Kozue Tanaka

Sequential changes in the non-coding control region sequences of JC polyomaviruses from the cerebrospinal fluid of patients with progressive multifocal leukoencephalopathy

Progressive multifocal leukoencephalopathy (PML) is caused by JC polyomavirus (JCV) infection in the brain. JCV isolates from PML patients have variable mutations in the non-coding control region (NCCR) of the genome. This study was conducted to examine sequential changes in NCCR patterns of JCV isolates obtained from the cerebrospinal fluid (CSF) of PML patients. CSF specimens were collected from PML patients at different time points, the NCCR sequences were determined, and their compositions were assessed by computer-based analysis. In patients showing a marked increase in JCV load, the most frequent NCCR sequences in the follow-up specimens were different from those in the initial samples. In contrast, the dominant NCCRs in the CSF remained unaltered during the follow-up of individuals in whom the viral load decreased after therapeutic intervention. These data demonstrate that the majority of JCV variants emerge with the progression of PML and that these changes are suppressed when the viral load is decreased.

Body weight-based natalizumab treatment in adult patients with multiple sclerosis

Natalizumab (NTZ), a monoclonal antibody against very late antigen-4 (VLA-4) to inhibit VLA-4-dependent transmigration of immune cells across the vascular endothelium into the central nervous system, is one of the most effective treatments available to reduce relapse frequency of patients with relapsing-remitting multiple sclerosis (MS). Progressive multifocal leukoencephalopathy (PML) caused by the JC polyomavirus, however, is a serious opportunistic brain infection which may occur during NTZ treatment. Seropositivity for JC virus antibodies, a history of immunosuppressive treatment, and NTZ treatment longer than 24 months are widely accepted as risk factors to develop PML [1]. One of the reasons for the higher PML prevalence of NTZ treatment-PML in the European Economic Area than in the USA is thought to be a more frequent use of cytotoxic immunosuppressive medication in Europe [2]. Foley et al. reported that body weights (BW) of NTZtreated patients in EU were lower than those in the US, and low BW could be a potential surrogate risk factor for PML in MS patients treated by NTZ. They also showed serum concentrations of NTZ and VLA4 saturations tended to be higher in lower BW patients [3]. Our simple regression analyses using an Excel software (Microsoft Office 2010, Tokyo) based on the value of median blood concentration at intervals of 5 kg BW shown in their poster [3] showed a linear relation between serum concentrations and BW (50–110 kg) (y = -0.5363x ? 75.71, R = 0.846). NTZ efficacy is optimized at saturations of VLA-4 on lymphocytes of more than 70 % [4]. The median saturation of VLA-4 on lymphocytes declines with increasing BW, although VLA-4 saturations were greater than 85 % even in patients heavier than 75 kg [3]. From our regression line, assuming a linear relationship, if NTZ is administered by BW and a standard BW of 75 kg is adopted for the standard dose of 300 mg (15 mL), only 220 mg (11 mL) of NTZ is needed in patients weighing 50 kg to obtain the same serum concentration as seen in patients weighing 75 kg. The median BW of 27 Japanese MS patients at one hospital (UTH) treated with fingolimod, was 66.0 kg for males (n = 11, 65.5 ± 7.9, 53.4–79.3 kg) and 52.1 kg for females (n = 16, 51.3 ± 7.2, 40.5–65.9 kg). The median BW of 114 Japanese patients in a clinical trial of fingolimod (55 kg for the fingolimod group and 58 kg for the placebo group: Novartis Pharma Japan), and 94 patients in a NTZ trial (53.7 kg for the NTZ group and 59.2 kg for the placebo group: Biogen Idec Japan), are lower than that of M. Tanaka (&) Multiple Sclerosis Center, Utano National Hospital, 8 Ondoyama, Narutaki, Ukyo-ku, Kyoto 616-8255, Japan e-mail: nra17777@nifty.com

Magnetic Resonance Imaging Finding in Divergence Paralysis

We report magnetic resonance imaging (MRI) findings in two patients with divergence paralysis that was secondary to multiple sclerosis and pontine infarction, respectively. In both patients, cranial MRI showed lesions in the unilateral tegmentum of the caudal pons. Therefore, these MRI findings suggested that involvement of the nucleus reticularis tegmenti pontis might be responsible for the divergence paralysis in our cases.

Pure Motor Monoparesis in the Leg due to a Lateral Medullary Infarction.

A 76-year-old man with essential hypertension abruptly presented with slight left-sided leg weakness, despite normal strength in the other extremities. Left-sided Babinskis reflex was detected. There were no other neurologic abnormalities. Cranial magnetic resonance imaging demonstrated a small infarction in the lower lateral medulla oblongata on the left side. Cranial magnetic resonance angiography demonstrated an absence of flow of the left vertebral artery. He became asymptomatic within 10 days under intravenous antiplatelet agent. The corticospinal tract fibers innervating the lower extremity caudal to the pyramidal decussation might be involved. We emphasize that this is a first reported case of pure motor monoparesis in the leg due to lateral medullary infarction.

Anterior Uveitis as an Initial Manifestation of Polymyalgia Rheumatica

A 74-year-old woman without contributory medical history presented with acute iridocyclitis in the right eye. Although the iridocyclitis disappeared within two weeks under topical steroid, she complained of acute progressing bilateral shoulder pain and morning stiffness of upper extremities. She was diagnosed as having polymyalgia rheumatica (PMR), and iridocyclitis was considered as its related manifestation. PMR and giant cell arteritis (GCA) are closely related conditions and frequently occur together. GCA with uveitis has been rarely noted. However, ocular symptoms in PMR have not been previously mentioned. This is a first reported case of PMR presented with uveitis, without a complication of GCA. This anterior uveitis might be caused by ischemia of the posterior ciliary arteries and their branches.

Isolated Unilateral Trochlear Nerve Palsy Due to Ipsilateral Dorsal Midbrain Infarction

A 67-year-old Japanese man with essential hypertension and diabetes mellitus abruptly developed isolated right-sided trochlear nerve palsy without pain. Four days later, cranial magnetic resonance imaging demonstrated a tiny ischaemic lesion in the caudal and dorsal midbrain on the right side, which might involve the trochlear fascicles after its decussation. The trochlear nerve palsy resolved within 4 days while treated with intravenous anti-platelet agent. This is a first reported case of isolated unilateral trochlear nerve palsy due to ipsilateral midbrain infarction.

Bilateral Horizontal Gaze Paresis as an Initial Manifestation of Wernicke Encephalopathy

A 62-year-old man with hypertension, diabetes mellitus and alcoholic chronic pancreatitis developed bilateral horizontal gaze paresis (BHGP) with convergence paralysis. He declared that alcohol intake was given up for 4 years. Cranial magnetic resonance imaging (MRI) findings were normal. Tiny pontine infarction was suspected. However, 5 days later, confusional status and bilateral total external ophthalmoplegia appeared. MRI demonstrated typical findings of Wernicke encephalopathy (WE). Decreased blood thiamine level was confirmed. Neurological symptoms and MRI findings rapidly normalized under intravenous thiamine therapy. He confessed his alcohol abuse. This is a first reported case of BHGP as an initial manifestation of WE.