Efficacy of Trihexyphenidyl on Apraxia of Eyelid Opening in Parkinsonism: A Case Report.

Apraxia of eyelid opening (AEO) is occasionally seen in Parkinson's disease (PD) or related diseases. However, many clinicians have trouble with the management of AEO by Parkinsonism. In this report, we describe a case of AEO in Parkinsonism improved by trihexyphenidyl (THP). The patient was a 64-year-old woman, who was previously healthy but developed bradykinesia. She was clinically diagnosed as PD due to an L-dopa challenge test, but no other detailed tests were performed. She started antiparkinsonian medications and her symptoms were improved at an early phase. However, her motor symptoms were gradually exacerbated over time, and antiparkinsonian medications were dosed up. At 69 years old, blepharospasm and AEO developed. Although other antiparkinsonian medications did not improve her AEO, THP cured AEO dramatically at 73 years old. In this report, we discuss a mechanism of AEO by Parkinsonism and the pathway of THP for the improvement of AEO.

Treatment of Subcortical Aphasia Due to Putaminal Hemorrhage With the Japanese Version of Melodic Intonation Therapy (MIT-J).

Melodic intonation therapy (MIT) is one of the rehabilitation methods for patients with non-fluent or dysfluent aphasia, mainly caused by stroke or brain injury. Although MIT is conducted in various languages, reports on the Japanese version of MIT (MIT-J) are limited. In this report, we describe a case about the efficacy of MIT-J in the subacute phase after stroke on subcortical aphasia. Our case was a 60-year-old right-handed woman who suffered from left putaminal hemorrhage. She was treated with acute therapy, including medications and rehabilitation, but non-fluent aphasia was preserved. Regardless of general speech therapies, her aphasia was not improved. In the subacute phase, we started MIT-J (protocol: 20 minutes per day, five days per week for two weeks). The effect of MIT-J was remarkable and in particular, speech intelligibility was improved. It is required to accumulate more cases to reveal the effect of MIT-J.

Lateral Medullary Infarction With Atonic Bladder and Lateropulsion.

Lateral medullary infarction (LMI), or Wallenberg syndrome, can develop various symptoms, but it is rare that ipsilateral axial lateropulsion (or body lateropulsion, BL) or atonic bladder (AB) are caused by LMI. This report describes a case of LMI with both BL and AB. A 77-year-old man, with a history of hypertension and diabetes, developed acute left BL and anuresis. A neurological exam showed right gaze nystagmus, slight dysarthria and dysphagia, right dysesthesia in the trunk, and ataxia in the left limbs and trunk. Horner's syndrome and paralysis were unremarkable. Brain magnetic resonance imaging revealed hyperintensity in the lateral medulla oblongata. Cystometry revealed AB, although the patient had the urge to urinate. Owing to acute therapy, although trunk ataxia was presented for several months, BL and anuresis were recovered on day 15 and day 35, respectively. Here, we describe the potential mechanisms of BL and AB caused by LMI.

Dural Arteriovenous Fistula in Neuro-Behçet's Disease: Association or Chance?

Behçet's disease (BD) is a multisystemic vasculitis disorder. Neuro-Behçet's disease (NBD) is a set of neurologic symptoms imputable to an underlying Behçet vasculitis. Among the wide range of vascular abnormalities secondary to BD, a dural arteriovenous fistula (dAVF) is not classically described. Whether a dAVF is associated with BD or dAVF is a chance occurrence is still a matter of debate. Herein, we describe an NBD case of a 48-year-old male, presenting with headache and fever, where a dAVF was seen on imaging. He was treated with prednisolone and colchicine, followed by the surgical resection for dAVF. Then, we discuss the possible association between BD and dAVF based on the latest literature.

Normal-Pressure Hydrocephalus-Like Appearance in Myotonic Dystrophy Type 1.

