Characteristics of people seeking consultation after progressing to severe dementia: A mixed-method analysis.

OBJECTIVES: This explores the characteristics of patients with worsening dementia who did not receive a specialized medical examination or care. METHODS: This study utilized a mixed methods analysis. Of the 2712 people who received the Mini Mental State of Examination (MMSE) at the Community Consultation Center for Citizens with MCI and Dementia between December 2007 and December 2019, 1413 people who scored 23 points or less were included. Participants were categorized into mild, moderate, and severe groups, based on their MMSE scores. Participants' characteristics-gender, age, presence or absence of an escort, demographics, family type, and presence or absence of a family doctor-were compared between the groups. To further understand the severe group's characteristics, clinical psychologists recorded consultation forms were categorized. RESULTS: More than 80% of the patients in each group had a family doctor. Moreover, all the severe groups had escorts, and the role of family members and supporters was important for the consultation. In the severe group, 29 patients had never received specialized medical care. Their characteristics were coded "non-existence" (fewer people or opportunities to notice their needs), "connection failure" (a lack of access or connections to consultations), and "evaluation failure" (not recognized as a problem requiring consultation). CONCLUSIONS: It is necessary to improve primary physician education, disseminate knowledge, and raise awareness about dementia, besides building and strengthening networks to alleviate the isolation of dementia patients and their families. The psychological aspects of family members' denial regarding their family members with dementia must be addressed through intervention.

Surgical Management of Incidental Profunda Femoris Artery Aneurysm: A Case Report.

Profunda femoris artery aneurysm is a rare vascular disorder, which is often diagnosed incidentally on identification of synchronous aneurysms. Herein, we report the case of a 63-year-old man, presenting with a hepatic cyst, who had left profunda femoris artery and left internal iliac artery aneurysms. We performed surgical intervention, including resection of the aneurysm and reconstruction of the profunda femoris artery using a prosthetic graft. The postoperative course was uneventful, and computed tomography revealed good graft patency. We believe surgical reconstruction of the profunda femoris artery should be completed except in complicated cases, such as rupture or aneurysm in the distal segment of the profunda femoris artery.

Undifferentiated intimal sarcoma mimicking a mycotic aneurysm.

Intimal sarcoma of arteries is a rare malignant tumor, which often mimics other vascular disorders; therefore, preoperative diagnosis is often challenging. We herein report a 71-year-old man who presented with fever and elevated inflammatory markers who had a mass in the left internal iliac artery with rapid growth. Based on clinical findings, a diagnosis of mycotic aneurysm was made. We performed surgical intervention, including resection of the affected vessels with omentopexy, although intraoperative findings were not typical of a mycotic aneurysm. Microscopic and immunohistochemical examination demonstrated undifferentiated intimal sarcoma. The patient died of multiorgan failure two months after the surgery. The vascular surgeon should consider the possibility of a diagnosis of intimal sarcoma for patients with atypical findings and the importance of histological and immunohistochemical examination for precise diagnosis in surgical vascular cases.

Peripheral Inflammatory Superior Mesenteric Artery Aneurysm Diagnosed by Intraoperative and Histological Findings: A Case Report.

Although rare, superior mesenteric artery aneurysms (SMAAs) are life-threatening due to their high rupture rate. We herein report a case involving an 80-year-old man who presented with acute cholecystitis and who was incidentally found to have a 36-mm peripheral SMAA. A surgical intervention was performed, involving resection of the SMAA and reconstruction of the superior mesenteric artery (SMA) using an autologous vein graft. Intraoperative and histological findings indicated an inflammatory aneurysm, and the postoperative course was uneventful. We believe that resection of the aneurysm and reconstruction of the SMA is the preferred procedure for SMAAs to maintain adequate mesenteric circulations.

Functional neuroimaging in Rasmussen syndrome.

