Kurt H. Wollinsky

CSF filtration is an effective treatment of Guillain–Barré syndrome: A randomized clinical trial

Objective To compare CSF filtration (CSFF) and plasma exchange (PE) in the treatment of patients with Guillain–Barré syndrome (GBS). MethodsIn a prospective controlled clinical trial, 37 patients with acute GBS were randomized to receive either CSFF or PE. Inclusion criteria were fulfillment of National Institute of Neurological and Communicative Disorders and Stroke criteria and disability to walk >5 m unassisted. ResultsWith similar baseline features in both groups (initial disability grades on the six-point grading scale of the GBS Study Group) the primary outcome variable (improvement within 28 days after randomization) was almost identical (test for equivalence p = 0.0014), the mean grade values being 0.82 in the CSFF group and 0.80 in the PE group. After 56 days, 56% (9 of 16 patients) of the CSFF group and 37% (7 of 19 patients) of the PE group had reached grade 2 (i.e., ability of unassisted walking >5 m). After 6 months, the probability to reach grade 2 was about 80% in both groups. In the CSFF group, transient pleocytosis occurred without apparent clinical complications. Clinically relevant complications were higher in the PE-treated group. ConclusionsAlthough the number of patients was small, the authors found that the treatment of GBS with CSFF is at least as effective as with PE. CSFF might work by removing from the CSF inflammatory mediators, autoantibodies, or other factors.

An endogenous pentapeptide acting as a sodium channel blocker in inflammatory autoimmune disorders of the central nervous system.

Reversible blockade of sodium channels by endogenous substances has been claimed to account for the fast exacerbations and relapses commonly seen in demyelinating autoimmune diseases. Evidence has been provided that in the cerebrospinal fluid of patients with multiple sclerosis or Guillain-Barré syndrome, a sodium-channel-blocking factor exists that has properties of local anesthetic agents. This factor could contribute to the nerve conduction block and paresis seen in these disorders. We describe here a previously unknown endogenous substance in human cerebrospinal fluid with distinct channel-blocking properties even at very low (0.00001 M) concentrations. The pentapeptide with the sequence Gln-Tyr-Asn-Ala-Asp exerted its blocking action by shifting the steady-state inactivation curve of the sodium channels to more-negative potentials, as most local anesthetics do. In the cerebrospinal fluid of healthy individuals, its concentration was about 3 μM, whereas in patients with multiple sclerosis and Guillain-Barré syndrome, it increased 300–1,400%. At these concentrations, the peptides blocking efficacy was higher than that of 50 μM lidocaine. At a concentration of 10 μM, lidocaine is able to ‘unmask’ subclinical lesions in multiple sclerosis; thus, the endogenous pentapeptide may well contribute to the fast changes of symptoms. Furthermore, it may become valuable as a marker of disease activity.

Longitudinal effects of noninvasive positive-pressure ventilation in patients with amyotrophic lateral sclerosis

Butz M, Wollinsky KH, Wiedemuth-Catrinescu U, Sperfeld A, Winter S, Mehrkens HH, Ludolph AC, Schreiber H: Longitudinal effects of noninvasive positive-pressure ventilation in patients with amyotrophic lateral sclerosis. Am J Phys Med Rehabil 2003;82:597–604. ObjectiveTo evaluate the duration of benefit on symptoms, quality of life, and survival derived from the use of noninvasive positive-pressure ventilation by patients with amyotrophic lateral sclerosis. DesignIn this prospective, cohort study, 30 of 36 consecutively referred symptomatic patients tolerated nightly noninvasive positive-pressure ventilation and undertook pulmonary function testing and 12 symptom and quality-of-life instruments concerning sleep quality, daytime sleepiness, physical fatigue, mental fatigue, and depression that were administered during a 10-mo period. ResultsWith treatment, there was a significant improvement in the majority of patients in sleep quality, daytime sleepiness, physical fatigue, and depression; however, significant improvements lasted for up to 10 mo only in sleep quality. Partial pressure of arterial oxygen, partial pressure of arterial carbon dioxide, and oxyhemoglobin saturation remained stable or even improved for up to 7 mo during use of part-time noninvasive positive-pressure ventilation. A total of 14 patients had survival prolonged by continuous dependence on noninvasive positive-pressure ventilation. ConclusionsNoninvasive positive-pressure ventilation provides a long-lasting benefit on symptoms and quality of life indicators for amyotrophic lateral sclerosis patients and should be offered to all patients with symptoms of sleep disordered breathing or inspiratory muscle dysfunction. It can also prolong tracheostomy-free survival.