Myotonic dystrophy type 1 (DM1) is one of the monogenic neurological diseases that neurologists most often experience. DM1 can develop several symptoms, including muscle weakness, gait disturbance, urinary incontinence, and cognitive decline. Other hand, normal pressure hydrocephalus (NPH) is more frequent in the elderly population and is characterized by a triad of symptoms, gait disturbance, urinary urge incontinence, and cognitive decline. Therefore, some symptoms overlap between DM1 and NPH. In this report, we described a case of DM1 that presented with a triad of NPH, and NPH-like changes in brain images. A 54-year-old man with DM1 visited our hospital for rehabilitation. He had a history of dyslipidemia, diabetes, and cataracts. He developed muscle weakness, blepharoptosis, and dysarthria at 43 years. Neuro-exam revealed percussion and grip myotonia, distal muscle weakness and atrophy, broad-based gait, and urinary incontinence. The mini-mental state examination score was 18. Brain magnetic resonance imaging revealed enlarged lateral and third ventricles and Evans index was 0.38 (NPH criterion; >0.3), which was mimicking for NPH. Tap test (TT) was evaluated twice. First TT improved clinical symptoms slightly, but second was unremarkable. Based on the second TT result, we could not diagnose with NPH and could prevent unnecessary surgical shunting. Brain imaging of DM1 can show an NPH-like appearance in patients older than 50. Although TT is the gold standard for diagnosing NPH, its sensitivity and specificity vary among reports. TT results should be interpreted with caution before performing a surgical shunt. If necessary, multiple TTs should be considered in DM1 patients.

Magnetic resonance imaging arterial spin labeling hypoperfusion with diffusion-weighted image hyperintensity is useful for diagnostic imaging of Creutzfeldt-Jakob disease.

Background and objectives: Magnetic resonance imaging with arterial spin labeling (ASL) perfusion imaging is a noninvasive method for quantifying cerebral blood flow (CBF). We aimed to evaluate the clinical utility of ASL perfusion imaging to aid in the diagnosis of Creutzfeldt-Jakob disease (CJD). Methods: This retrospective study enrolled 10 clinically diagnosed with probable sporadic CJD (sCJD) based on the National CJD Research & Surveillance Unit and EuroCJD criteria and 18 healthy controls (HCs). Diffusion-weighted images (DWIs), CBF images obtained from ASL, N-isopropyl-(123I)-p-iodoamphetamine (123IMP)-single-photon emission computed tomography (SPECT) images, and 18F-fluorodeoxyglucose (18FDG)-positron emission tomography (PET) images were analyzed. First, the cortical values obtained using volume-of-interest (VOI) analysis were normalized using the global mean in each modality. The cortical regions were classified into DWI-High (≥ +1 SD) and DWI-Normal (< +1 SD) regions according to the DWI-intensity values. The normalized cortical values were compared between the two regions for each modality. Second, each modality value was defined as ASL hypoperfusion (< -1 SD), SPECT hypoperfusion (< -1 SD), and PET low accumulation (< -1 SD). The overall agreement rate of DWIs with ASL-CBF, SPECT, and PET was calculated. Third, regression analyses between the normalized ASL-CBF values and normalized SPECT or PET values derived from the VOIs were performed using a scatter plot. Results: The mean values of ASL-CBF (N = 10), 123IMP-SPECT (N = 8), and 18FDG-PET (N = 3) in DWI-High regions were significantly lower than those in the DWI-Normal regions (p < 0.001 for all); however, HCs (N = 18) showed no significant differences in ASL-CBF between the two regions. The overall agreement rate of DWI (high or normal) with ASL-CBF (hypoperfusion or normal) (81.8%) was similar to that of SPECT (85.2%) and PET (78.5%) in CJD. The regression analysis showed that the normalized ASL-CBF values significantly correlated with the normalized SPECT (r = 0.44, p < 0.001) and PET values (r = 0.46, p < 0.001) in CJD. Discussion: Patients with CJD showed ASL hypoperfusion in lesions with DWI hyperintensity, suggesting that ASL-CBF could be beneficial for the diagnostic aid of CJD.

Metabolic changes in the plasma of mild Alzheimer's disease patients treated with Hachimijiogan.

