Do oral conditions influence the incidence of bloodstream infection after hematopoietic stem cell transplantation? A retrospective study in Japan.

PURPOSE: This study aimed to evaluate the incidence of bloodstream infection (BSI) among patients undergoing hematopoietic stem cell transplantation (HSCT) for teeth indicated for extraction. METHODS: Patients who underwent HSCT at Toranomon Hospital (Tokyo, Japan) between January 2017 and December 2019 were retrospectively evaluated. The incidence of BSI among patients with teeth indicated for extraction who did not undergo extraction (oral high-risk group) and patients who did not have this risk (oral low-risk group) was compared. RESULTS: Among the 191 consecutive patients included in this study, 119 patients were classified as undergoing high-risk transplantation. BSI after HSCT was observed in 32 out of 60 (53.3%) patients and 56 out of 131 (42.7%) patients in the oral low-risk and oral high-risk groups, respectively (p = 0.173). Multivariable analyses revealed that the presence of > 3 teeth as intraoral sources of infection and age over 50 years were determinants of BSI originating from the oral cavity after engraftment (odds ratio [OR], 9.11; 95% confidential interval [CI] 2.27-36.61]; p = 0.002; OR, 3.22; CI [1.47-7.08], p = 0.004, respectively). CONCLUSION: In patients undergoing HSCT, the presence of less than three intraoral sources of infection did not affect the incidence of BSI after HSCT.

[A case of polyneuropathy after COVID-19 vaccine].

A 43-year-old-woman developed paresthesia, weakness of limbs, dysphagia and deep sensory impairment 12 days after vaccination of Pfizer COVID-19 vaccine. Her deep tendon reflexes were absent and cerebrospinal fluid showed normal cell counts and protein level. Anti-ganglioside antibodies were negative, and F wave frequency was decreased in nerve conduction studies. We diagnosed her as immune mediated polyneuropathy caused by COVID-19 vaccine, and plasma exchange improved her symptoms. Compared with Guillain-Barré syndrome and polyneuropathy following COVID-19 infection and COVID-19 vaccination, deep sensory impairment was the most characteristic of this case. We supposed that non-antigen specific mechanism played an important role in the pathogenesis of this case.

An autopsy case of corticobasal syndrome with pure diffuse Lewy Body Disease.

Corticobasal syndrome (CBS) is associated with diverse pathological substrates such as tau, prion protein, transactive response and, rarely, alpha synuclein. We report the case of a54-year-old man, who presented with asymmetric levodopa-poor-responsive parkinsonism, frontal lobe signs and behavioral changes. He was diagnosed with CBS, and postmortem analyses revealed Lewy body disease Braak stage VI without comorbid pathologies. Retrospectively, the clinical course of our patient and previous reports indicate that CBS plus mood changes and autonomic dysfunction, including reduced uptake of metaiodobenzylguanidine, are predictive factors of Lewy body pathology, even if the clinical picture is atypical.

An adult nemaline myopathy patient with respiratory and heart failure harboring a novel NEB variant.

Nemaline myopathy is a heterogeneous disorder of skeletal muscle, and histologically characterized by the presence of nemaline bodies in muscle fibers. Patients with typical congenital form of nemaline myopathy initially present with proximal but later also distal muscle weakness, mostly involving facial and respiratory muscle. Cardiac involvement has been rarely observed especially in nebulin-related nemaline myopathy and there have been only two reports about nebulin-related nemaline myopathy patients with cardiac involvement. We present here the case of a 65-year-old woman manifesting slowly progressive distal myopathy with respiratory and heart failure. She harbored two variants in the nebulin gene, c.20131C > T (p.Arg6711Trp) and c.674C > T (p.Pro225Leu), and one of them, c.674C > T, was a novel variant. In this report, we discuss the pathogenicity of the novel variant and its association with clinical phenotypes including cardiac involvement.

[A case of paraneoplastic sensory neuronopathy with anti-Hu antibody associated with large cell neuroendocrine carcinoma of the endometrium].

