Guillain-Barré syndrome: the evolution of therapy.
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Combined Modality Therapy↗
Biomedical subjects
D R Cornblath
Publications and source records attributed to D R Cornblath.
Chronic inflammatory demyelinating polyneuropathy and paraproteinemic neuropathies.
Chronic inflammatory demyelinating polyneuropathy and the neuropathies associated with monoclonal gammopathies represent a significant proportion of initially undiagnosed neuropathies. Over the past year, a number of publications have provided information on the clinical characteristics, mechanisms, and possible relationships between these neuropathies. This review summarizes this recent information, with an emphasis on the relevance to therapy.
Chronic Disease↗
Inter- and intraexaminer reliability of nerve conduction measurements in patients with diabetic neuropathy.
We determined the inter- and intraexaminer reliability of nerve conduction measurements in six patients with diabetic peripheral neuropathy. Each patient was examined by six electromyographers on two separate occasions at least 1 week apart. We obtained attributes of nerve conduction at each examination and analyzed the data by analysis of variance. Intraexaminer reliability was high for 11 of 12 measurements, and interexaminer reliability was high for eight of twelve. Three of the four measurements that varied between examiners were either sensory or motor amplitudes, attributes frequently used to measure disease progression or to assess the result of therapeutic intervention. Our results suggest that longitudinal nerve conduction measurements used to assess worsening or improvement over time should optimally be performed by a single examiner to minimize the degree of variability associated with different examiners.
Analysis of Variance↗
Multifocal motor neuropathy: response to human immune globulin.
Multifocal motor neuropathy (MMN) is a progressive disorder producing asymmetrical weakness and muscle wasting. Case reports suggest that patients with MMN improve after cyclophosphamide therapy, but not after prednisone or plasmapheresis. Because MMN is likely to be immune mediated, we investigated the therapeutic response to human immune globulin (HIG) in an open, uncontrolled trial. Nine patients, ages 28 to 58 years, had chronic, progressive, asymmetrical, predominantly distal, limb weakness for 5 to 18 years. Sensation was normal, and reflexes were reduced asymmetrically. All had physiological evidence of multifocal motor demyelination with partial motor conduction block, and 7 had elevated serum titers of anti-GM1 IgM antibody. All patients were treated with HIG, 1.6 to 2.4 gm/kg, given intravenously over 3 to 5 days. Strength improved in all patients 3 to 10 days after treatment, with improvement peaking at 2 weeks and lasting for an average of 2 months. The range of functional improvement varied from dramatic to mild. The degree of partial motor conduction block was reduced, at least partially, in 7 of 8 patients. The serum anti-GM1 antibody titers did not change. Repeated courses of HIG resulted in similar improvements. We conclude that HIG may be an effective therapy for patients with MMN.
Adult↗
Acute motor axonal neuropathy: a frequent cause of acute flaccid paralysis in China.
In northern China, annual epidemics of acute-onset flaccid paralysis diagnosed clinically as Guillain-Barré syndrome have been recognized for at least 20 years. On the basis of an historical analysis of more than 3,200 patients, distinctive features include most cases occurring during the summer months among children and young adults, most of whom reside in rural areas. Of 90 patients with acute flaccid paralysis, 88 had a distinctive pattern that shares clinical and cerebrospinal fluid findings with demyelinating Guillain-Barré syndrome, but that differs from Guillain-Barré syndrome physiologically and pathologically. The clinical course is marked by rapidly progressive ascending tetraparesis, often with respiratory failure, but without fever, systemic illness, or sensory involvement. Cerebrospinal fluid is acellular, and elevations of protein content occur in the second or third week of illness. Electrodiagnostic studies show normal motor distal latencies and limb conduction velocities, but reduced compound muscle action potential amplitudes. Sensory nerve action potentials and, when elicitable, F waves are within the range of normal. Recovery is usually good. Autopsy studies have shown Wallerian-like degeneration of motor fibers. These studies establish that this is a distinctive syndrome, distinguishable from poliomyelitis and demyelinating Guillain-Barré syndrome.
Acute Disease↗
Intensive management and treatment of severe Guillain-Barré syndrome.