PURPOSE: For a diagnosis of Rasmussen syndrome (RS), clinical course together with electroencephalography (EEG) and magnetic resonance imaging (MRI) findings are considered important, but there are few reports on functional neuroimaging. This study investigated cerebral blood flow (CBF)-single photon emission computed tomography (SPECT), central benzodiazepine receptor (BZR)-SPECT, and fluorine-18 fluorodeoxy glucose-positron emission tomography (FDG-PET) in RS patients, and correlated neuroimaging results with MRI and pathological findings. METHODS: Twenty-three patients diagnosed with RS according to Bien's (2005) diagnostic criteria (including 12 patients with a histological diagnosis) were studied. CBF-SPECT, BZR-SPECT and FDG-PET images were visually evaluated, and the findings correlated with MRI and histological findings. RESULTS: Hypoperfusion areas were observed in 16 of 22 patients by interictal CBF-SPECT. Hyperperfusion areas were observed in 10 of 12 patients by ictal CBF-SPECT, which correlated with ictal onset area by ictal EEG (IOAE). In the limited data of BZR-SPECT in nine patients, lowered uptake was detected in all nine patients, including two with no MRI abnormalities. Lowered glucose metabolism was observed in affected areas in all five patients by FDG-PET. Histological examination revealed findings of chronic encephalitis in all 12 patients examined, concomitant with focal cortical dysplasia in five patients. CONCLUSION: In RS patients, functional neuroimaging reveals clear abnormal findings, even before the appearance of MRI abnormalities. BZR-SPECT and FDG-PET could detect the IOAE efficiently even in the absence of MRI abnormalities, while interictal CBF-SPECT occasionally failed to detect IOAE if MRI was normal. Based on BZR-SPECT, refractory epileptic seizures in RS may suggest possible impairment of inhibitory neurons.

Efficacy and Safety Evaluation of Tolvaptan on Management of Fluid Balance after Cardiovascular Surgery Using Cardiopulmonary Bypass.

Background: Tolvaptan is an orally administered selective vasopressin 2 receptor antagonist that promotes aquaresis. This study aimed to evaluate the efficacy and safety of tolvaptan on management of systemic fluid balance after cardiovascular surgery using cardiopulmonary bypass. . Methods: Sixty-four patients who underwent cardiovascular surgery using cardiopulmonary bypass in our hospital were enrolled for this prospective, randomized study. These patients were divided into three groups: tolvaptan 15 mg+furosemide 20 mg (TH group), tolvaptan 7.5 mg+furosemide 20 mg (TI group), and furosemide 40 mg+spironolactone 50 mg (C group). The endpoint was safety management of systemic fluid balance using tolvaptan without renal dysfunction and electrolyte imbalance. Results: The mean daily urine output in the TH and TL groups (2656±767 and 2505 ±684 mL) was significantly higher than that in the C group (1956±494 mL, TH vs C: p<0.01 and TL vs C: p=0.03). The lowest serum sodium level during medication in the TH group (139.3 ±2.3 mEq/L) was significantly higher than that in the C group (137.1±2.9 mEq/L, p=0.03) The lowest serum osmolality during medication in the TH group was significantly higher than that in the C group (284.8 ±4.3 vs 279.5± 6.3 mOsm/kg, p<0.01). None had critical hypernatremia, hyperosm6lality, or renal dysfunction in any. of the groups. Conclusions: Tolvaptan exerts, a strong diuretic effect compared with conventional diuretics (furosemide and spironolactone) during the postoperative period after an operation using cardiopulmonary bypass without adverse effects on electrolyte balance and renal function.

Semi-quantitative analyses of antibodies to N-methyl-d-aspartate type glutamate receptor subunits (GluN2B & GluN1) in the clinical course of Rasmussen syndrome.