Autotransfusion-bacterial contamination during hip arthroplasty and efficacy of cefuroxime prophylaxis : A randomized controlled study of 40 patients

40 patients undergoing primary hip arthroplasty, given autologous processed blood transfusion, were randomized a receive no antibiotic prophylaxis (group A, n 20) or cefuroxime (1.5 g single injection; group B, n 20). Bacterial contamination at various steps in the autotransfusion procedure was assessed in liquid and solid culture media. The operation field and the wound drainage blood were never contaminated either of the groups but some of the suction tips were. Parts of the Vacufix blood collection bags of group A contained bacteria, but none in group B. Processed red blood cell concentrates in both groups showed bacterial growth. Greater blood loss did not increase the contamination rate in general. Isolated bacteria included the species Staphylococcus epidermidis, coagulase-negative staphylococci and Propionibacteria in both groups, but with different cell counts. In addition, Corynebacterium bovis et minutissimum and Moraxelle were identified in group A. In conclusion, autologous blood transfusion was a safe procedure. If contamination occurred, the bacterial count was low, and the bacteria of low pathogenicity. Antibiotic prophylaxis with cefuroxime reduced this contamination of suction tips and collection bags and limited the transfer of autologous blood products.

Factors in the cerebrospinal fluid of multiple sclerosis patients interfering with voltage-dependent sodium channels

The effect of cerebrospinal fluid (CSF) from patients with multiple sclerosis (MS) on voltage-dependent Na+ channels in human myoballs was studied. The transient Na+ currents, elicited by whole-cell depolarization from -85 to -20 mV, were decreased to 75-25% the control value in the presence of CSF from all 7 MS patients investigated. The effect was complete in about 5 s and was fully reversible on admission of standard external fluid. Such decrease was not or only to a minor extent observed with 10 out of 11 control CSFs from patients without inflammatory neurological disease. The origin of the factors interfering with the Na+ channels is unknown. It is suggested that, in addition to demyelination, impaired Na+ channel function might cause the symptoms in MS.

On the nature of endogenous antiexcitatory factors in the cerebrospinal fluid of patients with demyelinating neurological disease

The cerebrospinal fluid (CSF) of patients with demyelinating neurological disease, such as Guillain—Barré syndrome or multiple sclerosis, contains factors that inhibit the excitatory Na+ current. Such antiexcitatory factors are occasionally also detectable in CSF from patients with other neurological diseases but were absent from an artificial CSF containing all major CSF constituents (electrolytes, amino acids, vitamins, metabolites, albumin). In an attempt to characterize these factors, unphysiological pCa or pH values were excluded by the application of the Ca2+ chelator EGTA and the use of buffers. Heating the CSF for 10 min to 95°C or digesting it with proteases did not destroy the antiexcitatory potency. Fractionation of the CSF contents according to molecular weight showed that the factors have a molecular weight <3 kD. This excludes proteins, such as antibodies or cytokines, as candidates. Small peptides are known to be resistant to some proteases and heating.

