Frans G. A. van der Meché

Clinical features and response to treatment in Guillain‐Barré syndrome associated with antibodies to GM1b ganglioside

GM1b is a minor ganglioside in human peripheral nerves. Serum anti‐GM1b antibodies frequently are present in patients with Guillain‐Barré syndrome (GBS). In this collaborative study, we investigated the antecedent infections, clinical features, and response to treatment of GBS patients with anti‐GM1b antibodies. Of 132 GBS patients who participated in the Dutch GBS trial that compared the effect of intravenous immunoglobulins and plasma exchange, 25 (19%) patients had anti‐GM1b antibodies. IgM antibodies were present in 14, IgG antibodies in 15, and both isotypes in 4 patients. The 25 patients with anti‐GM1b antibodies had a clinical pattern distinct from that of the other 107 GBS patients. They more often had an episode of gastrointestinal illness and frequently showed serological evidence of recent infection by Campylobacter jejuni. The anti‐GM1b–positive subgroup was marked by more rapidly progressive, more severe, and predominantly distal weakness. Cranial nerve involvement and sensory deficits were less common in the patients with anti‐GM1b antibodies. The presence of anti‐GM1b antibodies was associated with slower recovery. The clinical manifestations predominantly were associated with anti‐GM1b antibodies of the IgG isotype. Fourteen (56%) of the 25 patients with anti‐GM1b antibodies also had anti‐GM1 antibodies. The group of patients with both antibodies was clinically more homogeneous and had a more rapidly progressive, pure motor neuropathy. The subgroup of anti‐GM1b–positive GBS patients responded well to treatment with immunoglobulins but not to plasmapheresis. The distinctive clinical features of the patients with anti‐GM1b antibodies show that acute motor neuropathy represents a specific subgroup within GBS and that recognizing these patients may have consequences as to the choice of therapy. Ann Neurol 2000;47:314–321

Long-term results of uvulopalatopharyngoplasty for obstructive sleep apnea syndrome.

Objectives Assessment of the long‐term effect of uvulopalatopharyngoplasty (UPPP) on snoring, excessive daytime sleepiness, and nocturnal oxygen desaturation index (ODI) in patients with obstructive sleep apnea syndrome.

Psychometric evaluation of a new handicap scale in immune‐mediated polyneuropathies

A new handicap measure, the Rotterdam nine‐item handicap scale, was developed and its validity, reliability, and responsiveness evaluated in patients with immune‐mediated polyneuropathies. We evaluated 113 stable patients, of whom 83 had Guillain–Barré syndrome (GBS), 22 had chronic inflammatory demyelinating polyneuropathy (CIDP), and 8 had a gammopathy‐related polyneuropathy. We also studied 20 patients with recently diagnosed GBS (n = 7) or CIDP (n = 13) and changing clinical conditions (longitudinal group). Significant discriminatory validity and correlation with the Rankin scale were demonstrated for the Rotterdam nine‐item handicap scale (stable group: Spearmans test, r = −.76 to −.78; longitudinal group: intraclass correlation coefficient, r = .83; P < .0001). Also, good reliability (r = .89–.98; P < .0001) and high responsiveness values (standardized response mean values > .8) were obtained for the Rotterdam nine‐item handicap scale. In contrast to the Rankin scale, the Rotterdam scale not only provided information regarding mobility but also highlighted physical independence, occupation, and social integration. These results illustrate the clinical usefulness of the Rotterdam nine‐item handicap scale under these conditions.

Perception of prognostic risk in patients with multiple sclerosis: the relationship with anxiety, depression, and disease-related distress