OBJECTIVE: In Rasmussen syndrome (RS), in addition to the predominant involvement of cytotoxic T cells, heterogeneous autoantibodies against neural molecules are also found, but their function has not been elucidated. We examined antibodies to N-methyl-d-aspartate (NMDA) type glutamate receptor (GluR) subunits (GluN2B & GluN1) semi-quantitatively in cerebrospinal fluid (CSF) samples from RS patients, and evaluated their changes over time and their roles in immunopathogenesis. METHODS: Autoantibodies against N-terminal and C-terminal of GluN2B and GluN1 were examined in 40 CSF samples collected from 18 RS patients 5 to 180 months after the onset of RS. Epileptic patients without infectious etiology or progressive clinical course served as disease controls (n=23). Synthesized peptides encoding the extracellular and intracellular domains of human GluN2B and GluN1 subunits were used as antigens in ELISA. We defined the cut-off for these antibodies as mean +2 standard deviations (optimal density) of the disease controls. MRI were evaluated according to the MRI staging proposed by Bien et al. (2002b, Neurology 58, 250). RESULTS: CSF levels of antibodies against N-terminal and C-terminal of GluN2B were higher in RS patients than in disease controls (p<0.01). Likewise, CSF levels of antibodies against N-terminal and C-terminal of GluN1 were also higher in RS patients than in disease controls (p<0.01). All four antibodies tested were below cut-off levels in almost all CSF samples collected within one year from epilepsy onset. The proportions of CSF samples with these antibodies above cut-off levels were highest from 12 to 23 months after epilepsy onset, and declined after 24 months. CSF levels of these antibodies were higher when seizure occurred daily than when seizure occurred less frequently (p<0.01), and were higher at MRI stage 3 than at MRI stages 0, 2 and 4 (p<0.05), except for anti-GluN1-CT antibody at stage 2. CONCLUSIONS: Broad epitope recognition spectrum and delayed production of autoantibodies to NMDA type GluR in CSF of RS patients suggest that the autoantibodies are produced against NMDA type GluR antigens derived from cytotoxic T cell-mediated neuronal damages. These antibodies may impact the pathophysiology of RS in the most active stage, and could be a marker for active inflammation in the clinical course of RS. Further studies including passive transfer of the antibodies to mice may reveal the pivotal roles of the antibodies in RS.

Successful surgical treatment of traumatic transection of the innominate artery: a case report.

Blunt traumatic injury to the innominate artery is relatively rare. We present the case of a 40-year-old woman who fell from a fourth-floor window and was transferred to our hospital with multiple injuries, hemodynamic shock, and disturbance of consciousness. Computed tomography with image reconstruction revealed transection of the innominate artery near its origin. Emergent surgery required establishment of cardiopulmonary bypass before sternotomy in preparation for uncontrollable hemorrhage. Proximal aortic arch replacement with a branch to the right axillary artery was successfully performed using circulatory arrest and selective cerebral perfusion.

[Efficacy of repeated adrenocorticotropic hormone therapy in patients with intractable epileptic spasms].

OBJECTIVE: We examined the effectiveness of repeated adrenocorticotropic hormone (ACTH) therapy in short-term and long-term seizure control in patients with intractable epileptic spasms. METHODS: Twenty-five patients with intractable spasms, in whom epileptic seizures were not controlled or relapsed after the first ACTH therapy, were given repeated ACTH therapy. The short-term effect (seizure control longer than two months) of repeated ACTH therapy was analyzed, and the long-term effect was estimated by Kaplan-Meier method. RESULTS: Short-term seizure control by repeated ACTH therapy was achieved in 13 of 25 patients (52.0%), and in 5 of 13 patients, seizures were controlled by ACTH therapy at higher doses compared with the first ACTH therapy. Short-term effectiveness was obtained in 76.5% of patients who had epileptic spasms alone at the time of the second ACTH therapy, but was ineffective in all 8 patients who had multiple types of seizures, with relapses within 2 months. Short-term effectiveness was not associated with clinical factors such as onset age, age of repeated ACTH treatment, and EEG findings. Regarding the long-term effect of repeated ACTH therapy, the period until seizure relapse was significantly longer in patients with epileptic spasms alone compared to patients with multiple seizure types. Spasms were controlled in 5 of 25 cases (20.0%) at the final observation. In patients with multiple seizure types and patients with onset age older than eight months, seizure control was not obtained. Long-term outcome was good in patients with treatment lag within 2 months. CONCLUSION: In repeated ACTH therapy, seizure type seems to be one of the major determinants for short- and long-term seizure outcome.

Immunomodulatory therapy versus surgery for Rasmussen syndrome in early childhood.

