Tomoko Komagamine

The crucial role of Campylobacter jejuni genes in anti-ganglioside antibody induction in Guillain-Barre syndrome

Molecular mimicry of Campylobacter jejuni lipo-oligosaccharides (LOS) with gangliosides in nervous tissue is considered to induce cross-reactive antibodies that lead to Guillain-Barre syndrome (GBS), an acute polyneuropathy. To determine whether specific bacterial genes are crucial for the biosynthesis of ganglioside-like structures and the induction of anti-ganglioside antibodies, we characterized the C. jejuni LOS biosynthesis gene locus in GBS-associated and control strains. We demonstrated that specific types of the LOS biosynthesis gene locus are associated with GBS and with the expression of ganglioside-mimicking structures. Campylobacter knockout mutants of 2 potential GBS marker genes, both involved in LOS sialylation, expressed truncated LOS structures without sialic acid, showed reduced reactivity with GBS patient serum, and failed to induce an anti-ganglioside antibody response in mice. We demonstrate, for the first time, to our knowledge, that specific bacterial genes are crucial for the induction of anti-ganglioside antibodies.

Ganglioside mimicry as a cause of Guillain-Barré syndrome.

PURPOSE OF REVIEW Campylobacter jejuni is the most frequent agent of antecedent infection in an axonal variant of Guillain-Barré syndrome, acute motor axonal neuropathy, and anti-GM1 or anti-GD1a IgG antibody is also associated with acute motor axonal neuropathy. Molecular mimicry has been found between human GM1 ganglioside and the lipo-oligosaccharide of C. jejuni isolated from an acute motor axonal neuropathy patient. Progress has been made in Guillain-Barré syndrome research, especially on acute motor axonal neuropathy subsequent to C. jejuni enteritis. RECENT FINDINGS Sensitization of rabbits with C. jejuni lipo-oligosaccharide, as well as GM1, induced the production of anti-GM1 IgG antibody, and the subsequent development of acute flaccid paralysis. Pathological changes in rabbit peripheral nerves were identical to those seen in human acute motor axonal neuropathy. These findings provide conclusive evidence that molecular mimicry is a cause of human autoimmune disease. Ganglioside-like lipo-oligosaccharide is synthesized by sialyltransferase Cst-II, N-acetylgalactosaminyl-transferase CgtA, and galactosyltransferase CgtB. There is a strong association between the simultaneous presence of these genes and Guillain-Barré syndrome-associated C. jejuni strains. Knockout mutants of C. jejuni genes involved in lipo-oligosaccharide sialylation had reduced reactivity with anti-GM1 sera from Guillain-Barré syndrome patients, and did not induce an anti-GD1a IgG antibody response in mice. Lipo-oligosaccharide biosynthesis genes appear to be essential for the induction of anti-GM1 or anti-GD1a IgG antibody and the subsequent development of acute motor axonal neuropathy. SUMMARY The concept that carbohydrate mimicry causes autoimmune disease provides a clue to the resolution of the pathogenesis of other immune-mediated diseases.

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.

Oseltamivir-induced dyskinesia in Parkinson’s disease

Oseltamivir is widely used for the treatment of influenza, and Japan is known to be the country with the highest usage of this drug worldwide [1]. However, there are concerns regarding the abnormal behavior that is sometimes associated with oseltamivir treatment during influenza virus infection, especially in children and adolescents [2,3]. We report the first case in which a marked improvement in parkinsonism with an increase in dyskinesia was observed in a Parkinson’s disease (PD) patient following the administration of oseltamivir for influenza infection. Our department followed a 63-year-old woman with a 25-year history of PD symptoms. Five years after the initial onset of symptoms, motor fluctuation occurred. Seventeen years after the disease onset, her dyskinesia improvedwith the reduction of dopaminergic treatment, but she became akinetic. Therefore, she was treated with bilateral subthalamic nucleus deep brain stimulation (STN DBS). After surgery, her akinesia improved, but she was still impaired by bradykinesia: she was usually in a wheel chair and was only able to walk with a cane or pushcart. Her medications included levodopa/carbidopa (300 mg), pramipexole (4.5 mg), selegiline hydrochloride (5 mg) and zonisamide (25 mg). In February 2009, she presented to her local clinic with a high fever (39 C) (see Fig. 1). The Influenza B virus was detected, and 75 mg of oseltamivir was subsequently administered twice daily (for five days). In the evening on the first day of treatment she displayed abnormal behaviors. Risking serious injury, she rapidly ran up anddown the stairs for no apparent reason. Subsequently, unpredictable dyskinesia developed. Two days later, she became afebrile. On day 3, she was able to walk independently to the supermarket. On day 6, severe dyskinesia was noted in the limb and trunk in the outpatient clinic (see video, segment 1). She had been taking her dopaminergic medication regularly, and it was confirmed that her DBS system was switched on. Her motor function significantly improved with a reduction in the “off state.” This improvement in motor function lasted for 14 days until the STNDBS systemwas accidentally switched off when she passed through a security device at

Isolated Body Lateropulsion in a Patient with Pontine Infarction

A 72-year-old man with diabetes mellitus and hypertension was admitted to our hospital with lightheadedness. The patient showed lateropulsion to the right side, but his neurological findings were otherwise normal. Brain magnetic resonance images showed a fresh ischemic infarct in the left dorsal part of the lower pons. Body lateropulsion is characterized by an irresistible falling to one side and has been reported in lesions in several brain regions. However, it has rarely been reported in pontine lesions. We suggest that physicians should be aware that pontine lesions can cause isolated body lateropulsion without other neurological deficits.

