A Case of Pathologically Confirmed Corticobasal Degeneration Initially Presenting as Progressive Supranuclear Palsy Syndrome

Progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD) overlap clinically with parkinsonism or extrapyramidal signs and pathologically with tauopathy. Asymmetric parkinsonism and cortical dysfunctions are classical features of CBD. However, symmetric parkinsonism, frequent falls, and supranuclear gaze palsy are key features of PSP. Despite biochemically classified as 4R tauopathies, tufted astrocytes of PSP and astrocytic plaque of CBD show pathologically important differences. Herein, we report a 68-year-old man with pathologically confirmed CBD. He was clinically suspected to have PSP because of progressive gait disturbances, frequent falls, and vertical saccade limitation. Neurological examination performed at age 71 revealed symmetrical bradykinesia, axial rigidity, and postural instability with worsening of early existing symptoms. Magnetic resonance imaging of the brain taken at age 70 detected midbrain and left frontotemporal atrophy and right middle cerebral artery infarction. Left frontotemporoparietal hypometabolism and asymmetrically decreased fluoro-propyl-carbomethoxy-iodophenyl-tropane uptake in the basal ganglia were observed. The autopsy was performed at the time of his death (at age 72), which revealed severe pallor of the substantia nigra and mildly hypopigmented locus ceruleus. AT8 immunohistochemistry and Gallyas staining revealed tau-positive neuronal and glial inclusions, astrocytic plaques, ballooned neurons, and numerous threads in both gray and white matter. No abnormal inclusions were revealed by beta-amyloid, α-synuclein and TDP-43 immunohistochemistry. In our case, cerebral infarction, periventricular and deep white matter ischemic changes, and midbrain atrophy were likely to produce PSP–CBD overlapping symptoms. However, our patient was finally confirmed to have CBD based on pathological findings such as astrocytic plaques.     

Cortical Alzheimer Type Pathology Does Not Influence tau Pathology in Progressive Supranuclear Palsy

Alzheimer disease (AD) is characterized by numerous senile plaques (SP) in addition to widespread neocortical neurofibrillary tangles (NFT). Some elderly have pathologic aging (PA), which is characterized by numerous SP composed of diffuse amyloid deposits with few or no NFT confined to the limbic lobe. Both AD and PA represent a range of Alzheimer type pathology (ATP). Some cases of progressive supranuclear palsy (PSP) have concurrent ATP, but the relationship between ATP and PSP has not been addressed. In this study, a consecutive series of PSP cases were divided into three groups according to the degree of concurrent ATP – pure PSP, PSP/PA and PSP/AD. Braak NFT stage was significantly greater in PSP/AD compared with both PSP/PA and PSP. Among the pathologic variables studied in middle frontal, superior temporal and motor cortices, there were no differences between PSP and PSP/PA except for SP. In PSP/AD, there was greater neuronal tau pathology (pretangles, NFT and neuropil threads) in middle frontal and superior temporal cortices, probably a reflection of ATP since there was no comparable increase in PSP-related glial tau pathology in these regions. The APOEɛ4 allele frequency was significantly higher in PSP/PA and PSP/AD than in PSP. These results strongly argue that ATP in PSP represents independent disease processes even when present in the same brain.     

Corticobasal Ganglionic Degeneration and Progressive Supranuclear Palsy Presenting with Cognitive Decline

Corticobasal ganglionic degeneration (CBGD) and progressive supranuclear palsy (PSP) were originally described in the sixties as predominantly motor syndromes. Over the years, the detailed study of additional cases of CBGD has shown that it is a distinctive histological entity which can often present as dementia or aphasia. Although some pathological features of CBGD overlap with those of other forms of non-Alzheimer non-Lewy body dementia, the distribution and relative number of these abnormalities and the distinctive pattern of tau immunodeposits allows the distinction of CBGD from Pick's disease and fronto-temporal dementia. In contrast, PSP only rarely presents with prominent dementia or behavioral changes. In these unusual PSP cases, care must be taken to exclude the diagnoses of CBGD and familial tangle-only dementia.     