We examined seizure, cognitive, and motor outcomes in patients with Rasmussen syndrome or Rasmussen encephalitis (RS), after recent initiation of immunomodulatory therapies. Among 53 patients with a diagnosis of RS referred from all over Japan, 49 patients (male 22, female 27) with symptoms and findings characteristic of RS were evaluated. Regular intravenous immunoglobulin (IVIg) therapy was administered at a dose of 100mg/kg/day, etc. Regular steroid pulse therapy was conducted with methylprednisolone at a dose of 30mg/kg/day (children) or 1000mg/day (adults) for 3days. Tacrolimus was given at an initial dose of 0.1mg/kg/day (children). Mean onset age was 8.7±10.5years. Seizure-free rate was 71% after treatment by functional hemispherectomy (FH), and response rate for seizures was 81% by regular steroid pulse therapy, 42% by tacrolimus therapy, and 23% by regular IVIg therapy. Rate of patients with IQ higher than 80 (R80) was 50% by regular steroid pulse therapy, 43% by regular IVIg therapy, 29% by tacrolimus therapy, and 0% by FH. R80 after regular steroid pulse therapy was 100% in patients without MRI lesions, and 37% in those with advanced MRI lesions. Improvement of motor function (paresis) was observed only by immunomodulatory therapy. Motor function was aggravated in 100% of patients treated by FH, 62% by regular IVIg, and 10% by regular steroid pulse therapy. We suggest a new treatment strategy for RS using early immunomodulatory therapy: initiation of regular steroid pulse therapy after early diagnosis indicated by biomarkers, then switching to tacrolimus therapy after several months.

Open study of pranlukast add-on therapy in intractable partial epilepsy.

Innovative treatments of epileptic seizures are needed to improve the outcome of epilepsy. We studied the effect of pranlukast on seizure outcome in patients with intractable partial epilepsy. An open study was conducted to evaluate the clinical efficacy of 24-week pranlukast add-on therapy in 50 patients with intractable partial seizures. Serum concentrations of matrix metalloproteinase (MMP)-9 were determined using Biotrak Activity Assay System. Cytokines in cerebrospinal fluid (CSF) were measured by the BioPlex (BioRad) system and soluble TNF receptor1 (sTNFR1) in CSF was measured by the ELISA. Surface markers of lymphocytes in CSF were examined by cell-sorter. Seizure-free rate (SFR) was 13.6%, responder rate (RR) was 47.7%, and aggravation rate (AR) was 18.2% at the 13-24 week period after starting pranlukast. In patients with increased serum MMP-9 before pranlukast therapy (baseline), comparison of paired serum levels showed a significant decrease after pranlukast therapy. Baseline CSF levels of IL-1ß and IL-6 were elevated in patients compared with disease controls. Of four patients with paired data, three (including a responder to pranlukast) showed decreased pro-inflammatory cytokines (IL-1ß, IL-6, and TNFα), and four showed decreased sTNFR1, after pranlukast treatment, and only a responder had markedly decreased frequency of CD8+ T cells in CSF. Pranlukast reduces seizure frequencies probably by pleiotropic effects including normalization of MMP-9 in sera, reduced leakage of pro-inflammatory cytokines into CNS, and inhibition of extravasation of leucocytes from brain capillaries. Further investigations by double-blind control study and animal models are warranted.

[Experiences of caring for patients with lymphedema and dementia].

Recently, the importance of prevention and care of lymphedema patients has been recognized. To improve edema reduction and skin condition, continued care is necessary. However, everyday care requires time and effort, and patients may neglect the required routine. Therefore, it is necessary for patients to recognize the importance of lymphedema and acquire the knowledge and skills to care for their condition. In the case of patients with dementia, it is important to ensure 1) comfortable care for the patients, 2) flexibility of care according to the physical and mental state of the patients, and 3) education of visiting home care staff.

[A case of an end-of-life cancer patient in which lymphedema care improved the QOL enabling home hospice care].

Recently, the importance of prevention and care of lymphedema has been recognized. It appears that the complex physical therapy is relatively taboo for an end-of-life cancer patient with lymphedema. Therefore, an intervention of care is often difficult. In our case, the patient strongly desired a hospice care at home, so we introduced a home hospice care gradually taking a step by step approach with anticipated harmful symptoms. As a result, the home hospice care was doable with ADL and QOL improvements. For lymphedema care of an end-of-life cancer patient, a goal setting, sharing the patient's will based on anticipated symptoms, and an introduction of a gradual care were all important.

