Miho Akaza

Failure of mefloquine therapy in progressive multifocal leukoencephalopathy: report of two Japanese patients without human immunodeficiency virus infection.

Although progressive multifocal leukoencephalopathy (PML) cases showing responses to mefloquine therapy have been reported, the efficacy of mefloquine for PML remains unclear. We report on the failure of mefloquine therapy in two Japanese patients with PML unrelated to human immunodeficiency virus. One of the patients was a 47-year-old male who had been treated with chemotherapy for Waldenström macroglobulinemia, and the other was an 81-year-old male with idiopathic CD4(+) lymphocytopenia. Diagnosis of PML was established based on MRI findings and increased JC virus DNA in the cerebrospinal fluid in both patients. Mefloquine was initiated about 5 months and 2 months after the onset of PML, respectively. During mefloquine therapy, clinical and radiological progression was observed, and JC virus DNA in the cerebrospinal fluid was increased in both patients. Both patients died about 4 months and 2 months after initiation of mefloquine, respectively. Further studies are necessary to clarify the differences between mefloquine responders and non-responders in PML.

Motor nerve conduction study in cauda equina with high-voltage electrical stimulation in multifocal motor neuropathy and amyotrophic lateral sclerosis

In this study we aim to establish a motor nerve conduction study (NCS) for the cauda equina and examine its usefulness in multifocal motor neuropathy (MMN) and amyotrophic lateral sclerosis (ALS). NCS of the tibial nerve proximal to the knee was performed with an optimized high‐voltage electrical stimulation (HV‐ES) method in 21 normal subjects, 5 with MMN, and 11 with ALS. HV‐ES, but not magnetic stimulation, could supramaximally stimulate the cauda equina. Cauda equina motor conduction time determined by HV‐ES, but not that with F‐waves, correlated well with cauda equina length on magnetic resonance imaging. HV‐ES revealed proximal lesions in 4 MMN patients but in none of the ALS patients. Importantly, 1 patient with “MMN without conduction block (CB)” had a CB in the cauda equina. Cauda equina motor conduction is better evaluated by HV‐ES than with F‐wave study or magnetic stimulation. HV‐ES can help to distinguish MMN and “MMN without CB” from ALS. Muscle Nerve 43: 274–282, 2011

Chiasmal optic neuritis following mumps parotitis.

JO N 2810 became aware of bitemporal hemianopsia. On ophthalmological examination, the best corrected visual acuity was 20/16 left eye and 20/20 right eye. There was a right relative afferent pupillary defect. Funduscopic examination was normal, and the Goldmann perimetry test revealed bitemporal hemianopsia (Fig. 1A). Pattern-reversal visual evoked potentials by monocular stimulation showed a delayed P100 response from the left eye (latency 118 ms), and barely detectable responses from the right eye. Physical, neurological, and routine laboratory examinations were normal. Cerebrospinal fluid (CSF) analysis was normal (3 cells/mm3, protein 25 mg/dl), and there were no oligoclonal bands. Anti-mumps virus antibodies were elevated in the serum (enzyme-linked immunosorbent assay: IgM = 7.71, normally < 0.8, IgG = 19.9, normally < 2.0), but not in the CSF, on the 16th day of neurological illness. Reverse-transcription polymerase chain reaction detected no mumps genomic RNA in the CSF. Antinuclear antibody, anticardiolipin antibodies, lupus anticoagulant activity, and anti-SS-A/-B antibodies were absent. Serum angiotensin-converting enzyme and lysozyme were within normal ranges. Blood mitochondrial DNA analysis revealed no point mutations responsible for Leber’s hereditary optic neuropathy (LHON). Chest X-ray showed no hilar lymphadenopathy. Brain magnetic resonance imaging (MRI) was normal. However, MRI of the optic nerves revealed an enlarged optic chiasma, with an increased signal intensity on a T2-weighted image, and gadolinium enhancement on a T1weighted image (Fig. 1B, C). We treated the patient with corticosteroids (intravenous methylprednisolone, 1 g daily for 3 days, and then for another 3 days; plus oral prednisolone 60 mg daily followed by Takashi Irioka Miho Akaza Keisuke Nakao Tadashi Kanouchi Takanori Yokota Hidehiro Mizusawa

