Tomoko Nakazato

Case of Morvan syndrome with anti-Ma2/Ta antibodies

The anti‐paraneoplastic (Ma2/Ta) antibody is related to testicular, lung and ovarian cancers, and might cause paraneoplastic neurological disorders.

Demyelinating Peripheral Neuropathy Due to Renal Cell Carcinoma

Renal cell carcinoma (RCC) patients who develop a paraneoplastic syndrome may present with neuromuscular disorders. We herein report the case of a 50-year-old man who suffered from progressive gait disturbance and muscle weakness. The results of a nerve conduction study fulfilled the criteria of chronic inflammatory demyelinating polyneuropathy. An abdominal CT scan detected RCC, the pathological diagnosis of which was clear cell type. After tumor resection and a single course of intravenous immunoglobulin therapy, the patients symptoms drastically improved over the course of one year. The patients neurological symptoms preceded the detection of cancer. A proper diagnosis and the initiation of suitable therapies resulted in a favorable outcome.

Lymphomatoid Granulomatosis with Central Nervous System Involvement Successfully Treated with Cyclophosphamide, High-dose Cytarabine, Dexamethasone, Etoposide, and Rituximab (CHASER therapy) Followed by Brain Irradiation: A Case Study

Lymphomatoid granulomatosis (LYG) is a rare subtype of diffuse large B-cell lymphoma. It is an extranodal angiocentric and angiodestructive lymphoproliferative disease involving the lungs, skin, and central nervous system (CNS), including abundant reactive T cells with varying numbers of atypical clonal Epstein–Barr virus (EBV)-infected B cells [1]. Clinical diagnosis of LYG is difficult because of a lack of characteristic manifestations, suitable laboratory tests, and imaging findings. No optimal treatment for LYG has yet been established, especially in cases involving the CNS. Several previous reports of rituximab monotherapy, rituximab-containing chemotherapy, interferon alpha-2b, or hematopoietic stem cell transplantation have been published [2], as well as a report of cyclophosphamide (CPM), high-dose cytarabine, dexamethasone, etoposide, and rituximab (CHASER therapy) for lung lesions of LYG [3]. Spontaneous remission has also been reported in patients with LYG involving the CNS and lungs [4]. Here, we describe a case of LYG with lung onset responsive to corticosteroid treatment, but with subsequent CNS involvement resistant to corticosteroid and rituximab monotherapy, which was successfully treated with CHASER therapy followed by brain irradiation. We also propose the value of repetitive evaluation of specimens and gradient-echo T2*-weighted magnetic resonance imaging (T2*-MRI) for diagnosis of CNS involvement in LYG (CNS–LYG). A healthy 40-year-old woman presented with persistent fever, cough, and dyspnea 2 years before admission to our hospital. Thoracic computed tomography (CT) performed at a local hospital revealed diffuse ground-glass opacity with nodular lesions in both lungs (Figure 1A). Blood examination showed highly elevated soluble interleukin-2 receptor (11,726 U/ml), and slightly elevated aspartate aminotransferase (86 IU/L) and alanine transaminase (131 IU/L). EBV antiviral capsid antigen (VCA) IgG and Epstein–Barr nuclear antigen (EBNA) were positive, and EBV anti-VCA IgM was negative, indicating past EBV infection. Pathological diagnosis was performed using videoassisted thoracic surgery (VATS), revealing atypical large lymphoid cells infiltrating the regions around the blood vessels (Figure 2A). These infiltrating lymphocytes comprised a large number of CD3-positive T cells and a few large CD20-positive B cells (Figure 2B). However, the lymphocytes were negative for EBV-encoded small RNA (EBER) according to in situ hybridization. Although LYG was suspected from the results, a definitive diagnosis was not made at the time. Prednisolone (50 mg/day; 1 mg/kg/day) was administered orally. The patient’s fever and respiratory symptoms disappeared and thoracic CT revealed disappearance of the bilateral nodular lesions (Figure 1B). However, 1 month after initiation of steroid therapy, prednisolone was tapered to 30 mg/day and she developed neurological deficits, including left facial dysesthesia, dysarthria, and gait disturbance due to left dominant spastic paraplegia, limb ataxia, and sensory disturbance. CPM (100 mg/day) was added and prednisolone was repeatedly increased or decreased from 50 to 2.5 mg/day, with no improvement. The patient was therefore

Analysis of non-traumatic truncal back pain in patients who visited an emergency room

To investigate epidemiology of acute non‐traumatic back pain using modern diagnostic methods in patients who visited an emergency room.