OBJECTIVE The aim of the study was to investigate the impact of perception of prognostic risk on anxiety, depression, and disease-related distress in patients with multiple sclerosis (MS). STUDY DESIGN AND SETTING Perceived risk and perceived seriousness of the 2-year, 10-year, and lifetime prognosis of wheelchair dependence, disability status, anxiety, depression, and disease-related distress were assessed in 101 patients. Distress was measured as the intrusion and avoidance of MS-related thoughts and feelings. RESULTS Patients with higher perceptions of 2-year, 10-year, or lifetime risk were bothered by more intrusion of MS-related thoughts and feelings. Only higher perception of the 2-year risk of wheelchair dependence was significantly related with higher levels of anxiety, depression, and avoidance. Similarly, higher perception of the seriousness of wheelchair dependence was consistently associated with more intrusion and avoidance, but only perceived seriousness of the 2-year prospect of wheelchair dependence was significantly correlated with anxiety and depression. All relations were independent of clinically assessed disability status. CONCLUSION Perceptions of the short-term risk and seriousness of wheelchair dependence were significantly related to anxiety, depression, and disease-related distress in patients with MS. These findings underscore the importance of informing patients with chronic disorders about the short-term prognosis of important long-term consequences of disease.

Risk factors for treatment related clinical fluctuations in Guillain-Barré syndrome. Dutch Guillain-Barré study group

The risk factors for treatment related clinical fluctuations, relapses occurring after initial therapeutic induced stabilisation or improvement, were evaluated in a group of 172 patients with Guillain-Barré syndrome. Clinical, laboratory, and electrodiagnostic features of all 16 patients with Guillain-Barré syndrome with treatment related fluctuations, of whom 13 were retreated, were compared with those who did not have fluctuations. No significant differences were found between patients with Guillain-Barré syndrome treated with plasma exchange and patients treated with intravenous immune globulins either alone or in combination with high dose methylprednisolone. None of the patients with Guillain-Barré syndrome with preceding gastrointestinal illness, initial predominant distal weakness, acute motor neuropathy, or anti-GM1 antibodies showed treatment related fluctuations. On the other hand patients with fluctuations showed a trend to have the fluctuations after a protracted disease course. It is therefore suggested that treatment related clinical fluctuations are due to a more prolonged immune attack. There is no indication that the fluctuations are related to treatment modality. The results of this study may help the neurologist to identify patients with Guillain-Barré syndrome who are at risk for treatment related fluctuations.

Long-term sensory deficit after Guillain-Barré syndrome

Abstract In order to document the sensory deficit still present several years after onset of Guillain-Barré syndrome (GBS) and to determine if the sensory residua have a disrupting effect on daily life, 122 patients were asked to cooperate in a neurological examination and to complete a questionnaire three to six years after onset. On functional assessment 84 patients had no or only minor neurological symptoms or signs, 24 patients showed moderate recovery and 14 patients were left with severe residual signs. On neurological examination, residual sensory deficit was found in the arms of 38 % of the patients and in the legs of 66 % of the patients. Sensory disturbance was experienced as moderate to severe in the arms of 27 % of the patients and in the legs of 40 % of the patients. Muscle aches and cramps were still present in 48 %. There was a statistically significant relation between muscle aches and cramps and objective residual sensory deficit but not with residual weakness. Furthermore, in the group of patients with a pure motor GBS, significantly fewer people suffered from muscle aches and cramps than in the remaining patients (p=0.04). Twenty-five percent of patients changed jobs after their illness, and 44% gave up some leisure activities. It can be concluded that many patients still suffer from sensory deficit, and a considerable number experience these as moderately to seriously disruptive, especially in the legs. Muscle aches and cramps seems to be related to sensory rather than motor dysfunction.

Electrodiagnostic findings related to anti-GM1 and anti-GQ1b antibodies in Guillain-Barré syndrome.

Antibodies against the gangliosides GM1 and GQ1b may induce conduction failure in mice. To investigate their possible site of action in the Guillain‐Barré syndrome (GBS), we studied the relation between serum anti‐GM1 and anti‐GQ1b antibodies and electromyography in 124 GBS patients. Anti‐GM1 antibodies were found in 22 (18%) and anti‐GQ1b antibodies in 5 (4%) patients. Anti‐GM1 antibodies were associated with low distal compound muscle action potential amplitudes and relatively high compound sensory nerve action potential (CSNAP) amplitudes. In none of the patients with anti‐GQ1b antibodies could CSNAPs be detected. Patients with anti‐GM1 and anti‐GQ1b antibodies were heterogenous with respect to electrodiagnostic features exclusive for demyelination or axonal degeneration, although the anti‐GM1 positive patients tended to have more axonal degeneration. In conclusion, electromyographic studies indicate selective and more severe damage of motor nerves in patients with anti‐GM1 antibodies, while patients with anti‐GQ1b antibodies have more severe damage of sensory nerves. These antibodies may interfere with the electrophysiologic properties of different nerve fibers and thereby contribute to the clinical heterogeneity in GBS.

