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). METHODS: In 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. RESULTS: With 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. CONCLUSIONS: Although 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.

[Early rehabilitation in Baden-Wurttemberg--a study of all Baden-Wurrtemberg early rehabilitation centers]. / Frührehabilitation in Baden-Württemberg--Eine Untersuchung aller Frührehabilitationseinrichtungen Baden-Württembergs.

Over a period of 12 months, all persons among the 10.4 million inhabitants of the state of Baden-Württemberg were included in the study who had suffered severe brain damage and were treated in special early rehab units, comprising 147 beds for adults and 43 for children. With 830 patients admitted, the incidence of severe brain damage was 7.98/100.000 in adults and 1.11/100.000 in children. 50 to 70 year old patients were over-represented, those older than 70 years were underrepresented due to geriatric rehab facilities for the latter. Male patients dominated, while female were somewhat younger. 54% of the patients were admitted from the hospital which had performed primary care, with an average stay of 67 days. Average early rehab duration was 53 days (arithmetic average; median 40 days, some patients required up to one year). 32.8% of the patients had suffered traumatic brain damage (ICD 851, 852, 854) and 40.9% non-traumatic brain affection (ICD 430, 431, 433-438, 310, 348), including 12.2% CVA (ICD 433-438), 8.5% subarachnoid and 12.3% intracerebral hemorrhage. Severity as indexed by the early rehab Barthel index improved from an initial average of -119 to -34 at discharge. 80% of the patients showed an overall improvement (71% of them by up to 200 points and 46% by up to 100 points).

Selection of electrophysiological techniques to investigate axonal damage of peripheral motor nerve fibres.

After an acute peripheral nerve injury fibrillations and positive sharp waves can be registered in the denervated muscle. The time delay between injury and the manifestation of detectable electrophysiological alterations using conventional electromyography (EMG) lessens the diagnostic value for early treatment. We demonstrate that in radicular lesions the electromyographic examination of the paravertebral musculus multifidus allows diagnosis earlier by about a week compared to examination of limb muscles. Using the amplitude reduction of the compound muscle action potential (CMAP) after stimulation of the nerve distal to its lesion a further reduction of the delay for electrophysiologic proof in peripheral as well as in radicular lesions is possible. Based on these findings we propose a selective strategy using the decline of the CMAP starting with the third day after a peripheral nerve lesion, the electromyography of the deep paravertebral muscles in radicular lesions beginning at the end of the first week, and the conventional EMG investigation of limb muscles after two weeks following the injury.

Stiff man syndrome: neurophysiological findings in eight patients.

The neurophysiological findings in eight patients with the stiff man syndrome (SMS), including four of six tested with autoantibodies against glutamic acid decarboxylase, are presented. Neurophysiological findings did not make it possible to discriminate between patients with and those without autoimmunity against GABAergic neurons. Investigation of mono- and polysynaptic reflexes revealed abnormal results in a variable number of SMS patients, the abnormalities largely corresponding to those seen in spastic paresis. A stereotyped motor response to electrical stimulation of peripheral nerves was recorded from the trunk muscles of all patients investigated. This response was termed spasmodic reflex myoclonus and consisted of a sequence of 1-3 synchronous myoclonic bursts, 60-70 ms after median nerve stimulation, followed by a tonic decrescendo activity over a number of seconds. The recruitment order of muscles along the neuraxis in spasmodic reflex myoclonus suggested that the latter was generated in the spinal cord and conveyed via propriospinal tracts. It is thought that spasmodic reflex myoclonus may serve not only as a diagnostic tool, but also as a key to understanding some aspects of the pathophysiology of both spasms and stiffness in SMS. It is speculated that stiffness is a fragment of spasms, both being generated by common neuronal mechanisms tentatively ascribed to interneurons in the spinal grey matter.

Filtration of cerebrospinal fluid in acute inflammatory demyelinating polyneuropathy (Guillain-Barré syndrome).

