Takahide Nagashima

Clinical correlates of serum anti-GT1a IgG antibodies

Patients with the pharyngeal-cervical-brachial variant (PCB) of Guillain-Barré syndrome (GBS) have anti-GT1a IgG with or without GQ1b reactivity, whereas those with Fisher syndrome (FS) or Bickerstaffs brainstem encephalitis (BBE) have anti-GQ1b IgG antibodies which cross-react with GT1a. The nosological relationship between these conditions has yet to be established. To investigate the relationships between each manifestation and between clinical features and the coexistence of anti-GQ1b IgG, we reviewed neurological signs present during illnesses of 140 patients who had anti-GT1a IgG. Based on our criteria, FS was diagnosed for 64 (46%) patients, GBS for 22 (16%), BBE for 14 (10%), and PCB for 6 (4%). Overlapping conditions were diagnosed for some patients: FS and GBS (5%), PCB and FS (5%), BBE and GBS (4%), and PCB and BBE (1%). Patients who initially had bulbar palsy developed not only PCB but FS or BBE. The population of anti-GT1a-positive patients frequently had ophthalmoplegia, ataxia, and areflexia, whereas the subpopulation who had anti-GT1a IgG without GQ1b reactivity frequently had preceding diarrhea as well as oropharyngeal, neck, and limb weakness. Patients with anti-GT1a IgG presented a variety of clinical conditions, indicative of a continuous clinical spectrum. A major part of this clinical variation was due to the coexistence of anti-GQ1b IgG. The presence of a common autoantibody (anti-GT1a IgG) and overlapping illnesses suggests that PCB is closely related not only to GBS but to FS and BBE as well.

Reference values for voluntary and stimulated single-fibre EMG using concentric needle electrodes: A multicentre prospective study

OBJECTIVE The aim of this study is to establish reference values for single-fibre electromyography (SFEMG) using concentric needles in a prospective, multicentre study. METHODS Voluntary or stimulated SFEMG at the extensor digitorum communis (EDC) or frontalis (FRO) muscles was conducted in 56-63 of a total of 69 normal subjects below the age of 60years at six Japanese institutes. The cut-off values for mean consecutive difference (MCD) of individual potentials were calculated using +2.5 SD or 95% prediction limit (one-tail) of the upper 10th percentile MCD value for individual subjects. RESULTS The cut-off values for individual MCD (+2.5 SD) were 56.8μs for EDC-V (voluntary SFEMG for EDC), 58.8μs for EDC-S (stimulated SFEMG for EDC), 56.8μs for FRO-V (voluntary SFEMG for FRO) and 51.0μs for FRO-S (stimulated SFEMG for FRO). The false positive rates using these cut-off values were around 2%. CONCLUSIONS The +2.5 SD and 95% prediction limit might be two optimal cut-off values, depending on the clinical question. The obtained reference values were larger than those reported previously using concentric needles, but might better coincide with conventional values. SIGNIFICANCE This is the first multicentre study reporting reference values for SFEMG using concentric needles. The way to determine cut-off values and the statistically correct definition of the percentile were discussed.

Various immunization protocols for an acute motor axonal neuropathy rabbit model compared

Various ganglioside immunization protocols were examined to refine the procedure for establishing an animal model of acute motor axonal neuropathy. The most effective was subcutaneous injection of an emulsion of 2.5mg of bovine brain ganglioside mixtures, keyhole lympet hemocyanin, and complete Freunds adjuvant to Japanese white rabbits, repeated at 3-week intervals. Under that protocol, all the rabbits developed marked flaccid paralysis associated with plasma anti-GM1 IgG antibody. This acute motor axonal neuropathy rabbit model also could be reproduced by the use of incomplete Freunds adjuvant, methylated bovine serum albumin, and New Zealand white rabbits. These results provide useful information for the confirmation of and further research on the model.

Recurrent aseptic meningitis in association with Kikuchi-Fujimoto disease: case report and literature review

BackgroundKikuchi Fujimoto disease (KFD), or histiocytic necrotising lymphadenitis, is a benign and self-limiting condition characterised by primarily affecting the cervical lymph nodes. Recurrent aseptic meningitis in association with KFD is extremely rare and remains a diagnostic challenge.Case presentationWe report a 28-year-old man who presented 7 episodes of aseptic meningitis associated with KFD over the course of 7 years. Histopathological findings of enlarged lymph nodes led to the diagnosis of KFD. The patient’s headache and lymphadenopathy spontaneously resolved without any sequelae.ConclusionsA diagnosis of KFD should be considered when enlarged cervical lymph nodes are observed in patients with recurrent aseptic meningitis. A long-term prognosis remains uncertain, and careful follow-up is preferred.

Paraparetic Guillain-Barré syndrome: Extending the axonal spectrum

There are few reports of the paraparetic variant of Guillain‐Barré syndrome, and its pathophysiology is not well understood. We report a patient presenting with acute paraparesis following diarrhea. Serial nerve conduction studies suggested primary axonal injury, and not demyelination, predominantly in the lower limbs compared with the upper limbs. There was serological evidence of recent Campylobacter jejuni infection and strongly positive immunoglobulin G anti‐GD1a antibodies. Paraparetic Guillain‐Barré syndrome is likely to represent a regional form of Guillain‐Barré syndrome, with a nosological position within the axonal subtype.

