Clinical Application of 18F-THK5351 PET to Identify Inflammatory Lesions Through Imaging Astrogliosis in a Case of Cytomegalovirus Ventriculoencephalitis.

ABSTRACT: 18F-THK5351 PET is used to estimate the degree of astrogliosis. Because inflammatory lesions usually accompany astrogliosis, 18F-THK5351 PET is potentially worthy of clinical application in inflammatory disorders. Here, we report a case of cytomegalovirus ventriculoencephalitis in an immunocompromised 75-year-old woman who underwent 18F-THK5351 PET and conventional neuroimaging modalities, including 11C-methionine, 18F-FDG, and MRI. 18F-THK5351 PET was clearly superior to the other modalities in identifying inflammatory lesions and can therefore be a useful marker for identifying inflammatory lesions through imaging astrogliosis. This feature of 18F-THK5351 may contribute to the early diagnosis of cytomegalovirus ventriculoencephalitis.

High sensitivity of asymmetric 18F-THK5351 PET abnormality in patients with corticobasal syndrome.

Corticobasal syndrome (CBS) is characterized by symptoms related to the asymmetric involvement of the cerebral cortex and basal ganglia. However, early detection of asymmetric imaging abnormalities can be challenging. Previous studies reported asymmetric 18F-THK5351 PET abnormalities in CBS patients, but the sensitivity for detecting such abnormalities in larger patient samples, including early-stage cases, remains unclear. Patients clinically diagnosed with CBS were recruited. All patients displayed asymmetric symptoms in the cerebral cortex and basal ganglia. Asymmetric THK5351 PET abnormalities were determined through visual assessment. Brain MRI, perfusion SPECT, and dopamine transporter (DAT) SPECT results were retrospectively reviewed. The 15 patients had a median age of 72 years (59-86 years) and a disease duration of 2 years (0.5-7 years). Four patients met the probable and 11 met the possible CBS criteria according to Armstrong criteria at the time of PET examination. All patients, including early-stage cases, exhibited asymmetric tracer uptake contralateral to their symptom-dominant side in the cerebral cortex/subcortical white matter and striatum (100%). The sensitivity for detecting asymmetric imaging abnormalities contralateral to the symptom-dominant side was 86.7% for brain MRI, 81.8% for perfusion SPECT, and 90% for DAT SPECT. White matter volume reduction was observed in the subcortical region of the precentral gyrus with increased THK5351 uptake, occurring significantly more frequently than gray matter volume reduction. THK5351 PET may be a sensitive imaging technique for detecting asymmetric CBS pathologies, including those in early stages.

Correlations between cerebrospinal fluid homovanillic acid and dopamine transporter SPECT in degenerative parkinsonian syndromes.

Both cerebrospinal fluid (CSF) homovanillic acid (HVA) and striatal dopamine transporter (DAT) binding on single-photon emission computed tomography (SPECT) reflect nigrostriatal dopaminergic function, but studies on the relationship between the two have been limited. It is also unknown whether the reported variance in striatal DAT binding among diseases reflects the pathophysiology or characteristics of the subjects. We included 70 patients with Parkinson's disease (PD), 12 with progressive supranuclear palsy (PSP), 12 with multiple system atrophy, six with corticobasal syndrome, and nine with Alzheimer's disease as disease control, who underwent both CSF analysis and 123I-N-ω-fluoropropyl-2ß-carbomethoxy-3ß-(4-iodophenyl)nortropane (123I-ioflupane) SPECT. We evaluated the correlation between CSF HVA concentration and the specific binding ratio (SBR) of striatal DAT binding. We also compared the SBR for each diagnosis, controlling for CSF HVA concentration. The correlations between the two were significant in patients with PD (r = 0.34, p = 0.004) and PSP (r = 0.77, p = 0.004). The mean SBR value was the lowest in patients with PSP and was significantly lower in patients with PSP than in those with PD (p = 0.037) after adjusting for CSF HVA concentration. Our study demonstrates that striatal DAT binding correlates with CSF HVA concentration in both PD and PSP, and striatal DAT reduction would be more advanced in PSP than in PD at an equivalent dopamine level. Striatal DAT binding may correlate with dopamine levels in the brain. The pathophysiology of each diagnosis may explain this difference.

18 F-THK5351 PET Can Evaluate Tumor Extension in Intravascular Large B-Cell Lymphoma : Comparison With 11C-Methionine PET and 18F-FDG PET.