Immunohistochemical Study of Mitochondrial Ferritin in the Midbrain of Patients with Progressive Supranuclear Palsy

Mitochondrial ferritin (FtMt) is a novel ferritin that is localized in the mitochondria. FtMt expression is low in the liver and spleen, and high in the heart, testis, and brain. We previously detected FtMt in dopaminergic neurons in the substantia nigra pars compacta (SNc) in human and monkey midbrains. We investigated the localization and expression of FtMt in the midbrain of patients with progressive supranuclear palsy (PSP) and controls using a monoclonal antibody (C65-2) against human FtMt. FtMt immunoreactivity was weakly detected in neuromelanin-containing neurons in the SNc and ventral tegmental area (VTA) of control cases compared with PSP, which exhibited a remarkable increase in FtMt immunoreactivity. Preincubation of C65-2 with the immunizing FtMt peptide significantly reduced the staining, indicating the specificity of C65-2. Several puncta were observed outside the neurons of PSP, in contrast with the control cases. Double immunofluorescence histochemistry for FtMt and tyrosine hydroxylase (TH), glial fibrillary acidic protein, and Iba1 showed localization of FtMt in dopaminergic neurons, microglia, and astrocytes in PSP. Furthermore, FtMt immunoreactivity was detected in a few TH-negative neurons. In the SNc and VTA, FtMt immunoreactivity colocalized with phosphorylated tau immunoreactivity. Our results indicate that FtMt is involved in the pathology of PSP. Clarifying the involvement of FtMt in PSP is of great interest.     

Tau-positive dial Inclusions in Progressive Supranuclear Palsy, Corticobasal Degeneration and Pick''s Disease

The presence of tau-positive glial inclusions has been recently found a consistent feature in the brains of patients with progressive supranuclear palsy (PSP), corticobasal degeneration (CBD) and Pick's disease (PiD). These inclusions are classified based on cellular origin as tau-positive astrocytes, presumably either fibrillary or protoplasmic, coiled bodies and glial threads. Immunohistochemically, their major structural component is abnormal tau proteins, similar to those found in Alzheimer's disease. Nevertheless, their morphology, including ultrastructural profile, has been suggested to be distinctive for each disease. The profile and extent of particular glial inclusions correlate well with disease phenotype. Highly characteristic correlations include tufts of abnormal fibers in PSP, astrocytic plaques and dense glial threads in CBD and ramified astrocytes and small Pick body-like inclusions in PiD. The significance of the inclusions in disease pathogenesis and their biochemical characteristics remain to be clarified. Nevertheless, these distinctive glial lesions most likely reflect fundamental alterations in isoform composition of tau as well as its specific cellular and regional expression in sporadic tauopathies.     

Pathological and Clinical Spectrum of Progressive Supranuclear Palsy: With Special Reference to Astrocytic Tau Pathology

Progressive supranuclear palsy (PSP) is a four‐repeat tauopathy with tau‐positive, argyrophilic tuft‐shaped astrocytes (TAs). We performed a pathological and clinical investigation in 40 consecutive autopsied Japanese patients with pathological diagnoses of PSP or PSP‐like disease. Unequivocal TAs were present in 22 cases, all of which were confirmed to be PSP. Such TAs were hardly detected in the other 18 cases, which instead exhibited tau‐positive, argyrophilic astrocytes, appearing as comparatively small clusters with central nuclei of irregularly shaped, coarse structures (equivocal TAs). Cluster analysis of the distribution pattern of tau‐related pathology for these 18 cases identified two subgroups, pallido‐nigro‐luysian atrophy (PNLA) Type 1 (n = 9) and Type 2 (n = 9), the former being distinguished from the latter by the presence of tau‐related lesions in the motor cortex, pontine nucleus and cerebellar dentate nucleus in addition to the severely affected PNL system. The duration from symptom onset until becoming wheelchair‐bound was significantly longer in PNLA Type 1. Immunoblotting of samples from the three disease conditions revealed band patterns of low‐molecular‐mass tau fragments at ～35 kDa. These findings shed further light on the wide pathological and clinical spectrum of four‐repeat tauopathy, representing PSP in the broad sense rather than classical PSP.     