Background: Alzheimer's disease (AD), the most prevalent form of dementia, is a debilitating, progressive neurodegeneration. Amino acids play a wide variety of physiological and pathophysiological roles in the nervous system, and their levels and disorders related to their synthesis have been related to cognitive impairment, the core feature of AD. Our previous multicenter trial showed that hachimijiogan (HJG), a traditional Japanese herbal medicine (Kampo), has an adjuvant effect for Acetylcholine estelase inhibitors (AChEIs) and that it delays the deterioration of the cognitive dysfunction of female patients with mild AD. However, there are aspects of the molecular mechanism(s) by which HJG improves cognitive dysfunction that remain unclear. Objectives: To elucidate through metabolomic analysis the mechanism(s) of HJG for mild AD based on changes in plasma metabolites. Methods: Sixty-seven patients with mild AD were randomly assigned to either an HJG group taking HJG extract 7.5 g/day in addition to AChEI or to a control group treated only with AChEI (HJG:33, Control:34). Blood samples were collected before, 3 months, and 6 months after the first drug administration. Comprehensive metabolomic analyses of plasma samples were done by optimized LC-MS/MS and GC-MS/MS methods. The web-based software MetaboAnalyst 5.0 was used for partial least square-discriminant analysis (PLS-DA) to visualize and compare the dynamics of changes in the concentrations of the identified metabolites. Results: The VIP (Variable Importance in Projection) score of the PLS-DA analysis of female participants revealed a significantly higher increase in plasma metabolite levels after HJG administration for 6 months than was seen in the control group. In univariate analysis, the aspartic acid level of female participants showed a significantly higher increase from baseline after HJG administration for 6 months when compared with the control group. Conclusion: Aspartic acid was a major contributor to the difference between the female HJG and control group participants of this study. Several metabolites were shown to be related to the mechanism of HJG effectiveness for mild AD.

Case report: Clinically mild encephalitis/encephalopathy with a reversible splenial lesion: an autopsy case.

Clinically mild encephalitis/encephalopathy with a reversible splenial lesion is a clinicoradiological syndrome characterized by transient neuropsychiatric symptoms and hyperintensity of the splenium of the corpus callosum on diffusion-weighted MRI. Although intramyelinic edema and inflammatory cell infiltration can be predicted by MRI, the pathology of the splenium of the corpus callosum remains unknown. We encountered a case of clinically mild encephalitis/encephalopathy with a reversible splenial lesion and hypoglycemia in a patient who died of sepsis, and an autopsy was performed. The postmortem pathological findings included intramyelinic edema, myelin pallor, loss of fibrous astrocytes, microglial reactions, and minimal lymphocytic infiltration in the parenchyma. Based on these findings, transient demyelination following cytotoxic edema in the splenium of corpus callosum was strongly considered a pathogenesis of "clinically mild encephalitis/encephalopathy with a reversible splenial lesion" associated with hypoglycemia, and it could be generalized for the disease associated with the other causes. As cytotoxic edema could be the central pathology of the disease, the recently proposed term cytotoxic lesions of the corpus callosum may be applicable to this syndrome.

[Synchronous Lung Metastasis and Hilar Lymph Node Metastasis from Rectal Cancer-A Case Report].

A 64-year-old male was referred to our hospital with both advanced rectal cancer and lung tumor with swollen lymph nodes in the lung hilum. The patient underwent laparoscopic low anterior resection followed by systematic lobectomy of the lung 2 months later. Postoperative pathological examination revealed a diagnosis of metastatic lung tumor and metastasis in the lung hilum. However, hilar lymph node metastasis is considered a poor prognostic factor for lung metastasis. Herein, we report a case of synchronous lung metastasis and hilar lymph node metastasis from colorectal cancer that achieved 20 months of recurrence free survival with surgical therapy alone.

An exploratory, open-label, randomized, multicenter trial of hachimijiogan for mild Alzheimer's disease.

Background: Alzheimer's disease (AD) is a progressive neurodegeneration and is the most prevalent form of dementia. Intervention at an early stage is imperative. Although three acetylcholinesterase inhibitors (AChEIs) are currently approved for the treatment of mild AD, they are not sufficiently effective. Novel treatments for mild AD are of utmost importance. Objective: To assess the effectiveness of hachimijiogan (HJG), a traditional Japanese herbal medicine (Kampo), in the treatment of mild AD. Methods: This exploratory, open-label, randomized, multicenter trial enrolled patients with mild AD whose score on the Mini Mental State Examination (MMSE) was over 21points. All participants had been taking the same dosage of AChEI for more than 3 months. The participants were randomly assigned to an HJG group taking HJG extract 7.5 g/day in addition to AChEI or to a control group treated only with AChEI. The primary outcome was the change from baseline to 6 months post treatment initiation on the Alzheimer's Disease Assessment Scale-cognitive component- Japanese version(ADAS-Jcog). The secondary outcomes were change from baseline of the Instrumental Activity of Daily Life (IADL), Apathy scale, and Neuropsychiatric Inventory (NPI) -Q score. Results: Among the 77 enrollees, the data of 69(34 HJG and 35 control)were available for analysis. The difference in the change of ADAS-Jcog from baseline to 6 months of the HJG and control groups was 1.29 (90% Confidence interval (CI), -0.74 to 3.32 p = 0.293). In the subgroup analysis, the differences in the change from baseline to 3 and 6 months for women were 3.70 (90% CI ,0.50 to 6.91, p = 0.059) and 2.90 (90% CI,0.09 to 5.71, p = 0.090), respectively. For patients over 65 years, the difference at 3 months was 2.35 (90%CI, 0.01 to 4.68 p = 0.099). No significant differences were found between the HJG and control groups in IADL score, Apathy scale, or NPI-Q score. Conclusion: Although not conclusive, our data indicate that HJG has an adjuvant effect for acetylcholinesterase inhibitors and that it delays the deterioration of the cognitive dysfunction of mild Altzheimer's disease patients. Clinical Trial Registration: http://clinicaltrials.gov Japan Registry of clinical trials, identifier jRCTs 071190018.

