Tatsuyuki Aoki

Borrelia burgdorferi-seropositive chronic encephalomyelopathy: Lyme neuroborreliosis? An autopsied report.

A 36-year-old Japanese woman presented with progressive cerebellar signs and mental deterioration of subacute course after her return from the USA. Her serum antibody to spirochete Borrelia burgdorferi was significantly elevated. A necropsy 4 years after her initial neurological signs revealed multifocal inflammatory change in the cerebral cortex, thalamus, superior colliculus, dentate nucleus, inferior olivary nucleus and spinal cord. The lesions showed spongiform change, neuronal cell loss, astrocytosis and proliferation of activated microglial cells. The internal capsule was partially vacuolated and the spinal cord, notably at the thoracic level, was demyelinated and cavitated in the lateral funiculus. Microglial cells aggregated within and around the spongiform lesions and microglial nodules were present in the medulla oblongata. Use of Warthin-Starry stain demonstrated silver-impregnated organisms strongly suggesting B. burgdorferi in the central nervous tissues. The dentate nucleus and inferior olivary nucleus showed the most advanced lesions with profound fibrillary gliosis. Occlusive vascular change was relatively mild, and fibrous thickening of the leptomeninges with lymphocyte infiltrates was localized in the basal midbrain. The ataxic symptoms were due to the dentate and olivary nucleus lesions and mental deterioration was attributable to the cortical and thalamic lesions. Spongiform change, neuronal cell loss, and microglial activation are characteristic pathological features in the present case. The cerebellar ataxia and subsequent mental deterioration are unusual clinical features of Lyme neuroborreliosis. Spirochete B. burgdorferi can cause focal inflammatory parenchymal change in the central nervous tissues and the present case may be an encephalitic form of Lyme neuroborreliosis.

KP-1 Is a Marker for Extraneuronal Neurofibrillary Tangles and Senile Plaques in Alzheimer Diseased Brains

KP-1 immunostaining with microwave pretreatment in formalin-fixed, paraffin-embedded sections enhanced its immunoreactivity revealing extraneuronal neurofibrillary tangles (NFTs) called ghost tangles, senile plaques (SPs) and perivascular deposits as well as microglial labelling in Alzheimer-diseased brains. KP-1 stained cored and uncored SPs, granules within the SPs, perivascular β-amyloid protein (βAP) and star-like βAP deposits in cortical layer I, which was confirmed in comparison to silver-impregnated structures in the Reusche-stained or Gallyas-Schiff-stained sections. On double immunostaining with KP-1 and ubiquitin, ghost tangles were labelled by KP-1 and intraneuronal NFTs were positive for ubiquitin. A few KP-1-positive granules deposits different from amyloid core were found within the SPs and the outer margin of amyloid cores of SPs were stained by KP-1. KP-1-positive microglia were attached to the ubiquitin-positive intraneuronal NFTs. Microglia were more numerously labelled by CR3/43 than by KP-1, and CR3/43-positive microglia were found to be preferentially attached to SPs. As KP-1 recognizes lysosome-associated antigen CD68, similarities between KP-1 positivity and Reusche-stained structures suggested that lysosomal activity was associated with βAP deposits and ghost tangles were involved in lysosome-associated processes. It is speculated that lysosomes play a role in the process of ghost tangle formation and in βAP deposits leading to SP formation.

Non-familial olivopontocerebellar atrophy combined with late onset Alzheimer's disease: a clinico-pathological case report.

A 76-year-old woman with olivopontocerebellar atrophy (OPCA) presented with progressive intellectual deterioration. She showed cerebellar ataxia and muscle atrophy and weakness, and gradually developed generalized dementia with visuospatial disturbance. An autopsy revealed numerous senile plaques (SPs), neurofibrillary tangles (NFTs) and neuropil threads particularly in the CA1, subiculum and entorhinal cortex and to a lesser degree in the cerebral neocortex shown by immunostaining and specific silver impregnation techniques. The nucleus basalis of Meynert had numerous NFTs with fibrillary gliosis and neuronal cell loss. The basis pontis was markedly atrophied and the pontine nucleus had severe neuronal depopulation and gliosis. The pontine transverse fibers were demyelinated with their axons being fragmented. The cerebellar white matter was also severely degenerated. The striatum, Onufs and intermediolateral nuclei of the spinal cord remained unchanged. Ubiquitin immunohistochemistry and Gallyas silver impregnation technique revealed oligodendroglial inclusions in the pontine nucleus, corticopontine tract, cerebral and cerebellar white matter. On double immunostaining of KP1 and ubiquitin, globular neurite SPs encircled by KP1-positive fibrous structures were found in the hippocampus and cerebral neocortex. The curly neurite SPs contained KP1-positive granules. The KP1-positive microglial cells were distributed widely in the cerebral white matter and HLA-DR-positive ones were found around the SPs. The present case showed generalized dementia compatible with Alzheimers disease (AD) and had a pathologically limbic type of late onset AD. This is the first case where AD affected non-familial OPCA.