High-dose intravenous immunoglobulin therapy for myasthenia gravis

Abstract The objective of this open, retrospective study was to investigate whether intravenous immunoglobulin (IVIg) could induce a clinically obvious improvement in patients with generalized myasthenia gravis (MG), as judged by MG functional status. Fourteen patients with generalized MG were treated during at least one episode with 0.4 g IVIg per kilogram body weight per day for 5 consecutive days. Patients with confounding variables were excluded; this left 11 patients (16 episodes) to be further analysed. We defined improvement as at least a one-step improvement in MG functional status (according to the University of Virginia’s Modification of Osserman’s classification). Of the treatment episodes, 56% were classified as positive responses. If improvement occurred, onset of improvement started after 3 (1–12) days and peak effect was reached after 7 (4– 30) days (median and range). All four patients who required artificial ventilation could be weaned from it 8.5 (6–11) days after the start of IVIg (median and range). Of the patients treated on two occasions, only one patient had a positive response during both. In MG functional status 5, improvement was observed during five of seven episodes. None of the patients with MG functional status 3 responded. Patients with an acute relapse of MG seemed to respond equally well to IVIg compared with patients with subacute deterioration/ chronic-static state (50% versus 60%). The MG functional status at the start of IVIg and on the day of maximal improvement was compared for all episodes together, and significant improvement was noted (P = 0.0052). We did not see any serious side-effects after IVIg treatment. This retrospective analysis suggests that high-dose IVIg is an effective therapy in some patients with deterioration of generalized MG. If improvement occurs, it starts within a few days of the onset of IVIg and the effect seems to peak within 2 weeks.

Pulmonary function and resting breathing pattern in myotonic dystrophy.

In 17 patients with myotonic dystrophy, spirometric, flow-volume, and maximal mouth occlusion variables were obtained and compared with 8 normal subjects. Ventilatory CO2, response was measured by the estimation of the steady-state effect of a sufficiently large serial dead space. Variability of resting breathing pattern was expressed by the variation coefficients of respiratory cycle time and tidal volume.The group means of the total lung capacity (TLC), vital capacity (VC), forced expiratory volume in 1 sec (FEV)1, and forced inspiratory volume in 1 sec (FIV)1, showed a restrictive pattern. Only maximal static mouth pressure (Pi,max), measured at residual volume (RV) level, showed a significant positive correlation with both VC (p = 0.03) and FIV1, (p = 0.02), suggesting inspiratory muscle weakness as a determinant of the restriction.Although the differences were just not significant, both variation coefficients of the respiratory cycle time and tidal volume were larger in the group with a CO, sensitivity below the lower limit of normal compared to those with a normal ventilatory response to CO2. In 3 patients, fluctuations in FRC were also present. We hypothesize that, in addition to the already documented FRC fluctuations by uncoordinated spontaneous intercostal muscle action, a defect of integration of afferent neural input and chemical drive in the medullary region may also be present in these patients.

Breathing pattern awake and asleep in myotonic dystrophy.

Because myotonic dystrophy patients show marked irregularities of breathing both awake and asleep, variables related to breathing pattern under both conditions were measured in 11 patients, together with pulmonary function indices, ventilatory CO2 response and maximal mouth pressures. The aim of the study was to detect and explain a possible interrelationship between daytime and nocturnal irregularity. Awake, patients demonstrated significantly more variability in tidal volume and respiratory cycle time than controls. Asleep, periodic breathing occurred during up to 100% of the time spent in light sleep, but not during deep sleep. A strong correlation was found with age (r = 0.73, p = 0.01). No relationship was found between disturbed breathing awake and asleep. There was a tendency for increased variability of tidal volume awake in cases with a decreased ventilatory CO2 response (p = 0.1). The results indicate that different mechanisms may be involved in daytime and nocturnal irregularity. It is hypothesized that brain stem integrative functions may be impaired in myotonic dystrophy.