[A case of Hashimoto's encephalopathy with acute onset of psychiatric symptoms and diffuse deep white matter lesions on brain MRI].

A 51-year-old man developed acute disturbances in consciousness and psychiatric symptoms one month prior to admission. He was referred and admitted to the Department of Psychiatry of our hospital and transferred to the neurology department because diffuse white matter lesions were found on his brain during MRI. 123I-IMP-SPECT showed extensive cerebral hypoperfusion mainly in the frontal lobes. Anti-Tg, anti-TPO, and anti-NAE antibodies were positive. These findings led to a diagnosis of Hashimoto's encephalopathy. The patient responded to steroid pulse therapy, high-dose steroid therapy, and intravenous immunoglobulin therapy, showing improvement in symptoms and imaging findings. Hashimoto's encephalopathy often presents with MRI findings similar to those of limbic encephalitis, when the patient presents with acute consciousness disturbance and psychiatric symptoms. However, this case showed diffuse white matter lesions, which may be clinically important for the differential diagnosis.

Clinical and radiological diversity in genetically confirmed primary familial brain calcification.

Primary familial brain calcification (PFBC) is a rare neuropsychiatric disorder with characteristic symmetrical brain calcifications. Patients with PFBC may have a variety of symptoms, although they also may be clinically asymptomatic. Parkinsonism is one of the most common movement disorders; however, the underlying mechanism remains unclear. This condition is typically transmitted in an autosomal dominant fashion. To date, mutations in SLC20A2, PDGFRB, PDGFB, and XPR1 have been reported to cause PFBC. The aim of the study was to identify the genetic cause of brain calcification in probands from three PFBC families and in 8 sporadic patients and to perform clinical and radiological assessments focusing on parkinsonism in mutation carriers. Three familial PFBC probands and their relatives and eight sporadic patients affected with brain calcifications were enrolled in this study. Whole-exome sequencing identified three novel mutations: c.269G > T, p.(Gly90Val) and c.516+1G > A in SLC20A2 in familial cases, and c.602-1G > T in PDGFB in a sporadic patient. The c.516+1G > A mutation resulted in exon 4 skipping in SLC20A2 (p.Val144Glyfs*85). Dopamine transporter single photon emission computed tomography using 123I-ioflupane and 123I-metaiodobenzylguanidine cardiac scintigraphy revealed pre-synaptic dopaminergic deficit and cardiac sympathetic nerve dysfunction in two SLC20A2-related PFBC patients with parkinsonism.

Epidemic myalgia in adults associated with human parechovirus type 3 infection, Yamagata, Japan, 2008.

Human parechovirus has rarely been shown to cause clinical disease in adults. During June-August 2008, a total of 22 adults sought treatment at Yonezawa City Hospital in Yamagata, Japan, for muscle pain and weakness of all limbs; most also had fever and sore throat. All patients received a clinical diagnosis of epidemic myalgia; clinical laboratory findings suggested an acute inflammatory process. Laboratory confirmation of infection with human parechovirus type 3 (HPeV3) was made for 14 patients; we isolated HPeV3 from 7 patients, detected HPeV3 genome in 11, and observed serologic confirmation of infection in 11. Although HPeV3 is typically associated with disease in young children, our results suggest that this outbreak of myalgia among adults was associated with HPeV3 infection. Clinical consideration should be given to HPeV3 not only in young children but also in adults when an outbreak occurs in the community.

A comprehensive study of repetitive transcranial magnetic stimulation in Parkinson's disease.

The clinical benefits of repetitive transcranial magnetic stimulation (rTMS) for Parkinson's disease (PD) remain controversial. We performed a comprehensive study to examine whether rTMS is a safe and effective treatment for PD. Twelve PD patients received rTMS once a week. The crossover study design consisted of 4-week sham rTMS followed by 4-week real rTMS. The Unified Parkinson's Disease Rating Scale (UPDRS), Modified Hoehn and Yahr Stage, Schwab and England ADL Scale, Actigraph, Mini-Mental State Examination, Hamilton Depression Scale, Wechsler Adult Intelligence Scale-revised, and cerebral blood flow (CBF) and cerebrospinal fluid (CSF) examinations were used to evaluate the rTMS effects. Under both drug-on and drug-off conditions, the real rTMS improved the UPDRS scores significantly, while the sham rTMS did not. There were no significant changes in the results of the neuropsychological tests, CBF and CSF. rTMS seems to be a safe and effective therapeutic option for PD patients, especially in a wearing-off state.