An autopsied case of Creutzfeldt‐Jakob disease with the lateral geniculate body lesion showing antagonizing correlation between periodic synchronous discharges and photically induced giant evoked responses

We reported an necropsy finding of a patient with Creutzfeldt‐Jakob disease (CJD) who showed photo‐stimulated giant spikes that simultaneously suppressed periodic synchronous discharges (PSD) and the loss of pupillary light reflex during the course of the illness. The necropsy revealed extensive gray and white matter lesions, and both the lateral geniculate body (LGB) and pregeniculate body were primarily affected. The superior colliculus, optic nerve and tracts were not affected. The cerebral cortices particularly of the occipital lobe were severely damaged. The Gennari line, however, was spared from lesion. The primary involvement of the LGB has been reported infrequently in CJD, however, it appears to be associated with the unusual electroencephlograph (EEG) feature of the present case. The pregeniculate lesion contributed to the loss of pupillary reflex. This finding indicates that the visual pathway may be involved in the mechanism of the generation of PSD in CJD.

Antagonizing correlation between periodic synchronous discharges and photically induced giant evoked responses in Creutzfeldt--Jakob disease (Heidenhain type): a case study.

Abstract In a patient with Creutzfeldt‐Jakob disease (Heidenhain type), which was characterized by the initial onset of visual symptoms and proved by autopsy, there was an antagonizing correlation between spontaneously‐induced periodic synchronous discharges and photically induced giant evoked responses. In addition, the two electroencephalogram features appeared and disappeared in parallel with each other during the clinical course of the illness.

Age-Related Changes in Nerve Growth Factor Receptor Immunoreactive Neurons in the Magnocellular Basal Forebrain System in Rat Brain – an Immunocytochemical and Morphometric Study

Morphometrical changes with aging in nerve growth factor receptor (NGFR) immunoreactive neurons in the basal forebrain were studied in juvenile and aged rat brains by means of NGFR immunohistochemistry. The nucleus basalis of Meynert (NBM) had cell loss and atrophy of NGFR immunoreactive neurons, and the horizontal nucleus of diagonal band of Broca (HNDB) showed only atrophy of these neurons. The medial septal nucleus and vertical nucleus of diagonal band of Broca had no significant change. Neuropil NGFR immunostaining was reduced in its intensity in the aged rats. As nerve growth factor is synthesized in the target areas and retrogradely transported to the nerve cell body within the basal forebrain and NGFR immunoreactive neurons are largely cholinergic ones, degeneration of NGFR-positive neurons in the basal forebrain may be related to a decreased cholinergic activity. The degeneration of the dendrites of NGFR-immunoreactive neurons were reported to be extensively found in the basal forebrain nuclei, in contrast, degeneration of the cell body of NGFR-immunoreactive neurons was confined to those in the NBM and HNDB in the present study. These findings suggest that atrophic changes in the dendrites precede those in the cell bodies of NGFR-immunoreactive neurons.

Non-Alzheimer dementia with status spongiosus and neuronal cell loss showing unusual perineuronal structures and point mutation at 129 codon of prion protein.

The subject presented with intellectual decline followed by progressive muscle weakness of the bilateral upper limbs when he was 60 years old. He had a point mutation (methionin-valine) at 129 prion protein codon. He died at the age of 63 and necropsy revealed bilateral frontal lobe atrophy. The frontal cortex showed neuronal cell loss in layers II and III with spongiform change. Reusche silver impregnation technique for beta-peptide combined with ubiquitin immunostaining revealed perineuronal structures encircling degenerated neurons and ubiquitin-immunoreactive (IR) dot-like deposits. They were distributed particularly in the temporal neocortex and entorhinal cortex. They differed from either classic senile or diffuse plaque by the absence of amyloid core in the center and of amyloid fibrils. Ubiquitin-IR materials were also found as neuronal inclusions in the hippocampal granular cells. Nigral degeneration and neuronal loss in the hypoglossal nerve nucleus and in the anterior horn of the spinal cord were also found and spinal cord motoneurons had Bunina body inclusions. The clinical features and pathological findings were consistent with non-Alzheimer dementia with status spongiosus and neuronal cell loss. The unusual perineuronal structures found in our case might be a specific cellular pathology of dementia of the frontal lobe type.