INTRODUCTION: Acute Guillain-Barré syndrome (GBS) is a disease where cell-mediated and humoural immune reactions play a key role. Breakdown of the blood-nerve barrier, inflammation of the nerve roots and conduction block are leading symptoms. As it is likely that pathological humoural or cellular factors are concentrated in the subarachnoid space and since factors in the cerebrospinal fluid (CSF) of GBS patients were shown to block sodium channels, a direct therapeutic intervention in the intrathecal compartment seemed worthwhile. METHODS: For this purpose, we developed a technique to purify CSF from pathological factors. Filtration was achieved by withdrawal of CSF (through a lumbally inserted 18 G catheter) and reinfusion via specially developed filters. RESULTS: Twenty severely affected GBS patients were treated with 4 to 38 CSF filtrations. This eliminated cells (> 99%) and reduced the protein content. Clinical improvement was achieved probably by improvement of nerve conduction following a reduction of sodium channel blocking factors. The median time to one grade improvement was 19 days, to reach grade 2 (independent walking) was 42 days. Ventilated patients were weaned from the ventilator after 16 days (median). Patients for which CSF filtration was the first kind of treatment improved faster than patients that had not responded to other treatments, such as plasma exchange or intravenous immunoglobulins. DISCUSSION AND CONCLUSION: Severe side effects were not observed, except sometimes transient headache during the withdrawal phase. This therapy seams to shorten treatment time (in comparison to times reported in studies with and without GBS-specific treatment by plasma exchange or immunoglobulins) and to reduce the degree of remaining neurological deficits. An open randomized controlled study is currently being conducted to compare CSF filtration with plasma exchange.

Stiff man syndrome: clinical and laboratory findings in eight patients.

The clinical, biochemical, neuroimaging and neurophysiological findings of eight patients with stiff man syndromes (SMS) [four of six being tested with autoantibodies against glutamic acid decarboxylase (GAD)] are presented. In two patients (one GAD-positive, one GAD-negative), transient oculomotor disturbances suggested progressive encephalomyelitis with rigidity and myoclonus (PERM) as differential diagnosis. The catalogue of characteristic clinical symptoms of SMS is extended by three new symptoms: (1) an aura-like feeling reported by five patients to precede spontaneous spasmodic attacks; (2) a stereotyped motor pattern seen in seven patients during spasmodic jerks, consisting of brief opisthotonos, stiffening of the slightly abducted legs and inversion of the plantar-flexed feet; (3) a paroxysmal fear when crossing a free space unaided, or even thinking of it. Clinical findings did not enable us to discriminate between patients tested GAD-positive or GAD-negative. Cerebrospinal fluid contained elevated immunoglobulin levels or cell counts, or both, in the majority of patients. Autopsy of one patient revealed scattered lymphocyte cuffs around leptomeningeal, intracerebral and particularly intraspinal vessels, suggesting a mild inflammatory process. Whether SMS and PERM are closely related is discussed; they are possibly both manifestations of a spectrum of encephalomyelopathies having autoimmunity against GABAergic neurons in common.

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.

[Severe tetraparesis as the first manifestation of a chronic lymphatic leukemia]. / Schwere Tetraparese als Erstmanifestation einer chronischen lymphatischen Leukämie.

Uncertain gait and weakness on standing, progressing to flaccid paraparesis of both legs, developed in a 76-year-old woman. Proprioceptor reflexes of both legs were absent and there was pallaesthesia up to the pelvic rim. Electromyography pointed to polyneuritis. Administration of prednisone, 1 mg/kg daily for 10 days, was ineffective, as was one-time plasmapheresis. An incomplete tetraparesis developed. Blood white-cell count increased within 2 weeks by 10,400/microliters (52% lymphocytes) to 17,400/microliters. Blood smear, bone-marrow cytology and histology, as well as immunocytology, revealed lymphoplasmocytoid immunocytomas (chronic lymphocytic leukemia). Oral cytoreductive treatment was started with chlorambucil, 0.1 mg/kg daily, and prednisone, 100 mg daily. After 19 days the patient was able to walk with support, after 28 was walking unaided. Treatment was continued over eight cycles (14 days' treatment, 14 days' interval per cycle). 17 weeks after onset of treatment paraesthesias of the legs required renewed administration of chlorambucil, 0.1 mg/kg per day, for 3 months. The patient has now been free of symptoms during a follow-up period of 12 months.