OBJECTIVE: To review the management and therapeutic approaches to severe acute Guillain-Barré syndrome, with emphasis on the ventilatory dysfunction, and cardiovascular instability seen in patients with this syndrome. DATA SOURCES/STUDY SELECTION: Clinical studies on Guillain-Barré syndrome patients, physiologic studies on animals and humans. DATA EXTRACTION/SYNTHESIS: Guillain-Barré syndrome is an acutely evolving, immune-mediated, inflammatory disorder of the peripheral nervous system, leading to demyelination and axonal loss. Clinical hallmarks are symmetric flaccid muscle paresis and areflexia in the presence of an increased cerebrospinal fluid protein content, and electrophysiologic studies demonstrating evolving demyelination. The only well-investigated, efficacious immunomodulatory therapy is plasmapheresis. Plasmapheresis has been shown to decrease ventilator dependence in severe Guillain-Barré syndrome. Ventilatory failure and cardiovascular instability are the main reasons for intensive care support. Ventilatory failure is caused by involvement of airway and respiratory muscles, particularly the diaphragm. Cardiovascular instability is due to involvement of the autonomic nervous system and results in labile blood pressure, cardiac arrhythmias, and hypovolemia. After admission to the intensive care unit, the most serious complications result from mechanical ventilation, circulatory disturbances, thrombosis, starvation, and sepsis. Special emphasis should be given to psychologic support and management of pain. CONCLUSIONS: With modern intensive care support, the outcome is excellent (> 80% recovery). In severe cases, a higher frequency of persistent residual paresis occurs; however, the majority of this group ultimately have a good functional recovery.
Acute Disease↗
Phase I and pharmacologic study of paclitaxel and cisplatin with granulocyte colony-stimulating factor: neuromuscular toxicity is dose-limiting.
PURPOSE: To determine the maximum-tolerated doses (MTD), the principal toxicities, and the pharmacologic behavior of high doses of Taxol (paclitaxel; Bristol-Myers Squibb, New York, NY) combined with cisplatin and granulocyte colony-stimulating factor (G-CSF). PATIENTS AND METHODS: Untreated and minimally pretreated solid-tumor patients received 24-hour infusions of Taxol on day 1 followed by cisplatin on day 2 and G-CSF, 5 micrograms/kg/d subcutaneously (SC), beginning on day 3. Treatment was repeated every 3 weeks. Starting doses of Taxol and cisplatin were 135 and 75 mg/m2, respectively. RESULTS: The development of a severe peripheral neuropathy and/or severe myalgias precluded the chronic administration of Taxol and cisplatin with G-CSF at doses greater than 250 mg/m2 and 75 mg/m2, respectively. At this dose, the mean Taxol steady-state plasma concentration (Css) exceeds concentrations capable of inducing pertinent antimicrotubule effects in vitro. The severity of the neuropathy was related to the cumulative dose of Taxol, the magnitude of the dose administered during each treatment, and the presence of a pre-existing medical disorder associated with peripheral neuropathy. A proximal myopathy of modest severity also was documented. Although severe neutropenia occurred frequently, especially at the MTD, it was rarely associated with fever (8% of courses), and absolute neutrophil counts (ANCs) less than 500/microL never persisted for more than 5 days. Responses were noted in non-small-cell lung cancer (NSCLC) and head and neck, breast, and esophageal cancers. CONCLUSION: Taxol and cisplatin doses of 250 mg/m2 and 75 mg/m2, respectively, can be administered repetitively with G-CSF to untreated and minimally pretreated patients. However, these doses are not recommended for patients with pre-existing neuropathies until additional experience in high-risk patients is obtained. Although this Taxol dose is nearly 85% higher than the dose that can be combined with cisplatin in the absence of G-CSF, this high-dose regimen should not be used outside the investigational setting until a dose-response relationship has been demonstrated for Taxol in randomized clinical trials.
Adult↗
Conjugal amyotrophic lateral sclerosis: report of a young married couple.
We report a 38-year-old nurse who developed amyotrophic lateral sclerosis (ALS) beginning in September 1990. In May 1991, her 38-year-old husband developed dysarthria, which progressed to typical ALS. This is the fourth report in the literature of conjugal ALS occurring outside of Guam. Although this event is most likely due to coincidence, exogenous agents should be considered in the etiology of ALS.
Adult↗
High-titer selective serum anti-beta-tubulin antibodies in chronic inflammatory demyelinating polyneuropathy.