Salvage PTBD With Chemotherapy Improves Survival in Patients With Unresectable Malignant Biliary Obstruction - A Single Center Retrospective Study.

BACKGROUND/AIM: Malignant biliary obstruction (MBO) is a life-threatening condition. We aimed to investigate the outcome of salvage percutaneous transhepatic biliary drainage (PTBD) in patients with unresectable MBO due to failure of management by endoscopic retrograde cholangiopancreatography (ERCP) and/or prior surgical bypass. PATIENTS AND METHODS: Fifty-two consecutive patients (mean age, 69 years; 44.2% women) underwent salvage PTBD between 2013 and 2020. RESULTS: The median overall survival rate was 4.2 months, with a 95% confidence interval (CI) of 1.9-5.7. The median overall survival (OS) were 11.1 months and 1.9 months for patients who underwent chemotherapy (n=17) and best supportive care (n=35), respectively (p=0.0005). Independent factors predicting poor outcome were best supportive care, with a hazard ratio (HR) of 3.3 (95%CI=1.3-8.5), American Society of Anesthesiologists physical status classification (ASA) with a HR of 13.5 (95%CI=1.3-136.0) and Eastern Cooperative Oncology Group (ECOG) performance status of 4, with a HR of 3.3 (95%CI=1.0-6.2). CONCLUSION: Salvage PTBD with chemotherapy has the potential to achieve prolonged survival in patients with unresectable MBO, including those with failure of ERCP and/or surgical bypass.

Pancreaticoenterostomy With Seromuscular-parenchymal Anastomosis for Prevention of Postoperative Pancreatic Fistula in Distal Pancreatectomy.

BACKGROUND/AIM: There have been several attempts to prevent the development of a postoperative pancreatic fistula (POPF) after distal pancreatectomy (DP); however, there is no established method yet. In the present study, we investigated whether POPF can be prevented using pancreaticoenterostomy with seromuscular-parenchymal anastomosis. PATIENTS AND METHODS: We evaluated the incidence of POPF and complications in 20 patients who underwent DP since August 2014, wherein pancreaticoenterostomy with seromuscular-parenchymal anastomosis was performed. RESULTS: No patient developed POPF, and only 4 patients developed a biochemical leak. Postoperative complications (Clavien-Dindo classification: CD) occurred in 5 patients (Grade IIIa in 2 cases, Grade II in 2 cases, and Grade I in 1 case). In a case of CD Grade II, a gastric ulcer was formed at the pancreatico-gastric anastomosis. CONCLUSION: Although new complications, such as the formation of ulcers, consistent with pancreatic anastomosis, were noted, the present method was useful in preventing POPF.

Decreased numbers of gastric, colorectal, lung, and breast cancer surgeries performed in 17 cancer-designated hospitals in Gunma Prefecture of Japan during the COVID-19 pandemic.

PURPOSE: This study aims to clarify the influence of the COVID-19 pandemic on cancer surgery in Gunma Prefecture. METHODS: A total of 9839 cases (1406 gastric cancer, 3569 colorectal cancer, 1614 lung cancer, and 3250 breast cancer) from 17 hospitals in Gunma Prefecture were investigated. We compared the number of surgical cases, proportion of cases found by screening, and cStage at the time of the first visit by month in 2020 and 2021 with those in 2019. RESULTS: The rate of decline in cancer surgery was 8.9% in 2020 compared with 2019 (p = 0.0052). Compared with the same month of 2019, in some months of 2020 and 2021, significant decreases were observed in the number of surgeries for gastric and colorectal cancer, the percentage of surgical cases detected by screening in all four cancers, and the proportion of cancers with a relatively early cStage in gastric and breast cancer. CONCLUSIONS: The number of surgical cases of the four cancer types detected by cancer screening decreased in Gunma Prefecture owing to the influence of the COVID-19 pandemic. Furthermore, for some cancer types, the number of operations performed in patients with early-stage cancer is also decreased.

