cent in the PE-group, and advantage of 18.5 per cent for IgIV (p = 0.024)

High dose immunoglobulins and plasma exchange in the Guillain-Barre Syndrome / High dose immunoglobulins and plasma exchange in the Guillain-Barre Syndrome

Apresentamos o desenho metodologico e comunicamos os resultados e comunicamos os resultados iniciais do estudo multicentrico holandes, comparando o tratamento da sindrome de Guillain-Barre com imunoglobulinas humanas endovenosas em altas doses (IgIV) e plasmaferese (PE). O estudo multicentrico e randomico e conservador no sentido de que a principal finalidade e demonstrar um efeito igual de ambas as terapeuticas dentro de certos limites pre-definidos. Esta abordagem foi adequada, uma vez que IgIV e facil e rapidamente aplicavel, enquanto que a PE e terapeutica complexa, o que pode conduzir a demoras e numero insuficiente de sessoes. IgIV seria preferivel se os dois tratamentos tivessem efeito semelhante. Inicialmente estimamos que 200 pacientes seriam necessarios para a demonstracao de efeito comparavel dos dois tratamentos IgIV x PE (erro do tipo I igual 0,05 e do tipo II igual a 0,2). Na analise preliminar, apos o tratamento de 150 pacientes, o criterio de ponto final foi atingido. Quatro semanas apos a randomizacao 52,7 por cento de pacientes no grupo que utilizou PE apresentaram melhora funcional. A diferenca a favor da IgIV foi de 18,5 por cento (P igual 0,024).

Treatment related fluctuations in Guillain-Barré syndrome after high-dose immunoglobulins or plasma-exchange.

Since the introduction of plasma exchange as a treatment for Guillain-Barré syndrome (GBS) patients, treatment related fluctuations have been found to occur in about 10% of the patients. These fluctuations are considered additional evidence of the beneficial effect of plasma exchange. In this report the occurrence of such treatment related fluctuations is described in the 147 patients who took part in the Dutch Guillain-Barré trial comparing high dose intravenous immunoglobulin with plasma exchange. Six of 72 patients in the plasma exchange group and eight of 74 in the immunoglobulin group showed such fluctuation. These results support the biological effect of immunoglobulin. More general use of immunoglobulin should await the full analysis of the Dutch GBS trial which is in progress.

Interobserver agreement in the assessment of muscle strength and functional abilities in Guillain-Barré syndrome.

In studies of Guillain-Barré syndrome, functional deficit is usually assessed according to a functional scale consisting of several categories. The level of interobserver agreement in this scoring method is not known; furthermore, this method seems to be insensitive when applied to bedridden and artificially ventilated patients. We have developed an additional score (MRC-sumscore), reflecting muscle strength in general. Both scoring methods, tested in Guillain-Barré patients, have an almost perfect interobserver agreement. For the functional score kappa = 0.85, and for the MRC-sumscore r2 = 0.96. The MRC-sumscore is easily assessed and more sensitive than the functional score when patients are bedridden or artificially ventilated.

Axonal damage in Guillain-Barré syndrome.

In Guillain-Barré syndrome patients, severe axonal degeneration occasionally occurs, often resulting in permanent functional deficit. In order to assess the development of axonal degeneration, we followed a consecutive series of 42 patients longitudinally using clinical and neurophysiological methods. Eight patients were considered to have severe axonal degeneration: in these patients denervation potentials were eventually found and at least 1 nerve proved inexcitable, and clinical recovery was slow and incomplete. Five of these 8 patients initially showed a pronounced generalized conduction block, the physiological hallmark of demyelination, before signs of axonal degeneration developed. In the remaining three patients, the first evaluation revealed low amplitudes with only modest conduction block; this is consistent with predominantly distal demyelination, but might, alternatively, be explained by primary axonal degeneration. Caution is necessary in using distal CMAP parameters for prognostic purposes, because the distal CMAP may be relatively spared in the early phase of the disease despite severe axonal degeneration later.

In vivo effects of sera from Guillain-Barré subgroups: an electrophysiological and histological study on rat nerves.

Serum from 20 patients with Guillain-Barré syndrome (GBS), 10 healthy controls and 10 patients with recent cytomegalovirus, Epstein-Barr virus, or Campylobacter jejuni/coli infections was injected into rat sciatic nerve. The 20 GBS patients consisted of 2 groups of 10 patients with different electrophysiological and clinical disease patterns. The main aim of the study was to investigate possible differences in humoral (auto)-immunity between these subgroups. We found no statistically significant differences in electrophysiological or histological parameters between nerves injected with sera from the 2 GBS groups. The sera of the GBS groups caused significantly more compound muscle action potential reduction at 3 to 5 days postinjection than the healthy control sera. No significant difference in nerve conduction was found between nerves injected with GBS serum and serum of patients with proven infections without GBS. Histological analysis of the same nerves that were studied electrophysiologically showed no significant differences in demyelination or other histological parameters between patients and controls at 5 days postinjection. Based on the findings in this study that sera of GBS groups with important differences in disease pattern and sera of patients with proven infection but without GBS show similar in vivo effects on rat nerves, we suggest it may be more likely that these effects are caused by aspecific serum factors associated with immune-system activation, especially by precedent infections, than by specific disease-related factors such as anti-myelin antibodies.

The natural history of the Guillain-Barré syndrome in 18 children and 50 adults.

Plasma exchange (PE) is indicated in adult patients with a severe Guillain-Barré syndrome (GBS). For children this has not been proven. If the disease runs a milder course in children, the problems experienced with PE might outweight the benefit. In order to evaluate the need for such a specific treatment in children, we compared the severity of the disease between 18 children and 50 adults; no significant differences were found. The mean duration of hospitalisation of all children was 84 days, four children needed artificial ventilation for a mean of 21.5 days and two children died. We conclude therefore that PE is indicated in children with a severe GBS. The final decision, however, depends also on the practical feasibility of the procedure.