Comparative Biochemistry of Tau in Progressive Supranuclear Palsy, Corticobasal Degeneration, FTDP-17 and Pick''s Disease

Neurodegenerative disorders referred to as tauopathies have cellular hyperphosphorylated tau protein aggregates in the absence of amyloid deposits. Comparative biochemistry of tau aggregates shows that they differ in both phosphorylation and content of tau isoforms. The six tau isoforms found in human brain contain either three (3R) or four microtubule-binding domains (4R). In Alzheimer's disease, all six tau isoforms are abnormally phosphorylated and aggregate into paired helical filaments. They are detected by immunoblotting as a major tau triplet (tau55, 64 and 69). In corticobasal degeneration and progressive supranuclear palsy, only 4R-tau isoforms aggregate into twisted and straight filaments respectively. They appear as a major tau doublet (tau64 and 69). Finally, in Pick's disease, only 3R-tau isoforms aggregate into random coiled filaments. They are characterized by another major tau doublet (tau55 and 64). These differences in tau isoforms may be related to either the degeneration of particular cell populations in a given disorder or aberrant cell trafficking of particular tau isoforms. Finally, recent findings provide a direct link between a genetic defect in tau and its abnormal aggregation into filaments in fronto-temporal dementia with Parkinsonism linked to chromosome 17, demonstrating that tau aggregation is sufficient for nerve cell degeneration. Thus, tau mutations and polymorphisms may also be instrumental in many neurodegenerative disorders.     

Identification and Quantification of Oligodendrocyte Precursor Cells in Multiple System Atrophy,Progressive Supranuclear Palsy and Parkinson's Disease

Multiple system atrophy is a neurodegenerative disorder characterized pathologically by abnormal accumulations of α‐synuclein in the cytoplasm of oligodendrocytes, which are termed glial cytoplasmic inclusions (GCIs). Oligodendrocytes are responsible for myelinating axons and providing neurotrophic support, but in MSA, myelin loss, axonal loss and gliosis are consistent features suggesting that GCIs play a central role in disease pathogenesis. Oligodendroglial, myelin and axonal degeneration are also features of multiple sclerosis (MS) in which recent studies have highlighted the robust remyelination capacity of the central nervous system (CNS). The cells responsible for remyelination are called oligodendroglial precursor cells (OPCs). In this study, we investigated the role of OPCs in the pathogenesis of MSA and progressive supranuclear palsy (PSP), a neurodegenerative disease in which neuropathological changes include oligodendroglial inclusions composed of microtubule‐associated protein tau. Despite the lability of OPC‐specific antigens, we successfully identified OPCs and demonstrated that tau and α‐synuclein do not accumulate in OPCs. We also showed that the density of OPCs was increased in a white matter region of the MSA brain, which is also severely affected by GCIs and myelin degeneration. These findings raise the possibility that OPCs could be available to repair disease‐associated damage in MSA, consistent with their biological function.     

Distribution of Medical Service Use for Facial Palsy Between Medicine and Traditional Korean Medicine Based on Population-Based Data of Korea

We investigated the distribution of medical service uses for Bell’s palsy and Ramsay Hunt syndrome between medicine and traditional Korean medicine using the National Health Insurance Service National Sample Cohort data of Korea from 2006 to 2015. Patients were identified with diagnostic codes and medication or treatment claim codes. For Bell’s palsy, there were 5,970 (68.8%) patients who used traditional Korean medical service only, whereas for Ramsay Hunt syndrome, there were 749 (93.6%) patients who used medical service only. The proportion of traditional Korean medical service use was higher than that of medical service use in patients with Bell’s palsy, while the opposite was found in patients with Ramsay Hunt syndrome.     

