Asuka Asanome

Cerebral Microbleeds and Asymptomatic Cerebral Infarctions in Patients with Atrial Fibrillation

BACKGROUND Atrial fibrillation (AF) is a cardiac arrhythmia that does not infrequently induce ischemic strokes; however, little research has been reported on focal cerebral microangiopathic lesions in patients with AF. Recently cerebral microbleeds (CMBs) have been noticed for their potential implication in cerebral small vessel disease. Therefore, we had 2 goals in the present study: (1) to compare the prevalence of CMBs in patients with AF with that in patients without AF, and (2) to prove that CMBs could be a clinical predictive factor for the development of future cerebral microangiopathy in patients with AF without a history of symptomatic cerebral infarction in a prospective manner. METHODS We performed yearly brain magnetic resonance imaging (MRI) assessments for a maximum of 5 years in 131 patients with AF and 112 control patients. Seventy-seven patients with AF underwent more than 3 yearly MRI scans. RESULTS The Kaplan-Meier curve showed that the development of an asymptomatic cerebral infarction (ACI) was associated with the baseline presence of a CMB (P=.004). A multivariate Cox regression analysis revealed that the CMBs at baseline were significantly associated with an increment in not only the occurrence of ACIs (hazard ratio [HR], 5.414; 95% confidence interval [CI], 1.03-28.43; P=.046) but also in the consecutive development of CMBs (HR, 6.274; 95% CI, 1.43-27.56; P=.015). CONCLUSIONS Patients with AF had a significantly higher prevalence of CMBs. The presence of CMBs in the baseline MRI may predict the consequent onset of an ACI and increase in CMBs in patients with AF.

Biopsy‐proven case of Epstein–Barr virus (EBV)‐associated vasculitis of the central nervous system

A 75‐year‐old woman was admitted to our hospital with rapidly deteriorating consciousness disturbance. She had a 7‐year history of rheumatoid arthritis (RA), which had been treated with methotrexate (MTX) and prednisolone. Brain T2‐weighted MRI showed diffuse high‐intensity lesions in the cerebral subcortical and deep white matter, bilateral basal ganglia and thalamus. A cerebrospinal fluid examination revealed elevated protein levels and positive Epstein–Barr virus (EBV) DNA. Human immunodeficiency virus was negative. Brain biopsy showed perivascular lymphocytic infiltration in the parenchyma and meninx with EBV‐encoded small RNA (EBER). Since this case did not fulfill the criteria for chronic active EBV infection (CAEBV), she was diagnosed with Epstein–Barr virus (EBV)‐associated vasculitis of the central nervous system. High‐dose methylprednisolone, acyclovir, ganciclovir and foscarnet were not effective. Although EBV is a causative agent of infectious mononucleosis (IM), lymphomas and nasopharyngeal carcinomas, vasculitic pathology of the central nervous system with EBV reactivation in the elderly is rare. Immunosuppressive drugs such as steroids and MTX are widely used to treat autoimmune disorders, but may exacerbate the reactivation of EBV. This is the first case of biopsy‐proven EBV‐positive/HIV‐negative vasculitis during the treatment of RA with MTX and steroids. This case indicates that EBV‐associated vasculitis needs to be considered as a differential diagnosis of CNS vasculitis.

A case of pathology-proven neuromyelitis optica spectrum disorder with Sjögren syndrome manifesting aphasia and apraxia due to a localized cerebral white matter lesion

A woman with Sjögren syndrome manifesting as aphasia with a left deep cerebral white matter lesion tested positive for anti-aquaporin 4 (AQP4) antibody. Open biopsy of the lesion revealed active demyelination with edematous changes and the preservation of most axons, indicating a non-necrotic demyelinating lesion. Immunostaining for AQP4 was diffusely lost, whereas the loss of glial fibrillary acidic protein immunostaining was limited but with highly degenerated astrocytic foot processes in perivascular areas. These results suggested neuromyelitis optica spectrum disorder (NMOSD) pathology rather than Sjögren-related vasculitis. Only cerebral cortical symptoms with a cerebral white matter lesion could be observed in NMOSDs.

A case of midbrain infarction causing ipsilateral mydriasis, contralateral superior rectus palsy, and bilateral ptosis.