An 81-year-old woman was admitted to our hospital due to paresthesia of the extremities and difficulty in walking for three months. She underwent a total hysterectomy and bilateral salpingo-oophorectomy for large cell neuroendocrine carcinoma (LCNEC) of the endometrium seven months before the admission. The serum levels of neuron specific enolase (NSE) reduced after the surgery. She showed numbness of her limbs, disturbance of vibration, areflexia and autonomic dysfunction. Nerve conduction studies showed sensory dominant sensory neuronopathy. CT scan of her abdomen and pelvis revealed the recurrence of LCNEC of the endometrium. The serum levels of NSE was elevated and anti-Hu antibody was also positive. Other laboratory test, including autoantibodies were unremarkable. We diagnosed her as paraneoplastic sensory neuronopathy associated with postoperative recurrence of LCNEC of the endometrium. Here we show a clinical picture of anti-Hu positive paraneoplastic neurological syndrome with LCNEC of the endometrium.

Development of demyelinating lesions in progressive multifocal leukoencephalopathy (PML): Comparison of magnetic resonance images and neuropathology of post-mortem brain.

Progressive multifocal leukoencephalopathy (PML) is a demyelinating disorder caused by opportunistic infection of JC polyomavirus (JCV). Today, increased attention has been focused on PML development in multiple sclerosis (MS) patients under disease-modifying therapies (DMT). Although in the acquired immunodeficiency syndrome (AIDS) era, PML was thought to be a rapidly progressive disease with poor prognosis, drug-associated PML is relatively slow in progress, and a favorable outcome may be expected with early diagnosis. However, early PML diagnosis on magnetic resonance imaging (MRI) is frequently difficult, and JCV DNA copy number in cerebrospinal fluid (CSF) is usually low. To facilitate early PML diagnosis on MRI, the pre-mortem images were compared with neuropathology of the post-mortem brain, and underlying pathology corresponding to the MRI findings was evaluated. As a result, PML lesions of the autopsied brain were divided into three parts, based on the disease extension patterns: (A) Progressive white matter lesion in the right frontoparietal lobe including the precentral gyrus. Huge demyelinated lesions were formed with fusions of numerous small lesions. (B) Central lesion including deep gray matters, such as the putamen and thalamus. The left thalamic lesion was contiguous with the pontine tegmentum. (C) Infratentorial lesion of brainstem and cerebellum. Demyelination in the pontine basilar region and in cerebellar white matter was contiguous via middle cerebellar peduncles (MCPs). In addition, (D) satellite lesions were scattered all over the brain. These observations indicate that PML lesions likely evolve with three steps in a tract-dependent manner: (1) initiation; (2) extension/expansion of demyelinating lesions; and (3) fusion. Understanding of the PML disease evolution patterns would enable confident early diagnosis on MRI, which is essential for favorable prognosis with good functional outcome.

A controlled inflammation and a regulatory immune system are associated with more favorable prognosis of progressive multifocal leukoencephalopathy.

OBJECTIVE: In the present study, we analyzed the inflammatory profiles of brain tissues obtained from patients with progressive multifocal leukoencephalopathy (PML) due to John Cunningham (JC) virus infection to identify potential prognostic factors. METHODS: The study included seven patients (two men, five women) who had been pathologically diagnosed with PML, and all of whom were HIV negative. Fixed brain samples were analyzed via hematoxylin and eosin (HE) staining and Klüver-Barrera (KB) staining. We then performed immunohistochemistry (IHC) specific to JC virus capsid proteins (VP1 and VP2/3) and lymphocyte surface markers (CD4, CD8, CD138, and PD-1). RESULTS: The mean age at onset was 53.4, while the mean duration until biopsy/autopsy was 4.7 months. Four patients were included in the good prognosis (GP) group, while three were included in the poor prognosis (PP) group. Pathological analysis revealed a significantly larger number of CD4-positive T-cell infiltrations (P = .029) in the GP group, along with a preserved CD4:CD8 ratio. Larger numbers of CD138-positive plasma cells were also observed in the GP group (P = .029) than in the PP group. Linear regression analyses revealed a significant association between the numbers of CD138-positive plasma cells and PD-1-positive cells (R2 = 0.80). CONCLUSIONS: Viral loads in the cerebrospinal fluid, a controlled inflammatory response mediated by CD4- and CD8-positive T cells, and plasma cells are associated with PML prognosis. Our findings further indicate that regulatory plasma cells may regulate inflammatory T-cell activity via a PD-1/PD-L1 immuno-checkpoint pathway, thereby protecting the uninfected brain from excessive immune-mediated damage during an active JC virus infection.