The role of G-protein-coupled receptor kinase 5 in pathogenesis of sporadic Parkinson's disease.

Sporadic Parkinson's disease (sPD) is a common neurodegenerative disorder, characterized by selective degeneration of dopaminergic neurons in the substantia nigra. Although the pathogenesis of the disease remains undetermined, phosphorylation of alpha-synuclein and its oligomer formation seem to play a key role. However, the protein kinase(s) involved in the phosphorylation in the pathogenesis of sPD has not been identified. Here, we found that G-protein-coupled receptor kinase 5 (GRK5) accumulated in Lewy bodies and colocalized with alpha-synuclein in the pathological structures of the brains of sPD patients. In cotransfected cells, GRK5 phosphorylated Ser-129 of alpha-synuclein at the plasma membrane and induced translocation of phosphorylated alpha-synuclein to the perikaryal area. GRK5-catalyzed phosphorylation also promoted the formation of soluble oligomers and aggregates of alpha-synuclein. Genetic association study revealed haplotypic association of the GRK5 gene with susceptibility to sPD. The haplotype contained two functional single-nucleotide polymorphisms, m22.1 and m24, in introns of the GRK5 gene, which bound to YY1 (Yin Yang-1) and CREB-1 (cAMP response element-binding protein 1), respectively, and increased transcriptional activity of the reporter gene. The results suggest that phosphorylation of alpha-synuclein by GRK5 plays a crucial role in the pathogenesis of sPD.

Vogt-Koyanagi-Harada's disease presenting polymorphonuclear pleocytosis in the cerebrospinal fluid at the early active stage.

We report a 16-year-old woman with Vogt-Koyanagi-Harada's (VKH) disease, presenting polymorphonuclear pleocytosis in the cerebrospinal fluid (CSF) and neurological manifestation similar to meningoencephalitis. VKH disease, which has severe neurological manifestations including numerous CSF polymorphonuclear pleocytosis, should be considered as a differential diagnosis from infectious meningoencephalitis.

Topographical alterations of the midbrain and the substantia nigra following unilateral posteroventral pallidotomy in patients with Parkinson's disease using routine and multishot diffusion-weighted magnetic resonance imaging.

To determine whether posteroventral pallidotomy (PVP) induces topographical changes of the ipsilateral midbrain and degeneration of the substantia nigra in Parkinson's disease patients, we obtained magnetic resonance (MR) images of 18 patients who had undergone PVP and measured the width of the cerebral peduncle at the mid-point of the inner margin. Then, we assessed MR signal changes in the substantia nigra on T2-weighted images in all patients and on multishot diffusion-weighted images in seven patients. In MR images taken within 1 year of PVP, a comparison between the ratio of the ipsilateral side/contralateral side of the cerebral peduncle of patients after PVP and that of the unaffected side/affected side in the preoperative images revealed no significant difference ( P>0.05). In MR images 1 to 2 years after PVP, there was a significant difference in the ratio of the cerebral peduncle ( P<0.01). A significant difference was still evident in MR images more than 2 years after PVP ( P<0.001). On T2-weighted images obtained within 1 year of PVP, an area of patchy high signal appeared in the posterolateral region of the ipsilateral substantia nigra in six of 13 patients. However, there was no signal change in the substantia nigra in any T2-weighted images more than 1 year after PVP. Multishot diffusion-weighted images obtained from all six patients more than 1 year after PVP revealed an abnormal area of high signal in the posterolateral region of the ipsilateral substantia nigra, however, within 1 year of PVP such a signal change was not seen. PVP would induce degeneration of the ipsilateral substantia nigra and atrophy of the ipsilateral midbrain.