ABSTRACT: A 79-year-old man presenting with gait disturbance and cognitive decline was diagnosed with intravascular large B-cell lymphoma (IVLBCL) by random skin biopsy. Some IVLBCL lesions were identified by PET examinations using 11 C-methionine, 18 F-FDG, and 18 F-THK5351. 11 C-methionine and 18 F-FDG uptake, which likely reflects the presence of the lymphoma cells themselves, increased clearly in the left putamen but weakly in the left deep white matter. 18 F-THK5351 uptake increased in all lesions, likely reflecting perivascular astrogliosis caused by IVLBCL. Hence, 18 F-THK5351 PET can evaluate tumor extension in IVLBCL lesions where 11 C-methionine and 18 F-FDG PET may fail in its visualization.

Development of Polyneuropathy, Organomegaly, Endocrinopathy, M Protein, and Skin Changes Syndrome after Conversion from Plasmacytoma of Bone to Multiple Myeloma.

A 36-year-old man developed polyneuropathy, organomegaly, endocrinopathy, M protein, and skin changes (POEMS) syndrome after conversion from solitary plasmacytoma of bone to multiple myeloma. Twenty-four days following the neurological onset, he lost his independent walking ability. The level of serum vascular endothelial growth factor (VEGF) at diagnosis was 5,250 pg/mL. Three months after initiating treatment, he regained his independent walking ability in line with a reduction in the elevated serum VEGF level. Due to their genomic instability gained during conversion, myeloma cells may overproduce humoral factors and cytokines, possibly contributing to the development of neuropathy as well as the production of VEGF.

CSF P-Tau181 and Other Biomarkers in Patients With Neuronal Intranuclear Inclusion Disease.

BACKGROUND AND OBJECTIVES: CSF tau phosphorylated at threonine 181 (p-tau181) is a widely used biomarker for Alzheimer disease (AD) and has recently been regarded to reflect ß-amyloid and/or p-tau deposition in the AD brain. Neuronal intranuclear inclusion disease (NIID) is a neurodegenerative disease characterized by intranuclear inclusions in neurons, glial cells, and other somatic cells. Symptoms include dementia, neuropathy, and others. CSF biomarkers were not reported. The objective of this study was to investigate whether CSF biomarkers including p-tau181 are altered in patients with NIID. METHODS: This was a retrospective observational study. CSF concentrations of p-tau181, total tau, amyloid-beta 1-42 (Aß42), monoamine metabolites homovanillic acid (HVA), and 5-hydroxyindole acetic acid (5-HIAA) were compared between 12 patients with NIID, 120 patients with Alzheimer clinical syndrome biologically confirmed based on CSF biomarker profiles, and patients clinically diagnosed with other neurocognitive disorders (dementia with Lewy bodies [DLB], 24; frontotemporal dementia [FTD], 13; progressive supranuclear palsy [PSP], 21; and corticobasal syndrome [CBS], 13). Amyloid PET using Pittsburgh compound B (PiB) was performed in 6 patients with NIID. RESULTS: The mean age of patients with NIID, AD, DLB, FTD, PSP, and CBS was 71.3, 74.6, 76.8, 70.2, 75.5, and 71.9 years, respectively. CSF p-tau181 was significantly higher in NIID (72.7 ± 24.8 pg/mL) compared with DLB, PSP, and CBS and was comparable between NIID and AD. CSF p-tau181 was above the cutoff value (50.0 pg/mL) in 11 of 12 patients with NIID (91.7%). Within these patients, only 2 patients showed decreased CSF Aß42, and these patients showed negative or mild local accumulation in PiB PET, respectively. PiB PET scans were negative in the remaining 4 patients tested. The proportion of patients with increased CSF p-tau181 and normal Aß42 (A-T+) was significantly higher in NIID (75%) compared with DLB, PSP, and CBS (4.2%, 4.8%, and 7.7%, respectively). CSF HVA and 5-HIAA concentrations were significantly higher in patients with NIID compared with disease controls. DISCUSSION: CSF p-tau181 was increased in patients with NIID without amyloid accumulation. Although the deposition of p-tau has not been reported in NIID brains, the molecular mechanism of tau phosphorylation or secretion of p-tau may be altered in NIID.

Hypoxemia found after hospitalization with right hemiplegia due to cerebral infarction: platypnea-orthodeoxia syndrome in the older people.