Although chronic inflammatory demyelinating polyneuropathy (CIDP) is presumed to be an autoimmune disorder, no neural antigen has been recognized as an immune target. We found that serum IgM from a patient with CIDP and an IgM paraprotein reacted with a 53-kd protein by Western blot analysis. Amino acid sequence analysis identified this protein as beta-tubulin. We then studied sera from 70 CIDP patients, 35 Guillain-Barré syndrome (GBS) patients, and 483 disease (amyotrophic lateral sclerosis, Alzheimer's disease, multiple sclerosis, diabetes, and other polyneuropathies) and normal controls for selective high-titer anti-beta-tubulin using ELISA methodology. Forty-two percent (30/70) of patients with CIDP had selective high titer IgM reactivity against beta-tubulin; 23% (16/70) had selective high-titer IgG reactivity against beta-tubulin. Overall, 57% of CIDP patients, 20% of GBS patients, and 2% of control patients had selective, high serum IgM or IgG anti-beta-tubulin reactivity. Selective high-titer serum anti-beta-tubulin antibodies occur in a majority of patients with CIDP but are rare in other chronic neuropathies or CNS disorders.
Adult↗
Relapse in Guillain-Barré syndrome after treatment with human immune globulin.
Seven adult patients received human immune globulin intravenously as initial therapy for Guillain-Barré syndrome. Although all patients initially stabilized or improved, five patients deteriorated 1 to 16 days after completion of treatment. In all five patients, clinical worsening included loss of at least one functional grade together with a decreased forced vital capacity. We subsequently treated each patient with a course of plasma exchange, which led to varying degrees of clinical improvement in four. In contrast to previously reported relapse rates for Guillain-Barré syndrome, our experience suggests that clinically significant relapses may occur in patients more often following human immune globulin therapy than after either plasma exchange or no therapy.
Adolescent↗
Neurotoxicity of Taxol.
Neurotoxicity, manifested primarily by a motor and sensory polyneuropathy, is the principal nonhematological side effect of Taxol. Available evidence suggests that Taxol produces a toxic effect involving either axons or ganglion cell bodies, or both, rather than a myelinopathy. As with other toxic polyneuropathies, patients with preexisting peripheral neuropathies, such as those caused by diabetes mellitus or ethanol, appear to be particularly predisposed to developing neurological toxicity. The incidence and severity of the neuropathic manifestations also appear to be related to the Taxol dose level, the cumulative dose of Taxol, and possibly to the use of Taxol in combination with cisplatin. Rarely, manifestations of autonomic and central nervous system dysfunction occur. Taxol also induces myalgias in the peri-treatment period, especially when used in high doses, and a myopathy has been noted in patients treated with high doses of Taxol administered alone and in combination with cisplatin. Although dose-response relationships for Taxol have not been clearly established, these neuromuscular effects are likely to become a significant clinical problem if higher doses of Taxol are used with hematopoietic colony-stimulating factors. The neuromuscular effects of Taxol, including symptoms, physical and electrophysiological manifestations, and predisposing factors, as well as agents that may be used for neuroprotection, are discussed in this report.
Humans↗
Manipulating the immune system with immune globulin.
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Demyelinating Diseases↗
Werdnig-Hoffmann disease and chronic distal spinal muscular atrophy with apparent autosomal dominant inheritance.
We report on a family in which both Werdnig-Hoffmann disease (severe infantile-onset spinal muscular atrophy) and chronic distal spinal muscular atrophy occurred, with apparent autosomal dominant inheritance. The female proband clinically had Werdnig-Hoffmann disease and died at 10 months. In their second decade of life, the proband's father and his 2 brothers developed bilateral progressive atrophy and weakness of the hands and mild weakness in the distal parts of the legs. Their mother had no symptoms or signs of motor neuron disease but electromyography revealed distal denervation of the limbs. While the family studies suggest autosomal dominant inheritance, it is possible that the proband's condition was influenced by a maternally derived allelic or modifying trait.
Adult↗
Wallerian degeneration in human nerves: serial electrophysiological studies.
After nerve transection, the distal stump undergoes Wallerian degeneration (WD). Little information is available concerning sequential changes in nerve conduction measurements during WD in humans. Five patients with nerve injuries were studied temporally. Motor-evoked amplitudes were reduced by 50% at 3 to 5 days after injury; the response was absent by day 9. Sensory-evoked amplitudes were reduced by 50% at 7 days after injury; the response was absent by day 11. Sensory and motor nerves with shorter distal stumps showed earlier loss of amplitude than did those with longer distal stumps. Denervation potentials were seen 10 to 14 days after injury. Our results suggest that WD occurs earlier if the distal stump is shorter, and that motor-evoked responses are affected earlier than sensory-evoked responses. The time-lag between the loss of the motor-evoked response and the appearance of denervation potentials, the latter coinciding with reduction of sensory evoked responses, suggests that failure of neuromuscular transmission precedes axonal loss during WD.
