[Show abstract][Hide abstract] ABSTRACT: Genetic Creutzfeldt-Jakob disease (CJD) due to V180I mutation in the prion protein gene (PRNP) is of great interest because of the differences from sporadic CJD and other genetic prion diseases in terms of clinical features, as well as pathological and biochemical findings. However, few systematic observations about the clinical features in patients with this unique mutation have been published. Therefore, the goal of this study was to relate this mutation to other forms of CJD from a clinical perspective.
[Show abstract][Hide abstract] ABSTRACT: We herein describe the case of an 81-year-old Japanese woman with neuroleptic malignant syndrome that occurred 36 days after the initiation of combination therapy with tiapride (75 mg/day) and tetrabenazine (12.5 mg/day) for Huntington's disease. The patient had been treated with tiapride or tetrabenazine alone without any adverse effects before the administration of the combination therapy. She also had advanced breast cancer when the combination therapy was initiated. To the best of our knowledge, the occurrence of neuroleptic malignant syndrome due to combination therapy with tetrabenazine and tiapride has not been previously reported. Tetrabenazine should be administered very carefully in combination with other neuroleptic drugs, particularly in patients with a worsening general condition.
Internal medicine (Tokyo, Japan). 01/2014; 53(11):1201-4.
[Show abstract][Hide abstract] ABSTRACT: OBJECTIVE: More than 60% of patients worldwide with Creutzfeldt-Jakob disease (CJD) associated with dura mater graft (dCJD) have been diagnosed in Japan. The remarkable frequency of dura mater grafts in Japan may possibly contribute to the elevated incidence of dCJD, but reasons for the disproportionate use of this procedure in Japan remain unclear. We investigated differences between dCJD patients in Japan and those elsewhere to help explain the more frequent use of cadaveric dura mater and the high incidence of dCJD in Japan. METHODS: We obtained data on dCJD patients in Japan from the Japanese national CJD surveillance programme and on dCJD patients in other countries from the extant literature. We compared the demographic, clinical and pathological features of dCJD patients in Japan with those from other countries. RESULTS: Data were obtained for 142 dCJD patients in Japan and 53 dCJD patients elsewhere. The medical conditions preceding dura mater graft transplantation were significantly different between Japan and other countries (p<0.001); in Japan, there were more cases of cerebrovascular disease and hemifacial spasm or trigeminal neuralgia. Patients with dCJD in Japan received dura mater graft more often for non-life-threatening conditions, such as meningioma, hemifacial spasm and trigeminal neuralgia, than in other countries. CONCLUSIONS: Differences in the medical conditions precipitating dura mater graft may contribute to the frequent use of cadaveric dura mater and the higher incidence of dCJD in Japan.
Journal of neurology, neurosurgery, and psychiatry 04/2013; · 4.87 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: A 23-year-old man was admitted to our hospital with lumbago about two weeks previously, and headache six days previously. Brain MR imaging revealed no remarkable findings except for left ethmoid sinusitis; both MR angiography and venography showed no vascular abnormalities. On the day after admission, lumbar puncture was performed because right homonymous hemianopsia and nuchal stiffness developed. The cerebrospinal fluid appeared bloody, and the source of bleeding was searched for. MR images of the lumbar spine demonstrated an intradural tumor with heterogenous contrast enhancement, and this tumor was considered to be the source of the bleeding. Tumor resection was performed, but some parts of the tumor could not be resected because of adhesion to the cauda equina. The pathological findings of the tumor demonstrated myxopapillary ependymoma. Radiation therapy was added to treat the residual tumor because myxopapillary ependymoma tended to recur in spite of the benign nature of the tumor. Spinal myxopapillary ependymoma is rare, but it causes subarachnoid hemorrhage. Subarachnoid hemorrhage from spinal tumor should be suspected when headache accompanied with severe low back pain are present even in the absence of spinal signs.