Dropped head in polymyositis

An 84-year-old man who had a 2-month history of progressive head drop was admitted to our hospital. He had a past history of lung cancer at age 70 and bladder cancer at age 83. He took no medicine that causes muscular disturbance. After he showed dropped head, proximal muscle weakness gradually appeared in his limbs. His symptoms continued to worsen. On admission, a neurological examination revealed severe neck and proximal limb weakness. A muscle manual test showed 2/5 for neck extensors, 3/5 for flexors, 2/5 for deltoid, 4/5 for biceps and triceps brachii, 4/5 for lower extremity muscles, and 4/5 for sternocleidomastoideus and trapezius ones. Neck extensor and proximal limb muscles showed atrophy. Myalgia and grasp pain were apparent at the proximal muscles of the upper limbs. Deep tendon reflexes were diminished. A fine crackle was heard at the base of the lungs. There was no exanthema. Laboratory findings showed an elevated CK of 7,025 IU/L, but normal electrolytes and thyroid tests. Anti Jo-1 and acetylcholine antibodies were negative. A chest X-ray detected bilateral interstitional pneumonia and a respiratory function test restrictive ventilation dysfunction. MRI of the cervical muscles revealed inflammation of the neck extensors (Fig. 1). Electromyography showed myopathic changes and positive sharp waves at the deltoid, biceps brachii, rectus femoris, and neck extensor muscles. Repetitive nerve stimulation studies and the edrophonium test were negative. Muscle biopsy of the right brachial muscle showed irregular muscle fiber size, necrotic fibers, and foci of inflammatory infiltrates composed of T cells in perimysial non-necrotic fibers, consistent with PM, which was the diagnosis based on these results. Before we were to start treatment of PM, in a malignancy investigation colon carcinoma was detected by colon fiber endoscopy. Surgery for colon carcinoma therefore was scheduled first. His PM symptoms continued to worsen during the paraoperative period. He was given a 5-day course of 25 g of intravenous immunoglobulin (IVIg) daily. A few weeks after receiving IVIg, his muscle strength gradually began to improve. Subsequent MRI showed amelioration of the inflammation at his neck extensors. His CK level decreased day by day from 7,000 to 3,000. Twenty-two days after IVIg, administration of steroid at 60 mg/day was begun, after which his symptoms, including dropped head improved.

Deterioration of pre-existing hemiparesis due to an ipsilateral internal capsule infarction after a contralateral stroke

Although hemiparesis due to an ipsilateral brain lesion is rare in clinical practice, various pathomechanisms related to this condition have been reported [1–7]. Above all, deterioration of pre-existing hemiparesis due to an ipsilateral brain infarction after a contralateral stroke has been reported in two studies [1,2]. Agos patient [1], who had left hemiparesis associated with right putaminal hemorrhage, presented with deterioration of the left hemiparesis related to left corona radiata infarction. Songs patient [2], who had left hemiparesis associated with right thalamic hemorrhage, developed worsening of the left hemiparesis due to left corona radiata infarction. In these cases, functional MRI demonstrated activation of the ipsilateral motor cortex during paretic hand movement, suggesting that reorganization of the unaffected hemisphere had occurred after the first stroke, and that a new lesion in the reorganized area resulted in the deterioration of hemiparesis. On the other hand, these studies included no data of motor evoked potentials (MEP) following transcranial magnetic stimulation (TMS). A 79-year-old male noticed the deterioration of the pre-existing left hemiparesis, and was admitted to our hospital the next day. His past medical history included hypertension and right pontine infarction, for which he had been taking a depressor and aspirin. While the right pontine infarction at the age of around 60 had resulted in mild left hemiparesis, he became able to walk with a T-cane during recovery and needed no aid for activities of daily living. A neurological examination on admission demonstrated mild left hemiparesis. There was no visual field defect, facial palsy, dysarthria, sensory disturbance, or muscle weakness of the right limbs. Diffusion-weighted brain MRI showed an acute infarction in the posterior limb of the left internal capsule (Fig. 1A), and T2-weighted MRI demonstrated a previous infarction in the right ventral pons (Fig. 1B). MEP were recorded from the first dorsal interosseus (FDI) muscle using a pair of Ag-AgCl surface electrodes with a standard bellytendon arrangement. TMS was performed by Magstim 2002 (The Magstim Co., Ltd. UK) with a figure-of-8 coil of each loop of 7 cm in diameter (2.2 T) with 100% stimulator output. We placed the center of the coil over the scalp at 7 cm lateral to Cz to stimulate the finger area. We compared areas of the MEP with those of the compound muscle action potentials (CMAP) of the FDI muscle evoked by supramaximal ulnar nerve stimulation at the wrist. We obtained clear MEP of the right FDI muscle when stimulating the left motor cortex. Areas of the MEP were 40.2% of the areas of the CMAP (Fig. 1C). There were no clear MEP of the left FDI muscle when stimulating the left motor cortex

Can anti-AQP4 antibody damage the blood-brain barrier?