Action Potentials↗
Nerve conduction studies in amyotrophic lateral sclerosis.
Nerve conduction studies (NCS) are an integral part of the evaluation of amyotrophic lateral sclerosis (ALS) patients and are useful in distinguishing ALS from disorders that mimic it. The question often arises whether in the presence of severe atrophy and reduction of the compound muscle action potential amplitude, abnormal conduction velocity (CV), distal latency (DL), or F-wave latency (F) exceeds what can be expected from ALS alone. To determine the limits of abnormality in classic ALS, we prospectively evaluated NCS data from 61 patients who met a strict clinical definition of ALS. We related CV, DL, and F to distal evoked amplitude (AMP) in peroneal (n = 63 observations), median (n = 50), and ulnar (n = 52) nerves. In nerves with reduced AMP, CV rarely fell to less than 80% of the lower limit of normal, and DL and F rarely exceeded 1.25 times the upper limit of normal. Utilizing the entire data set and regression analyses, 95% confidence limits for expected values for CV, F, and DL as a function of AMP were calculated. These limits thus derived suggest criteria for NCS abnormalities in ALS and may be useful in differentiating ALS from other illnesses.
Action Potentials↗
Novel mutations in families with unusual and variable disorders of the skeletal muscle sodium channel.
Mutations in the skeletal muscle sodium channel gene (SCN4A) have been described in paramyotonia congenita (PMC) and hyperkalaemic periodic paralysis (HPP). We have found two mutations in SCN4A which affect regions of the sodium channel not previously associated with a disease phenotype. Furthermore, affected family members display an unusual mixture of clinical features reminiscent of PMC, HPP and of a third disorder, myotonia congenita (MC). The highly variable individual expression of these symptoms, including in some cases apparent non-penetrance, implies the existence of modifying factors. Mutations in SCN4A can produce a broad range of phenotypes in muscle diseases characterized by episodic abnormalities of membrane excitability.
Adult↗
Chronic demyelinating polyneuropathy associated with eosinophilia-myalgia syndrome.
Eosinophilia-myalgia syndrome (EMS) is a newly described syndrome associated with use of L-tryptophan. A neuropathy with features of axonal degeneration has also been described in conjunction with EMS. Demyelinating polyneuropathy is not a well recognised association of the syndrome. The two patients with EMS reported presented with profound weakness and sensory loss and were found to have clinical, electrophysiological and pathological evidence of a chronic demyelinating polyneuropathy. The concurrence of this neuropathy with EMS, as well as several other features of their illness, is suggestive of an immune mediated mechanism in the pathophysiology of EMS.
Aged↗
Clinical and electrophysiological aspects of acute paralytic disease of children and young adults in northern China.
Acute peripheral nervous system diseases leading to paralysis in children are rare in Europe and the USA, whereas epidemics of a Guillain-Barré-like syndrome occur annually among children in rural parts of northern China. To clarify the features of this disorder 36 patients, aged 15 months to 37 years (median 7) with this syndrome were investigated; 91% were from rural areas. In 47%, a prodromal illness was reported in the preceding 4 weeks. Leg weakness and resistance to neck flexion were the earliest symptoms. The weakness ascended rapidly and symmetrically to affect the arms and respiratory muscles, with maximum weakness occurring a mean of 6 days after onset of weakness. Bulbar weakness occurred in 61% of patients, but only 1 had extraocular paresis. Respiratory assistance was needed by 31% of patients. Tendon reflexes were lost as weakness developed. 42% of patients had raised concentrations of protein in the cerebrospinal fluid, and the mean cell count was 3 cells/microliters (range 0-12/microliters). Electrodiagnostic studies in 22 patients showed severe reductions in motor evoked amplitudes from distal stimulation. Sensory action potentials were normal. Electromyography revealed denervation potentials in limb muscles. The distinctive epidemiological, clinical, and neurophysiological characteristics of this illness suggest that the disorder is different from both Guillain-Barré syndrome and poliomyelitis. The neurophysiological findings support the hypothesis that the disorder is a reversible distal motor nerve terminal or anterior horn cell lesion.
Acute Disease↗