Bilateral atypical ulnar fractures occurring after long-term treatment with bisphosphonate for 7 years and with teriparatide for 2 years: a case report.

Most atypical fractures associated with the long-term treatment with bisphosphonates (BP) commonly develop in the femoral shaft or subtrochanteric region. We report a rare case of bilateral atypical ulnar fractures in an 86-year-old woman with osteoporosis who finished the treatment with teriparatide for 2 years after long-term treatment with BP. She slid down from an approximately 30-cm-tall seat and slightly contused her left elbow. Plain radiography revealed that both ulnae had a noncomminuted short oblique fracture with cortical thickening and sclerosis at the fracture site. Based on the clinical and radiological findings, she was diagnosed with bilateral atypical ulnar fractures. The fracture of the left ulna was completely displaced and treated surgically. On the other hand, since the right ulna was an incomplete fracture, it was treated conservatively. During surgery, drilling with Kirschner wire and curettage were performed in the osteosclerotic lesion, and an autologous cancellous bone graft was inserted from the ipsilateral olecranon. Bone union was achieved in both fractures at 1 year after surgery. There have been no reports regarding the development of atypical ulnar fractures occurring after the long-term treatment with BP and 2-year use of teriparatide, and the treatment strategies of such fractures have not been established. If teriparatide cannot be used after occurring atypical fractures, the use of low-intensity pulsed ultrasound (LIPUS) and subsequent treatment for osteoporosis are recommended for the bone union. In addition, the treatment of the osteosclerotic lesion and rigid internal fixation are required in surgery.

Correction to: Bilateral atypical ulnar fractures occurring after long-term treatment with bisphosphonate for 7 years and with teriparatide for 2 years: a case report.

The original version of this article, published on 10 September 2020 contained a mistake.

Changes of human menisci in osteoarthritic knee joints.

OBJECTIVE: To investigate the changes of knee menisci in osteoarthritis (OA) in human. METHODS: OA and control menisci were obtained from 42 end-stage OA knees with medial involvement and 28 non-arthritic knees of age-matched donors, respectively. The change of menisci in OA was evaluated by histology, and gene expression of major matrix components and anabolic factors was analyzed in the anterior horn segments by quantitative PCR (qPCR). In those regions of menisci, the rate of collagen neo-synthesis was evaluated by [(3)H]proline incorporation, and the change of matrix was investigated by ultrastructural observation and biomechanical measurement. RESULTS: In OA menisci, the change in histology was rather moderate in the anterior horn segments. However, despite the modest change in histology, the expression of type I, II, III procollagens was dramatically increased in those regions. The expression of insulin-like growth factor 1 (IGF-1) was markedly enhanced in OA menisci, which was considered to be responsible, at least partly, for the increase in procollagen gene expression. Interestingly, in spite of marked increase in procollagen gene expression, incorporation of [(3)H]proline increased only modestly in OA menisci, and impaired collagen synthesis was suggested. This finding was consistent with the results of ultrastructural observation and biomechanical measurement, which indicated that the change of meniscal matrix was modest in the macroscopically preserved areas of OA menisci. CONCLUSION: Although the expression of major matrix components was markedly enhanced, matrix synthesis was enhanced only modestly, and the changes of matrix in human OA menisci were rather modest in the non-degenerated areas.

Intracellular processing of aggregated tau differs between corticobasal degeneration and progressive supranuclear palsy.

Corticobasal degeneration (CBD) and progressive supranuclear palsy (PSP) are sporadic neurodegenerative diseases with intracytoplasmic aggregates of the microtubule-associated protein, tau, in neurons and glial cells. Immunoblot analysis of detergent-insoluble brain extracts of patients with CBD and PSP shows distinctive patterns of tau fragments. These results suggest differing intracellular processing of aggregated tau in these two diseases despite an identical composition of tau isoforms. Such biochemical differences may be related to the neuropathological features of these diseases.

Further observation of Japanese Creutzfeldt-Jacob disease with widespread amyloid plaques.

An autopsy case of Creutzfeld-Jacob disease with widespread amyloid plaques is reported. A 45-year-old Japanese man, whose father had died of a similar disease, had a 5-year illness characterized by progressive cerebellar signs. Mental changes and brain-stem signs developed in the late stage. Myoclonus frequently occurred. Akinetic mutism ensued. The autopsy revealed spongiform encephalopathy with widespread amyloid plaques and extensive degeneration of the white matter. This disease, Western Gerstmann-Sträussler-Scheinker disease and panencephalopathic type of Creutzfeld-Jacob disease are discussed.