Background: Aquaporin 4 (AQP4) is a water-channel protein predominantly expressed in astrocyte end feet that make up the blood-brain barrier (BBB). Recently, anti-AQP4 antibody has been identified as a specific biomarker of neuromyelitis optica (NMO). However, whether anti-AQP4 antibodies damage the BBB is unclear. Methods: We evaluated BBB damage in patients with NMO and multiple sclerosis by measuring albumin leakage (AL) and studied its correlation with anti-AQP4 antibody. Results: No obvious difference in AL was observed between patients with and without anti-AQP4 antibodies. In the multivariate analysis, anti-AQP4 antibody was not associated with BBB damage. Of the anti-AQP4-positive patients, 58.0% had normal AL values, and the degree of BBB damage was unrelated to the anti-AQP4 antibody titer. In addition, 41.9% of anti-AQP4-positive patients showed no gadolinium enhancement of the MRI. Conclusion: These results indicate that the presence of anti-AQP4 antibody alone in plasma is insufficient to disrupt the BBB.

P3-6-03. Visualization of nerve impulse traveling along the brachial plexus after ulnar nerve stimulation using 132ch SQUID magnetoneurography system

Using 132ch superconducting quantum interference device (SQUID) magnetoneurography sensor system, we succeeded in visualizing nerve impulse traveling along the brachial plexus (BP) after median nerve stimulation and propagating into the C5–C8 intervertebral foramen with participant’s X-ray imaging. Here we analyzed the nerve impulse traveling along BP following ulnar nerve stimulation at the wrist. Magnetoneurogram following wrist stimulation were measured over BP from 5 healthy volunteers. Somatosensory evoked potential (SEP) was simultaneously measured at Erb’s point for making sure to deliver supramaximal stimulation. Evoked action currents were estimated offline and superimposed on participant’s X-ray images. Similar to median nerve stimulation, the estimated currents distribution for the ulnar nerve stimulation comprised leading and trailing dipoles which traveled along the BP. Then, the estimated currents propagated into the C7 - Th1 intervertebral foramen. Together with our previous study on magnetoneurogram after median nerve stimulation, we consider magnetoneurogram testing as superior to conventional SEP for analyzing the conductive function of BP because the former enables us to evaluate the conductive function of the nerve from the lateral or medial cord of BP to C5 – Th1 intervertebral foramen after median or ulnar nerve stimulation.

T110. Visualization of nerve impulse traveling along the brachial plexus after ulnar nerve stimulation using magnetoneurography system

Introduction In somatosensory evoked potential (SEP) testing, an analysis of Erb’s potentials following median or ulnar nerve stimulation at the wrist may be useful to define a lesion of the lateral cord or the medial cord of the brachial plexus (BP) neuropathy. However, there have been few SEP studies on multiple site recording of Erb’s potentials so that traveling nature of the nerve impulse along BP has not been visualized yet. By analysis of magnetoneurogram with superconducting quantum interference device (SQUID) sensor system, we succeeded in visualizing the nerve impulse traveling along BP and then propagating into the C5–C8 intervertebral foramen after median nerve stimulation. Here we aimed to analyze the nerve impulse traveling along BP following ulnar nerve stimulation at the wrist. Methods Magnetoneurogram over BP of 5 healthy volunteers (Age range, 25–45 years; mean, 32.8 y.o) were measured after ulnar nerve stimulation (supramaximal stimulus; 5 Hz and averaging 2000 responses) using a newly developed 132 channel SQUID biomagnetometer with an X-ray imaging system (RICOH COMPANY, Ltd., Tokyo, Japan). At the same time, SEP was measured at Erb’s point using MEB-2300 (Nihon Kohden Corporation, Tokyo, Japan) for making sure to deliver supramaximal stimulation. After magnetoneurogram recording, evoked action currents were computationally reconstructed by a spatial filter method and the estimated electric currents map was superimposed over X-ray images. Results We were able to record the magnetic fields over the brachial plexus with good signal quality after ulnar nerve stimulation. Distribution of neural activity currents in the brachial plexus were estimated from the measured magnetic fields and visualized over X-ray images in all subjects. The currents distribution showed axonal activity pattern and passed medially to the coracoid process, crossed the clavicle, and reached the C7 - Th1 intervertebral foramen along the nerve path in the period between 8.0 ms and 13.0 ms after the stimulation. The conduction velocity calculated using the peak latency of the estimated current waveform on the nerve path was 67.13 ± 1.96 m/s. Conclusion By analysis of magnetoneurogram with participants’ X-ray image of the upper thorax,we succeeded in visualizing the nerve impulse traveling along (possibly) the medial cord of BP and then propagating into the C7 – Th1 intervertebral foramen after ulnar nerve stimulation at the wrist. Together with our previous study on magnetoneurogram after median nerve stimulation, we consider magnetoneurogram testing as superior to conventional SEP for analyzing the conductive function of BP because the former enables us to evaluate the conductive function of the nerve from the lateral or medial cord of BP to C5 – Th1 intervertebral foramen after median or ulnar nerve stimulation. We propose that the method of magnetoneurograph with the X-ray image can provide useful information for the non-invasive diagnosis of localization of conduction block in BP neuropathy.