The ‘Mickey Mouse ears’ sign: a bilateral cerebral peduncular infarction

The literature rarely reports bilateral cerebral peduncular infarction. We report the unique magnetic resonance imaging (MRI) finding of a bilateral cerebral peduncular infarction that simulated a ‘Mickey Mouse ears’ sign. A 62-year-old man with a history of diabetes and hypertension was admitted to our hospital with acute onset vertigo and an unsteady gait. At admission, his blood pressure was 198/118 mmHg, and his pulse rate was 60 beats/min. A neurological examination revealed truncal and bilateral limb ataxia. A diffusionweighted MRI showed an acute infarction in the bilateral cerebellum and occipital lobes (Fig. 1a). On the third day of hospitalization, despite anticoagulation and antiplatelet therapies, consciousness disturbance developed. Although the patient’s extraocular movement was preserved, his light reflexes were sluggish bilaterally. Tetraparesis with bilateral Babinski’s sign was noted. A diffusion-weighted MRI identified an acute bilateral cerebral peduncular infarction that looked like a ‘Mickey Mouse ears’ (Fig. 1b). An MR angiography showed decreased flow signals of the proximal bilateral P1 segments compared with images taken at admission, which showed severe stenosis at the proximal basilar artery and the absence of flow signals from the bilateral P1–P2 junctions of the posterior cerebral artery (Fig. 1c and d). The patient’s neurological symptoms progressed, and the patient died 2 days later. Bilateral cerebral peduncular infarction is extremely rare, and is associated with locked-in syndrome and a persistent vegetative state [1–4]. Table 1 demonstrates previously reported brain computed tomographic (CT) scans, MRI-confirmed bilateral cerebral peduncular infarcts [2,4–7] and pathologically confirmed cases [3,8]. Out of nine patients, five individuals showed locked-in syndrome, and two patients initially had unilateral cerebral peduncular infarcts that progressed bilaterally. Typically, locked-in syndrome has been attributed to ventral pontine lesions [9]. Although additional pontine involvements are shown in Table 1, the reported cases of bilateral cerebral peduncular infarcts without the involvement of the pons or thalamus [6,8], or with small pontine infarcts [7], suggest that cerebral peduncular infarcts are the cause of locked-in syndrome. The bilateral cerebral peduncular lesions without the involvement of the ventral portion of the pons that result in locked-in syndrome are also found in patients with multiple sclerosis [10]. Cerebral peduncles are supplied with blood via the perforating branches of the posterior communicating, posterior cerebral and superior cerebellar arteries or the anterior choroidal artery that branches from the internal carotid artery. In our patient, a decrease in the flow signals of the proximal portions of the P1 segments on the MR angiography corresponded to the occurrence of a bilateral cerebral peduncular infarction. This result suggests that perforating branches of the P1 segments, such as the directly perforating branches and the short circumflex branches, play a major role in supplying the ventral portions of the midbrain. Although rare, the ‘Mickey Mouse ears’ sign might be a reproducible finding. Furthermore, it provides clinical significance for predicting a patient’s symptoms and prognosis.

Selective muscle involvement in a family affected by a second LIM domain mutation of fhl1: An imaging study using computed tomography

Mutations in the four-and-a-half LIM domains 1 gene (fhl1) are associated with various phenotypes of hereditary myopathies, including reducing body myopathy. We describe here a mother, daughter and son suffering from FHL1 myopathy with a mutation in the second LIM domain of fhl1. We investigated whether there is a characteristic muscle involvement in both sexes. Despite the variety of symptoms exhibited by the male and female patients, the systemic imaging studies showed a similar pattern: the flexor muscles of the brachium and thigh were affected earlier than the extensor muscle with a profound degeneration of the paraspinal muscles. These findings may include one of the characteristic clinical features for suspecting a mutation in the second LIM domain.

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.

Temporal changes in the documentation of neurological findings among patients with acute ischaemic stroke in a single centre in Japan: a retrospective cross-sectional study

Objective To evaluate temporal differences in the documentation of neurological findings by the same physicians in patients with ischaemic stroke while in hospital. We also investigated differences in the rate of documentation of neurological findings in patients with stroke between internists and neurosurgeons. Design A retrospective medical chart review. Participants Hospitalised adult patients with acute ischaemic stroke who stayed 7 or more days in our hospital. Neurosurgeons (n=8) and internists (n=19) caring for these patients (including up to 10 patients per physician). Main outcome measures The documentation rate of any neurological finding in the patients on each day (from day 1 to 7 and on discharge). The documentation rates of eight neurological finding components (consciousness, mental status, cranial nerves, motor function, sensory function, coordination, reflexes and gait). We included only documentation by the same physician. Fisher’s exact test was used to evaluate differences in outcomes between neurosurgeons and internists. Results During the study period, we identified 172 patients with stroke who were cared for by 27 physicians. The documentation rates of any neurological findings were 94% (day 1), 58% (day 2), 35% (day 3), 40% (day 4), 32% (day 5), 30% (day 6) and 23% (day 7). On discharge, all eight neurological finding components were documented in less than 10% of all cases. The documentation rate was significantly higher by internists than that by neurosurgeons on each day but not on discharge. Conclusions The documentation rate of neurological findings by physicians during usual stroke care decreased to less than 50% after the third hospital day. Given the importance of temporal changes in the neurological symptoms of patients with stroke, further study is needed to determine whether this low documentation rate after the third hospital day was due to a lack of physician interest in neurological findings or other factors.