Foamy spheroid bodies in the substantia nigra. Report of an unusual case with recurrent attacks of peculiar twilight state.

An unusual case of recurrent attacks of peculiar twilight state persisting for 41 years is the subject of this clinicopathological report. During the attacks the patient had depersonalization, showing a stiff face, and the electroencephalogram showed constant 5 Hz diffuse theta waves. The unique and characteristic neuropathological finding were many foamy spheroid bodies (FSB) in the substantia nigra which sometimes contained varying numbers of fine or coarse eosinophilic granules. Ultrastructurally, the FSB contained various small electron-dense granules and/or membranous structures quite different from so-called spheroids (axonal swellings). Bodian staining demonstrated that some FSB were situated within the bundles of the neuronal processes, suggesting that the FSB has originated from the degeneration of the axon and/or dendrites in the substantia nigra.

Neuronal intranuclear inclusions in spinocerebellar ataxia type 2: triple-labeling immunofluorescent study.

Spinocerebellar ataxia type 2 (SCA2) is associated with an expansion of CAG/polyglutamine-repeat of a gene of unknown function. We performed an immunohistochemical study to identify the immunolocalization of the disease protein ataxin-2 in normal and SCA2 patients. Although normal and expanded ataxin-2 were ubiquitously localized to the cytoplasm of neurons, ubiquitinated intranuclear inclusions were observed selectively in 1-2% of neurons of affected brain regions except the cerebellum. Triple-labeling immunofluorescence revealed that ataxin-2, expanded polyglutamine and ubiquitin were colocalized to these neuronal intranuclear inclusions (NIs), indicating that SCA2 shares morphological characteristics common to other neurological disorders associated with an expansion of CAG/polyglutamine-repeat. Lack of NIs in the cerebellar lesion, however, suggests the discrepancy between formation of NIs and neuronal degeneration in SCA2.

Numerous glial fibrillary tangles in oligodendroglia in cases of subacute sclerosing panencephalitis with neurofibrillary tangles.

Both neurons and oligodendroglia are preferentially infected in subacute sclerosing panencephalitis (SSPE). Massive argyrophilic and tau-positive glial fibrillary tangles (GFT) were found in oligodendroglia in two autopsy cases of SSPE with neurofibrillary tangles (NFT). GFT shared common phosphorylated tau-epitopes with NFT, but were negative for ubiquitin. Electron microscopically, GFT consisted of compact bundles of irregularly woven tubules. Thus, GFT in SSPE differed from NFT showing regular constriction of tubules and from GFT in some other cytoskeletal disorders in which GFT reportedly consisted of straight tubules.

Morphologic difference of neuropil threads in Alzheimer's disease, corticobasal degeneration and progressive supranuclear palsy: a morphometric study.

Using Gallyas-Braak's silver stain, neuropil threads (NTs) in Alzheimer's disease (AD), corticobasal degeneration (CBD) and progressive supranuclear palsy (PSP) were analyzed morphologically and morphometrically. The NT density was highest in the cerebral cortical layer V in AD and CBD, and in the subcortical white matter in PSP. An overlaid, two-dimensional, camera lucida drawing revealed differences in the fine profile of NTs among these three disease groups. The differences were confirmed by computerized feature analysis which revealed differences in maximum length, breadth, Feret's angle and orientation of the NTs. Unlike a previous assumption that all NTs have a similar appearance, our study revealed that NTs in AD, CBD and PSP were distinctively different with respect to their morphology.

Extrapyramidal system involvement in motor neuron disease.

Three cases of motor neuron disease (MND), in which neuropathological findings were atypical, are reported. The first case manifested widespread and severe degeneration of the spinal cord, as in spinal fibrosis. Case 2 revealed severe degeneration of the pyramidal tract with many spheroids, which made it difficult to differentiate from primary amyotrophic lateral sclerosis. The last case revealed degeneration of the nigro-pallido-luysian system, even though no clinical manifestation of extrapyramidal and/or cerebellar symptoms had been noted throughout the clinical course. In MND, degeneration might occur in various locations other than the motor system.

The fine structure of neurofibrillary tangles in a case of atypical presenile dementia.

The neurofibrillary tangles in a case of atypical presenile dementia were studied by electron microscopy. The tangles consisted of 2 types of tubule: one straight, measuring about 15--20 nm in width, the other twisted. Both types of tubule appeared separately in each neuron; however, occasionally twisted tubules seemed to be distributed among the straight tubules. The implications of these findings are briefly discussed.

