Hideto Joki

Arterial spin-labeling magnetic resonance imaging for diagnosis of early seizure after stroke

BACKGROUND AND PURPOSE Arterial spin labeling (ASL) is a non-invasive modality of magnetic resonance imaging (MRI) used to evaluate cerebral perfusion without a contrast agent. The usefulness of ASL for diagnosis in the acute phase of late seizure after stroke was evaluated. METHODS Twelve consecutive patients diagnosed with late seizure after stroke were enrolled in this study. MRI including ASL was performed for each patient at the time of the emergency department visit. Eight of the patients underwent electroencephalography (EEG). RESULTS All patients showed hyperperfusion around the stroke lesion on ASL. Only 6 patients showed high signal intensity along the cerebral cortex around the stroke lesion on diffusion-weighted imaging. The patients who underwent EEG showed slow activity, but paroxysmal discharges such as spikes or sharp waves were not observed. CONCLUSIONS ASL was able to reveal hyperperfusion and was of great diagnostic value in the peri-ictal phase of late seizure after stroke.

Combination of infarctions in the posterior inferior cerebellar artery and anterior spinal artery territories

After an episode of vasodilator-induced systemic hypotension, a 75-year-old man developed ocular lateropulsion to the right, left-side-dominant quadriparesis, loss of superficial sensation below C4 dermatome level, and anuresis. Magnetic resonance imaging (MRI) showed infarcts in the right cerebellar hemisphere (posterior inferior cerebellar artery territory) and the upper cervical cord (anterior spinal artery territory); the combination of posterior inferior cerebellar artery (PICA) and anterior spinal artery (ASA) infarcts has not been reported previously. Angiography revealed severe stenosis in the bilateral vertebral arteries. Hemodynamic hypoperfusion of the stenotic vertebral arteries may cause this unusual combination.

A novel SCARB2 mutation causing late‐onset progressive myoclonus epilepsy

Progressive myoclonus epilepsy (PME) is a clinically heterogeneous disorder characterized by myoclonus, epilepsy, and progressive neurological deteriorations, typically with cerebellar signs and dementia. Recently, the scavenger receptor class, member 2 gene (SCARB2) was found to be mutated in PME with or without renal failure, in patients showing preserved intellect, disease onset at approximately 20 years of age, and death usually by 35. Here, we encountered two Japanese siblings (Fig. 1A) with late-onset PME without renal failure having a novel homozygous SCARB2 mutation. Patient 1 (III-9) developed normally. At age 43, myoclonic jerks were noted in her upper limbs when writing. After a few months, gait instability started, leading to falling without loss of consciousness. Action myoclonus and gait instability gradually worsened, and her speech was slurred. She became wheelchair bound at age 51, and bedridden at 54. Now, at 58, cognitive ability, ocular movements, and eyegrounds were preserved (i.e., no cherry-red spots). Generalized hyperhidrosis and dyspnea with marked myoclonus occurred in the stressed condition and/or during anxiety. Tonic clonic seizures also appeared. Biochemical examination indicated healthy renal function. Preserved alpha background activity with no epileptic discharge was found by EEG. Somatosensory-evoked potentials were normal. Brain MRI was normal with no apparent atrophy (Fig. 1B). Brain perfusion single-photon emission computed tomography (SPECT) showed decreased regional cerebral blood flow in the bilateral dorsolateral frontal lobes (Fig. 1C), which might be related to psychiatric symptoms. The elder brother of patient 1 (patient 2, III-3) developed normally. At age 52, gait instability was noted. At 57, voice and upper-limb tremor triggered by movements was recognized. At 62, he started using a wheelchair and dysphagia occurred. At 63, a convulsive seizure occurred once. At the same age, an acute ischemic stroke on his right corona radiata developed. At 68, regardless of his bedridden state and limb contracture with severe myoclonus triggered by movements, his mental function was preserved. Biochemical examination indicated normal renal function. To identify the causative mutation, whole exome sequencing was performed using genomic DNA from patient 1. As a result, three homozygous contiguous mutations were detected in exon 11 of SCARB2. Sanger sequencing confirmed a homozygous c.1385_1390delinsATGCATGCACC (p.Gly462Aspfs*34) in patient 1, instead of three contiguous mutations (Fig. 1D). The mutation was undetected in 200 Japanese control alleles as well as the public exome database of the National Heart, Lung, and Blood Institute exome sequencing project (5,378 exomes). The mutation cosegregated with those affected (Fig. 1D). To examine whether the frameshift mutation leads to nonsense-mediated messenger RNA (mRNA) decay (NMD), reverse-transcriptase polymerase chain reaction was performed. We confirmed that the amount of mutant SCARB2 mRNA is comparable to that of wild-type mRNA (Fig. 1E), indicating that mutant mRNA is not subjected to NMD and the abnormal gene product may be postulated. Loss-of-function mutations in SCARB2 are known to cause PME with or without renal failure. Residual SCARB2 function can be related to the exceptionally late-onset PME in these patients.