An 89-year-old woman was admitted to our hospital for subacute onset of right upper and lower limb weakness and was diagnosed with acute cerebral infarction. During rehabilitation, close observation revealed that her oxygen saturation decreased in the sitting position and improved in the recumbent position without any subjective symptoms of dyspnea. Transthoracic and transesophageal echocardiography and cardiac catheterization revealed a large patent foramen ovale with an atrial septal aneurysm with right-to-left shunting through the defect, and she was diagnosed with platypnea-orthodeoxia syndrome. Her right hemiplegia caused the trunk to collapse, so the patient slumped when in sitting position, and the trunk tilted to the right forward, resulting in an increased right-to-left shunt. Her peripheral capillary oxygen saturation improved in the upright sitting position supported by therapists. This case suggests that right hemiplegia may exacerbate the symptoms of platypnea-orthodeoxia syndrome. .

Spinal Cord Infarction in a Patient with Immune Thrombocytopenic Purpura.

Immune thrombocytopenic purpura (ITP) can increase the risk of not only hemorrhagic incidents but also thrombotic events. Although several patients with ITP who developed cerebral infarction have been reported, concurrence of spinal cord infarction and ITP has not been reported. We report the case of a female patient who developed spinal cord infarction during the exacerbation of her ITP. This case suggests a possible association between spinal cord infarction and ITP, which can cause paradoxical thrombosis.

Clinical Characteristics of Epidemic Myalgia Associated with Human Parechovirus Type 3 during the Summer of 2019.

Objective Epidemic myalgia associated with human parechovirus type 3 (EM-HPeV3) is characterized by severe muscle pain and weakness on the limbs and trunk with a fever. No outbreak of EM-HPeV3 has been reported since 2016, and its clinical characteristics have not been sufficiently clarified. We herein report a series of EM-HPeV3 cases during the summer of 2019 and clarify the clinical characteristics of EM-HPeV3. Methods The diagnosis of EM-HPeV3 was established when the patients met both of the following criteria: (1) Patients developed severe muscle pain and weakness with a fever within a week, and those symptoms resolved within a month; and (2) HPeV3 was detected in either a throat swab or fecal specimen of the patient by polymerase chain reaction. We reviewed the medical records of these patients retrospectively. Results Seven patients met the criteria (6 men and 1 woman, age 34 to 47 years old). Myalgia was observed on the thigh, lower legs, upper arms, and forearms in seven, five, two, and five patients, respectively. Four patients showed distal dominant weakness on the arms, while none of the patients showed proximal dominant weakness on the arms. Of the six patients examined, five showed reduced tendon reflexes on all four limbs. One patient showed slight myogenic change and increased insertion activities on needle electromyography. Conclusion We observed seven cases of EM-HPeV3 during the summer of 2019. Reduced tendon reflexes and distal dominancy of muscle pain and weakness on the arms are considered its distinct clinical features.

Epilepsia Partialis Continua as an Early Sign of Anti-Myelin Oligodendrocyte Glycoprotein Antibody-positive Encephalitis.

Anti-myelin oligodendrocyte glycoprotein (MOG) antibodies have been associated with steroid-responsive cortical encephalitis and comorbid generalized epilepsy. A 44-year-old woman developed repeated epilepsia partialis continua (EPC) without generalized seizures and was anti-MOG antibody-positive. Radiological abnormalities were detected in the bilateral medial frontoparietal cortices, but there were no cerebrospinal fluid abnormalities. She achieved remission with anti-epileptic drugs alone. However, encephalitis recurred four months later when pleocytosis appeared, and steroid therapy was effective. Altogether, EPC without typical cerebrospinal fluid features can be an early sign of anti-MOG antibody-positive encephalitis. Thus, patients with EPC of unknown etiology need to be screened for anti-MOG antibodies.

Dreamy State, Delusions, Audiovisual Hallucinations, and Metamorphopsia in a Lesional Lateral Temporal Lobe Epilepsy Followed by Ipsilateral Hippocampal Sclerosis.

We report a 65-year-old man who was diagnosed with focal status epilepticus generating a dreamy state, delusions with anxiety, complex audiovisual hallucinations, elementary auditory hallucinations, and metamorphopsia with a growing large lateral temporal lobe lesion. After administrating anti-seizure drugs, all the symptoms disappeared, and brain magnetic resonance imaging revealed ipsilateral hippocampal sclerosis. To the best of our knowledge, this is the first report to present all the symptoms in one epilepsy case. On the basis of semiology, electroencephalography, and brain magnetic resonance imaging, we speculated that epileptic activities that have originated from the lateral lesion might have propagated to the ipsilateral mesial temporal lobe, causing hippocampal sclerosis.