[Show abstract][Hide abstract] ABSTRACT: Details of abnormal prion protein (PrP(Sc)) propagation in the human central nervous system (CNS) are unclear. To assess the spread of PrP(Sc) through the human CNS, we evaluated dura mater graft-associated Creutzfeldt-Jakob disease (dCJD) cases focusing on sites of grafting and dCJD pathological subtypes.
A cross-sectional study.
nationwide surveillance data of human prion diseases in Japan over the past 12 years were applied for the study.
Clinical data were obtained from 84 dCJD patients.
The clinical courses in cases of dCJD were analysed according to the grafting sites (supratentorial and infratentorial groups) and the pathological subtypes (non-plaque and plaque types).
Of the 84 cases of dCJD in this study, 36 (43%) were included in the supratentorial group and 39 (46%) were included in the infratentorial group. As initial manifestations, vertigo (p=0.007) and diplopia (p=0.041) were significantly more frequent in the infratentorial group than in the supratentorial group. During their clinical course, cerebellar signs appeared more frequently in the infratentorial group than in the supratentorial group (p=0.024). In the non-plaque type cases (n=53), the infratentorial group developed vertigo more frequently than the supratentorial group (p=0.017); moreover, cerebellar signs appeared more frequently in the infratentorial group (p=0.014). However, there was no significant difference between groups in the plaque type (n=18).
The high frequency of clinical manifestations related to brain stem and cerebellar dysfunction in the non-plaque type dCJD with infratentorial grafting suggests that PrP(Sc) commonly shows direct propagation into the CNS from contaminated dura mater grafts.
BMJ Open 01/2013; 3(8):e003400. · 1.58 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: A national system for surveillance of prion diseases (PrDs) was established in Japan in April 1999. Here, we analyzed the relationships among prion protein gene (PRNP) mutations and the clinical features, cerebrospinal fluid (CSF) markers, and pathological characteristics of the major genotypes of genetic PrDs (gPrDs). We retrospectively analyzed age at onset and disease duration; the concentrations and incidences of 14-3-3 protein, tau protein, and abnormal prion protein (PrP(Sc)) in the CSF of 309 gPrD patients with P102L, P105L, E200K, V180I, or M232R mutations; and brain pathology in 32 autopsied patients. Three clinical phenotypes were seen: rapidly progressive Creutzfeldt-Jakob disease (CJD), which included 100% of E200K cases, 70% of M232R, and 21% of P102L; slowly progressive CJD, which included 100% of V180I and 30% of M232R; and Gerstmann-Sträussler-Scheinker disease, which included 100% of P105L and 79% of P102L. PrP(Sc) was detected in the CSF of more than 80% of patients with E200K, M232R, or P102L mutations but in only 39% of patients with V180I. V180I was accompanied by weak PrP immunoreactivity in the brain. Patients negative for PrP(Sc) in the CSF were older at disease onset than positive patients. Patients with mutations associated with high 14-3-3 protein levels in the CSF typically had synaptic deposition of PrP in the brain and a rapid course of disease. The presence of small PrP protein fragments in brain homogenates was not correlated with other clinicopathological features. Positivity for PrP(Sc) in the CSF may reflect the pathological process before or at disease onset, or abnormality in the secretion or metabolism of PrP(Sc). The amount of 14-3-3 protein in the CSF likely indicates the severity of the pathological process and accompanying neuronal damage. These characteristic features of the CSF in cases of gPrD will likely facilitate accurate diagnosis and clinicopathological study of the various disease subtypes.
PLoS ONE 01/2013; 8(3):e60003. · 3.73 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Familial amyloid polyneuropathy (FAP) is an autosomal dominant form of hereditary amyloidosis. Several studies reported coagulation factor X deficiency and excessive fibrinolysis in immunoglobulin light chain amyloidosis. However, few have investigated coagulation and fibrinolysis in FAP. The objective of this study was to determine abnormalities in plasma biomarkers of coagulation and fibrinolysis in FAP.