Liquorpheresis (CSF-filtration): An effective treatment in acute and chronic severe autoimmune polyradiculoneuritis (Guillain-Barré syndrome)

SummaryIn recent years, plasmapheresis has become a well established treatment of acute and chronic polyradiculoneuritis (Guillain-Barré syndrome, GBS). Nervertheless, there are still non-responders and there are particular risks associated with this treatment. Despite all efforts, the duration of severe forms of Guillain-Barré syndrome is still considerable. Inflammation and demyelination start intrathecally. We therefore used liquorpheresis (cerebrospinal fluid filtration) as a new effective therapeutic approach. Our first patient, severely disabled with acute GBS, artificially ventilated, had undergone plasma exchange without effect. Plasma immunoadsorption led only to transient improvement. After several liquorphereses, the patient recovered completely. In three additional patients with acute and two with chronic GBS an improvement of clinical signs in close temporal relation to liquorpheresis was observed. Twice, liquorpheresis was combined with immunoadsorption of cerebrospinal fluid. Liquorpheresis was well tolerated in all cases. This procedure may be effective by eliminating humoral or cell-bound factors responsible for the onset or/and maintenance of inflammation. Further controlled studies are necessary and are in progress.

A small sodium channel blocking factor in the cerebrospinal fluid is preferentially found in Guillain-Barré syndrome : a combined cell physiological and HPLC study

Abstract The cerebrospinal fluid (CSF) of patients with Guillain-Barré syndrome (GBS) contains a low molecular weight factor with sodium channel blocking activity. This study investigated whether such activity also exists in the CSF of patients with other neurological diseases. Further, using high-performance liquid chromatography (HPLC) we tested whether the electrophysiological effect of the CSF is correlated with the size of the corresponding peak in the chromatograms. The existence of sodium channel blocking activity was tested in 27 native CSF samples of three groups of patients (group 1: GBS, n = 13; group 2: other inflammatory diseases, n = 8; group 3: controls, n = 6). NH15-CA2 neuroblastoma × glioma cells in the whole-cell recording configuration was used as a system for assaying the sodium channel blocking activity of CSF specimens. CSF shifted the steady-state inactivation curve of the sodium channels reversibly by –10.2 ± 4.4 mV in group 1, –6.7 ± 3.9 mV in group 2, and – 3.5 ± 2.8 mV in group 3 (P < 0.01). The shift was greater in demyelinating (9.3 ± 4.7 mV) than in nondemyelinating (5.6 ± 3.9 mV) diseases (P < 0.04). HPLC analysis of CSFs showed a well separated peak containing the substance responsible for the electrophysiological effect at about 41 min elution time. The peak covered the molecular weight range of 600–800 Da. Sodium channel blocking activity of CSFs and areas of the corresponding peak in the chromatograms were well correlated. We conclude that sodium current inhibition by a low molecular weight factor is generally present but increased in GBS.

Liquorpheresis eliminates blocking factors from cerebrospinal fluid in polyradiculoneuritis (Guillain-Barré syndrome)

SummaryCerebrospinal fluid (CSF) derived from six patients with polyradiculoneuritis (Guillain-Barré syndrome, GBS) treated by liquorpheresis was injected into rat sciatic nerve. By measuring spinal evoked potentials after stimulation of the tibial nerve, we observed slowing or dispersion of nerve conduction in those cases where the CSF had been taken before liquorpheresis. CSF of the same patient, sampled after liquorpheresis, showed minor effects only. Impairment of nerve conduction was seen between 5 and 20 min after injection, normal function being restored on the third day. These results suggest that liquorpheresis eliminates blocking factors from the CSF of patients with GBS. We postulate this as the effect by which liquorpheresis improves neurological symptoms in Guillain-Barré syndrome.

The human endogenous local anesthetic-like factor (ELLF) is functionally neutralized by serum albumin

The cerebrospinal fluid (CSF) of patients with multiple sclerosis or Guillain-Barré syndrome contains a factor that inhibits excitation of nerve and muscle cells like local anesthetics. CSF samples containing the endogenous local anesthetic-like factor (ELLF) were analyzed by gel filtration chromatography and ultraviolet (UV) absorption at 210 nm. The active component was in a single peak corresponding to a molecular weight of 600-800 Da. This peak was decreased and the Na+ channel blocking activity was neutralized by the addition of 40 g/l human serum albumin to the CSF. When the albumin was separated from the CSF/albumin mixture by acetonitrile treatment, the Na+ channel blocking activity reappeared. The ELLF and its neutralization may be of relevance for the clinical fluctuations known with these diseases.