Effectiveness of a self-reporting yes/no survey for dementia screening-trial in Fukui, Japan.

Background: Early intervention for dementia patients is extremely important for the prevention of dementia. However, so far, it is not clear as to what kind of screening will be useful for the early detection of dementia. Objective: We aimed to investigate the relationship between the results of a short self-reporting yes/no survey selected in Kihon Checklist, developed by the Japanese Ministry of Health, Labor and Welfare to identify older adults who are at risk of requiring support/care, and other original items developed by Dementia Prevention Team, Fukui, Japan, and Mini-Mental State Examination (MMSE) scores, and determine the diagnostic efficacy of the self-reporting yes/no survey. Methods: Self-reporting yes/no surveys were conducted for 87,687 individuals aged ≥65 years, living in Fukui, Japan, and did not have Long-Term Care Insurance, Japan. According to the survey results, selected individuals were advised to visit a local hospital to be assessed with MMSE. Results: Individuals who could not make a call by looking up phone numbers and manage their own deposits and savings at the bank or automatic teller machine (ATM) had an increased risk of low MMSE score (≤23; odds ratio: 2.74 [1.89-3.97]; 95% confidence interval: 2.12 [1.46-3.07]). Conclusions: Self-reporting yes/no survey could effectively screen for dementia. Not being able to make a call by looking up phone numbers and not being able to manage their own deposits and savings at the bank or ATM are signs of dementia.

[Lung Metastases from Pancreatic Cancer Initially Suspected to be Primary Lung Cancer due to Lepidic Tumor Growth].

A 46-year-old patient man was pointed out multiple abnormal shadows on the chest X-ray. Computed tomography( CT) scans showed diffuse multiple granular shadows associated with ground-glass opacity in the surrounding area. Therefore, sarcoidosis or inflammatory lung disease was suspected. Bronchoscopic examination could not establish definitive diagnosis. Since an increase in the size and number of granular shadows was observed during the follow-up period, surgical biopsy was performed. Pathologically, adenocarcinoma with lepidic tumor growth into the surrounding area was observed suggesting primary lung cancer. Positron emission tomography (PET) after surgery for establishing stage of disease detected an abnormal accumulation in the pancreatic head which was demonstrated to be pancreatic cancer by biopsy. The final diagnosis of multiple lung tumor was metastases from pancreatic cancer.

Clioquinol Decreases Levels of Phosphorylated, Truncated, and Oligomerized Tau Protein.

The neuropathological hallmarks of Alzheimer's disease (AD) are senile plaques (SPs), which are composed of amyloid ß protein (Aß), and neurofibrillary tangles (NFTs), which consist of highly phosphorylated tau protein. As bio-metal imbalance may be involved in the formation of NFT and SPs, metal regulation may be a direction for AD treatment. Clioquinol (CQ) is a metal-protein attenuating compound with mild chelating effects for Zn2+ and Cu2+, and CQ can not only detach metals from SPs, but also decrease amyloid aggregation in the brain. Previous studies suggested that Cu2+ induces the hyperphosphorylation of tau. However, the effects of CQ on tau were not fully explored. To examine the effects of CQ on tau metabolism, we used a human neuroblastoma cell line, M1C cells, which express wild-type tau protein (4R0N) via tetracycline-off (TetOff) induction. In a morphological study and ATP assay, up to 10 µM CQ had no effect on cell viability; however, 100 µM CQ had cytotoxic effects. CQ decreased accumulation of Cu+ in the M1C cells (39.4% of the control), and both total and phosphorylated tau protein. It also decreased the activity of c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (p38 MAPK) (37.3% and 60.7% levels of the control, respectively), which are tau kinases. Of note, activation of protein phosphatase 2A (PP2A), which is a tau phosphatase, was also observed after CQ treatment. Fractionation experiments demonstrated a reduction of oligomeric tau in the tris insoluble, sarkosyl soluble fraction by CQ treatment. CQ also decreased caspase-cleaved tau, which accelerated the aggregation of tau protein. CQ activated autophagy and proteasome pathways, which are considered important for the degradation of tau protein. Although further studies are needed to elucidate the mechanisms responsible for the effects of CQ on tau, CQ may shed light on possible AD therapeutics.