We prospectively recruited eight FAP patients with transthyretin mutations and ten age-matched control patients with other neuropathies in our university. We examined plasma biomarkers of coagulation and fibrinolysis including prothrombin time, activated partial thromboplastin time, fibrinogen, fibrin/fibrinogen degradation products, D-dimer, α2-antiplasmin, antithrombin, plasminogen, thrombin-antithrombin complex, plasmin-α2-antiplasmin complex, prothrombin fragment 1+2, and coagulation factor X. The Mann-Whitney U test was performed for statistical comparisons between FAP and control groups.
FAP patients exhibited significantly decreased levels of coagulation factor X, plasminogen and α2-antiplasmin, and significantly increased levels of prothrombin fragment 1+2 compared to control patients.
Our results indicate abnormalities of coagulation and fibrinolysis in FAP patients.
Amyloid: the international journal of experimental and clinical investigation: the official journal of the International Society of Amyloidosis 05/2012; 19(3):129-32. · 2.12 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We describe a pair of monozygotic twins with an attenuated form of mucopolysaccharidosis type I (MPS-I). At age 24, they both developed cervical myelopathy as a cardinal manifestation. They each also had mild valve abnormalities and both inguinal and umbilical hernia, however, other characteristic features of MPS-I were absent or very mild. Magnetic resonance imaging revealed the cervical cord compressed by pachymeningeal hypertrophy. Surgery with dural plasty and laminoplasty resulted in decompression of the cervical cord with clinical improvement, revealing marked thickening of the dura mater. Both patients showed a marked decrease of alpha-L-iduronidase (IDUA) activity with c.252insC (p.P55fsX62; known) and c.1209C>A (p.T374N; novel) mutations of the IDUA gene (IDUA). Patients with MPS-I have been reported to present with various clinical phenotypes and severities even if they have identical mutations of IDUA. The quite similar, unique phenotype in monozygotic twins suggests that not only IDUA mutation but also other genetic factors than IDUA markedly influence the clinical manifestations of MPS-I.
Journal of the neurological sciences 03/2011; 302(1-2):121-5. · 2.32 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Total tau protein (t-tau) levels in cerebrospinal fluid (CSF) (CSF-tau) are markedly elevated in patients with Creutzfeldt-Jakob disease (CJD). Some CSF-tau may leak into the blood. We evaluated t-tau levels in serum (serum-tau) as a possible marker for the differential diagnosis of CJD from Alzheimer's disease (AD) and other rapidly progressive dementias (RPD). Serum- and CSF-tau levels were determined in patients with sporadic CJD (n = 12), AD (n = 10) and RPD but no CJD (non-CJD-RPD; n = 9) who showed RPD fulfilling the World Health Organization (WHO) criteria for possible CJD at onset and had a final diagnosis other than CJD. We also analyzed serum-tau levels in healthy volunteers as a control group (n = 10). Serum- as well as CSF-tau levels were significantly elevated in CJD group compared to those in AD, non-CJD-RPD and healthy control groups. Serum-tau would be a simple and useful marker to distinguish CJD from AD and non-CJD-RPD, requiring further large study to confirm this.