Progression of Hip Displacement during Radiographic Surveillance in Patients with Cerebral Palsy

Progression of hip displacement is common in patients with cerebral palsy (CP). We aimed to investigate the rate of progression of hip displacement in patients with CP by assessing changes in radiographic indices according to Gross Motor Function Classification System (GMFCS) level during hip surveillance. We analyzed the medical records of patients with CP aged < 20 years who underwent at least 6 months interval of serial hip radiographs before any surgical hip intervention, including reconstructive surgery. After panel consensus and reliability testing, radiographic measurements of migration percentage (MP), neck-shaft angle (NSA), acetabular index (AI), and pelvic obliquity (PO) were obtained during hip surveillance. For each GMFCS level, annual changes in radiographic indices were analyzed and adjusted for affecting factors, such as sex, laterality, and type of CP. A total of 197 patients were included in this study, and 1,097 radiographs were evaluated. GMFCS classifications were as follows: 100 patients were level I-III, 48 were level IV, and 49 were level V. MP increased significantly over the duration of hip surveillance in patients with GMFCS levels I-III, IV, and V by 0.3%/year (P < 0.001), 1.9%/year (P < 0.001), and 6.2%/year (P < 0.001), respectively. In patients with GMFCS level IV, NSA increased significantly by 3.4°/year (P < 0.001). Our results suggest that periodic monitoring and radiographic hip surveillance is warranted for patients with CP, especially those with GMFCS level IV or V. Furthermore, physicians can predict and inform parents or caregivers regarding the progression of hip displacement in patients with CP.     

Morphological Findings of Extraocular Myopathy with Chronic Progressive External Ophthalmoplegia

Mitochondrial diseases are a large group of disorders resulting from mutations of nuclear DNA (nDNA) and mitochondrial DNA (mtDNA). Patients present clinically with multiple manifestations, including myopathies and multiple system disorders. Establishing a specific diagnosis often requires extensive clinical and laboratory evaluation. In this study of 2 adult patients with presumptive mitochondrial disease, the authors have identified distinctive morphological changes in medial rectus muscle biopsies that confirm the diagnosis of chronic progressive external ophthalmoplegia (CPEO). These findings demonstrate the usefulness of electron microscopy using medial rectus muscle in the diagnosis of adult patients with a slowly progressive course of mild skeletal weakness and CPEO.     

Progressive multifocal leukoencephalopathy associated with prolonged hemodialysis treatment

Summary The association of progressive multifocal leukoencephalopathy (PML) with prolonged hemodialysis treatment (PHT), not previously reported, was observed in a 56-year-old Japanese man who received PHT for 11 years. He suffered from recurrent bouts of fever and progressive neurological signs, such as irritability, speech disturbance, gait disturbance and dysphagia for seven months, and finally fell into a deep coma and died. Clinical signs and symptoms were highly suggestive of progressive dialysis encephalopathy. Necropsy revealed that the PML mainly involved the brainstem and cerebellar white matter. The aluminium content of the brain tissue was lower than that of controls. Possibly the virus causing PML is one of the causes of progressive dialysis encephalopathy, since clinically PML is not easily distinguished from progressive dialysis encephalopathy. It is essential to differentiate PML of viral etiology from progressive dialysis encephalopathy of unknown cause.     

Progressive renal failure in a patient after one and two-thirds nephrectomy

Summary We report on a patient who lost one and two-thirds of his kidneys following surgery because of bilateral renal cell carcinoma. The serum creatinine following surgical intervention increased to about 7 mg% and fell to serum values of about 3 mg% in the year after one and two-thirds nephrectomy. The patient's renal function remained stable for 18 months, then it started to deteriorate and the patient developed progressive renal failure with proteinuria. The course of the disease suggests that an intrinsic renal mechanism was operative, which relates to glomerular hyperfiltration following surgical loss of renal tissue.     