A 68-year-old woman who had been diagnosed with advanced pancreatic cancer was admitted to our hospital because of fluctuating consciousness disturbance. We made the diagnosis of Trousseau syndrome, because magnetic resonance imaging demonstrated multiple acute cerebral infarcts. She showed disorientation, perseveration, and sensory aphasia, but no pupillary or oculomotor disturbance. On the day after admission, her level of consciousness deteriorated suddenly. The neurological examination revealed left pupillary mydriasis, bilateral ptosis, and downward rotation of the right eye. Although we could not evaluate the extraocular muscle motility in much detail due to her consciousness disturbance, the right eyeball rotated downward in the primary position when we forcibly opened the bilateral drooping eyelids. Elevation paresis of the right eyeball was also observed during tests of Bell’s phenomenon and oculocephalic reflexes. In dim light, the right pupil was 3 mm in diameter and reactive to light, but the left pupil was 4.5 mm and less reactive to light. The anisocoria increased in bright light, the right pupil measuring 2 mm and the left pupil 4 mm (Fig. 1). Diffusion-weighted magnetic resonance imaging revealed a small new lesion in the left paramedian area of the midbrain between red nucleus and periaqueductal gray matter at the level of the superior colliculi (Fig. 2a, b). The lesion in the present case was located in the left paramedian area of the most rostral midbrain, corresponding to the upper portion of the oculomotor nucleus. We ruled out the possibility of a supranuclear lesion by examinations of Bell’s phenomenon and the oculocephalic maneuver. We also ruled out fascicular oculomotor nerve palsy because the lesion was located between the red nucleus and periaqueductal gray matter. It is well known that the oculomotor nucleus consists of several subnuclei. The causal lesions of her symptoms are assumed to be due to the left Edinger–Westphal nucleus, central caudal nucleus, and left subnucleus to the superior rectus muscle. These three subnuclei are juxtaposed with each other within the medial area of the oculomotor nucleus complex. It has been shown that the fibers from subnucleus subserving the superior rectus muscle decussate within the caudal one-third to one-half of the oculomotor nucleus complex [1]. Meanwhile, in the rostral half of the nucleus, no crossing fibers are seen. We speculate that the lesion localized at the caudal one-third to one-half of the oculomotor nucleus may have selectively involved the crossing

A case of neurolymphomatosis that was diagnosed by acoustic nerve biopsy

A 58-year-old female was admitted to our hospital because of recurrent multiple cranial neuropathy (right facial palsy followed by involvement of the left trigeminal, facial, acoustic, pharyngeal, and vagal nerves and the right abducens nerve). Brain MRI showed gadolinium enhancement of the right abducens, bilateral facial/acoustic, and left pharyngeal/vagal nerves, and 18F-Fluorodeoxyglucose (FDG)-positron emission tomography revealed abnormal FDG uptake in the right facial, acoustic, pharyngeal, and vagal nerves and the left cervical lymph nodes. Blood and biochemical analyses did not show any abnormalities, including in the patients lactate dehydrogenase and soluble interleukin-2 receptor (sIL2R) levels. A cerebrospinal fluid (CSF) examination showed gradual increases in the patients cell counts and protein, β2-microglobulin, and sIL2R levels, but no malignant cells were detected. A thorough investigation involving repeated CSF examinations, whole-body computed tomography, bone marrow aspiration, random skin biopsies, and cervical lymph node aspiration biopsy examinations did not result in any definitive conclusions. Steroid therapy was ineffective, and the patient developed deafness in her left ear. Therefore, we performed a biopsy examination of the left acoustic nerve, which resulted in the patient being diagnosed with diffuse large B-cell lymphoma. High-dose MTX following the intrathecal administration of MTX, cytarabine, and prednisolone partially improved her symptoms, but she died after several episodes of clinical recurrence. Acoustic nerve biopsy may help diagnose neurolymphomatosis in carefully selected cases.

Three Japanese adult cases of brain lesions with anti-myelin oligodendrocyte glycoprotein antibodies lacking optic neuritis and myelitis

Anti‐myelin oligodendrocyte glycoprotein antibodies (MOG‐Ab) are positive in some patients with neuromyelitis optica/neuromyelitis optica spectrum disorders; however, their clinical diversity remains unclear.

A Sporadic Case of Fabry Disease Involving Repeated Fever, Psychiatric Symptoms, Headache, and Ischemic Stroke in an Adult Japanese Woman.

Fabry disease can cause various neurological manifestations. We describe the case of a Japanese woman with Fabry disease who presented with ischemic stroke, aseptic meningitis, and psychiatric symptoms. The patient had a mutation in intron 4 of her α-galactosidase A gene, which was not detected in her family. This case suggests that Fabry disease should be considered in young patients who exhibit central nervous system symptoms such as ischemic stroke, even if there is no family history of the condition. The episodes of aseptic meningitis and stroke experienced by our patient suggest that persistent inflammation might be the mechanism underlying Fabry disease.