In clinical diagnostic imaging of Alzheimer’s disease (AD), MRI and nuclear medicine studies such as cerebral blood flow SPECT are positioned as biomarkers expressing pathological conditions. With understanding its usefulness and limitations, it is important to conduct appropriate application and to utilize the correct evaluation of the result in clinical practice. Although FDG-PET and amyloid PET are still not covered for dementia by health insurance, they are extremely useful for differential diagnosis as well as early diagnosis of AD. As image biomarkers, they may have complementary implications. In addition, tau PET under development not only realizes more accurate evaluation of AD but also is expected to be applied in dementia other than AD. In the future, image biomarkers are indispensable for patient selection (early diagnosis) in mild cognitive impairment (MCI) or earlier stages and for judging the therapeutic effect of interventions in cases when early intervention for AD.

We investigated 17 adult cases (14 males and 3 females) of myalgia induced by human parechovirus type 3 (HPeV3) infection, treated during the summers of 2008, 2011, 2014, and 2016. The patients were aged between 21 and 50 years. The limbs and trunk of all patients were affected, and severe myalgia, muscle weakness, and decreased grip strength were observed. In addition to myalgia and muscle weakness, symptoms included fever in 14 (82%), upper respiratory inflammation in 8 (47%), gastroenteritis in 4 (24%), and scrotal pain in 4 (29% of males) patients. Tendon reflexes were preserved, and serum creatine kinase level increased in all but 1 patient. Spinal MRI was performed for 3 patients, with normal results. Musculoskeletal MRI scans showed abnormal signals in the femoral muscles in 2 of 5 patients. In a nerve conduction test, the frequency of F wave appearance in the median nerve was 40% or less in 5 of 9 patients, and repeater F waves were seen in 2 patients. Of these, 7 patients had infants in their families, and developed fever around the same time; they may have been infected by these infants. All patients recovered within 1–2 weeks. HPeV3 infection is characterized by severe myalgia, and is frequently observed in summer every 2–3 years.

We treated 11 cases (52.7 ± 14.9 years, all male) with varicella zoster virus (VZV) meningitis and 437 cases with adult aseptic meningitis from 2004 to 2016. The incidence rate of adult VZV meningitis in the cases with aseptic meningitis was 2.5%. Herpes zoster infections are reported to have occurred frequently in summer and autumn. VZV meningitis also occurred frequently in the similar seasons, in our patients. The diagnoses were confirmed in 9 cases with positive VZV-DNA in the cerebrospinal fluid and in 2 cases with high VZV-IgG indexes (> 2.0). For diagnosis confirmation, the former test was useful for cases within a week of disease onset, and the latter index was useful for cases after a week of disease onset. Zoster preceded the meningitis in 8 cases, while the meningitis preceded zoster in 1 case, and 2 cases did not have zoster (zoster sine herpete). Two patients were carriers of the hepatitis B virus, 1 patient was administered an influenza vaccine 4 days before the onset of meningitis, and 1 patient was orally administered prednisolone for 2 years, for treatment. Their immunological activities might have been suppressed. The neurological complications included trigeminal neuralgia, facial palsy (Ramsay Hunt syndrome), glossopharyngeal neuralgia, and Elsberg syndrome. Because the diseases in some patients can become severe, they require careful treatment.

A previously healthy 80-year-old woman presented to our service in a comatose state. On examination the patient had fever and neck stiffness. Laboratory investigation showed polymorphonuclear pleocytosis in cerebro-spinal fluid (CSF). These findings prompted us to a diagnosis of bacterial or viral meningitis and combination therapy consisting of ceftriaxone, vancomycin and acyclovir was started immediately. Two days later, culture of blood yielded Streptococcus pyogenes (group A streptococcus; GAS). The antibiotic therapy was converted to intravenous ampicillin for 14 days. Fever resolved quickly, however, somnolence persisted. Fluid attenuated inversion recovery image of the brain, taken on the day 29, showed focal hyperintense lesions on the right subcortical area in the temporal and parietal lobes. Three times repeated intravenous steroid pulse therapy (methylprednisolone 1,000 mg/day, 3 days) resulted in complete improvement of her consciousness disturbance. We considered the present case to be a steroid-responsive meningoencephalitis caused by GAS infection.