"Grumose degeneration" of Trétiakoff.

We reviewed Trétiakoff's "grumose degeneration (GD)" which described pathologic cellular change in the substantia nigra (SN). This term has been occasionally used up to the mid-1960s by Greenfield et al.; it has rarely been used after the 1970s. This study emphasises the following: (1) after the 1970s, GD has sometimes been signalled in the SN under various names, such as "spheroid with foamy appearance", "granular spheroid", "saccular structure", or "foamy spheroid body"; (2) the ultrastructure of GD is unknown, being entirely different from that of typical axonal swellings (so-called "spheroids"); (3) more attention should be paid to GD in the SN because its nature has remained unclarified since the original description; and (4) "GD" in the cerebellar dentate nucleus is essentially different from Trétiakoff's GD.

Three categories of the degenerative appearance of the human cerebellar dentate nucleus. A morphometric and morphological study.

This morphometric and morphological study demonstrates 3 categories (types A, B and C) of degenerative feature in the cerebellar dentate nucleus. Type A is characterized by neuronal loss, astrocytosis and granular and/or amorphous argyrophilic change around the neurons and neuronal processes, and this type was thought to be synonymous with the so-called grumose degeneration of the DN. Type B is characterized by extensive neuronal loss and astrocytosis without argyrophilic change, and it was considered that many diverse factors were responsible for type B. Type C features marked swelling of the neurons without neuronal loss, astrocytosis or argyrophilic change. The Purkinje cells were not involved in type A and C, but severely damaged in type B. Clinically, type A was observed in progressive supranuclear palsy and dentatorubropallidoluysian atrophy, type B extensively in many diseases including anoxic, toxic and infectious disorders, and type C in tardive dyskinesia manifesting with oral hyperkinesia. Types A and C may be more or less specific signs of degeneration of the dentate nucleus, whereas type B appears to be non-specific.

Asymmetrical temporal lobe atrophy with massive neuronal inclusions in multiple system atrophy.

This report concerns a rare association of asymmetrical temporal lobe atrophy with multiple system atrophy (MSA). A 53-year-old Japanese woman developed cerebellar ataxia and parkinsonism and was diagnosed as olivopontocerebellar atrophy (OPCA). This patient showed forgetfulness and subsequent disorientation even in the early stage of the disease. She fell into a decorticate state at the age of 64, and died a year later. The autopsy showed MSA with asymmetrical atrophy of temporal lobes, intraneuronal globular inclusions mostly confined to the hippocampus, amygdaloid nucleus, and most abundant in the granule cells in the dentate fascia. These inclusions were intensely argyrophilic and expressed marked immunoreactivity to ubiquitin, but not to neurofilament (NF), tau and paired helical filaments (PHF). Ultrastructurally, they were composed of scattered short filamentous structures of 15 to 30 nm in diameter, ribosome-like granules, mitochondria and lipofuscin. The lack of immunoreactivity against tau, NF and PHF suggests that the inclusions are distinct from Pick bodies. To our knowledge, MSA in association with asymmetrical temporal lobe atrophy with the present neuronal inclusions has not been reported. This case is distinct from MSA combined with atypical Pick's disease in the distribution and immunohistochemical properties of neuronal inclusions, and may present a new variant of MSA since the neuronal inclusions are similar, in many respects, to those of neuronal inclusions reported in MSA. Globular inclusions are also discussed in variants of Pick's disease, amyotrophic lateral sclerosis and Alzheimer's disease.

Regional quantitative analysis of tau-positive neurons in progressive supranuclear palsy: comparison with Alzheimer's disease.

In patients with progressive supranuclear palsy (PSP), various tau-positive abnormal structures are found in the cerebral cortex as well as in the subcortical nuclei. Similar tau-positive abnormalities are also identified in cortico-basal degeneration (CBD). It is therefore questionable as to whether PSP can be neuropathologically differentiated from CBD. It also remains nuclear whether neurofibrillary tangles (NFT) in the cerebral cortex of PSP patients consist of PSP-NFT or concomitant Alzheimer's disease (AD)-NFT, although there have been some reports suggesting that PSP- and AD-NFT are different with respect to distribution pattern and biochemical character. In this study, a regional quantitative analysis of the distribution and antigenicity of tau-positive neurons (TPN) was performed in PSP cases and compared with that in AD cases. TPN consisted of NFT with tangle-formation and pretangle neurons (PN) without tangle-formation. In addition, NFT were subdivided into mature and immature NFT according to the difference of staining properties with anti-tau-related antibodies. The comparison of the TPN of the PSP cases with those of the AD cases revealed that the degree of tangle-formation in the TPN of AD was similar in all of the examined regions, while that in the TPN of PSP varied according to the region and case. Moreover, the NFT in the PSP and AD cases had different distributions according to the cortical layer and subnucleus, even in the common predilection sites of PSP and AD, suggesting that NFT in these regions of the PSP cases consist mainly of PSP-NFT. In addition, the PSP cases could be divided into two groups according to the difference of the tangle-formation of TPN; group I with typical PSP pathology and group II with atypical PSP pathology similar to CBD. This suggests that there is a continuity between PSP and CBD with respect to the distribution and antigenicity of TPN.