[A case of hemichorea associated with lung adenocarcinoma].

An 81-year-old woman admitted to our hospital due to involuntary movement on her right extremities. Laboratory tests, including autoantibodies, were unremarkable and only age related changes were observed on brain MRI. Chest CT revealed lung adenocarcinoma. She was diagnosed as having paraneoplastic chorea. After removal of the tumor, her chorea was dramatically improved. One year after the operation, abnormal high intensity lesions were seen in bilateral caudate nuclei and globus pallidus on MRI. A part of the left caudate nucleus was enhanced by gadolinium. Here we show a clinical picture and neuroradiological findings of paraneoplastic chorea associated with lung adenocarcinoma.

[Malignant Lymphoma of the Brain, and Dementia].

A differential diagnosis of acute and subacute progressive dementias includes malignant lymphoma of the brain. We reviewed primary central nervous system lymphoma (PCNSL), intravascular lymphomatosis (IVL), lymphomatosis cerebri, and the relapse and invasion of systemic lymphomas. PCNSL is confined to the central nervous system; the infiltration and compression by the lymphoma result in adverse neurological symptoms. IVL is a rare form of malignant lymphoma that is characterized by the proliferation of primarily B-cell type lymphoma cells within the blood vessels of various organs. This causes ischemia and results in the associated neurological symptoms. Medical history and neuroimaging studies provide crucial informations to distinguish the lymphomas from other diseases that cause dementia, such an Alzheimer's disease. MRI imaging of the brain using contrast agent, and the biopsy of diseased tissues are essential for the diagnosis of the lymphomas. A histopathological examination is the most effective way to diagnose malignant lymphomas of the brain. Presently, the treatment of choice for PCNSL is the intravenous administration of high dose methotrexate with and without radiation therapy. Futhermore, Rituximab-containing chemotherapy has proved to greatly improve the prognosis of IVL. A better outcome can be achieved with the earlier diagnosis and treatment of the malignant lymphoma of the brain.

Depth perception from moving cast shadow in macaque monkey.

In the present study, we investigate whether the macaque monkey can perceive motion in depth using a moving cast shadow. To accomplish this, we conducted two experiments. In the first experiment, an adult Japanese monkey was trained in a motion discrimination task in depth by binocular disparity. A square was presented on the display so that it appeared with a binocular disparity of 0.12 degrees (initial position), and moved toward (approaching) or away from (receding) the monkey for 1s. The monkey was trained to discriminate the approaching and receding motion of the square by GO/delayed GO-type responses. The monkey showed a significantly high accuracy rate in the task, and the performance was maintained when the position, color, and shape of the moving object were changed. In the next experiment, the change in the disparity was gradually decreased in the motion discrimination task. The results showed that the performance of the monkey declined as the distance of the approaching and receding motion of the square decreased from the initial position. However, when a moving cast shadow was added to the stimulus, the monkey responded to the motion in depth induced by the cast shadow in the same way as by binocular disparity; the reward was delivered randomly or given in all trials to prevent the learning of the 2D motion of the shadow in the frontal plane. These results suggest that the macaque monkey can perceive motion in depth using a moving cast shadow as well as using binocular disparity.

Comparison of the effects of high- and low-frequency repetitive transcranial magnetic stimulation on upper limb hemiparesis in the early phase of stroke.