Perioperative Complications of Orthopedic Surgery for Lower Extremity in Patients with Cerebral Palsy

Because complications are more common in patients with cerebral palsy (CP), surgeons and anesthesiologists must be aware of perioperative morbidity and be prepared to recognize and treat perioperative complications. This study aimed to determine the incidence of and risk factors for perioperative complications of orthopedic surgery on the lower extremities in patients with CP. We reviewed the medical records of consecutive CP patients undergoing orthopedic surgery. Medical history, anesthesia emergence time, intraoperative body temperature, heart rate, blood pressure, immediate postoperative complications, Gross Motor Function Classification System (GMFCS) level, Cormack-Lehane classification, and American Society of Anesthesiologists physical status classification were analyzed. A total of 868 patients was included. Mean age at first surgery was 11.8 (7.6) yr. The incidences of intraoperative hypothermia, absolute hypotension, and absolute bradycardia were 26.2%, 4.4%, and 20.0%, respectively. Twenty (2.3%) patients had major complications, and 35 (4.0%) patients had minor complications postoperatively. The incidences of intraoperative hypothermia, absolute hypotension, and major postoperative complications were significantly higher in patients at GMFCS levels IV and V compared with patients at GMFCS levels I to III (P<0.001). History of pneumonia was associated with intraoperative absolute hypotension and major postoperative complications (P<0.001). These results revealed that GMFCS level, patient age, hip reconstructive surgery, and history of pneumonia are associated with adverse effects on intraoperative body temperature, the cardiovascular system, and immediate postoperative complications.     

Cryptococcal meningitis presenting with isolated sixth cranial nerve palsy in a patient with systemic lupus erythematosus

Cryptococcal meningitis is a rare complication of systemic lupus erythematosus (SLE). The nonspecific neurologic findings associated with this infection delays accurate diagnosis because initial neuropsychiatric manifestations of SLE are in instances indistinguishable from that of crytococcal meningitis. We report a case of cryptococcal meningitis presenting with unilateral sixth cranial nerve palsy in a male patient with SLE, which was successfully treated with antifungal agents.     

A catastrophic-onset longitudinal myelitis accompanied by bilateral internuclear ophthalmoplegia in a patient with systemic lupus erythematosus

Transverse myelitis (TM) extending from midbrain to the entire spinal cord accompanied by internuclear ophthalmoplegia is extremely rare but cause serious central nervous system complications in patients with systemic lupus erythematosus. We report a case of a 28-yr-old woman with TM extending from the midbrain to the conus medullaris longitudinally and internuclear ophthalmoplegia associated with systemic lupus erythematosus. Her neurological symptoms had an abrupt catastrophic onset and rapidly progressed to respiratory failure within 24 hr. Bilateral internuclear ophthalmoplegia was also followed by TM. Brain MR images showed definite brainstem lesions, which were deeply associated with internuclear ophthalmoplegia, and diffuse signal changes in the whole spinal cord, medulla, pons and midbrain. Clinical improvement of her ophthalmoplegia and of neurological dysfunction of the upper extremities was noted after prompt and aggressive treatment with intravenous pulsed methylprednisolone and cyclophosphamide. However, the neurological dysfunction of the lower limbs and bladder and colon paralysis were almost unchanged until six months passed.     

系统性硬皮病微循环和血液流变性改变与分析

报道６２例系统性硬皮病的微循环、血液流变性和免疫学改变并分析三者间的关系。提出管袢＂棒状＂扩张的畸变很有特色，对早期诊断和鉴别、分型很有价值。管袢数目减少者占患者的４８．４％，ＲＢＣ聚集９８．１％，流速减慢９８．４％，袢顶出血８０．６％；低和高切变率下ηｂ升高者分别为３４．３％和２２．９％，ηｂ降低者分别为３７．１％和２０％。ηｐ升高者２５．７％，降低者１１．４％；ＡＮＡ阳性者６９．４％，ＩｇＧ３８．７％、补体Ｃ４５９．６％、Ｃ３１９．１％、Ｙ－球蛋白３５．４％升高。统计学表明ＡＮＡ阳性组ηｐ高于ＡＮＡ阴性组，Ｐ＜０．０５。分析认为抗体的产生是血液流变性改变的原因，后者又引起微循环的异常。