The acute paralysis in Guillain-Barré syndrome is related to a Na+ channel blocking factor in the cerebrospinal fluid.

The effect of cerebrospinal fluid (CSF) from patients with severe polyradiculoneuritis (Guillain-Barré syndrome, GBS) on voltage-dependent Na+ channels of myoballs was studied. The transient Na+ currents, elicited by repetitive stimulation at 1 Hz, were inhibited by the CSF from most of the GBS patients to 10%-40% the control value. The inhibition was complete in about 5 s and was fully reversible. Such inhibition was never seen with control CSF. The blocking property of the CSF from GBS patients was lost after the number of cells and the protein content had been lowered by means of a clinical filtration technique for cerebrospinal fluid. The results demonstrate that in Guillain-Barré syndrome blocking factors of Na+ channels are present in the CSF, impairing neuron impulse conduction, and thereby causing muscular weakness and sensory disturbances in the affected patient.

Cerebrospinal fluid pheresis in Guillain Barré syndrome.

While plasmapheresis is established in the treatment of acute polyneuroradiculitis, disabling pareses may last long, persisting neurological deficits remain frequent, and costs and side-effects are considerable. Repeated filtration of cerebrospinal fluid may remove pathogenetically relevant cells and polypeptides. Observations in 12 severe Guillain-Barré patients treated with CSF pheresis indicate that it is a safe and effective procedure. We hypothesize mechanisms of action of and potential indications for CSF pheresis as a more general concept. In inflammatory demyelinating polyneuropathy, CSF filtration could be combined with 'dynamic' cerebrospinal fluid pheresis, intravenous immunoglobulin therapy, cryoprecipitation, and/or immuno-adsorption to increase its effectiveness.

Less drug fever with intrathecally applied interferon-beta (short communication).

Systemic therapy of encephalitis with human interferon-beta regularly causes fever up to more than 41 degrees C. Patients often developed hematological changes, nausea and tachycardia. Analyzing the temperature curves of 13 patients with repeated intrathecal, lumbar instillations of 1.0 x 10(6) IU natural IFN-beta, we found markedly less drug-associated fever. Mean temperature was maximal at 38.7 degrees C 12 h after instillation; individual temperature did not exceed 39.7 degrees C, and was elevated for less than 36 h. Day-time of application did not change these results. After the first IFN-beta instillations, the mean integral of temperature vs time was twice as high as after subsequent applications. One and a half days after intrathecal administration and from 39 degrees C on, fever is independent from lumbar IFN-beta. Lower dosage, a more than ten-fold reduction of costs and less interference led us to prefer intrathecal interferon-beta applications. Given the data presented, we cannot yet evaluate clinical efficacy of intrathecal IFN-beta.

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

Cerebrospinal 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.

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

In recent years, plasmapheresis has become a well established treatment of acute and chronic polyradiculoneuritis (Guillain-Barré syndrome, GBS). Nevertheless, 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.

Treatment of acute stroke with calcium antagonists.

Medical treatment in acute stroke is probably more successful when started rapidly after the onset of symptoms. Therefore a drug is necessary which can be applied by the first physician prior to the diagnosis ischaemic versus haemorrhagic stroke by means of imaging methods. In animal models of ischaemic cerebral damage, a cerebroprotective effect of some calcium antagonists could be demonstrated, among them flunarizine and nimodipine. Flunarizine is effective also in experimental cerebral haemorrhage. The results of the first clinical trials with calcium antagonists are encouraging but inconclusive up to now. In view of the limited possibilities of treatment after a stroke, prevention is stressed.

Electrophysiological follow up of experimental allergic neuritis mediated by a permanent T cell line in rats.