BACKGROUND: Recently, high-frequency repetitive transcranial magnetic stimulation (HF-rTMS) and low-frequency rTMS (LF-rTMS) are reported to improve motor function significantly in chronic hemiparetic stroke patients. However, few studies have investigated the safety and efficacy of these rTMS modalities introduced during the early phase of stroke. The purpose of this study was to clarify the rTMS modality that is more beneficial for upper limb hemiparesis in the early phase of stroke using a randomized controlled trial. METHODS: Twenty-nine patients with a hemispheric stroke lesion in the early phase of stroke were examined. Patients were randomly assigned into 3 groups: the HF-rTMS group (10 Hz rTMS to the lesional hemisphere [n = 9]), the LF-rTMS group (1 Hz rTMS to the nonlesional hemisphere [n = 11]), and the sham stimulation group [n = 9]). Patients received sessions for 5 consecutive days. Grip strength and tapping frequency were assessed before and after the intervention. Motor improvement of the affected upper limb after intervention was compared among the 3 groups. RESULTS: All patients completed the 5-day protocol. Both the HF-rTMS and LF-rTMS groups had significant increases in both grip strength and tapping frequency. Comparison of the extent of improvement showed a more significant increase in grip strength and tapping frequency in the HF-rTMS group compared to the sham stimulation group (each P < .05), and no difference between the LF-rTMS group and the sham stimulation group. CONCLUSIONS: HF-rTMS applied to the lesional hemisphere in the early phase of stroke was more beneficial for motor improvement of the affected upper limb than LF-rTMS.

[Villaret's syndrome caused by internal carotid artery dissection].

We report a patient with Villaret's syndrome (left hypoglossopharyngeal nerve, vagus nerve, accessory nerve, and hypoglossal nerve palsies and left Horner's sign) caused by internal carotid artery dissection. He had neck pain on the left side, Horner's sign on the left side and paralysis of the left hypoglossopharyngeal nerve, vagus nerve, accessory nerve, and hypoglossal nerve. Brain MRI revealed no signal from the left internal carotid artery and no brain infarction, although a tumor-like lesion was observed in the left internal carotid artery. Subsequent MRI studies revealed intramural hematoma in the left internal carotid artery, and on the basis of this finding, he was diagnosed with internal carotid artery dissection. He received anticoagulant and antiplatelet therapy. His symptoms improved gradually. The symptoms of internal carotid artery dissection are neck pain, Horner's sign, brain infarction, and lower cranial nerve palsy. A characteristic feature in this case was that brain infarction was not observed. Only 3 similar cases have been reported in the past In all these cases, the patients had a good clinical course and showed complete recovery from the symptoms. Compared with western countries, in Japan, carotid artery dissection is rare. Carotid artery dissection should be considered as a differential diagnosis of lower cranial nerve palsy.

Tremor in Klinefelter's syndrome improved by testosterone administration.

Tremor in Klinefelter's syndrome is believed to be essential tremor since the publication of "Klinefelter's syndrome and essential tremor" in 1969. However, the author also stated that tremor in Klinefelter's syndrome might differ from essential tremor. A 71-year-old man with Klinefelter's syndrome who suffers from postural hand tremor is described. The electromyogram indicated lower motor neuron disturbance and chronic neurogenic change. The muscle biopsy indicated neurogenic muscle atrophy. Upon testosterone administration, the amplitude of tremor was reduced and a gradual improvement in handwriting was observed. The tremor in this patient was different from essential tremor. The foresight by Baughman in 1969 proved to be true in this patient. This case report provides new insights into the pathogenesis and treatment of tremor in Klinefelter's syndrome, which would benefit patients who suffer from the tremor.

Reversible brainstem hypertensive encephalopathy (RBHE): Clinicoradiologic dissociation.

We report two cases of reversible brainstem hypertensive encephalopathy (RBHE) with unusual magnetic resonance (MR) findings. Patient 1, an 85-year-old man without a history of hypertension, developed acute severe hypertension and mild consciousness disturbance as the only symptoms. Patient 2, a 46-year-old man with an untreated hypertension, presented with extremely high blood pressure and general fatigue, vertigo, and mild dysarthria as the initial manifestations. In these patients, fluid-attenuated inversion recovery (FLAIR) and T2-weighted MR images revealed diffuse hyperintensities in the brainstem. Diffusion-weighted imaging (DWI) findings were normal, and apparent diffusion coefficient (ADC) values were increased in the brainstem. The supratentorial regions were largely spared, and mildly diffuse hyperintensities were noted in the white matter. There were no accompanying changes in the occipital lobe and cerebellum. The lesions completely resolved after stabilization of blood pressure. The normal DWI findings and high ADC values were consistent with vasogenic edema due to severe hypertension. The characteristics of RBHE are a very high blood pressure, mild clinical and neurologic symptoms, rapidly improved MR findings after initial treatment with the control of hypertension, and a marked clinicoradiologic dissociation.