[Remarkable effect of a modified ketogenic diet in a boy with focal seizures followed by epileptic spasms in a cluster].

A modified ketogenic diet was demonstrated to be remarkably effective in a child with intractable symptomatic focal epilepsy with combined seizures of focal seizures and epileptic spasms (ES) in a cluster (ESC). ES started at 8 months of age and disappeared with ACTH therapy. At the age of 13 months, the child began to have intractable focal seizures that, later, were followed by ESC 10 times a day. Brain MRI showed only a non-specific diffuse cerebral atrophy. Interictal EEG showed high amplitude diffuse disorganized slow waves with prominent sharp waves predominant over the bilateral occipital region. We started a modified ketogenic diet (mKD) treatment without fasting or a water/calorie limitation. Since the 20th day of mKD, the patient has been seizure free (6 months) without adverse effects. EEG showed remarkable improvement and he has some improvement in the developmental milestones. A modified ketogenic diet is easier to start and continue compared to the classic ketogenic diet, and should be tried in intractable epilepsies that are not treatable surgically early in life from the developmental prognosis point of view.

[Symptoms and clinical course of epilepsy with myoclonic absences].

There is no comprehensive study so far in Japan on epilepsy with myoclonic absences (EMA), characterized by myoclonic absences (MA) as a specific seizure type. We retrospectively studied 9 patients (4 males and 5 females) with EMA confirmed by ictal video EEG and polygraph (EEG+EMG) recordings. The age at MA onset ranged from 18 to 92 months and the age at the last follow-up ranged from 3 to 39 years. The patients had IQ of 40 to 79. Eight patients had been free from seizures for more than one year at the last follow up. MA was controlled by valproate sodium monotherapy or combination of valproate sodium and ethosuximide with appropriate plasma levels. Generalized tonic clonic seizures and severe mental retardation were not necessarily associated with poor seizure outcome. Patients with long MA duration or MA status epilepticus were prone to be refractory to medication. EMA can be divided into two subgroups based on the seizure outcome, favorable and unfavorable. Further large-scale study is required.

Contribution of cyclooxygenase-dependent mechanisms to contractile responses to donepezil in the rat urinary bladder.

Donepezil, an inhibitor of acetylcholinesterase, is used to improve cholinergic neurotransmission and cognitive function in Alzheimer's disease. In the present study, contractile effects of donepezil on the rat urinary bladder were examined and compared with those of the nonselective cholinesterase inhibitor neostigmine. Both donepezil and neostigmine produced concentration-dependent contractile responses of the isolated rat urinary bladder strips. The neostigmine-induced contractions were abolished by atropine. However, donepezil produced contractions of urinary bladders partly through atropine-insensitive mechanisms. The atropine-resistant component of donepezil-induced contraction was significantly reduced by the cyclooxygenase inhibitor indomethacin. These results suggest that cyclooxygenase-derived prostanoids contribute, at least in part, to contractile effects of donepezil in the rat urinary bladder.

[Effectiveness of topiramate in eleven patients with Dravet syndrome].

Dravet syndrome is a rare, but highly refractory epilepsy syndrome. As conventional drugs are not effective, introduction of new effective drugs in clinical use will benefit patients with this disease. We assessed the effectiveness of topiramate (TPM) as adjunctive therapy in 11 patients with Dravet syndrome. TPM was started at doses ranging from 10 to 50 mg/day (0.57 to 2.0 mg/kg/day), and the dosage was increased gradually up to the maximum dose (9 mg/kg/day) depending on efficacy and tolerability. The frequencies of convulsive seizures (generalized tonic-clonic seizures, unilateral seizures, partial onset generalized tonic-clonic seizures) during two months before starting TPM, two months after starting TPM, and the fifth and sixth months after starting TPM were determined. The mean dose (mean +/- SD) of TPM at the second month was 2.7 +/- 1.5 mg/kg/day (1.0-5.7 mg/kg/day, n= 11), and that at the sixth month was 4.5 +/- 2.2 mg/kg/day (1.0-7.3 mg/kg/day, n=10). Evaluation at the second month revealed that one of 11 patients (9%) became seizure-free, six patients (54%) showed greater than 50% seizure reduction, three patients (27%) showed less than 50% seizure reduction, and one patient (9%) had aggravation of convulsive seizures resulting in discontinuation of TPM at the first month. Evaluation at the sixth month revealed that one of 10 patients (10%) was seizure-free, seven patients (70%) had greater than 50% seizure reduction, two patients (20%) had less than 50% seizure reduction, and no patient (0%) had aggravation. Adverse effects were observed in five patients; dizziness in three patients, sleepiness in three patients, and oligohidrosis in one patient. In the present study, TPM was useful as an adjunctive therapy to reduce the frequency of convulsive seizures in patients with Dravet syndrome. A large-scale efficacy study of TPM for Dravet syndrome is warranted.

