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.

Development of a Risk Prediction Score to Identify High-Risk Groups for the Critical Coronavirus Disease 2019 (COVID-19) in Japan.

Coronavirus disease 2019 (COVID-19) emerged in mid-December 2019 and has rapidly spread worldwide. We conducted a retrospective analysis of data from patients with COVID-19 to construct a simple risk prediction score to be implemented in prehospital settings. Patients were classified into critical and non-critical groups based on disease severity during hospitalization. Multivariate analysis was performed to identify independent risk factors and develop a risk prediction score. A total of 234 patients were included in the study. The median age of the critical group was significantly older than that of the non-critical group (68.0 and 44.0 years, respectively), and the percentage of males in the critical group was higher than that in the non-critical group (90.2% and 60.6%, respectively). Multivariate analysis revealed that factors such as age ≥ 45 years, male sex, comorbidities such as hypertension and cancer, and having fever and dyspnea on admission were independently associated with the critical COVID-19 infection. No critical events were noted in patients with a total risk factor score of ≤ 2. Contrastingly, patients with a total risk factor score ≥ 4 were more likely to have critical COVID-19 infection. This risk prediction score may be useful in identifying critical COVID-19 infections.

[A case of CNS aspergillosis developing orbital apex syndrome and causing mycotic aneurysm and the subsequent cerebral infarction].

A 79-year-old woman, with no immune deficit, had presented progressive visual disturbance, diplopia and ptosis of her left eye over 2 weeks. T1-weighted MR images with gadolinium showed a heterogeneously enhanced lesion extending from the left orbital apex along the optic nerve to the cavernous sinus. Although we could not detect fungus by a transsphenoidal biopsy, we suspected fungal infection because of high level of galactomanan antigen in serum. Despite antifungal chemotherapy, her symptoms did not improve. CT image on day 40 showed an aneurysm in the left internal carotid artery, on day 43 cerebral infarction in the left internal carotid artery distribution and on day 45 she died. Autopsy disclosed that aspergillus hyphae invaded the left sphenoid sinus, cavernous sinus and wall of the aneurysm. In this case, fungal infection in the frontal skull base including orbital apex caused mycotic aneurysm in the intracavernous portion of the left internal carotid artery. Skull base aspergillosis presenting orbital apex syndrome is itself rare and in addition, the occurrence of cerebral infarction in the mycotic aneurysm has hardly been reported. We should have cerebrovascular disease in mind as a complication of CNS aspergillosis.

Ocular tilt reaction due to a cerebellar hemorrhage.

A 78-year-old man with essential hypertension abruptly developed complete ocular tilt reaction (OTR) which consisted of concomitant skew deviation with left hypertropia, extorsion of the right eye and intorsion of the left, and rightward head tilt. Cranial computed tomography demonstrated a localized cerebellar hemorrhage involving the left nodulus. The patient became asymptomatic within two weeks. This is a first reported case of complete OTR due to a cerebellar hemorrhage. Concomitant skew deviation is a common symptom of cerebellar lesions. Moreover, unilateral damage to the utricular pathway due to involvement of the left nodulus might cause rightward conjugate ocular torsion and rightward head tilt.

Clinico-anatomical analysis of the fibers to the inferior rectus muscle in the oculomotor fascicles.

We report two cases of isolated unilateral pupil-sparing partial fascicular oculomotor paresis. Patient 1 was a 72-year-old man who developed left-sided palsy of the inferior rectus muscle (IR), medial rectus muscle (MR), superior rectus muscle (SR), inferior oblique muscle (IO), and levator palpebrae superioris (LP) due to infarction of the left paramedian thalamic artery. Patient 2 was a 70-year-old woman who developed right-sided palsy of MR, SR, IO and LP due to infarction of the right superior paramedian mesencephalic artery. These results suggest that the fibers to IR may be located in the most rostral portion of the oculomotor fascicles.

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 Babinski's 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.

Alternating skew deviation due to hemorrhage in the cerebellar vermis.

A 76-year-old Japanese woman with essential hypertension and diabetes mellitus abruptly presented with nausea, dizziness, an occipital headache, truncal ataxia, gaze-evoked nystagmus and alternating skew deviation (ASD) with abducting eye hypertropia. Cranial computed tomography demonstrated hemorrhage in the cerebellar vermis and its vicinity. These symptoms gradually resolved within three weeks. This is the first reported case of ASD secondary to cerebellar hemorrhage without hydrocephalus. The vertical misalignment of the eyes during the right-sided gaze was consistently larger than during the left-sided gaze. We speculated that bilateral and asymmetrical damage to the utricular pathway due to the bilateral involvement of the nodulus and uvula might have caused the ASD.

Divergence paralysis caused by acute midbrain infarction.

A 41-year-old woman with idiopathic thrombocytopenic purpura and dyslipidemia abruptly developed vertigo, truncal ataxia and divergence paralysis. Cranial magnetic resonance imaging demonstrated the presence of infarction in the left superior paramedian mesencephalic artery involving the vicinity of the periaqueductal gray matter. The symptoms rapidly resolved under the administration of anti-platelet agents. The precise location of the hypothetical divergence center of the ocular motor system remains unclear because the lesions responsible for divergence paralysis are rarely identified on neuroimaging. We emphasize that this is a first reported case of DP caused by acute midbrain infarction and speculate that the mesencephalic reticular formation may be partially involved.

Isolated trochlear nerve palsy in Tolosa-Hunt syndrome.

A 67-year-old Japanese woman without contributory medical history developed acute onset of left-sided trochlear nerve palsy (TNP) with persistent and severe periorbital pain. There were no other neurological abnormalities. Funduscopic findings were normal. Cranial and orbital magnetic resonance (MR) imaging, and cranial MR angiography demonstrated no abnormalities. By administration of prednisolone 40 mg/day from the day after onset, periorbital pain was resolved within 24 hours, and TNP within 5 days. Thereafter, prednisolone was gradually tapered off. She remained asymptomatic under no medication. In the English language literature, this is the first reported case of Tolosa-Hunt syndrome presenting with isolated TNP.

Isolated shoulder palsy due to infarction of the cortical branch of the middle cerebral artery.

A 71-year-old man with hyperlipidemia abruptly developed left-sided isolated shoulder palsy. Cranial magnetic resonance imaging demonstrated infarction of the cortical branch of the right middle cerebral artery (MCA). In the primary motor cortex, there is broad somatotopic representation of various body parts in a particular arrangement, and the area corresponding to the shoulder is very small. Consequently, there have been only 3 reported cases of isolated shoulder palsy due to cerebral infarction, and its vascular supply remains uncertain. The present case indicates that the corresponding area to the shoulder receives its blood from the cortical branch of the MCA.

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.

Mefloquine treatment in a patient suffering from progressive multifocal leukoencephalopathy after umbilical cord blood transplant.

We report herein the case of a 37-year-old man who developed probable progressive multifocal leukoencephalopathy (PML) following an umbilical cord blood transplant. The patient showed favorable clinical, neuroradiological and virological responses after treatment with mefloquine, an anti-malarial drug. Mefloquine may offer some benefits as a treatment for PML in patients with or without human immunodeficiency virus type-1 infection. This report highlights the need to gather sufficient data to confirm the efficacy of mefloquine against this devastating viral disease of the central nervous system.