A 71-year-old man was admitted to our hospital because of abnormal behavior and generalized convulsion. Brain MRI revealed no abnormalities upon admission. Levels of serum lactate dehydrogenase and soluble interleukin-2 receptors were significantly elevated, whereas the initial bone marrow puncture and random skin biopsy findings were non-malignant. On the tenth day of admission, brain MRI revealed dot and strip-shaped low signal intensity lesions on susceptibility-weighted images (SWI) disseminated mainly within the cerebral cortex. Administration of high dose methyl-prednisolone improved neither his condition nor these MRI findings. Ground-glass opacities within the bilateral lungs later emerged on the chest CT. The results of a transbronchial lung biopsy and second bone marrow puncture were consistent with a diagnosis of intravascular large B-cell lymphoma (IVLBCL). Despite the lack of histopathological confirmation, the low signal intensities on brain SWI in this case were also considered IVLBCL lesions, reflective of micro-hemorrhagic changes.

A 28-year-old Japanese male without a significant past medical history presented with new-onset generalized clonic seizure and headache. A brain MRI revealed multiple enhanced lesions on both cerebral hemispheres. Laboratory exams showed no evidence of systemic inflammation or auto-immune antibodies such as ANCAs. Despite four courses of high-dose methylprednisolone pulse therapy and five treatments with plasmapheresis, his symptoms worsened and the MRI lesions progressed rapidly. During these treatments, we performed a targeted brain biopsy, that revealed histological findings consistent with a predominant angiitis of parenchymal and subdural small vessels. He was provided with diagnosis of central nervous system vasculitis (CNSV). Subsequent cyclophosphamide pulse therapy enabled a progressive successful improvement of his symptoms. While diagnostic methods for CNSV remain controversial, histological findings are thought to be more useful in obtaining a more definitive diagnosis than findings in image studies, such as MRI and angiography. We suggest that a brain biopsy should be considered during the early period of cases with suspected CNSV and rapid clinical deterioration. We also detected human herpesvirus 7 (HHV-7) using PCR technology in brain biopsy specimens, however the relationship between CNSV and HHV-7 infection is unknow.

We report a 59-year-old Japanese male who developed gradually worsening weakness and numbness of distal four extremities since age 50. His parents were first cousins, and blood and cerebral spinal examinations were unremarkable. Homozygous mutation of MME gene was detected and thus he was diagnosed as autosomal-recessive Charcot-Marie-Tooth disease 2T (AR-CMT2T); however, electrophysiological examinations revealed scattered demyelinative changes including elongated terminal latency in several peripheral nerve trunks. Sural nerve biopsy showed endoneurial edema and a lot of thinly myelinated nerve fibers with uneven distribution of remnant myelinated fibers within and between fascicles. Immunoglobulin treatment was initiated considering the possibility of superimposed inflammation and demyelination, and immediate clinical as well as electrophysiological improvements were noted. Our findings indicate that AR-CMT2T caused by MME mutation predisposes to a superimposed inflammatory demyelinating neuropathy. This is the first report which documented the co-existence of CMT2 and chronic inflammatory demyelinating polyneuropathy (CIDP); however, in the peripheral nervous system, neprilysin, a product of MME gene, is more abundant in myelin sheath than in axonal component. The fragility of myelin sheath due to mutated neprilysin may trigger the detrimental immune response against peripheral myelin in this patient.

We report a 40-year-old man who presented with multiple bone pseudofractures after about 20 years from the onset of Wilson’s disease (WD). At age 36, he first noticed pain in his left shoulder. At age 39, he had multiple chest pain. On neurologic examinations, dysarthria and dysphagia due to pseudobulbar palsy, rigidity and tremor on right upper lim were observed. WD was confirmed because of low levels of plasma cupper and ceruloplasmin in addition to ATP7B gene mutation. The chest X-ray revealed multiple fractures of the several ribs. We diagnosed osteomalacia due to Fanconi’s syndrome because of hypophosphatemia and the impairment of renal tubules for WD. After administration of vitamin D, there happened no new bone pseudofractures. Although bone pseudofractures accompanied by Wilson’s disease generally happen in childhood, we should be aware of this symptom even in adulthood.