María J. Sedano

Rituximab in treatment-resistant CIDP with antibodies against paranodal proteins.

Objective: To describe the response to rituximab in patients with treatment-resistant chronic inflammatory demyelinating polyneuropathy (CIDP) with antibodies against paranodal proteins and correlate the response with autoantibody titers. Methods: Patients with CIDP and IgG4 anti–contactin-1 (CNTN1) or anti–neurofascin-155 (NF155) antibodies who were resistant to IV immunoglobulin and corticosteroids were treated with rituximab and followed prospectively. Immunocytochemistry was used to detect anti-CNTN1 and anti-NF155 antibodies and ELISA with human recombinant CNTN1 and NF155 proteins was used to determine antibody titers. Results: Two patients had a marked improvement; another patient improved slightly after 10 years of stable, severe disease; and the fourth patient had an ischemic stroke unrelated to treatment and was lost to follow-up. Autoantibodies decreased in all patients after rituximab treatment. Conclusions: Rituximab treatment is an option for patients with CIDP with IgG4 anti-CNTN1/NF155 antibodies who are resistant to conventional therapies. Classification of evidence: This study provides Class IV evidence that rituximab is effective for patients with treatment-resistant CIDP with IgG4 anti-CNTN1 or anti-NF155 antibodies.

Diagnostic strategy for familial and sporadic cases of neuropathy associated with 17p11.2 deletion

Clinical, electrophysiologic and molecular studies were performed on at‐risk members of 14 families with hereditary neuropathy with liability to pressure palsies (HNPP), in order to detect asymptomatic carriers of the 17p11.2 deletion. Sporadic cases due to de novo deletion accounted for 21% of the investigated HNPP families. Approximately one half of deletion carriers were asymptomatic and did not display significant signs on clinical examination. The electrophysiologic hallmark in both symptomatic and asymptomatic deletion carriers was the presence of a nonuniform sensorimotor demyelinating polyneuropathy with conduction abnormalities preferentially located at common entrapment sites and distal nerve segments. A perfect correlation was found between the molecular and electrophysiologic analyses. A reliable screening method to detect clinically unaffected carriers of the deletion in families with HNPP was the evaluation of motor conduction in at least two nerves across usual entrapment sites, especially the ulnar nerve at the elbow, and evaluation of sensory conduction in the sural nerve. In sporadic cases due to a de novo deletion, electrophysiologic studies were suggestive but not sufficient for the diagnosis, and molecular analysis represented the most sensitive diagnostic tool.

Intravenous Lidocaine for Status Epilepticus

Summary: Intravenous lidocaine successfully controlled convulsive status epilepticus in eight patients. Lidocaine was administered, as a diazepam substitute, to elderly patients with chronic obstructive lung disease and to those patients unresponsive to the stated doses of intravenous diazepam. Although transient disappearance of seizures was noted after an initial dose of 100 mg, infusion of 200 mg was necessary to effectively control status. Continuous lidocaine infusion (3.5 mg/kg/h) was used in one case with good results. Undesirable side effects were not seen. The basic mechanisms for possible anticonvulsant action are reviewed. Lidocaine seems to be an effective and safe drug in convulsive status epilepticus. We suggest that lidocaine may be used as a first‐line drug, as a diazepam substitute, in the treatment of convulsive status epilepticus in patients in whom respiratory depression is undesirable and in those who do not respond to intravenous diazepam.

Progressive multifocal leukoencephalopathy and idiopathic CD4 lymphocytopenia

Idiopathic CD4 lymphocytopenia (ICL) is a syndrome described in patients with low counts of CD4 cells and no other causes for immunosuppression. A few cases of progressive multifocal leukoencephalopathy (PML) have been described in association with this entity. There is no effective treatment for any of them, and the clinical course and outcome are unpredictable. We report on a case of ICL with PML and review the literature, trying to identify the clinical features and the prognosis clues associated to these entities together. A 72-year-old man presented with acute onset gait instability that progressed to a severe cerebellar syndrome with cognitive decline. A cranial MRI showed findings consistent with PML, this diagnosis being confirmed by CSF analyses. Absolute number of CD4+ was 242 cells/μL. An extensive work-up including HIV tests was negative. Ten cases of PML and ICL have previously been reported. Factors contributing to the different outcomes are unknown. Although an effective treatment does not exist for PML, it has been recently demonstrated in vitro that several 5HT2A-receptor antagonists block the JC virus infection. Our patient greatly improved and remains stable 34 months after onset; we describe the potential role of mirtazapine in the treatment of PML.

