Immunohistochemical study of pseudohypertrophy of the inferior olivary nucleus.

OBJECTIVE: Pathogenesis of pseudohypertrophy of the inferior olivary nucleus (PH-IO) was analyzed based on immunohistochemical study. METHODS: Immunostained medullas with PH-IO were observed with confocal laser microscopy. RESULTS: αB-crystallin (αBC) was frequently expressed in the neurons and co-localized with microtubule-associated protein 2 (MAP2). The neurons were occasionally positive for SMI-31. αBC and SMI-31 were co-localized in some neurons. Synaptophysin (SYP)-immunoreactive dots were present around MAP2-positive hypertrophic neurons and hypertrophic thick neurites. Periphery-stained Lys-Asp-Glu-Leu (KDEL)-positive neurons were shown. Central chromatolytic neurons were found with Klüver-Barrera staining, which indicated that the rough endoplasmic reticulum (ER) was distributed to the periphery of the cytoplasm. CONCLUSIONS: αBC prevents microtubule disassembly and phosphorylation of the neurofilaments under stressful conditions. Our results indicated that αBC protected microtubules and neurofilaments in PH-IO. The retrograde transport of KDEL receptors from the Golgi complex to the ER is increased under stressful conditions. We considered that KDEL receptors were retro-transported to ER, and then the ER containing KDEL receptors was distributed to the periphery of the cytoplasm. PH-IO showed various immunohistochemical changes due to trans-synaptic degeneration.

Miller Fisher syndrome associated with influenza A infection.

A 36-year-old, previously healthy man presented with Miller Fisher syndrome (MFS) five days after he was diagnosed with an influenza A infection by a rapid antigen test. He had not received any recent vaccinations. He had no loss of consciousness. Bilateral ophthalmoplegia, blepharoptosis, areflexia, and ataxic gait were noted. One week after treatment with intravenous immunoglobulin, his ophthalmoplegia, blepharoptosis, and ataxic gait had gradually improved, and his deep tendon reflexes returned. Anti-GQ1b IgG antibodies were detected in his serum. There has been no previous report of postinfectious MFS following confirmed an influenza A infection in an adult.

[Acute non-herpetic encephalitides].

"Acute non-herpetic encephalitis" was consisted of several non-herpetic encephalitides including "acute juvenile female non-herpetic encephalitis (AJFNHE)" and "non-herpetic limbic encephalitis(NHLE)". In 1997, we first reported five young adult female patients with acute non-herpetic encephalitis who presented with severe prolonged coma and status epilepticus, but achieved a good recovery. Following this report, the results of a clinical analysis on 89 serial patients with encephalitides indicated that such patients presented specific and different clinical features, including the frequent detection of anti-glutamate receptor (GluR) antibody as compared with other etiologies of encephalitis. Since all of their 11 patients were young adult women, we designated these patients as "acute juvenile female non-herpetic encephalitis (AJFNHE)". In 2007, Dalmau et al. reported anti-N-methyl-D-aspartate receptor(NMDAR) encephalitis associated with ovarian teratoma. We recently reported the results of a nationwide survey on AJFNHE in Japan. This result was indicated that AJFNHE and anti-NMDAR encephalitis were inferred to be almost identical condition. AJFNHE thus represented a clinical concept based on the specific clinical features, and anti-NMDAR encephalitis represented a clinical entity based on the neuro-oncological findings including the NMDAR NR1 and NR2 heteromer antibody.

Depletion or preservation of cardiac sympathetic nerve - an autopsy-verified contrast in two cases of Alzheimer's disease with or without Lewy bodies.

We report autopsy findings of 2 patients with the clinical diagnosis of dementia with Lewy bodies (DLB) both with Alzheimer disease (AD) pathology. Lewy bodies and cardiac sympathetic nerve depletion were found in case 1, while these pathological changes were both absent in case 2 with pure AD pathology. This autopsy-verified contrast was detectable through reduced uptake of (123)I-metaiodobenzylguanidine cardiac scintigraphy as in case 1. Conversely, its preserved uptake, indicating preserved cardiac sympathetic nerve, may point to the absence of Lewy bodies, as in case 2, even though other clinical pictures are indistinguishable from DLB. (123)I-metaiodobenzylguanidine cardiac scintigraphy may be useful to distinguish clinically between pure AD and DLB.

Selective deposition of 4-repeat tau in cerebral infarcts.

The tau deposits found in neurodegenerative diseases are classified based on their isoforms, that is, 3-repeat (3R) tau and 4-repeat (4R) tau. These isoforms are distinguishable using the antibodies RD3 and RD4, respectively, and Gallyas (Gal) and Campbell-Switzer (CS) silver staining methods, respectively. Tau is also deposited in cerebral infarcts. To characterize the tau profile in these lesions, 21 brains from autopsied patients with cerebral infarcts were analyzed using immunohistochemistry with RD3, RD4, and the anti-paired helical filament antibody AT8 and with Gal and CS staining; all of these techniques identify Alzheimer disease-type neurofibrillary tangles. Fluorescence labeling followed by silver staining in mirror-section pairs was also used to compare the staining patterns. Neurons in and around ischemic foci exhibited the 4R-tau epitope until 34 days postinfarction; argyrophilia with Gal staining persisted longer. The 4R-tau/Gal-positive neurons were negative for 3R-tau and AT8 epitopes and lacked fibrillary structures and argyrophilia by CS staining; they are, therefore, distinct from neurons with neurofibrillary tangles. Positivity for 4R tau/Gal and negativity for 3R tau/CS were also seen in astrocytes and microglia around infarcts. Although this staining profile is characteristic of degenerative processes with 4R-tau deposition, lack of AT8 immunoreactivity and of fibrillary structures in neurons, astrocytes, and microglia indicates that selective 4R-tau deposition represents a stage without tau phosphorylation or fibril formation in cerebral infarcts.