Acute experimental allergic neuritis (EAN) was produced in Lewis rats by transfer of lymphocytes from a permanent T cell line specific for bovine P2 protein. In 3 groups of rats receiving 10(4), 10(5) and 10(6) total injected P2-specific lymphocytes, respectively, the time course of illness was followed by measuring several electrophysiological parameters including the H reflex or F wave and lumbospinal somatosensory evoked potentials (SEP). The severity and time course of both the electrophysiological and clinical (e.g., loss of weight and development of paresis) parameters of illness depended on the number of injected lymphocytes. Lower numbers of injected cells were correlated with a later onset and less severe symptoms as well as with an earlier and more complete recovery. According to clinical observation EAN mediated by lymphocytes is a monophasic illness. According to our electrophysiological measurements, however, the disease can be described by the following successive stages: (a) an early stage of hyperexcitability; (b) a stage of acute partial conduction block; (c) 14 days later a stage of maximal demyelination; and (d) a recovery phase. Although demyelination is the prominent feature of the disease, axonal degeneration also occurs to an extent directly related to the number of cells injected. Degeneration was not observed in rats from the group with the lowest number (10(4] of injected lymphocytes.

Treatment with an i.v. calcium overload blocker (flunarizine) in acute stroke. A pilot study.

In an open pilot study 55 patients suffering from acute stroke were treated with Flunarizine, a calcium overload blocker, in addition to standard therapy including diet, physiotherapy, adequate management of accompanying disorders, and hemodilution. The initial high-dose i.v. treatment (2 X 25 mg Flunarizine/day) and the subsequent oral regimen were well-tolerated. The main side effect was slight transient weariness. No adverse effects regarding blood pressure, heart rate, enzymes, blood analysis, renal function and, especially, no extrapyramidal motor symptoms or depression were detected. Flunarizine may be regarded as a relatively safe drug in acute stroke. The probable beneficial effect on the patient's recovery will be evaluated in a multicenter double-blind study.

Combined brachial root and plexus lesions--typical sequelae of motor-bike accidents.

A total of 20 patients with severe post-traumatic arm paralysis was examined using electromyography and sensory neurography to evaluate the type and localization of the lesion; 19 patients had been involved in a motor-bike accident. In more than 80% the brachial roots were involved. In 65% a combined radicular and plexus lesion was found. The poor prognosis of these injuries indicates the need for additional protective devices.

[Comparison of clinical findings and nuclear magnetic resonance tomography in syringohydromyelia and intramedullary tumors]. / Gegenüberstellung von klinischem Befund und Kernspintomogramm bei Syringohydromyelie und intramedullären Tumoren.

Magnetic resonance imaging allowed a distinct differentiation between syringohydromyelia (9 patients) and intramedullary tumour (2 patients). In syringohydromyelia the morphological evaluation showed a greater extension of the cavitation, especially in the caudal direction, than the estimation according to clinical findings. Tumours were visualised indirectly by changing the physiological shape of the spinal cord; therefore, small parts were not recognisable on magnetic resonance images but detected by the corresponding clinical symptoms. Clinical and morphological data were complementary and both necessary for a comprehensive appreciation of the pathological process.

[Generators of somatosensory evoked potentials following leg nerve stimulation]. / Generatoren der somatosensorisch evozierten Potentiale nach Beinnervenstimulation.

Stimulation of the tibial nerve results in complex spinal potentials evoked from the lumbosacral segments of the spinal cord. These potentials suggest the interaction of different generators. Characteristically a triphasic potential can be recorded from L1. It is composed out of an afferent volley in the dorsal roots (R-response) a synaptically strengthened S-response (N21) and a descending reflexly evoked ventral root discharge (A-wave). Above cervical segments of the spinal cord the evoked potentials are probably composed of the afferent volley in the posterior columns (N24), the activity of the nucleus gracilis (N27) and the volley in the medial lemniscus (P30). The primary cortical response P40 is regarded as the specific activity of the somatosensory foot area.