An Aerodynamic Study of Phonations in Patients With Parkinson Disease (PD)

BACKGROUND The precise comparison of the voice characteristics of Parkinson disease (PD) patients with age-matched normal subjects is still one of the important research projects. The present study aimed at comparing the voice characteristics in sustained phonations of PD patients with an age-matched control group. METHODS The subjects were 30 Japanese PD patients (15 males and 15 females). The control group consisted of 30 age-matched normal Japanese subjects (15 males and 15 females). Each subject was required to phonate into a mouthpiece attached to Vocal Function Analyzer (PS-77E; Nagashima Medical Instrumental Corporation, Tokyo, Japan) with the airway interruption system, and expiratory lung pressure, mean flow rate, fundamental frequency and intensity of voice, and pitch range were measured. Maximum phonation time was also assessed. RESULTS The highest pitch level was significantly lower in the PD group than that of the control group in both sexes, whereas the lowest pitch level was significantly higher in the PD group only in males. In both sexes, the pitch range was significantly narrower in the PD group than in the control group. There was no significant difference in intensity, mean flow rate, expiratory pressure, or maximum phonation time between the two groups, for both males and females. CONCLUSION Only remarkable difference in the voice characteristics between PD patients and age-matched normal elderlies was limited to the narrowing of the pitch range in PD patients. The restriction in pitch regulation in PD patients was considered to be because of difficulty in reciprocal control of the laryngeal muscles secondary to latent rigidity.

High-resolution magnetic resonance imaging findings of basilar artery plaque in a patient with branch atheromatous disease: a case report.

IntroductionIntracranial branch atheromatous disease is a type of ischemic stroke that is caused by narrowing or occlusion of the orifice of the penetrating artery by atheromatous plaque. Pontine branch atheromatous disease is usually diagnosed using indirect findings such as the extension of a lesion to the basal surface of the pons because of the difficulty of demonstrating plaque in the basilar artery.Case presentationA 72-year-old Japanese man developed sudden dysarthria and left hemiparesis, and his symptoms deteriorated thereafter. Brain magnetic resonance imaging revealed an acute infarction in the territory of the right paramedian pontine artery extending to the basal surface. Non-contrast-enhanced three-dimensional fast spin-echo T1 imaging with variable flip angles and three-dimensional fast imaging with steady-state acquisition revealed a plaque in the dorsal wall of the basilar artery that spread to the origin of the paramedian pontine artery that branched toward the infarction. Although antithrombotic agents were started, the left hemiparesis got worse and became flaccid on the following day.ConclusionsThis is the first report to confirm the pathological basis of branch atheromatous disease by three-dimensional images using the new modalities of 3-Tesla magnetic resonance imaging. The use of these techniques will foster better understanding of the clinicopathological mechanisms of branch atheromatous disease.

White matter hyperintensities on MRI in dementia with Lewy bodies, Parkinson's disease with dementia, and Alzheimer's disease

BACKGROUND In dementia with Lewy bodies (DLB) and Parkinsons disease with dementia (PDD), it is still debated whether white matter hyperintensities (WMH) on MRI reflect atherosclerotic cerebrovascular changes or Alzheimers disease (AD)-related pathology such as cerebral amyloid angiopathy. To examine AD-related pathology in DLB and PDD, we compared the severity of WMH and medial temporal lobe atrophy among patients with DLB, PDD, non-demented PD (PDND), and AD. METHODS We retrospectively studied sex- and age-matched outpatients with AD, DLB, PDD, and PDND, as well as subjects without central nervous system disorders as normal controls (n=50 each). All subjects underwent 1.5-T MRI examinations, and WMH detected by T2-weighted images or fluid-attenuated inversion recovery images were semiquantified according to the Fazekas method. Medial temporal lobe atrophy (MTA) was visually assessed by the MTA score. RESULTS WMH were more prominent in AD, DLB, and PDD patients than in PDND patients and normal controls (NCs). DLB as well as AD showed more severe WMH than PDD. Visual assessment of medial temporal lobe atrophy showed that AD patients had the most severe atrophy, followed by DLB, PDD, and PDND patients, and NC subjects in that order. MTA scores showed significant correlations with WMH severity. CONCLUSION Our results indicated that DLB was more similar to AD than to PDD in terms of MRI findings, suggesting that WMH in DLB may reflect mainly AD-related pathology rather than atherosclerotic cerebrovascular changes.