Cerebellar ataxia and the “hot cross bun” sign in association with human immunodeficiency virus infection

A 32-year-old man with human immunodeficiency virus (HIV) infection developed progressive cerebellar ataxia. His CD4 cell count was 245 cells/lL, and a screen for opportunistic infections, including JC virus (JCV), was negative. Cranial magnetic resonance imaging (MRI) showed mild atrophy of the cerebellar vermis and hyperintensity of the left middle cerebellar peduncle (Fig. 1a–c). Highly active antiretroviral therapy successfully suppressed cerebellar ataxia progression. MRI carried out 1 year after symptom onset showed the “hot cross bun” (HCB) sign (Fig. 1d–f), and the patient remained negative for opportunistic infections. Although HCB is typically detected in multiple system atrophy, Yadav et al. also reported it in progressive multifocal leukoencephalopathy (PML). The present case shows that the HCB sign could also be associated with cerebellar ataxia in HIV infection. Repeated surveillance for JCV infection is required to exclude PML and other JCVassociated cerebellar disorders including JCV granule cell neuronopathy.

Spinal cord concussion induced by neck massage.

This report provides additional evidence concerning spinal cord injuries induced by neck massage, following previous reports in the Annals of Physical and Rehabilitation Medicine [2]. A 65-year-old female with hypertension, hyperlipidemia, impaired glucose tolerance and a history of femoral hip joint replacement following an accidental femur fracture at 55 years of age received a cervical massage from her husband for her neck stiffness while sitting on the floor in the cervical flexure position due to pain in the neck and shoulders. The massage was performed in such a manner that her husband pressed her posterior neck and upper back gently with a thermoregulating roller. After the massage, the patient felt severe upper back pain

T44. Abnormalities of motor axonal properties in amyotrophic lateral sclerosis

Introduction To date, changes of axonal sodium and potassium currents have been reported in amyotrophic lateral sclerosis (ALS) (Bostock et al., 1995; Kanai et al., 2006), and the association to prognosis and characteristic symptoms such as fasciculations has been discussed. To confirm the previously reported changes, multiple axonal excitability properties were measured in patients with ALS, and compared with age-matched controls. Methods A total of 55 patients with sporadic ALS, who visited to Juntendo University Hospital from 2013 to 2017, were included in the study. Multiple excitability measurements were performed in the median nerve at the wrist using a computerized program (QTRAC with multiple excitability protocol, Institute of Neurology, London, UK). Results The age range of the patients was from 30 to 82 years old (median 62.7 years old), and there were 31 male and 24 female. As clinical phenotypes, 13 patients were bulber onset type, 31 were upper limbs onset type, 9 were lower limbs onset type, and 2 were multiple onset type. In ALS, there were extremely greater changes in depolarizing threshold electrotonus ( P P P Conclusion This study suggested increased persistent sodium currents and reduced potassium currents in motor axons, as well as previous studies. Both of these changes lead to axonal hyperexcitability, and may contribute to the generation of fasciculations. Because neuronal hyperexcitibility is one of hypotheses of cause of neuronal death in ALS, these changes may also contribute motor neuronal death in ALS.