LONG-TERM OUTCOME IN CHRONIC INFLAMMATORY DEMYELINATING POLYNEUROPATHY PATIENTS TREATED WITH INTRAVENOUS IMMUNOGLOBULIN: A RETROSPECTIVE STUDY

Introduction: The objective of this retrospective study was to describe the short‐ and long‐term patterns of IVIg use, safety, and response to treatment in patients with chronic inflammatory demyelinating polyneuropathy (CIDP). Methods: Response to therapy was defined as an improvement of ≥1 point on the modified Rankin score at short‐ and mid‐term visits. Patient status at long term was classified as remission, stability, or non‐responder. Results: Eighty‐six patients were included; 60.5% responded at short term and 54.6% at mid‐term. At long term, 25.6% of patients were in remission, 65.1% were stable, and 9.3% were non‐responders. The only variable associated with remission was a better response during the first 6 months of follow‐up. Conclusions: A significant percentage of patients did not require any additional drugs in the long term. This suggests that treatment effect or disease outcome may be stable over time, and treatment regimens should therefore be individualized to avoid overtreatment. Muscle Nerve 48: 870–876, 2013

Early axonal Guillain-Barré syndrome with normal peripheral conduction: imaging evidence for changes in proximal nerve segments

In early Guillain-Barre syndrome (GBS), including in its axonal forms, the most frequent electrophysiological findings are abnormalities of late responses (H reflex and F response) pointing to dysfunction in the proximal segments of the peripheral nerves.1 Ultrasonography and MRI are the imaging techniques of choice in any pathology of the peripheral nerve trunks.2 We report nerve imaging findings in a patient with early axonal GBS. An 18-year-old woman was admitted with a 1-day history of lower limb weakness and calf myalgias. Two weeks prior, she had an episode of profuse diarrhoea of 4-day duration attended at home by her family physician; stool culture was not carried out. Initial examination revealed a waddling gait, weakness of proximal lower limb muscles mainly involving ilio-psoas (Medical Research Council grade 4/5), lower limb areflexia and absence of sensory loss. Upper limb reflexes were brisk. In the next few days the patients lower limb weakness progressed, so that on day 6 after onset she was unable to walk, her muscle power being 2–3/5 proximally and 3–4/5 distally. Treatment with standard intravenous immunoglobulin (2 g/kg in 5 days) was administered. There has been progressive improvement; 3 months after onset, examination revealed mild waddling gait, paresis of hip abductors/flexors (3–4/5) and foot dorsiflexors (4/5), and lower limb areflexia. No serum IgG antiganglioside antibodies were detected. Campylobacter jejuni serology was not available. Cerebrospinal fluid showed a protein content of 70 mg/dL and no cells. Sequential nerve conduction …

Comment on paraparetic Guillain-Barré syndrome: Non-demyelinating reversible conduction failure restricted to the lower limbs: Letter to the Editor

We read with interest the study by Kimachi and colleagues in which they described a case of paraparetic Guillain–Barr e syndrome (GBS). Serial nerve conduction studies (NCS) showed non-demyelinating, reversible conduction block, and axonal degeneration in lower limb motor nerves. Magnetic resonance imaging (MRI) of the lumbar spine with gadolinium contrast showed enhancement of ventral spinal nerve roots. They concluded that patients with paraparetic GBS have axonal neuropathy, which is restricted to the lower limbs. Having recently reported a similar case, we offer some brief comments. Our patient was an 18-yearwoman admitted with a 1-day history of lower limb weakness and myalgias. She had a waddling gait, weakness of proximal lower limb muscles, lower limb areflexia, and no sensory loss. Upper limb reflexes were brisk. In the next few days her lower limb weakness progressed, so that, on day 6 after onset, she was unable to walk. No serum IgG antiganglioside antibodies were detected. On day 4, she had absent H-reflexes, but the remaining NCS were normal. On days 12 and 42, there was a reduction of compound muscle action potentials of the tibial and fibular nerves. On day 4, MRI of the lumbosacral spine showed contrast enhancement of the ventral roots. Ultrasonography findings were normal in upper and lower limb nerves; conversely, sonograms of ventral rami of C5–C7 nerves showed widespread changes (see Fig. 1 in the study by Berciano et al.). We concluded that this patient had paraparetic GBS, which could be categorized as acute motor axonal neuropathy (AMAN). The aforementioned MRI studies corroborate that contrast enhancement of intrathecal ventral spinal roots is an almost constant finding in early AMAN. Furthermore, ultrasonography revealed widespread changes in ventral rami of C5–C7 nerves, a finding that correlates well with autopsy studies in early GBS, suggesting that lesions are more prominent where the motor and sensory roots join to form the spinal nerve. Therefore, and in reference to the early stage of paraparetic GBS, we propose the following: (1) there may be isolated absence of H-reflexes, indicating that the pathogenic lesions could localized to anterior spinal roots, ventral rami of spinal nerves, or both; (2) there may be a dual mechanism of muscle weakness: distal conduction failure associated with either non-demyelinating reversible conduction failure or Wallerian-like degeneration, and proximal conduction block induced by spinal nerve inflammatory edema; and (3) abnormal sonograms of the ventral rami of C5–C7 nerves indicate that lesions, although subclinical, are not restricted to the lower limb nerves. In paraparetic GBS, Ropper and colleagues found that back, leg, or sciatic pain preceded weakness in all cases. Although this fits well with previous reports, it should be recognized that nerve trunk pain is an unexpected event in any “pure” motor syndrome like AMAN. Its pathogenic basis remains unsettled. We have proposed that extension of the inflammatory process from ventral rami of spinal nerves to abutting dorsal rami may be responsible for such pain in early GBS.