Late Seizures after Stroke in Clinical Practice: The Prevalence of Non-convulsive Seizures

Objective The prevalence of the non-convulsive type of late seizure after stroke is unknown. The aim of the present study was to clarify the characteristics of late seizure in clinical practice, mainly focusing on the prevalence of non-convulsive seizure. Methods A total of 178 consecutive patients who were admitted and diagnosed with late seizure after stroke were retrospectively enrolled, and the data of 127 patients for whom the complete seizure was observed by a bystander were analyzed. Clinical information was obtained from the medical records and nursing notes. Results A non-convulsive seizure was observed in 37 patients (29%). A focal seizure and its secondary generalization accounted for 79% of the seizure types. Status epilepticus was observed in 60 patients (47%), including 11 patients (9%) without convulsion. The patients with non-convulsive seizures were significantly younger than those with convulsive seizures, but there were no other significant differences between the two groups with respect to sex, classification or the lesion of stroke. Conclusion There was a high rate of non-convulsive seizures in patients with late seizure after stroke. A non-convulsive seizure may be caused by any type or location of preceding stroke. More attention is needed in the differential diagnosis of neurological deterioration after stroke.

A Case of McLeod Syndrome with A Novel XK Missense Mutation: McLeod Syndrome with a Novel XK Missense Mutation

McLeod syndrome was originally identified as a hematological variant known as the McLeod hematologic phenotype, which was serologically defined by acanthocytosis and weak antigenicity of Kell antigens associated with the absence of the Kx antigen. McLeod syndrome is now recognized as a rare X-linked neuroacanthocytosis affecting the peripheral and central nervous systems, red blood cells (RBCs), and internal organs. Loss-offunction mutations of the XK gene have been identified as the cause of McLeod hematologic phenotype and syndrome. Of 37 causative mutations, most are nonsense mutations, frameshift mutations resulting in a premature stop codon, or splice-site mutations resulting in mRNA truncation. To date, three missense mutations have been reported for the McLeod hematologic phenotype, but nevertheless, manifestation of McLeod syndrome is observed in only one missense mutation. In this report, we describe the clinical features of a patient with McLeod syndrome caused by a novel missense mutation of the XK gene.

Case of immune-mediated necrotizing myopathy associated with anti-signal recognition particle antibodies: Dramatic improvement after rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone therapy for intravascular large B-cell lymphoma

Immune‐mediated necrotizing myopathy associated with anti‐signal recognition particle antibodies (anti‐SRP myopathy) is representative of several subtypes of necrotizing immune‐mediated myopathy, and is characterized by rapidly progressive proximal muscle weakness, dysphagia and poor responsiveness to conventional immunosuppressive therapies. We report a 71‐year‐old man who developed anti‐SRP myopathy followed by malignant lymphoma, and whose condition dramatically improved with rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone therapy. He showed progressive proximal muscle weakness with severe dysphagia, and was diagnosed with anti‐SRP myopathy by antibody tests and pathological examination. He was treated with conventional immunosuppressive therapies, specifically corticosteroids, intravenous immunoglobulin and tacrolimus; however, none of these therapies were effective. Two months after starting tacrolimus, the patient developed intravascular large B‐cell lymphoma, which was suspected to be an iatrogenic immunodeficiency‐associated lymphoproliferative disorder. Rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone therapy resulted in not only complete remission of lymphoma, but also dramatic improvement of anti‐SRP myopathy. The present case suggests that rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone therapy is a potential treatment for anti‐SRP myopathy.

[Aseptic meningitis in a patient with cerebrospinal fluid anti-agalactosyl IgG antibody-positive preclinical rheumatoid arthritis: a case report].

A 69-year-old woman presented with non-fluent aphasia, ideomotor apraxia, right hemiparesis and convulsion. Her medical history was unremarkable, and she had not suffered from arthritis. DWI and FLAIR image of brain MRI showed hyperintensities in the subarachnoid space along the left frontal and both parietal lobes, and these lesions were associated with gadolinium enhancement. The levels of serum anti-cyclic citrullinated peptide antibody, anti-agalactosyl IgG antibody and matrix metalloproteinase-3 were elevated. The results of blood cultures were negative. Cerebrospinal fluid (CSF) analysis revealed monocytic pleocytosis and negative findings for infection or malignancy. The level of anti-agalactosyl IgG antibody in CSF was elevated. The antibody index (AI) of anti-agalactosyl IgG antibody (the ratio between the CSF/serum quotient for IgG antibodies, and the CSF/serum quotient for total IgG; normal value of AI < 1.3) showed considerably high value of 8.4, indicating the intrathecal-specific antibody synthesis. As a result, the pathogenesis of her disease was consistent with rheumatoid meningitis despite lack of arthritis. After intravenous administration of methylprednisolone, her symptoms, the level of anti-agalactosyl IgG antibody in CSF, and the MRI findings were ameliorated. Anti-agalactosyl IgG antibody in the CSF was a helpful biomarker in diagnosis and assessment of the severity of rheumatoid meningitis.