Clinical classification of 103 Japanese patients with Guillain-Barré syndrome

Guillain-Barré syndrome (GBS) is the commonest cause of flaccid paralysis worldwide. Miller Fisher syndrome (MFS) is a variant of GBS characterized by ophthalmoplegia and ataxia. Together GBS and MFS form a continuum of discrete and overlapping subtypes, the frequency of which remains unknown. We retrospectively analysed the clinical features (antecedent symptoms, pattern of neurological weakness or ataxia, presence of hypersomnolence) of 103 patients at a single hospital in Japan. Patients were then classified according to new diagnostic criteria (Wakerley et al., 2014). Laboratory data (neurophysiology and anti-ganglioside antibody profiles) were also analysed. According to the new diagnostic criteria, the 103 patients could be classified as follows: classic GBS 73 (71%), pharyngeal-cervical-brachial weakness 2 (2%), acute pharyngeal weakness 0 (0%), paraparetic GBS 1 (1%), bifacial weakness with paraesthesias 1 (1%), polyneuritis cranialis 0 (0%), classic MFS 18 (17%), acute ophthalmoparesis 1 (1%), acute ptosis 0 (0%), acute mydriasis 0 (0%), acute ataxic neuropathy 1 (1%), Bickerstaff brainstem encephalitis 3 (3%), acute ataxic hypersomnolence 0 (0%), GBS and MFS overlap 1 (1%), GBS and Bickerstaff brainstem encephalitis overlap 1 (1%), MFS and pharyngeal-cervical-brachial weakness overlap 1 (1%). Application of the new clinical diagnostic criteria allowed accurate retrospective diagnosis and classification of GBS and MFS subtypes.

Diffusion-weighted MRI abnormalities antedate the onset of sporadic Creutzfeldt-Jakob disease

Sporadic Creutzfeldt-Jakob disease (sCJD) is a fatal progressive neurodegenerative disease that presents with progressive dementia and is accompanied by behavioral and psychiatric features and myoclonus. Multimodal approaches, such as EEG, diffusion-weighted imaging (DWI) of brain MRI, and CSF examinations, have been applied to increase the diagnostic accuracy of sCJD. Previous studies have suggested that DWI MRI could be the most useful modality for sCJD diagnosis.1–3 Recently, a study that compared MRI and pathologic findings demonstrated that DWI signal changes correlated with the disease duration and the histopathologic degree of spongiosis.4 However, when DWI signal changes emerge during the prodromal or incipient phase of sCJD remains unclear. Here, we present serial MRI findings acquired from a patient with sCJD before and after the onset of clinical symptoms, demonstrating that the emergence of unilateral cortical hyperintensity on DWI antedates the onset of sCJD.

Demyelinating Guillain-Barré syndrome recurs more frequently than axonal subtypes

Guillain-Barré syndrome (GBS) is considered a monophasic disorder yet recurrences occur in up to 6% of patients. We retrospectively studied an Italian-Japanese population of 236 GBS and 73 Miller Fisher syndrome (MFS) patients and searched for factors which may be associated with recurrence. A recurrent patient was defined as having at least two episodes that fulfilled the diagnostic criteria for GBS and MFS with an identifiable recovery after each episode and a minimum of 2months between episodes. Preceding Campylobacter jejuni (C. jejuni) infection and antiganglioside antibodies were also assessed. Seven (3%) recurrent GBS and one (1.4%) recurrent MFS patients were identified. In the individual patient the clinical features during episodes were usually similar varying in severity whereas the preceding infection differed. None of the patients had GBS in one episode and MFS in the recurrence or vice versa. Recurrent GBS patients, compared with monophasic GBS, did not have preceding diarrhea at the first episode and considering the electrophysiological subtypes, acute inflammatory demyelinating polyneuropathies recurred more frequently than axonal GBS (6.5% vs 0.9%, p=0.04). In conclusion in a GBS population with a balanced number of demyelinating and axonal subtypes less frequent diarrhea and demyelination at electrophysiology were associated with recurrence.

Demyelinating hypertrophic inferior alveolar nerve mimicking a nerve tumor.

We herein report a patient with demyelinating inferior alveolar nerve hypertrophy, which was initially suspected to have a nerve tumor. A 39-year-old woman with childhood-onset polyneuropathy presented with tooth pain and visited a dental clinic. An X-ray examination of the mandible revealed enlargement of the mandibular canal, and a nerve tumor was suspected. CT scan and MRI showed hypertrophy of the inferior alveolar nerve along its entire length. We diagnosed the patient with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), which was supported by the spontaneous recovery reported in her childhood, the results from a nerve conduction study and MRI data. CIDP should be considered in the differential diagnosis of mandibular canal enlargement.

P1-06. Two CIDP patients with anti-CNTN1 IgG4 antibodies and nephrotic syndrome

Previous studies showed that CIDP patients with anti-CNTN1 IgG4 antibodies form a specific subtype, which shows subacute progression and poor prognosis. In contrast, nephropathy has been recognized as a rare complication in CIDP and other immune-mediated neuropathies. We here describe two CIDP patients with anti-CNTN1 IgG4 antibodies and nephrotic syndrome. The patients were 35- (P1) and 69-year-old (P2) males. Both patients developed subacute course of sensory and motor neuropathy. In parallel with neuropathy course, nephrotic syndrome was present. Nerve conduction studies revealed severe demyelinating polyneuropathy. The disease showed resistance to IVIg, cortico steroids, plasma exchange and cyclosporine, and the severe sensory disturbance and muscle atrophies were left. High titer of anti-CNTN1 IgG4 antibodies was detected in their serum. Renal biopsy in P1 showed membranous nephropathy with the deposition of IgG1 and IgG4 on the glomerular-basement membrane. These findings arise a possibility of existence of shared antigen between peripheral nerve and renal glomerular-basement membrane.