Journal of Neurology 03/2011; 258(8):1464-8. · 3.58 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We analysed the epidemiological data and clinical features of patients with prion diseases that had been registered by the Creutzfeldt-Jakob Disease Surveillance Committee, Japan, over the past 10 years, since 1999. We obtained information on 1685 Japanese patients suspected as having prion diseases and judged that 1222 patients had prion diseases, consisting of definite (n=180, 14.7%) and probable (n=1029, 84.2%) cases, except for dura mater graft-associated Creutzfeldt-Jakob disease which also included possible cases (n=13, 1.1%). They were classified into 922 (75.5%) with sporadic Creutzfeldt-Jakob disease, 216 (17.7%) with genetic prion diseases, 81 (6.6%) with acquired prion diseases, including 80 cases of dura mater graft-associated Creutzfeldt-Jakob disease and one case of variant Creutzfeldt-Jakob disease, and three cases of unclassified Creutzfeldt-Jakob disease (0.2%). The annual incidence rate of prion disease ranged from 0.65 in 1999 to 1.10 in 2006, with an average of 0.85, similar to European countries. Although methionine homozygosity at codon 129 polymorphism of the prion protein gene was reported to be very common (93%) in the general Japanese population, sporadic Creutzfeldt-Jakob disease in Japan was significantly associated with codon 129 homozygosity (97.5%), as reported in western countries. In sporadic Creutzfeldt-Jakob disease, MM1 type (Parchi's classification) is the most common, as in western countries. Among atypical sporadic Creutzfeldt-Jakob disease cases, the MM2 type appeared most common, probably related to the very high proportion of methionine allele in the Japanese population. As for iatrogenic Creutzfeldt-Jakob disease, only dura mater graft-associated Creutzfeldt-Jakob disease cases were reported in Japan and, combined with the data from previous surveillance systems, the total number of dura mater graft-associated Creutzfeldt-Jakob disease was 138, comprising the majority of worldwide dura mater graft-associated Creutzfeldt-Jakob disease patients. Regarding genetic prion diseases, the most common mutation of prion protein gene was V180I (41.2%), followed by P102L (18.1%), E200K (17.1%) and M232R (15.3%), and this distribution was quite different from that in Europe. In particular, V180I and M232R were quite rare mutations worldwide. Patients with V180I or M232R mutations rarely had a family history of prion diseases, indicating that a genetic test for sporadic cases is necessary to distinguish these from sporadic Creutzfeldt-Jakob disease. In conclusion, our prospective 10-year surveillance revealed a frequent occurrence of dura mater graft-associated Creutzfeldt-Jakob disease, and unique phenotypes of sporadic Creutzfeldt-Jakob disease and genetic prion diseases related to the characteristic distribution of prion protein gene mutations and polymorphisms in Japan, compared with those in western countries.
[Show abstract][Hide abstract] ABSTRACT: We report a 52-year-old Japanese man showing both upper and lower motor neuron signs with familial amyotrophic lateral sclerosis (ALS). Analysis of the TAR DNA-binding protein of 43 kDa (TDP-43) gene (TARDBP) revealed a glycine-to-serine substitution at position 298 (G298S). Cerebrospinal fluid (CSF) level of total tau protein (CSF-tau) of our patient was found to be highly elevated compared with those of sporadic ALS cases and controls. The elevated CSF-tau level might be related to the damage of neurons exhibiting a large number of TDP-43 inclusions in familial ALS with this mutation.
Internal Medicine 01/2010; 49(12):1209-12. · 0.97 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We report a Japanese man who presented with multiple cranial nerve palsies with hepatitis B virus-related multiple hepatocellular carcinoma (HCC). He presented with right III, IV, VI, IX, X, and XII cranial nerve palsies. Metastases involving the clivus and the right occipital bone from HCC were diagnosed by the findings of magnetic resonance imaging of the head, cerebral angiography, and 2-deoxy-2-[(18)F]fluoro-D-glucose positron emission tomography/computed tomography. In this case, over one-year survival and improvement of neurological signs were achieved by radiotherapy in spite of multiple skull metastases, which are extremely rare.
Internal Medicine 01/2010; 49(23):2631-4. · 0.97 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The Creutzfeldt-Jakob Disease (CJD) Surveillance Committee has identified 1,241 patients with prion diseases during 1999-2009, including 953 with sporadic CJD (sCJD) (76.8%), 207 with genetic prion diseases (16.7%), 78 with environmentally acquired prion diseases (6.3%), and 3 with unclassified CJD. Among atypical cases of sCJD, most common was MM2 type including the cortical and thalamic forms. The genetic cases included 84 with a PrP V180I mutation (40.6%), 37 with a P102L mutation (17.9%), 34 with a E200K mutation (16.4%), 32 with a M232R mutation (15.5%), 4 with a P105L mutation (1.9%), and so on. The environmentally acquired cases included 77 with dura mater graft-associated CJD (dCJD) and one with variant CJD (vCJD). Combined with the results by the previous surveillance systems, a total number of dCJD in Japan was 135. The vCJD patient had a history of short stay in the UK and presented with periodic electroencephalogram in the late stage. Although there was no evidence of association of surgical procedures or blood transfusion with sCJD, 4.5% of the sCJD patients underwent operations after the onset of sCJD, including neurosurgical for 0.8% and ophthalmic for 1.9%, requiring more attention on prion diseases to reduce the iatrogenic risk.