Corticobasal degeneration: widespread argentophilic threads and glia in addition to neurofibrillary tangles. Similarities of cytoskeletal abnormalities in corticobasal degeneration and progressive supranuclear palsy.

A 57-year-old man had exhibited cortical sensory disturbance, rigidity, spasticity, dementia, alien hand, grasp reflex, supranuclear ophthalmoplegia, pseudobulbar palsy, and neck dystonia for 4 years. Histological examination of autopsied specimens revealed neuronal loss in the cerebral cortex, with ballooned neurons, subthalamic nucleus, substantia nigra, basal ganglia, midbrain tegmentum, and the thalamus. There were neurofibrillary tangles in the subthalamic nucleus and the substantia nigra. Gallyas-Braak silver impregnation demonstrated numerous argentophilic tangles, threads, and a few argentophilic glia in the cerebral cortex, subcortical white matter, particularly in the precentral gyrus, subcortical nuclei, and the brainstem. These argentophilic structures were largely positive for tau, and negative for ubiquitin, paired helical filaments, and phosphorylated neurofilament. Ultrastructurally, 15-nm-wide straight tubules were observed in the neurons of the substantia nigra, globus pallidus, and the precentral cortex, coexisting with a few twisted tubules periodically constricted at 160- to 230-nm intervals. It was conclusively shown that Gallyas- and tau-positive cytoskeletal abnormalities occurred widely in brain of corticobasal degeneration. Both distribution and morphology of abnormal phosphorylated tau protein in corticobasal degeneration appear to resemble these features in progressive supranuclear palsy. These findings suggest a common cytoskeletal etiopathological significance in corticobasal degeneration and progressive supranuclear palsy.

Cordectomy for syringobulbo-myelia with sleep apnea secondary to a spinal extramedullary tumor: case report.

The case of a 40-year-old man with syringobulbo-myelia secondary to an unresectable spinal extramedullary tumor is described. Fifteen years previously, the patient had undergone a laminectomy of T8 through T12 for a "benign" spinal cord tumor at another hospital and had become paraplegic; the tumor (neurinoma) had been neglected for 12 years. Magnetic resonance imaging demonstrated a large thoracolumbar spinal tumor with syringobulbo-myelia. Polysomnography showed central-, peripheral-, and mixed-type sleep apneas. After the failure of an attempted syringoperitoneal shunt, cordectomy at the level of T6 was performed with a good result. The mechanisms of the formation of syringomyelia and sleep apnea secondary to a caudal spinal extramedullary tumor are discussed.

Pineal ganglioglioma in a patient with familial basal ganglia calcification and elevated serum alpha-fetoprotein: case report.

Pineal ganglioglioma was diagnosed in a 36-year-old man with familial basal ganglia calcification and elevated serum alpha-fetoprotein. The patient was treated surgically with a good result. Only four other cases of this tumor have been reported. His 38-year-old brother also showed basal ganglia calcification and elevated serum chorionic gonadotropin as well as alpha-fetoprotein. Familial basal ganglia calcification with elevated serum alpha-fetoprotein in a nonhepatic benign condition is rare. The pathogenesis of these conditions is discussed.

Cerebrospinal fluid edema: a rare complication of shunt operations for hydrocephalus. Report of three cases.

Three cases are presented in which a rare complication occurred after a shunt operation for hydrocephalus. On postoperative computerized tomography (CT) scans, extensive low-density areas appeared in the white matter along the ventricular catheter. After shunt revision, gradual resolution or disappearance of the low-density area was clearly demonstrated on CT. In one patient, a collection of cerebrospinal fluid (CSF) was confirmed at operation and appeared to lie in the extracellular spaces of the white matter. The phenomenon is considered to be localized CSF edema, different from porencephaly.