Yoshiyuki Numasawa

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

Structural connectivity in spatial attention network: reconstruction from left hemispatial neglect

Left hemispatial neglect (neglect) is an impaired state of spatial attention. We aimed to reconstruct structural connectivity in the spatial attention network and to identify disconnection patterns underlying neglect. We enrolled 59 right-handed patients who had their first-ever infarction in the right hemisphere and classified them into neglect group (34 patients with neglect) and control group (25 patients without neglect). The neglect group was further subcategorized into 6 subgroups based on infarcted vascular territories. Diffusion tensor imaging data were obtained from all patients. Fractional anisotropy maps were compared between neglect group/subgroups and the control group by using non-parametric voxel-based analysis, generating a lesion path mask. Probabilistic tractography analysis using the lesion path mask reconstructed the following structural connectivity in the spatial attention network, which is specifically damaged in neglect patients: (1) superior longitudinal fasciculus (SLF) I connecting the superior parietal lobule/intraparietal sulcus with the superior frontal gyrus/frontal eye field (SFG/FEF) (dorsal attention network); (2) SLF III/the arcuate fasciculus (AF) and the extreme capsule/inferior fronto-occipital fasciculus (IFOF) connecting the right inferior parietal lobule/temporoparietal junction/superior temporal gyrus (IPL/TPJ/STG) with the middle frontal gyrus/inferior frontal gyrus (ventral attention network); (3) the thalamic radiations to the spatial attention-related cortices; and (4) SLF II and IFOF interconnecting dorsal and ventral attention networks. Individual analysis indicated that isolated damage in SLF I, SLF II, SLF III/AF or the thalamic radiations to IPL/TPJ/STG due to posterior cerebral artery infarction, or simultaneous damage in four thalamic radiations due to anterior choroidal artery infarction, underlies different phenotypes of neglect.

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

Myasthenia Gravis Complicated with Peripheral T-cell Lymphoma, Not Otherwise Specified (PTCL-NOS), Following Thymectomy and Longstanding Tacrolimus Therapy

Myasthenia gravis (MG), a neuromuscular junction autoimmune disease, sometimes complicates second malignancies; however, T-cell lymphoproliferative disorders have rarely been reported. A 55-year-old man, who received oral tacrolimus and prednisolone for MG for 16 years after thymectomy, presented with left abdominal pain, lymphadenopathy, and splenomegaly. A lymph node biopsy revealed peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS). This is the first report of oral tacrolimus leading to a T-cell lymphoproliferative disorder in patient without a history of transplantation. Physicians should be aware of the possibility of rare T-cell lymphoproliferative disorders, such as PTCL-NOS, occurring as complications in MG patients on immunosuppressive regimens after thymectomy.

Depressive disorder may be associated with raphe nuclei lesions in patients with brainstem infarction

BACKGROUND Depression is a common symptom after stroke, but its neural substrates remain unclear. The ascending serotonergic system originates from the raphe nuclei in the brainstem. We hypothesized that depressive disorder due to brainstem infarction is associated with damage to the raphe nuclei. METHODS We prospectively enrolled 19 patients who had the first-ever acute isolated brainstem infarction in an observational cross-sectional study. All patients were evaluated by using the Montgomery Åsberg Depression Rating Scale (MADRS), the clinician-rated version of Apathy Evaluation Scale (AES-C) and Mini-Mental State Examination (MMSE). Depressive disorder was diagnosed according to DSM-5 and MADRS score of 12 or greater. Diffusion tensor imaging and proton density-weighted images were used to identify damage in the raphe nuclei. Accordingly, patients were classified into either the raphe-nuclei-damaged or intact group. Prevalence of depressive disorder and the MADRS, AES-C, and MMSE scores were compared between the two groups. RESULTS Depressive disorder was more frequent in the damaged group (n=6) than in the intact group (n=13) (83% vs. 15%; P=0.01). MADRS scores were higher in the damaged group than in the intact group (mean±1 SD, 17.5±7.9 vs. 7.0±4.4; P=0.002), whereas the AES-C and MMSE scores did not differ between groups. LIMITATIONS We did not assess the damage to the ascending projection fibers from the raphe nuclei. CONCLUSIONS Our results suggest that damage to the raphe nuclei underlies depressive disorder due to brainstem infarction, possibly via serotonergic denervation.

Bilateral Optic Tract Hyperintensity due to Pituitary Apoplexy

A 51-year-old man was admitted due to sudden headache, fever, and vomiting. A neurologic examination revealed neck stiffness, partial bitemporal hemianopsia, left ptosis, and ophthalmoplegia. Axial computed tomography and sagittal T1-weighted magnetic resonance imaging (MRI) showed a hemorrhagic pituitary mass in the sellar-suprasellar region (Picture A, B). Axial T2-weighted and fluid-attenuated inversion recovery (FLAIR) imaging demonstrated bilateral optic tract hyperintensity (Picture C, D, arrows). The corresponding apparent diffusion coefficient map revealed hyperintensity in the optic tracts. Accordingly, pituitary apoplexy with edema of the bilateral optic tracts was diagnosed. On follow-up MRI (21 days after treatment), the optic tracts appeared isointense (Picture E, F), and the hemorrhagic mass had shrunk. Optic tract hyperintensity on MRI has been reported to occur in pituitary-region tumors (1) but rarely due to pituitary apoplexy (2). In light of previous reports (1, 2) and our case, pituitary apoplexy may cause hyperintensity of the bilateral optic tracts on MRI when a hemorrhagic mass compresses the proximal optic tracts, leading to local venous congestion and subsequent vasogenic edema.

Persisting subacute infarct pattern as early MRI feature of brain intravascular lymphoma

A 67‐year‐old man was admitted to our hospital for gait disturbance due to muscle weakness of the right lower limb lasting for 2 months. Brain MRI demonstrated multiple small cerebral white matter lesions showing a subacute infarct pattern (approximately 10–21 days after ischemic stroke onset), characterized by both hyperintensities on diffusion‐weighted images and intermediate apparent diffusion coefficient (ADC) values. The ADC values of the lesions remained almost unchanged 4 months after onset and decreased in some lesions 8 months after onset. Random skin biopsy established a diagnosis of intravascular lymphoma (IVL). Brain lesions showing a persistent subacute infarct pattern on MRI may be an early feature of brain IVL.

Spinocerebellar Ataxia Type 31 with Blepharospasm

A 58-year-old man consulted our hospital due to a 2-year history of dysarthria and a 1-month history of blepharospasm. In addition to the ataxic dysarthria and blepharospasm, a neurological examination demonstrated slight ataxia of the trunk and lower limbs. Brain MRI demonstrated atrophy of the upper portion of the cerebellar vermis. Gene analysis established a diagnosis of spinocerebellar ataxia type 31 (SCA31). Single photon emission computed tomography (SPECT) with the three-dimensional stereotaxic ROI template (3DSRT) software program demonstrated hyperperfusion in the lenticular nucleus and thalamus. Although the association between SCA31 and blepharospasm in our patient remains unclear, we considered that this combination might be more than coincidental.

Fist sign in inclusion body myositis

Fist sign in inclusion body myositis Zen Kobayashi *, Emi Fukatsu , Sakiko Itaya , Miho Akaza , Kiyobumi Ota , Yoshiyuki Numasawa , Satoru Ishibashi , Hiroyuki Tomimitsu , Shuzo Shintani a a Department of Neurology, JA Toride Medical Center, Toride, Japan b Department of Rehabilitation, JA Toride Medical Center, Toride, Japan c Department of Neurology and Neurological Sciences, Graduate School, Tokyo Medical and Dental University, Tokyo, Japan