[Show abstract][Hide abstract] ABSTRACT: Up to February 2008, a total of 132 patients with dura mater graft-associated Creutzfeldt-Jakob disease (dCJD) have been identified in Japan, accounting for a majority of the world's patients with dCJD. The patients received dura mater grafts from 1978 to 1993. Lyodura (B. Braun, Melsungen, Germany) was used for all the patients in whom the brand name of the dura mater could be identified. After the incubation period of 1 to 25 years (mean, 11.8 years), CJD appeared from 1985 through to 2006. We analyzed clinical, pathological, and molecular features in 74 patients with dCJD who had been prospectively registered by the CJD Surveillance Committee. The cases of dCJD could be classified into two distinct clinicopathological phenotypes: a non-plaque type, showing typical features identical with those of classic CJD, and a plaque type, characterized by atypical features, including slow progression, lack of or late occurrence of periodic sharp wave complexes on EEG, and plaque formation in the brain. The plaque type accounted for one-third of the pathologically confirmed or clinically diagnosed cases of dCJD. The non-plaque type was associated with methionine homozygosity at codon 129 (129M/M) of the PrP gene in all patients, except for in one patient with the 129M/valine (V) genotype and type 1 protease-resistant PrP (PrP(res)), whereas the plaque type was always associated with the 129M/M genotype and the intermediate type between types 1 and 2 of PrP(res) in all cases. Thus, the clinicopathological and molecular features of the plaque type are distinct from those of the non-plaque type, suggesting contamination of the dura mater grafts with different prion strains.
[Show abstract][Hide abstract] ABSTRACT: There have been more than 400 patients who contracted Creutzfeldt-Jakob disease (CJD) via a medical procedure, that is, through the use of neurosurgical instruments, intracerebral electroencephalographic electrodes (EEG), human pituitary hormone, dura mater grafts, corneal transplant, and blood transfusion. The number of new patients with iatrogenic CJD has decreased; however, cases of variant CJD that was transmitted via blood transfusion have been reported since 2004. Clearly, iatrogenic transmission of CJD remains a serious problem. Recently, we investigated medical procedures (any surgery, neurosurgery, ophthalmic surgery, and blood transfusion) performed on patients registered by the CJD Surveillance Committee in Japan during a recent 9-year period. In a case-control study comprising 753 sporadic CJD (sCJD) patients and 210 control subjects, we found no evidence that prion disease was transmitted via the investigated medical procedures before onset of sCJD. In a review of previously reported case-control studies, blood transfusion was never shown to be a significant risk factor for CJD; our study yielded the same result. Some case-control studies reported that surgery was a significant risk factor for sCJD. However, when surgical procedures were categorized by type of surgery, the results were conflicting, which suggests that there is little possibility of prion transmission via surgical procedures. In our study, 4.5% of sCJD patients underwent surgery after onset of sCJD, including neurosurgeries in 0.8% and ophthalmic surgeries in 1.9%. The fact that some patients underwent surgery, including neurosurgery, even after the onset of sCJD indicates that we cannot exclude the possibility of prion transmission via medical procedures. We must remain vigilant against prion diseases to reduce the risk of iatrogenesis.
[Show abstract][Hide abstract] ABSTRACT: We describe a consanguineous family that had progressive myopathy with rimmed vacuole (RV) formation and amyloid deposition. Patient 1 is a 71-year-old woman with muscle atrophy in the lumbar girdle and lower extremities. Patient 2 is a 40-year-old man (the son of Patient 1) with fatty changes in the biceps femoris muscles. Muscle biopsies revealed myopathic and neurogenic degeneration with RV, necrotic fibers, and interstitial amyloid deposition. Amyloid deposition was detected only in the muscle tissue.