Nerve ultrasonography in early Guillain-Barré syndrome: a need for large prospective studies

Dear Editor, We read with interest the article by Grimm et al. (2014) describing the role of nerve ultrasonography in the acute phase of Guillain-Barré syndrome (GBS). We wish to call attention to the paper by Gallardo et al. (2014), published online on August 21, 2014, describing clinico-electrophysiological, ultrasonographic, and pathological studies in six consecutive early GBS patients. As in the Grimm et al. (2014) report, our study revealed ultrasonographic changes in cervical nerves (fifth to seventh) in four patients, which included significant increase of cross-sectional area, blurred boundaries of the corresponding ventral rami, or both. Autopsy study in one case showed widespread endoneurial inflammatory changes in cervical and lumbar nerves extending to epi-perineurium, this feature accounting for the observed loss of physiologic hyper-echoic epineurial rim. Such spinal nerve features corroborate the description by Haymaker and Kernohan (1949): “As a whole, the observed pathological changes were usually more prominent in the region where the motor and sensory roots join to form the spinal nerve. They occurred to a diminishing degree in the adjacent parts of the spinal roots, especially the anterior roots, and seldom reached the most proximal portion of the root.” Grimm et al. (2014) found that on ultrasonography there was significant increase of cross-sectional area in all scanned nerves excepting for ulnar nerve in upper limbs and sural nerve in lower limbs. Contrariwise, in our series upperand lower-limb nerve ultrasonography showed abnormal cross-sectional area (over mean+ 2SD) in just 8.8% of scanned nerves (Gallardo et al., 2014). Clearly, we need large and prospective ultrasonographic studies in GBS so that we can understand this better. Such studies should be done on a multinational, multicenter basis.

ID 79 – The usefulness of miotatic electronic reflex (T-reflex) in early stages of Guillain Barre syndrome. A case report

Objective Guillain-Barre Syndrome (GBS) diagnosis in its early stages remains a clinical challenge and thus new diagnostic techniques need to be incorporated. The aim of this work is to evaluate the usefulness of miotatic electronic reflex (T-reflex) in initial phases of GBS. Methods A 46-year-old woman was admitted with 7 days of distal paresthesias and intense interscapular pain. Serial electrodiagnostic studies (EDX) on 7th & 33rd day following clinical onset included motor and sensory nerve conduction, somatosensory evoked potentials (SEP) and T-reflex. Results First study showed minimal abnormalities in proximal motor nerve conduction (appearance of A waves and inconsistent F waves) and abolition of Achilles T-reflex bilaterally. Central and peripheral sensory nerve studies were normal. Second study (3 weeks after immunoglobulin treatment) showed disappearance of abnormalities detected in proximal motor nerve conduction and “ad integrum” recovery of Achilles T-reflex. Conclusions T-reflex provides a complete study of the miotatic reflex including 1A sensory fibers unexplored by conventional EDX. Therefore, this test can contribute to GBS diagnosis in its early stages and, as in this case, suggests the presence of dorsal roots conduction block. Thus, it would be desirable to incorporate T-reflex in GBS studies.