T112. Visualization of electrical activities in the carpal tunnel area by magnetoneurography of median nerve

Introduction In recent years, diagnosis of the carpal tunnel syndrome is mainly performed by electrophysiological examination. In particular, the utility and reliability of inching method were demonstrated by some reports. However, electrophysiological examination is affected by the surrounding tissues such as bone and soft tissue, and the inching method is not technically easy and requires many electrodes. On the other hand, the magnetic field is not affected by the surrounding tissue. We have developed the magnetometer for the spinal cord and the spinal nerve activity and succeeded in measuring electrophysiological activity in the spinal cord and spinal nerve roots. Now, we are working on magnetoneurography (MNG) which is measurement of magnetic fields generated by the peripheral nerve. In this study, we aimed to evaluate spatiotemporal spread of digital nerve-evoked currents in the median nerve at the carpal tunnel area using MNG. Methods Using a newly developed superconducting quantum interference device (SQUID) magnetometer, neuromagnetic fields of 9 healthy volunteers’ hands were measured at the surface of the carpal tunnel area after stimulation of the digital nerves at the index or middle finger. Current sources were estimated using spatial filter techniques and were superimposed on X-ray images of the hand. We set a virtual electrode in the carpal tunnel along the median nerve. We reconstructed the current waveform from the magnetic field and calculated the nerve conduction velocity from the peak latency. We also measured sensory nerve action potential just above the carpal tunnel, 3 cm distal and 3 cm proximal to the carpal tunnel in response to stimulation of the digital nerves of the index finger. The conduction velocity was calculated from the peak latency. Results Neuromagnetic fields propagating from the finger to the wrist were successfully measured in all subjects. Distribution of action currents calculated from MNG showed the axonal activity pattern showing the intra-axonal current and the depolarization/ repolarization current. Nerve conduction velocity estimated from the MNG was 55.3 m/s and corresponded with the sensory nerve conduction velocity. Conclusion We could visualize action current at any point in carpal tunnel with high resolution using MNG. Moreover, MNG is not affected by the surrounding bone and soft tissues and can be fused with morphological images such as X-rays. MNG is expected to contribute to the clinical diagnosis and treatment of carpal tunnel syndrome.

T108. Magnetic recordings of sensory action currents in the cervical cord

Introduction A prototype magnetospinography (MSG) system with highly sensitive SQUID sensors for humans has been developed to noninvasively measure spinal cord activity by our lab. Here, we report neural activity in dorsal column and dorsal horn in the cervical cord using MSG. Methods Eleven healthy volunteers participated in this study. Participants were laid in a magnetically shielded room and neuromagnetic fields were measured from the neck in response to electrical stimulation of the median nerve at wrist, using a newly developed 124-channel MSG system. Two thousand responses between −5 and 30 ms after the stimulation were averaged. Evoked action currents were reconstructed by a spatial filter, recursive null steering beamforemer and superimposed on the X-ray image of individual participant’s cervical spine. Just before magnetic recordings, somatosensory evoked potentials (SEP) also were recorded with the same stimulus setting. The recording places were set at ipsilateral-to-contralateral Erb’s point and C5 posterior-anterior cervical derivation. Results In all 11 healthy subjects, estimated “horizontal” electrical currents in the cervical canal which indicates depolarization in dorsal column were ascending sequentially. Their peak latency at C5 level and the N11 peak latency of SEP recorded with C5S-ACmontage matched well (r = 0.96, p  Conclusion MSG could visualize sequential electrical activities in dorsal column and dorsal horn in the cervical cord.