A substantial number of Rasmussen syndrome patients have increased IgG, CD4+ T cells, TNFalpha, and Granzyme B in CSF.

PURPOSE: We studied the immunologic molecules in cerebrospinal fluid (CSF) and discussed their evolutional changes in pediatric patients with Rasmussen syndrome (RS). METHODS: CSF samples collected from 27 patients with RS (average onset age, 7.5 +/- 5.6 years) were studied. Cell count, protein, glucose, albumin, chloride, and immunoglobulin G (IgG) levels were measured by conventional methods. Surface markers of lymphocytes in CSF were examined by a cell sorter. Granzyme B, interferon gamma (IFNgamma), interleukin 4 (IL-4), tumor necrosis factor alpha (TNFalpha), and IL-12 in CSF were quantitated by enzyme-linked immunosorbent assay (ELISA). Autoantibodies against GluR epsilon2 (NR2B) were examined by immunoblot. RESULTS: The data of the first CSF examination showed that IgG levels (Mann-Whitney U test, p < 0.01), CD4(+) T cells (p = 0.02), TNFalpha levels (p < 0.01), and Granzyme B levels (p < 0.01) were elevated compared with disease controls. White blood cell count, IFNgamma level, IL-12 level, and Granzyme B level were elevated, especially in the early stage of disease. CD4(+) T cells, CD8(+) cells, CD3(+) T cells, IgG levels, and TNFalpha levels were elevated at all stages of disease evolution. Protein levels and albumin levels were elevated in the progressed stage. Autoantibodies against GluR epsilon2 (NR2B) (IgG) were found in 50% of patients in the early stage, and the positive rate was low at the progressed stage. DISCUSSION: The present findings suggest that complex pathophysiologic mechanisms involving CD4(+) T cells and CD8(+) T cells change evolutionally during the progression of RS. A crucial cytotoxic process occurs in the early stage, and declines in the progressed stage.

Electroclinical features of epilepsy in patients with juvenile type dentatorubral-pallidoluysian atrophy.

PURPOSE: To clarify the electroclinical characteristics of epileptic seizures in patients with juvenile type dentatorubral-pallidoluysian atrophy (DRPLA). METHODS: Seventeen patients with juvenile type DRPLA confirmed by genetic analysis were studied retrospectively. The clinical records of all 17 patients and the ictal video electroencephalography (EEG) recordings from 12 of the 17 patients were reviewed. RESULTS: Electroclinical studies in 12 patients identified 11 habitual seizures in 6 patients as partial seizures on ictal video EEG recordings. Clinical manifestations composed mainly of versions of the head and loss of consciousness. These partial seizures were persistently recorded throughout the clinical course. Brief generalized seizures (atypical absence and myoclonic seizure) were observed in 6 of 12 patients at the early stage. In contrast, generalized tonic-clonic seizures (GTCS) were recorded in four advanced stage patients who were almost bedridden. Semiological studies in 17 patients showed that the prevalence of partial seizures was significantly higher in patients with younger epilepsy onset (below 10 years of age; chi(2) test, p < 0.05) and that the age of epilepsy onset was significantly lower in patients with partial seizures than in those without partial seizures (Mann-Whitney U test, p = 0.02). However, the number of CAG repeats and age at clinical onset were not significantly different between two groups. DISCUSSION: Partial seizure is one of the common epileptic features in juvenile type DRPLA, especially in patients with younger epilepsy onset. Seizure types may be affected in an age-dependent manner and change evolutionally during progression of the clinical stage.