Chronic motor neuropathies: response to interferon-beta1a after failure of conventional therapies

OBJECTIVES: The effect of interferon-beta1a (INF-beta1a; Rebif) was studied in patients with chronic motor neuropathies not improving after conventional treatments such as immunoglobulins, steroids, cyclophosphamide or plasma exchange. METHODS: A prospective open study was performed with a duration of 6-12 months. Three patients with a multifocal motor neuropathy and one patient with a pure motor form of chronic inflammatory demyelinating polyneuropathy were enrolled. Three patients had anti-GM1 antibodies. Treatment consisted of subcutaneous injections of IBF-beta1a (6 MIU), three times a week. Primary outcome was assessed at the level of disability using the nine hole peg test, the 10 metres walking test, and the modified Rankin scale. Secondary outcome was measured at the impairment level using a slightly modified MRC sumscore. RESULTS: All patients showed a significant improvement on the modified MRC sumscore. The time required to walk 10 metres and to fulfil the nine hole peg test was also significantly reduced in the first 3 months in most patients. However, the translation of these results to functional improvement on the modified Rankin was only seen in two patients. There were no severe adverse events. Motor conduction blocks were partially restored in one patient only. Anti-GM1 antibody titres did not change. CONCLUSION: These findings indicate that severely affected patients with chronic motor neuropathies not responding to conventional therapies may improve when treated with INF-beta1a. From this study it is suggested that INF-beta1a should be administered in patients with chronic motor neuropathies for a period of up to 3 months before deciding to cease treatment. A controlled trial is necessary to confirm these findings

Electrodiagnostic studies in Guillain-Barre syndrome

The Guillain-Barre syndrome (GBS) is a monophasic (sub)acute inflammatory demyelinating predominantly motor polyradiculo-neuropathy. Clinical criteria have been proposed by Asbury (Asbury et aI., 1978; Asbury and Cornblath, 1990). GBS is a selflimiting disease, however, up to 30% of the patients may need temporary artificial ventilation; about 15% remain disabled and mortality is estimated to be up to 5%. Therefore, GBS must be regarded as a serious disease. Plasma exchange (PE) and more recently high dose immune globulins ([vIg) have been proved to be succesful in shortening the duration of the disease, the duration of artificial ventilation and to improve outcome at 6 months (GBS study group, 19- 85; van del' Meche et aI., 1992; French cooperative group, 1992). In contrast to immune globulin therapy, plasma exchange is not always possible for haemodynamic reasons. In addition it is generally not feasible in children, not in all hospitals available, and is in general rather cumbersome. Therefore in the multicentre Dutch Guillain-Barn: Study the effectiveness of immune globulins versus plasma exchange was evaluated in 150 patients, with a main aim to demonstrate at least equal efficacy. This study revealed therapeutic effectiveness of both therapies with a limited but significant superiority of immune globulins over plasma exchange (van del' Meche et aI., 1992). [n the Dutch Guillain-Barre trial each patient was tested electrodiagnostically three times in an early stage of the disease according to a rigid protocol. The results of these electro diagnostic studies are the subject of this thesis

Motor Nerve Conduction Tests in Carpal Tunnel Syndrome

Background: For the preoperatively often required confirmation of clinically defined carpal tunnel syndrome (CTS), sensory as well as motor nerve conduction studies can be applied. The aim of this study was to test the sensitivity of specific motor nerve conduction tests in comparison with, as well as in addition to, sensory nerve conduction tests.Methods: In 162 patients with clinically defined CTS, sensory and motor nerve conduction tests were performed prospectively. Sensitivity and specificity of all tests were computed. Also, Receiver Operating Characteristic (ROC) analyses were conducted.Results: Sensitivity for all sensory tests was at least 79.4% (DIG1). All tests had a specificity of at least 95.7%. The motor conduction test with the highest sensitivity was the TLI-APB (81.3%); its specificity was 97.9%.Conclusion: In the electrophysiological confirmation of CTS, sensory nerve conduction tests and terminal latency index have a high sensitivity. If, however, sensory nerve action potentials cannot be recorded, all motor nerve conduction tests have a high sensitivity

The Diagnostic Sensitivity for Ulnar Neuropathy at the Elbow Is Not Increased by Addition of Needle EMG of ADM and FDI When Nerve Conduction Studies Are Normal

Introduction: The main objective of this study was to investigate whether electromyography (EMG) has additional value in the confirmation of the clinical diagnosis of ulnar nerve entrapment at the elbow (UNE) if nerve conduction studies (NCS) are normal.Methods: A prospective cross-sectional cohort observational study was conducted among patients with the clinical suspicion of UNE. A total of 199 arms were included, who were examined according to a standard neurophysiological protocol, i.e., NCS and EMG relevant to the ulnar nerve.Results: NCS were normal in 76 (38.2%) arms. No abnormal spontaneous muscle fiber activity was found with EMG in any of these cases. In 9 arms with normal NCS (11.8%), isolated abnormal MUAP configurations were found with EMG. Of these nine arms one UNE was diagnosed clinically, in which additional ultrasound and repeated NCS/EMG were negative. One had already been diagnosed with neuralgic amyotrophy and one with CTS. The other 6 arms had additional diagnostics which did not reveal an UNE.Conclusion: EMG as part of the standard neurophysiological protocol exclusively in the confirmation of the clinical diagnosis of UNE has limited added value if NCS are normal in a high prior-odds setting. However, removing EMG may prevent detecting concomitant and/or additional differential diagnoses

A novel seven-octapeptide repeat insertion in the prion protein gene (PRNP) in a Dutch pedigree with Gerstmann–Sträussler–Scheinker disease phenotype: comparison with similar cases from the literature

Human prion diseases can be sporadic, inherited or acquired by infection and show considerable phenotypic heterogeneity. We describe the clinical, histopathological and pathological prion protein (PrPSc) characteristics of a Dutch family with a novel 7-octapeptide repeat insertion (7-OPRI) in PRNP, the gene encoding the prion protein (PrP). Clinical features were available in four, neuropathological features in three and biochemical characteristics in two members of this family. The clinical phenotype was characterized by slowly progressive cognitive decline, personality change, lethargy, depression with anxiety and panic attacks, apraxia and a hypokinetic-rigid syndrome. Neuropathological findings consisted of numerous multi- and unicentric amyloid plaques throughout the cerebrum and cerebellum with varying degrees of spongiform degeneration. Genetic and molecular studies were performed in two male family members. One of them was homozygous for valine and the other heterozygous for methionine and valine at codon 129 of PRNP. Sequence analysis identified a novel 168 bp insertion [R2–R2–R2–R2–R3g–R2–R2] in the octapeptide repeat region of PRNP. Both patients carried the mutation on the allele with valine at codon 129. Western blot analysis showed type 1 PrPSc in both patients and detected a smaller ~8 kDa PrPSc fragment in the cerebellum in one patient. The features of this Dutch kindred define an unusual neuropathological phenotype and a novel PRNP haplotype among the previously documented 7-OPRI mutations, further expanding the spectrum of genotype–phenotype correlations in inherited prion diseases