T36. Motor axonal abnormalities in anti-MAG neuropathy

Introduction Anti-MAG antibody was known to be associated with polyneuropathy associated with immunoglobulin M (IgM) monoclonal gammopathy of undetermined significance, as we call anti-MAG neuropathy. Anti-MAG neuropathy is pathologically characterized by the presence of widely spaced myelin (WSM), which affects the structure of nodes of Ranvier. To help understand the physiological actions of anti-MAG antibody and WSM, we examined the effects on the excitability properties of peripheral motor axons. Methods Four patients with anti-MAG neuropathy were studied. Multiple excitability measurements were made in the median nerve at the wrist, using computerized threshold-tracking (QTRACS with TRONDNF excitability protocol), and compared with normal control data. Subsequently we performed mathematical modeling of the excitability data, using the Bostock model of the human motor axon to simulate axonal excitability measurements (QTRACP with MEMFIT). Results Nerve excitability studies showed significantly smaller supernormality in recovery cycle and greater changes in excitability with depolarizing currents in threshold electrotonus. Mathematical modeling suggested that the results could be partially explained by abnormal fast K+ current and/or Na+ current at nodes of Ranvier. Conclusion This study showed that patients with anti-MAG neuropathy exhibit abnormalities in their motor axons attributable to ion channel dysfunction at nodes. This suggests that anti-MAG antibody causes physiological dysfunction of nodes via changes caused by WSM in peripheral nerve.

3-2-01. Decreased motor axonal potassium currents in peripheral nerve hyperexcitability syndrome with negativity for anti-VGKC antibody and positivity for anti-CRMP5 antibody

Peripheral nerve hyperexcitability (PNH) syndromes are caused by spontaneous discharges originating from motor axons. Antibodies against voltage-gated potassium channels (VGKC) are detected in some patients with PNH syndrome, but the cause in the remaining patients has not yet been clarified. The index patient was a 46-year-old female with recurred thymoma and myasthenia gravis. Six month after the start of chemotherapy, she developed myokymia, fasciculations and muscle cramps in both her lower limbs. A nerve conduction studies revealed mild axonal polyneuropathy and a motor F-wave examination showed marked after-discharges. Needle electromyography showed fasciculation potentials and myokymic discharges. From these results, the patient was diagnosed with PNH syndrome. Nerve excitability study showed extremely greater supernormality in the recovery cycle and greater changes in depolarizing threshold electrotonus than control, suggesting decreased slow potassium currents in the motor axons. Serological tests revealed the absence of anti-VGKC antibody and the presence of anti-collapsin response mediator protein 5 (CRMP5) antibody. A recent study reported that CRMP5 plays an important role in axon–Schwann cell cooperation during development and nerve regeneration. The coexistence of nerve regeneration and anti-CRMP5 antibody may cause abnormal axon–Schwann cell interaction, which would result in slow potassium channel dysfunction and associated symptoms such as myokymia.

P256 Increased Barrett-Barrett conductance in motor axons of patients with anti-gad antibody

Objective Neurological disorders associated with anti-glutamic acid decarboxylase (GAD) antibody are diverse, including stiff-person syndrome, autoimmune cerebellar ataxia and epilepsy. To help understand the physiological actions of anti-GAD antibody, we examined the effects of the antibody on the excitability properties of peripheral motor axons. Methods Nine patients positive for anti-GAD antibody and without diabetic mellitus were studied. Multiple excitability measurements were made in the median nerve at the wrist, using computerized threshold-tracking (QTRACS with TRONDNF excitability protocol), and compared with normal control data. Subsequently we performed mathematical modeling of the excitability data, using the Bostock model of the human motor axon to simulate axonal excitability measurements (QTRACP with MEMFIT). Results Nerve excitability studies showed greater supernormality in recovery cycle and greater changes in excitability with polarizing currents in threshold electrotonus. Mathematical modeling indicated that the results could best be explained by an increase in the Barrett-Barrett conductance across the myelin sheath. Discussion The abnormalities are remarkably similar to those previously reported in episodic ataxia Type 2 (Tomlinson et al. Brain 2016;139:380–91) and attributed to nodal malformation. Conclusion This study showed that patients with anti-GAD antibody exhibit abnormalities in their motor axons attributable to an increase in Barrett-Barrett conductance. This in turn suggests that anti-GAD antibody causes Schwann cell dysfunction via changes in the GABAergic system of peripheral nerve. Significance The results of this study raise the possibility that anti-GAD antibody causes some clinical symptoms by affecting glial GABAergic systems.