Toxic Epidermal Necrolysis in a Patient with Autoimmune Limbic Encephalitis with Anti-Glutamate Receptor Antibodies.

We report on a 44-year-old woman who was diagnosed with toxic epidermal necrolysis (TEN) during the recovery phase from autoimmune limbic encephalitis with anti-glutamate receptor antibodies. Both, autoimmune limbic encephalitis and TEN are very rare diseases. The co-existence of the two diseases has not yet been reported. We speculate that the total of 18 drugs needed for the treatment of encephalitis might have increased the risk of TEN. Similar reports would be required to elucidate the pathophysiology of the co-existence.

Lenalidomide-Induced Ischemic Cerebrovascular Disease in Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal Gammopathy, and Skin Changes Syndrome.

We describe the case of a 34-year-old woman with polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS) syndrome. She developed transient ischemic attack after the introduction of lenalidomide plus dexamethasone (Rd) therapy despite no vascular risk factors. Magnetic resonance and computed tomography angiographies showed bilateral internal carotid artery stenosis. Rd therapy was suspended because of its thromboembolic risk. She had been neurologically stable during the suspension of Rd therapy. After Rd therapy was restarted, however, she repeated ischemic cerebrovascular disease. Rd therapy was switched to carfilzomib plus dexamethasone therapy. Thereafter, she had been neurologically stable. Multivessel stenosis is infrequently seen in POEMS syndrome. Therefore, magnetic resonance angiography should be performed before introducing Rd therapy in POEMS syndrome.

Serial neurophysiological and neurophysiological examinations for delayed facial nerve palsy in a patient with Fisher syndrome.

The patient was a 47-year-old man who presented with diplopia and gait instability with a gradual onset over the course of three days. Neurological examinations showed ophthalmoplegia, diminished tendon reflexes, and truncal ataxia. Tests for anti-GQ1b antibodies and several other antibodies to ganglioside complex were positive. We made a diagnosis of Fisher syndrome. After administration of intravenous immunoglobulin, the patient's symptoms gradually improved. However, bilateral facial palsy appeared during the recovery phase. Brain MRI showed intensive contrast enhancement of bilateral facial nerves. During the onset phase of facial palsy, the amplitude of the compound muscle action potential (CMAP) in the facial nerves was preserved. During the peak phase, the facial CMAP amplitude was within the lower limit of normal values, or mildly decreased. During the recovery phase, the CMAP amplitude was normalized, and the R1 and R2 responses of the blink reflex were prolonged. The delayed facial nerve palsy improved spontaneously, and the enhancement on brain MRI disappeared. Serial neurophysiological and neuroradiological examinations suggested that the main lesions existed in the proximal part of the facial nerves and the mild lesions existed in the facial nerve terminals, probably due to reversible conduction failure.

Expression of leukemia inhibitory factor in the endometrium in abnormal uterine cavities during the implantation window.

OBJECTIVE: To investigate the expression of the implantation factors leukemia inhibitory factor (LIF), interleukin-11 (IL-11), and IL-6ST/gp130 in the endometrium to examine the relationship between loss of implantation and abnormal uterine cavity. DESIGN: Case-control study. SETTING: Department of Obstetrics and Gynecology, Tokyo Medical University. PATIENT(S): Subjects comprised 41 patients in the abnormal uterine cavity group who underwent resection of a uterine submucosal myoma or an endometrial polyp by transcervical resectoscopy (TCR) and 18 patients in the control group who underwent laparoscopic surgery. INTERVENTION(S): In the abnormal uterine cavity group, endometrial tissue specimens were obtained before resection under hysteroscopy. In the control group, endometrial tissue specimens were obtained by curettage at the time of laparoscopic surgery. MAIN OUTCOME MEASUREMENT(S): We divided the patients into four groups according to menstrual cycle and measured the endometrial expression of LIF, IL-11, and IL-6ST/gp130 with the use of quantitative real-time reverse-transcription polymerase chain reaction. RESULT(S): Significant increases in LIF and IL-11 mRNA expression were recognized during the midsecretory phase of the menstrual cycle in the control group. However, no difference in IL-6ST/gp130 mRNA expression was observed in any phase during the menstrual cycle in either group. In terms of LIF and IL-11 mRNA expression at the midsecretory phase, the abnormal uterine cavity group showed a significantly decreased LIF mRNA expression compared with the control group. CONCLUSION(S): LIF mRNA expression was significantly decreased in abnormal uterine cavities during the midsecretory phase, indicating that endometrial cavity defects are a possible cause of poor reproductive outcomes.