[Small Bore Chest Tube Management for Traumatic Hemothorax Patients More than 24 Hours after Injury].

Thoracic drainage with a 28 Fr or 32 Fr chest tube is recommended as an initial treatment for traumatic hemothorax, however the recommended drainage tube size is unknown when thoracic drainage becomes necessary more than 24 hours after injury. In this report, the experience with the application of a small bore tube (16 Fr or less) for 18 cases of hemothorax requiring thoracic drainage more than 24 hours after injury is presented. The complications observed in 2 of 8 patients with 8 Fr size and none of 10 patients with 16 Fr size. It was considered that 16 Fr size tube is enough to manage the hemothorax developed more than 24 hours after injury.

[A case of asymptomatic Stanford type A aortic dissection with multiple perforator infarcts due to pseudointracavitary thrombus].

A 56-year-old man presented to our hospital as he presented progressive hemiplegia of the right upper limb with no other symptoms, including chest pain. Inter-arm blood pressure difference was not observed. Laboratory investigations revealed an elevated D-dimer value (2.4 µg/ml). Chest X-ray study showed normal findings without widened mediastinum. Brain MRI showed acute multiple brain infarcts in the left posterior limb of the internal capsule and right pons on diffusion-weighted imaging. Bilateral internal carotid arteries were non-occlusive in MRA. Carotid duplex ultrasonography revealed normal internal carotid artery flow velocities bilaterally. Because ischemic lesions were found in multiple vascular territories, and D-dimer value was elevated, the patient underwent thoracic contrast-enhanced-CT to exclude malignant tumors. Stanford type A aortic dissection limited to the ascending aorta was detected. As the plaque had accumulated in the false lumen, we suspected that plaque in the false lumen could be an embolic source. After ascending aortic replacement surgery, brain infarction did not recur during hospitalization. In cases of ischemic stroke wherein multiple vascular territories are detected, and D-dimer value is elevated, even in patients without chest pain, the possibility of painless Stanford type A aortic dissection should be ruled out as an embolic source.

Influences of Folate Supplementation on Homocysteine and Cognition in Patients with Folate Deficiency and Cognitive Impairment.

Although folate deficiency was reported to be associated with hyperhomocysteinemia, influence of folate supplementation on cognition remains controversial. Therefore, we explored the effects of folate supplementation on the cognition and Homocysteine (Hcy) level in relatively short periods in patients with folate deficiency and cognitive impairment. Enrolled 45 patients (mean age of 79.7 ± 7.9 years old) with folate deficiency (<3.6 ng/mL) with cognitive impairment underwent Mini-Mental State Examination (MMSE), and laboratory examinations, including folate, vitamin B12, and Hcy. The degree of hippocampal atrophy in MRI was estimated using a voxel-based specific regional analysis system for Alzheimer's disease (VSRAD). Patients were administrated folate (5 mg/day), then Hcy, and MMSE score were re-examined after 28 to 63 days. Mean Hcy significantly decreased from 25.0 ± 18.0 to 11.0 ± 4.3 nmol/mL (p < 0.001). Average MMSE scores also significantly changed from 20.1 ± 4.7 to 22.2 ± 4.3 (p < 0.001). The degree of change in the MMSE score and basic Hcy or Hcy change was significantly positively correlated, while degree of hippocampal atrophy in MRI did not. Although several factors should be taken into account, folate supplementation ameliorated cognitive impairment, at least for a short period, in patients with folate deficiency.

An autopsy case of tuberculous meningitis undiagnosed by nested-PCR of CSF samples and brain biopsy.

Nested polymerase chain reaction (PCR) testing of cerebrospinal fluid (CSF) has higher diagnostic sensitivity with regard to tuberculous meningitis (TBM) than conventional methods. Herein we describe the autopsy case of a 70-year-old woman with TBM that could not be diagnosed via nested PCR in CSF, even though it was performed three times. The clinical course, magnetic resonance imaging results, and elevated adenosine deaminase levels in CSF were consistent with TBM. We also performed a brain biopsy from the thickened leptomeninges of the patient, which showed granulomatous leptomeningitis consistent with TBM. However, we were not able to identify tuberculous bacilli by the acid-fast bacterial staining, single PCR test, and culture of the biopsy preparations. We finally diagnosed TBM in this case by the positive results of both the fourth PCR test and culture of her CSF, which were taken 7 days before her death. This case suggests that even the combination of repetitive nested PCR in CSF and brain biopsy lacks adequate sensitivity to exclude TBM in some patients.